A novel de novo variant in the RUNX2 gene causes cleidocranial dysplasia in a Malian girl.

Key Clinical Message: Cleidocranial dysplasia (CCD) is a rare genetic skeletal disorder with only few cases reported in Africa, mostly based on clinical and radiological findings. We report the first case in Mali, caused by a novel de novo variant in the RUNX2 gene. Abstract: Cleidocranial dysplasia (CCD) is a rare autosomal dominant skeletal dysplasia characterized by an aplastic/hypoplastic clavicles, patent sutures and fontanels, dental abnormalities and a variety of other skeletal changes. We report a novel de novo variant in the RUNX2 gene causing a severe phenotype of CCD in a Malian girl.

Comparing vaccination coverage before and during COVID-19 pandemic in children under one year in the health district of commune V in Bamako, Mali.

INTRODUCTION: Although an essential frontline service in the prevention of child morbidity and mortality, there are indications that routine vaccinations have been disrupted during the COVID-19 pandemic. The present study aimed to compare vaccination coverage before COVID-19 in Mali in 2019 and during COVID-19 in 2020. OBJECTIVE: To compare vaccination coverages before COVID-19 in Mali in 2019 and during COVID-19 in 2020. DESIGN: Cross-sectional study. SETTING AND PARTICIPANTS: We collected routine immunization data from 2019 to 2020 of children under one year in the health district of Commune V in Bamako which includes twelve community health centers (CSCom). RESULTS: Considering all vaccines together, coverage in 2019 was higher than in 2020 (88.7% vs. 71,6%) (p < 10- 3, Fig. 1). In 2020, low proportions of children vaccinated were observed in May (51.1%) two months after the first COVID-19 case in Mali on March 25, 2020. For all vaccines, the mean number of children vaccinated was significantly higher in 2019 (before COVID-19) as compared to 2020 (during COVID-19) (p < 0.05). However, in September and October 2019 BCG vaccine coverage was lower in 2019 as compared to 2020 (p < 10- 3). CONCLUSION: COVID-19 pandemic has affected routine childhood vaccine coverage in Commune V of Bamako, particularly in May 2020. Therefore, new strategies are needed to improve vaccine coverage in young children below 1.

Progress towards elimination of onchocerciasis transmission in Mali: A "pre-stop MDA" survey in 18 transmission zones.

BACKGROUND: Onchocerciasis control activities in Mali began in 1975 with vector larviciding carried out by the Onchocerciasis Control Programme (OCP), followed by the distribution of ivermectin from 1998 until the closure of the OCP in 2002. At that time, epidemiological evaluations, using skin snip microscopy and O-150 pool screening PCR in black flies, indicated that the disease had been largely controlled as a public health problem. Ivermectin distribution was nevertheless continued after 2002 in 34 of the 75 health districts in Mali as these were known to still be meso- or hyper-endemic for onchocerciasis. In addition, the onchocerciasis sites known to be hypo-endemic for onchocerciasis benefited from the distribution of ivermectin treatment as part of the mass drug administration (MDA) program for lymphatic filariasis. Various entomological and epidemiological evaluations have now indicated that Mali may have achieved successful interruption of onchocerciasis transmission. METHODS: A series of cross-sectional surveys to update vector breeding sites throughout the endemic areas, followed by a pre-stop ivermectin mass drug administration (Pre-stop MDA) survey, were undertaken in 2019-2020. Based on breeding site findings, historical epidemiological assessments, and vector collection site maps, 18 operational transmission zones (OTZ) were delineated within which a total of 104 first line villages were selected for evaluation. Dried blood spots (DBS) samples were collected from 10,400 children (5-9 years old) from these 104 first line villages and processed for the presence of OV16 antibody using a lab-based rapid diagnostic test. RESULTS: Within the 544 Simulium damnosum s.l. breeding sites visited in all five endemic onchocerciasis endemic regions of Mali 18.01% (98/544) were seen to be active with the presence of at least one stage of S. damnosum. The overall prevalence of OV16 positive children was 0.45% (47/10,400). However, two hotspots were identified: 2.60% (13/500) seroprevalence in the OTZ number 5 in Kayes Region and 1.40% (7/500) in the OTZ number 1 of Sikasso Region. CONCLUSION: These data show that onchocerciasis prevalence in the five endemic regions has declined to levels that indicate that Stop-MDA surveys should be now carried out in most of the OTZ except for one in the Kayes Region. This latter site will need additional ivermectin treatment before reevaluation, and an OTZ in the Sikasso Region requires revaluation before possibly reinitiating MDA.

Knowledge and factors influencing schistosomiasis control interventions in the hyperendemic health district of Kalabancoro in Mali, 2020.

Introduction: schistosomiasis is a public health concerns in many countries including Mali. In Kalabancoro District, during the 2017 assessments, the National schistosomiasis and soil-transmitted helminths control program reported prevalence´s of 10.83% and 50.83% for urinary schistosomiasis and intestinal schistosomiasis respectively. This district recorded the highest prevalence of intestinal schistosomiasis among the 46 districts evaluated. To better understand these high rates, this study investigated the knowledge of schistosomiasis in children and adults in this district. Methods: a cross-sectional study was conducted which involved 947 participants. A univariate analysis and multiple logistic regression were performed. Data collection was through questionnaire administration. Results: during the study, 76.1% of participants claimed to know about schistosomiasis (p<0.001) among them, 85.6% did not know the mode of contamination (p=0.001) and 66.3% knew the traditional treatment (p=0.004). Participants whose households were close to water impoundment were 2.16 times more likely to know schistosomiasis than those who were not (95% CI = [1.49 - 3.11]). Conclusion: most of the majority of participants reported being aware of schistosomiasis. However, the modes of transmission, prevention, and treatment of schistosomiasis were not well known. Misconceptions persist, hindering effective prevention and control. This is a tangible obstacle to the elimination of schistosomiasis in the Kalabancoro Health District and requires interventions tailored for these endemic communities.

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.

Serological Evaluation of Onchocerciasis and Lymphatic Filariasis Elimination in the Bakoye and Falémé Foci, Mali.

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 <2% in ≤14 year-olds, and 16% in ≥40 year-olds. Wb123 seropositivity was <2% in ≤39 year-olds, reaching 3% in ≥40 year-olds. CONCLUSIONS: Notwithstanding uncertainty in the biplex RDT sensitivity, Ov16 and Wb123 seroprevalence among children in Bakoye and Falémé is consistent with EOT (onchocerciasis) and EPHP (LF) since stopping treatment in 2016. The few Ov16-seropositive children should be skin-snip polymerase chain reaction tested and followed up.

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.

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.

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

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

Dynamics of antigenemia and transmission intensity of Wuchereria bancrofti following cessation of mass drug administration in a formerly highly endemic region of Mali.

BACKGROUND: 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. METHODS: 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. RESULTS: 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. CONCLUSION: 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.

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

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<0.0001). 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.

Wuchereria bancrofti transmission pattern in southern Mali prior to and following the institution of mass drug administration.

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).