Negri Body and EM of Rabies Virus

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1 Rhabdovirus Nearly 100% fatal after symptoms appear Bullet shaped virion Helical nucleocapsid Zoonotic Glycoprotein Binds to Nicotinic Ach receptors in the post-synaptic junction. Replicates in motor neurons and move retrograde Incubation weeks to months 1-3mm/day tingling and muscle spasm, dorsal root ganglia Biopsy and autopsy, Negri body eosinophilic inclusion Pyramidal cells of hippocampus and Purkinje cells Passive immunization and active vaccination Wake up with bat, vaccination

2 Negri Body and EM of Rabies Virus

3 Recent Rabies Case in Florida Man capture bat Puts in on porch in container and tells his 6 year old son not to touch it

4 Polio Naked Acid Stable Replicates in Peyer s patches in ileum then disseminate to: Anterior horn cells Asymmetric Three serotypes

5

6 Polio vaccine Salk Killed virus No IgA response NO RISK of reversion to paralytic polio NO HERD effect Sabin Oral, three serotypes of attenuated polio Has herd effect Produces IgA CAN revert to paralytic polio US uses only Salk now

7 Non-Polio Enteroviruses Many different serotype viral conjunctivitis hand, foot, and mouth disease meningitis pericarditis acute flaccid paralysis inflammatory muscle meningoencephalitis Severe form EV-D68 in 2014 with deaths from severe respiratory disease

8 Zika Recent attention to the virus Flavivirus Interesting neurologic complications and prolonged survival in semen

9 History Discovery in 1947 Zika Forest, Uganda In 2007 febrile illness on the Yap Islands in the Federated States of Micronesia 2014 ZIKV Pacific Islands 2015 ZIKV was identified for the first time in Brazil.

10 MMWR Many infants had excessive, redundant scalp skin Arthrogryposis (contractures of extremities) CT scans of infants brain Widespread brain calcifications Lissencephaly, Pachygyria All 35 infants tested negative for syphilis, toxoplasma, CMV, Rubella and HSV Borrowed from Dr. Parameswaran

11 First case of microcephaly in infant related to Zika in Hawaii, Feb 2016 Borrowed from Dr. Parameswaran

12 Zika Symptoms Fever Maculopapular rash Arthralgia Non-purulent conjunctivitis Travel

13

14 Guillain-Barre syndrome and Zika virus Higher than usual numbers of patients with Guillain-Barre syndrome noted in French Polynesia during Zika virus outbreak The first case had evidence for infection with Zika and Dengue Reports of increase in numbers of GBS from six countries recently in conjunction with Zika virus outbreaks Recent report of GBS with Chikungunya outbreak from French Polynesia Borrowed from Dr. Parameswaran

15 HSV 1 and 2 DS DNA Cold sores Genital Lesions Use to be able to predict on anatomy, not any more Viral infection in most cells results in lysis and death

16 Pathogenesis HSV infects some neuronal cells These cell do not die but are maintained in a repressed state called latency Virus can then become activated but does not damage the neuron Release of virions from neuron follows a complex process of anterograde transport down the length of neuronal axons Virus then enters epithelial cells and is called reactivation

17

18 Classical HSV

19 Cardinal Findings of HSV Painful erythematous vesicles (blisters) on an erythematous base Clustered in appearance Depending on the immune status of the host, the lesions can be locally invasive Dew drops on rose petals

20 Cold sore

21 Orofacial

22 Orofacial HSV

23 Genital

24 Genital

25 Genital

26 Genital Disease First episode is generally the worst Treatment of the primary infection has NO effect on rate of recurrence Women have higher incidence of developing herpes meningitis with primary infection Can prevent infection in discordant couples with daily suppression of the infected partner Prophylaxis for individual generally not recommended unless 6 or more episodes in a 6 month period

27 Other Manifestations Aseptic meningitis Mollaret s meningitis Herpetic Whitlow Herpes Simplex Encephalitis Herpes gladiatorum HSV keratitis Neonatal Herpes Herpes in pregnancy HSV in HIV

28 Herpetic Whitlow

29 Keratitis

30 HSV Encephalitis

31 Diagnosis and Treatment - HSV Diagnosis Mainly clinical Tzanck smear sometime helpful Multinucleated giant cells Intra-nuclear inclusion HSV viral culture or PCR Serology only useful in seroepidemiologic circumstances but could document primary infection. Need to know about IgM and IgG Treatment Acyclovir and congeners Mechanism in next lecture

32 Varicella-Zoster DS DNA Causes both chickenpox (childhood disease) and shingles Chickenpox Generally mild disease but may have major complication Fewer than 2 deaths/100,000 cases MUCH worse disease with complication in adults Over 30 deaths/100,000 cases Most from pneumonia

33 Chickenpox Prodrome may occur 1 to 2 days before the onset of rash Lassitude and fever to 103 F Malaise, pruritus, anorexia, and listlessness Skin manifestations Maculopapules, vesicles, and scabs in varying stages of evolution Clear vesicular fluid then pustulate and scab Dewdrop-like early - rapidly become purulent Small 5 mm-13 mm Central umbilication occurs as healing progresses. First trunk and face then centrifugally The hallmark of the infection is the appearance of lesions at all stages

34 Chickenpox

35 Chickenpox Complications CNS disease Herpes Zoster opthalmicus Pneumonia 1/400 adults Military study showed 16% of recruits had CXR abnormalities Only ¼ of those had cough Only 10% had pulmonary sx to go with CXR Reyes syndrome with concomitant aspirin

36 Zoster Shingles Reactivation of prior infection

37 Zoster

38 Herpes Zoster Opthalmicus

39 Diagnosis and Treatment - Zoster Diagnosis Mainly clinical Tzanck smear sometime helpful Multinucleated giant cells Intra-nuclear inclusion VZV viral culture or PCR Culture much more finicky than HSV culture Treatment Acyclovir and congeners Mechanism in next lecture

40 Varicella-Zoster Prevention Vaccine Live-attenuated virus NOT used in immunocompromised individuals or with those people in the same household Lower dose in childhood Higher dose in adult to prevent zoster Treatment Higher dose acyclovir

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