A randomized controlled trial of zinc supplementation as adjuvant therapy for dengue viral infection in Thai children

Abstract

Background:Zinc deficiency is common in developing countries and increases the risk for several infectious diseases. Low serum zinc levels have been reported in children with dengue virus infection (DVI). This study aimed to assess the effects of zinc supplementation on DVI outcomes.Methods:A double-blinded, randomized trial was conducted in 50 children with dengue fever (DF)/dengue hemorrhagic fever admitted to the pediatric unit of MSMC Srinakharinwirot University Hospital, Thailand, between January 2016 and April 2017. Bis-glycinate zinc or placebo was orally administered three times a day for 5 days or until defervescence. The primary outcome was to evaluate the DVI defervescence phase; the secondary outcome was to assess hospitalization length and presence of severe DVI and zinc deficiency.Results:The mean time of defervescence was 29.2 ± 24.0 h in the supplementation group and 38.1 ± 31.5 h in the placebo group (P = 0.270). Meantime of hospital staying was 62.5 ± 23.8 h in the supplementation group and 84.7 ± 34.0 h in placebo group with the mean difference of hospital staying between groups of 22.2 h (95% confidence interval [CI]: 5.5–38.5 h; P = 0.010). Overall prevalence of zinc deficiency was 46%. Serum zinc levels increased from baseline to the end of the study. the mean gain was 26.4 μg/dL (95% CI: 13.6–39.1 μg/dL) in the supplementation group and 14.4 μg/dL (95% CI: 7.4–21.3 μg/dL) in placebo group. No signs of severe DVI were observed in both groups. Zinc supplementation was well tolerated.Conclusions:Overcoming zinc deficiency among Thai children may reduce DF duration and limit the hospitalization, in addition to other advantages that normal serum zinc levels have on overall children health.

Micronutrient Supplementation and Clinical Outcomes in Patients with Dengue Fever

“…Zinc. Rerksuppaphol and Rerksuppaphol 25 conducted an RCT in 50 children (mean age 6.3 years) with DF at an academic medical center in Bangkok, Thailand. Patients were randomized to receive either: 1) 15 mg oral bis-glycinate zinc three times daily for 5 days or until defervescence, or 2) placebo.…”

“…14 Zinc supplementation was associated with shorter duration of hospitalization. 25 There is limited previous research investigating relationships between micronutrient supplementation and clinical outcomes in DF patients. A 2014 review by Ahmed et al 15 summarized existing work on micronutrients and dengue, but at the time of its publication, there were only two articles evaluating the use of micronutrient supplements in the clinical treatment of DF patients.…”

“…Six studies had small sample sizes, with 200 or fewer total participants. 13,[21][22][23][24][25] One study did not provide any information about the micronutrient doses provided and pooled data from multiple hospitals using multiple routes of administration. 13 One study investigated a wide array of laboratory parameters across many days and reported a handful of statistically significant results which may have limited clinical importance.…”

“…These studies have investigated associations between clinical outcomes and supplementation of various micronutrients, including vitamin C, 13,22 vitamin D, 23 vitamin E, 21,24 folic acid, 14 and zinc. 25 No prior literature review has summarized the findings of these clinical studies. Our goals in this review, therefore, were to consolidate and synthesize the findings of studies between 2010 and 2020, which investigated the role of micronutrient supplementation in the clinical care of patients with DF, and to identify gaps in the current literature to guide future research on this topic.…”

A Proposal of Early Diagnosis and Early Management in Dengue Infection and Possible COVID-19

“…66 A study of zinc supplementation as an adjunctive treatment for DENV infection in Thai children revealed that 46% of children admitted with DF/DHF had a zinc deficiency. 67 These children had a longer hospitalization than those with regular zinc levels, regardless of zinc supplementation. Although the time to defervescence does not benefit from zinc supplementation, children with basal normal zinc levels and with zinc supplementation demonstrated a shorter duration of fever.…”