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Flashcards in Microbiology Deck (75):
1

Herpesviruses

-large, double-strand DNA viruses
-icosahedral capsids surrounded by lipid envelopes
-complex: encode over 90 proteins, supply attachment/fusion glycoproteins of envelope, transcriptioinal regulators that redirect host RNA polymerase to viral genome; capsomeres, other glycoproteins required for virus spread from cell to cell

2

Herpesvirus treatment?

-several effective anti-herpetic drugs
-non are curative

3

Herpesvirus virulence?

-ability to establish latent infections in which virus genome, but not virus progeny is maintained in a quiescent state for the remainder of the host's life
-recurrent infections when latent virus reactivates to produce progeny again

4

HSV 1 & 2 replication

-in epithelial cells and reside latently in the trigeminal or sacral ganglia
-termed "neurotorpic herpesviruses"

5

HSV replication cycle

1) viral attachment proteins & cell surface receptors
2) when attached, HSV directly fuses with plasma membrane in pH dep. manner - released nucleocapsid migrates to cell's nucleus where the genome is released
3) initial transcription/translation produces proteins that act as transcriptional regulators that modify host RNA polymerase so that it preferentially transcribes viral genes over host genes
4) production of "early" proteins (able to replicate the virus genome) to produce progeny genomes

6

Herpes: Importance of Thymidine Kinase

1) Required to phosphorylate/activate acyclovir and derivatives (the drugs of choice to treat most HSV infections)
2) thymidine kinase mutants are a problem during treatment because their spontaneous occurrence renders HSV resistant to ACV

7

Herpes: Importance of Viral DNA Polymerase

-ultimate target of many anti-herpetic drugs
(including ACV)

8

Herpes: Virus assembly

-occurs in nucleus
-virus buds from the plasma membrane during release
-infected cells may fuse with uninfected cells, leads to syncitia (giant cells with more than one nucleus)

9

Smear to identify Herpes?

-Tzanck smear with multinucleated giant cells with nuclear inclusion bodies

10

Latency in Herpes?

-soon after primary infection in peripheral sensory neurons
-virus genome is maintained extrachromosomally in neurons in 10-100 copies per cell
-only gene expressed is LAT (latency-associated transcript), product is RNA species that silences a subset of cellular genes to prevent apoptosis of the infected neuron
-no virus particles are produced

11

Reactivation of Herpes?

-decline in cell mediated immunity from physical or mental stress or sunburn
-enters productive, lytic replication cycle
-recurrent infection in epithelial cells innervated by the latently-infected neurons
-cold sores "numbness at site after many years of recurrence"

12

Diseases of HSV 1

1. Gingivostomatitis
2. Herpes Labialis (fever blister)
3. Keratitis
4. Encephalitis
5. Herpetic whitlow (finger vesicle)
6. Conjunctivitis
7. Blepharitis

13

Diseases of HSV 2

1. Cervicitis
2. Vulvular vesicles
3. Penile vesicles
4. Meningitis
5. Vaginal vesicles
6. Urethritis (rare)
7. Perianal vesicles
8. Encephalitis

14

HSV Infection

-generally self-limiting
-skin, ocular, urogenital by HSV 1 or 2
-disseminated disease is problem in immunocompromised (often from reactivation)
-neonates are at risk
-can be severe and fatal

15

Symptoms of HSV Infection

-asymptomatic
-multiple blisters form on infected skin (oral, genital, or perianal) about 2 weeks after infection
-blisters soon rupture making mild, somewhat severely painful open vesicles take 2 weeks to heal in primary infection
-recurrent infections occur during lapses in cell-mediated immunity & resulting cold sores or genital lesions are limited in size & duration due to the presence of neutralizing antibody

16

Gingivostomatitis

-primary oral HSV
-vesicles can occur on the lips, tongue, and facial skin surrounding the mouth
-low grade fever or headache

17

Fever Blisters

-latent HSV reactivates in response to stress or sunburn, oral
-some of same sites as primary infection
-may itch or burn, several times per year and lesions heal in 7-10 days
-low grade fever or headache

18

HSV Genital Primary Infections in Males

-vesicles can occur anywhere on the penis or perianal regions and can cause urethritis (rarely)

19

HSV Genital Primary Infections in Females

-vesicles can be external or internal and can be difficult to detect even when present
-leads to mucopurulent cervicitis, vaginitis, and rarely urethritis

20

HSV virus shedding?

-can occur in absence of recurrent vesicles and well after lesions are unapparent

21

Other symptoms of primary and recurrent HSV?

-flu-like - fever, headache, swollen glands in addition to itching/burning skin in infected areas
Prodrome: can tip suffers of impending infection when muscle aches of legs and buttocks or others

22

Primary Ocular Infections in HSV?

-Blepharitis and conjunctivitis most often seen in children
-present as small vesicles or pustules around the eye lid

23

Recurrent Ocular Infections in HSV?

-Keratitis -results in significant corneal scarring if left untreated, characterized by red, painful eye, blurred vision, & photophobia

24

Encephalitis

-Recurrent HSV 1 infection in adults, headache, fever, confusion, seizures, from latent virus in tirgeminal ganglia which then involves temporal lobes
-Primary HSV 2 infection in neonates
-70% mortality if untreated, 20-25% if treated early

25

Meningitis

-10% of primary cases of HSV 2, headache, stiff neck, vomiting, resolves in 1 week

26

Neonatal Infections in HSV

-Symptoms in 1st/2nd week postpartum
-some limited to skin, eye, mouth with "zoster-form" rash on body - BEST outcome
-more severe involve CNS (encephalitis: seizures, coma, irritability) or disseminated involving multiple organ failure, 75% die or significant sequelae

27

Transmission of HSV

HSV 1: sexually "above belt", oral-from children to parents (60% pop. infected)
HSV 2: sexually (more genital infections) "below belt", mouth in oral sex

28

Diagnosing Genital Herpes

-culturing virus: 3-10 days, cytopathic effect (CPE)
-fluorescent antibody (FA) screening
-PCR screen from vesicle swabs (tell 1 from 2)
-serology: detects ab to glycoprotein G, indicated PAST infection
-Tzanck smear: look for GIANT CELLS with intranuclear inclusion bodies

29

Diagnose Keratitis

-slit lamp examination to detect infected corneal cells

30

Diagnosis Herpes Meningitis

-aimed at ruling out bacterial source (self limiting 7-10 days)
-CSF is cultured to look for CPE to indicate viral

31

Diagnose Herpes Encephalitis

-cultures from CSP are rarely positive
-serology is to late (1-2 weeks )
-normal EEG rules out herpes encephalitis
-PCR to confirm , southern blot in 24hrs.

32

Diagnose Neonatal/Congential Herpes

-skin, eye, mouth, CNS disease
-check liver enzymes for evidence of disseminated disease

33

Location of HPV?

-limited to epithelial cells of skin and mucosa

34

HPV serotypes that commonly cause anogenital warts?

HPV 6
HPV 11

35

HPV serotypes with high risk for cancer?

HPV 16
HPV 18

36

What HPV viral proteins play a role in the development?

-E6 & E7 bind and ultimately remove or inactivate 2 tumor suppressor proteins (p53 (6) & Rb (7))

37

HPV Microbiology

-circular, double-strand DNA genomes, 8 kb pairs
-small end of DNA virus complexity
-icosahedral capsid has L1 & L2made after DNA replication, self assemble to form capsids

38

Is HPV enveloped?

-no, more stable on skin and fomites

39

HPV virus replication & assembly?

-in nucleus, is released by lysing cells

40

HPV in non-permissive cells?

-late gene expression does not occur & instead of virus production, infection leads to formation of transformed cells capable of producing tumors

41

Benign Tumor Cells (HPV)?

-wart
-genome is maintained extra-chromosomally in 40-50 copies like bacterial plasmid

42

Malignant Tumor Cells (HPV)?

-cervical carcinomas
-portion of virus genome is integrated into host chromosome

43

Features of Transformed Cells (HPV)

1. Immortal
2. No longer contact inhibited in cell culture
3. No longer require serum-derived growth factors in cell culture
4. Non longer anchorage-dep. for growth in cell culture
5. Can lead to tumor formation in syngeneic animals

44

Diseases from HPV

-common & plantar warts
-flat warts
-anogenital warts: HPV 6/11
-sub-clinical papilloma infection: HPV 16,18,31
-cervical, penile, anal, oral, and neck cancers: HPV 16, 18, 31
-infantile laryngeal papillomas: HPV 6 & 11
-epidermodysplasia

45

Symptoms of HPV

-common & flat warts on hands & feet of children
-plantar warts on soles of feet that are painful (remove)
-penile, vulvar, perianal warts by 6 & 11 (condyloma acuminata or condyloma plana)

46

SPI detection in HPV

--brushing infected area with 5% acetic acid, turns warts white
-pap smear can detect koilocytotic (vacuolated cytoplasm) squamous epithelial cells

47

How much cervical cancer is caused by HPV?

90%, most will not lead to invasive cancer especially if detected early

48

Laryngeal Papillomas

-growths (HPV) in respiratory tract
-resp. distress can result and warts must be removed by surgery
-acquired at birth in 50% of cases
HPV 6 & 11 most common cause
-risk is 1 in 100-1000 if mom has warts, remove during pregnancy

49

Epidermodyysplasia Verruciformis

-warts begin to appear in early childhood on the face, trunk, & limbs
-warts are flat/reddish brown macular plaques from HPV
-give rise to nonmetastasizing tumors (not fatal)

50

Spread of HPV

-warts spread by direct contact with wart or fomites that recently contacted warts

51

HPV Epidemiology

-common/plantar warts most in children/young adults
-anogenital warts, most common sexually transmitted disease, normally happens b/f age 25
-HPV in US women is 15-60%
-2/3 sexual partners are effected, few get warts b/c of immune response

52

Cofactors to develop cervical cancer?

-smoking
-co-infection with HSV

53

Diagnosis of HPV

-can't routinely grow in cell culture
-diagnose common, plantar, anogenital by clinical appearance
-if abnormal pap smear, do colposcopy
-test for HPV DNA in cells

54

HPV Prevention

1. Gardasil - HPV 6,11,16,18

55

Chlamydia trachomatis Microbiology

-obligate intracellular parasite (gram -, no peptidoglycan)
-grown in tissue culture (not artificial media)
-intracellular development cycle with 2 alternating forms: infectious elementary body & reticulate body that grows within a membrane vacuole in cytoplasm of mucosal epithelial cells

56

What antibioticts are ineffective in Chlamydia and why?

-beta-lactam because chlamydiae resides in isosmotic intracellular environment

57

Primary virulence factor of chlamydiae?

1. grow inside eukaryotic cells
2. cause inflammation (heat shock protein, LPS is of low toxicity)

58

Neisseria gonorrhoeae Microbiology

-no capsule
-LPS is shed during infections & invokes an inflammatory response (much of pathology seen in localized and disseminated infections)
-antigenic variation (involves pili and outer membrane surface proteins)
-extracellular parasites: killed when phagocytosed by PMNs
-secrete IgA1ase

59

Ureaplasma Microbiology

-lack cell walls (peptidoglycan & outer membrane)
-not susceptible to any beta-lactams
-agents of genital tract infections (in women in pregnancy-poor birth outcome)
-overall impact is poorly understood

60

Gonorrhoeae Diseases

-cervicitis, urethritis
-salpingitis & PID
-epididymitis
-perihepatitis Fitz-Hugh-Curtis syndrome
-rectal infections
-pharyngitis (from oral sex)
-Conjuctivitis (in sexually active)
-disseminated (sepsis with rash, aseptic arthritis, endocarditis, meningitis)

61

Chlamydiae Diseases

-cervicitis, urethritis

-salpingitis & PID
-epididymitis
-perihepatitis Fitz-Hugh-Curtis syndrome
-prostatitis
-rectal infections
-Conjuctivitis (in sexually active)
-conjunctivitis in the newborn
-infant pneumonia
-Reiters Syndrome (reactive, non-septic arthritis)

62

Symptoms of Urethritis/cervicitis

-asymptomatic/inapparent/subclinical infections common in men and women

63

Symptoms of Urethritis in Men with Gonorrhoeae

-purulent penile discharge
-dysuria
-itch at distal urethra
-fever/swollen inguinal glands rare

64

Symptoms of Urethritis in Men with Chlamydiae

-less purulent, milky discharge
-dysuria
-itch at distal urethra
-fever/swollen inguinal glands rare

65

Cervicitis in women from Chlamydiae/Gonorrhoeae

-similar to urethritis
-discharge from endocervix
-bartholin gland may be involved

66

Symptoms of Disseminated infections in Chlamydiae?

-fever
-rash: few maculopapular/pustular peripheral lesions with hemorrhagic periphery often on fingers and toew
-septic arthritis
-rarely: endocarditis, meningitis

67

Symptoms of Infant Pneumonia in Chlamydiae

-vertical transmission
-afebrile
-repetitive staccato cough with tachypnea
-hyperinflation with bilateral infiltrates on chest radiograph
-wheezing is rare
-peripheral eosinophilia
-serum IgM level raised
DIFFERENTIALS: RSV, ureaplasma, CMV, adenovirus, parainfluenza virus, pertussis

68

Transmission of Chlamydiae/Gonorrhoeae/Ureaplasma

-sexually transmitted

69

High risk populations for Chlamydiae/Gonorrhoeae/Ureaplasma

-anyone having sex, esp. multiple partners
-inner city, African Americans
-15-24 yrs accounts for most infections

70

Diagnosis of Chlamydiae

-can't be detected by gram stain
-grow in tissue culture
-NAAT on urine or cervical/urethral exudates

71

Diagnosis of Gonorrhoeae

-gram(-) cocci, especially in polymorphic neutrophils
-gram stain more accurate in females
-grow in Thayer-Martin medium (chocolate blood agar), have antibiotics to inhibit normal flora
-oxidase positive
-NAAT on urine or cervical/urethral exudates

72

Treatment of Gonorrhoeae

-beta-lactam-resistance, tetracycline & macrolide resistance is common
-best choice single IM injection of ceftriaxone
-b/c of resistance: fluoroquinolones no longer recommended

73

Treatment of Chlamydiae

-beta-lactame-resistnace
-Azithromycine (1 pill)
-2nd: Doxycycline (10 day)
-infants, children, pregnant women: erythromycin

74

Lymphogranuloma Venereum (LGV)

-Ct STD
-more invasive than urethritis/cervicitis strains
-invasion of inguinal lymph nodes (swollen)
-suppuration of lymph nodes
-ulceration at site of entry
-Rare in US

75

Trachoma

-non-STD Ct infections
-significant, potentially blinding chronic disease
-in Asia, Middle East, Africa
-these strains don't cause urethritis
-spread by direct contact, formites, not sexually