Microbiology Flashcards

Question

Which Plasmodium spp infect younger RBCs, older RBCs, and any RBCs?

Answer 1

P. vivax and P. ovale infect younger erythrocytes (this is why the infected erythrocytes appear enlarged). P. malariae infects older erythrocytes. P. falciparum infects any erythrocytes.

Answer 2

True disease relapse is seen with P. vivax and P. ovale only, and results from the harboring of latent sporozoites = hypnozoites within the liver. Neither transfusion-transmitted disease nor transplacental infection is associated with relapse. Recrudescence results from a rebound of persisting (though depleted to levels that are undetectable) blood forms to clinically detectable levels.

Answer 3

The diagnosis is usually made by findings eggs in stool. The eggs of T. saginatum and T. solium are identical. They are 30-40 um, spherical, have a thick radially striated wall, and contain 3 pairs of hooks. The finding of such eggs is reportable as "Taenia species" only. Further characterization relies upon the differences in the scolex or proglottid. The scolex of T. saginata has 4 suckers and a smooth surface (unarmed rostellum); each proglottid is elongated and has >13 lateral uterine branches. The scolex of T. solium has 4 suckers and many tiny hair-like hooks on the surface (armed rostellum); each proglottid is short and has <13 lateral uterine branches. The eggs of T. saginata are not infectious to humans; thus, unlike T. solium, cysticercosis due to T. saginata does not occur.

Answer 4

The eggs of T. saginata are not infectious to humans. Hence, unlike T. solium, cysticercosis due to T. saginata does not occur.

Answer 5

Var capsulatum is found worldwide; in the US, it is found in the Ohio and Mississippi river valleys. Var duboisii is found in Africa. Var capsulatum causes primary pulmonary and mediastinal disease, then disseminates to reticuloendothelial system. Var duboisii causes primary pulmonary and mediastinal disease, then disseminates to skin and bone. In culture, var capsulatum is a hyaline septate mold with lollipop-like smooth microconidia and spiked macroconidia. In culture, var duboisii is indistinguishable from var capsulatum. In tissue, var capsulatum has 2-5 um budding yeasts. In tissue, var duboisii has 10-15 um thick-walled budding yeasts.

Answer 6

H. capsulatum yeast form is 2-5 um with narrow-based budding; mold form is hyphae with periodic lollipop-like microconidia and spiked macroconidia. C. immitis yeast form is 50-200 um spherules with 2-5 um nonbudding endospores; mold form is barrel-shaped arthroconidia. B. dermatitidis yeast form is 8-12 um with broad-based budding; mold form is hyphae with lollipops. S. schenckii yeast form is 2-5 um elongated (cigars) with narrow-based budding; mold form is daisy heads. P. braziliensis yeast form is 10-15 um mariner's wheel budding; mold form is hyphae with lollipops.

Answer 7

The septate hyaline molds other than the dermatophytes and Aspergillus spp. They can be grouped together as the hyalinohyphomyces due to their shared clinical significance. They include: Acremonium, Beuveria, Chrysosporium, Fusarium, Gliocladium, Pseudoallescheria, Penicillium, Paecilomyces, Scedosporium, Scopulariopsis, and Sepedonium. Hyalohyphomycosis is a term that refers to invasive fungal infections caused by hyaline septate molds that have not been further speciated.

Answer 8

Malassezia furfur. In KOH preps of skin scrapings and in histologic sections of affected skin, M. furfur appears as short hyphae and spherical yeasts. This "spaghetti and meatballs" or "frankfurters and meatballs" appearance distinguishes it from the usual hyphae-only appearance of typical dermatophytes. In culture, M. furfur grows as yeasts in just a few days on Saboraud medium when appropriately cultured: at 35 C and overlaid with olive oil.

Answer 9

Henderson-Patterson bodies = molluscum bodies, seen in molluscum contagiosum. They are eosinophilic intracytoplasmic inclusion bodies (accumulated virus particles) in keratinocytes of stratum spinosum and stratum granulosum.

Answer 10

Myospherulosis, AKA spherulocytosis AKA subcutaneous spherulocystic disease, is an iatrogenic benign mass formed by a foreign body-type granulomatous reaction to lipid-containing material and blood. Clinically, there are solid subcutaneous or dermal nodules. Grossly, is a large saccular cyst-like lesion Histologically, there are saclike structures with fungi-like spherules. The spherules are composed of erythrocytes damaged by endogenous and exogenous fat. The damaged erythrocytes are enclosed by a lipid membrane and later phagocytosed by histiocytes as part of the lipogranulomatous reaction that takes place in adipose tissue. The walls of the spherules are formed due to the physical emulsion phenomenon that occurs between lipid-containing materials and blood. Myospherulosis can be a result of fat necrosis, malignancy such as RCC, endogenous membranocystic degeneration of fat that occurs in lupus, or lipid/petrolatum-based medications being injected or applied to open wounds. It is called MYOspherulosis due to the involvement of skeletal muscle in some patients. It can be mistaken for true fungus, such as Coccidioides, because myospherulosis has parent bodies/pigmented bodies and spherules/endobodies that are similar in size and morphology to Coccidioides; however, myospherulosis has pigmented bodies, while Coccidioides is never pigmented.

Answer 11

Foreign body giant cells, Langhans giant cells, and Touton giant cells. All three types are transformed macrophages; mononuclear phagocytes fused under the influence of cytokines. Foreign body giant cells have nuclei that are randomly distributed but often aggregate as centrally located, overlapping nuclei. Langhans giant cells have a peripheral ring-like arrangement of nuclei in an arcuate configuration but no rim of clear cytoplasm. Touton giant cells have a ring of nuclei separating a peripheral clear or foamy rim of cytoplasm from central, more eosinophilic cytoplasm. The peripheral cytoplasm appears clear due to high lipid content. Touton giant cells are seen in lesions with high lipid content, such as xanthomas, xanthogranulomas, and fat necrosis. Touton giant cells can also be seen in dermatofibroma. Other types of multinucleated giant cells include epithelium-derived MGCs, which can be prominent in certain viral infections such as measles (Warthin-Finkeldey cells), RSV, HSV/VZV, and parainfluenza. Also, MCGs derived from neoplastic cells may be formed in a variety of neoplasms.

Answer 12

Human intestinal spirochetosis is defined histologically by the presence of spirochetal microorganisms attached to the apical cell membrane of colorectal epithelium. Human intestinal spirochetes include Brachyspira aalborgi and Brachyspira pilosicoli. Incidence is common in poorly developed areas, but low where living standards are high. Homosexuals and HIV+ individuals are at high risk. Most patients are asymptomatic, but children, homosexual and HIV+ men are more likely to be symptomatic regardless of invasion. The bacteria can be highlighted using silver stains, PAS, Giemsa, Alcian-blue (pH 2.5) and by immunohistochemistry. Intestinal spirochetosis often coexists with other enteric pathogens, including Entamoeba histolytica, Enterobius vermicularis, Helicobacter pylori, Shigella flexneri and Neisseria gonorrhoeae.

Answer 13

HHV8-negative plasma cell variant of CD is characterized by large sheets of mature plasma cells expanding interfollicular regions. While plasma cells are usually polyclonal, a subset of cases shows monoclonal plasma cells; these plasma cells are usually lambda light chain restricted. A subset of follicles may have hyaline vascular-like features; though, these features are often less distinct than in hyaline vascular CD. The HHV8-positive plasma cell variant of CD has interfollicular areas expanded by large sheets of mature, immature, and/or atypical plasma cells. These cases can have increased numbers of plasmablasts in the follicle mantle zones, and a subset of them evolves into HHV8-positive plasmablastic lymphoma.

Answer 14

ImmunoProliferative Small Intestinal Disease is a rare disorder that is considered a variant of MALT lymphoma with nearly complete plasmacytic differentiation. Its name results from its preferential involvement of the small intestine, but it is also known as IgA heavy chain disease, because the neoplastic cells in about one-half of cases produce an abnormal, truncated IgA heavy chain that is missing the variable and the first constant regions and that can be found in the serum. The plasma cells will be positive for CD138 but negative for kappa and lambda light chains. IPSID is suspected to result from Campylobacter infection, and early cases have a relatively high rate of response to broad-spectrum antibiotics. Although it was thought that IPSID was entirely an inflammatory process, it has been now confirmed as a clonal process. It is relatively common for IPSID to progress to a high-grade lymphoma indistinguishable from DLBCL.

Answer 15

Chromoblastomycosis is also known as "Chromomycosis," "Cladosporiosis," "Fonseca's disease," "Pedroso's disease," "Phaeosporotrichosis," and "Verrucous dermatitis." It is a long-term fungal infection of the skin and subcutanous tissue (a chronic subcutaneous mycosis). The infection occurs most commonly in tropical or subtropical climates, often in rural areas. It is caused by specific types of dematiaceous fungi which become implanted under the skin, often by thorns or splinters. The term chromoblastomycosis is restricted to the cases in which sclerotic cells/Medlar bodies/chromo bodies (an adaptive tissue form of the fungi) are present in tissue.

Answer 16

Chromoblastomycosis is a chronic fungal infection of the skin and the subcutaneous tissue caused by traumatic inoculation of a specific group of dematiaceous fungi (usually Fonsecaea pedrosoi, Phialophora verrucosa, Cladosporium carrionii, or Fonsecaea compacta) through the skin. Exophiala species may also be part of the group. The term chromoblastomycosis is restricted to the cases in which sclerotic cells/Medlar bodies/chromo bodies (an adaptive tissue form of the fungi) are present in tissue.

Answer 17

Medlar bodies, also called chromo bodies, are the adaptive tissue form ("sclerotic cells") of a specific group of dematiaceous fungi that cause chromoblastomycosis. They are round, brown, thick-walled structures that are 4-12 µm in diameter, resembling overlapping copper pennies. They divide by septation, resembling hot-cross buns.

Answer 18

Peliosis hepatis is characterised by randomly distributed multiple blood-filled cavities throughout the liver. The size of the cavities usually ranges between a few millimeters to 3 cm in diameter. The pathogenesis of peliosis hepatis is unknown. There are several hypotheses as to cause: it arises from sinusoidal epithelial damage, from increased sinusoidal pressure due to obstruction in blood outflow from the liver, or from hepatocellular necrosis. The condition is typically asymptomatic and is discovered following evaluation of abnormal liver function tests. However, when severe it can manifest as jaundice, hepatomegaly, liver failure and hemoperitoneum. Disease associations include… Infections: HIV, Bacillary peliosis (caused by Bartonella), Staphylococcus aureus. Chronic conditions: End stage renal failure, Kwashiorkor, tuberculosis and other chronic infections. Malignancy: Monoclonal gammopathies, Hodgkin disease, malignant histiocytosis, seminoma, hepatocellular adenoma, hepatocellular carcinoma. Renal transplants: It can be found in up to 20% patients, can be related to azathioprine or cyclosporine use, and may be associated with increased risk of transplant rejection. Drugs and toxins: Corticosteroids, androgens, azathioprine, tamoxifen.

Answer 19

Kaposi sarcoma (KS) is a low-grade vascular tumor associated with Kaposi sarcoma herpesvirus/human herpesvirus 8 (KSHV/HHV8) infection. Kaposi sarcoma lesions predominantly present at mucocutaneous sites, but may involve all organs and anatomic locations. Recognized epidemiologic-clinical forms of KS include classic, African (endemic), AIDS-associated (epidemic), and iatrogenic KS. New clinical manifestations have been described, such as antiretroviral therapy–related KS regression or flares. Kaposi sarcoma lesions evolve from early (patch stage) macules into plaques (plaque stage) that grow into larger nodules (tumor stage). Newer histologic variants include anaplastic, hyperkeratotic, lymphangioma-like, bullous, telangiectatic, ecchymotic, keloidal, pyogenic granuloma–like, micronodular, intravascular, glomeruloid and pigmented KS, as well as KS with sarcoidlike granulomas and KS with myoid nodules. Latency-associated nuclear antigen (HHV8) is the most specific immunohistochemical marker available to help distinguish KS from its mimics. KS remains one of the most common AIDS-defining malignancies.

Answer 20

With the advent of genomic technologies, proliferating KS spindle tumor cells are now known to be of endothelial origin, confirming former studies that used histochemistry and ultrastructural findings. Circulating blood mononuclear and endothelial “progenitor cells” are believed to be the source of early KS lesions. Infection with HHV8 reprograms the host's blood endothelial cells so that they resemble lymphatic endothelium, upregulating several lymphatic-associated genes such as lymphatic vessel endothelial receptor 1 (LYVE1), podoplanin, and vascular endothelial growth factor receptor 3 (VEGFR3). However, HHV8 infection alone appears to be insufficient for the development of KS. Kaposi sarcoma progression relies also on some degree of host immune dysfunction and the local inflammatory milieu. Kaposi sarcoma growth involves the upregulation of many key HHV8 gene products, such as the latency-associated nuclear antigen (LANA-1 or LNA-1). Like other herpesviruses, HHV8 remains latent within cells and has developed a variety of mechanisms to evade the host immune system.

Answer 21

Iatrogenic KS is associated with immunosuppression due to drugs or after transplantation. Kaposi sarcoma occurs mainly in renal transplant recipients, and infrequently after other solid organ or bone marrow transplants. Posttransplant KS may result from reactivation of latent HHV8 infection in recipients or from tumor cells contributed from organ donors. Transplant-associated KS has a protracted, but aggressive course. In transplant recipients, KS lesions may regress after discontinuation of immunosuppressive therapy.

Answer 22

Classical type: Mainly males aged 40-70 years, of Mediterranean or Jewish Ashkenazi origin. Skin of the lower extremities, but mucosal and visceral lesions may develop. Indolent. African type: Middle-aged black adults and children from equatorial Africa. Multiple localized skin tumors, involving lower extremities and/or lymph nodes. Progressive; lymphadenopathic form is aggressive. AIDS-associated type: Mainly homosexual males and IVDUs aged 20-50 years; now equally affects women and children in Africa. Disseminated mucocutaneous and visceral involvement. Aggressive; lesions may regress or flare with initiation of antiretroviral therapy. Iatrogenic type: Immunosuppressed persons of any age from autoimmune disease, drugs, or transplantation. Localized mucocutaneous or disseminated KS, with possible visceral lesions. Variable; may regress after immunosuppression is discontinued.

Answer 23

Early patch-stage KS is characterized by abnormal vessels lined by thin endothelial cells dissecting the dermis. Ramifying proliferating vessels often surround larger ectatic vessels and skin adnexa, producing the so-called promontory sign. This sign is not pathognomonic for KS, as it has also been described in other vascular lesions including benign vascular tumors and angiosarcoma. Sparse chronic inflammatory cells, extravasated red blood cells, and hemosiderin-laden macrophages are frequently present in patch KS lesions. These early histologic changes may be inconspicuous, and for that reason can be easily missed on biopsy. Plaque-stage KS lesions are characterized by a proliferation of both spindle cells and vessels, which in the skin involve most of the dermis, and sometimes even the subcutis. Well-developed KS tumors consist of several fascicles of these spindle-shaped tumor cells, often admixed with a variable chronic inflammatory infiltrate composed of lymphocytes, plasma cells, and dendritic cells. Kaposi sarcoma lesions also contain several hemosiderin-laden macrophages. Iron staining may help distinguish KS from similar-appearing interstitial granuloma annulare lesions that lack iron. In cross section, KS nodules display a sievelike appearance caused by the transection of spindle cells with intervening slitlike spaces. Eosinophilic and PAS–positive hyaline globules are a common finding in advanced KS lesions. These globules may be located within lesional cells or extracellularly. Typical KS lesions are devoid of marked cellular pleomorphism, necrosis, or a significant number of mitotic figures. In rare instances, AIDS-KS lesions may harbor concomitant pathologic findings, usually an opportunistic pathogen (eg, cryptococcosis, mycobacterial granulomas, or molluscum contagiosum).

Answer 24

These are at the two opposite ends of the spectrum of Kaposi sarcoma. Pre-KS lesions are also referred to as an "in situ" form of KS. These pre-KS lesions are characterized by groups of abnormal capillary-like vessels admixed with an inflammatory infiltrate, similar to patch-stage KS lesions. They are associated with lymphangiogenesis arising in the setting of chronic lymphedema. On the other end of the spectrum is anaplastic KS, sometimes referred to as pleomorphic KS. Anaplastic KS is an infiltrative, solid proliferation of spindle cells without vascular spaces, seen mainly in AIDS involving acral sites. This aggressive variant displays a greater degree of cellular and nuclear atypia, high mitotic index (eg, 5 to 20 mitoses per 10 high-power fields), and occasional necrosis.

Answer 25

Kaposi sarcoma lesional cells stain positively with the endothelial markers factor VIII–related antigen, CD31 (PECAM-1), and CD34. CD34 tends to show stronger expression than CD31 in advanced-stage lesions of KS. KS spindle cells also express several lymphatic specific markers such as D2-40 (which binds to the podoplanin antigen), LYVE-1 (a homologue of the CD44 glycoprotein receptor for hyaluronan), VEGFR-3 (the receptor for vascular endothelial growth factor C), and Prox-1. Bcl-2 also shows positivity in KS, related to the tumor's mechanisms of resisting apoptosis. The identification and localization of HHV8 within KS lesional cells by using LNA-1 (also called LANA-1) is the most diagnostically helpful immunostaining technique available to differentiate KS from its mimics. LNA-1 immunoreactivity in KS cells appears as stippled nuclear staining. However, HHV8 is not entirely limited to KS and has been detected in some angiosarcomas, hemangiomas, and dermatofibromas. LNA-1 IHC is favored over PCR detection of HHV8 in the evaluation of problematic vascular proliferations because contaminating mononuclear inflammatory cells may also harbor this herpesvirus, especially in HIV-positive patients.

Answer 26

Clinical history, such as HIV infection or status post transplant, may strongly support the diagnosis of KS. The differential diagnosis of patch-stage KS includes targetoid hemosiderotic hemangioma, fibrous histiocytoma, and interstitial granuloma annulare. The differential diagnosis of plaque-stage KS includes tufted angioma, targetoid hemosiderotic hemangioma, microvenular hemangioma, and acroangiodermatitis (“pseudo-Kaposi sarcoma”). The differential diagnosis of nodular KS includes bacillary angiomatosis, other vascular tumors (eg, spindle cell hemangioma and Kaposiform hemangioendothelioma), fibrohistiocytic tumors (eg, cellular, angiomatoid, and atypical variants of fibrous histiocytoma, and dermatofibrosarcoma protuberans), resolving dermal fasciitis, spindle cell melanoma, and several other spindle cell mesenchymal neoplasms (eg, cutaneous leiomyosarcoma).

Answer 27

Allergic reactions (drug reactions, asthma), parasitic infections (strongyloidiasis), schistosomiasis, filariasis, toxocariasis), metabolic abnormalities (adrenal insufficiency), humoral immunodeficiency (hyperimmunoglobulin E syndrome (Job syndrome), Wiskott-Aldrich syndrome, hyperimmunoglobulin M syndrome, immunoglobulin A deficiency), pulmonary eosinophilias (eosinophilic granulomatosis with polyangiitis (formerly Churg-Strauss syndrome), allergic bronchopulmonary aspergillosis, chronic and acute idiopathic eosinophilic pneumonias), autoimmune blistering skin diseases (dermatitis herpetiformis, bullous pemphigoid).

Answer 28

Progressive multifocal leukoencephalopathy (PML), also known as progressive multifocal leukoencephalitis, is a rare and usually fatal demyelinating disease characterized by progressive multifocal white matter damage and inflammation, due to the JC virus. It is almost always associated with immunosuppression, including immunosuppressive/biologic therapy for autoimmune diseases, such as natalizumab for multiple sclerosis, and other agents for rheumatoid arthritis or lymphoma. Lytic infection of CNS oligodendrocytes leads to their destruction and progressive demyelination, resulting in multifocal lesions. Although PML previously was relatively rare, it now occurs in 3-5% of HIV+ individuals, and is classified as an AIDS-defining illness. Biopsies show multiple foci of demyelination with enlarged and bizzare astrocytes, which are often multinucleated and have multiple large processes. Oligodendrocytes may have eosinophilic or basophilic nuclear inclusions, due to virions. Lymphocytic infiltration is variable. Necrosis with inflammation resembling an infarct may also be seen. Treatment consists of reversal of the immunosuppression, if possible.

Answer 29

Various infectious agents can mimic Crohn disease, the common being infections due to Yersinia and Mycobacterium tuberculosis. Yersinia infections very closely mimic Crohn disease: both diseases can show ileo-colonic involvement, fissuring ulcers, granulomas and transmural inflammation. Similarly granulomatous infection with mycobacteria can closely mimic Crohn disease with granulomas. However, granulomas in Mycobacterial infections are also seen in draining lymph nodes, as opposed to Crohn where they are restricted mostly to the intestine. Transverse ulcers are more characteristic of mycobacterial infection as opposed to longitudinal ulcers and cobblestoning in Crohn disease. Infectious colitis may show diffuse colonic involvement, increased chronic inflammatory cells and neutrophils. In contrast to Crohn disease, neutrophils are often more prominent in the lamina propria compared to the crypts. The architecture is generally preserved.

Answer 30

Morphologically, LYG is angiocentric and may show large zones of necrosis with preservation of viable cells around blood vessels, although necrosis may not be as prevalent in cases of grade 1 LYG. While on initial evaluation the lesion may appear to be a mixture of T- and B- lymphocytes, careful inspection will reveal the atypical morphology of the B-cells. Additionally, LYG is an EBV driven process and the neoplastic B-cells will be positive for EBV latent membrane protein in most cases.

Answer 31

EBV. LYG is an EBV driven process and the neoplastic B-cells will be positive for EBV latent membrane protein in most cases.

Answer 32

Salivary gland enlargement associated with a significant lymphoid infiltrate is recognized in HIV-positive patients. Because the lymphoid tissue usually exhibits morphologic and immunophenotypic features similar to those seen in florid follicular hyperplasia and the lesions often occur in association with enlarged lymph nodes, benign lymphoepithelial cystic lesions are thought to represent a manifestation of persistent, generalized lymphadenopathy. AKA benign lymphoepithelial lesion, benign lymphocpithelial cyst, cystic lymphoid hyperplasia, and HIV-related salivary gland disease. The lesion most commonly arises in the parotid gland where it occurs in 3-6% of adults and 1-10% of children with HIV. Overall, benign lymphoepithelial cystic lesions account for ~25% of enlarged salivary glands in the HIV positive patient population. The lesions are often cystic, bilateral, multiple, and associated with lymphadenopathy. Morphologically, they are characterized by epithelial-lined cysts, often with squamous metaplasia, follicular hyperplasia, glandular atrophy, and in some cases epimyoepithelial islands. In many patients, treatment with HAART results in smaller lesions or their complete resolution.

Answer 33

The risk of developing lymphoma for patients with HIV-related multicentric Castleman Disease is ~15x higher than it is for the general HIV-positive patient population. The survival of patients with HIV MCD who develop lymphoma is poor.

Answer 34

The incidence of non-Hodgkin lymphoma in HIV+ individuals is ~70 to 80x greater than that of the general population.

Answer 35

Although not considered an AIDS-defining illness, HIV+ individuals have a 5 to 15x greater risk of developing cHL than immunocompetent patients. The incidence of HIV cHL has increased with the advent of HAART. Furthermore, the relative risk of developing cHL is higher in patients on HAART than it is in those who are not.

Answer 36

The HIV-related plasmablastic lymphomas characteristically arise in the oral cavity (60% of cases); however, they can also occur in other mucosal sites, such as the sinonasal cavity and the GI tract, and in nonmucosal sites, such as the skin, soft tissue, and lymph nodes.

Answer 37

Progressive HIV-related lymphadenopathy/HIV-related benign lymphadenopathy. Benign lymphoepithelial cystic lesions. Multicentric Castleman disease. Lymphomas associated with HIV can be subcategorized as those occuring (1) also in immunocompetent patients (most cases), (2) more specifically in HIV+ patients (~5% of cases), and (3) in other immunodeficiency states (<5% of cases). The main entities in (1) are BL (~30% of HIV-related lymphomas), DLBCL (~40%), and cHL (~5-15%). These neoplastic entities account for most of the HIV-related lymphoma, although only the first 2 entities are AIDS-defining diseases. The neoplasms in (2) are highly associated with infection by EBV, KSHV/HHV8, or both. They include: Plasmablastic lymphoma. KSHV+/HHV8+ large B-cell lymphoma associated with MCD. Primary effusion lymphoma/Extracavitary primary effusion lymphoma. In (3), the HIV polymorphic lymphoid proliferations, which resemble the polymorphic poasttransplant-associated lymphoproliferative disorders seen in solid organ transplant recipients, comprise thie category of HIV-related lymphoma/lymphoma-like lymphoproliferative disorders.

Answer 38

Tests are available but may not detect early-stage or window-period infections: Chagas disease. Hepatitis (HBV, HCV). HIV-1,-2. HTLV, types I and II. West Nile Virus. Tests are available but not used in all donor centers: HIV group O. No licensed laboratory tests are available for blood donor screening: Babesiosis. CJD. Variant CJD. Malaria.

Answer 39

Hantavirus pulmonary syndrome. During the HPS prodrome, thrombocytopenia is the only dependable finding. Once pulmonary edema is established, however, there is a highly reproducible pentad of findings: thrombocytopenia, left-shifted neutrophilia, neutrophils with lack of significant toxic granulation, increased hemoglobin concentration (hemoconcentration), and >10% of lymphocytes having immunoblastic morphology. Having 4 of these 5 has a high sensitivity and specificity for HPS.

Answer 40

Isolated lymphopenia is uncommon but may be seen in SLE, HIV, SARS, anti-CD20 (rituxan) therapy, steroid therapy, and certain congenital immunodeficiencies (Bruton, SCID, DiGeorge, CVI).

Answer 41

Nonspecific reactive follicular hyperplasia (etiology unknown) is the most common scenario. HIV infection produces a profound variety called florid follicular hyperplasia. RA and Sjogren syndrome produce RFH, frequently with interfollicular plasmacytosis. Syphilis also produces a RFH with interfollicular plasmacytosis, but also causes capsular and trabecular thickening (due to chronicity) and capsular infiltration by plasma cells. Castleman disease.

Answer 42

Viral infections such as infectious mononucleosis, CMV, and postvaccinial lymphadenitis. Hypersensitivity reactions, such as from dilantin. Kimura disease.

Answer 43

Sinus histiocytosis, a nonspecific reaction to numerous lymph node stimuli. Sinus histiocytosis with massive lymphadenopathy (Rosai-Dorfman disease). Lymphangiogram effect. Whipple disease. Hemophagocytic syndrome. Dermatopathic lymphadenitis.

Answer 44

The diffuse pattern of nodal expansion, easy to confuse with lymphoma, is produced by several viruses, particularly EBV, but also CMV, HSV, measles, or post-vaccinia lymphadenitis.

Answer 45

The degree of leukoreduction depends on the goal. If meant to prevent febrile reactions, the unit must contain <5x10^6 WBCs.

Answer 46

Multiple risk factors can contribute to the development of this neoplastic process, such as viral hepatitis infection with HBV or HCV, cirrhosis (independently of cause), exposure to aflatoxin, use of anabolic steroids and tyrosemia.

Answer 47

Nonmolecular methods: Microscopic observation direct susceptibility assay (MODS assay). Light-emitting diode microscopy. MDR-XDRTB Colour Test. Colorimetric assays. Phage amplification assays. Molecular methods: Line probe assays. Automated nucleic acid amplification tests. Loop-mediated isothermal amplification. Oligonucleotide microarray.

Answer 48

An EBV-associated epithelial hyperplasia usually on the lateral tongue in immunocompromised patients, most commonly HIV+ males. The disease correlated with viral load and CD4 counts. Although not an AIDS-defining disease, is a marker of HIV disease progression. Micro: Marked acanthosis and parakeratosis. Epithelial hyperplasia with elongation of rete ridges. Viral cytopathic effect (balloon cells) in spinous layer. Candida can be seen in superficial keratin - coinfection is a common finding in OHL. Very little if any inflammation. No dysplasia. DDx: Frictional keratosis. Hyperplastic candidiasis. Leukoplakia. Lichen planus.

Answer 49

No. OHL is an EBV-associated epithelial hyperplasia usually on the lateral tongue in immunocompromised patients, most commonly HIV+ males but seen in transplant patients as well. The disease correlated with viral load and CD4 counts. Although not an AIDS-defining disease, is a marker of HIV disease progression.

Answer 50

Herpangina is a common viral infection of young children associated with blisters of soft palate or tonsillar pillars. It is caused by viruses belonging to the Enterovirus group (coxsackievirus, poliovirus, echovirus). Coxsackie A16 virus is the most common cause. Transmission is direct contact, usually oral-fecal route.

Answer 51

Herpangina is a common viral infection of young children associated with blisters of soft palate or tonsillar pillars. It is caused by viruses belonging to the Enterovirus group (coxsackievirus, poliovirus, echovirus). Coxsackie A16 virus is the most common cause, but other coxsackie viruses usually associated include A1 to A6, A8, A10, or A22.

Answer 52

A common viral illness of infants and children, which causes fever and blister eruptions of mouth and/or skin. Caused by virus belonging to Enterovirus group. Transmission is by direct contact. Virus is found in secretions, including saliva, nose and throat secretions, blister fluid, and stools.

Answer 53

AKA focal epithelial hyperplasia AKA multifocal epithelial hyperplasia. A benign, virus-induced epithelial proliferation of oral mucosa associated with HPV types 13 and 32. Majority of cases are in children. Micro: Prominent acanthosis and elongated broad rete ridges (since the thickened epithelium extends upward, elongated rete are at same depth as adjacent normal rete ridges). May see papillary surface. Mitosoid cells (represents ballooning and nuclear degeneration; represents an altered nucleus resembling a mitosis in an otherwise normal stratified squamous epithelium; can be seen throughout epithelium); do not misinterpret mitosoid cells as atypia. Koilocytic change in superficial keratinocytes can be seen. No dyskeratosis and/or atypia. DDx: Papilloma. Condyloma acuminatum. Oral verruca vulgaris.

Answer 54

HPV types 13 and 32.

Answer 55

SP: Benign proliferation of squamous epithelium in exophytic pattern with branching fibrovascular tissue cores exhibiting papillary pattern causally related to HPV infection (subtypes 6 and 11 detected in ~50% of cases, rarely HPV 16 detected). VV (AKA common wart or oral wart): Benign HPV-induced (subtypes 2, 4, 6, 40, or 57 detected in 100% of cases) proliferation of squamous epithelium, usually on skin, but also in oral cavity. CA (AKA veneral wart): HPV-related (subtypes 2, 6, 11, 53, or 54 in oral area, rarely 16, 18, or 31 (usually anogenital)) proliferation of squamous epithelium of genitalia, perianal region, oral cavity, or larynx.

Answer 56

Basically is a squamous cell carcinoma of oropharynx, the sites including soft palate, tonsils, uvula, base of tongue, and oropharyngeal wall comprising Waldeyer ring. Is also called oropharyngeal squamous cell carcinoma (OPSCC). What is typically called oral squamous cell carcinoma involves the sites of tongue (lateral and ventral), floor of mouth, lip, retromolar trigone, gingiva, buccal mucosa, and palate. HPV+ OPSCC is nonkeratinizing, while HPV- OPSCC is keratinizing. Other subtypes include: Hybrid-type OPSCC, which has features of both nonkeratinizing OPSCC and keratinizing SCC; is HPV+ most of the time. Lymphoepithelial-like OPSCC, which is similar in histology to EBV-related nasopharyngeal carcinoma; is HPV+. Papillary OPSCC, which is an uncommon variant; most are HPV+.

Answer 57

Malaria is the single most important disease hazard from travel to developing countries. Worldwide, there are over 200 million annual cases with over 600,000 annual deaths. Hematological indicators of poor prognosis in severe malaria include a platelet count < 50 x 10E9/L, prolonged PT >3 seconds, prolonged APTT, fibrinogen < 200mg/dl, hyperparasitemia > 100,00/uL (high mortality if >500,000/uL), > 20% parasites and > 5% neutrophils containing visible malarial pigment. Early recognition and prompt management are important.

Answer 58

AKA AIDS-related parotid cyst. HIV-SGD includes HIV-infected individuals with xerostomia, enlargement of one or more major salivary glands, or both. Mostly adult men 20-60 yo. M:F = 9:1. 98% in parotid, 2% in submandibular gland. Bilateral involvement in 60%. Early phases include florid follicular hyperplasia, attenuated to absent mantle lymphocytes, disruption of germinal centers (follicle lysis). MGCs localized to inter-/intrafollicular and periepithelial areas commonly seen. Multiple squamous epithelial-lined cysts and epimyoepithelial islands present.

Answer 59

HIV-SGD is typically multiple, possibly bilateral, and also contain lymphoepithelial islands. Their germinal centers are larger and more irregular, with interfollicular tissue containing numerous plasma cells, neutrophils, histiocytes, and large, irregular mononuclear or multinuclear cells.

Answer 60

The LRN is a laboratory testing and referral system formed as an outgrowth of the CDC's Health Alert Network. Its purpose is to prepare for and provide a coordinated, rapid response to bioterrorism and other public health emergencies. The LRN consists of four types of laboratories, designated Levels A, B, C, and D.

Answer 61

The LRN consists of four types of laboratories, designated Levels A, B, C, and D. Level A labs must always operate in compliance with accepted BSL-2 requirements. When handling any potential pathogen, all Level A labs should utilize BSL-3 practices for all culture manipulations that might produce aerosols. Level B labs operate in compliance with all BSL-2 requirements and always practice BSL-3 safety procedures. Level C labs operate in compliance with all BSL-3 safety requirements and are certified as BSL-3 facilities. Their staff is specially trained to handle highly pathogenic and potentially lethal agents.

Answer 62

A biosafety level is the level of the biocontainment precautions required to isolate dangerous biological agents in an enclosed facility. The levels of containment range from the lowest biosafety level 1 (BSL-1) to the highest at level 4 (BSL-4). Higher numbers indicate a greater risk to the external environment. In the United States, the CDC has specified these levels.

Answer 63

This level is suitable for work involving well-characterized agents not known to consistently cause disease in healthy adult humans, and of minimal potential hazard to laboratory personnel and the environment. It includes several kinds of bacteria and viruses including canine hepatitis, non-pathogenic E. coli, as well as some cell cultures and non-infectious bacteria. At this level, precautions against the biohazardous materials in question are minimal and most likely involve gloves and some sort of facial protection. The laboratory is not necessarily separated from the general traffic patterns in the building. Work is generally conducted on open bench tops using standard microbiological practices. Usually, contaminated materials are left in open (but separately indicated) waste receptacles. Decontamination procedures for this level are similar in most respects to modern precautions against everyday microorganisms (i.e., washing one's hands with anti-bacterial soap, washing all exposed surfaces of the lab with disinfectants, etc.). In a lab environment all materials used for cell and/or bacteria cultures are decontaminated via autoclave. Laboratory personnel have specific training in the procedures conducted in the laboratory and are supervised by a scientist with general training in micro or a related science.

Answer 64

This level is similar to Biosafety Level 1 and is suitable for work involving agents of moderate potential hazard to personnel and the environment. It includes various bacteria and viruses that cause only mild disease to humans, or are difficult to contract via aerosol in a lab setting, such as C. difficile, most Chlamydiae, hepatitis A, B, and C, orthopoxviruses (other than smallpox), influenza A, Lyme disease, Salmonella, mumps, measles, scrapie, MRSA, and VRSA. BSL-2 differs from BSL-1 in that: (1) laboratory personnel have specific training in handling pathogenic agents and are directed by scientists with advanced training, (2) access to the laboratory is limited when work is being conducted, (3) extreme precautions are taken with contaminated sharp items; and (4) certain procedures in which infectious aerosols or splashes may be created are conducted in biological safety cabinets or other physical containment equipment.

Answer 65

This level is applicable to clinical, diagnostic, teaching, research, or production facilities in which work is done with indigenous or exotic agents which may cause serious or potentially lethal disease after inhalation. It includes various bacteria, parasites and viruses that can cause severe to fatal disease in humans but for which treatments exist, such as F. tularensis, L. donovani, M. tuberculosis, C. psittaci, West Nile virus, Venezuelan equine encephalitis virus, Eastern equine encephalitis virus, SARS coronavirus, C. burnetii, Rift Valley fever virus, R. rickettsii, several species of Brucella and yellow fever virus. Lab personnel have specific training in handling pathogenic and potentially lethal agents, and are supervised by competent scientists who are experienced in working with these agents. This is considered a neutral or warm zone. All procedures involving the manipulation of infectious materials are conducted within biological safety cabinets, specially designed hoods, or other physical containment devices, or by personnel wearing appropriate personal protective clothing and equipment. The laboratory has special engineering and design features.

Answer 66

This level is required for work with dangerous and exotic agents that pose a high individual risk of aerosol-transmitted laboratory infections, agents which cause severe to fatal disease in humans for which vaccines or other treatments are not available, such as Bolivian and Argentine hemorrhagic fevers, Marburg virus, Ebola virus, Lassa virus, Crimean-Congo hemorrhagic fever, and various other hemorrhagic diseases. This level is also used for work with agents such as Smallpox that are considered dangerous enough to require the additional safety measures, regardless of vaccination availability. When dealing with biological hazards at this level the use of a positive pressure personnel suit, with a segregated air supply, is mandatory. The entrance and exit of a level four biolab will contain multiple showers, a vacuum room, a UV light room, and other safety precautions designed to destroy all traces of the biohazard. Multiple airlocks are employed and are electronically secured to prevent both doors opening at the same time. All air and water service going to and coming from a biosafety level 4 (or P4) lab will undergo similar decontamination procedures to eliminate the possibility of an accidental release. The facility is either in a separate building or in a controlled area within a building, which is completely isolated from all other areas of the building. A specific facility operations manual is prepared or adopted. Building protocols for preventing contamination often use negatively pressurized facilities, which, even if compromised, would severely inhibit an outbreak of aerosol pathogens.

Answer 67

Category A agents are the highest priority of agents that pose a national security risk. They: can be easily disseminated or transmitted from person to person; result in high mortality rates and have the potential for major public health impact; might cause public panic and social disruption; and require special action for public health preparedness. They include: anthrax (Bacillus anthracis), botulism (Clostridium botulinum), plague (Yersinia pestis), smallpox (variola major), tularemia (Francisella tularensis), and viral hemorrhagic fevers - filoviruses (i.e., Ebola, Marburg) and arenaviruses (i.e., Lassa, Machupo).

Answer 68

Second highest priority agents include those that: are moderately easy to disseminate; result in moderate morbidity rates and low mortality rates; and require specific enhancements of CDC's diagnostic capacity and enhanced disease surveillance. They include: Brucellosis (Brucella species), Epsilon toxin of Clostridium perfringens, Food safety threats (e.g., Salmonella species, Escherichia coli O157:H7, Shigella), Glanders (Burkholderia mallei), Melioidosis (Burkholderia pseudomallei), Psittacosis (Chlamydia psittaci), Q fever (Coxiella burnetii), Ricin toxin from Ricinus communis (castor beans), Staphylococcal enterotoxin B, Typhus fever (Rickettsia prowazekii), Viral encephalitis (alphaviruses [e.g., Venezuelan equine encephalitis, eastern equine encephalitis, western equine encephalitis]), Water safety threats (e.g., Vibrio cholerae, Cryptosporidium parvum).

Answer 69

Third highest priority agents include emerging pathogens that could be engineered for mass dissemination in the future because of: availability; ease of production and dissemination; and potential for high morbidity and mortality rates and major health impact. They include: emerging infectious diseases such as Nipah virus and hantavirus; other emerging pathogens that could be engineered for mass destruction.

Answer 70

B. anthracis is present in soil throughout the world; in the United States, it is found mostly along old cattle trails in Texas, Louisiana, Mississippi, Arkansas, New Mexico, Oklahoma, and some Midwestern states. However, anthrax is rare in the United States because it is controlled in animal populations by vaccination programs.

Answer 71

About 90% of all human anthrax cases reportedly occur in millworkers handling imported goat hair.

Answer 72

The word anthracis comes from the Greek word meaning “coal,” and the bacterium was so named because the microbe can cause a black scab (eschar) to form on the skin of cutaneous anthrax victims. For the same reason, it is sometimes called the “black carbuncle.”

Answer 73

Anthrax is the single greatest biowarfare threat because it is easy to cultivate spores, although production of a weaponized spore is not so simple. The media sometimes refer to “weapons grade” anthrax versus “nonweapons grade.” Criteria for weapons grade include small spore size, usually 1–3 microns; lack of clumping (usually accomplished by adding a polymer that prevents the natural tendency of spores to clump); the quantity of spores present; and an effective delivery system.

Answer 74

In nature, approximately 95% of human cases of anthrax are cutaneous infections, as opposed to inhalation anthrax or GI anthrax.

Answer 75

Anthrax spores can survive inside macrophages, eventually vegetating and growing to such numbers that they cause the cells to burst and release bacilli into the bloodstream. These bacteria produce four virulence factors; three are toxins that cause systemic symptoms: protective antigen toxin, the lethal factor, and the edema factor. Last, anthrax produces a capsule that protects it from destruction by the body's leukocytes. Once systemic symptoms occur, antibiotics are useless because they have no effect on the circulating toxins.

Answer 76

These bacteria produce four virulence factors; three are toxins that cause systemic symptoms: protective antigen toxin, the lethal factor, and the edema factor (the fourth is a capsule that protects it from destruction by the body's leukocytes). Once systemic symptoms occur, antibiotics are useless because they have no effect on the circulating toxins.

Answer 77

It has initial and acute phases. The initial phase is characterized by mild flu-like symptoms (e.g., malaise, fatigue, low-grade fever) followed by a period of apparent wellness for about a day. This is immediately followed by the acute phase, which eventually leads to more serious symptoms (e.g., acute respiratory distress). The incubation period can vary from 1–5 days, depending on the number of spores inhaled, but can be as long as 60 days. Shock and death usually occur 24–36 hours after the onset of respiratory distress. The fatality rate of inhalation anthrax approaches 90%, even with antibiotic therapy.

Answer 78

This form of anthrax occurs after spores are introduced beneath the skin by inoculation or contamination of a preexisting lesion or break in the skin. The incubation period is 2–7 days (rarely after 1 day) but more often lasts between 2 and 5 days. Lesions begin as small, painless pimples on exposed skin and progress to vesicles and eventually an ulceration that develops a black scab (eschar) at the center (within 2–6 days).

Answer 79

The fatality rate of inhalation anthrax approaches 90%, even with antibiotic therapy. Untreated cutaneous anthrax can have a fatality rate of up to 20%, but fatalities are rare (1%) with proper antibiotic treatment. The fatality rate for GI anthrax is 25%–60%.

Answer 80

This form of anthrax occurs by ingesting contaminated meat, in particular raw or undercooked, from infected animals. It has also been reported in association with animal-hide drums. The incubation period is 2–7 days.

Answer 81

Two types of GI anthrax are characterized by different symptoms: intestinal (e.g., nausea, vomiting, diarrhea) and oropharyngeal (e.g., neck swelling, difficulty swallowing). Shock and toxemia can characterize both forms of the disease, especially in the terminal stages.

Answer 82

Presumptively identify based on criteria below (direct smears, culture smears, colonies on sheep blood agar, and other criteria), and then submit culture to a Level B or C laboratory for final identification. Direct smears: Samples such as blood, CSF, and skin (eschar) show encapsulated gram-positive rods, single or in chains. Generally, spores not seen. Culture smears: Large gram-positive bacilli (1–1.5 by 3–5 µm), which may be gram-variable after 72 hours; spores can be found in culture, especially under non-CO2 atmosphere but are nonswollen and are terminal or subterminal. Colonies on sheep bloor agar plates: Rapidly growing 2–5 mm (overnight at 35° C), nonhemolytic, nonpigmented, dry “ground-glass” surface colonies with irregular edges having comma-shaped projections (Medusa head). The colony has a sticky (tenacious) consistency when teased with a loop. Other criteria: Nonmotile, catalase-positive, urease-negative, nitrate-positive, encapsulated bacillus that can be lysed by gamma phage (gamma phage typing is usually performed by Level B or C laboratory).

Answer 83

Diagnosis: Clinical evaluation and laboratory findings. Tests and specimens: Culture: Blood, CSF, wounds (definitive). Nasal culture: Determines extent of spore spread in population. Immunohistochemical (IHC): Tissue. PCR: Can confirm diagnosis if culture is negative. Serology: ELISA, IFA. Treatment: Antibiotics, including penicillin, quinolones, tetracycline. Treat inhalation anthrax for 60 days. Can combine antibiotics (30 days) and vaccine (3 doses at 0, 14, and 28 days). Full vaccination regimen is 6 doses at 0, 2, and 4 weeks and 6, 12, and 18 months followed by yearly boosters.

Answer 84

Diagnosis: Clinical evaluation and laboratory findings. Tests and specimens: Culture: Sputum, blood, lymph. Direct FA: Respiratory secretions. Serology: F1–V antigen (fusion protein) assay. Treatment: Antibiotics, including tetracycline; quinolones, streptomycin, gentamicin, and chloramphenicol for 10–14 days. Prophylaxis: Medication for 7 days. Formalin-killed vaccine given 0, 1, and 4–7 months. Boosters every 1–2 years.

Answer 85

Diagnosis: Difficult with many rule-outs; laboratory required. Tests and specimens: Culture: Nasal, sputum, respiratory specimens (can also use PCR); blood culture is definitive test. Serology: IFA, ELISA, and microagglutination (gold standard) to detect antibodies. Treatment: Combination antibiotics (6 weeks): Doxycycline and rifampin or quinolone and rifampin. Prophylaxis requires 3 weeks. Numerous vaccines (both killed or live attenuated) available with no proven success.

Answer 86

Diagnosis: Difficult with many rule-outs; laboratory required (key symptom: pneumonia with nonproductive cough). Tests and specimens: General laboratory tests not helpful. Culture: Bacterium does not grow on ordinary media, needs cysteine blood or chocolate agar. Capsular AG detection or PCR: Whole unclotted blood. Direct FA and PCR: Nasal, induced respiratory specimens. IHC: Tissue sometimes helpful. Serology: ELISA AB. Treatment: Antibiotics like gentamicin, streptomycin, ciprofloxacin. Prophylaxis: Doxycycline. Vaccine: Live attenuated available.

Answer 87

Diagnosis: Clinical evaluation; routine laboratory tests are of no value; toxin assay may be useful if toxin present in serum. Tests and specimens: PCR and toxin assay: Use nasal induced respiratory secretions and blood. Treatment: Supportive treatment: Antitoxin can be administered up to 24 hours after exposure: two types, trivalent and pentavalent. Also available is a pentavalent toxoid vaccine.

Answer 88

Diagnosis: Clinical findings (exanthems). Tests and specimens: Cell or chick embryo culture: Skin lesions ideal; nasal swabs, respiratory secretions, serum specimens can also be cultured. Electron microscopy: Identifies virus. PCR: Use same specimens as earlier. Agar gel precipitation: Skin lesions. Serology: Tests are available. Treatment: VIG must be used in conjunction with vaccinia vaccine if exposure occurs beyond a 3-day time frame. Within 3 days, only vaccinia vaccine need be given by scarification. Cidofovir offers promise.

Answer 89

Diagnosis: Difficult with many rule-outs; laboratory required. Tests and specimens: PCR or culture in cells/suckling mice: Nasal, induced respiratory secretions and serum. Serology: ELISA, IFA, and hemagglutination inhibition; detect AB. Treatment: Some drugs show promise. At present, no specific therapy. Treatment geared toward relieving symptoms. Some vaccines show promise (i.e., TC-84).

Answer 90

Diagnosis: Clinical evaluation; key finding is vascular involvement (i.e., petechiae, bleeding, postural hypotension, edema, etc.). Tests and specimens: General: Leukopenia, thrombocytopenia; elevated AST. Serology: ELISA, IFA, and PCR; detect different VHFs. Treatment: Management of hypotension and fluid loss. Aggressive supportive care needed. Ribavirin and immune globulin therapy show some promise. Several vaccines under development.

Answer 91

Presumptively identify based on criteria below (direct smears, culture smears, colonies on sheep blood agar, and other criteria), and then submit culture to a Level B or C laboratory for final identification. Direct smears: More likely to see bipolar staining (“safety pin”) from clinical specimens (blood, sputum, aspirates, etc.) than from cultures. Bipolarity is better seen using Wayson or Wright-Giemsa stain. Beware that bipolar staining is not always observed and is not unique to Y. pestis. Culture smears: Plump gram-negative rods (1–2 by 0.5 µm), single or in short chains. Colonies on sheep blood agar: Grow at 35° C (faster at room temperature) as gray-white, nonhemolytic, translucent, pinpoint colonies at 24 hours, but by 48 hours, colonies are 1–2 mm in diameter, becoming yellowish with age. Growth occurs with or without carbon dioxide. Colonies can appear as “fried egg” or with “hammered copper” shiny surface. On MacConkey, grow as pinpoint non–lactose-fermenting colonies after 24 hours; slightly larger at 48 hours. Other criteria: The bacterium is nonmotile at 35° C to 37° C and at room temperature (Y. pestis is the only Yersinia that is nonmotile at room temperature). It is oxidase and urease negative and catalase positive; growth in broth is flocculent and is described as “stalactite”; clumps at side and bottom of tube.

Answer 92

Yes. Pneumonic plague can be transmitted via large aerosol droplets from a coughing patient. It can be transmitted by cats too!

Answer 93

A rat flea (Xenopsylla cheopis, the oriental flea, or Pulex irritans, the human flea).

Answer 94

Yersinia pestis can be killed by polymorphonuclear cells, but they can survive in monocytes, where they produce a capsule to resist phagocytosis. These bacteria can then rapidly reach the lymph system and bloodstream and be disseminated to all organs, causing hemorrhage and necrosis.

Answer 95

A very low number; fewer than 100 organisms are necessary to cause human infection.

Answer 96

The bacterium is killed after heat exposure (15 minutes at 72° C/160° F) and within several hours of exposure to sunlight.

Answer 97

Bubonic, pneumonic, and septicemic.

Answer 98

The mortality rate of untreated pneumonic plague is 100%, and that of untreated bubonic plague is about 50%.

Answer 99

2-10 days for bubonic plague, 1-3 days for pneumonic plague.

Answer 100

Pneumonic plague patients transmit infection through large particle droplets (greater than 5 microns) generated by coughing, talking, or sneezing. A simple surgical-type mask can protect workers or family members. “Droplet Precautions” should be maintained for 3 complete days of antibiotic therapy, after which a person is no longer contagious. Because “droplets” occur only within 3–5 feet of a patient, central air conditioning systems do not need to be fitted with HEPA filters (i.e., they do not need to provide bacteria- and particle-free air).

Answer 101

Presumptively identify based on criteria below (direct smears, culture smears, colonies on sheep blood and chocolate agars, and other criteria) and then submit culture to a Level B or C laboratory for final identification and/or confirmation, although most Level A laboratories are able to completely identify Brucella. Direct smears: Blood and/or bone marrow most often submitted. Brucella appears as faintly staining, small gram-negative coccobacilli (0.5–0.7 by 0.6–1.5 µm), mostly seen as single cells appearing like “fine sand.” Culture smears: Similar to direct smears. Colonies on SBA and CA: Usually not visible or are pinpoint at 24 hours; at 48 hours, colonies are tiny, nonpigmented, and smooth with an entire edge, and are nonhemolytic on SBA. Growth of some strains is enhanced by carbon dioxide tension. Some strains grow on MacConkey; Thayer-Martin can be used as a selective medium. Blood cultures are held for 21 days for suspect cases. Other criteria: These coccobacilli are catalase, urease, and oxidase positive (B. canis is variable). They are nonmotile and do not require X and V factors. Brucellosis is one of the most commonly reported laboratory-acquired infections. Automated systems are not useful, nor are they recommended for identification. Remember that sniffing culture plates of Brucella can result in infection.

Answer 102

Brucellosis is a systemic zoonotic disease caused by Brucella melitensis, B. suis, B. abortus, and B. canis. These bacteria ordinarily cause disease in domestic animals, such as goats, sheep, and camels (B. melitensis); cattle (B. abortus); and pigs (B. suis). The primary pathogen of dogs, B. canis rarely causes disease in humans.

Answer 103

Human disease is called undulant fever, Malta fever, Bang's disease, Gibraltar fever, and Mediterranean fever and occurs worldwide.

Answer 104

Natural infection in humans occurs when bacteria are inhaled as aerosols, ingested in raw unpasteurized infected milk or meat, or introduced into abrasions in skin or through contact with conjunctival surfaces.

Answer 105

In developed countries, human infection is associated with the meat packing and dairy industries.

Answer 106

Brucellae are intracellular bacteria; they are able to survive phagocytosis and thus can be carried from lymph tissue to blood and deposited in numerous organs. Inside the phagocytes, the bacteria grow, and eventually their host cells are killed, and a new crop of bacteria is released. The “undulant” fever pattern observed with this disease corresponds to the release of bacteria into the blood, thereby causing fever. As these bacteria are eliminated, the fever subsides, only to recur when another crop of bacteria is released. Relapses are common.

Answer 107

Brucella species have two morphologically different colony types: smooth and rough. The smooth form is more pathogenic because of the presence of a capsule that protects the bacterium from phagocytosis and destruction.

Answer 108

B. melitensis and B. suis are more virulent than the other two species and have better intracellular survival.

Answer 109

Mortality rate is about 6% for B. melitensis but 1% for the other species.

Answer 110

The incubation period can be 1–8 weeks but is usually 3–4 weeks.

Answer 111

Onset is insidious, with malaise, fever, chills, sweats, headache, fatigue, myalgias, and arthralgias. Fever usually rises in the afternoon; it falls during the night and is accompanied by drenching sweat. Swollen lymph, spleen, and liver may also be present. The undulant fever can occur over weeks, months, or even years. Yet, there are many days when a patient has no fever and feels relatively well, only to experience another cycle of waxing and waning fever. Patients are often diagnosed with a fever of unknown origin. Cough occurs in about 20% of cases, but the radiograph appears normal. Gastrointestinal symptoms occur in up to 70% of adult cases, although less frequently in children.

Answer 112

Most deaths are associated with endocarditis or meningitis.

Answer 113

Brucellosis cannot be transmitted person-to-person, so that patient isolation is not required. However, contact precautions are indicated if a draining lesion is present. Brucellosis is contracted through eye contact (i.e., rubbing or touching your eyes), so hand washing with germicidal soap or alcohol-based hand sanitizers is an important protective strategy.

Answer 114

Presumptively identify based on criteria below (direct smear; culture smear; colonies on sheep blood, chocolate, and blood cysteine agars; and other criteria) and then submit culture to a Level B or C laboratory for final identification. Direct smear: Gram stain of blood, biopsy material, scrapings, or aspirates may be difficult to interpret because bacteria are tiny, pleomorphic, poorly staining gram-negative coccobacilli seen mostly as single cells. Culture smear: Very tiny (0.2–0.5 by 0.7–1.0 µm), poorly staining, pleomorphic, gram-negative coccobacilli. They are smaller than Haemophilus influenzae and Brucella spp. Their minuscule size should raise awareness. Colonies on sheep blood, chocolate, and blood cysteine agars: Grow poorly and slowly on SBA as 1–2 mm gray-white, nonhemolytic colonies after 48–72 hours. On CA and BCA, colonies are slightly larger, 1–3 mm, gray-white to bluish-gray with an entire edge and smooth flat surface. Colonies do not subculture well to SBA (viability is usually lost). Subcultures should be made onto CA, BCA, or Thayer-Martin agar. Carbon dioxide is not required for growth. No growth occurs on MacConkey or eosin methylene blue agar. Other criteria: F. tularensis is nonmotile and oxidase and urease negative; catalase can be weakly positive or negative. X and V factors are not required. Slow growth in thioglycollate broth with a dense band near top, which eventually diffuses downward with time.

Answer 115

The causative agent of tularemia (also known as “rabbit fever”) is Francisella tularensis. These bacteria are gram-negative bacilli that are nonmotile and have no spore form.

Answer 116

Humans acquire this zoonotic disease through contact with animals, usually through the inoculation of skin or their mucous membranes with blood or tissue fluids of infected animals or bites from infected ticks, mosquitoes, or flies. A less common method of acquiring infection is through inhalation of contaminated dusts or ingestion of contaminated foods or water.

Answer 117

Because the bacterium is highly contagious, as few as 25 inhaled organisms or as few as 10 organisms administered subcutaneously can cause infection.

Answer 118

F. tularensis produces a capsule that allows the organism to avoid immediate destruction by the body's phagocytes. It can survive as an intracellular parasite within cells of the lymph system.

Answer 119

Ulceroglandular tularemia (70%–85% of cases) typically presents with a skin ulcer, usually as the result of a tick bite, and swollen lymph nodes, fever, chills, headache, sweating, and coughing. Glandular tularemia (5%–12% of cases) is characterized by fever and swollen lymph nodes but no obvious skin lesion. Typhoidal tularemia (7%–14% cases) presents with acute onset of fever, chills, headache, vomiting, and diarrhea. Usually no skin lesions or swollen lymph nodes are present, but the condition is associated with primary or secondary pneumonia. Oculoglandular tularemia (1%–2% cases) presents with severe conjunctivitis and swollen lymph nodes, usually as the result of self-inoculating the organism into the conjunctivae. Oropharyngeal tularemia occurs in patients who have a primary lesion in the oropharynx. Patients present with severe headache and bilateral tonsillitis or severe streptococcal-type sore throat. Persistent swollen lymph nodes in the neck appear after 1–2 weeks. Pneumonic tularemia (8%–13% cases) is primarily a complication of the other forms, especially typhoidal tularemia. It is also acquired by inhaling of infectious aerosols or as a result of blood-borne dissemination. Lymph nodes in the lungs are enlarged. Sometimes, the pneumonia is not evident.

Answer 120

Ulceroglandular tularemia (70%–85% of cases) typically presents with a skin ulcer, usually as the result of a tick bite, and swollen lymph nodes, fever, chills, headache, sweating, and coughing.

Answer 121

Typhoidal tularemia (7%–14% cases) presents with acute onset of fever, chills, headache, vomiting, and diarrhea. Usually no skin lesions or swollen lymph nodes are present, but the condition is associated with primary or secondary pneumonia. This form has the highest mortality rate and is the most likely bioterror form.

Answer 122

Submit specimens immediately to public health laboratory for evaluation and referral, even if criminal activity is not suspected. Level A laboratories should not manipulate specimens, culture, identify, or perform toxin assays. Level A laboratory responsibility is limited to advising the medical staff on specimen selection, packing, shipping, and notifying the recipient laboratory about specimens from a suspected case. For suspect food samples, 25–50 g of food should be submitted in original containers that have been placed in a leakproof sealed system and transported at 4 C. If aerosolized release is suspected, collect nasal swabs for toxin testing and/or polymerase chain reaction analysis and transported at room temperature. For stool or enema fluid, collect 25–50 g into sterile leakproof containers and transport at 4 C. Collect approximately 10 mL of serum for serologic assays and transport at 4 C. Collect environmental and/or other samples on swabs and transport at 4 C.

Answer 123

Seven C. botulinum toxins are known: A, B, C, D, E, F, and G. Human illness is caused by four of the seven toxins: types A, B, E, and F. The toxins bind to synaptic vesicles of cholinergic nerves, preventing release of acetylcholinesterase at peripheral nerve endings (including neuromuscular junctions).

Answer 124

The classic type is food-borne botulism, which typically occurs in adults and is caused by ingestion of toxins present in contaminated food. C. botulinum grows in food and produces its toxin. The usual foods involved are canned alkaline foods that are eaten without cooking, and smoked and vacuum-packed foods. Under anaerobic conditions, C. botulinum spores grow into vegetative forms that produce toxin. Wound botulism, the rarest form, occurs when bacteria gain access to a wound site and then produce toxins in vivo. Infant botulism, the most common type, occurs when a child consumes food contaminated with C. botulinum rather than consuming pre-formed toxins. Toxin is produced in the infant's gut, de novo, and poisons from within. Some botulism patients do not have an obvious food or wound source; they fall into the “classification undetermined” group.

Answer 125

Most common - infant botulism. Least common - wound botulism.

Answer 126

Symptoms usually begin 18–24 hours after ingestion or inhalation of toxin, although this may take several days. Initial symptoms include double vision, lack of coordination of eye muscles, inability to swallow, speech difficulty, generalized weakness, and dizziness. These are followed by descending progressive weakness of the extremities and weakness of the respiratory muscles. No fever is present, and the patient may be totally alert and oriented. Neurologic examination shows flaccid muscle weakness of the tongue, larynx, respiratory muscles, and extremities. A patient remains fully conscious until shortly before death from respiratory paralysis or cardiac arrest.

Answer 127

No. Suppression of antibody production is probably caused by the toxins, in much the same way that toxic shock syndrome toxin-1 produced by Staphylococcus aureus prevents antibody production.

Answer 128

Food-bourne.

Answer 129

Smallpox is highest-level emergency; submit specimens immediately to public health laboratory. Virus is highly infectious; avoid manipulation; if necessary use Biological Safety Level-3 practices. Responsibility of Level A laboratories is limited to advising medical staff on specimen selection, packing and shipping sample, and communicating with reference laboratory. Level A laboratories should not culture, sample, or perform assays on specimens suspected of containing the virus. Clinical diagnosis is confirmed by Level D laboratory techniques. For biopsies, aseptically place two to four portions of tissue into sterile, leakproof, freezable container. For scabs, aseptically place scrapings/material into sterile, leakproof freezable container. For vesicular fluid, collect fluid from separate lesions onto separate sterile swabs. Always include material from base of each vesicle. These specimens are transported at 4 C within 6 hours, or stored at -20 to -70 C.

Answer 130

Plague is estimated to have killed >25 million. Smallpox is estimated to have killed ~500 million.

Answer 131

Two variants of smallpox are known: variola major, which is associated with a higher mortality rate of 15%–40%, and variola minor, which causes a milder disease and is associated with a mortality rate of only 1%.

Answer 132

It is currently assumed that an aerosol infective dose is low and presumably ranges from 10–100 organisms.

Answer 133

Postexposure immunization with smallpox vaccine (vaccinia virus) is effective and is recommended if given within 3 days of exposure. However, even if more than 3 days elapse, vaccination and vaccinia immune globulin may provide protection.

Answer 134

Smallpox is transmitted by large or small respiratory droplets, and by contact with skin lesions or secretions. Patients are considered more infectious if they are actively coughing. The incubation period is typically 12 days, with a range of 10–12 days. Clinical illness begins with a 2 to 3 day period of vague symptoms such as malaise, fever, headache, chills, and backache. The fever can last as long as 5 days or may be as short as 1 day. After the fever, an exanthem (eruption of skin or rash) appears that undergoes papular, pustular, and crustular stages. The latter falls off 2–4 weeks after the initial lesion and leaves a pink scar. An important characteristic of smallpox is that lesions in affected areas appear in the same state.

Answer 135

An important characteristic of smallpox is that lesions in affected areas appear in the same state. This differs from chickenpox, where lesions are not synchronous and occur in crops. Smallpox lesions are distributed centrifugally (more numerous on the face and extremities than on the trunk), unlike chickenpox. Hence, the smallpox exanthem is very characteristic and is a useful diagnostic tool.

Answer 136

The fatality rate is 15%–40% in unvaccinated patients and <1% in those vaccinated.

Answer 137

Patients with smallpox are infectious as soon as a rash occurs and remain infectious until scabs fall off, approximately 3 weeks later. Generally, respiratory droplets become infectious earlier than skin lesions. In hospitals, both airborne and contact precautions are required to prevent contagion.

Answer 138

Submit samples immediately to public health laboratory for evaluation and referral. Level A laboratory responsibility is limited to advising medical staff on specimen selection, packing and shipping sample, and communicating with reference laboratory. Serum and CSF are taken for or culture, PCR, or serologies (ELISA, FA, etc.). Nasal, respiratory samples (including induced samples) are taken for culture and PCR. Other specimens such as biopsy, autopsy, stool, etc., are sent for pathology, culture, hematology/chemistry analysis, etc. All samples are transported at 4 C within 6 hours or stored at -20 to -70 C.

Answer 139

Many can be, but the attack rate, that is, the number of people who would probably get the disease after being exposed to the agent, is much lower than for VEE, which has an attack rate of about 100%.

Answer 140

Eight serologically distinct viruses exist, but only two are important pathogens for humans: variants A/B and C.

Answer 141

Submit samples immediately to public health laboratory for evaluation and referral. Some viruses are highly infectious; avoid manipulation; if necessary, use Biological Safety Level-3 practices. Level A laboratory responsibility is limited to advising medical staff on specimen selection, packing and shipping sample, and communicating with reference laboratory. Serum is taken for culture, PCR, or serologies (ELISA, HI, FA, etc.). Other specimens such as biopsy, autopsy, etc., are taken for for pathology, culture, hematology/chemistry analysis, etc. Specimens are transported at 4 C within 6 hours, or stored at -20 to -70 C.

Answer 142

Dengue, which is transmissible only via mosquito. In general, VHFs are very difficult to weaponize because there is no real carrier state.

Answer 143

Ebola: contact. Marburg: contact. Lassa fever: contact. Argentine (Junin): contact and aerosol. Bolivian (Machupo): contact and aerosol. Crimean Congo: ticks and contact. Hantavirus: contact and aerosol. Rift Valley fever: mosquito and aerosol. Dengue: mosquito. Yellow fever: mosquito.

Answer 144

Crimean Congo.

Answer 145

Viral hepatitis after 11th birthday. Positive test for hepatitis B surface antigen. Repeat reactive test for anti-HBc on more than one occasion. Clinical or laboratory evidence of HCV, HTLV, or HIV infection by current FDA regulations. Previous donation associated with hepatitis, HIV, or HTLV transmission. Behavioral risk factors for HIV infection according to current FDA guidance. History of babesiosis or Chagas’ disease. Stigma of parenteral drug use. Injection of nonprescription drugs. Risk of vCJD according to current FDA guidelines.

Answer 146

Mucous membrane exposure to blood. Nonsterile skin or needle penetration. Sexual contact with an individual with a confirmed positive test for hepatitis B surface antigen. Sexual contact with an individual with viral hepatitis. Sexual contact with an individual with HIV infection or at higher risk for HIV infection. Incarceration in a correctional institution for longer than 72 consecutive hours. History of syphilis or gonorrhea.

Answer 147

Hep B surface antigen (EIA). Hep B core antibody (EIA). Hep C virus antibody (EIA). HIV-1 and HIV-2 antibodies (EIA) (combined HIV p24 antigen, HIV-1 antibodies, and HIV-2 antibodies acceptable). HTLV-I and HTLV-II antibodies (EIA). Trypanosoma cruzi antibodies (EIA). Serologic test for syphilis. Hep C RNA (NAT). HIV RNA (NAT). West Nile virus DNA (NAT).

Answer 148

Anaplasma phagocytophilum (formerly Ehrlichia phagocytophilum) is a gram-negative rickettsial bacterium that is unusual in its tropism to neutrophils. It causes anaplasmosis in sheep and cattle, also known as tick-borne fever and pasture fever, and also causes the zoonotic disease human granulocytic anaplasmosis.

Answer 149

False. HIV infection, although it may cause marked T cell dysfunction, does not increase the risk of TA-GVHD.

Answer 150

HIV - 1:1,467,000. HBV - 1:280,000-1:357,000. HCV - 1:1,149,000. HTLV-I/II - 1:641,000-1:1,900,000. West Nile virus - ~1:7,000,000.

Answer 151

Approximately 50% of blood donors are CMV seropositive, although the estimated risk of transmission by a seropositive transfusion is about 1%.

Answer 152

Most acute West Nile virus infections are asymptomatic, with a febrile illness occurring in about 1 in 5 infections and neuroinvasive disease in about 1 in 150 infections.

Answer 153

Birds are the natural reservoir, with mosquitoes serving as the vector of transmission. Humans are an accidental host, with infection occurring during times of mosquito activity.

Answer 154

Babesia species are endemic in North American mammals and are transmitted by ticks of the genus Ixodes.

Answer 155

A polyester-tipped swab on a plastic shaft is acceptable for most organisms. Calcium alginate should be avoided for collection of samples for viral culture, because it could inactivate herpes simplex virus (HSV); cotton may be toxic to Neisseria gonorrhoeae; and wooden shafts should be avoided, because the wood may be toxic to Chlamydia trachomatis. Swabs are not optimal for detection of anaerobes, mycobacteria, or fungi, and they should not be used when these organisms are suspected. An actual tissue sample or fluid aspirate is always superior to a swab specimen for the recovery of pathogenic organisms.

Answer 156

After collection, specimens should be placed in a biohazard bag and transported to the laboratory as soon as possible. If a delay is unavoidable, urine, sputum and other respiratory specimens, stool, and specimens for detection of C. trachomatis or viruses should be refrigerated to prevent overgrowth of normal flora. CSF and other body fluids, blood, and specimens collected for recovery of N. gonorrhoeae should be held at room temperature, because refrigeration adversely affects recovery of potential pathogens from these sources.

Answer 157

Optimally, all specimen containers but, at a minimum, those containing respiratory secretions and those submitted specifically for detection of mycobacteria or fungi should be opened in a biological safety cabinet. Specimens collected for virus isolation should be handled in a biological safety cabinet to prevent contamination of the cell cultures.

Answer 158

The optimal time to draw blood for cultures when bacteremia or fungemia is suspected is just before a chill but, because this is not predictable, most blood cultures are collected after the onset of fever and chills.

Answer 159

In adults with bacteremia, the number of colony-forming units (CFU) per milliliter of blood is frequently low. Therefore, for adults, collecting 20–30 mL of blood per culture set is strongly recommended. In infants and children, the concentration of microorganisms in blood is higher, and collection of 1–5 mL of blood per culture is adequate.

Answer 160

Organisms such as the coagulase-negative staphylococci, viridans streptococci, corynebacteria, Bacillus species, and Propionibacterium species are frequent blood culture contaminants but may also be true pathogens.

Answer 161

Diluting the blood specimen in broth medium in a 1:10 ratio provides optimal neutralization of the serum bactericidal activity. Incorporating 0.02–0.05% sodium polyanethol sulfonate in the blood culture medium inhibits coagulation, phagocytosis, and complement activation, and inactivates aminoglycosides. Methods that counteract the presence of antimicrobial agents are available as well.

Answer 162

Two commercial manual blood culture systems are available: the biphasic system and the lysis-centrifugation system. Examples of automated systems include one based on colorimetric detection of CO2 produced during microbial growth, one based on fluorescent technology and pH, and one that is based on measuring gas consumption and/or gas production.

Answer 163

Infections with species of Borrelia, except Borrelia burgdorferi (the etiologic agent of Lyme disease, most commonly diagnosed serologically), are diagnosed by detecting spirochetes in the peripheral blood during febrile periods. Organisms are visualized in wet preparations made by mixing a drop of blood with a drop of sodium citrate, and examining it with light- or dark-field microscopy, and in thin and thick blood films stained with Wright's or Giemsa stains, examined by light microscopy.

Answer 164

With the lysis–centrifugation technique, (1) a concentrate is prepared, (2) the sediment is inoculated to solid and/or liquid media, and (3) the cultures are incubated for up to 8 weeks. An alternative and perhaps more rapid approach is direct inoculation of the liquid medium developed by the manufacturer of automated and semiautomated broth culture systems specifically for recovery of mycobacteria.

Answer 165

With the lysis–centrifugation technique, (1) a concentrate is prepared, (2) the sediment is inoculated to solid and/or liquid media, and (3) the cultures are incubated for up to 8 weeks. An alternative and perhaps more rapid approach is direct inoculation of the liquid medium developed by the manufacturer of automated and semiautomated broth culture systems specifically for recovery of mycobacteria.

Answer 166

Positive blood cultures containing commonly isolated aerobic organisms are usually detected within 12–36 hours of incubation. The initial report is a Gram stain report only. Identification and susceptibility results can be expected within 24–48 hours after the Gram stain report. Cultures containing anaerobes are usually not detected for 48–72 hours, and identification is not available for 3–4 days after that. Fastidious organisms, such as those found in the HACEK group (Haemophilus, Actinobacillus, Cardiobacterium, Eikenella, Kingella) may not be detected until 3–5 days.

Answer 167

Bacille Calmette–Guerin is a live-attenuated strain of Mycobacterium bovis developed in 1921 as a vaccine for tuberculosis. The first published reports of its use in the bladder were in 1976. Intravesical BCG therapy has been demonstrated to reduce the recurrence rate and the risk of progression to muscle-invasive disease in patients with CIS (BCG is the gold standard for treatment of urothelial CIS), as well as superficial bladder tumors. High-risk patients treated with BCG following TURBT have lower cystectomy rates. The mechanism of action is induction of a massive influx of inflammatory cells and production of cytokines in the bladder mucosa and lumen that leads to an immune response against tumor cells. An intact immune system is a necessary prerequisite to successful BCG therapy.

Answer 168

The majority of cases occur in young to middle-aged males, either homosexual or bisexual, with HIV infection and severely immunocompromised. However, it can also occur in HIV-negative individuals who are immunocompromised as a result of solid-organ transplantation or cirrhosis. In rare instances, PEL can affect elderly individuals who are otherwise immunocompetent but live in geographic areas with high HHV8 prevalence, such as the Mediterranean region; these cases may be EBV negative.

Answer 169

Parvovirus B19.

Answer 170

An autoantibody with anti-P specificity is seen in patients with paroxysmal cold hemoglobinuria, a clinical syndrome that may occur in children following viral infection.

Answer 171

An autoantibody with anti-P specificity is seen in patients with paroxysmal cold hemoglobinuria, a clinical syndrome that may occur in children following viral infection. In PCH, autoanti-P is an IgG, biphasic hemolysin capable of binding RBCs at colder temperatures, followed by intravascular hemolysis at body temperature. This characteristic can be demonstrated in vitro in the Donath-Landsteiner test.

Answer 172

The P blood group antigen is the receptor for parvovirus B19. Pk can bind HIV and may confer resistance to HIV infection. The P1 and Pk antigens are receptors for shiga toxins, produced by Shigella dysenteriae and enterohemorrhagic Escherichia coli (EHEC) strains. In addition to gastroenteritis, EHEC infection is the most common cause of community-acquired hemolytic-uremic syndrome, probably reflecting toxin binding to Pk antigen on glomerular vascular endothelium and platelets. P, Pk, and LKE blood group antigens on uroepithelium are cell receptors for P-fimbriae, a bacterial adhesin and colonization factor expressed on uropathogenic E. coli strains. The Pk antigen also serves as a receptor for Streptococcus suis and Pseudomonas aeruginosa.

Answer 173

H. pylori binds H, Leb, and Ley antigens via BabA recognition of a terminal Fucα1–2Gal epitope and appears to explain the increased incidence of ulcers and stomach cancer among blood group O secretors. A Lewis null and/or nonsecretor phenotype has also been linked with a higher incidence of recurrent Candida vaginitis and urinary tract infection. A Le (a−b−) phenotype is associated with an increased incidence of heart disease. Conversely, a nonsecretor phenotype protects against Norovirus infection.

Answer 174

H. pylori binds H, Leb, and Ley antigens via BabA recognition of a terminal Fucα1–2Gal epitope.

Answer 175

P. vivax binds to the amino-terminal domain of DARC (Duffy Antigen Receptor for Chemokines)/the Duffy glycoprotein. Hence, Fy null individuals are resistant to most P. vivax strains.

Answer 176

Mycoplasma pneumoniae infection is associated with cold agglutinin disease secondary to anti-I, and infectious mononucleosis is associated with cold agglutinin disease secondary to anti-i.

Answer 177

Acute (onset/duration of <24 hours): Pyogenic bacteria. Subacute (onset/duration of 1-7 days): Enteroviruses, pyogenic bacteria. Chronic (persisting at least 4 weeks): M. tuberculosis, T. pallidum, Brucella sp., L. interrogans, B. burgdorferi, C. neoformans, C. immitis, H. capsulatum.

Answer 178

Neonates-3 months: Group B streptococcus, E. coli, L. monocytogenes (Listeria can cause meningitis in immunocompromised individuals in all age groups). 4 months-6 years (Incidence of meningitis due to HIB in the US has declined dramatically due to vaccination): S. pneumoniae. 6-45 years: N. meningitidis. >45 years: S. pneumoniae, L. monocytogenes, Group B streptococcus.

Answer 179

For CSF, in addition to smears stained with the Gram stain and bacterial culture, the supernatant of a centrifuged specimen or the original fluid may be used to perform latex agglutination tests for detection of antigens of Streptococcus agalactiae, S. pneumoniae, some serotypes of Neisseria meningitidis, Escherichia coli (the K1 capsular antigen cross-reacts with that of N. meningitidis type B), and H. influenzae type b.

Answer 180

Two types of rapid tests are available for diagnosis of meningitis caused by C. neoformans: those specific for the capsular antigen (latex agglutination and ELISA) and the nonspecific India ink preparation, which allow visualization of encapsulated yeast cells.

Answer 181

Currently, nucleic acid amplification tests are used most often for diagnosis of viral infections of the central nervous system. Other diagnostic methods are conventional cell culture (primarily for detection of enteroviruses, although PCR is preferred) and serologic tests for viruses that cause encephalitis (western equine, eastern equine, Venezuelan equine, St Louis, Japanese, and La Crosse and West Nile).

Answer 182

The HIV-1 family is divided into main (M), outlier (O), and non-M non-O (N) groups.

Answer 183

In the US, clade B is almost exclusively prevalent.

Answer 184

HIV testing is accomplished by ELISA, and repeat-reactive tests are confirmed by western blot testing for the presence of antibodies directed against the HIV proteins of the gag, pol, and env genes.

Answer 185

After initial infection and propagation of HIV in lymph nodes, a blood donor becomes infectious (defined as day 0), with HIV RNA being detectable in plasma and platelets on days 14-15. HIV DNA is detectable in leukocytes at days 17-20, and HIV antibodies are detectable between days 20 and 25.

Answer 186

After the introduction of testing for HIV RNA by NAT, p24 antigen testing no longer provided added benefit in reducing the risk of transfusion-transmitted HIV, and the FDA allowed discontinuation of antigen testing in the US as long as HIV NAT was being used. And also, HIV-1/HIV-2 antibody tests are performed as well.

Answer 187

AABB Standards requires the use of HBsAg and anti-HBc to test donors for HBV infection.

Answer 188

A solid-phase inhibition immunoassay, and a direct antiglobulin assay.

Answer 189

Japan, a country with moderate prevalence of HBV infection, modifies anti-HBc screening to accept donor with high amounts of anti-HBs, if also HBV NAT negative, because presence of anti-HBs in the absence of detectable HBV usually signifies a resolved infection and absence of circulating virus.

Answer 190

AABB Standards requires the use of anti-HCV and HCV RNA NAT to test donors for HCV infection.

Answer 191

A third-generation antiglobulin EIA is the primary screening test for antibodies to HCV. If the initial EIA is positive, the test is repeated. If the second EIA is "repeat reactive," a confirmatory/supplemental test is performed, which is currently a recombinant immunoblot assay (RIBA) against HCV antigens, which is FDA-approved for supplemental testing.

Answer 192

A donor with a reactive RIBA is permanently deferred from donating and is considered to be infected with HCV. Of EIA repeatedly reactive donors, 37% have a non-reactive or indeterminate RIBA test result and are rarely infectious for HCV. Whether or not the RIBA is reactive, if a blood donor is repeatedly reactive for anti-HCV by EIA, the donation cannot be used for transfusion. However, a donor who has a non-reactive RIBA and reactive EIA (without HCV NAT positivity) can be considered for re-entry by application to the FDA.

Answer 193

A PCR test performed on RNA tested by chemical methods on mini-pools of 16-24 donor blood samples; and a transcription-mediated amplification (TMA) test on nucleic acid preparations in a solid phase (probe-capture) method, also performed on mini-pools of donor samples. Both test methods are sensitive and specific and perform equally well in identifying HCV RNA.

Answer 194

A minipool NAT is done, with a recommended trigger for implementing individual NAT when two presumed viremic donors (PVD; defined as an initial reactive donor that repeats on the original sample) occur within a 7-day period; MP-NAT is resumed after 7 days without PVD donations or ongoing regional activity, or at the medical director's direction.

Answer 195

WNV infectivity of the donor is confirmed by either repeat NAT reactivity on a follow-up sample, or IgM and IgG antibody reactivity with neutralization testing on either the original (index) sample or a follow-up sample.

Answer 196

HTLV-1 predominantly infects CD4+ lymphocytes while HTLV-2 preferentially infects CD8+ lymphocytes (and, to a lesser extent, infects CD4+ lymphocytes, B lymphocytes and macrophages).

Answer 197

The FDA has approved the use of EIAs which detect both HTLV-1 and -2 antibodies. These tests typically use viral lysates as the capture reagent, and adherent donor antibodies are identified with an antiglobulin conjugate. There are no licensed confirmatory or supplemental tests for the HTLV-1/2 EIAs. One approach to supplemental testing to confirm a reactive anti-HTLV test is to repeat the test using an alternate manufacturer's EIA. Western blot and radioimmunoprecipitation (RIPA) tests are available.

Answer 198

There are no licensed confirmatory or supplemental tests for the HTLV-1/2 EIAs. One approach to supplemental testing to confirm a reactive anti-HTLV test is to repeat the test using an alternate manufacturer's EIA. Western blot and radioimmunoprecipitation (RIPA) tests are available.

Answer 199

Indications: Decreasing incidence of febrile non-hemolytic transfusion reactions. Decreasing incidence of HLA alloimmunization. Decreasing CMV transmission. Potential indications: Decreasing other HHV (i.e. EBV, HHV-6, HHV-7, HHV-8) transfusion transmitted infections. Possible decrease in transmission of prion disease. Controversial indication: Decreasing TRIM (Transfusion-Related ImmunoModulation).

Answer 200

Echovirus, coxsackie B virus, and uropathogenic and intestinal E. coli strains bearing Afa/Dr and X adhesins.

Answer 201

Anti-I and anti-i are antibodies of IgM isotype, reactive at room temperature. Autoantibodies to I are relatively common and are usually low-titered cold agglutinins. Some anti-I can have IH specificity, reacting stronger with group O and A2 RBC. Although generally benign, hemolysis secondary to high-titered anti-I is observed in cold autoimmune hemolytic anemia (CAIHA). CAIHA can occur in the setting of malignancy and occasionally infection (e.g., Mycoplasma pneumoniae). These antibodies display high thermal amplitude, often agglutinating RBCs at temperatures of 30°–34° C. In contrast, alloanti-I is relatively rare and is found as a naturally occurring antibody in iadult individuals.

Answer 202

Secondary WAIHA is often observed in autoimmune diseases (frequently systemic lupus erythematosus), in lymphoproliferative disorders, and following viral infections.

Answer 203

I: Acute CAD associated with Mycoplasma pneumoniae with antibody titers >1000 at 4° C. i: Acute CAD associated with mononucleosis. Pr: Rare cause of CAD. P: PCH associated with certain viral infections in children. H: Benign except as alloantibody in Bombay phenotype. IH: Benign.

Answer 204

Cold agglutinin disease (CAD) accounts for about 20% of total cases of AIHA. As with WAIHA, CAD may be idiopathic or secondary following infection or malignancy.

Answer 205

Some patients with Clostridium difficile infection or tuberculosis may manifest a leukemoid reaction with a WBC count greater than 50,000/mL. Conversely, typhoid fever, brucellosis, tularemia, rickettsial diseases, ehrlichiosis, leishmaniasis, and some cases of Staphylococcus aureus infection may be associated with leukopenia.

Answer 206

It may be related to coxsackievirus A or B6, echovirus, and adenovirus 12, and is rarely associated with splenomegaly or lymphadenopathy. Infection with EBV can cause atypical lymphocytosis (large and reactive lymphocytes with abundant basophilic cytoplasm) and lymphadenopathy. HTLV-1 may produce a transient lymphocytosis (usually <20,000/mL) with fever, rash, and lymphadenopathy. In contrast to most other bacterial infections, pertussis (whooping cough) is frequently accompanied by lymphocytosis.

Answer 207

SPS is used in most commercial blood culture products because it functions as an anticoagulant and prevents phagocytosis and complement activation. In addition, SPS neutralizes aminoglycoside antibiotics.

Answer 208

Specimens for culture of N. gonorrhoeae are best if plated immediately or transported in a medium containing activated charcoal to absorb inhibitory substances that hinder their recovery.

Answer 209

Thiosulfate-citrate-bile-sucrose (TCBS) agar is used to grow V. cholerae, which appear as yellow colonies as a result of the use of both citrate and sucrose. Alkaline peptone water (APW) broth is used as an enrichment broth and should be subcultured to TCBS agar for further evaluation of Vibrio colonies.

Answer 210

CNA agar inhibits the growth of gram-negative bacteria and is used to isolate gram-positive cocci from specimens. This medium is especially useful for stool and wound cultures because these may contain large numbers of gram-negative rods.

Answer 211

N. gonorrhoeae cultures must be incubated in 3-7% CO2 at 35 C. Cultures should be held a minimum of 48 hours before being considered negative.

Answer 212

MTM is a chocolate agar containing vancomycin, colistin, nystatin, and trimethoprim. These permit isolation of N. gonorrhoeae in specimens containing large numbers of gram-negative bacteria, including commensal Neisseria species.

Answer 213

CCFA is used for recovery of C. difficile from stool cultures. Cycloserine and cefoxitin inhibit growth of gram-negative coliforms in the stool specimen. C. difficile ferments fructose, forming acid that, in the presence of neutral red, causes the colonies to become yellow.

Answer 214

Enterobacteriaceae. DCA inhibits gram-positive organisms. N. gonorrhoeae and N. meningitidis are too fastidious to grow on DCA. Citrate and deoxycholate salts inhibit growth of gram-positive bacteria.

Answer 215

XLD agar is a highly selective medium used for recovery of Enterobacteriaceae from gastrointestinal specimens. XLD agar is selective for gram-negative coliforms because of a high concentration (0.25%) of deoxycholate, which inhibits gram-positive bacteria. In addition, XLD is differential for Shigella and Salmonella spp.

Answer 216

False. Haemophilus influenzae requires V and X factors, and Haemophilus parainfluenzae requires V factor.

Answer 217

The tubercle bacilli that make up the M. tuberculosis complex (MTBC; Mycobacterium tuberculosis, Mycobacterium bovis, M. bovis Bacille Calmette-Guérin strain [BCG], Mycobacterium caprae, Mycobacterium pinnipedii, Mycobacterium africanum, Mycobacterium microtii, and Mycobacterium canettii) are the etiologic agents of human tuberculosis (TB).

Answer 218

Among new cases of TB, approximately 5% (or 500,000) worldwide are due to MDR-TB, defined as tubercle bacilli that are resistant to rifampin and isoniazid. MDR-TB does not respond to the standard 6-month treatment regimen and may require up to 2 years of treatment with drugs that are more toxic than first-line agents and about 100 times more costly. Mismanagement of drugs used to treat MDR-TB can result in XDR-TB, defined as MDR-TB plus resistance to any fluoroquinolone and any second-line injectable antituberculosis agent (e.g., amikacin, kanamycin, capreomycin).

Answer 219

The usual host response to infection with MTBC is activation of the cell-mediated immune system. During primary (initial) infection, inhaled bacilli travel to the alveolar spaces, where they are ingested by resident macrophages. These macrophages are unable to kill the bacilli, which multiply intracellularly during the first several days after infection. Macrophages infected with mycobacteria migrate to regional tracheobronchial lymph nodes and present sensitizing antigen(s) to immunocompetent T cells, or they enter the lymphatics and blood and travel back to the lungs (primarily the apices) and to distant organs such as lymph nodes, kidneys, epiphyseal areas of the long bones, vertebral bodies, and meninges, where bacilli continue to multiply until the cellular immune response is activated. Immunocompetent T cells migrate from regional lymph nodes to the site of infection in the lung, releasing chemotactic, migration-inhibitory, and mitogenic cytokines. Cytokines and lytic enzymes released by activated macrophages also contribute to concomitant local tissue destruction. Over time, the activated T cell population declines and is replaced by long-lived memory immune T cells, which protect against reinfection with MTBC and provide some cross-protection against infection with other mycobacteria.

Answer 220

Candida (previously Torulopsis) glabrata consists of small, uniform, round budding yeast forms surrounded by clear halos on Pap stain. Unlike other Candida species, it does not form pseudohyphae in vivo or in culture.

Answer 221

The major HPV capsid protein L1.

Answer 222

Oropharynx, tonsils, and base of tongue.

Answer 223

Spontaneous bacterial peritonitis.

Answer 224

Biliary obstruction (extrahepatic biliary atresia). Sepsis or TORCH infection. Neonatal hepatitis (idiopathic, Wilson disease, alpha-1 antitrypsin deficiency). Metabolic disorders (galactosemia, hereditary fructose intolerance, glycogen storage disease). Inherited disorders of bilirubin transport (Dubin-Johnson syndrome, Rotor syndrome). Parenteral alimentation.

Answer 225

The AST:ALT is over 2 in 80% of patients with toxic, ischemic, and alcoholic hepatitis. It is usually <1 in viral hepatitis.

Answer 226

Jaundice occurs in 70% of patients with alcoholic hepatitis and acute hepatitis A, and occurs in 20-30% of patients with acute hepatitis B and acute hepatitis C.

Answer 227

A benign acquired condition (associated with celiac disease, lymphoma, HIV infection, monoclonal gammopathy, rheumatoid arthritis, and ulcerative colitis) with an incidence of ~1%, in which apparently healthy individuals have markedly elevated serum amylase levels (with low urine amylase levels), due to Ig-amylase complexes.

Answer 228

Uncomplicated UTI often refers to cases of cystitis in healthy young adult nonpregnant females without anatomic genitourinary anomalies. Some authors also include pyelonephritis in healthy young adult females, cystitis in young adult males, and cystitis in healthy postmenopausal women, Complicated UTI often refers to one arising in association with pregnancy, diabetes, stone, structural genitourinary anomalies, spinal injury, children, and males.

Answer 229

Acute interstitial nephritis, not UTI.

Answer 230

E. coli causes ~80%. S. saprophyticus is a very common cause in young sexually active women, and causes ~15% of community-acquired UTIs. Other enterobacteriaceae, especially Klebsiella spp and Enterobacter spp, cause a significant number of the remaining cases.

Answer 231

Ureaplasma urealyticum, Chlamydia spp, or Mycoplasma hominis.

Answer 232

Corynebacterium group D2 appears to be a significant cause of hospital-acquired UTI.

Answer 233

Noninflammatory bacterial diarrhea: Vibrio spp, E. coli (especially ETEC and EPEC), C. perfringens, S. aureus, and B. cereus. Inflammatory bacterial diarrhea: C. difficile, Salmonella, Shigella, Campylobacter.

Answer 234

Prolonged (>5 days) illness and fever.

Answer 235

Enterohemorrhagic E. coli (O157:H7). This may also be seen with amebiasis (capable of destroying leukocytes).

Answer 236

South and Central America: Varieties of E. coli (ETEC, EIEC). The far East: Campylobacter, Salmonella, Shigella.

Answer 237

Salmonella.

Answer 238

Pediatric: Rotavirus. Adult: Norwalk virus.

Answer 239

Oropharynx, tonsils, and base of tongue.

Answer 240

COPD: H. influenzae, M. catarrhalis, L. pneumophila. Alcoholic: S. pneumoniae, anaerobes, GN aerobic bacilli. Neutropenia: Aerobic GN bacilli, Animal exposure: C. burnetii, C. psittaci, C. neoformans, H. capsulatum, Hantavirus, F. tularensis, Sandstorm exposure: Coccidioidomycosis, Bronchiectasis/CF: P. aeruginosa, P. cepacia, S. aureus. Community-acquired PNA in immunocompetent healthy adults: M. pneumoniae, C. pneumoniae, S. pneumoniae, H. influenzae. Elderly nursing home tenants: S. pneumoniae, H. influenzae, aerobic GN bacilli, anaerobes, Hospitalized ventilated patients: S. aureus, S. pneumoniae, P. aeruginosa, K. pneumoniae, Serratia spp, Enterobacter spp, E. coli, fungi. .

Answer 241

5-10% of adults are colonized with S. pneumoniae, and 5% are colonized with M. catarrhalis.

Answer 242

H. influenzae and M. catarrhalis.

Answer 243

The gold standard is culture, but this is not widely available. Commonly used serologic criteria used to evaluate C pneumoniae PNA are an IgM titer exceeding 1:16 or a 4-fold increase in the IgG titer by microimmunofluorescence (MIF). Serology is limited by a commonly delayed Ab response: the IgM Ab response may take as long as 6 weeks, and the IgG Ab response may take as long as 8 weeks to appear in primary infections.

Answer 244

Legionellosis refers to 2 distinct clinical syndromes: Legionnaires disease, which most often manifests as severe pneumonia accompanied by multisystemic disease, and Pontiac fever, which is an acute, febrile, self-limited, viral-like illness.

Answer 245

Although more than 70 Legionella serogroups have been identified among 50 species, L pneumophila causes most legionellosis. L pneumophila serogroup 1 alone is responsible for 70-90% of cases in adults. In a pediatric series, L pneumophila serogroup 1 accounted for only 48% of cases, serogroup 6 accounted for 33%, and the remaining cases involved other serotypes and species. Legionella micdadei and L dumoffii are the second and third most common species to cause Legionnaires disease in children, respectively,

Answer 246

While SARS-CoV appears to grow well in cell culture (Vero E6 cell lines), real-time PCR, performed on nasopharyngeal specimens, is the preferred means of laboratory diagnosis.

Answer 247

Most frequent is S. aureus. Less common causes include enterococci and certain streptococci, especially S. milleri.

Answer 248

Viridans streptococci (S. sanguis, S. mutans, S. mitis), group B streptococci, group D streptococci (S. bovis), Enterococci (S. faecalis), and other HACEK organisms.

Answer 249

Most common is S. epidermidis, followed by S. aureus. Cases arising a very long time after valve replacement tend to have a microbial DDx resembling that of subacute bacterial endocarditis.

Answer 250

In most cases, the basic valvular abnormality is due to rheumatic heart disease, most often affecting the mitral valve. Other cases are related to mitral valve prolapse, nodular dystrophic (age-related) calcification of the aortic valve, and congenital heart disease.

Answer 251

Non-infectious: Libman-Sacks endocarditis, nonbacterial thrombotic (marantic) endocarditis, carcinoid heart syndrome. Infectious: C. burnetii, Bartonella, Chlamydia, Legionella.

Answer 252

Bartonella species, especially B. quintanta (associated with homelessness and chronic alcohol use) and B. henslae (associated with cat (kitten, usually) exposure), account for approximately 1% of all infective endocarditis cases and 10% of blood culture negative endocarditis.

Answer 253

High titer (1:800) IgG has a high predictive value (IgM is usually gone by the time of presentation). Culture is difficult but should be attempted. PCR on blood or excised heart valves may be attempted.

Answer 254

C. burnetti and T. whipplei.

Answer 255

Candida spp > Aspergillus spp.

Answer 256

Toxoplasma.

Answer 257

Herpes encephalitis, which can present with a bloody CSF, very high protein, and low glucose.

Answer 258

HSV-1, arboviruses (St. Louis encephalitis, California encephalitis, West Nile virus, Western equine encephalitis, Eastern equine encephalitis), HHV-6, mumps virus, measles virus, and varicella-zoster virus.

Answer 259

The Enteroviruses (coxsackie A and B, echoviruses, poliovirus). Summer/fall outbreaks are typical.

Answer 260

HSV, mumps virus, HIV, LCMV (lymphocytic choriomeningitis virus).

Answer 261

LCM is a rodent-borne viral infectious disease that presents as aseptic meningitis, encephalitis, or meningoencephalitis. Its causative agent is the lymphocytic choriomeningitis virus, a member of the family Arenaviridae. Although LCMV is most commonly recognized as causing neurological disease, as its name implies, infection without symptoms or mild febrile illnesses are common clinical manifestations. Additionally, pregnancy-related infection has been associated with congenital hydrocephalus, chorioretinitis, and mental retardation.

Answer 262

Acute lymphocytic choriomeningitis (LCM) can be diagnosed via detection of IgM antibodies by ELISA from serum or CSF. This is the preferred diagnostic test.

Answer 263

Immunization has led to a major decline in H. flu meningitis (causes about 5% of cases now), and S. pneumoniae is now the most common agent (causes about 50% of cases now).

Answer 264

GBS, GN aerobic bacilli (E. coli, Klebsiellae), L. monocytogenes.

Answer 265

N. meningitidis, S. pneumoniae, H. influenzae type B.

Answer 266

In adults, S. pneumoniae, followed by N. meningitidis. In elderly adults, S. pneumoniae, followed by L. monocytogenes, followed by GN aerobic bacilli.

Answer 267

PCR on CSF.

Answer 268

HHV-6, the virus that causes exanthem subitum, is a common cause of viral encephalitis in children, and is thought to contribute to many cases of febrile seizures in children.

Answer 269

Arthropod-borne viruses, i.e., arboviruses, are viruses that are maintained in nature through biological transmission between susceptible vertebrate hosts by blood feeding arthropods (mosquitoes, psychodids, ceratopogonids, and ticks). Vertebrate infection occurs when the infected arthropod takes a blood meal. The term 'arbovirus' has no taxonomic significance. Arboviruses that cause human encephalitis are members of three virus families: the Togaviridae (genus Alphavirus), Flaviviridae, and Bunyaviridae. Some systems also include the virus family Reoviridae.

Answer 270

One of 17 (numbers vary) genera in the Picornaviridae family. This family is a large and diverse group of small RNA viruses characterized by a single positive-strand genomic RNA. The enterovirus genus is divided into 12 (numbers vary) species (Enterovirus A-H, Enterovirus J, Rhinovirus A-C) and there are numerous serotypes. But the important point is: The human enteroviruses include polioviruses, group A and B coxsackieviruses, echoviruses, enteroviruses, and rhinoviruses.

Answer 271

Lymphocytic choriomeningitis virus is the most common cause of aseptic meningitis in winter/spring. The mumps virus used to be the most common cuase, but immunization has altered this pattern in the US.

Answer 272

H. influenzae is broadly divided into strains that do not possess an outer capsule (nontypeable strains) and strains that are encapsulated (typeable, based on capsular proteins). The typeable strains are further divided into 6 serotypes.

Answer 273

N. meningitidis serotypes B, C, and Y cause a large number of cases of bacterial meningitis.

Answer 274

H. influenzae - 5%, N. meningitidis - 10-15%, Pneumococcus species - 15-35%, L. monocytogenes - 15-30%.

Answer 275

Extremes of age (70 yo), corticosteroid therapy, transplant, DM, HIV, iron overload.

Answer 276

C. neoformans.

Answer 277

Low glucose (500 mg/dL), and high WBC (>1000/mL, predominantly neutrophils).

Answer 278

Coagulase-negative staphylococci (30-40%), S. aureus (10-20%), mixed flora (10%), streptococci (10%), GN bacilli (5%), enterococci (5%), and anaerobes (2-4%).

Answer 279

Early - developing 24 months after implantation.

Answer 280

C. septicum, S. bovis.

Answer 281

Neonates: S. agalactiae (GBS), E. coli. Infants and young children: S. pneumoniae, N. meningitidis, H. influenzae. Young adults: S. pneumoniae, N. meningitidis, H. influenzae. Elderly adults: S. pneumoniae, N. meningitidis, H. influenzae, L. monocytogenes.

Answer 282

Cryptococcus.

Answer 283

Viral meningitis: Enteroviridae (Coxsackie, Echovirus, Enterovirus). Viral encephalitis: Alphaviridae (Eastern and Western Equine encephalitis), Flaviviridae (St. Louis encephalitis), HSV-1.

Answer 284

Capnocytophaga canimorsus, Pasteurella multocida, Staphylococcus intermedius.

Answer 285

M. fortuitum-chelonae, M. marinum, M. haemophilum, M. ulcerans, M. leprae.

Answer 286

C. difficile.

Answer 287

S. aureus.

Answer 288

S. aureus, P. aeruginosa.

Answer 289

Actinobacillus actinomycetemcomitans.

Answer 290

Francisella tularensis.

Answer 291

Burkholderia mallei.

Answer 292

Burkholderia pseudomallei.

Answer 293

Rickettsia rickettsiae.

Answer 294

Toxocara canis/cati.

Answer 295

Ancylostoma braziliensis.

Answer 296

Most common overall: S. pyogenes (GAS). Animal bite-associated: Pasteurella multocida. Freshwater-associated: Aeromonas hydrophila. Saltwater-associated: Vibrio vulnificus.

Answer 297

P. aeruginosa.

Answer 298

S. pyogenes (GAS), C. diphtheriae.

Answer 299

Bordetella pertussis.

Answer 300

H. influenzae type B.

Answer 301

Haemophilus ducreyi.

Answer 302

C. trachomatis.

Answer 303

Monoarticular in children and adults: S. aureus. Polyarticular in young adults: N. gonorrhea.

Answer 304

Parainfluenza virus, serotypes 1-3.

Answer 305

Infants/children: RSV. Adults: Influenza A (orthomyxovirus).

Answer 306

Community-acquired: S. pneumoniae, L. pneumoniae, H. influenzae, S. aureus, M. pneumoniae. Chronic alcoholics: K. pneumoniae. Cystic fibrosis: P. aeruginosa. Atypical/walking pneumonia: M. pneumoniae, Chlamydia pneumoniae. Nosocomial pneumonia: E. coli, P. aeruginosa, S. aureus, L. pneumoniae.

Answer 307

Malassezia furfur.

Answer 308

Spontaneous: S. pneumoniae. Secondary: mixed - E. coli, enterococci, B. fragilis, other anaerobes.

Answer 309

With short incubation period (1-8 h): S. aureus, B. cereus. Fried rice: B. cereus. Traveler's diarrhea: E. coli (ETEC). Hamburgers in fast food restaurants: E. coli (EHEC). Antibiotic-associated colitis: C. difficile. Viral: Rotavirus, Norwalk virus, enteric adenoviruses.

Answer 310

S. aureus.

Answer 311

Usually polymicrobial: S. pyogenes and anaerobes such as B. fragilis.

Answer 312

Pig-associated: Brucella suis. Goat-associated: Brucella melitensis. Dog-associated: Brucella canis.

Answer 313

Francisella tularensis.

Answer 314

Yersinia pestis.

Answer 315

Bartonella bacilliformis.

Answer 316

C. perfringens.

Answer 317

Mycobacterium leprae.

Answer 318

Streptobacillus moniliformis.

Answer 319

Coccidioides immitis.

Answer 320

Dermatophytosis (Tinea capitis, Tinea cruris, etc.): Epidermophyton, Microsporon, Trichophyton spp. Black piedra: Piedraia hortae. White piedra: Trichosporon beigelii. Tinea versicolor: M. furfur. Tinea nigra palmaris/plantaris: Phaeoannelomyces werneckii.

Answer 321

Sporotrichosis: Sporothrix shenckii. Chromoblastomycosis: Phialophora, Cladosporium, Fonsacea. Lobomycosis: Loboa loboi. Phaeohyphomycosis: Exophiala jeanselmei, Phialophora, Wangiella dermatitidis. Eumycotic mycetoma: Exophiala, Wangiella, P. boydii (scedosporium). Rhinosporidiosis: Rhinosporidium seeberi.

Answer 322

Klebsiella rhinoscleromatosus.

Answer 323

Actinomyces, Nocardia, Streptomyces.

Answer 324

Measles: Rubeola virus. German measles: Rubella virus.

Answer 325

Erysipelas: S. pyogenes (GAS). Erysipeloid: Erysipelothrix rhusiopathiae.

Answer 326

Varicella zoster virus.

Answer 327

S. aureus.

Answer 328

Labial herpes: HSV type 1. Genital herpes: HSV type 2.

Answer 329

Parvovirus B19.

Answer 330

Chagas disease: Trypanosoma cruzi. African sleeping sickness: Trypanosoma brucei.

Answer 331

Trypanosoma cruzi.

Answer 332

Trypanosoma brucei.

Answer 333

Chrysosporium parvum.

Answer 334

Aspergillus niger.

Answer 335

Measles virus (reactivation).

Answer 336

Coxsackie A.

Answer 337

Coxsackie B.

Answer 338

Hand-foot-mouth disease: Coxsackie A. Viral myocarditis: Coxsackie B.

Answer 339

S. pyogenes (GAS).

Answer 340

S. aureus.

Answer 341

S. pneumoniae.

Answer 342

Primary culture refers to the stage of the culture after the cells are isolated from the tissue and proliferated under the appropriate conditions until they occupy all of the available substrate. After the first subculture/transfer/passage a primary cell culture becomes a secondary cell culture or cell line. After a limited number of transfers (usually around 50), cell lines become exhausted and no longer replicate. However, individual cells may acquire an unlimited ability to replicate and cell lines that continue to proliferate after having been transferred at least 70 times are considered established cell lines.

Answer 343

Secondary cell cultures/cell lines are usually diploid. Established cell lines are often heteroploid.

Answer 344

Uninfected diploid cell lines are morphologically fibroblastic and consist of long slender parallel cells. Uninfected established cell lines morphologically appear as polygonal epithelioid cells.

Answer 345

Mycoplasma spp or Simian viruses. Mycoplasma contamination results in poor cell growth and inhibition of viral infection. Simian viral contamination may result in a false-positive hemadsorption; this problem is the reason for running parallel control hemadsorption tests on uninoculated tubes.

Answer 346

Anopheles mosquitos. Of the approximately 430 Anopheles species, only 30-40 transmit malaria.

Answer 347

Most human cases of Babesiosis in the United States are caused by Babesia microti, which is spread in nature by Ixodes scapularis ticks (also called blacklegged ticks or deer ticks).

Answer 348

Overall, infection in people is caused by more than 20 species of Leishmania parasites, which are spread by about 30 species from some sandfly genera of the Phlebotominae subfamily.

Answer 349

Louse-borne relapsing fever (LBRF) is caused by Borrelia recurrentis, while tick-borne relapsing fever (TBRF) is caused by at least 15 different Borrelia species. LBRF and TBRF vary significantly in terms of epidemiology. The human body louse transmits B recurrentis, which causes an epidemic form of relapsing fever, while a soft-bodied tick (Ornithodoros) transmits multiple Borrelia species that cause endemic relapsing fever.

Answer 350

The tsetse fly (Glossina species).

Answer 351

T. b. rhodesiense (East African sleeping sickness) is found in focal areas of eastern and southeastern Africa. Each year a few hundred cases are reported to the World Health Organization. T. b. gambiense (West African sleeping sickness) is found predominantly in central Africa and in limited areas of West Africa. Most of the sleeping sickness in Africa is caused by this form of the parasite.

Answer 352

Triatomine bugs (also called reduviid bugs, "kissing" bugs, assassin bugs, cone-nosed bugs, and blood suckers).

Answer 353

African trypanosomiasis = (East or West) African sleeping sickness, caused by T. brucei. American trypanosomiasis = Chagas disease, caused by T. cruzi.

Answer 354

The filarid nematodes Wuchereria bancrofti, Brugia malayi, and (less-commonly) B. timori. Wuchereria bancrofti is encountered in tropical areas worldwide; Brugia malayi is limited to Asia; and Brugia timori is restricted to some islands of Indonesia.

Answer 355

Several different species of mosquitos, depending on geographic area. The most common mosquito vector species are within the genera Culex, Anopheles, Mansonia, and Aedes.

Answer 356

B. malayi is transmitted by a mosquito vector. The principal mosquito vectors include Mansonia, Anopheles, and Aedes mosquitoes.

Answer 357

The vector for Loa loa filariasis are flies from two species of the genus Chrysops (AKA African deerflies, mango flies, mangrove flies, yellow flies, or day-biting flies), C. silacea and C. dimidiata.

Answer 358

Loiasis, also known as African eye worm, is caused by the parasitic worm Loa loa. It is transmitted through the repeated bites of African deerflies (AKA mango flies, mangrove flies, yellow flies, or day-biting flies) of the genus Chrysops. The flies that transmit the parasite breed in the high-canopied rain forest of West and Central Africa. In addition to eye worm, the infection is most commonly associated with recurrent episodes of itchy swellings (local angioedema) known as Calabar swellings.

Answer 359

Loa loa, Mansonella streptocerca, and Onchocerca volvulus.

Answer 360

Infection by filarid nematodes in the genus Mansonella: M. ozzardi, M. perstans, and M. streptocerca. M. streptocerca is found in Africa and causes subcutaneous filariasis; M. perstans occurs in both Africa and South America and causes serous cavity filariasis; and M, ozzardi occurs only in the Americas, from Mexico south to South America and in the Caribbean and causes serous cavity filariasis.

Answer 361

All 3: M. ozzardi, M. perstans, and M. streptocerca, have the (biting) midge (genus Culicoides) as their vector. Additionally, M. ozzardi has blackflies (genus Simulium) as a vector.

Answer 362

Mansonella perstans and Mansonella ozzardi.

Answer 363

The blackfly (genus Simulium).

Answer 364

Dirofilariais is caused by filarial nematodes (roundworms) of the genus Dirofilaria. The three species most commonly reported to cause disease in humans are D. immitis (the dog heartworm), D. repens, and D. tenuis. Dogs and wild canids are the main natural hosts for D. immitis and D. repens and raccoons for D. tenuis.

Answer 365

Mosquito (Aedes, Culex, Anopheles, Mansonia).

Answer 366

Schistosomiasis is caused by digenetic blood trematodes. The three main species infecting humans are Schistosoma haematobium, S. japonicum, and S. mansoni. Two other species, more localized geographically, are S. mekongi and S. intercalatum. In addition, other species of schistosomes, which parasitize birds and mammals, can cause cercarial dermatitis in humans.

Answer 367

S. mansoni is found in parts of South America and the Caribbean, Africa, and the Middle East; S. haematobium in Africa and the Middle East; and S. japonicum in the Far East. S. mekongi and S. intercalatum are found focally in Southeast Asia and central West Africa, respectively.

Answer 368

There is no vector; there is direct penetration of skin by free-swimming cercaria. Infection occurs when skin comes in contact with contaminated freshwater in which certain types of snails that carry the parasite are living. The parasite leaves the snail and enters the water where it can survive for about 48 hours.

Answer 369

There is no vector. Ingestion of infected pork leads to intestinal infestation. Ingestion of eggs (usually from an infected food preparer) leads to cysticercosis.

Answer 370

Although RMSF cases have been reported throughout most of the contiguous United States, five states (North Carolina, Oklahoma, Arkansas, Tennessee, and Missouri) account for over 60% of RMSF cases. The primary tick that transmits R. rickettsii in these states is the American dog tick (Dermacentor variabilis Dermacentor andersoni).

Answer 371

Ticks are the vector for R. rickettsii (Rocky Mountain Spotted Fever). In the United States, these include the American dog tick (Dermacentor variabilis), Rocky Mountain wood tick (Dermacentor andersoni), and brown dog tick (Rhipicephalus sanguineus).

Answer 372

All 3 are in the typhus group of Rickettsia species. R. prowazekii causes epidemic typhus (AKA louse-borne typhus, classic typhus, and sylvatic typhus) (vector - human body louse) and recrudescent typhus (no vector). R. typhi causes murine typhus (vector - fleas). R. felis cause murine typhuslike/cat-flea typhus (vector - fleas).

Answer 373

Human body louse (Pediculus humanus corporis).

Answer 374

The organism had been reclassified in 1995 as Orientia tsutsugamushi and causes scrub typhus. The vector is larval trombiculid mites, particularly genus Leptotrombidium ("chiggers", parasitic larval/chigger stage of the mite).

Answer 375

Rickettsia typhi causes murine/endemic typhus. Vectors are fleas (Xenopsylla cheopis, the Oriental rat flea, and Ctenocephalides felis, the cat flea). (and lice?)

Answer 376

Bartonella bacteria cause several diseases in humans. The three most common are cat scratch disease, caused by B. henselae; trench fever, caused by B. quintana; and Carrion´s disease or Oroya fever (acute phase of infection) and Verruga peruana or Peruvian wart (chronic phase of infection), caused by B. bacilliformis.

Answer 377

Cats (from a scratch or bite) (and kittens are more likely to be infected). Although B. henselae is found in fleas that cats carry, so far there is no evidence that a bite from an infected flea can give you CSD.

Answer 378

Boutonneuse fever, Mediterranean spotted fever, Israeli tick typhus, Astrakhan spotted fever, Kenya tick typhus, Indian tick typhus, or other names that designate the locality of occurrence while having distinct clinical features.

Answer 379

The brown dog tick, Rhipicephalus sanguineus.

Answer 380

Rickettsialpox.

Answer 381

The vector is the colorless mite Liponyssoides sanguineus (formerly Allodermanyssus sanguineus), which is found on mice.

Answer 382

E. chaffeensis causes human monocytic erlichiosis. The vector is the Lone Star tick (Amblyomma americanum).

Answer 383

A. phagocytophila (formerly known as Ehrlichia phagocytophila) causes human granulocytic anaplasmosis. The vector is Ixodes ticks (I. scapularis in the Northeast and upper Midwest (AKA deer tick, black-legged tick, and bear tick) and I. pacificus (AKA Western black-legged tick) in the western US).

Answer 384

Sandfly (genus Lutzomyia).

Answer 385

The human body louse.

Answer 386

None. Acquired from contact with (or via inhalation) infected animals or contaminated animal products,

Answer 387

F. hepatica (AKA common liver fluke or sheep liver fluke) has no vector. People usually become infected by eating raw watercress or other water plants contaminated with immature parasite larvae, or from contaminated water (by drinking it or washing food with it).

Answer 388

In the United States, ticks that transmit tularemia to humans include the dog tick (Dermacentor variabilis), the wood tick (Dermacentor andersoni), and the lone star tick (Amblyomma americanum). Deer flies (Chrysops spp.) have been shown to transmit tularemia in the western United States. F. tularensis also can be contracted from animal contact or via inhalation.

Answer 389

There is no vector. People become infected by contact with fluids from infected animals (goats and sheep (B. melitensis), cattle (B. abortus) or pigs (B. suis)) or derived food products like unpasteurized milk and cheese. People may also be infected by inhalation of contaminated dust or aerosols.

Answer 390

A mixture of polyclonal Ig in association with a monoclonal Ig, typically IgM or IgA, with rheumatoid factor activity defines type II CG. This type of CG, also called essential mixed cryoglobulinemia, accounts for 40-60% of cases. Type II CGs are often due to persistent viral infections, particularly hepatitic C and human immunodeficiency virus infections.

Answer 391

Grape-like clusters of rounded cells.

Answer 392

HSV shows rapid (1-3 days), sweeping CPE. Polio shows slow, random, focal CPE.

Answer 393

EBV does not grow in routine cell culture. EBV proliferates only in B-lymphocytes. Lymphocyte cultures take 4 weeks. Viral serology is the preferred method.

Answer 394

Influenza and parainfluenza grow only on PMK (Primary Monkey Kidney). They often display minimal to no CPE but can be detected in cell culture by hemadsorption (they express hemagglutinins with which they can adsorb guinea pig RBCs to the surface of the culture cells).

Answer 395

They grow mainly in HDF (Human Diploid Fibroblasts) and show slow (up to 2 weeks), focal clusters (plaques) of CPE.

Answer 396

Enterovirus has +++ growth on PMK (Primary Monkey Kidney) and HDF (Human Diploid Fibroblasts) and has angular tear-shaped cells.

Answer 397

Influenza A and B viruses: 2-5 days. Parainfluenza virus: 3-10 days. HSV: 1-4 days. VZV: ~14 days (>5 days) (or may fail to grow at all). CMV: ~14 days (>5 days). RSV: ~14 days (>5 days) (or may fail to grow at all). Adenovirus: 2-7 days or longer. Coxsackie A and B viruses: 1-7 days. Echovirus: 1-7 days. Mumps virus: 3-10 days. Poliovirus: 1-7 days.

Answer 398

EBV. BK virus. JC virus. Arboviruses (West Nile virus, St. Louis encephalitis virus, Dengue virus). Most agents of viral gastroenteritis.

Answer 399

A Warthin–Finkeldey cell is a type of giant multinucleate cell found in hyperplastic lymph nodes early in the course of measles and also in HIV-infected individuals. as well as in Kimura disease, and more rarely in a number of neoplastic (e.g. lymphoma) and non-neoplastic lymph node disorders.

Answer 400

Influenza: -/-/-. RSV: -/-/+, HSV: +/-/+, adenovirus: +/-/-, CMV: +/+/-, measles: +/+/+, rabies: -/+/-.

Answer 401

Negri bodies are eosinophilic, sharply outlined, pathognomonic inclusion bodies (2–10 µm in diameter) (?0.25 to 27 µm?) found in the cytoplasm of certain nerve cells containing the rabies virus, most frequently in the pyramidal cells of Ammon's horn, and the Purkinje cells of the cerebellum. They are also found in the cells of the medulla and various other ganglia. The inclusions consist of ribonuclear proteins produced by the virus.

Answer 402

With viral infections, elevated IgM titers, or rising IgG titers (4-fold between acute and convalescent samples, 7-10 days apart) are indicative of acute infection. Usually, virus-specific IgM is detectable during the first week of a primary infection and becomes undetectable within 1-4 months. Virus-specific IgG begins to emerge 1-2 weeks into a primary infection and peaks between 4-8 weeks, then declines continually but usually remains detectable for life. In secondary infection (reactivation or new infection with the same virus), there may or may not be a re-emergence of IgM; and IgG, usually detectable from the start, increases for the next 4-8 weeks.

Answer 403

As a general rule, DNA viruses replicate within the nucleus while RNA viruses replicate within the cytoplasm. Exceptions are known to this rule: Poxviruses (DNA viruses) replicate within the cytoplasm and orthomyxoviruses and hepatitis D virus (RNA viruses) replicate within the nucleus.

Answer 404

~20% of the population has HSV-2 seropositivity, but only ~2% of the population has genital herpes.

Answer 405

Clean an area with an intact vesicle for best results. If no intact vesicles are present, use the edge of the most recently appearing erosion or ulcer. Remove a blister roof with a no. 15 blade, blot any excess blister fluid, then scrape the base of the vesicle, erosion, or ulcer with the scalpel blade, spreading a thin layer of the resultant material onto a glass slide. After staining, if typical HSV cytopathic effect is observed, the diagnosis can be made.

Answer 406

Dorsal root ganglia.

Answer 407

Congenital varicella is diagnosed when there is evidence of maternal varicella infection during pregnancy, skin lesions on the newborn that have a dermatomal distribution, and serologic evidence of infection in the newborn (either IgM or persistent IgG beyond 7 months). Perinatal varicella arises when maternal infection occurs within a few days of delivery.

Answer 408

When a woman is infected during pregnancy, the overall incidence of congenital varicella is 1-5%. The incidence is lowest when maternal infection occurs in the 1st trimester and highest in the 3rd. In contrast, the likelihood of perinatal varicella is 50-60%.

Answer 409

AKA herpes zoster oticus. It is caused by reactivation of latent VZV infection in the geniculate ganglion of the facial nerve with subsequent spread of the inflammatory process to involve the eighth cranial nerve. The syndrome typically includes the triad of ipsilateral facial paralysis, ear pain, and vesicles in the auditory canal and auricle. Vertigo, tinnitus, and hearing loss can also occur.

Answer 410

CMV. Congenital CMV results from transplacental infection and is most likely to occur when a pregnant woman experiences primary CMV infection during gestation. 30-40% of pregnancies with primary CMV infection result in congenital CMV. In contrast, reactivation infection during pregnancy results in <1% incidence of transplacental transmission.

Answer 411

Sensorineural hearing loss is detected in ~70%of newborns with symptomatic congenital CMV infection and in ~15% with asymptomatic infection. This hearing loss almost always is progressive, eventually producing severe to profound hearing loss in the affected ear(s).

Answer 412

The proportion of humans with evidence of prior CMV infection varies throughout the world, with seroprevalence rates ranging between 40 to 100 percent of the adult population. Seroprevalence generally correlates inversely with a country's socioeconomic development, with highest rates observed in developing countries.

Answer 413

Naegleria fowleri causes a rapidly fatal infection of the CNS known as primary amebic meningoencephalitis. Acanthamoeba spp and Balamuthia mandrillaris can cause granulomatous amebic encephalitis, which is a subacute or chronic infection of the CNS seen mainly in immunocompromised individuals.

Answer 414

EBV belongs to the gamma-herpesvirus subfamily of herpes virus along with HHV-8. The virus gains entry into the body by infection of B-lymphocytes by the interaction between the major viral glycoprotein gp350 and the complement receptor CR2 which is expressed on B-cells. Following primary infection there is the expression of lytic cycle proteins resulting in the release of infectious virus and generalized seeding of B-cells throughout the body.

Answer 415

These include six EBV nuclear antigens (EBNA-1, 2, 3A, 3B, 3C, and LP), three latent membrane proteins (LMP1, 2A, 2B) localized in the plasma membrane of the infected B cells, and two small non-polyadenylated nuclear RNAs, EBER1 and EBER2 (which far often used as sensitive markers for the presence of EBV within a cell). Three patterns of latency (I, II, and III) are identified depending on the expression of these genes.

Answer 416

BZLF1, which represents the Z gene of the virus that is implicated in the switch from latency to lytic cycle of the virus causing its replication; all of the other markers including EBER-1 are considered latency genes and do not necessarily reflect replicating virus or active infection.

Answer 417

Endemic Burkitt lymphoma: 95-100%. Sporadic Burkitt lymphoma: 20-30%. Infectious mononucleosis: 100%. Nasopharyngeal carcinoma: 100%. Chronic active EBV infection: 100%. Mixed cellularity Hodgkin lymphoma: 60-80%. Nodular sclerosis Hodgkin lymphoma: 20-40% Fatal IM/X linked lymphoproliferative syndrome: 100%. Primary CNS lymphoma: 100%. Posttransplant lymphoproliferative disorder: 80%. Oral hairy leukoplakia: 100%. Smooth muscle cell derived tumor in immunodeficient individuals: 100%. Nasal T/NK cell lymphomas: 100%. Angioimmunoblastic lymphadenopathy: 30%. Gastric carcinoma (undifferentiated carcinoma of the nasopharyngeal type): 100%. Gastric carcinoma (adenocarcinoma: 5-15%).

Answer 418

The most severe clinical form of hereditary elliptocytosis. Severe thermal burns. Clostridial sepsis, presumably a function of the clostridial hemolysins (a-toxin, containing phospholipase C/lecithinase). Artifactual in vitro poikilocytosis due to overheating of blood samples after removal from the body, most commonly inside of motor vehicles ("pseudopyropoikilocytosis").

Answer 419

They require concurrent replication of helper viruses like adenovirus or herpesvirus.

Answer 420

Many women of reproductive age are parvovirus B19 seronegative and are thus susceptible to a primary infection during pregnancy. The rate of vertical transmission from mother or fetus is ~33%. The risk of fetal demise is greatest in the early second trimester, when fetal immunity is sluggish. The most commonly recognized clinical manifestation of severe parvovirus B19 induced anemia is non-immune hydrops fetalis. Parvovirus is thought to cause ~10% of non-immune fetal hydrops cases.

Answer 421

~30% of FHLH cases are due to mutations in the gene encoding perforin (PRF1, 10q21-22), and 20-25% of cases are due to mutations in Munc 13-14 (UNC13D, 17q25). Acquired forms of HLH are typically triggered by infections, especially viral infection such as EBV, CMV, other herpes viruses, and parvovirus B19. Other forms of infection which trigger HLH include bacterial, fungal, and protozoan infections, especially Leishmaniasis. It is important to note that genetic forms of HLH may also be triggered by infection, and isolation of a causative agent does not distinguish primary and secondary forms. Malignancies associated with HLH include primary lymphomas, an association that is more common in adults than in children. Specifically, ALCL is a frequent associated malignancy. HLH in the setting of autoimmune disease has been distinguished from other forms and is called "macrophage activation syndrome" or " reactive hemophagocytic syndrome." This is most often reported in association with systemic-onset juvenile idiopathic arthritis, but may also be seen with LE and other collagen vascular diseases.

Answer 422

A rare mature CD4+ T-cell neoplasm caused by HTLV-1. Endemic areas: southern Japan, Africa, the Caribbean basin, and Latin America. Mean age 60 yo, range 20-80 yo. M:F = 1.5:1. 4 variants: acute (60%), lymphomatous (20%), chronic (15%), smoldering (5%).

Answer 423

Major paths of viral transmission are breast feeding, blood exposure, and unprotected sex. The lifetime risk of progression to ATLL in an HTLV-1-positive patient is 2.1% for women and 6.6% for men.

Answer 424

S. hemolyticus.

Answer 425

Resistant.

Answer 426

Sensitive.

Answer 427

Yes. So don't confuse it with Staphylococcus.

Answer 428

Staphylococcus.

Answer 429

Gamma hemolysis.

Answer 430

Alpha hemolysis.

Answer 431

The "A" is for group A Streptococcus. GAS is sensitive to bacitracin.

Answer 432

Enterococcus faecium is arabinose fermentation positive, while Enterococcus faecalis is arabinose fermentation negative.

Answer 433

No. Enterococcus has natural resistance to cephalosporins, so they should not be tested for antibiotic susceptibility to it, and it should never be treated with cephalosporins.

Answer 434

Enterococcus is bile esculin positive and 6.5% NaCl positive, while S. bovis is bile esculin positive and 6.5% NaCl negative.

Answer 435

The "P" is for Pneumococcus. Strep pneumo is inhibited by optochin.

Answer 436

Ethylhydrocupreine (hydrochloride). It is a chemical, not an antibiotic. It is used for the presumptive identification of Streptococcus pneumoniae, which is optochin sensitive, from other alpha-hemolytic streptococci such as Streptococcus viridans, which are optochin resistant.

Answer 437

Acinetobacter is normal flora in the female genital tract that is morphologically very similar to Neisseria, but males do not have Acinetobacter as normal flora in the urethra.

Answer 438

N. gonorrhea: gluc +, mal -, lac -, suc -. N. meningitidis: gluc +, mal +, lac -, suc -. N. lactamica: gluc +, mal +, lac +, suc -.

Answer 439

Corynebacterium jeikeium.

Answer 440

Bacillus anthracis.

Answer 441

Erysipelothrix rhusiopathiae.

Answer 442

Proteus vulgaris is indole positive, and Proteus mirabilis is indole negative.

Answer 443

Ring. Trophozoite. Schizont. Gametocyte.

Answer 444

P. falciparum: RBC - normal; multiple infection of RBC more common than in other species; Maurer's clefts (under certain staining conditions). Parasite - delicate cytoplasm; 1 to 2 small chromatin dots; occasional appliqué (accolé) forms. P. vivax: RBC - normal to 1.25x, round; occasionally fine Schüffner's dots; multiple infection of RBC not uncommon. Parasite - large cytoplasm with occasional pseudopods; large chromatin dot. P. ovale: RBC - normal to 1.25x, round to oval; occasionally Schüffner's dots; occasionally fimbriated; multiple infection of RBC not uncommon. Parasite - sturdy cytoplasm; large chromatin. P. malariae: RBC - normal to 0.75x. Parasite - sturdy cytoplasm; large chromatin. P. knowlesi: RBC - normal to 0.75x; multiple infection not uncommon. Parasite - delicate cytoplasm; 1 to 2 prominent chromatin dots; occasional appliqué (accolé) forms.

Answer 445

Ring. Trophozoite. Schizont. Gametocyte.

Answer 446

P. falciparum: RBC - normal; multiple infection of RBC more common than in other species; Maurer's clefts (under certain staining conditions). Parasite - delicate cytoplasm; 1 to 2 small chromatin dots; occasional appliqué (accolé) forms. P. vivax: RBC - normal to 1.25x, round; occasionally fine Schüffner's dots; multiple infection of RBC not uncommon. Parasite - large cytoplasm with occasional pseudopods; large chromatin dot. P. ovale: RBC - normal to 1.25x, round to oval; occasionally Schüffner's dots; occasionally fimbriated; multiple infection of RBC not uncommon. Parasite - sturdy cytoplasm; large chromatin. P. malariae: RBC - normal to 0.75x. Parasite - sturdy cytoplasm; large chromatin. P. knowlesi: RBC - normal to 0.75x; multiple infection not uncommon. Parasite - delicate cytoplasm; 1 to 2 prominent chromatin dots; occasional appliqué (accolé) forms.

Answer 447

Ring. Trophozoite. Schizont. Gametocyte.

Answer 448

P. falciparum: RBC - normal; multiple infection of RBC more common than in other species; Maurer's clefts (under certain staining conditions). Parasite - delicate cytoplasm; 1 to 2 small chromatin dots; occasional appliqué (accolé) forms. P. vivax: RBC - normal to 1.25x, round; occasionally fine Schüffner's dots; multiple infection of RBC not uncommon. Parasite - large cytoplasm with occasional pseudopods; large chromatin dot. P. ovale: RBC - normal to 1.25x, round to oval; occasionally Schüffner's dots; occasionally fimbriated; multiple infection of RBC not uncommon. Parasite - sturdy cytoplasm; large chromatin. P. malariae: RBC - normal to 0.75x. Parasite - sturdy cytoplasm; large chromatin. P. knowlesi: RBC - normal to 0.75x; multiple infection not uncommon. Parasite - delicate cytoplasm; 1 to 2 prominent chromatin dots; occasional appliqué (accolé) forms.

Answer 449

P. falciparum: RBC - normal; rarely, Maurer's clefts (under certain staining conditions). Parasite - seldom seen in peripheral blood; compact cytoplasm; dark pigment. P. vivax: RBC - enlarged 1.5 to 2x; may be distorted; fine Schüffner's dots. Parasite - large amoeboid cytoplasm; large chromatin; fine, yellowish-brown pigment. P. ovale: RBC - normal to 1.25x; round to oval; some fimbriated; Schüffner's dots. Parasite - compact with large chromatin; dark-brown pigment. P. malariae: RBC - normal to 0.75x; rarely, Ziemann's stippling (under certain staining conditions). Parasite - compact cytoplasm; large chromatin; occasional band forms; coarse, dark-brown pigment. P. knowlesi: RBC - normal to 0.75x; rarely, Sinton and Mulligan's stippling (under certain staining conditions). Parasite - compact cytoplasm; large chromatin; occasional band forms; coarse, dark-brown pigment.

Answer 450

P. falciparum: RBC - normal; rarely, Maurer's clefts (under certain staining conditions). Parasite - seldom seen in peripheral blood; mature = 8 to 24 small merozoites; dark pigment, clumped in one mass. P. vivax: RBC - enlarged 1.5 to 2x; may be distorted; fine Schüffner's dots. Parasite - large, may almost fill RBC; mature = 12 to 24 merozoites; yellowish-brown, coalesced pigment. P. ovale: RBC - normal to 1.25x, round to oval, some fimbriated, Schüffner's dots. Parasite - mature = 6 to 14 merozoites with large nuclei, clustered around mass of dark-brown pigment. P. malariae: RBC - normal to 0.75x; rarely, Ziemann's stippling (under certain staining conditions). Parasite - mature = 6 to 12 merozoites with large nuclei, clustered around mass of coarse, dark-brown pigment; occasional rosettes. P. knowlesi: RBC - normal to 0.75x; rarely, Sinton and Mulligan's stippling (under certain staining conditions). Parasite - mature = up to 16 merozoites with large nuclei, clustered around mass of coarse, dark-brown pigment; occasional rosettes; mature merozoites appear segmented.

Answer 451

P. falciparum: RBC - distorted by parasite. Parasite - crescent or sausage shape; chromatin in a single mass (macrogametocyte) or diffuse (microgametocyte); dark pigment mass. P. vivax: RBC - enlarged 1.5 to 2x; may be distorted; fine Schüffner's dots. Parasite - round to oval; compact; may almost fill RBC; chromatin compact, eccentric (macrogametocyte) or diffuse (microgametocyte); scattered brown pigment. P. ovale: RBC - normal to 1.25x; round to oval, some fimbriated; Schüffner's dots. Parasite - round to oval; compact; may almost fill RBC; chromatin compact, eccentric (macrogametocyte) or more diffuse (microgametocyte); scattered brown pigment. P. malariae: RBC - normal to 0.75x; rarely, Ziemann's stippling (under certain staining conditions). Parasite - round to oval; compact; may almost fill RBC; chromatin compact, eccentric (macrogametocyte) or more diffuse (microgametocyte); scattered brown pigment. P. knowlesi: RBC - normal to 0.75x; rarely, Sinton and Mulligan's stippling (under certain staining conditions). Parasite - round to oval; compact; may almost fill RBC; chromatin compact, eccentric (macrogametocyte) or more diffuse (microgametocyte); scattered brown pigment.

Answer 452

H. influenzae: requires V and X. H. parainfluenzae: requires V only. H. hemolyticus: requires V and X. H. parahemolyticus: requires V only. H. ducreyi: requires X only.

Answer 453

Haemophilus (now Aggregatibacter) aphrophilus (although some include multiple species): oxidase neg, catalase neg, non-hemolytic. Actinobacillus (also now Aggregatibacter) actinomycetemcomitans: oxidase neg, catalase pos, non-hemolytic. Cardiobacterium hominis: oxidase pos, catalase neg, slight alpha-hemolysis. Eikinella corrodens: oxidase pos, catalase neg, non-hemolytic but pits the agar. Kingella kingae: oxidase pos, catalase neg, small zone of beta-hemolysis.

Answer 454

Pasteurella is small coccobacilli. Capnocytophaga is very pleomorphic rods.

Answer 455

Pasteurella is small coccobacilli. Capnocytophaga is very pleomorphic rods.

Answer 456

Campylobacter jejuni grows at 37 and 42 C. Campylobacter fetus grows at 37 and 25 C.

Answer 457

The CAMP test is used to identify Streptococcus agalactiae (group B) (CAMP positive) and to differentiate it from Streptococcus pyogenes (group A) (CAMP negative) and nongroup B Streptococcus (CAMP negative). Also, it can be used to identify pathogenic Listeria monocytogenes (CAMP positive). The reverse CAMP test is used to identify Clostridium perfringens (reverse CAMP positive).

Answer 458

The beta-lysin produced by beta-hemolytic Staphylococcus aureus acts synergistically with the CAMP factor (an extracellular protein) produced by both beta-hemolytic and nonhemolytic Streptococcus agalactiae (group B). This synergistic reaction results in an enhanced and very visible zone of hemolysis in the region between the two cultures. A loopful of beta-toxin-producing S. aureus is streaked in a line down the center of a BAP. The test organism (suspect GBS) is streaked perpendicular to the line of S. aureus (within 2 mm but not touching), and incubated in ambient air at 35 C for 24 hrs. A positive result is indicated by an arrowhead-shaped enhanced zone of beta-hemolysis in the area between the 2 cultures with the point of the arrowhead towards the S. aureus streak. A similar procedure is used for identification of pathogenic Listeria monocytogenes (CAMP positive) (replace the streak of Strep with a streak of suspected L. monocytogenes).

Answer 459

"Christie, Atkins, Munch-Petersen," for the 3 researchers who described the phenomenon.

Answer 460

The basic principle is the same as the CAMP test, except that Streptococcus agalactiae (group B) and Clostridium perfringens are streaked perpendicular to each other instead of S. agalactiae and Staphylococcus aureus (and anaerobic incubation in this case for the Clostridium). A synergistic reaction between the CAMP factor produced by the S. agalactiae and the alpha toxin produced by the C. perfringens results in an enhanced and visible arrowhead-shaped zone of hemolysis in the region between the two cultures. A variation of the reverse CAMP test with inhibition (not enhancement) of hemolysis is used for identification of Arcanobacterium haemolyticum (uses S. aureus).

Answer 461

C. perfringens does not sporulate on ordinary media. C. tetani has a round, terminal endospore. The remaining species have an oval, sub terminal endospore.

Answer 462

All Candida species except some isolates of Candida krusei and Candida lusitania. It is not adequately active against Scedosporium apiospermum, Aspergillus terreus, Trichosporon spp., most of the species causing mycetoma and systemic infections due to Sporothrix schenkii.

Answer 463

It is active against most Candida species with the absolute exception of Candida krusei and partial exception of Candida glabrata and a small number of isolates of Candida albicans, Candida tropicalis, Candida parapsilosis and other rare species. Also, it is not active against Aspergillus or Mucorales.

Answer 464

Acquired resistance to posaconazole does occur in Aspergillus fumigatus and Candida albicans but is otherwise rare.

Answer 465

Parental karyotyping (karyotyping of an abortus is often indicated as well). Endometrial bxs may be obtained to exclude luteal phase defect (endometrial histology that is 2 or more days discrepant with dates). Endometrial culture may be obtained to exclude subclinical infection with U. urealyticum or C. trachomatis. Thyroid function tests. Tests for lupus anticoagulants.

Answer 466

Trichosporon beigelii. Candida tropicalis. Cryptococcus neoformans. Yeast of Blastomyces. Yeast of Histoplasma.

Answer 467

Rhinocladiella-like (palm leaf). Phialaphora-like (flower bouquet in a vase). Cladosporium-like (end-to-end ovals in a branching arrangement).

Answer 468

Candida (used to be Torulopsis) glabrata.

Answer 469

C. albicans is sucrose negative. C. stellatoidea is sucrose positive.

Answer 470

The yeast in incubated in plasma for 4 hours, then observed for germ tubes. If it is incubated for longer than 4 hours, you run the risk of false positives since other species can start forming structures similar to germ tubes.

Answer 471

Tinea versicolor is a 2-4 um budding yeast with a collarette - a "bud scar" or overhanging lip, making the yeast look like a bowling pin.

Answer 472

Epidermophyton floccosum.

Answer 473

Trichophyton rubrum.

Answer 474

M. canis has spindle-shaped macroconidia with pointed, slightly upturned ends, and transverse septae. M. gypseum has oval-shaped macroconidia with blunt ends and transverse septae.

Answer 475

Cryptococcus.

Answer 476

Cryptococcus.

Answer 477

P. marneffei.

Answer 478

Zygomycetes. These are individual long hollow tubes rather than in hyphae. Organisms with hyphae are hardier since each hyphal form can regenerate the organism, but the Zygomycetes are more likely to be killed and not grow in culture when the tissue is ground up.

Answer 479

AKA intestinal lipodystrophy. It is a rare systemic infection due to Tropheryma whippelii, a gram positive intracellular actinomycete. It usually affects proximal intestine and mesenteric lymph nodes, and usually white males ages 30-49 yo. DDx: histoplasmosis, MAI, mineral oil ingestion.

Answer 480

Whipple disease has wide open lymphatic channels and characteristic large open round spaces due to dissolved lipids in mucosa and submucosa (appears as large fat vacuoles). MAI has a conspicuous absence of dilated lymphatics or large fatty vacuoles.

Answer 481

Cutaneous extranodal marginal zone lymphoma.

Answer 482

Q fever, caused by Coxiella burnetii. Fibrin ring granulomas are small, non-necrotizing granulomas that are usually found in the liver and bone marrow in patients with Q fever. These granulomas characteristically contain a ring-like structure consisting of fibrinoid material; they may or may not have a centrally located fat vacuole(s). This type of granuloma, although uncommon, may be seen in many other conditions including a variety of infections (CMV, EBV, MAI, hepatitis A, infectious mononucleosis, visceral leishmaniasis, Lyme disease, Boutonneuse fever, toxoplasmosis) Hodgkin disease, non-Hodgkin lymphomas, and drug reactions.

Answer 483

Lymphomatoid granulomatosis is an angiocentric and angiodestructive EBV-driven B-cell lymphoproliferative disease, in which the neoplastic B-cells are admixed with reactive T-cells.

Answer 484

Brain, kidney, liver, and skin.

Answer 485

The lymphoma cells show marked intrasinusoidal infiltration in the spleen, liver, and bone marrow; lymph node involvement is uncommon. The lymphoma cells are cytotoxic T-cells, usually of the delta-gamma receptor type, which express TIA-1 but are usually negative for perforin. The typical phenotype is CD2+, CD3+, CD7+, CD4-, CD5-, CD8- (usually). EBV is negative.

Answer 486

DLBCL. Classic Hodgkin lymphoma is also common, but not as common as DLBCL.

Answer 487

Amoebic colitis. Antibiotic-associated (pseudomembranous) colitis. Chemotherapy-induced colitis. Colitis complicating obstruction. Heavy metal toxicity (gold salt therapy). Hemolytic uremic syndrome. Ischemic colitis. Neutropenic enterocolitis (typhilitis). Shigellosis.

Answer 488

Parvovirus B19 infects erythroid progenitor cells, causing a maturation arrest at the pronormoblast stage. The bone marrow shows numerous giant pronormoblasts, a reduction of the more mature forms, and viral nuclear inclusions.

Answer 489

Acute episodes of anemia: Aplastic crisis (Parvovirus B19 accounts for nearly 70% of aplastic crises in children). Splenic sequestration (these episodes often occur during a viral illness). Hyperhemolytic crisis (this complication has been associated in many patients with concomitant G6PD deficiency). Slowly progressive worsening of anemia: Progressive renal insufficiency (with decreasing erythropoietin) or supervening iron/folate/B12 deficiency.

Answer 490

Acute pain crisis is thought to be due to a vasoocclusive event within bone. Acute chest syndrome is thought to be related to either vasoocclusive events or bacterial PNA.

Answer 491

S. pneumoniae infections, including pneumococcal sepsis, pneumonia, meningitis, and arthritis, are the most common overall. Other common infections include Salmonella, Haemophilus (HITB), and M. pneumoniae.

Answer 492

The 2 genomic types of EBV are EBV1 and EBV2. They do not differ in disease association, but EBV1 is the predominant type in the West, whereas EBV1 and EBV2 are evenly distributed elsewhere.

Answer 493

EBV enters the body through the pharyngeal mucosa and subsequently infects B lymphocytes via the C3d receptor (CD21). Reacting to the virus, CD8+ T lymphocytes are responsible for the peripheral blood atypical lymphocytosis that is seen. The site of EBV latency is the B lymphocyte. The EBV genome persists in episomal form within a small population of B lymphocytes, where it usually causes no additional effects.

Answer 494

The classic IM presentation, seen primarily in adolescents, includes sore throat (pharyngitis), lymph node enlargement, tonsillar enlargement, and fever. In primary infection of older adults these findings are less likely; instead, hepatitis and jaundice become more common.

Answer 495

X-linked lymphoproliferative disorder. It is a manifestation of fulminant acute/primary EBV infection that is frequently fatal and appears confined to males of rare kindreds.

Answer 496

The mechanism of death is usually hepatic necrosis, associated with a pronounced T/NK cell infiltrate. In other cases, affected individuals have manifested hemophagocytosis, agammaglobulinemia, and B cell lymphoma. The underlying genetic defect is found in the SH2D1A (also called SAP) gene that is normally expressed in T and NK cells. The SAP protein is a transmembrane signaling protein that becomes involved in the usual course of immune reaction to viral infection. In those harboring this mutation, for as yet unknown reasons, EBV in particular results in uncontrolled activation of T/NK cells.

Answer 497

A leukocytosis consisting of >50% lymphocytes and >10% atypical lymphocytes, fever, pharyngitis, adenopathy, and a positive serologic test. These criteria are quite restrictive, and many patients routinely diagnosed with mono do not qualify.

Answer 498

Infectious mononucleosis. Streptococcal pharyngitis. Pharyngitis due to other viruses (CMV, HIV, etc.). Toxoplasmosis.

Answer 499

Mononucleosis syndrome can be induced by several drugs, particularly anticonvulsants such as phenytoin, carbamazepine, and antibiotics, such as isoniazid or minocycline. Also, patients with lymphadenopathy and splenomegaly may also have lymphoma.

Answer 500

Primary: Infectious mononucleosis. X-linked lymphoproliferative disorder. Hepatitis. Latent: Burkitt lymphoma (100% of endemic BL, 25% of sporadic BL). Hodgkin lymphoma (EBV in 50-70% of cases). Primary effusion lymphoma (EBV in 70% of cases, HHV8 in 100% of cases). Lymphomatoid granulomatosis. Post-transplant lymphoproliferative disorder (EBV in >95%). Oral hairy leukoplakia. Nasopharyngeal carcinoma (nearly 100% EBV positive in Chinese and Inuit populations, 75% EBV positive in US).

Answer 501

In primary effusion lymphoma, HHV8 is positive in 100% of cases, and EBV is positive in 70% of cases.

Answer 502

The heterophile Ab is fairly specific but not very sensitive for EBV infection, being present in 80% of infected teens and adults, 40% of all infected children, and 20% of infected children under 4.

Answer 503

? They emerge during the first week of symptoms, 3-4 wks after infection, and return to undetectable levels by 3-6 mos. ? They present in peak levels 2-6 wks after primary infection, and they may remain positive in low levels for up to a year.

Answer 504

Toxoplasmosis, rubella, CMV, HIV, SLE, RA, lymphoma/leukemia.

Answer 505

IgG and IgM anti-viral capsid antigen (anti-VCA). IgG anti-EBV early antigen (EBV-EA). IgG anti-EBV nuclear antigen (EBNA). These have very high sensitivity (>94%) and specificity (>95%) for EBV infectious mononucleosis.

Answer 506

Following infection, the first marker to appear is IgM anti-VCA. IgG anti-VCA emerges shortly after the IgM and slightly before the heterophile antibody. IgG anti-EA and IgG anti-EBNA begin to appear 1 to 2 months into infection. IgG anti-EBNA and IgG anti-VCA persist indefinitely.

Answer 507

Early acute: -/+, +, +, -, -. Acute: +/-, +, +, +, -/+. Convalescent: -, -, +, +, +. Remote: -, -, -/+, +, +.

Answer 508

There are two subsets of EA IgG: anti-D and anti-R. The presence of anti-D antibodies is consistent with recent infection since titers disappear after recovery, but their absence does not exclude acute illness because the antibodies are not expressed in a significant number of patients. Anti-R antibodies are only occasionally present in IM.

Answer 509

EBV-encoded RNA; nuclear RNA portions of EBER 1 and 2 genes. Nuclear stain.

Answer 510

EBER is located to the nuclei of RS/H cells, with little to no expression in the background small lymphocytes. LMP1 is expressed in the cytoplasm and surface membrane of RS/H cells but is rarely expressed in latently infected background lymphocytes of Hodgkin lymphoma.

Answer 511

Oral hairy leukoplakia is the only EBV-related lesion that is negative for EBER by ISH.

Answer 512

All six EBNA proteins are transcribed from a large precursor transcriptional unit, initiated from one of two promoters, one in the BamHI C fragment (Cp) and the other in the BamHI W fragment (Wp) of the EBV genome. During the initial stages of EBV infection, transcription originates from Wp, and then switches to Cp.

Answer 513

First disease (Measles, Hard measles, 14-day measles, Rubeola, Morbilli) - Measles virus. Second disease (Scarlet fever, Scarlatina) - Streptococcus pyogenes. Third disease (Rubella, German measles, 3-day measles) - Rubella virus. Fourth disease (Staphylococcal scalded skin syndrome, Ritter's disease, Filatow-Dukes' disease) - Staphylococcus aureus. Fifth disease (Erythema infectiosum, slapped cheek disease) - Parvovirus (Erythrovirus) B19. Sixth disease (Roseola infantum, Exanthem subitum, 3-day fever, rose rash of infants, "sudden rash") - HHV6B or HHV7.

Answer 514

HHV6 is the etiologic agent of roseola infantum (sixth disease, exanthem subitum, 3-day fever, rose rash of infants, "sudden rash"). Fully-developed roseola manifests in 10% of those with acute HHV6 infection, with the remaining children displaying a nonspecific febrile illness. HHV6 is highly neurotropic and is one of the causes of viral encephalitis. Due to its combined propensity to produce fever and CNS infection, HHV6 is responsible for a significant proportion of childhood febrile seizures.

Answer 515

HHV8. It is associated with all clinical variants of Kaposi sarcoma, with primary effusion lymphoma, and the subset of multicentric Castleman disease seen in HIV+ patients. IHC for LANA-1 shows a characteristic speckled nuclear pattern in cells harboring KSHV.

Answer 516

Adenoviruses are grouped into over 40 serotypes. Most of the respiratory infections are caused by serotypes 1-14, with types 4 and 7 associated with epidemic outbreaks of respiratory disease. Types 11 and 21 are associated with hemorrhagic cystitis. Types 40 and 41 are associated with childhood gastroenteritis.

Answer 517

No. KS is the most common HIV-associated malignancy, leading to angiosarcomatous change of epithelial and mucous membrane-associated connective tissue. Although specifically due to the HHV8 virus, it is considered to be due to the convergence of immune evasion, oncogenesis, inflammation and angiogenesis. Although HHV8 was first detected in, and is usually associated with HIV+ patients, KS can be initiated through non-viral mechanisms, including iatrogenic immunosuppression and elevated expression of cytokines and angiogenic growth factors.

Answer 518

SHb is formed when hemoglobin is oxidized in the presence of sulfur. If further oxidized, SHb precipitates to form Heinz bodies. SHb cannot transport oxygen. Unlike methemoglobin, SHb cannot be reduced to Hb. SHb may increase after exposure to sulfonamides and in the presence of C. perfringens bacteremia (enterogenous cyanosis).

Answer 519

Dientamoeba fragilis.

Answer 520

Cryptosporidium is 4-6 um diameter, while Cyclospora is 7.5-10 um diameter.

Answer 521

They are morphologically identical. The two can be distinguished by antigen testing or molecular methods, but few places do that, so it is reported out as E. histolytica/dispar.

Answer 522

E. histolytica: Trophs have a single nucleus and single central karyosome. Mature cysts have 4 nuclei each with a single central karyosome and thick blunt-ended chromatoid bars. E. coli: Trophs with bacteria in the cytoplasm and a single nucleus with a single eccentric karyosome. Mature cysts have 8 nuclei each with sharp-ended/splintered chromatoid bars.

Answer 523

Fungus, based on gene sequencing. Phylum Microspora, order Microsporida. But they are usually lumped with the protozoans since they act like them therapeutically and diagnostically.

Answer 524

Encephalitozoon, Enterocytozoon in GI disease. Encephalitozoon, Nosema, Vittaforma and others in ocular disease. Encephalitozoon in disseminated disease in immunosuppressed patients.

Answer 525

Infection. In particular, infection with Yersinia enterocolitica is a significant cause of morbidity in patients with thalassemia and other iron overload syndromes.

Answer 526

In CNPA, Aspergillus infection results in semi-invasive, chronic, indolent, cavitary disease in patients who have preexisting lung disease or are mildly immunocompromised. It is characterized by necrotizing granulomas containing Aspergillus hyphae. The granulomas may cause extensive parenchymal consolidation, may lead to bronchiectatic cavities, or may be exclusively bronchocentric. The bronchocentric cases may be accompanied by nonnecrotizing granulomas in a lymphangitic distribution. A nonnecrotizing vasculitis can occur. Eosinophils are not prominent. ABA is a noninvasive form of Aspergillus lung disease characterized by a hypersensitivity response to Aspergillus antigens, occuring mostly in asthmatic patients. Less commonly, other fungi such as Curvularia and Candida may cause similar morphologic changes. ABA results in a distinctive tissue reaction characterized by the triad of mucoid impaction of bronchi, bronchocentric granulomatosis, and eosinophilic pneumonia. However, an individual component of the triad may be present in isolation. Also, each of the features of the triad can occur in isolation in other conditions.

Answer 527

Mucoid impaction of bronchi is characterized by obstruction of proximal bronchi by large, laminated, gelatinous mucus plugs filled with viable and necrotic eos, neuts, fibrin, and necrotic debris. Charcot-Leyden crystals are often present. Aspergillus hyphae may be found within the mucus. Bronchocentric granulomatosis is characterized by necrotizing granulomas centered exclusively on bronchi and bronchioles distal to the bronchi affected by mucoid impaction. The necrotic centers of the granulomas are rich in eos and necrotic debris. Eosinophilic pneumonia is usually a focal finding in ABA. The main histologic feature is filling of the alveolar spaces with eos, often accompanied by histiocytes. The interstitium is usually thickened by a combination of eos, lymphs, and plasma cells. A mild nonnecrotizing vasculitis may be present. (An individual component of the triad may be present in isolation. Also, each of the features of the triad can occur in isolation in other conditions.)

Answer 528

Parvovirus culture is not readily available, since it requires nucleated red blood cells.

Answer 529

Urothelial cells with BK virus. Oligodendroglial cells with JC virus.

Answer 530

The incubation period for human papillomavirus after primary exposure is 2-4 months.

Answer 531

E6 and E7 genes.

Answer 532

A rare condition with probable AR inheritance, characterized by the appearance of HPV-induced wart-like lesions early in childhood, with malignant transformation in ~50% of patients during adulthood, often in skin surfaces with sun exposure. Multiple HPV types have been isolated from these lesions, but HPV types 5 and 8 appear to have the most malignant potential in these individuals. It is associated with a gene locus on chromosome 17 which seems to impair defenses against several specific HPV types. Unlike other types of wart, EV does not appear to be transmissible by contact with healthy subjects. Lesions resembling EV are sometimes seen in organ transplant recipients.

Answer 533

HPV 5 has been associated with psoriasis and epidermodysplasia verruciformis.

Answer 534

Juvenile-onset form (presents at 2-4 years of age), in which HPV is thought to be acquired during passage through the birth canal and is more aggressive. Adult form (presents at 20-40 years of age), thought to be sexually transmitted, in which papillomas are fewer.

Answer 535

The papillomas arise most often on the true vocal cords. Malignant transformation is rare, but the lesions can be life-threatening because of airway obstruction, particularly in children. An HPV subtype is sometimes requested as HPV 11 is associated with more aggressive disease than HPV 6.

Answer 536

A condition caused by HPV 16 that presents in younger males (but can occur in females) as multiple small pearly papules on the anogenital skin. Histologically, it resembles SCCIS, but rarely results in invasive carcinoma. While histologically difficult to distinguish from true SCCIS (Bowen disease and erythroplasia of Queyrat), it is usually easily distinguished clinically.

Answer 537

AKA giant condyloma (accuminatum) of Buschke and Lowenstein. Is a slow-growing, locally destructive verrucous plaque that typically appears on the penis but may occur elsewhere in the anogenital region. M:F = 3.5:1. It most commonly is considered to be a regional variant of verrucous carcinoma, together with oral florid papillomatosis and epithelioma cuniculatum. It is commonly associated with HPV 6 or 11.

Answer 538

HAV: fecal-oral, 15-30 days, 0%. HBV: parenteral, 15-150 days, 10%. HCV: parenteral, 30-150 days, 50%. HEV: fecal-oral, 15-42 days, <1%. HGV: parenteral, unknown, unknown.

Answer 539

HEV has a 20-30% fatality rate in pregnancy.

Answer 540

Polyagglutination happens most often as a consequence of infections, when bacterial enzymes strip off parts of antigens normally present of the surface of the RBC. This action exposes antigens that are normally hidden, called "cryptantigens" (examples include T, Th, Tk, and Tx antigens). Most people have IgM antibodies that react against these cryptantigens, making them incompatible with most other people's serum (most people that have polyagglutination lack the anti-cryptantigen antibody themselves). By definition, polyagglutination resulting from bacteria is transient, and effective treatment of the infection eliminates the polyagglutination.

Answer 541

The hepatitis B virus is a DNA virus whose intact virion is called the Dane particle.

Answer 542

HBeAg indicates active viral replication. In the hepatocyte, the genome of HBV can be present in 2 forms: as replicating virus or integrated into the host genome as a non-replicating form. HBeAg is only produced when the virus is in replicating form; thus, it can be used as a surrogate for HBV DNA production. Antibody against HBeAg (anti-HBe) is found when HBe becomes negative. The presence of anti-HBe does not imply resolved infection or immunity.

Answer 543

In acute HBV infection, serologic markers begin to emerge between 2 to 10 weeks following exposure.

Answer 544

HBV DNA, then HBsAg, then HBeAg, then IgM anti-HBc. HBsAg becomes detectable before clinical symptoms appear. The development of clinical symptoms roughly coincides with the development of antibodies (anti-HBs, anti-HBc).

Answer 545

The brief interval between disappearance of HBsAg and appearance of HBsAb, which was seen with older less sensitive assays. This could lead to a false-negative serologic diagnosis unless IgM anti-HBc was measured. With present more sensitive assays, this window has narrowed considerably.

Answer 546

IgM anti-HBc emerges shortly after HBsAg and persists for many months. It is eventually replaced by IgG anti-HBc, sometimes 18-24 months after infection. IgG anti-HBc indicates past infection, either resolved (anti-HBs+) or in the chronic phase (HBsAg+). In patients who develop chronic HBV infection, IgM anti-HBc may reemerge during acute flares.

Answer 547

1. The "window period" (the brief interval between disappearance of HBsAg and appearance of HBsAb). 2. Chronic HBV infection in which levels of HBsAg have fallen to undetectable levels. 3. Remote resolved HBV infection in which levels of anti-HBs have fallen to undetectable levels (common in HIV infection). 4. Nonspecific false-positives. The presence of circulating HBV DNA in this setting is consistent with chronic HBV infection (with undetectably low HBsAg).

Answer 548

Acute HBV: +, + (IgM), -. Chronic HBV: +, + (IgG), -. Resolved HBV: -, +, +.

Answer 549

Chronic HBV infection is defined by persistence of HBsAg after the acute phase (for more than 6 months). Persistent HBsAg without clinical hepatitis is called the chronic carrier state.

Answer 550

HBV chronicity develops in 5% of healthy adults, 10% of immunocompromised adults, and 90% of neonates who have become infected transplacentally.

Answer 551

C, X, P, and S.

Answer 552

The core protein (HBcAg) is encoded by C, with HBeAg produced by proteolytic processing of the pre-core protein. S encodes the surface antigen (HBsAg). The HBsAg gene is one long open reading frame but contains three in frame "start" (ATG) codons that divide the gene into three sections, pre-S1, pre-S2, and S. P encodes the DNA polymerase. The function of the protein coded for by X is not fully understood.

Answer 553

The HBV genome can undergo mutation, altering clinical features, with one such mutation taking the form of so-called HBeAg-negative chronic hep B. This is characterized by circulating HBV DNA, fluctuating aminotransferases, and a tendency towards fulminant hepatitis with liver failure. This form of hep B results from mutations in the C region of the genome (encodes HBcAg and HBeAg), the most common mutation leading to a premature stop codon that impairs synthesis of HBeAg.

Answer 554

Mutations in the HBV P gene (encodes the DNA polymerase) often arise during treatment with lamivudine, resulting in decreased binding of lamivudine. These mutations may lead to abrupt progression of chronic hepatitis B in patients previously stable on treatment.

Answer 555

The traditional way is to use the HBe antigen status, but there are limitations -a tendency of HBe antigen to be undetectable in reactivation disease or to never appear in pre-core mutation- that make HBV DNA a better analyte for this purpose. Currently, those with >10^5 copies of HBV DNA per mL are considered replicative.

Answer 556

Histologic response: Decrease in the histologic activity index (HAI) of 2 or more in the liver biopsy. Biochemical response: Normalization of serum ALT. Virologic response: Either a negative HBeAg or an undetectable HBV DNA level (<10^5 copies/mL).

Answer 557

55-85% of people infected with HCV will develop chronic infection. 10-15% of those with chronic HCV will develop cirrhosis. Those with cirrhosis due to HCV have a 5% chance of developing HCC.

Answer 558

Hematologic diseases such as essential mixed cryoglobulinemia, lymphoma, and aplastic anemia. Renal disease, particularly membranoproliferative glomerulonephritis. Autoimmune disorders such as thyroiditis and the presence of autoantibodies. Dermatologic conditions such as porphyria cutanea tarda and lichen planus. Diabetes mellitus.

Answer 559

HBV is a DNA virus; the rest are RNA viruses.

Answer 560

There is not a good way to distinguish acute from chronic HCV infection (and it isn't really important to distinguish anyway). IgM and IgG anti-HCV cannot be reliably used to distinguish acute from chronic HCV infection.

Answer 561

Undetectable HCV RNA for a period of 24 weeks/6 months after the end of treatment.

Answer 562

Genotype 1 has a low (40%) rate of response. Genotypes 2 and 3 have a high (70%) rate of response. Genotypes 4 through 9 have not been sufficiently studied due to low prevalence.

Answer 563

In the US, the most common HCV genotype is 1 (80%). Genotype 1 is further subdivided into 1a (60%) and 1b (20%), but significance has not been assigned to these subgenotypes. Genotype 2 represents 20%, and genotype 3 represents 5%.

Answer 564

Molecular or serologic assays are available. The molecular assays involve direct sequencing of portions of the HCV genome (such as the 5V noncoding region), hybridization with genotype-specific sequences, or RFLP analysis. Serologic assays detect serum antibodies against genotype-specific antigens.

Answer 565

Qualitative assays are based upon conventional PCR or TMA platforms. Quantitative assays for HCV RNA can be performed by RT-PCR, TMA, or bDNA. These techniques must be capable of detecting as little as 50 IU/mL, since this is the definition of a sustained virologic response. Furthermore, they must be equally sensitive to RNA from the different genotypes. The same testing platform should be used throughout treatment, since quantitative results are not directly comparable between methods.

Answer 566

Many viruses (influenza, parainfluenza, measles, mumps, and some picornaviruses) contain surface glycoproteins known as hemagglutinins (HA). These are capable of binding RBCs. As these viruses replicate in cell culture, HA molecules appear on the cell surface. If RBCs of the appropriate species are added to the cell culture tube in which the virus is replicating, they will adhere to the cell sheet – a phenomenon known as hemadsorption. The presence of hemadsorbing viruses can therefore be detected several days before a cytopathic effect becomes apparent. Identification can then be confirmed using methods such as hemagglutination inhibition, hemadsorption inhibition, or, most commonly nowadays, IF.

Answer 567

Many viruses (influenza, parainfluenza, measles, mumps, and some picornaviruses) contain surface glycoproteins known as hemagglutinins and are hemadsorbing.

Answer 568

Unlike the more common flu strains, H5N1 affects predominantly children and young adults, with a median age of 15 yrs. Lymphopenia is characteristic, without significant changes in the neutrophil, RBC, or platelet counts. The virus has tropism for non-ciliated epithelial cells of the lower respiratory tract, leading to an ARDS/DAD-like clinicopathologic picture and may explain the low rate of human-to-human transmission.

Answer 569

Influenza A is more common and causes more serious disease. Symptoms include abrupt onset of fever with myalgias, HA, sore throat and cough. Influenza B produces milder symptoms with a stronger GI component, and characteristic features of calf myositis and ocular pain with movement.

Answer 570

Neuraminidase inhibitors and the adamantanes. The neuraminidase inhibitors, zanamivir and oseltamivir, are active against both influenza A and B. The adamantanes, amantadine and rimantadine, are only active against influenza A. Due to a marked increase in resistant isolates, the Advisory Committee on Immunization Practices (ACIP) (2011) recommends that adamantanes not be used in the US for the treatment of influenza, except in selected circumstances.

Answer 571

Parainfluenza viruses 1 and 2 cause the most cases of croup in children between the ages of 2 and 6. RSV is the most common cause of respiratory bronchiolitis ("viral pneumonia") in infants under age 2.

Answer 572

Classic measles infection in immunocompetent patients. Modified measles (an attenuated infection in patients with preexisting, but incompletely protective, anti-measles antibody). Atypical measles (in patients immunized with the killed virus vaccine and subsequently exposed to wild-type measles virus; is rare since the killed virus vaccine was used in the US from 1963-67). Neurologic syndromes following measles infection, including acute disseminated encephalomyelitis (ADEM) and subacute sclerosing panencephalitis (SSPE). Severe measles. Complications of measles including secondary infection, giant cell pneumonia, and measles inclusion body encephalitis.

Answer 573

With natural infection, the risk of SSPE is 0.001% (with higher risk if measles is acquired at an early age), with an incubation period of 7-10 yrs. With vaccination, the risk of SSPE is 0.0001% with an incubation period of 3 yrs.

Answer 574

Mumps infection is frequently accompanied by a nonspecific prodrome consisting of low-grade fever, malaise, HA, myalgias, and anorexia. These symptoms are generally followed within 48 hrs by the development of parotitis, a classic feature of mumps infection seen in 95% of symptomatic cases. The parotitis is due to direct infection of ductal epithelium and local inflammation. Symptomatic infection in adults is usually more severe than in children.

Answer 575

RSV causes 90% of respiratory bronchiolitis in infants and almost 50% of lower respiratory tract infections in children. Immunity to RSV is short-lived, and recurrence throughout childhood is the rule, although infections are progressively less severe with bronchiolitis uncommon after 12 mos.

Answer 576

PIVs are single-stranded, enveloped RNA viruses belonging to the genus Paramyxovirus in the Paramyxoviridae family. This family also includes mumps, measles, respiratory syncytial viruses, human metapneumovirus, and Nipah and Hendra viruses.

Answer 577

RT-PCR. It demonstrates excellent sensitivity and same-day turnaround time. Cell culture should be performed as well, in case the PCR test is negative.

Answer 578

Bunyaviridae. Togaviridae. Reoviridae. Some sources list Flaviviridae, some list Rhabdoviridae as a fourth family.

Answer 579

Hantaviruses (Sin Nombre, Black Creek, Prospect Hill). California encephalitis. Several hemorrhagic fever viruses (Crimean-Congo, Rift Valley fever, LaCrosse).

Answer 580

Bunyaviruses: Crimean-Congo Hemorrhagic Fever (CCHF), Rift Valley Fever virus, LaCrosse virus. Togaviruses: Flaviviruses (Dengue and Yellow Fever virus) and Togaviruses (Chikungunya virus). Arenaviruses: Lassa fever virus. Filoviruses: Marburg and Ebola viruses.

Answer 581

Bunyaviruses, and specifically, the hantaviruses.

Answer 582

Alphavirus (Eastern Equine, Western Equine, and Venezuelan encephalitis), flavivirus (St. Louis Encephalitis, dengue, yellow fever), and rubivirus (rubella virus).

Answer 583

First trimester infections have the most serious fetal implications. Defects in neonates infected in the first trimester include hearing impairment (60%), heart defects (45%) (PDA in 20% and peripheral pulmonic stenosis in 12%), microcephaly (27%), cataracts (25%), low birth weight (<2500 g) (23%), hepatosplenomegaly (19%).

Answer 584

Liver. There is extensive midzonal necrosis, Councilman bodies, microvesicular fatty metamorphosis, and absence of an inflammatory component.

Answer 585

Colorado tick fever virus, rotavirus.

Answer 586

Lymphocytic choriomeningitis virus (lymphocytic choriomeningitis). Junin virus (Argentine hemorrhagic fever). Machupo virus (Bolivian hemorrhagic fever). Lassa virus (Lassa fever). Guanarito virus (Venezuelan hemorrhagic fever). Sabia virus (Brazilian hemorrhagic fever). Chapare virus (Chapare hemorrhagic fever). Lujo virus (Lujo hemorrhagic fever).

Answer 587

Cryptococcal meningitis causes little inflammatory reaction in the meninges.

Answer 588

Thrombocytopenia. Eczema. Recurrent bacterial, viral, and fungal infections (susceptibility to infections associated with adaptive and innate immune deficiency).

Answer 589

Acute disseminated encephalomyelitis is an acute postviral or postvaccinal demyelinating disease. The typical lesion seen is a perivenular demyelination.

Answer 590

Rabies - hippocampal pyramidal cells, neurons of the cerebral cortex, Purkinje cells. CMV - ependymal cells. HIV - cerebral microglial/monocyte/macrophage cells. JC virus - oligodendrocytes, astrocytes. HSV1 - cortical neurons.

Answer 591

Parasitic infection. Churg-Strauss syndrome. Hyper-IgE (Job) syndrome. IgE myeloma. Hodgkin lymphoma. IgE is not uniformly elevated in allergic states so is not a useful screening test in that setting.

Answer 592

An excellent screening test for neutrophils is simply the neutrophil count and peripheral smear, since most inherited defects in this arm of the immune system have readily identifiable numerical and/or morphologic findings. Also, myeloperoxidase staining can show myeloperoxidase deficiency, an AR trait which produces at most a mild immunodeficiency. But additionally, one can specifically look at chemotaxis, phagocytosis, and oxidative burst functions with various assays.

Answer 593

The nitroblue tetrazolium test.

Answer 594

It is a test used to screen for chronic granulomatous disease. Yellow NBT dye is added to neutrophils which are then stimulated. Cells capable of a normal oxidative burst will reduce the yellow NBT to a purple-blue formazan precipitate, and are said to be f+. Normal individuals will have nearly 100% f+ cells. An abnormal result, with perhaps less than 10% f+ dlls, is expected in CGD, in which deficiency of NADPH oxidase prevents the oxidative burst.

Answer 595

SLE causes low C3 and C4. MPGN causes low C3, but normal C4. Terminal complement deficiency is an inherited autosomal co-dominant condition with low C5, C6, C7, C8, C9 levels that causes susceptibility to infections by Neisseria. Properdin deficiency is an X-linked disorder that also causes susceptibility to neisserial infections. C1-inhibitor deficiency/hereditary angioedema will have low C4 with normal C1 and C3 levels.

Answer 596

Recurrent bacterial sinopulmonary infections due to staphylococci, streptococci, and hemophilus. Also, recalcitrant intestinal infection with G. lamblia. Opportunistic fungal and viral infections are not a particular problem.

Answer 597

Recurrent bacterial sinopulmonary infections due to staphylococci, streptococci, and hemophilus. Also, recalcitrant intestinal infection with G. lamblia. Opportunistic fungal and viral infections are not a particular problem.

Answer 598

Polio, hepatitis, and enteroviruses.

Answer 599

Most pts suffer from recurrent upper and lower respiratory tract infections (S. pneumonia, H. influenza, and Mycoplasma), intestinal bacterial overgrowth, and intestinal G. lamblia infection. The development of bronchiectasis is extremely common.

Answer 600

Selective IgA deficiency is the most common inherited immunodeficiency, affecting around 1 in 700 people. They are susceptible to recurrent respiratory and GI bacterial infections, a high incidence of autoimmunity, and are at risk for anaphylaxis due to transfusion of IgA-containing blood products.

Answer 601

They have high levels of specific IgE anti-staphylococcal antibody, exquisite susceptibility to staphylococcal infection, eosinophilia and eczema. These appear to result from a defect in granulocyte chemotaxis.

Answer 602

Pneumococci and other encapsulated bacteria, Pneumocystic carinii, and herpes virus. They also have a 12% incidence of fatal malignancies.

Answer 603

Chronic mucocutaneous candidiasis is a highly selective defect in T cell immunity to candidal infection that leads to chronic, recalcitrant, mucocutaneous candidal infection. Affected individuals often have associated endocrinopathies.

Answer 604

Typically as a fulminant and often fatal immune response to EBV infection. EBV infection induces a fulminant hemophagocytic syndrome, the development of a neoplastic B cell proliferation, and/or fulminant hepatic failure, concomitant with an inverted CD4:CD8 ratio in the peripheral blood.

Answer 605

Affected individuals often have a common variable immunodeficiency-like immune system defect, especially manifesting hypogammaglobulinemia with or without decreased B, T, or NK subsets. The median survival is about 10 years of age.

Answer 606

SH2D1A, which encodes for SH2 domain protein-containing protein 1A/SLAM-associated protein (SAP). XIAP (also known as BIRC4), which encodes for baculoviral IAP repeat-containing protein 4 (X-linked inhibitor of apoptosis; XIAP), respectively. The former is sometimes referred to as XLP1, and the latter XLP2.

Answer 607

SH2D1A: 83-97%. XIAP: 12%.

Answer 608

Molecular testing (sequence analysis or deletion/duplication analysis) for one of the causative genes: SH3D1A or XIAP. Also, SAP and XIAP protein expression by flow cytometry may be used as a screening test prior to molecular genetic testing of the SH2D1A or XIAP genes.

Answer 609

CGD is caused by mutation of one of five genes that encode the subunits of phagocyte NADPH oxidase: biallelic mutations in CYBA, NCF1, NCF2, and NCF4 cause autosomal recessive CGD; mutation of CYBB causes X-linked CGD.

Answer 610

Is it almost never seen. CGD is characterized by chronic suppurative infections due to bacteria and fungi that are catalase positive, especially Staphylococci, Enterobacter, and Aspergillus.

Answer 611

Most cervical adenocarcinomas are HPV related. HPV 16 and 18 are detected with equal prevalence in most subtypes, except in endometrioid and well-differentiated villoglandular adenocarcinoma where HPV 16 is the predominant types, and minimal deviation adenocarcinoma and mutinous adenocarcinoma with gastric phenotype which seem to be HPV unrelated.

Answer 612

Deficiency of classical pathway components (C1q, C2, C4) lead to autoimmune phenomena such as lupus. Deficiency of C2 and C3 lead to recurrent infections with gram-positive encapsulated organisms. Deficiency of membrane attack complex components (C5-C9) leads to recurrent serious systemic infections, especially due to N. meningitidis and N. gonorrhea.

Answer 613

SLE, other autoimmune diseases (Sjogren syndrome, scleroderma, RA), multiple sclerosis, infections, malignancies, and fibromyalgia.

Answer 614

Cold agglutinins are IgM antibodies directed against I or i antigens on RBCs. In cold agglutinin disease, they are monoclonal IgM kappa antibodies. In infectious mono, they are anti-i antibodies. In Mycoplasma pneumonia, they are anti-I antibodies.

Answer 615

Mycoplasma pneumonia is associated with anti-I cold agglutinin. Titers are found in 50% of infected individuals, peaking at 14 to 21 days.

Answer 616

The presence of any two of the following bands is a positive result: p24, gp41, and gp120/160. Distinguishing the gp120 band from the gp 160 band is often very difficult, and these 2 glycoproteins can be considered as one reactant for purposes of interpreting WB test results.

Answer 617

p24 is capsid protein/viral core protein encoded by gag. gp41 is transmembrane envelope glycoprotein encoded by env. gp160 is viral envelope precursor encoded by env. gp120 is viral envelope protein that binds to CD4 encoded by env.

Answer 618

RFs are IgM antibodies directed against the Fc fragment of IgG. RF may be "falsely" positive in a multitude of conditions including SBE, syphilis, infectious mononucleosis, and many rheumatologic diseases.

Answer 619

Cryoglobulins may be present in Waldenstrom macroglobulinemia, myeloma, CLL, SLE, CAH, and viral infections.

Answer 620

M1, M2, and M7 are on inner mitochondrial membranes, while M3, M4, M5, M6, M8, and M9 are on outer mitochondrial membranes. Anti-M1: syphilis. Anti-M2, anti-M4, anti-M8, anti-M9: primary biliary cirrhosis (anti-M2 is a specific marker for the diagnosis of PBC). Anti-M3: phenopyrazon-induced pseudolupus syndrome. Anti-M5: undefined collagen diseases. Anti-M6: iproniazid-induced hepatitis. Anti-M7: cardiomyopathy.

Answer 621

Sarcoidosis. ACE is nearly always elevated in active sarcoidosis. Inactive sarcoidosis is associated with normal levels of ACE.

Answer 622

Primary biliary cirrhosis, Gaucher disease, and leprosy. All of these have in common the formation of granulomas; however, most other granulomatous diseases are not associated with an elevated ACE.

Answer 623

Coxsackie B virus infection - development of IDDM. HBV infection - polyarteritis nodosum. K. pneumoniae infection - onset of ankylosing spondylitis. Aldomet - WAIHA. Penicillamine - systemic vasculitis. Procainamide, hydralazine, and isoniazid - drug-induced SLE.

Answer 624

EBV, CMV, Adenovirus, HIV, HHV-6.

Answer 625

The Enterobacteriaceae is a large family of Gram-negative bacteria that includes, along with many harmless symbionts, many of the more familiar pathogens, such as Salmonella, Escherichia coli, Yersinia pestis, Klebsiella and Shigella. Other disease-causing bacteria in this family include Proteus, Enterobacter, Serratia, and Citrobacter. Members of the Enterobacteriaceae are trivially referred to as enterobacteria or enterics.

Answer 626

Although there are a few exceptions, all Enterobacteriaceae are oxidase negative, reduce nitrates, and ferment glucose with acid production.

Answer 627

Virulent strains of M. tuberculosis form microscopic "serpentine cords" in which AFB are arranged in parallel chains. The phenomenon is purely in vitro and is seen much better in liquid media as compared to solid media. Cord formation is correlated with virulence. A "cord factor" (trehalose-6,6'-dimycolate) has been extracted from virulent bacilli. This factor inhibits migration of leukocytes, causes chronic granulomas, and can serve as an immunologic "adjuvant". However, "pseudocording"/loose aggregates and true cords have been seen with other Mycobacterial species as well.

Answer 628

It binds avidly to pulmonary surfactant.

Answer 629

A. fumigatus is green on front and white on back. A. flavus is yellow on front and white on back. A. niger is black on front and white on back.

Answer 630

A. fumigatus has a flask-shaped vesicle at the end of the stalk, a single row of phialides (uniseriate) that is bunched closer to the end of the vesicle, and the spores are pointed away from the stalk. A. flavus has a double row of phialides (biseriate) and the phialides surround the vesicle on all sides. A. niger has densely black conidia.

Answer 631

Direct microscopy (KOH preps or histology), because cultures are often negative (even in specimens containing visible fungal forms) and there are no reliable serologic tests for Ab or Ag, and no DNA tests at this time.

Answer 632

The yeast is grown in serum for 2 hrs, then examined for germ tube formation.

Answer 633

Cryptococcus will look slightly spaced out because of the presence of the capsule, but C. glabrata will be tightly packed together.

Answer 634

C. neoformans var. neoformans, and C. neoformans var. gattii. While the former is associated with pigeon droppings and soil, the latter is associated with Eucalyptus trees in Australia and Southern california (but human cases are seen in British Columbia and the Pacific Northwest).

Answer 635

30 C: fluffy white mold; tuberculated macroconidia (spiny large spores). 37 C: small, rough (coral-like) dry colony; 2-4 um yeasts with narrow necked budding.

Answer 636

Leishmania has discrete organisms with a nucleus and kinetoplast bound by a membrane; PAS negative. Histoplasma has a more amorphous look, some (but not all) are budding; PAS positive.

Answer 637

Very fluffy white mold on the plate. Hyphae are thick-walled and barrel-shaped with gaps between the barrels.

Answer 638

The colony has a diffusible orange pigment. The conidia look like Aspergillus without the flask-shaped vesicle. The yeasts are oval and have a cross-wall in each cell.

Answer 639

Mollaret's meningitis is a form of recurrent benign aseptic/lymphocytic meningitis, an uncommon illness characterized by greater than three episodes of fever and meningismus lasting two to five days, followed by spontaneous resolution. The most common etiologic agent in Mollaret's meningitis is HSV, especially HSV-2, although some patients do not have evidence of genital lesions at the time of presentation. Also, noninfectious etiologies for Mollaret's meningitis have also been proposed (intracranial epidermoid cyst or other cystic abnormalities in the brain with intermittent leakage causing meningeal irritation).

Answer 640

The most common etiologic agent in Mollaret's meningitis is HSV, especially HSV-2, although some patients do not have evidence of genital lesions at the time of presentation. Also, noninfectious etiologies for Mollaret's meningitis have also been proposed (intracranial epidermoid cyst or other cystic abnormalities in the brain with intermittent leakage causing meningeal irritation).

Answer 641

Cytologic findings are nonspecific, but there is often a markedly increased cellularity with pleocytosis, and marked predominance of monocytes. So-called "Mollaret cells," monocytes with deep nuclear clefts that impart a footprint-like appearance to the nucleus, are seen within the first 24 hours of the onset of symptoms. They are characteristic of but not specific for MM; they can be seen in other diseases like sarcoidois and Behcet disease. The background shows mostly small mature lymphocytes, but plasma cells and neutrophils can be seen as well.

Answer 642

Oxalic acid is a fermentation by-product of Aspergillus, and the precipitation of calcium oxalate crystals in alkaline tissue environments infected by the fungus is a recognized phenomenon. The crystals are themselves potent agents of tissue destruction, causing extensive necrosis. Oxalate deposition is most commonly associated with A. niger, but it has been observed in association with other Aspergillus species, including A. fumigatus and A. flavus. Visualization of oxalate crystals in respiratory tract cytological specimens has been described as a reliable marker for the presence of Aspergillus infection and may precede the appearance of positive fungal culture results or radiographic identification of an aspergilloma by 1 year. The typical appearance of calcium oxalate crystals is that of birefringent needlelike crystals in rosette, wheat-sheaf, or fanlike arrangements; they are nonstaining and difficult to identify by ordinary light microscopy. Of greatest diagnostic value is the observation of both oxalate crystals and typical fungal elements in a single specimen.

Answer 643

A false-positive test. An HIV-1 primer site mutation causing failure of PCR amplification (some methods address this concern by interrogating multiple gene targets). HIV-2 infection. Use of an insensitive viral load assay (some HIV-1 quantitative methods are unable to accurately distinguish the presence of absence of HIV-1 RNA below the limit of detection; with this type of assay, a result of less than 75 copies/mL could represent either no HIV-1 RNA or less than 75 copies/mL). An elite controller AKA elite suppressor (these patients develop Ab to HIV-1 but have extremely low level or undetectable viral loads (less than 50 copies/mL); they are asymptomatic and have HIV-1 control that is similar to that of those taking ART).

Answer 644

Pseudokoilocytes can be seen in conditions such as inflammation (Trichomonas and Chlamydia), pregnancy (navicular cells), androgenic effect, and immature squamous metaplasia.

Answer 645

HPV is a nonencapsulated double-stranded DNA virus. Integration of viral genetic material into the host genome is the critical event in malignant transformation of the cell, which results in disruption of the viral genome E1-E2 region. Disruption of the E2 gene causes overexpression of E6 and E7 genes. The integration sites in the host genome as random.

Answer 646

Malaria risk.

Answer 647

Ulcerative colitis often exhibits contiguous involvement of the colon and involves the rectum whereas C. difficile colitis can be discontiguous and may spare the rectum. In the setting of ischemia, secondary infections may complicate the picture. The presence of pseudomembranes and inflammation with submucosal extension can be seen in both C. difficile colitis and ischemic colitis. In the later stages of ischemic colitis, fibrosis of the lamina propria and hemosiderin-laden macrophages are important diagnostic clues that are not present in pseudomembranous colitis

Answer 648

The cyst wall is composed of a laminated membrane lined by a germinal layer. The laminated layer is no more than 1 mm thick and acellular. The germinal layer is 10-25 um thick and contains nuclei but may be too degenerated to be seen clearly. Scolices develop from the germinal layer. They contain calcareous bodies which can be seen free floating in the degenerated cyst contents.

Answer 649

S. mansoni and S. japonicum eggs.

Answer 650

T. brucei.

Answer 651

In lymphatic filariasis, the adults cause more problems; they live in lymph nodes and cause obstruction. The juveniles (microfilaria) are in blood and cause less problems. In onchocerciasis, the juveniles (microfilaria) cause more problems; they migrate through skin and soft tissues. The adults stay put in subcutaneous nodules.

Answer 652

W. bancrofti has a mosquito vector that likes to bite 9 PM to 3 AM. B. malayi has a mosquito vector that usually bites in the evening. L. loa has a deerfly vector that bites during the daytime.

Answer 653

W. bancrofti: in blood; sheathed, nuclei stop short of the end of the tail. B. malayi: in blood; sheathed; 2 small nuclei in the tail. L. loa: in blood; sheathed; nuclei continue to the end of the tail. O. volvulus: in skin; unsheathed.

Answer 654

Desmin, actin, and cytokeratin.

Answer 655

Anisakis simplex is a nematode present in fish throughout the world. Histologically, Anisakis larvae have distinctive Y-shaped lateral cords.

Answer 656

Only certain types of H. pylori are carcinogenic and need environmental and host factors to result in carcinoma.

Answer 657

Enterobius and Schistosoma mansoni. But the latter has a large spine so they can be distinguished easily.

Answer 658

The eggs become infective after 4-6 hrs, and remain infective for up to a week in cool moist conditions. The eggs can be infective by ingestion or inhalation.

Answer 659

Eggs are deposited from human feces to soil where, after two to three weeks, they become embryonated and enter the “infective” stage.

Answer 660

The unfertilized eggs are elongated and lack the thick shell of the fertilized egg. Fertile eggs are 55-75 um long and by 35-50 um wide, with a thick transparent shell and a ruffled ("like bark") outer layer.

Answer 661

Necator americanus and Ancylostoma duodenale.

Answer 662

The eggs cannot be speciated.

Answer 663

Strongyloides stercoralis.

Answer 664

Then you have to distinguish hookworm larvae from Strongyloides larvae, and they look similar. If you do need to distinguish them: hookworm larvae have a long buccal canal and no genital primordium, while Strongyloides larvae a short buccal canal and a prominent genital primordium.

Answer 665

Phylum Platyhelminthes (flatworms).

Answer 666

The trematodes.

Answer 667

Both are 26-30 um long by by 15-17 um wide, with a prominent wide operculum with flanges. They can be differentiated by the presence or absence of an aboperculum: Chlornorchis has an abopercular spine, while Opisthorchis does not. But it's not clinically important to distinguish them.

Answer 668

Fasciolopsis is clinically more benign, because it lives attached to small intestine mucosa. Fasciola, on the other hand, lives in the bile ducts, causing biliary obstruction and fibrosis, and eventually invading liver parenchyma.

Answer 669

130-159 um long, with a small operculum that is hard to visualize but pressing the coverslip can cause the operculum to pop open, making it easier to see.

Answer 670

Size. Chlonorchis/Opisthorchis is 26-30 um long. Paragonimus is 68-118 um long.

Answer 671

30-45 um in diameter, radial striations, hooklets visible in the middle.

Answer 672

The H. nana eggs are 30-40 by 40-60 um and have polar filaments between the outer shell and the central zygote with hooklets. The H. diminuta eggs are 70-86 by 60-80 um and have a striated outer wall and a lucent space in between the wall and the central zygote with hooklets.

Answer 673

All produce pyoverdin. P. aeruginosa also produces pyocyanin.

Answer 674

Only pyoverdin pigment fluoresces under UV light.

Answer 675

C. jejuni.

Answer 676

H. influenzae: +/+. H. parainfluenzae: -/+. H. haemolyticus: +/+. H. parahaemolyticus: -/+. H. aphrophilus: -/-. H. paraphrophilus: -/+. H. ducreyi: +/-.

Answer 677

Abscesses containing nuclear dust and neutrophils. Bacteria are difficult to see, even with special stains such as Giemsa or Gram. Histiocytes surround the abscesses and are also seen in the walls of bronchi filled with pus. Venous thrombosis is common.

Answer 678

Smears of blood or bone marrow specimens stained with Wright or Giemsa reagents show Erlichia organisms as round or oval violet bodies, about 1 um in diameter, in the cytoplasm of neutrophils, lymphocytes, monocytes, and macrophages. Clusters of organisms (morulae) can be seen. The bone marrow usually shows erythrophagocytosis and a decrease in myeloid cells and megakaryocytes. In tissue sections, the organism is best seen with Brown-Hopps stain.

Answer 679

Silver stains, such as Steiner, Dieterle, and Warthin-Starry.

Answer 680

Both. It is at least as sensitive as GMS staining, less technically demanding to perform, and, in most cases, much easier to evaluate.

Answer 681

True. Although cytomegalic changes are generally easily identified, they may be obscured by inflammation, and in some settings such as AIDS, not be well developed, in which case IHC or ISH improves detection of CMV infection.

Answer 682

M (major), O (outlier), and N (nonmajor and nonoutlier).

Answer 683

True. Regression models have shown that HIV-1 RNA viral load alone explains half of the variability in prediction of the onset of AIDS and death.

Answer 684

The 4th generation EIA tests simultaneously detect both p24 antigen and HIV-1 antibody, while the 3rd generation EIA tests detect antibody only.

Answer 685

>1,000 copies/mL.

Answer 686

Genotypic resistance testing and phenotypic resistance testing.

Answer 687

Portions of the RT and protease (PR) genes, which correspond to regions with mutations induced in response to therapy with NRTIs, NNRTIs, and PIs. Typically for ART-naïve individuals, sequencing of these regions is adequate to detect the important mutations.

Answer 688

CT: cryptic plasmid, MOMP gene, unspecified "genomic" target in some FDA-approved assays, rRNA. NG: cytosine DNA methyltransferase, pilin inverting protein gene, Opa gene, repeat sequences, rRNA.

Answer 689

Hospital-acquired: type II. Community-acquired: type IV.

Answer 690

PBP2A AKA PBP2' (Penicillin binding protein 2A). This protein alters binding of beta-lactams.

Answer 691

The mecA gene codes for penicillin binding protein 2A, the mecI gene codes for a repressor protein (represses mecA), and the mecR1 gene for a β-lactam-sensing The mecA gene codes for penicillin binding protein 2A (causes altered binding of beta-lactams and confers resistance to them), the mecI gene codes for a repressor protein (represses mecA transcription under conditions without beta-lactams in the environment), and the mecR1 gene for a β-lactam-sensing transmembrane signaling protein (mecR1 is a sensor-inducer of mecA - transcription of mecA is induced by beta-lactams when detected by the mecR1 protein product). signaling protein (mecR1 is induced by beta-lactams).

Answer 692

Mutations in UL97 viral protein kinase/phosphotransferase gene are associated with gancyclovir resistance. Mutations in UL54 viral DNA polymerase gene are associated with resistance to cidofovir and foscarnet.

Answer 693

Influenza A infects humans, pigs, and birds. Influenza B only infects humans.

Answer 694

Influenza A cases the most severe illness, influenza B is not as severe as influenza A, and influenza C causes the least severe illness.

Answer 695

Influenza A changes by antigenic drift and antigenic shift. Influenza B changes by antigenic drift only.

Answer 696

The NA (neuraminidase) gene.

Answer 697

A precore mutant is a variety of hepatitis B virus that does not produce hepatitis B virus e antigen (HBeAg). The G1764A and A1762T mutations are usually responsible for the decreased preCore (PC) mRNA synthesis. The G1896A mutation is the most prevalent and produces a translation stop codon at amino acid position 28 in the HBeAg sequence, with inhibition of HBeAg synthesis. Precore and core mutant HBV is associated with fulminant hepatitis and increased risk of HCC.

Answer 698

UL23, which encodes a viral thymidine kinase. Nucleoside analogues, such as acyclovir, are selectively phosphorylated to a monophosphate derivative in infected cells by the virus-encoded thymidine kinase (TK). The affinity of ACV for HSV-TK is ~200 times greater than for human TK. Viral mutations conferring resistance to ACV have been found most in the UL23 gene, which encodes the activating/phosphorylating TK enzyme.

Answer 699

Responsible for resistance phenomena are mutations in the CMV phosphotransferase gene (UL97) and the polymerase gene (UL54). Most frequently, mutations in the UL97 gene are associated with resistance to gancyclovir. Resistance against gancyclovir, foscarnet, and cidofovir is associated to mutations in the UL54 gene. The manifestation of multidrug resistance is mostly associated with combined UL97/UL54 mutations. Normally, mutations in the UL97 gene occur initially followed by UL54 mutation after therapy switch. The appearance of UL54 mutation alone without any detection of UL97 mutation is rare.

Answer 700

Sequences in the 5' non-translated region. The 5' NTR is the most highly conserved region for all members of the genus and is involved in viral protein translation.

Answer 701

The gradient of conserved sequences for HCV is: 5'UTR > core > NS5B (polymerase). The most conserved areas have the best chance of amplification and less chance of under-quantification so the 5'UTR is used for viral load. The less conserved areas give better genotype resolution so core or NS5B is used for genotyping. Using the 5'UTR for genotyping may not distinguish GT1a from GT1b, and GT1 vs some GT6.

Answer 702

The HCV protease (NS3/4 part of the genome) (protease inhibitors). The HCV polymerase (NS5B part of the genome) (nucleoside/nucleotide & nonnucleoside inhibitors).

Answer 703

Shorter therapy: genotypes 2 and 3 (24 weeks). Longer therapy: genotypes 1, 4, 5, and 6 (48 weeks).

Answer 704

The 2 subtypes have different codon usage. GT1b requires 2 nucleotide changes in the arginine codon for the mutation, while GT1a uses a different codon requiring only 1 change.

Answer 705

The IL28B SNP status. For the rs12979860 SNP, genotype CC is favorable while CT and TT are unfavorable. For the rs8099917 SNP, TT is favorable while TG and GG are unfavorable. The favorable genotypes have a higher chance of spontaneous clearance of the HCV infection, and higher sustained virology response to treatment. The unfavorable genotypes have a higher risk of HCV chronicity, and increased risk of treatment failure. These effects (positive and negative) are most pronounced in HCV genotype 1 .

Answer 706

E1 and E2. This is important to know because if you want an assay to detect integrated forms as well you can't target this region.

Answer 707

For detection, the 5'UTR. For typing, the VP1-3 regions (sequence based). However, EV is an RNA virus and the genome is still variable, so there are limited target sites and you still risk non-detection.

Answer 708

The insertion sequence IS481 has different copy numbers among species: B. pertussis 50‐100+copies/cell, B. holmesii 8‐10 copies/cell, and some strains of B. bronchiseptica 1 copy/cell, and some labs use this target for pertussis detection. The insertion sequence IS1001 is present in B. parapertussis and B. holmesii so can be used for parapertussis detection. The targets that are specific for B. pertussis include: Promoter region (PTp1 and PTp2); DNA region upstream of the porin gene; Repeated insertion sequences (IS); Pertussis toxin promoter (ptxA-Pr) (but the pertussis toxin operon is present in B. pertussis, B. parapertussis, and B. bronchiseptica); ACT gene; BP3385, BP283, and BP485.

Answer 709

tcdA - enterotoxin. tcdB - cytotoxin. tcdC - negative regulator. tcdD - positive regulator. tcdE - holin-like protein.

Microbiology Flashcards

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