Norwalk-like virus-associated gastroenteritis in a large, high-density encampment--Virginia, July 2001.
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Caliciviridae Infections↗
Biomedical subjects
J S Bresee
Publications and source records attributed to J S Bresee.
Multistate outbreak of Norwalk-like virus gastroenteritis associated with a common caterer.
In February 2000, an outbreak of gastroenteritis occurred among employees of a car dealership in New York. The same meal was also supplied to 52 dealerships nationwide, and 13 states reported illness at dealerships where the banquet was served. A retrospective cohort study was conducted to identify risk factors associated with the illness. Stool samples were collected to detect Norwalk-like virus, and sera were drawn and tested for immunoglobulin A antibodies to the outbreak strain. By univariate analysis, illness was significantly associated with consumption of any of four salads served at the banquet (relative risk = 3.8, 95% confidence interval: 2.5, 5.6). Norwalk-like virus was detected by reverse transcription-polymerase chain reaction assay in 32 of 59 stool samples from eight states. Nucleotide sequences of a 213-base pair fragment from 16 stool specimens collected from cases in eight states were identical, confirming a common source outbreak. Two of 15 workers at caterer A had elevated immunoglobulin A titers to an antigenically related Norwalk-like virus strain. This study highlights the value of molecular techniques to complement classic epidemiologic methods in outbreak investigations and underscores the critical role of food handlers in the spread of foodborne disease associated with Norwalk-like virus.
Adolescent↗
Rotavirus vaccine and intussusception. Where do we go from here?
Since the discovery of rotavirus in 1973, vaccine technology has moved from the use of monovalent attenuated animal rotavirus strains to the development of multivalent human-animal reassortment vaccines. The first licensed vaccine, a rhesus-human tetravalent vaccine, was licensed in 1998. This vaccine was withdrawn from the market a year later when it was noted that administration of vaccine was associated with an increased risk of intussusception. The future of rotavirus vaccine is dependent on the reasons for this association that have yet to be discovered.
Animals↗
Cost of diarrhea-associated hospitalizations and outpatient visits in an insured population of young children in the United States.
OBJECTIVE: To assess the financial and clinical burden of diarrhea- and rotavirus-associated disease among a population of privately insured US children. METHODS: For the period 1993 through 1996, we analyzed medical claims data from a large, administrative database containing information on approximately 300,000 children <5 years of age to examine trends in, and costs associated, with hospitalizations and outpatient visits for diarrhea. RESULTS: An annual average of 1,186 diarrhea-associated hospitalizations (35 per 10,000 children <5 years) and 33 386 outpatient visits (943 per 10,000 children <5 years) were reported, accounting for 4% of all hospitalizations and 2% of all outpatient visits among children <5 years of age. Diarrhea-associated hospitalizations and outpatient visits showed a distinct winter-spring peak consistent with that of rotavirus infection. The excess of diarrhea-associated events occurring during the winter-spring peak accounted for an average of 50% of all diarrhea-associated hospitalizations and 18% of all diarrhea-associated outpatient visits. The median cost (in 1998 constant dollars) of a diarrhea-associated hospitalization was $2,307, and that for a rotavirus-associated hospitalization was $2,303. Median costs of diarrhea- and rotavirus-associated outpatient visits were $47 and $57, respectively. CONCLUSIONS: Diarrhea is an important cause of morbidity in this insured population of young children. The epidemiologic features of diarrhea-associated events suggest that rotavirus is an important contributor to the overall morbidity from diarrhea. These disease burden and cost estimates should provide useful information with which to assess the costs and benefits of future interventions for rotavirus-associated illness.
Child, Preschool↗
Safety and immunogenicity of tetravalent rhesus-based rotavirus vaccine in Bangladesh.
BACKGROUND: Rotavirus is the most common cause of severe gastroenteritis among children worldwide. OBJECTIVES: To compare the safety, immunogenicity and shedding patterns of rhesus rotavirus (RRV)-tetravalent vaccine vs. placebo among infants in rural Bangladesh. METHODS: A double blinded, placebo-controlled trial was conducted in which infants (n = 120) were randomly assigned to receive three doses of either vaccine or placebo administered at approximately 6, 10 and 14 weeks of age together with routine immunizations. Data on possible adverse effects of vaccinations were collected daily for 7 days after each dose. Stool samples were collected after each dose, and serum samples were obtained before the first and after the third vaccination. RESULTS: Fever (> or = 38 degrees C), as measured by study assistants, was noted more frequently among vaccinees (15%) than among placebo recipients (2%) during the 7 days after vaccination but was not reported more frequently by parents of vaccinees vs. placebo recipients. Overall 87% of vaccinees had an antibody response (measured by IgA or anti-RRV-neutralizing antibodies) after vaccination compared with 32% of placebo recipients. Rates of seroconversion were higher among subjects with lower levels of prevaccination antibodies and those who shed rotavirus after vaccination. Vaccine strain viruses were detected in stools from placebo vaccine recipients who had evidence of IgA seroconversion. CONCLUSIONS: In this population RRV-tetravalent vaccine was comparably immunogenic and safe as in trials conducted in developed countries, where this vaccine has been proved effective in preventing severe rotavirus diarrhea. These data support continued evaluation of rotavirus vaccines in developing countries.
Antibodies, Viral↗
Molecular and serologic characterization of novel serotype G8 human rotavirus strains detected in Blantyre, Malawi.
During a 2-year study of diarrhea among children in Blantyre, Malawi, greater than 50% of rotavirus strains genotyped by using reverse transcription-polymerase chain reaction possessed previously unrecognized combinations of the neutralization proteins VP7 and VP4. Serotype G8 rotaviruses, which have been identified recently in several African countries, were found to possess P[4] or P[6] VP4 genotype specificity. Two of these short electropherotype rotaviruses were further investigated: these comprised a P[6], G8 representative strain (MW23) and a P[4], G8 representative strain (MW333). The VP7 gene sequences of both strains exhibited greatest homology to human and animal serotype G8 rotaviruses. Sequence analysis of the VP4 gene of MW23 indicated closest identity to the P2A[6], G9 strain US1205 from the United States. The VP4 gene of MW333 was most closely related to the P[4], G12 strain L26 isolated in the Philippines and the Australian P[4], G2 strain RV-5. The NSP4 gene sequences of both strains were classified in NSP4 genetic group I. RNA-RNA hybridization demonstrated that each of these two strains is related to the DS-1 genogroup of human rotaviruses. Subgroup analysis and virus neutralization confirmed complete antigenic characterization of MW23 as subgroup I, P2A[6], G8 and MW333 as subgroup I, P1B[4], G8. The similarity of the VP7 gene sequences of the prototype strains described in this report to bovine serotype G8 rotaviruses suggests that they may represent human/bovine reassortant viruses.
Animals↗
Risk of influenza A (H5N1) infection among health care workers exposed to patients with influenza A (H5N1), Hong Kong.
The first outbreak of avian influenza A (H5N1) occurred among humans in Hong Kong in 1997. To estimate the risk of person-to-person transmission, a retrospective cohort study was conducted to compare the prevalence of H5N1 antibody among health care workers (HCWs) exposed to H5N1 case-patients with the prevalence among nonexposed HCWs. Information on H5N1 case-patient and poultry exposures and blood samples for H5N1-specific antibody testing were collected. Eight (3.7%) of 217 exposed and 2 (0.7%) of 309 nonexposed HCWs were H5N1 seropositive (P=.01). The difference remained significant after controlling for poultry exposure (P=.01). This study presents the first epidemiologic evidence that H5N1 viruses were transmitted from patients to HCWs. Human-to-human transmission of avian influenza may increase the chances for the emergence of a novel influenza virus with pandemic potential.
Adult↗
Cold weather seasonality of gastroenteritis associated with Norwalk-like viruses.
Norwalk-like viruses (NLVs) are the most common cause of acute nonbacterial gastroenteritis in adults, but little is known about their seasonality. The lack of specific diagnostic tools impeded study of these viruses in the past, and surveys using electron microscopy often grouped NLVs with other unrelated viruses. A search of the scientific literature found eight surveys of gastroenteritis, which were conducted for at least 1 year, that specifically identified NLVs. Unpublished data from laboratories of 4 NLV researchers were also used. These surveys, which were conducted in eight countries, reported sporadic cases and outbreaks of NLV-associated gastroenteritis among all age groups. The monthly occurrence of these cases and outbreaks was plotted, and while transmission occurred year-round in most surveys, a cold weather peak was demonstrated in 11 of the 12 studies. This key epidemiologic feature of the viruses has important implications concerning their mode of transmission and for understanding the etiology of acute gastroenteritis in adults.
Adult↗
The epidemiology of enteric caliciviruses from humans: a reassessment using new diagnostics.
In the United States, acute gastroenteritis is one of the most commonly noted illnesses on hospital discharge records and death certificates, yet few of these cases have an etiologic diagnosis. The application of new molecular diagnostic methods has shown caliciviruses (previously referred to as the Norwalk family of viruses or small round structured viruses) to be the most common cause of acute gastroenteritis (AGE) outbreaks in the United States, and they may emerge as a common cause of sporadic cases of AGE among both children and adults. Novel molecular methods have permitted outbreak strains to be traced back to their common source and have led to the first identification of virus in implicated vehicles of infection-water, shellfish, and foods contaminated both at their source and by food handlers. The broad application of these methods to routine diagnosis in hospitals and public health laboratories is advancing our appreciation of the full burden of calicivirus-associated diarrhea, and it is opening new avenues for its prevention and control.
Acute Disease↗
Surveillance of rotavirus strains in the United States: identification of unusual strains. The National Rotavirus Strain Surveillance System collaborating laboratories.
Rotavirus strains from 964 fecal specimens collected from children at 11 U.S. hospital laboratories from November 1997 to March 1998 and from samples collected at 12 laboratories from November 1998 to March 1999 were typed for G and P proteins. Serotype G1 was the predominant serotype in 1997-1998 (88%), followed by G2 (6.2%), G9 (3.3%), and G3 (1.5%). This pattern was similar to that seen in 1998-1999: G1 (79%), G2 (15%), G9 (3.0%), G4 (1.6%), and G3 (0.3%). Novel P[9] strains were identified in both seasons, and analysis of a 364-nucleotide fragment from gene segment 4 of one of the strains demonstrated 97.3% nucleotide identity with the prototype P3[9],G3 strain, AU1, isolated in Japan. This is the first report of a human AU1-like strain in the United States. These results reinforce our initial findings that serotype G9 persists in the United States but has not become a predominant strain and that the common serotypes G1 to G4 account for almost 90% of strains in circulation. Other uncommon strains exist in the United States but may have been overlooked before because of their low prevalence and the use of inadequate diagnostic tools.
Child↗
Rotavirus vaccines and vaccination in Latin America.
Worldwide, rotaviruses account for more than 125 million cases of infantile gastroenteritis and nearly 1 million deaths per year, mainly in developing countries. Rather than other control measures, vaccination is most likely to have a major impact on rotavirus disease incidence. The peak incidence of rotavirus diarrhea occurs between 6 and 24 months of age. In developing countries, however, cases are not uncommon among children younger than 6 months. G serotypes 1 to 4 are responsible for most disease, but there are indications that in Brazil that G type 5 is of emerging epidemiological importance. Both homotypic and heterotypic responses are elicited during natural rotavirus infection, and the immunological response at the intestinal mucosal surface is probably the more consistent predictor of clinical immunity. With the primary objective of protecting children against life-threatening dehydrating diarrhea, many approaches to rotavirus vaccine development have been attempted. One vaccine, the tetravalent rhesus-human reassortant rotavirus vaccine (RRV-TV), was given licensing approval in the United States of America, introduced to the market, and later withdrawn. A number of studies have found better efficacy of RRV-TV in developed countries than in developing ones. Field trials with a 4 x 10(4) plaque-forming units (PFU) preparation of RRV-TV have been carried out in two countries in Latin America, Brazil and Peru. Those trials yielded protective efficacy rates against all rotavirus diarrhea ranging from 18% to 35%. Data from a large catchment trial in Venezuela with a higher RRV-TV dose, of 4 x 10(5) PFU/dose, indicated an efficacy rate of 48% against all rotavirus diarrhea and 88% against severe rotavirus diarrhea. It appears that breast-feeding does not compromise the efficacy of RRV-TV if three doses of the vaccine are administered. Similarly, possible interference of oral poliovirus vaccine with the "take" of the rotavirus vaccine can be overcome by giving three doses of the rotavirus vaccine or by using a higher-titer formulation of it. Wild enteroviruses, however, may cause primary rotavirus vaccine failure in developing countries. Studies in Peru with RRV-TV have shown a trend towards higher vaccine efficacy rates against "pure" (rotavirus-only) diarrheal episodes. Economic analyses made in the United States indicate that a vaccine that costs less than US$ 9 per dose would lead to a net savings in medical costs. To date, however, cost-benefit studies have not been done in developing countries. In the future, it is possible that some Latin American countries might adapt their polio production facilities to the preparation of rotavirus vaccines for human use. A year after RRV-TV was licensed for vaccination of infants in the United States, the occurrence of intussusception as an adverse event led to the vaccine's withdrawal from the market. The implications of that action, particularly for Latin America, will be addressed in this article, including the need to explore alternative rotavirus candidate vaccines, particularly through the conduct of parallel clinical trials in both developed and developing countries.
Animals↗
Reye's syndrome in the United States from 1981 through 1997.
BACKGROUND: Reye's syndrome is characterized by encephalopathy and fatty degeneration of the liver, usually after influenza or varicella. Beginning in 1980, warnings were issued about the use of salicylates in children with those viral infections because of the risk of Reye's syndrome. METHODS: To describe the pattern of Reye's syndrome in the United States, characteristics of the patients, and risk factors for poor outcomes, we analyzed national surveillance data collected from December 1980 through November 1997. The surveillance system is based on voluntary reporting with the use of a standard case-report form. RESULTS: From December 1980 through November 1997 (surveillance years 1981 through 1997), 1207 cases of Reye's syndrome were reported in patients less than 18 years of age. Among those for whom data on race and sex were available, 93 percent were white and 52 percent were girls. The number of reported cases of Reye's syndrome declined sharply after the association of Reye's syndrome with aspirin was reported. After a peak of 555 cases in children reported in 1980, there have been no more than 36 cases per year since 1987. Antecedent illnesses were reported in 93 percent of the children, and detectable blood salicylate levels in 82 percent. The overall case fatality rate was 31 percent. The case fatality rate was highest in children under five years of age (relative risk, 1.8; 95 percent confidence interval, 1.5 to 2.1) and in those with a serum ammonia level above 45 microg per deciliter (26 micromol per liter) (relative risk, 3.4; 95 percent confidence interval, 1.9 to 6.2). CONCLUSIONS: Since 1980, when the association between Reye's syndrome and the use of aspirin during varicella or influenza-like illness was first reported, there has been a sharp decline in the number of infants and children reported to have Reye's syndrome. Because Reye's syndrome is now very rare, any infant or child suspected of having this disorder should undergo extensive investigation to rule out the treatable inborn metabolic disorders that can mimic Reye's syndrome.
Adolescent↗
Current status and future priorities for rotavirus vaccine development, evaluation and implementation in developing countries.
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Developing Countries↗
Trends in hospitalizations associated with gastroenteritis among adults in the United States, 1979-1995.
Gastroenteritis (GE) is among the most common illnesses of humans but the burden of disease, its epidemiology, and the distribution of pathogens in adults have not been fully examined. This information is needed to plan prevention strategies particularly for high-risk groups. This study is a retrospective analysis of data from the National Hospital Discharge Survey for the years 1979 through 1995 which describes the disease burden and epidemiology of hospitalizations associated with GE among adults in the United States. Diarrhoea was listed as a diagnosis on an average of 452,000 hospital discharges per year representing 1.5% of all hospitalizations among adults. The annual number of GE hospitalizations has decreased by 20% from approximately 500,000 in 1979 to 400,000 in 1995. The aetiology of 78% of cases coded as GE was undetermined. Until the aetiology of disease can be better established, specific strategies for prevention cannot be developed.
Adult↗
An outbreak of acute gastroenteritis in a geriatric long-term-care facility: combined application of epidemiological and molecular diagnostic methods.
OBJECTIVE: To assess possible transmission modes of, and risk factors for, gastroenteritis associated with Norwalk-like viruses (NLVs) in a geriatric long-term-care facility. METHODS: During a prolonged outbreak of acute gastroenteritis, epidemiological data on illness among residents and employees were collected in conjunction with stool, vomitus, and environmental specimens for viral testing. NLVs were identified by electron microscopy in stool and vomitus specimens, and further characterized by reverse-transcriptase polymerase chain reaction and nucleotide sequencing. Potential risk factors were examined through medical-record review, personal interview, and a self-administered questionnaire sent to all employees. RESULTS: During the outbreak period, 52 (57%) of 91 residents and 34 (35%) of 90 employees developed acute gastroenteritis. Four case-residents were hospitalized; three residents died at the facility shortly after onset of illness. A point source was not identified; no association between food or water consumption and gastroenteritis was identified. A single NLV strain genetically related to Toronto virus was the only pathogen identified. Residents were at significantly higher risk of gastroenteritis if they were physically debilitated (relative risk [RR], 3.5; 95% confidence interval [CI95], 1.0-12.9), as were employees exposed to residents with acute gastroenteritis (RR, 2.6; CI95, 1.1-6.5) or ill household members (RR, 2.3; CI95, 1.4-3.6). Adherence to infection control measures among the nursing staff may have reduced the risk of gastroenteritis, but the reduction did not reach statistical significance. CONCLUSIONS: In the absence of evidence for food-borne or waterborne transmission, NLVs likely spread among residents and employees of a long-term-care facility through person-to-person or airborne droplet transmission. Rapid notification of local health officials, collection of clinical specimens, and institution of infection control measures are necessary if viral gastroenteritis transmission is to be limited in institutional settings.
Adult↗
First rotavirus vaccine licensed: is there really a need?
The first rotavirus vaccine was licensed in the United States on 31 August 1998 for the prevention of severe rotavirus diarrhea in children. Despite this landmark in new vaccines, many pediatricians and public health professionals in Europe are uncertain of the need for this vaccine for the routine immunization of infants. In Europe, ample evidence suggests that rotavirus is the most common cause of hospitalizations for severe diarrhea among children, but proper studies documenting the disease burden of rotavirus or the cost-effectiveness of a rotavirus immunization program have only been conducted in the United Kingdom following epidemiologic models used in the United States. All children are infected with rotavirus during their first few years of life, 30-50% of diarrheal hospitalizations among children <5 years are due to this agent, and, by the age of 5 years, between 1 in 40 and 1 in 77 children in Europe and the United States may be hospitalized for rotavirus. The first vaccine is a live, oral preparation combining four different serotypes of rotavirus and administered in three doses with other childhood immunizations. The good efficacy against severe rotavirus diarrhea, the low risk of adverse side effects and the positive cost-effectiveness equation have led the two major immunization advisory groups in the U.S. to recommend this vaccine for routine use in American infants. European physicians and policy-makers should re-examine the epidemiology and disease burden of rotavirus diarrhea now that an effective method of prevention is at hand.
Child↗
Rotavirus G and P types in children with acute diarrhea in Blantyre, Malawi, from 1997 to 1998: predominance of novel P[6]G8 strains.
One hundred rotavirus strains detected in children with acute diarrhea in Blantyre, Malawi, between July 1997 and January 1998 were characterized for G (VP7) and P (VP4) types by using multiplex, heminested, reverse transcription-polymerase chain reaction. A novel P[6]G8 rotavirus strain was identified in 42% of the specimens. The remaining strains comprised P[8]G3 (20%), P[6]G3 (10%), P[4]G8 (9%), P[6]G9 (3%), P[8]G4 (2%), P[6]G4 (2%), and P[4]G3 (1%). Rotavirus strains with mixed G or P types were identified in 2% of the specimens. Nine percent of the strains were nontypeable with the primers used. The P[6] genotype was identified in 57% of strains overall. This first description of serotype G8 rotavirus as a predominant strain has important implications for vaccine development in Africa. The finding of novel P/G combinations (P[6]G8 and P[4]G8) highlights the extraordinary diversity of rotaviruses in some countries.
Acute Disease↗
Cost-effectiveness analysis of a rotavirus immunization program for the United States.
CONTEXT: Rotavirus is the most common cause of severe diarrhea in children, and a live, oral vaccine may soon be licensed for prevention. OBJECTIVE: To estimate the economic impact of a national rotavirus immunization program in the United States. DESIGN: Cost-effectiveness was analyzed from the perspectives of the health care system and society. A decision tree used estimates of disease burden, costs, vaccine coverage, efficacy, and price obtained from published and unpublished sources. INTERVENTION: The proposed vaccine would be administered to infants at ages 2, 4, and 6 months as part of the routine schedule of childhood immunizations. MAIN OUTCOME MEASURES: Total costs, outcomes prevented, and incremental cost-effectiveness. RESULTS: A routine, universal rotavirus immunization program would prevent 1.08 million cases of diarrhea, avoiding 34000 hospitalizations, 95000 emergency department visits, and 227000 physician visits in the first 5 years of life. At $20 per dose, the program would cost $289 million and realize a net loss of $107 million to the health care system-$103 per case prevented. The program would provide a net savings of $296 million to society. Threshold analysis identified a break-even price per dose of $9 for the health care system and $51 for the societal perspective. Greater disease burden and greater vaccine efficacy and lower vaccine price increased cost-effectiveness. CONCLUSIONS: A US rotavirus immunization program would be cost-effective from the perspectives of society and the health care system, although the cost of the immunization program would not be fully offset by the reduction in health care cost of rotavirus diarrhea unless the price fell to $9 per dose.
Child↗