Profil épidémiologique de la rougeole au Mali de 2009 à 2018: Epidemiological profile of measles in Mali from 2009 to 2018

Introduction: La rougeole, maladie virale hautement contagieuse causée par un Morbillivirus, reste un important problèeme de santé publique dans de nombreux pays malgré l'existence d'un vaccin efficace. La surveillance de la rougeole est l'un des aspects clés de la lutte contre cette maladie. La présente étude avait pour objectif de décrire la mortalité et la morbidité de la rougeole au Mali entre 2009 et 2018. Méthodes: Il s'agissait d'étude transversale descriptive. Les données de surveillance de la rougeole au Mali de 2009 à 2018 ont été analysées en personne, lieu et temps. Résultats: De 2009 à 2018, le nombre de cas confirmés de rougeole était de 6461 dont 29 décès soit une létalité de 0,45%. La confirmation des cas avait été faite par le laboratoire pour 2551 cas (39,48%), par lien épidémiologique pour 3738 cas (57,85%) et cliniquement pour 172 cas (2,66%). Les enfants de moins de 5 ans représentaient 50,97% des cas et 75,86% des décès. La majorité des cas (95,71 %) n'avaient jamais été vaccinés contre la rougeole. Les incidences les plus élevées avaient été observées en 2009 (22,65 pour 100 000 hbts) et 2010 (11,81 pour 100 000 hbts). Tombouctou, Gao et Mopti avaient enregistrés les plus grands nombres de cas en 2009 et Bamako, Koulikoro et Mopti en 2010. Conclusion: La majorité des cas et des décès étaient les enfants non vaccinés de moins de cinq ans. Un renforcement du programme élargi de vaccination de routine, une riposte aux épidéemies et des stratéegies de vaccination couvrant tout le pays sont nécessaires. Introduction: Measles, a highly contagious viral disease caused by a Morbillivirus, remains an important public health problem in many countries despite the availability of an effective vaccine. Measles surveillance is one of the key aspects of measles control. The objective of this study was to describe measles mortality and morbidity in Mali between 2009 and 2018. Methods: This was a descriptive cross-sectional study. Measles surveillance data in Mali from 2009 to 2018 were analysed by person, place and time. Results: From 2009 to 2018, the number of confirmed measles cases was 6461 including 29 deaths, i.e. a case-fatality rate of 0.45%. Cases were confirmed by the laboratory for 2551 cases (39.48%), by epidemiological link for 3738 cases (57.85%) and clinically for 172 cases (2.66%). Children under 5 years of age represented 50.97% of cases and 75.86% of deaths. The majority of cases (95.71%) had never been vaccinated against measles. The highest incidences were observed in 2009 (22.65 per 100,000 inhabitants) and 2010 (11.81 per 100,000 inhabitants). Timbuktu, Gao and Mopti had the highest number of cases in 2009 and Bamako, Koulikoro and Mopti in 2010. Conclusion: The majority of cases and deaths were among unvaccinated children under five years of age. Strengthening of the routine expanded programme of immunisation, response to epidemics and nationwide immunisation strategies are needed

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

The evolving SARS-CoV-2 epidemic in Africa: Insights from rapidly expanding genomic surveillance

INTRODUCTION Investment in Africa over the past year with regard to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) sequencing has led to a massive increase in the number of sequences, which, to date, exceeds 100,000 sequences generated to track the pandemic on the continent. These sequences have profoundly affected how public health officials in Africa have navigated the COVID-19 pandemic. RATIONALE We demonstrate how the first 100,000 SARS-CoV-2 sequences from Africa have helped monitor the epidemic on the continent, how genomic surveillance expanded over the course of the pandemic, and how we adapted our sequencing methods to deal with an evolving virus. Finally, we also examine how viral lineages have spread across the continent in a phylogeographic framework to gain insights into the underlying temporal and spatial transmission dynamics for several variants of concern (VOCs). RESULTS Our results indicate that the number of countries in Africa that can sequence the virus within their own borders is growing and that this is coupled with a shorter turnaround time from the time of sampling to sequence submission. Ongoing evolution necessitated the continual updating of primer sets, and, as a result, eight primer sets were designed in tandem with viral evolution and used to ensure effective sequencing of the virus. The pandemic unfolded through multiple waves of infection that were each driven by distinct genetic lineages, with B.1-like ancestral strains associated with the first pandemic wave of infections in 2020. Successive waves on the continent were fueled by different VOCs, with Alpha and Beta cocirculating in distinct spatial patterns during the second wave and Delta and Omicron affecting the whole continent during the third and fourth waves, respectively. Phylogeographic reconstruction points toward distinct differences in viral importation and exportation patterns associated with the Alpha, Beta, Delta, and Omicron variants and subvariants, when considering both Africa versus the rest of the world and viral dissemination within the continent. Our epidemiological and phylogenetic inferences therefore underscore the heterogeneous nature of the pandemic on the continent and highlight key insights and challenges, for instance, recognizing the limitations of low testing proportions. We also highlight the early warning capacity that genomic surveillance in Africa has had for the rest of the world with the detection of new lineages and variants, the most recent being the characterization of various Omicron subvariants. CONCLUSION Sustained investment for diagnostics and genomic surveillance in Africa is needed as the virus continues to evolve. This is important not only to help combat SARS-CoV-2 on the continent but also because it can be used as a platform to help address the many emerging and reemerging infectious disease threats in Africa. In particular, capacity building for local sequencing within countries or within the continent should be prioritized because this is generally associated with shorter turnaround times, providing the most benefit to local public health authorities tasked with pandemic response and mitigation and allowing for the fastest reaction to localized outbreaks. These investments are crucial for pandemic preparedness and response and will serve the health of the continent well into the 21st century

SNPs on ABC Transporters and in vivo Malaria Parasite Non Clearance after Chloroquine Treatment in Malian Children

Background: pfcrt K76T mutation was demonstrated to play a central role in the P. falciparum resistance to chloroquine. Aim: To find any association between mutant alleles of pfcrt K76T, pfmdr1 N86Y, pfG30 and pfG47 and the in vivo parasite non clearance after chloroquine treatment in Mali. Methodology: We carried out a chloroquine efficacy study in 196 children suffering from uncomplicated malaria in a rural village of Kollé, Mali, using WHO protocol. Subjects were treated with standard dose of chloroquine and followed for 14 days. Parasite DNA was extracted from finger prick blood blotted onto filter paper and genotypes were analyzed by different PCR methods. Results: The mutant alleles pfcrt 76T and pfmdr1 86Y were associated with parasite non clearance with p=0.00001 and 0.03 respectively. However, the association of SNPs on pfG30 and pfG47 genes with parasite non clearance was not statistically significant, p =0.43 and 0.57 respectively. The logistic regression analysis showed that the mutant allele pfmdr186Y contributed positively to the pfcrt 76T parasites non clearance (p=0.02). Conclusion: These findings have shown that pfcrt76T and pfmdr1 86Y alleles are associated with the in vivo parasite non clearance, but not SNPs on the new putative transporters genes

An Intensive Longitudinal Cohort Study of Malian Children and Adults Reveals No Evidence of Acquired Immunity to Plasmodium falciparum Infection

Background In experimental models of human and mouse malaria, sterilizing liver stage immunity that blocks progression of Plasmodium infection to the symptomatic blood stage can be readily demonstrated. However, it remains unclear whether individuals in malaria-endemic areas acquire such immunity. Methods In Mali, 251 healthy children and adults aged 4–25 years who were free of blood-stage Plasmodium infection by polymerase chain reaction (PCR) were enrolled in a longitudinal study just prior to an intense 6-month malaria season. Subsequent clinical malaria episodes were detected by weekly active surveillance and self-referral. Asymptomatic P. falciparum infections were detected by blood-smear microscopy and PCR analysis of dried blood spots that had been collected every 2 weeks for 7 months. Results As expected, the risk of clinical malaria decreased with increasing age (log-rank test, P = .0038). However, analysis of PCR data showed no age-related differences in P. falciparum infection risk (log-rank test, P = .37). Conclusions Despite years of exposure to intense P. falciparum transmission, there is no evidence of acquired, sterile immunity to P. falciparum infection in this population, even as clinical immunity to blood-stage malaria is clearly acquired. Understanding why repeated P. falciparum infections do not induce sterile protection may lead to insights for developing vaccines that target the liver stage in malaria-endemic populations

Naturally Acquired Antibodies Specific for Plasmodium falciparum Reticulocyte-Binding Protein Homologue 5 Inhibit Parasite Growth and Predict Protection From Malaria

Background. Plasmodium falciparum reticulocyte-binding protein homologue 5 (PfRH5) is a blood-stage parasite protein essential for host erythrocyte invasion. PfRH5-specific antibodies raised in animals inhibit parasite growth in vitro, but the relevance of naturally acquired PfRH5-specific antibodies in humans is unclear. Methods. We assessed pre–malaria season PfRH5-specific immunoglobulin G (IgG) levels in 357 Malian children and adults who were uninfected with Plasmodium. Subsequent P. falciparum infections were detected by polymerase chain reaction every 2 weeks and malaria episodes by weekly physical examination and self-referral for 7 months. The primary outcome was time between the first P. falciparum infection and the first febrile malaria episode. PfRH5-specific IgG was assayed for parasite growth-inhibitory activity. Results. The presence of PfRH5-specific IgG at enrollment was associated with a longer time between the first blood-stage infection and the first malaria episode (PfRH5-seropositive median: 71 days, PfRH5-seronegative median: 18 days; P = .001). This association remained significant after adjustment for age and other factors associated with malaria risk/exposure (hazard ratio, .62; P = .02). Concentrated PfRH5-specific IgG purified from Malians inhibited P. falciparum growth in vitro. Conclusions. Naturally acquired PfRH5-specific IgG inhibits parasite growth in vitro and predicts protection from malaria. These findings strongly support efforts to develop PfRH5 as an urgently needed blood-stage malaria vaccine. Clinical Trials Registration NCT01322581