Molecular markers of resistance to amodiaquine plus sulfadoxine–pyrimethamine in an area with seasonal malaria chemoprevention in south central Niger

Grais, Rebecca F.; Laminou, Ibrahim Maman; Woi-Messe, Lynda; Makarimi, Rockyath; Bouriema, Seidou H.; Langendorf, Céline; Amambua-Ngwa, Alfred; D’Alessandro, Umberto; Guérin, Philippe J; Fandeur, Thierry; Sibley, Carol H.

doi:10.1186/s12936-018-2242-4

Cited by 38 publications

(41 citation statements)

References 28 publications

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“…The frequency of quadruple mutants and quintuple mutants was still low (< 50% and < 5% respectively) after the fourth year of SMC implementation. Based on these results, SP maintains it's e cacy in SMC as shown by other authors (23)(24)(25)(26).…”

Section: Discussionsupporting

confidence: 78%

Impact of Seasonal Malaria Chemoprevention in Children 5 to 10 Years in Kita and Bafoulabe Districts, Mali.

Diawara¹,

Mihigo²,

Konaté³

et al. 2020

Preprint

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Background : Seasonal malaria chemoprevention (SMC) is the administration of complete therapeutic courses of antimalarial to all children 3–59 months old during the malaria transmission season. This study measured coverage, impact and cost of adding SMC in children aged 5-10 years. Methods : A non-randomized, pre-post design, with an intervention (Kita) and control (Bafoulabe) district implemented SMC for children 5-10 years old through the health system in 2017 and 2018. SMC implementation consisted of the administration of SP + AQ at monthly intervals in children 5-10 years in July, August, September and October annually. Baseline and endline household surveys were conducted in both districts. Separate surveys to measure adherence and tolerance to treatment occurred annually in the intervention district (200 households) following each of the four treatment rounds. Routine data on malaria cases tested and treated and information on SMC campaign and treatment costs were collected. Results : A total of 310 and 323 children 5 to 10 years were included in Kita and Bafoulabe respectively in the baseline survey in July 2017, plasmodium infection prevalence was comparable in the two districts (p=0.07): 27.7% in the intervention district (Kita) against 21.7% in the comparison district (Bafoulabé). Mild anemia was found in 14.2% of children in Kita vs 10.5% in Bafoulabé. Household survey found 89.1% of SMC coverage rate, child’s mothers were interviewed with 93.3% during the SMC campaign in Kita. The most side effect reported by parents was vomiting with 9.3%. One year after SMC implementation in 5 to 10 years in Kita, three doses coverage was 81.2%, there was a reduction by 40% (OR=0.60, CI:0.41-0.89) of malaria parasite carriage; 21% and 62% reduction of simple malaria and severe malaria prevalence respectively in the pilot district vs control. Mild anemia and severe anemia were comparable in the two districts. The level of malaria molecular resistance rate remains below the threshold. Quintuple mutation (dhfr triple +dhps437+dhps540) remained <5% after intervention in both districts.Conclusion: The SMC strategy contributed to malaria prevention in 5-10 year old children and should be integrated to SMC for children 3-59 months. Keywords : Malaria, Seasonal Malaria Chemoprevention, Sulfadoxine-Pyriméthamine, Amodiaquine, Anemia.

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Section: Discussionsupporting

confidence: 78%

Impact of Seasonal Malaria Chemoprevention in Children 5 to 10 Years in Kita and Bafoulabe Districts, Mali.

Diawara¹,

Mihigo²,

Konaté³

et al. 2020

Preprint

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“…5 Programme National de Lutte contre le Paludisme (PNLP) South Kivu, Bukavu, Democratic Republic of Congo. 6 MSF, North Kivu, Goma, Democratic Republic of Congo. 7 MSF, Bukavu, Democratic Republic of Congo.…”

Section: Acknowledgementsmentioning

confidence: 99%

“…Intermittent preventive treatment of malaria in pregnancy (IPTp) and intermittent preventive therapy for infants (IPTi) use SP alone, while seasonal malaria chemoprophylaxis (SMC) combines SP with amodiaquine. The efficacy of SP for these interventions is influenced by drug resistance levels in parasite populations [4] and the drug resistance levels are influenced by the use of SP in target populations [5,6].…”

Section: Introductionmentioning

confidence: 99%

Markers of sulfadoxine–pyrimethamine resistance in Eastern Democratic Republic of Congo; implications for malaria chemoprevention

Lenthe

Meulen

Lassovski³

et al. 2019

Malar J

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Background: Sulfadoxine-pyrimethamine (SP) is a cornerstone of malaria chemoprophylaxis and is considered for programmes in the Democratic Republic of Congo (DRC). However, SP efficacy is threatened by drug resistance, that is conferred by mutations in the dhfr and dhps genes. The World Health Organization has specified that intermittent preventive treatment for infants (IPTi) with SP should be implemented only if the prevalence of the dhps K540E mutation is under 50%. There are limited current data on the prevalence of resistance-conferring mutations available from Eastern DRC. The current study aimed to address this knowledge gap. Methods: Dried blood-spot samples were collected from clinically suspected malaria patients [outpatient department (OPD)] and pregnant women attending antenatal care (ANC) in four sites in North and South Kivu, DRC. Quantitative PCR (qPCR) was performed on samples from individuals with positive and with negative rapid diagnostic test (RDT) results. Dhps K450E and A581G and dhfr I164L were assessed by nested PCR followed by allele-specific primer extension and detection by multiplex bead-based assays. Results: Across populations, Plasmodium falciparum parasite prevalence was 47.9% (1160/2421) by RDT and 71.7 (1763/2421) by qPCR. Median parasite density measured by qPCR in RDT-negative qPCR-positive samples was very low with a median of 2.3 parasites/µL (IQR 0.5-25.2). Resistance genotyping was successfully performed in RDT-positive samples and RDT-negative/qPCR-positive samples with success rates of 86.2% (937/1086) and 55.5% (361/651), respectively. The presence of dhps K540E was high across sites (50.3-87.9%), with strong evidence for differences between sites (p < 0.001). Dhps A581G mutants were less prevalent (12.7-47.2%). The dhfr I164L mutation was found in one sample. Conclusions: The prevalence of the SP resistance marker dhps K540E exceeds 50% in all four study sites in North and South Kivu, DRC. K540E mutations regularly co-occurred with mutations in dhps A581G but not with the dhfr I164L mutation. The current results do not support implementation of IPTi with SP in the study area.

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“…Eighty per cent of global malaria deaths happened in 14 sub-Saharan African countries and India. 2 This mortality in sub-Saharan Africa is aggravated by the high proportion of deaths in under 5 years age groups (approximately 90% malariarelated deaths), more than any other malaria-endemic region. 2 In general, pregnant women and children under the age of 5 years are the most vulnerable due to depressed immunity or the absence of partial immunity against the disease.…”

Section: Introductionmentioning

confidence: 99%

<p>Trends in Molecular Markers Associated with Resistance to Sulfadoxine-Pyrimethamine (SP) Among <em>Plasmodium falciparum</em> Isolates on Bioko Island, Equatorial Guinea: 2011–2017</p>

Lin¹,

Li²,

Huang

et al. 2020

IDR

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Antimalarial drug resistance is one of the major challenges in global efforts to control and eliminate malaria. In 2006, sulfadoxine-pyrimethamine (SP) replaced with artemisinin-based combination therapy (ACT) on Bioko Island, Equatorial Guinea, in response to increasing SP resistance, which is associated with mutations in the dihydrofolate reductase (Pfdhfr) and dihydropteroate synthase (Pfdhps) genes. Patients and Methods: To evaluate the trend of molecular markers associated with SP resistance on Bioko Island from 2011 to 2017, 179 samples collected during active case detection were analysed by PCR and DNA sequencing. Results: Pfdhfr and Pfdhps gene sequences were obtained for 90.5% (162/179) and 77.1% (138/179) of the samples, respectively. For Pfdhfr, 97.5% (158/162), 95.7% (155/162) and 98.1% (159/162) of the samples contained N51I, C59R and S108N mutant alleles, respectively. And Pfdhps S436A, A437G, K540E, A581G, and A613S mutations were observed in 25.4% (35/138), 88.4% (122/138), 5.1% (7/138), 1.4% (2/138), and 7.2% (10/138) of the samples, respectively. Two classes of previously described Pfdhfr-Pfdhps haplotypes associated with SP resistance and their frequencies were identified: partial (IRNI-SGKAA, 59.4%) and full (IRNI-SGEAA, 5.5%) resistance. Although no significant difference was observed in different time periods (p>0.05), our study confirmed a slowly increasing trend of the frequencies of these SP-resistance markers in Bioko parasites over the 7 years investigated. Conclusion: The findings reveal the general existence of SP-resistance markers on Bioko Island even after the replacement of SP as a first-line treatment for uncomplicated malaria. Continuous molecular monitoring and additional control efforts in the region are urgently needed.

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Molecular markers of resistance to amodiaquine plus sulfadoxine–pyrimethamine in an area with seasonal malaria chemoprevention in south central Niger

Cited by 38 publications

References 28 publications

Impact of Seasonal Malaria Chemoprevention in Children 5 to 10 Years in Kita and Bafoulabe Districts, Mali.

Impact of Seasonal Malaria Chemoprevention in Children 5 to 10 Years in Kita and Bafoulabe Districts, Mali.

Markers of sulfadoxine–pyrimethamine resistance in Eastern Democratic Republic of Congo; implications for malaria chemoprevention

<p>Trends in Molecular Markers Associated with Resistance to Sulfadoxine-Pyrimethamine (SP) Among <em>Plasmodium falciparum</em> Isolates on Bioko Island, Equatorial Guinea: 2011–2017</p>

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