Genetic diversity of Plasmodium vivax metacaspase 1 and Plasmodium vivax multi-drug resistance 1 genes of field isolates from Mauritania, Sudan and Oman.

BACKGROUND: Plasmodium vivax is the second most important human malaria parasite, widely spread across the world. This parasite is associated with important issues in the process toward malaria elimination, including potential for relapse and increased resistance to chloroquine. Plasmodium vivax multi-drug resistant (pvmdr1) is suspected to be a marker of resistance although definitive evidence is lacking. Progress has been made in knowledge of biological factors affecting parasite growth, including mechanisms of regulated cell death and the suspected role of metacaspase. Plasmodium vivax metacaspase1 (PvMCA1-cd) has been described with a catalytic domain composed of histidine (H372) and cysteine (C428) residues. The aim of this study was to test for a link between the conserved histidine and cysteine residues in PvMCA1-cd, and the polymorphism of the P. vivax multi-drug resistant gene (pvmdr1). RESULTS: Thirty P. vivax isolates were collected from Mauritania, Sudan, and Oman. Among the 28 P. vivax isolates successfully sequenced, only 4 samples showed the conserved His (372)-Cys (428) residues in PvMCA1-cd. Single nucleotide polymorphisms observed were H372T (46.4%), H372D (39.3%), and C428R (85.7%). A new polymorphic catalytic domain was observed at His (282)-Cys (305) residues. Sequences alignment analysis of pvmdr1 showed SNP in the three codons 958, 976 and 1076. A single SNP was identified at the codon M958Y (60%), 2 SNPs were found at the position 976: Y976F (13%) and Y976V (57%), and 3 SNPs were identified at the position 1076: F1076L (40%), F1076T (53%) and F1076I (3%). Only one isolate was wildtype in all three codons (MYF), 27% were single MYL mutants, and 10% were double MFL mutants. Three new haplotypes were also identified: the triple mutant YVT was most prevalent (53.3%) distributed in the three countries, while triple YFL and YVI mutants (3%), were only found in samples from Sudan and Mauritania. CONCLUSIONS: Triple or quadruple mutants for metacaspase genes and double or triple mutants for Pvmdr1 were observed in 24/28 and 19/28 samples. There was no difference in the frequency of mutations between PvMCA1-cd and Pvmdr1 (P > 0.2). Histidine and cysteine residues in PvMCA1-cd are highly polymorphic and linkage disequilibrium with SNPs of Pvmdr1 gene may be expected from these three areas with different patterns of P. vivax transmission.

The Progress Towards National Malaria Elimination: The Experience of Oman.

Objectives: Despite a significant reduction in the global case incidence and mortality of malaria in the past 20 years, malaria continues to wreak havoc on people's health across the globe. Oman is a malaria-free country, meeting the World Health Organization's (WHO) criteria, having no indigenous malaria case documented since 2010, and maintaining that status for three consecutive years. Oman has a national strategy for prevention of re-establishment of malaria and to maintain their malaria-free status. In this paper, we explore Oman's malaria elimination progress and provide recommendations for accelerating and sustaining malaria free status using WHO malaria elimination strategies. Methods: Secondary data from the years 1976 to 2020 was extracted from official sources utilized to assess progress. A review and epidemiological analysis of malaria cases, species classification, and source of infection was conducted. The data and situation were compared to WHO malaria elimination pillars. Results: The number of malaria cases reported from 1976 to 2020 was 298 070, a decline from 1.6 to 0.1 per 1000 population. Of the 4415 cases reported between 1994-2004, 98.0% were classified as imported and 73.0% of people diagnosed with malaria were 20-34 years old. The number of autochthonous cases began to decline in 1994 from a high of 4415 cases (3.6 per 1000 population) to zero by 2004 with no deaths attributed to autochthonous malaria cases after the year 2000. By 2020, Plasmodium falciparum accounted for 86.0% of cases, P. vivax cases declined to 9.0% and P. malaria and P. ovale comprised the remaining 6.0% of case notifications. Conclusions: Oman achieved malaria elimination status in 2013. To maintain this status, it is essential to adopt a national prevention strategy of re-establishment of malaria and maintain malaria-free status targets.

An outbreak of locally acquired Plasmodium vivax malaria among migrant workers in Oman.

Plasmodium vivax is the most widely distributed human malaria parasite. Outside sub-Saharan Africa, the proportion of P. vivax malaria is rising. A major cause for concern is the re-emergence of Plasmodium vivax in malaria-free areas. Oman, situated in the south-eastern corner of the Arabian Peninsula, has long been an area of vivax malaria transmission but no locally acquired cases were reported in 2004. However, local transmission has been registered in small outbreaks since 2007. In this study, a local outbreak of 54 cases over 50 days in 2014 was analyzed retrospectively and stained blood slides have been obtained for parasite identification and genotyping. The aim of this study was to identify the geographical origin of these cases, in an attempt to differentiate between imported cases and local transmission. Using circumsporozoite protein (csp), merozoite surface protein 1 (msp1), and merozoite surface protein 3 (msp3) markers for genotyping of parasite DNA obtained by scrapping off the surface of smears, genetic diversity and phylogenetic analysis were performed. The study found that the samples had very low genetic diversity, a temperate genotype, and a high genetic distance, with most of the reference strains coming from endemic countries. We conclude that a small outbreak of imported malaria is not associated with re-emergence of malaria transmission in Oman, as no new cases have been seen since the outbreak ended.