Towards a re-emergence of chloroquine sensitivity in Côte d’Ivoire?

Dagnogo, Olefongo; Ako, Aristide Berenger; Ouattara, Lacinan; Dago, Noel Dougba; Coulibaly, David N’golo; Touré, Abdoulaye; Djaman, Joseph Allico

doi:10.1186/s12936-018-2551-7

Cited by 21 publications

(21 citation statements)

References 28 publications

(28 reference statements)

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“…This may be a result of the withdrawal of chloroquine and the introduction of ACT in 2006 in Kenya, which may have promoted the re-emergence of chloroquine-sensitive isolates. This is consistent with other studies conducted in Kenya [ 49 , 58 ], Malawi [ 59 ], Côte d’Ivoire [ 60 ], and Tanzania [ 8 ], which have reported re-emergence of chloroquine-susceptible parasites following years of discontinuation of chloroquine use. A small proportion of parasites (< 5%) contained a mixed (N75 D ) or mutated (75 E ) nucleotide at codon 75, yielding haplotypes CV IDT , CVM DT , and CV IET .…”

Section: Discussionsupporting

confidence: 92%

Assessment of molecular markers of anti-malarial drug resistance among children participating in a therapeutic efficacy study in western Kenya

Chebore

Zhou

Westercamp

et al. 2020

Malar J

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Background: Anti-malarial drug resistance remains a major threat to global malaria control efforts. In Africa, Plasmodium falciparum remains susceptible to artemisinin-based combination therapy (ACT), but the emergence of resistant parasites in multiple countries in Southeast Asia and concerns over emergence and/or spread of resistant parasites in Africa warrants continuous monitoring. The World Health Organization recommends that surveillance for molecular markers of resistance be included within therapeutic efficacy studies (TES). The current study assessed molecular markers associated with resistance to Artemether−lumefantrine (AL) and Dihydroartemisinin−piperaquine (DP) from samples collected from children aged 6-59 months enrolled in a TES conducted in Siaya County, western Kenya from 2016 to 2017. Methods: Three hundred and twenty-three samples collected pre-treatment (day-0) and 110 samples collected at the day of recurrent parasitaemia (up to day 42) were tested for the presence of drug resistance markers in the Pfk13 propeller domain, and the Pfmdr1 and Pfcrt genes by Sanger sequencing. Additionally, the Pfpm2 gene copy number was assessed by real-time polymerase chain reaction. Results: No mutations previously associated with artemisinin resistance were detected in the Pfk13 propeller region. However, other non-synonymous mutations in the Pfk13 propeller region were detected. The most common mutation found on day-0 and at day of recurrence in the Pfmdr1 multidrug resistance marker was at codon 184F. Very few mutations were found in the Pfcrt marker (< 5%). Within the DP arm, all recrudescent cases (8 sample pairs) that were tested for Pfpm2 gene copy number had a single gene copy. None of the associations between observed mutations and treatment outcomes were statistically significant. Conclusion: The results indicate absence of Pfk13 mutations associated with parasite resistance to artemisinin in this area and a very high proportion of wild-type parasites for Pfcrt. Although the frequency of Pfmdr1 184F mutations was high in these samples, the association with treatment failure did not reach statistical significance. As the spread of

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Section: Discussionsupporting

confidence: 92%

Assessment of molecular markers of anti-malarial drug resistance among children participating in a therapeutic efficacy study in western Kenya

Chebore

Zhou

Westercamp

et al. 2020

Malar J

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“…The most common quintuple haplotypes identified in Pfcrt gene were CVMNK and CVIET. This concords with previously published studies in other regions [ 101 , 102 ]. It is important to note that one study reported the presence of Pfcrt SVMNT haplotype with a prevalence of 4.4% [ 59 ], which is lower than the 19.0% [ 15 ] and 56.9% [ 14 ] reported in the Korogwe District, Tanzania and Luanda, Angola, respectively.…”

Section: Discussionsupporting

confidence: 90%

Drug resistance markers within an evolving efficacy of anti-malarial drugs in Cameroon: a systematic review and meta-analysis (1998–2020)

Niba

Nji

Evehe

et al. 2021

Malar J

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Background Malaria remains highly endemic in Cameroon. The rapid emergence and spread of drug resistance was responsible for the change from monotherapies to artemisinin-based combinations. This systematic review and meta-analysis aimed to determine the prevalence and distribution of Plasmodium falciparum drug resistance markers within an evolving efficacy of anti-malarial drugs in Cameroon from January 1998 to August 2020. Methods The PRISMA-P and PRISMA statements were adopted in the inclusion of studies on single nucleotide polymorphisms (SNPs) of P. falciparum anti-malarial drug resistance genes (Pfcrt, Pfmdr1, Pfdhfr, Pfdhps, Pfatp6, Pfcytb and Pfk13). The heterogeneity of the included studies was evaluated using the Cochran’s Q and I2 statistics. The random effects model was used as standard in the determination of heterogeneity between studies. Results Out of the 902 records screened, 48 studies were included in this aggregated meta-analysis of molecular data. A total of 18,706 SNPs of the anti-malarial drug resistance genes were genotyped from 47,382 samples which yielded a pooled prevalence of 35.4% (95% CI 29.1–42.3%). Between 1998 and 2020, there was significant decline (P < 0.0001 for all) in key mutants including Pfcrt 76 T (79.9%-43.0%), Pfmdr1 86Y (82.7%-30.5%), Pfdhfr 51I (72.2%-66.9%), Pfdhfr 59R (76.5%-67.8%), Pfdhfr 108 N (80.8%-67.6%). The only exception was Pfdhps 437G which increased over time (30.4%-46.9%, P < 0.0001) and Pfdhps 540E that remained largely unchanged (0.0%-0.4%, P = 0.201). Exploring mutant haplotypes, the study observed a significant increase in the prevalence of Pfcrt CVIET mixed quintuple haplotype from 57.1% in 1998 to 57.9% in 2020 (P < 0.0001). In addition, within the same study period, there was no significant change in the triple Pfdhfr IRN mutant haplotype (66.2% to 67.3%, P = 0.427). The Pfk13 amino acid polymorphisms associated with artemisinin resistance were not detected. Conclusions This review reported an overall decline in the prevalence of P. falciparum gene mutations conferring resistance to 4-aminoquinolines and amino alcohols for a period over two decades. Resistance to artemisinins measured by the presence of SNPs in the Pfk13 gene does not seem to be a problem in Cameroon. Systematic review registration PROSPERO CRD42020162620

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“…Similar findings associating resistance markers with CQ use have been reported elsewhere: persisting high levels of mutant Pfcrt haplotypes in infections from Brazil and, in contrast, the reappearance of wild type forms in Nigeria have been attributed to differences in the selective pressure by CQ use (Gbotosho et al, 2012). Moreover, the slow reappearance of CQ sensitive parasites harboring Pfcrt -K76 haplotype in low P. vivax prevalence areas of Gambella and Benishangul-Gumuz corroborates observations from other African countries such as Malawi (Kublin et al, 2003), Côte d’Ivoire (Dagnogo et al, 2018), Zambia (Mwanza et al, 2016),Tanzania (Mohammed et al, 2013) and Kenya (Achieng et al, 2015).…”

Section: Discussionsupporting

confidence: 83%

Prevalence of Plasmodium falciparum Pfcrt and Pfmdr1 alleles in settings with different levels of Plasmodium vivax co-endemicity in Ethiopia

Hailemeskel

Menberu

Shumie

et al. 2019

International Journal for Parasitology: Drugs and Drug Resistan

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Plasmodium falciparum and P. vivax co-exist at different endemicity levels across Ethiopia. For over two decades Artemether-Lumefantrine (AL) is the first line treatment for uncomplicated P. falciparum, while chloroquine (CQ) is still used to treat P. vivax. It is currently unclear whether a shift from CQ to AL for P. falciparum treatment has implications for AL efficacy and results in a reversal of mutations in genes associated to CQ resistance, given the high co-endemicity of the two species and the continued availability of CQ for the treatment of P. vivax. This study thus assessed the prevalence of Pfcrt-K76T and Pfmdr1-N86Y point mutations in P. falciparum. 18S RNA gene based nested PCR confirmed P. falciparum samples (N = 183) collected through community and health facility targeted cross-sectional surveys from settings with varying P. vivax and P. falciparum endemicity were used. The proportion of Plasmodium infections that were P. vivax was 62.2% in Adama, 41.4% in Babile, 30.0% in Benishangul-Gumuz to 6.9% in Gambella. The Pfcrt-76T mutant haplotype was observed more from samples with higher endemicity of P. vivax as being 98.4% (61/62), 100% (31/31), 65.2% (15/23) and 41.5% (22/53) in samples from Adama, Babile, Benishangul-Gumuz and Gambella, respectively. However, a relatively higher proportion of Pfmdr1-N86 allele (77.3–100%) were maintained in all sites. The observed high level of the mutant Pfcrt-76T allele in P. vivax co-endemic sites might require that utilization of CQ needs to be re-evaluated in settings co-endemic for the two species. A country-wide assessment is recommended to clarify the implication of the observed level of variation in drug resistance markers on the efficacy of AL-based treatment against uncomplicated P. falciparum malaria.

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Towards a re-emergence of chloroquine sensitivity in Côte d’Ivoire?

Cited by 21 publications

References 28 publications

Assessment of molecular markers of anti-malarial drug resistance among children participating in a therapeutic efficacy study in western Kenya

Assessment of molecular markers of anti-malarial drug resistance among children participating in a therapeutic efficacy study in western Kenya

Drug resistance markers within an evolving efficacy of anti-malarial drugs in Cameroon: a systematic review and meta-analysis (1998–2020)

Prevalence of Plasmodium falciparum Pfcrt and Pfmdr1 alleles in settings with different levels of Plasmodium vivax co-endemicity in Ethiopia

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