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Background: Fibersol-2 has innumerable beneficial effects on human health. It is a fermentable, non-viscous, water-soluble, indigestible dextrin containing 90% dietary fiber produced from corn starch. We aimed to evaluate whether additional intake of Fibersol-2 along with oral rehydration solution treatment can reduce the duration of watery diarrhea and daily stool output in children 1–3 years as well as recovery of such children within 72 hours, compared to placebo. Methods: This placebo-controlled double-blinded, randomized parallel two arm trial conducted in Kumudini Women's Medical College Hospital in rural Bangladesh between March and October, 2018 used 5 gm of either Fibersol-2 or placebo dissolved in 50-ml drinking water which was given orally to ninety-two children with watery diarrhea on enrollment twice daily for a period of 7 days. Randomization was done using a randomization table. We randomly allocated 45 (49%) and 47 (51%) children in Fibersol-2 and placebo groups, respectively. Outcome measures were duration of resolution of watery diarrhea, daily stool output and the proportion of children recovered within 72 hours. Primary and safety analyses were by intention to treat. This trial was registered at ClinicalTrials.gov, number NCT03565393. Results: There was no significant difference observed in terms of duration of resolution of diarrhea (adjusted mean difference 8.20, 95% CI -2.74 to 19.15, p = 0.14, adjusted effect size 0.03); the daily stool output (adjusted mean difference 73.57, 95% CI -94.17 to 241.32, p = 0.38, adjusted effect size 0.33) and the proportion of children recovered within 72 hours (adjusted odds ratio 0.49, 95% CI = 0.12 to 1.96, p = 0.31, adjusted risk difference -0.06 (95% CI -0.19 to -0.06), after regression analysis between Fibersol-2 and placebo. Conclusion: No beneficial role of Fibersol-2 was observed in diarrheal children aged 1–3 years. Trial registration: This trial is registered at ClinicalTrials.gov, number NCT03565393. The authors confirmed that all ongoing and related trials for this drug/intervention are registered. https://clinicaltrials.gov/ct2/show/NCT03565393. [ABSTRACT FROM AUTHOR]

Background: Fibersol-2 has some beneficial effects on human health. We aimed to evaluate the digestive tolerability and acceptability of Fibersol-2 in healthy and diarrheal children, as well as improvement in stool consistencies in young diarrheal children. Methods: Sixty children of either sex, aged 1–3 years having four groups (healthy children/low dose, healthy children/high dose, children with diarrhea/low dose and children with diarrhea/high dose) were enrolled into this exploratory study between 1st August to 23rd October 2017. Two presumptive doses, low (2.5g) and high (5g), twice daily with 50 ml drinking water for seven days were the interventions. Outcomes were to observe the development of possible abdominal symptoms, such as pain, distension, rumbling, and bloating during the intervention and post-intervention periods in healthy and diarrheal children as well as improvement in stool consistencies in diarrheal children. Results: Among the diarrheal children, the median (IQR) duration of resolution of diarrhea was 3.9 (2.9, 5.1) days vs. 3.5 (2.0, 8.0) days, p = 0.885; in low dose and high dose groups, respectively. Significant difference was observed in terms of abdominal pain (27% vs. 7%, p = 0.038) and distension (40% vs. 0%, p<0.001) in diarrheal children, compared to healthy children during the pre-intervention period. We also observed significant difference in respect of abdominal distension (23% vs. 0%, p = 0.011), rumbling (27% vs. 0%, p = 0.005) and bloating (43% vs. 3%, p = 0.001) in diarrheal children, compared to healthy children during the intervention period. However, no significant difference was observed in relation to abdominal pain (p = 0.347) and distension (p = 0.165) during the pre-intervention period, compared to the intervention period in diarrheal children. Moreover, no significant difference was observed during the post-intervention period for the diarrheal and healthy children. Conclusion: Fibersol-2 was found to be well tolerated in healthy and diarrheal children aged 1–3 years. Trial registration: This study was registered as part of a randomized trial at ClinicalTrials.gov, number NCT03565393. The authors confirmed that all ongoing and related trials for this drug/intervention were registered. [ABSTRACT FROM AUTHOR]

Background Diarrheal disease is the second leading cause of disease in children less than 5 y of age. Poor water, sanitation, and hygiene conditions are the primary routes of exposure and infection. Sanitation and hygiene interventions are estimated to generate a 36% and 48% reduction in diarrheal risk in young children, respectively. Little is known about whether the number of households sharing a sanitation facility affects a child's risk of diarrhea. The objective of this study was to describe sanitation and hygiene access across the Global Enteric Multicenter Study (GEMS) sites in Africa and South Asia and to assess sanitation and hygiene exposures, including shared sanitation access, as risk factors for moderate-to-severe diarrhea (MSD) in children less than 5 y of age. Methods/Findings The GEMS matched case-control study was conducted between December 1, 2007, and March 3, 2011, at seven sites in Basse, The Gambia; Nyanza Province, Kenya; Bamako, Mali; Manhiça, Mozambique; Mirzapur, Bangladesh; Kolkata, India; and Karachi, Pakistan. Data was collected for 8,592 case children aged Conclusions This study suggests that sharing a sanitation facility with just one to two other households can increase the risk of MSD in young children, compared to using a private facility. Interventions aimed at increasing access to private household sanitation facilities may reduce the burden of MSD in children. These findings support the current World Health Organization/ United Nations Children's Emergency Fund (UNICEF) system that categorizes shared sanitation as unimproved., Author(s): Kelly K. Baker 1,2,*, Ciara E. O'Reilly 3, Myron M. Levine 1, Karen L. Kotloff 1, James P. Nataro 1,4, Tracy L. Ayers 3, Tamer H. Farag 1,5, Dilruba [...]

Background: To take advantage of emerging opportunities to reduce morbidity and mortality from diarrheal disease, we need to better understand the determinants of life-threatening severe dehydration (SD) in resource-poor settings. Methodology/findings: We analyzed records of patients admitted with acute diarrheal disease over twenty-two years at the International Centre for Diarrhoeal Disease Research, Bangladesh (1993–2014). Patients presenting with and without SD were compared by multivariable logistic regression models, which included socio-demographic factors and pathogens isolated. Generalized additive models evaluated non-linearities between age or household income and SD. Among 55,956 admitted patients, 13,457 (24%) presented with SD. Vibrio cholerae was the most common pathogen isolated (12,405 patients; 22%), and had the strongest association with SD (AOR 4.77; 95% CI: 4.41–5.51); detection of multiple pathogens did not exacerbate SD risk. The highest proportion of severely dehydrated patients presented in a narrow window only 4–12 hours after symptom onset. Risk of presenting with SD increased sharply from zero to ten years of age and remained high throughout adolescence and adulthood. Adult women had a 38% increased odds (AOR 1.38; 95% CI: 1.30–1.46) of SD compared to adult men. The probability of SD increased sharply at low incomes. These findings were consistent across pathogens. Conclusions/significance: There remain underappreciated populations vulnerable to life-threatening diarrheal disease that include adult women and the very poor. In addition to efforts that address diarrheal disease in young children, there is a need to develop interventions for these other high-risk populations that are accessible within 4 hours of symptom onset. [ABSTRACT FROM AUTHOR]

Background: Micronutrient deficiencies can compromise the development potential of school-aged children, and their later health and productivity as adults. School feeding and school-based fortification approaches have been utilized globally to redress nutritional deficiencies in this age group. Objective: We explored the acceptability and micronutrient impact of a Bangladesh Government supported school-based micronutrient fortification program for children attending rural primary schools in 10 disadvantaged sub-districts. Methods: We applied a mixed methods approach. The quantitative component assessed the impact of micronutrient fortification on 351 children aged 6–11 years using a cohort pre-post research design with a control group. The qualitative component explored the acceptability of the intervention using focus group discussions, body mapping and semi-structured interviews with teachers, school-going children and school authorities. Results: Daily consumption of fortified biscuits by primary school children had a significant positive impact on mean levels of iron, folic acid, vitamin B12, retinol and vitamin D controlling for sex, baseline deficiency status, CRP, and H. pylori. Levels of anemia and vitamin D deficiency were also significantly reduced. Qualitative findings indicated the widespread acceptability of the daily biscuit. Teachers perceived students to be more attentive in class, less tired, and some attributed better school performance to biscuit consumption. Children reported similar improvements in concentration and energy levels. Conclusions: This study is among the first in Bangladesh to comprehensively assess a school-based fortification program in terms of its acceptability and impact on micronutrient status of children aged 6–11 years of age. While results strongly support this modality of school feeding, research on the cognitive impacts of micronutrient fortified biscuits will help clarify the case for scaled-up investments in school- based feeding program in Bangladesh and other low and middle income countries. [ABSTRACT FROM AUTHOR]

Background: Childhood rotavirus diarrhea is still one of the major public health challenges. The present study aimed to determine changing characteristics of rotavirus diarrhea in under-5 children at two periods of time. Methods: We enrolled 5,357 under-5 children with rotavirus positive in two different time periods; i) 1993-1997 (n = 2,493), and ii) 2008–2012 (n = 2,864) considering beginning and ending of two decades. These children were enrolled in the urban Dhaka Hospital of icddr,b. Results: Overall, proportion of rotavirus was about 25% in 1993–97, which was 42% in 2008–12 (68% rise; p<0.001). Significant higher proportion of children were stunted [38% vs. 22%; aOR-1.33 (95% CI-1.09-1.62)], had vomiting [87% vs. 74%; aOR-2.58 (95% CI-2.02-3.28)], fever [10% vs. 8%; aOR-1.31 (95% CI-0.96-1.78)], family members >5 [38% vs. 35%; aOR-1.32 (95% CI-1.10-1.58)] required more intravenous fluid [9% vs. 3%; aOR-4.93 (95% CI-3.19-7.63)], had higher co-infection with Shigella [3% vs. 1%; aOR-3.36 (95% CI-1.61-7.03)], Vibrio cholerae [4% vs. 1%; aOR-3.70 (95% CI-2.12-6.46)]; and ETEC [13% vs. 7%; aOR-2.21 (95% CI-1.65-2.97)]; however, significantly lower proportion of them used sanitary toilets [54% vs. 78%; aOR-0.66 (95% CI-0.54-0.80)], boiled drinking water [16% vs. 38%; aOR-0.60 (95% CI-0.48-0.74)], used antimicrobial at home [63% vs. 82%; aOR-0.56 (95% CI-0.46-0.69)] and had some or severe dehydration [18% vs. 34%; aOR-0.15 (95% CI-0.12-0.20)] in 1st observation period compared to that of 2nd. Conclusion: Proportion of episodes of under-5 rotavirus diarrhea increased over the period. Concomitant changes in host, socio-demographic and clinical characteristics, and co-infections were also observed. Thus, vaccination campaign which is prevailing in private sector should also be introduced in public sector. [ABSTRACT FROM AUTHOR]

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. Methods: Stool samples from 843 children presenting to Kumudini Hospital during 2009–2010 with new episodes of MSD (diarrhea accompanied by dehydration, dysentery or hospitalization) were analyzed. Housefly density was measured twice weekly in six randomly selected sentinel households. Poisson time series regression was performed and autoregression-adjusted attributable fractions (AFs) were calculated using the Bruzzi method, with standard errors via jackknife procedure. Findings: Dramatic springtime peaks in housefly density in 2009 and 2010 were followed one to two months later by peaks of Shigella-associated MSD among toddlers and pre-school children. Poisson time series regression showed that housefly density was associated with Shigella cases at three lags (six weeks) (Incidence Rate Ratio = 1.39 [95% CI: 1.23 to 1.58] for each log increase in fly count), an association that was not confounded by ambient air temperature. Autocorrelation-adjusted AF calculations showed that a housefly control intervention could have prevented approximately 37% of the Shigella cases over the study period. Interpretation: Houseflies may play an important role in the seasonal transmission of Shigella in some developing country ecologies. Interventions to control houseflies should be evaluated as possible additions to the public health arsenal to diminish Shigella (and perhaps other causes of) diarrheal infection. Author Summary: Whereas previous researchers have noted that seasonal peaks in the numbers of houseflies and patients suffering from Shigella diarrheal infection seemed to coincide, this is the first research to quantify the association using time-series statistical methods. The results show that houseflies could account for approximately 37% of all cases of shigellosis in an area in rural Bangladesh. This research adds to the existing published experimental and observational evidence from other parts of the world implicating houseflies as mechanical transmission vectors for Shigella. The results can be used to advocate for cluster-randomized intervention trials that can demonstrate how much control of housefly density can diminish Shigella disease incidence. This question should be answered because there are currently no licensed Shigella vaccines, and rising antibiotic resistance is limiting treatment options. Control of houseflies using methods such as baited fly traps could be an affordable, effective intervention to add to the public health arsenal for routine use and in the context of disaster response. [ABSTRACT FROM AUTHOR]

Background: Shigellosis continues to be a public health challenge for developing countries, including Bangladesh. The aim of the study is to demonstrate recent changes in Shigella sero-groups and their geographical diversity. Methods: Data were extracted from data archive of four diarrheal disease surveillance systems. A 2% sub sample from urban Dhaka Hospital (2008–2011; n = 10,650), and 10% from urban Mirpur Treatment Centre (2009–2011; n = 3,585), were enrolled systematically; whereas, all patients coming from the Health and Demographic Surveillance System area in rural Matlab (2008–2011; n = 6,399) and rural Mirzapur (2010–2011; n = 2,812) were included irrespective of age, sex, and disease severity. A fresh stool specimen was collected for identification of Shigella spp. Of them, 315 (3%) were positive for Shigella in Dhaka, 490 (8%) from Matlab, 109 (3%) from Mirpur and 369 (13%) from Mirzapur and considered as analyzable sample size. Results: Among all Shigella isolates regardless of age, significant decreases in percentage of S. flexneri over time was observed in Mirpur (55→29%; p value of χ2-for trend = 0.019) and Mirzapur (59→47%; p = 0.025). A non-significant decrease was also seen in Dhaka (58→48%), while in Matlab there was a non-significant increase (73→81%). Similar patterns were observed among under-5 children at all sites. Emergence of S. sonnei was found in Dhaka (8→25%; p<0.001) and Mirpur (10→33%; p = 0.015), whereas it decreased in Mirzapur (32→23%; p = 0.056). The emergence of S. boydii was seen in all ages in Mirzapur [(3→28%; p<0.001); (3→27%; p<0.001)]. On the other hand, we saw non-significant percent reductions in S. boydii in Dhaka [overall (25→16%); under-5 (16→9%)]. Decreasing rates of Shigella dysenteriae were observed in Matlab, Mirpur and Mirzapur; whereas, in Dhaka it remained unchanged. Conclusion and Significance: Emergence of S. sonnei and S. boydii as important infectious diarrhea etiologies and variations in geographical diversity underscore the need for monitoring, with possible implications for vaccine development. [ABSTRACT FROM AUTHOR]

Background: Lack of breast feeding is associated with higher morbidity and case-fatality from both bacterial and viral etiologic diarrheas. However, there is very limited data on the characteristics of non–breastfed infants attending hospital with diarrheal illnesses caused by common bacterial and viral pathogens. Our objective was to assess the impact of lack of breast feeding on diarrheal illnesses in infants living in urban Bangladesh. Methods: We extracted data of infants (0–11 months) for analyses from the data archive of Diarrheal Disease Surveillance System (DDSS) of the Dhaka Hospital of icddr,b for the period 2008–2011. Results: The prevalence of breastfeeding in infants attending the hospital with diarrhea reduced from 31% in 2008 to 17% in 2011, with corresponding increase in the prevalence of non-breastfed (chi square for trend <0.001). Among breastfed infants, the incidence of rotavirus infections was higher (43%) among the 0–5 months age group than infants aged 9–11 months (18%). On the other hand, among non-breastfed infants, the incidence of rotavirus infections was much higher (82%) among 9–11 months old infants compared to those in 0–5 months age group (57%) (chi square for trend <0.001). Very similar trends were also observed in the incidence of cholera and ETEC diarrheas among different age groups of breastfed and non-breastfed infants (chi square for trend 0.020 and 0.001 respectively). However, for shigellosis, the statistical difference remained unchanged among both the groups (chi square for trend 0.240). Conclusion and Significance: We observed protective role of breastfeeding in infantile diarrhea caused by the major viral and common bacterial agents. These findings underscore the importance of promotion and expansion of breastfeeding campaigns in Bangladesh and elsewhere. [ABSTRACT FROM AUTHOR]

Objective:To identify maternal and antenatal factors associated with stillbirths and neonatal deaths in rural Bangladesh. Study Design:A prospective cohort study is being conducted to evaluate a maternal and child nutrition program in rural Bangladesh. Cases were all stillbirths and neonatal deaths that occurred in the cohort between March 7, 2011 and December 30, 2011. Verbal autopsies were used to determine cause of death. For each case, four controls were randomly selected from cohort members alive at age 3-months. Multivariable logistic regression was used to identify factors associated with these deaths. Results:Overall, 112 adverse pregnancy outcomes (44 stillbirths, 19/1,000 births; 68 neonatal deaths, 29/1,000 live births) were reported. Of the stillbirths 25 (56.8%) were fresh. The main causes of neonatal death were birth asphyxia (35%), sepsis (28%) and preterm birth (19%). History of bleeding during pregnancy was the strongest risk factor for stillbirths (adjusted odds ratio 22.4 [95% confidence interval 2.5, 197.5]) and neonatal deaths (adjusted odds ratio 19.6 [95% confidence interval 2.1, 178.8]). Adequate maternal nutrition was associated with decreased risk of neonatal death (adjusted odds ratio 0.4 [95% confidence interval 0.2, 0.8]). Conclusions:Identifying high-risk pregnancies during gestation and ensuring adequate antenatal and obstetric care needs to be a priority for any community-based maternal and child health program in similar settings. [ABSTRACT FROM AUTHOR]

Background: Enterotoxigenic Escherichia coli (ETEC) encoding heat-stable enterotoxin (ST) alone or with heat-labile enterotoxin (LT) cause moderate-to-severe diarrhea (MSD) in developing country children. The Global Enteric Multicenter Study (GEMS) identified ETEC encoding ST among the top four enteropathogens. Since the GEMS objective was to provide evidence to guide development and implementation of enteric vaccines and other interventions to diminish diarrheal disease morbidity and mortality, we examined colonization factor (CF) prevalence among ETEC isolates from children age <5 years with MSD and from matched controls in four African and three Asian sites. We also assessed strength of association of specific CFs with MSD., Methodology/principal Findings: MSD cases enrolled at healthcare facilities over three years and matched controls were tested in a standardized manner for many enteropathogens. To identify ETEC, three E. coli colonies per child were tested by polymerase chain reaction (PCR) to detect genes encoding LT, ST; confirmed ETEC were examined by PCR for major CFs (Colonization Factor Antigen I [CFA/I] or Coli Surface [CS] antigens CS1-CS6) and minor CFs (CS7, CS12, CS13, CS14, CS17, CS18, CS19, CS20, CS21, CS30). ETEC from 806 cases had a single toxin/CF profile in three tested strains per child. Major CFs, components of multiple ETEC vaccine candidates, were detected in 66.0% of LT/ST and ST-only cases and were associated with MSD versus matched controls by conditional logistic regression (p≤0.006); major CFs detected in only 25.0% of LT-only cases weren't associated with MSD. ETEC encoding exclusively CS14, identified among 19.9% of 291 ST-only and 1.5% of 259 LT/ST strains, were associated with MSD (p = 0.0011). No other minor CF exhibited prevalence ≥5% and significant association with MSD., Conclusions/significance: Major CF-based efficacious ETEC vaccines could potentially prevent up to 66% of pediatric MSD cases due to ST-encoding ETEC in developing countries; adding CS14 extends coverage to ~77%., Competing Interests: I have read the journal's policy and the authors of this manuscript have the following competing interests. We note that the following authors are involved in the development of vaccines to prevent diarrhea caused by enterotoxigenic Escherichia coli: James P. Nataro: Has been named in patents for technology that may have relevance for ETEC vaccine technology; JPN is also a co-investigator on grants from non-profit agencies that support ETEC vaccine development. Halvor Sommerfelt: Has been named in patents for technology that may have relevance for ETEC vaccine technology including: INT Application Number PCT/IB2014/000267; INT Publication Number WO2014128555 A2 “ETEC Vaccine”. European Patent Application No. 14711297.3 United States Patent Application No. 14/769,342. China Patent Application No. 201480022329.6. Puntervoll P, Sommerfelt H, Clements J, Nataro JP, Zhang W, Taxt A. HS is also a co-investigator on grants from non-profit agencies that support ETEC vaccine development Ann-Mari Svennerholm: Has shares in the University of Göteborg spin-out biotech company Gotovax AB which is entitled to royalty from Scandinavian Biopharma on sales in travelers of the ETEC vaccine Etvax if it becomes a commercial product. A-MS is a co-inventor on ETEC vaccine patent application owned by Scandinavian Biopharma and has a research grant from the Swedish Foundation for Strategic Research for infection biology research. Myron M. Levine: Is a co-inventor of patents for ETEC vaccine technology including US patent #6,902,736 B2. “Isolation and characterization of the CSA operon (ETEC-CS4 pili) and methods of using same.” He is a member of the Scientific Advisory Board of the PaxVax Corporation. MML is also the recipient for grants relevant to ETEC vaccine development including the Enteric Center of Excellence for Translational Research (Enteric-CETR) “Immunoprophylactic Strategies to Control Emerging Enteric Infections” (NIAID U19AI109776; MML, PI)

Background: Micronutrient deficiencies can compromise the development potential of school-aged children, and their later health and productivity as adults. School feeding and school-based fortification approaches have been utilized globally to redress nutritional deficiencies in this age group., Objective: We explored the acceptability and micronutrient impact of a Bangladesh Government supported school-based micronutrient fortification program for children attending rural primary schools in 10 disadvantaged sub-districts., Methods: We applied a mixed methods approach. The quantitative component assessed the impact of micronutrient fortification on 351 children aged 6-11 years using a cohort pre-post research design with a control group. The qualitative component explored the acceptability of the intervention using focus group discussions, body mapping and semi-structured interviews with teachers, school-going children and school authorities., Results: Daily consumption of fortified biscuits by primary school children had a significant positive impact on mean levels of iron, folic acid, vitamin B12, retinol and vitamin D controlling for sex, baseline deficiency status, CRP, and H. pylori. Levels of anemia and vitamin D deficiency were also significantly reduced. Qualitative findings indicated the widespread acceptability of the daily biscuit. Teachers perceived students to be more attentive in class, less tired, and some attributed better school performance to biscuit consumption. Children reported similar improvements in concentration and energy levels., Conclusions: This study is among the first in Bangladesh to comprehensively assess a school-based fortification program in terms of its acceptability and impact on micronutrient status of children aged 6-11 years of age. While results strongly support this modality of school feeding, research on the cognitive impacts of micronutrient fortified biscuits will help clarify the case for scaled-up investments in school- based feeding program in Bangladesh and other low and middle income countries.

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.

Background: Shigellosis continues to be a public health challenge for developing countries, including Bangladesh. The aim of the study is to demonstrate recent changes in Shigella sero-groups and their geographical diversity., Methods: Data were extracted from data archive of four diarrheal disease surveillance systems. A 2% sub sample from urban Dhaka Hospital (2008-2011; n = 10,650), and 10% from urban Mirpur Treatment Centre (2009-2011; n = 3,585), were enrolled systematically; whereas, all patients coming from the Health and Demographic Surveillance System area in rural Matlab (2008-2011; n = 6,399) and rural Mirzapur (2010-2011; n = 2,812) were included irrespective of age, sex, and disease severity. A fresh stool specimen was collected for identification of Shigella spp. Of them, 315 (3%) were positive for Shigella in Dhaka, 490 (8%) from Matlab, 109 (3%) from Mirpur and 369 (13%) from Mirzapur and considered as analyzable sample size., Results: Among all Shigella isolates regardless of age, significant decreases in percentage of S. flexneri over time was observed in Mirpur (55→29%; p value of χ(2)-for trend = 0.019) and Mirzapur (59→47%; p = 0.025). A non-significant decrease was also seen in Dhaka (58→48%), while in Matlab there was a non-significant increase (73→81%). Similar patterns were observed among under-5 children at all sites. Emergence of S. sonnei was found in Dhaka (8→25%; p<0.001) and Mirpur (10→33%; p = 0.015), whereas it decreased in Mirzapur (32→23%; p = 0.056). The emergence of S. boydii was seen in all ages in Mirzapur [(3→28%; p<0.001); (3→27%; p<0.001)]. On the other hand, we saw non-significant percent reductions in S. boydii in Dhaka [overall (25→16%); under-5 (16→9%)]. Decreasing rates of Shigella dysenteriae were observed in Matlab, Mirpur and Mirzapur; whereas, in Dhaka it remained unchanged., Conclusion and Significance: Emergence of S. sonnei and S. boydii as important infectious diarrhea etiologies and variations in geographical diversity underscore the need for monitoring, with possible implications for vaccine development.