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.

Applying the One Health principles: a trans-sectoral coordination framework for preventing and responding to Rift Valley fever outbreaks.

Rift Valley fever (RVF) is a good example of a disease for which a One Health approach can significantly improve the management of outbreaks: RVF is a vector- borne zoonotic disease, its dynamics differ between eco-epidemiological patterns and are modulated by eco-climatic factors. Therefore, collaboration between sectors, disciplines and role players, as well as an understanding of the local epidemiology of the disease, are key prerequisites for proper risk assessment and outbreak control. These principles drove the Food and Agriculture Organization of the United Nations (FAO) and the World Health Organization (WHO) to develop an inter-sectoral strategic approach, with specific actions recommended for each of the four periods in the development of the outbreak (forecasting and preparedness, alert, epidemic control, post-epidemic). Through several outbreak response missions between 2006 and 2012 in various countries, an implementation framework was developed by WHO, FAO and the national authorities of affected countries and used to build national response action plans. The framework proposes a structured attribution of duty and responsibilities to committees made up of representatives of the various institutional and operational role players, and with clear mandates and terms of reference (TOR). Such an approach, ensuring real-time sharing of information, coherence in the various aspects of the response, and ownership of the strategy, has proven its efficiency. It could also be used, with appropriate adjustments in the TOR, for other zoonotic diseases.

Strategic approach to control of viral haemorrhagic fever outbreaks in the Eastern Mediterranean Region: report from a regional consultation.

The viral haemorrhagic fevers (VHF) are a growing public health threat in the Eastern Mediterranean Region. Nearly all of them are of zoonotic origin. VHF often cause outbreaks with high fatalities and, except for yellow fever, currently there are no specific treatment or vaccination options available. In response to this growing threat, the Regional Office for the Eastern Mediterranean of the World Health Organization convened a technical consultation in Tehran on 27-30 November 2011 to review the current gaps in prevention and control of VHF outbreaks in the Region. The meeting recommended a number of strategic public health approaches for prevention and control of VHF outbreaks through synergizing effective collaboration between the human and animal health sectors on areas that involve better preparedness, early detection and rapid response. Implementation of these approaches would require working together with vision, commitment and a sense of purpose involving partnerships and cooperation from all relevant sectors.

Strategic approach to control of viral haemorrhagic fever outbreaks in the Eastern Mediterranean Region: report from a regional consultation

The viral haemorrhagic fevers [VHF] are a growing public health threat in the Eastern Mediterranean Region. Nearly all of them are of zoonotic origin. VHF often cause outbreaks with high fatalities and, except for yellow fever, currently there are no specific treatment or vaccination options available. In response to this growing threat, the Regional Office for the Eastern Mediterranean of the World Health Organization convened a technical consultation in Tehran on 27-30 November 2011 to review the current gaps in prevention and control of VHF outbreaks in the Region. The meeting recommended a number of strategic public health approaches for prevention and control of VHF outbreaks through synergizing effective collaboration between the human and animal health sectors on areas that involve better preparedness, early detection and rapid response. Implementation of these approaches would require working together with vision, commitment and a sense of purpose involving partnerships and cooperation from all relevant sectors

Establishment of public health security in Saudi Arabia for the 2009 Hajj in response to pandemic influenza A H1N1.

Mass gatherings of people challenge public health capacities at host locations and the visitors' places of origin. Hajj--the yearly pilgrimage by Muslims to Saudi Arabia--is one of the largest, most culturally and geographically diverse mass gatherings in the world. With the 2009 pandemic influenza A H1N1 and upcoming Hajj, the Saudi Arabian Ministry of Health (MoH) convened a preparedness consultation in June, 2009. Consultants from global public health agencies met in their official capacities with their Saudi Arabian counterparts. The MoH aimed to pool and share public health knowledge about mass gatherings, and review the country's preparedness plans, focusing on the prevention and control of pandemic influenza. This process resulted in several practical recommendations, many to be put into practice before the start of Hajj and the rest during Hajj. These preparedness plans should ensure the optimum provision of health services for pilgrims to Saudi Arabia, and minimum disease transmission on their return home. Review of the implementation of these recommendations and their effect will not only inform future mass gatherings in Saudi Arabia, but will also strengthen preparedness efforts in other settings.

Risk factors for Nipah virus encephalitis in Bangladesh.

Nipah virus (NiV) is a paramyxovirus that causes severe encephalitis in humans. During January 2004, twelve patients with NiV encephalitis (NiVE) were identified in west-central Bangladesh. A case-control study was conducted to identify factors associated with NiV infection. NiVE patients from the outbreak were enrolled in a matched case-control study. Exact odds ratios (ORs) and 95% confidence intervals (CIs) were calculated by using a matched analysis. Climbing trees (83% of cases vs. 51% of controls, OR 8.2, 95% CI 1.25-infinity) and contact with another NiVE patient (67% of cases vs. 9% of controls, OR 21.4, 95% CI 2.78-966.1) were associated with infection. We did not identify an increased risk for NiV infection among persons who had contact with a potential intermediate host. Although we cannot rule out person-to-person transmission, case-patients were likely infected from contact with fruit bats or their secretions.

Clinical presentation of nipah virus infection in Bangladesh.

BACKGROUND: In Bangladesh, 4 outbreaks of Nipah virus infection were identified during the period 2001-2004. METHODS: We characterized the clinical features of Nipah virus-infected individuals affected by these outbreaks. We classified patients as having confirmed cases of Nipah virus infection if they had antibodies reactive with Nipah virus antigen. Patients were considered to have probable cases of Nipah virus infection if they had symptoms consistent with Nipah virus infection during the same time and in the same community as patients with confirmed cases. RESULTS: We identified 92 patients with Nipah virus infection, 67 (73%) of whom died. Although all age groups were affected, 2 outbreaks principally affected young persons (median age, 12 years); 62% of the affected persons were male. Fever, altered mental status, headache, cough, respiratory difficulty, vomiting, and convulsions were the most common signs and symptoms; clinical and radiographic features of acute respiratory distress syndrome of Nipah illness were identified during the fourth outbreak. Among those who died, death occurred a median of 6 days (range, 2-36 days) after the onset of illness. Patients who died were more likely than survivors to have a temperature >37.8 degrees C, altered mental status, difficulty breathing, and abnormal plantar reflexes. Among patients with Nipah virus infection who had well-defined exposure to another patient infected with Nipah virus, the median incubation period was 9 days (range, 6-11 days). CONCLUSIONS: Nipah virus infection produced rapidly progressive severe illness affecting the central nervous and respiratory systems. Clinical characteristics of Nipah virus infection in Bangladesh, including a severe respiratory component, appear distinct from clinical characteristics reported during earlier outbreaks in other countries.

[Emergent pathogens, international surveillance and international health regulations (2005)]. / Les pathogènes émergents, la veille internationale et le Règlement sanitaire international (2005).

In order to address the vitality of the microbial world, to detect emerging infectious diseases, to determine their potential threat to public health, and to establish effective interventions, the World Health Organization (WHO) has developed and coordinates the Global Outbreak Alert and Response Network (GOARN) which connects several surveillance networks. Some of these networks are specific to epidemic-prone diseases, such as influenza, dengue, yellow fever or meningitis. Others were especially designed to track unusual events--such as the emergence of SARS--that are naturally-occurring, accidental, or deliberately created (biological weapons, bio-terrorism). Lastly, a special effort is being made at the international level to modernize the International Health Regulations, now obsolete, and to support all the countries in the reinforcement of their outbreak alert and response capacity.

[Clinical management of patients and deceased during the Ebola outbreak from October to December 2003 in Republic of Congo]. / Prise en charge des malades et des défunts lors de l'epidémie de fièvre hémorragique due au virus Ebola d'octobre a décembre 2003 au Congo.

Outbreaks of Ebola virus hemorrhagic fever (EVHF) have been reported since 2001 in the Cuvette Ouest department, a forested area located in the Western North of Congo. At the end of October 2003 a new alarm came from this department which was quickly confirmed as being an epidemic of EVHF. The outbreak response was organized by the ministry of health with the assistance of an international team under the aegis of WHO. The case management of suspect cases was done in an isolation ward set up at the hospital; when patients refused to go to the ward for care they were isolated in their house according to a protocol "transmission risks reduction at home". Safe burials were performed by specialized teams which respected the major aspects of the funeral to allow the process of mourning of the families. An active surveillance system was set up in order to organize the detection of new cases and the follow-up of their contacts. A case definition was adopted. From October 11 to December 2, 2003, 35 cases including 29 deaths were reported, 16 cases were laboratory confirmed. The first four cases had been exposed to monkey meat (Cercopithecus nictitans). The epidemic spread was due to family transmission. The population interpretation of the disease, in particular questions around wizards and evil-minded persons, is a factor which must be taken into account by the medical teams during communication meetings for behavioral change of the populations. The case management of patient in isolation wards to prevent the transmission of the virus in the community remains the most effective means to dam up Ebola virus hemorrhagic fever outbreaks. The good perception by the community of the safe funerary procedures is an important aspect in the establishment of confidence relations with the local population.

Medical anthropology and Ebola in Congo: cultural models and humanistic care.

Seldom have medical anthropologists been involved in efforts to control high mortality diseases such as Ebola hemorrhagic fever (EHF) This paper describes the results of two distinct but complementary interventions during the first phases of an outbreak in the Republic of Congo in 2003. The first approach emphasized understanding local peoples cultural models and political-economic explanations for the disease while the second approach focused on providing more humanitarian care of patients by identifying and incorporating local beliefs and practices into patient care and response efforts.

[Multiple Ebola virus haemorrhagic fever outbreaks in Gabon, from October 2001 to April 2002]. / Plusieurs epidémies de fièvre hémorragique due au virus Ebola au Gabon, d'octobre 2001 a avril 2002.

Outbreaks of Ebola virus haemorrhagic fever have been reported from 1994 to 1996 in the province of Ogooué Ivindo, a forest zone situated in the Northeast of Gabon. Each time, the great primates had been identified as the initial source of human infection. End of November 2001 a new alert came from this province, rapidly confirmed as a EVHV outbreak. The response was given by the Ministry of Health with the help of an international team under the aegis of WHO. An active monitoring system was implemented in the three districts hit by the epidemic (Zadié, Ivindo and Mpassa) to organize the detection of cases and their follow-up. A case definition has been set up, the suspected cases were isolated at hospital, at home or in lazarets and serological tests were performed. These tests consisted of the detection of antigen or specific IgG and the RT-PCR. A classification of cases was made according to the results of biological tests, clinical and epidemiological data. The contact subjects were kept watch over for 21 days. 65 cases were recorded among which 53 deaths. The first human case, a hunter died on the 28th of October 2001. The epidemic spreads over through family transmission and nosocomial contamination. Four distinct primary foci have been identified together with an isolated case situated in the South East of Gabon, 580 km away from the epicenter. Deaths happened within a delay of 6 days. The last death has been recorded on the 22nd of March 2002 and the end of the outbreak was declared on the 6th of May 2002. The epidemic spreads over the Gabon just next. Unexplained deaths of animals had been mentionned in the nearby forests as soon as August 2001: great primates and cephalophus. Samples taken from their carcasses confirmed a concomitant animal epidemic.

[Isolated case of haemorrhagic fever observed in Gabon during the 2002 outbreak of Ebola but distant from epidemic zones]. / Cas isolé de fièvre hémorragique survenu au gabon en 2002 pendant l'epidémie d'ebola mais distant des régions epidémiques.

During the last outbreak of Ebola virus haemorrhagic fever that occurred concurrently in Gabon and Congo, several primary foci were identified in the Ogooue Ivindo province (Northeast Gabon), where previous outbreaks had occurred. A 48-year-old woman living in Franceville located 580 Km from the epicentre presented fever with haemorrhagic signs. She was evacuated to Libreville where Ebola infection was suspected. Diagnosis was confirmed at the Centre International de Recherches Médicales of Franceville on the basis of detection of specific antibodies. Symptoms had already subsided by the time diagnosis was documented. An epidemiological investigation was undertaken to identify the source of contamination and detect secondary cases. No human or nonhuman primate source of contamination could be formally identified. Direct contact with the virus reservoir could not be ruled out. No secondary cases were detected. The favourable outcome, absence of secondary, and failure to identify a source of contamination suggest that epidemiologically undefined cases may go unnoticed during and outside of outbreaks.

[Practical guidelines for the management of Ebola infected patients in the field]. / Recommandations pratiques pour la prise en charge sur le terrain des patients infectés par le virus Ebola.

Ebola hemorrhagic fever appears after an incubation of 3 days to 3 weeks. The first symptoms are fever accompanied by general and hemorrhagic signs leading to death in 50 to 90% of cases. During epidemics definition of cases permits prompt diagnosis. Due to the high risk of person-to-person and nosocomial transmission associated with Ebola hemorrhagic fever, management is based on isolation of patients and institution of protected care. Hands and soiled material are often decontaminated using sodium hypochlorite. Patient waste is decontaminated and incinerated. Treatment is essentially supportive. There is currently no vaccine available. Persons having been in close contact with patient should be kept under medical surveillance for 21 days. Recovering patients should use condoms for three months. Bodies of deceased patients should be handled by trained teams and buried quickly.

[Outbreak of Ebola hemorrhagic fever in the Republic of the Congo, 2003: a new strategy?]. / L'épidémie de fièvre hémorragique à virus Ebola en République du Congo, 2003: une nouvelle stratégie?

This article describes the last Ebola haemorrhagic fever (EHF) outbreak that occurred in the Cuvette Ouest Region of the Republic of Congo from January to April 2003. Epidemiological study demonstrated that the first patient, in whom diagnosis was made retrospectively, became ill on December 25, 2002. Subsequently until May 7, 2003, a total of 143 cases were recorded in the Mbomo and Kéllé health districts including 129 fatalities. Thirteen cases were laboratory confirmed and 130 were epidemiologically linked. Fifty-three percent of patients were male. Age ranged form 5 days to 80 years. Transmission involved direct contact with an infected person especially within families. Epidemiological data traced introduction of Ebola virus into the population to three primary cases mainly involving hunters. In all three cases development of the disease followed contact with non-human primates (gorillas) and other mammals (antelope) that had either been killed or found dead. Three health care workers were infected during the epidemic but nosocomial transmission played a minor role in the epidemic. On June 5, the Minister of Health and Population of the Congo Republic officially declared that the outbreak of EHF was over in the Cuvette Ouest Region. The last case was recorded on April 22 in the small village of Ndjoukou.

Human infection due to Ebola virus, subtype Côte d'Ivoire: clinical and biologic presentation.

In November 1994 after 15 years of epidemiologic silence, Ebola virus reemerged in Africa and, for the first time, in West Africa. In Côte d'Ivoire, a 34-year-old female ethologist was infected while conducting a necropsy on a wild chimpanzee. Eight days later, the patient developed a syndrome that did not respond to antimalarial drugs and was characterized by high fever, headache, chills, myalgia, and cough. The patient had abdominal pain, diarrhea, vomiting, and a macular rash, and was repatriated to Switzerland. The patient suffered from prostration and weight loss but recovered without sequelae. Laboratory findings included aspartate aminotransferase and alanine aminotransferase activity highly elevated, thrombocytopenia, lymphopenia, and, subsequently, neutrophilia. A new subtype of Ebola was isolated from the patient's blood on days 4 and 8. No serologic conversion was detected among contact persons in Côte d'Ivoire (n = 22) or Switzerland (n = 52), suggesting that infection-control precautions were satisfactory.

Histopathological and immunohistochemical studies of lesions associated with Ebola virus in a naturally infected chimpanzee.

Lesions caused by the Côte d'Ivoire subtype of Ebola virus in a naturally infected young chimpanzee were characterized by histopathological and immunohistochemical methods. The predominant lesions consisted of multifocal necrosis in the liver and diffuse fibrinoid necrosis in the red pulp of the spleen. In these sites, macrophages contained large eosinophilic intracytoplasmic inclusion bodies. Immunohistochemical staining indicated that macrophages were a major site of viral replication. The absence of bronchiolar and pulmonary lesions and the paucity of antigen-containing macrophages in the lung suggested that aerosol transmission by this animal was unlikely. There were necrotic foci and antigen-containing macrophages in intestinal lymph nodes, in association with lesions caused by intestinal parasites, suggesting the possibility of virus entry through the digestive tract.

Ebola virus outbreak among wild chimpanzees living in a rain forest of Côte d'Ivoire.

An outbreak of Ebola in nature is described for the first time. During a few weeks in November 1994, approximately 25% of 43 members of a wild chimpanzee community disappeared or were found dead in the Taï National Park, Côte d'Ivoire. A retrospective cohort study was done on the chimpanzee community. Laboratory procedures included histology, immunohistochemistry, bacteriology, and serology. Ebola-specific immunohistochemical staining was positive for autopsy tissue sections from 1 chimpanzee. Demographic, epidemiologic, and ecologic investigations were compatible with a point-source epidemic. Contact activities associated with a case (e.g., touching dead bodies or grooming) did not constitute significant risk factors, whereas consumption of meat did. The relative risk of meat consumption was 5.2 (95% confidence interval, 1.3-21.1). A similar outbreak occurred in November 1992 among the same community. A high mortality rate among apes tends to indicate that they are not the reservoir for the disease causing the illness. These points will have to be investigated by additional studies.