Feasibility and safety of integrating mass drug administration for helminth control with seasonal malaria chemoprevention among Senegalese children: a randomized controlled, observer-blind trial

Abstract

Background: The overlap in the epidemiology of malaria and helminths has been identified as a potential area to exploit for the development of an integrated control strategy that may help to achieve elimination of malaria and helminths. A randomized, controlled, observer-blind trial was conducted to assess the feasibility and safety of combining mass drug administration (MDA) for schistosomiasis and soil transmitted helminths (STH) with seasonal malaria chemoprevention (SMC) among children living in Senegal.

Methods: Female and male children aged 1-14 years were randomized 1:1:1, to receive Vitamin A and Zinc on Day 0, followed by SMC drugs (sulfadoxine-pyrimethamine and amodiaquine) on Days 1-3 (control group); or praziquantel and Vitamin A on Day 0, followed by SMC drugs on Days 1-3 (treatment group 1); or albendazole and praziquantel on Day 0, followed by SMC drugs on Days 1-3 (treatment group 2). Safety assessment was performed by collecting adverse events from all children for six subsequent days following administration of the study drugs. Pre- and post-intervention, blood samples were collected for determination of haemoglobin concentration, malaria microscopy, and PCR assays. Stool samples were analyzed using Kato-Katz, Merthiolate-iodine-formalin and PCR methods. Urine filtration, PCR and circulating cathodic antigen tests were also performed.

Results: From 9 to 22 June 2022, 627 children aged 1-14 years were randomized into the three groups described above. Mild, transient vomiting was observed in 12.6% (26/206) of children in treatment group 2, in 10.6% (22/207) in group 1, and in 4.2% (9/214) in the control group (p = 0.005). Pre-intervention, the geometric mean value of Plasmodium falciparum parasite density was highest among children who received albendazole, praziquantel with SMC drugs. Post-intervention, the parasite density was highest among children who received SMC drugs only. Children who received praziquantel and SMC drugs had a lower risk of developing severe anaemia than their counterparts who received SMC drugs alone (OR = 0.81, 95% CI 0.13-5.00, p = 0.63).

Conclusions: Integration of MDA for helminths with SMC drugs was safe and feasible among Senegalese children. These findings support further evaluation of the integrated control model.

Trial registration: The study is registered at Clinical Trial.gov NCT05354258.

Keywords: Co-infection; Falciparum malaria; Integrated control strategy; Schistosomiasis; Soil-transmitted helminthiasis.

Fig. 1

Map of Senegal showing the study site. Source: Ndiaye et al. Malaria Journal 2013, 12:240 http://www.malariajournal.com/content/12/1/240

Fig. 2

CONSORT diagram showing the flow of the study participants, Saraya, 2022

Fig. 3

Distribution of adverse events across the treatment arms in the first 6 days post-administration of SMC and anthelminthic drugs. Key: Group 1 = control group, Group 2 = Treatment group 1, Group 3 = Treatment group 2

Fig. 4

Pre-and post-intervention P. falciparum Intensity Geometric Mean and 95% confidence intervals across the three study groups. Key: Group 1 = control group, Group 2 = Treatment group 1, Group 3 = Treatment group 2