Virus Flashcards
Alphavirus Example
EEE, WEE, Venezuelan EE, RRV, Chikungunya
Flavivirus Example
Dengue, Zika, JEV, MVE, West Nile, Yellow Fever, St Louis Encephalitis
Bunyavirus Example
California encephalitis, La Crosse, Rift Valley Fever
Rabies Transmission
Terrestrial mammals (99% dogs), Bats (Americas only), rare reports of tissue/organ transplant
Rabies Virology
Bullet-shaped RNA wrapped in five proteins - matrix, envelope, nucleo, phospho and RNA polymerase
Rabies Pathogenesis
Exposure -> centripetal retrograde axonal transport to brain along motor neurons, evades immune surveillance > CNS transynaptic spread, replication, inclusion (Negri) body formation, neurons intact but dysfunctional > centrifugal neuronal transport to salivary glands (viral excretion) carried to skin, heart, muscle tongue, but no viraemia
Rabies Natural history
Once clinical signs evident, there is no treatment or survival
Rabies Deaths per annum
60,000 (21,000 India)
Rabies Furious rabies
80% cases - brain stem, cranial nerves, limbic system higher centres
Rabies Paralytic rabies
20% cases - medulla, spinal cord, spinal nerves
Rabies Prodromal symptom
Pruritus
Rabies Clinical furious
Phases of arousal and lucid, CN II, VII, VIII, autonomic stimulation, arrhythmia, priapism, survive <7d
Rabies Hydrophobic spasm
Provoked by drinking > Inspiratory spasm, becomes more severe, can cause oesophageal tears and pneumothorax
Rabies Clinical paralytic
Ascending paralysis (?GBS) loss of reflexes, bulbar sx, survive <30d
Rabies Differential diagnosis
Post-vaccinal, paralytic polio, Flavivirus, Herpes B virus
Rabies Clinical care
Palliative, barrier nursing (low evidence, but improves anxiety), vaccination of staff and household, inform public health authorities
Rabies Diagnosis
Nuchal biopsy - immunofluorescence rabies Ag on innervation of hair follicle; saliva PCR (variably released); viral tissue culture; brain biopsy Negri bodies (inclusion in cytoplasm of Purkinje cells)
Rabies Treatment
Only if American bat virus, early Ab response, ICU available - Milwaukee protocol discredited
Rabies Pre-exposure vaccination
Endemic area, rabies lab worker, endemic animal handlers, travellers to dog rabies enzootic areas (esp children), HCW looking after rabies pt - at least 2 (WHO) ideally 3 (UK) vaccines
Rabies Vaccine administration
IM deltoid (NOT gluteal), intradermal improves availability, accessibility and affordability in LMIC
Rabies Post-exposure management
Cat 2+ Scrub with soap and water 15min, avoid suturing, give vaccine x2 (RIG and vax x4 if cat 3 AND unvaccinated)
Rabies Category 1 exposure
Touching or feeding animals. Licks intact skin, includes drinking milk from rabid cow
Rabies Category 2 exposure
Nibbling of uncovered skin, minor scratches or abrasions without bleeding, treat as cat 3 if bat exposure, bites on head/neck/face/hands/genitals (highly innervated) - stop Rx if animal well after 10d/proven negative
Rabies Category 3 exposure
Single or multiple transdermal bites/scratches, contamination of mucous membranes or broken skin with saliva, exposures due to bats, includes raw meat of rabid animal - stop Rx if animal well after 10d/proven negative
Rabies Immunosuppressed
PrEP x3, Ab response 2-4w later, PEP x5 and RIG for cat 2+
Rabies Prevention
Mass dog vaccination (IM or oral), educate children, vigorous washing of all bites, vaccination
Rabies PEP
RIG up to 1y after, but not if vax given >7d ago
JEV Outcome
1/3 die 1/3-1/2 longterm disability
JEV Epidemiology
Asia/Pacific. Main cause of viral encephalitis in Asia >3 billion people at risk
JEV Transmission
Arbovirus, Culex
JEV Amplifying host
Pigs, Water birds also involved, vaccination will not eradicate due to animal reservoir
JEV Symptoms
> 99% asymptomatic, acute meningoencephalitis syndrome with seizures, Parkinsonism (basal ganglia predilection) - CFR 30% in encephalitis
JEV Diagnosis
Gold standard seroneutralisation - paired, and not available outside large reference centres, ELISA available poor spec in serum, also perform on CSF
JEV Vaccination
Ixiaro (UK - inactivated), Imojev (Aus - live chimeric). WHO recommended strategy in endemic setting: one-time campaign in the primary target population as defined by local epidemiology (typically children <15), followed by incorporation of JE vaccine into routine immunisation program. WHO recommended strategy in travellers: JE vaccination is recommended for travellers to endemic areas with extensive outdoor exposure during the transmission season
HPV WHO 2030 Targets
90% fully vaccinated by 15y, 70% women screened by 35-45, 90% CaCx receive treatment and care
HPV Genotype
CaCx 16/18, Anogenital warts 6/11
HPV Epidemiology
Most infections will clear within 8m
HPV Ab response
50% women develop no measurable Ab response following infection
HPV HIV co-infection
Increase CaCx x6, Anal cancer x10, increased anogenital warts, HPV is RF for HIV acquisition, HIV decreases HPV clearance
HPV CaCx diagnosis
Visual inspection (VIA) and HPV diagnostics have lower sens/spec in WLHIV compared with general population
HPV WHO HPV screening
General HPV DNA from 30 every 5-10y; WLHIV HPV DNA from 25 every 3-5y
HPV WHO Vaccine recommendation
2 doses from 9yo, option for 1-dose 9-20yo - aim before sexual debut
Dengue Epidemiology
40-50% world population at risk, 70% cases in Asia, most abundant vector-borne viral disease globally, steadily increasing burden with urbanisation and climate change (increasing and longer wet seasons) Explosive outbreaks in Sth America not predictable and can cripple healthcare systems, mortality increases when healthcare systems compromised. Mortality relatively low, morbidity through economic and health burden is significant with lost productivity in young fit healthy workers
Dengue Vector
Aedes aegypti (violin white markings) feed off multiple people in a day, do not fly far, Aedes albopictus (white line) forest mosquito adapted to urban environment, spread from Asia in used-tyre trade, eggs can withstand desiccation, hatch when rains
Dengue Virology
DENV ssRNA flavivirus, 4 serotypes, 3 structural proteins (C M E), 7 non-structural proteins (NS)
Dengue Clinical presentation
Incubate 5-7d, ~75% asymptomatic, ‘break bone fever’ Fever, retroorbital headache, maculopapular rashes, myalgia, joint pain, only a quarter of those infected have symptoms
Dengue Rash
Petechiae acute, islands of white in a sea of red recovery
Dengue Disease phases
Febrile, Critical, Recovery. Febrile is high viraemia, start of inflammatory host response (high fever, severe myalgias) vast majority go to recovery phase, some however to Critical where capillary leakage occurs, days 4-6 with maximal host inflammatory response, risk for shock, bleeding, organ impairment, and recovery phase usually >d7 where host inflammatory response resolves
Dengue Warning signs
Abdominal pain or tenderness, persistent vomiting, clinical fluid accumulation, mucosal bleed, lethargy/restlessness, liver enlargement >2cm, increase HCT with concurrent rapid decrease in Plt
Dengue Severe dengue
Plasma leakage, haemorrhage, organ impairment AST or ALT >=1000, CNS impaired consciousness, heart/other organ impairment
Dengue Tourniquet test
Take blood pressure, inflate cuff again to midway between sBP and dBP, maintain 5min, deflate, wait 2min, count petechiae at antecubital fossa, likely dengue >=10 petechiae
Dengue Probable dengue
Epi risk, fever and 2 of: N&V, rash, aches/pains, tourniquet test positive, leukopaenia, any warning sign
Dengue Host risk factors for severe disease
Pregnant, Comorbidities esp DM & uncontrolled HTN, >60, over and undernutrition
Dengue Viral factors for severe disease
DENV2, high viral load
Dengue Host immune response for severe disease
Dengue Adaptive humoral immune response
Primary infection usually non-severe, invokes homotypic (long-lasting) and heterotypic immunity (wanes after 1-2y). Strong association between secondary infection with heterotypic serotype and severe disease. Infants of dengue immune mothers at greater risk for severe disease during first year (while maternal Ab waning)
Dengue Antibody dependent enhancement
Heterotypic non-neutralising IgG from previous dengue binds to dengue virus, recognised by Fcg receptor on macrophage/monocyte -> massively increased uptake and replication -> increased viral load -> enhanced immunopathogenic cascade (cytokine release) - the secondary infection causes expansion of the T cells with low avidity, this fails to obtain viral control, but with high cytokine production and excess proinflammatory cytokines causes severe clinical phenotype of tissue damage and vascular leakage. Hyperinflammation is self-fulfilling upregulated macrophage activity similar to HLH, adds weight to consideration of immunomodulation as future treatment options (JAK1/2 bari, IL-6 toci) +/- N-AC to minimise liver damage
Dengue Plasma leak
Breakdown of glycocalyx structure, disruption of osmotic barrier, exposes adhesion molecules and activation of endothelial cells with leakage of protein-rich fluid through paracellular gaps, this result sin extravascular fluid accumulation (hypovolaemia, shock, pulmonary oedema, pleural effusions)
Dengue Thrombocytopaenia cause
Multifactorial: bone marrow suppression, platelet dysfunction, peripheral destruction (immune clearance of Ab coated Plt, complement-mediated plt lysis, plt consumption by DIC, plt apoptosis) - plt transfusion not indicated unless bleeding. Nadir usually d4-6
Dengue Diagnosis
1st week PCR or NS1Ag, 2nd week IgM, RDT often combine NS1 and Ab testing
Dengue Febrile phase management
Supportive Clinical: look for warning signs, Lab: monitor Hb/HCT & Plt, AST & ALT, US: to identify early fluid accumulation from plasma leakage, including GB wall thickening, ascites and pleural effusions
Dengue Critical phase management
Clinical: haemodynamic Ax, clammy, tachycardia, narrow PP precede hypotensive shock, assess fluid & mucosal bleeding, Lab: rising HCT suggests significant plasma leakage, coagulopathy shows prolonged APTT and low fibrinogen with normal PT, US to assess serosal fluid accumulation, TTE to assess cardiac function in fluid refractory shock or if myocarditis suspected
Dengue Recovery phase management
Clinical: significant risk of fluid overload if IV fluids continued, Lab: most lab parameters normalise, Hb may fall temporarily below baseline as extravasated fluid is reabsorbed, ALT & AST gradually normalise by often lag, Bradyarrhythmias may occur but are usually benign
Dengue Treatment
Supportive, no antiviral or adjunctive therapies have shown benefit, meticulous fluid balance, oral paracetamol (avoid NSAIDs). Dengue-specific/host directed treatment awaited
Dengue Vaccine
Dengvaxia efficacious and safe in seropositive persons 72-80% against dengue, >90% against severe dengue. Dengvaxia increases risk of severe dengue in seronegative persons RR2-3 -> Ab dependent enhancement, overall population level benefit favourable but huge loss of vaccine confidence, Qdenga in pipeline no safety concerns in seronegative
Dengue Vector control
Environmental management: elimination of containers (piped water systems, mosquito-proofing water storage, disposal of waste), Chemical control with larvicides, insecticides, indoor residual spraying, biological control (Wolbachia)
Dengue Wolbachia
Intracellular bacteria, introduced to Aedes can reduce dengue transmission
Arbovirus Definition & key concepts
Arthropod borne virus. Resurgence of arbovirus due to urbanisation, climate change, increased population mobility. Most of the diseases have high asymptomatic rate and short incubation time. Difficult diagnostics with short-lived PCR positivity and high serological cross-reactivity among flavivirus. No specific treatment drugs available. Difficult vector control. Need for more research into therapeutics and vaccines
VHF Family
Filoviridae -Ebola (Zaire, Sudan, Bundibugyo, Tai Forest) and Marburg, Arenaviridae - Lassa, Nairoviridae - Crimean-congo haemorrhagic fever
VHF Burden of disease
~36,000 cases per year, not all lab confirmed, likely significantly underestimated
VHF Transmission zoonotic
Initial trigger almost always zoonotic - spillover to humans (animal/vector and human overlap) - unpredictable combination of factors - shedding patterns, land use, human-vector interface. Exception is human reservoirs where viable virus persists in survivors after recovery (ie Ebola sexual transmission).
VHF Transmission person to person
Person-to-person transmission drives outbreaks. R0 estimates 1.34-4.7. Direct contact with contaminated body fluids or objects through broken skin or mucous membranes. High potential for exposure in households due to caring practices and late presentation to healthcare due to fear. Super-spreading events: funeral ceremonies, markets, cultural obligations. Increased population movement: shift into more dense urban environments changes exposure risk. Nosocomial transmission due to poor IPC - pregnancy is very high risk, undetected cases, slow diagnosis of suspect cases. Ongoing exposure to a common zoonotic transmitter can resemble person-to-person spread (eg Lassa with ongoing exposure to same rodent)
VHF Spectrum of illness
Asymptomatic Ebola 3-6%, CCF 70% Lassa 80%, Marburg unknown. Difficulty identifying due to non-specific common symptoms and case definition. Asymptomatic are unlikely to transmit due to lack of body fluids and low viral load. Pauci-symptomatic transmission potential may depend on type of symptoms (dry vs wet). Symptomatic - extent of exposure to a symptomatic case and whether that case is dry or wet is strongly associated with risk of infection. Ebola - many contacts with high exposure do not become infected
VHF Prevention and control
Prevention of VHF outbreaks is difficult due to unpredictability of spillover, challenging control of hosts. Curtailing onward transmission in humans is feasible: interventions to achieve shorter, less severe outbreaks. Critical foundation is community confidence and involvement
VHF Epidemiology of interventions
Reduce exposure, break transmission, speed care for infected, reduce severity and fatality. Active case detection (reduce delay from onset to isolation, speed care provision), earlier and more rapid isolation and care (improve outcome, reduce exposure), triage and suspect management (avert undetected cases in routine services, also confidence in safety in healthcare setting), faster more frequent testing (reduce time to care, better management of suspect and quarantine), IPC healthcare facilities (prevent transmission, avert amplification), IPC household (human and animal - prevent/reduce exposure), IPC community (adapt public health measures - avert exposure), contact tracing (early detection, break transmission), quarantine (reduce time to detection, reduce unwitting transmission but risk of opposite effect). Community collaboration is essential
VHF Community engagement
Engaging with the sociocultural dimensions of epidemics is critical to mounting an effective outbreak response - take the time to establish trust (despite feeling the need to ‘save time’, failing to engage community is likely to have the reverse effect) “If the community are kept outside, they will not come inside for treatment”
VHF Key points
Global burden of VHF is likely underestimated and transmission missed. Zoonotic spillover is unpredictable and hard to prevent. Curtailing human-human transmission and transmission at the human-animal interface is feasible and more effective if communities are involved at a deeper more functional level from the beginning. Outbreak response interventions aim to break transmission through reducing exposure using IPC, earlier detection, diagnosis, isolation and treatment to achieve shorter, less severe outbreaks. Forethought, preparedness, organisation is important. One size does not fit all and adaptation by, and integration of, affected populations are critical to successful outbreak control.
Ebola Epidemiology
> 20 Ebola outbreaks since 1976 >33,000 infections, >15,000 deaths. CFR EBOV 40-80%, SUDV 40-55%, BDBV 35-40%, TAFV 0%
Ebola West Africa
Post conflict environment, porous borders, no institutional memory of Ebola (HCW initially not trained to respond and protect themselves, community resistance to the Ebola outbreak response). Multiple factors leading to severe consequences: magnitude of outbreak, multiplication of foci and need for multiple ETCs, delayed community response, care delays, burial practices, high number of HCWs infected
Ebola Virology
ssRNA virus, NP and GP are targets for PCR and vaccines. Lipid envelope easily destroyed by soap, chlorine, UV light. Incubation 2-21d
Ebola Pathogenesis
Virus infects dendritic cell, travels throughout body, immune system dysregulation -> death of lymphocytes and excessive cytokine release -> Circulatory system (capillary leakage and third spacing, coagulopathy, endothelium damage, low BP). Multiple organ dysfunction: Brain (encephalopathy), Liver (hepatocyte injury or dysfunction -> raised ALT/AST, reduced clotting factors, hypoalbuminaemia, hypoglycaemia), GIT (vomiting and diarrhoea -> fluid and electrolyte imbalance, disrupted acid base), spleen (cytokine dysregulation, death of lymphocytes), kidney (AKI, fluid electrolyte and acid-base derangement), skeletal muscle (injury with elevated CK)
Ebola Differential diagnosis
Clinical manifestations are non-specific. Consider malaria, typhoid, diarrhoeal diseases (Shigella, Cholera), Rickettsioses, other VHFs
Ebola Phases of illness
Early (fever, asthenia, headache, myalgia, arthralgia, anorexia)- > GI (diarrhoea, emesis) >Terminal (fever and GI Sx subside, confusion and delirium worsen -> comatose, olig/anuric, death either gradual or sudden from arrhythmia)
Ebola Longterm sequelae
Neurologic (headache, seizures, peripheral neuropathy), Ophthal (intraocular inflammation), MSK (arthralgia/arthritis), Sexual (ED, testicular pain, dysmenorrhoea, pelvic pain), Abdo (pain, N&V), Hearing loss/tinnitus, Mental health (depression, anxiety, PTSD)
Ebola Clinical management
Supportive (but aggressive) GI loss from diarrhoea and vomiting (aggressive fluids to keep up with losses), Monitor and replace electrolyte abnormalities (potassium, glucose, bicarb), septic shock physiology (aggressive fluids, but monitor for vascular leak, pulmonary oedema), symptomatic management (N&V, diarrhoea, seizures, myalgia, abdominal pain), prophylactic abx (gut translocation). ALIMA ‘Cube’ - clear box for care
Ebola Therapeutics
Remdesivir, MBP134 used in Uganda. Investigational: Zmapp, MAb114, Regeneron
Ebola Key points
EBOV disease is an important high consequence infectious disease. Orthoebolavirus has a weak lipid envelope that is easily susceptible to robust IPC measures. EBOD mimics many other tropical diseases (especially when early in patient course) -> know epidemiology. Treatment and prevention (vaccine) options exist (only for EVD), when available, they need to be provided alongside optimised supportive care
Lassa Epidemiology
Zoonosis (multimammate rodent - Mastomys natalensis) - household contacts usually have same zoonotic exposure, less common to have human-to-human transmission. Highest numbers in Nigeria during Dec-May. Suspected case = malaise, fever, headache, sore throat, cough, N&V&D, myalgia, chest pain, HEARING LOSS (much more common in Lassa than other VHF) and either history of contact with rodent excreta/urine OR with probable/confirmed human case, Confirmed is suspected case + lab confirmation (IgM, PCR or viral culture), Probable is suspected case who died or absconded without collection of specimen
Lassa Management
Supportive care (fluid, renal, haem, resp), antiviral (ribavirin). Research into various agents, and experimental vaccines - no approved vaccine at present
CCHF Epidemiology
Tick-borne, characterised by fever, thrombocytopaenia and haemorrhage. Treatment is mainly supportive +/- ribavirin. Russians discovered it and passaged it through psychiatric patients for 20 years until they had the ability to culture it (!). Significant spectrum of disease severity - mild cases present minimal risk of nosocomial transmission as does standard laboratory management of patient samples.
CCHF Transmission
Large ruminants (cattle, camels) do not become unwell despite viraemia, migratory birds are a risk for transmitting infected ticks to new countries. Less person-to-person transmission than EBOV or Lassa, rare in the community, but in a highly viraemic patient within the hospital is a risk for nosocomial transmission
CCHF Children
Rare to get severe disease or death, generally fever, anorexia, N&V and abdominal pain, less likely haemorrhagic manifestations
CCHF Treatment
Supportive, ribavirin (most effective if given in first 6d of illness), side effect is dose-dependent haemolytic anaemia (evidence for ribavirin is weak) - large-scale multi-country trials of therapeutics are urgently required
CCHF Diagnosis
PCR, LFA in development
Yellow fever Virology
SSRNA + virus, Flavivirus, incubation 3-6d (max 15d), endemic in Africa and South America. Transmitted A aegypti
Yellow fever Transmission cycle
Sylvatic: non-human primates - mosquitoes. Urban: human - mosquito. Intermediate (Savanna): human or non-human primate - mosquito
Yellow fever Clinical
Most asymptomatic, Mild fever, headache, chills, muscle pain, nausea - most self-limiting for 1 week. 10-25% haemorrhagic manifestation, kidney and liver damage. CFR 20-50%
Yellow fever Vaccine
Live attenuated YFV. Pros: safe, massively used since 1938, fast neutralising immune response, one dose has long-lasting protection 10d post administration if >2yo. Cons: need for embryonated egg, need for strict cold chain. AE 1:100,000 hypersensitivity. 1:200-400,000 vaccine-associated viscerotropic disease, 1:150-250,000 vaccine-associated neurotropic disease
Yellow fever Vaccine contraindications
<6m, anaphylaxis to previous dose or to any component of vaccine (including egg), thymus disorder, acquired immunodeficiency, immunosuppressed, first degree relative with vaccine-derived viscero or neurotropic disease (that was not related to a known medical risk factor), >60 and travelling to low risk location
Yellow fever Vaccine precautions
6-8m, >60, Pregnant or breastfeeding, low dose steroid or non-biological oral immunomodulators, HIV (even with CD4>200 and suppressed VL)
Yellow fever Fractional dose vaccine
Minimum potency 1000 IU/dose (20% of vax) - consider fractional dose in response to an emergency situation in which current vaccine supply is insufficient, but this will not provide durable response
Dengue Vaccine challenges
Existence of 4 DENV types each capable of causing infection, disease, and death. No validated immune correlation of protection. Immunologic assays are unable to precisely define DENV type specific immune responses. Requirements for very large efficacy trials to demonstrate benefit across diverse populations and clinical endpoints
Dengue Prevention in travellers
Mosquito prevention (day time), risk highest during and shortly after rainy season. Vaccination Qdenga may be offered to >4yo and older who have had dengue infection in the past and are planning to travel to areas where there is a risk of dengue infection or areas with an ongoing outbreak
Zika Virology
ssRNA+ flavivirus
Zika Congenital
Risk T1 8% T2 6% T3 4%. Medium and longterm sequelae: seizures, hearing loss, visual impairment, dysphagia, developmental delay
Zika Sexual transmission
1% of ZIKV in Europe and US acquired through sexual transmission. M to F»_space; F to M/M to M. Persistence of virus in semen 54d, likely non-infectious at 30d. Male traveller if female partner pregnant - use condoms for rest of pregnancy, if female not pregnant avoid conception (and use barrier) for 3 months. Female traveller if pregnant - use condoms 2 months (if male travelled with her - for the rest of pregnancy), if not pregnant avoid conception for 2-3 months
Zika Clinical
50-80% asymptomatic, 20-50% mild disease, <1% complications - include neurologic (GBS, acute myelitis, meningoencephalitis), ocular (uveitis), TTP, transient myocarditis
Chikungunya Virology
Alphavirus, Togaviridae, incubation 2-6d. Viraemia usually lasts 5-7d, IgM detectable 3-8d after sx onset, persist 1-3m, IgG detectable 4-10d after sx onset, persists for years
JEV Virology
Flavivirus
Zika Epidemiology
South America, South/SE Asia, Sub-Saharan Africa
Chikungunya Epidemiology
Asia, Africa, Americas
Chikungunya Clinical
incubation 2-6d, then 1w of fever, myalgia, rash. Polyarthralgia/polyarthritis can last weeks to months
Chikungunya Vaccine
Recommended >18y travelling to country/territory where there is an outbreak. Consider >65, particularly those with underlying medical conditions, or persons staying for a cumulative period of 6 months or more
Oropouche Virology
Orthobunyavirus
Oropouche Epidemiology
Northern South America - Brazil. Transmitted by midges (Culicoides paraensis) and mosquitoes (Aedes). Reservoir pale-throated sloths, non-human primates, birds. Most infections are mild (similar to dengue), approx 4% develop neuroinvasive disease
BBV/TB Epidemiology
New diagnoses 2023: HCV 1.1mil HBV 1.2mil, HIV 1.3mil, TB 2.2mil. Living with…in 2023: HIV 40mil, HCV 50mil, TB 10.6mil (1.8bil inc LTBI), HBV 254mil. Deaths in 2023: HCV 290,000, HIV 630,000, HBV 820,000, TB 1.3mil
Hepatitis Epidemiology
Greatest number of deaths to viral hepatitis in SE Asia. Huge impact made with HIV care, hepatitis lacking behind
Hepatitis WHO targets
2030: 95% reduction in new cases, 65% reduction in deaths. Previous: 30% reduction in HBV cases, 10% reduction in HBV-related deaths by 2020
Hepatitis Differential diagnosis
HAV, HBV +/- HDV, HCV, HEV, Leptospirosis, YF, VHF, CMV/EBV, Alcohol and other toxins, ischaemia, autoimmune, NAFLD (accumulaton of NCDs in LMIC is one of leading causes of chronic liver disease, affects 25% of the population), Malaria. ALT in 1000s think autoimmune or acute viral hepatitis
HAV Summary
Faecal-oral (inc frozen foods). Incubation 4-8w <6yo asymptomatic, >6yo symptomatic jaundice 70%. Spontaneous resolution over 1-2 weeks, liver failure rare, no chronic HAV. Diagnosis by serology (IgM/IgG). Vaccine effective in ~95% of cases and lasts for at least 20 years (cannot give in under 6m population. LMIC most are exposed and infected in childhood -> immune
HBV Summary
Blood/body fluid exposure. Incubation 1-6m. Course: 30% symptomatic, 95% of cases in adults will resolve, liver failure may occur (1%) Children much higher risk of chronic infection 95% infants. Diagnosis serology (acute cIgM, chronic sAg/cAb, immune sAb) Recombinant HBsAg is the vaccine 3 doses 95%effective in healthy people. HBV is a neglected tropical disease, 91% undiagnosed, no idea of those who have it know how many are linked to care, engaged with care, on treatment, or suppressed. Mismatch between what people need and what is happening
HCV Summary
Blood/body fluid exposure (Chemsex is RF, but sexual transmission not as pronounced as HIV/HBV). Incubation 2w-6m. Course <30% symptomatic, most cases become chronic (75-80%), liver failure may occur (1-2%). Diagnosis HCV Ab, RNA (Ag tests also available). No vaccine, reinfection common in high-risk groups. Treatment: acute and chronic HCV can be treated with DAAs upon initial diagnosis (based on detectable HCV RNA)
HEV Summary
Faecal-oral GT1-2 drinking water GT3-4 animal (raw pork liver sausage - Mikhail Surenovich Balayan). Incubation 4-8w often preceded by prodrome and diarrhoeal illness. Course mild or symptomatic, typically resolves spontaneously over 1-2 weeks, liver failure rare except in pregnancy (acute liver failure 20%) chronicity recognised in immunocompromised. Diagnosis by serology (IgM/IgG) and molecular testing (HEV RNA). HEV vaccine licensed in China, global trials underway in women of childbearing age. Chronic HEV can occur in transplant, probably happens in HIV but not well described
HBV Antivirals in acute HBV
RCTs have not demonstrated efficacy but have confirmed safety. Consider TDF/3TC if two of (in HIC): hepatic encephalopathy, Bili >171, INR >1.6
HIV/HBV Coinfection
Common, 7.4% globally, much more likely to develop chronic HBV (30%), used TDF or 3TC backbone. Without treatment progression to cirrhosis can be rapid. Treatment does not completely prevent disease progression - likely had a period of significant disease activity
HBV Prevention of MTCT
Maternal TDF from 30/40 to 4w post partum. Infant HBV and HBIg on first day of life
HCC Epidemiology
In UK, >90% of those with HCC are asymptomatic at diagnosis. In West Africa, late presentation with weight loss, abdominal pain, abdominal swelling, jaundice. Late presentation = poor outcomes. Can develop HCC without cirrhosis. Length of time from HBV infection is the greatest risk. 50% of HCCs are due to HBV
HBV Treatment
Contol viraemia by stopping reverse transcription, but cannot (at the moment) get rid of what is in the nucleus. Therefore, if immunosuppressed later in life, will reemerge
HDV Summary
Blood/body fluid exposure (MTCT is rare). 5% of HBsAg carriers (high seroprevalence in Middle East, Centra Asia and South America, and high risk groups IVDU, MSM, SW (a/w HCV, HIV) - up to 80%). Incubation up to 3m. Usually found on screening of acute hepatitis or progressive chronic liver disease. Virion/parasite - dependent on replicating architecture of other viruses, predominantly HBV. If coinfected simultaneously generally acute self-limiting. If D adds to chronic B, 5% acute liver failure 80-100% develop chronicity. HDV suppresses both HBV and HCV replication (DNA/RNA levels do not predict outcome). Diagnosis serology IgM/IgG or molecular testing (RNA) - guidelines for testing are inconsistent (EASL: low HBV DNA and high ALT). Treatment IFNa <30% SVR at 6 months
HCV Treatment
Natural hx 15% resolve, 85% chronic, of those 20% develop cirrhosis, and of those 75% slowly progressive with 25% HCC (transplant or death). Revolutionary treatment - short courses of oral therapy cure rates 95%. However, risk of reactivation of HBV infection during or following HCV treatment up to 24% - including those who have isolated HBV cAb - mechanism is not well understood, but clearly some interaction between the two viruses. Egypt have done an amazing job targeting their population and treating
