Diarrhea In Young Children Research Articles

Antagonism of MAVS Signaling by Rotavirus Infection

Abstract The single most important cause of severe gastroenteritis and diarrhea in young children, rotaviruses (RVs) are responsible for an annual 450,000 deaths worldwide. Despite the availability of several vaccines, RV global mortality is still high and significantly less effective in the poorest countries where the burden of disease is greatest. Therefore, there remains an urgent need for a deeper understanding of the basic mechanisms of RV pathogenesis and host-pathogen interaction to develop improved vaccines and novel antiviral therapeutics. The host protein MAVS plays a pivotal role in restricting the replication of many RNA viruses by relaying antiviral signaling from the cytoplasmic RNA sensors RIG-I and MDA5 to downstream interferon (IFN) induction. Multiple virus-encoded factors, including HCV NS3/4A, antagonize the antiviral activity of MAVS by proteolytic cleavage. We recently observed that RV infection specifically mediates the degradation of full-length MAVS but not the truncated variant mini-MAVS. This process is independent of well-characterized IFN antagonist RV NSP1. Given the importance of IFN in suppressing the replication of certain RV strains in vivo, we hypothesize that RVs utilize one or more viral proteins to dampen IFN responses by targeting MAVS signaling. We will mechanistically determine the viral and host factors responsible for MAVS degradation and examine whether it takes place in intestinal epithelial cells in vivo. The current study will broaden our knowledge of RV pathogenesis and provide a molecular basis for the rational design of a new-generation of attenuated RV vaccines.

Mapping Antigenic Epitopes on the Human Bocavirus Capsid.

Human bocaviruses (HBoV1 to -4) are emerging pathogens associated with pneumonia and/or diarrhea in young children. Currently, there is no treatment or vaccination, so there is a need to study these pathogens to understand their disease mechanisms on a molecular and structural level for the development of control strategies. Here, we report the structures of six HBoV monoclonal antibody (MAb) fragment complexes, HBoV1-15C6, HBoV2-15C6, HBoV4-15C6, HBoV1-4C2, HBoV1-9G12, and HBoV1-12C1, determined by cryo-electron microscopy and three-dimensional image reconstruction to 18.0- to 8.5-Å resolution. Of these, the 15C6 MAb cross-reacted with HBoV1, HBoV2, and HBoV4, while the 4C2, 12C1, and 9G12 MAbs recognized only HBoV1. Pseudoatomic modeling mapped the 15C6 footprint to the capsid surface DE and HI loops, at the 5-fold axis and the depression surrounding it, respectively, which are conserved motifs in Parvoviridae The footprints for 4C2, 12C1, and 9G12 span the surface loops that assemble portions of the 2-/5-fold wall (a raised surface feature between the 2-fold and 5-fold axes of symmetry) and the shoulder of the 3-fold protrusions. The MAb footprints, cross reactive and strain specific, coincide with regions with high and low sequence/structural identities, respectively, on the capsid surfaces of the HBoVs and identify potential regions for the development of peptide vaccines for these viruses. Human bocaviruses (HBoVs) may cause severe respiratory and gastrointestinal infections in young children. The nonenveloped parvovirus capsid carries determinants of host and tissue tropism, pathogenicity, genome packaging, assembly, and antigenicity important for virus infection. This information is currently unavailable for the HBoVs and other bocaparvoviruses. This study identifies three strain-specific antigenic epitopes on the HBoV1 capsid and a cross-reactive epitope on the HBoV1, HBoV2, and HBoV4 capsids using structures of capsid-antibody complexes determined using cryo-electron microscopy and image reconstruction. This is the first study to report the highly conserved parvovirus DE loop at the 5-fold axis as a determinant of antigenicity. Additionally, knowledge of the strain-specific and conserved antigenic epitopes of the bocaviruses can be instrumental in characterization of the virus life cycle, development of peptide vaccines, and generation of gene delivery vectors for cystic fibrosis given the strict tropism of HBoV1 for human airway epithelial cells.

Structural, Mechanistic, and Antigenic Characterization of the Human Astrovirus Capsid.

ABSTRACTHuman astroviruses (HAstVs) are nonenveloped, positive-sense, single-stranded RNA viruses that are a leading cause of viral gastroenteritis. HAstV particles display T=3 icosahedral symmetry formed by 180 copies of the capsid protein (CP), which undergoes proteolytic maturation to generate infectious HAstV particles. Little is known about the molecular features that govern HAstV particle assembly, maturation, infectivity, and immunogenicity. Here we report the crystal structures of the two main structural domains of the HAstV CP: the core domain at 2.60-Å resolution and the spike domain at 0.95-Å resolution. Fitting of these structures into the previously determined 25-Å-resolution electron cryomicroscopy density maps of HAstV allowed us to characterize the molecular features on the surfaces of immature and mature T=3 HAstV particles. The highly electropositive inner surface of HAstV supports a model in which interaction of the HAstV CP core with viral RNA is a driving force in T=3 HAstV particle formation. Additionally, mapping of conserved residues onto the HAstV CP core and spike domains in the context of the immature and mature HAstV particles revealed dramatic changes to the exposure of conserved residues during virus maturation. Indeed, we show that antibodies raised against mature HAstV have reactivity to both the HAstV CP core and spike domains, revealing for the first time that the CP core domain is antigenic. Together, these data provide new molecular insights into HAstV that have practical applications for the development of vaccines and antiviral therapies.IMPORTANCE Astroviruses are a leading cause of viral diarrhea in young children, immunocompromised individuals, and the elderly. Despite the prevalence of astroviruses, little is known at the molecular level about how the astrovirus particle assembles and is converted into an infectious, mature virus. In this paper, we describe the high-resolution structures of the two main astrovirus capsid proteins. Fitting these structures into previously determined low-resolution maps of astrovirus allowed us to characterize the molecular surfaces of immature and mature astroviruses. Our studies provide the first evidence that astroviruses undergo viral RNA-dependent assembly. We also provide new insight into the molecular mechanisms that lead to astrovirus maturation and infectivity. Finally, we show that both capsid proteins contribute to the adaptive immune response against astrovirus. Together, these studies will help to guide the development of vaccines and antiviral drugs targeting astrovirus.

Immunogenicity of a prototype enterotoxigenic Escherichia coli adhesin vaccine in mice and nonhuman primates

Enterotoxigenic Escherichia coli (ETEC) are the most common cause of bacterial diarrhea in young children in developing countries and in travelers. Efforts to develop an ETEC vaccine have intensified in the past decade, and intestinal colonization factors (CFs) are somatic components of most investigational vaccines. CFA/I and related Class 5 fimbrial CFs feature a major stalk-forming subunit and a minor, antigenically conserved tip adhesin. We hypothesized that the tip adhesin is critical for stimulating antibodies that specifically inhibit ETEC attachment to the small intestine. To address this, we compared the capacity of donor strand complemented CfaE (dscCfaE), a stabilized form of the CFA/I fimbrial tip adhesin, and CFA/I fimbriae to elicit anti-adhesive antibodies in mice, using hemagglutination inhibition (HAI) as proxy for neutralization of intestinal adhesion. When given with genetically attenuated heat-labile enterotoxin LTR192G as adjuvant by intranasal (IN) or orogastric (OG) vaccination, dscCfaE exceeded CFA/I fimbriae in eliciting serum HAI titers and anti-CfaE antibody titers. Based on these findings, we vaccinated Aotus nancymaae nonhuman primates (NHP) with dscCfaE alone or admixed with one of two adjuvants, LTR192G and cholera toxin B-subunit, by IN and OG administration. Only IN vaccination with dscCfaE with either adjuvant elicited substantial serum HAI titers and IgA and IgG anti-adhesin responses, with the latter detectable a year after vaccination. In conclusion, we have shown that dscCfaE elicits robust HAI and anti-adhesin antibody responses in both mice and NHPs when given with adjuvant by IN vaccination, encouraging further evaluation of an ETEC adhesin-based vaccine approach.

Genetic modification of the diarrhoeal pathogen Cryptosporidium parvum.

Recent studies into the global causes of severe diarrhea in young children have identified the protozoan parasite Cryptosporidium as the second most important diarrheal pathogen after rotavirus1–3. Diarrheal disease is estimated to be responsible for 10.5% of overall child mortality4. Cryptosporidium is also an opportunistic pathogen in the context of HIV-AIDS and organ transplantation5,6. There is no vaccine and only a single approved drug that provides no benefit for those in gravest danger, malnourished children and immunocompromised patients7,8. Cryptosporidiosis drug and vaccine development is limited by the poor tractability of the parasite, which includes lack of continuous culture, facile animal models, and molecular genetic tools3,9. Here we describe an experimental framework to genetically modify this important human pathogen. We establish and optimize transfection of C. parvum sporozoites in tissue culture. To isolate stable transgenics we develop a mouse model that delivers sporozoites directly into the intestine, a Cryptosporidium CRISPR/Cas9 system, and in vivo selection for aminoglycoside resistance. We derive reporter parasites suitable for in vitro and in vivo drug screening, and we evaluate the basis of drug susceptibility by gene knock out. We anticipate the ability to genetically engineer the parasite will be transformative for Cryptosporidium research. Genetic reporters will provide quantitative correlates for disease, cure and protection and the role of parasite genes in these processes is now open to rigorous investigation.

Microbial aetiology of acute diarrhoea in children under five years of age in Khartoum, Sudan.

Diarrhoea is one of leading causes of morbidity and mortality worldwide. Recent estimations suggested the number of deaths is close to 2.5 million. This study examined the causative agents of diarrhoea in children under 5 years of age in suburban areas of Khartoum, Sudan. A total of 437 stool samples obtained from children with diarrhoea were examined by culture and PCR for bacteria, by microscopy and PCR for parasites and by immunoassay for detection of rotavirus A. Of the 437 samples analysed, 211 (48 %) tested positive for diarrhoeagenic Escherichia coli, 96 (22 %) for rotavirus A, 36 (8 %) for Shigella spp., 17 (4 %) for Salmonella spp., 8 (2 %) for Campylobacter spp., 47 (11 %) for Giardia intestinalis and 22 (5 %) for Entamoeba histolytica. All isolates of E. coli (211, 100 %) and Salmonella (17, 100 %), and 30 (83 %) isolates of Shigella were sensitive to chloramphenicol; 17 (100 %) isolates of Salmonella, 200 (94 %) isolates of E. coli and (78 %) 28 isolates of Shigella spp. were sensitive to gentamicin. In contrast, resistance to ampicillin was demonstrated in 100 (47 %) isolates of E. coli and 16 (44 %) isolates of Shigella spp. In conclusion, E. coli proved to be the main cause of diarrhoea in young children in this study, followed by rotavirus A and protozoa. Determination of diarrhoea aetiology and antibiotic susceptibility patterns of diarrhoeal pathogens and improved hygiene are important for clinical management and controlled strategic planning to reduce the burden of infection.

Molecular characterization and multiple infections of rotavirus, norovirus, sapovirus, astrovirus and adenovirus in outpatients with sporadic gastroenteritis in Shanghai, China, 2010-2011.

Rotavirus (RV), norovirus (NoV), sapovirus (SaV), human astrovirus (HAstV) and human adenovirus (HAdV) are significant because they are the most common pathogens that cause diarrhea in young children. The aim of this study was to investigate the genetic characteristics and compare the roles of these five viruses in outpatient children with diarrhea in Shanghai. A total of 436 fecal samples were collected from pediatric patients with acute gastroenteritis from January 2010 to December 2011. The selected samples were subjected to reverse transcription PCR (RT-PCR) or PCR to detect and genotype RV, NoV, SaV, HAstV and HAdV. RV (43.3 %, 189/436) was the most prevalent virus, followed by NoV (28.9 %, 126/436), HAdV (7.1 %, 31/436). HAstV (1.8 %, 8/436) and SaV (0.5 %, 2/436). The percentage of multiple infection cases was 14.9 % (65/436), and RV + NoV was the predominant mixed infection. The RV genotype combinations of P[8]G3 (52/189, 27.5 %), P[8]G1 (51/189, 26.9 %) and P[8]G9 (48/189, 25.4 %) occurred most frequently. The predominant NoV genotype was GII.4 (73.0 %, 92/126), and the majority of GII.4 clustered as GII.4-2006b (65.2 %, 60/92). Two of the SaV cases were identified as GI.2 and GII.1. All HAstV-positive samples belonged to HAstV-1. The predominant HAdV type was HAdV-41 (45.2 %, 14/31). This study clearly shows the diversity of the viral causative agents of acute gastroenteritis in outpatient children in Shanghai, which will provide baseline information for future vaccination strategies and development in this area.

Environmental predictors of diarrhoeal infection for rural and urban communities in south India in children and adults.

Diarrhoeal diseases are major causes of morbidity and mortality in developing countries. This longitudinal study aimed to identify controllable environmental drivers of intestinal infections amidst a highly contaminated drinking water supply in urban slums and villages of Vellore, Tamil Nadu in southern India. Three hundred households with children (<5 years) residing in two semi-urban slums and three villages were visited weekly for 12-18 months to monitor gastrointestinal morbidity. Households were surveyed at baseline to obtain information on environmental and behavioural factors relevant to diarrhoea. There were 258 diarrhoeal episodes during the follow-up period, resulting in an overall incidence rate of 0·12 episodes/person-year. Incidence and longitudinal prevalence rates of diarrhoea were twofold higher in the slums compared to rural communities (P < 0·0002). Regardless of study site, diarrhoeal incidence was highest in infants (<1 year) at 1·07 episodes/person-year, and decreased gradually with increasing age. Increasing diarrhoeal rates were associated with presence of children (<5 years), domesticated animals and low socioeconomic status. In rural communities, open-field defecation was associated with diarrhoea in young children. This study demonstrates the contribution of site-specific environmental and behavioural factors in influencing endemic rates of urban and rural diarrhoea in a region with highly contaminated drinking water.

Large increase of rotavirus diarrhoea in the hospital setting associated with emergence of G12 genotype in a highly vaccinated population in Nicaragua

Rotaviruses (RVs) are a major cause of severe diarrhoea in young children. Nicaragua introduced routine immunization with the pentavalent RV vaccine (RV5) in 2006, which greatly reduced the incidence of diarrhoea. A remaining concern has been the possible emergence of new RV strains to which the vaccination has less effect. In this study, 837 children with diarrhoea in hospital settings were investigated for RV between May 2011 and July 2013. RVs were subsequently typed by multiplex PCR and/or sequencing. Fecal anti-RV IgA titres for a subset of RV-infected (n = 137) and noninfected children (n = 52) were determined with an in-house enzyme-linked immunosorbent assay. The RV detection rate was 8% in 2011, followed by a sharp increase to 29% in 2012 and 19% in 2013. This was associated with emergence and predominance of genotype G12 RV, from 0% in 2011 to 66% in 2012 and 82% in 2013, infecting children from 1 month to 10 years of age. Two sequenced G12 strains showed a Wa-like genome with genotype G12-P[8]-I1-R1-C1-M1-A1-N1-T1-E1-H1, similar to the globally emerging G12 strains. Fecal anti-RV IgA analysis showed that most G12-infected and noninfected children had been in contact with either vaccine or wild RV strains, but such antibodies did not prevent symptomatic G12 infection. A marked increase of RV was evident in the hospital setting associated with a nationwide emergence and predominance of RV G12 genotype in a population with high RV5 vaccine coverage.

Viral Agents of Diarrhea in Young Children in Two Primary Health Centers in Edo State, Nigeria.

Enteric viruses have been shown to be responsible for diarrhea among children during their early childhood. This study was carried out to determine the prevalence of rotavirus, adenovirus, and norovirus infection in young children with diarrhea in two primary health centers in Edo State, Nigeria. A total of 223 stool specimens were collected from children aged 0–36 months with clinical signs of diarrhea and 59 apparently healthy age-matched children as control. These specimens were investigated for three viral agents using immunochromatographic technique (ICT). The overall results showed that at least one viral agent was detected in 95/223 (42.6%) of the children with diarrhea while the control had none. The prevalence of rotavirus was 28.3%, adenovirus 19.3%, and norovirus 3.6%. There was a significant association between age group and infection (P < 0.0001). Seasonal pattern of enteric viruses was not statistically significant (P = 0.17). The overall coinfection rate was 7.6% and rotavirus-adenovirus coinfection had the highest with 5.4%. Rotavirus was the most prevalent viral agent. Coinfections are not uncommon among the population studied. The most commonly associated clinical symptom of viral diarrhea in this study was vomiting. Viral diagnostic tests are advocated for primary health care facilities in this locality.

Epidemiological study of bloody diarrhoea among children in baghdad in Iraq

Introduction: Diarrhoea is a preventable and treatable disease; however it is still a major public health problem particularly in the developing world. Bloody diarrhoea in young children is usually a sign of invasive enteric infection that carries risk of serious morbidity and death. In Iraq, diarrhoea is the second common cause of mortalities among children.

Structure and function of enterotoxigenic Escherichia coli fimbriae from differing assembly pathways.

Pathogenic enterotoxigenic Escherichia coli (ETEC) are the major bacterial cause of diarrhea in young children in developing countries and in travelers, causing significant mortality in children. Adhesive fimbriae are a prime virulence factor for ETEC, initiating colonization of the small intestinal epithelium. Similar to other Gram-negative bacteria, ETEC express one or more diverse fimbriae, some assembled by the chaperone-usher pathway and others by the alternate chaperone pathway. Here, we elucidate structural and biophysical aspects and adaptations of each fimbrial type to its respective host niche. CS20 fimbriae are compared with colonization factor antigen I (CFA/I) fimbriae, which are two ETEC fimbriae assembled via different pathways, and with P-fimbriae from uropathogenic E. coli. Many fimbriae unwind from their native helical filament to an extended linear conformation under force, thereby sustaining adhesion by reducing load at the point of contact between the bacterium and the target cell. CFA/I fimbriae require the least force to unwind, followed by CS20 fimbriae and then P-fimbriae, which require the highest unwinding force. We conclude from our electron microscopy reconstructions, modeling and force spectroscopy data that the target niche plays a central role in the biophysical properties of fimbriae that are critical for bacterial pathophysiology.

Genetic susceptibility to norovirus GII.3 and GII.4 infections in Chinese pediatric diarrheal disease.

Noroviruses (NoVs) are a leading cause of viral diarrhea in young children. Secretor status has been confirmed to be linked with Norwalk virus (NoV GI.1) infection but there is limited information about whether secretor genotypes are associated with pediatric NoV epidemic strains in vivo. In this study, fecal specimens and serum samples were collected from 124 hospitalized children with acute diarrhea in Xi'an, China. TaqMan real-time reverse transcription polymerase chain reaction was used to detect NoVs in fecal samples, and NoV-positive samples were further verified using conventional reverse transcription polymerase chain reaction and sequenced. DNA was extracted from sera and TaqMan single-nucleotide polymorphism genotyping assay was applied to determine the FUT2 A385T polymorphism. Only NoV GII.3 and GII.4 genotypes were found in NoV-positive samples, and NoVs were detected in 25% (15/60), 40.5% (17/42) and 9.1% (2/22) of children with homozygous secretor genotype (Se 385 Se 385), heterozygous secretor genotype (Se 385 se 385) and homozygous weak secretor genotype (se 385 se 385), respectively. Children with secretor genotypes Se 385 Se 385 and Se 385 se 385 were significantly (P < 0.05) more susceptible to combined NoV GII.3 and GII.4 infections than children with weak secretor genotype se 385 se 385. These findings indicate that secretor positivity is significantly associated with GII.3 and GII.4 infections in Chinese pediatric diarrheal disease and the weak secretor phenotype does not completely protect children from GII.3 and GII.4 infections.

Maternal Knowledge and Practices towards Sanitation and Their Relationships with Occurrence of Diarrhoea in Children

&lt;p&gt;Diarrhoea, a major contributor of childhood morbidity and mortality is mostly caused by poor hygiene and sanitation. Literature reveal that hygiene practices at household levels greatly affects the occurrence of diarrhoea among children. A cross sectional study was conducted to determine association between hygiene knowledge and practices of mothers with occurrence of diarrhoea in young children below 3 years in the tribal villages of Gujarat. Structured questionnaire was used to elicit information on personal hygiene (PH), food Hygiene (FH), and environmental Hygiene (EH) practices of 536 mothers with children between 6-36 months of age. Past one month diarrhoeal episodes were recorded using the recall method. The mean percent scores for FH, PH and EH practices were 77%, 88% and 80% respectively. Almost 35% children suffered from diarrhoea in the past one month of which 10 were admitted to the hospital. Diarrhoeal incidences were associated with FH and EH practices (p&amp;lt;0.001) and not with PH practices. Improvement in the environmental and personal hygiene practices of the mothers can contribute largely in reducing the prevalence of diarrhoea among children in Chikhli taluka of Gujarat.&lt;/p&gt;

Maternal Knowledge and Practices towards Sanitation and Their Relationships with Occurrence of Diarrhoea in Children

&lt;p&gt;Diarrhoea, a major contributor of childhood morbidity and mortality is mostly caused by poor hygiene and sanitation. Literature reveal that hygiene practices at household levels greatly affects the occurrence of diarrhoea among children. A cross sectional study was conducted to determine association between hygiene knowledge and practices of mothers with occurrence of diarrhoea in young children below 3 years in the tribal villages of Gujarat. Structured questionnaire was used to elicit information on personal hygiene (PH), food Hygiene (FH), and environmental Hygiene (EH) practices of 536 mothers with children between 6-36 months of age. Past one month diarrhoeal episodes were recorded using the recall method. The mean percent scores for FH, PH and EH practices were 77%, 88% and 80% respectively. Almost 35% children suffered from diarrhoea in the past one month of which 10 were admitted to the hospital. Diarrhoeal incidences were associated with FH and EH practices (p&amp;lt;0.001) and not with PH practices. Improvement in the environmental and personal hygiene practices of the mothers can contribute largely in reducing the prevalence of diarrhoea among children in Chikhli taluka of Gujarat.&lt;/p&gt;

Cost effectiveness of a pentavalent rotavirus vaccine in Oman.

BackgroundRotavirus gastroenteritis (RGE) is the leading cause of diarrhea in young children in Oman, incurring substantial healthcare and economic burden. We propose to formally assess the potential cost effectiveness of implementing universal vaccination with a pentavalent rotavirus vaccine (RV5) on reducing the health care burden and costs associated with rotavirus gastroenteritis (RGE) in OmanMethodsA Markov model was used to compare two birth cohorts, including children who were administered the RV5 vaccination versus those who were not, in a hypothetical group of 65,500 children followed for their first 5 years of life in Oman. The efficacy of the vaccine in reducing RGE-related hospitalizations, emergency department (ED) and office visits, and days of parental work loss for children receiving the vaccine was based on the results of the Rotavirus Efficacy and Safety Trial (REST). The outcome of interest was cost per quality-adjusted life year (QALY) gained from health care system and societal perspectives.ResultsA universal RV5 vaccination program is projected to reduce, hospitalizations, ED visits, outpatient visits and parental work days lost due to rotavirus infections by 89%, 80%, 67% and 74%, respectively. In the absence of RV5 vaccination, RGE-related societal costs are projected to be 2,023,038 Omani Rial (OMR) (5,259,899 United States dollars [USD]), including 1,338,977 OMR (3,481,340 USD) in direct medical costs. However, with the introduction of RV5, direct medical costs are projected to be 216,646 OMR (563,280 USD). Costs per QALY saved would be 1,140 OMR (2,964 USD) from the health care payer perspective. An RV5 vaccination program would be considered cost saving, from the societal perspective.ConclusionsUniversal RV5 vaccination in Oman is likely to significantly reduce the health care burden and costs associated with rotavirus gastroenteritis and may be cost-effective from the payer perspective and cost saving from the societal perspective.

The Molecular epidemiology of rotavirus infections in samples received from a private pathology practice during the 2010 and 2011 seasons

The molecular epidemiology of rotavirus infections in samples received from a private pathology practice during the 2010 and 2011 seasons. Rotaviruses have been identified as the most common cause of severe diarrhoea in young children. The WHO protocol on burden of disease requires research on seasonality, age of infection and genotyping of strains. Stool samples were collected from March 2010 to August 2011, and the analysis included enzyme linked immunosorbent assays, polyacrylamide gel electrophoresis, and reverse-transcription polymerase chain reaction.

Shared sanitation and the prevalence of diarrhea in young children: evidence from 51 countries, 2001-2011.

Shared sanitation is defined as unimproved because of concerns that it creates unsanitary conditions; this policy is being reconsidered. We assessed whether sharing a toilet facility was associated with an increased prevalence of diarrhea among children < 5 years of age. We use data from Demographic and Health Surveys conducted in 51 countries. Crude and adjusted prevalence ratios (PRs) for diarrhea, comparing children from households that used a shared facility with children from households that used a non-shared facility, were estimated for each country and pooled across countries. Unadjusted PRs varied across countries, ranging from 2.15 to 0.65. The pooled PR was 1.09; differences in socioeconomic status explained approximately half of this increased prevalence (adjusted PR = 1.05). Shared sanitation appears to be a risk factor for diarrhea although differences in socioeconomic status are important. The heterogeneity across countries, however, suggests that the social and economic context is an important factor.

Oral zinc and common childhood infections—An update

Zinc is an essential micronutrient important for growth and for normal function of the immune system. Many children in developing countries have inadequate zinc nutrition. Routine zinc supplementation reduces the risk of respiratory infections and diarrhea, the two leading causes of morbidity and mortality in young children worldwide. In childhood diarrhea oral zinc also reduces illness duration and risk of persistent episodes. Oral zinc is therefore recommended for the treatment of acute diarrhea in young children. The results from the studies that have measured the therapeutic effect of zinc on acute respiratory infections, however, are conflicting. Moreover, the results of therapeutic zinc for childhood malaria also are so far not promising.This paper gives a brief outline of the current evidence from clinical trials on therapeutic effect of oral zinc on childhood respiratory infections, pneumonia and malaria and also of new evidence of the effect on serious bacterial illness in young infants.

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 36.8% of the wealthiest households. Soap, detergent, and ash were used for multiple hygiene purposes and were kept together at handwashing areas. Caretakers preferred soap for handwashing, but frequently relied on ash, or a detergent/ash mixture, as a low-cost alternative. Moderate-to-severe diarrhea was equally likely for children of caretakers who kept soap versus those who kept ash (matched OR = 0.91; 0.62–1.32). Contact with ash and water reduced concentrations of bacterial enteropathogens, without mechanical scrubbing. Thus, washing hands with ash is a prevalent behavior in Mirzapur and may help diminish transmission of diarrheal pathogens to children.