Burden Of Diarrhea Research Articles

Epidemiological significance of the occurrence and persistence of rotaviruses in water and sewage: a critical review and proposal for routine microbiological monitoring.

Globally, waterborne gastroenteritis attributable to rotaviruses is on the increase due to the rapid increase in population growth, poor socioeconomic conditions, and drastic changes in climatic conditions. The burden of diarrhea is quite alarming in developing nations where the majority of the populations still rely on untreated surface water that is usually polluted for their immediate water needs. Humans and animals of all ages are affected by rotaviruses. In humans, the preponderance of cases occurs in children under 5 years. Global efforts in advancing water/wastewater treatment technologies have not yet realized the objective of complete viral removal from wastewater. Most times, surface waters are impacted heavily by inadequately treated wastewater run-offs thereby exposing people or animals to preventable health risks. The relative stability of rotaviruses in aquatic matrices during wastewater treatment, poor correlation of bacteriological indicators with the presence of rotaviruses, and their infectiousness at a low dose informed the proposal for inclusion in the routine microbiological water screening panel. Environmental monitoring data have been shown to provide early warnings that can complement clinical data used to monitor the impact of current rotavirus vaccination in a community. This review was therefore undertaken to critically appraise rotavirus excretion and emission pathways, and the existence, viability and persistence in the receiving aquatic milieu. The efficiency of the current wastewater treatment modality for rotavirus removal, correlation of the current bacteriological water quality assessment strategy, public health risks and current laboratory methods for an epidemiological study were also discussed.

Seasonal Variability Influence on the Prevalence of Diarrhoea among Under-Five-Year-old Children in Kersa District, Eastern Ethiopia: A Community-Based Longitudinal Study

Background:The health effects of climate change have been found to be a global concern for the last 2 centuries. However, the effect of climate variability on diarrhoea among under-five-year-old children is perhaps undocumented or otherwise unknown. The aim of the present study was to determine the effect of climate variability on diarrhoea among children under 5 years of age.Methods:A community-based longitudinal study was conducted over 8 repeated visits from June 2016 to May 2018 at the Kersa Demographic Surveillance and Health Research Center. A total of 500 randomly selected households and their 48 improved water sources were included in the survey from 3 agro-ecological zones, the rural and urban areas of the study area. Data was collected on household characteristics, diarrhoea, WASH practices, water quality and quantity in households, and improved water sources. A structured pre-tested questionnaire, an observational check list and laboratory tests were used for data collection. The data was entered into Epi Data Version 3.01 and transferred to Stata Version 12 for analysis. Multilevel mixed-effect Poisson regression was used to determine the relationship between predictors and outcome variables. A P-value of less than .05 was the cut-off point for statistically significant.Results:The prevalence of diarrhoea in 2 weeks among children under 5 years of age was 17.2% (95% CI: 15.8-19.71). Rainfall, E. coli contamination of drinking water at the source and in the home, 20 L of water consumption per capita per day, sharing water sources with animals and home water treatment by residents of the mid- and lowlands were all predictors of diarrhoea. The space-time scan statistic confirmed that child diarrhoea had random variation in both space and time.Conclusion:Climate variability has influenced the prevalence of diarrhoea among under-five-year-old children. Climate-resilient measures should be taken to reduce the burden of diarrhoea in the community.

Enteropathogen Changes After Rotavirus Vaccine Scale-up.

To inform next steps in pediatric diarrhea burden reduction by understanding the shifting enteropathogen landscape after rotavirus vaccine implementation. We conducted a case-control study of 1788 medically attended children younger than 5 years, with and without gastroenteritis, after universal rotavirus vaccine implementation in Peru. We tested case and control stools for 5 viruses, 19 bacteria, and parasites; calculated coinfection-adjusted attributable fractions (AFs) to determine pathogen-specific burdens; and evaluated pathogen-specific gastroenteritis severity using Clark and Vesikari scales. Six pathogens were independently positively associated with gastroenteritis: norovirus genogroup II (GII) (AF 29.1, 95% confidence interval [CI]: 28.0-32.3), rotavirus (AF 8.9, 95% CI: 6.8-9.7), sapovirus (AF 6.3, 95% CI: 4.3-7.4), astrovirus (AF 2.8, 95% CI: 0.0-4.0); enterotoxigenic Escherichia coli heat stable and/or heat labile and heat stable (AF 2.4, 95% CI: 0.6-3.1), and Shigella spp. (AF 2.0, 95% CI: 0.4-2.2). Among typeable rotavirus cases, we most frequently identified partially heterotypic strain G12P[8] (54 of 81, 67%). Mean severity was significantly higher for norovirus GII-positive cases relative to norovirus GII-negative cases (Vesikari [12.7 vs 11.8; P < .001] and Clark [11.7 vs 11.4; P = .016]), and cases in the 6- to 12-month age range relative to cases in other age groups (Vesikari [12.7 vs 12.0; P = .0002] and Clark [12.0 vs 11.4; P = .0016]). Norovirus is well recognized as the leading cause of pediatric gastroenteritis in settings with universal rotavirus vaccination. However, sapovirus is often overlooked. Both norovirus and sapovirus contribute significantly to the severe pediatric disease burden in this setting. Decision-makers should consider multivalent vaccine acquisition strategies to target multiple caliciviruses in similar countries after successful rotavirus vaccine implementation.

Circulating Genotypes of Rotavirus Prior to Rotarix?vaccine Introduction in Kathmandu, Nepal.

In Nepal, it is estimated that about 3 million children under 5 years of age are prone to diarrhea and previous studies have shown rotavirus as the major etiological agent. Given the high burden of rotavirus, Rotarix® vaccine was introduced in the national immunization schedule in July 2020. This study was carried out in a tertiary health center from January- September 2018 to determine the burden of rotavirus diarrhea as well as genotypic variations in the circulating virus prior to vaccine introduction in Kathmandu, Nepal. Hospital based cross sectional study was conducted among children less than 5 years of age attending Kanti Children's Hospital. Rotavirus antigen detection was performed by enzyme immunoassay using ProSpecT Rotavirus Microplate Assay. Rotavirus A positive samples were further confirmed by genotyping using Reverse-Transcription Polymerase Chain Reaction. A total of 530 children that included 184 males and 346 females were enrolled in this study. Rotavirus antigen was detected in 112 (21.1%) stool samples. Of the total 112 positive EIA stool samples that were genotyped, G12P[6] (30.3%) was found to be the most common type, followed by G3P[8] (26.8%), mixed type (14.3%), and G1P[6] (13.4%). Continued surveillance should be carried out nationwide in Nepal to understand the effectiveness of the vaccination program and to report any new trends in the circulating genotypes.

Direct and indirect costs of acute diarrhea in children under five years of age in Indonesia: Health facilities and community survey

SummaryBackgroundDiarrhea remains a major cause of child morbidity and mortality in low- and middle-income countries. Reliable data on the economic burden of diarrhea is required to support the selection of appropriate health intervention programs. This study aimed to estimate the costs of acute diarrhea in children under five years of age in Indonesia, a large middle-income country with a substantial diarrheal burden.MethodsDirect medical cost data were extracted retrospectively for 1050 children under five years of age with acute diarrhea receiving inpatient care across 45 health facilities in seven Indonesian provinces during 2017–2020. Direct medical costs for children treated in outpatient settings were estimated by collecting unit costs associated with standard diarrhea case management in children. A structured interview of 240 caregivers of inpatients was also conducted retrospectively to estimate direct non-medical costs as well as indirect costs from caregiver income loss.ResultsThe weighted average direct medical cost for treatment of acute diarrhea as an inpatient and outpatient across health facility types was US$99.8 (SD±$56.8)(35% room costs, 29% professional fees, 26% medication costs, 10% diagnostic costs) and US$7.6 (SD±$4.3) (34% diagnostic costs, 28% medication costs, 27% professional fees, 10% registration fees), respectively. The average direct non-medical household cost for an acute diarrheal admission was US$4.90 and the indirect cost was US$9.90.ConclusionThere is a significant economic burden associated with acute diarrhea in children in Indonesia. This study, based on a wide variety of health care settings and geographical regions, provides data to inform the economic evaluation of rotavirus vaccines and other diarrheal prevention programs.FundingThis work was supported by a research grant from the Murdoch Children's Research Institute (MCRI) and PATH; and the Indonesian Technical Advisory Group on Immunization (ITAGI).

Impact of Monovalent Rotavirus Vaccine on Rotavirus Hospitalizations among Children Younger Than 5 Years of Age in the Ouest and Artibonite Departments, Haiti, 2013 to 2019.

Rotavirus is responsible for 26% of diarrheal deaths in Latin America and the Caribbean. Haiti introduced the monovalent rotavirus vaccine in April 2014. The objective of this analysis is to describe the impact of the rotavirus vaccine on hospitalizations among Haitian children younger than 5 years old during the first 5 years after introduction. This analysis includes all children with diarrhea who were enrolled as part of a sentinel surveillance system at two hospitals from May 2013 to April 2019. We compare the proportion of rotavirus-positive specimens in each post-vaccine introduction year to the pre-vaccine period. To account for the potential dilution of the proportion of rotavirus-positive specimens from a waning cholera outbreak, we also analyzed annual trends in the absolute number of positive stools, fit a two-component finite-mixture model to the negative specimens, and fit a negative binomial time series model to the pre-vaccine rotavirus-positive specimens to predict the number of rotavirus diarrhea hospital admissions in the absence of rotavirus vaccination. The overall percentage of rotavirus-positive specimens declined by 22% the first year after introduction, increased by 17% the second year, and declined by 33% to 50% the subsequent 3 years. All sensitivity analyses confirmed an overall decline. We observed a clear annual rotavirus seasonality before and after vaccine introduction, with the greatest activity in December through April, and a biennial pattern, with high sharp peaks and flatter longer periods of increased rotavirus activity in alternating years, consistent with suboptimal vaccination coverage. Overall, our study shows evidence that the introduction of the rotavirus vaccine reduced the burden of severe rotavirus diarrhea.

Combating Childhood Infections in LMICs: evaluating the contribution of Big Data Big data, biomarkers and proteomics: informing childhood diarrhoeal disease management in Low- and Middle-Income Countries

<h2>Abstract</h2> Despite efforts to reduce the global burden of childhood diarrhoea, 50% of all cases globally occur in children under five years in Low–Income and Middle- Income Countries (LMICs) and knowledge gaps remain regarding the aetiological diagnosis, introduction of diarrhoeal vaccines, and the role of environmental enteric dysfunction and severe acute malnutrition. Biomarkers may assist in understanding disease processes, from diagnostics, to management of childhood diarrhoea and the sequelae to vaccine development. Proteomics has the potential to assist in the identification of new biomarkers to understand the processes in the development of childhood diarrhoea and to aid in developing new vaccines. Centralised repositories that enable mining of large data sets to better characterise risk factors, the proteome of both the patient and the different diarrhoeal pathogens, and the environment, could inform patient management and vaccine development, providing a systems biological approach to address the burden of childhood diarrhoea in LMICs.

High proportion of norovirus infection and predominance of GII.3 [P12] genotype among the children younger than 5 in Sabah, Malaysian Borneo.

Globally, norovirus (NoV) has become one of the important causes of acute gastroenteritis (AGE) in children. It is responsible for death of children younger than 5 years in developing countries. Although there is limited information and the rate of child mortality caused by diarrhea is low in Malaysia, the burden of diarrhea is high, especially in Sabah. NoV GI, GII and GIV genogroups are known to infect humans, and GII.4 is the predominant genotype distributed worldwide. Better understanding of the etiology of NoV will help to inform policies for prevention and control. The aim of this study was to determine the burden and genotype distribution of NoV in children younger than 5 years with AGE who attended health-care facilities in Sabah, Malaysia. Diarrhea stool samples were collected from 299 children with AGE and NoV was detected by amplifying the capsid and RNA-dependent RNA polymerase gene and reverse transcription-polymerase chain reaction (RT-PCR) analysis. Nucleotide sequencing of the amplicons was used for genotypes and phylogenetic analyses . NoV-positive stool samples were found in 17.7% (53/299) among which 13/53 (24.5%), 38/53 (71.7%), and 2/53 (3.8%) identified as NoV GI, GII and combination of GI and GII, respectively. The most common genotypes were GII.3 [P12] (80%) followed by GII.6 [P7] (13.3%), and GII.17 [P17] (6.7%). In the phylogenetic tree, all Sabahan NoV samples were shown to share ancestry with their respective genotype from predominantly East Asian countries and to some extent Australia and Europe. However, the Sabahan strains formed independent clusters with significant bootstrap values, indicating a clonal spread after the strains had entered Sabah.

Prevalence, Pattern and Genetic Diversity of Rotaviruses among Children under 5 Years of Age with Acute Gastroenteritis in South Africa: A Systematic Review and Meta-Analysis.

Rotavirus is the most significant cause of severe acute gastroenteritis among children under 5 years of age, worldwide. Sub-Saharan Africa particularly bears the brunt of the diarrheal deaths. A meta-analysis was conducted on 43 eligible studies published between 1982 and 2020 to estimate the pooled prevalence of rotavirus infection and changes in the main rotavirus strains circulating before and after vaccine introduction among under-five children in South Africa. The pooled national prevalence of rotavirus infection was estimated at 24% (95% CI: 21–27%) for the pre-vaccination period and decreased to 23% (95% CI: 21–25%) in the post-vaccination period. However, an increased number of cases was observed in the KwaZulu-Natal (21–28%) and Western Cape (18–24%) regions post-vaccination. The most dominant genotype combinations in the pre-vaccine era was G1P[8], followed by G2P[4], G3P[8], and G1P[6]. After vaccine introduction, a greater genotype diversity was observed, with G9P[8] emerging as the predominant genotype combination, followed by G2P[4], G12P[8], and G1P[8]. The introduction of the rotavirus vaccine was associated with a reduction in the burden of rotavirus-associated diarrhea in South Africa, although not without regional fluctuation. The observed changing patterns of genotype distribution highlights the need for ongoing surveillance to monitor the disease trend and to identify any potential effects associated with the dynamics of genotype changes on vaccine pressure/failure.

Risk Factors of Childhood Diarrhoeal Diseases in Bangladesh: Evidence from a Nationwide Cross-sectional Survey

Globally, different episodes of diarrhoeal diseases are one of the leading causes of childhood morbidity and mortality, especially in developing countries. Diarrhoeal diseases among children under five years of age have been considered as the major causes of morbidity and mortality in Bangladesh although it has declined recently. In this study, the most recently published Multiple Indicator Cluster Survey 2019 (MICS 2019) data were used to observe the prevalence of childhood diarrhoea and to identify the socio-economic and demographic risk factors of childhood diarrhoea in Bangladesh. The chi-square test was used in this study to identify the risk factors of childhood diarrhoeal diseases in Bangladesh. The overall prevalence of diarrhoea among children under five years of age in Bangladesh was found 6.9% in the last two weeks preceding the survey. The findings of the study identified that child age less than two years, an unimproved facility of toilet or source of drinking water, floor material made of earth/sand, no handwashing place observed in dwelling/ yard/plot, lower or no education of mothers and household heads, lower economic status, three or more under-five children living in the family are the most potential risk factors of childhood diarrhea in Bangladesh. Improved source of drinking water supply, better sanitation, hygiene practice, mother’s knowledge and consciousness about diarrhoea and, timely treatment and can reduce the burden of childhood diarrhoea in Bangladesh. The quality of existing child healthcare services like oral rehydration therapy (ORT) during diarrhoea, rotavirus vaccination programs should be improved at all stages without any discrimination which will contribute to a reduction in childhood morbidity and mortality due to diarrhoea in Bangladesh.

The Lancet Commission on water, sanitation and hygiene, and health

The Lancet Commission on water, sanitation and hygiene, and health

Etiology and Incidence of Moderate-to-Severe Diarrhea in Young Children in Niger

High-resolution data on the etiology of childhood diarrhea in countries with the highest burden and mortality remain sparse and are needed to inform burden estimates and prioritize interventions. We tested stool specimens collected between October 2014 and December 2017 from children under 2 years of age from the per-protocol population of a placebo-controlled clinical trial of a bovine rotavirus pentavalent vaccine (Rotasiil) in Niger. We tested 1729 episodes of moderate-to-severe diarrhea (Vesikari score ≥ 7) using quantitative PCR and estimated pathogen-specific burdens by age, season, severity, and trial intervention arm. The 4 pathogens with the highest attributable incidence of diarrhea were Shigella (7.2 attributable episodes per 100 child-years; 95% confidence interval: 5.2, 9.7), Cryptosporidium (6.5; 5.8, 7.2), rotavirus (6.4; 5.9, 6.7), and heat-stabile toxin-producing enterotoxigenic Escherichia coli (ST-ETEC) (6.2; 3.1, 7.7). Cryptosporidium was the leading etiology of severe diarrhea (Vesikari score ≥ 11) and diarrhea requiring hospitalization. Shigella was the leading etiology of diarrhea in children 12-23 months of age but also had a substantial burden in the first year of life, with 60.5% of episodes of severe shigellosis occurring in infants. Shigella, Cryptosporidium, and ST-ETEC incidence peaked during the warmer and wetter period and coincided with peak all-cause diarrhea incidence. In this high-burden setting, the leading diarrheal pathogens were Shigella, Cryptosporidium, rotavirus, and ST-ETEC, and each was disproportionately seen in infants. Vaccine development should target these pathogens, and the impact of vaccine schedule on diarrhea burden in the youngest children will need to be considered.

Diarrhoeal diseases in Soweto, South Africa, 2020: a cross-sectional community survey

BackgroundIn South Africa, there are limited data on the burden of diarrhoea at a community level, specifically in older children and adults. This community survey estimated rates of and factors associated with diarrhoea across all ages and determined the proportion of cases presenting to healthcare facilities.MethodsHouseholds were enrolled from an existing urban health and demographic surveillance site. A household representative was interviewed to determine associated factors and occurrence of diarrhoea in the household, for all household members, in the past 2 weeks (including symptoms and health seeking behaviour). Diarrhoeal rate of any severity was calculated for < 5 years, 5–15 years and > 15 years age groups. Factors associated with diarrhoea and health seeking behaviour were investigated using binomial logistic regression.ResultsDiarrhoeal rate among respondents (2.5 episodes/person-year (95% CI, 1.8–3.5)) was significantly higher than for other household members (1.0 episodes/person-year (95% CI, 0.8–1.4); IRR = 2.4 (95% CI, 1.5–3.7) p < 0.001). Diarrhoeal rates were similar between age groups, however younger children (< 5 years) were more likely to present to healthcare facilities than adults (OR = 5.9 (95% CI, 1.1–31.4), p = 0.039). Oral rehydration solution was used in 44.8% of cases. Having a child between 5 and 15 years in the household was associated with diarrhoea (OR = 2.3 (95% CI, 1.3–3.9), p = 0.003) and, while 26.4% of cases sought healthcare, only 4.6% were hospitalised and only 3.4% of cases had a stool specimen collected. While the majority of cases were mild, 13.8% of cases felt they required healthcare but were unable to access it.ConclusionDiarrhoeal rate was high across all age groups in this community; however, older children and adults were less likely to present to healthcare, and are therefore underrepresented through facility-based clinical surveillance. Current diarrhoeal surveillance represents a fraction of the overall cases occurring in the community.

Cost of illness for severe and non-severe diarrhea borne by households in a low-income urban community of Bangladesh: A cross-sectional study.

The illness cost borne by households, known as out-of-pocket expenditure, was 74% of the total health expenditure in Bangladesh in 2017. Calculating economic burden of diarrhea of low-income urban community is important to identify potential cost savings strategies and prioritize policy decision to improve the quality of life of this population. This study aimed to estimate cost of illness and monthly percent expenditure borne by households due diarrhea in a low-income urban settlement of Dhaka, Bangladesh. We conducted this study in East Arichpur area of Tongi township in Dhaka, Bangladesh from September 17, 2015 to July 26, 2016. We used the World Health Organization (WHO) definition of three or more loose stool in 24 hours to enroll patients and enrolled 106 severe patients and 158 non-severe patients from Tongi General Hospital, local pharmacy and study community. The team enrolled patients between the first to third day of the illness (≤ 72 hours) and continued daily follow-up by phone until recovery. We considered direct and indirect costs to calculate cost-per-episode. We applied the published incidence rate to estimate the annual cost of diarrhea. The estimated average cost of illness for patient with severe diarrhea was US$ 27.39 [95% CI: 24.55, 30.23] (2,147 BDT), 17% of the average monthly income of the households. The average cost of illness for patient with non-severe diarrhea was US$ 6.36 [95% CI: 5.19, 7.55] (499 BDT), 4% of the average monthly income of households. A single diarrheal episode substantially affects financial condition of low-income urban community residents: a severe episode can cost almost equivalent to 4.35 days (17%) and a non-severe episode can cost almost equivalent to 1 day (4%) of household’s income. Preventing diarrhea preserves health and supports financial livelihoods.

Burden and etiology of moderate and severe diarrhea in children less than 5\xa0years of age living in north and south of China: Prospective, population-based surveillance

BackgroundDiarrhea remains the leading cause of childhood illness in China. Better understanding of burden and etiology of diarrheal diseases is important for development of effective prevention measures.MethodsPopulation-based diarrhea surveillance was conducted in Sanjiang (southern China) year-round and Zhengding (northern China) in autumn/winter. Stool specimens were collected from children < 5 years of age experiencing diarrhea. The TaqMan Array Card (TAC), based on multiplex real-time PCR, was applied to detect multiple enteric microbial agents simultaneously. Results using these methods were compared to those derived from conventional PCR assays.ResultsDuring the study period, 6,380 children in Zhengding and 3,581 children in Sanjiang < 5 years of age participated. Three hundred and forty (31.2%) and 279 (22.9%) diarrhea episodes were identified as moderate-to-severe in the two counties, with incidence of 60.4 and 88.3 cases per 1,000 child-years in Zhengding and Sanjiang, respectively. The five most frequently detected bacterial and viral agents in Sanjiang were adenovirus, enterovirus, enteroaggregative Escherichia coli (EAEC), rotavirus, and sapovirus all the year round, while the most common viral agents in Zhengding were rotavirus, followed by astrovirus and adenovirus during the cool season. Compared to conventional PCR assay, the average incremental detection via the TAC method was twofold.ConclusionOur study demonstrated high diversity and prevalence of multiple major bacterial and viral agents, including rotavirus and calicivirus, among children in China. Further studies are needed to define the public health significance of neglected but frequently detected pathogens such as EAEC, enterotoxigenic E. coli, Campylobacter, adenovirus, and enterovirus.

Health-related quality of life (QoL) in platinum-resistant ovarian cancer patients treated with olaparib and pegylated liposomal doxorubicin (PLD), a multicenter single-arm phase II clinical trial (ROLANDO, GEICO-1601).

5549 Background: The prognosis for patients with platinum-resistant/refractory ovarian cancer (PROC) is poor, and the aim of treatment is focused primarily on symptom control and maintenance of QoL. The objective of this study was to assess the impact on QoL of the combination of pegylated liposomal doxorubicin (PLD) with olaparib (OLA) in PROC patients (pts). Methods: ROLANDO is a single arm phase II trial that enrolled pts with high-grade serous or endometrioid and at least one previous PROC recurrence (between 28 days - 6 months after last platinum). Up to 4 previous lines (up to 5 in BRCA-mut) were allowed. Pts received 6 cycles of PLD 40 mg/m2 intravenously every 28 days + OLA 300 mg b.i.d. followed by OLA 300 mg b.i.d. monotherapy until progression or unacceptable toxicity. QoL was measured by European Organization for Research and Treatment of Cancer QLQ C30 questionnaire evaluating functional status, and symptom intensity and QLQ OV-28 ovarian cancer specific module, both filled out by pts every 4 months (mo) regardless of disease progression. Questionnaire compliance was reported as percentage of the initial number of pts. Changes between baseline and subsequent visits (Wilcoxon rank test) were evaluated. P values &lt; 0.05 were considered significant. Results: From 2017 to 2020, 31 pts were recruited. Median age was 57 y.o., ECOG 0/1: 32.3%/67.7%. Median of prior lines was 2 (range 1-5) and pts were on study treatment for a median of 5 mo (range 1.4-19.5) for OLA and 5 cycles (range 2 - 6) for PLD. QoL information was available at baseline for 30 (97%) pts and decayed to 22 (71%), 13 (42%), 6 (19%) and 4 (13%) pts at 4, 8, 12, and 16 mo respectively. Global health status measured by QLQ C30 and QLQ OV-28 scores was maintained throughout all time points with no significant differences. Significant transient improvement was seen in social functioning after 12 mo (p = 0.013). Nausea-vomiting (p = 0.02), hair loss (p = 0.012) and constipation (p = 0.037) showed a significant increase at 4 mo overlapping with PLD administration, and returned to baseline levels afterwards. This was in line with the reported adverse reactions frequency of nausea (58.1%) and vomiting (45.2%). Dyspnea showed a transient significant increase at 12 mo (p = 0.012), whereas insomnia (p = 0.038) and attitude towards disease (p = 0.007) improved at 16 mo. Symptoms such as appetite and constipation did not change after 12 mo. Most functional scales (physical, role, emotional, cognitive, body, sexuality) and symptom scales (fatigue, pain, appetite loss, diarrhoea, neurologic, hormonal and economic burden) had no statistically significant changes. Conclusions: Pts treated with OLA+PLD combination reported no signs of clinically relevant deterioration of QoL while on treatment. All QoL items changes were transient in no more than 1 time-point. Clinical trial information: NCT03161132.

The economic burden of diarrhea in children under 5 years in Bangladesh

BackgroundDiarrhea is a leading cause of morbidity and mortality among under-five children in Bangladesh. Hospitalization for diarrhea can pose a significant burden on households and health systems. The aim of this study was to estimate the cost of illness due to diarrhea from the healthcare facility, caregiver, and societal perspectives in Bangladesh. MethodA cross-sectional study with an ingredient-based costing approach was conducted in 48 healthcare facilities in Bangladesh. In total, 899 caregivers of under-five children with diarrhea were interviewed face-to-face between August 2017 and May 2018, followed up over phone after 7–14 days of discharge, to capture all expenses and time costs related to the entire episode of diarrhea. ResultsThe average cost per episode for caregivers was US$62, with $29 direct and $34 indirect costs. From the societal perspective, average cost per episode of diarrhea was $71. In 2018, an estimated $79 million of economic costs were incurred for treating diarrhea in Bangladesh. Using 10% of income as threshold, over 46% of interviewed households faced catastrophic expenditure from diarrheal disease. ConclusionThe economic costs incurred by caregivers for treating per-episode of diarrhea was around 4% of the annual national gross domestic product per-capita. Investment in vaccination can help to reduce the prevalence of diarrheal diseases and avert this public health burden.

Contribution of Noncanonical Antigens to Virulence and Adaptive Immunity in Human Infection with Enterotoxigenic E. coli

Enterotoxigenic Escherichia coli (ETEC) contributes significantly to the substantial burden of infectious diarrhea among children living in low- and middle-income countries. In the absence of a vaccine for ETEC, children succumb to acute dehydration as well as nondiarrheal sequelae related to these infections, including malnutrition. The considerable diversity of ETEC genomes has complicated canonical vaccine development approaches defined by a subset of ETEC pathovar-specific antigens known as colonization factors (CFs). To identify additional conserved immunogens unique to this pathovar, we employed an "open-aperture" approach to capture all potential conserved ETEC surface antigens, in which we mined the genomic sequences of 89 ETEC isolates, bioinformatically selected potential surface-exposed pathovar-specific antigens conserved in more than 40% of the genomes (n = 118), and assembled the representative proteins onto microarrays, complemented with known or putative colonization factor subunit molecules (n = 52) and toxin subunits. These arrays were then used to interrogate samples from individuals with acute symptomatic ETEC infections. Surprisingly, in this approach, we found that immune responses were largely constrained to a small number of antigens, including individual colonization factor antigens and EtpA, an extracellular adhesin. In a Bangladeshi cohort of naturally infected children <2 years of age, both EtpA and a second antigen, EatA, elicited significant serologic responses that were associated with protection from symptomatic illness. In addition, children infected with ETEC isolates bearing either etpA or eatA genes were significantly more likely to develop symptomatic disease. These studies support a role for antigens not presently targeted by vaccines (noncanonical) in virulence and the development of adaptive immune responses during ETEC infections. These findings may inform vaccine design efforts to complement existing approaches.

Economic burden of childhood diarrhea in Burundi

BackgroundIn 2016, diarrhea killed around 7 children aged under 5 years per 1000 live births in Burundi. The objective of this study was to estimate the economic burden associated with diarrhea in Burundi and to examine factors affecting the cost to provide economic evidence useful for the policymaking about clinical management of diarrhea.MethodsThe study was designed as a prospective cost-of-illness study using an incidence-based approach from the societal perspective. The study included patients aged under 5 years with acute non-bloody diarrhea who visited Buyenzi health center and Prince Regent Charles hospital from November to December 2019. Data were collected through interviews with patients’ caregivers and review of patients’ medical and financial records. Multiple linear regression was performed to identify factors affecting cost, and a cost model was used to generate predictions of various clinical and care management costs. All costs were converted into international dollars for the year 2019.ResultsOne hundred thirty-eight patients with an average age of 14.45 months were included in this study. Twenty-one percent of the total patients included were admitted. The average total cost per episode of diarrhea was Int$109.01. Outpatient visit and hospitalization costs per episode of diarrhea were Int$59.87 and Int$292, respectively. The costs were significantly affected by the health facility type, patient type, health insurance scheme, complications with dehydration, and duration of the episode before consultation. Our model indicates that the prevention of one case of dehydration results in savings of Int$16.81, accounting for approximately 11 times of the primary treatment cost of one case of diarrhea in the community-based management program for diarrhea in Burundi.ConclusionDiarrhea is associated with a substantial economic burden to society. Evidence from this study provides useful information to support health interventions aimed at prevention of diarrhea and dehydration related to diarrhea in Burundi. Appropriate and timely care provided to patients with diarrhea in their communities and primary health centers can significantly reduce the economic burden of diarrhea. Implementing a health policy to provide inexpensive treatment to prevent dehydration can save significant amount of health expenditure.

Rotavirus disease burden pre-vaccine introduction in young children in Rural Southern Mozambique, an area of high HIV prevalence.

BackgroundRotavirus vaccines have been adopted in African countries since 2009, including Mozambique (2015). Disease burden data are needed to evaluate the impact of rotavirus vaccine. We report the burden of rotavirus-associated diarrhea in Mozambique from the Global Enteric Multicenter Study (GEMS) before vaccine introduction.MethodsA case-control study (GEMS), was conducted in Manhiça district, recruiting children aged 0–59 months with moderate-to-severe diarrhea (MSD) and less-severe-diarrhea (LSD) between December 2007 and November 2012; including 1–3 matched (age, sex and neighborhood) healthy community controls. Clinical and epidemiological data and stool samples (for laboratory investigation) were collected. Association of rotavirus with MSD or LSD was determined by conditional logistic regression and adjusted attributable fractions (AF) calculated, and risk factors for rotavirus diarrhea assessed.ResultsOverall 915 cases and 1,977 controls for MSD, and 431 cases and 430 controls for LSD were enrolled. Rotavirus positivity was 44% (217/495) for cases and 15% (160/1046) of controls, with AF = 34.9% (95% CI: 32.85–37.06) and adjusted Odds Ratio (aOR) of 6.4 p< 0.0001 in infants with MSD compared to 30% (46/155) in cases and 14% (22/154) in controls yielding AF = 18.7%, (95% CI: 12.02–25.39) and aOR = 2.8, p = 0.0011 in infants with LSD. The proportion of children with rotavirus was 32% (21/66) among HIV-positive children and 23% (128/566) among HIV-negative ones for MSD. Presence of animals in the compound (OR = 1.9; p = 0.0151) and giving stored water to the child (OR = 2.0, p = 0.0483) were risk factors for MSD; while animals in the compound (OR = 2.37, p = 0.007); not having routine access to water on a daily basis (OR = 1.53, p = 0.015) and washing hands before cooking (OR = 1.76, p = 0.0197) were risk factors for LSD.ConclusionThe implementation of vaccination against rotavirus may likely result in a significant reduction of rotavirus-associated diarrhea, suggesting the need for monitoring of vaccine impact.