Informing the pandemic response: the role of the WHO's COVID-19 Weekly Epidemiological Update.

On 31 December 2019, the Municipal Health Commission of Wuhan, China, reported a cluster of atypical pneumonia cases. On 5 January 2020, the WHO publicly released a Disease Outbreak News (DON) report, providing information about the pneumonia cases, implemented response interventions, and WHO's risk assessment and advice on public health and social measures. Following 9 additional DON reports and 209 daily situation reports, on 17 August 2020, WHO published the first edition of the COVID-19 Weekly Epidemiological Update (WEU). On 1 September 2023, the 158th edition of the WEU was published on WHO's website, marking its final issue. Since then, the WEU has been replaced by comprehensive global epidemiological updates on COVID-19 released every 4 weeks. During the span of its publication, the webpage that hosts the WEU and the COVID-19 Operational Updates was accessed annually over 1.4 million times on average, with visits originating from more than 100 countries. This article provides an in-depth analysis of the WEU process, from data collection to publication, focusing on the scope, technical details, main features, underlying methods, impact and limitations. We also discuss WHO's experience in disseminating epidemiological information on the COVID-19 pandemic at the global level and provide recommendations for enhancing collaboration and information sharing to support future health emergency responses.

Surveillance for variants of SARS-CoV-2 to inform risk assessments.

Since the beginning of the coronavirus disease 2019 (COVID-19) pandemic, numerous severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants have emerged, some leading to large increases in infections, hospitalizations and deaths globally. The virus's impact on public health depends on many factors, including the emergence of new viral variants and their global spread. Consequently, the early detection and surveillance of variants and characterization of their clinical effects are vital for assessing their health risk. The unprecedented capacity for viral genomic sequencing and data sharing built globally during the pandemic has enabled new variants to be rapidly detected and assessed. This article describes the main variants circulating globally between January 2020 and June 2023, the genetic features driving variant evolution, and the epidemiological impact of these variants across countries and regions. Second, we report how integrating genetic variant surveillance with epidemiological data and event-based surveillance, through a network of World Health Organization partners, supported risk assessment and helped provide guidance on pandemic responses. In addition, given the evolutionary characteristics of circulating variants and the immune status of populations, we propose future directions for the sustainable genomic surveillance of SARS-CoV-2 variants, both nationally and internationally: (i) optimizing variant surveillance by including environmental monitoring; (ii) coordinating laboratory assessment of variant evolution and phenotype; (iii) linking data on circulating variants with clinical data; and (iv) expanding genomic surveillance to additional pathogens. Experience during the COVID-19 pandemic has shown that genomic surveillance of pathogens can provide essential, timely and evidence-based information for public health decision-making.

Depuis le début de la pandémie de coronavirus survenue en 2019 (COVID-19), de nombreux variants du coronavirus 2 du syndrome respiratoire aigu sévère (SARS-CoV-2) sont apparus, certains entraînant une forte augmentation du nombre d'infections, d'hospitalisations et de décès dans le monde. L'impact du virus sur la santé publique dépend de nombreux facteurs, notamment l'émergence de nouveaux variants viraux et leur propagation à l'échelle mondiale. Par conséquent, la détection précoce et la surveillance des variants ainsi que la caractérisation de leurs effets cliniques sont essentielles pour évaluer leur risque pour la santé. La capacité sans précédent de séquençage du génome viral et de partage des données, capacité mise en place à l'échelle mondiale pendant la pandémie, a permis de détecter et d'évaluer rapidement de nouveaux variants. Le présent article décrit les principaux variants circulant dans le monde entre janvier 2020 et juin 2023, les caractéristiques génétiques à l'origine de leur évolution et leur impact épidémiologique dans les différents pays et régions. Ensuite, nous expliquerons comment l'intégration de la surveillance des variants génétiques aux données épidémiologiques et à la surveillance fondée sur les événements, par l'intermédiaire d'un réseau de partenaires de l'Organisation mondiale de la santé, a permis de faciliter l'évaluation des risques et de fournir des orientations sur les mesures à prendre en période de pandémie. En outre, compte tenu des caractéristiques évolutives des variants en circulation et de l'état immunitaire des populations, nous proposons des orientations futures pour une surveillance génomique durable des variants du SARS-CoV-2, au niveau tant national qu'international: (i) optimiser la surveillance des variants en incluant le suivi environnemental; (ii) coordonner l'évaluation en laboratoire de l'évolution des variants et du phénotype; (iii) établir un lien entre les données sur les variants en circulation et les données cliniques; et (iv) étendre la surveillance génomique à d'autres agents pathogènes. L'expérience de la pandémie de COVID-19 a mis en évidence que la surveillance génomique des agents pathogènes peut fournir en temps utile des informations essentielles fondées sur des preuves en vue de la prise de décisions en matière de santé publique.

Desde el inicio de la pandemia de la enfermedad por coronavirus de 2019 (COVID-19), han aparecido numerosas variantes del coronavirus de tipo 2 causante del síndrome respiratorio agudo severo (SRAS-CoV-2), algunas de las que han provocado un gran aumento de las infecciones, hospitalizaciones y muertes en todo el mundo. El impacto del virus en la salud pública depende de muchos factores, entre ellos la aparición de nuevas variantes víricas y su propagación mundial. En consecuencia, la detección y vigilancia tempranas de las variantes y la caracterización de sus efectos clínicos son vitales para evaluar su riesgo sanitario. La capacidad sin precedentes de secuenciación genómica viral y de intercambio de datos creada a nivel mundial durante la pandemia ha permitido detectar y evaluar rápidamente variantes nuevas. En este artículo se describen las principales variantes que circulan a nivel mundial entre enero de 2020 y junio de 2023, la característica genética que impulsa la evolución de las variantes y el impacto epidemiológico de estas variantes en los diferentes países y regiones. En segundo lugar, se informa de cómo la integración de la vigilancia de variantes genéticas con los datos epidemiológicos y la vigilancia basada en eventos, a través de una red de asociados de la Organización Mundial de la Salud, apoyó la evaluación de riesgos y ayudó a proporcionar orientación sobre las respuestas a la pandemia. Además, dadas las características evolutivas de las variantes circulantes y el estado inmunitario de las poblaciones, se proponen orientaciones futuras para la vigilancia genómica sostenible de las variantes del SRAS-CoV-2, tanto a nivel nacional como internacional: (i) optimizar la vigilancia de las variantes mediante la inclusión de la monitorización ambiental; (ii) coordinar la evaluación de laboratorio de la evolución y el fenotipo de las variantes; (iii) vincular los datos sobre las variantes circulantes con los datos clínicos; y (iv) ampliar la vigilancia genómica a patógenos adicionales. La experiencia durante la pandemia de la COVID-19 ha demostrado que la vigilancia genómica de patógenos puede proporcionar información esencial, oportuna y basada en evidencias para la toma de decisiones en materia de salud pública.

WHO Global Situational Alert System: a mixed methods multistage approach to identify country-level COVID-19 alerts.

BACKGROUND: Globally, since 1 January 2020 and as of 24 January 2023, there have been over 664 million cases of COVID-19 and over 6.7 million deaths reported to WHO. WHO developed an evidence-based alert system, assessing public health risk on a weekly basis in 237 countries, territories and areas from May 2021 to June 2022. This aimed to facilitate the early identification of situations where healthcare capacity may become overstretched. METHODS: The process involved a three-stage mixed methods approach. In the first stage, future deaths were predicted from the time series of reported cases and deaths to produce an initial alert level. In the second stage, this alert level was adjusted by incorporating a range of contextual indicators and accounting for the quality of information available using a Bayes classifier. In the third stage, countries with an alert level of 'High' or above were added to an operational watchlist and assistance was deployed as needed. RESULTS: Since June 2021, the system has supported the release of more than US$27 million from WHO emergency funding, over 450 000 rapid antigen diagnostic testing kits and over 6000 oxygen concentrators. Retrospective evaluation indicated that the first two stages were needed to maximise sensitivity, where 44% (IQR 29%-67%) of weekly watchlist alerts would not have been identified using only reported cases and deaths. The alerts were timely and valid in most cases; however, this could only be assessed on a non-representative sample of countries with hospitalisation data available. CONCLUSIONS: The system provided a standardised approach to monitor the pandemic at the country level by incorporating all available data on epidemiological analytics and contextual assessments. While this system was developed for COVID-19, a similar system could be used for future outbreaks and emergencies, with necessary adjustments to parameters and indicators.

Description of the first global outbreak of mpox: an analysis of global surveillance data.

BACKGROUND: In May 2022, several countries with no history of sustained community transmission of mpox (formerly known as monkeypox) notified WHO of new mpox cases. These cases were soon followed by a large-scale outbreak, which unfolded across the world, driven by local, in-country transmission within previously unaffected countries. On July 23, 2022, WHO declared the outbreak a Public Health Emergency of International Concern. Here, we aim to describe the main epidemiological features of this outbreak, the largest reported to date. METHODS: In this analysis of global surveillance data we analysed data for all confirmed mpox cases reported by WHO Member States through the global surveillance system from Jan 1, 2022, to Jan 29, 2023. Data included daily aggregated numbers of mpox cases by country and a case reporting form (CRF) containing information on demographics, clinical presentation, epidemiological exposure factors, and laboratory testing. We used the data to (1) describe the key epidemiological and clinical features of cases; (2) analyse risk factors for hospitalisation (by multivariable mixed-effects binary logistic regression); and (3) retrospectively analyse transmission trends. Sequencing data from GISAID and GenBank were used to analyse monkeypox virus (MPXV) genetic diversity. FINDINGS: Data from 82 807 cases with submitted CRFs were included in the analysis. Cases were primarily due to clade IIb MPXV (mainly lineage B.1, followed by lineage A.2). The outbreak was driven by transmission among males (73 560 [96·4%] of 76 293 cases) who self-identify as men who have sex with men (25 938 [86·9%] of 29 854 cases). The most common reported route of transmission was sexual contact (14 941 [68·7%] of 21 749). 3927 (7·3%) of 54 117 cases were hospitalised, with increased odds for those aged younger than 5 years (adjusted odds ratio 2·12 [95% CI 1·32-3·40], p=0·0020), aged 65 years and older (1·54 [1·05-2·25], p=0·026), female cases (1·61 [1·35-1·91], p<0·0001), and for cases who are immunosuppressed either due to being HIV positive and immunosuppressed (2·00 [1·68-2·37], p<0·0001), or other immunocompromising conditions (3·47 [1·84-6·54], p=0·0001). INTERPRETATION: Continued global surveillance allowed WHO to monitor the epidemic, identify risk factors, and inform the public health response. The outbreak can be attributed to clade IIb MPXV spread by newly described modes of transmission. FUNDING: WHO Contingency Fund for Emergencies. TRANSLATIONS: For the French and Spanish translations of the abstract see Supplementary Materials section.

Measuring the unknown: An estimator and simulation study for assessing case reporting during epidemics.

The fraction of cases reported, known as 'reporting', is a key performance indicator in an outbreak response, and an essential factor to consider when modelling epidemics and assessing their impact on populations. Unfortunately, its estimation is inherently difficult, as it relates to the part of an epidemic which is, by definition, not observed. We introduce a simple statistical method for estimating reporting, initially developed for the response to Ebola in Eastern Democratic Republic of the Congo (DRC), 2018-2020. This approach uses transmission chain data typically gathered through case investigation and contact tracing, and uses the proportion of investigated cases with a known, reported infector as a proxy for reporting. Using simulated epidemics, we study how this method performs for different outbreak sizes and reporting levels. Results suggest that our method has low bias, reasonable precision, and despite sub-optimal coverage, usually provides estimates within close range (5-10%) of the true value. Being fast and simple, this method could be useful for estimating reporting in real-time in settings where person-to-person transmission is the main driver of the epidemic, and where case investigation is routinely performed as part of surveillance and contact tracing activities.

How to improve outbreak response: a case study of integrated outbreak analytics from Ebola in Eastern Democratic Republic of the Congo.

The emerging field of outbreak analytics calls attention to the need for data from multiple sources to inform evidence-based decision making in managing infectious diseases outbreaks. To date, these approaches have not systematically integrated evidence from social and behavioural sciences. During the 2018-2020 Ebola outbreak in Eastern Democratic Republic of the Congo, an innovative solution to systematic and timely generation of integrated and actionable social science evidence emerged in the form of the Cellulle d'Analyse en Sciences Sociales (Social Sciences Analytics Cell) (CASS), a social science analytical cell. CASS worked closely with data scientists and epidemiologists operating under the Epidemiological Cell to produce integrated outbreak analytics (IOA), where quantitative epidemiological analyses were complemented by behavioural field studies and social science analyses to help better explain and understand drivers and barriers to outbreak dynamics. The primary activity of the CASS was to conduct operational social science analyses that were useful to decision makers. This included ensuring that research questions were relevant, driven by epidemiological data from the field, that research could be conducted rapidly (ie, often within days), that findings were regularly and systematically presented to partners and that recommendations were co-developed with response actors. The implementation of the recommendations based on CASS analytics was also monitored over time, to measure their impact on response operations. This practice paper presents the CASS logic model, developed through a field-based externally led consultation, and documents key factors contributing to the usefulness and adaption of CASS and IOA to guide replication for future outbreaks.

Increased transmissibility and global spread of SARS-CoV-2 variants of concern as at June 2021.

We present a global analysis of the spread of recently emerged SARS-CoV-2 variants and estimate changes in effective reproduction numbers at country-specific level using sequence data from GISAID. Nearly all investigated countries demonstrated rapid replacement of previously circulating lineages by the World Health Organization-designated variants of concern, with estimated transmissibility increases of 29% (95% CI: 24-33), 25% (95% CI: 20-30), 38% (95% CI: 29-48) and 97% (95% CI: 76-117), respectively, for B.1.1.7, B.1.351, P.1 and B.1.617.2.

Social Contact Patterns and Implications for Infectious Disease Transmission: A Systematic Review and Meta-Analysis of Contact Surveys.

BACKGROUND: Transmission of respiratory pathogens such as SARS-CoV-2 depends on patterns of contact and mixing across populations. Understanding this is crucial to predict pathogen spread and the effectiveness of control efforts. Most analyses of contact patterns to date have focussed on high-income settings. METHODS: Here, we conduct a systematic review and individual-participant meta-analysis of surveys carried out in low- and middle-income countries and compare patterns of contact in these settings to surveys previously carried out in high-income countries. Using individual-level data from 28,503 participants and 413,069 contacts across 27 surveys we explored how contact characteristics (number, location, duration and whether physical) vary across income settings. RESULTS: Contact rates declined with age in high- and upper-middle-income settings, but not in low-income settings, where adults aged 65+ made similar numbers of contacts as younger individuals and mixed with all age-groups. Across all settings, increasing household size was a key determinant of contact frequency and characteristics, but low-income settings were characterised by the largest, most intergenerational households. A higher proportion of contacts were made at home in low-income settings, and work/school contacts were more frequent in high-income strata. We also observed contrasting effects of gender across income-strata on the frequency, duration and type of contacts individuals made. CONCLUSIONS: These differences in contact patterns between settings have material consequences for both spread of respiratory pathogens, as well as the effectiveness of different non-pharmaceutical interventions. FUNDING: This work is primarily being funded by joint Centre funding from the UK Medical Research Council and DFID (MR/R015600/1).

An outbreak of acute jaundice syndrome (AJS) among the Rohingya refugees in Cox's Bazar, Bangladesh: Findings from enhanced epidemiological surveillance.

In the summer of 2017, an estimated 745,000 Rohingya fled to Bangladesh in what has been described as one of the largest and fastest growing refugee crises in the world. Among numerous health concerns, an outbreak of acute jaundice syndrome (AJS) was detected by the disease surveillance system in early 2018 among the refugee population. This paper describes the investigation into the increase in AJS cases, the process and results of the investigation, which were strongly suggestive of a large outbreak due to hepatitis A virus (HAV). An enhanced serological investigation was conducted between 28 February to 26 March 2018 to determine the etiologies and risk factors associated with the outbreak. A total of 275 samples were collected from 18 health facilities reporting AJS cases. Blood samples were collected from all patients fulfilling the study specific case definition and inclusion criteria, and tested for antibody responses using enzyme-linked immunosorbent assay (ELISA). Out of the 275 samples, 206 were positive for one of the agents tested. The laboratory results confirmed multiple etiologies including 154 (56%) samples tested positive for hepatitis A, 1 (0.4%) positive for hepatitis E, 36 (13%) positive for hepatitis B, 25 (9%) positive for hepatitis C, and 14 (5%) positive for leptospirosis. Among all specimens tested 24 (9%) showed evidence of co-infections with multiple etiologies. Hepatitis A and E are commonly found in refugee camps and have similar clinical presentations. In the absence of robust testing capacity when the epidemic was identified through syndromic reporting, a particular concern was that of a hepatitis E outbreak, for which immunity tends to be limited, and which may be particularly severe among pregnant women. This report highlights the challenges of identifying causative agents in such settings and the resources required to do so. Results from the month-long enhanced investigation did not point out widespread hepatitis E virus (HEV) transmission, but instead strongly suggested a large-scale hepatitis A outbreak of milder consequences, and highlighted a number of other concomitant causes of AJS (acute hepatitis B, hepatitis C, Leptospirosis), albeit most likely at sporadic level. Results strengthen the need for further water and sanitation interventions and are a stark reminder of the risk of other epidemics transmitted through similar routes in such settings, particularly dysentery and cholera. It also highlights the need to ensure clinical management capacity for potentially chronic conditions in this vulnerable population.

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.

Factors associated with delayed presentation to healthcare facilities for Lassa fever cases, Nigeria 2019: a retrospective cohort study.

BACKGROUND: Large outbreaks of Lassa fever (LF) occur annually in Nigeria. The case fatality rate among hospitalised cases is ~ 20%. The antiviral drug ribavirin along with supportive care and rehydration are the recommended treatments but must be administered early (within 6 days of symptom onset) for optimal results. We aimed to identify factors associated with late presentation of LF cases to a healthcare facility to inform interventions. METHODS: We undertook a retrospective cohort study of all laboratory confirmed LF cases reported in Nigeria from December 2018 to April 2019. We performed descriptive epidemiology and a univariate Cox proportional-hazards regression analysis to investigate the effect of clinical (symptom severity), epidemiological (age, sex, education, occupation, residential State) and exposure (travel, attendance at funeral, exposure to rodents or confirmed case) factors on time to presentation. RESULTS: Of 389 cases, median presentation time was 6 days (IQR 4-10 days), with 53% attending within 6 days. There were no differences in presentation times by sex but differences were noted by age-group; 60+ year-olds had the longest delays while 13-17 year-olds had the shortest. By sex and age, there were differences seen among the younger ages, with 0-4-year-old females presenting earlier than males (4 days and 73% vs. 10 days and 30%). For 5-12 and 13-17 year-olds, males presented sooner than females (males: 5 days, 65% and 3 days, 85% vs. females: 6 days, 50% and 5 days, 61%, respectively). Presentation times differed across occupations 4.5-9 days and 20-60%, transporters (people who drive informal public transport vehicles) had the longest delays. Other data were limited (41-95% missing). However, the Cox regression showed no factors were statistically associated with longer presentation time. CONCLUSIONS: Whilst we observed important differences in presentation delays across factors, our sample size was insufficient to show any statistically significant differences that might exist. However, almost half of cases presented after 6 days of onset, highlighting the need for more accurate and complete surveillance data to determine if there is a systemic or specific cause for delays, so to inform, monitor and evaluate public health strategies and improve outcomes.

Considerations for planning COVID-19 treatment services in humanitarian responses.

The COVID-19 pandemic has the potential to cause high morbidity and mortality in crisis-affected populations. Delivering COVID-19 treatment services in crisis settings will likely entail complex trade-offs between offering services of clinical benefit and minimising risks of nosocomial infection, while allocating resources appropriately and safeguarding other essential services. This paper outlines considerations for humanitarian actors planning COVID-19 treatment services where vaccination is not yet widely available. We suggest key decision-making considerations: allocation of resources to COVID-19 treatment services and the design of clinical services should be based on community preferences, likely opportunity costs, and a clearly articulated package of care across different health system levels. Moreover, appropriate service planning requires information on the expected COVID-19 burden and the resilience of the health system. We explore COVID-19 treatment service options at the patient level (diagnosis, management, location and level of treatment) and measures to reduce nosocomial transmission (cohorting patients, protecting healthcare workers). Lastly, we propose key indicators for monitoring COVID-19 health services.

Learning from each other in the COVID-19 pandemic.

The increase in cases of coronavirus disease 2019 (COVID-19) worldwide has been paralleled by increasing information, and misinformation. Accurate public health messaging is essential to counter this, but education may also have a role. Early in the outbreak, The London School of Hygiene & Tropical Medicine partnered with FutureLearn to develop a massive open online course (MOOC) on COVID-19. Our approach was grounded in social constructivism, supporting participation, sharing uncertainties, and encouraging discussion. The first run of the course included over 200,000 participants from 184 countries, with over 88,000 comments at the end of the three-week run. Many participants supported each other's learning in their responses and further questions. Our experience suggests that open education can complement traditional messaging, potentially providing a sustainable approach to countering the spread of misinformation in public health.

Assessment of a health facility based active case finding system for Ebola virus disease in Mbandaka, Democratic Republic of the Congo, June-July 2018.

BACKGROUND: The ninth outbreak of Ebola Virus Disease (EVD) in the Democratic Republic of the Congo occurred in Équateur Province from 8 May-24 July 2018. A system of health facility (HF)-based active case finding (ACF) was implemented in Mbandaka, a regional capital with four confirmed EVD cases, following completion of contact tracing. The goal of this HF-based ACF system was to look for undetected EVD cases among patients that visited HFs beginning one week prior to the system's implementation. METHODS: From 23 June - 24 July 2018, ACF teams visited HFs in Mbandaka and reviewed all medical records as far back as 17 June for any consultations meeting the suspected EVD case definition. The teams then assessed whether to validate these as suspected EVD cases based on factors such as recovery, epidemiological links, and their clinical judgement. ACF teams also assessed HFs' awareness of EVD symptoms and the process for alerting suspected cases. We calculated descriptive statistics regarding the characteristics of reviewed consultations, alert cases, and visited HFs. We also used univariate and multivariate random effects logistic regression models to evaluate the impact of repeated ACF visits to the same HF on the staff's awareness of EVD. RESULTS: ACF teams reviewed 37,746 consultations, of which 690 met the definition of a suspected case of EVD. Two were validated as suspected EVD cases and transferred to the Ebola Treatment Unit for testing; both tested negative. Repeated ACF visits to the same HF were significantly associated with improved EVD awareness (p < 0.001) in univariate and multivariate analyses. CONCLUSION: HF-based ACF during EVD outbreaks may improve EVD awareness and reveal many individuals meeting the suspected case definition. However, many who meet this definition may not have EVD, depending on the population size covered by ACF and amount of ongoing EVD transmission. Given the burdensome procedure of testing suspected EVD cases, future HF-based ACF systems would benefit from improved clarity on which patients require further testing.

Pneumococcal conjugate vaccine use during humanitarian crises.

Streptococcus pneumoniae is a common human commensal that causes a sizeable part of the overall childhood mortality in low income settings. Populations affected by humanitarian crises are at especially high risk, because a multitude of risk factors that are enhanced during crises increase pneumococcal transmission and disease severity. Pneumococcal conjugate vaccines (PCVs) provide effective protection and have been introduced into the majority of routine childhood immunisation programmes globally, though several barriers have hitherto limited their uptake during humanitarian crises. When PCV coverage cannot be sustained during crises or when PCV has not been part of routine programmes, mass vaccination campaigns offer a quick acting and programmatically feasible bridging solution until services can be restored. However, we currently face a paucity of evidence on which to base the structure of such campaigns. We believe that, now that PCV can be procured at a substantially reduced price through the Humanitarian Mechanism, this lack of information is a remaining hurdle to PCV use in humanitarian crises. Considering the difficulties in conducting research in crises, we propose an evidence generation pathway consisting of primary data collection in combination with mathematical modelling followed by quasi-experimental evaluation of a PCV intervention, which can inform on optimal vaccination strategies that consider age targeting, dosing regimens and impact duration.

Event-based surveillance at health facility and community level in low-income and middle-income countries: a systematic review.

BACKGROUND: The International Health Regulations require member states to establish "capacity to detect, assess, notify and report events". Event-based surveillance (EBS) can contribute to rapid detection of acute public health events. This is particularly relevant in low-income and middle-income countries (LMICs) which may have poor public health infrastructure. To identify best practices, we reviewed the literature on the implementation of EBS in LMICs to describe EBS structures and to evaluate EBS systems. METHODS: We conducted a systematic literature search of six databases to identify articles that evaluated EBS in LMICs and additionally searched for grey literature. We used a framework approach to facilitate qualitative data synthesis and exploration of patterns across and within articles. RESULTS: We identified 778 records, of which we included 15 studies concerning 13 different EBS systems. The 13 EBS systems were set up as community-based surveillance, health facility-based surveillance or open surveillance (ie, notification by non-defined individuals and institutions). Four systems were set up in outbreak settings and nine outside outbreaks. All EBS systems were integrated into existing routine surveillance systems and pre-existing response structures to some extent. EBS was described as useful in detecting a large scope of events, reaching remote areas and guiding outbreak response. CONCLUSION: Health facility and community-based EBS provide valuable information that can strengthen the early warning function of national surveillance systems. Integration into existing early warning and response systems was described as key to generate data for action and to facilitate rapid verification and response. Priority in its implementation should be given to settings that would particularly benefit from EBS strengths. This includes areas most prone to outbreaks and where traditional 'routine' surveillance is suboptimal.

Patient-led active tuberculosis case-finding in the Democratic Republic of the Congo.

OBJECTIVE: To investigate the effect of using volunteer screeners in active tuberculosis case-finding in South Kivu, the Democratic Republic of the Congo, especially among groups at high risk of tuberculosis infection. METHODS: To identify and screen high-risk groups in remote communities, we trained volunteer screeners, mainly those who had themselves received treatment for tuberculosis or had a family history of the disease. A non-profit organization was created and screeners received training on the disease and its transmission at 3-day workshops. Screeners recorded the number of people screened, reporting a prolonged cough and who attended a clinic for testing, as well as test results. Data were evaluated every quarter during the 3-year period of the intervention (2014-2016). FINDINGS: Acceptability of the intervention was high. Volunteers screened 650 434 individuals in their communities, 73 418 of whom reported a prolonged cough; 50 368 subsequently attended a clinic for tuberculosis testing. Tuberculosis was diagnosed in 1 in 151 people screened, costing 0.29 United States dollars (US$) per person screened and US$ 44 per person diagnosed. Although members of high-risk groups with poorer access to health care represented only 5.1% (33 002/650 434) of those screened, they contributed 19.7% (845/4300) of tuberculosis diagnoses (1 diagnosis per 39 screened). The intervention resulted in an additional 4300 sputum-smear-positive pulmonary tuberculosis diagnoses, 42% (4 300/10 247) of the provincial total for that period. CONCLUSION: Patient-led active tuberculosis case-finding represents a valuable complement to traditional case-finding, and should be used to assist health systems in the elimination of tuberculosis.

Identifying human encounters that shape the transmission of Streptococcus pneumoniae and other acute respiratory infections.

Although patterns of social contacts are believed to be an important determinant of infectious disease transmission, it remains unclear how the frequency and nature of human interactions shape an individual's risk of infection. We analysed data on daily social encounters individually matched to data on S. pneumoniae carriage and acute respiratory symptoms (ARS), from 566 individuals who took part in a survey in South-West Uganda. We found that the frequency of physical (i.e. skin-to-skin), long (≥1 h) and household contacts - which capture some measure of close (i.e. relatively intimate) contact - was higher among pneumococcal carriers than non-carriers, and among people with ARS compared to those without, irrespective of their age. With each additional physical encounter the age-adjusted risk of carriage and ARS increased by 6% (95%CI 2-9%) and 7% (2-13%) respectively. In contrast, the number of casual contacts (<5 min long) was not associated with either pneumococcal carriage or ARS. A detailed analysis by age of contacts showed that the number of close contacts with young children (<5 years) was particularly higher among older children and adult carriers than non-carriers, while the higher number of contacts among people suffering from ARS was more homogeneous across contacts of all ages. Our findings provide key evidence that the frequency of close interpersonal contact is important for transmission of respiratory infections, but not that of casual contacts. Those results are essential for both improving disease prevention and control efforts as well as informing research on infectious disease dynamics and transmission models, and more studies should be undertaken to further validate our results.

Predicting the impact of pneumococcal conjugate vaccine programme options in Vietnam.

Although catch-up campaigns (CCs) at the introduction of pneumococcal conjugate vaccines (PCVs) may accelerate their impact, supply constraints may limit their benefit if the need for additional PCV doses results in introduction delay. We studied the impact of PCV13 introduction with and without CC in Nha Trang, Vietnam - a country that has not yet introduced PCV - through a dynamic transmission model. We modelled the impact on carriage and invasive pneumococcal disease (IPD) of routine vaccination (RV) only and that of RV with CCs targeting <1y olds (CC1), <2y olds (CC2) and <5y olds (CC5). The model was fitted to nasopharyngeal carriage data, and post-PCV predictions were based on best estimates of parameters governing post-PCV dynamics. With RV only, elimination in carriage of vaccine-type (VT) serotypes is predicted to occur across all age groups within 10 years after introduction, with near-complete replacement by non-VT. Most of the benefit of CCs is predicted to occur within the first 3 years with the highest impact at one year, when IPD incidence is predicted to be 11% (95%CrI 9 - 14%) lower than RV with CC1, 25% (21 - 30 %) lower with CC2 and 38% (32 - 46%) lower with CC5. However, CCs would only prevent more cases of IPD insofar as such campaigns do not delay introduction by more than about 6, 12 and 18 months for CC1, CC2 and CC5. Those findings are important to help guide vaccine introduction in countries that have not yet introduced PCV, particularly in Asia.

Social mixing in Fiji: Who-eats-with-whom contact patterns and the implications of age and ethnic heterogeneity for disease dynamics in the Pacific Islands.

Empirical data on contact patterns can inform dynamic models of infectious disease transmission. Such information has not been widely reported from Pacific islands, nor strongly multi-ethnic settings, and few attempts have been made to quantify contact patterns relevant for the spread of gastrointestinal infections. As part of enteric fever investigations, we conducted a cross-sectional survey of the general public in Fiji, finding that within the 9,650 mealtime contacts reported by 1,814 participants, there was strong like-with-like mixing by age and ethnicity, with higher contact rates amongst iTaukei than non-iTaukei Fijians. Extra-domiciliary lunchtime contacts follow these mixing patterns, indicating the overall data do not simply reflect household structures. Inter-ethnic mixing was most common amongst school-age children. Serological responses indicative of recent Salmonella Typhi infection were found to be associated, after adjusting for age, with increased contact rates between meal-sharing iTaukei, with no association observed for other contact groups. Animal ownership and travel within the geographical division were common. These are novel data that identify ethnicity as an important social mixing variable, and use retrospective mealtime contacts as a socially acceptable metric of relevance to enteric, contact and respiratory diseases that can be collected in a single visit to participants. Application of these data to other island settings will enable communicable disease models to incorporate locally relevant mixing patterns in parameterisation.