Institut Pasteur de Dakar

The advent of multiplexing technologies, allowing antibodies to hundreds of antigens to be measured in a single test, has led to enormous increases in the amount of data generated by serological surveys. New modelling methods are required to exploit this data. This study extends serocatalytic models to consider up to three antibody responses targeting the same pathogen simultaneously. These models were fitted to data from cross-sectional serological surveys of Plasmodium falciparum malaria in the Senegalese villages of Dielmo and Ndiop, and model predictions were validated against 22 years of longitudinal epidemiological data. The most accurate reconstruction of historical clinical incidence of P. falciparum was provided by a combination of antibodies to Apical Membrane Antigen 1 (PfAMA1) and Glutamate-Rich Protein (PfGlurpR2). This model estimated a 76% (95% CrI: 61% - 86%) drop in transmission in 2004 (95% CrI: 2001 - 2008) coinciding with changing anti-malarial treatment. Multiplex serocatalytic models provided more accurate estimates of past clinical incidence than singleplex serocatalytic models, with the most accurate multiplex model (PfAMA1 + PfGlurpR2) outperforming all singleplex models (KruskalWallis p < 0.01). Finally, models with three antigens did not provide more accurate estimation than models with two antigens.

RH5-interacting protein (RIPR) is essential for the invasion of Plasmodium into host red blood cells and is currently being studied as a novel malaria vaccine candidate in Phase 1a clinical trials. To study the genetic diversity of RIPR, deep amplicon sequencing was used to identify RIPR mutations in Plasmodium falciparum clinical isolates (n = 89) collected in Kédougou, a high malaria transmission region of Senegal. We identified non-synonymous single-nucleotide polymorphisms (SNPs) in 64/89 (71.9%) of samples. In total, 26 non-synonymous SNPs were identified, including 15 novel SNPs. Sixteen of 26 SNPs could be threaded onto existing PfRIPR crystal structures to predict the effects of SNPs on RIPR stability. Seven of 16 mutations were predicted to destabilize PfRIPR, while two of 16 were predicted to increase the stability of RIPR. Additionally, we identified 3 SNPs (Q737K, T738K, and V840L) in the EGF5-8 domains of PfRIPR where neutralizing antibodies are known to bind.

BACKGROUND:WHO recommends fractional dose vaccination to address yellow fever vaccine shortages during outbreaks. In adults, a 500 IU dose has recently been shown to be non-inferior to the full standard dose, but the minimum effective dose for children is unknown. METHODS:We conducted a randomised, double-blind, non-inferiority trial at two centres in Kenya and Uganda, including infants aged 9-12 months with no previous yellow fever vaccination or infection. Participants were randomly assigned 1:1 in blocks of variable sizes of four, six, or eight to receive either the standard dose (>13 000 IU) or 500 IU of the Institut Pasteur de Dakar (Dakar, Senegal) 17D-204 yellow fever vaccine, co-administered with the measles-rubella vaccine. The primary outcome was seroconversion 28 days post-vaccination, defined as a four-fold or greater increase in antibody titre at day 28 from baseline (day 0), as measured by the 50% plaque reduction neutralisation test. Non-inferiority was shown if the lower bound of the 95% CI for the difference in seroconversion rates between doses exceeded -10 percentage points. Safety was assessed in the safety population, which included all participants who received a study vaccine dose. This study is registered with ClinicalTrials.gov (NCT04059471) and is complete. FINDINGS:Between Oct 7, 2021, and June 14, 2023, 420 infants were enrolled and randomly assigned (210 participants in each group). The seroconversion rate at day 28 was 99% (95% CI 96-100; 177 of 179 infants) for the standard dose and 93% (88-96; 166 of 179 infants) for the 500 IU dose in the per-protocol population. The difference in seroconversion rate was -6·15 percentage points (95% CI -10·27 to -2·02); therefore, non-inferiority was not met for the 500 IU dose. 12 serious adverse events were reported in the study (eight in the 500 IU dose group and four in the standard dose group), but all were considered unrelated to vaccination. INTERPRETATION:Compared with the standard yellow fever vaccine dose, a dose of 500 IU did not meet the non-inferiority criterion, suggesting that minimum dose requirements in adults are not generalisable to infants. Therefore, standard yellow fever doses should be used for infants in the routine WHO Expanded Programme on Immunization. FUNDING:European and Developing Countries Clinical Trials Partnership and the Wellcome Trust.

Rash is a common childhood infection, mainly caused by viruses. Hand, foot, and mouth disease (HFMD), a common viral rash infection, has become one of the most common infectious diseases in Asian countries and caused outbreaks in children and adults worldwide. Following the introduction of enterovirus A71 (EVA71) vaccines, Coxsackievirus A6 (CVA6) has recently emerged. However, the disease is not commonly reported in Africa, where studies are scarce. In the current study, we focused on the HFMD outbreak that occurred in Cape Verde in July 2023 during field investigations around a cluster of patients with rash and fever. Samples collected from patients were tested using Measles and Rubella-specific immunoglobulin M and quantitative reverse transcription PCR (qRT-PCR) of a panel of viruses causing rashes and subjected to genome sequencing followed by phylogenetic analysis. Eighteen out of the 22 samples were tested positive for CVA6 RNA by real-time RT-PCR, of which two tested also positive for EVA71 and Coxsackievirus A16 (CVA16). Subsequent sequencing revealed that all CVA6 sequences belonged to the D genotype, particularly the D3 sub-genotype recently described in China. Our study uncovers the first-ever reported outbreak of CVA6 associated with atypical HFMD in children from Cape Verde and highlights thus the need to implement an active hospital-based HFMD surveillance in Africa.