SARS-CoV-2 Variants and Vaccines.

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.

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.

COVID-19 Mortality and Progress Toward Vaccinating Older Adults - World Health Organization, Worldwide, 2020-2022.

After the emergence of SARS-CoV-2 in late 2019, transmission expanded globally, and on January 30, 2020, COVID-19 was declared a public health emergency of international concern.* Analysis of the early Wuhan, China outbreak (1), subsequently confirmed by multiple other studies (2,3), found that 80% of deaths occurred among persons aged ≥60 years. In anticipation of the time needed for the global vaccine supply to meet all needs, the World Health Organization (WHO) published the Strategic Advisory Group of Experts on Immunization (SAGE) Values Framework and a roadmap for prioritizing use of COVID-19 vaccines in late 2020 (4,5), followed by a strategy brief to outline urgent actions in October 2021.† WHO described the general principles, objectives, and priorities needed to support country planning of vaccine rollout to minimize severe disease and death. A July 2022 update to the strategy brief§ prioritized vaccination of populations at increased risk, including older adults,¶ with the goal of 100% coverage with a complete COVID-19 vaccination series** for at-risk populations. Using available public data on COVID-19 mortality (reported deaths and model estimates) for 2020 and 2021 and the most recent reported COVID-19 vaccination coverage data from WHO, investigators performed descriptive analyses to examine age-specific mortality and global vaccination rollout among older adults (as defined by each country), stratified by country World Bank income status. Data quality and COVID-19 death reporting frequency varied by data source; however, persons aged ≥60 years accounted for >80% of the overall COVID-19 mortality across all income groups, with upper- and lower-middle-income countries accounting for 80% of the overall estimated excess mortality. Effective COVID-19 vaccines were authorized for use in December 2020, with global supply scaled up sufficiently to meet country needs by late 2021 (6). COVID-19 vaccines are safe and highly effective in reducing severe COVID-19, hospitalizations, and mortality (7,8); nevertheless, country-reported median completed primary series coverage among adults aged ≥60 years only reached 76% by the end of 2022, substantially below the WHO goal, especially in middle- and low-income countries. Increased efforts are needed to increase primary series and booster dose coverage among all older adults as recommended by WHO and national health authorities.

Global SARS-CoV-2 seroprevalence from January 2020 to April 2022: A systematic review and meta-analysis of standardized population-based studies.

BACKGROUND: Our understanding of the global scale of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) infection remains incomplete: Routine surveillance data underestimate infection and cannot infer on population immunity; there is a predominance of asymptomatic infections, and uneven access to diagnostics. We meta-analyzed SARS-CoV-2 seroprevalence studies, standardized to those described in the World Health Organization's Unity protocol (WHO Unity) for general population seroepidemiological studies, to estimate the extent of population infection and seropositivity to the virus 2 years into the pandemic. METHODS AND FINDINGS: We conducted a systematic review and meta-analysis, searching MEDLINE, Embase, Web of Science, preprints, and grey literature for SARS-CoV-2 seroprevalence published between January 1, 2020 and May 20, 2022. The review protocol is registered with PROSPERO (CRD42020183634). We included general population cross-sectional and cohort studies meeting an assay quality threshold (90% sensitivity, 97% specificity; exceptions for humanitarian settings). We excluded studies with an unclear or closed population sample frame. Eligible studies-those aligned with the WHO Unity protocol-were extracted and critically appraised in duplicate, with risk of bias evaluated using a modified Joanna Briggs Institute checklist. We meta-analyzed seroprevalence by country and month, pooling to estimate regional and global seroprevalence over time; compared seroprevalence from infection to confirmed cases to estimate underascertainment; meta-analyzed differences in seroprevalence between demographic subgroups such as age and sex; and identified national factors associated with seroprevalence using meta-regression. We identified 513 full texts reporting 965 distinct seroprevalence studies (41% low- and middle-income countries [LMICs]) sampling 5,346,069 participants between January 2020 and April 2022, including 459 low/moderate risk of bias studies with national/subnational scope in further analysis. By September 2021, global SARS-CoV-2 seroprevalence from infection or vaccination was 59.2%, 95% CI [56.1% to 62.2%]. Overall seroprevalence rose steeply in 2021 due to infection in some regions (e.g., 26.6% [24.6 to 28.8] to 86.7% [84.6% to 88.5%] in Africa in December 2021) and vaccination and infection in others (e.g., 9.6% [8.3% to 11.0%] in June 2020 to 95.9% [92.6% to 97.8%] in December 2021, in European high-income countries [HICs]). After the emergence of Omicron in March 2022, infection-induced seroprevalence rose to 47.9% [41.0% to 54.9%] in Europe HIC and 33.7% [31.6% to 36.0%] in Americas HIC. In 2021 Quarter Three (July to September), median seroprevalence to cumulative incidence ratios ranged from around 2:1 in the Americas and Europe HICs to over 100:1 in Africa (LMICs). Children 0 to 9 years and adults 60+ were at lower risk of seropositivity than adults 20 to 29 (p < 0.001 and p = 0.005, respectively). In a multivariable model using prevaccination data, stringent public health and social measures were associated with lower seroprevalence (p = 0.02). The main limitations of our methodology include that some estimates were driven by certain countries or populations being overrepresented. CONCLUSIONS: In this study, we observed that global seroprevalence has risen considerably over time and with regional variation; however, over one-third of the global population are seronegative to the SARS-CoV-2 virus. Our estimates of infections based on seroprevalence far exceed reported Coronavirus Disease 2019 (COVID-19) cases. Quality and standardized seroprevalence studies are essential to inform COVID-19 response, particularly in resource-limited regions.

Surface‒Aerosol Stability and Pathogenicity of Diverse Middle East Respiratory Syndrome Coronavirus Strains, 2012‒2018.

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

Middle East respiratory syndrome.

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.

The role of rapid diagnostics in managing Ebola epidemics.

Ebola emerged in West Africa around December 2013 and swept through Guinea, Sierra Leone and Liberia, giving rise to 27,748 confirmed, probable and suspected cases reported by 29 July 2015. Case diagnoses during the epidemic have relied on polymerase chain reaction-based tests. Owing to limited laboratory capacity and local transport infrastructure, the delays from sample collection to test results being available have often been 2 days or more. Point-of-care rapid diagnostic tests offer the potential to substantially reduce these delays. We review Ebola rapid diagnostic tests approved by the World Health Organization and those currently in development. Such rapid diagnostic tests could allow early triaging of patients, thereby reducing the potential for nosocomial transmission. In addition, despite the lower test accuracy, rapid diagnostic test-based diagnosis may be beneficial in some contexts because of the reduced time spent by uninfected individuals in health-care settings where they may be at increased risk of infection; this also frees up hospital beds. We use mathematical modelling to explore the potential benefits of diagnostic testing strategies involving rapid diagnostic tests alone and in combination with polymerase chain reaction testing. Our analysis indicates that the use of rapid diagnostic tests with sensitivity and specificity comparable with those currently under development always enhances control, whether evaluated at a health-care-unit or population level. If such tests had been available throughout the recent epidemic, we estimate, for Sierra Leone, that their use in combination with confirmatory polymerase chain-reaction testing might have reduced the scale of the epidemic by over a third.

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.

Pharmacologic Treatments and Supportive Care for Middle East Respiratory Syndrome.

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.

Worldwide Reduction in MERS Cases and Deaths since 2016.

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.

Transmissibility of MERS-CoV Infection in Closed Setting, Riyadh, Saudi Arabia, 2015.

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.

A Review of Asymptomatic and Subclinical Middle East Respiratory Syndrome Coronavirus Infections.

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.

A case-crossover analysis of the impact of weather on primary cases of Middle East respiratory syndrome.

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.

Unraveling the drivers of MERS-CoV transmission.

With more than 1,700 laboratory-confirmed infections, Middle East respiratory syndrome coronavirus (MERS-CoV) remains a significant threat for public health. However, the lack of detailed data on modes of transmission from the animal reservoir and between humans means that the drivers of MERS-CoV epidemics remain poorly characterized. Here, we develop a statistical framework to provide a comprehensive analysis of the transmission patterns underlying the 681 MERS-CoV cases detected in the Kingdom of Saudi Arabia (KSA) between January 2013 and July 2014. We assess how infections from the animal reservoir, the different levels of mixing, and heterogeneities in transmission have contributed to the buildup of MERS-CoV epidemics in KSA. We estimate that 12% [95% credible interval (CI): 9%, 15%] of cases were infected from the reservoir, the rest via human-to-human transmission in clusters (60%; CI: 57%, 63%), within (23%; CI: 20%, 27%), or between (5%; CI: 2%, 8%) regions. The reproduction number at the start of a cluster was 0.45 (CI: 0.33, 0.58) on average, but with large SD (0.53; CI: 0.35, 0.78). It was >1 in 12% (CI: 6%, 18%) of clusters but fell by approximately one-half (47% CI: 34%, 63%) its original value after 10 cases on average. The ongoing exposure of humans to MERS-CoV from the reservoir is of major concern, given the continued risk of substantial outbreaks in health care systems. The approach we present allows the study of infectious disease transmission when data linking cases to each other remain limited and uncertain.

Middle East respiratory syndrome coronavirus (MERS-CoV) neutralising antibodies in a high-risk human population, Morocco, November 2017 to January 2018.

BackgroundMiddle 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.AimWe 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.MethodsWe 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.ResultsSerum 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%).ConclusionsThis study provides evidence of zoonotic transmission of MERS-CoV in Morocco in people who have direct or indirect exposure to dromedary camels.

Association between Zika virus and microcephaly in French Polynesia, 2013-15: a retrospective study.

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.

Estimating the Severity and Subclinical Burden of Middle East Respiratory Syndrome Coronavirus Infection in the Kingdom of Saudi Arabia.

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.

Environmental contamination and risk factors for transmission of highly pathogenic avian influenza A(H5N1) to humans, Cambodia, 2006-2010.

BACKGROUND: Highly pathogenic avian influenza A (H5N1) virus has been of public health concern since 2003. Probable risk factors for A(H5N1) transmission to human have been demonstrated in several studies or epidemiological reports. However, transmission patterns may differ according to demographic characteristics of the population and local practices. This article aggregates these data from three studies with data collected in the previous surveys in 2006 and 2007 to further examine the risks factors associated with presence of anti-A(H5) antibodies among villagers residing within outbreak areas. METHODS: We aggregated 5-year data (2006-2010) from serology survey and matched case-control studies in Cambodia to further examine the risks factors associated with A(H5N1) infection among villagers in the outbreak areas. RESULTS: Serotesting among villagers detected 35 (1.5 % [0-2.6]) positive cases suggesting recent exposure to A(H5N1) virus. Practices associated with A(H5N1) infection among all ages were: having poultry cage or nesting area under or adjacent to the house (OR: 6.7 [1.6-28.3]; p = 0.010) and transporting poultry to market (OR: 17.6 [1.6-193.7]; p = 0.019). Practices found as risk factors for the infection among age under 20 years were swimming/bathing in ponds also accessed by domestic poultry (OR: 4.6 [1.1-19.1]; p = 0.038). Association with consuming wild birds reached borderline significance (p = 0.066). CONCLUSION: Our results suggest that swimming/bathing in contaminated pond water and close contact with poultry may present a risk of A(H5N1) transmission to human.

Yellow Fever in Africa: estimating the burden of disease and impact of mass vaccination from outbreak and serological data.

BACKGROUND: Yellow fever is a vector-borne disease affecting humans and non-human primates in tropical areas of Africa and South America. While eradication is not feasible due to the wildlife reservoir, large scale vaccination activities in Africa during the 1940s to 1960s reduced yellow fever incidence for several decades. However, after a period of low vaccination coverage, yellow fever has resurged in the continent. Since 2006 there has been substantial funding for large preventive mass vaccination campaigns in the most affected countries in Africa to curb the rising burden of disease and control future outbreaks. Contemporary estimates of the yellow fever disease burden are lacking, and the present study aimed to update the previous estimates on the basis of more recent yellow fever occurrence data and improved estimation methods. METHODS AND FINDINGS: Generalised linear regression models were fitted to a dataset of the locations of yellow fever outbreaks within the last 25 years to estimate the probability of outbreak reports across the endemic zone. Environmental variables and indicators for the surveillance quality in the affected countries were used as covariates. By comparing probabilities of outbreak reports estimated in the regression with the force of infection estimated for a limited set of locations for which serological surveys were available, the detection probability per case and the force of infection were estimated across the endemic zone. The yellow fever burden in Africa was estimated for the year 2013 as 130,000 (95% CI 51,000-380,000) cases with fever and jaundice or haemorrhage including 78,000 (95% CI 19,000-180,000) deaths, taking into account the current level of vaccination coverage. The impact of the recent mass vaccination campaigns was assessed by evaluating the difference between the estimates obtained for the current vaccination coverage and for a hypothetical scenario excluding these vaccination campaigns. Vaccination campaigns were estimated to have reduced the number of cases and deaths by 27% (95% CI 22%-31%) across the region, achieving up to an 82% reduction in countries targeted by these campaigns. A limitation of our study is the high level of uncertainty in our estimates arising from the sparseness of data available from both surveillance and serological surveys. CONCLUSIONS: With the estimation method presented here, spatial estimates of transmission intensity can be combined with vaccination coverage levels to evaluate the impact of past or proposed vaccination campaigns, thereby helping to allocate resources efficiently for yellow fever control. This method has been used by the Global Alliance for Vaccines and Immunization (GAVI Alliance) to estimate the potential impact of future vaccination campaigns.