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Nous assistons de plus en plus à l’émergence de certaines maladies, comme les fièvres hémorragiques virales (FHV). Certaines de ces maladies se transmettent de personne à personne par contact direct ou indirect avec des patients symptomatiques. Les vecteurs ou les réservoirs sont des moyens de transmission faciles pour ces fièvres hémorragiques virales. La fièvre de Lassa, a été révélée au Mali en 2009 chez l’homme. Depuis plusieurs études ont été menées sur les rongeurs avec une séroprévalence qui atteint parfois 50% au sud du Mali. Chez l’homme, la prévalence allait de 14,5 à 44% et une incidence de 6,3%. Pour la Fièvre Hémorragique de Crimée Congo, les auteurs ont retrouvés une séroprévalence humaine de 4,5%. Chez les bovins, des traces sérologiques ont été retrouvées dans tout le pays allant de 15% à 95%. Le Mali a connue deux incursions séparées de la Maladie à virus Ebola à partir de la Guinée Conakry. Le diagnostic des 103 échantillons de cas suspects a été réalisé au Laboratoire SEREFO/UCRC avec 10 cas positif au virus Ebola. La dengue était présente avec une séroprévalence allant de 40% à 93%. Un cas humain de la Fièvre de la Vallée du Rift a été identifié au Mali en 2017, mais la maladie est présente chez les bovins surtout dans les régions septentrionales du pays. Le diagnostic a été réalisé surtout par la méthode ELISA (recherche d’IgG ou d’IgM). La biologie moléculaire a été utilisée dans certains cas

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The objective of this study was to produce a malaria distribution map that would constitute a useful tool for development and health planners in West Africa. The recently created continental database of malaria survey results (MARA/ARMA 1998) provides the opportunity for producing empirical models and maps of malaria distribution at a regional and eventually at a continental level. This paper reports on the mapping of malaria distribution for sub-Saharan West Africa based on these data. The strategy was to undertake a spatial statistical analysis of malaria parasite prevalence in relation to those potential bio-physical environmental factors involved in the distribution of malaria transmission intensity which are readily available at any map location. The resulting model was then used to predict parasite prevalence for the whole of West Africa. We also produced estimates of the proportion of population of each country in the region exposed to various categories of risk to show the impact that malaria is having on individual countries. The data represent a very large sample of children in West Africa. It constitutes a first attempt to produce a malaria risk map of the West African region, based entirely on malariometric data. We anticipate that it will provide useful additional guidance to control programme managers, and that it can be refined once sufficient additional data become available. [ABSTRACT FROM AUTHOR]

Background: Attractive targeted sugar baits (ATSBs) have the potential to significantly reduce infective female Anopheles mosquitoes in arid areas, such as in Northern Mali. Malaria is epidemic in the north due to the limited viability of Anopheles species in the desert climate. The goal of this study was to determine of the effect of ATSB on the number of older female An. gambiae and on the number of sporozoite-positive females in villages in northern Mali., Methods: Villages were located in the north of Mali. In this study, 5677 ATSB stations were deployed, two on each home, in ten villages during late July and early August 2019. Ten villages served as controls. After a pre-treatment monitoring period in July, An. gambiae populations were monitored again from August to December using CDC-UV light traps, pyrethrum spray catches (PSC), and human landing catches (HLC). Mosquitoes were dissected to estimate their age, while ELISA detected sporozoite positivity. The monthly entomological inoculation rates (EIRs) were calculated for HLC indoors and outdoors. Data from villages were compared using t-tests, while bait station weighted density versus amount of collected females was checked with a Pearson's correlation., Results: A total of 2703 female An. gambiae were caught from treated villages, 4582 from control villages, a 41.0% difference. Dissection of 1759 females showed that ATSB significantly reduced the number of older females. The proportion of older females in treated villages was 0.93% compared to 9.4% in control villages. ELISA analysis of 7285 females showed that bait stations reduced the number of sporozoite-positive females. The infective females in treated villages was 0.30% compared to 2.73% in the controls. The greater the density of bait stations deployed, the fewer the older, infective females (P < 0.05). EIRs were low in control villages except in months when An. gambiae populations were high. EIRs in ATSB placement villages remained zero. Significant reductions (P < 0.0001) in An. gambiae males were observed., Conclusions: Bait stations reduced all measures of vector populations in this study. In a low-transmission setting, ATSB has the potential to greatly reduce malaria., (© 2024. The Author(s).)

Introduction: Seasonal malaria chemoprevention (SMC) with Sulfadoxine pyrimethamine plus amodiaquine (SP + AQ) consist of a monthly administration of therapeutic dose to children under five years of age during the high risk of malaria in area where malaria is highly seasonal. According to SMC recommendation, both non-infected and asymptomatic Plasmodium falciparum infected children will receive similar treatment. The gap in our knowledge is how the effect of asymptomatic infection on the efficacy of SMC in preventing clinical malaria over a four-week period. Thus, this study aimed to assess the risk of clinical malaria and its association with children's infection status when SMC treatment is given., Methodology: The study was carried out in the Koulikoro health district in Mali and concerned children under 10 years of age. A total of 726 and 1452 children were randomly selected and followed over the SMC campaign in the years 2019 and 2020 respectively. Prevalence of asymptomatic P. falciparum infection was determined each round by microscopy before SMC drugs intake. Children were passively followed over a four-week period to determine incidence of clinical malaria. R-Studio software was used for analysis. The risk of clinical malaria by infection status was estimated using a logistic regression. A Kaplan-Meier curve was used to determine the survival time between infected and uninfected children. The Pearson Chi-square test was used to compare proportions with the significant level at p< 0.05., Results: The average prevalence of asymptomatic infection was 11.0% both years, and it was higher among children aged 5 to 9 years old in 2019 (p<0.001) and 2020 (p=0.016). The risk of clinical malaria was significantly higher among asymptomatic infected children 2019: (RR=3.05, CI [2.04-4.72]) and 2020 (RR=1.43, CI [1.04-1.97]) transmission seasons. Likewise, the time of the first malaria occurrence was statistically lower among infected children regardless the year (p<0.001 in 2019 and p=0.01 in 2020)., Conclusion: Results show a high risk of clinical malaria in asymptomatic infected children during SMC delivery. Screening for P. falciparum infection before the SMC treatment could significantly enhance the impact of the strategy on malaria morbidity in endemic areas., Competing Interests: Conflict of interest The authors declare that they have no competing interests.

Background: In Africa, the relationship between childhood nutritional status and malaria remains complex and difficult to interpret. Understanding it is important in the improvement of malaria control strategies. This study aimed to assess the influence of nutritional status on the occurrence of multiple malaria episodes in children aged 6 to 59 months between 2013 and 2017 living in the village of Dangassa, Mali., Methods: A community-based longitudinal study was conducted using cross-sectional surveys (CSSs) at the beginning (June) and end (November) of the malaria transmission season associated with passive case detection (PCD) at the Dangassa Community Health Centre. Children with asymptomatic malaria infection during cross-sectional surveys were selected and their malaria episodes followed by PCD. Malaria indicators in person-months were estimated using an ordinal-logistic model repeated on subjects during follow-up periods., Results: The incidence rate (IR) during the period of high transmission (June to October), for 1 episode and for 2 + episodes peaked in 2013 with 65 children (IR = 95.73 per 1000 person-months) and 24 cases (IR = 35.35 per 1000 person-months), respectively. As expected, the risk of multiple episodes occurring during the period of high transmission was 3.23 compared to the period of low transmission after adjusting for other model parameters (95% CI [2.45-4.26], p = 0.000). Children with anaemia were at high risk of having multiple episodes (OR = 1.6, 95% CI [1.12-2.30], p = 0.011). However, the risk of having 2 + episodes for anemic children was higher during the period of low transmission (RR = 1.67, 95% CI [1.15-2.42], p = 0.007) compared to the period of high transmission (RR = 1.58, 95% CI [1.09-2.29], p = 0.016). The trend indicated that anemic and underweight children were significantly associated with multiple malaria episodes during the period of low transmission (p < 0.001)., Conclusion: Results show that multiple episodes of malaria are significantly related to the nutritional status (anaemia and underweight) of the child during the two transmission seasons and more pronounced during the dry season (period of low transmission). Further research including other malnutrition parameters will be needed to confirm these findings., (© 2024. The Author(s).)

Diagnostics for febrile illnesses other than malaria are not readily available in rural sub-Saharan Africa. This study assessed exposure to three mosquito-borne arboviruses-dengue virus (DENV), Zika virus (ZIKV), and chikungunya virus (CHIKV)-in southern Mali. Seroprevalence for DENV, CHIKV, and ZIKV was analyzed by detection of IgG antibodies and determined to be 77.2%, 31.2%, and 25.8%, respectively. Among study participants, 11.3% were IgG-positive for all three arboviruses. DENV had the highest seroprevalence rate at all sites; the highest seroprevalence of CHIKV and ZIKV was observed in Bamba. The seroprevalence for all three arboviruses increased with age, and the highest seroprevalence was observed among adults older than 50 years. The prevalence of Plasmodium spp. in the cohort was analyzed by microscopy and determined to be 44.5% (N = 600) with Plasmodium falciparum representing 95.1% of all infections. This study demonstrates the co-circulation of arboviruses in a region hyperendemic for malaria and highlights the needs for arbovirus diagnostics in rural sub-Saharan Africa.

Background: In Africa, the relationship between nutritional status and malaria remains complex and difficult to interpret in children. Understanding it is important in the development of malaria control strategies. This study evaluated the effect of nutritional status on the occurrence of multiple malaria episodes in children aged 6 to 59 months between 2013 and 2017 living in the village of Dangassa, Mali., Methods: A community-based longitudinal study was conducted using cross-sectional surveys (SSCs) at the beginning (June) and end (November) of the malaria transmission season associated with passive case detection (PCD) at the Dangassa Community Health Center. Children with asymptomatic malaria infection during cross-sectional surveys were selected and their malaria episodes followed by PCD. Palustrine indicators in person-months were estimated using an ordinal-logistic model repeated on subjects during follow-up periods., Results: The incidence rate (IR) during the period of high transmission (June to October), for 1 episode and for 2 + episodes peaked in 2013 with 65 children (IR = 95.73 per 1000 person-months) and 24 cases (IR = 35.35 per 1000 person-months), respectively. As expected, the risk of multiple episodes occurring during the period of high transmission was 3.23 compared to the period of low transmission after adjusting for other model parameters (95% CI = [2.45-4.26], p = 0.000). Children with anemia were at high risk of having multiple episodes (OR = 1.6, 95% CI [1.12-2.30], p = 0.011). However, the risk of having 2 + episodes for anemic children was higher during the period of low transmission (RR = 1.67, 95% CI [1.15-2.42], p = 0.007) compared to the period of high transmission (RR = 1.58, 95% CI [1.09-2.29], p = 0.016). The trend indicated that anemic and underweight children were significantly associated with multiple malaria episodes during the period of low transmission (p < = 0.001)., Conclusion: Our results indicate that multiple episodes of malaria are significantly related to the nutritional status (anemia and underweight) of the child during the two transmission seasons and more pronounced during the dry season (period of low transmission). Further research including other malnutrition parameters will be needed to confirm our findings., Competing Interests: Competing interests The authors have declared that they have no competing interests.

Objectives: Following the scaling-up of malaria control strategies in Mali, understanding the changes in age-specific prevalence of infection and risk factors associated with remains necessary to determine new priorities to progress toward disease elimination. This study aimed to estimate the risk of clinical malaria using longitudinal data across three different transmission settings in Mali., Methods: Cohort-based longitudinal studies were performed from April 2018 to December 2022. Incidence of malaria was measured through community health center-based passive case detection. Generalized estimation equation model was used to assess risk factors for clinical malaria., Results: A total of 21,453 clinical presentations were reported from 4500 participants, mainly from July to November. Data shows a significant association between malaria episodes, sex, age group, season, and year. Women had lower risk, the risk of clinical episode increased with age up to 14 years then declined, and in both sites, the dry-season risk of clinical episode was significantly lower compared to the rainy season., Conclusion: Determining factors associated with the occurrence of clinical malaria across different ecological settings across the country could help in the development of new strategies aiming to accelerate malaria elimination in an area where malaria transmission remains intense., Competing Interests: The authors have no competing interests to declare., (© 2023 The Authors.)

In Mali, malaria vector control relies mostly on long-lasting insecticidal nets and indoor residual spraying (IRS). From 2008 to 2016, an IRS program was implemented in the district of Koulikoro. After a significant reduction in malaria indicators, IRS was stopped in 2016. This study evaluated the effect of IRS withdrawal on entomological parameters of malaria transmission and incidence in children aged 6 months to 10 years in the district of Koulikoro. Entomological parameters of malaria transmission during the last year of IRS implementation in 2016 were compared with those obtained 2 years after IRS withdrawal in 2018 in two villages of Koulikoro. Mosquito vectors were collected by mouth aspiration and pyrethrum spray catches in the villages to monitor these transmission parameters. A sharp increase (10.8 times higher) in vector abundance after IRS withdrawal was observed. The infection rate of Anopheles gambiae sensu lato to Plasmodium falciparum increased from zero during IRS implementation to 14.8% after IRS withdrawal. The average entomological inoculation rate, which was undetectable before, was 1.22 infected bites per person per month 2 years after IRS was withdrawn, and the cumulative malaria incidence rate observed after IRS was 4.12 times (15.2% versus 3.7%) higher than that observed in 2016 in the villages before IRS withdrawal. This study showed a resurgence of malaria transmission and incidence in the Koulikoro health district after IRS was withdrawn. Thus, to manage the potential consequences of malaria transmission resurgence, alternative approaches are needed when stopping successful malaria control interventions.

Distinct cytomegaloviruses (CMVs) are widely distributed across their mammalian hosts in a highly host species-restricted pattern. To date, evidence demonstrating this has been limited largely to PCR-based approaches targeting small, conserved genomic regions, and only a few complete genomes of isolated viruses representing distinct CMV species have been sequenced. We have now combined direct isolation of infectious viruses from tissues with complete genome sequencing to provide a view of CMV diversity in a wild animal population. We targeted Natal multimammate mice ( Mastomys natalensis ), which are common in sub-Saharan Africa, are known to carry a variety of zoonotic pathogens, and are regarded as the primary source of Lassa virus (LASV) spillover into humans. Using transformed epithelial cells prepared from M. natalensis kidneys, we isolated CMVs from the salivary gland tissue of 14 of 37 (36 %) animals from a field study site in Mali. Genome sequencing showed that these primary isolates represent three different M. natalensis CMVs (MnatCMVs: MnatCMV1, MnatCMV2 and MnatCMV3), with some animals carrying multiple MnatCMVs or multiple strains of a single MnatCMV presumably as a result of coinfection or superinfection. Including primary isolates and plaque-purified isolates, we sequenced and annotated the genomes of two MnatCMV1 strains (derived from sequencing 14 viruses), six MnatCMV2 strains (25 viruses) and ten MnatCMV3 strains (21 viruses), totalling 18 MnatCMV strains isolated as 60 infectious viruses. Phylogenetic analysis showed that these MnatCMVs group with other murid viruses in the genus Muromegalovirus (subfamily Betaherpesvirinae , family Orthoherpesviridae ), and that MnatCMV1 and MnatCMV2 are more closely related to each other than to MnatCMV3. The availability of MnatCMV isolates and the characterization of their genomes will serve as the prelude to the generation of a MnatCMV-based vaccine to target LASV in the M. natalensis reservoir.

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 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 = 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 = 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., Competing Interests: We declare any competing interests here. All authors read and approved the version submitted., (© 2023 The Authors.)

The Mali National Malaria Control Program (NMCP) recently established a phased set of goals for eliminating malaria in Mali by 2030. Over the past decade, the scale-up of NMCP-led malaria control interventions has led to considerable progress, as evidenced by multiple malariometric indicators. The West Africa International Center of Excellence in Malaria Research (WA-ICEMR) is a multidisciplinary research program that works closely with the NMCP and its partners to address critical research needs for malaria control. This coordinated effort includes assessing the effectiveness of control interventions based on key malaria research topics, including immune status, parasite genetic diversity, insecticide and drug resistance, diagnostic accuracy, malaria vector populations and biting behaviors, and vectorial capacity. Several signature accomplishments of the WA-ICEMR include identifying changing malaria age demographic profiles, testing innovative approaches to improve control strategies, and providing regular reporting on drug and insecticide resistance status. The NMCP and WA-ICEMR partnership between the WA-ICEMR and the NMCP offers a comprehensive research platform that informs the design and implementation of malaria prevention and control research programs. These efforts build local expertise and capacity for the next generation of malaria researchers and guide local policy, which is crucial in sustaining efforts toward eliminating malaria in West Africa.

This article highlights over a decade of signature achievements by the West Africa International Centers for Excellence in Malaria Research (WA-ICEMR) and its partners toward guiding malaria prevention and control strategies. Since 2010, the WA-ICEMR has performed longitudinal studies to monitor and assess malaria control interventions with respect to space-time patterns, vector transmission indicators, and drug resistance markers. These activities were facilitated and supported by the Mali National Malaria Control Program. Research activities included large-scale active and passive surveillance and expanded coverage of universal long-lasting insecticide-treated bed nets and seasonal malaria chemoprevention (SMC). The findings revealed substantial declines in malaria occurrence after the scale-up of control interventions in WA-ICEMR study sites. WA-ICEMR studies showed that SMC using sulfadoxine-pyrimethamine plus amodiaquine was highly effective in preventing malaria among children under 5 years of age. An alternative SMC regimen (dihydroartemisinin plus piperaquine) was shown to be potentially more effective and provided advantages for acceptability and compliance over the standard SMC regimen. Other findings discussed in this article include higher observed multiplicity of infection rates for malaria in historically high-endemic areas, continued antimalarial drug sensitivity to Plasmodium falciparum, high outdoor malaria transmission rates, and increased insecticide resistance over the past decade. The progress achieved by the WA-ICEMR and its partners highlights the critical need for maintaining current malaria control interventions while developing novel strategies to disrupt malaria transmission. Enhanced evaluation of these strategies through research partnerships is particularly needed in the wake of reported artemisinin resistance in Southeast Asia and East Africa.

Little is known about the temporal patterns of infection and transmission of Lassa virus (LASV) within its natural reservoir ( Mastomys natalensis ). Here, we characterize infection dynamics and transmissibility of a LASV isolate (Soromba-R) in adult lab-reared M. natalensis originating from Mali. The lab-reared M. natalenesis proved to be highly susceptible to LASV isolates from geographically distinct regions of West Africa via multiple routes of exposure, with 50% infectious doses of < 1 TCID 50 . Postinoculation, LASV Soromba-R established a systemic infection with no signs of clinical disease. Viral RNA was detected in all nine tissues examined with peak concentrations detected between days 7 and 14 postinfection within most organs. There was an overall trend toward clearance of virus within 40 days of infection in most organs. The exception is lung specimens, which retained positivity throughout the course of the 85-day study. Direct (contact) and indirect (fomite) transmission experiments demonstrated 40% of experimentally infected M. natalensis were capable of transmitting LASV to naïve animals, with peak transmissibility occurring between 28 and 42 days post-inoculation. No differences in patterns of infection or transmission were noted between male and female experimentally infected rodents. Adult lab-reared M. natalensis are highly susceptible to genetically distinct LASV strains developing a temporary asymptomatic infection associated with virus shedding resulting in contact and fomite transmission within a cohort., (Published by Oxford University Press on behalf of National Academy of Sciences 2022.)

Background: Over the past decade, three strategies have reduced severe malaria cases and deaths in endemic regions of Africa, Asia and the Americas, specifically: (1) artemisinin-based combination therapy (ACT); (2) insecticide-treated bed nets (ITNs); and, (3) intermittent preventive treatment with sulfadoxine-pyrimethamine in pregnancy (IPTp). The rationale for this study was to examine communities in Dangassa, Mali where, in 2015, two additional control strategies were implemented: ITN universal coverage and seasonal malaria chemoprevention (SMC) among children under 5 years old., Methods: This was a prospective study based on a rolling longitudinal cohort of 1401 subjects participating in bi-annual smear surveys for the prevalence of asymptomatic Plasmodium falciparum infection and continuous surveillance for the incidence of human disease (uncomplicated malaria), performed in the years from 2012 to 2020. Entomological collections were performed to examine the intensity of transmission based on pyrethroid spray catches, human landing catches and enzyme-linked immunosorbent assay (ELISA) testing for circumsporozoite antigen., Results: A total of 1401 participants of all ages were enrolled in the study in 2012 after random sampling of households from the community census list. Prevalence of infection was extremely high in Dangassa, varying from 9.5 to 62.8% at the start of the rainy season and from 15.1 to 66.7% at the end of the rainy season. Likewise, the number of vectors per house, biting rates, sporozoites rates, and entomological inoculation rates (EIRs) were substantially greater in Dangassa., Discussion: The findings for this study are consistent with the progressive implementation of effective malaria control strategies in Dangassa. At baseline (2012-2014), prevalence of P. falciparum was above 60% followed by a significant year-to-year decease starting in 2015. Incidence of uncomplicated infection was greater among children  < 5 years old, while asymptomatic infection was more frequent among the 5-14 years old. A significant decrease in EIR was also observed from 2015 to 2020. Likewise, vector density, sporozoite rates, and EIRs decreased substantially during the study period., Conclusion: Efficient implementation of two main malaria prevention strategies in Dangassa substantially contribute to a reduction of both asymptomatic and symptomatic malaria from 2015 to 2020., (© 2022. The Author(s).)

Seasonal malaria chemoprevention (SMC) was adopted in Mali in 2012 for preventing malaria in children younger than 5 years. Although this strategy has been highly effective in reducing childhood malaria, an uptick in malaria occurrence has occurred in children 5 to 15 years of age. This study aimed to investigate the feasibility of providing SMC to older children. A cohort of 350 children age 5 to 14 years were monitored during the 2019 transmission season in Dangassa, Mali. The intervention group received five monthly rounds of sulfadoxine-pyrimethamine plus amodiaquine, whereas the control group consisted of untreated children. Community acceptance for extending SMC was assessed during the final round. Logistic regression models were applied to compare the risk of Plasmodium falciparum malaria infection, anemia, and fever between the intervention and control groups. Kaplan-Meier survival analyses were used to compare the time to P. falciparum parasitemia infection between the groups. The community acceptance rate was 96.5% (139 of 144). Significant declines were observed in the prevalence of P. falciparum parasitemia (adjusted odds ratio, 0.22; 95% CI, 0.11-0.42) and anemia (adjusted odds ratio, 0.15; 95% CI, 0.07-0.28) in the intervention group compared with the control group. The cumulative incidence of P. falciparum infections was significantly greater (75.4%, 104 of 138) in the control group compared with the intervention group (40.7%, 61 of 143, P = 0.001). This study reveals that expanding SMC to older children is likely feasible, has high community acceptance, and is in reducing uncomplicated malaria and anemia in older children.

Mali had 2 reported introductions of Ebola virus (EBOV) during the 2013-2016 West Africa epidemic. Previously, no evidence for EBOV circulation was reported in Mali. We performed an EBOV serosurvey study in southern Mali. We found low seroprevalence in the population, indicating local exposure to EBOV or closely related ebola viruses.

Background: Insecticide-based vector control is responsible for reducing malaria mortality and morbidity. Its success depends on a better knowledge of the vector, its distribution, and resistance status to the insecticides used. In this paper, we assessed Anopheles gambiae sensu lato (A gambiae s.l.) population resistance to pyrethroids in different ecological settings., Methods: The World Health Organization standard bioassay test was used to assess F0A gambiae s.l. susceptibility to pyrethroids. Biochemical Synergist assays were conducted with piperonyl butoxide (PBO), S,S,S-tributyl phosphotritioate, and diethyl maleate. L1014F, L1014S, and N1575Y knockdown resistance (kdr) mutations were investigated using TaqMan genotyping., Results: Anopheles gambiae sensu lato was composed of Anopheles arabienisis, Anopheles coluzzii, and A gambiae in all study sites. Anopheles gambiae sensu lato showed a strong phenotypic resistance to deltamethrin and permethrin in all sites (13% to 41% mortality). In many sites, pre-exposure to synergists partially improved the mortality rate suggesting the presence of detoxifying enzymes. The 3 kdr (L1014F, L1014S, and N1575Y) mutations were found, with a predominance of L1014F, in all species., Conclusions: Multiple resistance mechanisms to pyrethroids were observed in A gambiae s.l. in Mali. The PBO provided a better partial restoration of susceptibility to pyrethroids, suggesting that the efficacy of long-lasting insecticidal nets may be improved with PBO., (© World Health Organization, 2021. All rights reserved. The World Health Organization has granted the Publisher permission for the reproduction of this article.)

Malaria vector control in Mali relies heavily on the use of long-lasting insecticidal nets (LLINs) and indoor residual spraying (IRS) in selected districts. As part of strengthening vector control strategies in Koulikoro district, the National Malaria Control Programme (NMCP) through the support from the US President's Malaria Initiative (PMI) has strategically driven the implementation of IRS, with the LLINs coverage also rising from 93.3% and 98.2%. Due to the increased reports of vector resistance to both pyrethroid and carbamates, there was a campaign for the use of pirimiphos-methyl, an organophosphate at Koulikoro between 2015 and 2016. In this study, the effect of IRS on malaria transmission was assessed, by comparing some key entomological indices between Koulikoro, where IRS was implemented and its neighboring district, Banamba that has never received IRS as vector control intervention. The study was conducted in two villages of each district (Koulikoro and Banamba). Pyrethrum spray catches and entry window trapping were used to collect mosquitoes on a monthly basis. WHO tube tests were carried out to assess mosquito susceptibility to insecticides. Mosquitoes were identified to species level by PCR and their infection to P. falciparum was detected by Enzyme Linked-Immuno-Sorbent Assay (ELISA). Of the 527 specimens identified, An. coluzzii was the most frequent species (95%) followed by An. gambiae (4%) and An. arabiensis (1%). Its density was rainfall dependent in the no-IRS area, and almost independent in the IRS area. The infection rate (IR) in the no-IRS area was 0.96%, while it was null in the IRS area. In the no-IRS area, the entomological inoculation rate (EIR) was 0.21 infective bites /person month with a peak in September. High resistance to pyrethroids and carbamates and susceptibility to organophosphates was observed at all sites. The introduction of pirimiphos-methyl based IRS for vector control resulted in a significant decrease in malaria transmission. An. gambiae s.l., the main malaria vector in the area, was resistant to pyrethroids and carbamates but remained susceptible to the organophosphate pirimiphos-methyl., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Mastomys natalensis are a ubiquitous and often dominant rodent across sub-Saharan Africa. Importantly, they are a natural reservoir for microbial pathogens including Lassa virus (LASV), the etiological agent of Lassa fever in humans. Lassa-infected rodents have been documented across West Africa and coincide with regions where annual outbreaks occur. Zoonotic transmission to humans most often occurs directly from infected rodents. Little is known about LASV infection kinetics and transmissibility in M. natalensis , primarily due to available animals. Here, we describe the establishment of a laboratory breeding colony of genetically confirmed M. natalensis from wild-captured rodents. This colony will provide a convenient source of animals to study LASV and other emerging pathogens that utilize M. natalensis in their enzootic lifecycles.

Background: Implementation and upscale of effective malaria vector control strategies necessitates understanding the multi-factorial aspects of transmission patterns. The primary aims of this study are to determine the vector composition, biting rates, trophic preference, and the overall importance of distinguishing outdoor versus indoor malaria transmission through a study at two communities in rural Mali., Methods: Mosquito collection was carried out between July 2012 and June 2016 at two rural Mali communities (Dangassa and Koïla Bamanan) using pyrethrum spray-catch and human landing catch approaches at both indoor and outdoor locations. Species of Anopheles gambiae complex were identified by polymerase chain reaction (PCR). Enzyme-Linked -Immuno-Sorbent Assay (ELISA) were used to determine the origin of mosquito blood meals and presence of Plasmodium falciparum sporozoite infections., Results: A total of 11,237 An. gambiae sensu lato (s.l.) were collected during the study period (5239 and 5998 from the Dangassa and Koïla Bamanan sites, respectively). Of the 679 identified by PCR in Dangassa, Anopheles coluzzii was the predominant species with 91.4% of the catch followed by An. gambiae (8.0%) and Anopheles arabiensis (0.6%). At the same time in Koïla Bamanan, of the 623 An. gambiae s.l., An. coluzzii accounted for 99% of the catch, An. arabiensis 0.8% and An. gambiae 0.2%. Human Blood Index (HBI) measures were significantly higher in Dangassa (79.4%; 95% Bayesian credible interval (BCI) [77.4, 81.4]) than in Koïla Bamanan (15.9%; 95% BCI [14.7, 17.1]). The human biting rates were higher during the second half of the night at both sites. In Dangassa, the sporozoite rate was comparable between outdoor and indoor mosquito collections. For outdoor collections, the sporozoite positive rate was 3.6% (95% BCI [2.1-4.3]) and indoor collections were 3.1% (95% BCI [2.4-5.0]). In Koïla Bamanan, the sporozoite rate was higher indoors at 4.3% (95% BCI [2.7-6.3]) compared with outdoors at 2.4% (95% BCI [1.1-4.2]). In Dangassa, corrected entomological inoculation rates (cEIRs) using HBI were 13.74 [95% BCI 9.21-19.14] infective bites/person/month (ib/p/m) at indoor, and 18.66 [95% BCI 12.55-25.81] ib/p/m at outdoor. For Koïla Bamanan, cEIRs were 1.57 [95% BCI 2.34-2.72] ib/p/m and 0.94 [95% BCI 0.43-1.64] ib/p/m for indoor and outdoor, respectively. EIRs were significantly higher at the Dangassa site than the Koïla Bamanan site., Conclusion: The findings in this work may indicate the occurrence of active, outdoor residual malaria transmission is comparable to indoor transmission in some geographic settings. The high outdoor transmission patterns observed here highlight the need for additional strategies to combat outdoor malaria transmission to complement traditional indoor preventive approaches such as long-lasting insecticidal nets (LLINs) and indoor residual spraying (IRS) which typically focus on resting mosquitoes.

Laboratory-controlled physiological data for the multimammate rat ( Mastomys natalensis ) are scarce, despite this species being a known reservoir and vector for zoonotic viruses, including the highly pathogenic Lassa virus, as well as other arenaviruses and many species of bacteria. For this reason, M. natalensis is an important rodent for the study of host-virus interactions within laboratory settings. Herein, we provide basic blood parameters for age- and sex-distributed animals in regards to blood counts, cell phenotypes and serum chemistry of a specific-pathogen-monitored M. natalensis breeding colony, to facilitate scientific insight into this important and widespread rodent species.

The multimammate mouse (Mastomys natalensis; M. natalensis) serves as the main reservoir for the zoonotic arenavirus Lassa virus (LASV), and this has led to considerable investigation into the distribution of LASV and other related arenaviruses in this host species. In contrast to the situation with arenaviruses, the presence of other viruses in M. natalensis remains largely unexplored. In this study, herpesviruses and polyomaviruses were identified and partially characterized by PCR methods, sequencing, and phylogenetic analysis. In tissues sampled from M. natalensis populations in Côte d'Ivoire and Mali, six new DNA viruses (four betaherpesviruses, one gammaherpesvirus and one polyomavirus) were identified. Phylogenetic analysis based on glycoprotein B amino acid sequences showed that the herpesviruses clustered with cytomegaloviruses and rhadinoviruses of multiple rodent species. The complete circular genome of the newly identified polyomavirus was amplified by PCR. Amino acid sequence analysis of the large T antigen or VP1 showed that this virus clustered with a known polyomavirus from a house mouse (species Mus musculus polyomavirus 1). These two polyomaviruses form a clade with other rodent polyomaviruses, and the newly identified virus represents the third known polyomavirus of M. natalensis. This study represents the first identification of herpesviruses and the discovery of a novel polyomavirus in M. natalensis. In contrast to arenaviruses, we anticipate that these newly identified viruses represent a low zoonotic risk due to the normally highly restricted specificity of members of these two DNA virus families to their individual mammalian host species.

Mali aims to reach the pre-elimination stage of malaria by the next decade. This study used functional regression models to predict the incidence of malaria as a function of past meteorological patterns to better prevent and to act proactively against impending malaria outbreaks. All data were collected over a five-year period (2012-2017) from 1400 persons who sought treatment at Dangassa's community health center. Rainfall, temperature, humidity, and wind speed variables were collected. Functional Generalized Spectral Additive Model (FGSAM), Functional Generalized Linear Model (FGLM), and Functional Generalized Kernel Additive Model (FGKAM) were used to predict malaria incidence as a function of the pattern of meteorological indicators over a continuum of the 18 weeks preceding the week of interest. Their respective outcomes were compared in terms of predictive abilities. The results showed that (1) the highest malaria incidence rate occurred in the village 10 to 12 weeks after we observed a pattern of air humidity levels >65%, combined with two or more consecutive rain episodes and a mean wind speed <1.8 m/s; (2) among the three models, the FGLM obtained the best results in terms of prediction; and (3) FGSAM was shown to be a good compromise between FGLM and FGKAM in terms of flexibility and simplicity. The models showed that some meteorological conditions may provide a basis for detection of future outbreaks of malaria. The models developed in this paper are useful for implementing preventive strategies using past meteorological and past malaria incidence.

Background: Koulikoro Health District is one of three districts of Mali where the indoor residual spray (IRS) has been implemented from 2008 to 2016. With widespread of resistance to pyrethroid, IRS was shifted from pyrethroid to pirimiphos-methyl from 2014 to 2016. The objective of this study was to assess the added value of IRS to LLINs on the prevalence of parasitaemia and malaria incidence among children under 10 years old., Methods: A comparative study was carried out to assess the effects of pirimiphos-methyl based IRS on malaria prevalence and incidence among children from 6 months to 10 years old in selected pyrethroid resistance villages of two health districts in Mali: one where IRS was implemented in combination with LLINs (intervention area) and one with LLINs-only (control area). Two cross-sectional surveys were carried out at the beginning (June) and end of the rainy season (October) to assess seasonal changes in malaria parasitaemia by microscopy. A passive detection case (PCD) was set-up in each study village for 9 months to estimate the incidence of malaria using RDT., Results: There was an increase of 220% in malaria prevalence from June to October in the control area (14% to 42%) versus only 53% in the IRS area (9.2% to 13.2%). Thus, the proportional rise in malaria prevalence from the dry to the rainy season in 2016 was 4-times greater in the control area compared to the IRS area. The overall malaria incidence rate was 2.7 per 100 person-months in the IRS area compared with 6.8 per 100 person-month in the control areas. The Log-rank test of Kaplan-Meier survival analysis showed that children living in IRS area remain much longer free from malaria (Hazard ratio (HR) = 0.45, CI 95% 0.37-0.54) than children of the control area (P < 0.0001)., Conclusions: IRS using pirimiphos-methyl has been successful in reducing substantially both the prevalence and the incidence of malaria in children under 10 years old in the area of pyrethroid resistance of Koulikoro, Mali. Pirimiphos-methyl is a better alternative than pyrethroids for IRS in areas with widespread of pyrethroid resistance.

Malaria transmission largely depends on environmental, climatic, and hydrological conditions. In Mali, malaria epidemiological patterns are nested within three ecological zones. This study aimed at assessing the relationship between those conditions and the incidence of malaria in Dangassa and Koila, Mali. Malaria data was collected through passive case detection at community health facilities of each study site from June 2015 to January 2017. Climate and environmental data were obtained over the same time period from the Goddard Earth Sciences (Giovanni) platform and hydrological data from Mali hydraulic services. A generalized additive model was used to determine the lagged time between each principal component analysis derived component and the incidence of malaria cases, and also used to analyze the relationship between malaria and the lagged components in a multivariate approach. Malaria transmission patterns were bimodal at both sites, but peak and lull periods were longer lasting for Koila study site. Temperatures were associated with malaria incidence in both sites. In Dangassa, the wind speed ( p = 0.005) and river heights ( p = 0.010) contributed to increasing malaria incidence, in contrast to Koila, where it was humidity ( p < 0.001) and vegetation ( p = 0.004). The relationships between environmental factors and malaria incidence differed between the two settings, implying different malaria dynamics and adjustments in the conception and plan of interventions.

Background: The long-lasting insecticidal nets (LLINs) and indoor residual spraying of insecticide (IRS) are major malaria vector control strategies in Mali. The success of control strategies depends on a better understanding of the status of malaria vectors with respect to the insecticides used. In this study we evaluate the level of resistance of Anopheles gambiae (sensu lato) to bendiocarb and the molecular mechanism that underlies it., Methods: Larvae of An. gambiae (s.l.) were collected from breeding habitats encountered in the three study sites and bioassayed with bendiocarb. The ace-1 target site substitution G119S was genotyped using a TaqMan assay., Results: The three species of the An. gambiae complex in Mali, i.e. An. arabiensis, An. coluzzii and An. gambiae (s.s.) were found in sympatry in the three surveyed localities with different frequencies. We observed a resistance and suspicious resistance of the three species to bendiocarb with a mortality rate ranging from 37% to 86%. The allelic frequency of the G119S mutation was higher in An. gambiae (s.s.) compared to the other two species; 42.86%, 25.61% and 16.67% respectively in Dangassa, Koula, and Karadié. The allelic frequency of G119S in An. coluzzii ranged from 4.5% to 8.33% and from 1.43% to 21.15% for An. arabiensis. After exposure to bendiocarb, the G119S mutation was found only in survivors. The survival of Anopheles gambiae (s.l) populations from the three surveyed localities was associated with the presence of the mutation., Conclusions: The study highlights the implication of G119S mutation in bendiocarb resistance in An. gambiae (s.s.), An. arabiensis and An. coluzzii populations from the three surveyed localities.

Background: Seasonal malaria chemoprevention (SMC) is a new strategy to prevent malaria in children under 5 years old. It has been recommended by the World Health Organization since 2012 in malaria-endemic areas with seasonal transmission. This study aimed to assess the changes in malaria indicators through two consecutive years of SMC routine implementation in children under 5 years old in Dangassa, where malaria is endemic with a long and high transmission season., Methods: From 2012 to 2016, a cohort study was conducted in Dangassa village. The study team based in the village followed all malaria clinical cases in children under 5 years old at the community health centre. During the study, SMC was routinely implemented in collaboration with the National Malaria Control Programme. The Cox regression model was used in order to compare malaria risk during the study., Results: The Cox regression model showed a significant reduction in malaria clinical incidence, both in 2015 (HR = 0.27 (0.18-0.40), 95% CI) and in 2016 (HR = 0.23 (0.15-0.35), 95% CI) of SMC implementation compared to October 2013. Gametocyte and fever prevalence was lower between September and October during SMC implementation (2015 and 2016) compared to the same period before SMC implementation (2013-2014). A slight increase of malaria incidence was observed in December at the end of SMC implementation., Conclusion: SMC has significantly reduced both malaria incidence and gametocyte prevalence and improved haemoglobin levels in children under 5 years old after 2 years of routine implementation.

Background: Because clustering of Plasmodium falciparum infection had been noted previously, the clustering of infection was examined at four field sites in West Africa: Dangassa and Dioro in Mali, Gambissara in The Gambia and Madina Fall in Senegal., Methods: Clustering of infection was defined by the percent of persons with positive slides for asexual P. falciparum sleeping in a house which had been geopositioned. Data from each site were then tested for spatial, temporal and spatio-temporal clustering in relation to the prevalence of infection from smear surveys., Results: These studies suggest that clustering of P. falciparum infection also affects the effectiveness of control interventions. For example, the clustering of infection in Madina Fall disappeared in 2014-2016 after vector control eliminated the only breeding site in 2013. In contrast, the temporal clustering of infection in Dioro (rainy season of 2014, dry season of 2015) was consistent with the loss of funding for Dioro in the second quarter of 2014 and disappeared when funds again became available in late 2015. The clustering of infection in rural (western) areas of Gambissara was consistent with known rural-urban differences in the prevalence of infection and with the thatched roofs, open eaves and mud walls of houses in rural Gambissara. In contrast, the most intense transmission was in Dangassa, where the only encouraging observation was a lower prevalence of infection in the dry season. Taken together, these results suggest: (a) the transmission of infection was stopped in Madina Fall by eliminating the only known breeding site, (b) the prevalence of infection was reduced in Dioro after financial support became available again for malaria control in the second half of 2015, (c) improvements in housing should improve malaria control by reducing the number of vectors in rural communities such as western Gambissara, and (d) beginning malaria control during the dry season may reduce transmission in hyperendemic areas such as Dangassa., Conclusions: From a conceptual perspective, testing for spatial, temporal and spatio-temporal clustering based on epidemiologic data permits the generation of hypotheses for the clustering observed and the testing of candidate interventions to confirm or refute those hypotheses.

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&#95;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&#95;51I-59R-108N pyrimethamine-resistance genotype was 14.1% and 19.6%, respectively in Dangassa and Nioro-du-Sahel. Mutations in the Pfdhps&#95;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&#95;N86Y mutation was identified in only three samples (two in Dangassa and one in Nioro-du-Sahel). The lumefantrine-reduced susceptibility Pfmdr1&#95;Y184F mutation was found in 39.9% and 48.2% of samples in Dangassa and Nioro-du-Sahel, respectively. One piperaquine-resistance Exo&#95;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.

Rift Valley fever virus (RVFV) outbreaks have considerable impact on human and animal health. Here, we are reporting a serosurvey of cattle from all regions of Mali. These demonstrated that few had been exposed to RVFV from 2005 to 2014. Recent outbreaks of RVF in Niger and a single human case in Mali provide justification for further entomological and ecological studies of this virus.