Viruses Flashcards
Hepatitis A transmission
fecal-oral route, potential sources of transmission and outbreaks -daycare, IVDU, travel
clinical manifestations of hep A
Incubation period: 14-28 days, prodromal phase 7 days, fever, malaise, anorexia, nausea, vomiting; Icteric phase: jaundice, scleral icterus, dark urine
Lab abnormalities in hep A
ALT>AST, Bili <10 but elevated. Usually ALT and AST elevate first and then the bili. Peak 1 month after the exposure
How to diagnose Hepatitis A
HAV in the stool avail 1 week after, the ALT will increase immediately, the IgM anti-HAV will increase at week 1, IgG will start to increase at Week 2
*IgM anti-HAV is to diagnose acute HAV infection
Prevention of Hep A
Vaccine: inactived HAV 2 dose vax (age>1year)
Or PEP: HAV vaccine/immunoglobulin after exposure within 2 weeks
4 genotypes of Hepatitis E that affect humans
HEV1, HEV2, HEV3, HEV4
Epidemiology of HEV1, 2, 3, 4
All in developing regions
HEV1 and 2-humans are the reservoir
HEV3 and HEV4-ANimals are the reservoir
Clinical Manifestations of Hep E
Incubation period: 2-6 weeks
Acute icteric hepatitis: occurs more frequently in HEV1 and 2 (usually about 2-6 weeks)
Extrahepatic manifestations: GBS, Neuralgic amyotrophy, encephalitis, myelitis
Renal: IgA nephropathy ,MPGN
Extrahepatic manifestations of Hepatitis E
GBS, neuralgic amyotrophy, encephalitis, myelitits
IgA nephropathy, MPGN, cryoglobulinemia
which Hep E type causes chronic infection
HE3 and 4 -usually immunocompromised, chronic hepatitis, fibrosis, cirrhosis
Diagnosis of HEV
-Acute: anti-HEV IgM or HEV RNA
-Chronic: IgG (several years) ; HEV RNA in serum>6 months
Treatment of HEV
ribavirin usually used for immunosuppressed
how do you prevent HEV
there is only a recombinant vax 3 dose series in china
epidemiology of hepatitis C genotypes
1: Most common, High/middle income countries
3: 25%, in south asia
4: 15% in Africa, middle east
2, 6, 5, 7, 8: not as common
transmission of HCV
Percutaneous exposure to blood, IVDU, needle stick, tattoos. Vertical or MSM less common
diagnosis of HCV
Anti-HCV Abs (12 weeks of infection); HCV RNA quantification/detection; HCV Core Antigen; genotype important for treatment
Priority groups for treatment chronic HCV infection
substantial fibrosis (F2 or F3), Cirrhosis (F4), liver transplant patients
how to treat HCV
Interferon free direct acting antiviral
(NS3/4 protease drugs (PREVIR)
(NSSA INhibitors (ASVIR))
(NSSB polymarse inhibitor (BUVIR))
Typical treatment regimen for HCV with or without cirrhosis
Sofosbuvir/velpatasvir 12 weeks
which 4 subtypes of influenza have caused most human disease
H1N1, H1N2, H2N2, H3N2
is influenza a or b worse in children
B
what things can you die from if you cannot make antibodies i.e. if you are agammaglobulinemic
-enterovirus
-s. pneumo, h influenza, n meningitis (encapsulated)
-Giardia
three types of anti-virals
- M2 ion channel blocker (amatidine, rimantidine)
- Neuroaminidase inhibitor (oseltamavir)
- Inhibition of polymerase acidic endonuclease (xofluza)
which influenza strain causes worse disease in the elderly
H3N2
what are the enteroviruses
polio, coxsackie, echovirus, enterovirus
how do enteroviruses enter body, what diseases do they cause
entry via aerosol or ingestion, replication in the oro-pharynx and in the peyers patches–>primary and secondary viremia–>
POLIO, Coxsackie–BRAIN
ECho, Polio, Cox–>Meningitis
Hep A–>Liver
Echo, Coxsackie–>SKIN (hand foot mouth)
echo, cox A and B–>Muscle (myocarditis, pericarditis, pleurodynia)
EV 68
rhinovirus, primary respiratory diseases (sometimes pneumonia, CN palsies, acute flaccid paralysis)
EV 71
aspetic meningitis, encephalitis including brainstem encephalitis, polio like syndrome
eczema coxsackie
what virus causes myocarditis
coxsackie B -causes cardiomyopathy
Treatment of Enteroviruses
Ribavirin, Amantidine, Pleconaril, IVIG
Transmission of polio, reservoir
Fecal-oral route; humans are the only reservoir
TYpe 1 is the main one
two polio vaccines
IPV-inactived (Salk)
Oral vaccine (Sabin)
OPV
IPV
VAPP
cVDPV
WT
Oral polio vaccine (sabin)
Inactived polio vaccine (Salk)
VAPP (Vaccine associated paralytic polio)
cVDPV -Circulating, vaccine-derived polio
WT-Wild type virus
VAPP
Vaccine associated paralytic polo (type 3)
what are the types of polio that are concerning
type 3-VAPP
But now Type 2-cVDPV
Clinical spectrum in a high resource setting of measles
diarrhea, otitis media, pneumonia, encephalomyelitis
immunocompromsed hosts with measles
progressive, giant cell encephalitis, pneumonitis
in low resource settings, what does measles look like
blindness (vitamin A deficiency), diarrhea, pneumonia
conjunctivitis, coryza, koplicks spots
measles
koplik spots
Measles treatment
normally, self limiting –>Vitamin A for 2 days
Immunocompromised-ribavirin , immune serum
neonates- immune serum
what protective/immunity factors in measles
Antibodies are good (a lot of IgG1-passed to the fetus)
Neutralizing antibodies
Early ADCC (Boys do this better-androgen)
Strong T cell immunity is critical
What is the measles vaccine
live attenuated vaccine
fever malaise partotitis orchitis
mumps
transient arthralgia, viremia, mild febrile illness with rash
rubella
what is the risk of rubella vaccine in post pubertal women
bad arthralgias
what are the Congenital rubella clinical sx
deafness, heart disease, CNS defect, neonatal purpura, cataract
if you don’t achieve 90% of rubella coverage, what happens
you will paradoxically increase the amount of the rubella because the women will be getting rubella at a later age (i.e. when they are child bearing age)
Natural history of Hepatitis B
1)Incubation: 4-7 weeks before HBV DNA and HBsAg become detectable
2) Acute HBV infxn: 1/3 of adults develop symptoms (fever, fatigue, malaise, abdominal pain)
3) Progression to Chronic HBV Infection
chronic HBV Infection definition
detection of HBsAg on 2 occasions measured 6 months apart
What are the common extrahepatic manifestations of Hep B
Renal: MGN, MPGN
Rheum: Polyarteritis Nodosa
Aplastic Anemia
Vasculitis
Positive HBsAg, Anti-HBs, Anti-HBc, HBV DNA detected positive
Infected with Hep B: cant tell if it is chronic or acute though; unless HBsAg>6 months
HBsAg negative, Anti-HBs Positive, Anti-HBc positive, HBV DNA not Detected
Resolved infection (the presence of HBsAg is no longer detected)
HBsAg negative, Anti-HBs Posivite, Anti-HBc, HBV DNA not detected
immunity-vaccination
if the core protein is isolated positive
false positive
What is host immunity in Chronic HBV infection
the phase when HBV target and destroy infected liver cells; intermittent process (patients can transition between the phases)
What are the phases of chronic HBV Infection
Immunotolerance, HBeAg positive immunoactive disease, HBeAg negative inactive disease, HBeAg-negative immunoreactive disease
What is HBeAg
its a marker of high viral HBV
What is the difference between perinatal infection labs and infection in adults labs HBV
ALT is normal in Perinatal infection, ALT is >2 times upper limit of normal when adult; You have none to mild inflammation of the liver histology when perinatal; asymptomatic and treatment is not indicated in perinatal
Draw out the graph of HBV antigen concentrations and weeks after exposure
What are the ways to assess liver damage with HBV in a non-invasive way
What is the APRI cut off for cirrhosis? Fibrosis?
2.0 cirrhosis=METAVIR F4=Fibro Scan?11-14kPa
Fibrosis=1.5, METAVIR>F2=Fibroscan >7-8.5
Patient with HBsAg, APRI >2. What do you do
Treat with tenofovir or entecavir
45year old patient with HBsAg positive, ALT is elevated, HBV >20,000
Treat with tenofovir or entecavir
50year old patient with HBsAg Positive , APRI<1.5, ALT normal
Defer treatment, monitor
18 year old with HBsAg positive, ALT normal
Defer treatment and monitor
What is theh monitoring for +HBV infection
Every 6 months, look for HCC; Every 12 months, check Labs and APRI or fibro scan
What are the treatments for HBV in children
entecavir
What are the treatments for HBV in Pregnancy
antiviral therapy to reduce the risk of perinatal transmission in HBsAg-positive pregnant women with an HBV DNA Level>200,000 IU/mL; TDF starting at 30-32 weeks, until 3 weeks pp
What is the definition of virological cure
eradication of HBV DNA from Blood and liver, continued positive anti-HBc
What is the definition of functional cure
HBsAg loss, undetectable levels of HBV DNA in peripheral blood
What is the definition of Partial cure
Detectable HBsAG, Low <2000 to undetectable HBV DNA
What is the vaccine schedule for Hep B
3 doses, first dose within 24 hours of birt
How to transmit Hepatitis D
Perenteral transmission, Sexual Transmission, Intrafamilial transmission, perinatal transmission (very rare)
Diagnosis of Hep D:
HDAg: Indicator of acute infection, short lived
HBsAg: Must be present for HDV Infectivity -correlates with HDV RNA
HDV RNA-Marker of HDV replication -positive in chronic infection, used for monitoring
Anti-HDV IgM: Acute infection
Anti-HDV IgG: Long term, even after the viral clearance
What is the only drug that is properly studied in HDV
PEG-IFN alpha 48 weeks, If HCV, add ribavirin, if HBV, add tenofovir
Genotypes of yellow fever and where are they located
IA West Africa,
IB South America,
II Central and East Africa
Vector of yellow fever
aedes aegypti
What is the incubation period of yellow fever and what is the clinical preentation?
3-6 days, asymptomatic (5-50%), 60-80%, hemorrhagic fever 5-10%
Describe the 2 periods of yellow fever
3-6 days after bite–>fever with headache, conjunctival injection, bradycardia, leukenia and neutropenia.
for hte next 2-24 hours, you may feel better and have symptoms abate.
After 3-8 days: Headache, epigastric pain, vomiting, hypotension, shock, hemorrhage, thrombocytopenia
What is the LFT pattern in yellow fever?
What about other labs?
AST>ALT
Wide range of WBC
Albuminuria
Transaminase elevation AST
Direct bili incr to 10 max
May have thrombocytoenia and prolonged PT/TT
DDx of patients with fever, headache, LFT elevation from the jungle
Malaria
Hepatitis
Dengue
Yellow Fever
salmonella
Brucella
Hemorrhagic fevers (Typhoid)
Lepto
How do you diagnose yellow fever?
Serology-IgM, IgG
Pt visited forested area in sub-sarahan Africa, had an acute onset of fever, chills, myalgia, lumbosacral pain. Patient has gingival hemorrhage. Labs show AST>ALT. PT/PTT increased. On histology, councilman body found.
Yellow fever
What are the vaccines in yellow fever?
live attenuated virus vaccine
What is YEL-AND? When does it happen?
Yellow fever vaccine associated neurotropic disease, onset 11 days after vaccination (2-28 days) ; meningoencephalitis due to direct viral invasion of CNS
Who experiences the most side effects from yellow fever vax?
Thymus disease, immunosuppression (but not AIDS),
What is YEL-AVD?
yellow fever vaccine-associated neurotropic disease. after yellow fever vaccine, headache, malaise, myalgias, sometimes rhabdo
Transmission of Mpox
Entry via broken skin, respiratory tract, mucous membranes (incubation period 7-10)-prairie dog
what are the different clades of Mpox
Clade I: Central African Clade
Clade II: West African Clade
what is the suspected case definition for Mpox
A person of any age presenting since 01/22 with an unexplained acute rash or one or more acute skin lesions AND
one of theh following-
HA, Fever, LAD, Myalgia, Back pain, Asthenia
AND
No explanation of the rash
What is the definition of a probable Mpox infection
A person who meets the case definition for suspected cases (acute rash, lesions AND Ha, fever, LAd, myalgia, back pain, or asthenia) AND
has an epi link, direct physical contact with skin or skin lesions; has had multiple sexual partners 21 days before symptoms or has detectable levels or orthopoxvirus IgM antibody
rapid Mpox diagnosis
clinical presentation of Mpox
Incubation period 5-21 days, invasive phase (1-5 days) fever, flu like ililness, LAD, then the erruptive phase (macules–>papules–>vesicles–>pustules–>scabs)
DDx of monkey pox like skin rash
Chickenpox, molluscum contangiosum, disseminated gonoccoal infection, Orf, enterovirus, measles, syphilis
difference between monkeypox and chickenpox
biggest difference is the rash distribution (face/palms and soles in mpox) v. absent on palms and soles on chicken pox
when can you end isolation in mpox
No new lesions x 48 hours/crusted over, avoid contact with immunosuppressed, pregnant; use condoms for 8 weeks
complications of mpox
secondary bacterial infections, bronchopneumonia, sepsis, encephatitis, keratitis
Infection control with mpox
negative pressure room, antichamber for donning and doffing
Treatment of mpox
brincidofovir (FDA approved), DNA polymerase inhibitor (can cause transaminitis)/ Tecovrimat (emergency approved)
What type of virus is Mpox
Orthopoxvirus: enveloped double stranded DNA virus that replicates in hte cytoplasm (large genome!)
Which clade has higher mortality in mpox
Clade I -central African countries
Pregnancy complications
LAD, rash on palms/soles, peripheral>central rash
Mpox
Who has the highest rates of complications in Mpox
HIV CD4<100
How do you diagnose Mpox
PCR swabbing of the lesions
What are the VHF
zoonoses, enveloped RNA viruses, biosafety level 4
30yoM from Sierra Leone (W Africa) who presents with fatigue, headache, joint paints, vomiting, nausea, diarrhea, abdomen pain. abdomen diffusely tender. No bleeding, no rash. Looks unwell
ssRNA zoonotic filovirus EBOLA
What are the top strains of ebola
zaire, sudan, bundibugyo
How do you get ebola? Incubation? Case fatality rate?
Human-to-human contact with bodily fluids, NOT aerosolized, not via mosquitos
Incubation period: 2-21 days
Case fatality rate 30-90%
clinical features of ebola (case definition)
sudden onset fever, HA, vomiting, abdominal pain, diarrhea, anorexia, lethargy
how to diagnose ebola
RT-PCR
Treatment of ebola stages:
Stage1-Ha, fever, myalgia; tx analgesia, zinc
Stage 2: vomiting/nausea; Tx abx, PPI, IVF, antiemetic
Stage 3: Hiccups, seizures, hemorrhage, coma; Tx Vitamin K, TXA, FFP
Ebola Zaire treatment
mAb 114 or REGN EB3
Vaccines for ebola zaire
rVSV-EBOV (single dose)
Ad26-MVA-Filo
what is clinically indistinguishable from Ebola
Marburg virus-no approved vaccines or treatment
what type of virus is lassa? Reservoir lassa
arena virus-Reservoir: Mastomys Natalensis (rodent)
transmission of lassa
spillover-contamination of food, water, environment, Dry season; incubation 3-21 days (human to human spread)
patient from nigeria with sore throat, vomiting, high fever, facial swelling ; low plt, proteinuria, renal failure, AST>ALT; non-malarial disease
Lassa Virus
What is a comlication of lassa
sensorineural hearing loss
What is the treatment of lassa fever
ribavirin, favipiravir, mAb
What is hantavirus
ssRNA virus, bunyavirus
old world Hanta Virus
RENAL syndrome ; proteinuria, polyuric
NEW world Hantavirus
cardiopulmonary syndrome: pulmonary edema, leaky syndrme
Andes orthohantavirus
Patagonia, long tailed pygmy rice rat -peak in spring/summer, in Argentina and Chile
Andes orthohantavirus incubation–>prodrome–>sx
9-40days; flu like, fever, headache –>severe sx respiratory compromise, pulmonary edema, encephalopathy
patient who sacrified cattle and had a tick bite/crushing
Crimean-Congo Hemorrhagic Fever
Vector of CCHF
Hyalomma tick
Clinical course of CCHF
3-7 incubation
Pre-hemorrhagic period 7-14 days (myalgia, fever, nausea, vomiting)
Hemorrhagic period (15-16) bleeding, bruising
Treatment of CCHF
ribavirin
What kind of virus is Nipah Virus
Zoonotic, SS RNA, henipavirus (paramyxo)
Reservoir of Nipah
Intermediate host
Pteropus bat–>eats the date palm sap
Intermediate host: Pig, Horse, (anmials)
Clinical course Nipah
Acte-nonspecific fever, behavioral changes
Subacute/late onset: Encephalitis
Long term: relapse of encephalitis
DDx of encephalitis in Asia
HSV, VZV, JEV, Dengue, Rabies
Rickettsia, T,
Cerebral malaria, Neurocysticercosis
What kind of virus is rabies
lyssa
Route of infection of rabies
Broken skin, intact mucosa –>virus binds to motor or sensory nerve ending
CSF findings in rabies encephalomyelitis
pleocytosis, leukocytes <100, mononuclear, rabies virus +, rabies Ab, Negri Bodies
What are the strategies for personal protection against rabies?
- Post exposure PPx (Bite, then get rabies immunoglobulin)
- Pre-exposure + post exposure (Pre-exp get the rabies vax, if you get bite, post exposure booster -no RIG, vaccine only)
Treatment of wound after dog bite
- clean wound
- tetanus
- don’t suture
4.PEP-vaccine Rig if dont have vaccine (4 dose IM over 21-28 days or 3 or 2 dose multisite ID over 7 days)
