Diarrhea is the second leading cause of morbidity and mortality among children worldwide^. It is responsible for nearly 10% of all deaths in children under five years of age and accounts for about 500,000 child deaths in developing countries every year[1,2]. Global burden and severity causing mortality are more prevalent in the first two years of life, suggesting an increased emphasis on prevention and treatment in neonates and children less than two years is crucial. Nearly a third of episodes of severe diarrhea are preventable by vaccination (i.e., against rotavirus and cholera)[3].It remains one of the most common reasons for hospital admission, with an estimated 1731 million episodes of childhood diarrhea reported in 2011, of which 2% progressed to severe disease [4]. Undernutrition is a crucial risk factor for morbidity and mortality associated with diarrhea. It is also a significant cause of malnutrition, mainly prolonged, and interventions to improve nutrition should be prioritized [5].

In 2013, the WHO and the United Nations Children's Fund (UNICEF) formulated the Integrated Global Action Plan for Pneumonia and Diarrhea (GAPPD) was launched in 2013 by the WHO and the United Nations Children's Fund (UNICEF) to devise a framework for ending preventable child deaths due to diarrhea and pneumonia by 2025. The GAPPD emphasizes a 'protect, prevent, and treat' approach that integrates interventions with proven effectiveness. Currently, WHO recommends treatment with oral rehydration salts (ORS) and continues feeding for the prevention and treatment of dehydration, as well as Zinc to shorten the duration and severity of the episodes [6]. The World Health Organization (WHO) and UNICEF recommend daily 20 mg zinc supplements for 10 – 14 days for children with acute diarrhea, and 10 mg per day for infants under six months old, to reduce the severity of the episode and prevent further occurrences in next two to three months, thereby decreasing the morbidity. Diarrhea is more common in children with zinc deficiency and responds quickly to zinc supplementation.

Mechanism of action of Zinc includes it restores mucosal barrier integrity and enterocyte brush‐border enzyme activity, promotes the production of antibodies and circulating T lymphocytes against intestinal pathogens and has a direct effect on ion channels.

14 days along with Danger signs explained (fever, refusal to feed, respiratory distress, blood in stool, decreased urination).

In the present study, severity of diarrhea was based on stool frequency (times/day) and duration (hours). Assessment of stool consistency was not considered as it is subjective and difficult to follow a standard parameter. Dysentery was characterized by acute diarrhea mixed with blood, while cholera and diarrhea caused by a rotavirus were characterized by acute watery diarrhea. We suspected cholera if symptoms occurred during known diarrheal outbreaks involving children and adults or frequent, voluminous, loose quickly led to severe dehydration with hypovolemic shock. Parents were advised to follow-up after 48-72hours; those who couldn't come were contacted telephonically to evaluate the response of therapy in terms of remission that is defined as stool passed <3 times with regular consistency. Data were analyzed using SPSS software version 21.0. Patient characteristics were reported as means ± standard deviations, medians (ranges), or n (%) as appropriate. For statistical significance,a p-value less than 0.05 was considered significant.

In the present study total number of eligible participants was 110 after fulfilling inclusion and exclusion criteria. However,six patients were excluded (1 Patient developed severe dehydration, five patients left the study) so a total number of patient enrolled was 104 (n=104) Patients have divided them into two groups of 52 subjects each: those who received Zinc-Probiotic combination therapy (Group A) and those who received Zinc therapy alone (Group B)Mean age of patients in Group A is 14.02 ± 13.2 months and 12.9 ± 11.4 months in Group B. Mean weight of patients in Group A is 8.5 ± 2.7 kg and 7.8 ± 2.4 kg in Group B.

In group A male 62%(32)& female 38%(20) and in group B male 65%(34)& female 35%(18). A greater number of the patients was male in both groups. Fever was present in 48 %(25) of children in Group A as compared to 46 %(24) in group B. Vomiting was present in 46 %(24) in Group A as compared to 37 %(19) in Group B. Considering nutritional assessment (using the WHO classification of weight for age), 80% (42) of subjects belongs to good nutrition in combination group as compared to 61% (32) in Zinc-only group.

[12,13]. Among gender, more males are predominant in both groups (61.5% versus 65.3%), similar to Azim M et al., Hatta M et al., Sultana M et al.[12,14,15]. This male gender predisposition for acute watery diarrhea is still unclear. However, the DHAKA study concluded varied environmental exposures or physiologic biological sex differences could be an underlying mechanism instead of cultural bias in care-seeking behavior that favors boys [16].

The mean weight of both groups was almost similar (8.5 ± 2.7 versus 7.81 ± 2.4 kg) also with other studies as Azim M et al.(8.21 ± 2.6 versus 8.09 ± 2.7), Sultana M et al.(8.6 ± 1.57 versus 8.5 ± 2.16)[12,15]. Malnutrition increases the risk of severity as well as mortality from common childhood illnesses, including diarrhea. Conversely, diarrhea can also cause acute malnutrition and, if not appropriately addressed, frequent bouts can negatively affect child development and lead to chronic malnutrition [17].In the present study majority of the patient in both groups fall under normal nutrition parameters (80.7% versus 61.5%) only.

In the combination group, 7% and 11.5% of patients fall under mild to moderate acute malnutrition compare to 23% and 15.3% in Zinc only group. In contrast, in Sultana M et al[15] majority of the patient in the combination group fell under mild malnutrition (58.2%), only 14.5% were under moderate malnutrition, and in the zinc group,the incidence of mild and moderate malnutrition was similar 30.9% and 32.7% respectively. The variability is expected as it depends upon population studies, growth curve used and sample size.

Maternal education is an essential predictor of diarrheal disorder in children. In the present study majority of mothers in both groups were educated till SSC (40.3% versus 30.7%) also 26.9% in the combination group and 19.2% in Zinc only group don't know how to prepare ORS, which is a significant risk factor for electrolyte imbalance (hypernatremic and hyponatremic dehydration) which further increase the mortality in acute watery diarrhea. A previous epidemiological study by Desmennu AT also concluded that children with mothers of lower educational attainment have a higher risk of experiencing childhood diarrhea than those whose mothers are better educated as they are involved in practices that benefit the health of their children [18].

This study demonstrates combination therapy is more effective for decreasing the severity and early resolution of acute watery diarrhea in children. Also, our study has shown a significant association of maternal variables with risk factors for acute watery diarrhea, which are preventable.

The authors would like to thank all the patients and their mothers for participating in the study.

MN: manuscript preparation, acquisition, literature research and statistical analysis; MN, RA: conceptualized, drafted the proposal, analysis, manuscript editing and review, provided intellectual inputs to the manuscript; MN is the guarantor for this paper