My research work

Assessing malaria burden and tracking drug resistance

Portfolio

I am working on fieldwork and live systematic reviews for real-time surveillance and mapping of malaria parasites carrying molecular markers of antimalarial drug resistance across the Democratic Republic of Congo, Africa and globally. I am also advocating evidence-based malaria control measures that take into account temporal and spatial variations. The aim is to support public health decision-making and surveillance efforts.

Assessing malaria burden and tracking malaria drug resistance

The landscape of antimalarial drug resistance in the Democratic Republic of Congo

This research proposes a baseline for the establishment of malaria surveillance in the DR Congo, a country which accounts for more than 10% of malaria cases in the world and which provide a considerable epidemiological burden for resistance to antimalarial drugs. It is obviously urgent to establish lasting surveillance activities against this resistance, especially at a time when malaria resistance to artemisinin has emerged and is spreading in regions bordering this vast country. The systematic review exercise proposed by this research is also a way of providing both a detailed analysis and a regional overview of the malaria drug resistance problem. It is not surprising that this work was able to highlight a parasite collected in 2014, encoding the PfK13 R561H mutation and having been overlooked in its primary study in 2016. This parasite becomes the oldest evidence of parasites carrying this mutation which has been implicated in the emergence of artemisinin resistance in Africa since 2019. The discussion here also provides evidence-based guidance for actions against chloroquine resistance, for implementing sulfadoxine-pyrimethamine based chemoprevention strategies and drug resistance surveillance activities. We believe that our findings will appeal to the readership of your journal and will attract the attention of policy makers and health practitioners in the DR Congo and beyond.

Last update : 30 June 2023
Next update : 30 December 2023
We carried out a systematic mapping review before July 2023 by searching for relevant articles through seven databases (PubMed, Embase, Scopus, African Journal Online, African Index Medicus, Bioline and Web of Science). The following figure displays locations of each primary survey. Shaded areas represent the country’s provinces that were not surveyed. Yellow circles reflect individual surveys conducted at different locations with a diameter proportional to the size of the samples that were successfully investigated for molecular markers of antimalarial drug resistance. Detailed analyses can be found in the related article.

Impact of seasonal malaria chemoprevention on drug resistance in the Sahel

Seasonal malaria chemoprevention is an important intervention recommended for children aged 3–59 months living in highly seasonal transmission areas of the Sahel subregion of Africa to provide protection against malaria during the rainy season. In The Lancet Infectious Diseases, Colin J Sutherland and colleagues report on the prevalence of Plasmodium falciparum genetic variants associated with drug resistance before and after the implementation of seasonal malaria chemoprevention with sulfadoxine–pyrimethamine plus amodiaquine in areas across seven Sahelian countries (Burkina Faso, Chad, Guinea, Mali, Nigeria, Niger, and The Gambia). In these areas, monthly seasonal malaria chemoprevention was scaled up among children younger than 5 years in 2016, and community surveys including a collection of dried blood spot samples were conducted at baseline from December, 2015, to March, 2016, and two years later, from December, 2017, to March, 2018 (periods theoretically following the malaria transmission seasons in the study areas). In parallel, individuals aged 10–30 years not receiving seasonal malaria chemoprevention drugs were surveyed as a control population. Infections with P falciparum parasites were monitored, with attention paid to isolates harbouring specific molecular markers to sulfadoxine–pyrimethamine (ie, alleles in the dhfr and dhps genes) and to amodiaquine (ie, alleles in the crt and mdr1 genes).

Emergence of artemisinin resistant malaria in Africa

The spread of Plasmodium falciparum isolates carrying mutations in the kelch13 (Pfkelch13) gene associated with artemisinin resistance (PfART-R) in southeast Asia threatens malaria control and elimination efforts. Emergence of PfART-R in Africa would result in a major public health problem. In this systematic review, we investigate the frequency and spatial distribution of Pfkelch13 mutants in Africa, including mutants linked to PfART-R in southeast Asia. Seven databases were searched (PubMed, Embase, Scopus, African Journal Online, African Index Medicus, Bioline, and Web of Science) for relevant articles about polymorphisms of the Pfkelch13 gene in Africa before January, 2019. Following PRISMA guidelines, 53 studies that sequenced the Pfkelch13 gene of 23 100 sample isolates in 41 sub-Saharan African countries were included. The Pfkelch13 sequence was highly polymorphic (292 alleles, including 255 in the Pfkelch13-propeller domain) but with mutations occurring at very low relative frequencies. Non-synonymous mutations were found in only 626 isolates (2·7%) from west, central, and east Africa. According to WHO, nine different mutations linked to PfART-R in southeast Asia (Phe446Ile, Cys469Tyr, Met476Ile, Arg515Lys, Ser522Cys, Pro553Leu, Val568Gly, Pro574Leu, and Ala675Val) were detected, mainly in east Africa. Several other Pfkelch13 mutations, such as those structurally similar to southeast Asia PfART-R mutations, were also identified, but their relevance for drug resistance is still unknown. This systematic review shows that Africa, thought to not have established PfART-R, reported resistance-related mutants in the past 5 years. Surveillance using PfART-R molecular markers can provide valuable decision-making information to sustain the effectiveness of artemisinin in Africa.

Malaria resistance to sulfadoxine-pyrimethamine among pregnant women in the Democratic Republic of Congo

Methods Laboring women (n = 844) and respective newborns were investigated. Blood samples collected from women were tested for malaria using rapid diagnostic test (RDT), blood smears examination, and real-time PCR. The hemoglobin level was measured by HemoCue© analyzer. A PCR-RFLP method was applied for detecting N51I, C59R, and S108N mutations on dhfr along with A437G and K540E mutations on dhps in P. falciparum positive samples. Logistic regression models assessed relationships between IPTp-SP uptake and pregnancy outcomes. Results P. falciparum malaria was detected at delivery in 10.8% of women and was statistically associated with fever during the pregnancy (OR = 2.9 [1.5; 6.3]; p = 0.004) and maternal anemia (OR = 3.9 [2.4; 6.3]; p < 0.001). One out of five parasites was a quintuple mutant encoding dhfr mutations 51I, 59R, and 108 N along with dhps mutations 437G and 540E. The molecular profile of parasites (i.e., 32.6% of parasites carrying dhps K540E) was suitable with continued use of SP for IPTp. IPTp-SP uptake was not associated with reduced maternal malaria, fever reported in pregnancy, or fetal deaths (p > 0.05). Conversely, three or more doses of SP were associated with reduced maternal anemia at delivery (OR = 0.4 [0.2; 0.9]; p = 0.024), shortened gestation (OR = 0.4 [0.2; 0.8]; p = 0.009), and low-birth weights (OR = 0.2 [0.1; 0.5]; p < 0.001). Conclusion IPTp-SP was not associated with reduced maternal malaria in our study, but evidence was found of a prophylactic effect against adverse pregnancy outcomes. To counteract further loss of clinical effects of IPTp-SP in the study population, alternative strategies able to improve its anti-malarial efficacy such as combination of SP with partner molecules should be implemented.

Assessing the burden of malaria for guiding public health strategies

Care-seeking behaviour and socio-economic burden associated with uncomplicated malaria in the Democratic Republic of Congo

Background This study aimed to estimate the socio-economic costs of uncomplicated malaria and to explore health care-seeking behaviours that are likely to influence these costs in the Democratic Republic of Congo (DRC), a country ranked worldwide as the second most affected by malaria. Methods In 2017, a cross-sectional survey included patients with uncomplicated malaria in 64 healthcare facilities from 10 sentinel sites of the National Malaria Control Programme (NMCP) in the DRC. A standard questionnaire was used to assess health care-seeking behaviours of patients. Health-related quality of life (HRQL) and disutility weights (DW) of illness were evaluated by using the EuroQol Group’s descriptive system (EQ-5D-3L) and its visual analogue scale (EQ VAS). Malaria costs were estimated from a patient’s perspective. Probabilistic sensitivity analyses (PSA) evaluated the uncertainty around the cost estimates. Generalized regression models were fitted to assess the effect of potential predictive factors on the time lost and the DW during illness. Results In total, 1080 patients (age: 13.1 ± 14 years; M/F ratio: 1.1) were included. The average total costs amounted to US$ 36.3 [95% CI 35.5–37.2] per malaria episode, including US$ 16.7 [95% CI 16.3–17.1] as direct costs and US$ 19.6 [95% CI 18.9–20.3] indirect costs. During care seeking, economically active patients and their relatives lost respectively 3.3 ± 1.8 and 3.4 ± 2.1 working days. This time loss occurred mostly at the pre-hospital stage and was the parameter associated the most with the uncertainty around malaria cost estimates. Patients self-rated an average 0.36 ± 0.2 DW and an average 0.62 ± 0.3 EQ-5D index score per episode. A lack of health insurance coverage (896 out of 1080; 82.9%) incurred substantially higher costs, lower quality of life, and heavier DW while leading to longer time lost during illness. Residing in rural areas incurred a disproportionally higher socioeconomic burden of uncomplicated malaria with longer time lost due to illness and limited access to health insurance mechanisms. Conclusion Uncomplicated malaria is associated with high economic costs of care in the DRC. Efforts to reduce the cost-of-illness should target time lost at the pre-hospital stage and social disparities in the population, while reinforcing measures for malaria control in the country.