Haemoflagellates Flashcards

Question

What is this? What is the differential Diagnosis?

Answer 1

* Cutaneous Leishmaniasis * CL - Differential diagnosis * tropical and traumatic ulcerative lesions * foreign-body reactions * superinfected insect bites * myiasis * impetigo * fungal and mycobacterial infections, * sarcoidosis * neoplasms.

Answer 2

* A is a T. bruceii trypanosome in the CSF, adjacent to a number of blood cells * B is a morular cell of Mott - a plasma cells with globular cytoplasmic inclusions containing immunoblobulin proteins * CSF * should be examined within 20 min * direct micro for trypanosomes * WCC \> 5 WBCs/mm³indicates CSF involvement requiring treatment * elevated protein, IGM * centrifugation * presence of IgM and neopterin are indicators of CNS involvement * morula cells of Mott are rarely seen

Answer 3

* it is a Card Agglutination Test for Tryponosomes (CATT test) * useful for population screening for HAT in Tb gambiense but not rhodesiense. * in Gambiense screening should be done on basis of cervical lymphadenopathy aspirate if this is apparent * otherwise CATT. positives should be repeated on diluted blood sample and investigated if this is possible * in Rodesiense, CATT is of no use. Population screening is done on the basis of risk and the presence of symptoms.

Answer 4

* provided free of charge to endemic countries through WHO partnership * Sanofi-aventis: pentamidine, melarsoprol, eflornithine * Bayer: suramin

Answer 5

* Gambiense * Stage 1 * pentamidine: may cause pancreatitis, diabetes * or Suramin: nephrotoxicity and hypersensitivity reactions * Stage 2 * Eflornithine (DMFO or difluromethornithine) * or Malarsoprol (MelB) + prednisolone * or (recently introduced) NECT - nifurtimox + ethornithine Combination Therapy: effective, better side effect profile. * Rhodesiense * Stage 1 * Suramin (does not cross BBB) * Stage 2 * Melarsoprol (?+ prednisolol): arsenical may cause hypersensitivity encephalopathy in 15%, of which 50% mortality * exfoliative dermatitis (Stevens Johnson) * _{table below from Lancet 2010; 375:148-159}

Answer 6

* Pentamidine: 1-10% * Melarsoprol: 20-30% * Gambiense: use either melarsoprol (MelB) or eflornithine, whichever not used previously; or nifurtimox; or combination nifurtimox and MelB. * Rhodesiense: melarsoprol. If further relapse consider **eflornithine plus melarsoprol** **(**rct shows more effective, easier to use

Answer 7

* All should have f/u LP's for 2 years * Gambiense: LP q 6 months * Rhodesiense: LP q 3 mo x 1 yr the q 6 mo * If initially Stage 1, but f/u: 1. csf 6-19 WBC's/mm³ ⇒ rpt LP 1-2 mo 2. .csf \> 20 wbc/mm³ ⇒ then tx as stage 2 * If initiallly Stage 2, CSF WCC at f/u is more important than actual value

Answer 8

* Case detection & treatment: * low prevalence - passive surveillance * suspect high risk areas or epidemics: spot or regular surveillance using mobile teams * Vector control: * any situation: traps, insecticides, education * epidemic/priority development area: traps, insecticides, education, spraying

Answer 9

1. Triatomine bug takes a blood meal and passes metacyclic trypanomastigote in feces, enters human via bite wound or conjunctiva 2. trypanomastigote penetrates various cells at bite wound; inside cells transform into amastigotes 3. amastigotes multiply by binary fission in cells of infected tissues 4. intracellular amistigotes transform into trypanomastigotes, then burst out of cell into bloodstream; some infect other cells and transform into intracellular amastigotes and so on in intrahuman infective cycle with ongoing tissue damage. 5. triatomine bug takes a blood meal and ingests trypanomastigotes 6. epimastigotes in midgut 7. multiply by binary fission 8. metacyclic trypomastigotes in hindgut and so on ...

Answer 10

* has been associated with outbreaks of disease in new areas * a high proportion of sylvatic animals and domestic dogs are infected * sylvatic bugs enter houses and bugs or bug feces finds its way into food and fruit juices, also among cane that is pulped with infected bugs on it * orally transmitted disease has a higher infectious dose and is associated with greater morbidity and mortality

Answer 11

* approximately 10 million in endemic areas, primarily South and Central America, Mexico, southern US * cases elsewhere associated with immigration * 325,000 cases in Europe * 100,000 cases in Europe, most in Spain

Answer 12

* Acute * Incubation 6-10 d post bug exposure * 10-20 d post transfusion * mostly mild sx, only 1-2% diagnosed * **mostly \<15 yr age** * in cases of extremely high inoculum with eg. drinking contaminated sugar cane or juice, may get acute infection suff severe to kill * Indeterminate * life-long, from 8-10 wk following acute phase * assymptomatic for 10-30 yr * Chronic * 10-40% of total population infected * Cardiac/GI tract/other

Answer 13

* mean age: 38 yrs * rural areas, or at periphery of towns * low educational level * manual labour * seek care due to +ve serology, abnormal ecg or symptoms (cardiac or GI)

Answer 14

* disease duration * male sex * intense physical activity * parasite strain * exposure to reinfection * genetic background, black? * age * severity of acute infection * nutritional status * alcoholism * comorbidities

Answer 15

* local multiplication in macrophages at site of innoculation * tissue dissemination - prediliction for muscle ⇒ amistigotes in 'pseudocysts' ⇒ destruction of Purkinje fibres + ganglia in conducting system of heart; destruction of autonomic ganglia of gut tissue * organ localisation: amastigotes become scarce * ?autoimmune mechanisms involved in continued muscle deterioration?

Answer 16

* often mild/assymptomatic * local redness + swlling + nodes * Chagoma at bite site * Romana's sign - periorbital swelling * fever, nodes, hepatosplenomegaly * tachycardia, peripheral edema * +/- anemia; +/- morbilliform rash * +/- meningoencephalitis; +/- myocarditis

Answer 17

* Cardiovascular: cardiomyopathy leading to * arrhythmias, thrombosis, emboli, cardiac failure (esp Rt sided) * megaesophagus often assoicated with parotid hypertrophy ('cat face') * megacolon * other, eg neurological, endocrine

Answer 18

* an aneurysm associated with circumscribed thinning of the apical region of left ventricle * myocarditis is frequently associated with the acute stage, usually returns to normal without treatment * after assymptomatic period of 10-13 yrs, chronic Chagas heart disease, characterized by myocardial fibrosis is seen in high percentage of carriers of T. cruzi

Answer 19

* Chagas esophagopathy * a) anectasic * b)-d) mild to severe megaesophagus * *Trypanosoma cruzi*

Answer 20

* parotid hypertrophy conferring "feline facies" to patient with Chagas Disease * megaesophagus

Answer 21

* A) megaesophagus and megastomach * B) megaseophagus and megaduodenum * C) megabulp and megajejunum * D) megacolon * All GI complications of chronic Chagas disease * mainly Brasil, ascribed to different pathogenic properties of regional strains of T. cruzi

Answer 22

* Megacolon caused by degeneration of Auerbach and Meissner plexuses in Chagas Disease

Answer 23

* immunosuppression produces a "recrudescence" of a previously stable chronic infection that may be clinically similar to acute Chagas * post-transplant patients may develop skin lesions resembling cellulitis that may necrose * HIV +ve: meningoencephalitis is common * subcortical brain abscesses similar radiologically to cerebral toxo * (but toxo commoner in thalamus and basal ganglia) * cardiac failure and arrhythmias also common

Answer 24

* **peripheral blood identification by microscopy** * ****for diagnosis in Acute Chagas * **serology** * ****very important in Chagas because trypanosomes only readily identifiable in blood in Acute phase. * rapid Ab tests available, important for blood donor screening but cross-reactions with Leishmania, T. rangeli (non-pathogenic trypanasome) * Xenodiagnosis * PCR * culture * animal inoculation

Answer 25

* *T. cruzi* in Geimsa stained blood film * C-shaped trepanomastigote, note darkly staining nucleus and kinetoplast, flagellum

Answer 26

* Serological methods important as T. cruzi trypomastigotes only found in blood during early acute phase of infection. * Antibodies can be demonstrated 1 month after infection. * Immune Fluorescent AB/Enzyme-linked Immunosorbent Assay & many rapid tests now available, important for blood donor screening. * Rapid Ab test - 'Stat Pack' * Cross reaction occurs with *Leishmania* and *T. rangeli* (non-pathogenic trypanosome transmitted by *Rhodnius* bugs in Latin America.

Answer 27

* *T. rangeli* is a non-pathogenic typanosome transmitted by *Rhodnius* bugs in Latin America, which is also a vector of Chagas. * Serology for *T. cruzi* cross reacts with *T. rangeli* (also with Leishmaniasis)

Answer 28

* a little boy with Romana's sign undergoing xenodiagnosis * as Romana's sign occurs with Acute Chagas, the blood should bear trypanomastigotes and infection shoud stil be detectable at this stage by direct microscopy

Answer 29

* Acute Chagas * nitroderivatives: * Nifurtimox or Benznidazole * Adverse effects highly dose dependent: * hypersensitivity (rash, fever, generalized edema, lymphadenopathy, joint and muscle pain.) * Bone marrow depression * peripheral polyneuropathy * treats symptoms of Acute Chagas, but does not decrease parasitemia and has little effect on course of Chronic Chagas * poroconazole * not validated by RCT

Answer 30

* Pires L., *et al*, Am J Trop Med Hyg. 2000 Sep-Oct;63(3-4):111-8. * randomized 10 yr f/u of 91 chronic Chagas pts and 41 controls * "These results show that nitroderivative therapy for T. cruzi infections is unsatisfactory and cannot be recommended since it fails to eradicate the parasite or change the progression of heart disease in chronic Chagas patients." * other concerns: * severe side effects lead to non-compliance in pts older than 20 yrs * rx may release parasitemia due to drug-induced immunosuppression and ecological pressure for parasite resistance, probably through selection of highly virulent clone * lack of clinical findings showing benefit of treatment * treatment may be oncogenic: high incidence of malignant lymphoproliferative tumours in transplanted Chagas pts vs non-Chagas transplant controls & such tumours can be produced experimentally in animals with benznidazole * treatment with nitroderivatives does not eradicate infection or abrogate humoral or cell-mediated immune responses associated with autoimmunity and pathogenesis of typical Chagas heart complications

Answer 31

* Symptomatic rx or surgery for megabowel, depending on severity and responsiveness * Symptomatic treatment for cardiac complications * nb Dr. Wilson, Recife, 40 pacemakers per week

Answer 32

* House interior insecticide spraying * screening blood donors for t. cruzi * improving housing * Food hygeine

Answer 33

* 90% cases from Bangladesh, India, Nepal, Sudan, Ethiopia & Brazil * but note also southern Europe * 350 million at risk of infection * 1.5 -2 million cases/year * 75% cases are Cutaneous Leishmaniasis * Visceral Leishmaniasis causes

Answer 34

* Incubation:1-2mths-\>10yrs * Asymptomatic–subclin–acute–subacute-chronic * Onset usually insidious, low grade fever, progressive splenomegaly, hepatomegaly, anaemia, wasting, pigmentation, nodes, intercurrent infections. * Postkala-azar dermal leishmaniasis (PKDL )after drug treatment

Answer 35

* Incubation: 1-2 mnths ⇒ 10 yrs * Clinical Spectrum: Assymptomatic-subclinical-acute-chronic * Onset usually insidious, low grade fever, progressive splenomegaly, hepatomegaly, anemia, wasting, pigmentation, nodes, intercurrent infections * sometimes abrupt onset with high swinging fever * Post kala-azar dermal leishmaniasis (PKDL)

Answer 36

* Massive splenomegaly DDx: * Hyper-reactive malaria splenomegaly (HMS) * Portal hypertension * Splenic hydatid cyst * lymphoma, leukemia, myelodysplasia * hemoglobinopathies, hemolytic anemias * glycogen storage and other metabolic diseases * Stills disease * amyloidosis

Answer 37

* any diseases included in the differential diagnosis of massive splenomegaly (attached image) plus: * Bacterial endocarditis, brucellosis * HIV, Infectious Monocleosis (IMN), CMV, Toxo * Leptospirosis, Relapsing fever * Trypanosomiasis * Schistosomiasis * Typhoid, Typhus * Tuberculosis * Syphilis * SLE, RA, other autoimmune diseases

Answer 38

* Measles, pneumonia, bacillary dysentery, TB, Brucellosis, HIV * Malnutrition * Malabsorption * Bleeding * Nephritis * Uveitis * PKDL * Death: 0-50% treated; 85-90% untreated

Answer 39

* presence of anemia, leukopenia, thrombocytopenia * Serological: IFA (Immune Fluorescent Ab), ELISA, DAT, K39 Dipstick * these are all good tests with good sensitivity and specificity * because of regional variations, an RDT for one area eg rK39 may be excellent in one area (rK39) but not good elsewhere * Parasitological: (see image) * Aspirate from spleen, lymph node, marrow, liver or * buffy coat * Leismanin skin test NEGATIVE (only turns positive after curative treatment)

Answer 40

* *L. donovani* bodies (amastigotes) in a splenic aspirate * \>90% S & S * bone marrow, liver, lymph node

Answer 41

* because VL a chronic disease, Ab detection tests likely positive in most cases * Types * IFAT (+ve early; -ve 6-9 mo post cure) * ELISA: rk 39 Ag best * DAT * Dipstick (rk39)

Answer 42

* rK39 Dipstick for Antibody detection for Visceral Leishmaniasis * useful, but geographically very specific * i.e. in India sensitivity ~100%, specificity ~98% but poor in Sudan

Answer 43

* DAT-FD (Direct Agglutination Test using freeze dried Ag) best * Sens/Spec ~95% * Main advantage is it is applicable in all regions and for all VL species * Cost 1-2 Euro/test * Limitations: * need to do multiple dilutions * so takes a long time ~18 hrs * Remains positive long after 'cure'

Answer 44

* It is fast \<3 hr to process * Detects Ab (serum/blood on filter paper) * Single serum dilution at cut off 1:800 or 1:1600 * qualitative results similar to DAT * Uses freeze-dried Ag thus higher Ag stability, reproducability, specificity and sensitivity.

Answer 45

* serology detects assymptomatics * serology detects past infections * test remains positive after treatment * MAY BE NEGATIVE IN HIV-COINFECTED PTS. * (in which case Ag detection is useful)

Answer 46

* useful for diagnosis and monitoring response to treatment * K39 and K26 Ag detection in urine 96% sensitive and 100% specific in VL * Not detectable 3 wks after treatment * Latex agglutination test (KAtex; Kalon Biological, UK) * geographic variation in sensitivity (48-95% and specificity 82-00%. * high sensitivity in two studies of HIV co-infected pts during clinical episodes when parasite load was high * negative following satisfactory clinical response * may be helpful in monitoring effect of treatment and efficacy of treatment and relapses

Answer 47

* variants as per picture * process is likely auto-immune reaction to residual skin trypanosomes, possibly related to upregulation of interferon gamma and other cytokines in skin after treatment of VL * in Sudan most cases resolve spontaneously, only severe cases need treatment * in India all need treatment * (Lancet Infect Dis. 2003 Feb;3(2):87-98. Post-kala-azar dermal leishmaniasis. Zijlstra EE1, Musa AM, Khalil EA, el-Hassan IM, el-Hassan AM.) * also some suggestion pattern of UV exposure may influence pattern of PKDL

Answer 48

* capable of detecting infection with a single parasite * increasingly used for dx of VL and monitoring for relapse in HIV co-infected pts * high sensitivity (82-100% for bone marrow and 72-100% for per blood. * may be useful as test of cure * PCR based RDT's currently under development for field use.

Answer 49

* Pentavalent antimonials (SbV) * Sodium stilboglucamate ('SSG' or Pentostam) * Meglumine antimonoate (Glucantime) * nb widespread antimony resistance in Nepal, Bangladesh, India (but not Brazil or Sudan) * AmBisome - liposomal amphotericin B * Aminosidine (paromomycin) - alone or prefferably in combination with SSG (synergistic) * Pentamidine - ? 2nd line treatment * Oral miltefosine * Treat intercurrent infections, provide supportive care.

Answer 50

* Antimony resistance in Asia: India, Bangladesh, Nepal

Answer 51

* originally developed as oral neoplastic agent * first hightly effective **oral** rx for VL * 100 mg/day (or 2.5 mg/kg/d in children) x 4 wk ⇒\>95% cure * side effects: GI upset, rarely severe BUT * abortifacient, teratogenic ?decreased male fertility * Long half lif (2-3 wks) + narrow therapeutic index, therefore possible risk of developing resistance * therefore consider combination treatment

Answer 52

* Visceral Leishmaniasis * 15-20 mg/kg/day IM * may be used alone for 21 days or * **combination treatment** with SSG or pentamidine, allowing a shorter duration of treatment * MSF regimen: SSG + PM x 17 days

Answer 53

* Post Kala Azar Dermal Leishmaniasis (PKDL) * Bangladesh 18% within 2 yrs of Rx for VL * Sudan 50% within 6 months of Rx for VL * Increased risk with interrupted/short course SSG * Dx: Skin Biopsy; Buffy PCR (+ve in 40-75% of cases) * Rx: Miltefosine 95% cure rate; other anti-leish Rx

Answer 54

* Köbner phenomenon in PKDL * likely reflects autoimmune component related to upregulation of interferon gamma, interleukin 10 and other cytokines post tx of VL

Answer 55

* PKDL resembling lepromatous leprosy

Answer 56

* PKDL response to 2 month therapy with miltefosine

Answer 57

* recognized since 1986 * HIV & VL are mutually reinforcing: HIV increases susceptibility to VL and VL accelerates progression of HIV infection * increased risk of treatment failure for VL in HIV * reactivation of latent VL infection * VL spread more widely through Asia, Southern Europe, South America with expansion of HIV epidemic, some evidence of HIV and VL being spread particularly through IVDU (see attached map)

Answer 58

* 96 European pts (29-33 yrs) * Male 86% * Fever, hepatomegaly, splenomegaly, lymphadenopathy, pancytopenia, hypergammaglobulinemia common (70-90%) * Positive serology for VL in only 50% * Atypical clinical features: * dysphagia * cutaneous or mucocutaneous skin lesions * nodular or ulcerative lesions on tongue, esophagus, stomach, rectum, larynx, lungs * course variable from assymptomatic to rapidly progressive * 30% die during or within one month of treatment * mean survival 12 months * only 16% survive \> 3 yrs * relapses inevitable q 3-6 months * **HAART may delay onset/control relapses**

Answer 59

* Serology: ONLY 50% POSITIVE * Parasitological dx: * 50% in blood * 94% in bone marrow

Answer 60

* Toxicity of pentavalent antimony increased * outcome with meglumin antimonate v conventional amph B similar * relapse rates similar (30-40%) * possibilities for prevention of relapse: * monthly/fortnightly pentamidine/AmBisome * daily miltefosine

Answer 61

* leishmaniasis may be unmasked by HAART * VL, PKDL, cutaneous manifestations * may be associated with unusual sites of disease (eg. eye) * response to standard tx variable

Answer 62

* The pathogenesis of leishmaniasis in transplant patients via * reactivation * or de novo infection via * transfusion of leishmania-infected blood or * infected sandfly

Answer 63

1. Cutaneous Leishmaniasis (CL) 2. Diffuse Cutaneous Leishmaniasis (DCL) 3. Leishmaniasis Recidivans (LR) 4. Mucosal Leishmaniasis (ML) * 90% cases occur in Afghanistan, Algeria, Brazil, Pakistan, Peru, Saudi Arabia, Syria

Answer 64

* Giemsa staining of touch preparation of a cutaneous lesion showing presence of intracellular parasites inside macrophages

Answer 65

* Leishmaniaisis Recidivans (LR). * This is characterized by a relapse of cutaneous disease within the sites of previous healed CL lesions. * can occur decades after resolution of the primary lesions and often form within the edge of the previous scar. * The lesions in leishmaniasis recidivans (LR) are reminiscent of those in discoid lupus or lupoid leishmaniasis and require treatment often with dual therapy.

Answer 66

* Chiclero's ulcer caused by L. mexicana * Forest worker typically * Infection results in a single ulcerative lesion, most commonly involving the ear pinna, without a tendency for cutaneous metastasis, lymphatic or mucosal involvement. * The majority of cases of “Chiclero's ulcer” spontaneously re-epithelialize without treatment within 3–9 months.

Answer 67

* sporotrichoid lymphatic spread of cutaneous leishmaniasis * (due to L. major from Afghanistan)

Answer 68

* severe ulcerating cutaneous leishmaniasis lesion * (in pt co-infected with HIV) * Differential dx * tropical and traumatic ulcerative lesions * foreign body reactions * superinfected insect bites * myiasis * impetigo * fungal * mycobacterial infections * lupus vulgaris (cut tb) * buruli ulcer * sarcoidosis * neoplasms

Answer 69

* cutaneous leishmaniasis ulcer * dx by core biopsy edge of ulcer +/- scrape centre * impression smear ⇒ giemsa stain * histology * pcr * culture

Answer 70

* (Leishmania tropica) amastigotes from impression smear of a biopsy specimen from skin lesion * left: intact macrophage filled with amistigotes * right: amistigotes being freed from rupturing macrophage

Answer 71

* Leishmanin test or Montenegro test * Uses promastigote suspension as Ag (area and species specific) * Positive in most cases of CL and MCL (except some L. aethiopica and DCL) * Negative in VL but may become +ve after successful treatment * may be positive due to previous exposure

Answer 72

* Mucocutaneous leishmaniasis, "a dreaded complication of New World Cutaneous Leishmaniasis" * aka espundia, from latin for sponge * Most cases caused by *Vianna subgenus, esp L. braziliensis, L. panamensis, L. guyanensis* * Onset usually few years after resolution of original cutaneous lesion, may occur while primary lesion still present or even decades later * hematogenous or lymphatic spread from skin to nasopharyngeal mucosa (rarely urogenital) * nodule initially, then widespread destruction with chronic granulomatous destructive lesions, secondary bacterial infection * risk in endemic areas 1-10% within 1-5 yrs, possibly higher

Answer 73

* mucocutaneous leishmaniasis * ddx: * histoplasmosis * mucormycosis * leprosy * midline granuloma/lymphoma * neoplasms * rhinoscleroma - chronic granulomatous condition caused by *Klebsielly rhinoscleromatis* * sarcoidosis * syphilis * tertiary yaws * Wegener's granulomatosis

Answer 74

* adequate systemic treatment of CL is assumed (but not proven) to decrease already low risk (\<5%) of developing mucosal disease * ML harder to treat than CL and becomes increasingly difficult as it progresses * Currently best treatment options are: * pentavalent antimony drugs (cure rates about 75% for mild disease & 10-63% for more advanced disease) **OR** * conventional amphotericin B * with concomitant steroids if respiratory compromise develops

Answer 75

* Based on one unrandomized trial in Bolivia (Clin Infect Dis. 2007 Feb 1; 44(3):350-6) * oral miltefosine at least as effective as parenteral amphotericin B * cure rates approx. those of parenteral pentavalent antimony for mild and extensive disease in neighbouring Peru * less toxic than antimony and much less toxic than amph B * oral vs parenteral * trial suggests miltefosine should be TOC for mucosal disease in North and South America

Answer 76

* is patient at risk of mucosal leishmaniasis? * locationoflesion(s)(eg,ontheface) * number,size,evolution,persistence * other features (eg, nodular lymphangitis).

Answer 77

1. paromomycin ong (available in Israel) 2. intralesional antimony therapy 3. heat treatment, cryotherapy 4. Topical amphotericin B (*L. majorI)*

Answer 78

* generally for treatment (or no treatment) for rel benign, cosmetically unimportant lesions, esp if caused by *L. Major* (old world) or *L. mexicana* (new world) * Ketoconazole - modest activity against *L. mexicana* and *L (V) panamensis*; usefulness against *L. major* infection unclear. * Itraconazole - better tolerated than ketoconazole but may be less effective, at leasta against the *Viannia* subgenus. * Fluconazole (*L. major*) - po x 6 wk (NEJM 2002) * Miltefosine

Answer 79

* Parenteral treatment: * IV/IM antimony therapy prob still best option if optimal effectiveness important * short-course pentamidine (effective in Colombia, predominantly *Viannia* subgenus)

Answer 80

* Diffuse Cutaneous Leishmaniasis * Old World: *L. aethiopica -* Ethiopia, Kenya * New World: *L. mexicana, amazonensis, venezualiensis* * A single lesion gives rise to multiple soft, fleshy nodules or plaques * may be extensively depigmented * ulceration is rare because Cell Mediated Immunity is lacking to Leishmania Ags * Treatment of DCR: * Old World: SSG + aminosidine or Pentamidine (causes diabetes in 10%, pancreatitis) * New World: SSG

Answer 81

* leishmaniasis recidivans (caused by *L.tropica* in Kabul, Afghanistan) * found in Iran and Iraq * Chronic with waxing and waning for 20-40 years, characterized by central healing and scarring with active lesions around edge "lupoid leishmaniasis" - mimics lupus vulgaris * Organisms are scanty in lesion, so culture may be helpful * Tx: SSG (parenteral, intralesional), heat treatment.

Answer 82

* destroy sandfly habitats * eliminate/treat reservoirs for leishmania * avoid bites * residual insecticides * habitation improvement * also vaccines under development: * Leishmania antigens + sandfly salivary antigens * live attenuated *L. major* promastigote vaccine developed but risk of aggressive lesion or LR. has not progressed, remains experimental

Answer 83

* T. brucei rhodesiense: Glossina morsitans * T. brucei gambiense: Glossina palpalis A *Glossina morsitans* bit Aunt Betsey. Tsk, Tsk, tsetse.

Answer 84

* T. b. rhodesiense * animals **SOMETIMES** humans are the host * predominantly *Glossina morsitans* * Habitats primarily savanah

Answer 85

* Flies infected with *T. b. gambiense* are common in riverine sites * Likely fly would be *Glossina palpalis group* * Main host for *T. b. gambiense* is human and transmission is Human to Human * (However *G. palpalis* group feeds on riverine wildlife such as lizards and there is controversial speculation about animal reservoir for *T. b. gambiense*)

Answer 86

* *Glossina morsitans* * Initially using chemical cues such as CO2 and odours to locate their hosts. When they get closer they use visual cues, predominantly using blue colours. * riverine tsetse (*G. palpalis group)* less responsive to host odours because of restricted topography of riverine habitats.

Answer 87

* female produces single egg which develops into larva within her uterus * every nine days mother produces larvum which burrows into ground, where it pupates * adult fly emerges from the pupa after **about 30 days** * **50 days elapse between the emergence of one female fly and its progeny**

Answer 88

1. They have a slow reproductive strategy so only have to kill a few (~4%/day) to eliminate a population. 2. Only adults are vulnerable (hard to find the larvae and pupae underground) so need to kill them as they emerge from the ground. 3. Males and females rely on blood for growth and reproduction; they range widely seeking hosts (riverine tsetse ~300 m, savannah tsetse ~500 to 1000 m) ... so might kill them when they visit hosts but areas cleared of tsetse rapidly reinvaded.

Answer 89

* ground spraying long lasting insecticide such as DDT & deldrin killing tsetse as they rest on treated surfaces * insecticide lasts long enough for pupae to emerge * sequential aerosol spraying (endosulfan, deltamethrin) at night * rpt x 5 cycles by which time all flies will have emerged * insecticidal baits for animal hosts eg warthog, treat cattle * tsetse odour-baited traps

Answer 90

* important research by Casas-Sanchez and Acosta-Serrano 2016 demonstrating via mouse model that mice infected with *T.b.gambiense* and *T.b.rhodesiense* via *G. morsitans* developed significant skin populations of stumpy forms of tryps that resided in the skin and could give rise to Tsetse reinfection * this, together with other research demonstrating tryps in historical skin biopsies from assymtomatic people, has raised sig new questions that throw into doubt the WHO plan to eliminate HAT by 2020. * do skin tryps hide in skin and evade immune system * are tryps in human skin involved in transmission of ghat * are there assymptomatic carriers bearing skin tryps * is GHAT anthroponotic? * is there a previously unrecognized animal reservoir?

Answer 91

* Amastigotes are the tissue stage of Leishmania lifecycle and are seen in tissue taken for diagnostic testing (eg skin biopsy, bone marrow, splenic biopsy). Amastigotes of the various species of Leishmania are morphologically indistinguishable and are identified by molecular tests. The lifecycle stage of Leishmania that infects the human host is the promastigote – these transform into intracellular amastigotes, which are taken up by the sandfly vector.

Answer 92

* T. brucei on left, T. cruzi on right * motile blood stage forms primarily distinguished by size of kinetocyte, much more prominent in T. cruzi * T. cruzi forms C-shape * T. brucei has dividing forms present in blood * also both short stumpies and long slender forms * geographically distinct & different vectors * T. Cruzi South and Central America & transmitted by triatomine bugs * T. brucei Sub Saharan Africa and transmitted by Tsetse Fly

Answer 93

* T. cruzi treated with Nifurtimox or Benznidazole (poroconazole in trials) * T. brucei gambiense treated with (Stage 1) Pentamidine or Suramin; (Stage 2) eflornithine or melarsoprol or recently NECT (nifurtimox + eflornithine combination) * T. Brucei rhodesiense treated with (St. 1 ) Suramin; (St.2) Melarsoprolol

Answer 94

* Rx for disseminated * Sodium stibogluconate IV * Liposomal amphotericin * Pentamidine parenteral • Oral miltefosine * ? Length of secondary suppression

Answer 95

* There are two forms of Human African Trypanosomiasis (HAT). Rhodesian HAT caused by Trypanosoma brucei rhodesiense transmitted largely by savannah tsetse (Glossina). Gambian HAT caused by T. b. gambiense transmitted by riverine tsetse. Rhodesian HAT is a zoonosis found in East and Southern Africa, with wild hosts (buffalo, warthog, bushbuck) and livestock (cattle) acting as reservoir hosts. The progression of disease is acute with patients presenting symptoms in weeks and death occurring in months. Treatment of first and second stages of the disease is with suramin and malarsoprol respectively. Gambian HAT is an anthroponosis found in Central and West Africa. This is the chronic form of the disease with the neurological symptoms presenting ~18 months after initial infection and death typically occurring ~3 y post-infection. First and second stage treatment of the disease is with pentamidine and NECT (Nifurtimox- Eflornithine Combination Therapy) respectively. There are no vaccines or preventive drugs for these diseases, the disease is ultimately fatal if untreated.

Answer 96

* L. chagasi and L. amazonis are the chief causes of Leishmaniasis in the New World. * L. tropica is the chief cause of Old World disease. * L. infantum is the chief cause in the Mediterranean as far as China. * L. donovani predominates in India and East Africa.

Answer 97

* L. infantum (Med, Middle East, Central Asia, China) is a disease of dogs and humans. * L. donovani in India is a disease only of humans. In East Africa there may be a rodent reservoir. * In Europe and North America it is a zoonosis, found in dogs

Answer 98

* 1. acquired via bite of Triatomine bug 2. acquired via ingestion of food contaminated with triatomine insects or feces (eg fruit juice) or ingesting contaminated uncooked meat. (widespread mammalian zoonosis) 3. infected blood (but now widespread screening) 3. transplant recipients (ditto) 4. Congenital transmission. Unlike toxoplasma, Chagas can be transmitted placental through successive pregnancies. 5. IVDU

Answer 99

* **DAT on plasma or urine is reliable, sensitive and easy to carry out in a remote area**. A new reliable freeze-dried version (DAT-FD) with a sensitivity and specificity \>95% is now available for use in the field. * **The demonstration of amastigotes in splenic aspirate or bone marrow is probably the ideal way to prove the diagnosis.** Promastigotes are very temporary occupants of blood. * The fast agglutination test (FAST) that detects antibodies on filter paper gives accurate results in \<3 h and is used widely nowadays. * In India the K39 RDT is accurate, cheap and available. * These tests have replaced the largely insensitive fluorescent antibody test (FAT). * The Formol Gel Test (FGT) depends on a reversal of the albumin/globulin ratio in the blood, which occurs because of a raised plasma IgG, and simultaneous albuminuria. Not specific. * ELISA testing gives highly accurate results, but this test is not available in the majority of remote hospitals.

Answer 100

* an destructive form of lymphoma affecting nasal sinuses and/or septum * dx by histology

Answer 101

* Rhinoscleroma is a chronic granulomatous condition of the nose and other structures of the upper respiratory tract. Rhinoscleroma is a result of infection by the bacterium Klebsiella rhinoscleromatis. It is a disease of low resource economies, poor nutrition and overcrowding.

Answer 102

* histoplasmosis * leprosy * midline granuloma * neoplasms * blastomycosis * rhinoscleroma (Klebsiella spp) * sarcoidosis * syphilis * tertiary yaws

Answer 103

* choice of first and second line drugs varies by region, may depend on local practices

Answer 104

* **Early-stage symptoms** * -non-specific, onset 1–3 weeks after tsetse fly bite * headache, malaise, arthralgia, weight loss, fatigue, and intermittent fever with rigors—the latter suggesting an alternative or additional diagnosis of malaria. * lymphadenopathy or enlargement of spleen, liver, or both * myocarditis, pericarditis, and congestive cardiac failure * iritis, keratitis, and conjunctivitis * endocrine dysfunction including menstrual abnormalities, impotence, alopecia, and gynaecomastia * fertility problems including sterility, prematurity, abortion, and stillbirths * Winterbottom’s sign a typical feature of T b gambiense HAT. * travellers and expatriates from non-endemic countries presentation atypical, with acute febrile illness irrespective of the variant of HAT * diarrhoea, hepatomegaly, or jaundice were frequent early- stage symptoms that could result in an erroneous gastroenterological diagnosis * Another finding that has begun to challenge the classical symptom complex is the occurrence of neurological features during early-stage disease, eg two different areas in Uganda had altered gait and tremors, somnolence, urinary incontinence, and cranial neuropathies—findings that can hardly be explained by non- specific effects of systemic infection on the CNS. ?early CNS invasion

Answer 105

* wide constellation of symptoms and signs can occur, with almost all regions of the nervous system potentially involved. * mental disturbances, motor system disturbances, sensory system involvement, and abnormal reflexes. * typical sleep disturbances that give the disease its name occur in 74% of patients: reversal of the normal sleep/ wake cycle, with nocturnal insomnia and daytime somnolence, uncontrollable episodes of sleep, and an alteration of the structure of sleep itself, with the early onset of rapid eye movement sleep rather than at the end of stage 4 sleep. * Motor disturbances can occur, with motor weakness reported in 35% of cases, gait dis- turbance in 22%, tremor in 21%, abnormal movements in 11%, and speech disturbances in 14% of cases. * Myelitis, myelopathy, muscle fasciculation, and peripheral motor neuropathy * Psychiatric involvement: 25% of patients displaying behavioural disturbances. * lassitude, hallucinations, delirium, anxiety, irritability, and excessive sexual impulses. Headache also common, occurring in 79% of patients in one study. * sensory disturbances such as deep hyperaesthesia, pruritus, anaesthesia and paraesthesia, seizures, and visual problems such as optic neuritis, double vision, optic atrophy, and papilloedema. * In travellers and expatriates with HAT from non-endemic countries both lymphadenopathy and sleep disturbances are only occasionally found and progression to late-stage disease is rapid. By contrast, in African immigrants, HAT is characterised by low-grade fever and neurological and psychiatric symptoms and signs.

Answer 106

* The Mazzotti reaction, first described in 1948, is a symptom complex seen in patients after undergoing treatment of onchocerciasis with the medication diethylcarbamazine (DEC). Mazzotti reactions can be life-threatening, and are characterized by fever, urticaria, swollen and tender lymph nodes, tachycardia, hypotension, arthralgias, oedema, and abdominal pain that occur within seven days of treatment of microfilariasis. The Mazzotti reaction correlates with intensity of infection; however, there are probably multiple infection intensity-dependent mechanisms responsible for mediating this complex reaction.[1] * Patch test * The phenomenon is so common when DEC is used for the treatment of onchocerciasis that this drug is the basis of a skin patch test used to confirm that diagnosis. The drug patch is placed on the skin, and if the patient is infected with the microfilaria of O. volvulus, localized pruritus and urticaria are seen at the application site.

Answer 107

* through the bite of an infected phlebotamine sandfly. * It depends * L. infantum is primarily zoonotic * L. donovanis is primarily anthropotic but both can participate in anthropo-zoonotic cycles * Becaus L. donovani is primarily anthropotic, control of the disease might be more responsive to treatment programmes directed at humans * Because L. infantum has a large sylvatic zoonotic reservoir, it would be hard to eradicate.

Answer 108

* The diagnosis of African Trypanosomiasis is made through laboratory methods, because the clinical features of infection are not sufficiently specific. The diagnosis rests on finding the parasite in body fluid or tissue by microscopy. The parasite load in T. b. rhodesienseinfection is substantially higher than the level in T. b. gambiense infection. T. b. rhodesiense parasites can easily be found in blood. They can also be found in lymph node fluid or in fluid or biopsy of a chancre. Serologic testing is not widely available and is not used in the diagnosis, since microscopic detection of the parasite is straightforward. The classic method for diagnosing T. b. gambiense infection is by microscopic examination of lymph node aspirate, usually from a posterior cervical node. It is often difficult to detect T. b. gambiense in blood. Concentration techniques and serial examinations are frequently needed. Serologic testing is available outside the U.S. for T. b. gambiense; however, it normally is used for screening purposes only and the definitive diagnosis rests on microscopic observation of the parasite. All patients diagnosed with African trypanosomiasis must have their cerebrospinal fluid examined to determine whether there is involvement of the central nervous system, since the choice of treatment drug(s) will depend on the disease stage. The World Health Organization criteria for central nervous system involvement include increased protein in cerebrospinal fluid and a white cell count of more than 5. Trypanosomes can often be observed in cerebrospinal fluid in persons with second stage infection.

Haemoflagellates Flashcards

(139 cards)