Acceptability of and Adherence to Dispersible Zinc Tablet in the Treatment of Acute Childhood Diarrhoea

Zinc treatment is now recommended by the World Health Organization as part of the routine management of acute childhood diarrhoea. A dispersible zinc tablet formulation was developed taking into account the taste, cost, and feasibility to distribute and store. Only limited information is available on the acceptability of and adherence to dispersible zinc tablet. No study has formally assessed whether the formulation is acceptable to children and if caretakers can adhere to the instructions regarding preparation, dosage, and duration of treatment. This community-based study aimed at determining the acceptability of and adherence to a dispersible zinc tablet formulation in a cohort of children (n=320) aged less than five years. Caretakers of children with acute childhood diarrhoea were prescribed zinc tablet treatment and followed up after 2-3 weeks. The formulation was acceptable to children; 90.1% of 303 caretakers perceived that the tablets were equally or even more acceptable to their children com-pared to other medicines. Ninety-eight percent of the children received the standard dose of one tablet per day, and 55.8% completed the full 10-day course of zinc treatment. Adherence rates did not vary by age or gender of the child. These findings indicate that the tablet formulation is acceptable, but further efforts are required to enhance adherence

Diarrhoeal disease and subsequent risk of death in infants and children residing in low-income and middle-income countries: Analysis of the gems case-control study and 12-month gems-1a follow-on study

Background: The Global Enteric Multicenter Study (GEMS) was a 3-year case-control study that measured the burden, aetiology, and consequences of moderate-to-severe diarrhoea (MSD) in children aged 0-59 months. GEMS-1A, a 12-month follow-on study, comprised two parallel case-control studies, one assessing MSD and the other less-severe diarrhoea (LSD). In this report, we analyse the risk of death with each diarrhoea type and the specific pathogens associated with fatal outcomes.Methods: GEMS was a prospective, age-stratified, matched case-control study done at seven sites in Africa and Asia. Children aged 0-59 months with MSD seeking care at sentinel health centres were recruited along with one to three randomly selected matched community control children without diarrhoea. In the 12-month GEMS-1A follow-on study, children with LSD and matched controls, in addition to children with MSD and matched controls, were recruited at six of the seven sites; only cases of MSD and controls were enrolled at the seventh site. We compared risk of death during the period between enrolment and one follow-up household visit done about 60 days later (range 50-90 days) in children with MSD and LSD and in their respective controls. Approximately 50 pathogens were detected using, as appropriate, classic bacteriology, immunoassays, gel-based PCR and reverse transcriptase PCR, and quantitative real-time PCR (qPCR). Specimens from a subset of GEMS cases and controls were also tested by a TaqMan Array Card that compartmentalised probe-based qPCR for 32 enteropathogens.Findings: 223 (2·0%) of 11 108 children with MSD and 43 (0·3%) of 16 369 matched controls died between study enrolment and the follow-up visit at about 60 days (hazard ratio [HR] 8·16, 95% CI 5·69-11·68, p\u3c0·0001). 12 (0·4%) of 2962 children with LSD and seven (0·2%) of 4074 matched controls died during the follow-up period (HR 2·78, 95% CI 0·95-8·11, p=0·061). Risk of death was lower in children with dysenteric MSD than in children with non-dysenteric MSD (HR 0·20, 95% CI 0·05-0·87, p=0·032), and lower in children with LSD than in those with non-dysenteric MSD (HR 0·29, 0·14-0·59, p=0·0006). In children younger than 24 months with MSD, infection with typical enteropathogenic Escherichia coli, enterotoxigenic E coli encoding heat-stable toxin, enteroaggregative E coli, Shigella spp (non-dysentery cases), Aeromonas spp, Cryptosporidium spp, and Entamoeba histolytica increased risk of death. Of 61 deaths in children aged 12-59 months with non-dysenteric MSD, 31 occurred among 942 children qPCR-positive for Shigella spp and 30 deaths occurred in 1384 qPCR-negative children (HR 2·2, 95% CI 1·2-3·9, p=0·0090), showing that Shigella was strongly associated with increased risk of death.Interpretation: Risk of death is increased following MSD and, to a lesser extent, LSD. Considering there are approximately three times more cases of LSD than MSD in the population, more deaths are expected among children with LSD than in those with MSD. Because the major attributable LSD-associated and MSD-associated pathogens are the same, implementing vaccines and rapid diagnosis and treatment interventions against these major pathogens are rational investments.Funding: Bill & Melinda Gates Foundation

The incidence, aetiology, and adverse clinical consequences of less severe diarrhoeal episodes among infants and children residing in low-income and middle-income countries: A 12-month case-control study as a follow-on to the global enteric multicenter study (GEMS)

Background: Diarrheal diseases remain a leading cause of illness and death among children younger than 5 years in low-income and middle-income countries. The Global Enteric Multicenter Study (GEMS) has described the incidence, aetiology, and sequelae of medically attended moderate-to-severe diarrhoea (MSD) among children aged 0-59 months residing in censused populations in sub-Saharan Africa and south Asia, where most child deaths occur. To further characterise this disease burden and guide interventions, we extended this study to include children with episodes of less-severe diarrhoea (LSD) seeking care at health centres serving six GEMS sites.Methods: We report a 1-year, multisite, age-stratified, matched case-control study following on to the GEMS study. Six sites (Bamako, Mali; Manhiça, Mozambique; Basse, The Gambia; Mirzapur, Bangladesh; Kolkata, India; and Bin Qasim Town, Karachi, Pakistan) participated in this study. Children aged 0-59 months at each site who sought care at a sentinel hospital or health centre during a 12-month period were screened for diarrhoea. New (onset after ≥7 diarrhoea-free days) and acute (onset within the previous 7 days) episodes of diarrhoea in children who had sunken eyes, whose skin lost turgor, who received intravenous hydration, who had dysentery, or who were hospitalised were eligible for inclusion as MSD. The remaining new and acute diarrhoea episodes among children who sought care at the same health centres were considered LSD. We aimed to enrol the first eight or nine eligible children with MSD and LSD at each site during each fortnight in three age strata: infants (aged 0-11 months), toddlers (aged 12-23 months), and young children (aged 24-59 months). For each included case of MSD or LSD, we enrolled one to three community control children without diarrhoea during the previous 7 days. From patients and controls we collected clinical and epidemiological data, anthropometric measurements, and faecal samples to identify enteropathogens at enrolment, and we performed a follow-up home visit about 60 days later to ascertain vital status, clinical outcome, and interval growth. Primary outcomes were to characterise, for MSD and LSD, the pathogen-specific attributable risk and population-based incidence values, and to assess the frequency of adverse clinical consequences associated with these two diarrhoeal syndromes.Findings: From Oct 31, 2011, to Nov 14, 2012, we recruited 2368 children with MSD, 3174 with LSD, and one to three randomly selected community control children without diarrhoea matched to cases with MSD (n=3597) or LSD (n=4236). Weighted adjusted population attributable fractions showed that most attributable cases of MSD and LSD were due to rotavirus, Cryptosporidium spp, enterotoxigenic Escherichia coli encoding heat-stable toxin (with or without genes encoding heat-labile enterotoxin), and Shigella spp. The attributable incidence per 100 child-years for LSD versus MSD, by age stratum, for rotavirus was 22·3 versus 5·5 (0-11 months), 9·8 versus 2·9 (12-23 months), and 0·5 versus 0·2 (24-59 months); for Cryptosporidium spp was 3·6 versus 2·3 (0-11 months), 4·3 versus 0·6 (12-23 months), and 0·3 versus 0·1 (24-59 months); for enterotoxigenic E coli encoding heat-stable toxin was 4·2 versus 0·1 (0-11 months), 5·2 versus 0·0 (12-23 months), and 1·1 versus 0·2 (24-59 months); and for Shigella spp was 1·0 versus 1·3 (0-11 months), 3·1 versus 2·4 (12-23 months), and 0·8 versus 0·7 (24-59 months). Participants with both MSD and LSD had significantly more linear growth faltering than controls at follow-up.Interpretation: Inclusion of participants with LSD markedly expands the population of children who experience adverse clinical and nutritional outcomes from acute diarrhoeal diseases. Since MSD and LSD have similar aetiologies, interventions targeting rotavirus, Shigella spp, enterotoxigenic E coli producing heat-stable toxin, and Cryptosporidium spp might substantially reduce the diarrhoeal disease burden and its associated nutritional faltering

Selección de cepa de Bacillus Spp probiótica autóctona con mayor actividad enzimática

El presente estudio se enfocó en la determinación de actividad enzimática de cepas de Bacillus spp autóctonas (XSCD-9, xsc-9, X2-10) previamente estudiadas, estas cepas fueron procesadas mediante técnicas de laboratorio para esto se realizaron pruebas probióticas de halos de hidrólisis, unidades de Anson, a si como también la determinación de un medio de cultivo industrial económico y efectivo para la optima reproducción y producción de enzimas proteolíticas de los microorganismos candidatos, en donde resulto como mayor productora de enzimas proteolíticas con 17.5336 UA y 30 mm de halo de hidrólisis, fue la cepa X2-10 que corresponde a un Bacillus cereus según su secuenciación, con la composición de la corrida #3 (Melaza: 75 g/1, Levadura torula: 50 g/1, Calcio: 1.5 g/1, Temperatura: 39°C.) la cual fue evaluada atreves del método estadístico coeficiente de variación, presentando el porcentaje más bajo de las 3 cepas candidatas estudiadas

Predictors of diarrheal mortality and patterns of caregiver health seeking behavior in in Karachi, Pakistan

Background: Pakistan is unfortunately among the five countries that contributed to the most deaths due to diarrhea and pneumonia in 2010. To explore factors associated with diarrheal deaths we assessed care-seeking behavior and other predictors of diarrhea-related mortality in children in selected low-income peri-urban communities of Karachi, Pakistan.Methods: A mixed methods study (qualitative and quantitative) using matched case-control design and focus group discussions with parents of children with moderate to severe diarrhea (MSD) was undertaken. Cases were children Demographic, clinical, and care-related behavioral predictors of mortality were assessed. Conditional logistic regression was performed, matched adjusted odds ratios (mOR) are reported.Results: Parents of 77 cases and 154 controls were interviewed. Cases were less likely to receive appropriate care compared to controls (mOR=0.2, 95% confidence interval (CI) 0.05-0.91). Refusal for hospital admission (OR=8.9, 95% CI 2.6-30.8), and delays in reaching the health facility (OR=3.6, 95% CI 1.0-12.9) were significant independent predictors of mortality. We found strong beliefs in traditional and spiritual healing in the population; use of both modern and traditional/spiritual treatments concurrently was common.Conclusion: Appropriate care seeking behavior predicts survival in children with diarrhea in Pakistan. There is a complex belief system relating to traditional and standard therapies. Health education for appropriate health care seeking should be implemented in order to achieve a substantial decline in diarrheal disease mortality in Pakistan

Risk factors for death among children 0–59 months of age with moderate-to-severe diarrhea in Manhiça district, southern Mozambique

Background: Despite major improvements in child survival rates, the number of deaths due to diarrhea remains unacceptably high. We aimed to describe diarrhea-associated mortality and evaluate risk factors for death among Mozambican children with moderate-to-severe diarrhea (MSD). Methods: Between December 2007 and November 2012, children under-five with MSD were enrolled in Manhiça district, as part of the Global Enteric Multicenter study (GEMS). Clinical, epidemiological, and socio-demographic characteristics were collected. Anthropometric measurements were performed and stool samples collected upon recruitment. A follow-up visit ~ 60 days post-enrolment was conducted and verbal autopsies performed in all death cases. Results: Of the 916 MSD-cases analyzed; 90% (821/916) completed 60 days follow-up and 69 patients died. The case fatality rate at follow-up was 8% (69/821), and the mortality rate 10.2 (95%CI: 7.75–13.59) deaths per 1000 persons-week at risk. Nearly half of the deaths 48% (33/69) among study participants clustered within 2 weeks of the onset of diarrhea. Typical enteropathogenic Escherichia coli (typical EPEC) and Cryptosporidium were the two pathogens associated to an increased risk of death in the univariate analysis with (HR = 4.16, p = 0.0461) and (H = 2.84, p = 0.0001) respectively. Conversely, Rotavirus infection was associated to a decreased risk of death (HR = 0.52, p = 0.0198). According to the multivariate analysis, risk factors for death included co-morbidities such as malnutrition (HR = 4.13, p < 0.0001), pneumonia/lower respiratory infection (HR = 3.51, p < 0.0001) or invasive bacterial disease (IBD) (HR = 6. 80, p = 0.0009), presenting on arrival with lethargy or overt unconsciousness (HR = 1.73, p = 0.0302) or wrinkled skin (HR = 1.71, p = 0.0393), and cryptosporidium infection (HR = 2.14, p = 0.0038). When restricting the analysis to those with available HIV results (n = 191, 22% of the total study sample), HIV was shown to be a significant risk factor for death (HR = 5.05, p = 0.0009). Verbal autopsies were conducted in 100% of study deaths, and highlighted diarrhea as the main underlying cause of death 39%, (27/69); followed by HIV/AIDS related deaths 29.0% (20/69) and sepsis 11.6% (8/69).Conclusion: Preventive strategies targeting Cryptosporidium, malnutrition and early identification and treatment of associated co-morbidities could contribute to the prevention of the majority of diarrhea associated deaths in Mozambican children

Pneumonia mortality and healthcare utilization in young children in rural Bangladesh: a prospective verbal autopsy study

BackgroundThe present study aimed to examine the risk factors for death due to pneumonia in young children and healthcare behaviors of the guardians for children in rural Bangladesh. A prospective autopsy study was conducted among guardians of children aged 4 weeks to 59 months in Mirzapur, Bangladesh, from 2008 to 2012.ResultsPneumonia was the primary cause of death, accounting for 26.4% (n = 81) of all 307 deaths. Of the pneumonia deaths, 58% (n = 47) deaths occurred in younger infants (aged 4 weeks to < 6 months) and 24.7% (n = 20) in older infants (aged 6–11 months). The median duration of illness before pneumonia death was 8 days (interquartile range [IQR] 3–20 days). Prior to death, 91.4% (n = 74) children with pneumonia sought treatment, and of those who sought treatment, 52.7% (n = 39) sought treatment ≥ 2 days after the onset of disease. Younger infants of 4 weeks to < 6 months old were at 5.5-time (95% confidence interval [CI] 2.5, 12.0) and older infants aged 6–11 months were at 3-time (1.2, 7.5) greater risk of dying from pneumonia than older children aged 12–59 months. Children with a prolonged duration of illness (2–10 days) prior to death were at more risk for death by pneumonia than those who died from other causes (5.8 [2.1, 16.1]). Children who died from pneumonia sought treatment 3.4-time more than children who died from other causes. Delayed treatment seeking (≥ 2 days) behavior was 4.9-time more common in children who died from pneumonia than those who died from other causes. Children who died from pneumonia more often had access to care from multiple sources (5.7-time) than children who died from other causes.ConclusionsDelay in seeking appropriate care and access to multiple sources for treatment are the underlying risk factors for pneumonia death in young children in Bangladesh. These results indicate the perplexity in guardians’ decisions to secure appropriate treatment for children with pneumonia. Therefore, it further underscores the importance of focusing on mass media coverage that can outline the benefits of seeking care early in the progression of pneumonia and the potential negative consequences of seeking care late

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 0.7% to 4.4% for infants (0–11 months of age), from 0.4% to 4.7% for toddlers (12–23 months of age), and from 0.3% to 2.4% for preschoolers (24–59 months of age). The proportion of MSD episodes at each site taken to an SHC within 7 days of diarrhea onset was 15–56%, 17–64%, and 7–33% in the three age strata, respectively. High cost of care and insufficient knowledge about danger signs were associated with lack of any care-seeking outside the home. Most children were not offered recommended fluids and continuing feeds at home. We have shown the utility of serial HUASs as a tool for optimizing operational and methodological issues related to the performance of a large case-control study and deriving population-based incidence rates of MSD. Moreover, the surveys suggest key targets for educational interventions that might improve the outcome of diarrheal diseases in low-resource settings

Enteric viral pathogens and child growth among under-five children: findings from South Asia and sub-Saharan Africa.

Enteric viral pathogens are associated with a significant burden of childhood morbidity and mortality. We investigated the relationship between viral pathogens and child growth among under-5 children. We analyzed data from 5572/22,567 children enrolled in the Global Enteric Multicenter Study across seven study sites (2007-2011). Multiple linear regression was used to examine the association between the viral pathogens and changes of length/height-for-age (HAZ), weight-for-age (WAZ), and weight-for-length/height (WHZ) z-scores, stratified by diarrheal symptoms and adjusted for potential covariates. Rotavirus (18.51%) and norovirus (7.33%) were the most prevalent enteric viral pathogens among symptomatic and asymptomatic under-5 children, respectively. Infection with individual enteric viral pathogens hurts child growth in asymptomatic children. However, the relationship with HAZ was less clear and statistically non-significant. On the other hand, the combined viral pathogens demonstrated a strong negative influence on child growth [WAZ: β coef.: - 0.10 (95%, CI - 0.15, - 0.05); P < 0.001 and WHZ: β: - 0.12 (95% CI - 0.17, - 0.07); P < 0.001] among asymptomatic children. Infection with any viral pathogen was associated with growth shortfalls [HAZ: β: - 0.05 (95% CI - 0.09, 0.00); P = 0.03 and WAZ: β: - 0.11 (95% CI - 0.16, - 0.07); P < 0.001 and WHZ: β: - 0.13 (95% CI - 0.18, - 0.09); P < 0.001], though the relationship with HAZ was less evident and became statistically non-significant in older children. Notably, among symptomatic children with moderate-to-severe diarrhea, individual enteric viral pathogens, as well as the combined effects of these pathogens [WHZ: β: 0.07; (95% CI 0.01, 0.14); P = 0.03] and the presence of any virus [HAZ: β: 0.09 (95% CI 0.05, 0.13) & WAZ: β: 0.08 (95% CI 0.03, 0.12); P < 0.001], exhibited positive effects on child growth. While previous studies hypothesized that several viral pathogens had a conflicting controversial role in child growth, we find clear indications that enteric viral pathogens are associated with growth shortfalls, specifically among asymptomatic children. These findings highlight the need for preventive strategies targeting children with enteric viral pathogens, which could address the consequences of growth faltering