Lancet Microbe最新文献

Nipah virus disease is a bat-borne zoonosis with person-to-person transmission, a case-fatality rate of 38-75%, and well recognised potential to cause a pandemic. The first reported outbreak of Nipah virus disease occurred in Malaysia and Singapore in 1998, which has since been followed by multiple outbreaks in Bangladesh and India. To date, no therapeutics or vaccines have been approved to treat Nipah virus disease, and only few such candidates are in development. In this Review, we aim to assess the safety and efficacy of the therapeutic options (monoclonal antibodies and small molecules) for Nipah virus disease and other henipaviral diseases to support prioritisation of drug candidates for further evaluation in clinical trials. At present, sufficient evidence exists to suggest trialling 1F5, m102.4, and remdesivir (alone or in combination) for prophylaxis and early treatment of Nipah virus disease. In addition to well designed clinical efficacy trials, in-vivo pharmacokinetic-pharmacodynamic studies are needed to optimise the selection and dosing of therapeutic candidates in animal challenge and natural human infection.

Background: Yellow fever vaccination is considered to provide effective long-term immunity. However, yellow fever breakthrough infections in vaccinated patients have been reported. In this systematic review and meta-analysis we aimed to identify and summarise all documented symptomatic yellow fever breakthrough infections in the literature occurring less than 10 years and 10 years or more after primary yellow fever vaccination.

Methods: We searched MEDLINE (Ovid), Embase (Ovid), and Global Index Medicus for records published between Jan 1, 1936 (introduction of yellow fever vaccination) and June 16, 2023. We included prospective and retrospective cohort studies, case series and reports, and epidemiological reports from national and international health organisations reporting symptomatic yellow fever among individuals vaccinated 30 days or more before symptom onset. We excluded cases vaccinated less than 30 days before symptom onset. The primary outcome for the meta-analysis was the proportions of vaccinees among virologically confirmed and probable cases of yellow fever (IgM seroconversion without seroconversion to other flaviviruses). Risk of bias was assessed with an adapted version of the Newcastle-Ottawa Scale. Records of moderate or good quality (probable or confirmed yellow fever diagnosis with documented proof of previous vaccination) were included for random-effects meta-analysis. This systematic review and meta-analysis is registered with PROSPERO, number CRD42023450205.

Findings: After reviewing 1975 records, 37 records reported a total of 6951 yellow fever cases, of which 537 were vaccinated. 31 records were of low quality. Nine confirmed and 24 probable cases with proof of previous yellow fever vaccination were identified, all from Brazil. Confirmed cases were vaccinated 3 months to 3 years before symptom onset; of these patients two fell severely ill and died. The pooled proportion of verified yellow fever breakthrough infections among probable and confirmed cases was 3% (95% CI 1-19%). No confirmed yellow fever breakthrough infections were identified occurring 10 years or more after yellow fever vaccination.

Interpretation: Yellow fever breakthrough infections documented in literature are rare, and not necessarily more common 10 years or more after primary yellow fever vaccination. This finding suggests that a single dose of yellow fever vaccination is sufficient to provide lifelong protective immunity against symptomatic yellow fever.

Funding: None.

Background: The population structure of the malaria parasite Plasmodium falciparum can reveal underlying adaptive evolutionary processes. Selective pressures to maintain complex genetic backgrounds can encourage inbreeding, producing distinct parasite clusters identifiable by population structure analyses.

Methods: We analysed population structure in 3783 P falciparum genomes from 21 countries across Africa, provided by the MalariaGEN Pf7 dataset. We used Principal Coordinate Analysis to cluster parasites, identity by descent (IBD) methods to identify genomic regions shared by cluster members, and linkage analyses to establish their co-inheritance patterns. Structural variants were reconstructed by de novo assembly and verified by long-read sequencing.

Findings: We identified a strongly differentiated cluster of parasites, named AF1, comprising 47 (1·2%) of 3783 samples analysed, distributed over 13 countries across Africa, at locations over 7000 km apart. Members of this cluster share a complex genetic background, consisting of up to 23 loci harbouring many highly differentiated variants, rarely observed outside the cluster. IBD analyses revealed common ancestry at these loci, irrespective of sampling location. Outside the shared loci, however, AF1 members appear to outbreed with sympatric parasites. The AF1 differentiated variants comprise structural variations, including a gene conversion involving the dblmsp and dblmsp2 genes, and numerous single nucleotide polymorphisms. Several of the genes harbouring these mutations are functionally related, often involved in interactions with red blood cells including invasion, egress, and erythrocyte antigen export.

Interpretation: We propose that AF1 parasites have adapted to some unidentified evolutionary niche, probably involving interactions with host erythrocytes. This adaptation involves a complex compendium of interacting variants that are rarely observed in Africa, which remains mostly intact despite recombination events. The term cryptotype was used to describe a common background interspersed with genomic regions of local origin.

Funding: Bill & Melinda Gates Foundation.