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

Abstract

The clinical response following treatment with chloroquine, and the prevalence of two Plasmodium falciparum DNA polymorphisms known to associate with drug resistance, namely PfCRT K76T and Pfpgh N86Y 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 K76T nor PfpghN86Y. All post treatment samples in the two areas were carrying the mutant allele of Pfcrt K76T. The higher frequency of PfpghN86Y in Haj Yousif (0.86) than Gadaref (0.72), where chloroquine resistance is higher suggests a minor role, if any, for PfpghN86Y 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.

• Authors: Nawal Tagelsir, Zeinab Ibrahim, Abdelrahman Medani, Omaima Salih, Amel Hamad, Haider Giha, Atif El-Agib, Baldip Khan, Najeeb Saeed, Muntaser Ibrahim
• Journal: Acta tropica (Acta Trop) Vol. 97 Issue 1 Pg. 19-25 (Jan 2006) ISSN: 0001-706X [Print] Netherlands
• PMID: 16171768 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• ATP Binding Cassette Transporter, Subfamily B, Member 1
• Antimalarials
• Membrane Proteins
• Membrane Transport Proteins
• PfCRT protein, Plasmodium falciparum
• Protozoan Proteins
• Chloroquine

Topics

• ATP Binding Cassette Transporter, Subfamily B, Member 1 (genetics)
• Adolescent
• Adult
• Animals
• Antimalarials (pharmacology, therapeutic use)
• Chloroquine (pharmacology, therapeutic use)
• Drug Resistance
• Female
• Humans
• Malaria, Falciparum (drug therapy, parasitology)
• Male
• Membrane Proteins (genetics)
• Membrane Transport Proteins
• Parasitic Sensitivity Tests
• Plasmodium falciparum (drug effects, genetics)
• Polymorphism, Genetic
• Protozoan Proteins (genetics)
• Sudan
• Treatment Outcome