Effect of Primaquine on Gametocyte Carriage in the Case-Management of Uncomplicated Falciparum Malaria with Acts: Nigerian Perspective

Abstract

Background: Drugs that kill or inhibit sexual stages of Plasmodium such as Primaqiune (PQ) could potentially amplify or synergize the impact of first line antimalarials by blocking transmission to mosquitoes. This study examined the effect of Primaquine on gametocyte carriage in the case management of uncomplicated falciparum malaria with artemisinin-based combination therapy (ACT) with the overall purpose of possibly recommending it as an adjunct drug for malaria control. Methods: A total of 181 patients with uncomplicated falciparum malaria, normal glucose-6-phosphate dehydrogenase (G6PD) enzyme levels, and haemoglobin levels ≥ 8 g/dL completed this two-arm randomized blinded clinical trial to test the efficacy of a single dose PQ (0.75 mg/kg) on falciparum gametocytaemia. 88 subjects were assigned to a standard 3-day course of Dihydroartemisinin-Piperaquine (DHP) alone (n = 88) while 93 others had DHP combined with a single dose of PQ on day 3 (n = 93). A 28-day follow-up schedule carried out in the outpatient clinic of a Primary health facility in Vom, Plateau State Nigeria where study participants were seen on days 1, 3, 7 and then weekly to assess the presence of asexual parasites and gametocytes by microscopy. A Kaplan-Meier analysis was employed to determine the survival function of gametocytes on day 3. The data was analyzed using Epi info version 7.1.5. Results: With a gametocyte prevalence of 27.1%, gametocyte carriage rate was lower in the PQ group due to higher probability of clearing gametocytes (Breslow test χ2 = 8.306, df = 1, p = 0.004) and significantly less likely to harbor gametocytes by day 7 when compared to the DHP-alone group (χ2 = 6.218, df = 1, p = 0.013). Conclusion: Addition of single-dose 0.75 mg/kg PQ was associated with reduced gametocyte carriage as a result of faster gametocyte clearance and lower incidence of gametocyte development in DHP-treated patients. PQ as gametocytocidal drug may be useful in combination with artemisinin-based combination therapy (ACT) regimen to clear gametocytes and thereby interrupt malaria transmission to mosquito vector more effectively than ACT alone.