Plasmodium falciparum Genetic Diversity in Continental Equatorial Guinea before and after Introduction of Artemisinin-Based Combination Therapy

Guerra, Mónica; Neres, Rita; Salgueiro, Patrícia; Mendes, Cristina; Ndong-Mabale, Nicolás; Berzosa, Pedro; Sousa, Bruno de; Arez, Ana Paula

doi:10.1128/aac.02556-15

Cited by 17 publications

(21 citation statements)

References 82 publications

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“…Additional studies comparing the genetic diversity in K13PD before and after the introduction of ACTs in Africa have generally been consistent with our findings from Uganda, with no significant difference in the proportion of parasites with a NS-SNP before and after the introduction of ACTs (35)(36)(37)(38). However, a report from Kenya described a significant decrease, and one from Comoros described an increase in K13PD polymorphisms following the introduction ACTs (39,40).…”

Section: Discussionsupporting

confidence: 89%

The Diversity of the Plasmodium falciparum K13 Propeller Domain Did Not Increase after Implementation of Artemisinin-Based Combination Therapy in Uganda

Conrad

Nsobya

Rosenthal

2019

Antimicrob Agents Chemother

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Artemisinin-based combination therapies (ACTs) are the standard of care to treat uncomplicated falciparum malaria. However, resistance to artemisinins, defined as delayed parasite clearance after therapy, has emerged in Southeast Asia, and the spread of resistance to sub-Saharan Africa could have devastating consequences. Artemisinin resistance has been associated in Southeast Asia with multiple nonsynonymous single nucleotide polymorphisms (NS-SNPs) in the propeller domain of the gene encoding the Plasmodium falciparum K13 protein (K13PD). Some K13PD NS-SNPs have been seen in Africa, but the relevance of these mutations is unclear. To assess whether ACT use has selected for specific K13PD mutations, we compared the K13PD genetic diversity in clinical isolates collected before and after the implementation of ACT use from seven sites across Uganda. We detected K13PD NS-SNPs in 16 of 683 (2.3%) clinical isolates collected between 1999 and 2004 and in 26 of 716 (3.6%) isolates collected between 2012 and 2016 (P = 0.16), representing a total of 29 different polymorphisms at 27 codons. Individual NS-SNPs were usually detected only once, and none were found in more than 0.7% of the isolates. Three SNPs (C469F, P574L, and A675V) associated with delayed clearance in Southeast Asia were seen in samples collected between 2012 and 2016, each in a single isolate. No differences in diversity following implementation of ACT use were found at any of the seven sites, nor was there evidence of selective pressures acting on the locus. Our results suggest that selection by ACTs is not impacting on K13PD diversity in Uganda.

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Section: Discussionsupporting

confidence: 89%

The Diversity of the Plasmodium falciparum K13 Propeller Domain Did Not Increase after Implementation of Artemisinin-Based Combination Therapy in Uganda

Conrad

Nsobya

Rosenthal

2019

Antimicrob Agents Chemother

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“…Plasmodium falciparum asexual parasitaemia was classified according to the following criteria: low (< 800 parasites/μl), moderate (800–8000 parasites/μl), and high (≥ 8000 parasites/μl) similarly to what have done in Guerra et al [ 4 ].…”

Section: Methodsmentioning

confidence: 99%

“…Associated risk factors of malaria at the microeconomic level were analysed in the context of a study which integrated analysis of malaria prevalence, molecular characterization of Plasmodium populations (anti-malarial resistance-associated mutations) and characterization of malaria risk determinants in two rural villages, Ngonamanga and Miyobo, of mainland Equatorial Guinea. Previous analysis hinted differences between the two villages, regarding frequency of anti-malarial resistance associated mutations and Plasmodium falciparum diversity associated to different socioeconomic characteristics, populations migration and different accessibilities to anti-malarial treatment [ 4 ]. In the present report, the association of socioeconomic status of families/households with local malaria burden was evaluated.…”

Section: Introductionmentioning

confidence: 99%

“…Sampling took place in two villages of mainland Equatorial Guinea, Ngonamanga and Miyobo (red stars). Ngonamanga (Litoral province, N 02°09′34,5″; E 009°47′54,4″) is a coastland village, isolated from the main trade routes, having an older population, whereas Miyobo (Centro Sur province, N 01°44′56,40″; E 10°10′40,05″) is a village in the interior, but closer to a developing city Niefang and nearby a main road, having a younger population [ 4 ] …”

Section: Introductionmentioning

confidence: 99%

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Malaria determining risk factors at the household level in two rural villages of mainland Equatorial Guinea

Guerra

Sousa

Ndong-Mabale

et al. 2018

Malar J

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BackgroundAfter the introduction of an artemisinin-based combination therapy, the reduction of prevalence of malaria infections has shown a remarkable progress during the last decade. However due to the lack of a consistent malaria control programme and socioeconomic inequalities, Plasmodium infection is still one of the major cause of disease in Equatorial Guinea, namely in the rural communities. This study explored the associated risk factors of malaria transmission at the microeconomic level (households) in two rural villages of mainland Equatorial Guinea.MethodsThis survey involved 232 individuals living in 69 households located in two rural villages, Ngonamanga and Miyobo, of coastal and interior of Equatorial Guinea, respectively. Malaria prevalence was measured by PCR and parasitaemia level by optical microscopy; household socioeconomic status (SES) was measured based on house characteristics using a 2-step cluster analysis. Logistic regression analysis was performed to investigate the relationship of a diverse set of independent variables on being diagnosed with malaria and on showing high levels of parasitaemia.ResultsThe prevalence of Plasmodium spp. infection was 69%, with 80% of households having at least one parasitaemic member. The majority of houses have eaves (80%), walls of clay/wood (90%) and zinc roof (99%) and only 10% of them have basic sanitation facilities. The studied areas showed reduced rates of indoor residual spraying coverage (9%), and long-lasting insecticide-treated net ownership (35%), with none of these preventive tools showing any significant effects on malaria risk in these areas. Neither the risk of malaria infection (PCR positive result) or the development of high parasitaemia did show association with SES.ConclusionsThis study has contributed to reinforce the importance of living conditions associated to a high risk of malaria infection and vulnerability to develop high parasitaemia. This study also contributes to future malaria control interventions to be implemented in mainland Equatorial Guinea or in other countries with similar environmental conditions.Electronic supplementary materialThe online version of this article (10.1186/s12936-018-2354-x) contains supplementary material, which is available to authorized users.

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“…K13-propeller mutations have become the molecular marker of artemisinin-resistance detection. This mutation has been found in a Chinese migrant worker returned home from Equatorial Guinea [ 27 ], but studies has not yet detected the k13 mutations linked with artemisinin resistance in the local population [ 28 ]. A therapeutic efficacy study is in progress in Equatorial Guinea.…”

Section: Discussionmentioning

confidence: 99%

The use and preference of artemether as a first-choice treatment for malaria: results from a cross-sectional survey in the Bata district, Equatorial Guinea

Romay‐Barja

Ncogo

Nseng

et al. 2018

Malar J

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BackgroundMalaria is endemic in Equatorial Guinea with stable transmission, and it remains a major cause of morbidity and mortality in children under 5 years of age. Adherence to artemisinin-based combination therapy (ACT) as a first-line treatment for uncomplicated malaria is critical to malaria control. Six years after the introduction of artesunate-amodiaquine (AS/AQ) therapy in Equatorial Guinea, adherence to the first-line treatment seems to be low in the Bata district. The factors associated with the choice of malaria treatment have not been studied previously in this area; therefore, this study aimed to analyse the preference and use of artemether as malaria treatment and its related factors in the Bata district of Equatorial Guinea.MethodsIn 2013, a cross-sectional study was conducted in the Bata district, which involved 428 households. Bivariate and multivariate statistical analyses were conducted to determine the relevance of socio-economic, geographical, and behavioural factors that played a role in the preference and use of artemether as malaria treatment.ResultsArtemether was considered the best treatment for malaria by 110 caregivers (26%), and was the antimalarial most administrated in the Bata district. It was prescribed to 117 children (27.34%); while, only 6.78% were administered AS/AQ. Caregivers living ≤ 3 km from the nearest health facility were almost two times more likely to consider artemether as the best treatment than those living farther away (95% CI 0.31–0.86). Caregivers with at least a secondary school education were 2.7 times more likely to consider artemether as the best treatment than those less educated. Children whose caregivers considered artemether the best treatment against malaria were five times more likely to be treated with artemether than children with caregivers who did not consider it the best (OR 5.07, 95% CI 2.93–8.78). In contrast, children that reported weakness as a symptom were less likely to be treated with artemether than those with other symptoms (OR 0.47, 95% CI 0.28–0.78).ConclusionCaregivers, public and private health staff, and drug sellers need to understand the importance of using ACT to treat uncomplicated malaria and the dangers of using artemisinin monotherapy.

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Plasmodium falciparum Genetic Diversity in Continental Equatorial Guinea before and after Introduction of Artemisinin-Based Combination Therapy

Cited by 17 publications

References 82 publications

The Diversity of the Plasmodium falciparum K13 Propeller Domain Did Not Increase after Implementation of Artemisinin-Based Combination Therapy in Uganda

The Diversity of the Plasmodium falciparum K13 Propeller Domain Did Not Increase after Implementation of Artemisinin-Based Combination Therapy in Uganda

Malaria determining risk factors at the household level in two rural villages of mainland Equatorial Guinea

The use and preference of artemether as a first-choice treatment for malaria: results from a cross-sectional survey in the Bata district, Equatorial Guinea

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