Search

Nipah virus – Bangladesh (NiVB) is a bat-borne zoonosis transmitted between people through the respiratory route, posing a pandemic risk. The risk posed by related henipaviruses, including Hendra virus (HeV) and Nipah virus – Malaysia (NiVM) is less clear. We conducted a broad search of the literature encompassing both human infections and animal models to synthesize evidence about potential for person-to-person spread of these henipaviruses. More than 600 human infections have been reported in the literature, but information about biological processes related to transmission is limited; information on viral shedding was only available for 40 case-patients. There is substantial evidence demonstrating person-to-person transmission of NiVB, though there is also evidence that NiVMhas been transmitted from person to person. Less direct evidence is available about the risk for person-to-person transmission of HeV, but animals infected with HeV shed more virus in the respiratory tract than those infected with NiVMsuggesting potential for transmission. As the family of known henipaviruses continues to grow, shared protocols for conducting and reporting from human investigations and animal experiments are urgently needed to advance our understanding of transmission risk.

IntroductionNon-fatal shooting rates vary tremendously within cities in the USA. Factors related to structural racism (both historical and contemporary) could help explain differences in non-fatal shooting rates at the neighbourhood level. Most research assessing the relationship between structural racism and firearm violence only includes one dimension of structural racism. Our study uses an intersectional approach to examine how the interaction of two forms of structural racism is associated with spatial non-fatal shooting disparities in Baltimore, Maryland.MethodsWe present three additive interaction measures to describe the relationship between historical redlining and contemporary racialized economic segregation on neighbourhood-level non-fatal shootings.ResultsOur findings revealed that sustained disadvantage census tracts (tracts that experience contemporary socioeconomic disadvantage and were historically redlined) have the highest burden of non-fatal shootings. Sustained disadvantage tracts had on average 24 more non-fatal shootings a year per 10 000 residents compared with similarly populated sustained advantage tracts (tracts that experience contemporary socioeconomic advantage and were not historically redlined). Moreover, we found that between 2015 and 2019, the interaction between redlining and racialized economic segregation explained over one-third of non-fatal shootings (approximately 650 shootings) in sustained disadvantage tracts.ConclusionThese findings suggest that the intersection of historical and contemporary structural racism is a fundamental cause of firearm violence inequities in Baltimore. Intersectionality can advance injury prevention research and practice by (1) serving as an analytical tool to expose inequities in injury-related outcomes and (2) informing the development and implementation of injury prevention interventions and policies that prioritise health equity and racial justice.

Summary Background Between 2014 and 2017, successive cholera epidemics occurred in South Sudan within the context of civil war, population displacement, flooding, and drought. We aim to describe the spatiotemporal and molecular features of the three distinct epidemic waves and explore the role of vaccination campaigns, precipitation, and population movement in shaping cholera spread in this complex setting. Methods In this descriptive epidemiological study, we analysed cholera linelist data to describe the spatiotemporal progression of the epidemics. We placed whole-genome sequence data from pandemic Vibrio cholerae collected throughout these epidemics into the global phylogenetic context. Using whole-genome sequence data in combination with other molecular attributes, we characterise the relatedness of strains circulating in each wave and the region. We investigated the association of rainfall and the instantaneous basic reproduction number using distributed lag non-linear models, compared county-level attack rates between those with early and late reactive vaccination campaigns, and explored the consistency of the spatial patterns of displacement and suspected cholera case reports. Findings The 2014 (6389 cases) and 2015 (1818 cases) cholera epidemics in South Sudan remained spatially limited whereas the 2016–17 epidemic (20 438 cases) spread among settlements along the Nile river. Initial cases of each epidemic were reported in or around Juba soon after the start of the rainy season, but we found no evidence that rainfall modulated transmission during each epidemic. All isolates analysed had similar genotypic and phenotypic characteristics, closely related to sequences from Uganda and Democratic Republic of the Congo. Large-scale population movements between counties of South Sudan with cholera outbreaks were consistent with the spatial distribution of cases. 21 of 26 vaccination campaigns occurred during or after the county-level epidemic peak. Counties vaccinated on or after the peak incidence week had 2·2 times (95% CI 2·1–2·3) higher attack rates than those where vaccination occurred before the peak. Interpretation Pandemic V cholerae of the same clonal origin was isolated throughout the study period despite interepidemic periods of no reported cases. Although the complex emergency in South Sudan probably shaped some of the observed spatial and temporal patterns of cases, the full scope of transmission determinants remains unclear. Timely and well targeted use of vaccines can reduce the burden of cholera; however, rapid vaccine deployment in complex emergencies remains challenging. Funding The Bill & Melinda Gates Foundation.

Administration of many childhood vaccines requires that multiple doses be delivered within a narrow time window to provide adequate protection and reduce disease transmission. Accurately quantifying vaccination coverage is complicated by limited individual-level data and multiple vaccination mechanisms (routine and supplementary vaccination programs). We analyzed 12,541 vaccination cards from 6 districts across Madagascar for children born in 2015 and 2016. For 3 vaccines—pentavalent diphtheria-tetanus-pertussis-hepatitis B-Haemophilus influenzae type b vaccine (DTP-HB-Hib; 3 doses), 10-valent pneumococcal conjugate vaccine (PCV10; 3 doses), and rotavirus vaccine (2 doses)—we used dates of vaccination and birth to estimate coverage at 1 year of age and timeliness of delivery. Vaccination coverage at age 1 year for the first dose was consistently high, with decreases for subsequent doses (DTP-HB-Hib: 91%, 81%, and 72%; PCV10: 82%, 74%, and 64%; rotavirus: 73% and 63%). Coverage levels between urban districts and their rural counterparts did not differ consistently. For each dose of DTP-HB-Hib, the overall percentage of individuals receiving late doses was 29%, 7%, and 6%, respectively; estimates were similar for other vaccines. Supplementary vaccination weeks, held to help children who had missed routine care to catch up, did not appear to increase the likelihood of being vaccinated. Maintaining population-level immunity with multiple-dose vaccines requires a robust stand-alone routine immunization program.

BackgroundRelatively few COVID-19 cases and deaths have been reported through much of sub-Saharan Africa, including South Sudan, although the extent of SARS-CoV-2 spread remains unclear due to weak surveillance systems and few population-representative serosurveys.MethodsWe conducted a representative household-based cross-sectional serosurvey in Juba, South Sudan. We quantified IgG antibody responses to SARS-CoV-2 spike protein receptor-binding domain and estimated seroprevalence using a Bayesian regression model accounting for test performance.ResultsWe recruited 2,214 participants from August 10 to September 11, 2020 and 22.3% had anti-SARS-CoV-2 IgG titers above levels in pre-pandemic samples. After accounting for waning antibody levels, age, and sex, we estimated that 38.5% (32.1 - 46.8) of the population had been infected with SARS-CoV-2. For each RT-PCR confirmed COVID-19 case, 104 (87-126) infections were unreported. Background antibody reactivity was higher in pre-pandemic samples from Juba compared to Boston, where the serological test was validated. The estimated proportion of the population infected ranged from 30.1% to 60.6% depending on assumptions about test performance and prevalence of clinically severe infections.ConclusionsSARS-CoV-2 has spread extensively within Juba. Validation of serological tests in sub-Saharan African populations is critical to improve our ability to use serosurveillance to understand and mitigate transmission.

Pertussis is a highly contagious infectious disease and remains an important cause of mortality and morbidity worldwide. Over the last decade, vaccination has greatly reduced the burden of pertussis. Yet, uncertainty in individual vaccination coverage and ineffective case surveillance systems make it difficult to estimate burden and the related quantity of population-level susceptibility, which determines population risk. These issues are more pronounced in low-income settings where coverage is often overestimated, and case numbers are under-reported. Serological data provide a direct characterisation of the landscape of susceptibility to infection; and can be combined with vaccination coverage and basic theory to estimate rates of exposure to natural infection. Here, we analysed cross-sectional data on seropositivity against pertussis to identify spatial and age patterns of susceptibility in children in Madagascar. A large proportion of individuals surveyed were seronegative; however, there were patterns suggestive of natural infection in all the regions analysed. Improvements in vaccination coverage are needed to help prevent additional burden of pertussis in the country.

BackgroundBetween 2014 and 2017, successive cholera epidemics occurred in South Sudan within the context of civil war, population displacement, flooding, and drought. Understanding the determinants of cholera spread in complex settings like this can provide valuable insights for mitigating future cholera risk.MethodsWe analyzed cholera linelist and molecular data to describe the spatio-temporal progression of the epidemics. We explored the role of rainfall, population movement and vaccination campaigns in shaping the explaining incidence and the spatial distribution of reported cases.FindingsSouth Sudan experienced three distinct cholera epidemic waves of cholera ranging from 6-18 months with more than 28,000 cases reported and more than 2 million cholera vaccine doses delivered to curb transmission. The 2014 and 2015 epidemics remained spatially limited while the 2016/17 epidemic exploded along the Nile river. Initial cases of each epidemic were reported in or around Juba soon after the start of the rainy season, but we found no evidence that rainfall modulated transmission during each epidemic. All isolates analyzed had similar genotypic and phenotypic characteristics, closely related to sequences from Uganda and Democratic Republic of Congo. The direction of large-scale population movements between counties with cholera outbreaks was consistent with the spatial distribution of outbreaks. As of September 2020, zero cholera cases have been confirmed within South Sudan since 2017.InterpretationThe three epidemic waves were caused byV. choleraeof the same clonal origin despite the periods of no reported cases between waves. While the complex emergency likely shaped some of the observed spatial and temporal patterns of reported cases, the full scope of transmission determinants remains unclear. Timely and well targeted use of cholera vaccine can avert cases and deaths, however, most of the vaccine campaigns occurred after the epidemic peak highlighting the challenges of delivering vaccines quickly in response to an outbreak in settings like South Sudan. These analyses provide a multi-faceted template for examining cholera dynamics through epidemiological, microbiological, climatic, and behavioral lenses.FundingTheBill and Melinda Gates Foundation

IgM and IgA responses to SARS-CoV-2 RBD in severe COVID patients decay rapidly, while IgG responses persist for over 3 months., We measured plasma and/or serum antibody responses to the receptor-binding domain (RBD) of the spike (S) protein of SARS-CoV-2 in 343 North American patients infected with SARS-CoV-2 (of which 93% required hospitalization) up to 122 days after symptom onset and compared them to responses in 1548 individuals whose blood samples were obtained prior to the pandemic. After setting seropositivity thresholds for perfect specificity (100%), we estimated sensitivities of 95% for IgG, 90% for IgA, and 81% for IgM for detecting infected individuals between 15 and 28 days after symptom onset. While the median time to seroconversion was nearly 12 days across all three isotypes tested, IgA and IgM antibodies against RBD were short-lived with median times to seroreversion of 71 and 49 days after symptom onset. In contrast, anti-RBD IgG responses decayed slowly through 90 days with only 3 seropositive individuals seroreverting within this time period. IgG antibodies to SARS-CoV-2 RBD were strongly correlated with anti-S neutralizing antibody titers, which demonstrated little to no decrease over 75 days since symptom onset. We observed no cross-reactivity of the SARS-CoV-2 RBD-targeted antibodies with other widely circulating coronaviruses (HKU1, 229 E, OC43, NL63). These data suggest that RBD-targeted antibodies are excellent markers of previous and recent infection, that differential isotype measurements can help distinguish between recent and older infections, and that IgG responses persist over the first few months after infection and are highly correlated with neutralizing antibodies.

BACKGROUNDCharacterizing the humoral immune response to SARS-CoV-2 and developing accurate serologic assays are needed for diagnostic purposes and estimating population-level seroprevalence.METHODSWe measured the kinetics of early antibody responses to the receptor-binding domain (RBD) of the spike (S) protein of SARS-CoV-2 in a cohort of 259 symptomatic North American patients infected with SARS-CoV-2 (up to 75 days after symptom onset) compared to antibody levels in 1548 individuals whose blood samples were obtained prior to the pandemic.RESULTSBetween 14-28 days from onset of symptoms, IgG, IgA, or IgM antibody responses to RBD were all accurate in identifying recently infected individuals, with 100% specificity and a sensitivity of 97%, 91%, and 81% respectively. Although the estimated median time to becoming seropositive was similar across isotypes, IgA and IgM antibodies against RBD were short-lived with most individuals estimated to become seronegative again by 51 and 47 days after symptom onset, respectively. IgG antibodies against RBD lasted longer and persisted through 75 days post-symptoms. IgG antibodies to SARS-CoV-2 RBD were highly correlated with neutralizing antibodies targeting the S protein. No cross-reactivity of the SARS-CoV-2 RBD-targeted antibodies was observed with several known circulating coronaviruses, HKU1, OC 229 E, OC43, and NL63.CONCLUSIONSAmong symptomatic SARS-CoV-2 cases, RBD-targeted antibodies can be indicative of previous and recent infection. IgG antibodies are correlated with neutralizing antibodies and are possibly a correlate of protective immunity.