Presumptive treatment with sulphadoxine-pyrimethamine versus weekly chloroquine for malaria prophylaxis in children with sickle cell anaemia in Uganda: a randomized controlled trial

Victoria Nakibuuka, Grace Ndeezi, Deborah Nakiboneka, Christopher M Ndugwa, James K Tumwine, Victoria Nakibuuka, Grace Ndeezi, Deborah Nakiboneka, Christopher M Ndugwa, James K Tumwine

Abstract

Background: Malaria carries high case fatality among children with sickle cell anaemia. In Uganda, chloroquine is used for prophylaxis in these children despite unacceptably high levels of resistance. Intermittent presumptive treatment with sulphadoxine-pyrimethamine (SP) has shown great potential for reducing prevalence of malaria and anaemia among pregnant women and infants.

Objective: To compare the efficacy of monthly SP presumptive treatment, versus weekly chloroquine for malaria prophylaxis in children attending the Sickle Cell Clinic, Mulago Hospital.

Methods: Two hundred and forty two children with sickle cell anaemia were randomized to presumptive treatment with SP or weekly chloroquine for malaria prophylaxis. Active detection of malaria was made at each weekly visit to the clinic over one month. The primary outcome measure was the proportion of children with one malaria episode at one month follow-up. The secondary outcome measures included malaria-related admissions and adverse effects of the drugs.

Results: Ninety-three percent (114/122) of the children in the chloroquine group and 94% (113/120) in the SP group completed one month follow up. SP reduced prevalence of malaria by 50% compared to chloroquine [OR = 0.50, (95% CI 0.26-0.97)]; p = 0.042. Six percent (7/122) of the children receiving weekly chloroquine had malaria related admissions compared to 2.5% (3/120) on presumptive treatment with SP. No serious drug effects were reported in both treatment groups

Conclusion: Presumptive treatment with SP was more efficacious than weekly chloroquine in reducing prevalence of malaria in children with sickle cell anaemia. Continued use of chloroquine for malaria chemoprophylaxis in children with sickle cell anaemia in Uganda does not seem to be justified.

Trial registration: ClinicalTrials.gov NCT00124267.

Figures

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Figure 1
Trial profile.

References

    1. Hendricks RG, Hendricks ED, Matthew DG. Disorders of the blood in paediatrics in the Tropics. Blackwell Scientific Publications, London; 1991. pp. 336–72.
    1. Paul D, Bernard J, Geerlings P, Bernard J, Brabin , Teunis A, Eggelete Analysis of the effects of malaria chemoprophylaxis in children on haematological responses, morbidity and mortality. Bull World Health Organ. 2003;81:205–216.
    1. Graham S, Ndugwa CM. Sickle cell disease in Uganda: a time for action. East Afr Med J. 2003;80:384–387.
    1. World Health Organization . Prevalence of sickle cell disease. WHO, Geneva; 2005.
    1. Serjeant G. Mortality from Sickle cell Disease in Africa. BMJ. 2005;330:432–433. doi: 10.1136/bmj.330.7489.432.
    1. Serjeant G. The geography of sickle cell disease. 1994.
    1. Meremikwu M. Clinical Evidence Sickle Cell Disease. BMJ. 2009.
    1. Jumah A, Nlemadim E, Kaine W. Types of anaemic crises in paeditric patients with sickle cell anaemia seen in Enugu, Nigeria. Arch Dis Childhood. 2004;89:572–576. doi: 10.1136/adc.2003.037374.
    1. Kagwa- Nyanzi Causes of death among sickle cell anaemia patients at Mulago Hospital, Kampala, Uganda. East Afr Med J. 1970;47:338–343.
    1. Warley MA, Hamilton DJS, Marsden PD, Brown RE, Merselis JG, Wilks N. Chemoprophylaxis of homozygous sicklers with antimalarials and long acting penicillin. BMJ. 1965;5453:86–88. doi: 10.1136/bmj.2.5453.86.
    1. Dorsey G, Kamya M, Njama D, Cattamanchi A, Kyabayinze D, Gasasira A, Rosenthal PJ. Sulfadoxine/pyrimethamine alone or amodiaquine or artesunate for treatment of uncomplicated malaria. Lancet. 2002;360:2031–38. doi: 10.1016/S0140-6736(02)12021-6.
    1. Legros D, Johnson K, Houpiklan P, Makanga M, Kabakyenga JK, Taylor WR. Clinical efficacy of chloroquine or sulfadoxine - pyrimethamine in children under five from south- western Uganda with uncomplicated falciparum malaria. Trans R Soc Trop Med Hyg. 2004;96:199–201. doi: 10.1016/S0035-9203(02)90304-4.
    1. Wolde B, Pickering J, Wotton K. Chloroquine chemoprophylaxis in children during peak transmission period in Ethiopia. J Trop Med Hyg. 1994;97:215–218.
    1. Kamugisha A. Prevalence and factors associated with aplastic crises in sickle cell anaemia children at Mulago Hospital. Makerere University, Dissertation; 2005.
    1. Schellenberg D, Menendez C, Elizeus Kahigwa Aponte J, Vidal J, Marcel T, Mshinda H, Alonso P. Intermittent treatment for malaria and anaemia control at the time of routine vaccination in the Tanzanian infants, randomized, placebo controlled trial. Lancet. 2001;357:1471–1477. doi: 10.1016/S0140-6736(05)71421-5.
    1. O'Meara WP, Breman JG, Mckenzie FE. The promise and challenges of intermittent preventive treatment for malaria. Malar J. 2005;4:1475–2875. doi: 10.1186/1475-2875-4-33.
    1. Njama-Meya D, Clark TD, Nzarubara B Staedke S, Kamya M. Treatment of malaria restricted to Laboratory confirmed cases: a prospective cohort in Ugandan children. Malar J. 2007;6:7. doi: 10.1186/1475-2875-6-7.
    1. Schellenberg D, Menendez C, Kahigwa E. Intermittent treatment for malaria and anaemia control at the time of routine vaccination in the Tanzanian infants Randomised placebo controlled trial. Lancet. 2001;57:1471–1477. doi: 10.1016/S0140-6736(00)04643-2.
    1. Dobrovolny CG, White WC, Coaey GR. Chloroquine and chloroguanide as suppressants of malaria in Guatemala. Am J Trop Med Hyg. 1953;12:808–845.
    1. Chandramohan D, Owusu S, Carnerio I, Awine T, Amponsa K, Mensah N, Jaffar S, Baiden R, Hodgson A, Binka F, Green Wood B. Cluster randomized trial of intermittent preventive treatment for malaria in infants in area of high seasonal transmision in Ghana. BMJ. 2005;331:727–733. doi: 10.1136/bmj.331.7519.727.
    1. White NJ. Intermittent presumptive treatment for malaria. PLoS Med. 2005;2:e3. doi: 10.1371/journal.pmed.0020003.
    1. Egan A, Crawley J, Schellenberg D. Intermittent preventive treatment for malaria control in infants moving towards evidence based policy and public health action. Trop Med Int Health. 2005;10:815–817. doi: 10.1111/j.1365-3156.2005.01474.x.
    1. Kamya M, Bakyaita NN, Talisuna AO, Were WM, Staedke SG. Increasing anti malarial drug resistance in Uganda and revision of the national drug policy. Trop Med Int Health. 2002;7:1031–1041. doi: 10.1046/j.1365-3156.2002.00974.x.
    1. Mirjam S, Wondimagegn P, Isabel B, Maha E, Roewer S, Alano A, Loscher T, Ulrich B, Mockenhaupt F. High prevalence of drug resistance mutations in Plasmodium falciparum and P lasmodium vivax in southern Ethiopia. Malar J. 2006;5:54. doi: 10.1186/1475-2875-5-54.
    1. Mahamadou A, Thera MA, Paul S, Coulibaly D, Traore K, Garba MN, Cissoko Y, Kone A, Guindo A, Dicko A, Baevoqui AH, Djimde A, Lyke KE, Diallo DA, Doumbo OK, Plowe CV. Impact of trimethoprim-sulfamethoxazole prophylaxis on falciparum malaria infection and disease. J Infect Dis. 2005;192:1823–1829. doi: 10.1086/498249.
    1. Felicia U, Ifeoma E. Effects of pyrimethamine versus proguanil in malarial chemprophyalaxis in children with sickle cell disease, a randomized placebo controlled pen label study. Curr Ther Res Clin E. 2003;64:616–625. doi: 10.1016/j.curtheres.2003.09.003.

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