Case-area targeted interventions during a large-scale cholera epidemic: A prospective cohort study in Northeast Nigeria.

BACKGROUND: Cholera outbreaks are on the rise globally, with conflict-affected settings particularly at risk. Case-area targeted interventions (CATIs), a strategy whereby teams provide a package of interventions to case and neighboring households within a predefined "ring," are increasingly employed in cholera responses. However, evidence on their ability to attenuate incidence is limited. METHODS AND FINDINGS: We conducted a prospective observational cohort study in 3 conflict-affected states in Nigeria in 2021. Enumerators within rapid response teams observed CATI implementation during a cholera outbreak and collected data on household demographics; existing water, sanitation, and hygiene (WASH) infrastructure; and CATI interventions. Descriptive statistics showed that CATIs were delivered to 46,864 case and neighbor households, with 80.0% of cases and 33.5% of neighbors receiving all intended supplies and activities, in a context with operational challenges of population density, supply stock outs, and security constraints. We then applied prospective Poisson space-time scan statistics (STSS) across 3 models for each state: (1) an unadjusted model with case and population data; (2) an environmentally adjusted model adjusting for distance to cholera treatment centers and existing WASH infrastructure (improved water source, improved latrine, and handwashing station); and (3) a fully adjusted model adjusting for environmental and CATI variables (supply of Aquatabs and soap, hygiene promotion, bedding and latrine disinfection activities, ring coverage, and response timeliness). We ran the STSS each day of our study period to evaluate the space-time dynamics of the cholera outbreaks. Compared to the unadjusted model, significant cholera clustering was attenuated in the environmentally adjusted model (from 572 to 18 clusters) but there was still risk of cholera transmission. Two states still yielded significant clusters (range 8-10 total clusters, relative risk of 2.2-5.5, 16.6-19.9 day duration, including 11.1-56.8 cholera cases). Cholera clustering was completely attenuated in the fully adjusted model, with no significant anomalous clusters across time and space. Associated measures including quantity, relative risk, significance, likelihood of recurrence, size, and duration of clusters reinforced the results. Key limitations include selection bias, remote data monitoring, and the lack of a control group. CONCLUSIONS: CATIs were associated with significant reductions in cholera clustering in Northeast Nigeria despite operational challenges. Our results provide a strong justification for rapid implementation and scale-up CATIs in cholera-response, particularly in conflict settings where WASH access is often limited.

The emergence and regression of political priority for refugee integration into the Jordanian health system: an analysis using the Kingdon's multiple streams model.

BACKGROUND: The prolonged presence of Syrian refugees in Jordan has highlighted the need for sustainable health service delivery models for refugees. In 2012, the Jordanian government adopted a policy that granted Syrian refugees access, free of charge, to the national health system. However since 2012, successive policy revisions have limited refugee access. This paper seeks to understand factors that initially put refugee integration into the health system on the policy agenda, as well as how these same factors later affected commitment to sustain the policy. METHODS: This paper draws on data from a document review of 197 peer-reviewed and grey literature publications, a media analysis of newspaper articles retrieved from four officially recognized newspapers in Jordan, and 33 semi-structured key informant interviews. We used Kingdon's Multiple Streams Model - a well-established tool for analyzing policy adoption - to understand how political priority developed for integration of refugees into the health system. RESULTS: We find that several factors helped bring attention to the issue, namely concerns over infectious disease transmission to host communities, high rates of chronic conditions among the refugee population and the increasingly urban and dispersed nature of refugees. At the outset of the conflict, the national mood was receptive to refugees. Politicians and government officials quickly recognized the crisis as an opportunity to secure material and technical support from the international humanitarian community. At the same time, global pressures for integrating refugees into national health systems helped move the integration agenda forward in Jordan and the region more broadly. Since 2012, there were several modifications to the policy that signal profound changes in national views around the continued presence of Syrian refugees in the country, as well as reduced external financial support which has undermined the sustainability of the policy. CONCLUSION: This case study underscores the dynamic nature of policymaking and the challenge of sustaining government commitment to the right to health among refugees. Our analysis has important implications for advocates seeking to advance and maintain momentum for the integration of refugees into national health systems.

COVID-19 epidemiology, health services utilisation and health care seeking behaviour during the first year of the COVID-19 pandemic in Mweso health zone, Democratic Republic of Congo.

Background: Although the evidence about coronavirus disease 2019 (COVID-19) has increased exponentially since the beginning of the pandemic, less is known about the direct and indirect effects of the pandemic in humanitarian settings. In the Democratic Republic of the Congo (DRC), most studies occurred in Kinshasa and other cities. Limited research was conducted in remote conflict-affected settings. We investigated the COVID-19 epidemiology, health service utilisation, and health care-seeking behaviour during the first year of the pandemic (March 2020-March 2021) in the Mweso health zone, North Kivu, DRC. Methods: This mixed-methods study includes a descriptive epidemiological analysis of reported COVID-19 cases data extracted from the provincial line list, interrupted time series analysis of health service utilisation using routine health service data, qualitative perceptions of health care workers about how health services were affected, and community members' health care seeking behaviour from a representative household survey and focus group discussions. Results: The COVID-19 epidemiology in North Kivu aligns with evidence reported globally, yet case fatality rates were high due to underreporting. Testing capacity was limited and initially mainly available in the province's capital. Health service utilisation showed different patterns - child measles vaccinations experienced a decrease at the beginning of the pandemic, while outpatient consultations, malaria, and pneumonia showed an increase over time. Such increases might have been driven by insecurity and population displacements rather than COVID-19. Community members continued seeking care during the first months of the COVID-19 pandemic and visited the same health facilities as before COVID-19. Financial constraints, not COVID-19, were the main barrier reported to accessing health care. Conclusions: The first year of the COVID-19 pandemic in the Mweso health zone was characterised by low testing capacity and an underestimation of reported COVID-19 infections. The increase in health care utilisation should be further explored to understand the role of factors unrelated to COVID-19, such as insecurity, population displacement, and poverty, which remain major challenges to successfully providing health services and improving the population's health. Measles vaccination coverage dropped, which exacerbated the ongoing measles outbreak. Improved decentralised testing capacity will be crucial for future epidemics and enhanced efforts to maintain child vaccination coverage.

Structural basis for inhibition of coagulation factor VIII reveals a shared antigenic hotspot on the C1 domain.

BACKGROUND: Hemophilia A arises from dysfunctional or deficient coagulation factor (F)VIII and leads to inefficient fibrin clot formation and uncontrolled bleeding events. The development of antibody inhibitors is a clinical complication in hemophilia A patients receiving FVIII replacement therapy. LE2E9 is an anti-C1 domain inhibitor previously isolated from a mild/moderate hemophilia A patient and disrupts FVIII interactions with von Willebrand factor and FIXa, though the intermolecular contacts that underpin LE2E9-mediated FVIII neutralization are undefined. OBJECTIVES: To determine the structure of the complex between FVIII and LE2E9 and characterize its mechanism of inhibition. METHODS: FVIII was bound to the antigen binding fragment (Fab) of NB2E9, a recombinant construct of LE2E9, and its structure was determined by cryogenic electron microscopy. RESULTS: This report communicates the 3.46 Å structure of FVIII bound to NB2E9, with its epitope comprising FVIII residues S2040 to Y2043, K2065 to W2070, and R2150 to H2155. Structural analysis reveals that the LE2E9 epitope overlaps with portions of the epitope for 2A9, a murine-derived inhibitor, suggesting that these residues represent a shared antigenic region on the C1 domain between FVIII-/- mice and hemophilia A patients. Furthermore, the FVIII:NB2E9 structure elucidates the orientation of the LE2E9 glycan, illustrating how the glycan sterically blocks interactions between the FVIII C1 domain and the von Willebrand factor D' domain. A putative model of the FVIIIa:FIXa complex suggests potential clashing between the NB2E9 glycan and FIXa light chain. CONCLUSION: These results describe an antigenic "hotspot" on the FVIII C1 domain and provide a structural basis for engineering FVIII replacement therapeutics with reduced antigenicity.

Health care utilisation in Cox's Bazar district, Bangladesh, during the first year of the COVID-19 pandemic: A mixed-methods study among host communities.

To respond to the COVID-19 pandemic, countries introduced public health and social measures that had indirect societal, economic consequences. Concerns during epidemics include continuity of routine health services. We investigate how healthcare utilisation and healthcare seeking behaviour changed during the first year of the COVID-19 pandemic among host communities in Cox's Bazar, Bangladesh. This mixed-methods study combines quantitative analyses of routine health data and population-based findings about healthcare seeking behaviours. Trends in consultations changed according to facility level (higher-level facilities included Upazila Health Complexes and District Hospitals; lower-level facilities included Community Clinics and Union Health and Family Welfare Centers). At the pandemic's beginning, drops were seen at higher-level health facilities for outpatient department (OPD) consultations, respiratory infections, and antenatal care. Minor reductions or increases were seen at lower-level facilities for the same services. Half of the subdistricts reported a cumulative increase in OPD and respiratory tract infection consultations. Most subdistricts reported a cumulative decrease in antenatal care. Child vaccinations dropped in all subdistricts, half of which did not catch-up, resulting in a cumulative decrease of delivered doses. Fear of contracting COVID-19 and financial constraints were the main reasons for decreased access. Drivers of healthcare seeking behaviours should be better understood to guide preparedness and service delivery modalities at primary and secondary levels.

Syphilis prevalence and correlates of infection among Venezuelan refugees and migrants in Colombia: findings of a cross-sectional biobehavioral survey.

Background: Population-based estimates of syphilis prevalence are critical to informing public health response. We aimed to measure syphilis prevalence among Venezuelan refugees and migrants in Colombia to inform public health programming. Methods: Between July 2021 and February 2022, we surveyed 6221 adult Venezuelan refugees and migrants in four cities in Colombia using respondent-driven sampling (RDS). Participants completed a survey and dual-rapid HIV/treponemal syphilis screening. Confirmatory laboratory-based rapid plasma reagin testing was conducted on whole blood samples. Active syphilis infection was defined as RPR titer ≥ 1:8 and no self-reported syphilis treatment. We used multivariable regression models to identify associations with active syphilis infection among subgroups by gender and history of pregnancy (cisgender men n = 2123, cisgender women n = 4044, transgender/nonbinary people n = 47, pregnant women n = 150). Findings: Population (RDS-weighted) prevalence of laboratory-confirmed syphilis was 5.1% (95% CI: 4.6-5.6). Syphilis prevalence was 5.8% (weighted) among men; lifetime sexually transmitted infections (STI) diagnosis, same-sex relationships, HIV infection, and partner number were independently associated with syphilis infection. Syphilis prevalence was 4.6% (weighted) in women; correlates of infection included: lifetime STI diagnosis, food insecurity, current engagement in sex work, current pregnancy, any unsafe night in Colombia, irregular migration status, and no healthcare utilization in Colombia. 14.9% (unweighted) of transgender participants had syphilis infection; correlates of infection included partner number and HIV infection. The prevalence of syphilis was 9.0% (weighted) among pregnant women, which was associated with lifetime STI diagnosis. Interpretation: Syphilis among Venezuelans in Colombia is high. Correlates of infection are distinct among demographic groups, spanning sexual and social vulnerabilities, suggesting tailored public health strategies. Funding: US President's Emergency Plan for AIDS Relief through the U.S. Centers for Disease Control and Prevention.

Persistent Food Insecurity and Material Hardships: A Latent Class Analysis of Experiences among Venezuelan Refugees and Migrants in Urban Colombia.

The causes and conditions of displacement often increase the vulnerability of migrant and refugee populations to food insecurity, alongside other material hardships. We aimed to examine the multidimensional aspects and patterns of food insecurity and other material hardships in a cross-sectional sample of 6221 Venezuelan refugees and migrants in urban Colombia using a latent class analysis. Using multinomial and logistic regression models, we investigated the demographic and migratory experiences associated with identified classes and how class membership is associated with multiple health outcomes among Venezuelan refugees and migrants, respectively. Approximately two thirds of the sample was comprised cisgender women, and the participants had a median age of 32 years (IQR: 26-41). Four heterogeneous classes of food insecurity and material hardships emerged: Class 1-low food insecurity and material hardship; Class 2-high food insecurity and material hardship; Class 3-high income hardship with insufficient food intake; and Class 4-income hardship with food affordability challenges. Class 2 reflected the most severe food insecurity and material hardships and had the highest class membership; Venezuelans with an irregular migration status were almost 1.5 times more likely to belong to this class. Food insecurity and material hardship class membership was independently associated with self-rated health, mental health symptoms, and recent violence victimization and marginally associated with infectious disease outcomes (laboratory-confirmed HIV and/or syphilis infection). Social safety nets, social protection, and other interventions that reduce and prevent material hardships and food insecurity among refugees and migrants, alongside the host community, may improve public health, support development, and reduce healthcare costs. In the long term, regularization and social policies for migrants aimed at enhancing refugees' and migrants' social and economic inclusion may contribute to improving food security in this population.

The impact of policy and policy communication on COVID-19 vaccination inequalities among Venezuelan refugees and migrants in Colombia: a comparative cross-sectional interrupted time-series analysis.

INTRODUCTION: Equitable access to vaccines for migrants and refugees is necessary to ensure their right to health and to achieve public health goals of reducing vaccine-preventable illness. Public health policies require regulatory frameworks and communication to effect uptake of effective vaccines among the target population. In Colombia, the National COVID-19 Vaccination Plan implicitly included Venezuelan refugees and migrants; however, initial communication of the policy indicated that vaccine availability was restricted to people with regular migration status. We estimated the impact of a public announcement, which clarified access for refugees and migrants, on vaccination coverage among Venezuelans living in Colombia. METHODS: Between 30 July 2021 and 5 February 2022, 6221 adult Venezuelans participated in a cross-sectional, population-based health survey. We used a comparative cross-sectional time-series analysis to estimate the effect of the October 2021 announcement on the average biweekly change in COVID-19 vaccine coverage of Venezuelans with regular and irregular migration status. RESULTS: 71% of Venezuelans had an irregular status. The baseline (preannouncement) vaccine coverage was lower among people with an irregular status but increased at similar rates as those with a regular status. After the announcement, there was a level change of 14.49% (95% CI: 1.57 to 27.42, p=0.03) in vaccination rates among individuals with irregular migration status with a 4.61% increase in vaccination rate per biweekly period (95% CI: 1.71 to 7.51, p=0.004). By February 2022, there was a 26.2% relative increase in vaccinations among individuals with irregular migration status compared with what was expected without the announcement. CONCLUSION: While there was no policy change, communication clarifying the policy drastically reduced vaccination inequalities across migration status. Lessons can be translated from the COVID-19 pandemic into more effective global, regional and local public health emergency preparedness and response to displacement.