Monitoring Temporal Changes in SARS-CoV-2 Spike Antibody Levels and Variant-Specific Risk for Infection, Dominican Republic, March 2021-August 2022.

To assess changes in SARS-CoV-2 spike binding antibody prevalence in the Dominican Republic and implications for immunologic protection against variants of concern, we prospectively enrolled 2,300 patients with undifferentiated febrile illnesses in a study during March 2021-August 2022. We tested serum samples for spike antibodies and tested nasopharyngeal samples for acute SARS-CoV-2 infection using a reverse transcription PCR nucleic acid amplification test. Geometric mean spike antibody titers increased from 6.6 (95% CI 5.1-8.7) binding antibody units (BAU)/mL during March-June 2021 to 1,332 (95% CI 1,055-1,682) BAU/mL during May-August 2022. Multivariable binomial odds ratios for acute infection were 0.55 (95% CI 0.40-0.74), 0.38 (95% CI 0.27-0.55), and 0.27 (95% CI 0.18-0.40) for the second, third, and fourth versus the first anti-spike quartile; findings were similar by viral strain. Combining serologic and virologic screening might enable monitoring of discrete population immunologic markers and their implications for emergent variant transmission.

SARS-CoV-2 seroprevalence, cumulative infections, and immunity to symptomatic infection - A multistage national household survey and modelling study, Dominican Republic, June-October 2021.

Background: Population-level SARS-CoV-2 immunological protection is poorly understood but can guide vaccination and non-pharmaceutical intervention priorities. Our objective was to characterise cumulative infections and immunological protection in the Dominican Republic. Methods: Household members ≥5 years were enrolled in a three-stage national household cluster serosurvey in the Dominican Republic. We measured pan-immunoglobulin antibodies against the SARS-CoV-2 spike (anti-S) and nucleocapsid glycoproteins, and pseudovirus neutralising activity against the ancestral and B.1.617.2 (Delta) strains. Seroprevalence and cumulative prior infections were weighted and adjusted for assay performance and seroreversion. Binary classification machine learning methods and pseudovirus neutralising correlates of protection were used to estimate 50% and 80% protection against symptomatic infection. Findings: Between 30 Jun and 12 Oct 2021 we enrolled 6683 individuals from 3832 households. We estimate that 85.0% (CI 82.1-88.0) of the ≥5 years population had been immunologically exposed and 77.5% (CI 71.3-83) had been previously infected. Protective immunity sufficient to provide at least 50% protection against symptomatic SARS-CoV-2 infection was estimated in 78.1% (CI 74.3-82) and 66.3% (CI 62.8-70) of the population for the ancestral and Delta strains respectively. Younger (5-14 years, OR 0.47 [CI 0.36-0.61]) and older (≥75-years, 0.40 [CI 0.28-0.56]) age, working outdoors (0.53 [0.39-0.73]), smoking (0.66 [0.52-0.84]), urban setting (1.30 [1.14-1.49]), and three vs no vaccine doses (18.41 [10.69-35.04]) were associated with 50% protection against the ancestral strain. Interpretation: Cumulative infections substantially exceeded prior estimates and overall immunological exposure was high. After controlling for confounders, markedly lower immunological protection was observed to the ancestral and Delta strains across certain subgroups, findings that can guide public health interventions and may be generalisable to other settings and viral strains. Funding: This study was funded by the US CDC.

A health systems resilience research agenda: moving from concept to practice.

Health system resilience, known as the ability for health systems to absorb, adapt or transform to maintain essential functions when stressed or shocked, has quickly gained popularity following shocks like COVID-19. The concept is relatively new in health policy and systems research and the existing research remains mostly theoretical. Research to date has viewed resilience as an outcome that can be measured through performance outcomes, as an ability of complex adaptive systems that is derived from dynamic behaviour and interactions, or as both. However, there is little congruence on the theory and the existing frameworks have not been widely used, which as diluted the research applications for health system resilience. A global group of health system researchers were convened in March 2021 to discuss and identify priorities for health system resilience research and implementation based on lessons from COVID-19 and other health emergencies. Five research priority areas were identified: (1) measuring and managing systems dynamic performance, (2) the linkages between societal resilience and health system resilience, (3) the effect of governance on the capacity for resilience, (4) creating legitimacy and (5) the influence of the private sector on health system resilience. A key to filling these research gaps will be longitudinal and comparative case studies that use cocreation and coproduction approaches that go beyond researchers to include policy-makers, practitioners and the public.

Design thinking during a health emergency: building a national data collection and reporting system.

BACKGROUND: Design thinking allows challenging problems to be redefined in order to identify alternative user-center strategies and solutions. To address the many challenges associated with collecting and reporting data during the 2014 Ebola outbreak in Guinea, Liberia and Sierra Leone, we used a design thinking approach to build the Global Ebola Laboratory Data collection and reporting system. MAIN TEXT: We used the five-stage Design Thinking model proposed by Hasso-Plattner Institute of Design at Stanford in Guinea, Liberia and Sierra Leone. This approach offers a flexible model which focuses on empathizing, defining, ideating, prototyping, and testing. A strong focus of the methodology includes end-users' feedback from the beginning to the end of the process. This is an iterative methodology that continues to adapt according to the needs of the system. The stages do not need to be sequential and can be run in parallel, out of order, and repeated as necessary. Design thinking was used to develop a data collection and reporting system, which contains all laboratory data from the three countries during one of the most complicated multi-country outbreaks to date. The data collection and reporting system was used to orient the response interventions at the district, national, and international levels within the three countries including generating situation reports, monitoring the epidemiological and operational situations, providing forecasts of the epidemic, and supporting Ebola-related research and the Ebola National Survivors programs within each country. CONCLUSIONS: Our study demonstrates the numerous benefits that arise when using a design thinking methodology during an outbreak to solve acute challenges within the national health information system and the authors recommend it's use during future complex outbreaks.

Systems thinking for health emergencies: use of process mapping during outbreak response.

Process mapping is a systems thinking approach used to understand, analyse and optimise processes within complex systems. We aim to demonstrate how this methodology can be applied during disease outbreaks to strengthen response and health systems. Process mapping exercises were conducted during three unique emerging disease outbreak contexts with different: mode of transmission, size, and health system infrastructure. System functioning improved considerably in each country. In Sierra Leone, laboratory testing was accelerated from 6 days to within 24 hours. In the Democratic Republic of Congo, time to suspected case notification reduced from 7 to 3 days. In Nigeria, key data reached the national level in 48 hours instead of 5 days. Our research shows that despite the chaos and complexities associated with emerging pathogen outbreaks, the implementation of a process mapping exercise can address immediate response priorities while simultaneously strengthening components of a health system.

Enhancing laboratory capacity during Ebola virus disease (EVD) heightened surveillance in Liberia: lessons learned and recommendations.

INTRODUCTION: Following a declaration by the World Health Organization that Liberia had successfully interrupted Ebola virus transmission on May 9th, 2015; the country entered a period of enhanced surveillance. The number of cases had significantly reduced prior to the declaration, leading to closure of eight out of eleven Ebola testing laboratories. Enhanced surveillance led to an abrupt increase in demand for laboratory services. We report interventions, achievements, lessons learned and recommendations drawn from enhancing laboratory capacity. METHODS: Using archived data, we reported before and after interventions that aimed at increasing laboratory capacity. Laboratory capacity was defined by number of laboratories with Ebola Virus Disease (EVD) testing capacity, number of competent staff, number of specimens tested, specimen backlog, daily and surge testing capacity, and turnaround time. Using Stata 14 (Stata Corporation, College Station, TX, USA), medians and trends were reported for all continuous variables. RESULTS: Between May and December 2015, interventions including recruitment and training of eight staff, establishment of one EVD laboratory facility, implementation of ten Ebola GeneXpert diagnostic platforms, and establishment of working shifts yielded an 8-fold increase in number of specimens tested, a reduction in specimens backlog to zero, and restoration of turn-around time to 24 hours. This enabled a more efficient surveillance system that facilitated timely detection and containment of two EVD clusters observed thereafter. CONCLUSION: Effective enhancement of laboratory services during high demand periods requires a combination of context-specific interventions. Building and ensuring sustainability of local capacity is an integral part of effective surveillance and disease outbreak response efforts.

Outbreak analytics: a developing data science for informing the response to emerging pathogens.

Despite continued efforts to improve health systems worldwide, emerging pathogen epidemics remain a major public health concern. Effective response to such outbreaks relies on timely intervention, ideally informed by all available sources of data. The collection, visualization and analysis of outbreak data are becoming increasingly complex, owing to the diversity in types of data, questions and available methods to address them. Recent advances have led to the rise of outbreak analytics, an emerging data science focused on the technological and methodological aspects of the outbreak data pipeline, from collection to analysis, modelling and reporting to inform outbreak response. In this article, we assess the current state of the field. After laying out the context of outbreak response, we critically review the most common analytics components, their inter-dependencies, data requirements and the type of information they can provide to inform operations in real time. We discuss some challenges and opportunities and conclude on the potential role of outbreak analytics for improving our understanding of, and response to outbreaks of emerging pathogens. This article is part of the theme issue 'Modelling infectious disease outbreaks in humans, animals and plants: epidemic forecasting and control'. This theme issue is linked with the earlier issue 'Modelling infectious disease outbreaks in humans, animals and plants: approaches and important themes'.

Ebola Virus Infection Associated with Transmission from Survivors.

Ebola virus (EBOV) can persist in immunologically protected body sites in survivors of Ebola virus disease, creating the potential to initiate new chains of transmission. From the outbreak in West Africa during 2014-2016, we identified 13 possible events of viral persistence-derived transmission of EBOV (VPDTe) and applied predefined criteria to classify transmission events based on the strength of evidence for VPDTe and source and route of transmission. For 8 events, a recipient case was identified; possible source cases were identified for 5 of these 8. For 5 events, a recipient case or chain of transmission could not be confidently determined. Five events met our criteria for sexual transmission (male-to-female). One VPDTe event led to at least 4 generations of cases; transmission was limited after the other events. VPDTe has increased the importance of Ebola survivor services and sustained surveillance and response capacity in regions with previously widespread transmission.

Emergence of Monkeypox - West and Central Africa, 1970-2017.

The recent apparent increase in human monkeypox cases across a wide geographic area, the potential for further spread, and the lack of reliable surveillance have raised the level of concern for this emerging zoonosis. In November 2017, the World Health Organization (WHO), in collaboration with CDC, hosted an informal consultation on monkeypox with researchers, global health partners, ministries of health, and orthopoxvirus experts to review and discuss human monkeypox in African countries where cases have been recently detected and also identify components of surveillance and response that need improvement. Endemic human monkeypox has been reported from more countries in the past decade than during the previous 40 years. Since 2016, confirmed cases of monkeypox have occurred in Central African Republic, Democratic Republic of the Congo, Liberia, Nigeria, Republic of the Congo, and Sierra Leone and in captive chimpanzees in Cameroon. Many countries with endemic monkeypox lack recent experience and specific knowledge about the disease to detect cases, treat patients, and prevent further spread of the virus. Specific improvements in surveillance capacity, laboratory diagnostics, and infection control measures are needed to launch an efficient response. Further, gaps in knowledge about the epidemiology and ecology of the virus need to be addressed to design, recommend, and implement needed prevention and control measures.

Development of risk reduction behavioral counseling for Ebola virus disease survivors enrolled in the Sierra Leone Ebola Virus Persistence Study, 2015-2016.

BACKGROUND: During the 2014-2016 West Africa Ebola Virus Disease (EVD) epidemic, the public health community had concerns that sexual transmission of the Ebola virus (EBOV) from EVD survivors was a risk, due to EBOV persistence in body fluids of EVD survivors, particularly semen. The Sierra Leone Ebola Virus Persistence Study was initiated to investigate this risk by assessing EBOV persistence in numerous body fluids of EVD survivors and providing risk reduction counseling based on test results for semen, vaginal fluid, menstrual blood, urine, rectal fluid, sweat, tears, saliva, and breast milk. This publication describes implementation of the counseling protocol and the key lessons learned. METHODOLOGY/PRINCIPAL FINDINGS: The Ebola Virus Persistence Risk Reduction Behavioral Counseling Protocol was developed from a framework used to prevent transmission of HIV and other sexually transmitted infections. The framework helped to identify barriers to risk reduction and facilitated the development of a personalized risk-reduction plan, particularly around condom use and abstinence. Pre-test and post-test counseling sessions included risk reduction guidance, and post-test counseling was based on the participants' individual test results. The behavioral counseling protocol enabled study staff to translate the study's body fluid test results into individualized information for study participants. CONCLUSIONS/SIGNIFICANCE: The Ebola Virus Persistence Risk Reduction Behavioral Counseling Protocol provided guidance to mitigate the risk of EBOV transmission from EVD survivors. It has since been shared with and adapted by other EVD survivor body fluid testing programs and studies in Ebola-affected countries.

Implementation of a study to examine the persistence of Ebola virus in the body fluids of Ebola virus disease survivors in Sierra Leone: Methodology and lessons learned.

BACKGROUND: The 2013-2016 West African Ebola virus disease epidemic was unprecedented in terms of the number of cases and survivors. Prior to this epidemic there was limited data available on the persistence of Ebola virus in survivors' body fluids and the potential risk of transmission, including sexual transmission. METHODOLOGY/PRINCIPAL FINDINGS: Given the urgent need to determine the persistence of Ebola virus in survivors' body fluids, an observational cohort study was designed and implemented during the epidemic response operation in Sierra Leone. This publication describes study implementation methodology and the key lessons learned. Challenges encountered during implementation included unforeseen duration of follow-up, complexity of interpreting and communicating laboratory results to survivors, and the urgency of translating research findings into public health practice. Strong community engagement helped rapidly implement the study during the epidemic. The study was conducted in two phases. The first phase was initiated within five months of initial protocol discussions and assessed persistence of Ebola virus in semen of 100 adult men. The second phase assessed the persistence of virus in multiple body fluids (semen or vaginal fluid, menstrual blood, breast milk, and urine, rectal fluid, sweat, saliva, tears), of 120 men and 120 women. CONCLUSION/SIGNIFICANCE: Data from this study informed national and global guidelines in real time and demonstrated the need to implement semen testing programs among Ebola virus disease survivors. The lessons learned and study tools developed accelerated the implementation of such programs in Ebola virus disease affected countries, and also informed studies examining persistence of Zika virus. Research is a vital component of the public health response to an epidemic of a poorly characterized disease. Adequate resources should be rapidly made available to answer critical research questions, in order to better inform response efforts.

Development, Use, and Impact of a Global Laboratory Database During the 2014 Ebola Outbreak in West Africa.

Background: The international impact, rapid widespread transmission, and reporting delays during the 2014 Ebola outbreak in West Africa highlighted the need for a global, centralized database to inform outbreak response. The World Health Organization and Emerging and Dangerous Pathogens Laboratory Network addressed this need by supporting the development of a global laboratory database. Methods: Specimens were collected in the affected countries from patients and dead bodies meeting the case definitions for Ebola virus disease. Test results were entered in nationally standardized spreadsheets and consolidated onto a central server. Results: From March 2014 through August 2016, 256343 specimens tested for Ebola virus disease were captured in the database. Thirty-one specimen types were collected, and a variety of diagnostic tests were performed. Regular analysis of data described the functionality of laboratory and response systems, positivity rates, and the geographic distribution of specimens. Conclusion: With data standardization and end user buy-in, the collection and analysis of large amounts of data with multiple stakeholders and collaborators across various user-access levels was made possible and contributed to outbreak response needs. The usefulness and value of a multifunctional global laboratory database is far reaching, with uses including virtual biobanking, disease forecasting, and adaption to other disease outbreaks.

Ebola RNA Persistence in Semen of Ebola Virus Disease Survivors - Final Report.

BACKGROUND: Ebola virus has been detected in the semen of men after their recovery from Ebola virus disease (EVD). We report the presence of Ebola virus RNA in semen in a cohort of survivors of EVD in Sierra Leone. METHODS: We enrolled a convenience sample of 220 adult male survivors of EVD in Sierra Leone, at various times after discharge from an Ebola treatment unit (ETU), in two phases (100 participants were in phase 1, and 120 in phase 2). Semen specimens obtained at baseline were tested by means of a quantitative reverse-transcriptase-polymerase-chain-reaction (RT-PCR) assay with the use of the target sequences of NP and VP40 (in phase 1) or NP and GP (in phase 2). This study did not evaluate directly the risk of sexual transmission of EVD. RESULTS: Of 210 participants who provided an initial semen specimen for analysis, 57 (27%) had positive results on quantitative RT-PCR. Ebola virus RNA was detected in the semen of all 7 men with a specimen obtained within 3 months after ETU discharge, in 26 of 42 (62%) with a specimen obtained at 4 to 6 months, in 15 of 60 (25%) with a specimen obtained at 7 to 9 months, in 4 of 26 (15%) with a specimen obtained at 10 to 12 months, in 4 of 38 (11%) with a specimen obtained at 13 to 15 months, in 1 of 25 (4%) with a specimen obtained at 16 to 18 months, and in no men with a specimen obtained at 19 months or later. Among the 46 participants with a positive result in phase 1, the median baseline cycle-threshold values (higher values indicate lower RNA values) for the NP and VP40 targets were lower within 3 months after ETU discharge (32.4 and 31.3, respectively; in 7 men) than at 4 to 6 months (34.3 and 33.1; in 25), at 7 to 9 months (37.4 and 36.6; in 13), and at 10 to 12 months (37.7 and 36.9; in 1). In phase 2, a total of 11 participants had positive results for NP and GP targets (samples obtained at 4.1 to 15.7 months after ETU discharge); cycle-threshold values ranged from 32.7 to 38.0 for NP and from 31.1 to 37.7 for GP. CONCLUSIONS: These data showed the long-term presence of Ebola virus RNA in semen and declining persistence with increasing time after ETU discharge. (Funded by the World Health Organization and others.).

An outbreak investigation of congenital rubella syndrome in Solomon Islands, 2013.

INTRODUCTION: During May 2012, a rubella outbreak was declared in Solomon Islands. A suspected case of congenital rubella syndrome (CRS) was reported from one hospital 11 months later in 2013. This report describes the subsequent CRS investigation, findings and measures implemented. METHODS: Prospective CRS surveillance was conducted at the newborn nursery, paediatric and post-natal wards, and the paediatric cardiology and ophthalmology clinics of the study hospital from April to July 2013. Retrospective case finding by reviewing medical records was also undertaken to identify additional cases born between January and March 2013 for the same wards and clinics. Cases were identified using established World Health Organization case definitions for CRS. RESULTS: A total of 13 CRS cases were identified, including two laboratory-confirmed, four clinically confirmed and seven suspected cases. Five CRS cases were retrospectively identified, including four suspected and one clinically confirmed case. There was no geospatial clustering of residences. The mothers of the cases were aged between 20 and 36 years. Three of the six mothers available for interview recalled an acute illness with rash during the first trimester of pregnancy. DISCUSSION: Additional CRS cases not captured in this investigation are likely. Caring for CRS cases is a challenge in resource-poor settings. Rubella vaccination is safe and effective and can prevent the serious consequences of CRS. Well planned and funded vaccination activities can prevent future CRS cases.

Evaluation of Minnesota and Illinois hospital respiratory protection programs and health care worker respirator use.

The objective of this study was to assess respiratory protection programs for aerosol-transmissible diseases in acute care hospitals for conformance with regulatory requirements and public health guidelines. Twenty-eight representative hospitals were selected by size, location, and ownership in Minnesota and Illinois. Interviews were conducted with 363 health care workers and 171 managers from high-risk departments. Written programs from each hospital were reviewed for required elements. Seventy-seven health care workers were observed donning and doffing a FFR. The most serious deficiency in many written programs was failure to identify a program administrator. Most written programs lacked adequate details about medical evaluation, fit-testing, and training and did not include a comprehensive risk assessment for aerosol transmissible diseases; tuberculosis was often the only pathogen addressed. Employees with the highest probability of tuberculosis exposure were most likely to pick a respirator for close contact, but higher levels of respiratory protection were rarely selected for aerosol-generating procedures. Surgical masks were most commonly selected for close contact with droplet disease- or influenza-infected patients; better protection (e.g., respirator) was rarely selected for higher-risk exposures. Most of the observed health care workers had access to a NIOSH-certified N95 FFR, properly positioned the facepiece, and formed the nose clip. The most frequent deficiencies were failure to correctly place straps, perform a user seal check, and remove the respirator using straps.

Establishing an early warning alert and response network following the Solomon Islands tsunami in 2013.

PROBLEM: On 6 February 2013, an 8.0 magnitude earthquake generated a tsunami that struck the Santa Cruz Islands, Solomon Islands, killing 10 people and displacing over 4700. APPROACH: A post-disaster assessment of the risk of epidemic disease transmission recommended the implementation of an early warning alert and response network (EWARN) to rapidly detect, assess and respond to potential outbreaks in the aftermath of the tsunami. LOCAL SETTING: Almost 40% of the Santa Cruz Islands' population were displaced by the disaster, and living in cramped temporary camps with poor or absent sanitation facilities and insufficient access to clean water. There was no early warning disease surveillance system. RELEVANT CHANGES: By 25 February, an EWARN was operational in five health facilities that served 90% of the displaced population. Eight priority diseases or syndromes were reported weekly; unexpected health events were reported immediately. Between 25 February and 19 May, 1177 target diseases or syndrome cases were reported. Seven alerts were investigated. No sustained transmission or epidemics were identified. Reporting compliance was 85%. The EWARN was then transitioned to the routine four-syndrome early warning disease surveillance system. LESSON LEARNT: It was necessary to conduct a detailed assessment to evaluate the risk and potential impact of serious infectious disease outbreaks, to assess whether and how enhanced early warning disease surveillance should be implemented. Local capacities and available resources should be considered in planning EWARN implementation. An EWARN can be an opportunity to establish or strengthen early warning disease surveillance capabilities.

A global, multi-disciplinary, multi-sectorial initiative to combat leptospirosis: Global Leptospirosis Environmental Action Network (GLEAN).

Leptospirosis has emerged as a major public health problem in both animals and humans. The true burden of this epidemic and endemic disease is likely to be grossly under-estimated due to the non-specific clinical presentations of the disease and the difficulty of laboratory confirmation. The complexity that surrounds the transmission dynamics, particularly in epidemic situations, requires a coordinated, multi-disciplinary effort. Therefore, the Global Leptospirosis Environmental Action Network (GLEAN) was developed to improve global and local strategies of how to predict, prevent, detect, and intervene in leptospirosis outbreaks in order to prevent and control leptospirosis in high-risk populations.

Rapid tests for diagnosis of leptospirosis: current tools and emerging technologies.

Leptospirosis is an emerging zoonosis with a worldwide distribution but is more commonly found in impoverished populations in developing countries and tropical regions with frequent flooding. The rapid detection of leptospirosis is a critical step to effectively manage the disease and to control outbreaks in both human and animal populations. Therefore, there is a need for accurate and rapid diagnostic tests and appropriate surveillance and alert systems to identify outbreaks. This review describes current in-house methods and commercialized tests for the rapid diagnosis of acute leptospirosis. It focuses on diagnostic tests that can be performed with minimal training and limited equipment in less-developed and newly industrialized countries, particularly in resource-limited settings and with results in minutes to less than 4 hours. We also describe recent technological advances in the field of diagnostic tests that could allow for the development of innovative rapid tests in the near future.