Genetic Mutation of Malaria Drug Resistance Genes after Adoption of Artemisinin Combination Therapy in Sudan

Abstract

This study was carried out in three states in Sudan (Sennar, Khartoum and River Nile) to detect the prevalence of antimalrial genetic markers; Plasmodium falciparum chloroquine resistance transporter (Pfcrt), P.f multidrug resistance gene-1 (Pfmdr-1), P.f dihydorofolate reductase (Pfdhfr) and P.f dihydropotrate synthesize (Pfdhps). A cross-sectional study was carried out during the period from July 2015 to December 2017. 300 patients were included in this study their age ranged between 1- 90 years old of mean age was 31 ± 23 years, from them 133 were males and 167 were females. Blood samples were taken from all patients to detect malaria parasite by using Giemsa stained blood smears. Out of 300 positive malaria samples, the prevalence rates of these genes were 32%, 36%, 36.7% and 33% respectively by using of restriction fragments length polymorphisms - polymerase chain reaction (RFLP-PCR) method. The highest prevalence mutant allele rate (47%) was reported in Khartoum state with Pfmdr, while the lowest prevalence rate (28%) was reported in two genes (Pfcrt in Sennar and Pfdhfr in Khartoum). Among the gender, the rates were 22% and 10% in females and males respectively. The highest rate (15.7%) was reported in both Pfmdr-1 and Pfdhfr among age group 20-50 years old, while the lowest prevalence rate (3.7%) was reported in Pfdhps among age group 11-19 years old. Also, the highest prevalence rate (12.7%) was reported in Pfdhfr among parasite count ++, while the lowest prevalence rate 3% was reported among parasite count ++++. The highest prevalence rate (37%) of single point mutation of Pfcrt K76T was reported in River Nile, while the lowest prevalence rate (28%) was reported in Sennar. In females reported 22% and males 10%. Among age groups the highest prevalence rate (10.7%) of Pfcrt K76T was reported in age group 20- 50 years, while the lowest prevalence rate (7.7%) was reported among both age groups (<10 and >50). The highest prevalence rate (12%) was reported among parasite count ++, while the lowest prevalence rate (3%) was reported among parasite count ++++. The results revealed that, the highest prevalence rate (15.7%) of single point mutation of Pfmdr-1 N86Y was reported in Khartoum state, while the lowest prevalence rate (9.7%) was reported in Sennar state. The result showed equal rate of 18% among the gender with presence of mixed allele with a rate of 0.7%. Also, the results revealed that, the highest Pfmdr-1 N86Y rate of 15.7% was reported among age group 20-50 years, while the lowest prevalence rate of 4.7% was V reported among age group 11 -19 years . The prevalence rate among parasite count was 10.7% among the + and ++ followed by 10.3% and 4.3% among +++ and ++++ respectively. From the results, the highest prevalence rate (14.3%) of single point mutation Pfdhfr C59Rwas reported in Khartoum, while the lowest prevalence rate (9.3%) was reported in River Nile with the presence of mixed allele (1.7% and 4%) in River Nile and Khartoum respectively. Among the gender, the prevalence rates of 20.7% and 16%were among females and males respectively with the presence of mixed allele 1.3% and 4.3% respectively. The highest rate (15.7%) was reported among age group 20 -50 years, while the lowest rate (5.7%) was reported among age group 11 -19 years with the presence of mixed allele among all age groups. The highest prevalence rate (12.7%) of Pfdhfr C59R was reported among parasite count ++, while the lowest prevalence rate (3%) was reported among parasite count ++++ with the presence of mixed allele among all parasite counts. From the results, the prevalence rate of single point mutation of Pfdhps A436G (13%) was reported in Khartoum and (10%) in both Sennar and River Nile with the presence of mixed allele in Khartoum and River Nile with rates of 1.7% and 3% respectively. Among gender 19.3% rates was reported among females and 13.7% among males with mixed allele of 3% and 1.7% respectively. However, the highest prevalence rate (15.7%) was reported among age group 20- 50 years, while the lowest rate (3.7%) was reported among age group 11-19 years with mixed allele among all age groups except the age group 11-19 years. The highest prevalence rate (11%) of Pfdhps A436G was reported among parasite count ++, while the lowest prevalence rate (3.7%) was reported among parasite count ++++ with the presence of mixed allele among all parasite counts. The study indicated that, the genetic mutation of malaria drug resistance markers after adoption of artemisinin combination therapy were still found in the study areas.