Exportation of Monkeypox Virus From the African Continent.

BACKGROUND: The largest West African monkeypox outbreak began September 2017, in Nigeria. Four individuals traveling from Nigeria to the United Kingdom (n = 2), Israel (n = 1), and Singapore (n = 1) became the first human monkeypox cases exported from Africa, and a related nosocomial transmission event in the United Kingdom became the first confirmed human-to-human monkeypox transmission event outside of Africa. METHODS: Epidemiological and molecular data for exported and Nigerian cases were analyzed jointly to better understand the exportations in the temporal and geographic context of the outbreak. RESULTS: Isolates from all travelers and a Bayelsa case shared a most recent common ancestor and traveled to Bayelsa, Delta, or Rivers states. Genetic variation for this cluster was lower than would be expected from a random sampling of genomes from this outbreak, but data did not support direct links between travelers. CONCLUSIONS: Monophyly of exportation cases and the Bayelsa sample, along with the intermediate levels of genetic variation, suggest a small pool of related isolates is the likely source for the exported infections. This may be the result of the level of genetic variation present in monkeypox isolates circulating within the contiguous region of Bayelsa, Delta, and Rivers states, or another more restricted, yet unidentified source pool.

Ebola RNA Persistence in Semen of Ebola Virus Disease Survivors - Final Report.

BACKGROUND: Ebola virus has been detected in the semen of men after their recovery from Ebola virus disease (EVD). We report the presence of Ebola virus RNA in semen in a cohort of survivors of EVD in Sierra Leone. METHODS: We enrolled a convenience sample of 220 adult male survivors of EVD in Sierra Leone, at various times after discharge from an Ebola treatment unit (ETU), in two phases (100 participants were in phase 1, and 120 in phase 2). Semen specimens obtained at baseline were tested by means of a quantitative reverse-transcriptase-polymerase-chain-reaction (RT-PCR) assay with the use of the target sequences of NP and VP40 (in phase 1) or NP and GP (in phase 2). This study did not evaluate directly the risk of sexual transmission of EVD. RESULTS: Of 210 participants who provided an initial semen specimen for analysis, 57 (27%) had positive results on quantitative RT-PCR. Ebola virus RNA was detected in the semen of all 7 men with a specimen obtained within 3 months after ETU discharge, in 26 of 42 (62%) with a specimen obtained at 4 to 6 months, in 15 of 60 (25%) with a specimen obtained at 7 to 9 months, in 4 of 26 (15%) with a specimen obtained at 10 to 12 months, in 4 of 38 (11%) with a specimen obtained at 13 to 15 months, in 1 of 25 (4%) with a specimen obtained at 16 to 18 months, and in no men with a specimen obtained at 19 months or later. Among the 46 participants with a positive result in phase 1, the median baseline cycle-threshold values (higher values indicate lower RNA values) for the NP and VP40 targets were lower within 3 months after ETU discharge (32.4 and 31.3, respectively; in 7 men) than at 4 to 6 months (34.3 and 33.1; in 25), at 7 to 9 months (37.4 and 36.6; in 13), and at 10 to 12 months (37.7 and 36.9; in 1). In phase 2, a total of 11 participants had positive results for NP and GP targets (samples obtained at 4.1 to 15.7 months after ETU discharge); cycle-threshold values ranged from 32.7 to 38.0 for NP and from 31.1 to 37.7 for GP. CONCLUSIONS: These data showed the long-term presence of Ebola virus RNA in semen and declining persistence with increasing time after ETU discharge. (Funded by the World Health Organization and others.).

Design thinking during a health emergency: building a national data collection and reporting system.

BACKGROUND: Design thinking allows challenging problems to be redefined in order to identify alternative user-center strategies and solutions. To address the many challenges associated with collecting and reporting data during the 2014 Ebola outbreak in Guinea, Liberia and Sierra Leone, we used a design thinking approach to build the Global Ebola Laboratory Data collection and reporting system. MAIN TEXT: We used the five-stage Design Thinking model proposed by Hasso-Plattner Institute of Design at Stanford in Guinea, Liberia and Sierra Leone. This approach offers a flexible model which focuses on empathizing, defining, ideating, prototyping, and testing. A strong focus of the methodology includes end-users' feedback from the beginning to the end of the process. This is an iterative methodology that continues to adapt according to the needs of the system. The stages do not need to be sequential and can be run in parallel, out of order, and repeated as necessary. Design thinking was used to develop a data collection and reporting system, which contains all laboratory data from the three countries during one of the most complicated multi-country outbreaks to date. The data collection and reporting system was used to orient the response interventions at the district, national, and international levels within the three countries including generating situation reports, monitoring the epidemiological and operational situations, providing forecasts of the epidemic, and supporting Ebola-related research and the Ebola National Survivors programs within each country. CONCLUSIONS: Our study demonstrates the numerous benefits that arise when using a design thinking methodology during an outbreak to solve acute challenges within the national health information system and the authors recommend it's use during future complex outbreaks.

Measures to control protracted large Lassa fever outbreak in Nigeria, 1 January to 28 April 2019.

Lassa fever cases have increased in Nigeria since 2016 with the highest number, 633 cases, reported in 2018. From 1 January to 28 April 2019, 554 laboratory-confirmed cases including 124 deaths were reported in 21 states in Nigeria. A public health emergency was declared on 22 January by the Nigeria Centre for Disease Control. We describe the various outbreak responses that have been implemented, including establishment of emergency thresholds and guidelines for case management.

A new hepatitis E virus genotype 2 strain identified from an outbreak in Nigeria, 2017.

BACKGROUND: In 2017 the Nigerian Ministry of Health notified the World Health Organization (WHO) of an outbreak of hepatitis E located in the north-east region of the country with 146 cases with 2 deaths. The analysis of the hepatitis E virus (HEV) genotypes responsible for the outbreak revealed the predominance of HEV genotypes 1 (HEV-1) and 2 (HEV-2). Molecular data of HEV-2 genomes are limited; therefore we characterized a HEV-2 strain of the outbreak in more detail. FINDING: The full-length genome sequence of an HEV-2 strain (NG/17-0500) from the outbreak was amplified using newly designed consensus primers. Comparison with other HEV complete genome sequences, including the only HEV-2 strain (Mex-14) with available complete genome sequences and the availability of data of partial HEV-2 sequences from Sub-Saharan Africa, suggests that NG/17-0500 belongs to HEV subtype 2b (HEV-2b). CONCLUSIONS: We identified a novel HEV-2b strain from Sub-Saharan Africa, which is the second complete HEV-2 sequence to date, whose natural history and epidemiology merit further investigation.

Development, Use, and Impact of a Global Laboratory Database During the 2014 Ebola Outbreak in West Africa.

Background: The international impact, rapid widespread transmission, and reporting delays during the 2014 Ebola outbreak in West Africa highlighted the need for a global, centralized database to inform outbreak response. The World Health Organization and Emerging and Dangerous Pathogens Laboratory Network addressed this need by supporting the development of a global laboratory database. Methods: Specimens were collected in the affected countries from patients and dead bodies meeting the case definitions for Ebola virus disease. Test results were entered in nationally standardized spreadsheets and consolidated onto a central server. Results: From March 2014 through August 2016, 256343 specimens tested for Ebola virus disease were captured in the database. Thirty-one specimen types were collected, and a variety of diagnostic tests were performed. Regular analysis of data described the functionality of laboratory and response systems, positivity rates, and the geographic distribution of specimens. Conclusion: With data standardization and end user buy-in, the collection and analysis of large amounts of data with multiple stakeholders and collaborators across various user-access levels was made possible and contributed to outbreak response needs. The usefulness and value of a multifunctional global laboratory database is far reaching, with uses including virtual biobanking, disease forecasting, and adaption to other disease outbreaks.

Epidemiological and virological characterization of 2009 pandemic influenza A virus subtype H1N1 in Madagascar.

BACKGROUND: Madagascar was one of the first African countries to be affected by the 2009 pandemic of influenza A virus subtype H1N1 [A(H1N1)pdm2009] infection. The outbreak started in the capital city, Antananarivo, and then spread throughout the country from October 2009 through February 2010. METHODS: Specimens from patients presenting with influenza-like illness were collected and shipped to the National Influenza Center in Madagascar for analyses, together with forms containing patient demographic and clinical information. RESULTS: Of the 2303 specimens tested, 1016 (44.1%) and 131 (5.7%) yielded A(H1N1)pdm09 and seasonal influenza virus, respectively. Most specimens (42.0%) received were collected from patients <10 years old. Patients <20 years old were more likely than patients >50 years old to be infected with A(H1N1)pdm09 (odds ratio, 2.1; 95% confidence interval, 1.7-2.6; P < .01). Although phylogenetic analyses of A(H1N1)pdm09 suggested multiple introductions of the virus into Madagascar, no antigenic differences between A(H1N1)pdm09 viruses recovered in Madagascar and those that circulated worldwide were observed. CONCLUSIONS: The high proportion of respiratory specimens positive for A(H1N1)pdm09 is consistent with a widespread transmission of the pandemic in Madagascar. The age distribution of cases of A(H1N1)pdm09 infection suggests that children and young adults could be targeted for interventions that aim to reduce transmission during an influenza pandemic.

Introduction of 2009 pandemic influenza A virus subtype H1N1 into South Africa: clinical presentation, epidemiology, and transmissibility of the first 100 cases.

BACKGROUND: We documented the introduction of 2009 pandemic influenza A virus subtype H1N1 (A[H1N1]pdm09) into South Africa and describe its clinical presentation, epidemiology, and transmissibility. METHODS: We conducted a prospective descriptive study of the first 100 laboratory-confirmed cases of A(H1N1)pdm09 infections identified through active case finding and surveillance. Infected patients and the attending clinicians were interviewed, and close contacts were followed up to investigate household transmission. FINDINGS: The first case was confirmed on 14 June 2009, and by 15 July 2009, 100 cases were diagnosed. Forty-two percent of patients reported international travel within 7 days prior to onset of illness. Patients ranged in age from 4 to 70 years (median age, 21.5 years). Seventeen percent of household contacts developed influenza-like illness, and 10% of household contacts had laboratory-confirmed A(H1N1)pdm09 infection. We found a mean serial interval (± SD) of 2.3 ± 1.3 days (range, 1-5 days) between successive laboratory-confirmed cases in the transmission chain. CONCLUSIONS: A(H1N1)pdm09 established itself rapidly in South Africa. Transmissibility of the virus was comparable to observations from outside of Africa and to seasonal influenza virus strains.

Evolutionary dynamics of 2009 pandemic influenza A virus subtype H1N1 in South Africa during 2009-2010.

BACKGROUND: The 2009 pandemic influenza A virus subtype H1N1 (A[H1N1]pdm09) was first detected in June 2009 in South Africa and later resulted in extensive transmission throughout Africa. Established routine surveillance programs and collaboration between private and public sector laboratories allowed for comprehensive molecular epidemiological and antigenic investigation of the first and second waves of 2009-2010 pandemic influenza in South Africa. METHODS: We used reverse-transcription polymerase chain reaction to screen for influenza virus in 9792 specimens recovered during 2009 and 6915 specimens recovered during 2010 from inpatients and outpatients with influenza-like illness or severe acute respiratory illness symptoms identified by surveillance programs. Influenza-positive specimens were subjected to genetic and antigenic characterization. Bayesian and maximum likelihood analyses of the hemagglutinin genes of 96 A(H1N1)pdm09 strains were used for molecular epidemiological investigations. Hemagglutination inhibition assays and sequencing of the PB2 and neuraminidase genes were used to investigate pathogenicity and resistance mutations. RESULTS: The A(H1N1)pdm09 epidemic occurred as a second epidemic peak following seasonal influenza A virus subtype H3N2 cases in 2009 and in 2010. Progressive drift away from the A/California/7/2009 vaccine strain was observed at both the nucleotide and amino acid level, with 2010 strains clustering separate to 2009 strains. A few unique clusters of amino acid changes in severe cases were identified, but most strains were antigenically similar to the vaccine strain, and no resistance or known pathogenicity mutations were detected. CONCLUSION: Despite limited drift observed over the 2 seasons in South Africa, circulating A(H1N1)pdm09 strains remained antigenically similar to strains identified in other northern and southern hemisphere countries from 2010 and 2011.

Respiratory viral coinfections identified by a 10-plex real-time reverse-transcription polymerase chain reaction assay in patients hospitalized with severe acute respiratory illness--South Africa, 2009-2010.

BACKGROUND: Data about respiratory coinfections with 2009 pandemic influenza A virus subtype H1N1 during the 2009-2010 influenza pandemic in Africa are limited. We used an existing surveillance program for severe acute respiratory illness to evaluate a new multiplex real-time polymerase chain reaction assay and investigate the role of influenza virus and other respiratory viruses in pneumonia hospitalizations during and after the influenza pandemic in South Africa. METHODS: The multiplex assay was developed to detect 10 respiratory viruses, including influenza A and B viruses, parainfluenza virus types 1-3, respiratory syncytial virus (RSV), enterovirus, human metapneumovirus (hMPV), adenovirus (AdV), and rhinovirus (RV), followed by influenza virus subtyping. Nasopharyngeal and oropharyngeal specimens were collected from patients hospitalized with pneumonia at 6 hospitals during 2009-2010. RESULTS: Validation against external quality controls confirmed the high sensitivity (91%) and specificity (100%) and user-friendliness, compared with other PCR technologies. Of 8173 patients, 40% had single-virus infections, 17% had coinfections, and 43% remained negative. The most common viruses were RV (25%), RSV (14%), AdV (13%), and influenza A virus (5%). Influenza virus, RSV, PIV type 3, and hMPV showed seasonal patterns. CONCLUSION: The data provide a better understanding of the viral etiology of hospitalized cases of pneumonia and demonstrate the usefulness of this multiplex assay in respiratory disease surveillance in South Africa.

Health Emergency Risk Management in World Health Organization - South-East Asia Region during 2014-2023: synthesis of experiences.

Health Emergency Risk Management (ERM) has become increasingly critical on the global stage, prompted by the escalating frequency and severity of natural disasters and disease outbreaks. This paper offers a comprehensive synthesis of the World Health Organization's (WHO) experiences in the South-East Asia Region during the period 2014-2023, shedding light on its efforts to manage health emergencies and enhance resilience. The South-East Asia Region's unique environmental and economic diversity exposes it to significant health risks, including emerging infectious diseases and their implications for development, particularly in low-income countries. Here we document the transition from reactive emergency responses to proactive preparedness, catalyzed by prioritizing ERM as one of the regional flagship priorities in 2014. Key components of this initiative included capacity-building, the establishment of the South-East Asia Regional Health Emergency Fund (SEARHEF), and the implementation of the International Health Regulations (IHR 2005). This synthesis highlights the region's achievements in event reporting, development of national actions plan, successful Early Warning, Alert, and Response System (EWARS) implementation, and improvements in core capacities under IHR (2005). It also underscores the challenges associated with cross-border data sharing and regional collaboration that could strengthen ERM and enhance readiness for effective synergistic response.

Strengthening pathogen genomic surveillance for health emergencies: insights from the World Health Organization's regional initiatives.

The onset of the COVID-19 pandemic triggered a rapid scale-up in the use of genomic surveillance as a pandemic preparedness and response tool. As a result, the number of countries with in-country SARS-CoV-2 genomic sequencing capability increased by 40% from February 2021 to July 2022. The Global Genomic Surveillance Strategy for Pathogens with Pandemic and Epidemic Potential 2022-2032 was launched by the World Health Organization (WHO) in March 2022 to bring greater coherence to ongoing work to strengthen genomic surveillance. This paper describes how WHO's tailored regional approaches contribute to expanding and further institutionalizing the use of genomic surveillance to guide pandemic preparedness and response measures as part of a harmonized global undertaking. Challenges to achieving this vision include difficulties obtaining sequencing equipment and supplies, shortages of skilled staff, and obstacles to maximizing the utility of genomic data to inform risk assessment and public health action. WHO is helping to overcome these challenges in collaboration with partners. Through its global headquarters, six regional offices, and 153 country offices, WHO is providing support for country-driven efforts to strengthen genomic surveillance in its 194 Member States, with activities reflecting regional specificities. WHO's regional offices serve as platforms for those countries in their respective regions to share resources and knowledge, engage stakeholders in ways that reflect national and regional priorities, and develop regionally aligned approaches to implementing and sustaining genomic surveillance within public health systems.

Melioidosis in Africa: Time to Raise Awareness and Build Capacity for Its Detection, Diagnosis, and Treatment.

Melioidosis is a tropical infectious disease caused by the soil-dwelling bacterium Burkholderia pseudomallei with a mortality of up to 50% in low resource settings. Only a few cases have been reported from African countries. However, studies on the global burden of melioidosis showed that Africa holds a significant unrecognized disease burden, with Nigeria being at the top of the list. The first World Health Organization African Melioidosis Workshop was organized in Lagos, Nigeria, with representatives of health authorities, microbiology laboratories, and clinical centers from across the continent. Dedicated hands-on training was given on laboratory diagnostics of B. pseudomallei. This report summarises the meeting objectives, including raising awareness of melioidosis and building capacity for the detection, diagnosis, biosafety, treatment, and prevention across Africa. Further, collaboration with regional and international experts provided a platform for sharing ideas on best practices.

Global disparities in SARS-CoV-2 genomic surveillance.

Genomic sequencing is essential to track the evolution and spread of SARS-CoV-2, optimize molecular tests, treatments, vaccines, and guide public health responses. To investigate the global SARS-CoV-2 genomic surveillance, we used sequences shared via GISAID to estimate the impact of sequencing intensity and turnaround times on variant detection in 189 countries. In the first two years of the pandemic, 78% of high-income countries sequenced >0.5% of their COVID-19 cases, while 42% of low- and middle-income countries reached that mark. Around 25% of the genomes from high income countries were submitted within 21 days, a pattern observed in 5% of the genomes from low- and middle-income countries. We found that sequencing around 0.5% of the cases, with a turnaround time <21 days, could provide a benchmark for SARS-CoV-2 genomic surveillance. Socioeconomic inequalities undermine the global pandemic preparedness, and efforts must be made to support low- and middle-income countries improve their local sequencing capacity.

Trivalent inactivated influenza vaccine in African adults infected with human immunodeficient virus: double blind, randomized clinical trial of efficacy, immunogenicity, and safety.

BACKGROUND: Data on the efficacy of trivalent, inactivated influenza vaccine (TIV) in HIV-infected adults, particularly in Africa, are limited. This study evaluated the safety, immunogenicity, and efficacy of TIV in HIV-infected adults. METHODS: In Johannesburg, South Africa, we undertook a randomized, double-blind, placebo-controlled trial involving 506 HIV-infected adults. Subjects included 157 individuals who were antiretroviral treatment (ART) naive and 349 on stable-ART. Participants were randomly assigned to receive TIV or normal saline intramuscularly. Oropharyngeal swabs were obtained at illness visits during the influenza season and tested by shell vial culture and RT PCR assay for influenza virus. Immune response was evaluated by hemagglutinin antibody inhibition assay (HAI) in a nested cohort. The primary study outcome involved vaccine efficacy against influenza confirmed illness. This trial is registered with ClinicalTrials.gov, number NCT00757900. RESULTS: The efficacy of TIV against confirmed influenza illness was 75.5% (95% CI: 9.2%-95.6%); with a risk difference of 0.18 per 100 person-weeks in TIV recipients. Among TIV recipients, seroconversion, measured by HAI titers, was evident in 52.6% for H1N1, 60.8% for H3N2, and 53.6% for influenza B virus. This compared with 2.2%, 2.2%, and 4.4% of placebo recipients (P < .0001). The frequency of local and systemic adverse events post-immunization was similar between study groups. CONCLUSIONS: TIV immunization is safe and efficacious in African HIV-infected adults without underlying co-morbidities. Further evaluation of effectiveness is warranted in severely immunocompromized HIV-infected adults and those with co-morbidities such as tuberculosis.

PIPDeploy: Development and implementation of a gamified table top simulation exercise to strengthen national pandemic vaccine preparedness and readiness.

Successful emergency vaccination campaigns rely on effective deployment and vaccination plans. This applies to localised outbreaks as well as for pandemics. In the wake of the 2009 H1N1 influenza pandemic, analysis of the global Vaccine Deployment Initiative, through which the World Health Organization (WHO) donated pandemic influenza vaccines to countries in need, revealed that an absence of vaccine deployment plans in many countries significantly hindered vaccine deployment. Through the Pandemic Influenza Preparedness Framework adopted by the World Health Assembly in 2011, WHO is engaging in several capacity building activities to improve pandemic influenza preparedness and response and make provisions for access to vaccines and sharing of other benefits. The Framework calls for the development and exercise of operational plans for deployment of influenza vaccines to enhance pandemic preparedness. To this end, WHO has supported the development of PIPDeploy, an interactive, in-person table top simulation exercise to facilitate learning for emergency preparedness. It employs various game design elements including a game board, time pressure, leaderboards and teams to enhance participants' motivation. PIPDeploy formed part of five WHO Pandemic Influenza Vaccine Deployment Workshops attended by national-level managers responsible for pandemic influenza vaccine response predominantly in non-producing countries. The purpose of this study was to describe the features and application of PIPDeploy, and present findings of the evaluation of participants' experiences during the simulation involving a "hot wash" discussion and collection of quantitative data. The simulation's instructional approach was widely accepted by participants, who reported that the format was novel and engaging. They reflected on its utility for identifying gaps in their own vaccine deployment plans and regulatory frameworks for importation of vaccine products. All participants found the simulation relevant to their professional objectives. A range of other potential applications were suggested, including PIPDeploy's adaptation to sub-national contexts and to other epidemic diseases.

Regional sequencing collaboration reveals persistence of the T12 Vibrio cholerae O1 lineage in West Africa.

Background: Despite recent insights into cholera transmission patterns in Africa, regional and local dynamics in West Africa-where cholera outbreaks occur every few years-are still poorly understood. Coordinated genomic surveillance of Vibrio cholerae in the areas most affected may reveal transmission patterns important for cholera control. Methods: During a regional sequencing workshop in Nigeria, we sequenced 46 recent V. cholerae isolates from Cameroon, Niger, and Nigeria (37 from 2018 to 2019) to better understand the relationship between the V. cholerae bacterium circulating in these three countries. Results: From these isolates, we generated 44 whole Vibrio cholerae O1 sequences and analyzed them in the context of 1280 published V. cholerae O1 genomes. All sequences belonged to the T12 V. cholerae seventh pandemic lineage. Conclusions: Phylogenetic analysis of newly generated and previously published V. cholerae genomes suggested that the T12 lineage has been continuously transmitted within West Africa since it was first observed in the region in 2009, despite lack of reported cholera in the intervening years. The results from this regional sequencing effort provide a model for future regionally coordinated surveillance efforts. Funding: Funding for this project was provided by Bill and Melinda Gates Foundation OPP1195157.

Global disparities in SARS-CoV-2 genomic surveillance.

Genomic sequencing provides critical information to track the evolution and spread of SARS-CoV-2, optimize molecular tests, treatments and vaccines, and guide public health responses. To investigate the spatiotemporal heterogeneity in the global SARS-CoV-2 genomic surveillance, we estimated the impact of sequencing intensity and turnaround times (TAT) on variant detection in 167 countries. Most countries submit genomes >21 days after sample collection, and 77% of low and middle income countries sequenced <0.5% of their cases. We found that sequencing at least 0.5% of the cases, with a TAT <21 days, could be a benchmark for SARS-CoV-2 genomic surveillance efforts. Socioeconomic inequalities substantially impact our ability to quickly detect SARS-CoV-2 variants, and undermine the global pandemic preparedness.