Pharmacoeconomic Rationale of Zinc Supplementation In The Management of Acute Diarrhea In Children With Rotavirus Infection In Indonesia

Mohamad Saifudin Hakim, Serhii Soloviov, Hera Nirwati, Yati Soenarto, Iryna Dzyublyk, Maryia Leleka, Viktor Trokhymchuk


Rotavirus is one of the most important causative agents of gastroenteritis in both infants and children worldwide, resulting in a high mortality and burden of disease, mainly in low-income, developing countries. Oral rehydration therapy with zinc supplementation is currently the recommended way to prevent death from diarrheal dehydration. In this study, we aimed to estimate the effectiveness of zinc supplementation in combination therapy of patients with suspected rotavirus infection in Indonesia. The perspective of this pharmacoeconomic study refer to the economic vantage point of cost-of-illness analysis. Achievement of this goal was possible with the construction of a decision tree model and determination of decision rules for inclusion of zinc supplementation into the combination therapy. The input parameters of the model were hospitalization days of patients stratified by the presence or absence of rotavirus infection as well as the additional inclusion of zinc supplementation. The criterion for prediction and decision making was the global rotavirus prevalence. The feature of the simulation was that the costs were expressed as relative to each other, which allowed to unify the proposed methodology. Retrospective analysis of clinical database of Indonesian patients with acute diarrhea has shown that zinc supplementation would be rational in case of rotavirus prevalence among these patients is higher than 81.5%. It was shown that additional zinc supplementation would be costeffective with probability of 0.62 and 0.53 – in the positive range of cost ratio variation or if costs for less than 43% of baseline therapy per day costs on an average.


iarrhea, modelling, rotavirus, treatment, zinc supplementation

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Crane J., Naeher T., Shulgina I., Zhu C., Boedeker E. Effect of zinc in enteropathogenic Escherichia coli infection. Infect Immun 2007; 75(12): 5974-5984.

GBD 2015 Mortality and Causes of Death Collaborators. Global, regional, and national life expectancy, all-cause mortality, and cause-specific mortality for 249 causes of death, 1980–2015: a systematic analysis for the Global Burden of Disease Study 2015. Lancet 2016; 388: 1459–1544.

Goel MK, Khanna P, Kishore J. Understanding survival analysis: Kaplan-Meier estimate. Int J Ayurveda Res 2010; 1(4): 274-278.

Hakim MS, Nirwati H, Aman AT, Soenarto Y, Pan Q. Significance of continuous rotavirus and norovirus surveillance in Indonesia. World J Pediatr 2018; 14(1): 4-12.

Kawai K, O'Brien MA, Goveia MG, Mast TC, El Khoury AC. Burden of rotavirus gastroenteritis and distribution of rotavirus strains in Asia: a systematic review. Vaccine 2012; 30:1244-1254.

Kelleher S., Casa I., Carbajal N., Lonnerdal B. Supplementation of infant formula with the probiotic Lactobacillus reuteri and zinc: impact on enteric infection and nutrition in infant rhesus monkeys. J Pediatr Gastroenterol Nutr 2002; 35: 162-168.

Wazny K, Zipursky A, Black R, et al. Setting research priorities to reduce mortality and morbidity of childhood diarrhoeal disease in the next 15 Years. PLoS Med 2013; 10(5): e1001446.

Lanata CF, Fischer-Walker CL, Olascoaga AC, et al. Child Health Epidemiology Reference Group of the World Health Organization and UNICEF. Global causes of diarrheal disease mortality in children <5 years of age: a systematic review. PloS One 2013; 8:e72788

Miller RG. Survival analysis. John Wiley & Sons 1997.

Nirwati H, Wibawa T, Aman AT, Wahab A, Soenarto Y. Detection of group A rotavirus strains circulating among children with acute diarrhea in Indonesia. Springerplus 2016; 5: 97.

Prasad А. Zinc in human health: effect of zinc on immune cells. Mol Med 2008: 14(5–6): 353-357.

Roy S., Hossain M., Khatun W. et al. Zinc supplementation in children with cholera in Bangladesh: randomised controlled trial. BMJ 2008; 336(7638): 266-268.

Sato RC and Zouain DM. "Markov Models in health care." Einstein (São Paulo) 8.3. 2010.

Sazawal S, Black RE, Bhan MK, et al. Zinc supplementation in young children with acute diarrhea in India. N Engl J Med 1995; 333: 839-844.

Soenarto Y, Aman AT, Bakri A, et al. Burden of severe rotavirus diarrhea in Indonesia. J Infect Dis 2009; 200 Suppl 1: S188-194.

Solovyov S.O., Dzyublyk I.V., Zaliska O.M., Sakhno G.O.. Analytical substantiation of the inclusion of an antiviral drug in the treatment of patients with suspected acute viral diseases. Annals of the Mechnikovsky Institute 2016; 4: 18-26.

Tate JE, Burton AH, Boschi-Pinto C, Parashar UD; World Health Organization–Coordinated Global Rotavirus Surveillance Network. Global, regional, and national estimates of rotavirus mortality in children <5 years of age, 2000–2013. Clin Infect Dis 2016; 62(Suppl 2): S96–S105.

Unger CC, Salam SS, Sarker MSA, et al. Treating diarrheal disease in children under five: the global picture. Archives of Disease in Childhood 2014; 99: 273.

Walker С., Black R. Zinc for the treatment of diarrhea: effect on diarrhea morbidity, mortality and incidence of future episodes. Intern J Epidemiology 2010; 39: 63-69.

Wilopo SA, Soenarto Y, Bresee JS, et al. Rotavirus surveillance to determine disease burden and epidemiology in Java, Indonesia, August 2001 through April 2004. Vaccine 2009; 27 (Suppl 5): F61-66.



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