Breastfeeding and the risk of rotavirus diarrhea in hospitalized infants in Uganda: a matched case control study

<p>Abstract</p> <p>Background</p> <p><it>Rotavirus </it>is responsible for over 25 million outpatient visits, over 2 million hospitalizations and 527,000 deaths annually, worldwide. It is estimated that breastfeeding in accordance with the World Health Organization recommendations would save 1.45 million children's lives each year in the developing countries. The few studies that examined the effect of breastfeeding on <it>rotavirus </it>diarrhea produced conflicting results. This study aimed to determine the effect of breastfeeding on <it>rotavirus </it>diarrhea among admitted infants in Uganda.</p> <p>Methods</p> <p>The study was conducted in the Pediatrics medical emergency unit of a National Referral hospital during a peak incidence time for rotavirus from February to April 2008. It was an age matched case-control study with a ratio of 1:1. We consecutively enrolled infants presenting at the study site during this period whose caretakers consented to participate in the study. A minimum sample size of 90 pairs was adequate with power of 80% to detect a 30% decrease in breastfeeding rate among the cases assuming a breastfeeding rate of 80% in the controls. The infants with <it>rotavirus </it>positive results were the "cases". We used the commercial enzyme immunoassay kit (DAKO IDEIA™ rotavirus EIA detection kit) to diagnose the cases. The "controls" were admitted children with no diarrhea. We compared the cases and controls for antecedent breastfeeding patterns.</p> <p>Results</p> <p>Ninety-one matched case-control age-matched pairs with an age caliper of one month were included in the analysis. Breastfeeding was not protective against rotavirus diarrhea (OR 1.08: 95% CI 0.52 - 2.25; p = 0.8) in the conditional logistic model.</p> <p>Conclusions</p> <p>Our study findings did not reveal breastfeeding as protective against <it>rotavirus </it>diarrhea in infants. This suggests searching for other complementary preventive methods such as rotavirus vaccination and zinc supplementation to reduce the problem of <it>rotavirus </it>diarrhea in infants irrespective of their feeding practices.</p

Incidence of rotavirus infection in children with gastroenteritis attending Jos university teaching hospital, Nigeria

This study was conducted to determine the incidence of rotavirus infection in children with gastroenteritis attending Jos university teaching hospital, Plateau State. A total of 160 children with acute diarrhea were selected by random sampling. Stool samples were obtained and assayed for rotavirus antigens by enzyme linked immunosorbent assay technique using standard diagnostic BIOLINE Rotavirus kit. Demographic data of parents were also recorded. Rotavirus were detected in faeces of 22(13.8%) children with acute diarrhea, 90.9% of positive cases of rotavirus gastroenteritis were under 2 years of age with highest prevalence in children 7-12 months of age. Males excreted rotavirus at a significant higher rate than females (P < 0.05). Rotavirus excretion was highest when all three symptoms (diarrhea, fever and vomiting) occurred in the same child (7.5%) and lower when 2 symptoms occurred together (diarrhea and vomiting) with 3.8%, diarrhea and fever with 1.3% and lowest when diarrhea occurred alone with 1.3%. Playing with toys, attending day care, distance of source of water from toilet, eating of food not requiring cooking and playing with other children may serve as predisposing factors of rotavirus disease in these children

Prevalence and factors associated with rotavirus infection among children admitted with acute diarrhea in Uganda

<p>Abstract</p> <p>Background</p> <p>Rotavirus remains the commonest cause of severe dehydrating diarrhea among children worldwide. Children in developing countries die more because of several factors including poorer access to hydration therapy and greater prevalence of malnutrition. Hitherto, the magnitude of rotavirus disease in Uganda has remained unknown. This study was therefore done to determine the prevalence and factors associated with rotavirus infection among children aged 3-59 months admitted with acute diarrhea to paediatric emergency ward of Mulago Hospital, Uganda</p> <p>Methods</p> <p>Three hundred and ninety children, aged between 3-59 months with acute diarrhoea were recruited. The clinical history, socio-demographic characteristics, physical examination findings and laboratory investigations were recorded. Stool samples were tested for rotavirus antigens using the DAKO IDEIA rotavirus EIA detection kit.</p> <p>Results</p> <p>The prevalence of rotavirus infection was 45.4%. On multivariate analysis rotavirus was significantly associated with a higher education (above secondary) level of the mother [OR 1.8; 95% CI 1.1-2.7]; dehydration [OR 1.8; 95% CI 1.1-3.0] and breastfeeding [OR 2.6; 95% CI 1.4-4.0]. Although age was significantly associated with rotavirus on bivariate analysis; this association disappeared on multivariate analysis. No significant association was found between rotavirus infection and nutritional status, HIV status and attendance of day care or school.</p> <p>Conclusions</p> <p>Rotavirus infection is highly prevalent among children with acute diarrhoea admitted to Mulago Hospital in Uganda.</p

A gastrointestinal rotavirus infection mouse model for immune modulation studies

<p>Abstract</p> <p>Background</p> <p>Rotaviruses are the single most important cause of severe diarrhea in young children worldwide. The current study was conducted to assess whether colostrum containing rotavirus-specific antibodies (Gastrogard-R^®) could protect against rotavirus infection. In addition, this illness model was used to study modulatory effects of intervention on several immune parameters after re-infection.</p> <p>Methods</p> <p>BALB/c mice were treated by gavage once daily with Gastrogard-R^®from the age of 4 to 10 days, and were inoculated with rhesus rotavirus (RRV) at 7 days of age. A secondary inoculation with epizootic-diarrhea infant-mouse (EDIM) virus was administered at 17 days of age. Disease symptoms were scored daily and viral shedding was measured in fecal samples during the post-inoculation periods. Rotavirus-specific IgM, IgG and IgG subclasses in serum, T cell proliferation and rotavirus-specific delayed-type hypersensitivity (DTH) responses were also measured.</p> <p>Results</p> <p>Primary inoculation with RRV induced a mild but consistent level of diarrhea during 3-4 days post-inoculation. All mice receiving Gastrogard-R^®were 100% protected against rotavirus-induced diarrhea. Mice receiving both RRV and EDIM inoculation had a lower faecal-viral load following EDIM inoculation then mice receiving EDIM alone or Gastrogard-R^®. Mice receiving Gastrogard-R^®however displayed an enhanced rotavirus-specific T-cell proliferation whereas rotavirus-specific antibody subtypes were not affected.</p> <p>Conclusions</p> <p>Preventing RRV-induced diarrhea by Gastrogard-R^®early in life showed a diminished protection against EDIM re-infection, but a rotavirus-specific immune response was developed including both B cell and T cell responses. In general, this intervention model can be used for studying clinical symptoms as well as the immune responses required for protection against viral re-infection.</p

Astrovirus MLB1 Is Not Associated with Diarrhea in a Cohort of Indian Children

Astroviruses are a known cause of human diarrhea. Recently the highly divergent astrovirus MLB1 (MLB1) was identified in a stool sample from a patient with diarrhea. It has subsequently been detected in stool from individuals with and without diarrhea. To determine whether MLB1 is associated with diarrhea, we conducted a case control study of MLB1. In parallel, the prevalence of the classic human astroviruses (HAstVs) was also determined in the same case control cohort. 400 cases and 400 paired controls from a longitudinal birth cohort in Vellore, India were analyzed by RT-PCR. While HAstVs were associated with diarrhea (p = 0.029) in this cohort, MLB1 was not; 14 of the controls and 4 cases were positive for MLB1. Furthermore, MLB1 viral load did not differ significantly between the cases and controls. The role of MLB1 in human health still remains unknown and future studies are needed

Metagenomic Analysis of Human Diarrhea: Viral Detection and Discovery

Worldwide, approximately 1.8 million children die from diarrhea annually, and millions more suffer multiple episodes of nonfatal diarrhea. On average, in up to 40% of cases, no etiologic agent can be identified. The advent of metagenomic sequencing has enabled systematic and unbiased characterization of microbial populations; thus, metagenomic approaches have the potential to define the spectrum of viruses, including novel viruses, present in stool during episodes of acute diarrhea. The detection of novel or unexpected viruses would then enable investigations to assess whether these agents play a causal role in human diarrhea. In this study, we characterized the eukaryotic viral communities present in diarrhea specimens from 12 children by employing a strategy of “micro-mass sequencing” that entails minimal starting sample quantity (<100 mg stool), minimal sample purification, and limited sequencing (384 reads per sample). Using this methodology we detected known enteric viruses as well as multiple sequences from putatively novel viruses with only limited sequence similarity to viruses in GenBank

Immunogenicity and safety of concomitant administration of a measles, mumps and rubella vaccine (M-M-RvaxPro®) and a varicella vaccine (VARIVAX®) by intramuscular or subcutaneous routes at separate injection sites: a randomised clinical trial

<p>Abstract</p> <p>Background</p> <p>When this trial was initiated, the combined measles, mumps and rubella (MMR) vaccine was licensed for subcutaneous administration in all European countries and for intramuscular administration in some countries, whereas varicella vaccine was licensed only for subcutaneous administration. This study evaluated the intramuscular administration of an MMR vaccine (M-M-RvaxPro^®) and a varicella vaccine (VARIVAX^®) compared with the subcutaneous route.</p> <p>Methods</p> <p>An open-label randomised trial was performed in France and Germany. Healthy children, aged 12 to18 months, received single injections of M-M-RvaxPro and VARIVAX concomitantly at separate injection sites. Both vaccines were administered either intramuscularly (IM group, <it>n </it>= 374) or subcutaneously (SC group, <it>n </it>= 378). Immunogenicity was assessed before vaccination and 42 days after vaccination. Injection-site erythema, swelling and pain were recorded from days 0 to 4 after vaccination. Body temperature was monitored daily between 0 and 42 days after vaccination. Other adverse events were recorded up to 42 days after vaccination and serious adverse events until the second study visit.</p> <p>Results</p> <p>Antibody response rates at day 42 in the per-protocol set of children initially seronegative to measles, mumps, rubella or varicella were similar between the IM and SC groups for all four antigens. Response rates were 94 to 96% for measles, 98% for both mumps and rubella and 86 to 88% for varicella. For children initially seronegative to varicella, 99% achieved the seroconversion threshold (antibody concentrations of ≥ 1.25 gpELISA units/ml). Erythema and swelling were the most frequently reported injection-site reactions for both vaccines. Most injection-site reactions were of mild intensity or small size (≤ 2.5 cm). There was a trend for lower rates of injection-site erythema and swelling in the IM group. The incidence and nature of systemic adverse events were comparable for the two routes of administration, except varicella-like rashes, which were less frequent in the IM group.</p> <p>Conclusion</p> <p>The immunogenicities of M-M-RvaxPro and VARIVAX administered by the intramuscular route were comparable with those following subcutaneous administration, and the tolerability of the two vaccines was comparable regardless of administration route. Integration of both administration routes in the current European indications for the two vaccines will now allow physicians in Europe to choose their preferred administration route in routine clinical practice.</p> <p>Trial registration</p> <p>ClinicalTrials.gov NCT00432523</p

Incidence and risk factors for community-acquired acute gastroenteritis in north-west Germany in 2004

In developed countries, acute gastroenteritis (AGE) is a major source of morbidity. However, only a few studies have estimated its incidence and the associated medical burden. This population-based study determined the incidence of community-acquired AGE patients seeking medical care and the relative role of various pathogens. Stool samples from patients with AGE presenting to a general practitioner (GP), pediatrician, or specialist in internal medicine for that reason were screened for various bacterial and viral enteropathogens. A control group was established as well. Incidences were calculated by the number of positive patients divided by the general population. The study was performed in north-west Germany in 2004. The incidence of AGE patients requiring medical consultation was 4,020/100,000 inhabitants. Children (<5 years of age) were at the highest risk (13,810/100,000 inhabitants). Of the patients, 6.6% were tested positive for an enteropathogenic bacteria and 17.7% for a viral agent. The predominant pathogens were norovirus (626/100,000) and rotavirus (270/100,000). Salmonella was the most frequently detected bacteria (162/100,000). The results presented confirm AGE and, specifically, AGE of viral origin as a major public health burden in developed countries

Health and economic impact of rotavirus vaccination in GAVI-eligible countries

<p>Abstract</p> <p>Background</p> <p>Rotavirus infection is responsible for about 500,000 deaths annually, and the disease burden is disproportionately borne by children in low-income countries. Recently the World Health Organization (WHO) has released a global recommendation that all countries include infant rotavirus vaccination in their national immunization programs. Our objective was to provide information on the expected health, economic and financial consequences of rotavirus vaccines in the 72 GAVI support-eligible countries.</p> <p>Methods</p> <p>We synthesized population-level data from various sources (primarily from global-level databases) for the 72 countries eligible for the support by the GAVI Alliance (GAVI-eligible countries) in order to estimate the health and economic impact associated with rotavirus vaccination programs. The primary outcome measure was incremental cost (in 2005 international dollars [I$]) per disability-adjusted life year (DALY) averted. We also projected the expected reduction in rotavirus disease burden and financial resources required associated with a variety of scale-up scenarios.</p> <p>Results</p> <p>Under the base-case assumptions (70$25 per vaccinated child (~$5 per dose), the number of countries with the incremental cost per DALY averted less than I$200 was 47. Using the WHO's cost-effectiveness threshold based on per capita GDP, the vaccines were considered cost-effective in 68 of the 72 countries (~94%). A 10-year routine rotavirus vaccination would prevent 0.9-2.8 million rotavirus associated deaths among children under age 5 in the poorest parts of the world, depending on vaccine scale-up scenarios. Over the same intervention period, rotavirus vaccination programs would also prevent 4.5-13.3 million estimated cases of hospitalization and 41-107 million cases of outpatient clinic visits in the same population.</p> <p>Conclusions</p> <p>Our findings suggest that rotavirus vaccination would be considered a worthwhile investment for improving general development as well as childhood health level in most low-income countries, with a favorable cost-effectiveness profile even under a vaccine price ($1.5-$5.0 per dose) higher than those of traditional childhood vaccines.</p