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.

Community Clustering of Food Insecurity and Malnutrition Associated With Systemic Drivers in Chad.

BACKGROUND: Chad suffers from protracted hunger, facing high food insecurity (Integrated Food Security Phase Classification 3 and above), and acute malnutrition levels that surpass the emergency threshold (15% global acute malnutrition) yearly. The Food Security Sector, with European Union support, leads an inclusive effort to increase synergy between humanitarian, development, and peace-building actors to understand and address drivers of hunger. OBJECTIVE: To understand the spatial distribution of child wasting and household food insecurity and systemic drivers (conflict, livelihoods, vegetation, cultural norms) as well as better understand the relationship between child wasting and household food insecurity in Kanem and Bahr el Ghazal (BeG) region, Chad, with the goal of improving nexus programming and targeting. METHODS: A cross-sectional randomized cluster survey was conducted in August 2021 in Kanem and BeG across 86 villages, reaching 7002 households and 6136 children. Data were collected on child anthropometry, household food security, and livelihoods. Using mixed methods, primary data were triangulated with secondary geospatial data on vegetation index and conflicts as well as qualitative interviews with local actors. Analysis was conducted using comparison tests, linear and logistic crude, and adjusted models, as well as looking at the design effect as a measure of clustering of outcomes at the community level. RESULTS: The geospatial distribution of hunger indicators shows child wasting and food insecurity are highly clustered. However, communities with a high prevalence of child wasting were not those with the highest levels of food insecurity, indicating different pathways. Clustering of food insecurity and child wasting is due to basic drivers of conflict, health, and seasonal access to natural resources. CONCLUSIONS: The high levels of food insecurity and child wasting are each concentrated in specific survey clusters and are not necessarily connected. They result from different causal pathways at the community level linked to the systemic drivers of the rule of access to natural resources, environmental seasonality, and livelihoods. This suggests a greater need for an integrated humanitarian, development, and peace-building interventions to address the persistent high prevalence of food insecurity and child wasting. It also suggests that these community-level and systemic drivers require greater consideration from the start in research design and data collection.

Plain language titleUnderstanding Linkages Between Household Food Insecurity, Child Malnutrition, and Their Respective Clustered Drivers in ChadPlain language summaryChad experiences emergency levels of household food insecurity and child malnutrition. To address this issue, the United Nations Food and Agricultural Organization has undertaken a collaborative effort to enhance cooperation among humanitarian, development, and peace-building actors. The objective of this study was to examine how child malnutrition, food insecurity, and their drivers cluster across communities in Kanem and Bahr El Ghazal to improve response planning and targeting. The study collected data in August 2021 on malnutrition, food security, livelihoods, vegetation, and conflict and carried out interviews with local informants. In total, the research covers 86 villages, 7,002 households, and 6,136 children. The research shows that the 2 measures of hunger, child malnutrition and food insecurity, are highly clustered, affecting some communities more than others. However, villages with a high prevalence of child acute malnutrition did not have the highest levels of food insecurity, suggesting different community-level drivers. The clustering of food insecurity and malnutrition at the village level was linked to the diversity of livelihoods, the experience of conflict, health, and seasonal limitations in accessing natural resources. These findings are crucial for informing the targeting and design of integrated humanitarian, development, and peace programs. Taking a systemic approach and fostering strong coordination across interventions to address the drivers of food insecurity and malnutrition holds great potential for tackling hunger in Chad.

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.

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.

Prevalence of trachoma in the Kayes region of Mali eight years after stopping mass drug administration.

BACKGROUND: In 2009, three years after stopping mass treatment with azithromycin, a trachoma impact survey in four health districts in the Kayes region of Mali found a prevalence of trachomatous inflammation-follicular (TF) among children aged 1 to 9 years of >5% and a trachomatous trichiasis (TT) prevalence within the general population (≥1-year-old) of <1%. As a result, the government's national trachoma program expanded trichiasis surgery and related activities required to achieve trachoma elimination. METHODOLOGY/PRINCIPAL FINDINGS: In 2015, to assess progress towards elimination, a follow-up impact survey was conducted in the Kayes, Kéniéba, Nioro and Yélimané health districts. The survey used district level two-stage cluster random sampling methodology with 20 clusters of 30 households in each evaluation unit. Subjects were eligible for examination if they were ≥1 year. TF and TT cases were identified and confirmed by experienced ophthalmologists. In total 14,159 people were enumerated and 11,620 (82%) were examined. TF prevalence (95% confidence interval (CI)) was 0.5% (0.3-1%) in Kayes, 0.8% (0.4-1.7%) in Kéniéba, 0.2% (0-0.9%) in Nioro and 0.3% (0.1-1%) in Yélimané. TT prevalence (95% CI) was 0.04% (0-0.25%) in Kayes, 0.29% (0.11-0.6%) in Kéniéba, 0.04% (0-0.25%) in Nioro and 0.07% (0-0.27%) in Yélimané. CONCLUSIONS/SIGNIFICANCE: Eight years after stopping MDA and intensifying trichiasis surgery outreach campaigns, all four districts reached the TF elimination threshold of <5% and three of four districts reached the TT elimination threshold of <0.1%.

Lessons Learned From Enhancing Vaccine Pharmacovigilance Activities During PsA-TT Introduction in African Countries, 2010-2013.

BACKGROUND: The rollout of the group A meningococcal vaccine, PsA-TT, in Africa's meningitis belt countries represented the first introduction of a vaccine specifically designed for this part of the world. During the first year alone, the number of people who received the vaccine through mass vaccination campaigns was several hundredfold higher than that of subjects who participated in the closely monitored clinical trials. Implementation of a system to identify rare but potentially serious vaccine reactions was therefore a high priority in the design and implementation of those campaigns. METHODS: National authorities and their technical partners set up effective vaccine pharmacovigilance systems, including conducting active surveillance projects. RESULTS: Implementation of national expert advisory groups to review serious adverse events following immunization in all countries and active monitoring of conditions of interest in 3 early-adopter countries did not identify particular concerns with the safety profile of PsA-TT, which had already provided tremendous public health benefits. CONCLUSIONS: Lessons learned from this experience will help to improve preparations for future vaccine introductions in resource-poor settings and capitalize on such efforts to advance vaccine safety systems in the future.

Active Surveillance for Adverse Events After a Mass Vaccination Campaign With a Group A Meningococcal Conjugate Vaccine (PsA-TT) in Mali.

BACKGROUND: The monovalent meningococcal A conjugate vaccine (PsA-TT, MenAfriVac) was developed for use in the "meningitis belt" of sub-Saharan Africa. Mali was 1 of 3 countries selected for early introduction. As this is a new vaccine, postlicensure surveillance is particularly important to identify and characterize possible safety issues. METHODS: The national vaccination campaign was phased from September 2010 to November 2011. We conducted postlicensure safety surveillance for PsA-TT in 40 government clinics from southern Mali serving approximately 400 000 people 1-29 years of age. We conducted analyses with individual-level data and population-level data, and we calculated rates of adverse events using the conditional exact test, a modified vaccine cohort risk interval method, and a modified self-controlled case series method for each outcome of interest, including 18 prespecified adverse events and 18 syndromic categories. RESULTS: An increased rate of clinic visits for fever within 3 days after vaccination was found using multiple methods for all age groups. Although other signals were found with some methods, complete assessment of all other prespecified outcomes and syndromic categories did not reveal that PsA-TT was consistently associated with any other health problem. CONCLUSIONS: No new safety concerns were identified in this study. These results are consistent with prelicensure data and other studies indicating that PsA-TT is safe. The approach presented could serve as a model for future active postlicensure vaccine safety monitoring associated with large-scale immunization campaigns in low-income countries.

A cluster randomized study of the safety of integrated treatment of trachoma and lymphatic filariasis in children and adults in Sikasso, Mali.

BACKGROUND: Neglected tropical diseases are co-endemic in many areas of the world, including sub Saharan Africa. Currently lymphatic filariasis (albendazole/ivermectin) and trachoma (azithromycin) are treated separately. Consequently, financial and logistical benefit can be gained from integration of preventive chemotherapy programs in such areas. METHODOLOGY/FINDINGS: 4 villages in two co-endemic districts (Kolondièba and Bougouni) of Sikasso, Mali, were randomly assigned to coadministered treatment (ivermectin/albendazole/azithromycin) or standard therapy (ivermectin/albendazole with azithromycin 1 week later). These villages had previously undergone 4 annual MDA campaigns with ivermectin/albendazole and 2 with azithromycin. One village was randomly assigned to each treatment arm in each district. There were 7515 eligible individuals in the 4 villages, 3011(40.1%) of whom participated in the study. No serious adverse events occurred, and the majority of adverse events were mild in intensity (mainly headache, abdominal pain, diarrhoea and "other signs/symptoms"). The median time to the onset of the first event, of any type, was later (8 days) in the two standard treatment villages than in the co-administration villages. Overall the number of subjects reporting any event was similar in the co-administration group compared to the standard treatment group [18.7% (281/1501) vs. 15.8% (239/1510)]. However, the event frequency was higher in the coadministration group (30.4%) than in the standard treatment group (11.0%) in Kolondièba, while the opposite was observed in Bougouni (7.1% and 20.9% respectively). Additionally, the overall frequency of adverse events in the co-administration group (18.7%) was comparable to or lower than published frequencies for ivermectin+albendazole alone. CONCLUSIONS: These data suggest that co-administration of ivermectin+albendazole and azithromycin is safe; however the small number of villages studied and the large differences between them resulted in an inability to calculate a meaningful overall estimate of the difference in adverse event rates between the regimens. Further work is therefore needed before co-administration can be definitively recommended. TRIAL REGISTRATION: ClinicalTrials.gov; NCT01586169.

Life-threatening malaria in African children: a prospective study in a mesoendemic urban setting.

BACKGROUND: The population exposed to malaria within African cities has steadily increased. However, comprehensive data on life-threatening malaria features and risk factors in children from urban areas with seasonal malaria transmission, such as in Bamako (Mali), are lacking. METHODS: Children admitted to the Gabriel Touré Hospital in Bamako with severe malarial anemia (SMA) and/or cerebral malaria (CM) were prospectively included in the study. Indicators of either SMA or CM were analyzed using logistic regression; and death hazard ratios (HRs) were estimated through survival analysis. RESULTS: The study included 455 children: 66% presented with CM, 34% with SMA, 3% with hypoglycemia (HG); 5% with dehydration; 17% with respiratory distress (RD); 25% with splenomegaly; and 92% with hepatomegaly. The children with CM were older than those with SMA. CM was more often associated with dehydration, HG, and RD, whereas SMA was more often associated with splenomegaly. The overall case fatality rate was 16%, and 94% of the children who died had CM. HG [HR: 2.37; 95% confidence interval (CI): 1.04-5.39; P = 0.040], RD (HR: 4.23; 95% CI: 2.46-7.30; P < 10(-6)) and a deep coma with a Blantyre score of less than 3 (HR: 6.78, 95% CI: 2.43-18.91; P < 10(-3)), were all independent predictors of death. CONCLUSIONS: These findings delineate the patterns of severe malaria in children in a West African mesoendemic urban setting. They validate practicable prognostic indicators of life-threatening malaria for use in the limited facilities available in African health centers and provide a frame of reference for further research addressing life-threatening malaria in this setting.

Familial aggregation of cerebral malaria and severe malarial anemia.

BACKGROUND: The predominant manifestations of severe malaria in African children are cerebral malaria (CM) and severe malarial anemia (SMA). As a first step toward a family-based approach to identify the environmental and genetic pathways that contribute to severe malaria, we tested whether it aggregates within families. METHODS: Family history of severe malaria was explored during face-to-face interviews with parents. Logistic regression was used to determine whether CM and SMA aggregate within individuals and within families. The pattern of familial aggregation was then expressed as familial odds ratios that were adjusted for relevant risk factors. RESULTS: This study was of 2811 inhabitants of Bamako, Mali, clustered in 407 nuclear families. The probands were 136 children with severe malaria and 271 healthy children from the community. Within-person association of CM and SMA was significant (odds ratio, 6.15 [95% confidence interval (CI), 2.62-14.41]). Over a lifetime, with each additional affected relative, the odds of a person contracting CM increased by 1.98 times (95% CI, 1.59-2.45), and the odds of having SMA increased by 1.91 times (95% CI, 1.05-3.47). Over a lifetime, for a child whose sibling had a history of CM, the odds of having CM were 2.49 times greater (95% CI, 1.51-4.10) than the odds for a child whose sibling had no such history; for a child whose sibling had a history of SMA, the odds of having SMA were 4.92 times greater (95% CI, 1.21-19.9) than the odds for a child whose sibling had no such history. CONCLUSION: Our data suggest strong familial aggregation of CM and SMA.

Risk factors for severe malaria in Bamako, Mali: a matched case-control study.

The aim of this case-control study was to identify epidemiological risk factors for severe malaria among children living in Bamako, a malaria-endemic area. For this, 260 healthy community controls were matched to 130 patients with severe malaria. Conditional multiple logistic regression analysis indicated that all examined independent factors associated with severe malaria are directly related to characteristics of the child's mother, with the exception of the child's own yellow fever vaccination history (odds ratio (OR): 1.93, 95% confidence intervals (CI(95%)) [1.10-3.37]). The following characteristics were all associated with a decreased risk of severe malaria in the child: maternal education (OR: 0.52, CI(95%) [0.31-0.86]), the mother's adequate knowledge about malaria (OR: 0.46, 95% CI(95%) [0.25-0.86]), her use of mosquito bed nets (OR: 0.53, CI(95%) [0.30-0.92]) and breast-feeding for at least 2 years (OR: 0.57, CI(95%) [0.33-0.94]). Conversely, chronic maternal disease (OR: ?3.16, CI(95%) [1.31-7.61]) was associated with an increased risk of severe malaria. These findings strongly support the hypothesis that maternal factors are central to the development of severe malaria in children. Programmes aiming to improve both maternal health and maternal education may reduce the incidence of severe malaria in children and should therefore be advocated in Bamako and in areas with similar epidemiological patterns for malaria.