203: VIRAL GASTROENTERITIS • Histopathology:
o Lesions in upper jejunum: villous blunting, microvilli
Overview shortening, epithelial vacuolization, crypt
• Definition: Acute infectious gastroenteritis is inflammation of hyperplasia, lamina propria infiltration.
the stomach and intestines caused by viral infection. o Malabsorption of carbohydrates/fats; decreased
• Epidemiology: brush-border enzymes.
o Affects persons of all ages worldwide. o Gastric motor delay → nausea, vomiting.
o Leading cause of death among children in • No changes in stomach or colon.
developing countries (~0.5 million deaths annually). Clinical Manifestations
o Responsible for 6–8% of hospitalizations among • Incubation: 12–72 hours (average 24 h).
children in industrialized countries. • Duration: 12–60 h.
o Elderly and immunocompromised individuals are at • Symptoms:
risk for severe complications and death. o Nausea, vomiting (children more frequent),
o Rarely fatal in healthy young adults but incurs abdominal cramps, diarrhea (adults more frequent).
medical and social costs. o Constitutional: headache, fever, chills, myalgias.
• Etiology: • Stools: loose, watery, no blood/mucus/leukocytes.
o Primarily caused by RNA viruses, occasionally by • Labs: usually normal WBC; rare leukocytosis with relative
DNA viruses (e.g., adenovirus types 40 and 41). lymphopenia.
o Characteristic symptoms: acute vomiting and/or • Death: rare; usually from severe dehydration in vulnerable
diarrhea, sometimes with fever, nausea, abdominal populations.
cramps, anorexia, malaise. Immunity
• Clinical distinction: • ~50% of exposed individuals become ill and develop short-
o Viral gastroenteritis vs. bacterial gastroenteritis can term immunity.
be suggested by epidemiology and clinical features, • Genetic predisposition influences susceptibility (HBGA
but laboratory tests are required for confirmation. phenotypes).
• Functional antibodies that block norovirus binding correlate
Human Caliciviruses with protection.
Etiologic Agent • In vitro neutralization demonstrated using human intestinal
• Norwalk virus: prototype strain. enteroid (HIE) systems.
• Characteristics: Diagnosis
o Small (27–40 nm), nonenveloped, icosahedral, • PCR-based detection in stool/vomitus.
round. • Virus-like particles (VLPs) in enzyme immunoassays (EIAs)
o Single positive-strand RNA genome (~7.5 kb). for stool or serology.
o Single virion-associated protein (60 kDa). • Limitations: high antigenic/genetic diversity; mostly research
• Classification: Family Caliciviridae, two genera: or outbreak use; commercial EIAs limited.
o Noroviruses (previously Norwalk-like viruses) Treatment
o Sapoviruses (previously Sapporo-like viruses) • Self-limited illness.
o 35 human-infecting norovirus genotypes in 5 • Oral rehydration therapy sufficient for mild disease.
genogroups (GI, GII, GIV, GVIII, GIX).
• IV fluids if severe dehydration.
Epidemiology
• No specific antiviral therapy available.
• Infections common worldwide; most adults have antibodies.
Prevention
• Earlier antibody acquisition in developing countries (fecal–
• Control of contaminated food/water, exclusion of sick food
oral transmission).
handlers.
• Occur year-round; peaks in cold months in temperate
• Good personal hygiene, disinfection of fomites.
climates.
• Vaccines (VLP-based) under development:
• Noroviruses:
o Monovalent GI.1 intranasal: 47% efficacy in
o Most common cause of mild gastroenteritis in the
challenge study.
community.
o Bivalent GI.1/GII.4 intramuscular: reduced disease
o Cause traveler’s diarrhea and outbreaks in military
severity; 61.8% efficacy for moderate/severe cases
and institutional settings.
in field study.
o Leading cause of medically attended gastroenteritis
• Challenges: duration of protection, heterotypic protection
in children after rotavirus vaccination.
against emerging strains.
• Sapoviruses: primarily cause gastroenteritis in children.
• Transmission: Rotavirus
o Fecal–oral route; present in vomitus. Etiologic Agent
o Low infectious dose; transmission via aerosol,
• Family Reoviridae; genome: 11 segments of double-strand
fomites, person-to-person.
RNA.
o Viral shedding occurs during acute illness and may
• Triple-layered, nonenveloped icosahedral capsid (75 nm).
persist for weeks post-recovery, prolonged in
• Structural proteins:
immunocompromised.
Pathogenesis o VP6: major protein; determines group specificity
(A–G).
• Attachment may involve human histo-blood group antigens
(HBGA) on gastroduodenal epithelium.
, o VP7 (G-protein) and VP4 (P-protein): serotype o Routine infant immunization in U.S.: >70–80%
specificity, induce neutralizing antibodies. decline in hospitalizations.
• Segmented genome allows genetic reassortment (important o Herd immunity effect observed.
for evolution and vaccine development). • WHO recommends global use (since 2009).
Epidemiology • Low-income countries: moderate efficacy (50–65%), but
• Nearly all children infected by 3–5 years of age. substantial public health benefit.
• Neonatal infections often asymptomatic (maternal • Indian vaccines (Rotavac, Rotasiil) implemented since 2016;
antibodies). WHO prequalified in 2018.
• Severe disease most common in first infections (4–23 months • Surveillance: low risk of intussusception; benefits outweigh
of age). risks.
• Reinfections common; disease severity decreases with each.
• Tropical: year-round; temperate: fall/winter peak. Other Viral Agents of Gastroenteritis
• Pre-vaccine U.S. pattern: seasonal spread from Southwest to Enteric Adenoviruses
Northeast. • Serotypes 40, 41 (subgroup F): 70–80 nm, double-strand
• Post-vaccine changes: declines in hospitalizations, biennial DNA.
activity pattern. • Cause 2–12% of diarrhea in young children.
• Transmission: predominantly fecal–oral; possible person-to- • Types 31, 42–49: diarrhea in HIV-infected or
person or environmental contamination. immunocompromised.
• G serotypes: G1–G4, G9 most common. • Difficult to cultivate; detectable by EIA.
• Group B: epidemics in adults (China, India); Group C: small Astroviruses
proportion of pediatric cases. • 28–30 nm, icosahedral, positive-sense RNA.
Pathogenesis • At least 7 serotypes; serotype 1 most common.
• Infects and destroys mature enterocytes in proximal small • Pediatric pathogen: 2–10% of mild/moderate diarrhea.
intestine villi. • Detected via immunoassays and molecular methods.
• Secretory diarrhea due to: Toroviruses
o Villous epithelial loss. • 100–140 nm, enveloped, positive-strand RNA.
o Crypt cell hyperplasia. • Cause gastroenteritis in horses (Berne virus) and cattle
o Reduced brush-border enzymes → osmotic (Breda virus).
diarrhea. • Human role unclear; associations with nosocomial
• NSP4 protein acts as enterotoxin → secretory diarrhea. gastroenteritis and neonatal necrotizing enterocolitis.
• Enteric nervous system activation may contribute. Picobirnaviruses
• Rotavirus antigenemia and viremia common in children. • Small, bisegmented, double-strand RNA.
Clinical Manifestations • Gastroenteritis in animals; human role unclear.
• Incubation: 1–3 days. • Associations noted in HIV-infected adults.
• Abrupt onset; vomiting often precedes diarrhea. Other viruses
• Fever: up to 1/3 with >39°C. • Enteroviruses, reoviruses, pestiviruses, aichivirus, parvovirus
• Stools: loose, watery; rarely with RBC/WBC. B.
• Duration: 3–7 days. • Diarrhea also reported in respiratory virus infections: SARS-
• Possible associations (causal not proven): SIDS, NEC, CoV, influenza A/H5N1, H1N1.
intussusception, Kawasaki disease, type 1 diabetes.
• Severe disease: immunocompromised children and post-
bone marrow transplant patients.
Immunity
• Secretory IgA in intestine correlates with protection.
• Immunity short-lived; reinfections confer progressively greater
protection.
• Immunologic memory reduces disease severity.
Diagnosis
• Confirmed via EIA, viral RNA detection (gel electrophoresis,
hybridization, PCR).
• Clinically indistinguishable from other enteric viruses.
Treatment
• Early rehydration essential (oral or IV depending on severity).
• Probiotics, bismuth, enkephalinase inhibitors, nitazoxanide:
roles not clearly defined.
• Antibiotics and antimotility agents: avoid.
• Chronic symptomatic disease in immunocompromised may
respond to oral immunoglobulins or colostrum.
Prevention
• Vaccines: RotaTeq (Merck) and Rotarix (GSK) licensed in
2006.
o Efficacy: 85–98% against severe disease.
,204: ENTEROVIRUS, PARECHOVIRUS, AND REOVIRUS • Severe disease occurs in immunodeficient patients,
INFECTIONS especially agammaglobulinemia
C. Epidemiology
I. Enteroviruses • Global distribution
A. Classification and Characterization • Mostly subclinical:
• Family: Picornaviridae o Nonpoliovirus: >50% subclinical
• Named for their ability to replicate in the gastrointestinal tract; o Poliovirus: >90% subclinical
not a prominent cause of gastroenteritis. • Symptomatic infections: nonspecific febrile illness, <1 week
• Human enteroviruses: >115 serotypes: incubation
o Poliovirus: 3 serotypes • Higher incidence:
o Coxsackievirus A: 23 serotypes o Infants, young children, socioeconomically
o Coxsackievirus B: 6 serotypes disadvantaged areas, crowded/tropical regions
o Echovirus: 29 serotypes • Transmission:
o Enteroviruses 68–71 o Fecal–oral, oral–oral
o Novel enteroviruses (starting with 73) identified by o Virus present in stool and throat before and during
molecular techniques symptomatic disease
• Reclassified into four species: A–D o Less common: eye inoculation (EV70), airborne
• Echoviruses 22 and 23 → Parechoviruses 1 and 2 (Coxsackie A21)
• CDC surveillance (2014–2016): most common o Vertical (placenta) transmission: severe neonatal
o Enterovirus D68 (55.9%) disease
o Echovirus 30 o Nosocomial outbreaks in nurseries
o Coxsackievirus A6 o Blood transfusions/insect bites: not documented
o Echovirus 18 • Seasonality:
o Coxsackievirus B3 o Temperate climates: summer/fall
• Structure: o Tropics: no clear seasonal pattern
o Single-stranded RNA genome D. Clinical Features
o Icosahedral capsid (4 viral proteins) 1. Poliovirus Infection
o No lipid envelope • Most infections asymptomatic
o Acid-stable, chlorine-sensitive, resistant to • Minor illness (abortive poliomyelitis): fever, malaise, sore
alcohol/detergents throat, anorexia, myalgia, headache; resolves ~3 days
o Can persist at room temperature for days • Nonparalytic poliomyelitis (aseptic meningitis): 1% of
B. Pathogenesis and Immunity infections
• Infection pathway (based on poliovirus studies): o CSF: lymphocytic pleocytosis, normal glucose,
1. Ingestion → infects GI epithelial cells normal/slightly elevated protein
2. Replicates in tonsils/Peyer’s patches • Paralytic poliomyelitis:
3. Spreads to regional lymph nodes → viremia o Biphasic: aseptic meningitis → recovery → fever &
4. Replication in reticuloendothelial organs paralysis
5. Secondary viremia may occur → symptomatic o Weakness: asymmetric, proximal > distal,
disease commonly legs, arms, bulbar muscles
• CNS invasion: o Bulbar involvement → dysphagia, dysphonia,
o May occur via bloodstream or retrograde axonal respiratory compromise
transport through neuromuscular junction o Risk factors: older age, pregnancy, trauma,
o Poliovirus receptor (immunoglobulin superfamily) is tonsillectomy, IM injections
primate-specific • Vaccine-associated poliomyelitis:
o Experimental evidence: nerve transection prevents o Risk: 1 per 2.5 million OPV doses
CNS spread in animal models o Higher in immunodeficient individuals (~2000×)
• Viral shedding: o Reduced after IPV/OPV regimen changes
o Oropharynx: up to 3 weeks • Postpolio syndrome:
o GI tract: up to 12 weeks o Onset 20–40 years after acute disease
o Hypogammaglobulinemic patients: >20 years o New weakness, fatigue, fasciculations, pain,
o Oral attenuated vaccine may revert to neurovirulent atrophy
phenotype o Slow progression, plateau periods
• Immune response: o Cause: degeneration of compensatory motor
o Humoral immunity critical neurons
▪ IgM: short-term (<6 months) 2. Other Enteroviruses
▪ IgG: lifelong, serotype-specific • Symptomatic disease in the U.S.: 5–10 million/year
▪ VP1 capsid protein: main neutralizing • Neonates: generalized sepsis-like illness; may develop
antibody target myocarditis, hepatitis, DIC, meningitis, pneumonia
o Secretory IgA reduces GI replication and shedding • Aseptic meningitis & encephalitis:
o Cellular immunity: uncertain significance o Children/young adults: 90% of identified cases
o Breast milk IgA protective in neonates o CSF: pleocytosis, lymphocytic shift, normal
glucose, normal/slightly elevated protein
o Neurologic sequelae rare
, • Acute flaccid myelitis: • Glucocorticoids contraindicated
o Fever/respiratory symptoms → flaccid paralysis • Infection control:
(children > adults) o Hand hygiene, gowns, gloves
o CSF: lymphocytic pleocytosis, mildly elevated o Enteric precautions: 7 days post-onset
protein • Vaccines:
o MRI: anterior horn gray matter changes o Inactivated EV71 vaccine: licensed in China
o Enterovirus D68 most frequently detected G. Prevention and Eradication of Poliovirus
o Supportive treatment; persistent deficits common • Historical control:
• Pleurodynia (Bornholm disease): o IPV introduced 1955; OPV 1961
o Fever, spasmodic pleuritic/abdominal pain o Wild-type polio eradicated in Western Hemisphere
o Coxsackievirus B; symptoms resolve in days • Global eradication efforts:
o Treatment: NSAIDs, heat o WHO resolution 1988; wild-type 2 & 3 eradicated in
• Myocarditis & pericarditis: 2015 & 2019
o Commonly Coxsackie B o Americas certified polio-free 1994
o Neonates: severe disease; older children/adults: full o Polio still endemic in Pakistan & Afghanistan (2020)
recovery • Vaccine-derived poliovirus (VDPV):
o ECG: ST/T-wave changes; enzymes elevated o OPV can revert to neurovirulence → outbreaks
o Chronic sequelae: dilated cardiomyopathy, o Cases mostly in
constrictive pericarditis immunocompromised/unvaccinated populations
• Exanthems: o Bivalent OPV (types 1 & 3) replaced trivalent in
o Summer/fall in children 2016; monovalent OPV2 for type 2 outbreaks
o Echovirus 9 & 16: discrete or roseola-like rashes • Vaccination strategies:
• Hand-foot-and-mouth disease (HFMD): o IPV used in industrialized countries; OPV in
o Incubation: 4–6 days; fever, malaise, anorexia developing countries
o Vesicular lesions: buccal mucosa, hands, feet o OPV: intestinal immunity, lower reinfection risk,
o Etiology: Coxsackie A16, Enterovirus 71 cheaper, easy administration
o Severe EV71 complications: CNS disease, o IPV: safe, effective, induces IgG & IgA
myocarditis, pulmonary hemorrhage o Childhood IPV schedule (U.S.): 2, 4, 6–18 months;
• Herpangina: 4–6 years
o Coxsackie A; fever, sore throat, vesicular lesions • Concerns about discontinuing vaccination:
on soft palate/tonsillar pillars/uvula o Long-term shedding by immunocompromised
• Acute hemorrhagic conjunctivitis: persons
o EV70 or Coxsackie A24; eye pain, photophobia, o Vaccine-derived and lab strains remain
watery discharge, subconjunctival hemorrhage o Antivirals/monoclonal antibodies under
o Epidemics: China, India, Japan, Thailand development for persistent excretors
• Other manifestations: mild respiratory illness, pneumonia,
type 1 diabetes (association with islet cell autoantibodies), II. Parechoviruses
parotitis, polymyositis, arthritis, nephritis • Family: Picornaviridae, like enteroviruses
E. Diagnosis • 16 serotypes, common in early childhood
• Culture: • Seasonal patterns:
o Traditional method: stool, throat, nasopharyngeal, o HPeV-1: year-round
CSF, serum, body fluids o Others: summer/fall
o Multiple sites recommended; positive CSF culture • Clinical manifestations:
indicative of disease o Similar to enteroviruses
o Coxsackie A may require special culture conditions o Generalized neonatal disease
• PCR: o Aseptic meningitis, encephalitis, seizures, transient
o Pan-enterovirus primers for CSF, serum, urine, paralysis
stool, throat, tissues o Exanthems, respiratory disease, hepatitis,
o Highly sensitive/specific; rapid gastroenteritis
o Useful in immunodeficient patients • HPeV-1: most common, usually mild
• Serology: • Severe/fatal cases associated with HPeV-1, HPeV-3, HPeV-6
o Limited due to multiple serotypes in infants
o Neutralizing antibodies best for epidemiology • Detection: nasopharynx, stool, respiratory secretions
o IgM: acute or chronic infection • PCR with pan-enterovirus primers does not detect HPeVs
• Identification of serotype: primarily epidemiologic; crucial
during poliovirus suspicion
F. Treatment
• Supportive for mild disease
• IV/Intrathecal immunoglobulin:
o For chronic enteroviral meningoencephalitis in
immunodeficient patients
o High-titer IVIG may reduce viremia in neonates
• Investigational antivirals: pleconaril, pocapavir, vapendavir
o Lesions in upper jejunum: villous blunting, microvilli
Overview shortening, epithelial vacuolization, crypt
• Definition: Acute infectious gastroenteritis is inflammation of hyperplasia, lamina propria infiltration.
the stomach and intestines caused by viral infection. o Malabsorption of carbohydrates/fats; decreased
• Epidemiology: brush-border enzymes.
o Affects persons of all ages worldwide. o Gastric motor delay → nausea, vomiting.
o Leading cause of death among children in • No changes in stomach or colon.
developing countries (~0.5 million deaths annually). Clinical Manifestations
o Responsible for 6–8% of hospitalizations among • Incubation: 12–72 hours (average 24 h).
children in industrialized countries. • Duration: 12–60 h.
o Elderly and immunocompromised individuals are at • Symptoms:
risk for severe complications and death. o Nausea, vomiting (children more frequent),
o Rarely fatal in healthy young adults but incurs abdominal cramps, diarrhea (adults more frequent).
medical and social costs. o Constitutional: headache, fever, chills, myalgias.
• Etiology: • Stools: loose, watery, no blood/mucus/leukocytes.
o Primarily caused by RNA viruses, occasionally by • Labs: usually normal WBC; rare leukocytosis with relative
DNA viruses (e.g., adenovirus types 40 and 41). lymphopenia.
o Characteristic symptoms: acute vomiting and/or • Death: rare; usually from severe dehydration in vulnerable
diarrhea, sometimes with fever, nausea, abdominal populations.
cramps, anorexia, malaise. Immunity
• Clinical distinction: • ~50% of exposed individuals become ill and develop short-
o Viral gastroenteritis vs. bacterial gastroenteritis can term immunity.
be suggested by epidemiology and clinical features, • Genetic predisposition influences susceptibility (HBGA
but laboratory tests are required for confirmation. phenotypes).
• Functional antibodies that block norovirus binding correlate
Human Caliciviruses with protection.
Etiologic Agent • In vitro neutralization demonstrated using human intestinal
• Norwalk virus: prototype strain. enteroid (HIE) systems.
• Characteristics: Diagnosis
o Small (27–40 nm), nonenveloped, icosahedral, • PCR-based detection in stool/vomitus.
round. • Virus-like particles (VLPs) in enzyme immunoassays (EIAs)
o Single positive-strand RNA genome (~7.5 kb). for stool or serology.
o Single virion-associated protein (60 kDa). • Limitations: high antigenic/genetic diversity; mostly research
• Classification: Family Caliciviridae, two genera: or outbreak use; commercial EIAs limited.
o Noroviruses (previously Norwalk-like viruses) Treatment
o Sapoviruses (previously Sapporo-like viruses) • Self-limited illness.
o 35 human-infecting norovirus genotypes in 5 • Oral rehydration therapy sufficient for mild disease.
genogroups (GI, GII, GIV, GVIII, GIX).
• IV fluids if severe dehydration.
Epidemiology
• No specific antiviral therapy available.
• Infections common worldwide; most adults have antibodies.
Prevention
• Earlier antibody acquisition in developing countries (fecal–
• Control of contaminated food/water, exclusion of sick food
oral transmission).
handlers.
• Occur year-round; peaks in cold months in temperate
• Good personal hygiene, disinfection of fomites.
climates.
• Vaccines (VLP-based) under development:
• Noroviruses:
o Monovalent GI.1 intranasal: 47% efficacy in
o Most common cause of mild gastroenteritis in the
challenge study.
community.
o Bivalent GI.1/GII.4 intramuscular: reduced disease
o Cause traveler’s diarrhea and outbreaks in military
severity; 61.8% efficacy for moderate/severe cases
and institutional settings.
in field study.
o Leading cause of medically attended gastroenteritis
• Challenges: duration of protection, heterotypic protection
in children after rotavirus vaccination.
against emerging strains.
• Sapoviruses: primarily cause gastroenteritis in children.
• Transmission: Rotavirus
o Fecal–oral route; present in vomitus. Etiologic Agent
o Low infectious dose; transmission via aerosol,
• Family Reoviridae; genome: 11 segments of double-strand
fomites, person-to-person.
RNA.
o Viral shedding occurs during acute illness and may
• Triple-layered, nonenveloped icosahedral capsid (75 nm).
persist for weeks post-recovery, prolonged in
• Structural proteins:
immunocompromised.
Pathogenesis o VP6: major protein; determines group specificity
(A–G).
• Attachment may involve human histo-blood group antigens
(HBGA) on gastroduodenal epithelium.
, o VP7 (G-protein) and VP4 (P-protein): serotype o Routine infant immunization in U.S.: >70–80%
specificity, induce neutralizing antibodies. decline in hospitalizations.
• Segmented genome allows genetic reassortment (important o Herd immunity effect observed.
for evolution and vaccine development). • WHO recommends global use (since 2009).
Epidemiology • Low-income countries: moderate efficacy (50–65%), but
• Nearly all children infected by 3–5 years of age. substantial public health benefit.
• Neonatal infections often asymptomatic (maternal • Indian vaccines (Rotavac, Rotasiil) implemented since 2016;
antibodies). WHO prequalified in 2018.
• Severe disease most common in first infections (4–23 months • Surveillance: low risk of intussusception; benefits outweigh
of age). risks.
• Reinfections common; disease severity decreases with each.
• Tropical: year-round; temperate: fall/winter peak. Other Viral Agents of Gastroenteritis
• Pre-vaccine U.S. pattern: seasonal spread from Southwest to Enteric Adenoviruses
Northeast. • Serotypes 40, 41 (subgroup F): 70–80 nm, double-strand
• Post-vaccine changes: declines in hospitalizations, biennial DNA.
activity pattern. • Cause 2–12% of diarrhea in young children.
• Transmission: predominantly fecal–oral; possible person-to- • Types 31, 42–49: diarrhea in HIV-infected or
person or environmental contamination. immunocompromised.
• G serotypes: G1–G4, G9 most common. • Difficult to cultivate; detectable by EIA.
• Group B: epidemics in adults (China, India); Group C: small Astroviruses
proportion of pediatric cases. • 28–30 nm, icosahedral, positive-sense RNA.
Pathogenesis • At least 7 serotypes; serotype 1 most common.
• Infects and destroys mature enterocytes in proximal small • Pediatric pathogen: 2–10% of mild/moderate diarrhea.
intestine villi. • Detected via immunoassays and molecular methods.
• Secretory diarrhea due to: Toroviruses
o Villous epithelial loss. • 100–140 nm, enveloped, positive-strand RNA.
o Crypt cell hyperplasia. • Cause gastroenteritis in horses (Berne virus) and cattle
o Reduced brush-border enzymes → osmotic (Breda virus).
diarrhea. • Human role unclear; associations with nosocomial
• NSP4 protein acts as enterotoxin → secretory diarrhea. gastroenteritis and neonatal necrotizing enterocolitis.
• Enteric nervous system activation may contribute. Picobirnaviruses
• Rotavirus antigenemia and viremia common in children. • Small, bisegmented, double-strand RNA.
Clinical Manifestations • Gastroenteritis in animals; human role unclear.
• Incubation: 1–3 days. • Associations noted in HIV-infected adults.
• Abrupt onset; vomiting often precedes diarrhea. Other viruses
• Fever: up to 1/3 with >39°C. • Enteroviruses, reoviruses, pestiviruses, aichivirus, parvovirus
• Stools: loose, watery; rarely with RBC/WBC. B.
• Duration: 3–7 days. • Diarrhea also reported in respiratory virus infections: SARS-
• Possible associations (causal not proven): SIDS, NEC, CoV, influenza A/H5N1, H1N1.
intussusception, Kawasaki disease, type 1 diabetes.
• Severe disease: immunocompromised children and post-
bone marrow transplant patients.
Immunity
• Secretory IgA in intestine correlates with protection.
• Immunity short-lived; reinfections confer progressively greater
protection.
• Immunologic memory reduces disease severity.
Diagnosis
• Confirmed via EIA, viral RNA detection (gel electrophoresis,
hybridization, PCR).
• Clinically indistinguishable from other enteric viruses.
Treatment
• Early rehydration essential (oral or IV depending on severity).
• Probiotics, bismuth, enkephalinase inhibitors, nitazoxanide:
roles not clearly defined.
• Antibiotics and antimotility agents: avoid.
• Chronic symptomatic disease in immunocompromised may
respond to oral immunoglobulins or colostrum.
Prevention
• Vaccines: RotaTeq (Merck) and Rotarix (GSK) licensed in
2006.
o Efficacy: 85–98% against severe disease.
,204: ENTEROVIRUS, PARECHOVIRUS, AND REOVIRUS • Severe disease occurs in immunodeficient patients,
INFECTIONS especially agammaglobulinemia
C. Epidemiology
I. Enteroviruses • Global distribution
A. Classification and Characterization • Mostly subclinical:
• Family: Picornaviridae o Nonpoliovirus: >50% subclinical
• Named for their ability to replicate in the gastrointestinal tract; o Poliovirus: >90% subclinical
not a prominent cause of gastroenteritis. • Symptomatic infections: nonspecific febrile illness, <1 week
• Human enteroviruses: >115 serotypes: incubation
o Poliovirus: 3 serotypes • Higher incidence:
o Coxsackievirus A: 23 serotypes o Infants, young children, socioeconomically
o Coxsackievirus B: 6 serotypes disadvantaged areas, crowded/tropical regions
o Echovirus: 29 serotypes • Transmission:
o Enteroviruses 68–71 o Fecal–oral, oral–oral
o Novel enteroviruses (starting with 73) identified by o Virus present in stool and throat before and during
molecular techniques symptomatic disease
• Reclassified into four species: A–D o Less common: eye inoculation (EV70), airborne
• Echoviruses 22 and 23 → Parechoviruses 1 and 2 (Coxsackie A21)
• CDC surveillance (2014–2016): most common o Vertical (placenta) transmission: severe neonatal
o Enterovirus D68 (55.9%) disease
o Echovirus 30 o Nosocomial outbreaks in nurseries
o Coxsackievirus A6 o Blood transfusions/insect bites: not documented
o Echovirus 18 • Seasonality:
o Coxsackievirus B3 o Temperate climates: summer/fall
• Structure: o Tropics: no clear seasonal pattern
o Single-stranded RNA genome D. Clinical Features
o Icosahedral capsid (4 viral proteins) 1. Poliovirus Infection
o No lipid envelope • Most infections asymptomatic
o Acid-stable, chlorine-sensitive, resistant to • Minor illness (abortive poliomyelitis): fever, malaise, sore
alcohol/detergents throat, anorexia, myalgia, headache; resolves ~3 days
o Can persist at room temperature for days • Nonparalytic poliomyelitis (aseptic meningitis): 1% of
B. Pathogenesis and Immunity infections
• Infection pathway (based on poliovirus studies): o CSF: lymphocytic pleocytosis, normal glucose,
1. Ingestion → infects GI epithelial cells normal/slightly elevated protein
2. Replicates in tonsils/Peyer’s patches • Paralytic poliomyelitis:
3. Spreads to regional lymph nodes → viremia o Biphasic: aseptic meningitis → recovery → fever &
4. Replication in reticuloendothelial organs paralysis
5. Secondary viremia may occur → symptomatic o Weakness: asymmetric, proximal > distal,
disease commonly legs, arms, bulbar muscles
• CNS invasion: o Bulbar involvement → dysphagia, dysphonia,
o May occur via bloodstream or retrograde axonal respiratory compromise
transport through neuromuscular junction o Risk factors: older age, pregnancy, trauma,
o Poliovirus receptor (immunoglobulin superfamily) is tonsillectomy, IM injections
primate-specific • Vaccine-associated poliomyelitis:
o Experimental evidence: nerve transection prevents o Risk: 1 per 2.5 million OPV doses
CNS spread in animal models o Higher in immunodeficient individuals (~2000×)
• Viral shedding: o Reduced after IPV/OPV regimen changes
o Oropharynx: up to 3 weeks • Postpolio syndrome:
o GI tract: up to 12 weeks o Onset 20–40 years after acute disease
o Hypogammaglobulinemic patients: >20 years o New weakness, fatigue, fasciculations, pain,
o Oral attenuated vaccine may revert to neurovirulent atrophy
phenotype o Slow progression, plateau periods
• Immune response: o Cause: degeneration of compensatory motor
o Humoral immunity critical neurons
▪ IgM: short-term (<6 months) 2. Other Enteroviruses
▪ IgG: lifelong, serotype-specific • Symptomatic disease in the U.S.: 5–10 million/year
▪ VP1 capsid protein: main neutralizing • Neonates: generalized sepsis-like illness; may develop
antibody target myocarditis, hepatitis, DIC, meningitis, pneumonia
o Secretory IgA reduces GI replication and shedding • Aseptic meningitis & encephalitis:
o Cellular immunity: uncertain significance o Children/young adults: 90% of identified cases
o Breast milk IgA protective in neonates o CSF: pleocytosis, lymphocytic shift, normal
glucose, normal/slightly elevated protein
o Neurologic sequelae rare
, • Acute flaccid myelitis: • Glucocorticoids contraindicated
o Fever/respiratory symptoms → flaccid paralysis • Infection control:
(children > adults) o Hand hygiene, gowns, gloves
o CSF: lymphocytic pleocytosis, mildly elevated o Enteric precautions: 7 days post-onset
protein • Vaccines:
o MRI: anterior horn gray matter changes o Inactivated EV71 vaccine: licensed in China
o Enterovirus D68 most frequently detected G. Prevention and Eradication of Poliovirus
o Supportive treatment; persistent deficits common • Historical control:
• Pleurodynia (Bornholm disease): o IPV introduced 1955; OPV 1961
o Fever, spasmodic pleuritic/abdominal pain o Wild-type polio eradicated in Western Hemisphere
o Coxsackievirus B; symptoms resolve in days • Global eradication efforts:
o Treatment: NSAIDs, heat o WHO resolution 1988; wild-type 2 & 3 eradicated in
• Myocarditis & pericarditis: 2015 & 2019
o Commonly Coxsackie B o Americas certified polio-free 1994
o Neonates: severe disease; older children/adults: full o Polio still endemic in Pakistan & Afghanistan (2020)
recovery • Vaccine-derived poliovirus (VDPV):
o ECG: ST/T-wave changes; enzymes elevated o OPV can revert to neurovirulence → outbreaks
o Chronic sequelae: dilated cardiomyopathy, o Cases mostly in
constrictive pericarditis immunocompromised/unvaccinated populations
• Exanthems: o Bivalent OPV (types 1 & 3) replaced trivalent in
o Summer/fall in children 2016; monovalent OPV2 for type 2 outbreaks
o Echovirus 9 & 16: discrete or roseola-like rashes • Vaccination strategies:
• Hand-foot-and-mouth disease (HFMD): o IPV used in industrialized countries; OPV in
o Incubation: 4–6 days; fever, malaise, anorexia developing countries
o Vesicular lesions: buccal mucosa, hands, feet o OPV: intestinal immunity, lower reinfection risk,
o Etiology: Coxsackie A16, Enterovirus 71 cheaper, easy administration
o Severe EV71 complications: CNS disease, o IPV: safe, effective, induces IgG & IgA
myocarditis, pulmonary hemorrhage o Childhood IPV schedule (U.S.): 2, 4, 6–18 months;
• Herpangina: 4–6 years
o Coxsackie A; fever, sore throat, vesicular lesions • Concerns about discontinuing vaccination:
on soft palate/tonsillar pillars/uvula o Long-term shedding by immunocompromised
• Acute hemorrhagic conjunctivitis: persons
o EV70 or Coxsackie A24; eye pain, photophobia, o Vaccine-derived and lab strains remain
watery discharge, subconjunctival hemorrhage o Antivirals/monoclonal antibodies under
o Epidemics: China, India, Japan, Thailand development for persistent excretors
• Other manifestations: mild respiratory illness, pneumonia,
type 1 diabetes (association with islet cell autoantibodies), II. Parechoviruses
parotitis, polymyositis, arthritis, nephritis • Family: Picornaviridae, like enteroviruses
E. Diagnosis • 16 serotypes, common in early childhood
• Culture: • Seasonal patterns:
o Traditional method: stool, throat, nasopharyngeal, o HPeV-1: year-round
CSF, serum, body fluids o Others: summer/fall
o Multiple sites recommended; positive CSF culture • Clinical manifestations:
indicative of disease o Similar to enteroviruses
o Coxsackie A may require special culture conditions o Generalized neonatal disease
• PCR: o Aseptic meningitis, encephalitis, seizures, transient
o Pan-enterovirus primers for CSF, serum, urine, paralysis
stool, throat, tissues o Exanthems, respiratory disease, hepatitis,
o Highly sensitive/specific; rapid gastroenteritis
o Useful in immunodeficient patients • HPeV-1: most common, usually mild
• Serology: • Severe/fatal cases associated with HPeV-1, HPeV-3, HPeV-6
o Limited due to multiple serotypes in infants
o Neutralizing antibodies best for epidemiology • Detection: nasopharynx, stool, respiratory secretions
o IgM: acute or chronic infection • PCR with pan-enterovirus primers does not detect HPeVs
• Identification of serotype: primarily epidemiologic; crucial
during poliovirus suspicion
F. Treatment
• Supportive for mild disease
• IV/Intrathecal immunoglobulin:
o For chronic enteroviral meningoencephalitis in
immunodeficient patients
o High-titer IVIG may reduce viremia in neonates
• Investigational antivirals: pleconaril, pocapavir, vapendavir
