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A Community-Randomized Evaluation of the Effect of Intermittent Preventive Treatment in Infants on Antimalarial Drug Resistance in Southern Tanzania

Pearce, Richard J. ; Ord, Rosalynn ; Kaur, Haprarksh ; Lupala, Cecylia ; Schellenberg, Joanna ; Shirima, Kitzito ; Manzi, Fatuma ; Alonso, Pedro ; Tanner, Marcel ; Mshinda, Hassan ; Roper, Cally ; Schellenberg, David

In: The Journal of Infectious Diseases, 2013, vol. 207, no. 5, p. 848-859

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    Titre
    • A Community-Randomized Evaluation of the Effect of Intermittent Preventive Treatment in Infants on Antimalarial Drug Resistance in Southern Tanzania
    Auteur
    • Pearce, Richard J.. London School of Hygiene and Tropical Medicine, London, United Kingdom
    • Ord, Rosalynn. London School of Hygiene and Tropical Medicine, London, United Kingdom
    • Kaur, Haprarksh. London School of Hygiene and Tropical Medicine, London, United Kingdom
    • Lupala, Cecylia. Ifakara Health Institute, Tanzania
    • Schellenberg, Joanna. London School of Hygiene and Tropical Medicine, London, United Kingdom
    • Shirima, Kitzito. Ifakara Health Institute, Tanzania
    • Manzi, Fatuma. Ifakara Health Institute, Tanzania
    • Alonso, Pedro. Barcelona Centre for International Health Research, Hospital Clinic, Universitat de Barcelona, Spain
    • Tanner, Marcel. Swiss Tropical Institute, Basle, Switzerland
    • Mshinda, Hassan. Ifakara Health Institute, Tanzania
    • Roper, Cally. London School of Hygiene and Tropical Medicine, London, United Kingdom
    • Schellenberg, David. London School of Hygiene and Tropical Medicine, London, United Kingdom
    Type de document
    • Postprint
    Langue
    • Anglais
    Publié dans
    • The Journal of Infectious Diseases, 2013, vol. 207, no. 5, p. 848-859. Oxford University Press
    Autre version électronique
    Identifiant OAI-PMH
    • oai:doc.rero.ch:297689
    Summary
    Background. Intermittent preventive treatment in infants (IPTi) is the administration of sulfadoxine-pyrimethamine (SP) at 2, 3, and 9 months of age to prevent malaria. We investigated the influence of IPTi on drug resistance. Methods. Twenty-four areas were randomly assigned to receive or not receive IPTi. Blood collected during representative household surveys at baseline and 15 and 27 months after implementation was tested for SP and resistance markers. Results. The frequency of SP in blood was similar in the IPTi and comparison areas at baseline and at 15 months. dhfr and dhps mutations were also similar at baseline and then increased similarly in both arms after 15 months of SP-IPTi. First-line treatment was switched from SP to artemether-lumefantrine before the final survey, when SP positivity fell among infants in comparison areas but increased in IPTi areas. This was accompanied by an increase in dhfr but not dhps mutations in IPTi areas (P = .004 and P = .18, respectively). Conclusions. IPTi did not increase drug pressure or the selection on dhfr and dhps mutants, when SP was the first-line malaria treatment. Introduction of artemether-lumefantrine was followed by an increase in dhfr mutations, consistent with weak selection attributable to SP-IPTi, but not by an increase in dhps mutations, suggesting a fitness cost of this mutation