Abstract
Antimalarial drug resistance has been a major contributor to the failure of the battle against malaria in many developing countries. The P. falciparum genes, pfcrt and pfmdr-1, have been implicated in chloroquine resistance. The objective of this study was to determine the presence of mutant alleles of these chloroquine resistance genes among isolates of P. falciparum from children presenting with severe malaria in Ghana. Venous blood samples were taken from patients, and plasma chloroquine levels measured. P. falciparum chromosomal DNA was isolated from the blood samples, and subjected to PCR, restriction digestion and sequencing. Resulting data were analysed using the STATA statistical software. Of 140 children recruited into the study, 109 (77.9%) had detectable pre-treatment chloroquine levels. PCR and restriction digestion analysis of the pfcrt gene indicated that 124 (88.6%) had the mutant T76 gene, and that this correlated with higher chloroquine levels. Sequence analysis of these showed consistent genetic sequences for chloroquine resistant and sensitive parasites with respect to Pfcrt codons 72 through 76.The Pfcrt T76 mutation was found in 88.4% of isolates having the Pfmdr-1Y86 mutation. The Pfmdr-1 Y86 mutation was found in 67.6% of isolates having the Pfcrt T76 mutation. The study affirms Pfcrt as a better chloroquine resistance marker. Both mutations are independently selected by chloroquine levels and that one mutation (Y86) might modify/increase the effect of the other (T76). This study also depicts the much-overlooked antimalarial drug resistance situation in the area and emphasizes the need for a proper treatment strategy.
Highlights
Malaria affects approximately 40% of the world's population especially those living in the world's poorest nations.[1]
Demographic characteristics Blood samples of 140 children, all diagnosed with severe malaria, were available for analysis
Pre-treatment plasma chloroquine levels Of the 140 children presenting with severe malaria to the Komfo Anokye Teaching Hospital, 109 (77.9%) had detectable pre-treatment plasma chloroquine levels, whilst the remaining 31 (22.1%) had no detectable plasma chloroquine
Summary
Malaria affects approximately 40% of the world's population especially those living in the world's poorest nations.[1]. Shortages of resources undeniably remain the significant obstacles to malaria control in several developing countries, but drug resistance has been a major additional contributor to the failure of the battle against the disease in many of these countries.[3] As a matter of fact, the continuous changing patterns of drug resistance necessitate the use of drugs that are more expensive and may have dangerous side effects. Artemisinin and its derivatives have, in the past decade, become the first line of treatment in some parts of the world.[4] their indiscriminate use for self-treatment of suspected uncomplicated malaria may be ringing the alarm bell for the development of resistance to them in the ensuing decade.[5]
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