Determination of a Viral Load Threshold To Distinguish Symptomatic versus Asymptomatic Rotavirus Infection in a High-Disease-Burden African Population.

We evaluated quantitative real-time PCR to establish the diagnosis of rotavirus gastroenteritis in a high-disease-burden population in Malawi using enzyme immunoassay as the gold standard diagnostic test. In 146 children with acute gastroenteritis and 65 asymptomatic children, we defined a cutoff point in the threshold cycle value (26.7) that predicts rotavirus-attributable gastroenteritis in this population. These data will inform the evaluation of direct and indirect rotavirus vaccine effects in Africa.

The efficacy and safety of rotavirus vaccines in countries in Africa and Asia with high child mortality.

Rotavirus remains a leading cause of diarrhoeal morbidity and mortality in young children and rotavirus vaccines are critical for reducing global disease burden. This report addresses the performance of rotavirus vaccines in countries with high child mortality. We performed a sensitivity analysis as part of a systematic review on rotavirus vaccines to inform development of World Health Organization vaccine recommendations. The efficacy of four prequalified vaccines against severe rotavirus gastroenteritis was similar across high mortality settings in Asia and Africa. Within the first year following vaccination, vaccine efficacy for the four vaccines ranged from 48% to 57% while in the second year, efficacy ranged from 29% to 54%. The four vaccines showed no increase in intussusception risk in these settings. All four vaccines appear to prevent significant numbers of severe rotavirus gastroenteritis episodes with no measurable increase in intussusception risk in high mortality settings in Africa and Asia.

Hospital-based surveillance of rotavirus and other viral agents of diarrhea in children and adults in Russia, 2005-2007.

During a 2-year period in 2005-2007, we conducted surveillance of group A rotaviruses and other enteric agents among patients hospitalized with acute gastroenteritis in 8 different cities of the Russian Federation. Fecal specimens were gathered from 3208 children (including 2848 children aged <5 years) and 1354 adults who were admitted to hospitals in Moscow, St. Petersburg, Chelyabinsk, Nizhnii Novgorod, Tyumen, Khabarovsk, Makhachkala, and Yakutsk. Polymerase chain reaction was performed to detect rotaviruses of groups A and C, noroviruses of genogroups I and II, astrovirus, sapovirus, and enteric adenoviruses (group F). Group A rotavirus was the most common viral pathogen detected among children aged <5 years (43.6%), followed by norovirus (12.5%), whereas norovirus was the pathogen most commonly detected in adults (11.9%). P and G genotypes were determined for 515 rotavirus specimens, and the most prevalent genotypes were G1P[8] (44.9%), G4P[8] (40.0%), G2P[4] (8.5%), and G3P[8] (6.6%). This study is the first multicenter study of rotaviruses in the Russian Federation and documents the important burden of disease caused by this pathogen, which soon may be preventable by vaccination.

Experiences with rotavirus vaccines: can we improve rotavirus vaccine impact in developing countries?

Rotavirus vaccines have been introduced into over 95 countries globally and demonstrate substantial impact in reducing diarrheal mortality and diarrheal hospitalizations in young children. The vaccines are also considered by WHO as "very cost effective" interventions for young children, particularly in countries with high diarrheal disease burden. Yet the full potential impact of rotavirus immunization is yet to be realized. Large countries with big birth cohorts and where disease burden is high in Africa and Asia have not yet implemented rotavirus vaccines at all or at scale. Significant advances have been made demonstrating the impact of the vaccines in low- and lower-middle income countries, yet the modest effectiveness of the vaccines in these settings is challenging. Current research highlights these challenges and considers alternative strategies to overcome them, including alternative immunization schedules and host factors that may inform us of new opportunities.

Diversity of Rotavirus Strains Circulating in Botswana before and after introduction of the Monovalent Rotavirus Vaccine.

BACKGROUND: Globally, rotavirus is the leading cause of acute gastroenteritis (AGE) in children aged <5 years. Botswana introduced the monovalent rotavirus vaccine (Rotarix) in July 2012. To study the impact of this vaccine on rotavirus genotypes circulating in Botswana, a comparison of the genotypes pre-vaccination (2011-2012) and post-vaccination (2013-2018) periods was conducted. SUBJECTS AND METHODS: Residual samples from 284 children <5 years of age that tested positive for rotavirus by enzyme immunoassay were genotyped. One hundred and five samples were from the pre-vaccination period and 179 were from the post-vaccination period. Genotyping was performed using two multiplexed one-step reverse transcription polymerase chain reaction (RT-PCR) assays for the amplification and genotyping of rotavirus VP7 (G) and VP4 (P) genes. RESULTS: Prior to vaccine introduction, the predominant rotavirus circulating genotypes were G9P[8] (n = 63, 60%) and G1P[8] (n = 22, 21%). During the vaccine period, G2P[4] was the predominant genotype (n = 49, 28%), followed by G9P[8] (n = 40, 22%) and G1P[8] (n = 33, 18.5%). There was a significant decline in the prevalence of G9P[8] (p = 0.001) in the post-vaccination period. There was also a notable decline in G1P[8]. A spike in G2P[4] was observed in 2013, one year post-vaccine introduction. Rotavirus strain G3P[4] (n = 8) was only detected in the post-vaccine introduction period. In 2018 there was a marked increase in genotype G3P[8] (p = 0.0003). CONCLUSIONS: The distribution of circulating rotavirus genotypes in Botswana changed after vaccine implementation. Further studies are needed to examine whether these changes are related to vaccination or simply represent natural secular variation.

Sustained impact of rotavirus vaccine on rotavirus hospitalisations in Lusaka, Zambia, 2009-2016.

BACKGROUND: Monovalent rotavirus vaccine (RV1) was introduced in Lusaka in February 2012 and rolled out countrywide in November 2013 in the routine Expanded Programme on Immunisation and administered at 6 and 10 weeks with no catch up dose. Reported here is the monitoring of rotavirus acute gastroenteritis hospitalisations at the University Teaching Hospital, Lusaka, Zambia as part of efforts to document the impact of rotavirus vaccine. METHODS: Children <5 years hospitalised for acute gastroenteritis (AGE) from January 2009 to December 2016 were recruited into the rotavirus disease burden active surveillance and had their stools tested for rotavirus by enzyme immunoassay. We compared rotavirus-associated AGE hospitalisations of the pre-vaccine era (2009-2011) with the post-rotavirus vaccine introduction period (2013-2016). RESULTS: With the increase in RV1 coverage in Lusaka, rotavirus AGE declined significantly from 40% of diarrhoea hospitalisation in the pre-vaccine era to 29% of diarrhoea hospitalisation in the post-vaccine era (p < 0.001) in children <5 years. After a decreasing trend in rotavirus positivity from 2013 to 2015, positivity increased to 37% in 2016. However, the post-vaccine years (2012-2016) saw substantial decline in the number tested (median decline: 34% (range: 20-43%)) and the number of positive results (median decline: 52% (range: 30-65%). CONCLUSION: A sustained and significant decline in rotavirus AGE hospitalisations was observed in children <5 years since the introduction of RV1 in Lusaka, Zambia. Despite an increase in rotavirus positivity in 2016, the total number of children enrolled and the number of rotavirus positive children remained below baseline. The reason for the increase in rotavirus positivity in 2016 is unknown but could be due to an accumulation of susceptible children and the shifting of disease to children of older age groups. This finding underscores the need for continued monitoring of rotavirus vaccine impact.

Potential safety issues and other factors that may affect the introduction and uptake of rotavirus vaccines.

Rotavirus vaccines have demonstrated significant impact in reducing the burden of morbidity and mortality from childhood diarrhoea in countries that have implemented routine vaccination to date. Despite this success, in many countries, rotavirus vaccine coverage remains lower than that of other routine childhood vaccines. Several issues may potentially affect vaccine uptake, namely safety concerns related to intussusception with consequent age restrictions on rotavirus vaccination, contamination with porcine circovirus, vaccine-derived reassortant strains and hospitalization in newborn nurseries at time of administration of live oral rotavirus vaccine. In addition to these safety concerns, other factors may also affect uptake, including lower vaccine efficacy in the developing world, potential emergence of strains escaping from vaccine protection resulting in lower overall impact of a vaccination programme and sustainable vaccine financing. Although further work is needed to address some of these concerns, global policy bodies have reaffirmed that the benefits of rotavirus vaccination outweigh the risks, and vaccine use is recommended globally.

Use of stool collection kits delivered to patients can improve confirmation of etiology in foodborne disease outbreaks.

BACKGROUND: In 68% of foodborne disease outbreaks, no etiologic pathogen is identified. In two-thirds of outbreaks with no identified etiology, no stool specimens are submitted for testing. METHODS: From April 2001 to March 2003, we pilot-tested use of prepackaged, self-contained stool specimen collection kits in 3 states, delivered to and from patients by courier or mail, to improve rates of specimen collection in the outbreak setting. Specimens were tested for bacterial and viral pathogens at health department laboratories, and results were correlated with epidemiological investigation data. RESULTS: Specimens were returned by > or =1 person in 52 (96%) of 54 outbreaks in which kits were deployed; in total, 263 (76%) of 347 persons who received kits returned specimens. Resolution of symptoms was the most commonly cited reason for nonsubmission of kits. An etiology was confirmed in 37 (71%) of 52 outbreaks with specimens returned; 28 (76%) were attributable to norovirus, and 9 (24%) were attributed to bacterial pathogens. Stool kits were well received and cost an average of approximately 43 dollars per specimen returned. CONCLUSIONS: In two-thirds of foodborne disease outbreaks in which delivered stool collection kits were successfully deployed, an etiologic organism was identified. Delivery of kits to and from patients to improve rates of stool collection in outbreaks in which specimens might otherwise not be submitted could substantially reduce the number of outbreaks with an unknown etiology.

Use of state hospital discharge data to assess the morbidity from rotavirus diarrhea and to monitor the impact of a rotavirus immunization program: A pilot study in Connecticut.

OBJECTIVES: Now that rotavirus vaccines have been licensed and recommended for routine immunization of US infants, there is an urgent need for data to assess the morbidity from rotavirus diarrhea and to monitor the impact of a rotavirus immunization program. In a pilot study, we have assessed the usefulness of state hospital discharge data on diarrhea in children to provide this information by examining data from Connecticut. DESIGN: Retrospective analysis of discharge records from acute care, nongovernmental hospitals in Connecticut. Patients. Children 1 month through 4 years of age with a diarrhea-associated diagnosis listed on the discharge record. Setting. Connecticut, 1987 through 1996. RESULTS: During the 10-year study period, a total of 11 324 diarrhea-associated hospitalizations (49.4 hospitalizations per 10,000 children) were reported. Diarrhea-associated hospitalizations peaked during February through April, especially among children 4 to 35 months of age. The seasonality and age distribution of diarrhea-associated hospitalizations of presumed noninfectious and viral etiologies resembled those of rotavirus-associated hospitalizations. During 1993 to 1996, rotavirus was coded for 10.4% of diarrhea-associated hospitalizations increasing from 8.6% in 1993 to 14.7% in 1996. The unadjusted median cost of a diarrhea-associated hospitalization during 1987 to 1996 and 1993 to 1996 was $1,941 and $2,428, respectively. CONCLUSIONS: Diarrhea causes substantial morbidity in children from Connecticut. The winter seasonal peak of diarrhea-associated hospitalizations in children 4 to 35 months of age coinciding with the peak of rotavirus-specific hospitalizations suggests that rotavirus is an important contributor to the overall morbidity. Although our findings suggest incomplete coding of rotavirus cases, state hospital discharge data should provide sensitive and timely information to monitor the impact of a rotavirus immunization program in Connecticut.

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.

Epidemiology of diarrheal disease among children enrolled in four West Coast health maintenance organizations. Vaccine Safety Datalink Team.

BACKGROUND: We used information from the Vaccine Safety Datalink (VSD) about approximately 1 million children enrolled in four health maintenance organizations to assess the morbidity from diarrhea and estimate the disease burden of rotavirus. METHODS: We examined trends of diarrhea-associated hospitalizations and emergency room (ER) visits among VSD children ages 1 month through 4 years during October, 1992, through September, 1994 (two rotavirus seasons) and estimated the morbidity from rotavirus on the basis of characteristic patterns of age and seasonality. RESULTS: Overall diarrhea was associated with 6.3% of hospitalizations and 4% of ER visits. During a child's first 5 years of life, we estimated that 1 in 57 was hospitalized and 1 in 21 required an ER visit because of diarrhea. Each year the number of diarrhea-associated hospitalizations and ER visits was greatest in winter among children ages 4 to 23 months and peaked in November in California and during February in Oregon and Washington. The winter seasonality of diarrhea-associated hospitalizations reflected the trends for diarrhea of presumed noninfectious and viral etiologies, which together accounted for most (92.9%) hospitalizations. CONCLUSIONS: Diarrhea is an important cause of morbidity among VSD children. The epidemiologic patterns of diarrhea-associated hospitalizations and ER visits resembled those reported previously for rotavirus diarrhea, suggesting that rotavirus may be a major contributor to the overall morbidity from diarrhea. Enhanced surveillance by screening for rotavirus in a sample of children with diarrhea will permit a more accurate assessment of the disease burden of this pathogen and the cost effectiveness of a rotavirus immunization program.

Topical antimicrobials applied to the umbilical cord stump: a new intervention against neonatal tetanus.

BACKGROUND: Previous case-control studies of neonatal tetanus (NNT), a leading cause of infant mortality in developing countries, have suggested that antimicrobials applied after delivery to the umbilical cord stump may protect against this disease. However, assessment of their protective effect has been limited by the low prevalence of antimicrobial use in developing countries. METHODS: We conducted a population-based, matched, case-control study to assess the use of antimicrobials and other factors potentially related to NNT in rural parts of Bangladesh. We studied 359 cases (infants who were normal at birth but who died between the 3rd and 30th day of life after an illness characterized by signs of NNT), each matched to three living controls for gender, residence, and date of birth. RESULTS: In univariate analyses, the application of either antibiotics or disinfectants at delivery, and the continuous or any application of disinfectants were protective against NNT. The application of antibiotics at delivery (odds ratio [OR] = 0.21, P = 0.019), hand washing by the delivery attendant (OR = 0.64, P = 0.005), and prior maternal immunization with tetanus toxoid (OR = 0.50, P < 0.001) remained protective in conditional logistic-regression analyses. Application of animal dung to the umbilical stump (OR = 2.31, P = 0.047) was hazardous. CONCLUSIONS: Effective and inexpensive topical antimicrobials provide a new prevention opportunity that could be used by traditional birth attendants and mothers to provide additional benefits to NNT control programmes based on maternal immunization with tetanus toxoid. Promotion of hygienic delivery and cord-care practices and increasing tetanus toxoid coverage remain cornerstones for the prevention of NNT deaths.

PIP: Neonatal tetanus (NNT) is a leading cause of infant mortality in developing countries. Findings from previous case-control studies of NNT have suggested that antimicrobials applied following delivery to the umbilical cord stump may protect against the disease. However, assessment of their protective effect has been hampered by the low prevalence of antimicrobial use in developing countries. The authors conducted a population-based, matched, case-control study to assess the use of antimicrobials and other factors potentially related to NNT in rural parts of Bangladesh. 359 cases were studied, infants who were normal at birth but who died between the 3rd and 30th day of life after an illness characterized by signs of NNT. Each case was matched to 3 living controls for gender, residence, and date of birth. Univariate analyses found the application of either antibiotics or disinfectants at delivery, and the continuous or any application of disinfectants to protect against NNT. The application of antibiotics at delivery, hand washing by the delivery attendant, and prior maternal immunization with tetanus toxoid remained protective in conditional logistic-regression analyses. The application of animal dung to the umbilical stump was hazardous.

Nipah virus infection among abattoir workers in Malaysia, 1998-1999.

BACKGROUND: An outbreak of encephalitis primarily affecting pig farmers occurred during 1998-1999 in Malaysia and was linked to a new paramyxovirus, Nipah virus, which infected pigs, humans, dogs, and cats. Because five abattoir workers were also affected, a survey was conducted to assess the risk of Nipah infection among abattoir workers. METHODS: Workers from all 143 registered abattoirs in 11 of 13 states in Malaysia were invited to participate in this cross-sectional study. Participants were interviewed to ascertain information on illness and activities performed at the abattoir. A serum sample was obtained to test for Nipah virus antibody. RESULTS: Seven (1.6 %) of 435 abattoir workers who slaughtered pigs versus zero (0%) of 233 workers who slaughtered ruminants showed antibody to Nipah virus (P = 0.05). All antibody-positive workers were from abattoirs in the three states that reported outbreak cases among pig farmers. Workers in these three states were more likely than those in other states to have Nipah antibody (7/144 [4.86%] versus 0/291 [0%], P < 0.001) and report symptoms suggestive of Nipah disease in pigs admitted to the abattoirs (P = 0.001). CONCLUSIONS: Nipah infection was not widespread among abattoir workers in Malaysia and was linked to exposure to pigs. Since it may be difficult to identify Nipah-infected pigs capable of transmitting virus by clinical symptoms, using personal protective equipment, conducting surveillance for Nipah infection on pig farms which supply abattoirs, and avoiding handling and processing of potentially infected pigs are presently the best strategies to prevent transmission of Nipah virus in abattoirs.

Diarrheal mortality in US infants. Influence of birth weight on risk factors for death.

OBJECTIVES: To examine diarrhea-associated deaths among very low-birth-weight (VLBW) (< 1500 g) infants and low- and normal-birth-weight (LNBW) (> or = 1500 g) infants at birth and to identify specific interventions to prevent these deaths. DESIGN: Retrospective analyses of linked infant and birth death data on diarrhea of all causes compiled by the National Center for Health Statistics, Centers for Disease Control and Prevention, Atlanta, Ga. PATIENTS: Infants aged 27 days through 11 months who died with diarrhea. SETTING: United States, 1991. RESULTS: A majority (56%, n = 143) of the 257 diarrhea-associated deaths reported among US infants in 1991 occurred among VLBW infants. Compared with LNBW infants, VLBW infants had a 100-fold greater diarrheal mortality (269 deaths per 100,000 live births for VLBW infants vs 2.8 deaths per 100,000 live births for LNBW infants), died at a younger age, and more often died in the hospital. Diarrhea-associated deaths among VLBW infants were strongly associated with prematurity and a low 1-minute Apgar score whereas African American race, less maternal education, and a low 1-minute Apgar score were associated with increased diarrheal mortality among LNBW infants. CONCLUSIONS: Infants of VLBW are at an increased risk for diarrheal deaths and new efforts are required to understand and improve the diagnosis of and therapy for diarrhea among these infants. For LNBW infants, diarrheal deaths remain a social problem and efforts need to focus on improved education and home-based rehydration therapy for children whose mothers fit the high-risk profile and who may lack adequate access to health care.

Assessment of Nipah virus transmission among pork sellers in Seremban, Malaysia.

Between September 1998 and May 1999, 265 cases of encephalitis were reported from among those involved in pig rearing. A few cases were also reported among abattoir workers. This raised questions of the risk of transmission among those who handled raw pork. A serosurvey was conducted among pork sellers in Seremban town, which is about 20 km from one of the pig rearing areas which had reported cases of encephalitis. It was found that out of the 28 pork sellers tested, only one tested positive for Nipah virus antibodies and that this pork seller also worked in an abattoir in the same district, removing the urinary bladders from slaughtered pigs. Based on these findings, it was concluded that the risk of transmission of the virus from handling raw pork appeared to be low.

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.

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.

Diarrhea-associated hospitalizations among children in Hawaii.

OBJECTIVE: To estimate the burden of diarrhea-associated hospitalizations among children in Hawaii. DESIGN: Retrospective analysis of hospital discharge records. PATIENTS: Children from 1 month through 4 years of age with a diarrhea-associated diagnosis listed on the hospital discharge record in Hawaii. SETTING: Acute care hospitals in the state of Hawaii, 1994 through 1997. RESULTS: During 1994-1997, 2288 children (11.3% of all hospitalizations for children < 5 years of age) had a diarrhea-associated diagnosis listed at hospital discharge. The average annual incidence (per 10,000 children) of diarrhea-associated hospitalizations was 62.3; the incidence was higher for children < 1 year (101.6) than for those 1 through 4 years of age (52.7). Rates for Hawaii were lower than national rates during 1993 through 1995 (US annual rate of 89 per 10,000 children). The median length of hospital stay was 2 days for diarrhea-associated hospitalizations, and 3 days for hospitalizations specifically associated with rotavirus-related diarrhea. Diarrhea-associated hospitalizations were highest during the period December through June. CONCLUSIONS: Diarrhea is an important cause of hospitalization among children in Hawaii, where approximately 1 in 32 children may be hospitalized by 5 years of age. The age-specific and temporal trends reported here are consistent with those previously described for rotavirus-associated hospitalizations, suggesting that this pathogen is a major contributor to the overall morbidity from diarrhea.

Evaluation of rotavirus vaccines in Asia--are there lessons to be learnt?

Rotavirus mortality is highest in the Asia-Pacific region and rotavirus vaccines could have enormous impact here. Yet, live-attenuated orally administered rotavirus vaccines have been evaluated in a small number of immunogenicity studies in some Asian countries, where the immune responses have been documented to be moderate in low-income countries with high diarrhoeal disease burden and mortality, and high in middle-/high-income countries with little reported rotavirus deaths. This review of these rotavirus clinical trials examines the results observed and attempts to draw lessons to inform decision-making, aid design of additional clinical trials and guide vaccine development by local manufacturers.