ABSTRACT.
Zinc supplementation is an added intervention with oral rehydration solution (ORS) for treating childhood diarrhea as per World Health Organization recommendations. Our study aimed to determine the prevalence of zinc administration in addition to ORS for childhood diarrhea before hospitalization and the nutritional profile of those children admitted to the outpatient department of the largest diarrheal facility in Bangladesh. This study used a screening dataset of a clinical trial (www.clinicaltrials.gov; NCT04039828) on zinc supplementation at a Dhaka hospital (International Centre for Diarrhoeal Disease Research, Bangladesh) between September 2019 and March 2020. A total of 1,399 children aged 3–59 months were included in our study. Children were divided into two groups (one group received zinc and another did not) and were analyzed accordingly; 39.24% (n = 549) children received zinc along with ORS for the current diarrheal episode prior to hospitalization. Percentages of underweight (weight-for-age z-score < −2 SD), stunting (length/height-for-age z-score < −2 SD), wasting (weight-for-length/height z-score < −2 SD), and overweight (weight-for-age z-score > +2 SD) among these children were 13.87% (n = 194), 14.22% (n = 199), 12.08% (n = 169), and 3.43% (n = 48), respectively. In logistic regression after adjusting age, sex, and nutritional status (underweight, stunting, wasting, and overweight), association of dehydration (adjusted odds ratio [aOR]: 0.06; 95% CI: 0.03–0.11; P < 0.01), bloody diarrhea (aOR: 0.18; 95% CI: 0.11–0.92; P < 0.01), and fever (aOR: 0.27; 95% CI: 0.18–0.41; P < 0.01) were less with children who received zinc at home. Bangladesh is one of the leading zinc coverage areas globally but lags behind the target for zinc coverage in diarrheal illness among under-five children. Policymakers should scale up and formulate guidelines with sustainable strategies to encourage zinc supplementation in diarrheal episodes in Bangladesh and elsewhere.
INTRODUCTION
We are now living in the third decade of the 21st century with better, available, and inexpensive treatment facilities and options for diarrhea, such as oral rehydration saline (ORS) and zinc therapy. To prevent diarrhea, we also focus on providing safe water and improved hygiene and sanitation. Despite these improvements, diarrhea is the most common pediatric illness and public health concern.1,2 It is also regarded as one of the significant causes of childhood death, and the scenario is even worse in low- and middle-income countries, mainly in South Asia and sub-Saharan Africa.3–5 In 2020 worldwide, an estimated 5.0 million children died of preventable and treatable diseases.6,7 Worldwide, diarrhea is responsible for an estimated 1.2 million deaths of under-five children annually.6,8–10 It also constitutes a considerable burden on the nutritional status of children. In Bangladesh, the death of under-five children is a national issue, and diarrhea is one of the leading infectious causes of under-five mortality.11 As stated in Bangladesh demographic and health survey, almost 5% of under-five children suffered from acute diarrheal illnesses 2 weeks preceding the survey, and 38% of under-five children were taken to a health facility or provider for treatment.12
Most of the diarrheal cases in under-five children caused by the viral pathogen are treatable at home by ORS administration. Zinc supplementation (10 mg for infants < 6 months old and 20 mg for children 6–59 months old) for 10–14 days has been included in the treatment along with ORS in an acute diarrheal episode, and it is jointly recommended by the World Health Organization (WHO), United Nations International Children’s Emergency Fund (UNICEF), United States Agency for International Development (USAID), and other worldwide experts.13 Zinc plays a fundamental part in regulating the host's resistance to infectious organisms and lessening diarrheal disease risk, severity, and duration.14 Zinc deficiency was responsible for 14.4% of diarrheal deaths, 10.4% of malaria deaths, and 6.7% of pneumonia deaths among under-five children in 2004.15 According to the national micronutrient status survey (2011–2012), zinc deficiency was highly prevalent in Bangladesh, with a rate of 44.6% among under-five children.16 Multiple health organizations, accompanied by the government of Bangladesh, are closely working in Bangladesh to build up a system of diarrheal treatment with the use of ORS and zinc only from home and without using irrational antibiotics.17 Despite mass media messages linking zinc supplementation and ORS use, mothers or caregivers seek medical care from the hospital, and the workload is increasing in outpatient departments (OPDs) day by day. Therefore, in this study, we intended to determine the prevalence of zinc administration in addition to ORS for childhood diarrhea before hospitalization and the nutritional profile of those children admitted to the OPD of the largest diarrheal facility in Bangladesh.
MATERIALS AND METHODS
Study design, participants, and study site.
For this study, data were extracted from the screening dataset of a clinical trial entitled “Zinc sulfate acceptability study in children with acute diarrhea: A prospective, open-label, interventional study” (ClinicalTrials.gov ID: NCT04039828).18 This was a hospital-based study in which a total of 1,399 children aged 3–59 months were screened between September 2019 and March 2020. The children had been admitted between 8:30 am and 5:00 pm to the OPD unit of Dhaka Hospital, International Center for Diarrheal Disease Research, Bangladesh (icddr,b), for management of diarrheal illnesses.
The icddr,b is the world’s largest diarrheal disease hospital.19 This hospital serves about 200,000 patients each year free of cost.20 Most (∼60%) hospital patients are under-five children. Immediately upon arrival, patients are examined clinically by a senior staff nurse for signs of dehydration. Then primary data collection and anthropometric measurements are done. The z-scores for different anthropometric indices (weight-for-length/height z-score [WLZ/WHZ], weight-for-age z-score [WAZ], and length/height-for-age z-score [LAZ/HAZ]) were calculated following the WHO’s recent child growth standard.21 After the assessment, irrespective of the dehydration status and other clinical conditions, all children are admitted to the hospital and then sent to different hospital units (OPD/inpatient wards) according to their clinical condition. The noncomplicated diarrheal patient with no/some dehydration is initially sent to OPD. After observing the patient for 4 hours, if the patient is ready for home management, the patient is discharged with advice. If any deteriorating sign appears (e.g., fever, electrolyte imbalance, sepsis, excessive vomiting, no urine output), the patient is transferred to the inpatient ward if necessary. Figure 1 shows the workflow at the OPD. Our study used a pretested questionnaire and only included children from the OPD.
Figure 1.
Workflow at the outpatient department.
Ethical consideration.
Ethical approval was obtained from the Institutional Review Board (IRB) of the icddr,b (the IRB comprises the Research Review Committee and the Ethical Review Committee). Moreover, in this study screening data sets were analyzed anonymously. According to the IRB-approved protocol, because our study population was between 3 and 59 months of age, we obtained verbal consent for screening from the parents/caregivers of the child.
Data collection.
Demographic data were collected in a pretested structured questionnaire from the parent/caregiver of each study participant, and anthropometric measurements were done by trained study staff. Data also included diarrheal duration and zinc intake history at home to treat present diarrheal illness. According to standard operating procedures, participants’ weight, length or height, mid- to upper-arm circumference, and temperature were determined. A registered study physician also assessed different clinical parameters (e.g., edema, congenital anomaly). This study includes only children who were admitted into OPD.
Operational definitions.
ORS is an oral powder containing a mixture of glucose, sodium chloride, potassium chloride, and sodium citrate. After being dissolved in the requisite volume of water, ORS is intended for the prevention and treatment of dehydration due to diarrhea, including maintenance therapy. The WHO recommends that the solution contain 2.6 g sodium chloride, 1.5 g potassium chloride, 2.9 g sodium citrate, and 13.5 g anhydrous glucose dissolved in each liter of drinking water.22,23 The following terms were also used in our analysis: “stunted” indicates LAZ/HAZ value < −2 SD of WHO growth standards, “wasted” indicates WLZ/WHZ value < −2 SD of WHO growth standards, “underweight” indicates WAZ value < −2 SD of WHO growth standards, and “overweight” indicates WAZ value > +2 SD of WHO growth standards.24
Statistical analysis.
Data were entered into the pretested clinical record forms, and all statistical analyses were performed using the statistical software STATA 15.0 (Stata Corporation, College Station, TX). First, general baseline characteristics of the children were presented using frequencies, with percentages for categorical variables and mean with SD for symmetrical continuous variables. The continuous asymmetric variable was reported with median and interquartile range. Pearson’s χ2 test or Fisher’s exact test were applied to compare categorical variables. Student’s t-test and Mann-Whitney U test were used to compare the parametric and nonparametric continuous variables between the groups. We determined the association by unadjusted odds ratios (ORs) and adjusted ORs (aORs) with 95% CIs obtained from bivariate and multivariate analyses, respectively. Outcome variables were the presence of dehydration, fever, and bloody stool, and each outcome variable was analyzed with a separate model. A probability of <0.05 was considered statistically significant.
RESULTS
Descriptive information of the study participants.
Table 1 provides the descriptive characteristics of the study participants, detailing the frequency distribution of baseline demographic and clinical characteristics of the study participants attending the OPD. A total of 1,399 patients were screened from the OPD between September 2019 and March 2020. The participants’ mean (± SD) age was 17.02 ± 10.06 months. A higher proportion of the participants were male (57.54%); 15.30% of children presented with some dehydration, and others were nondehydrated during admission to the OPD; 11.87% of children presented with bloody diarrhea (visible blood in stool); and 12.22% of children presented with fever (axillary temperature ≥ 38 °C).
Table 1.
Baseline characteristics of the study participants
| Characteristics | Value |
|---|---|
| Age, months (mean ± SD) | 17.02 ± 10.06 |
| Sex, n (%) | |
| Male | 805 (57.54) |
| Female | 594 (42.46) |
| Dehydration, n (%) | |
| Some dehydration | 214 (15.30) |
| No dehydration | 1,185 (84.70) |
| Characteristics of diarrheal stool, n (%) | |
| Watery diarrhea | 1,233 (88.13) |
| Bloody diarrhea (visible blood in stool) | 166 (11.87) |
| Presence of fever (axillary temperature ≥ 38°C), n (%) | |
| Yes | 171 (12.22) |
| No | 1,228 (87.78) |
Table 2 shows that the overall prevalence of underweight, stunting, wasting, and overweight was 13.87%, 14.22%, 12.08%, and 3.43%, respectively, among our study children aged between 3 and 59 months. The underweight, stunting, and wasting rates were higher among boys than among girls, and the differences in the stunting rate were statistically significant (P < 0.05).
Table 2.
Nutritional status of OPD children based on WAZ, LAZ/HAZ, and WLZ/WHZ scores
| Nutritional status | n (%) | P value | ||
|---|---|---|---|---|
| All (N = 1,399) | Boys (N = 805) | Girls (N = 594) | ||
| Underweight (WAZ < −2 SD) | 194 (13.87) | 116 (14.41) | 78 (13.13) | 0.49 |
| Stunted (LAZ/HAZ < −2 SD) | 199 (14.22) | 129 (16.02) | 70 (11.78) | 0.03 |
| Wasted (WLZ/WHZ < −2 SD) | 169 (12.08) | 101 (12.55) | 68 (11.45) | 0.53 |
| Overweight (WAZ > +2 SD) | 48 (3.43) | 25 (3.11) | 23 (3.87) | 0.44 |
Bold values are statistically significant at P < 0.05. LAZ/HAZ = length/height for age z-score; OPD = outpatient department; WAZ = weight for age z-score; WLZ/WHZ = weight for length/height z-score.
Details of age-specific mean z-scores for WAZ, LAZ/HAZ, and WLZ/WHZ are shown in Figure 2, which shows a gradual decline in LAZ/HAZ and WAZ with the increase of the age of children and an increase after the age of 4.
Figure 2.
Age-wise distribution of mean length/height for age z-scores (LAZ/HAZ), weight for age z-scores (WAZ), and weight for length/height z-scores (WLZ/WHZ).
Table 3 compares the different clinical parameters between the children who received zinc supplementation prior to hospitalization and those who did not receive zinc supplementation. It shows that dehydration (1.82% versus 24.00%, P < 0.01), bloody diarrhea (3.64% versus 17.18%, P < 0.01), and fever (5.28% versus 16.71%, P < 0.01) were significantly lower among children who received zinc supplementation at home prior to hospitalization.
Table 3.
Association of use of zinc supplementation with different clinical characteristics of the participants
| Characteristics | On zinc treatment (N = 549) | Without zinc treatment (N = 850) | Unadjusted OR (95% CI) | P value |
|---|---|---|---|---|
| Age, months (mean ± SD) | 16.02 ± 9.17 | 17.67 ± 10.55 | 0.98 (0.97–0.99) | < 0.01 |
| Male patient, n (%) | 322 (58.65) | 483 (56.82) | 0.93 (0.75–1.15) | 0.50 |
| Presented with dehydration, n (%) | 10 (1.82) | 204 (24.00) | 0.06 (0.03–0.11) | < 0.01 |
| Presented with bloody diarrhea, n (%) | 20 (3.64) | 146 (17.18) | 0.18 (0.11–0.29) | < 0.01 |
| Fever (axillary temperature ≥ 38°C), n (%) | 29 (5.28) | 142 (16.71) | 0.28 (0.18–0.42) | < 0.01 |
| Wasted, n (%) | 71 (12.93) | 98 (11.53) | 1.14 (0.82–1.58) | 0.43 |
| Underweight, n (%) | 70 (12.75) | 124 (14.59) | 0.85 (0.62–1.17) | 0.33 |
| Stunted, n (%) | 66 (12.02) | 133 (15.65) | 0.74 (0.54–1.01) | 0.06 |
| Overweight, n (%) | 22 (4.01) | 26 (3.06) | 1.32 (0.74–2.36) | 0.34 |
Bold values are statistically significant at P < 0.05. OR = odds ratio.
After adjusting for each participant’s age, sex, and nutritional status (underweight, stunting, wasting, overweight), we found that associations of dehydration (aOR: 0.06; 95% CI: 0.03–0.11), bloody diarrhea (aOR: 0.18; 95% CI: 0.11–0.29), and fever (aOR: 0.27; 95% CI: 0.18–0.41) were less with children who received zinc supplementation at home prior to hospitalization (Table 4).
Table 4.
Logistic regression analysis to detect independent association of outcome with zinc supplementation prior to hospitalization
| Adjusted OR (95% CI) | P value | |
|---|---|---|
| Presence of dehydration | 0.05 (0.03–0.10) | < 0.01 |
| Bloody diarrhea | 0.18 (0.11–0.29) | < 0.01 |
| Fever (axillary temperature ≥ 38°C) | 0.27 (0.18–0.41) | < 0.01 |
Bold values are statistically significant at P < 0.05. OR = odds ratio. Each of the variables was analyzed in a separate model after adjusting for age, sex, and nutritional status (underweight, stunting, wasting, overweight).
DISCUSSION
This study reveals the prevalence of zinc use among children admitted to the OPD in a diarrheal disease hospital in Bangladesh. Our study’s most important observation is that only 39.24% of children received zinc treatment at home before hospitalization. We have observed that the proportion of dehydration, bloody diarrhea, and fever is significantly lower in children with a history of zinc supplementation at home compared with those without a history of zinc intake. Our study also shows the decline in the nutritional profile of the children, with an increase in age among patients attending the pediatric diarrheal OPD.
Zinc deficiency is widespread among children in developing countries.25 It is a considerable burden in low- and middle-income countries like Bangladesh. The zinc shortage exacerbates the net loss of zinc during a diarrheal episode.26 Moreover, adding zinc during diarrheal episodes reduces the duration and severity of diarrhea.27 It is also observed that introducing zinc in diarrheal illness increases oral rehydration solution use, reduces unnecessary antibiotics consumption, and above all reduces the need for hospital visits for acute diarrhea.28 A Bangladeshi study reported that zinc treatment reduces diarrhea-related hospitalization by 24% and provides an overall reduction in mortality (risk ratio: 0.49; 95% CI: 0.25–0.94).29
Although there is increased availability of zinc through UNICEF and manufacturers in several developing countries, the benefits of zinc are not broadly acknowledged among physicians, healthcare providers, or pharmacists, and, as a result, zinc is not given for most diarrheal cases.30 In Bangladesh, despite promotion of zinc use during diarrheal episodes, the percentage of zinc use at home is not satisfactory.
An Ethiopian study has reported that individual as well as community factors (e.g., maternal education, household size, and distance from a community health facility) have a significant association with ORS and zinc use in diarrheal illness.31
We found that dehydration, fever, and bloody diarrhea were less likely to be associated with children who received zinc supplementation at home prior to hospitalization. Diarrheal children with no dehydration usually take treatment at home. However, an Iranian study revealed that hospitalized diarrheal children were independently associated with bloody and watery diarrhea and infection with rotavirus or Salmonella.32 Although we could not assess other confounding variables for hospitalization at the OPD, we found that around 12% of children had bloody diarrhea and fever, and about 15.30% had dehydration during admission. Because zinc can decrease the number of days with watery stool, it can also decrease dehydration.33 The likely mechanism of action for the effect of zinc supplementation on diarrhea includes enhanced water and electrolytes absorption by the intestinal epithelium,34,35 regeneration of gut epithelium or the re-establishment of its function,36,37 and improved levels of enterocyte brush-border enzymes.38,39 Our observation also supports these findings because we found a significantly lower percentage of dehydrating cases in children who received zinc at home. A randomized clinical trial conducted in Bangladesh reported that zinc supplementation during a diarrheal episode shortens the diarrheal period by 24 hours, drops the incidence of diarrhea by 15%, and thereby lessens diarrhea-related hospital admissions.29 Because the Dhaka Hospital of the icddr,b is located in the capital, most of the attending patients are from urban and peri-urban regions. Probably this is another possible explanation for the lower percentage of dehydrating cases in the OPD.
The role of zinc in dysentery is also well established.29 Zinc can reduce the duration of both nondysenteric diarrhea and dysentery. Zinc supplementation inhibits toxin-induced cholera, but not Escherichia coli heat-stable enterotoxin-induced ion secretion, in cultured Caco-2 cells.40 Zinc supplementation during diarrheal episodes enhances serum zinc concentration and helps children improve zinc status during the convalescent period.41 Children who take zinc at home are also less likely to be associated with bloody stool/fever.
Another significant observation of our study is the nutritional status of the children attending the pediatric diarrheal OPD.We assessed anthropometry for children with diarrhea admitted to the OPD. In our study, prevalence rates of underweight, stunting, wasting, and overweight among diarrheal children admitted to the OPD were 13.87%, 14.22%, 12.08%, and 3.43%, respectively, whereas the national nutrition survey of Bangladesh showed that, in the community, the prevalence rates of underweight, stunting, and wasting were 22%, 31%, and 8%, respectively.12 Different Bangladesh studies have documented improvement in the nutritional status of children.42 As shown in our research, undernutrition rates are lower than studies conducted in North India by Gupta and Jindal43 (41.9% underweight, 47.2% stunting, and 18.9% wasting). Our analysis also found that boys were more stunted than girls, and the result was statistically significant. A meta-analysis of 16 demographic and health surveys in sub-Saharan Africa found that male children below 5 years of age were more likely to be stunted than their female counterparts.44 Bork and Diallo45 did a study in rural Senegal and found that boys had lower HAZs than girls, and these sex differences increased up to 39 months of age from infancy. We have also observed that a higher percentage of OPD admission cases among the study population were under 24 months of age. This could be due to the fact that younger children often report to the hospital with rotavirus diarrhea, and after the period of 24 months, the prevalence of rotaviral diarrhea is significantly lower.46
Despite several integrated approaches from national and international policymakers, effective scaling up of zinc interventions in acute diarrhea, cost-effective quality local products, recommended masking of metallic taste of zinc and training of both ends of the treatment table, recommended palatability of zinc products in children, as well as adherence of the caregivers to total 10 days of zinc regimen is yet to be reached.47–53 Implementation research is necessary to determine the reasons for the reduced use of zinc at home and to increase its coverage.54 Research is also required to develop effective policies to raise caregivers’ awareness.54
This study has some limitations. Data were collected from the screening archives, which captured limited information, restricting us from additional analyzing the possible association with different variables, such as socio-economic status, WASH (safe drinking water, sanitation, and hygiene) practices, caregiver’s perception of zinc use, availability of zinc, use of antibiotics, and determining factors for adherence of zinc/ORS supplementation. No microbiological assessment was done in our study. We could not include all age groups of children. We could not follow the screened participants to observe the outcome of diarrhea or the average length of hospital stays of those admitted to the general ward from the OPD.
CONCLUSIONS
Despite established guidelines for zinc use during diarrheal illness, only 39.24% of children are within this practice. The timely introduction of zinc along with oral rehydration solutions can reduce unnecessary admission of diarrheal patients at higher centers, thereby saving the working hours of the attending parents, the workload of health care providers, and the patient load of hospitals having limited beds against the vast demand. Policymakers should take the necessary steps to increase caregivers’ awareness of the use of zinc in diarrheal illness in addition to ORS. Healthcare providers should emphasize health education among parents, especially on the exact nutritional necessities in terms of quality and quantity of the child at definite age groups, to reduce malnutrition by ensuring the availability of supplemental feed.
ACKNOWLEDGMENTS
The International Centre for Diarrhoeal Disease Research, Bangladesh gratefully acknowledges the following core donors who provide unrestricted support to research efforts: The Government of the People’s Republic of Bangladesh, Global Affairs Canada (GAC), the Swedish International Development Cooperation Agency (SIDA), the UK Department for International Developments (UKAid).
The American Society of Tropical Medicine and Hygiene (ASTMH) assisted with publication expenses.
REFERENCES
- 1. Liu L, Johnson HL, Cousens S, Perin J, Scott S, Lawn JE, Rudan I, Campbell H, Cibulskis R, Li M, 2012. Global, regional, and national causes of child mortality: an updated systematic analysis for 2010 with time trends since 2000. Lancet 379: 2151–2161. [DOI] [PubMed] [Google Scholar]
- 2. CDC , 2015. Diarrhea: Common Illness, Global Killer. Washington, DC: Department of Health and Human Services. [Google Scholar]
- 3. Black RE, Morris SS, Bryce J, 2003. Where and why are 10 million children dying every year? Lancet 361: 2226–2234. [DOI] [PubMed] [Google Scholar]
- 4. UNICEF , 2016. Global Strategy for Women’s, Children’s and Adolescents’ Health (2016–2030). Available at: https://data.unicef.org/resources/global-strategy-womens-childrens-adolescents-health/. Accessed October 3, 2021.
- 5. Chowdhury F, Khan IA, Patel S, Siddiq AU, Saha NC, Khan AI, Saha A, Cravioto A, Clemens J, Qadri F, 2015. Diarrheal illness and healthcare seeking behavior among a population at high risk for diarrhea in Dhaka, Bangladesh. PLoS One 10: e0130105. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 6. UNICEF , 2021. UNICEF Data: Under-five Mortality. Available at: https://data.unicef.org/topic/child-survival/under-five-mortality/. Accessed October 3, 2022.
- 7. WHO , 2022. WHO Fact Sheets: Child Mortality (Under 5 Years). Geneva, Switzerland: World Health Organization. Available at: https://www.who.int/news-room/fact-sheets/detail/levels-and-trends-in-child-under-5-mortality-in-2020. Accessed October 3, 2022.
- 8. Weldesamuel GT, Alemayoh TT, Atalay HT, Zemichael TM, 2019. Modern health-seeking behaviour and associated factors among mothers having under 5-years old children in Shire town, Tigray, Ethiopia: a cross-sectional study 2018. Afr J Prim Health Care Fam Med 11: 1–6. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 9. Das SK, Nasrin D, Ahmed S, Wu Y, Ferdous F, Farzana FD, Khan SH, Malek MA, El Arifeen S, Levine MM, 2013. Health care-seeking behavior for childhood diarrhea in Mirzapur, rural Bangladesh. Am J Trop Med Hyg 89: 62. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 10. Rehydration Project , 2021. Diarrhoea, Diarrhea, Dehydration and Oral Rehydration. Available at: https://rehydrate.org/diarrhoea/. Accessed September 21, 2021.
- 11. UNICEF , 2015. Committing to Child Survival: A Promise Renewed: eSocialSciences. Available at: https://www.unicef.org/media/50721/file/APR_2015_9_Sep_15.pdf. Accessed 23 September 2021.
- 12. National Institute of Population Research and Training (NIPORT), and ICF , 2019. Bangladesh Demographic and Health Survey, 2017–18: NIPORT. Available at: https://dhsprogram.com/pubs/pdf/PR104/PR104.pdf. Accessed September, 23, 2021.
- 13. WHO , 2004. WHO-UNICEF Joint Statement on the Clinical Management of Acute Diarrhea. Geneva, Switzerland: World Health Organization. Available at: https://apps.who.int/iris/bitstream/handle/10665/68627/WHO_FCH_CAH_04.7.pdf;jsessionid=9E4E992CC6CD1FB2439EB1DCF9B75A6B?sequence=1. Accessed September 23, 2021. [Google Scholar]
- 14. Scrimgeour AG, Lukaski HC, 2008. Zinc and diarrheal disease: current status and future perspectives. Curr Opin Clin Nutr Metab Care 11: 711–717. [DOI] [PubMed] [Google Scholar]
- 15. Fischer Walker C, Ezzati M, Black R, 2009. Global and regional child mortality and burden of disease attributable to zinc deficiency. Eur J Clin Nutr 63: 591–597. [DOI] [PubMed] [Google Scholar]
- 16. UNICEF , 2013. National Micronutrients Status Survey. Institute of Public Health and Nutrition. Available at: https://www.unicef.org/bangladesh/media/4631/file/National. Accessed August 23, 2021.
- 17. Rahman AS, Islam MR, Koehlmoos TP, Raihan MJ, Hasan MM, Ahmed T, Larson CP, 2014. Impact of NGO training and support intervention on diarrhoea management practices in a rural community of Bangladesh: an uncontrolled, single-arm trial. PLoS One 9: e112308. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 18. Nuzhat S, Ahmed T, Alam J, Billal SM, Khan AI, Hossain MI, 2022. New formulation zinc sulphate acceptability and adherence in children with acute diarrhoea: a prospective, open‐label, interventional study in Bangladesh. J Paediatr Child Health 58: 1215–1220. [DOI] [PubMed] [Google Scholar]
- 19. Parvin I, Shahunja K, Khan SH, Alam T, Shahrin L, Ackhter MM, Sarmin M, Dash S, Rahman MW, Shahid ASMSB, 2020. Changing susceptibility pattern of Vibrio cholerae O1 isolates to commonly used antibiotics in the largest diarrheal disease hospital in Bangladesh during 2000–2018. Am J Trop Med Hyg 103: 652. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 20. Zaman K, Aziz AB, Yunus M, Qadri F, Ross AG, Clemens JD, 2021. Rotavirus vaccine trials in International Centre for Diarrhoeal Disease Research, Bangladesh (icddr, b) and future use of the vaccine in Bangladesh. J Infect Dis 224: S801–S804. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 21. WHO , 2006. WHO Child Growth Standards: Length/Height-For-Age, Weight-For-Age, Weight-For-Length, Weight-For-Height and Body Mass Index-For-Age: Methods and Development. Geneva, Switzerland: World Health Organization. [Google Scholar]
- 22. WHO , 2006. Implementing the New Recommendations on the Clinical Management of Diarrhoea: Guidelines for Policy Makers and Programme Managers. Geneva, Switzerland: World Health Organization. [Google Scholar]
- 23. USAID , 2022. Module III Oral Rehydration. Available at: https://www.ghsupplychain.org/sites/default/files/2019-02/MNCH%20Commodities-OralRehydration.pdf. Accessed October 30, 2022.
- 24. WHO , 2006. The WHO Child Growth Standards. Geneva, Switzerland: World Health Organization. Available at: https://www.who.int/tools/child-growth-standards/standards. Accessed September 23, 2021. [Google Scholar]
- 25. Sandstead HH, 1991. Zinc deficiency: a public health problem? Am J Dis Child 145: 853–859. [DOI] [PubMed] [Google Scholar]
- 26. Castillo-Duran C, Vial P, Uauy R, 1988. Trace mineral balance during acute diarrhea in infants. J Pediatr 113: 452–457. [DOI] [PubMed] [Google Scholar]
- 27. Bhutta ZA. et al. , 2000. Therapeutic effects of oral zinc in acute and persistent diarrhea in children in developing countries: pooled analysis of randomized controlled trials. Am J Clin Nutr 72: 1516–1522. [DOI] [PubMed] [Google Scholar]
- 28. Bhandari N, Mazumder S, Taneja S, Dube B, Agarwal R, Mahalanabis D, Fontaine O, Black RE, Bhan MK, 2008. Effectiveness of zinc supplementation plus oral rehydration salts compared with oral rehydration salts alone as a treatment for acute diarrhea in a primary care setting: a cluster randomized trial. Pediatrics 121: e1279–e1285. [DOI] [PubMed] [Google Scholar]
- 29. Baqui AH, Black RE, El Arifeen S, Yunus M, Chakraborty J, Ahmed S, Vaughan JP, 2002. Effect of zinc supplementation started during diarrhoea on morbidity and mortality in Bangladeshi children: community randomised trial. BMJ 325: 1059. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 30. Walker CLF, Fontaine O, Young MW, Black RE, 2009. Zinc and low osmolarity oral rehydration salts for diarrhoea: a renewed call to action. Bull World Health Organ 87: 780–786. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 31. Kassa SF, Alemu TG, Techane MA, Wubneh CA, Assimamaw NT, Belay GM, Tamir TT, Muhye AB, Kassie DG, Wondim A, 2022. The co-utilization of oral rehydration solution and zinc for treating diarrhea and its associated factors among under-five children in Ethiopia: further analysis of EDHS 2016. Patient Prefer Adherence 16: 1713. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 32. Khalili B, Shahabi GA, Khalili M, Mardani M, Cuevas LE, 2006. Risk factors for hospitalization of children with diarrhea in Shahrekord, Iran. Iran J Clin Infect Dis 1: 131–136. [Google Scholar]
- 33. Sazawal S, Black RE, Bhan MK, Bhandari N, Sinha A, Jalla S, 1995. Zinc supplementation in young children with acute diarrhea in India. N Engl J Med 333: 839–844. [DOI] [PubMed] [Google Scholar]
- 34. Golden B, Golden M, 1985. Zinc, sodium and potassium losses in the diarrhoeas of malnutrition and zinc deficiency. Trace Elements in Man and Animals—TEMA 5: Proceedings of the Fifth International Symposium on Trace Elements in Man and Animals. Available at: https://www.academia.edu/29471204/Zinc_sodium_and_potassium_losses_in_the_diarrhoeas_of_malnutrition_and_zinc_deficiency. Accessed September 23, 2021. [Google Scholar]
- 35. Roy S, Draser B, Tomkins A, 1986. The impact of zinc deficiency on the intestinal response to cholera toxin. Proc Nutr Soc 45: A39. [Google Scholar]
- 36. Roy S, Behrens R, Haider R, Akramuzzaman S, Mahalanabis D, Wahed M, Tomkins A, 1992. Impact of zinc supplementation on intestinal permeability in Bangladeshi children with acute diarrhoea and persistent diarrhoea syndrome. J Pediatr Gastroenterol Nutr 15: 289–296. [DOI] [PubMed] [Google Scholar]
- 37. Bates C, Bates P, Dardenne M, Prentice A, Lunn P, Northrop-Clewes C, Hoare S, Cole T, Horan S, Longman S, 1993. A trial of zinc supplementation in young rural Gambian children. Br J Nutr 69: 243–255. [DOI] [PubMed] [Google Scholar]
- 38. Gebhard RL, Karouani R, Prigge WF, McClain CJ, 1983. The effect of severe zinc deficiency on activity of intestinal disaccharidases and 3-hydroxy-3-methylglutaryl coenzyme A reductase in the rat. J Nutr 113: 855–859. [DOI] [PubMed] [Google Scholar]
- 39. Jones P, Peters T, 1981. Oral zinc supplements in non-responsive coeliac syndrome: effect on jejunal morphology, enterocyte production, and brush border disaccharidase activities. Gut 22: 194–198. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 40. Canani RB, Cirillo P, Buccigrossi V, Ruotolo S, Passariello A, De Luca P, Porcaro F, De Marco G, Guarino A, 2005. Zinc inhibits cholera toxin–induced, but not Escherichia coli heat-stable enterotoxin–induced, ion secretion in human enterocytes. J Infect Dis 191: 1072–1077. [DOI] [PubMed] [Google Scholar]
- 41. Baqui AH, Black RE, Fischer Walker CL, Arifeen S, Zaman K, Yunus M, Wahed MA, Caulfield LE, 2006. Zinc supplementation and serum zinc during diarrhea. Indian J Pediatr 73: 493–497. [DOI] [PubMed] [Google Scholar]
- 42. Gillespie S, van den Bold M, Team SoCS , 2017. Stories of change in nutrition: an overview. Glob Food Secur 13: 1–11. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 43. Gupta M, Jindal R, 2016. Assessment of nutritional status of under five children attending outpatient department at a tertiary care hospital: a study from North India. Int J Sci Res Educ 4: 5283–5287. [Google Scholar]
- 44. Wamani H, Åstrøm AN, Peterson S, Tumwine JK, Tylleskär T, 2007. Boys are more stunted than girls in sub-Saharan Africa: a meta-analysis of 16 demographic and health surveys. BMC Pediatr 7: 1–10. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 45. Bork KA, Diallo A, 2017. Boys are more stunted than girls from early infancy to 3 years of age in rural Senegal. J Nutr 147: 940–947. [DOI] [PubMed] [Google Scholar]
- 46. Odimayo M, Olanrewaju W, Omilabu S, Adegboro B, 2008. Prevalence of rotavirus-induced diarrhoea among children under 5 years in Ilorin, Nigeria. J Trop Pediatr 54: 343–346. [DOI] [PubMed] [Google Scholar]
- 47. Nasrin D, Larson CP, Sultana S, Khan TU, 2005. Acceptability of and adherence to dispersible zinc tablet in the treatment of acute childhood diarrhoea. J Health Popul Nutr 23: 215–221. [PubMed] [Google Scholar]
- 48. Lamberti LM, Walker CLF, Taneja S, Mazumder S, Black RE, 2015. Adherence to zinc supplementation guidelines for the treatment of diarrhea among children under–five in Uttar Pradesh, India. J Glob Health 5: 020410. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 49. Valekar SS, Fernandez K, Chawla P, Pandve H, 2014. Compliance of zinc supplementation by care givers of children suffering from diarrhea. Indian J Community Health 26: 137–141. [Google Scholar]
- 50. Ahmed S, Nasrin D, Ferdous F, Farzana FD, Kaur G, Chisti MJ, Das SK, Faruque ASG, 2013. Acceptability and compliance to a 10-day regimen of zinc treatment in diarrhea in rural Bangladesh. Food Nutr Sci 4: 357–364. [Google Scholar]
- 51. Omuemu VO, Ofuani IJ, Kubeyinje IC, 2012. Knowledge and use of zinc supplementation in the management of childhood diarrhoea among health care workers in public primary health facilities in Benin-City, Nigeria. Glob J Health Sci 4: 68. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 52. Pathak D, Pathak A, Marrone G, Diwan V, Lundborg CS, 2011. Adherence to treatment guidelines for acute diarrhoea in children up to 12 years in Ujjain, India-a cross-sectional prescription analysis. BMC Infect Dis 11: 1–9. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 53. Akhter S, Larson CP, 2009. Willingness to pay for zinc treatment of childhood diarrhoea in a rural population of Bangladesh. Health Policy Plan 25: 230–236. [DOI] [PubMed] [Google Scholar]
- 54. WHO , 2022. Stakeholder Consultative Meeting on Prevention and Management of Childhood Pneumonia and Diarrhoea: Report, 12–14 October 2021. Geneva, Switzerland: World Health Organization. Available at: https://apps.who.int/iris/bitstream/handle/10665/352846/9789240046702-eng.pdf?sequence=1. Accessed August 11, 2022. [Google Scholar]


