Shigella isolates from the global enteric multicenter study inform vaccine development.

Background: Shigella, a major diarrheal disease pathogen worldwide, is the target of vaccine development. The Global Enteric Multicenter Study (GEMS) investigated burden and etiology of moderate-to-severe diarrheal disease in children aged <60 months and matched controls without diarrhea during 3 years at 4 sites in Africa and 3 in Asia. Shigella was 1 of the 4 most common pathogens across sites and age strata.

Association between moderate-to-severe diarrhea in young children in the global enteric multicenter study (GEMS) and types of handwashing materials used by caretakers in Mirzapur, Bangladesh.

Handwashing practices among caretakers of case and control children < 5 years of age enrolled in the Global Enteric Multicenter Study in Mirzapur, Bangladesh were characterized and analyzed for association with moderate-to-severe diarrhea. Soap or detergent ownership was common, yet 48% of case and 47.7% of control caretakers also kept ashes for handwashing, including 36.

High genotypic diversity among rotavirus strains infecting Gambian children.

Background: Rotavirus is the leading cause of diarrhea in children <5 years of age. In light of the implementation of rotavirus vaccines of limited valency, it is important to characterize the genotypic diversity of circulating rotavirus in sub-Saharan Africa.

Methods: We collected stool samples from children 0-59 months of age who presented at the health centres as cases with moderate-to-severe diarrhea in the Upper River Region of The Gambia.

Quality of piped and stored water in households with children under five years of age enrolled in the Mali site of the Global Enteric Multi-Center Study (GEMS).

Water, sanitation, and hygiene information was collected during a matched case-control study of moderate and severe diarrhea (MSD) among 4,096 children < 5 years of age in Bamako, Mali. Primary use of piped water (conditional odds ratio [cOR] = 0.45; 0.

Housefly population density correlates with shigellosis among children in Mirzapur, Bangladesh: a time series analysis.

Background: Shigella infections are a public health problem in developing and transitional countries because of high transmissibility, severity of clinical disease, widespread antibiotic resistance and lack of a licensed vaccine. Whereas Shigellae are known to be transmitted primarily by direct fecal-oral contact and less commonly by contaminated food and water, the role of the housefly Musca domestica as a mechanical vector of transmission is less appreciated. We sought to assess the contribution of houseflies to Shigella-associated moderate-to-severe diarrhea (MSD) among children less than five years old in Mirzapur, Bangladesh, a site where shigellosis is hyperendemic, and to model the potential impact of a housefly control intervention.

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.

Shigella antigen-specific B memory cells are associated with decreased disease severity in subjects challenged with wild-type Shigella flexneri 2a.

The role of Shigella-specific B memory (BM) in protection has not been evaluated in human challenge studies. We utilized cryopreserved pre- and post-challenge peripheral blood mononuclear cells and sera from wild-type Shigella flexneri 2a (wt-2457T) challenges. Challenged volunteers were either naïve or subjects who had previously ingested wt-2457T or been immunized with hybrid Escherichia coli-Shigella live oral candidate vaccine (EcSf2a-2).

Health care seeking for childhood diarrhea in developing countries: evidence from seven sites in Africa and Asia.

We performed serial Health Care Utilization and Attitudes Surveys (HUASs) among caretakers of children ages 0-59 months randomly selected from demographically defined populations participating in the Global Enteric Multicenter Study (GEMS), a case-control study of moderate-to-severe diarrhea (MSD) in seven developing countries. The surveys aimed to estimate the proportion of children with MSD who would present to sentinel health centers (SHCs) where GEMS case recruitment would occur and provide a basis for adjusting disease incidence rates to include cases not seen at the SHCs. The proportion of children at each site reported to have had an incident episode of MSD during the 7 days preceding the survey ranged from 0.

Health care-seeking behavior for childhood diarrhea in Mirzapur, rural Bangladesh.

We evaluated patterns of health care use for diarrhea among children 0-59 months of age residing in Mirzapur, Bangladesh, using a baseline survey conducted during May-June 2007 to inform the design of a planned diarrheal etiology case/control study. Caretakers of 7.4% of 1,128 children reported a diarrheal illness in the preceding 14 days; among 95 children with diarrhea, 24.

Determinants of health care seeking for diarrheal illness in young children in urban slums of Kolkata, India.

Maternal practices regarding children's health care have been recognized as an important factor associated with mortality rates among children < 5 years of age. We focused on health care-seeking practices of primary caretakers of children < 5 years of age with diarrheal disease in Kolkata. We interviewed caretakers of 1,058 children in a baseline survey and 6,077 children on six subsequent surveys.

Seeking care for pediatric diarrheal illness from traditional healers in Bamako, Mali.

Diarrhea is a leading cause of child mortality worldwide. Early recognition of symptoms and referral to medical treatment are essential. In 2007, we conducted a Healthcare Utilization and Attitudes Survey (HUAS) of 1,000 children randomly selected from a population census to define care-seeking patterns for diarrheal disease in Bamako, Mali, in preparation for the Global Enteric Multicenter Study (GEMS).

Health care-seeking behavior during childhood diarrheal illness: results of health care utilization and attitudes surveys of caretakers in western Kenya, 2007-2010.

We interviewed caretakers of 1,043 children < 5 years old in a baseline cross-sectional survey (April to May 2007) and > 20,000 children on five separate subsequent occasions (May of 2009 to December 31, 2010) to assess healthcare seeking patterns for diarrhea. Diarrhea prevalence during the preceding 2 weeks ranged from 26% at baseline to 4-11% during 2009-2010. Caretakers were less likely to seek healthcare outside the home for infants (versus older children) with diarrhea (adjusted odds ratio [aOR] = 0.

Health care use patterns for diarrhea in children in low-income periurban communities of Karachi, Pakistan.

Diarrhea causes 16% of all child deaths in Pakistan. We assessed patterns of healthcare use among caretakers of a randomly selected sample of 959 children ages 0-59 months in low-income periurban settlements of Karachi through a cross-sectional survey. A diarrheal episode was reported to have occurred in the previous 2 weeks among 298 (31.

Health care utilization and attitudes survey in cases of moderate-to-severe diarrhea among children ages 0-59 months in the District of Manhica, southern Mozambique.

In the predominantly rural Manhiça district, in southern Mozambique, diarrhea is one of the leading causes of death among children under 5 years. Caretakers randomly selected from the Demographic Surveillance Database were invited to participate in a community-based survey on use of healthcare services for gastroenteritis. Of those caretakers reporting an episode of diarrhea during the recall period, 65.

Health Care Utilization and Attitudes Survey: understanding diarrheal disease in rural Gambia.

Diarrheal disease causes ∼1.34 million deaths per year among children under 5 years of age globally. We conducted a Health Care Utilization and Attitudes Survey of 1,012 primary caregivers of children aged 0-11, 12-23, and 24-59 months randomly selected from a Demographic Surveillance population in rural Gambia.

Quantitative PCR for detection of Shigella improves ascertainment of Shigella burden in children with moderate-to-severe diarrhea in low-income countries.

Estimates of the prevalence of Shigella spp. are limited by the suboptimal sensitivity of current diagnostic and surveillance methods. We used a quantitative PCR (qPCR) assay to detect Shigella in the stool samples of 3,533 children aged <59 months from the Gambia, Mali, Kenya, and Bangladesh, with or without moderate-to-severe diarrhea (MSD).

Progress and pitfalls in Shigella vaccine research.

Renewed awareness of the substantial morbidity and mortality that Shigella infection causes among young children in developing countries, combined with technological innovations in vaccinology, has led to the development of novel vaccine strategies in the past 5 years. Along with advancement of classic vaccines in clinical trials and new sophisticated measurements of immunological responses, much new data has been produced, lending promise to the potential for production of safe and effective Shigella vaccines. Herein, we review the latest progress in Shigella vaccine development within the framework of persistent obstacles.

Determinants of household costs associated with childhood diarrhea in 3 South Asian settings.

In addition to being a major cause of mortality in South Asia, childhood diarrhea creates economic burden for affected households. We used survey data from sites in Bangladesh, India, and Pakistan to estimate the costs borne by households due to childhood diarrhea, including direct medical costs, direct nonmedical costs, and productivity losses. Mean cost per episode was $1.

Exploring household economic impacts of childhood diarrheal illnesses in 3 African settings.

Beyond the morbidity and mortality burden of childhood diarrhea in sub-Saharan African are significant economic costs to affected households. Using survey data from 3 of the 4 sites in sub-Saharan Africa (Gambia, Kenya, Mali) participating in the Global Enteric Multicenter Study (GEMS), we estimated the direct medical, direct nonmedical, and indirect (productivity losses) costs borne by households due to diarrhea in young children. Mean cost per episode was $2.

Diagnostic microbiologic methods in the GEMS-1 case/control study.

To understand the etiology of moderate-to-severe diarrhea among children in high mortality areas of sub-Saharan Africa and South Asia, we performed a comprehensive case/control study of children aged <5 years at 7 sites. Each site employed an identical case/control study design and each utilized a uniform comprehensive set of microbiological assays to identify the likely bacterial, viral and protozoal etiologies. The selected assays effected a balanced consideration of cost, robustness and performance, and all assays were performed at the study sites.

Case/control studies with follow-up: Constructing the source population to estimate effects of risk factors on development, disease, and survival.

If individuals in a case/control study are subsequently observed as a cohort of cases and a cohort of controls, weighted regression analyses can be used to estimate the association between the exposures initially recorded and events occurring during the follow-up of the 2 cohorts. Such analyses can be conceptualized as being undertaken on a reconstructed source population from which cases and controls stem. To simulate this population, the cohort of cases is added to the cohort of controls expanded with the reciprocal of the case disease incidence odds (the sampling weight) to include all individuals in the source population who did not develop the case disease.

Data management and other logistical challenges for the GEMS: the data coordinating center perspective.

The Cooperative Studies Program Coordinating Center provided the data management, administrative, and statistical support to the Global Enteric Multicenter Study (GEMS). The GEMS study, the largest epidemiological study in the diarrheal disease area among children <5 years of age, was carried out in 4 African countries and 3 Asian countries. Given the geographical and geopolitical differences among the countries, the administration of a centralized data management operation was a major challenge.