No evidence of lymphatic filariasis transmission in Bamako urban setting after three mass drug administration rounds.

Lymphatic filariasis (LF) elimination activities started in Mali in 2005 in the most endemic areas and reached countrywide coverage in 2009. In 2004, the district of Bamako was endemic for LF with a prevalence of 1.5%. The current study was designed to determine LF endemicity level in the urban area of Bamako after three rounds of ivermectin and albendazole mass drug administration (MDA). A cross-sectional study was conducted in 2011 in Bamako city, consisting of human prevalence and entomological surveys. Volunteers aged 14 years and above were invited to participate and tested for evidence of Wuchereria bancrofti using night time blood thick smear microfilarial count and blood spots for LF antibodies using the SD BIOLINE Oncho/LF IgG4 Biplex rapid test (Ov16/Wb123). Mosquitoes were collected using CDC light and gravid traps and tested using molecular methods. Poolscreen software v2.0 was used to estimate vector transmission potential. Of the 899 volunteers, one (0.11%) was found to be positive for LF using the Oncho/LF IgG4 Biplex rapid test, and none was found to have Wuchereria bancrofti microfilariae. No mosquitoes were found infected among 6174 Culex spp. (85.2%), 16 Anopheles gambiae s.l. (An. gambiae s.l.) (0.2%), 26 Aedes spp. (0.4%), 858 Ceratopogonidae (11.8%) and 170 other insects not identified (2.3%) tested. Our data indicate that there was no active LF transmission in the low prevalence urban district of Bamako after three MDA rounds. These data helped the National LF programme move forward towards the elimination goal.

Comparison of Different Sampling Methods to Catch Lymphatic Filariasis Vectors in a Sudan Savannah Area of Mali.

There is a need for better tools to monitor the transmission of lymphatic filariasis and malaria in areas undergoing interventions to interrupt transmission. Therefore, mosquito collection methods other than human landing catch (HLC) are needed. This study aimed to compare the Ifakara tent trap type C (ITTC) and the Biogents sentinel trap (BGST) to the HLC in areas with different vector densities. Mosquitoes were collected in two villages in Mali from July to December in 2011 and 2012. The three methods were implemented at each site with one ITTC, one BGST, and one HLC unit that consisted of one room with two collectors-one indoor and the other outdoor. The Anopheles collected in 2011 were individually dissected, whereas those from 2012 were screened in pools using reverse transcription-polymerase chain reaction (RT-PCR) to determine the maximum infection prevalence likelihood (MIPL) for Wuchereria bancrofti and Plasmodium falciparum. The dissection of the females also allowed to assess the parity rates, as well its results. Over the 2 years, the HLC method collected 1,019 Anopheles, yields that were 34- and 1.5-fold higher than those with the BGST and ITTC, respectively. None of the dissected Anopheles were infected. The RT-PCR results showed comparable MIPL between HLC and ITTC for W. bancrofti with one infected pool from each trap's yield (respectively 0.03% [0.0009-0.2%] and 0.04% [0.001-0.2%]). For P. falciparum, no infected pool was recovered from BGST. The ITTC is a good alternative to HLC for xenomonitoring of program activities.

Prevalence and Risk Factors Associated with Epilepsy in Six Health Districts of Mali: A Community-Based Cross-Sectional and Nested Case-Control Study.

INTRODUCTION: In resource-limited countries, epilepsy prevalence is underestimated and little is known about its risk factors. OBJECTIVES: This study aimed to determine the prevalence and risk factors for epilepsy in six health districts (HDs) in Mali. METHODS: A community-based cross-sectional and nested case-control study was conducted in 180 villages with the highest number of suspicious epilepsy cases (SECs) in the six study HDs. The SECs were observed as part of a Phase 1 screening conducted by community health workers. For the nested case-control study, one case was matched with at least one control based on residence and age. A case of epilepsy was a person diagnosed with convulsive epilepsy after clinical assessment by a neurologist. A control was a person diagnosed as normal after neurological assessment by a neurologist. Data were collected on sociodemographic characteristics, familial and medical history of epilepsy, consanguinity, place of delivery, preterm birth, length/type of delivery, and history of meningitis and cerebral malaria. A univariate and multivariate binomial logistic regression model was used to analyse factors associated with epilepsy. RESULTS: A total of 1,506 cases of epilepsy and 2,199 controls were enrolled in six HDs. The mean prevalence of epilepsy was 2‰, with the highest in Kenieba (3‰), a previously meso-endemic-onchocerciasis HD, and the lowest in Kadiolo (1.5‰), a hypo-endemic-onchocerciasis HD. Age (adjusted odds ratio [aOR] = 1.02 [95% confidence intervals [CI] 1.02-1.03]), history of cerebral malaria (aOR = 11.41 [95% CI 8.86-14.85]), history of meningitis (aOR = 1.95 [95% CI 1.16-3.29]), living in the HD of Tominian (aOR = 1.69 [95% CI 1.29-2.22]), delayed delivery (aOR = 3.21 [95% CI 2.07-5.07]), and dystocia (aOR = 3.37 [95% CI 2.03-5.73]) were all significantly associated with epilepsy. CONCLUSION: The prevalence of epilepsy (3‰) in a previously meso-endemic-onchocerciasis HD was much lower than the prevalence (13.35‰) documented in onchocerciasis endemic areas in 2,000. This decrease epilepsy prevalence in the previously meso-endemic region was induced by onchocerciasis, and the reduction was due to an effective community direct treatment with ivermectin programme. Cerebral malaria and obstetrical complications were the main risk factors for epilepsy and interventions improving malaria prevention/treatment and optimizing prenatal and obstetrical care need to be implemented to reduce incidence.

Evaluation of mass drug administration for schistosomiasis and soil-transmitted helminths in school-aged children in Bankass, Mali.

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.

Individuals co-exposed to sand fly saliva and filarial parasites exhibit altered monocyte function.

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.

Factors hindering health care delivery in nomadic communities: a cross-sectional study in Timbuktu, Mali.

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.

Using community health workers as an alternative approach for epidemiological research on epilepsy in six health districts in Mali.

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, Kéniéba, 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.

Lymphedema in three previously Wuchereria bancrofti-endemic health districts in Mali after cessation of mass drug administration.

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.

Integrated seroprevalence-based assessment of Wuchereria bancrofti and Onchocerca volvulus in two lymphatic filariasis evaluation units of Mali with the SD Bioline Onchocerciasis/LF IgG4 Rapid Test.

BACKGROUND: Mali has become increasingly interested in the evaluation of transmission of both Wuchereria bancrofti and Onchocerca volvulus as prevalences of both infections move toward their respective elimination targets. The SD Bioline Onchocerciasis/LF IgG4 Rapid Test was used in 2 evaluation units (EU) to assess its performance as an integrated surveillance tool for elimination of lymphatic filariasis (LF) and onchocerciasis. METHODOLOGY/PRINCIPAL FINDINGS: A cross sectional survey with SD Bioline Onchocerciasis/LF IgG4 Rapid Test was piggy-backed onto a transmission assessment survey (TAS) (using the immunochromatographic card test (ICT) Binax Filariasis Now test for filarial adult circulating antigen (CFA) detection) for LF in Mali among 6-7 year old children in 2016 as part of the TAS in two EUs namely Kadiolo-Kolondieba in the region of Sikasso and Bafoulabe -Kita-Oussoubidiagna-Yelimane in the region of Kayes. In the EU of Kadiolo- Kolondieba, of the 1,625 children tested, the overall prevalence of W. bancrofti CFA was 0.62% (10/1,625) [CI = 0.31-1.09]; while that of IgG4 to Wb123 was 0.19% (3/1,600) [CI = 0.04-0.50]. The number of positives tested with the two tests were statistically comparable (p = 0.09). In the EU of Bafoulabe-Kita-Oussoubidiagna-Yelimane, an overall prevalence of W. bancrofti CFA was 0% (0/1,700) and that of Wb123 IgG4 antibody was 0.06% (1/1,700), with no statistically significant difference between the two rates (p = 0.99). In the EU of Kadiolo- Kolondieba, the prevalence of Ov16-specific IgG4 was 0.19% (3/1,600) [CI = 0.04-0.50]. All 3 positives were in the previously O. volvulus-hyperendemic district of Kolondieba. In the EU of Bafoulabe-Kita-Oussoubidiagna-Yelimane, an overall prevalence of Ov16-specific IgG4 was 0.18% (3/1,700) [CI = 0.04-0.47]. These 3 Ov16 IgG4 positives were from previously O.volvulus-mesoendemic district of Kita. CONCLUSIONS/SIGNIFICANCE: The SD Bioline Onchocerciasis/LF IgG4 Rapid test appears to be a good tool for integrated exposure measures of LF and onchocerciasis in co-endemic areas.

Factors Associated with Wuchereria bancrofti Microfilaremia in an Endemic Area of Mali.

Although Wuchereria bancrofti (Wb), the causative agent of lymphatic filariasis, is endemic throughout Mali, the prevalence of Wb microfilaremia (Mf) can vary widely between villages despite similar prevalence of infection as assessed by circulating antigen. To examine this variation, cross-sectional data obtained during screening prior to an interventional study in two neighboring villages in Mali were analyzed. The overall prevalence of Wb, as assessed by Wb CAg (circulating antigen), was 50.3% among 373 participants, aged 14-65. Wuchereria bancrofti Mf-positive and negative individuals appeared randomly distributed across the two villages (Moran's I spatial statistic = -0.01, Z score =0.1, P>0.05). Among the 187 subjects positive for Wb CAg, 117 (62.5%) had detectable Mansonella perstans microfilaremia (Mp Mf) and 64 (34.2%) had detectable Wb microfilaremia. The prevalence of Mp microfilaremia was 73.4% in the Wb Mf-positive group (as compared to 56.9% in the Wb Mf-negative group; p=0.01), and median Wb Mf load was increased in co-infected subjects (267Mf/ml vs 100 Mf/ml; p<0.001). In multivariate analysis, village of residence, Mp Mf positivity and gender were significantly associated with Wb Mf positivity. After controlling for age, gender, and village of residence, the odds of being Wb Mf positive was 2.67 times higher in Mp positive individuals (95% confidence interval [1.42-5.01]). Given the geographical overlap between Mp and Wb in Africa, a better understanding of the distribution and prevalence of Mp could assist national lymphatic filariasis control programs in predicting areas of high Wb Mf prevalence that may require closer surveillance.

A cross-sectional study of the filarial and Leishmania co-endemicity in two ecologically distinct settings in Mali.

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 < 0.0001). Among the filarial infected population, nearly 10% (14/142) were also positive for Leishmania with an overall prevalence of co-infection of 1.50% (14/930) varying from 2.82% (12/425) in Tieneguebougou and Bougoudiana to 0.39% (2/505) in Boundioba (P = 0.0048). CONCLUSION: This study established the existence of co-endemicity of filarial and Leishmania infections in specific regions of Mali. Since both filarial and Leishmania infections are vector-borne with mosquitoes and sand flies as respective vectors, an integrated vector control approach should be considered in co-endemic areas. The effect of potential interaction between filarial and Leishmania parasites on the disease outcomes may be further studied.

The Impact of Six Annual Rounds of Mass Drug Administration on Wuchereria bancrofti Infections in Humans and in Mosquitoes in Mali.

Wuchereria bancrofti prevalence and transmission were assessed in six endemic villages in Sikasso, Mali prior to and yearly during mass drug administration (MDA) with albendazole and ivermectin from 2002 to 2007. Microfilaremia was determined by calibrated thick smear of night blood in adult volunteers and circulating filarial antigen was measured using immunochromatographic card test in children < 5 years of age. Mosquitoes were collected by human landing catch from July to December. None of the 686 subjects tested were microfilaremic 12 months after the sixth MDA round. More importantly, circulating antigen was not detected in any of the 120 children tested, as compared with 53% (103/194) before the institution of MDA. The number of infective bites/human/year decreased from 4.8 in 2002 to 0.04 in 2007, and only one mosquito containing a single infective larva was observed 12 months after the final MDA round. Whether this dramatic reduction in transmission will be sustained following cessation of MDA remains to be seen.