Khitam Muhsen

Burden and aetiology of diarrhoeal disease in infants and young children in developing countries (the Global Enteric Multicenter Study, GEMS): a prospective, case-control study

BACKGROUND Diarrhoeal diseases cause illness and death among children younger than 5 years in low-income countries. We designed the Global Enteric Multicenter Study (GEMS) to identify the aetiology and population-based burden of paediatric diarrhoeal disease in sub-Saharan Africa and south Asia. METHODS The GEMS is a 3-year, prospective, age-stratified, matched case-control study of moderate-to-severe diarrhoea in children aged 0-59 months residing in censused populations at four sites in Africa and three in Asia. We recruited children with moderate-to-severe diarrhoea seeking care at health centres along with one to three randomly selected matched community control children without diarrhoea. From patients with moderate-to-severe diarrhoea and controls, we obtained clinical and epidemiological data, anthropometric measurements, and a faecal sample to identify enteropathogens at enrolment; one follow-up home visit was made about 60 days later to ascertain vital status, clinical outcome, and interval growth. FINDINGS We enrolled 9439 children with moderate-to-severe diarrhoea and 13,129 control children without diarrhoea. By analysing adjusted population attributable fractions, most attributable cases of moderate-to-severe diarrhoea were due to four pathogens: rotavirus, Cryptosporidium, enterotoxigenic Escherichia coli producing heat-stable toxin (ST-ETEC; with or without co-expression of heat-labile enterotoxin), and Shigella. Other pathogens were important in selected sites (eg, Aeromonas, Vibrio cholerae O1, Campylobacter jejuni). Odds of dying during follow-up were 8·5-fold higher in patients with moderate-to-severe diarrhoea than in controls (odd ratio 8·5, 95% CI 5·8-12·5, p<0·0001); most deaths (167 [87·9%]) occurred during the first 2 years of life. Pathogens associated with increased risk of case death were ST-ETEC (hazard ratio [HR] 1·9; 0·99-3·5) and typical enteropathogenic E coli (HR 2·6; 1·6-4·1) in infants aged 0-11 months, and Cryptosporidium (HR 2·3; 1·3-4·3) in toddlers aged 12-23 months. INTERPRETATION Interventions targeting five pathogens (rotavirus, Shigella, ST-ETEC, Cryptosporidium, typical enteropathogenic E coli) can substantially reduce the burden of moderate-to-severe diarrhoea. New methods and accelerated implementation of existing interventions (rotavirus vaccine and zinc) are needed to prevent disease and improve outcomes. FUNDING The Bill & Melinda Gates Foundation.

Helicobacter pylori Infection and Iron Stores: A Systematic Review and Meta‐analysis

Background and Aims:  We carried out a systematic literature review and meta‐analysis to evaluate the existing evidence on the association between Helicobacter pylori infection and iron stores.

A Systematic Review and Meta-analysis of the Association Between Giardia lamblia and Endemic Pediatric Diarrhea in Developing Countries

In this systematic review and meta-analysis, Giardia lamblia was not associated with acute pediatric diarrhea in nonindustrialized settings but was positively linked to persistent diarrhea.

The Global Enteric Multicenter Study (GEMS): Impetus, Rationale, and Genesis

Diarrheal disease remains one of the top 2 causes of young child mortality in the developing world. Whereas improvements in water/sanitation infrastructure and hygiene can diminish transmission of enteric pathogens, vaccines can also hasten the decline of diarrheal disease morbidity and mortality. From 1980 through approximately 2004, various case/control and small cohort studies were undertaken to address the etiology of pediatric diarrhea in developing countries. Many studies had methodological limitations and came to divergent conclusions, making it difficult to prioritize the relative importance of different pathogens. Consequently, in the first years of the millennium there was no consensus on what diarrheal disease vaccines should be developed or implemented; however, there was consensus on the need for a well-designed study to obtain information on the etiology and burden of more severe forms of diarrheal disease to guide global investment and implementation decisions. Accordingly, the Global Enteric Multicenter Study (GEMS) was designed to overcome drawbacks of earlier studies and determine the etiology and population-based burden of pediatric diarrheal disease. GEMS, which includes one of the largest case/control studies of an infectious disease syndrome ever undertaken (target approximately 12 600 analyzable cases and 12 600 controls), was rolled out in 4 sites in sub-Saharan Africa (Gambia, Kenya, Mali, Mozambique) and 3 in South Asia (Bangladesh, India, Pakistan), with each site linked to a population under demographic surveillance (total approximately 467 000 child years of observation among children <5 years of age). GEMS data will guide investment and help prioritize strategies to mitigate the morbidity and mortality of pediatric diarrheal disease.

The Burden of Cryptosporidium Diarrheal Disease among Children < 24 Months of Age in Moderate/High Mortality Regions of Sub-Saharan Africa and South Asia, Utilizing Data from the Global Enteric Multicenter Study (GEMS)

Background The importance of Cryptosporidium as a pediatric enteropathogen in developing countries is recognized. Methods Data from the Global Enteric Multicenter Study (GEMS), a 3-year, 7-site, case-control study of moderate-to-severe diarrhea (MSD) and GEMS-1A (1-year study of MSD and less-severe diarrhea [LSD]) were analyzed. Stools from 12,110 MSD and 3,174 LSD cases among children aged <60 months and from 21,527 randomly-selected controls matched by age, sex and community were immunoassay-tested for Cryptosporidium. Species of a subset of Cryptosporidium-positive specimens were identified by PCR; GP60 sequencing identified anthroponotic C. parvum. Combined annual Cryptosporidium-attributable diarrhea incidences among children aged <24 months for African and Asian GEMS sites were extrapolated to sub-Saharan Africa and South Asian regions to estimate region-wide MSD and LSD burdens. Attributable and excess mortality due to Cryptosporidium diarrhea were estimated. Findings Cryptosporidium was significantly associated with MSD and LSD below age 24 months. Among Cryptosporidium-positive MSD cases, C. hominis was detected in 77.8% (95% CI, 73.0%-81.9%) and C. parvum in 9.9% (95% CI, 7.1%-13.6%); 92% of C. parvum tested were anthroponotic genotypes. Annual Cryptosporidium-attributable MSD incidence was 3.48 (95% CI, 2.27–4.67) and 3.18 (95% CI, 1.85–4.52) per 100 child-years in African and Asian infants, respectively, and 1.41 (95% CI, 0.73–2.08) and 1.36 (95% CI, 0.66–2.05) per 100 child-years in toddlers. Corresponding Cryptosporidium-attributable LSD incidences per 100 child-years were 2.52 (95% CI, 0.33–5.01) and 4.88 (95% CI, 0.82–8.92) in infants and 4.04 (95% CI, 0.56–7.51) and 4.71 (95% CI, 0.24–9.18) in toddlers. We estimate 2.9 and 4.7 million Cryptosporidium-attributable cases annually in children aged <24 months in the sub-Saharan Africa and India/Pakistan/Bangladesh/Nepal/Afghanistan regions, respectively, and ~202,000 Cryptosporidium-attributable deaths (regions combined). ~59,000 excess deaths occurred among Cryptosporidium-attributable diarrhea cases over expected if cases had been Cryptosporidium-negative. Conclusions The enormous African/Asian Cryptosporidium disease burden warrants investments to develop vaccines, diagnostics and therapies.

Effectiveness of rotavirus vaccines for prevention of rotavirus gastroenteritis-associated hospitalizations in Israel: a case-control study.

The association between rotavirus gastroenteritis (RVGE)-associated hospitalization and rotavirus vaccine receipt was examined, and vaccine effectiveness was estimated in a case-control study conducted between 11/2007 and 12/2009 among Israeli children age eligible for rotavirus vaccination. Cases (n=111) were hospitalized children with diarrhea testing positive for rotavirus by immunochromatography. Controls (n=216) were hospitalized children with diarrhea testing negative for rotavirus. Among controls 36 (16.7%) children were vaccinated against rotavirus compared with two children (1.8%) among cases (p

Incidence, Characteristics, and Economic Burden of Rotavirus Gastroenteritis Associated with Hospitalization of Israeli Children <5 Years of Age, 2007–2008

BACKGROUND Limited data exist on the epidemiology and burden of rotavirus gastroenteritis in Israel. Objectives. Our objective was to examine the incidence, characteristics, and economic burden of rotavirus gastroenteritis associated with hospitalization of children <5 years of age in Israel. METHODS A prospective study was initiated in pediatric wards at 3 hospitals in northern Israel. Presence of rotavirus in stool specimens was detected by immunochromatography, and G and P genotypes were determined by reverse-transcriptase polymerase chain reaction. Demographic data, clinical manifestations, and expenditures related to a childs illness were studied using parental interviews. RESULTS From November 2007 through October 2008, 472 children hospitalized with gastroenteritis were enrolled in the study. Rotavirus gastroenteritis was diagnosed in 39.1% of children, with a peak identification rate during November 2007-January 2008 (62.5%-71.0%). Most cases of rotavirus gastroenteritis (87.2%) occurred in children <2 years of age. In infections with 1 rotavirus genotype, G1P[8] was the most frequently detected (49.1%), followed by G1P[4] (11.1%) and G9P[8] (9.3%). Mixed rotavirus isolates were identified in 28.9% of the children. The estimated incidence of primary hospitalizations for rotavirus gastroenteritis among children aged 0-5 years was 5.7 hospitalizations per 1000 children per year (95% confidence interval, 5.1-6.3 hospitalizations per 1000 children per year), resulting in an estimate of 4099 annual national hospitalizations (95% confidence interval, 3668-4531 hospitalizations per year). This figure represents approximately 6.5% of the total annual hospitalizations among Israeli children <5 years of age. The annual calculated cost of hospitalizations for rotavirus gastroenteritis was US

Is the Association Between Helicobacter pylori Infection and Anemia Age Dependent

7,680,444, including US

Serum Bactericidal Assays To Evaluate Typhoidal and Nontyphoidal Salmonella Vaccines

4,578,489 (59.6%) in direct costs to the health care system and US

Evaluation of Four Different Systems for Extraction of RNA from Stool Suspensions Using MS-2 Coliphage as an Exogenous Control for RT-PCR Inhibition

3,101,955 in overall household costs. CONCLUSIONS Our findings are important for decision making regarding implementation and evaluation of a routine immunization program against rotavirus gastroenteritis.