We present a global analysis of the spread of recently emerged SARS-CoV-2 variants and estimate changes in effective reproduction numbers at country-specific level using sequence data from GISAID. Nearly all investigated countries demonstrated rapid replacement of previously circulating lineages by the World Health Organization-designated variants of concern, with estimated transmissibility increases of 29% (95% CI: 24–33), 25% (95% CI: 20–30), 38% (95% CI: 29–48) and 97% (95% CI: 76–117), respectively, for B.1.1.7, B.1.351, P.1 and B.1.617.2.

SummaryBackgroundAvailable incidence data for invasive salmonella disease in sub-Saharan Africa are scarce. Standardised, multicountry data are required to better understand the nature and burden of disease in Africa. We aimed to measure the adjusted incidence estimates of typhoid fever and invasive non-typhoidal salmonella (iNTS) disease in sub-Saharan Africa, and the antimicrobial susceptibility profiles of the causative agents.MethodsWe established a systematic, standardised surveillance of blood culture-based febrile illness in 13 African sentinel sites with previous reports of typhoid fever: Burkina Faso (two sites), Ethiopia, Ghana, Guinea-Bissau, Kenya, Madagascar (two sites), Senegal, South Africa, Sudan, and Tanzania (two sites). We used census data and health-care records to define study catchment areas and populations. Eligible participants were either inpatients or outpatients who resided within the catchment area and presented with tympanic (≥38·0°C) or axillary temperature (≥37·5°C). Inpatients with a reported history of fever for 72 h or longer were excluded. We also implemented a health-care utilisation survey in a sample of households randomly selected from each study area to investigate health-seeking behaviour in cases of self-reported fever lasting less than 3 days. Typhoid fever and iNTS disease incidences were corrected for health-care-seeking behaviour and recruitment.FindingsBetween March 1, 2010, and Jan 31, 2014, 135 Salmonella enterica serotype Typhi (S Typhi) and 94 iNTS isolates were cultured from the blood of 13 431 febrile patients. Salmonella spp accounted for 33% or more of all bacterial pathogens at nine sites. The adjusted incidence rate (AIR) of S Typhi per 100 000 person-years of observation ranged from 0 (95% CI 0–0) in Sudan to 383 (274–535) at one site in Burkina Faso; the AIR of iNTS ranged from 0 in Sudan, Ethiopia, Madagascar (Isotry site), and South Africa to 237 (178–316) at the second site in Burkina Faso. The AIR of iNTS and typhoid fever in individuals younger than 15 years old was typically higher than in those aged 15 years or older. Multidrug-resistant S Typhi was isolated in Ghana, Kenya, and Tanzania (both sites combined), and multidrug-resistant iNTS was isolated in Burkina Faso (both sites combined), Ghana, Kenya, and Guinea-Bissau.InterpretationTyphoid fever and iNTS disease are major causes of invasive bacterial febrile illness in the sampled locations, most commonly affecting children in both low and high population density settings. The development of iNTS vaccines and the introduction of S Typhi conjugate vaccines should be considered for high-incidence settings, such as those identified in this study.FundingBill & Melinda Gates Foundation.

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There is paucity of data regarding the geographical distribution, incidence, and phylogenetics of multi-drug resistant (MDR) Salmonella Typhi in sub-Saharan Africa. Here we present a phylogenetic reconstruction of whole genome sequenced 249 contemporaneous S. Typhi isolated between 2008-2015 in 11 sub-Saharan African countries, in context of the 2,057 global S. Typhi genomic framework. Despite the broad genetic diversity, the majority of organisms (225/249; 90%) belong to only three genotypes, 4.3.1 (H58) (99/249; 40%), 3.1.1 (97/249; 39%), and 2.3.2 (29/249; 12%). Genotypes 4.3.1 and 3.1.1 are confined within East and West Africa, respectively. MDR phenotype is found in over 50% of organisms restricted within these dominant genotypes. High incidences of MDR S. Typhi are calculated in locations with a high burden of typhoid, specifically in children aged <15 years. Antimicrobial stewardship, MDR surveillance, and the introduction of typhoid conjugate vaccines will be critical for the control of MDR typhoid in Africa.

During the past two decades, several epitopes that induce neutralizing antibodies (Abs) have been identified in the human immunodeficiency virus (HIV) envelope through studies of polyclonal and monoclonal Abs (MAbs). These epitopes include the V3 region defined with polyclonal Abs (30, 33) and several MAbs, such as 447-52D (16); the membrane-proximal external region in gp41 defined by MAbs 2F5 and 4E10 (6); the CD4-binding site on gp120 defined by MAb immunoglobulin G1b12 (IgG1b12) (7); and a glycan-rich region on gp120 defined by MAb 2G12 (37). With the exception of V3, none of these epitopes induce neutralizing Abs in the majority of infected humans. Thus, Abs to the membrane-proximal external region of gp41 (G. Shaw, H. Li, J. Decker, S. Allen, E. Hunter, E. Delaporte, M. Peters, B. Hahn, and F. Bibollet-Ruche, Abstr. AIDS Vaccine 2005, abstr. 29, 2005 (45), the CD4 binding site defined by IgG1b12 (25), and the designated carbohydrate moieties on gp120 (23, 37) are rare or absent from the sera of most HIV-infected individuals, and the epitope recognized by 2F5 (9,11,29) and the peptide mimotope for IgG1b12 (44) have failed to induce neutralizing Abs when used as experimental immunogens. Moreover, the recently described auto-reactive character of MAbs 2F5, 4E10, and IgG1b12, which recognize cardiolipin and/or double-stranded DNA, indicates that these epitopes may be problematic for the design of an anti-HIV vaccine (22). In contrast, the immunogenicity of the V3 region is reflected by the presence of anti-V3 Abs in the sera of essentially all HIV-infected individuals (38).Opinions about the V3 loop as an antigen for the induction of neutralizing Abs have changed over time. Early optimism related to the ability of anti-V3 MAbs to neutralize T-cell-lineadapted viruses was replaced by skepticism when it was suggested that the V3 of primary isolate JR-FL was "cryptic" (5). More recent data suggest that V3 is accessible on the surfaces of most virions (31) and that anti-V3 MAbs, such as 447-52D, can neutralize 62 to 92% of primary isolates that carry the epitope for which V3 is specific (3, 43). Nonetheless, recent studies have shown that V3 is masked in many viruses by the V1/V2 region (32) and/or by carbohydrate moieties on the envelope (39), both of which may contribute to the resistance of primary isolates (26,28). Moreover, it has been demonstrated in several studies that, despite the sequence variation in the V3 loop, many human anti-V3 Abs are cross-reactive (3,