Naturally acquired antibodies specific for Plasmodium falciparum reticulocyte-binding protein homologue 5 inhibit parasite growth and predict protection from malaria.

BACKGROUND: Plasmodium falciparum reticulocyte-binding protein homologue 5 (PfRH5) is a blood-stage parasite protein essential for host erythrocyte invasion. PfRH5-specific antibodies raised in animals inhibit parasite growth in vitro, but the relevance of naturally acquired PfRH5-specific antibodies in humans is unclear. METHODS: We assessed pre-malaria season PfRH5-specific immunoglobulin G (IgG) levels in 357 Malian children and adults who were uninfected with Plasmodium. Subsequent P. falciparum infections were detected by polymerase chain reaction every 2 weeks and malaria episodes by weekly physical examination and self-referral for 7 months. The primary outcome was time between the first P. falciparum infection and the first febrile malaria episode. PfRH5-specific IgG was assayed for parasite growth-inhibitory activity. RESULTS: The presence of PfRH5-specific IgG at enrollment was associated with a longer time between the first blood-stage infection and the first malaria episode (PfRH5-seropositive median: 71 days, PfRH5-seronegative median: 18 days; P = .001). This association remained significant after adjustment for age and other factors associated with malaria risk/exposure (hazard ratio, .62; P = .02). Concentrated PfRH5-specific IgG purified from Malians inhibited P. falciparum growth in vitro. CONCLUSIONS: Naturally acquired PfRH5-specific IgG inhibits parasite growth in vitro and predicts protection from malaria. These findings strongly support efforts to develop PfRH5 as an urgently needed blood-stage malaria vaccine. CLINICAL TRIALS REGISTRATION: NCT01322581.

An intensive longitudinal cohort study of Malian children and adults reveals no evidence of acquired immunity to Plasmodium falciparum infection.

BACKGROUND: In experimental models of human and mouse malaria, sterilizing liver stage immunity that blocks progression of Plasmodium infection to the symptomatic blood stage can be readily demonstrated. However, it remains unclear whether individuals in malaria-endemic areas acquire such immunity. METHODS: In Mali, 251 healthy children and adults aged 4-25 years who were free of blood-stage Plasmodium infection by polymerase chain reaction (PCR) were enrolled in a longitudinal study just prior to an intense 6-month malaria season. Subsequent clinical malaria episodes were detected by weekly active surveillance and self-referral. Asymptomatic P. falciparum infections were detected by blood-smear microscopy and PCR analysis of dried blood spots that had been collected every 2 weeks for 7 months. RESULTS: As expected, the risk of clinical malaria decreased with increasing age (log-rank test, P = .0038). However, analysis of PCR data showed no age-related differences in P. falciparum infection risk (log-rank test, P = .37). CONCLUSIONS: Despite years of exposure to intense P. falciparum transmission, there is no evidence of acquired, sterile immunity to P. falciparum infection in this population, even as clinical immunity to blood-stage malaria is clearly acquired. Understanding why repeated P. falciparum infections do not induce sterile protection may lead to insights for developing vaccines that target the liver stage in malaria-endemic populations.

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.

[Epidemiological profile of COVID-19 in Tombouctou region in Mali]. / Profil epidemiologique de la COVID-19 dans la region de Tombouctou au Mali.

INTRODUCTION: The objective of our study was to establish the epidemiological profile of COVID-19 in Tombouctou. MATERIAL AND METHODS: This was a descriptive cross-sectional study of COVID-19 surveillance data from Tombouctou from April 3 to October 1, 2020. Our variables of interest were extracted from the surveillance database and analyzed with Excel 2013. The frequencies, rate, and ratio were computed. RESULTS: Overall, 1851 suspects from all districts of the region were screened by RT-PCR, including 572 confirmed, which indicate a positivity rate of 30.90%. The 15-34 age group was the most represented with 48% of the confirmed cases. The sex ratio (male / female) of confirmed cases was 2.67. The city of Tombouctou was the epicenter of COVID-19. The Tombouctou region had a detection rate of around 2‰ (1851/928,000) and peaked between weeks 22 and 23 with a case fatality of 2.8%. CONCLUSION: Young people and men were most likely to be infected with COVID-19. We recommend increasing awareness of compliance with barrier measures.

INTRODUCTION: L'objectif de notre étude était d'établir le profil épidémiologique de la COVID-19 à Tombouctou. MATÉRIEL ET MÉTHODES: Il s'agissait d'une étude transversale descriptive des données de surveillance de la COVID-19 de la Région de Tombouctou du 3 avril au 1er octobre 2020. Nos variables d'intérêts ont été extraites de la base de données de surveillance et analysées sur Excel 2013. Les fréquences, taux et ratio ont été calculés. RÉSULTATS: Au total 1851 cas suspects en provenance de tous les districts de la région ont été testés à la RT-PCR dont 572 confirmés soit un taux de positivité de 30,90%. La tranche d'âge de 15-34 ans était la plus représentée avec une proportion de 48% de l'effectif des confirmés. Le sex ratio (homme/femme) des cas confirmés était de 2,67. La ville de Tombouctou était l'épicentre de la COVID-19. La région de Tombouctou avait un taux de dépistage d'environ 2‰ (1851/928.000) et a connu son pic entre les semaines 22 et 23 avec une létalité de 2,8%. CONCLUSION: Les jeunes et les hommes seraient les plus susceptibles d'être infectés par la COVID-19. Nous recommandons le renforcement de la sensibilisation pour le respect des mesures barrières.