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Background In 2004, Mali implemented mass drug administration (MDA) aimed at controlling schistosomiasis and soil-transmitted helminths. Despite several rounds of MDA, the health district of Bankass reported low coverage (64.8%) for praziquantel and albendazole in 2017, meaning that this district was still facing challenges in accomplishing the targeted 75% coverage. This study aimed to explore the barriers and gaps that hindered MDA implementation in Bankass. Methods A cross-sectional study was performed. Questionnaires were administrated to all school-aged children in randomly selected villages. Technical directors of community health centers and community drug distributors in the selected villages were included in the interviews. Results A total of 2128 children and 52 health workers were interviewed. Coverage rates were 93.51% (1990/2128) for praziquantel and 95.25% (2027/2128) for albendazole. Among the untreated children, 31.63% (31/98) reported being unaware of the campaign and 26.53% (26/98) were unable to reach the distribution points. Most of the health workers suggested increasing incentives. Conclusion The data showed satisfactory coverage >90%, in contrast with lower rates initially reported by the district health information system. These results raise concerns about the reliability of programmatic data and highlight the importance of population-based surveys for the evaluation of control interventions.

Background In Mali, cutaneous leishmaniasis (CL) and filariasis are co-endemic. Previous studies in animal models of infection have shown that sand fly saliva enhance infectivity of Leishmania parasites in naïve hosts while saliva-specific adaptive immune responses may protect against cutaneous and visceral leishmaniasis. In contrast, the human immune response to Phlebotomus duboscqi (Pd) saliva, the principal sand fly vector in Mali, was found to be dichotomously polarized with some individuals having a Th1-dominated response and others having a Th2-biased response. We hypothesized that co-infection with filarial parasites may be an underlying factor that modulates the immune response to Pd saliva in endemic regions. Methodology/Principal findings To understand which cell types may be responsible for polarizing human responses to sand fly saliva, we investigated the effect of salivary glands (SG) of Pd on human monocytes. To this end, elutriated monocytes were cultured in vitro, alone, or with SG, microfilariae antigen (MF ag) of Brugia malayi, or LPS, a positive control. The mRNA expression of genes involved in inflammatory or regulatory responses was then measured as were cytokines and chemokines associated with these responses. Monocytes of individuals who were not exposed to sand fly bites (mainly North American controls) significantly upregulated the production of IL-6 and CCL4; cytokines that enhance leishmania parasite establishment, in response to SG from Pd or other vector species. This selective inflammatory response was lost in individuals that were exposed to sand fly bites which was not changed by co-infection with filarial parasites. Furthermore, infection with filarial parasites resulted in upregulation of CCL22, a type-2 associated chemokine, both at the mRNA levels and by its observed effect on the frequency of recruited monocytes. Conclusions/Significance Together, our data suggest that SG or recombinant salivary proteins from Pd alter human monocyte function by upregulating selective inflammatory cytokines., Author summary In Mali, cutaneous leishmaniasis (CL) and filariasis are co-endemic. We hypothesized that co-infection with helminth parasites may modulate the immune response to saliva of the CL vector Phlebotomus duboscqi (Pd). Hence, we investigated the effect of Pd salivary glands (SG) on human monocytes in subjects exposed or unexposed to sand fly bites in the context of a concomitant filaria infection. Monocytes of unexposed individuals selectively upregulated the production of IL-6 and CCL4 in response to SG from Pd or other vector species. In contrast, monocytes of individuals exposed to sand fly bites lost their responsiveness to SG, microfilariae antigen and LPS, irrespective of co-infection with filaria. Nevertheless, infection with filaria significantly upreguled the frequency of CCL22+monocytes, IL-10+mDCs and regulatory T cells. Together, our data suggest that repeated exposure to Pd saliva alters human monocyte function towards a tolerized phenotype while co-infection with filaria favors a Leishmania-promoting Th2/regulatory response.

Background In Mali, nomadic populations are spread over one third of the territory. Their lifestyle, characterized by constant mobility, excludes them from, or at best places them at the edge of, health delivery services. This study aimed to describe nomadic populations’ characteristics, determine their perception on the current health services, and identify issues associated with community-based health interventions. Methods To develop a better health policy and strategic approaches adapted to nomadic populations, we conducted a cross-sectional study in the region of Timbuktu to describe the difficulties in accessing health services. The study consisted in administering questionnaires to community members in the communes of Ber and Gossi, in the Timbuktu region, to understand their perceptions of health services delivery in their settings. Results We interviewed 520 individuals, all members of the nomadic communities of the two study communes. Their median age was 38 years old with extremes ranging from 18 to 86 years old. Their main activities were livestock breeding (27%), housekeeping (26.4%), local trading (11%), farming (6%) and artisans (5.5%). The average distance to the local health center was 40.94 km and 23.19 km respectively in Gossi and Ber. In terms of barriers to access to health care, participants complained mainly about the transportation options (79.4%), the quality of provided services (39.2%) and the high cost of available health services (35.7%). Additionally, more than a quarter of our participants stated that they would not allow themselves to be examined by a health care worker of the opposite gender. Conclusion This study shows that nomadic populations do not have access to community-based health interventions. A number of factors were revealed to be important barriers per these communities’ perception including the quality of services, poverty, lifestyle, gender and current health policy strategies in the region. To be successful, future interventions should take these factors into account by adapting policies and methods.

Background Ivermectin-based onchocerciasis elimination, reported in 2009–2012, for Bakoye and Falémé, Mali, supported policy-shifting from morbidity control to elimination of transmission (EOT). These foci are coendemic with lymphatic filariasis (LF). In 2007–2016 mass ivermectin plus albendazole administration was implemented. We report Ov16 (onchocerciasis) and Wb123 (LF) seroprevalence after 24–25 years of treatment to determine if onchocerciasis EOT and LF elimination as a public health problem (EPHP) have been achieved. Methods The SD Bioline Onchocerciasis/LF Ig[immunoglobulin]G4 biplex rapid diagnostic test (RDT) was used in 2186 children aged 3–10 years in 13 villages (plus 2 hamlets) in Bakoye and in 2270 children in 15 villages (plus 1 hamlet) in Falémé. In Bakoye, all-age serosurveys were conducted in 3 historically hyperendemic villages (1867 individuals aged 3 -78 years). Results In Bakoye, IgG4 seropositivity was 0.27% (95% confidence interval [CI] = .13%–.60%) for both Ov16 and Wb123 antigens. In Falémé, Ov16 and Wb123 seroprevalence was 0.04% (95% CI = .01%–.25%) and 0.09% (95% CI = .02%–.32%), respectively. Ov16-seropositive children were from historically meso/hyperendemic villages. Ov16 positivity was, Ov16–Wb123 (onchocerciasis– lymphatic filariasis [LF]) seroprevalence was measured in children aged ≤10 years to determine if onchocerciasis and elimination was achieved in 2 coendemic foci (Bakoye and Falémé) in Mali under long-term ivermectin treatment, which stopped in 2016. These goals seem to have been achieved.

Background Access to community-based healthcare services is one of the key characteristics in successful public health policy. In Mali, community-based interventions do not reach nomadic communities, remote and hard-to-reach areas. Methods: In order to determine a better healthcare strategy for these nomadic populations, we conducted a cross-sectional survey in the administrative region of Timbuktu in Mali using the administration of questionnaires to community members. Results: A total of 520 individuals from two nomadic communities, Gossi and Ber, were included in the questionnaire survey. Inhabitants of the two nomadic communities were livestock breeders (27%), housekeepers (26.4%), local traders (11%), farmers (6 %) and artisans (5.5%). The median age of the study participants was 38 years (18-86 years). The participants from Gossi and Ber lived at a mean distance of 40.94 km and 23.19 km from the closest health center, respectively. The major complaints with respect to accessing healthcare were cost (35.7%), distance to the health center (46.2%), quality of the provided services (39.2 %) and means of transportation (79.4%). More than 25% of the participants from the community stated that they will never accept to being examined by a health care provider of the opposite gender. Conclusion It appears from the interviews results that these nomadic populations have health needs not presently covered by the current health delivery system. Tackling the method and organization of health care delivery by adapting them to the local lifestyle, culture and values could lead to significant improvements health outcomes.

Background Lymphedema is a public health problem in countries with lymphatic filariasis (LF) including Mali. We studied the epidemiology and clinical presentation of lymphedema in three previously LF-endemic health districts of Mali after at least five consecutive rounds of mass drug administration (MDA) with albendazole and ivermectin. Methods From 2016 to 2018, we used passive and active case finding methods to identify lymphedema cases in three health districts with high pre-MDA LF prevalence: Kolondieba (66%), Bougouni (44%) and Kolokani (34%). Results Three hundred and thirty nine cases of lymphedema were identified, 235 (69.32%) through active case finding. Their median age was 56 years (range 2–90) and 286 (84.36%) were women. Lymphedema was reported in 226 (78.5%) people aged 41 years and older compared to 73 (21.5%) people below the age of 41 years (Chi2 = 17.28, df = 5, p = 0.004). One hundred and seventy five cases of lymphedema were found in Kolondieba (66 per 100,000 people), 116 in Bougouni (19 per 100,000) and 48 in Kolokani (16 per 100,000). Stage III lymphedema was observed in 131 (38.64%), stage II in 108 (31.86%), stage IV in 46 (13.57%), stage I in 23 (6.78%), stage V in 21 (6.19%) and stage VI in ten (2.95%). In the three study districts, lymphedema affected the legs in 281 (82.89%), the arms in 42 (12.39%) and both in 16 (4.72%) (Chi2 = 13.63, p = 0.008). Conclusion Health districts in Mali with the highest pre-MDA LF prevalences had the highest prevalence of lymphedema. Efforts to actively identify lymphedema cases should be scaled up in previous LF-endemic areas, and should be supplemented by a morbidity management and disability prevention plan at the peripheral health system level.

Background In Mali, the burden of epilepsy is underestimated due to socio-cultural barriers that keep most people with epilepsy out of the local health facilities. The objective of this study was to evaluate the performance of trained community health workers (CHWs) in identifying epilepsy cases (active case detection) as compared to the passive cases detection (PCD) during outpatient visits at the community health centers in the health districts (HDs) of Kolokani, Kayes, Kenieba, Sikasso, Kadiolo, and Tominian. Methods A two-phase cross-sectional study was conducted from February to December 2019. In phase 1, trained CHWs conducted a census in 1017 villages organized into 174 community health centers which are part of the six study HDs to identify suspected epilepsy cases (SEC). Investigators used a modified epilepsy screening questionnaire from a validated standard questionnaire with the following three (3) questions: (i) Does or did the subject have a loss of consciousness and/or a loss of urine and/or drooling? (ii) Does or did the subject have an uncontrollable shake or abnormal movements of limb(s) (convulsions), with sudden onset and duration of a few minutes? (iii) Has or had the subject ever been told that he or she has epilepsy? During phase 2, neurologists confirmed the supposedly SEC (censed by the CHWs) in the first 30 villages with the highest number of SEC in each HD that were reported during phase 1. Results Of a total of 4830 SEC, 422 (10%) were identified by PCD during routine outpatient visits and 4408 (90%) through the active case detection (ACD) using the trained CHWs. The majority of SEC reported by the CHWs (PCD) were confirmed by neurologists, i.e. 82.9% (1645/1985). Phenobarbital was available in only 26 (14.9%) of the 174 surveyed health centers. Confirmed cases of epilepsy were reported in all the 174 health centers with prevalence varying from 91/100,00 to 285/100,000. Conclusion Active case detection of epilepsy using trained CHWs is an effective approach for epidemiological studies of epilepsy in the community settings as compared to the passive approach.

Background Filariasis and leishmaniasis are two neglected tropical diseases in Mali. Due to distribution and associated clinical features, both diseases are of concern to public health. The goal of this study was to determine the prevalence of co-infection with filarial (Wuchereria bancrofti and Mansonella perstans) and Leishmania major parasites in two ecologically distinct areas of Mali, the Kolokani district (villages of Tieneguebougou and Bougoudiana) in North Sudan Savanna area, and the district of Kolondieba (village of Boundioba) in the South Sudan Savanna area. Methods The prevalence of co-infection (filarial and Leishmania) was measured based on (i) Mansonella perstans microfilaremia count and/or filariasis immunochromatographic test (ICT) for Wuchereria bancrofti-specific circulating antigen, and (ii) the prevalence of delayed type hypersensitivity (DTH) responses to Leishmania measured by leishmanin skin test (LST). Results In this study, a total of 930 volunteers between the age of 18 and 65 were included from the two endemic areas of Kolokani and Kolondieba. In general, in both areas, filarial infection was more prevalent than Leishmania infection with an overall prevalence of 15.27% (142/930) including 8.7% (81/930) for Mansonella perstans and 8% (74/930) for Wuchereria bancrofti-specific circulating antigen. The prevalence of Leishmania major infection was 7.7% (72/930) and was significantly higher in Tieneguebougou and Bougoudiana (15.05%; 64/425) than in Boundioba (2.04%; 8/505) (χ2 = 58.66, P

After seven annual rounds of mass drug administration (MDA) in six Malian villages highly endemic for Wuchereria bancrofti (overall prevalence rate of 42.7%), treatment was discontinued in 2008. Surveillance was performed over the ensuing 5 years to detect recrudescence. Circulating filarial antigen (CFA) was measured using immunochromatographic card tests (ICT) and Og4C3 ELISA in 6–7 year-olds. Antibody to the W. bancrofti infective larval stage (L3) antigen, Wb123, was tested in the same population in 2012. Microfilaraemia was assessed in ICT-positive subjects. Anopheles gambiae complex specimens were collected monthly using human landing catch (HLC) and pyrethrum spray catch (PSC). Anopheles gambiae complex infection with W. bancrofti was determined by dissection and reverse transcriptase polymerase chain reaction (RT-PCR) of mosquito pools. Annual CFA prevalence rates using ICT in children increased over time from 0% (0/289) in 2009 to 2.7% (8/301) in 2011, 3.9% (11/285) in 2012 and 4.5% (14/309) in 2013 (trend χ 2 = 11.85, df =3, P = 0.0006). Wb123 antibody positivity rates in 2013 were similar to the CFA prevalence by ELISA (5/285). Although two W. bancrofti-infected Anopheles were observed by dissection among 12,951 mosquitoes collected by HLC, none had L3 larvae when tested by L3-specific RT-PCR. No positive pools were detected among the mosquitoes collected by pyrethrum spray catch. Whereas ICT in 6–7 year-olds was the major surveillance tool, ICT positivity was also assessed in older children and adults (8–65 years old). CFA prevalence decreased in this group from 4.9% (39/800) to 3.5% (28/795) and 2.8% (50/1,812) in 2009, 2011 and 2012, respectively (trend χ 2 = 7.361, df =2, P = 0.0067). Some ICT-positive individuals were microfilaraemic in 2009 [2.6% (1/39)] and 2011 [8.3% (3/36)], but none were positive in 2012 or 2013. Although ICT rates in children increased over the 5-year surveillance period, the decrease in ICT prevalence in the older group suggests a reduction in transmission intensity. This was consistent with the failure to detect infective mosquitoes or microfilaraemia. The threshold of ICT positivity in children may need to be re-assessed and other adjunct surveillance tools considered.

Historically the western sahelian dry regions of Mali are known to be highly endemic for cutaneous leishmaniasis (CL) caused by Leishmania major, while cases are rarely reported from the Southern savanna forest of the country. Here, we report baseline prevalence of CL infection in 3 ecologically distinct districts of Mali (dry sahelian, north savanna and southern savanna forest areas). We screened 195 to 250 subjects from 50 to 60 randomly selected households in each of the 6 villages (four from the western sahelian district of Diema in Kayes region, one from the central district of Kolokani and one from the southern savanna district of Kolodieba, region of Sikasso). The screening consisted of: 1] A Leishmanin Skin Test (LST) for detection of exposure to Leishmania parasites; 2] clinical examination of suspected lesions, followed by validation with PCR and 3] finger prick blood sample to determine antibody levels to sand fly saliva. LST positivity was higher in the western district of Diema (49.9%) than in Kolokani (24.9%) and was much lower in Kolondieba (2.6%). LST positivity increased with age rising from 13.8% to 88% in Diema for age groups 2–5 years and 41–65 years, respectively. All eight PCR-confirmed L. major CL cases were diagnosed in subjects below 18 years of age and all were residents of the district of Diema. Exposure to sand fly bites, measured by anti-saliva antibody titers, was comparable in individuals living in all three districts. However, antibody titers were significantly higher in LST positive individuals (P, Author Summary It is generally assumed that neglected tropical diseases (NTDS) such as leishmaniasis are concentrated in poor populations. It affects as many as 12 million people, with 1.5 to 2 million new cases every year around the world. Depending on the species of Leishmania, the host can develop cutaneous leishmaniasis (CL) or visceral leishmaniasis. In Mali, CL caused by Leishmania major is transmitted through the bite of infected sand flies belonging to the species Phlebotomus duboscqi. The objectives of this study were to determine the baseline prevalence of LST positivity, a test of previous exposure to Leishmania parasites, the prevalence of CL lesions, and the level of anti-P. duboscqi salivary antibodies, indicative of exposure to vector bites, in populations living in western, central and southern Mali, three ecologically distinct study sites. LST positivity was higher in the western district of Diema (85.1%) than in Kolokani (24.6%) and was much lower in Kolondieba (2.7%). All eight PCR-confirmed L. major CL cases were diagnosed in subjects below 18 years of age and all were residents of the district of Diema. Exposure to sand fly bites, measured by anti-saliva antibody titers, was established in individuals living in these three districts and antibody titers were higher in LST positive individuals (P

Historically the western sahelian dry regions of Mali are known to be highly endemic for cutaneous leishmaniasis (CL) caused by Leishmania major, while cases are rarely reported from the Southern savanna forest of the country. Here, we report baseline prevalence of CL infection in 3 ecologically distinct districts of Mali (dry sahelian, north savanna and southern savanna forest areas). We screened 195 to 250 subjects from 50 to 60 randomly selected households in each of the 6 villages (four from the western sahelian district of Diema in Kayes region, one from the central district of Kolokani and one from the southern savanna district of Kolodieba, region of Sikasso). The screening consisted of: 1] A Leishmanin Skin Test (LST) for detection of exposure to Leishmania parasites; 2] clinical examination of suspected lesions, followed by validation with PCR and 3] finger prick blood sample to determine antibody levels to sand fly saliva. LST positivity was higher in the western district of Diema (49.9%) than in Kolokani (24.9%) and was much lower in Kolondieba (2.6%). LST positivity increased with age rising from 13.8% to 88% in Diema for age groups 2-5 years and 41-65 years, respectively. All eight PCR-confirmed L. major CL cases were diagnosed in subjects below 18 years of age and all were residents of the district of Diema. Exposure to sand fly bites, measured by anti-saliva antibody titers, was comparable in individuals living in all three districts. However, antibody titers were significantly higher in LST positive individuals (P0.0001). In conclusion, CL transmission remains active in the western region of Mali where lesions were mainly prevalent among children under 18 years old. LST positivity correlated to higher levels of antibodies to sand fly salivary proteins, suggesting their potential as a risk marker for CL acquisition in Mali.

Background The Global Programme to Eliminate Lymphatic Filariasis (GPELF) was launched in 2000 with the goal of stopping transmission of lymphatic filariasis (LF) through yearly mass drug administration (MDA). Although preliminary surveys of the human population in Mali suggested that Wuchereria bancrofti infection was highly endemic in the Sikasso district, baseline entomological data were required to confirm high levels of transmission prior to the selection of villages in this region for a study of the impact of MDA on transmission of LF by anopheline vectors. Methods W. bancrofti transmission was assessed in 2001 (pre-MDA) and 2002 (post-MDA) in the Central District of Sikasso in southern Mali by dissection of Anopheles mosquitoes caught using the human landing catch (HLC) method. The relative frequencies and molecular forms of An. gambiae complex were determined. Results The majority (86%) of the anopheline vectors captured were identified as An. gambiae complex, and these accounted for >90% of the entomological inoculation rate (EIR) during both years of the study. There was a dramatic decrease in the number of An. gambiae complex mosquitoes captured and in the An. gambiae complex infectivity rates following MDA, accounting for the observed decrease in EIR in 2002 (from 12.55 to 3.79 infective bites per person during the transmission season). An. funestus complex mosquitoes were responsible for a low level of transmission, which was similar during both years of the study (1.2 infective bites per person during the transmission season in 2001 and 1.03 in 2002). Conclusions Based on the entomological data from this study, the district of Sikasso was confirmed as an area of high W. bancrofti transmission. This led to the selection of this area for a multi-national study on the effects of MDA on LF transmission by anopheline vectors. Comparison of vector transmission parameters prior to and immediately following the first round of MDA demonstrated a significant decrease in overall transmission. Importantly, the dramatic variability in EIR over the transmission season suggests that the efficacy of MDA can be maximized by delivering drug at the beginning of the rainy season (just prior to the peak of transmission).