Sensitivity of contact-tracing for COVID-19 in Thailand: a capture-recapture application.

BACKGROUND: We investigate the completeness of contact tracing for COVID-19 during the first wave of the COVID-19 pandemic in Thailand, from early January 2020 to 30 June 2020. METHODS: Uni-list capture-recapture models were applied to the frequency distributions of index cases to inform two questions: (1) the unobserved number of index cases with contacts, and (2) the unobserved number of index cases with secondary cases among their contacts. RESULTS: Generalized linear models (using Poisson and logistic families) did not return any significant predictor (age, sex, nationality, number of contacts per case) on the risk of transmission and hence capture-recapture models did not adjust for observed heterogeneity. Best fitting models, a zero truncated negative binomial for question 1 and zero-truncated Poisson for question 2, returned sensitivity estimates for contact tracing performance of 77.6% (95% CI = 73.75-81.54%) and 67.6% (95% CI = 53.84-81.38%), respectively. A zero-inflated negative binomial model on the distribution of index cases with secondary cases allowed the estimation of the effective reproduction number at 0.14 (95% CI = 0.09-0.22), and the overdispersion parameter at 0.1. CONCLUSION: Completeness of COVID-19 contact tracing in Thailand during the first wave appeared moderate, with around 67% of infectious transmission chains detected. Overdispersion was present suggesting that most of the index cases did not result in infectious transmission chains and the majority of transmission events stemmed from a small proportion of index cases.

Novel Use of Capture-Recapture Methods to Estimate Completeness of Contact Tracing during an Ebola Outbreak, Democratic Republic of the Congo, 2018-2020.

Despite its critical role in containing outbreaks, the efficacy of contact tracing, measured as the sensitivity of case detection, remains an elusive metric. We estimated the sensitivity of contact tracing by applying unilist capture-recapture methods on data from the 2018-2020 outbreak of Ebola virus disease in the Democratic Republic of the Congo. To compute sensitivity, we applied different distributional assumptions to the zero-truncated count data to estimate the number of unobserved case-patients with any contacts and infected contacts. Geometric distributions were the best-fitting models. Our results indicate that contact tracing efforts identified almost all (n = 792, 99%) of case-patients with any contacts but only half (n = 207, 48%) of case-patients with infected contacts, suggesting that contact tracing efforts performed well at identifying contacts during the listing stage but performed poorly during the contact follow-up stage. We discuss extensions to our work and potential applications for the ongoing coronavirus pandemic.

Epidemiological, clinical, and public health response characteristics of a large outbreak of diphtheria among the Rohingya population in Cox's Bazar, Bangladesh, 2017 to 2019: A retrospective study.

BACKGROUND: Unrest in Myanmar in August 2017 resulted in the movement of over 700,000 Rohingya refugees to overcrowded camps in Cox's Bazar, Bangladesh. A large outbreak of diphtheria subsequently began in this population. METHODS AND FINDINGS: Data were collected during mass vaccination campaigns (MVCs), contact tracing activities, and from 9 Diphtheria Treatment Centers (DTCs) operated by national and international organizations. These data were used to describe the epidemiological and clinical features and the control measures to prevent transmission, during the first 2 years of the outbreak. Between November 10, 2017 and November 9, 2019, 7,064 cases were reported: 285 (4.0%) laboratory-confirmed, 3,610 (51.1%) probable, and 3,169 (44.9%) suspected cases. The crude attack rate was 51.5 cases per 10,000 person-years, and epidemic doubling time was 4.4 days (95% confidence interval [CI] 4.2-4.7) during the exponential growth phase. The median age was 10 years (range 0-85), and 3,126 (44.3%) were male. The typical symptoms were sore throat (93.5%), fever (86.0%), pseudomembrane (34.7%), and gross cervical lymphadenopathy (GCL; 30.6%). Diphtheria antitoxin (DAT) was administered to 1,062 (89.0%) out of 1,193 eligible patients, with adverse reactions following among 229 (21.6%). There were 45 deaths (case fatality ratio [CFR] 0.6%). Household contacts for 5,702 (80.7%) of 7,064 cases were successfully traced. A total of 41,452 contacts were identified, of whom 40,364 (97.4%) consented to begin chemoprophylaxis; adherence was 55.0% (N = 22,218) at 3-day follow-up. Unvaccinated household contacts were vaccinated with 3 doses (with 4-week interval), while a booster dose was administered if the primary vaccination schedule had been completed. The proportion of contacts vaccinated was 64.7% overall. Three MVC rounds were conducted, with administrative coverage varying between 88.5% and 110.4%. Pentavalent vaccine was administered to those aged 6 weeks to 6 years, while tetanus and diphtheria (Td) vaccine was administered to those aged 7 years and older. Lack of adequate diagnostic capacity to confirm cases was the main limitation, with a majority of cases unconfirmed and the proportion of true diphtheria cases unknown. CONCLUSIONS: To our knowledge, this is the largest reported diphtheria outbreak in refugee settings. We observed that high population density, poor living conditions, and fast growth rate were associated with explosive expansion of the outbreak during the initial exponential growth phase. Three rounds of mass vaccinations targeting those aged 6 weeks to 14 years were associated with only modestly reduced transmission, and additional public health measures were necessary to end the outbreak. This outbreak has a long-lasting tail, with Rt oscillating at around 1 for an extended period. An adequate global DAT stockpile needs to be maintained. All populations must have access to health services and routine vaccination, and this access must be maintained during humanitarian crises.

Early Insights from Statistical and Mathematical Modeling of Key Epidemiologic Parameters of COVID-19.

We report key epidemiologic parameter estimates for coronavirus disease identified in peer-reviewed publications, preprint articles, and online reports. Range estimates for incubation period were 1.8-6.9 days, serial interval 4.0-7.5 days, and doubling time 2.3-7.4 days. The effective reproductive number varied widely, with reductions attributable to interventions. Case burden and infection fatality ratios increased with patient age. Implementation of combined interventions could reduce cases and delay epidemic peak up to 1 month. These parameters for transmission, disease severity, and intervention effectiveness are critical for guiding policy decisions. Estimates will likely change as new information becomes available.

World Health Organization Early Warning, Alert and Response System in the Rohingya Crisis, Bangladesh, 2017-2018.

The Early Warning, Alert and Response System (EWARS) is a web-based system and mobile application for outbreak detection and response in emergency settings. EWARS provided timely information on epidemic-potential diseases among >700,000 Rohingya refugees across settlements. EWARS helped in targeting new measles vaccination campaigns and investigating suspected outbreaks of acute jaundice syndrome.

Optimizing the timing of an end-of-outbreak declaration: Ebola virus disease in the Democratic Republic of the Congo.

Following the apparent final case in an Ebola virus disease (EVD) outbreak, the decision to declare the outbreak over must balance societal benefits of relaxing interventions against the risk of resurgence. Estimates of the end-of-outbreak probability (the probability that no future cases will occur) provide quantitative evidence that can inform the timing of an end-of-outbreak declaration. An existing modeling approach for estimating the end-of-outbreak probability requires comprehensive contact tracing data describing who infected whom to be available, but such data are often unavailable or incomplete during outbreaks. Here, we develop a Markov chain Monte Carlo-based approach that extends the previous method and does not require contact tracing data. Considering data from two EVD outbreaks in the Democratic Republic of the Congo, we find that data describing who infected whom are not required to resolve uncertainty about when to declare an outbreak over.

Factors Associated with Reliable Contact Tracing During the 2021 Ebola Virus Disease Outbreak in Guinea.

BACKGROUND: In 2021, an Ebola virus disease (EVD) outbreak was declared in Guinea, linked to persistent virus from the 2014-2016 West Africa Epidemic. This paper analyzes factors associated with contact tracing reliability (defined as completion of a 21-day daily follow-up) during the 2021 outbreak, and transitively, provides recommendations for enhancing contact tracing reliability in future. METHODS: We conducted a descriptive and analytical cross-sectional study using multivariate regression analysis of contact tracing data from 1071 EVD contacts of 23 EVD cases (16 confirmed and 7 probable). RESULTS: Findings revealed statistically significant factors affecting contact tracing reliability. Unmarried contacts were 12.76× more likely to miss follow-up than those married (OR = 12.76; 95% CI [3.39-48.05]; p < 0.001). Rural-dwelling contacts had 99% lower odds of being missed during the 21-day follow-up, compared to those living in urban areas (OR = 0.01; 95% CI [0.00-0.02]; p < 0.01). Contacts who did not receive food donations were 3× more likely to be missed (OR = 3.09; 95% CI [1.68-5.65]; p < 0.001) compared to those who received them. Contacts in health areas with a single team were 8× more likely to be missed (OR = 8.16; 95% CI [5.57-11.96]; p < 0.01) than those in health areas with two or more teams (OR = 1.00; 95% CI [1.68-5.65]; p < 0.001). Unvaccinated contacts were 30.1× more likely to be missed compared to vaccinated contacts (OR = 30.1; 95% CI [5.12-176.83]; p < 0.001). CONCLUSION: Findings suggest that contact tracing reliability can be significantly influenced by various demographic and organizational factors. Considering and understanding these factors-and where possible addressing them-may be crucial when designing and implementing contact tracing strategies during future outbreaks in low-resource settings.

Investing in preparedness for rapid detection and control of epidemics: analysis of health system reforms and their effect on 2021 Ebola virus disease epidemic response in Guinea.

The 2014-2016 West Africa Ebola Virus Disease (EVD) Epidemic devastated Guinea's health system and constituted a public health emergency of international concern. Following the crisis, Guinea invested in the establishment of basic health system reforms and crucial legal instruments for strengthening national health security in line with the WHO's recommendations for ensuring better preparedness for (and, therefore, a response to) health emergencies. The investments included the scaling up of Integrated Disease Surveillance and Response; Joint External Evaluation of International Health Regulation capacities; National Action Plan for Health Security; Simulation Exercises; One Health platforms; creation of decentralised structures such as regional and prefectural Emergency Operation Centres; Risk assessment and hazard identification; Expanding human resources capacity; Early Warning Alert System and community preparedness. These investments were tested in the subsequent 2021 EVD outbreak and other epidemics. In this case, there was a timely declaration and response to the 2021 EVD epidemic, a lower-case burden and mortality rate, a shorter duration of the epidemic and a significant reduction in the cost of the response. Similarly, there was timely detection, response and containment of other epidemics including Lassa fever and Marburg virus disease. Findings suggest the utility of the preparedness activities for the early detection and efficient containment of outbreaks, which, therefore, underlines the need for all countries at risk of infectious disease epidemics to invest in similar reforms. Doing so promises to be not only cost-effective but also lifesaving.

A community-based contact isolation strategy to reduce the spread of Ebola virus disease: an analysis of the 2018-2020 outbreak in the Democratic Republic of the Congo.

INTRODUCTION: Despite tremendous progress in the development of diagnostics, vaccines and therapeutics for Ebola virus disease (EVD), challenges remain in the implementation of holistic strategies to rapidly curtail outbreaks. We investigated the effectiveness of a community-based contact isolation strategy to limit the spread of the disease in the Democratic Republic of Congo (DRC). METHODS: We did a quasi-experimental comparison study. Eligible participants were EVD contacts registered from 12 June 2019 to 18 May 2020 in Beni and Mabalako Health Zones. Intervention group participants were isolated to specific community sites for the duration of their follow-up. Comparison group participants underwent contact tracing without isolation. The primary outcome was measured as the reproduction number (R) in the two groups. Secondary outcomes were the delay from symptom onset to isolation and case management, case fatality rate (CFR) and vaccination uptake. RESULTS: 27 324 EVD contacts were included in the study; 585 in the intervention group and 26 739 in the comparison group. The intervention group generated 32 confirmed cases (5.5%) in the first generation, while the comparison group generated 87 (0.3%). However, the 32 confirmed cases arising from the intervention contacts did not generate any additional transmission (R=0.00), whereas the 87 confirmed cases arising from the comparison group generated 99 secondary cases (R=1.14). The average delay between symptom onset and case isolation was shorter (1.3 vs 4.8 days; p<0.0001), CFR lower (12.5% vs 48.4%; p=0.0001) and postexposure vaccination uptake higher (86.0% vs 56.8%; p<0.0001) in the intervention group compared with the comparison group. A significant difference was also found between intervention and comparison groups in survival rate at the discharge of hospitalised confirmed patients (87.9% vs 47.7%, respectively; p=0.0004). CONCLUSION: The community-based contact isolation strategy used in DRC shows promise as a potentially effective approach for the rapid cessation of EVD transmission, highlighting the importance of rapidly implemented, community-oriented and trust-building control strategies.

Feasibility, acceptability, and effectiveness of non-pharmaceutical interventions against infectious diseases among crisis-affected populations: a scoping review.

BACKGROUND: Non-pharmaceutical interventions (NPIs) are a crucial suite of measures to prevent and control infectious disease outbreaks. Despite being particularly important for crisis-affected populations and those living in informal settlements, who typically reside in overcrowded and resource limited settings with inadequate access to healthcare, guidance on NPI implementation rarely takes the specific needs of such populations into account. We therefore conducted a systematic scoping review of the published evidence to describe the landscape of research and identify evidence gaps concerning the acceptability, feasibility, and effectiveness of NPIs among crisis-affected populations and informal settlements. METHODS: We systematically reviewed peer-reviewed articles published between 1970 and 2020 to collate available evidence on the feasibility, acceptability, and effectiveness of NPIs in crisis-affected populations and informal settlements. We performed quality assessments of each study using a standardised questionnaire. We analysed the data to produce descriptive summaries according to a number of categories: date of publication; geographical region of intervention; typology of crisis, shelter, modes of transmission, NPI, research design; study design; and study quality. RESULTS: Our review included 158 studies published in 85 peer-reviewed articles. Most research used low quality study designs. The acceptability, feasibility, and effectiveness of NPIs was highly context dependent. In general, simple and cost-effective interventions such as community-level environmental cleaning and provision of water, sanitation and hygiene services, and distribution of items for personal protection such as insecticide-treated nets, were both highly feasible and acceptable. Logistical, financial, and human resource constraints affected both the implementation and sustainability of measures. Community engagement emerged as a strong factor contributing to the effectiveness of NPIs. Conversely, measures that involve potential restriction on personal liberty such as case isolation and patient care and burial restrictions were found to be less acceptable, despite apparent effectiveness. CONCLUSIONS: Overall, the evidence base was variable, with substantial knowledge gaps which varied between settings and pathogens. Based on the current landscape, robust evidence-based guidance is not possible, and a research agenda is urgently required that focusses on these specific vulnerable populations. Although implementation of NPIs presents unique practical challenges in these settings, it is critical that such an agenda is put in place, and that the lessons learned from historical and present experiences are documented to build a firm evidence base.

People-centred surveillance: a narrative review of community-based surveillance among crisis-affected populations.

Outbreaks of disease in settings affected by crises grow rapidly due to late detection and weakened public health systems. Where surveillance is underfunctioning, community-based surveillance can contribute to rapid outbreak detection and response, a core capacity of the International Health Regulations. We reviewed articles describing the potential for community-based surveillance to detect diseases of epidemic potential, outbreaks, and mortality among populations affected by crises. Surveillance objectives have included the early warning of outbreaks, active case finding during outbreaks, case finding for eradication programmes, and mortality surveillance. Community-based surveillance can provide sensitive and timely detection, identify valid signals for diseases with salient symptoms, and provide continuity in remote areas during cycles of insecurity. Effectiveness appears to be mediated by operational requirements for continuous supervision of large community networks, verification of a large number of signals, and integration of community-based surveillance within the routine investigation and response infrastructure. Similar to all community health systems, community-based surveillance requires simple design, reliable supervision, and early and routine monitoring and evaluation to ensure data validity. Research priorities include the evaluation of syndromic case definitions, electronic data collection for community members, sentinel site designs, and statistical techniques to counterbalance false positive signals.

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'.

Measles seroprevalence in Chiradzulu district, Malawi: Implications for evaluating vaccine coverage.

INTRODUCTION: Self-reported measles vaccination coverage is frequently used to inform vaccination strategies in resource-poor settings. However, little is known to what extent this is a reliable indicator of underlying seroprotection, information that could provide guidance ensuring the success of measles control and elimination strategies. METHODS: As part of a study exploring HIV infection and measles susceptibility, we conveniently sampled consenting HIV-uninfected patients presenting at the HIV voluntary counselling and testing centre, and HIV-infected patients presenting for regular care, in Chiradzulu district hospital, Malawi, between January and September 2012. RESULTS: A total of 2106 participants were recruited between January and September 2012, three quarters of whom were HIV positive. Vaccination cards were available for just 7 participants (0.36%). 91.9% of participants were measles seropositive. Older age (OR=1.11 per year increase in age; 95%CI: 1.09-1.14) and being female (OR=1.90; 95%CI: 1.26-2.87) were both associated with significantly increased odds for seroprotection. Prior vaccination history was associated with lower odds (Odds Ratio (OR)=0.44; 95% confidence interval (CI): 0.22-0.85) for confirmed seropositivity. Previous measles infection was not significantly associated with seroprotection (OR=1.31; 95%CI: 0.49-3.51). Protection by history and serological status were concordant for 64.3% of participants <35 years old. However, analysis by age group reveals important differences in concordance between the ages, with a greater degree of discordance among younger ages. Vaccination and/or infection history as a predictor of seropositivity was 75.8% sensitive, but just 10.3% specific. CONCLUSION: Reported vaccination and previous infection were poor predictors of seropositivity, suggesting these may be unreliable indicators of seroprotection status. Such serosurveys may be indicated in similar settings in which overestimation of the proportion of seroprotected individuals could have important ramifications if used to guide vaccination strategies.

Exploring HIV infection and susceptibility to measles among older children and adults in Malawi: a facility-based study.

BACKGROUND: HIV infection increases measles susceptibility in infants, but little is known about this relationship among older children and adults. We conducted a facility-based study to explore whether HIV status and/or CD4 count were associated with either measles seroprotection and/or measles antibody concentration. METHODS: A convenience sample was recruited comprising HIV-infected patients presenting for follow-up care, and HIV-uninfected individuals presenting for HIV testing at Chiradzulu District Hospital, Malawi, from January to September 2012. We recorded age, sex, and reported measles vaccination and infection history. Blood samples were taken to determine the CD4 count and measles antibody concentration. RESULTS: One thousand nine hundred and thirty-five participants were recruited (1434 HIV-infected and 501 HIV-uninfected). The majority of adults and approximately half the children were seroprotected against measles, with lower odds among HIV-infected children (adjusted odds ratio 0.27, 95% confidence interval 0.10-0.69; p=0.006), but not adults. Among HIV-infected participants, neither CD4 count (p=0.16) nor time on antiretroviral therapy (p=0.25) were associated with measles antibody concentration, while older age (p<0.001) and female sex (p<0.001) were independently associated with this measure. CONCLUSIONS: We found no evidence that HIV infection contributes to the risk of measles infection among adults, but HIV-infected children (including at ages older than previously reported), were less likely to be seroprotected in this sample.

Descriptive epidemiology of typhoid fever during an epidemic in Harare, Zimbabwe, 2012.

BACKGROUND: Typhoid fever remains a significant public health problem in developing countries. In October 2011, a typhoid fever epidemic was declared in Harare, Zimbabwe - the fourth enteric infection epidemic since 2008. To orient control activities, we described the epidemiology and spatiotemporal clustering of the epidemic in Dzivaresekwa and Kuwadzana, the two most affected suburbs of Harare. METHODS: A typhoid fever case-patient register was analysed to describe the epidemic. To explore clustering, we constructed a dataset comprising GPS coordinates of case-patient residences and randomly sampled residential locations (spatial controls). The scale and significance of clustering was explored with Ripley K functions. Cluster locations were determined by a random labelling technique and confirmed using Kulldorff's spatial scan statistic. PRINCIPAL FINDINGS: We analysed data from 2570 confirmed and suspected case-patients, and found significant spatiotemporal clustering of typhoid fever in two non-overlapping areas, which appeared to be linked to environmental sources. Peak relative risk was more than six times greater than in areas lying outside the cluster ranges. Clusters were identified in similar geographical ranges by both random labelling and Kulldorff's spatial scan statistic. The spatial scale at which typhoid fever clustered was highly localised, with significant clustering at distances up to 4.5 km and peak levels at approximately 3.5 km. The epicentre of infection transmission shifted from one cluster to the other during the course of the epidemic. CONCLUSIONS: This study demonstrated highly localised clustering of typhoid fever during an epidemic in an urban African setting, and highlights the importance of spatiotemporal analysis for making timely decisions about targetting prevention and control activities and reinforcing treatment during epidemics. This approach should be integrated into existing surveillance systems to facilitate early detection of epidemics and identify their spatial range.

Emerging filoviral disease in Uganda: proposed explanations and research directions.

Outbreaks of Ebola and Marburg virus diseases have recently increased in frequency in Uganda. This increase is probably caused by a combination of improved surveillance and laboratory capacity, increased contact between humans and the natural reservoir of the viruses, and fluctuations in viral load and prevalence within this reservoir. The roles of these proposed explanations must be investigated in order to guide appropriate responses to the changing epidemiological profile. Other African settings in which multiple filoviral outbreaks have occurred could also benefit from such information.

High levels of mortality, malnutrition, and measles, among recently-displaced Somali refugees in Dagahaley camp, Dadaab refugee camp complex, Kenya, 2011.

BACKGROUND: Following a rapid influx of over 200,000 displaced Somalis into the Dadaab refugee camp complex in Kenya, Médecins Sans Frontières conducted a mortality and nutrition survey of the population living in Bulo Bacte, a self-settled area surrounding Dagahaley camp (part of this complex). METHODS: The survey was conducted between 31st July and 10th August 2011. We exhaustively interviewed representatives from all households in Bulo Bacte, collecting information on deaths, births, and population movements during the recall period (15th February 2011 to survey date), in order to provide estimates of retrospective death rates. We recorded the mid-upper arm circumference and presence or absence of bipedal oedema of all children of height 67-<110 cm to provide estimates of global and severe acute malnutrition. RESULTS: The surveyed population included 26,583 individuals, of whom 6,488 (24.4%) were children aged under 5 years. There were 360 deaths reported during the 177 days of the recall period, of which 186 (52%) were among children aged under 5 years. The crude death rate for the entire recall period was 0.8 per 10,000 person-days. The under-5 death rate was 1.8 per 10,000 person-days. More than two-thirds of all deaths were reported to have been associated with diarrhoea (25%), cough or other breathing difficulties (24%), or with fever (19%). Measles accounted for a reported 17% of all deaths; this was due to a measles outbreak that occurred between June and October 2011.Global acute malnutrition was observed in 13.4%, and severe acute malnutrition in 3.0%, of children measuring 67-<110 cm. Among children measuring 110-< 140 cm, 9.8% met the admission criteria for entry into the nutritional programme. Trends of decreasing death rates and malnutrition prevalence with length of stay in Bulo Bacte were observed. CONCLUSIONS: We report high death rates and prevalence of malnutrition among this population, reflecting at least a partial failure of the various humanitarian and governmental actors to adequately safeguard the welfare of this population. An outbreak of measles and long delays before registration should not have occurred. The recommendations for measles vaccination among crisis-affected populations should be revised to take into account the epidemiologic context. Organisations must be sensitive and reactive to changes in the health status of the populations they assist.