Subcutaneous Administration of a Monoclonal Antibody to Prevent Malaria.

BACKGROUND: Subcutaneous administration of the monoclonal antibody L9LS protected adults against controlled Plasmodium falciparum infection in a phase 1 trial. Whether a monoclonal antibody administered subcutaneously can protect children from P. falciparum infection in a region where this organism is endemic is unclear. METHODS: We conducted a phase 2 trial in Mali to assess the safety and efficacy of subcutaneous administration of L9LS in children 6 to 10 years of age over a 6-month malaria season. In part A of the trial, safety was assessed at three dose levels in adults, followed by assessment at two dose levels in children. In part B of the trial, children were randomly assigned, in a 1:1:1 ratio, to receive 150 mg of L9LS, 300 mg of L9LS, or placebo. The primary efficacy end point, assessed in a time-to-event analysis, was the first P. falciparum infection, as detected on blood smear performed at least every 2 weeks for 24 weeks. A secondary efficacy end point was the first episode of clinical malaria, as assessed in a time-to-event analysis. RESULTS: No safety concerns were identified in the dose-escalation part of the trial (part A). In part B, 225 children underwent randomization, with 75 children assigned to each group. No safety concerns were identified in part B. P. falciparum infection occurred in 36 participants (48%) in the 150-mg group, in 30 (40%) in the 300-mg group, and in 61 (81%) in the placebo group. The efficacy of L9LS against P. falciparum infection, as compared with placebo, was 66% (adjusted confidence interval [95% CI], 45 to 79) with the 150-mg dose and 70% (adjusted 95% CI, 50 to 82) with the 300-mg dose (P<0.001 for both comparisons). Efficacy against clinical malaria was 67% (adjusted 95% CI, 39 to 82) with the 150-mg dose and 77% (adjusted 95% CI, 55 to 89) with the 300-mg dose (P<0.001 for both comparisons). CONCLUSIONS: Subcutaneous administration of L9LS to children was protective against P. falciparum infection and clinical malaria over a period of 6 months. (Funded by the National Institute of Allergy and Infectious Diseases; ClinicalTrials.gov number, NCT05304611.).

SARS-CoV-2 seroprevalence and living conditions in Bamako (Mali): a cross-sectional multistage household survey after the first epidemic wave, 2020.

OBJECTIVES: In low-income settings with limited access to diagnosis, COVID-19 information is scarce. In September 2020, after the first COVID-19 wave, Mali reported 3086 confirmed cases and 130 deaths. Most reports originated from Bamako, with 1532 cases and 81 deaths (2.42 million inhabitants). This observed prevalence of 0.06% appeared very low. Our objective was to estimate SARS-CoV-2 infection among inhabitants of Bamako, after the first epidemic wave. We assessed demographic, social and living conditions, health behaviours and knowledges associated with SARS-CoV-2 seropositivity. SETTINGS: We conducted a cross-sectional multistage household survey during September 2020, in three neighbourhoods of the commune VI (Bamako), where 30% of the cases were reported. PARTICIPANTS: We recruited 1526 inhabitants in 3 areas, that is, 306 households, and 1327 serological results (≥1 years), 220 household questionnaires and collected answers for 962 participants (≥12 years). PRIMARY AND SECONDARY OUTCOME MEASURES: We measured serological status, detecting SARS-CoV-2 spike protein antibodies in blood sampled. We documented housing conditions and individual health behaviours through questionnaires among participants. We estimated the number of SARS-CoV-2 infections and deaths in the population of Bamako using the age and sex distributions. RESULTS: The prevalence of SARS-CoV-2 seropositivity was 16.4% (95% CI 15.1% to 19.1%) after adjusting on the population structure. This suggested that ~400 000 cases and ~2000 deaths could have occurred of which only 0.4% of cases and 5% of deaths were officially reported. Questionnaires analyses suggested strong agreement with washing hands but lower acceptability of movement restrictions (lockdown/curfew), and mask wearing. CONCLUSIONS: The first wave of SARS-CoV-2 spread broadly in Bamako. Expected fatalities remained limited largely due to the population age structure and the low prevalence of comorbidities. Improving diagnostic capacities to encourage testing and preventive behaviours, and avoiding the spread of false information remain key pillars, regardless of the developed or developing setting. ETHICS: This study was registered in the registry of the ethics committee of the Faculty of Medicine and Odonto-Stomatology and the Faculty of Pharmacy, Bamako, Mali, under the number: 2020/162/CA/FMOS/FAPH.

Safety and Efficacy of a Monoclonal Antibody against Malaria in Mali.

BACKGROUND: CIS43LS is a monoclonal antibody that was shown to protect against controlled Plasmodium falciparum infection in a phase 1 clinical trial. Whether a monoclonal antibody can prevent P. falciparum infection in a region in which the infection is endemic is unknown. METHODS: We conducted a phase 2 trial to assess the safety and efficacy of a single intravenous infusion of CIS43LS against P. falciparum infection in healthy adults in Mali over a 6-month malaria season. In Part A, safety was assessed at three escalating dose levels. In Part B, participants were randomly assigned (in a 1:1:1 ratio) to receive 10 mg of CIS43LS per kilogram of body weight, 40 mg of CIS43LS per kilogram, or placebo. The primary efficacy end point, assessed in a time-to-event analysis, was the first P. falciparum infection detected on blood-smear examination, which was performed at least every 2 weeks for 24 weeks. At enrollment, all the participants received artemether-lumefantrine to clear possible P. falciparum infection. RESULTS: In Part B, 330 adults underwent randomization; 110 were assigned to each trial group. The risk of moderate headache was 3.3 times as high with 40 mg of CIS43LS per kilogram as with placebo. P. falciparum infections were detected on blood-smear examination in 39 participants (35.5%) who received 10 mg of CIS43LS per kilogram, 20 (18.2%) who received 40 mg of CIS43LS per kilogram, and 86 (78.2%) who received placebo. At 6 months, the efficacy of 40 mg of CIS43LS per kilogram as compared with placebo was 88.2% (adjusted 95% confidence interval [CI], 79.3 to 93.3; P<0.001), and the efficacy of 10 mg of CIS43LS per kilogram as compared with placebo was 75.0% (adjusted 95% CI, 61.0 to 84.0; P<0.001). CONCLUSIONS: CIS43LS was protective against P. falciparum infection over a 6-month malaria season in Mali without evident safety concerns. (Funded by the National Institute of Allergy and Infectious Diseases; ClinicalTrials.gov number, NCT04329104.).

Spatio-Temporal Variability of Malaria Incidence in the Health District of Kati, Mali, 2015-2019.

INTRODUCTION: Despite the implementation of control strategies at the national scale, the malaria burden remains high in Mali, with more than 2.8 million cases reported in 2019. In this context, a new approach is needed, which accounts for the spatio-temporal variability of malaria transmission at the local scale. This study aimed to describe the spatio-temporal variability of malaria incidence and the associated meteorological and environmental factors in the health district of Kati, Mali. METHODS: Daily malaria cases were collected from the consultation records of the 35 health areas of Kati's health district, for the period 2015-2019. Data on rainfall, relative humidity, temperature, wind speed, the normalized difference vegetation index, air pressure, and land use-land cover were extracted from open-access remote sensing sources, while data on the Niger River's height and flow were obtained from the National Department of Hydraulics. To reduce the dimension and account for collinearity, strongly correlated meteorological and environmental variables were combined into synthetic indicators (SI), using a principal component analysis. A generalized additive model was built to determine the lag and the relationship between the main SIs and malaria incidence. The transmission periods were determined using a change-point analysis. High-risk clusters (hotspots) were detected using the SatScan method and were ranked according to risk level, using a classification and regression tree analysis. RESULTS: The peak of the malaria incidence generally occurred in October. Peak incidence decreased from 60 cases per 1000 person-weeks in 2015, to 27 cases per 1000 person-weeks in 2019. The relationship between the first SI (river flow and height, relative humidity, and rainfall) and malaria incidence was positive and almost linear. A non-linear relationship was found between the second SI (air pressure and temperature) and malaria incidence. Two transmission periods were determined per year: a low transmission period from January to July-corresponding to a persisting transmission during the dry season-and a high transmission period from July to December. The spatial distribution of malaria hotspots varied according to the transmission period. DISCUSSION: Our study confirmed the important variability of malaria incidence and found malaria transmission to be associated with several meteorological and environmental factors in the Kati district. The persistence of malaria during the dry season and the spatio-temporal variability of malaria hotspots reinforce the need for innovative and targeted strategies.