High frequency of Plasmodium falciparum PfCRT K76T and PfpghN86Y in patients clearing infection after chloroquine treatment in the Sudan

• Published in: Acta tropica 2006, Vol.97 (1), p.19-25
• Main Authors: Tagelsir, Nawal, Ibrahim, Zeinab, Medani, AbdelRahman, Salih, Omaima, Hamad, Amel, Giha, Haider, El-Agib, Atif, Khan, Baldip, Saeed, Najeeb, Ibrahim, Muntaser
• Format: Article
• Language: English
• Subjects: Adolescent; Adult; Animals; Antimalarials - pharmacology; Antimalarials - therapeutic use; ATP-Binding Cassette, Sub-Family B, Member 1 - genetics; Biological and medical sciences; Chloroquine - pharmacology; Chloroquine - therapeutic use; Chloroquine resistance transporter gene; Drug Resistance; Female; Human protozoal diseases; Humans; Infectious diseases; Malaria; Malaria, Falciparum - drug therapy; Malaria, Falciparum - parasitology; Male; Medical sciences; Membrane Proteins - genetics; Membrane Transport Proteins; Multi-drug resistance gene; Parasitic diseases; Parasitic Sensitivity Tests; Plasmodium falciparum; Plasmodium falciparum - drug effects; Plasmodium falciparum - genetics; Polymorphism, Genetic; Protozoal diseases; Protozoan Proteins - genetics; Sudan; Treatment Outcome
• ISSN: 0001-706X; 1873-6254
• DOI: 10.1016/j.actatropica.2005.07.030

The clinical response following treatment with chloroquine, and the prevalence of two Plasmodium falciparum DNA polymorphisms known to associate with drug resistance, namely PfCRT K76 T and Pfpgh N86 Y were investigated in two sites in central and eastern Sudan. Patient's sensitivity to chloroquine was determined according to the standard in vivo test as recommended by the WHO protocol in days 0, 3, 7 and 14, respectively. Clinical un-responsiveness was 75.9% in Gadaref in eastern Sudan and 32.1% in Haj Yousif of the Khartoum state. Difference between the two sites in treatment outcome is not tantamount to allele frequency and genotype distribution of neither Pfcrt K76 T nor Pfpgh N86 Y. All post treatment samples in the two areas were carrying the mutant allele of Pfcrt K76 T. The higher frequency of Pfpgh N86 Y in Haj Yousif (0.86) than Gadaref (0.72), where chloroquine resistance is higher suggests a minor role, if any, for Pfpgh N86 Y in resistance to chloroquine. Age effect on the clearance of parasitemia was evident in both areas, more significantly though in Gedaref ( P < 0.000) than Haj Yousif ( P = 0.043) These results add to reports in the literature, pointing to the complexity of factors that may contribute to a clinical outcome following chloroquine treatment, particularly, in this case are elements of the host immunity that are yet to be identified.