Publisher Correction: Genomic insights into the 2016-2017 cholera epidemic in Yemen.

In the HTML version of this Letter, the affiliations for authors Andrew S. Azman, Dhirendra Kumar and Thandavarayan Ramamurthy were inverted (the PDF and print versions of the Letter were correct); the affiliations have been corrected online.

Genomic insights into the 2016-2017 cholera epidemic in Yemen.

Yemen is currently experiencing, to our knowledge, the largest cholera epidemic in recent history. The first cases were declared in September 2016, and over 1.1 million cases and 2,300 deaths have since been reported1. Here we investigate the phylogenetic relationships, pathogenesis and determinants of antimicrobial resistance by sequencing the genomes of Vibrio cholerae isolates from the epidemic in Yemen and recent isolates from neighbouring regions. These 116 genomic sequences were placed within the phylogenetic context of a global collection of 1,087 isolates of the seventh pandemic V. cholerae serogroups O1 and O139 biotype El Tor2-4. We show that the isolates from Yemen that were collected during the two epidemiological waves of the epidemic1-the first between 28 September 2016 and 23 April 2017 (25,839 suspected cases) and the second beginning on 24 April 2017 (more than 1 million suspected cases)-are V. cholerae serotype Ogawa isolates from a single sublineage of the seventh pandemic V. cholerae O1 El Tor (7PET) lineage. Using genomic approaches, we link the epidemic in Yemen to global radiations of pandemic V. cholerae and show that this sublineage originated from South Asia and that it caused outbreaks in East Africa before appearing in Yemen. Furthermore, we show that the isolates from Yemen are susceptible to several antibiotics that are commonly used to treat cholera and to polymyxin B, resistance to which is used as a marker of the El Tor biotype.

Screening of ZIKA virus infection among dengue-like illness patients with negative RT-PCR for dengue virus in Punjab - Pakistan.

OBJECTIVE: To detect ZIKV using reverse transcription-polymerase chain reaction (RT-PCR) among clinical samples tested negative for Dengue virus (DENV) by RT-PCR in Punjab, 2016. METHODS: A descriptive cross-sectional study was carried out for duration of two months. Total of 506 samples were collected within seven days from onset of illness from all over hospitals of Punjab, Pakistan of which 350 were selected simply randomly to test for presence of ZIKV by using "Trioplex Real-Time RT-PCR Assay (Trioplex)". Cohen's kappa coefficient (κ) and 95% confidence interval (CI) were used to assess the degree of concordance between DENV positive results of non-structural protein 1 (NS1) and IgM solid-phase enzyme immunoassay (ELISA). RESULTS: No samples were positive for any ZIKV, DENV or Chikungunya virus (CHIKV) by Trioplex. Among the 350 samples, 26 samples were positive concordant and the degree of concordance between NS1- and IgM-ELISA was 13% and κ coefficient was -0.71 (95% CI -0.79, -0.63). CONCLUSION: At study time, no samples were positive for ZIKV. Strengthening laboratory capacity to confirm arboviruses for Punjab's laboratories is warranted. Trioplex RT-PCR has 100% sensitivity so there are nominal chances of false negative results. Establishing syndromic surveillance for Zika and conducting a sero-surveillance survey for Zika in areas with high human and Aedes mosquito density are recommended in Punjab.

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.

Current and future distribution of Aedes aegypti and Aedes albopictus (Diptera: Culicidae) in WHO Eastern Mediterranean Region.

BACKGROUND: Aedes-borne diseases as dengue, zika, chikungunya and yellow fever are an emerging problem worldwide, being transmitted by Aedes aegypti and Aedes albopictus. Lack of up to date information about the distribution of Aedes species hampers surveillance and control. Global databases have been compiled but these did not capture data in the WHO Eastern Mediterranean Region (EMR), and any models built using these datasets fail to identify highly suitable areas where one or both species may occur. The first objective of this study was therefore to update the existing Ae. aegypti (Linnaeus, 1762) and Ae. albopictus (Skuse, 1895) compendia and the second objective was to generate species distribution models targeted to the EMR. A final objective was to engage the WHO points of contacts within the region to provide feedback and hence validate all model outputs. METHODS: The Ae. aegypti and Ae. albopictus compendia provided by Kraemer et al. (Sci Data 2:150035, 2015; Dryad Digit Repos, 2015) were used as starting points. These datasets were extended with more recent species and disease data. In the next step, these sets were filtered using the Köppen-Geiger classification and the Mahalanobis distance. The occurrence data were supplemented with pseudo-absence data as input to Random Forests. The resulting suitability and maximum risk of establishment maps were combined into hard-classified maps per country for expert validation. RESULTS: The EMR datasets consisted of 1995 presence locations for Ae. aegypti and 2868 presence locations for Ae. albopictus. The resulting suitability maps indicated that there exist areas with high suitability and/or maximum risk of establishment for these disease vectors in contrast with previous model output. Precipitation and host availability, expressed as population density and night-time lights, were the most important variables for Ae. aegypti. Host availability was the most important predictor in case of Ae. albopictus. Internal validation was assessed geographically. External validation showed high agreement between the predicted maps and the experts' extensive knowledge of the terrain. CONCLUSION: Maps of distribution and maximum risk of establishment were created for Ae. aegypti and Ae. albopictus for the WHO EMR. These region-specific maps highlighted data gaps and these gaps will be filled using targeted monitoring and surveillance. This will increase the awareness and preparedness of the different countries for Aedes borne diseases.

Real-Time Surveillance in Emergencies Using the Early Warning Alert and Response Network.

Humanitarian emergencies often result in population displacement and increase the risk for transmission of communicable diseases. To address the increased risk for outbreaks during humanitarian emergencies, the World Health Organization developed the Early Warning Alert and Response Network (EWARN) for early detection of epidemic-prone diseases. The US Centers for Disease Control and Prevention has worked with the World Health Organization, ministries of health, and other partners to support EWARN through the implementation and evaluation of these systems and the development of standardized guidance. Although protocols have been developed for the implementation and evaluation of EWARN, a need persists for standardized training and additional guidance on supporting these systems remotely when access to affected areas is restricted. Continued collaboration between partners and the Centers for Disease Control and Prevention for surveillance during emergencies is necessary to strengthen capacity and support global health security.

Closing the knowledge gaps on MERS: three and half years since its detection, what have we learnt and what needs to be done urgently? (Editorial).

The Middle East respiratory syndrome coronavirus (MERS-Cov), first detected in 2012, continues to cause health concerns owing to the grave uncertainties that have surrounded the virus since it emerged. Three and half years after the first known human infection was detected, cases continue to be reported every month, over 85% of which have been from Saudi Arabia and other countries in the Arabian Peninsula. Despite its low levels of transmission, the virus presents an uncertain future as a number of critical knowledge gaps on the source and route of transmission have hindered the global response to this emerging infection.

Preparedness for Ebola: Can it transform our current public health system? (Editorial).

The devastating Ebola outbreak that raged in west Africa most of 2014 and 2015 has finally come to an end. The epidemic reached unprecedented levels with far reaching implications for global health security. The epidemic, which started in December 2013, killed more than 11 000 people and infected at least 28 600, more than the total deaths and cases combined reported in the entire history of the disease. In addition, it resulted in an unquantified increase in indirect mortality as well as severe societal consequences.

Mental health crisis in Somalia: a review and a way forward.

BACKGROUND: Somalia has been without an effective government since the collapse of the military regime in 1991. Years of conflict, disasters, and insecurity have all contributed to very low scores for most health indicators due to poor governance, protracted conflict, underdevelopment, economic decline, poverty, social and gender inequality, and environmental degradation. The three-decade long protracted conflict has led to widespread psychosocial trauma, social deprivation and substance abuse with devastating consequences on mental health. A WHO study showed Somalia has one of the highest rates of mental illness in the world. The main aim of this study is to assist policy makers in setting priorities for the design and delivery of interventions to promote mental health and psychosocial wellbeing in Somalia. METHODS: The study uses a systematic mapping technique (from January 1991 to May 2020) and data collected from public domain, to collect, collate, and present mental health data mainly from WHO's Global Health Observatory. Since there is no primary database for Somalia's public health research, the bibliographic databases used for mental health in this study included Medline, PubMed, CINAHL, PsycINFO, and Google Scholar. Data were extracted using techniques for web data mining for public health. RESULTS: Systematic mapping of mental health-related issues in Somalia showed that policy-related determinants and mental health services dominated (74.4%), followed by the disaster-related determinants and women's health consequences (39.3%). The ratio of the number of beds for mental health in general hospitals (per 100,000 population) in Somalia in 2017 is 0.5 compared to the Eastern Mediterranean region (EMR) at 6.4 and globally at 24. One of the biggest casualties of the civil war was loss of essential human resources in healthcare as most either fled the country or were part of the victims of the war. CONCLUSIONS: The vast scale of the mental health problems in Somalia and the priority setting guidelines for interventions to address the issues outlined in this paper, prompt a dire need that the Somali government and its national/international partners should prioritize and emphasize the need to invest in the prevention and the treatment of mental illness across the country.

Investing in mental health in Somalia: harnessing community mental health services through task shifting.

Background: The increase of mental health issues globally has been well documented and now reflected in the United Nations' Sustainable Development Goals as a matter of global health significance. At the same time, studies show the mental health situations in conflict and post-conflict settings much higher than the rest of the world, lack the financial, health services and human resource capacity to address the challenges. Methods: The study used a descriptive literature review and collected data from public domain, mostly mental health data from WHO's Global Health Observatory. Since there is no primary database for Somalia's public health research, the bibliographic databases used for mental health in this study included Medline, PubMed, CINAHL, PsycINFO, and Google Scholar. Results: The review of the mental health literature shows one of the biggest casualties of the civil war was loss of essential human resources in healthcare as most either fled the country or were part of the victims of the war. Conclusion: In an attempt to address the human resource gap, there are calls to task-shift so that available human resource can be utilized efficiently and effectively. This policy paper discusses the case of Somalia, the impact of decade-long civil conflict on mental health and health services, the significant gap in mental health service delivery and how to strategically and evidently task-shift in closing the mental health gap in service delivery.

Adverse events following introduction of the ChAdOx1 nCoV-19 vaccine in Somalia in 2021: findings from a fragile setting and implications for the future.

Background: Vaccination against coronavirus disease 2019 (COVID-19) began in Somalia on 16 March 2021 with the Covishield (ChAdOx1 nCoV-19) vaccine. However, by the end of 2021, only a small percentage of the population had been fully vaccinated. As side effects play an important role in determining public confidence in vaccines and their uptake, this study aimed to examine reported adverse events following immunization (AEFIs) of vaccine recipients. Methods: This cross-sectional-survey-based study was conducted between March and October 2021 in Somalia. Vaccine recipients who were eligible to receive the first dose of the Covishield vaccine in the first phase of COVID-19 vaccination were eligible for study inclusion. P<0.05 was considered to indicate significance. Results: Of the 149,985 respondents who had received the first dose of the Covishield vaccine, 378 reported side effects. This represented a reported AEFI rate of 2.5 per 1000 population. Amongst those who reported adverse events, males (2.8 per 1000; P<0.001), respondents aged 35-49 years (3.3 per 1000; P=0.001) and teachers (3.5 per 1000; P=0.000) had higher rates of adverse events compared with females, other age groups and other occupations. Amongst population settlement types, a higher rate of AEFIs was observed amongst refugees (23.9 per 1000; P=0.000) and internally displaced populations (19 per 1000; P=0.000). Nearly half of the vaccine recipients who reported side effects (48%) reported one local symptom, and most symptoms were mild in nature. The probability of having acute and severe side effects was found to be 66% lower among males compared with females [odds ratio (OR) 0.44, 95% confidence interval (CI) 0.26-0.73; P=0.002]. Respondents aged >60 years (OR 1.52, 95% CI 0.64-3.62; P=0.34) were more likely to develop acute and severe AEFIs. None of the study population reported any severe life-threatening symptoms or death. Conclusion: Some variables (sex, profession, age) put recipients at higher odds of acute and severe AEFIs, but the Covishield vaccine generally produced mild side effects in a small proportion of the vaccinated population in Somalia. This study confirms that COVID-19 vaccines are safe, and their benefits clearly outweigh any associated risk.

Survival analysis of all critically ill patients with COVID-19 admitted to the main hospital in Mogadishu, Somalia, 30 March-12 June 2020: which interventions are proving effective in fragile states?

OBJECTIVES: To determine risk factors for death in patients with coronavirus disease 2019 (COVID-19) admitted to the main hospital in Somalia, and identify interventions contributing to improved clinical outcome in a low-resource and fragile setting. METHODS: A survival analysis was conducted of all patients with COVID-19 admitted to the main hospital in Somalia from 30 March to 12 June 2020. RESULTS: Of the 131 patients admitted to the hospital with COVID-19, 52 (40%) died and 79 (60%) survived. The main factors associated with the risk of in-hospital death were age ≥60 years {survival probability on day 21 was 0.789 [95% confidence interval (CI) 0.658-0.874] in patients aged <60 years vs 0.339 (95% CI 0.205-0.478) in patients aged ≥60 years}, cardiovascular disease [survival probability 0.478 (95% CI 0.332-0.610) in patients with cardiovascular disease vs 0.719 (95% CI 0.601-0.807) in patients without cardiovascular disease] and non-invasive ventilation on admission (patients who were not ventilated but received oxygen were significantly more likely to survive than patients who were ventilated; P<0.001). CONCLUSION: Considering the risk factors (age ≥60 years, presence of cardiovascular disease and use of non-invasive ventilation) is critical when managing patients with severe COVID-19, especially in low-resource settings where availability of skilled healthcare workers for critical care units is limited. These findings also highlight the importance of use of medical oxygen for severely ill patients, and the critical aspect of deciding whether or not to ventilate critical patients with COVID-19 in order to improve clinical outcome.

Structure, function and performance of Early Warning Alert and Response Network (EWARN) in emergencies in the Eastern Mediterranean Region.

INTRODUCTION: The Eastern Mediterranean Region (EMR) has experienced several protracted humanitarian crises. The affected population are served by eight Early Warning Alert and Response Network (EWARN) systems for outbreak detection and response. This study aimed to compare structure, function and performance of the systems' adherence to current guidance, and noted emerging lessons. METHODS: This study included a review of published and unpublished literature, a structured survey and interviews. RESULTS: Findings showed that all systems adhered to basic EWARN structure. Four of eight systems had electronic platforms, while one was implementing one. Regarding key EWARN function of outbreak detection: of the 35 health conditions, 26 were communicable diseases and nine were non-communicable; two systems focused on epidemic-prone diseases. Half the systems achieved ≥60% population coverage, five achieved ≥80% reporting timeliness, six achieved ≥80% reporting completeness, and seven achieved verification of ≥80% of alerts of suspected outbreaks. CONCLUSION: The findings showed that the systems followed the EWARN structure, while increasing adoption of electronic platforms. Performance, including timeliness and completeness of reporting, and timely verification of alerts were optimal for most of the systems. However, population coverage was low for most of the systems, and the EWARN's primary focus of outbreak detection was undermined by the increasing number of non-epidemic diseases.

Pandemic influenza preparedness (PIP) framework: Progress challenges in improving influenza preparedness response capacities in the Eastern Mediterranean Region, 2014-2017.

Influenza viruses with pandemic potential have been detected in humans in the Eastern Mediterranean Region. The Pandemic Influenza Preparedness (PIP) Framework aims to improve the sharing of influenza viruses with pandemic potential and increase access of developing countries to vaccines and other life-saving products during a pandemic. Under the Framework, countries have been supported to enhance their capacities to detect, prepare for and respond to pandemic influenza. In the Eastern Mediterranean Region, seven countries are priority countries for Laboratory and Surveillance (L&S) support: Afghanistan, Djibouti, Egypt, Jordan, Lebanon, Morocco and Yemen. During 2014-2017, US$ 2.7 million was invested in regional capacity-building and US$ 4.6 million directly in the priority countries. Countries were supported to strengthen influenza diagnostic capacities to improve detection, enhance influenza surveillance systems including sentinel surveillance for severe acute respiratory infection and influenza-like illness, and increase global sharing of surveillance data and influenza viruses. This paper highlights the progress made in improving influenza preparedness and response capacities in the Region from 2014 to 2017, and the challenges faced. By 2017, 18 of the 22 countries of the Region had laboratory-testing capacity, 19 had functioning sentinel influenza surveillance systems and 22 had trained national rapid response teams. The number of countries correctly identifying all influenza viruses in the WHO external quality assurance panel increased from 9 countries scoring 100% in 2014 to 15 countries in 2017, and the number sharing influenza viruses with WHO collaborating centres increased by 75% (from eight to 14 countries); more than half now share influenza data with regional or global surveillance platforms. Seven countries have estimated influenza disease burden and seven have introduced influenza vaccination for high-risk groups. Challenges included: protracted complex emergencies faced by nine countries which hindered implementation of influenza surveillance in areas with the most needs, high staff turnover, achieving timely virus sharing and limited utilization of influenza data where they are available to inform vaccine policies or establish threshold values to measure the start and severity of influenza seasons.

What Have We Learned About Middle East Respiratory Syndrome Coronavirus Emergence in Humans? A Systematic Literature Review.

BACKGROUND: Middle East respiratory syndrome coronavirus (MERS-CoV) was first identified in humans in 2012. A systematic literature review was conducted to synthesize current knowledge and identify critical knowledge gaps. MATERIALS AND METHODS: We conducted a systematic review on MERS-CoV using PRISMA guidelines. We identified 407 relevant, peer-reviewed publications and selected 208 of these based on their contributions to four key areas: virology; clinical characteristics, outcomes, therapeutic and preventive options; epidemiology and transmission; and animal interface and the search for natural hosts of MERS-CoV. RESULTS: Dipeptidyl peptidase 4 (DPP4/CD26) was identified as the human receptor for MERS-CoV, and a variety of molecular and serological assays developed. Dromedary camels remain the only documented zoonotic source of human infection, but MERS-like CoVs have been detected in bat species globally, as well as in dromedary camels throughout the Middle East and Africa. However, despite evidence of camel-to-human MERS-CoV transmission and cases apparently related to camel contact, the source of many primary cases remains unknown. There have been sustained health care-associated human outbreaks in Saudi Arabia and South Korea, the latter originating from one traveler returning from the Middle East. Transmission mechanisms are poorly understood; for health care, this may include environmental contamination. Various potential therapeutics have been identified, but not yet evaluated in human clinical trials. At least one candidate vaccine has progressed to Phase I trials. CONCLUSIONS: There has been substantial MERS-CoV research since 2012, but significant knowledge gaps persist, especially in epidemiology and natural history of the infection. There have been few rigorous studies of baseline prevalence, transmission, and spectrum of disease. Terms such as "camel exposure" and the epidemiological relationships of cases should be clearly defined and standardized. We strongly recommend a shared and accessible registry or database. Coronaviruses will likely continue to emerge, arguing for a unified "One Health" approach.

Enhancing surveillance for early detection of Zika virus infection: strategies for the countries of Eastern Mediterranean Region.

BACKGROUND: Zika virus infection (ZIKV) has caused major outbreaks in tropic and sub-tropic areas. No case from ZIKV has yet been reported in the countries of the Eastern Mediterranean Region (EMR) despite the presence of competent vector Aedes mosquitoes in many of these countries. AIMS: This study addresses appropriate surveillance strategies for early detection of ZIKV infection, which is important for EMR countries with established Aedes populations, but with no known or documented autochthonous transmission of ZIKV. METHODS: The WHO Regional Office for the Eastern Mediterranean developed a strategic framework for enhancing surveillance for ZIKV infection in EMR countries with established Aedes populations through a consultative process and review of available evidence. RESULTS: The framework calls for enhancing surveillance for early detection of ZIKV infection using a combination of both syndromic and event-based surveillance approaches. CONCLUSIONS: Enhancing surveillance for ZIKAV would require no shift in the existing system. A number of considerations would be required to integrate this syndromic and event-based surveillance approaches within the existing system.