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Sexual transmission chains of Ebola virus (EBOV) have been verified and linked to EBOV RNA persistence in semen, post-recovery. The rate of semen persistence over time, including the average duration of persistence among Ebola virus disease (EVD) survivors, is not well known. This cohort study aimed to analyze population estimates of EBOV RNA persistence rates in semen over time, and associated risk factors in a population of survivors from Sierra Leone. In this cohort study from May 2015 to April 2017 in Sierra Leone, recruitment was conducted in 2 phases; the first enrolled 100 male participants from the Western Area District in the capital of Freetown, and the second enrolled 120 men from the Western Area District and from Lungi, Port Loko District. Mean age of participants was 31 years. The men provided semen for testing, analyzed by quantitative reverse transcription PCR (qRT-PCR) for the presence of EBOV RNA. Follow-up occurred every 2 weeks until the endpoint, defined as 2 consecutive negative qRT-PCR results of semen specimen testing for EBOV RNA. Participants were matched with the Sierra Leone EVD case database to retrieve cycle threshold (Ct) values from the qRT-PCR analysis done in blood during acute disease. A purposive sampling strategy was used, and the included sample composition was compared to the national EVD survivor database to understand deviations from the general male survivor population. At 180 days (6 months) after Ebola treatment unit (ETU) discharge, the EBOV RNA semen positive rate was 75.4% (95% CI 66.9%-82.0%). The median persistence duration was 204 days, with 50% of men having cleared their semen of EBOV RNA after this time. At 270 days, persistence was 26.8% (95% CI 20.0%-34.2%), and at 360 days, 6.0% (95% CI 3.1%-10.2%). Longer persistence was significantly associated with severe acute disease, with probability of persistence in this population at 1 year at 10.1% (95% CI 4.6%-19.8%) compared to the probability approaching 0% for those with mild acute disease. Age showed a dose-response pattern, where the youngest men (≤25 years) were 3.17 (95% CI 1.60, 6.29) times more likely to be EBOV RNA negative in semen, and men aged 26-35 years were 1.85 (95% CI 1.04, 3.28) times more likely to be negative, than men aged >35 years. Among participants with both severe acute EVD and a higher age (>35 years), persistence remained above 20% (95% CI 6.0%-50.6%) at 1 year. Uptake of safe sex recommendations 3 months after ETU discharge was low among a third of survivors. The sample was largely representative of male survivors in Sierra Leone. A limitation of this study is the lack of knowledge about infectiousness. In this study we observed that EBOV RNA persistence in semen was a frequent phenomenon, with high population rates over time. This finding will inform forthcoming updated recommendations on risk reduction strategies relating to sexual transmission of EBOV. Our findings support implementation of a semen testing program as part of epidemic preparedness and response. Further, the results will enable planning of the magnitude of testing and targeted counseling needs over time.

Sexual transmission chains of Ebola virus (EBOV) have been verified and linked to EBOV RNA persistence in semen, post-recovery. The rate of semen persistence over time, including the average duration of persistence among Ebola virus disease (EVD) survivors, is not well known. This cohort study aimed to analyze population estimates of EBOV RNA persistence rates in semen over time, and associated risk factors in a population of survivors from Sierra Leone. In this cohort study from May 2015 to April 2017 in Sierra Leone, recruitment was conducted in 2 phases; the first enrolled 100 male participants from the Western Area District in the capital of Freetown, and the second enrolled 120 men from the Western Area District and from Lungi, Port Loko District. Mean age of participants was 31 years. The men provided semen for testing, analyzed by quantitative reverse transcription PCR (qRT-PCR) for the presence of EBOV RNA. Follow-up occurred every 2 weeks until the endpoint, defined as 2 consecutive negative qRT-PCR results of semen specimen testing for EBOV RNA. Participants were matched with the Sierra Leone EVD case database to retrieve cycle threshold (Ct) values from the qRT-PCR analysis done in blood during acute disease. A purposive sampling strategy was used, and the included sample composition was compared to the national EVD survivor database to understand deviations from the general male survivor population. At 180 days (6 months) after Ebola treatment unit (ETU) discharge, the EBOV RNA semen positive rate was 75.4% (95% CI 66.9%-82.0%). The median persistence duration was 204 days, with 50% of men having cleared their semen of EBOV RNA after this time. At 270 days, persistence was 26.8% (95% CI 20.0%-34.2%), and at 360 days, 6.0% (95% CI 3.1%-10.2%). Longer persistence was significantly associated with severe acute disease, with probability of persistence in this population at 1 year at 10.1% (95% CI 4.6%-19.8%) compared to the probability approaching 0% for those with mild acute disease. Age showed a dose-response pattern, where the youngest men ([less than or equal to]25 years) were 3.17 (95% CI 1.60, 6.29) times more likely to be EBOV RNA negative in semen, and men aged 26-35 years were 1.85 (95% CI 1.04, 3.28) times more likely to be negative, than men aged >35 years. Among participants with both severe acute EVD and a higher age (>35 years), persistence remained above 20% (95% CI 6.0%-50.6%) at 1 year. Uptake of safe sex recommendations 3 months after ETU discharge was low among a third of survivors. The sample was largely representative of male survivors in Sierra Leone. A limitation of this study is the lack of knowledge about infectiousness. In this study we observed that EBOV RNA persistence in semen was a frequent phenomenon, with high population rates over time. This finding will inform forthcoming updated recommendations on risk reduction strategies relating to sexual transmission of EBOV. Our findings support implementation of a semen testing program as part of epidemic preparedness and response. Further, the results will enable planning of the magnitude of testing and targeted counseling needs over time.

During the 2014-2016 West Africa Ebola Virus Disease (EVD) epidemic, the public health community had concerns that sexual transmission of the Ebola virus (EBOV) from EVD survivors was a risk, due to EBOV persistence in body fluids of EVD survivors, particularly semen. The Sierra Leone Ebola Virus Persistence Study was initiated to investigate this risk by assessing EBOV persistence in numerous body fluids of EVD survivors and providing risk reduction counseling based on test results for semen, vaginal fluid, menstrual blood, urine, rectal fluid, sweat, tears, saliva, and breast milk. This publication describes implementation of the counseling protocol and the key lessons learned. The Ebola Virus Persistence Risk Reduction Behavioral Counseling Protocol was developed from a framework used to prevent transmission of HIV and other sexually transmitted infections. The framework helped to identify barriers to risk reduction and facilitated the development of a personalized risk-reduction plan, particularly around condom use and abstinence. Pre-test and post-test counseling sessions included risk reduction guidance, and post-test counseling was based on the participants' individual test results. The behavioral counseling protocol enabled study staff to translate the study's body fluid test results into individualized information for study participants. The Ebola Virus Persistence Risk Reduction Behavioral Counseling Protocol provided guidance to mitigate the risk of EBOV transmission from EVD survivors. It has since been shared with and adapted by other EVD survivor body fluid testing programs and studies in Ebola-affected countries.

The COVID-19 pandemic has amplified pre-existing challenges to health promotion and care across the world, and particularly in low- and middle-income countries (LMICs). This qualitative study draws on data from a panel of immunisation experts and uses a novel framework of vaccine delivery domains to explore perspectives from those who live and work in these settings on the challenges to implementing COVID-19 vaccine programs in LMICs. We conducted a thematic content analysis of 96 participant free text replies to questions from Round I of a three-round Delphi consensus study amongst global experts on COVID-19 vaccine implementation. Participant responses highlighted challenges to vaccine program implementation including issues related to equity; governance, decision-making, and financing; regulatory structures, planning, and coordination; prioritisation, demand generation, and communication; vaccine, cold chain, logistics, and infrastructure; service delivery, human resources, and supplies; and surveillance, monitoring, and evaluation. We reflect on our findings in light of global efforts to address vaccine inequity and emphasise three key areas salient to improving vaccination efforts during novel infectious disease outbreaks: 1) Ensuring safe and sustainable service delivery in communities and at points of care; 2) Strengthening systems for end-to-end delivery of vaccines, therapeutics, diagnostics, and essential supplies; 3) Transforming structural paradigms towards vaccine equity.

The 2013–2016 Ebola outbreak in West Africa is the largest on record with 28 616 confirmed, probable and suspected cases and 11 310 deaths officially recorded by 10 June 2016, the true burden probably considerably higher. The case fatality ratio (CFR: proportion of cases that are fatal) is a key indicator of disease severity useful for gauging the appropriate public health response and for evaluating treatment benefits, if estimated accurately. We analysed individual-level clinical outcome data from Guinea, Liberia and Sierra Leone officially reported to the World Health Organization. The overall mean CFR was 62.9% (95% CI: 61.9% to 64.0%) among confirmed cases with recorded clinical outcomes. Age was the most important modifier of survival probabilities, but country, stage of the epidemic and whether patients were hospitalized also played roles. We developed a statistical analysis to detect outliers in CFR between districts of residence and treatment centres (TCs), adjusting for known factors influencing survival and identified eight districts and three TCs with a CFR significantly different from the average. From the current dataset, we cannot determine whether the observed variation in CFR seen by district or treatment centre reflects real differences in survival, related to the quality of care or other factors or was caused by differences in reporting practices or case ascertainment. This article is part of the themed issue ‘The 2013–2016 West African Ebola epidemic: data, decision-making and disease control’.

The COVID-19 pandemic has amplified pre-existing challenges to health promotion and care across the world, and particularly in low- and middle-income countries (LMICs). This qualitative study draws on data from a panel of immunisation experts and uses a novel framework of vaccine delivery domains to explore perspectives from those who live and work in these settings on the challenges to implementing COVID-19 vaccine programs in LMICs. We conducted a thematic content analysis of 96 participant free text replies to questions from Round I of a three-round Delphi consensus study amongst global experts on COVID-19 vaccine implementation. Participant responses highlighted challenges to vaccine program implementation including issues related to equity; governance, decision-making, and financing; regulatory structures, planning, and coordination; prioritisation, demand generation, and communication; vaccine, cold chain, logistics, and infrastructure; service delivery, human resources, and supplies; and surveillance, monitoring, and evaluation. We reflect on our findings in light of global efforts to address vaccine inequity and emphasise three key areas salient to improving vaccination efforts during novel infectious disease outbreaks: 1) Ensuring safe and sustainable service delivery in communities and at points of care; 2) Strengthening systems for end-to-end delivery of vaccines, therapeutics, diagnostics, and essential supplies; 3) Transforming structural paradigms towards vaccine equity.

The COVID-19 pandemic has amplified pre-existing challenges to health promotion and care across the world, and particularly in low- and middle-income countries (LMICs). This qualitative study draws on data from a panel of immunisation experts and uses a novel framework of vaccine delivery domains to explore perspectives from those who live and work in these settings on the challenges to implementing COVID-19 vaccine programs in LMICs. We conducted a thematic content analysis of 96 participant free text replies to questions from Round I of a three-round Delphi consensus study amongst global experts on COVID-19 vaccine implementation. Participant responses highlighted challenges to vaccine program implementation including issues related to equity; governance, decision-making, and financing; regulatory structures, planning, and coordination; prioritisation, demand generation, and communication; vaccine, cold chain, logistics, and infrastructure; service delivery, human resources, and supplies; and surveillance, monitoring, and evaluation. We reflect on our findings in light of global efforts to address vaccine inequity and emphasise three key areas salient to improving vaccination efforts during novel infectious disease outbreaks: 1) Ensuring safe and sustainable service delivery in communities and at points of care; 2) Strengthening systems for end-to-end delivery of vaccines, therapeutics, diagnostics, and essential supplies; 3) Transforming structural paradigms towards vaccine equity.

Canada eliminated measles in 1998, but the risk of outbreaks remains due to sub-optimal vaccine coverage and imported cases. To address limitations of vaccine coverage data, we measured measles seroprevalence among a convenience sample of individuals serologically tested in Ontario, Canada. We linked measles IgG serology data from 349,451 individuals tested during 2014–2016 to health administrative databases and used a cross-sectional design to measure measles IgG seroprevalence. We estimated seroprevalence overall and by sociodemographic factors. Using the manufacturer-recommended threshold of ≥275 mIU/mL, measles seroprevalence was 83.5 % (95% CI, 83.4–83.6 %), below the 90–95 % herd immunity threshold. However, using the often cited >120 mIU/mL threshold, seroprevalence was 97.1 % (95% CI, 97.0–97.1 %). Using a threshold of ≥275 mIU/mL, seroprevalence varied by age, with the lowest observed among adolescents aged 12–19 years (75.3 %; 95% CI, 74.8–75.7 %) and young adults aged 20–29 years (75.8 %; 95% CI, 75.5–76.1 %), and highest among the oldest cohorts aged ≥50 years (96.9 %; 95% CI, 96.8–97.0 %). When using a lower threshold of protection (>120 mIU/mL), large differences in seroprevalence by age were not observed. Among individuals born in or after 1985, immigrants had lower seroprevalence (≥275 mIU/mL) (71.0 %; 95% CI, 70.6–71.5 %) compared to those born in Canada (77.8 %; 95% CI, 77.6–78.1 %). The uncertainty of the exact correlate of protection for measles complicates the interpretation of seroprevalence data when assessing whether this convenience sample of individuals serologically tested for measles is adequately protected to prevent future outbreaks. Measles seroprevalence varied significantly by age and immigrant status, with highest seronegativity (<275 mIU/mL) observed among adolescents, young adults, and young immigrants. It is possible that sustaining measles elimination in Ontario will be challenging in the face of ongoing measles importations from abroad, and immunity gaps in some population groups.

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. 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. 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. 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.).

The recent outbreak of Ebola virus devastated parts of West Africa, infecting more than 28,000 people and causing more than 11,000 deaths. In this report, public health authorities discuss many of the challenges associated with responding to and containing the virus. Summary Between December 2013 and April 2016, the largest epidemic of Ebola virus disease (EVD) to date generated more than 28,000 cases and more than 11,000 deaths in the large, mobile populations of Guinea, Liberia, and Sierra Leone. Tracking the rapid rise and slower decline of the West African epidemic has reinforced some common understandings about the epidemiology and control of EVD but has also generated new insights. Despite having more information about the geographic distribution of the disease, the risk of human infection from animals and from survivors of EVD remains unpredictable over a wide area of equatorial Africa. . . .