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BACKGROUND: The declaration of Coronavirus disease 2019 (COVID-19) as a Public Health Emergency of International Concern (PHEIC) on 30 January 2020 required rapid implementation of early investigations to inform appropriate national and global public health actions. METHODS: The suite of existing pandemic preparedness generic epidemiological early investigation protocols was rapidly adapted for COVID-19, branded the 'UNITY studies' and promoted globally for the implementation of standardized and quality studies. Ten protocols were developed investigating household (HH) transmission, the first few cases (FFX), population seroprevalence (SEROPREV), health facilities transmission (n = 2), vaccine effectiveness (n = 2), pregnancy outcomes and transmission, school transmission, and surface contamination. Implementation was supported by WHO and its partners globally, with emphasis to support building surveillance and research capacities in low- and middle-income countries (LMIC). RESULTS: WHO generic protocols were rapidly developed and published on the WHO website, 5/10 protocols within the first 3 months of the response. As of 30 June 2021, 172 investigations were implemented by 97 countries, of which 62 (64%) were LMIC. The majority of countries implemented population seroprevalence (71 countries) and first few cases/household transmission (37 countries) studies. CONCLUSION: The widespread adoption of UNITY protocols across all WHO regions indicates that they addressed subnational and national needs to support local public health decision-making to prevent and control the pandemic.

Summary Viral variants of concern may emerge with dangerous resistance to the immunity generated by the current vaccines to prevent coronavirus disease 2019 (Covid-19). Moreover, if some variants of concern have increased transmissibility or virulence, the importance of efficient public health measures and vaccination programs will increase. The global response must be both timely and science based.

International audience

A group convened and led by the Virus Evolution Working Group of the World Health Organization reports on its deliberations and announces a naming scheme that will enable clear communication about SARS-CoV-2 variants of interest and concern.

Available animal and cell line models have suggested that specific therapeutics might be effective in treating Middle East respiratory syndrome (MERS). We conducted a systematic review of evidence for treatment with pharmacologic and supportive therapies. We developed a protocol and searched 5 databases for studies describing treatment of MERS and deaths in MERS patients. Risk of bias (RoB) was assessed by using ROBINS-I tool. We retrieved 3,660 unique citations; 20 observational studies met eligibility, and we studied 13 therapies. Most studies were at serious or critical RoB; no studies were at low RoB. One study, at moderate RoB, showed reduced mortality rates in severe MERS patients with extracorporeal membrane oxygenation; no other studies showed a significant lifesaving benefit to any treatment. The existing literature on treatments for MERS is observational and at moderate to critical RoB. Clinical trials are needed to guide treatment decisions.

Summary The Middle East respiratory syndrome coronavirus (MERS-CoV) is a lethal zoonotic pathogen that was first identified in humans in Saudi Arabia and Jordan in 2012. Intermittent sporadic cases, community clusters, and nosocomial outbreaks of MERS-CoV continue to occur. Between April 2012 and December 2019, 2499 laboratory-confirmed cases of MERS-CoV infection, including 858 deaths (34·3% mortality) were reported from 27 countries to WHO, the majority of which were reported by Saudi Arabia (2106 cases, 780 deaths). Large outbreaks of human-to-human transmission have occurred, the largest in Riyadh and Jeddah in 2014 and in South Korea in 2015. MERS-CoV remains a high-threat pathogen identified by WHO as a priority pathogen because it causes severe disease that has a high mortality rate, epidemic potential, and no medical countermeasures. This Seminar provides an update on the current knowledge and perspectives on MERS epidemiology, virology, mode of transmission, pathogenesis, diagnosis, clinical features, management, infection control, development of new therapeutics and vaccines, and highlights unanswered questions and priorities for research, improved management, and prevention.

IntroductionEstimating COVID-19 cumulative incidence in Africa remains problematic due to challenges in contact tracing, routine surveillance systems and laboratory testing capacities and strategies. We undertook a meta-analysis of population-based seroprevalence studies to estimate SARS-CoV-2 seroprevalence in Africa to inform evidence-based decision making on public health and social measures (PHSM) and vaccine strategy.MethodsWe searched for seroprevalence studies conducted in Africa published 1 January 2020–30 December 2021 in Medline, Embase, Web of Science and Europe PMC (preprints), grey literature, media releases and early results from WHO Unity studies. All studies were screened, extracted, assessed for risk of bias and evaluated for alignment with the WHO Unity seroprevalence protocol. We conducted descriptive analyses of seroprevalence and meta-analysed seroprevalence differences by demographic groups, place and time. We estimated the extent of undetected infections by comparing seroprevalence and cumulative incidence of confirmed cases reported to WHO.PROSPERO: CRD42020183634.ResultsWe identified 56 full texts or early results, reporting 153 distinct seroprevalence studies in Africa. Of these, 97 (63%) were low/moderate risk of bias studies. SARS-CoV-2 seroprevalence rose from 3.0% (95% CI 1.0% to 9.2%) in April–June 2020 to 65.1% (95% CI 56.3% to 73.0%) in July–September 2021. The ratios of seroprevalence from infection to cumulative incidence of confirmed cases was large (overall: 100:1, ranging from 18:1 to 954:1) and steady over time. Seroprevalence was highly heterogeneous both within countries—urban versus rural (lower seroprevalence for rural geographic areas), children versus adults (children aged 0–9 years had the lowest seroprevalence)—and between countries and African subregions.ConclusionWe report high seroprevalence in Africa suggesting greater population exposure to SARS-CoV-2 and potential protection against COVID-19 severe disease than indicated by surveillance data. As seroprevalence was heterogeneous, targeted PHSM and vaccination strategies need to be tailored to local epidemiological situations.

Middle East Respiratory Syndrome coronavirus (MERS-CoV) is a coronavirus that infects both humans and dromedary camels and is responsible for an ongoing outbreak of severe respiratory illness in humans in the Middle East. While some mutations found in camel-derived MERS-CoV strains have been characterized, the majority of natural variation found across MERS-CoV isolates remains unstudied. Here we report on the environmental stability, replication kinetics and pathogenicity of several diverse isolates of MERS-CoV as well as SARS-CoV-2 to serve as a basis of comparison with other stability studies. While most of the MERS-CoV isolates exhibited similar stability and pathogenicity in our experiments, the camel derived isolate, C/KSA/13, exhibited reduced surface stability while another camel isolate, C/BF/15, had reduced pathogenicity in a small animal model. These results suggest that while betacoronaviruses may have similar environmental stability profiles, individual variation can influence this phenotype, underscoring the importance of continual, global viral surveillance.

The past 30 years have exposed the global public health and economic threats posed by the emergence of infectious pathogens with epidemic and pandemic potential. Severe acute respiratory syndrome (SARS), middle east respiratory syndrome (MERS), influenza, Ebola, Marburg, Lassa, Nipah, Zika, and now SARS coronavirus 2 (SARS-CoV-2) each have been the “Disease X” of their time. The risk of future emergence is driven by multiple forces, including climate change, ecosystem changes, and increasing urbanization. The next Disease X could appear at any time, and the world needs to be better prepared.

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.

To investigate a cluster of Middle East respiratory syndrome (MERS) cases in a women-only dormitory in Riyadh, Saudi Arabia, in October 2015, we collected epidemiologic information, nasopharyngeal/oropharyngeal swab samples, and blood samples from 828 residents during November 2015 and December 2015–January 2016. We found confirmed infection for 19 (8 by reverse transcription PCR and 11 by serologic testing). Infection attack rates varied (2.7%–32.3%) by dormitory building. No deaths occurred. Independent risk factors for infection were direct contact with a confirmed case-patient and sharing a room with a confirmed case-patient; a protective factor was having an air conditioner in the bedroom. For 9 women from whom a second serum sample was collected, antibodies remained detectable at titers >1:20 by pseudoparticle neutralization tests (n = 8) and 90% plaque-reduction neutralization tests (n = 2). In closed high-contact settings, MERS coronavirus was highly infectious and pathogenicity was relatively low.

The epidemiology of Middle East respiratory syndrome coronavirus (MERS-CoV) since 2012 has been largely characterized by recurrent zoonotic spillover from dromedary camels followed by limited human-to-human transmission, predominantly in health-care settings. The full extent of infection of MERS-CoV is not clear, nor is the extent and/or role of asymptomatic infections in transmission. We conducted a review of molecular and serological investigations through PubMed and EMBASE from September 2012 to November 15, 2018, to measure subclinical or asymptomatic MERS-CoV infection within and outside of health-care settings. We performed retrospective analysis of laboratory-confirmed MERS-CoV infections reported to the World Health Organization to November 27, 2018, to summarize what is known about asymptomatic infections identified through national surveillance systems. We identified 23 studies reporting evidence of MERS-CoV infection outside of health-care settings, mainly of camel workers, with seroprevalence ranges of 0%–67% depending on the study location. We identified 20 studies in health-care settings of health-care worker (HCW) and family contacts, of which 11 documented molecular evidence of MERS-CoV infection among asymptomatic contacts. Since 2012, 298 laboratory-confirmed cases were reported as asymptomatic to the World Health Organization, 164 of whom were HCWs. The potential to transmit MERS-CoV to others has been demonstrated in viral-shedding studies of asymptomatic MERS infections. Our results highlight the possibility for onward transmission of MERS-CoV from asymptomatic individuals. Screening of HCW contacts of patients with confirmed MERS-CoV is currently recommended, but systematic screening of non-HCW contacts outside of health-care facilities should be encouraged.

Well‐designed population‐based seroepidemiologic studies can be used to refine estimates of infection severity and transmission, and are therefore an important component of epidemic surveillance. However, the interpretation of the results of seroepidemiologic studies for SARS‐CoV‐2 has been hampered to date principally by heterogeneity in the quality of the reporting of the results of the study and a lack of standardized methods and reporting. We provide here the ROSES‐S: Reporting of Seroepidemiologic studies—SARS‐CoV‐2. This is an updated checklist of 22 items that should be included in the reporting of all SARS‐CoV‐2 seroepidemiologic studies, irrespective of study design.

Background: Approximately half of the reported laboratory-confirmed infections of Middle East respiratory syndrome coronavirus (MERS-CoV) have occurred in healthcare settings, and healthcare workers constitute over one third of all secondary infections. This study aimed to describe secondary cases of MERS-CoV infection among healthcare workers and to identify risk factors for death. Methods: A retrospective analysis was conducted on epidemiological data of laboratory-confirmed MERS-CoV cases reported to the World Health Organization from September 2012 to 2 June 2018. We compared all secondary cases among healthcare workers with secondary cases among non-healthcare workers. Multivariable logistic regression identified risk factors for death. Results: Of the 2223 laboratory-confirmed MERS-CoV cases reported to WHO, 415 were healthcare workers and 1783 were non-healthcare workers. Compared with non-healthcare workers cases, healthcare workers cases were younger (P

This article summarizes progress in research on Middle East Respiratory Syndrome (MERS) since a FAO-OIE-WHO Global Technical Meeting held at WHO Headquarters in Geneva on 25–27 September 2017. The meeting reviewed the latest scientific findings and identified and prioritized the global activities necessary to prevent, manage and control the disease. Critical needs for research and technical guidance identified during the meeting have been used to update the WHO R&D MERS-CoV Roadmap for diagnostics, therapeutics and vaccines and a broader public health research agenda. Since the 2017 meeting, progress has been made on several key actions in animal populations, at the animal/human interface and in human populations. This report also summarizes the latest scientific studies on MERS since 2017, including data from more than 50 research studies examining the presence of MERS-CoV infection in dromedary camels., Highlights • A global technical meeting on MERS was held in Geneva in September, 2017, organized by WHO, FAO and OIE. • This report summarizes the latest scientific literature and progress in research on MERS since that meeting. • It includes a summary of more than 50 field studies examining the presence of MERS-CoV infection in dromedary camels. • Zoonotic transmission of MERS requires a One Health approach is necessary to prevent, detect, and respond to the disease. • The critical needs identified in this report inform the WHO R&D MERS Roadmap and a broader public health research agenda.

As a World Health Organization Research and Development Blueprint priority pathogen, there is a need to better understand the geographic distribution of Middle East Respiratory Syndrome Coronavirus (MERS-CoV) and its potential to infect mammals and humans. This database documents cases of MERS-CoV globally, with specific attention paid to zoonotic transmission. An initial literature search was conducted in PubMed, Web of Science, and Scopus; after screening articles according to the inclusion/exclusion criteria, a total of 208 sources were selected for extraction and geo-positioning. Each MERS-CoV occurrence was assigned one of the following classifications based upon published contextual information: index, unspecified, secondary, mammal, environmental, or imported. In total, this database is comprised of 861 unique geo-positioned MERS-CoV occurrences. The purpose of this article is to share a collated MERS-CoV database and extraction protocol that can be utilized in future mapping efforts for both MERS-CoV and other infectious diseases. More broadly, it may also provide useful data for the development of targeted MERS-CoV surveillance, which would prove invaluable in preventing future zoonotic spillover., Measurement(s)Middle East Respiratory Syndrome • geographic locationTechnology Type(s)digital curationFactor Type(s)geographic distribution of Middle East Respiratory Syndrome Coronavirus (MERS-CoV) • yearSample Characteristic - OrganismMiddle East respiratory syndrome-related coronavirusSample Characteristic - LocationEarth (planet) Machine-accessible metadata file describing the reported data: 10.6084/m9.figshare.11108801

International audience; Since 2012, Middle East respiratory syndrome (MERS) coronavirus has infected 2,442 persons worldwide. Case-based data analysis suggests that since 2016, as many as 1,465 cases and 293-520 deaths might have been averted. Efforts to reduce the global MERS threat are working, but countries must maintain vigilance to prevent further infections.

Background Middle East respiratory syndrome coronavirus (MERS-CoV) remains a major concern for global public health. Dromedaries are the source of human zoonotic infection. MERS-CoV is enzootic among dromedaries on the Arabian Peninsula, the Middle East and in Africa. Over 70% of infected dromedaries are found in Africa. However, all known zoonotic cases of MERS have occurred in the Arabian Peninsula with none being reported in Africa. Aim We aimed to investigate serological evidence of MERS-CoV infection in humans living in camel-herding areas in Morocco to provide insights on whether zoonotic transmission is taking place. Methods We carried out a cross sectional seroprevalence study from November 2017 through January 2018. We adapted a generic World Health Organization MERS-CoV questionnaire and protocol to assess demographic and risk factors of infection among a presumed high-risk population. ELISA, MERS-CoV spike pseudoparticle neutralisation tests (ppNT) and plaque neutralisation tests (PRNT) were used to assess MERS-CoV seropositivity. Results Serum samples were collected from camel slaughterhouse workers (n = 137), camel herders (n = 156) and individuals of the general population without occupational contact with camels but living in camel herding areas (n = 186). MERS-CoV neutralising antibodies with ≥ 90% reduction of plaque numbers were detected in two (1.5%) slaughterhouse workers, none of the camel herders and one individual from the general population (0.5%). Conclusions This study provides evidence of zoonotic transmission of MERS-CoV in Morocco in people who have direct or indirect exposure to dromedary camels.

Since its emergence in 2012, 2,260 cases and 803 deaths due to Middle East respiratory syndrome coronavirus (MERS-CoV) have been reported to the World Health Organization. Most cases were due to transmission in healthcare settings, sometimes causing large outbreaks. We analyzed epidemiologic and clinical data of laboratory-confirmed MERS-CoV cases from eleven healthcare-associated outbreaks in the Kingdom of Saudi Arabia and the Republic of Korea between 2015–2017. We quantified key epidemiological differences between outbreaks. Twenty-five percent (n = 105/422) of MERS cases who acquired infection in a hospital setting were healthcare personnel. In multivariate analyses, age ≥65 (OR 4.8, 95%CI: 2.6–8.7) and the presence of underlying comorbidities (OR: 2.7, 95% CI: 1.3–5.7) were associated with increased mortality whereas working as healthcare personnel was protective (OR 0.07, 95% CI: 0.01–0.34). At the start of these outbreaks, the reproduction number ranged from 1.0 to 5.7; it dropped below 1 within 2 to 6 weeks. This study provides a comprehensive characterization of MERS HCA-outbreaks. Our results highlight heterogeneities in the epidemiological profile of healthcare-associated outbreaks. The limitations of our study stress the urgent need for standardized data collection for high-threat respiratory pathogens, such as MERS-CoV.

Human infection with Middle East Respiratory Syndrome Coronavirus (MERS-CoV) is driven by recurring dromedary-to-human spill-over events, leading decision-makers to consider dromedary vaccination. Dromedary vaccine candidates in the development pipeline are showing hopeful results, but gaps in our understanding of the epidemiology of MERS-CoV in dromedaries must be addressed to design and evaluate potential vaccination strategies. We systematically reviewed the published literature reporting seroprevalence and/or prevalence of active MERS-CoV infection in dromedary populations from both cross-sectional and longitudinal studies, including 60 studies in our qualitative syntheses. MERS-CoV seroprevalence increased with age up to 80-100% in adult dromedaries supporting geographically wide spread endemicity of MERS-CoV in dromedaries in both the Arabian Peninsula and countries exporting dromedaries from Africa. The high prevalence of active infection measured in juveniles and at sites where dromedary populations mix should guide further investigation – particularly of dromedary movement – and inform vaccination strategy design.

Background Middle East respiratory syndrome coronavirus (MERS-CoV) is endemic in dromedary camels in the Arabian Peninsula, and zoonotic transmission to people is a sporadic event. In the absence of epidemiological data on the reservoir species, patterns of zoonotic transmission have largely been approximated from primary human cases. This study aimed to identify meteorological factors that may increase the risk of primary MERS infections in humans. Methods A case-crossover design was used to identify associations between primary MERS cases and preceding weather conditions within the 2-week incubation period in Saudi Arabia using univariable conditional logistic regression. Cases with symptom onset between January 2015 – December 2017 were obtained from a publicly available line list of human MERS cases maintained by the World Health Organization. The complete case dataset (N = 1191) was reduced to approximate the cases most likely to represent spillover transmission from camels (N = 446). Data from meteorological stations closest to the largest city in each province were used to calculate the daily mean, minimum, and maximum temperature (οC), relative humidity (%), wind speed (m/s), and visibility (m). Weather variables were categorized according to strata; temperature and humidity into tertiles, and visibility and wind speed into halves. Results Lowest temperature (Odds Ratio = 1.27; 95% Confidence Interval = 1.04–1.56) and humidity (OR = 1.35; 95% CI = 1.10–1.65) were associated with increased cases 8–10 days later. High visibility was associated with an increased number of cases 7 days later (OR = 1.26; 95% CI = 1.01–1.57), while wind speed also showed statistically significant associations with cases 5–6 days later. Conclusions Results suggest that primary MERS human cases in Saudi Arabia are more likely to occur when conditions are relatively cold and dry. This is similar to seasonal patterns that have been described for other respiratory diseases in temperate climates. It was hypothesized that low visibility would be positively associated with primary cases of MERS, however the opposite relationship was seen. This may reflect behavioural changes in different weather conditions. This analysis provides key initial evidence of an environmental component contributing to the development of primary MERS-CoV infections.

Diagnostics play a central role in the early detection and control of outbreaks and can enable a more nuanced understanding of the disease kinetics and risk factors for the Middle East respiratory syndrome-coronavirus (MERS-CoV), one of the high-priority pathogens identified by the WHO. In this review we identified sources for molecular and serological diagnostic tests used in MERS-CoV detection, case management and outbreak investigations, as well as surveillance for humans and animals (camels), and summarised the performance of currently available tests, diagnostic needs, and associated challenges for diagnostic test development and implementation. A more detailed understanding of the kinetics of infection of MERS-CoV is needed in order to optimise the use of existing assays. Notably, MERS-CoV point-of-care tests are needed in order to optimise supportive care and to minimise transmission risk. However, for new test development, sourcing clinical material continues to be a major challenge to achieving assay validation. Harmonisation and standardisation of laboratory methods are essential for surveillance and for a rapid and effective international response to emerging diseases. Routine external quality assessment, along with well-characterised and up-to-date proficiency panels, would provide insight into MERS-CoV diagnostic performance worldwide. A defined set of Target Product Profiles for diagnostic technologies will be developed by WHO to address these gaps in MERS-CoV outbreak management.

The emergence of the Middle East Respiratory Syndrome Corona Virus (MERS-CoV) in the Middle East in 2012 was associated with an overwhelming uncertainty about its epidemiological and clinical characteristics. Once dromedary camels (Camelus dromedarius) was found to be the natural reservoir of the virus, the public health systems across the Arabian Peninsula encountered an unprecedented pressure to control its transmission. This view point describes how the One Health approach was used in Qatar to manage the MERS-CoV outbreak during the period 2012–2017.One Health focuses on the association between the human, animals and environment sectors for total health and wellbeing of these three sectors. To manage the MERS outbreak in Qatar through a One Health approach, the Qatar National Outbreak Control Taskforce (OCT) was reactivated in November 2012. The animal health sector was invited to join the OCT. Later on, technical expertise was requested from the WHO, FAO, CDC, EMC, and PHE. Subsequently, a comprehensive One Health roadmap was delivered through leadership and coordination; surveillance and investigation; epidemiological studies and increase of local diagnostic capacity.The joint OCT, once trained had easy access to allocated resources and high risk areas to provide more evidence on the potential source of the virus and to investigate all reported cases within 24–48 h. Lack of sufficient technical guidance on veterinary surveillance and poor risk perception among the vulnerable population constituted major obstacles to maintain systematic One Health performance. Keywords: One Health, MERS-CoV, Qatar

The World Health Organization (WHO) launched the first web-based learning course on COVID-19 on January 26, 2020, four days before the director general of the WHO declared a public health emergency of international concern. The WHO is expanding access to web-based learning for COVID-19 through its open-learning platform for health emergencies, OpenWHO. Throughout the pandemic, OpenWHO has continued to publish learning offerings based on the WHO’s emerging evidence-based knowledge for managing the COVID-19 pandemic. This study presents the various findings derived from the analysis of the performance of the OpenWHO platform during the pandemic, along with the core benefits of massive web-based learning formats. publishedVersion

Summary Background The emergence of Zika virus in the Americas has coincided with increased reports of babies born with microcephaly. On Feb 1, 2016, WHO declared the suspected link between Zika virus and microcephaly to be a Public Health Emergency of International Concern. This association, however, has not been precisely quantified. Methods We retrospectively analysed data from a Zika virus outbreak in French Polynesia, which was the largest documented outbreak before that in the Americas. We used serological and surveillance data to estimate the probability of infection with Zika virus for each week of the epidemic and searched medical records to identify all cases of microcephaly from September, 2013, to July, 2015. Simple models were used to assess periods of risk in pregnancy when Zika virus might increase the risk of microcephaly and estimate the associated risk. Findings The Zika virus outbreak began in October, 2013, and ended in April, 2014, and 66% (95% CI 62–70) of the general population were infected. Of the eight microcephaly cases identified during the 23-month study period, seven (88%) occurred in the 4-month period March 1 to July 10, 2014. The timing of these cases was best explained by a period of risk in the first trimester of pregnancy. In this model, the baseline prevalence of microcephaly was two cases (95% CI 0–8) per 10 000 neonates, and the risk of microcephaly associated with Zika virus infection was 95 cases (34–191) per 10 000 women infected in the first trimester. We could not rule out an increased risk of microcephaly from infection in other trimesters, but models that excluded the first trimester were not supported by the data. Interpretation Our findings provide a quantitative estimate of the risk of microcephaly in fetuses and neonates whose mothers are infected with Zika virus. Funding Labex-IBEID, NIH-MIDAS, AXA Research fund, EU-PREDEMICS.

Not all persons infected with Middle East respiratory syndrome coronavirus (MERS-CoV) develop severe symptoms, which likely leads to an underestimation of the number of people infected and an overestimation of the severity. To estimate the number of MERS-CoV infections that have occurred in the Kingdom of Saudi Arabia, we applied a statistical model to a line list describing 721 MERS-CoV infections detected between June 7, 2012, and July 25, 2014. We estimated that 1,528 (95% confidence interval (CI): 1,327, 1,883) MERS-CoV infections occurred in this interval, which is 2.1 (95% CI: 1.8, 2.6) times the number reported. The probability of developing symptoms ranged from 11% (95% CI: 4, 25) in persons under 10 years of age to 88% (95% CI: 72, 97) in those 70 years of age or older. An estimated 22% (95% CI: 18, 25) of those infected with MERS-CoV died. MERS-CoV is deadly, but this work shows that its clinical severity differs markedly between groups and that many cases likely go undiagnosed.

Background\ud \ud On May 8, 2018, the Government of the Democratic Republic of the Congo reported an outbreak of Ebola virus disease in Équateur Province in the northwest of the country. The remoteness of most affected communities and the involvement of an urban centre connected to the capital city and neighbouring countries makes this outbreak the most complex and high risk ever experienced by the Democratic Republic of the Congo. We provide early epidemiological information arising from the ongoing investigation of this outbreak.\ud Methods\ud \ud We classified cases as suspected, probable, or confirmed using national case definitions of the Democratic Republic of the Congo Ministère de la Santé Publique. We investigated all cases to obtain demographic characteristics, determine possible exposures, describe signs and symptoms, and identify contacts to be followed up for 21 days. We also estimated the reproduction number and projected number of cases for the 4-week period from May 25, to June 21, 2018.\ud Findings\ud \ud As of May 30, 2018, 50 cases (37 confirmed, 13 probable) of Zaire ebolavirus were reported in the Democratic Republic of the Congo. 21 (42%) were reported in Bikoro, 25 (50%) in Iboko, and four (8%) in Wangata health zones. Wangata is part of Mbandaka, the urban capital of Équateur Province, which is connected to major national and international transport routes. By May 30, 2018, 25 deaths from Ebola virus disease had been reported, with a case fatality ratio of 56% (95% CI 39–72) after adjustment for censoring. This case fatality ratio is consistent with estimates for the 2014–16 west African Ebola virus disease epidemic (p=0·427). The median age of people with confirmed or probable infection was 40 years (range 8–80) and 30 (60%) were male. The most commonly reported signs and symptoms in people with confirmed or probable Ebola virus disease were fever (40 [95%] of 42 cases), intense general fatigue (37 [90%] of 41 cases), and loss of appetite (37 [90%] of 41 cases). Gastrointestinal symptoms were frequently reported, and 14 (33%) of 43 people reported haemorrhagic signs. Time from illness onset and hospitalisation to sample testing decreased over time. By May 30, 2018, 1458 contacts had been identified, of which 746 (51%) remained under active follow-up. The estimated reproduction number was 1·03 (95% credible interval 0·83–1·37) and the cumulative case incidence for the outbreak by June 21, 2018, is projected to be 78 confirmed cases (37–281), assuming heterogeneous transmissibility.\ud Interpretation\ud \ud The ongoing Ebola virus outbreak in the Democratic Republic of the Congo has similar epidemiological features to previous Ebola virus disease outbreaks. Early detection, rapid patient isolation, contact tracing, and the ongoing vaccination programme should sufficiently control the outbreak. The forecast of the number of cases does not exceed the current capacity to respond if the epidemiological situation does not change. The information presented, although preliminary, has been essential in guiding the ongoing investigation and response to this outbreak.

Background Yellow fever virus (YFV) is a vector-borne flavivirus endemic to Africa and Latin America. Ninety per cent of the global burden occurs in Africa where it is primarily transmitted by Aedes spp, with Aedes aegypti the main vector for urban yellow fever (YF). Mosquito life cycle and viral replication in the mosquito are heavily dependent on climate, particularly temperature and rainfall. We aimed to assess whether seasonal variations in climatic factors are associated with the seasonality of YF reports. Methodology/Principal findings We constructed a temperature suitability index for YFV transmission, capturing the temperature dependence of mosquito behaviour and viral replication within the mosquito. We then fitted a series of multilevel logistic regression models to a dataset of YF reports across Africa, considering location and seasonality of occurrence for seasonal models, against the temperature suitability index, rainfall and the Enhanced Vegetation Index (EVI) as covariates alongside further demographic indicators. Model fit was assessed by the Area Under the Curve (AUC), and models were ranked by Akaike’s Information Criterion which was used to weight model outputs to create combined model predictions. The seasonal model accurately captured both the geographic and temporal heterogeneities in YF transmission (AUC = 0.81), and did not perform significantly worse than the annual model which only captured the geographic distribution. The interaction between temperature suitability and rainfall accounted for much of the occurrence of YF, which offers a statistical explanation for the spatio-temporal variability in transmission. Conclusions/Significance The description of seasonality offers an explanation for heterogeneities in the West-East YF burden across Africa. Annual climatic variables may indicate a transmission suitability not always reflected in seasonal interactions. This finding, in conjunction with forecasted data, could highlight areas of increased transmission and provide insights into the occurrence of large outbreaks, such as those seen in Angola, the Democratic Republic of the Congo and Brazil., Author summary In this article, we describe the development of a model to quantify the seasonal dynamics of yellow fever virus (YFV) transmission across Africa. YFV is a flavivirus transmitted, within Africa, primarily by Aedes spp where it causes an estimated 78,000 deaths a year despite the presence of a safe and effective vaccine. The importance of sufficient vaccination, made difficult by a global shortage, has been highlighted by recent large scale, devastating, outbreaks in Angola, the Democratic Republic of the Congo and Brazil. Here we describe a novel way of parameterising the effect of temperature on YFV transmission and implement statistical models to predict both the geographic and temporal heterogeneities in transmissions, while demonstrating their robustness in comparison to models simply predicting geographic distribution. We believe this quantification of seasonality could lead to more precise applications of vaccination campaigns and vector-control programmes. In turn this would help maximise their impact, especially vital with limited resources, and could contribute to lessening the risk of large scale outbreaks. Not only this, but the methods described here could be applied to other Aedes-borne diseases and as such provide a useful tool in understanding, and combatting, several other important diseases such as dengue and zika.

Background Arboviral infections are a public health concern and an escalating problem worldwide. Estimating the burden of these diseases represents a major challenge that is complicated by the large number of unapparent infections, especially those of dengue fever. Serological surveys are thus required to identify the distribution of these diseases and measure their impact. Therefore, we undertook a scoping review of the literature to describe and summarize epidemiological practices, findings and insights related to seroprevalence studies of dengue, chikungunya and Zika virus, which have rapidly expanded across the globe in recent years. Methodology/Principal findings Relevant studies were retrieved through a literature search of MEDLINE, WHOLIS, Lilacs, SciELO and Scopus (2000 to 2018). In total, 1389 publications were identified. Studies addressing the seroprevalence of dengue, chikungunya and/or Zika written in English or French and meeting the inclusion and exclusion criteria were included. In total, 147 studies were included, from which 185 data points were retrieved, as some studies used several different samples. Most of the studies were exclusively conducted on dengue (66.5%), but 16% were exclusively conducted on chikungunya, and 7 were exclusively conducted on Zika; the remainder were conducted on multiple arboviruses. A wide range of designs were applied, but most studies were conducted in the general population (39%) and in households (41%). Although several assays were used, enzyme-linked immunosorbent assays (ELISAs) were the predominant test used (77%). The temporal distribution of chikungunya studies followed the virus during its rapid expansion since 2004. The results revealed heterogeneity of arboviruses seroprevalence between continents and within a given country for dengue, chikungunya and Zika viruses, ranging from 0 to 100%, 76% and 73% respectively. Conclusions/Significance Serological surveys provide the most direct measurement for defining the immunity landscape for infectious diseases, but the methodology remains difficult to implement. Overall, dengue, chikungunya and Zika serosurveys followed the expansion of these arboviruses, but there remain gaps in their geographic distribution. This review addresses the challenges for researchers regarding study design biases. Moreover, the development of reliable, rapid and affordable diagnosis tools represents a significant issue concerning the ability of seroprevalence surveys to differentiate infections when multiple viruses co-circulate., Author summary Arthropod-borne viruses (arboviruses) are among the most important of the emerging infectious disease public health problems facing the world. The actual impact of arboviruses worldwide remains unknown, and estimating the true burden of these diseases represents a current challenge. Serological surveys are the most reliable tool for estimating the impact of arboviruses outbreaks in a given territory, and the results of such surveys have implications for potential mitigation measures such as vaccination. We undertook a thorough review of the literature produced from 2000 to March 15, 2018, addressing the seroprevalence of dengue, chikungunya and/or Zika to describe and summarize methodological approaches and map the geographical distribution of seroprevalence studies for these three viruses worldwide. A total of 185 studies addressing the seroprevalence of dengue, chikungunya and/or Zika were included in the review. Most of the studies were exclusively conducted on dengue (66.5%), but 16% were exclusively conducted on chikungunya, and 7 studies were exclusively conducted on Zika; the remainder were conducted on multiple arboviruses. Our study reveals that a wide range of methodological designs were applied regarding population, recruitment and/or laboratory testing. This study also highlights the high seroprevalence heterogeneity between continents and within a given country for dengue, chikungunya and Zika viruses. The results underscore existing gaps in seroprevalence studies distribution worldwide and the need to develop the most sensitive and specific diagnosis tool to provide recommendations for future serological studies.