Plasmodium falciparum population structure in Sudan post artemisinin-based combination therapy.
Over the past decade, Sudan has stepped up malaria control backed by WHO, and this has resulted in significant reduction in parasite rate, malaria morbidity and mortality. The present study analyzed Plasmodium falciparum parasites in four geographical separated areas, to examine whether the success in malaria control following the use of artemisinin-based combination therapy (ACT) has disrupted the population structure and evolution of the parasite. We examined 319 P. falciparum isolates collected between October 2009 and October 2012 in four different areas in Sudan (Jazira [central Sudan], Southern Darfur [western Sudan], Upper Nile [southern Sudan] and Kasala [eastern Sudan]). Twelve microsatellites were analyzed for allelic diversity, multi-locus haplotype and inter-population differentiation. Level of diversity was compared to that detected for three of the above microsatellites among P. falciparum parasites in central and eastern Sudan in 1999, prior to introduction of ACT. Diversity at each locus (unbiased heterozygosity [H]) was high in all areas (Jazira, H=0.67), (Southern Darfur, H=0.71), (Upper Nile, H=0.71), and (Kasala, H=0.63). Microsatellites were distributed widely and private alleles, detected in a single population, were rare. The extent of diversity in the above sites was similar to that seen, in 1999, in central (Khartoum, H=0.73) and eastern Sudan (Gedaref, H=0.75). Significant Linkage disequilibrium (LD) was observed between the microsatellites in all populations. Pairwise FST analysis revealed that parasites in the four areas could be considered as one population. However, the parasites in Sudan clustered away from parasites in West Africa and the Arabian Peninsula. Despite marked reduction in malaria risk in Sudan, the extent of diversity and parasite genetic structure are indicative of a large population size. Further considerable reduction in transmission would be needed before fragmented sub-population can be seen. In addition, the large divergence of P. falciparum in Sudan from West Africa and Arabian Peninsula populations may result from differential evolutionary pressures acting at the population level, which shall be considered in eradication plans.
Department of Biochemistry, Faculty of Medicine and Health Sciences, Sultan Qaboos University, Muscat, Oman; Tropical Medicine Research Institute, National Centre for Research, Sudan.
Amani M A
AM
Bakhiet
Tropical Medicine Research Institute, National Centre for Research, Sudan; Department of Biology, Faculty of Science, University of Hail, Saudi Arabia.
Abdel-Muhsin A
AM
Abdel-Muhsin
Tropical Medicine Research Institute, National Centre for Research, Sudan.
Salah-Eldin G
SE
Elzaki
Department of Biochemistry, Faculty of Medicine and Health Sciences, Sultan Qaboos University, Muscat, Oman.
Zainab
Z
Al-Hashami
Department of Biochemistry, Faculty of Medicine and Health Sciences, Sultan Qaboos University, Muscat, Oman.
Hamida S
HS
Albarwani
Department of Biochemistry, Faculty of Medicine and Health Sciences, Sultan Qaboos University, Muscat, Oman.
Badar A
BA
AlQamashoui
Department of Biochemistry, Faculty of Medicine and Health Sciences, Sultan Qaboos University, Muscat, Oman.
Salama
S
Al-Hamidhi
Department of Microbiology and Immunology, Faculty of Medicine and Health Sciences, Sultan Qaboos University, Muscat, Oman.
Mohamed A
MA
Idris
Tropical Medicine Research Institute, National Centre for Research, Sudan.
Atif A
AA
Elagib
Research Centre in Biodiversity and Genetic Resources (CIBIO), University of Porto, Rua Padre Armando Quintas 7, Vairão 4485-661, Portugal.
Albano
A
Beja-Pereira
Department of Biochemistry, Faculty of Medicine and Health Sciences, Sultan Qaboos University, Muscat, Oman. Electronic address: H.babiker@ed.ac.uk.
Hamza A
HA
Babiker
D000962:Antimalarials / Q000627:therapeutic use; D037621:Artemisinins / Q000627:therapeutic use; D004359:Drug Therapy, Combination; D014644:Genetic Variation; D005838:Genotype; D006239:Haplotypes; D006801:Humans; D015810:Linkage Disequilibrium / Q000235:genetics*; D016778:Malaria, Falciparum / Q000188:drug therapy / Q000469:parasitology*; D018895:Microsatellite Repeats / Q000235:genetics*; D010963:Plasmodium falciparum / Q000235:genetics*; D013397:Sudan; D018911:Trinucleotide Repeats / Q000235:genetics
D000962:Antimalarials; D037621:Artemisinins; C031327:artemisinin
Genetic diversity; Plasmodium falciparum; Population structure; Sudan