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Molecular surveillance of drug-resistant Plasmodium falciparum in two distinct geographical areas of Nigeria

Analyse von Therapie-resistenten Malariaerregern in zwei Regionen Nigerias

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Zusammenfassung

Die Entwicklung von therapie-resistenter Plasmodium falciparum-Malaria ist seit langem als Haupthindernis zur Bekämpfung von Mortalität und Morbidität erkannt. Wir haben daher die Verbreitung von Genveränderungen, die mit der Resistenz gegen Chloroquine und Pyrimethamin assoziiert sind, in P. falciparum-Isolaten aus zwei geographisch distinkten Gegenden in Nigeria untersucht. Mit Hilfe von RT-PCR und DNA-Sequenzierung wurde die Prävalenz dieser Mutationen bestimmt. Die Prävalenz der pfcrt T76-Mutation in den beiden Gegenden war 92.3 % gegen 86 % in Osogbo verglichen mit 93 % in Lafia (P = 0.4453). Sequenzanalyse des pfcrt Haplotyps (Aminosäuren 72–76) ergab CVIET als einzigen resistenten Haplotyp an beiden Orten. Die Häufigkeit von pfmdr1-Polymorphismen war höher in Lafia (39 %) als in Osogbo (35 %); die kombinierte Prävalenz in beiden Orten war 45.5 % (P = 0.6604). Die Prävalenz der pfdhfr-Triplemutante war hoch in beiden Gegenden: in Osogbo 84 % gegenüber 91 % in Lafia für I51, sowie 88 % gegen 87 % und 96 % gegen 96 % für die R59 and N108 Mutationen. Die kombinierte Prävalenz von pfcrt- und pfmdr1–Mutationen in Osogbo und Lafia war 44.2 % mit einem Risiko von 0.4164; die kombinierte Prävalenz aller Genveränderungen in pfcrt, pfmdr1 and pfdhfr war 40.4 % mit einem Risiko von 1.081. Diese Ergebnisse zeigen die weite Verbreitung der Resistenz gegen Chloroquin und Pyrimethamin in beiden untersuchten Regionen.

Summary

Drug resistance against P. falciparum has been recognized as the crucial obstacle to curbing mortality and morbidity from malaria. We therefore determined the baseline distribution of pfcrt and pfmdr1 genes associated with resistance to chloroquine and pfdhfr gene associated with resistance to pyrimethamine in P. falciparum isolates collected from two geographically distinct areas of Nigeria. We use RT-PCR assays and sequencing to determine the prevalence of these mutations. The combined prevalence of pfcrt T76 mutation in the two sites was 92.3% with 86% from Osogbo compared to 93% from Lafia. Sequencing analysis of the (Pfcrt) K76T haplotype (amino acids 72–76) revealed CVIET as the only resistance haplotype present in the two areas. The frequency of pfmdr1 polymorphisms was higher in Lafia (39%) compared to that in Osogbo (35%) and the combined prevalence from the two sites was 45.5%. The prevalence of the pfdhfr triple mutant alleles was high in both locations. The Osogbo vs Lafia prevalence for pfdhfr mutations was 84% vs 91%, 88% vs 87% and 96% vs 96% for I51, R59 and N108, respectively. None of the samples from the two locations had the T108 mutation. The combined prevalence of pfcrt and pfmdr1 in Osogbo and Lafia was 44.2% with a risk ratio of 0.4164 while the combined prevalence of pfcrt, pfmdr1 and pfdhfr was 40.4% with a risk ratio of 1.081. These results strongly suggest the widespread distribution of CQ and pyrimethamine resistance without any marked distinction between the two locations.

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Authors and Affiliations

  1. Institute of Tropical Medicine, University of Tübingen, Tübingen, Germany

    Olusola Ojurongbe & Jürgen F. Kun

  2. Department of Medical Microbiology & Parasitology College of Health Sciences, Ladoke Akintola University of Technology, Osogbo, Nigeria

    Olusola Ojurongbe & Segun I. Oyedeji

  3. Department of Medical Microbiology and Parasitology College of Medicine, University of Lagos, Lagos, Nigeria

    Wellington A. Oyibo & Adetola F. Fagbenro-Beyioku

  4. Department of Biotechnology, Bells University, Sango Ota, Nigeria

    Segun I. Oyedeji

Authors
  1. Olusola Ojurongbe
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  2. Segun I. Oyedeji
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  3. Wellington A. Oyibo
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  4. Adetola F. Fagbenro-Beyioku
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  5. Jürgen F. Kun
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Correspondence to Jürgen F. Kun.

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Ojurongbe, O., Oyedeji, S., Oyibo, W. et al. Molecular surveillance of drug-resistant Plasmodium falciparum in two distinct geographical areas of Nigeria. Wien Klin Wochenschr 122, 681–685 (2010). https://doi.org/10.1007/s00508-010-1484-0

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  • DOI: https://doi.org/10.1007/s00508-010-1484-0

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