Large differences in prevalence of Pfcrt and Pfmdr1 mutations between Mwanza, Tanzania and Iganga, Uganda—A reflection of differences in policies regarding withdrawal of chloroquine?

Kamugisha, Erasmus; Bujila, Ioana; Lahdo, Mona; Pello-Esso, Samtou; Minde, Mercy; Kongola, Gilbert; Naiwumbwe, Halima; Kiwuwa, Steven M.; Kaddumukasa, Mark; Kironde, Fred; Swedberg, Göte

doi:10.1016/j.actatropica.2011.11.004

Cited by 28 publications

(22 citation statements)

References 16 publications

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“…For example, in Burkina Faso the drug resistance frequency was between 29.6% and 46.0% with CYP2C8*2 allele frequency between 9.9% and 24.2%, according to ethnicity . In Uganda, the overall frequency of CYP2C8*2 was 10.5%, but the overall frequency of pfmdr1 86Y was much higher (81.2%), similarly to that of Zanzibar (Cavaco et al, 2013) and in line with other studies from Uganda (Kamugisha et al, 2012).…”

Section: Resultssupporting

confidence: 77%

Absence of the human CYP2C8*3 allele in Ugandan children exposed to Plasmodium falciparum malaria

Paganotti

Cosentino

Russo

et al. 2014

Infection, Genetics and Evolution

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Section: Resultssupporting

confidence: 77%

Absence of the human CYP2C8*3 allele in Ugandan children exposed to Plasmodium falciparum malaria

Paganotti

Cosentino

Russo

et al. 2014

Infection, Genetics and Evolution

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“…A gradual decrease in the prevalence of CQR haplotypes has also been observed in China and Kenya (33,45). Although the antimalarial activity of CQ would likely still be poor in our study area (as the prevalence of pfcrt codons 72 to 76 [CVIET] is close to 64%), reintroduction of CQ as a partner drug in ACTs or in intermittent presumptive treatment for adults (IPTa) may become possible in Angola should the CVMNK haplotype become predominant, as occurred in Malawi (22,24,26). Nevertheless, we should be aware that the decline in rates of CQR mutations depends on geographic, epidemiologic, and parasite genetic factors (26,38).…”

Section: Discussionmentioning

confidence: 99%

Various pfcrt and pfmdr1 Genotypes of Plasmodium falciparum Cocirculate with P. malariae, P. ovale spp., and P. vivax in Northern Angola

Fançony

Gamboa

Sebastião

et al. 2012

Antimicrob Agents Chemother

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dArtemisinin-based combination therapy for malaria has become widely available across Africa. Populations of Plasmodium falciparum that were previously dominated by chloroquine (CQ)-resistant genotypes are now under different drug selection pressures. P. malariae, P. ovale curtisi, and P. ovale wallikeri are sympatric with P. falciparum across the continent and are frequently present as coinfections. The prevalence of human Plasmodium species was determined by PCR using DNA from blood spots collected during a cross-sectional survey in northern Angola. P. falciparum was genotyped at resistance-associated loci in pfcrt and pfmdr1 by real-time PCR or by direct sequencing of amplicons. Of the 3,316 samples collected, 541 (16.3%) contained Plasmodium species infections; 477 (88.2%) of these were P. falciparum alone, 6.5% were P. falciparum and P. malariae together, and 1.1% were P. vivax alone. The majority of the remainder (3.7%) harbored P. ovale curtisi or P. ovale wallikeri alone or in combination with other species. Of 430 P. falciparum isolates genotyped for pfcrt, 61.6% carried the wild-type allele CVMNK at codons 72 to 76, either alone or in combination with the resistant allele CVIET. No other pfcrt allele was found. Wildtype alleles dominated at codons 86, 184, 1034, 1042, and 1246 of the pfmdr1 locus among the sequenced isolates. In contrast to previous studies, P. falciparum in the study area comprises an approximately equal mix of genotypes associated with CQ sensitivity and with CQ resistance, suggesting either lower drug pressure due to poor access to treatment in rural areas or a rapid impact of the policy change away from the use of standard monotherapies.

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“…16 However, recent studies in 2009-2010 in Mwanza, Tanzania, and Iganga, Uganda found a striking difference of 59.5% and 0% in the prevalence of Pfcrt CVMNK wild types, respectively. 36 Thus, the re-emergence of CQ susceptibility appears to evolve at different rates probably because of co-varying factors such as treatments given (also dependent on differences in diagnostic practices and transmission intensity) and the continued use of CQ and/or related drugs maintaining the drug pressure on Pfcrt, e.g., amodiaquine. In adition, the ACT drug combination AL has been shown to select for Pfcrt wild types.…”

Section: Resultsmentioning

confidence: 99%

Rapid Selection of Plasmodium falciparum Chloroquine Resistance Transporter Gene and Multidrug Resistance Gene-1 Haplotypes Associated with Past Chloroquine and Present Artemether-Lumefantrine Use in Inhambane District, Southern Mozambique

Thomsen¹,

Madsen²,

Hansson³

et al. 2013

The American Society of Tropical Medicine and Hygiene

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Abstract. Chloroquine (CQ) use in Mozambique was stopped in 2002 and artemether-lumefantrine (AL) was implemented in 2008. In light of no use of CQ and extensive use of AL, we determined the frequency of molecular markers of Plasmodium falciparum drug resistance/tolerance to CQ and AL in persons living in Linga-Linga, an isolated peninsula and in Furvela village, which is located 8 km inland. The P. falciparum chloroquine resistance transporter gene CVMNK wild type increased in frequency from 43.9% in 2009 to 66.4% in 2010 (P 0.001), and combined P. falciparum multidrug resistance gene 1 N86-184F-D1246 haplotype increased significantly between years (P = 0.039). The combination of P. falciparum chloroquine resistance transporter gene CVMNK and P. falciparum multidrug resistance gene NFD increased from 24.3% (2009) to 45.3% in (2010, P = 0.017). The rapid changes observed may largely be caused by decreased use of CQ and large-scale use of AL. In the absence of a clear AL-resistance marker and the (almost) continent-wide use of AL in sub-Saharan Africa, and when considering CQ reintroduction, continued monitoring of these markers is needed.

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Large differences in prevalence of Pfcrt and Pfmdr1 mutations between Mwanza, Tanzania and Iganga, Uganda—A reflection of differences in policies regarding withdrawal of chloroquine?

Cited by 28 publications

References 16 publications

Absence of the human CYP2C8*3 allele in Ugandan children exposed to Plasmodium falciparum malaria

Absence of the human CYP2C8*3 allele in Ugandan children exposed to Plasmodium falciparum malaria

Various pfcrt and pfmdr1 Genotypes of Plasmodium falciparum Cocirculate with P. malariae, P. ovale spp., and P. vivax in Northern Angola

Rapid Selection of Plasmodium falciparum Chloroquine Resistance Transporter Gene and Multidrug Resistance Gene-1 Haplotypes Associated with Past Chloroquine and Present Artemether-Lumefantrine Use in Inhambane District, Southern Mozambique

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