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PubMed2001

Epidemiology of rotavirus in India.

Rotavirus is the leading cause of childhood diarrhea worldwide, causing an estimated 600,000 deaths each year. To assess the potential benefits of a national rotavirus immunization program in India, we analyzed 40 published studies of rotavirus that were conducted between 1976 and 1997 and included a total of approximately 13,000 Indian pediatric inpatients. Pediatric studies featuring 100 or more patients and lasting at least 12 months in duration and all neonatal studies were analyzed. Rotavirus was detected in a median of 18% of pediatric patients and 28% of neonates surveyed. Fifty percent of all children hospitalized with rotavirus by age 5 were hospitalized by the age of 6 months, 75% by the age of 9 months, and almost 100% by the age of 2 years. Rotavirus was most prevalent (31%) in children between 7 and 12 months of age, followed by children between 1 and 2 years of age (20%), and children < 7 months of age (13%). VP7 genotypes G1 and G2 were most commonly isolated although significant heterogeneity of serotypes was observed. P[11], G9 strains were most frequently isolated among neonates. In 1998; approximately 98,000 childhood deaths were caused by rotavirus. These data underscore the urgent need for safe and effective interventions against rotavirus such as vaccines. The significant diversity of rotavirus strains and young age of hospitalization pose unique challenges to the formulation of a rotavirus immunization program in India, but raise the possibility of utilizing a neonatal vaccine to provide effective coverage.

Child, Preschool↗
PubMed2003

Possible mechanisms of protection elicited by candidate rotavirus vaccines as determined with the adult mouse model.

Rotaviruses cause extensive morbidity and mortality worldwide each year, supporting the need for a vaccine that is effective against rotavirus disease in all socioeconomic environments. Vaccines evaluated in clinical trials have all been live viruses that are delivered orally to mimic the excellent protection against severe rotavirus disease consistently observed after natural infection. The mechanisms by which either these vaccine candidates or natural rotavirus infections elicit protection are poorly understood. Therefore, it is not surprising that several of these candidate vaccines have provided little or no protection and have been discontinued. Two candidate vaccines are presently in phase III trials. These two were developed on the basis of very different views regarding the importance of one specific immune effector, that is, serotype-specific neutralizing antibody. One of these candidates (RotaTeq) is composed of five bovine/human reassortant rotavirus strains containing neutralization proteins representative of dominant human serotypes. The other candidate (Rotarix) is composed of only a single strain of human rotavirus. Very recent data obtained with Rotarix support the suggestion that factors other than neutralizing antibody can play important roles in protection against rotavirus disease after live rotavirus immunization. These results must be confirmed in subsequent studies in different locales with circulating rotaviruses belonging to a variety of serotypes in order to establish there overall applicability. Mechanisms by which rotavirus immunization with live viruses or other immunogens elicit protection have been most extensively examined in an adult mouse model and were reported to be multi-factorial. That is, CD8 and CD4 T cells as well as B cells were all found to play significant roles. The importance of each lymphocyte population as effectors of protection was found to be dependent on the immunogen and the route of immunization. The results of studies in the adult mouse model that appear to be most pertinent to the present vaccine candidates are presented and discussed.

Animals↗
PubMed1995

Evaluation of the protective efficacy of a serotype 1 bovine-human rotavirus reassortant vaccine in infants.

The objective of this study was to evaluate the efficacy of a live, attenuated bovine (strain WC3) x human (strain WI79, serotype G1) rotavirus reassortant (WI79-9) virus vaccine for prevention of symptomatic rotavirus gastroenteritis in infants. The study was a prospective, randomized, double-blind, placebo-controlled trial, conducted over a single rotavirus season in 325 infants who were 2 to 8 months old at enrollment. Subjects were randomized to receive either placebo or WI79-9 virus vaccine at 10(7.3) plaque-forming units in three oral doses each separated by 2 months. Subjects were followed for 7 days after each dose for occurrence of adverse events and during the subsequent winter for development of rotavirus gastroenteritis. Administration of WI79-9 virus vaccine was well-tolerated, and the rates of low grade fever after each dose were no higher in vaccine recipients (8 to 21%) than in placebo recipients (14 to 19%). The protective efficacy of the WI79-9 vaccine during a subsequent epidemic of predominantly serotype G1 rotavirus was 87.0% (95% confidence limits, 62.6 to 95.5%) against relatively severe rotavirus gastroenteritis (rotavirus gastroenteritis with a clinical severity score of > 8) and was 64.1% (95% confidence limits 35.9 to 79.9%) against all symptomatic rotavirus episodes. The WI79-9 vaccine was safe and effective in prevention of homotypic human rotavirus infection in infants. Further studies of reassortant vaccines based on the bovine WC3 rotavirus should be performed.

Confidence Intervals↗
PubMed2005

Nonmedical costs associated with rotavirus disease requiring hospitalization.

BACKGROUND: As the most common cause of severe diarrhea among children, rotavirus has a significant economic impact. Previous studies focused on the direct medical costs of rotavirus infections; however, nonmedical costs account for the majority of the financial burden from this disease. Herein, we report the results from the largest prospective study in the United States determining the nonmedical costs of severe rotavirus infections. METHODS: Prospective, active, gastroenteritis case surveillance was conducted between November 1997 and December 1999 at 3 pediatric medical centers. Rotavirus infection was identified for 548 children admitted between 2 weeks and 5 years of age. Detailed information about nonmedical costs during the prehospitalization, hospitalization and posthospitalization periods was obtained through interviews. RESULTS: The average nonmedical cost per case of rotavirus disease was USD $448.77, including $359.04 for missed work, $56.66 for transportation, $11.90 for oral rehydration solutions, $9.59 for diapers, $6.83 for child care changes, $3.82 for special foods and $0.93 for formula changes. More than one-half of these expenses (53%) occurred outside the hospitalization period, and 80% of the cost was attributable to missed work. CONCLUSIONS: With an estimated 50,000 hospitalizations attributable to rotavirus each year in the United States, the nonmedical costs of severe rotavirus infections may exceed USD $22 million annually. Previous cost effectiveness analyses of rotavirus vaccines substantially underestimated this burden, suggesting that the nonmedical costs associated with mild to moderate rotavirus disease have been similarly underestimated. These findings are needed to assess accurately the cost effectiveness of future rotavirus immunization strategies.

Antigens, Viral↗
PubMed1988

The present status of rotavirus vaccine development.

Rotavirus infection is one of the most important causes of morbidity in young children throughout the world. The high associated mortality in Southeast Asia (and elsewhere) warrants the development of a vaccine. It is probable that most of the life-threatening watery diarrhoea due to rotavirus infection occurs as a result of primary infection in children aged 6-18 months after protection due to maternal antibody has diminished. Thus rotavirus vaccines are targeted at young infants from birth to 3 months of age. At present three candidate rotavirus vaccines (RIT-4237, MMU-18007, WC3) have undergone trials in young children. A bovine rotavirus strain (RIT-4237), was shown to be safe, immunogenic and efficacious in prevention of severe rotavirus diarrhoea in young children in Finland. However it was found to be weakly immunogenic in infants in developing countries, and to have only low efficacy in prevention of disease. A simian rotavirus strain (RRV, MMU-18006) has proved to be highly immunogenic and its reactinogenicity to be diminished by pre-existing maternal antibody (in infants aged 1-4 months). It has high efficacy against clinically severe rotavirus infection. However protection is homotypic against human serotype 3 only so that eventually a multivalent vaccine incorporating reassortant rotavirus strains that protect against human serotypes 1, 2, 4 (and other newer serotypes) may be required. It is hoped that, once safe immunogenic and protective candidate rotavirus vaccines are identified, they can be administered in an acceptable form with no alteration to existing immunization schedules.

Adult↗
PubMed2003

A review of rotavirus diarrhea in Pakistan: how much do we know?

INTRODUCTION: Rotavirus diarrhea has a worldwide distribution, infecting almost all children by the age of 3-5 years. EPIDEMIOLOGY: A comparable etiological 2-year survey carried out by the W.H.O Diarrheal Disease control (CDD) Program in 1991, in a multicenter study in 5 developing countries including Pakistan revealed that Rotavirus was found to be the most frequently detected pathogen in diarrheal episodes, during the first year of life, with the highest incidence (20%) occurring among 6-11 months old. Two other studies done in Pakistan, in under five children done in Lahore (between 1985 and 1991) and Rawalpindi (between May 1983 and April 1984) showed that Rotavirus was the second most common Diarrhea causing enteric pathogen following E.Coli TRANSMISSION: Rotaviruses are shed in high concentrations 2 days before and as many as 10 days after onset of symptoms in immunocompetent hosts, thus being an important source of viral transmission. CLINICAL COURSE: A multicenter study in 5 developing countries including Pakistan conducted by WHO CDD program revealed that only 1.8 % of cases presented with severe dehydration and these were mostly due to Rotavirus, V. Cholerae and ETEC13. DIAGNOSTIC TESTS: A study conducted in local hospitals in Pakistan during the period of October 1985-April 1986 compared the different diagnostic modalities for the detection of rotavirus in the faeces of children with acute diarrhea. The study all methods detected Rotavirus to varying degrees but ELISA was found to be the most sensitive method with 72.4% stools being positive. PREVENTIVE STRATEGIES: A study was conducted in Lahore (Pakistan) among 72 infants 6 weeks old in 1991 to assess safety and efficacy of RRV vaccine. It was found that of all infants given RRV with OPV, 50% had a two to four-fold rise in neutralization titers against rotavirus. RRV was found to be safe and not associated with adverse reactions in the 6 weeks old infants. CONCLUSION: With regards to Pakistan, there is a great need for defining rotavirus associated disease burden and strain prevalence. We also need to conduct Rotavirus vaccine trials to assess its efficacy and safety in our setting.

Child, Preschool↗
PubMed1990

Prospective study of diarrheal diseases in Venezuelan children to evaluate the efficacy of rhesus rotavirus vaccine.

The efficacy of a rhesus rotavirus vaccine (MMU 18006, serotype 3) against infantile diarrhea was evaluated by active home surveillance of a group of 320 children 1-10 months of age in Caracas, Venezuela. During a 1 year period following oral administration of vaccine or placebo under a double-masked code, over 600 diarrheal episodes were detected. Etiologic studies revealed that heat-stable toxin (ST) producing enterotoxigenic E. coli (ETEC) was the most common diarrheal agent detected (34%) followed by enteropathogenic E. coli (EPEC, 10.9%), heat-labile toxin (LT) producing ETEC (7.6%), rotavirus (6.9%), Cryptosporidium (4.8%) and Campylobacter (1.3%). ST-producing ETEC were also recovered from over 20% of control stool specimens obtained during diarrhea-free periods, whereas EPEC, rotavirus, Cryptosporidium, and Campylobacter were rarely detected in such control specimens. Rotavirus was responsible for about one-half of the more severe cases of diarrhea. Twenty-two of 151 infants who received placebo (14.6%) and eight of 151 receiving a 10(4) PFU dose of vaccine (5.3%) had rotavirus diarrhea during the follow-up period for an efficacy level of 64% against any rotavirus diarrhea. However, vaccine efficacy reached 90% against the more severe cases of rotavirus diarrhea and was noticeably high in the 1-4 month age group. Serotypic analysis of the rotaviruses detected suggests that the resistance induced by the vaccine was type specific since significant protection was only evident against serotype 3 rotaviruses. A 10(3) PFU dose tested initially in 18 children did not appear to protect against rotavirus diarrhea.

Complement Fixation Tests↗
PubMed1992

Salivary antibody titers in adults challenged with a human rotavirus.

To determine whether salivary antibody is a reliable indicator of rotavirus infection and mucosal rotavirus antibody concentrations, salivary rotavirus antibody titers were determined as a function of time following inoculation of 24 adult volunteers with a virulent strain of human rotavirus (CJN). Twenty of the subjects became infected and all produced detectable amounts of salivary rotavirus IgA. These antibody concentrations remained undetectable in the four uninfected subjects. Rises of greater than or equal to fourfold in either salivary rotavirus IgA or neutralizing antibody to the challenge virus were detected in all but two subjects. The titers of both antibodies were maximal at 13 days after inoculation and decreased significantly (p less than .02) by 27 days, a result very similar to that previously found with stool rotavirus IgA in CJN-infected subjects. These results suggest that salivary rotavirus antibody titers are an accurate reflection of mucosal rotavirus antibody and a possible surrogate for intestinal rotavirus antibody.

Adolescent↗
PubMed2004

Measurement of antirotavirus IgM/IgA/IgG responses in the serum samples of Indian children following rotavirus diarrhoea and their mothers.

Rotavirus specific, serum IgM/IgA/IgG levels among hospitalized children and their respective mothers were determined. Children were grouped as having rotavirus diarrhoea (RVD) and non-rotavirus diarrhoea (NRVD) on the basis of fecal excretion measured by ELISA and RT-PCR. Although IgM seropositivity was observed among children of both the groups, it was significantly higher in the acute as well as convalescent phase serum samples (P < 0.05 for both) of RVD group. Five out of ten acute sera from the NRVD group were positive for IgM and seven showed IgA/IgG seroconversion indicating rotavirus infection among these children in the past. It was noted that, three out of 24 mothers' sera from RVD group, showed presence of IgM in the serum collected during convalescence of their children. The observation suggests, subclinical rotavirus infection among mothers probably contacted from their children. This is supported by the seroconversion for IgA/IgG among these three mothers. Such a phenomenon was not noticed among the mothers from NRVD group. In general, IgA positivity did not vary significantly among the children from both the groups. IgA seropositivity was significantly higher (P < 0.001) from children of RVD group as compared to healthy group of children following rotavirus infection. From RVD group, all the child patients and 12 mothers out of 24 (50%) showed IgA/IgG seroconversion. None of the mothers from NRVD group showed seroconversion. Serum samples of healthy children and adults, showed IgM positivity at equal level (10%), but a significant difference (P < 0.01) was observed in IgA positivity. In conclusion, subclinical transmission of rotavirus infection from children to their mothers may occur. Seroconversion alone cannot be considered as a marker of rotavirus diarrhoea in children. Moreover, about 40-50% of subjects lacked rotavirus specific IgA at protective levels, making them susceptible to rotavirus infection.

Adult↗
PubMed1996

Natural history of human rotavirus infection.

Rotavirus infections occur repeatedly in humans from birth to old age. Most are asymptomatic or are associated with mild enteric symptoms. Infection in young children can be accompanied by severe life-threatening diarrhea, most commonly after primary infection. Annual childhood morbidity rates for severe diarrhea are similar worldwide. Mortality rates are low in developed countries but approach 1,000,000 annually in young children in developing countries. Rotaviruses can be classified into Groups A-E according to antigenic groups on VP6, the major capsid antigen. Only Group A,B and C rotaviruses have been shown to infect humans, and most human rotavirus disease is caused by Group A viruses. These are further classified into G and P types based on identification of antigens on the outer capsid proteins VP7 and VP4 respectively. Most severe infections in young children are caused by serotypes G1-4, and during the last two decades, G1 infections appear to have predominated worldwide. In general the more densely populated countries show the most complex patterns of occurrence of serotypes. Clinical rotavirus disease can be accompanied by shedding of > 10(12) rotavirus particles/gm feces. The virus is highly infectious and appears to retain infectivity over many months. In temperate climates, disease is most common during the colder months, when it is likely that rapid spread within families and communities occurs. Nosocomial infections are frequent, and rotaviruses can become endemic within obstetric hospital nurseries for the newborn. Few (if any) human rotavirus infections appear to be zoonoses, even though Group A rotaviruses are widespread in the young of all mammalian species. However infection of humans with reassortant rotavirus strains derived from human-animal sources can occur. The extent to which this contributes to new epidemic strains within particular countries (or worldwide) remains to be determined.

Age Factors↗
PubMed1993

Immunogens of rotaviruses.

Rotaviruses cause gastroenteritis in neonates of many animal species including cattle, swine, horses, dogs, cats, chickens and turkeys. Rotavirions are nonenveloped, are about 75 nm in diameter, have a double capsid, and contain 11 double-stranded RNA segments as their genome. Several antigenically distinct groups of rotaviruses have been identified and have been alphabetically designated as A through G. Group A rotaviruses were the first group of rotaviruses isolated and are the most commonly detected rotaviruses in diarrheic animals. Group A rotaviruses have two surface proteins, VP4 and VP7, both of which are important in serotype determination and in inducing neutralizing antibodies and protective immunity. Multiple serotypes of group A rotavirus based on glycoprotein VP7 (designated as G types) and based on VP4 (P types) have been identified. The immune response to rotaviruses is essentially serotype specific, however, cross-reactive or heterotypic epitopes have also been identified. Currently acceptable methods for immunogen quantitation include the induction of neutralizing antibody in host or laboratory animals. The in vivo efficacy of vaccines against rotavirus-associated gastroenteritis remains the standard method against which in vitro methods must be compared. Several animal models have been developed which could potentially be used in evaluating the efficacy of candidate vaccines. Monoclonal antibodies to rotavirus immunogens are also currently available and serve as valuable reagents for in vitro quantitation of rotaviral immunogens.

Animals↗
PubMed2004

Estimating hospital admissions due to rotavirus gastroenteritis from hospital episode statistics.

OBJECTIVES: To determine the proportion of hospital admissions, in children < 5 years old, coded for intestinal infectious disease or non-infectious gastroenteritis, using ICD-10 codes, that were due to rotavirus infection. To assess how many children admitted with rotavirus gastroenteritis were given the specific ICD-10 code (A080) for this disease. METHODS: Sixteen-month prospective, observational study of children < 5 years old, admitted to district general hospital with: acute gastroenteritis (> or =3 loose stools/day), proven rotavirus infection and those coded as intestinal infectious disease or non-infectious gastroenteritis. RESULTS: Four hundred and twenty children < 5 years old were admitted with acute gastroenteritis. Rotavirus was detected in 170 children's stools. Acute rotavirus gastroenteritis accounted for 81/397 (20%) children coded as having non-infectious gastroenteritis and 32/81 (40%) coded for intestinal infectious disease. Only 18 children were coded for rotavirus gastroenteritis. Potentially preventable rotavirus gastroenteritis occurred in 122 children; 78 coded as non-infectious gastroenteritis (20%) and 26 coded for intestinal infectious disease (34%). CONCLUSIONS: The proportion of children coded with diarrhoeal diseases and found to have rotavirus is less than previously estimated. Using the specific code for rotavirus infection to estimate hospital admissions would be a gross underestimate. Hospital episode statistics cannot reliably estimate the burden of disease due to rotavirus.

Child, Preschool↗
PubMed2006

Effects of the potency and composition of the multivalent human-bovine (WC3) reassortant rotavirus vaccine on efficacy, safety and immunogenicity in healthy infants.

BACKGROUND: Rotavirus gastroenteritis, which causes substantial infant mortality and morbidity worldwide, is a vaccine-preventable disease. The purpose of this study was to evaluate different compositions and potencies (vaccine virus titers) of a live multivalent human-bovine (WC3) reassortant rotavirus vaccine in order to select the potency and composition of the vaccine for further development. METHODS: The efficacy, safety, and immunogenicity of a G1, G2, G3, G4, and P1A pentavalent composition at three different potencies, a G1, G2, G3, G4 quadrivalent composition, and a P1A monovalent composition of an oral human-bovine (WC3) reassortant rotavirus vaccine were compared in a blinded, placebo-controlled trial conducted between 1998 and 2001 enrolling 1,946 healthy Finnish infants 2-8 months of age. RESULTS: All potencies of the pentavalent and quadrivalent vaccines were efficacious (58-74%) against wild-type rotavirus gastroenteritis of any severity and 100% protective against severe rotavirus disease caused by vaccine G-serotypes through the first rotavirus season post-vaccination. The monovalent P1A vaccine was 53% efficacious against moderate-and-severe rotavirus gastroenteritis. Protection against rotavirus gastroenteritis of any severity was demonstrated through two and three rotavirus seasons for all vaccine compositions. After the third dose, the percentage of infants with >or=3-fold rise in baseline serum neutralizing antibody titers against G1 ranged from 62% to 86% for recipients of the pentavalent vaccine, depending on the potency. The incidence of fever, irritability, vomiting, and diarrhea did not significantly differ between vaccine and placebo groups. A 7-month-old male developed intussusception 9 days after the first dose of the low-potency pentavalent vaccine. CONCLUSIONS: Based on the results of this trial, a pentavalent composition (G1, G2, G3, G4, and P1A) of human-bovine (WC3) reassortant rotavirus vaccine with a potency similar to that of the middle-potency pentavalent vaccine ( approximately 8 x 10(6) plaque-forming units/dose) was selected for further development.

Animals↗
PubMed1999

Epidemiology of rotavirus in infants and protection against symptomatic illness afforded by primary infection and vaccination.

This study assessed the frequency of symptomatic and asymptomatic primary and secondary infections with rotavirus in children under 24 months and determined protection against symptomatic illness afforded by rhesus and human-rhesus rotavirus reassortant vaccines. Successive cohorts of children (n 236) were followed through five winter rotavirus seasons with cultures of each reported episode of diarrheal disease and serologic determination of rotavirus exposure on paired sera bracketing the winter. An average of 46% of children experienced rotavirus infection in each season with almost all infected by two years of age. The relative risk of rotavirus associated gastroenteritis in naive children versus naturally immune children was 2.4 (1.1, 5.3). The relative risk of rotavirus associated gastroenteritis in naive children versus vaccinees was 4.1 (1.6, 10.7). In a community with predominantly serotype G1 rotavirus rhesus rotavirus-based vaccines are as protective against rotavirus gastroenteritis as prior natural infection.

Antibodies, Viral↗
PubMedDate not supplied

Evaluation of reverse transcription and polymerase chain reaction (RT/PCR) for the detection of rotaviruses: applications of the assay.

Our aim was to evaluate the reverse transcription and polymerase chain reaction (RT/PCR) technique for the detection of rotavirus shedding by infected children as a routine diagnostic procedure, in comparison to the enzyme-linked immunosorbent assay (ELISA), electron microscopy (EM) and polyacrylamide gel electrophoresis (PAGE) of rotavirus double-stranded RNA. Two-hundred and twenty stool specimens were collected from infants and young children with diarrhoea, and 10-20% faecal suspensions were made. Several methods of rotavirus dsRNA extraction were assayed. Electrophoretic analysis of viral RNA was carried out on 10% polyacrylamide gels followed by silver staining. RT/PCR was performed using oligonucleotide primers specific for both 3' and 5' ends of the rotavirus gene encoding VP7 which are highly conserved among group A rotaviruses. Following RNA extraction with phenol-chloroform and ethanol precipitation, RT/PCR could detect rotaviral RNA in only 11 of 25 samples known to contain rotaviruses by conventional methods. The purification of RNA extracts by CF11 cellulose and the application of the RNAID method were equally effective in extracting RNA and/or removing inhibitory substances from the faecal samples. RT/PCR led to the detection of 66 positive samples from 220 specimens tested (30%), whilst 64 specimens were positive by ELISA (29%), 59 (26.8%) by PAGE and 56 (25.4%) by EM. In our study, RT/PCR was 100 times more sensitive than the ELISA test in detecting rotaviruses serially diluted in a faecal suspension. Although RT/PCR is theoretically much more sensitive than ELISA, PAGE and EM for detection of rotaviruses, great care must be taken to remove inhibitory substances from the enzymatic reactions. We do not consider that RT/PCR should replace immunoassays with high sensitivity and specificity for rotavirus testing in faecal samples, although this technique has other applications, like the search for rotavirus in different clinical specimens (sera, cerebrospinal fluid, respiratory secretions, etc.) and in environmental samples, as well as the typing of viral strains using serotype-specific primers.

Child↗
PubMed1985

Antibody to human rotavirus in cow's milk.

Rotavirus infection is an important cause of gastroenteritis in infants and young children. Since the virus replicates in the intestinal lumen, we investigated the presence and effectiveness of rotavirus antibody in three forms of milk: raw milk, pasteurized milk, and commercially available infant formulas. Both raw and pasteurized milk contained detectable levels of IgG1 antibody directed at rotavirus. On the other hand, little or no anti-rotavirus antibody was detected in commercially available infant formulas or other sterile milk preparations. The milk samples with rotavirus antibody were capable of inhibiting the replication of simian, bovine, and human rotaviruses in tissue culture. In addition, they were capable of protecting mice from infection and disease in a murine model of rotavirus infection. On the other hand, the formula preparations were incapable of modifying the in vitro replication of rotavirus strains in tissue culture and did not prevent symptomatic gastroenteritis in the mouse model. We conclude that the alteration of milk-processing procedures or the addition of effective antibodies to milk preparations commonly used in the nutrition of young children may alter the clinical course of rotavirus infection or decrease the transmission of rotavirus throughout susceptible populations.

Animals↗
PubMed2001

Rotavirus and central nervous system symptoms: cause or contaminant? Case reports and review.

Rotavirus is a common cause of severe gastroenteritis in children. In 2 patients with rotavirus gastroenteritis who developed encephalopathy, rotavirus RNA was detected in the cerebrospinal fluid (CSF) by reverse transcription-polymerase chain reaction; in 1 patient, rotavirus RNA was detected on 2 occasions 3 weeks apart. There are increasing reports of cases in which patients who have seizures after an episode of rotavirus diarrhea have evidence of rotavirus in their CSF. A search of 2 large hospital discharge databases suggested that seizures are noted as part of the discharge diagnosis in the records of, at most, <4% of patients with rotavirus diarrhea versus 7% of patients with bacterial diarrhea. Although evidence suggesting that rotavirus is a cause of central nervous system sequelae remains inconclusive, the 2 case reports presented in this study further illustrate a possible association. Further study is required to determine whether detection of rotavirus in CSF represents a true pathogen, CSF contamination that occurs at the time of lumbar puncture or in the laboratory, or carriage of rotavirus RNA in trafficking lymphocytes.

Central Nervous System Diseases↗
PubMed2005

Estimates of rotavirus disease burden in Hong Kong: hospital-based surveillance.

BACKGROUND: We conducted prospective, hospital-based surveillance for rotavirus disease for a 2-year period at 4 of 12 public government (Hospital Authority [HA]) hospitals in Hong Kong. It has been estimated that HA hospitals provide 90% of inpatient care in Hong Kong. METHODS: Information was collected for children <5 years old who had a primary or secondary diagnosis of diarrhea or for whom a stool sample was tested for the presence of rotavirus (by enzyme immunoassay) or bacteria (by culture). Surveillance data were compared with routine discharge information from the HA's computerized Clinical Management System (CMS). RESULTS: During a 2-year period (1 April 2001 through 31 March 2003), 7391 children were admitted to the hospital with diarrhea or developed diarrhea during their hospital stay. Of these children, 5881 (80%) had a stool sample tested for the presence of rotavirus, and 30% were positive for rotavirus (representing 24% of all diarrhea-associated admissions). CMS data underreported the total percentage of diarrhea-associated admissions (15% vs. 20%) and the percentage of diarrhea-associated admissions that were the result of rotavirus infection (13% vs. 24%). Estimated rates of hospitalization for rotavirus infection (8.8 admissions/1000 children <5 years old and 18.4 admissions/1000 children <1 year old) were 4-fold higher than our previous estimates, which were determined on the basis of CMS data alone. We estimate that the cumulative risk of hospitalization with rotavirus diarrhea by age 5 years is 1 in 24. Combined active and passive (CMS) surveillance data indicate that 4.6% of all general pediatric admissions to HA hospitals in Hong Kong were associated with rotavirus infection. CONCLUSION: Our study combined passive surveillance data from all Hong Kong HA hospitals with active surveillance data from 4 sentinel hospitals. The estimates of rotavirus disease burden obtained will help emphasize the effect of this important disease and create awareness of the potential for rotavirus vaccines. The surveillance model developed could also be a powerful tool for monitoring the effect of a vaccine.

Child, Preschool↗