Discrepant Prevalence and Incidence of Leishmania Infection between Two Neighboring Villages in Central Mali Based on Leishmanin Skin Test Surveys

Leishmaniasis is a vector-borne disease transmitted to humans by the bite of an infected sand fly. Leishmaniasis is present in more than 88 countries and affects more than 12 million people. Depending on the species of Leishmania, the host can develop cutaneous leishmaniasis (CL), which is characterized by skin ulcers in uncovered parts of the body or a more severe form, visceral leishmaniasis, which affects the liver and spleen and is fatal if not treated. This study aims to establish the past and present infection with Leishmania parasites in two villages where recent cases have been diagnosed by the dermatology center (CNAM) in Bamako. This was achieved using a Leishmania-specific skin test that was administered annually to permanent residents of Kemena and Sougoula villages from 2006 to 2008. The results show that transmission of Leishmania is active and stable in these two villages. Moreover, despite sharing similar cultural and environmental features, the individuals from Kemena presented three times the risk of Leishmania infection compared with those from Sougoula. Our findings raise awareness of the continued presence of CL in Mali

A comprehensive analysis of drug resistance molecular markers and Plasmodium falciparum genetic diversity in two malaria endemic sites in Mali.

BACKGROUND: Drug resistance is one of the greatest challenges of malaria control programme in Mali. Recent advances in next-generation sequencing (NGS) technologies provide new and effective ways of tracking drug-resistant malaria parasites in Africa. The diversity and the prevalence of Plasmodium falciparum drug-resistance molecular markers were assessed in Dangassa and Nioro-du-Sahel in Mali, two sites with distinct malaria transmission patterns. Dangassa has an intense seasonal malaria transmission, whereas Nioro-du-Sahel has an unstable and short seasonal malaria transmission. METHODS: Up to 270 dried blood spot samples (214 in Dangassa and 56 in Nioro-du-Sahel) were collected from P. falciparum positive patients in 2016. Samples were analysed on the Agena MassARRAY® iPLEX platform. Specific codons were targeted in Pfcrt, Pfmdr1, Pfdhfr, and Pfdhps, Pfarps10, Pfferredoxin, Pfexonuclease and Pfmdr2 genes. The Sanger's 101-SNPs-barcode method was used to assess the genetic diversity of P. falciparum and to determine the parasite species. RESULTS: The Pfcrt_76T chloroquine-resistance genotype was found at a rate of 64.4% in Dangassa and 45.2% in Nioro-du-Sahel (p = 0.025). The Pfdhfr_51I-59R-108N pyrimethamine-resistance genotype was 14.1% and 19.6%, respectively in Dangassa and Nioro-du-Sahel. Mutations in the Pfdhps_S436-A437-K540-A581-613A sulfadoxine-resistance gene was significantly more prevalent in Dangassa as compared to Nioro-du-Sahel (p = 0.035). Up to 17.8% of the isolates from Dangassa vs 7% from Nioro-du-Sahel harboured at least two codon substitutions in this haplotype. The amodiaquine-resistance Pfmdr1_N86Y mutation was identified in only three samples (two in Dangassa and one in Nioro-du-Sahel). The lumefantrine-reduced susceptibility Pfmdr1_Y184F mutation was found in 39.9% and 48.2% of samples in Dangassa and Nioro-du-Sahel, respectively. One piperaquine-resistance Exo_E415G mutation was found in Dangassa, while no artemisinin resistance genetic-background were identified. A high P. falciparum diversity was observed, but no clear genetic aggregation was found at either study sites. Higher multiplicity of infection was observed in Dangassa with both COIL (p = 0.04) and Real McCOIL (p = 0.02) methods relative to Nioro-du-Sahel. CONCLUSIONS: This study reveals high prevalence of chloroquine and pyrimethamine-resistance markers as well as high codon substitution rate in the sulfadoxine-resistance gene. High genetic diversity of P. falciparum was observed. These observations suggest that the use of artemisinins is relevant in both Dangassa and Nioro-du-Sahel

Étude de la corrélation entre les tendances migratoires internationaux et les tendances macroéconomiques Maliennes

Le Mali, pays sahélien enclavé couvrant une superficie de 1.241.238 km², est marqué par d’importants mouvements migratoires, tant sur le plan interne qu’international. Les pratiques migratoires sont anciennes, il est héritier d’un passé culturel marqué par la présence de grands empires et royaumes. Il est largement admis que les conditions socioéconomiques, politiques sécuritaires et même environnementales sont entre autres les déterminants essentiels des migrations et qu’au retour ces mouvements migratoires contribuent au développement du milieu d’origine, sinon national. C’est dans ce contexte que cet article, présente d’une part, les principaux déterminants du phénomène migratoire du Mali de la période récente en fournissant un rappel historique de systèmes migratoires au Mali, d’autre part, il abordera la question de la contribution de la migration au développement économique du pays par le biais du transfert de fonds. Les équations de modèle économétrique en série temporelle sont exposées afin de déterminer la corrélation existante entre les variables, tendances migratoires et certains indicateurs de macroéconomiques du Mali

Seasonal Malaria Chemoprevention Therapy in Children Up To 9 Years of Age: Protocol for a Cluster-Randomized Trial Study

BackgroundSeasonal malaria chemoprevention (SMC) is recommended by the World Health Organization for the sub-Sahel region in sub-Saharan Africa for preventing malaria in children 3 months old to younger than 5 years. Since 2016, the Malian National Malaria Control Program has deployed SMC countrywide during its high malaria transmission season at a rate of 4 monthly cycles annually. The standard SMC regimen includes sulfadoxine-pyrimethamine (SP) plus amodiaquine (AQ). Resistance against SP is suspected to be rising across West Africa; therefore, assessing the effectiveness of an alternative antimalarial drug for SMC is needed to provide a second-line regimen when it is ultimately needed. It is not well understood whether SMC effectively prevents malaria in children aged 5 years or older. ObjectiveThe primary goal of the study is to compare 2 SMC regimens (SP-AQ and dihydroartemisinin-piperaquine [DHA-PQ]) in preventing uncomplicated Plasmodium falciparum malaria in children 3 months to 9 years old. Secondly, we will assess the possible use of DHA-PQ as an alternative SMC drug in areas where resistance to SP or AQ may increase following intensive use. MethodsThe study design is a 3-arm cluster-randomized design comparing the SP-AQ and DHA-PQ arms in 2 age groups (younger than 5 years and 5-9 years) and a control group for children aged 5-9 years. Standard SMC (SP-AQ) for children younger than 5 years was provided to the control arm, while SMC with SP-AQ was delivered to children aged 3 months to 9 years (arm 2), and SMC with DHA-PQ will be implemented in study arm 3 for children up to 9 years of age. The study was performed in Mali’s Koulikoro District, a rural area in southwest Mali with historically high malaria transmission rates. The study’s primary outcome is P falciparum incidence for 2 SMC regimens in children up to 9 years of age. Should DHA-PQ provide an acceptable alternative to SP-AQ, a plausible second-line prevention option would be available in the event of SP resistance or drug supply shortages. A significant byproduct of this effort included bolstering district health information systems for rapid identification of severe malaria cases. ResultsThe study began on July 1, 2019. Through November 2022, a total of 4556 children 3 months old to younger than 5 years were enrolled. Data collection ended in spring 2023, and the findings are expected to be published later in early 2024. ConclusionsRoutine evaluation of antimalarial drugs is needed to establish appropriate SMC age targets. The study goals here may impact public health policy and provide alternative therapies in the event of drug shortages or resistance. Trial RegistrationClinicalTrials.gov NCT04149106, https://clinicaltrials.gov/ct2/show/NCT04149106 International Registered Report Identifier (IRRID)DERR1-10.2196/5166

Ex-vivo Sensitivity of Plasmodium falciparum to Common Anti-malarial Drugs: The Case of Kéniéroba, a Malaria Endemic Village in Mali

Abstract Background In 2006, the National Malaria Control Program in Mali recommended artemisinin-based combination therapy as the first-line treatment for uncomplicated malaria. Since the introduction of artemisinin-based combination therapy, few reports are available on the level of resistance of Plasmodium falciparum to the most common anti-malarial drugs in Mali. Methods From 2016 to 2017, we assessed the ex-vivo drug sensitivity of P. falciparum isolates in Kéniéroba, a village located in a rural area of southern Mali. We collected P. falciparum isolates from malaria-infected children living in Kéniéroba. The isolates were tested for ex-vivo sensitivity to commonly used anti-malarial drugs, namely chloroquine, quinine, amodiaquine, mefloquine, lumefantrine, dihydroartermisinin, and piperaquine. We used the 50% inhibitory concentration determination method, which is based on the incorporation of SYBR® Green into the parasite’s genetic material. Results Plasmodium falciparum isolates were found to have a reduced ex-vivo sensitivity to quinine (25.7%), chloroquine (12.2%), amodiaquine (2.7%), and mefloquine (1.3%). In contrast, the isolates were 100% sensitive to lumefantrine, dihydroartermisinin, and piperaquine. A statistically significant correlation was found between 50% inhibitory concentration values of quinine and amodiaquine (r = 0.80; p < 0.0001). Conclusions Plasmodium falciparum isolates were highly sensitive to dihydroartermisinin, lumefantrine, and piperaquine and less sensitive to amodiaquine (n = 2), mefloquine (n = 1), and quinine (n = 19). Therefore, our data support the previously reported increasing trend in chloroquine sensitivity in Mali

Correction: Prevalence of Cutaneous Leishmaniasis in Districts of High and Low Endemicity in Mali.

[This corrects the article DOI: 10.1371/journal.pntd.0005141.]

Effect of a fifth round of seasonal malaria chemoprevention in children aged 5–14&nbsp;years in Dangassa, an area of long transmission in Mali

Despite a significant reduction in the burden of malaria in children under five years-old, the efficient implementation of seasonal malaria chemoprevention (SMC) at large scale remains a major concern in areas with long malaria transmission. Low coverage rate in the unattainable areas during the rainy season, a shift in the risk of malaria to older children and the rebound in malaria incidence after stopping drug administration are mainly reported in these areas. These gaps represent a major challenge in the efficient implementation of SMC measures. An open randomized study was conducted to assess the effect of a fifth additional round to current regime of SMC in older children living in Dangassa, a rural malaria endemic area. Poisson regression Model was used to estimate the reduction in malaria incidence in the intervention group compared to the control group including age groups (5-9 and 10-14&nbsp;years) and the use of long-lasting insecticidal nets (LLINs; Yes or No) with a threshold at 5%. Overall, a downward trend in participation rate was observed from August (94.3%) to November (87.2%). In November (round 4), the risk of malaria incidence was similar in both groups (IRR&nbsp;=&nbsp;0.66, 95%CI [0.35-1.22]). In December (round 5), a decrease of 51% in malaria incidence was observed in intervention group compared to control group adjusted for age groups and the use of LLINs (IRR&nbsp;=&nbsp;0.49, 95%CI [0.26-0.94]), of which 17% of reduction is attributable to the 5th round in the intervention group. An additional fifth round of SMC resulted in a significant reduction of malaria incidence in the intervention group. The number of SMC rounds could be adapted to the local condition of malaria transmission

Prevalence of LST positivity by age group for the district of Diema (A) and for all study sites (B).

<p>Prevalence of LST positivity by age group for the district of Diema (A) and for all study sites (B).</p

Map of Mali showing the study sites in different districts.

<p>Map of Mali showing the study sites in different districts.</p