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"Nilles, Eric"
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Institutional trust and misinformation in the response to the 2018–19 Ebola outbreak in North Kivu, DR Congo: a population-based survey
2019
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).
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.
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).
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.
The Harvard Humanitarian Initiative Innovation Fund.
Journal Article
Transmission Dynamics of Zika Virus in Island Populations: A Modelling Analysis of the 2013–14 French Polynesia Outbreak
by
Edmunds, W. John
,
Funk, Sebastian
,
Mallet, Henri-Pierre
in
Aedes
,
Archipelagoes
,
Biology and life sciences
2016
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.
Journal Article
Human Leptospirosis Infection in Fiji: An Eco-epidemiological Approach to Identifying Risk Factors and Environmental Drivers for Transmission
2016
Leptospirosis is an important zoonotic disease in the Pacific Islands. In Fiji, two successive cyclones and severe flooding in 2012 resulted in outbreaks with 576 reported cases and 7% case-fatality. We conducted a cross-sectional seroprevalence study and used an eco-epidemiological approach to characterize risk factors and drivers for human leptospirosis infection in Fiji, and aimed to provide an evidence base for improving the effectiveness of public health mitigation and intervention strategies. Antibodies indicative of previous or recent infection were found in 19.4% of 2152 participants (81 communities on the 3 main islands). Questionnaires and geographic information systems data were used to assess variables related to demographics, individual behaviour, contact with animals, socioeconomics, living conditions, land use, and the natural environment. On multivariable logistic regression analysis, variables associated with the presence of Leptospira antibodies included male gender (OR 1.55), iTaukei ethnicity (OR 3.51), living in villages (OR 1.64), lack of treated water at home (OR 1.52), working outdoors (1.64), living in rural areas (OR 1.43), high poverty rate (OR 1.74), living <100m from a major river (OR 1.41), pigs in the community (OR 1.54), high cattle density in the district (OR 1.04 per head/sqkm), and high maximum rainfall in the wettest month (OR 1.003 per mm). Risk factors and drivers for human leptospirosis infection in Fiji are complex and multifactorial, with environmental factors playing crucial roles. With global climate change, severe weather events and flooding are expected to intensify in the South Pacific. Population growth could also lead to more intensive livestock farming; and urbanization in developing countries is often associated with urban and peri-urban slums where diseases of poverty proliferate. Climate change, flooding, population growth, urbanization, poverty and agricultural intensification are important drivers of zoonotic disease transmission; these factors may independently, or potentially synergistically, lead to enhanced leptospirosis transmission in Fiji and other similar settings.
Journal Article
Longitudinal SARS-CoV-2 Nucleocapsid Antibody Kinetics, Seroreversion, and Implications for Seroepidemiologic Studies
by
Goodman, Kirsten
,
Schram, Haley
,
Donahue, Lauren
in
Antibodies
,
Antibodies, Viral
,
Asymptomatic
2022
Given widespread use of spike antibody in generating coronavirus disease vaccines, SARS-CoV-2 nucleocapsid antibodies are increasingly used to indicate previous infection in serologic surveys. However, longitudinal kinetics and seroreversion are poorly defined. We found substantial seroreversion of nucleocapsid total immunoglobulin, underscoring the need to account for seroreversion in seroepidemiologic studies.
Journal Article
Humoral signatures of protective and pathological SARS-CoV-2 infection in children
by
Atyeo, Caroline
,
Fischer, Eric S.
,
Burke, John S.
in
631/250/2152/2153
,
631/250/2152/2153/1291
,
631/250/255
2021
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.
A study of multisystem inflammatory syndrome in children (MIS-C) shows maintenance of elevated levels of monocyte-activating pathogen-specific IgG not seen in children infected with SARS-CoV-2 who do not develop MIS-C.
Journal Article
Seroepidemiology of human leptospirosis in the Dominican Republic: A multistage cluster survey, 2021
2024
Little is known about the epidemiology of leptospirosis in the Dominican Republic, the second most populous country in the Caribbean. We report on findings from a multi-stage household survey across two regions in the country that reveals a previously under-estimated burden of human Leptospira infection. Our findings, based on the reference-standard microscopic agglutination test, indicate a complex picture of serogroup diversity, spatial heterogeneity in infection and risk, and a marked discrepancy between reported cases and serologically estimated infections. Given an overall seroprevalence of 11.3% (95% CI: 10.8–13.0%) and a lower estimated force of infection (0.30% per year [0.27%–0.35%]) the number of infections may exceed national reported case data by 145-fold or more. Icterohaemorrhagiae, associated with severe Weil’s disease, was the most commonly identified serogroup with a serogroup-specific prevalence of 4.4%. Consistent with other settings, risk factors including age, male sex, and rat exposure were associated with higher seroprevalence. Our study highlights the need for targeted public health interventions informed by serogroup-specific dynamics, detailed spatial analyses, knowledge of local animal reservoirs, and strengthened laboratory surveillance to effectively control this pathogen.
Journal Article
SARS-CoV-2 antibodies protect against reinfection for at least 6 months in a multicentre seroepidemiological workplace cohort
2022
Identifying the potential for SARS-CoV-2 reinfection is crucial for understanding possible long-term epidemic dynamics. We analysed longitudinal PCR and serological testing data from a prospective cohort of 4,411 United States employees in 4 states between April 2020 and February 2021. We conducted a multivariable logistic regression investigating the association between baseline serological status and subsequent PCR test result in order to calculate an odds ratio for reinfection. We estimated an odds ratio for reinfection ranging from 0.14 (95% CI: 0.019 to 0.63) to 0.28 (95% CI: 0.05 to 1.1), implying that the presence of SARS-CoV-2 antibodies at baseline is associated with around 72% to 86% reduced odds of a subsequent PCR positive test based on our point estimates. This suggests that primary infection with SARS-CoV-2 provides protection against reinfection in the majority of individuals, at least over a 6-month time period. We also highlight 2 major sources of bias and uncertainty to be considered when estimating the relative risk of reinfection, confounders and the choice of baseline time point, and show how to account for both in reinfection analysis.
Journal Article
Leptospirosis in the Caribbean Region between 2000 and 2022: A scoping review of morbidity and mortality
by
Martin, Beatris Mario
,
Jian, Holly
,
Vernal, Sebastian
in
Caribbean Region - epidemiology
,
Cross-Sectional Studies
,
Humans
2026
Leptospirosis remains an important yet underreported public health concern in the Caribbean. Urbanisation, biodiversity loss and human encroachment into natural habitats have contributed to shifts in its epidemiological patterns. However, accurate assessment of disease burden is hindered by limited diagnostic capacity, surveillance challenges, and scarce research. We aim to describe geographical and temporal distribution of leptospirosis epidemiology in Caribbean Island Countries and Territories (CRICTs) and identify patterns and gaps in knowledge.
We conducted a systematic search across PubMed, Web of Science, Embase, Scopus, and the Latin America and Caribbean Health Sciences Literature databases, between 2000-2022, without language restrictions. Eligible publications were routine surveillance-based studies or cross-sectional seroprevalence surveys. We followed the Preferred Reporting Items for Systematic Reviews and Meta-analyses extension for Scoping Reviews (PRISMA-ScR) protocol. Of 110 full-text articles reviewed, 16 met inclusion criteria, documenting leptospirosis in 15 of 27 CRICTs (55.6%). Between 2000-2010, we identified an average of 2.6 studies per year, compared to just 1.2 between 2011-2022. Nine studies (60.0%) reported surveillance data, and six (40.0%) were seroprevalence surveys. Two studies reported hospitalisation rate (12.5%), and five studies, case fatality rate (31.3%). There were more than one publication from Guadeloupe, Jamaica, Puerto Rico, St. Lucia and Trinidad and Tobago. Although most studies acknowledged links between leptospirosis and extreme weather, only three were specifically designed to investigate this association.
Our findings highlight critical gaps in leptospirosis burden and research across the Caribbean. The scarcity of recent studies investigating epidemiological differences across rural and urban settings, and the impact of environmental changes, contributes to limited characterisation of evolving transmission patterns across the region. Strengthening regional research capacity and surveillance systems is essential to inform targeted public health strategies and reduce the disease's burden locally.
Journal Article
Using serological data to understand unobserved SARS-CoV-2 risk in health-care settings
2020
During past outbreaks of severe acute respiratory syndrome and Middle East respiratory syndrome, many infections occurred within health-care settings.1 Since the emergence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), growing evidence of nosocomial transmission has been observed, but tracking such outbreaks is challenging because a substantial proportion of infected individuals might exhibit mild or no symptoms.2 In The Lancet Infectious Diseases, Kasper Iversen and colleagues3 report results from a large seroprevalence survey of almost 30 000 hospital employees in Denmark.3 The authors found that 1163 (4·04%) of 28 792 staff were seropositive overall, which was slightly higher than the 3·04% (142 of 4672) prevalence observed among local blood donors (risk ratio [RR] 1·33 [95% CI 1·12–1·58]). Staff working in dedicated COVID-19 wards showed substantially higher rates of seropositivity (1·65 [1·34–2·03]; p<0·001) than other frontline health-care workers working in hospitals, reflecting increased risk for this group, a pattern that has also been reported in neighbouring Sweden.4 Although Iversen and colleagues used a point-of-care lateral flow immunoassay, which is generally considered less conclusive than enzyme-linked immunosorbent assays or similar laboratory-based methods,5 the authors did a comprehensive pre-study test assessment and estimated a sensitivity of 82·5–90·6% and specificity of 99·2–99·5%. Important questions remain about the precise role of humoral and cellular immunity following SARS-CoV-2 exposure, and whether seropositivity or antibody titres can be considered a proxy measure of protective immunity.8 If the seroprevalence estimated in the Danish hospital staff does indeed reflect the extent of immunity that would prevent infection, this would be substantially below the level required to generate localised herd immunity that could stop future nosocomial transmission.
Journal Article
Phylogeographical analysis of the dominant multidrug-resistant H58 clade of Salmonella Typhi identifies inter- and intracontinental transmission events
by
Dolecek, Christiane
,
Hogg, Geoff
,
Edwards, David J
in
45/23
,
631/326/1320
,
Acquisitions & mergers
2015
Vanessa Wong and colleagues report whole-genome sequencing of 1,832
Salmonella enterica
serovar Typhi isolates from 63 endemic countries. They identify mutations that define the multidrug resistant (MDR) H58 lineage and report numerous inter- and intracontinental transmissions of this lineage as well as an ongoing MDR typhoid epidemic in Africa.
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.
Journal Article