The emergence of multidrug-resistant (MDR) typhoid is a major global health threat affecting many countries where the disease is endemic. Here whole-genome sequence analysis of 1,832 Salmonella enterica serovar Typhi (S. Typhi) identifies a single dominant MDR lineage, H58, that has emerged and spread throughout Asia and Africa over the last 30 years. Our analysis identifies numerous transmissions of H58, including multiple transfers from Asia to Africa and an ongoing, unrecognized MDR epidemic within Africa itself. Notably, our analysis indicates that H58 lineages are displacing antibiotic-sensitive isolates, transforming the global population structure of this pathogen. H58 isolates can harbor a complex MDR element residing either on transmissible IncHI1 plasmids or within multiple chromosomal integration sites. We also identify new mutations that define the H58 lineage. This phylogeographical analysis provides a framework to facilitate global management of MDR typhoid and is applicable to similar MDR lineages emerging in other bacterial species.
Background The current outbreak of Ebola in eastern DR Congo, beginning in 2018, emerged in a complex and violent political and security environment. Community-level prevention and outbreak control measures appear to be dependent on public trust in relevant authorities and information, but little scholarship has explored these issues. We aimed to investigate the role of trust and misinformation on individual preventive behaviours during an outbreak of Ebola virus disease (EVD).Methods We surveyed 961 adults between Sept 1 and Sept 16, 2018. We used a multistage sampling design in Beni and Butembo in North Kivu, DR Congo. Of 412 avenues and cells (the lowest administrative structures; 99 in Beni and 313 in Butembo), we randomly selected 30 in each city. In each avenue or cell, 16 households were selected using the WHO Expanded Programme on Immunization's random walk approach. In each household, one adult (aged ≥18 years) was randomly selected for interview. Standardised questionnaires were administered by experienced interviewers. We used multivariate models to examine the intermediate variables of interest, including institutional trust and belief in selected misinformation, with outcomes of interest related to EVD prevention behaviours. Findings Among 961 respondents, 349 (31•9%, 95% CI 27•4-36•9) trusted that local authorities represent their interest. Belief in misinformation was widespread, with 230 (25•5%, 21•7-29•6) respondents believing that the Ebola outbreak was not real. Low institutional trust and belief in misinformation were associated with a decreased likelihood of adopting preventive behaviours, including acceptance of Ebola vaccines (odds ratio 0•22, 95% CI 0•21-0•22, and 1•40, 1•39-1•42) and seeking formal health care (0•06, 0•05-0•06, and 1•16, 1•15-1•17). Interpretation The findings underscore the practical implications of mistrust and misinformation for outbreak control. These factors are associated with low compliance with messages of social and behavioural change and refusal to seek formal medical care or accept vaccines, which in turn increases the risk of spread of EVD. Funding The Harvard Humanitarian Initiative Innovation Fund.
Between October 2013 and April 2014, more than 30,000 cases of Zika virus (ZIKV) disease were estimated to have attended healthcare facilities in French Polynesia. ZIKV has also been reported in Africa and Asia, and in 2015 the virus spread to South America and the Caribbean. Infection with ZIKV has been associated with neurological complications including Guillain-Barré Syndrome (GBS) and microcephaly, which led the World Health Organization to declare a Public Health Emergency of International Concern in February 2015. To better understand the transmission dynamics of ZIKV, we used a mathematical model to examine the 2013–14 outbreak on the six major archipelagos of French Polynesia. Our median estimates for the basic reproduction number ranged from 2.6–4.8, with an estimated 11.5% (95% CI: 7.32–17.9%) of total infections reported. As a result, we estimated that 94% (95% CI: 91–97%) of the total population of the six archipelagos were infected during the outbreak. Based on the demography of French Polynesia, our results imply that if ZIKV infection provides complete protection against future infection, it would take 12–20 years before there are a sufficient number of susceptible individuals for ZIKV to re-emerge, which is on the same timescale as the circulation of dengue virus serotypes in the region. Our analysis suggests that ZIKV may exhibit similar dynamics to dengue virus in island populations, with transmission characterized by large, sporadic outbreaks with a high proportion of asymptomatic or unreported cases.
The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic continues to spread relentlessly, associated with a high frequency of respiratory failure and mortality. Children experience largely asymptomatic disease, with rare reports of multisystem inflammatory syndrome in children (MIS-C). Identifying immune mechanisms that result in these disparate clinical phenotypes in children could provide critical insights into coronavirus disease 2019 (COVID-19) pathogenesis. Using systems serology, in this study we observed in 25 children with acute mild COVID-19 a functional phagocyte and complement-activating IgG response to SARS-CoV-2, similar to the acute responses generated in adults with mild disease. Conversely, IgA and neutrophil responses were significantly expanded in adults with severe disease. Moreover, weeks after the resolution of SARS-CoV-2 infection, children who develop MIS-C maintained highly inflammatory monocyte-activating SARS-CoV-2 IgG antibodies, distinguishable from acute disease in children but with antibody levels similar to those in convalescent adults. Collectively, these data provide unique insights into the potential mechanisms of IgG and IgA that might underlie differential disease severity as well as unexpected complications in children infected with SARS-CoV-2.
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