Effect of Adding a Six-Week Course of Doxycycline to Intensive Hygiene-Based Care for Improving Lymphedema in a Rural Setting of Mali: A Double-Blind, Randomized Controlled 24-Month Trial.

Lymphedema (LE) is one the most disfiguring chronic manifestations of lymphatic filariasis. Its management relies primarily on limb hygiene and local care. A previous study in Ghana demonstrating a beneficial effect of doxycycline on LE led to the current multicenter trial on the efficacy of doxycycline in filarial LE. A randomized placebo-controlled trial was initiated in two rural health districts in Mali. Patients with LE stages 1-3 were randomized to receive either doxycycline (200 mg/day) or placebo over a 6-week monitored treatment period and were then followed every 6 months for 2 years. Both groups received materials for limb hygiene that was carried out daily for the entire 2-year study. The primary endpoint was lack of progression in LE stage at 24 months. One hundred patients were enrolled in each study arm. The baseline sociodemographic characteristics of each group were largely similar. There was no significant difference at month 24 after treatment initiation in the number of subjects showing progression in LE stage between the two treatment arms (P = 0.5921). Importantly, however, the number of attacks of acute adenolymphangitis (ADLA) was reduced in both arms, but there was no significant difference between the two groups at any follow-up time point (all P >0.23). Doxycycline was well tolerated in those receiving the drug. When added to daily self-administered limb hygiene, a 6-week course of doxycycline (200 mg) was not superior to placebo in increasing the improvement associated with hygiene alone in LE volume, stage, or frequency of ADLA attacks over a 24-month period.

A Comprehensive Study on the Hematological Progression of Sickle Cell Disease Patients with COVID-19 at the Center for Research and Control of Sickle Cell Disease, Bamako.

The Coronavirus disease 2019 pandemic is a real crisis that has exposed the unpreparedness of many healthcare systems worldwide. Several underlying health conditions have been identified as risk factors, including sickle cell disease, a chronic illness with various complications that can increase the risk of severe COVID-19 infection. Our study aimed to investigate the profile of sickle cell patients diagnosed with COVID-19 and explore any potential relationship between these two conditions. We analyzed data from 11 sickle cell patients who contracted COVID-19 between June and December 2020 and were treated at the CRLD (Center for Sickle Cell Disease and Research). The patients' COVID-19 diagnosis was confirmed using the (Real-Time Reverse Transcriptase-Polymerase Chain Reaction) RT-PCR technique on nasopharyngeal swab samples and/or based on clinical and radiological findings, including CT scans. The patients consisted of 7 males and 4 females, with a mean age of 40 ± 12 years. The sickle cell phenotypes observed were SC (45.4%), SS (36.37%), and Sß± thalassemia (18.2%). During the COVID-19 infection, we observed a slight increase in white blood cell and platelet counts, but a decrease in mean hemoglobin levels and red blood cells. Only 3 out of 11 patients (28%) had a fever at the time of diagnosis. Three patients required red blood cell transfusions due to severe anemia, and 7 out of 11 patients (63.6%) were hospitalized, with one patient admitted to the intensive care unit due to pulmonary embolism. All patients recovered from COVID-19.

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.

Pott's disease in Abidjan: experience of the department of rheumatology of university teaching hospital of Cocody: about 420 cases.

INTRODUCTION: Pott's disease continues to be rife primarily in ivorian's setting. This large-scale study presents the Ivorian experience in the management of this disease. AIM: To determine the epidemiological, clinical, paraclinical, therapeutic and evolutionary profile of Pott's disease in Abidjan and to identify the factors associated with neurological compressions. METHODS: Retrospective and analytical study of 420 files of patients suffering from presumptive or confirmed Pott's disease, hospitalized in the rheumatology department of Cocody University Hospital from January 2010 to December 2019. RESULTS: The hospital frequency of tuberculous spondylodiscitis was 10.2%. Our study population consisted of 223 men and 197 women with an average age of 43.8 ± 15.5 years. A tuberculosis history and a notion of tuberculosis contagion were noted in 4.3% and 13.8% of cases respectively. The mean diagnostic time was 9.67 ± 10.11 months. The main clinical data were spinal syndrome (98.80%) and also tuberculous impregnation signs (84.76%). Neurological complications were noted in 11.66% of cases. Bacilloscopy and PCR BK were positive in 33.71% and 57.14% of cases respectively. Computed tomography was the most requested and performed diagnostic imaging (92.86%). The associated tuberculous targets (11.2%) were visceral (78.70%), in particular pulmonary (75.67%). The mean duration of anti-tuberculosis treatment was 12.42 months with a cure of 97.14% of patients. Diagnostic delay (P = 0.01), gibbosity (P = 0.009), and presence of soft tissue abscesses (P = 0.004) were significantly associated with neurological compressions. CONCLUSION: Pott's disease is common in Abidjan and affects young adults. It manifests as a spinal syndrome with tuberculous impregnation signs. Computed tomography was the most performed diagnostic imaging. The factors associated with neurological compressions are: diagnostic delay, gibbosity and soft tissue abscesses.

Correction: Onchocerciasis: Target product profiles of in vitro diagnostics to support onchocerciasis elimination mapping and mass drug administration stopping decisions.

[This corrects the article DOI: 10.1371/journal.pntd.0010682.].

Assessment of lung injury severity using ultrasound in critically ill COVID-19 patients in resource limited settings.

BACKGROUND: Lung ultrasound is a non-invasive tool available at the bedside for the assessment of critically ill patients. The objective of this study was to evaluate the usefulness of lung ultrasound in assessing the severity of SARS-CoV-2 infection in critically-ill patients in a low-income setting. METHODS: We conducted a 12-month observational study in a university hospital intensive care unit (ICU) in Mali, on patients admitted for COVID-19 as diagnosed by a positive polymerase chain reaction for SARS-CoV-2 and/or typical lung computed tomography scan findings. RESULTS: The inclusion criteria was met by 156 patients with a median age of 59 years. Almost all patients (96%) had respiratory failure at admission and many needed respiratory support (121/156, 78%). The feasibility of lung ultrasound was very good, with 1802/1872 (96%) quadrants assessed. The reproducibility was good with an intra-class correlation coefficient of elementary patterns of 0.74 (95% CI 0.65, 0.82) and a coefficient of repeatability of lung ultrasound score < 3 for an overall score of 24. Confluent B lines were the most common lesions found in patients (155/156). The overall mean ultrasound score was 23 ± 5.4, and was significantly correlated with oxygen saturation (Pearson correlation coefficient of - 0.38, p < 0.001). More than half of the patients died (86/156, 55.1%). The factors associated with mortality, as shown by multivariable analysis, were: the patients' age; number of organ failures; therapeutic anticoagulation, and lung ultrasound score. CONCLUSION: Lung ultrasound was feasible and contributed to characterize lung injury in critically-ill COVID-19 patients in a low income setting. Lung ultrasound score was associated with oxygenation impairment and mortality.

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.

Onchocerciasis: Target product profiles of in vitro diagnostics to support onchocerciasis elimination mapping and mass drug administration stopping decisions.

In June 2021, the World Health Organization (WHO), recognizing the need for new diagnostics to support the control and elimination of onchocerciasis, published the target product profiles (TPPs) of new tests that would support the two most immediate needs: (a) mapping onchocerciasis in areas of low prevalence and (b) deciding when to stop mass drug administration programs. In both instances, the test should ideally detect an antigen specific for live, adult O. volvulus female worms. The preferred format is a field-deployable rapid test. For mapping, the test needs to be ≥ 60% sensitive and ≥ 99.8% specific, while to support stopping decisions, the test must be ≥ 89% sensitive and ≥ 99.8% specific. The requirement for extremely high specificity is dictated by the need to detect with sufficient statistical confidence the low seroprevalence threshold set by WHO. Surveys designed to detect a 1-2% prevalence of a given biomarker, as is the case here, cannot tolerate more than 0.2% of false-positives. Otherwise, the background noise would drown out the signal. It is recognized that reaching and demonstrating such a stringent specificity criterion will be challenging, but test developers can expect to be assisted by national governments and implementing partners for adequately powered field validation.

Seroreactivity of the Severe Acute Respiratory Syndrome Coronavirus 2 Recombinant S Protein, Receptor-Binding Domain, and Its Receptor-Binding Motif in COVID-19 Patients and Their Cross-Reactivity With Pre-COVID-19 Samples From Malaria-Endemic Areas.

Despite the global interest and the unprecedented number of scientific studies triggered by the COVID-19 pandemic, few data are available from developing and low-income countries. In these regions, communities live under the threat of various transmissible diseases aside from COVID-19, including malaria. This study aims to determine the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) seroreactivity of antibodies from COVID-19 and pre-COVID-19 samples of individuals in Mali (West Africa). Blood samples from COVID-19 patients (n = 266) at Bamako Dermatology Hospital (HDB) and pre-COVID-19 donors (n = 283) from a previous malaria survey conducted in Dangassa village were tested by ELISA to assess IgG antibodies specific to the full-length spike (S) protein, the receptor-binding domain (RBD), and the receptor-binding motif (RBM436-507). Study participants were categorized by age, gender, treatment duration for COVID-19, and comorbidities. In addition, the cross-seroreactivity of samples from pre-COVID-19, malaria-positive patients against the three antigens was assessed. Recognition of the SARS-CoV-2 proteins by sera from COVID-19 patients was 80.5% for S, 71.1% for RBD, and 31.9% for RBM (p < 0.001). While antibody responses to S and RBD tended to be age-dependent, responses to RBM were not. Responses were not gender-dependent for any of the antigens. Higher antibody levels to S, RBD, and RBM at hospital entry were associated with shorter treatment durations, particularly for RBD (p < 0.01). In contrast, higher body weights negatively influenced the anti-S antibody response, and asthma and diabetes weakened the anti-RBM antibody responses. Although lower, a significant cross-reactive antibody response to S (21.9%), RBD (6.7%), and RBM (8.8%) was detected in the pre-COVID-19 and malaria samples. Cross-reactive antibody responses to RBM were mostly associated (p < 0.01) with the absence of current Plasmodium falciparum infection, warranting further study.

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.

[Care of covid-19 patients at the dermatology hospital of Bamako]. / Prise en charge des patients covid-19 a l'hopital de dermatologie de Bamako.

AIM: To assess the COVID-19 patients' treatment duration according to the place of treatment at the Dermatology Hospital of Bamako (DHB). METHODS: This was a cross-sectional study comparing the management of COVID-19 PCR-positive patients in the hospital to that of those managed at home from March 2020 to April 2021 until two consecutive negative PCR 48 hours apart. RESULTS: Among the 1109 patients, 369 were hospitalized, 497 followed at home. As of April 31, 2021, 81.2% (900/1109) of the patients recovered, 1.3% (14/1109) were transferred to another health structure, and 2.5% (28/1109) died. No statistically significant difference was observed between the mean duration of the treatment for patients treated at home (10 days) in (95% CI, 9.69-10.3) and those managed at hospital (10 days95% CI, 9.76-10.23) (Mantel-Cox test, p= 0.060). CONCLUSION: These results suggest that the place of treatment do not influence the time to recovery. This is particularly important given the current burden of COVID-19 management on the health workforce.

OBJECTIF: Evaluer la durée du traitement des patients COVID-19 selon le lieu de pris en charge à l'Hôpital de Dermatologie de Bamako (HDB). MÉTHODOLOGIE: Il s'agissait d'une étude transversale comparant la prise en charge des patients COVID-19 PCR-positifs à l'hôpital à celle à domicile de mars 2020 à avril 2021 jusqu'à l'obtention de deux tests PCR négatifs consécutifs à 48 heures d'intervalle. RÉSULTATS: Parmi les 1109 patients, 369 ont été hospitalisés, 497 suivis à domicile. Au 31 avril 2021, 81,2% (900/1109) des patients se sont rétablis, 1,3% (14/1109) ont été transférés dans une autre structure de santé et 2,5% (28/1109) sont décédés. Aucune différence statistiquement significative n'a été observée entre la durée moyenne du traitement pour les patients traités à domicile (10 jours) en (IC 95 %, 9,69-10,3) et ceux pris en charge à l'hôpital (10 jours IC 95 %, 9,76-10,23) (test de Mantel-Cox, p= 0,060). CONCLUSION: Ces résultats suggèrent que le lieu de traitement n'influence pas le temps de récupération. Ceci est particulièrement important étant donné la charge actuelle de la gestion des COVID-19 sur le personnel de santé.

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.