Background: Artisanal mining creates enabling breeding ground for the vector of malaria parasites. There is paucity of data on the effects of artisanal mining on malaria. This study assessed burden of malaria and caregivers’ health-seeking behaviour for children under five in artisanal mining communities in East Akim District in Ghana. Methods: A cross-sectional study involving caregivers and their children under five was conducted in three artisanal mining communities in the East Akim District in Ghana. Caregivers were interviewed using a structured questionnaire. Finger prick blood samples were collected and analysed for haemoglobin concentration using a rapid diagnostic test, and thick and thin blood smears were analysed to confirm the presence of malaria parasites. Results: Of the 372 children under 5 years included in the study, 197 (53.1%) were male, with a mean age (± SD) of 23.0 ± 12.7 months. The proportion of children with malaria (Plasmodium falciparum and P. malariae) was 98.1% and 1.9%, respectively, whilst the proportion with anaemia (Hb < 11.0 g/dl) was 39.5% (n = 147). Almost all caregivers were female (98.9%), and 28.6% (n = 106) did not have access to any malaria control information. Caregivers associated malaria infection with mosquito bites (68.3%, n = 254) and poor sanitation (21.2%, n = 79). Malaria in children under five was significantly associated with anaemia (OR 11.07, 95% CI 6.59–18.68, n = 111/160, 69.4%; P < 0.0001), residing close to stagnant water (≤ 25 m) from an artisanal mining site (AOR 2.91, 95% CI 1.47–5.76, P = 0.002) and caregiver age younger than 30 years (OR 0.44, 95% CI 0.208–0.917, n = 162, 43.55%, P = 0.001). Conclusions: There is a high burden of malaria and anaemia among children under five in artisanal mining communities of the East Akim District, and far higher than in non-artisanal mining sites. Interventions are needed to effectively regulate mining activities in these communities, and strengthen malaria control and health education campaigns to curtail the high malaria burden and improve health-seeking behaviour. Graphical

Up-to-date knowledge of key epidemiological aspects of each Plasmodium species is necessary for making informed decisions on targeted interventions and control strategies to eliminate each of them. This study aims to describe the epidemiology of plasmodial species in Mali, where malaria is hyperendemic and seasonal. Data reports collected during high-transmission season over six consecutive years were analyzed to summarize malaria epidemiology. Malaria species and density were from blood smear microscopy. Data from 6870 symptomatic and 1740 asymptomatic participants were analyzed. The median age of participants was 12 years, and the sex ratio (male/female) was 0.81. Malaria prevalence from all Plasmodium species was 65.20% (95% CI: 60.10–69.89%) and 22.41% (CI: 16.60–28.79%) for passive and active screening, respectively. P. falciparum was the most prevalent species encountered in active and passive screening (59.33%, 19.31%). This prevalence was followed by P. malariae (1.50%, 1.15%) and P. ovale (0.32%, 0.06%). Regarding frequency, P. falciparum was more frequent in symptomatic individuals (96.77% vs. 93.24%, p = 0.014). In contrast, P. malariae was more frequent in asymptomatic individuals (5.64% vs. 2.45%, p < 0.001). P. ovale remained the least frequent species (less than 1%), and no P. vivax was detected. The most frequent coinfections were P. falciparum and P. malariae (0.56%). Children aged 5–9 presented the highest frequency of P. falciparum infections (41.91%). Non-falciparum species were primarily detected in adolescents (10–14 years) with frequencies above 50%. Only P. falciparum infections had parasitemias greater than 100,000 parasites per µL of blood. P. falciparum gametocytes were found with variable prevalence across age groups. Our data highlight that P. falciparum represented the first burden, but other non-falciparum species were also important. Increasing attention to P. malariae and P. ovale is essential if malaria elimination is to be achieved.

The selection and combination of dose regimens for antimalarials involve complex considerations including pharmacokinetic and pharmacodynamic interactions. In this study, we use immediate ex vivo P. falciparum field isolates to evaluate the effect of cabamiquine and pyronaridine as standalone treatments and in combination therapy. We feed the data into a pharmacometrics model to generate an interaction map and simulate meaningful clinical dose ratios. We demonstrate that the pharmacometrics model of parasite growth and killing provides a detailed description of parasite kinetics against cabamiquine-susceptible and resistant parasites. Pyronaridine monotherapy provides suboptimal killing rates at doses as high as 720 mg. In contrast, the combination of a single dose of 330 mg cabamiquine and 360 mg pyronaridine provides over 90% parasite killing in most of the simulated patients. The described methodology that combines a rapid, 3R-compliant in vitro method and modelling to set meaningful doses for new antimalarials could contribute to clinical drug development.

The widespread circulation of the Anopheles vector is observed during the rainy season and clearly decreases during the dry season, when only a few mosquitoes are able to survive. This study aimed to identify the major species sustaining continued malaria transmission across seasons. This cross-sectional study was conducted in a malaria-endemic area. Mosquitoes were captured in Faladie using pyrethroid spray catches during rainy and dry seasons. The collected mosquitoes were identified using morphological keys, combined with molecular techniques such as PCR-RFLP (IGS regions) for Anopheles (An.) gambiae s.l. identification. Plasmodium spp. positivity in each mosquito was characterized by qPCR using parasite 18 S genes. A total of 1082 and 1705 mosquitoes were captured inside the same houses in the rainy and dry seasons, respectively. In the rainy season, 454 (41.9%) were Anopheles, 624 (57.7%) Culex and 4 (0.4%) Aedes. During the dry season, 65 (3.81%) mosquitoes were Anopheles, while 1,640 (96.19%) were Culex. Morphologically, the anopheline population consisted of 100% An. gambiae s.l. The Anopheles species diversity in the rainy season comprised the sister taxa, An. gambiae s.s. and An. Coluzzii, followed by an An. gambiae/An. coluzzii hybrid and An. arabiensis. However, An. coluzzii was found as the only vector across the rainy and dry seasons that sustained malaria transmission. Plasmodium falciparum infection rates were 9.7% and 1.7%, respectively, for the rainy and dry seasons. An. coluzzii species can survive both the dry and the rainy seasons and sustain malaria through cross-seasonal transmission. This highlights the importance of tackling An. coluzzii species and residual malaria transmission to eradicate the disease in endemic areas.

Le paludisme est causé chez l'homme par cinq espèces de parasites. Parmi ceux-ci, nous avons Plasmodium malariae (P. malariae), largement répandu en Afrique tropicale et d'autres régions endémiques du monde. Au cours de son cycle intra-érythrocytaire, P. malariae peut envahir l’érythrocytes à différents stades de sa maturation et aussi provoquer des symptômes chez l'homme. Le fardeau de ce parasite dans la population, son dynamisme de développement et sa biologie d'invasion des érythrocytes sont particulièrement peu explorés. Dans cette thèse, nous avons cherché à décrire l'épidémiologie des espèces plasmodiales détectées dans une zone rurale du Mali, à caractériser les mécanismes phénotypiques d'invasion des cellules érythrocytaires par P. malariae, à étudier l'invasion de P. malariae avec des enzymes et des anticorps connus pour inhiber l'invasion de P. falciparum et identifier d'éventuels ligands moléculaires de P. malariae essentiels à l'invasion des érythrocytes. Nous avons compilé les données des registres de diagnostic du paludisme pour déterminer les caractéristiques et le fardeau que les espèces de Plasmodium rencontrées constituent sur les populations du Mali. Nous avons réalisé des expériences avec des isolats cliniques de terrain infectés par P. malariae pour étudier la biologie de l’invasion de P. malariae. Dans un premier temps, nous avons montré que la prévalence du paludisme a progressivement diminué au fil des ans et que la densité parasitaire des différentes espèces variait en fonction de l'état clinique (symptomatique/asymptomatique) et de l'âge des individus. Les espèces P. malariae et P. ovale avaient une faible parasitémie et la fréquence de P. malariae était plus élevée chez les porteurs asymptomatiques à la fin de la saison de transmission (décembre). P. falciparum était de loin l'espèce la plus dominante suivie de P. malariae. P. ovale reste la troisième espèce quel que soit le type de dépistage. Nos données montrent que P. falciparum représente bien le fardeau majeur, mais pour une intervention réussie, il est essentiel d'augmenter l'attention envers les autres espèces rencontrées. Dans un second temps, en étudiant la biologie de P. malariae, nous n'avons pas observé de différence notable dans le dynamisme de développement et la morphologie des parasites P. malariae en ex vivo et ceux en infection naturelle et que P. malariae envahit bien les érythrocytes en culture ex vivo avec un taux d'invasion plus élevé à 48 heures par rapport à 24 heures. Aucune réduction d'invasion n'a été induite par les anticorps testés, en revanche, les enzymes utilisées ont significativement bloqué l'invasion des érythrocytes par les mérozoïtes de P. malariae suggérant que P. malariae pourrait utiliser des voies d'invasion alternatives. Nous avons aussi montré que P. malariae envahit préférentiellement les réticulocytes aux normocytes. Ce travail de thèse apporte d’importants résultats pour notre compréhension de l’épidémiologie des espèces plasmodiales au Mali, du dynamisme biologique et particulièrement les mécanismes d’invasion érythrocytaire de P. malariae non encore explorés à ce jour.