Phylogeographical analysis of the dominant multidrug-resistant H58 clade of Salmonella Typhi identifies inter- and intracontinental transmission events.

The emergence of multidrug-resistant (MDR) typhoid is a major global health threat affecting many countries where the disease is endemic. Here whole-genome sequence analysis of 1,832 Salmonella enterica serovar Typhi (S. Typhi) identifies a single dominant MDR lineage, H58, that has emerged and spread throughout Asia and Africa over the last 30 years. Our analysis identifies numerous transmissions of H58, including multiple transfers from Asia to Africa and an ongoing, unrecognized MDR epidemic within Africa itself. Notably, our analysis indicates that H58 lineages are displacing antibiotic-sensitive isolates, transforming the global population structure of this pathogen. H58 isolates can harbor a complex MDR element residing either on transmissible IncHI1 plasmids or within multiple chromosomal integration sites. We also identify new mutations that define the H58 lineage. This phylogeographical analysis provides a framework to facilitate global management of MDR typhoid and is applicable to similar MDR lineages emerging in other bacterial species

Global respiratory syncytial virus–related infant community deaths

Background Respiratory syncytial virus (RSV) is a leading cause of pediatric death, with >99% of mortality occurring in low- and lower middle-income countries. At least half of RSV-related deaths are estimated to occur in the community, but clinical characteristics of this group of children remain poorly characterized. Methods The RSV Global Online Mortality Database (RSV GOLD), a global registry of under-5 children who have died with RSV-related illness, describes clinical characteristics of children dying of RSV through global data sharing. RSV GOLD acts as a collaborative platform for global deaths, including community mortality studies described in this supplement. We aimed to compare the age distribution of infant deaths <6 months occurring in the community with in-hospital. Results We studied 829 RSV-related deaths <1 year of age from 38 developing countries, including 166 community deaths from 12 countries. There were 629 deaths that occurred <6 months, of which 156 (25%) occurred in the community. Among infants who died before 6 months of age, median age at death in the community (1.5 months; IQR: 0.8−3.3) was lower than in-hospital (2.4 months; IQR: 1.5−4.0; P < .0001). The proportion of neonatal deaths was higher in the community (29%, 46/156) than in-hospital (12%, 57/473, P < 0.0001). Conclusions We observed that children in the community die at a younger age. We expect that maternal vaccination or immunoprophylaxis against RSV will have a larger impact on RSV-related mortality in the community than in-hospital. This case series of RSV-related community deaths, made possible through global data sharing, allowed us to assess the potential impact of future RSV vaccines

Disparities by sex in care-seeking behaviors and treatment outcomes for pneumonia among children admitted to hospitals in Bangladesh.

BackgroundIncidence of community acquired pneumonia is high globally. In Bangladesh, more male children than female children are brought to hospitals for pneumonia. We examined if there was disparities in the severity of illness and outcome by sex among children who were admitted with pneumonia to hospitals in Bangladesh.MethodsHospitalized children, aged 2 to 59 months, meeting a case definition of pneumonia were recruited in seven hospitals following parental consent. At baseline, study doctors obtained socio-demographic characteristics and care seeking behaviors for pneumonia, and then clinical data were collected throughout the hospital stay. Multivariate analysis was performed to determine if the sex of the child had a relationship with either illness severity on admission or outcome in the hospital.ResultsBetween May 2004 and December 2008, 6,856 children, including 35% females, were recruited. A total of 1,371 (19.9%) children had non-severe pneumonia, 4,118 (60.0%) had severe pneumonia, and 1,367 (19.9%) had very severe pneumonia. A higher proportion of hospitalized females had very severe pneumonia as compared to males (21.5% versus 19.1%; P = 0.01), but there was no difference by sex in the proportion of children with severe or non-severe pneumonia. There was no difference by sex observed in the clinical management provided in the hospital, but a greater proportion of females (4.7%) as compared to males (3.6%) died in hospitals (P = 0.04). In multivariate analyses, female sex was associated with very severe pneumonia on admission (OR: 1.26, 95% CI: 1.09-1.47) and fatal outcome in the hospitals (OR: 1.31, 95% CI: 1.01-1.71). Death in female children admitted with very severe pneumonia was 4 times higher than that reported in males (OR: 4.37, 95% CI: 3.24-5.89).ConclusionOur data demonstrates a sex-based disparity in the severity of pneumonia and deaths among children admitted to hospitals in Bangladesh, despite no existing disparity by sex in hospital treatment. These findings call for further investigations to explore the determinants of health seeking behavior by parents with children with pneumonia in a community that favors males to females, and to understand the role of differences by sex in childhood pneumonia outcomes in Bangladesh

Symptomatic and asymptomatic enteric protozoan parasitic infection and their association with subsequent growth parameters in under five children in South Asia and sub-Saharan Africa.

BackgroundEntamoeba histolytica, Giardia, and Cryptosporidium are common intestinal protozoan parasites that contribute to a high burden of childhood morbidity and mortality. Our study quantified the association between intestinal protozoan parasites and child anthropometric outcomes among children under-5.MethodsWe analyzed data from 7,800 children enrolled in the Global Enteric Multicenter Study (GEMS) across seven study sites that were positive for intestinal protozoan parasites between December 2007 and March 2011. Parasites were assessed using stool immunoassays (ELISA). We applied multiple linear regression to test the association between any or concurrent parasite and child anthropometric outcomes: length/height-for-age (HAZ), weight-for-age (WAZ), and weight-for-length/height (WHZ) z-score after 60 days of enrollment. Models were stratified by diarrheal symptoms, driven by the study design, and adjusted for potential covariates.FindingsDuring the follow-up at day 60 after enrollment, child anthropometric outcomes, among the asymptomatic children showed, negative associations between Giardia with HAZ [β: -0.13; 95% CI: -0.17, -0.09; pConclusionsWhile some studies have found that Giardia is not associated with (or protective against) acute diarrhea, our findings suggest that it is associated with growth shortfall. This observation underscores the need for preventive strategies targeting enteric protozoan parasites among young children, to reduce the burden of childhood malnutrition

Baseline characteristics of the symptomatic children having stool positive for enteric protozoan parasites (<i>Cryptosporidium</i>, <i>Giardia</i>, and <i>Entamoeba histolytica</i>) in seven sites of GEMS.

Baseline characteristics of the symptomatic children having stool positive for enteric protozoan parasites (Cryptosporidium, Giardia, and Entamoeba histolytica) in seven sites of GEMS.</p

Associations between enteric protozoan parasites co-infections and child anthropometric measurements among under 5 asymptomatic and symptomatic MSD children in South Asia and sub-Saharan Africa using multiple linear regression modeling (Dependent variables: HAZ/LAZ, WAZ, and WHZ).

Associations between enteric protozoan parasites co-infections and child anthropometric measurements among under 5 asymptomatic and symptomatic MSD children in South Asia and sub-Saharan Africa using multiple linear regression modeling (Dependent variables: HAZ/LAZ, WAZ, and WHZ).</p

Among symptomatic children: association between enteric protozoan parasites infection and child anthropometric measurements: results of multiple linear regression modeling (dependent variables—HAZ/LAZ, WAZ, and WHZ) among the different age groups.

Among symptomatic children: association between enteric protozoan parasites infection and child anthropometric measurements: results of multiple linear regression modeling (dependent variables—HAZ/LAZ, WAZ, and WHZ) among the different age groups.</p

Study flow diagram.

BackgroundEntamoeba histolytica, Giardia, and Cryptosporidium are common intestinal protozoan parasites that contribute to a high burden of childhood morbidity and mortality. Our study quantified the association between intestinal protozoan parasites and child anthropometric outcomes among children under-5.MethodsWe analyzed data from 7,800 children enrolled in the Global Enteric Multicenter Study (GEMS) across seven study sites that were positive for intestinal protozoan parasites between December 2007 and March 2011. Parasites were assessed using stool immunoassays (ELISA). We applied multiple linear regression to test the association between any or concurrent parasite and child anthropometric outcomes: length/height-for-age (HAZ), weight-for-age (WAZ), and weight-for-length/height (WHZ) z-score after 60 days of enrollment. Models were stratified by diarrheal symptoms, driven by the study design, and adjusted for potential covariates.FindingsDuring the follow-up at day 60 after enrollment, child anthropometric outcomes, among the asymptomatic children showed, negative associations between Giardia with HAZ [β: -0.13; 95% CI: -0.17, -0.09; pCryptosporidium with WAZ [β: -0.15; 95% CI: -0.22, -0.09; pGiardia and anthropometry; negative associations were found between Cryptosporidium with HAZ [β: -0.17; 95% CI: -0.23, -0.11; pGiardia had a negative association with HAZ [β: -0.09; 95% CI: -0.15, -0.04; p = 0.001]. No significant associations were found between E. histolytica with child growth.ConclusionsWhile some studies have found that Giardia is not associated with (or protective against) acute diarrhea, our findings suggest that it is associated with growth shortfall. This observation underscores the need for preventive strategies targeting enteric protozoan parasites among young children, to reduce the burden of childhood malnutrition.</div

Age-specific association between enteric protozoan parasites co-infections and child anthropometric measurements among symptomatic MSD and asymptomatic children on growth measures among under 5 children in South Asia and sub-Saharan Africa using multiple linear regression modeling (Dependent variables: HAZ/LAZ, WAZ, and WHZ).

a. Age-specific association between enteric protozoan parasites co-infections and child anthropometric measurements among symptomatic MSD children on growth measures among under 5 children in South Asia and sub-Saharan Africa using multiple linear regression modeling (Dependent variables: HAZ/LAZ, WAZ, and WHZ). b. Age-specific association between enteric protozoan parasites co-infections and child anthropometric measurements among asymptomatic children on growth measures among under 5 children in South Asia and sub-Saharan Africa using multiple linear regression modeling (Dependent variables: HAZ/LAZ, WAZ, and WHZ). (DOCX)</p