Viral Diarrheas and Viral Hepatitides

Causative virus
Reovirus (rotavirus)

Chromosomal structure
dsRNA (+) naked, segmented (11) 5 serological groups: A-E (A most responsible)

Transmission| Epidemiology
Yearly epidemic More in cooler months (Nov-Mar) Mainly infantile diarrheas Transmission: fecaloral Incubation <48 h

PATHOGENESIS| SYMPTOMS
Pathogenesis: 1. Malabsorption: lactase at brush border 2. Alteration of tight junctions by NSP4 and VP8 (viral toxins) 3. Virus induced fluid and electrolyte modulation Watery, non-blood diarrhea (may have occult blood) due to malabsorption, secretion Dehydration, sudden onset of vomiting, low grade fever, abdo cramps

LAB ID| IMMUNITY

From stool samples, culture ELISA RT-PCR Northern blot SDS/PAGE/western blot EM Immunity Innate: IFN-a, IL-1, IFN-

Prevention and Treatment

Oral , live attenuated rotavirus vaccines (2): Rotateq, Rotarix No available anti-viral therapy Severe cases: rehydration is recommended Prevention: good personal and community hygiene

Protection: IgM, IgG, IgA responses at level of intestinal mucosa (GALT)

Low CD 8 response ELISA-antigen Serology PCR EM No antiviral therapy, treatment symptomatic Prevention: good personal and community hygiene

Astrovirus

ssRNA (+) naked 8 serotypes (HAstV1/2 most responsible)

Yearly epidemic Can cause outbreaks in daycares, hospitals, institutionalized pop. Trans.: fecal-oral High risk: <5 yoa, elderly, immunocomp, personnel attending to sick Incubation: 3-4 d

Pathogenesis: Poorly understood Watery, non bloody diarrhea (2-3 days) + vomiting, lowgrade fever, anorexia, abdo cramps

Immunity Mucosal immune response, immunity wanes later in life Cell-med imm.: Th1 cytokines IFN-, TNF-a

Causative

Chromosomal

Transmission|

PATHOGENESIS|

LAB ID|

Prevention and 1

Viral Diarrheas and Viral Hepatitides

virus
Adenovirus (enteric)

structure
dsDNA naked enteric serotypes:40,41 (51 total)

Epidemiology
Occasional outbreaks in institutionalized setting Trans.: fecal-oral No seasonality Affects children <2 (Ab developed by 3 yoa) Incubation: 8-10 d

SYMPTOMS
Pathogenesis: Replication in epithelial cells of gut, direct viral cytotoxicity, cell-mediated cytotoxicity, cytokine-mediated; modulation of host immune response: down-reg. Of apoptosis, ag. Presentation mod. Watery, mucous (st), nonbloody diarrhea (3-11 d) Vomitting, fever are common

IMMUNITY
ELISA-antigen Serology PCR EM Immunity Mucosal immune response, immunity wanes later in life Cell-med imm.: Th1 cytokines IFN-, TNF-a Identification of norovirus only (research/epi.) From stool samples IEM, EM, EIA-Ab,Ag, ELISA-Ag, RT-PCR Immunity NoV-builds up over time

Treatment
No antiviral therapy Prevention: good personal and community hygiene

Caliciviruses (noroviruses

ssRNA naked Two genera: Norovirus and Sapovirus Cannot be grown in culture 5 genogroups (no serotypes)

Represent most of non-bacterial gastroenteritis outbreaks Trans.: fecal-oral

Main culprits: water, shellfish,fruits, veggies, pasta, cold cuts, sandwiches

Inactivated by bleach, iodine, glutaraldehyde) Incubation<50 h

Pathogenesis: Decrease in microvilli enzymatic activity carbohydrate malabsorption, steatorrhea (decreased trehalose hydrolysisdiarrhea) Flattening, broadening of intestinal villi, crypt hyperplasia, vacuolization of cytoplasma, PMN, MN lamina propria infiltration Sudden onset of vomiting +/diarrhea No blood, mucous, leukocytes, no fever (1-3 d)

No antiviral therapy/vaccines Prevention: good personal and community hygiene

Viral Diarrheas and Viral Hepatitides

VIRAL HEPATITIDES

Acute hepatitides
o o o o o o Preceded by prodromal period: headache, fever, fatigue, N&V, anorexia, RUQ and epigastric discomfort Later on specific signs: dark urine, acholic stools, jaundice Complete recovery 1-2 mo after onset of disease Typical signs: elevated ALT, AST, serum bilirubin, normal ALP or slightly elevated May have co-infection with HBV, HDV, HCV, HIV; coinfection influences outcome Serious presentation: fulminant hepatitis, which can lead to acute liver failure More common with HBV, fulm HCV exceptional Fulminant HAV=rare, fulminant HEV frequent in pregnant women HSV infection can be a cause of acute liver failure

PATHOGENESIS

TRANSMISSION|EPI

IMMUNITY

LAB TREATMENT AND DIAGNOSIS PREVENTION

Peak shedding prior to jaundice Vaccine available (formalin inactivated, whole virus) Prevention Improve sanitation Resistant to: low pH, drying, detergents, solvents, heat stable

REPLICATIVE CYCLE

HEP A

ssRNA(+) Picornaviridae No particularly lytic Egress hepatocyes through apical canalicular membrane

In children most often and clinically inapparent Largely via fecal oral route, also by blood Contaminated food and water (ice cubes!) Risk factors lined to poor socioeconomical conditions Acute liver failure can occur in children, more common in adults >50 yoa Trans.: fecal oral route Distributed worldwide, assoc with wet season In travelers returning from endemic locales,

Liver injury due to CD8 and NK cell response against hepatocytes expressing HAV epitopes Interferences with TLR-3 induced antiviral state by cleaving IFN-B promoter stimulator

(+)ssRNA molecule used for protein synthesis serves as template for (-) ssRNA more protein Vpg-primer for viral RNA synthesis

Some viral particles

remain associated with cell membrane, others egress cell in noncytolytic fashion

HEP E

ssRNA (+), Hepeviridae non-enveloped

Anti-HEV IgM=acute infection Anti-HEV IgG= resolved infection

No vaccine or antiviral therapy Prevention Management of water supplies, avoid

Viral Diarrheas and Viral Hepatitides

close contact w/pigs Usual in older age gp.: normally immune to HAV Very resistant to low pH

questionable water sources

Chronic Hepatitiis
Asymptomatic-liver failure Serious manifestation-hepatocellular carcinoma: HBV most cases lead to cirrhosis, but there may be progression to HCC There is a three fold increase in the risk of HCC in HBV-HDV coinfected individuals, compared to those infected with HBV Only Typical signs: ALT>AST AST>ALT, ALP normal or slightly elevated, serum bilirubin elevated Hep. B: more copies in HBeAg + infections] HBV-HDV coinfection does not increase likelihood of chronicity, but HBV-HDV superinfection does Treatment is based on Type I IFNs IFN-a induction of anti-viral state

PATHOGENESIS

TRANSMISSION|EPI

IMMUNITY

LAB TREATMENT AND DIAGNOSIS PREVENTION

ELISA (serology), PCR(viral load) Treatment Based on use of IFN Type I, IL-2, IL-12, corticosterpids, NA analogues-lamivvudine, telbuivudine, entecavir, adefovir Prevention Immnization (Engerix-B, Recombivax, Twinrix(HAV and HBV vacc.), avoiding risk behaviour

REPLICATIVE CYCLE

HEP B

Gapped, circular dsDNA, Reverse transcriptase

Worlwide Low prevalence: sexual transmission and IV drug use are risk factors High prevalence: perinatal transmission more likely Assoc with chronicity and serious liver problems Long incubation 60180 d

Virus is resistant can remain infectious for up to a week or longer Risk of LT complications, depends age at initial infection

Receptors carboxypeptidase D and glycine decarboxylase After entry: nucleocapsid transported to nuclear pore complex for uncoating Intact HBV virions=Dane particles

Viral Diarrheas and Viral Hepatitides

PATHOGENESIS

TRANSMISSION|EPI

IMMUNITY

LAB TREATMENT AND DIAGNOSIS PREVENTION

HCV inhibits HBV so HBV PCR testing is warranted for chronic HCV patients (the reverse is also true) ELISA, RIBA and RT-PCR (to determine viral loac) Treatment based on Type I IFNs (a and B) and comb therapy with ribavarin or amantadine If chronic: supportive or liver transplant Prevention Management of water supplies, avoid questionable water sources

REPLICATIVE CYCLE

HEP C

ssRNA (+), Flaviridae enveloped

Trans.: blood, blood products, perinatally (sexually-rare) Distributed worldwide, assoc with wet season Common: coinfection with HBV Groups at risk: IV drug users, transfusion, health care workers Incubation: 6-8 weeks Steatosis is an important feature May progress fibrosisHCC Increased risk Trans: parenterally, sexually, percutaneous transmission is most efficient In superinfection+likeli hood of fulminant hepatitis

Anti-HEV IgM=acute infection Anti-HEV IgG= resolved infection

Virion binds and enters hepatocytes entry by endocytosis uncoated RNA translated by ribosomes into polyprotein nonstructural protein production, as well as capsid and envelope proteins Original (+) ssRNA used to make (-) ssRNA= template for more ssRNA

HEP D

Delta virus Enveloped defective ssRNA (-), circular Depends on HBV (core) for replication

Coinfection: antiHDV IgM(low, assoc. with anti-HBc IgM) and HBsAG Superinfection: anti-HDV igM (high, assoc with anti-HBcIgM) and HBsAg

See HBV- similar

Depends on HBV core protein