High prevalence of drug-resistance mutations in Plasmodium falciparum and Plasmodium vivax in southern Ethiopia

Schunk, Mirjam; Kumma, Wondimagegn Paulos; Miranda, Isabel Barreto; Osman, Maha E.; Roewer, Susanne; Alano, Abraham; Löscher, Thomas; Bienzle, Ulrich; Mockenhaupt, Frank P.

doi:10.1186/1475-2875-5-54

Cited by 58 publications

(32 citation statements)

References 22 publications

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“…The finding of this study does not support a previous study conducted in Ethiopia that reported a 100% frequency of the pfcrt T76 mutation, and an 81% frequency of the mutation pfmdr1 Y86 in P. falciparum [ 41 ] . However, the current finding is in line with studies conducted in two East African countries [ 27 , 42 ], where the frequency of the pfcrt -76 resistance alleles were repopulated with the sensitive ones after many years of CQ withdrawal.…”

Section: Discussioncontrasting

confidence: 99%

“…Concerning pfmdr1 , while wild-type pfmdr1 is thought to transport and accumulate CQ in the parasites’ food vacuole, mutations N86Y, S1034C, N1042D, and D1246Y interfere with transportation of the anti-malarial drugs, leading to reduced CQ-sensitivity [ 14 ]. The percentage of wild-type alleles at codon 86 of pfmdr1 was 85.1% (166/195), which is higher than 81% present in Schunk in 2006 and 84.5% in Eshetu in 2010 [ 41 , 52 ]. It should be clear that the study by Schunk in 2006 was conducted 7 years before the current study.…”

Section: Discussionmentioning

confidence: 99%

“…CQ-susceptible alleles clearly have a selective advantage over resistant ones, pfmdr1 Y86 having rebounded from 100% to 11% in 6 years (for samples collected on 2009 from East Ethiopia) to eight years time (for samples collected on 2011from South Ethiopia). On the other hand, N86Y mutation was rebounded from 81% to 9% [ 41 , 52 ].…”

Section: Discussionmentioning

confidence: 99%

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Return of chloroquine-sensitive Plasmodium falciparum parasites and emergence of chloroquine-resistant Plasmodium vivax in Ethiopia

Mekonnen

Aseffa

Berhe

et al. 2014

Malar J

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BackgroundIncreased resistance by Plasmodium falciparum parasites led to the withdrawal of the antimalarial drugs chloroquine and sulphadoxine-pyrimethamine in Ethiopia. Since 2004 artemether-lumefantrine has served to treat uncomplicated P. falciparum malaria. However, increasing reports on delayed parasite clearance to artemisinin opens up a new challenge in anti-malarial therapy. With the complete withdrawal of CQ for the treatment of Plasmodium falciparum malaria, this study assessed the evolution of CQ resistance by investigating the prevalence of mutant alleles in the pfmdr1 and pfcrt genes in P. falciparum and pvmdr1 gene in Plasmodium vivax in Southern and Eastern Ethiopia.MethodsOf the 1,416 febrile patients attending primary health facilities in Southern Ethiopia, 329 febrile patients positive for P. falciparum or P. vivax were recruited. Similarly of the 1,304 febrile patients from Eastern Ethiopia, 81 febrile patients positive for P. falciparum or P. vivax were included in the study. Of the 410 finger prick blood samples collected from malaria patients, we used direct sequencing to investigate the prevalence of mutations in pfcrt and pfmdr1. This included determining the gene copy number in pfmdr1 in 195 P. falciparum clinical isolates, and mutations in the pvmdr1 locus in 215 P. vivax clinical isolates.ResultsThe pfcrt K76 CQ-sensitive allele was observed in 84.1% of the investigated P.falciparum clinical isolates. The pfcrt double mutations (K76T and C72S) were observed less than 3%. The pfcrt SVMNT haplotype was also found to be present in clinical isolates from Ethiopia. The pfcrt CVMNK-sensitive haplotypes were frequently observed (95.9%). The pfmdr1 mutation N86Y was observed only in 14.9% compared to 85.1% of the clinical isolates that carried sensitive alleles. Also, the sensitive pfmdr1 Y184 allele was more common, in 94.9% of clinical isolates. None of the investigated P. falciparum clinical isolates carried S1034C, N1042D and D1246Y pfmdr1 polymorphisms. All investigated P. falciparum clinical isolates from Southern and Eastern Ethiopia carried only a single copy of the mutant pfmdr1 gene.ConclusionThe study reports for the first time the return of chloroquine sensitive P. falciparum in Ethiopia. These findings support the rationale for the use of CQ-based combination drugs as a possible future alternative.

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Section: Discussioncontrasting

confidence: 99%

Section: Discussionmentioning

confidence: 99%

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Return of chloroquine-sensitive Plasmodium falciparum parasites and emergence of chloroquine-resistant Plasmodium vivax in Ethiopia

Mekonnen

Aseffa

Berhe

et al. 2014

Malar J

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“…Nevertheless, spread of insecticide-resistant vectors [19,20] and drug-resistant malaria parasites [21,22] may result in disease outbreaks. Therefore, control of larvae, which has so far been given little attention, should be reintroduced and implemented together with the existing strategy.…”

Section: Introductionmentioning

confidence: 99%

Abundance and dynamics of anopheline larvae in a highland malarious area of south-central Ethiopia

et al. 2012

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BackgroundMalaria is a public health problem in Ethiopia, and increasingly so in highland areas, possibly because of global warming. This study describes the distribution, breeding habitat and monthly dynamics of anopheline larvae in Butajira, a highland area in south-central Ethiopia.MethodsA study of the abundance and dynamics of Anopheles larvae was undertaken at different sites and altitudes in Butajira from July 2008 to June 2010. The sites included Hobe (1817 m.a.s.l), Dirama (1995m.a.s.l.) and Wurib (2196m.a.s.l.). Potential anopheline larval habitats were surveyed once per month in each village. The recorded characteristics of the habitats included habitat type, pH, surface debris, emergent plants, algae, substrate, turbidity, temperature, length, width, depth, distance to the nearest house and anophelines. The Spearman correlation coefficient and Mann–Whitney U test were used to calculate the degree of association between the density of anopheline species and key environmental factors.ResultsAmong the different types of habitat surveyed, the Odamo, Akamuja and Assas streams and Beko swamp were positive for anopheline larvae. A total of 3,957 third and fourth instar larvae were collected from the three localities, and they represented ten species of anophelines. These were: Anopheles cinereus (32.5%), An. arabiensis (31.4%), An. chrysti (23%), An. demeilloni (12.2%), An. pretoriensis (0.6%), An. azaniae (0.1%), An. rufipes(0.1%), An. sergentii (0.06%), An. garnhami (0.06%) and An. pharoensis (0.03%). The density of anopheline larvae was highest during the dry months. An. arabiensis was widely distributed, and its density decreased from the lowest elevation in Hobe to the highest in Wurib. The density of An. arabiensis larvae was correlated positively with larval habitat temperature (r = 0.33, p < 0.05) and negatively with depth of larval habitat (r = −0.56, p < 0.05).ConclusionTen species of anophelines were identified, including two known vectors of malaria (An. arabiensis and An. pharoensis), along streams in Butajira. Larvae of An. arabiensis were found in streams at 2200m.a.s.l. This possible expansion of the malaria vector to highland areas indicates an increasing risk of malaria because a large proportion of the Ethiopian population live above this altitude.

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“…Vivax malaria is an acute and painful disease that, unlike falciparum malaria, may relapse owing to a unique characteristic of the life cycles of P. vivax and P. ovale: the generation of dormant hypnozoites in the liver (Sattabongkot et al, 2004). Treatment for malaria includes sulfadoxinepyrimethamine, chloroquine, pyrimethamine and mefloquine, but drug resistance to these drugs is a growing concern and new drugs are urgently needed (Maguire et al, 2006;Schunk et al, 2006). To address this need, the Structural Genomics of Pathogenic Protozoans consortium (SGPP; http://www.sgpp.org) sought to determine protein structures from major tropical eukaryotic pathogens, including Plasmodium.…”

Section: Introductionmentioning

confidence: 99%

The structure ofPlasmodium vivaxphosphatidylethanolamine-binding protein suggests a functional motif containing a left-handed helix

et al. 2007

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PDB Reference: phosphatidylethanolaminebinding protein, 2gzq, r2gzqsf.The structure of a putative Raf kinase inhibitor protein (RKIP) homolog from the eukaryotic parasite Plasmodium vivax has been studied to a resolution of 1.3 Å using multiple-wavelength anomalous diffraction at the Se K edge. This protozoan protein is topologically similar to previously studied members of the phosphatidylethanolamine-binding protein (PEBP) sequence family, but exhibits a distinctive left-handed -helical region at one side of the canonical phospholipid-binding site. Re-examination of previously determined PEBP structures suggests that the P. vivax protein and yeast carboxypeptidase Y inhibitor may represent a structurally distinct subfamily of the diverse PEBPsequence family.

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High prevalence of drug-resistance mutations in Plasmodium falciparum and Plasmodium vivax in southern Ethiopia

Cited by 58 publications

References 22 publications

Return of chloroquine-sensitive Plasmodium falciparum parasites and emergence of chloroquine-resistant Plasmodium vivax in Ethiopia

Return of chloroquine-sensitive Plasmodium falciparum parasites and emergence of chloroquine-resistant Plasmodium vivax in Ethiopia

Abundance and dynamics of anopheline larvae in a highland malarious area of south-central Ethiopia

The structure ofPlasmodium vivaxphosphatidylethanolamine-binding protein suggests a functional motif containing a left-handed helix

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