Persistence of Ebola virus in semen among Ebola virus disease survivors in Sierra Leone: A cohort study of frequency, duration, and risk factors.

BACKGROUND: 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. METHODS AND FINDINGS: 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. CONCLUSIONS: 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.

Containing Hemorrhagic Fever Epidemic, The Ebola Experience in Uganda ( O ct ob er 2000 – January 2001)

Document reports success to combat Ebola in Uganda. Relates the importance of control interventions addressed weakness prior to outbreak detection and aimed at improving preparedness for future out break detection and response.

Containing a haemorrhagic fever epidemic: the Ebola experience in Uganda (October 2000-January 2001).

INTRODUCTION: The Ebola virus, belonging to the family of filoviruses, was first recognized in 1976 when it caused concurrent outbreaks in Yambuku in the Democratic Republic of Congo (DRC), and in the town of Nzara in Sudan. Both countries share borders with Uganda. A total of 425 cases and 224 deaths attributed to Ebola haemorrhagic fever (EHF) were recorded in Uganda in 2000/01. Although there was delayed detection at the community level, prompt and efficient outbreak investigation led to the confirmation of the causative agent on 14 October 2000 by the National Institute of Virology in South Africa, and the subsequent institution of control interventions. CONTROL INTERVENTIONS: Public health interventions to contain the epidemic aimed at minimizing transmission in the health care setting and in the community, reducing the case fatality rate due to the epidemic, strengthening co-ordination for the response and building capacity for on-going surveillance and control. Co-ordination of the control interventions was organized through the Interministerial Committee, National Ebola Task Force, District Ebola Task Forces, and the Technical Committees at national and district levels. The World Health Organization (WHO) under the Global Outbreak Alert and Response Network co-ordinated the international response. The post-outbreak control interventions addressed weaknesses prior to outbreak detection and aimed at improving preparations for future outbreak detection and response. Challenges to control efforts included inadequate and poor quality protective materials, deaths of health workers, numerous rumors and the rejection of convalescent cases by members of the community. CONCLUSIONS: This was recognized as the largest reported outbreak of EHF in the world. Control interventions were very successful in containing the epidemic. The community structures used to contain the epidemic have continued to perform well after containment of the outbreak, and have proved useful in the identification of other outbreaks. This was also the first outbreak response co-ordinated by the WHO under the Global Outbreak Alert and Response Network, a voluntary organization recently created to co-ordinate technical and financial resources to developing countries during outbreaks.

An outbreak of Ebola in Uganda.

An outbreak of Ebola disease was reported from Gulu district, Uganda, on 8 October 2000. The outbreak was characterized by fever and haemorrhagic manifestations, and affected health workers and the general population of Rwot-Obillo, a village 14 km north of Gulu town. Later, the outbreak spread to other parts of the country including Mbarara and Masindi districts. Response measures included surveillance, community mobilization, case and logistics management. Three coordination committees were formed: National Task Force (NTF), a District Task Force (DTF) and an Interministerial Task Force (IMTF). The NTF and DTF were responsible for coordination and follow-up of implementation of activities at the national and district levels, respectively, while the IMTF provided political direction and handled sensitive issues related to stigma, trade, tourism and international relations. The international response was coordinated by the World Health Organization (WHO) under the umbrella organization of the Global Outbreak and Alert Response Network. A WHO/CDC case definition for Ebola was adapted and used to capture four categories of cases, namely, the 'alert', 'suspected', 'probable' and 'confirmed cases'. Guidelines for identification and management of cases were developed and disseminated to all persons responsible for surveillance, case management, contact tracing and Information Education Communication (IEC). For the duration of the epidemic that lasted up to 16 January 2001, a total of 425 cases with 224 deaths were reported countrywide. The case fatality rate was 53%. The attack rate (AR) was highest in women. The average AR for Gulu district was 12.6 cases/10 000 inhabitants when the contacts of all cases were considered and was 4.5 cases/10 000 if limited only to contacts of laboratory confirmed cases. The secondary AR was 2.5% when nearly 5000 contacts were followed up for 21 days. Uganda was finally declared Ebola free on 27 February 2001, 42 days after the last case was reported. The Government's role in coordination of both local and international support was vital. The NTF and the corresponding district committees harmonized implementation of a mutually agreed programme. Community mobilization using community-based resource persons and political organs, such as Members of Parliament was effective in getting information to the public. This was critical in controlling the epidemic. Past experience in epidemic management has shown that in the absence of regular provision of information to the public, there are bound to be deleterious rumours. Consequently rumour was managed by frank and open discussion of the epidemic, providing daily updates, fact sheets and press releases. Information was regularly disseminated to communities through mass media and press conferences. Thus all levels of the community spontaneously demonstrated solidarity and response to public health interventions. Even in areas of relative insecurity, rebel abductions diminished considerably.

O'nyong-nyong fever in south-central Uganda, 1996-1997: clinical features and validation of a clinical case definition for surveillance purposes.

O'nyong-nyong (ONN) fever, caused by infection with a mosquito-borne central African alphavirus, is an acute, nonfatal illness characterized by polyarthralgia. During 1996-1997, south-central Uganda experienced the second ONN fever epidemic ever recognized. Among 391 persons interviewed and sampled, 40 cases of confirmed and 21 of presumptive, well-characterized acute, recent, or previous ONN fever were identified through active case-finding efforts or during a household serosurvey and by the application of clinical and laboratory criteria. Among confirmed cases, the knees and ankles were the joints most commonly affected. The median duration of arthralgia was 6 days (range, 2-21 days) and of immobilization was 4 days (range, 1-14 days). In the majority, generalized skin rash was reported, and nearly half had lymphadenopathy, mainly of the cervical region. Viremia was documented in 16 cases, primarily during the first 3 days of illness, and in some of these, body temperature was normal. During this epidemic, the combination of fever, arthralgia, and lymphadenopathy had a specificity of 83% and a sensitivity of 61% in the identification of cases of ONN fever and thus could be useful for surveillance purposes.

O'nyong-nyong fever in south-central Uganda, 1996-1997: description of the epidemic and results of a household-based seroprevalence survey.

O'nyong-nyong (ONN) fever, an acute, nonfatal illness characterized by polyarthralgia, is caused by infection with a mosquito-borne central African alphavirus. During 1996-1997, south-central Uganda experienced the second ONN fever epidemic ever recognized. During January and early February 1997, active case-finding and a household cluster serosurvey were conducted in two affected and two comparison areas. A confirmed case was defined as an acute febrile illness with polyarthralgia occurring within the previous 9 months plus serologic confirmation or isolation of ONN virus from blood. In affected (n=129) and comparison (n=115) areas, the estimated infection rates were 45% and 3%, respectively, and the estimated attack rates were 29% and 0%, respectively, for an apparent:inapparent infection ratio of nearly 2 in affected areas. In villages sampled near Lake Kijanebalola, Rakai District, the estimated infection and attack rates were 68% and 41%, respectively, and 55% of sampled households had >/=1 case of ONN fever. In conclusion, this epidemic was focused near lakes and swamps, where it was associated with high infection and attack rates.