Prevalence of Plasmodium falciparum haplotypes associated with resistance to sulfadoxine–pyrimethamine and amodiaquine before and after upscaling of seasonal malaria chemoprevention in seven African countries: a genomic surveillance study

Beshir, Khalid B.; Muwanguzi, Julian; Nader, Johanna; Mansukhani, Raoul; Traoré, Aliou; Gamougam, Kadidja; Ceesay, Sainey; Bazié, Thomas; Kolie, Fassou; Lamine, Mahaman Moustapha; Cairns, Matt; Snell, Paul; Scott, Susana; Diallo, Abdoulaye; Merle, Corinne; Ndiaye, Jean Louis; Razafindralambo, Lanto; Moroso, Diego; Ouédraogo, Jean‐Bosco; Zongo, Issaka; Kessely, Hamit; Doumagoum, Daugla; Bojang, Kalifa; Ceesay, Serign J.; Loua, Kovana Marcel; Maiga, Hamma; Dicko, Alassane; Sagara, Issaka; Laminou, Ibrahim Maman; Ogboi, Sonny Johnbull; Eloike, Tony; Milligan, Paul; Sutherland, Colin J.

doi:10.1016/s1473-3099(22)00593-x

Cited by 29 publications

(23 citation statements)

References 30 publications

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“…A recent ACCESS-SMC study in samples collected in 2016 in Sokoto State in Nigeria found no dhps -540E but 2 years after implementation of SMC the prevalence was found to be 0.23%. 9 The study sequenced more than 5000 samples in the Sahel and sub-Sahel regions of Africa with seasonal transmission, and found only two samples harbouring parasites predicted to encode full resistance to SMC (SP/amodiaquine). Similarly, dhps- 540E was also previously reported in Ibadan (0.5%) and Lagos (Kosofe) (1.2%), though the sample size in Ibadan was small.…”

Section: Discussionmentioning

confidence: 99%

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Baseline prevalence of molecular marker of sulfadoxine/pyrimethamine resistance in Ebonyi and Osun states, Nigeria: amplicon deep sequencing ofdhps-540

Olukosi

Ajibaye

Omoniwa

et al. 2023

Journal of Antimicrobial Chemotherapy

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Background Chemoprevention plays an important role in malaria control strategy. Perennial malaria chemoprevention (PMC) using sulfadoxine/pyrimethamine (SP) is a WHO-approved strategy to combat malaria in young children and may lead to drug pressure. Introducing SP-PMC may therefore be compromised due to the emergence of Plasmodium falciparum resistant to SP, particularly mutation at K540E of the dihydropteroate synthase (dhps) gene. Molecular surveillance of resistance markers can support assessment of antimalarial efficacy and effectiveness. High prevalence of 540E is associated with reduced effectiveness of SP, and areas with more than 50% prevalence are considered unsuitable for intermittent preventative treatment in pregnancy (IPTp) implementation. Assessing 540E prevalence is an important undertaking before implementation of SP-PMC. Methods We conducted a rapid surveillance of dhps-540E to assess the suitability of SP as PMC in field studies from Ebonyi and Osun states in Nigeria. We used an in-house developed amplicon deep-sequencing method targeting part of the dhps gene. Results Our data reveal that 18.56% of individuals evaluated carried the 540E mutation mixed with the WT K540. Mutant variant 540E alone was not found, and 80% of isolates harboured only WT (K540). Clonal analysis of the sequencing data shows a very low proportion of 540E circulating in both states. Conclusions Our data show that both states are suitable for SP-PMC implementation and, based on this finding, SP-PMC was implemented in Osun in 2022. Continuous monitoring of 540E will be required to ensure the chemoprevention effectiveness of SP in Nigeria.

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Section: Discussionmentioning

confidence: 99%

“… 7 There is paucity of data on the frequency and prevalence of genotypes associated with SP resistance in Nigeria, although recent evidence suggests the emergence of new variants in some areas. 9 , 10 …”

Section: Introductionmentioning

confidence: 99%

Baseline prevalence of molecular marker of sulfadoxine/pyrimethamine resistance in Ebonyi and Osun states, Nigeria: amplicon deep sequencing ofdhps-540

Olukosi

Ajibaye

Omoniwa

et al. 2023

Journal of Antimicrobial Chemotherapy

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“…By not including resistance explicitly and using efficacy data from the first decade in 2000 to calibrate PMC’s effect size, the predicted impact of PMC might be overestimated. However, the relationship between chemoprevention use and resistance is complex [ 60 ], and continued monitoring will be crucial during and after the implementation of PMC, as is being done for SMC [ 61 ].…”

Section: Discussionmentioning

confidence: 99%

Perennial malaria chemoprevention with and without malaria vaccination to reduce malaria burden in young children: a modelling analysis

Runge

Stahlfeld

Ambrose

et al. 2023

Malar J

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Background A recent WHO recommendation for perennial malaria chemoprevention (PMC) encourages countries to adapt dose timing and number to local conditions. However, knowledge gaps on the epidemiological impact of PMC and possible combination with the malaria vaccine RTS,S hinder informed policy decisions in countries where malaria burden in young children remains high. Methods The EMOD malaria model was used to predict the impact of PMC with and without RTS,S on clinical and severe malaria cases in children under the age of two years (U2). PMC and RTS,S effect sizes were fit to trial data. PMC was simulated with three to seven doses (PMC-3-7) before the age of eighteen months and RTS,S with three doses, shown to be effective at nine months. Simulations were run for transmission intensities of one to 128 infectious bites per person per year, corresponding to incidences of < 1 to 5500 cases per 1000 population U2. Intervention coverage was either set to 80% or based on 2018 household survey data for Southern Nigeria as a sample use case. The protective efficacy (PE) for clinical and severe cases in children U2 was calculated in comparison to no PMC and no RTS,S. Results The projected impact of PMC or RTS,S was greater at moderate to high transmission than at low or very high transmission. Across the simulated transmission levels, PE estimates of PMC-3 at 80% coverage ranged from 5.7 to 8.8% for clinical, and from 6.1 to 13.6% for severe malaria (PE of RTS,S 10–32% and 24.6–27.5% for clinical and severe malaria, respectively. In children U2, PMC with seven doses nearly averted as many cases as RTS,S, while the combination of both was more impactful than either intervention alone. When operational coverage, as seen in Southern Nigeria, increased to a hypothetical target of 80%, cases were reduced beyond the relative increase in coverage. Conclusions PMC can substantially reduce clinical and severe cases in the first two years of life in areas with high malaria burden and perennial transmission. A better understanding of the malaria risk profile by age in early childhood and on feasible coverage by age, is needed for selecting an appropriate PMC schedule in a given setting.

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“…An additional mutation within pfdhps at A581G defines the sextuple mutant (IRN ISGEGA), which has been associated with decreased efficacy of IPTp-SP, resulting in low infant birth weight and increased placental inflammation ( 12 – 14 ). Additionally, a recent large study in seven West African countries implementing seasonal malaria chemoprophylaxis with SP plus amodiaquine showed strong evidence of selection of the VAGKGS pfdhps haplotype, characterized by the rare I431V mutation, during the study period ( 15 ), although its exact effect on parasite susceptibility to SP is still unknown.…”

Section: Introductionmentioning

confidence: 99%

Molecular Markers of Sulfadoxine-Pyrimethamine Resistance in Samples from Children with Uncomplicated Plasmodium falciparum at Three Sites in Angola in 2019

Rosillo

Dimbu

Cândido

et al. 2023

Antimicrob Agents Chemother

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Sulfadoxine-pyrimethamine (SP) is used for prevention of malaria in pregnant women in Angola. We sequenced the Plasmodium falciparum dihydrofolate reductase ( pfdhfr ) and dihydropteroate synthase ( pfdhps ) genes, implicated in SP resistance, in samples collected during a 2019 study of artemisinin-based combination therapy efficacy in Benguela, Lunda Sul, and Zaire provinces.

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Prevalence of Plasmodium falciparum haplotypes associated with resistance to sulfadoxine–pyrimethamine and amodiaquine before and after upscaling of seasonal malaria chemoprevention in seven African countries: a genomic surveillance study

Cited by 29 publications

References 30 publications

Baseline prevalence of molecular marker of sulfadoxine/pyrimethamine resistance in Ebonyi and Osun states, Nigeria: amplicon deep sequencing ofdhps-540

Baseline prevalence of molecular marker of sulfadoxine/pyrimethamine resistance in Ebonyi and Osun states, Nigeria: amplicon deep sequencing ofdhps-540

Perennial malaria chemoprevention with and without malaria vaccination to reduce malaria burden in young children: a modelling analysis

Molecular Markers of Sulfadoxine-Pyrimethamine Resistance in Samples from Children with Uncomplicated Plasmodium falciparum at Three Sites in Angola in 2019

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