Monthly sulphadoxine-pyrimethamine combination versus daily proguanil for malaria chemoprophylaxis in sickle cell disease: a randomized controlled study at the Jos University Teaching Hospital

Abstract

Background: Malaria carries a high case fatality among patients with sickle cell disease. In Jos University Teaching Hospital, at the time of this study, the use of Proguanil was the acceptable mode of chemoprophylaxis for preventing malaria in these patients. Intermittent Preventive Treatment (IPT) with Sulphadoxine-Pyrimethamine [SP] has shown great potential for reducing the prevalence of malaria and anaemia among pregnant women, infants and travellers. We hypothesised that monthly SP was superior to daily Proguanil in reducing malaria parasitaemia, clinical malaria attacks and sickle cell crises in such patients.

Objective: To assess the efficacy and affordability of monthly SP versus daily Proguanil for malaria chemoprophylaxis in patients attending Sickle Cell Clinic at Jos University Teaching Hospital, Plateau State, Nigeria.

Methods: One hundred and fifty four patients [114 children and 40 adults] with Sickle Cell Disease in their steady state were randomized to monthly SP or daily Proguanil for malaria chemoprophylaxis. Active detection of malaria parasite in the peripheral blood and packed cell volumes were done at each monthly visit to the clinic over a period of three months. The primary outcome measure was the proportion of patients with malaria parasite in the peripheral blood at the end of 3 months. The secondary outcome measures included episodes of clinical malaria attacks, frequency and type of sickle cell crises and adverse effects of the medication.

Results: Ninety four percent [72/77] of patients in the SP group and 91% [70/77] in the Proguanil group respectively completed three months of follow up. SP reduced the prevalence of malaria parasitaemia by 25% [(14%) 10/72] compared to 6.4% [(30%) 21/70] in the proguanil group. [X² 54; p = 0.01]. Seventeen percent [12/72] of the patients receiving monthly SP had malaria attacks compared to 57% [40/70] on prophylaxis with Proguanil. [X² =25; p< 0.0003]. Thirty three percent [24/72] of the patients receiving SP had at least an episode of bone pain crises compared to 69% [48/70] of the patients receiving Proguanil. [X² =17.6; p<0.0001]. SP was 8 times cheaper than Proguanil.

Conclusion:  Monthly chemoprophylaxis with SP was more efficacious than daily Proguanil in reducing the prevalence of asymptomatic malaria parasitaemia, clinical malaria attack and sickle cell crises in patients with sickle cell disease. SP was 8 times cheaper than Proguanil. No significant side effect was recorded in both groups. The current practice of routinely prescribing daily Proguanil to SCD patients for malaria chemoprophylaxis needs to be reviewed.

Keywords: Sickle Cell Disease, Malaria Chemoprophylaxis, sickle cell crisis