Prevalence of Molecular Markers Linked to Sulfadoxine/Pyrimethamine Resistance in Plasmodium Falciparum at Pawe, North Western Ethiopia
| dc.contributor.advisor | Petros Beyene (Professor) | |
| dc.contributor.author | Kifle Sofonias | |
| dc.date.accessioned | 2018-07-10T13:43:17Z | |
| dc.date.accessioned | 2023-11-08T16:33:43Z | |
| dc.date.available | 2018-07-10T13:43:17Z | |
| dc.date.available | 2023-11-08T16:33:43Z | |
| dc.date.issued | 2008-12 | |
| dc.description.abstract | In 1999, following high treatment failure rates of chloroquine, the Ethiopian Ministry of Health gave directives for the use of Sulfadoxine/pyrimethamine (SP) as first line drug for the treatment of uncomplicated falciparum malaria. In 2004, this decision was altered due to high treatement failure of SP and Arthemether-Lumfantrine (CoartemĀ® Pfdhfr; Pfdhps; dot blot hybridization; Ethiopia ) was introduced. The study investigated the impact of withdrawal of SP on the change in frequency of SP resistance-related haplotypes in Pfdhfr (codons 51, 59 and 108) and Pfdhps (codons 437 and 540) genes by PCR based dot blot hybridization. Plasmodium falciparum positive blood samples were collected from a total of 159 patients during two cross sectional surveys in 2005 (N=80) and 2007/08 (N=79) from Pawe, North Western Ethiopia. It was determined that the frequency of SP resistance associated triple mutant Pfdhfr haplotype decreased significantly from 50.79% to 15.87% (P<0.001), while Pfdhps double mutant haplotype remained high and changed only mariginally from 69.2% to 55.38% (P>0.05) both of which showed that the prevalence of mutatnt alleles that cofer drug resistance are decreasing in the absence of drug pressure. The combined Pfdhfr/Pfdhps quintuple mutant haplotype that has been previously recognized to be the most important determinant of SP resistance was significantly decreased from 40.68% to 13.56% (P<0.005). The frequency of triple wild Pfdhfr halpotype increased from 0.00% to 11.11 % (P<0.025), double Pfdhps wild haplotype increased from 13.84% to 30.77% (P<0.05) and the combined Pfdhfr/Pfdhps quintuple wild haplotype increased significantly from 0.00% to 10.17% (P<0.05), indicating reemergence of SP sensitive parasites. On the whole, a significant decrease of mutant alleles and subsequent increase of susceptible alleles were observed, which might be explained by the reduction of residual drug-resistant parasites caused by the strong drug pressure imposed when SP was the first-line drug, followed by lower fitness of these resistant parasites in the absence of drug pressure. Although the prevalence of mutant alleles are significantly decreasing, higher percentages of mutatnt alleles remain prevalent in 2007/08 isolates in Pawe. Therefore, further multi-centered studies in malaria endemic areas from where SP has been withdrawn will be required by using molecular markers, which are effective indicators of SP resistance/sensitivity, to assess reintroduction of this safe and affordable drug. Key words: Plasmodium falciparum; Sulfadoxine/Pyrimethamine; Antimalarial drug resistance | en_US |
| dc.identifier.uri | http://etd.aau.edu.et/handle/123456789/7734 | |
| dc.language.iso | en | en_US |
| dc.publisher | Addis Ababa University | en_US |
| dc.subject | Plasmodium falciparum | en_US |
| dc.subject | Sulfadoxine/Pyrimethamine | en_US |
| dc.subject | Antimalarial drug resistance | en_US |
| dc.subject | Pfdhfr; Pfdhps | en_US |
| dc.subject | dot blot hybridization | en_US |
| dc.subject | Ethiopia | en_US |
| dc.title | Prevalence of Molecular Markers Linked to Sulfadoxine/Pyrimethamine Resistance in Plasmodium Falciparum at Pawe, North Western Ethiopia | en_US |
| dc.type | Thesis | en_US |