Risk Factors for Ebola Virus Persistence in Semen of Survivors in Liberia.

BACKGROUND: Long-term persistence of Ebola virus (EBOV) in immunologically privileged sites has been implicated in recent outbreaks of Ebola virus disease (EVD) in Guinea and the Democratic Republic of Congo. This study was designed to understand how the acute course of EVD, convalescence, and host immune and genetic factors may play a role in prolonged viral persistence in semen. METHODS: A cohort of 131 male EVD survivors in Liberia were enrolled in a case-case study. "Early clearers" were defined as those with 2 consecutive negative EBOV semen test results by real-time reverse-transcription polymerase chain reaction (rRT-PCR) ≥2 weeks apart within 1 year after discharge from the Ebola treatment unit or acute EVD. "Late clearers" had detectable EBOV RNA by rRT-PCR >1 year after discharge from the Ebola treatment unit or acute EVD. Retrospective histories of their EVD clinical course were collected by questionnaire, followed by complete physical examinations and blood work. RESULTS: Compared with early clearers, late clearers were older (median, 42.5 years; P < .001) and experienced fewer severe clinical symptoms (median 2, P = .006). Late clearers had more lens opacifications (odds ratio, 3.9 [95% confidence interval, 1.1-13.3]; P = .03), after accounting for age, higher total serum immunoglobulin G3 (IgG3) titers (P = .005), and increased expression of the HLA-C*03:04 allele (0.14 [.02-.70]; P = .007). CONCLUSIONS: Older age, decreased illness severity, elevated total serum IgG3 and HLA-C*03:04 allele expression may be risk factors for the persistence of EBOV in the semen of EVD survivors. EBOV persistence in semen may also be associated with its persistence in other immunologically protected sites, such as the eye.

Pathology and Pathogenesis of Lassa Fever: Novel Immunohistochemical Findings in Fatal Cases and Clinico-pathologic Correlation.

BACKGROUND: Lassa fever is a zoonotic, acute viral illness first identified in Nigeria in 1969. An estimate shows that the "at risk" seronegative population (in Sierra Leone, Guinea, and Nigeria) may be as high as 59 million, with an annual incidence of all illnesses of 3 million, and fatalities up to 67 000, demonstrating the serious impact of the disease on the region and global health. METHODS: Histopathologic evaluation, immunohistochemical assay, and electron microscopic examination were performed on postmortem tissue samples from 12 confirmed Lassa fever cases. RESULTS: Lassa fever virus antigens and viral particles were observed in multiple organ systems and cells, including cells in the mononuclear phagocytic system and other specialized cells where it had not been described previously. CONCLUSIONS: The immunolocalization of Lassa fever virus antigens in fatal cases provides novel insightful information with clinical and pathogenetic implications. The extensive involvement of the mononuclear phagocytic system, including tissue macrophages and endothelial cells, suggests participation of inflammatory mediators from this lineage with the resulting vascular dilatation and increasing permeability. Other findings indicate the pathogenesis of Lassa fever is multifactorial and additional studies are needed.

Use of Ebola Vaccine: Recommendations of the Advisory Committee on Immunization Practices, United States, 2020.

This report summarizes the recommendations of the Advisory Committee on Immunization Practices (ACIP) for use of the rVSVΔG-ZEBOV-GP Ebola vaccine (Ervebo) in the United States. The vaccine contains rice-derived recombinant human serum albumin and live attenuated recombinant vesicular stomatitis virus (VSV) in which the gene encoding the glycoprotein of VSV was replaced with the gene encoding the glycoprotein of Ebola virus species Zaire ebolavirus. Persons with a history of severe allergic reaction (e.g., anaphylaxis) to rice protein should not receive Ervebo. This is the first and only vaccine currently licensed by the Food and Drug Administration for the prevention of Ebola virus disease (EVD). These guidelines will be updated based on availability of new data or as new vaccines are licensed to protect against EVD.ACIP recommends preexposure vaccination with Ervebo for adults aged ≥18 years in the U.S. population who are at highest risk for potential occupational exposure to Ebola virus species Zaire ebolavirus because they are responding to an outbreak of EVD, work as health care personnel at federally designated Ebola treatment centers in the United States, or work as laboratorians or other staff at biosafety level 4 facilities in the United States. Recommendations for use of Ervebo in additional populations at risk for exposure and other settings will be considered and discussed by ACIP in the future.

Characteristics of Ebola Virus Disease Survivor Blood and Semen in Liberia: Serology and Reverse Transcription Polymerase Chain Reaction (RT-PCR).

INTRODUCTION: Ebola virus (EBOV), species Zaire ebolavirus, may persist in the semen of male survivors of Ebola virus disease (EVD). We conducted a study of male survivors of the 2014-2016 EVD outbreak in Liberia and evaluated their immune responses to EBOV. We report here findings from the serologic testing of blood for EBOV-specific antibodies, molecular testing for EBOV in blood and semen, and serologic testing of peripheral blood mononuclear cells (PBMCs) in a subset of study participants. METHODS: We tested for EBOV RNA in blood by quantitative reverse transcription polymerase chain reaction (qRT-PCR), and for anti-EBOV-specific immunoglobulin M (IgM) and immunoglobulin G (IgG) antibodies by enzyme-linked immunosorbent assay (ELISA) for 126 study participants. We performed PBMC analysis on a subgroup of 26 IgG-negative participants. RESULTS: All 126 participants tested negative for EBOV RNA in blood by qRT-PCR. The blood of 26 participants tested negative for EBOV-specific IgG antibodies by ELISA. PBMCs were collected from 23/26 EBOV IgG-negative participants. Of these, 1/23 participants had PBMCs that produced anti-EBOV-specific IgG antibodies upon stimulation with EBOV-specific glycoprotein (GP) and nucleoprotein (NP) antigens. CONCLUSIONS: The blood of EVD survivors, collected when they did not have symptoms meeting the case definition for acute or relapsed EVD, is unlikely to pose a risk for EBOV transmission. We identified 1 IgM/IgG negative participant who had PBMCs that produced anti-EBOV-specific antibodies upon stimulation. Immunogenicity following acute EBOV infection may exist along a spectrum, and absence of antibody response should not be exclusionary in determining an individual's status as a survivor of EVD.

Seoul Virus Infection and Spread in United States Home-Based Ratteries: Rat and Human Testing Results From a Multistate Outbreak Investigation.

BACKGROUND: During 2017, a multistate outbreak investigation occurred after the confirmation of Seoul virus (SEOV) infections in people and pet rats. A total of 147 humans and 897 rats were tested. METHODS: In addition to immunoglobulin (Ig)G and IgM serology and traditional reverse-transcription polymerase chain reaction (RT-PCR), novel quantitative RT-PCR primers/probe were developed, and whole genome sequencing was performed. RESULTS: Seventeen people had SEOV IgM, indicating recent infection; 7 reported symptoms and 3 were hospitalized. All patients recovered. Thirty-one facilities in 11 US states had SEOV infection, and among those with ≥10 rats tested, rat IgG prevalence ranged 2%-70% and SEOV RT-PCR positivity ranged 0%-70%. Human laboratory-confirmed cases were significantly associated with rat IgG positivity and RT-PCR positivity (P = .03 and P = .006, respectively). Genomic sequencing identified >99.5% homology between SEOV sequences in this outbreak, and these were >99% identical to SEOV associated with previous pet rat infections in England, the Netherlands, and France. Frequent trade of rats between home-based ratteries contributed to transmission of SEOV between facilities. CONCLUSIONS: Pet rat owners, breeders, and the healthcare and public health community should be aware and take steps to prevent SEOV transmission in pet rats and to humans. Biosecurity measures and diagnostic testing can prevent further infections.

A retrospective cohort investigation of seroprevalence of Marburg virus and ebolaviruses in two different ecological zones in Uganda.

BACKGROUND: Uganda has experienced seven Ebola Virus Disease (EVD) outbreaks and four Marburg Virus Disease (MVD) outbreaks between 2000 and 2019. We investigated the seroprevalence and risk factors for Marburg virus and ebolaviruses in gold mining communities around Kitaka gold mine in Western Uganda and compared them to non-mining communities in Central Uganda. METHODS: A questionnaire was administered and human blood samples were collected from three exposure groups in Western Uganda (gold miners, household members of miners, non-miners living within 50 km of Kitaka mine). The unexposed controls group sampled was community members in Central Uganda far away from any gold mining activity which we considered as low-risk for filovirus infection. ELISA serology was used to analyse samples, detecting IgG antibodies against Marburg virus and ebolaviruses (filoviruses). Data were analysed in STATA software using risk ratios and odds ratios. RESULTS: Miners in western Uganda were 5.4 times more likely to be filovirus seropositive compared to the control group in central Uganda (RR = 5.4; 95% CI 1.5-19.7) whereas people living in high-risk areas in Ibanda and Kamwenge districts were 3.6 more likely to be seropositive compared to control group in Luweeero district (RR = 3.6; 95% CI 1.1-12.2). Among all participants, filovirus seropositivity was 2.6% (19/724) of which 2.3% (17/724) were reactive to Sudan virus only and 0.1% (1/724) to Marburg virus. One individual seropositive for Sudan virus also had IgG antibodies reactive to Bundibugyo virus. The risk factors for filovirus seropositivity identified included mining (AOR = 3.4; 95% CI 1.3-8.5), male sex (AOR = 3.1; 95% CI 1.01-9.5), going inside mines (AOR = 3.1; 95% CI 1.2-8.2), cleaning corpses (AOR = 3.1; 95% CI 1.04-9.1) and contact with suspect filovirus cases (AOR = 3.9, 95% CI 1.04-14.5). CONCLUSIONS: These findings indicate that filovirus outbreaks may go undetected in Uganda and people involved in artisan gold mining are more likely to be exposed to infection with either Marburg virus or ebolaviruses, likely due to increased risk of exposure to bats. This calls for active surveillance in known high-risk areas for early detection and response to prevent filovirus epidemics.

Lassa Fever in Travelers from West Africa, 1969-2016.

Lassa virus is a rodentborne arenavirus responsible for human cases of Lassa fever, a viral hemorrhagic fever, in West Africa and in travelers arriving to non-Lassa-endemic countries from West Africa. We describe a retrospective review performed through literature search of clinical and epidemiologic characteristics of all imported Lassa fever cases worldwide during 1969-2016. Our findings demonstrate that approximately half of imported cases had distinctive clinical features (defined as fever and >1 of the following: pharyngitis, sore throat, tonsillitis, conjunctivitis, oropharyngeal ulcers, or proteinuria). Delays in clinical suspicion of this diagnosis were common. In addition, no secondary transmission of Lassa fever to contacts of patients with low-risk exposures occurred, and infection of high-risk contacts was rare. Future public health investigations of such cases should focus on timely recognition of distinctive clinical features, earlier treatment of patients, and targeted public health responses focused on high-risk contacts.

New Lineage of Lassa Virus, Togo, 2016.

We describe a strain of Lassa virus representing a putative new lineage that was isolated from a cluster of human infections with an epidemiologic link to Togo. This finding extends the known range of Lassa virus to Togo.

Clinical Management of Ebola Virus Disease Patients in Low-Resource Settings.

The low-resource environment deprives healthcare providers caring for patients with Ebola virus disease (EVD) of many of the means employed for the critically ill that are available in better resourced settings, such as advanced therapeutic interventions and abundant staff. In addition to these limitations may be added those imposed by the remote tropical locations, where EVD outbreaks occur. In this setting, a safe environment is created where healthcare workers may care for their patients over the evolving course of their acute illness into their convalescent period. Clinical management of EVD combines supportive and symptomatic care while also addressing the patient's emotional and mental health needs. A variety of specific therapies directly targeting the virus has become available, but none of these has, as of yet, conclusively demonstrated an impact. Healthcare workers caring for EVD patients must be constantly aware that they are part of a larger epidemic control operation, and their actions have consequences that go beyond their patients to their families and the community affected by the outbreak.

Ebola Virus Disease in Pregnancy: Clinical, Histopathologic, and Immunohistochemical Findings.

Here we describe clinicopathologic features of Ebola virus disease in pregnancy. One woman infected with Sudan virus in Gulu, Uganda, in 2000 had a stillbirth and survived, and another woman infected with Bundibugyo virus had a live birth with maternal and infant death in Isiro, the Democratic Republic of the Congo in 2012. Ebolavirus antigen was seen in the syncytiotrophoblast and placental maternal mononuclear cells by immunohistochemical analysis, and no antigen was seen in fetal placental stromal cells or fetal organs. In the Gulu case, ebolavirus antigen localized to malarial parasite pigment-laden macrophages. These data suggest that trophoblast infection may be a mechanism of transplacental ebolavirus transmission.

Favipiravir and Ribavirin Treatment of Epidemiologically Linked Cases of Lassa Fever.

Two patients with Lassa fever are described who are the first human cases treated with a combination of ribavirin and favipiravir. Both patients survived but developed transaminitis and had prolonged detectable virus RNA in blood and semen, suggesting that the possibility of sexual transmission of Lassa virus should be considered.

Seoul Virus Infection in Humans, France, 2014-2016.

We report detection of Seoul virus in 3 patients in France over a 2-year period. These patients accounted for 3 of the 4 Seoul virus infections among 434 hantavirus infections (1.7%) reported during this time. More attention should be given to this virus in Europe where surveillance has been focused mostly on Puumala and Dobrava-Belgrade hantaviruses.

Isolated Case of Marburg Virus Disease, Kampala, Uganda, 2014.

In September 2014, a single fatal case of Marburg virus was identified in a healthcare worker in Kampala, Uganda. The source of infection was not identified, and no secondary cases were identified. We describe the rapid identification, laboratory diagnosis, and case investigation of the third Marburg virus outbreak in Uganda.

Exposure Characteristics of Hantavirus Pulmonary Syndrome Patients, United States, 1993-2015.

Those at highest risk are persons in occupations with potential for rodent exposure and American Indian women 40--64 years of age.

Ebola Virus RNA in Semen from an HIV-Positive Survivor of Ebola.

Ebola virus is known to persist in semen of male survivors of Ebola virus disease (EVD). However, maximum duration of, or risk factors for, virus persistence are unknown. We report an EVD survivor with preexisting HIV infection, whose semen was positive for Ebola virus RNA 565 days after recovery from EVD.

High clinical suspicion of donor-derived disease leads to timely recognition and early intervention to treat solid organ transplant-transmitted lymphocytic choriomeningitis virus.

Despite careful donor screening, unexpected donor-derived infections continue to occur in organ transplant recipients (OTRs). Lymphocytic choriomeningitis virus (LCMV) is one such transplant-transmitted infection that in previous reports has resulted in a high mortality among the affected OTRs. We report a LCMV case cluster that occurred 3 weeks post-transplant in three OTRs who received allografts from a common organ donor in March 2013. Following confirmation of LCMV infection at Centers for Disease Control and Prevention, immunosuppression was promptly reduced and ribavirin and/or intravenous immunoglobulin therapy were initiated in OTRs. The liver recipient died, but right kidney recipients survived without significant sequelae and left kidney recipient survived acute LCMV infection with residual mental status deficit. Our series highlights how early recognition led to prompt therapeutic intervention, which may have contributed to more favorable outcome in the kidney transplant recipients.

Addressing Infection Prevention and Control in the First U.S. Community Hospital to Care for Patients With Ebola Virus Disease: Context for National Recommendations and Future Strategies.

Health care personnel (HCP) caring for patients with Ebola virus disease (EVD) are at increased risk for infection with the virus. In 2014, a Texas hospital became the first U.S. community hospital to care for a patient with EVD; 2 nurses were infected while providing care. This article describes infection control measures developed to strengthen the hospital's capacity to safely diagnose and treat patients with EVD. After admission of the first patient with EVD, a multidisciplinary team from the Centers for Disease Control and Prevention (CDC) joined the hospital's infection preventionists to implement a system of occupational safety and health controls for direct patient care, handling of clinical specimens, and managing regulated medical waste. Existing engineering and administrative controls were strengthened. The personal protective equipment (PPE) ensemble was standardized, HCP were trained on donning and doffing PPE, and a system of trained observers supervising PPE donning and doffing was implemented. Caring for patients with EVD placed substantial demands on a community hospital. The experiences of the authors and others informed national policies for the care of patients with EVD and protection of HCP, including new guidance for PPE, a rapid system for deploying CDC staff to assist hospitals ("Ebola Response Team"), and a framework for a tiered approach to hospital preparedness. The designation of regional Ebola treatment centers and the establishment of the National Ebola Training and Education Center address the need for HCP to be prepared to safely care for patients with EVD and other high-consequence emerging infectious diseases.

The Epi Info Viral Hemorrhagic Fever (VHF) Application: A Resource for Outbreak Data Management and Contact Tracing in the 2014-2016 West Africa Ebola Epidemic.

The Epi Info Viral Hemorrhagic Fever application (Epi Info VHF) was developed in response to challenges managing outbreak data during four 2012 filovirus outbreaks. Development goals included combining case and contact data in a relational database, facilitating data-driven contact tracing, and improving outbreak data consistency and use. The application was first deployed in Guinea, when the West Africa Ebola epidemic was detected, in March 2014, and has been used in 7 African countries and 2 US states. Epi Info VHF enabled reporting of compatible data from multiple countries, contributing to international Ebola knowledge. However, challenges were encountered in accommodating the epidemic's unexpectedly large magnitude, addressing country-specific needs within 1 software product, and using the application in settings with limited Internet access and information technology support. Use of Epi Info VHF in the West Africa Ebola epidemic highlighted the fundamental importance of good data management for effective outbreak response, regardless of the software used.

Resurgence of Ebola Virus Disease in Guinea Linked to a Survivor With Virus Persistence in Seminal Fluid for More Than 500 Days.

We report on an Ebola virus disease (EVD) survivor who showed Ebola virus in seminal fluid 531 days after onset of disease. The persisting virus was sexually transmitted in February 2016, about 470 days after onset of symptoms, and caused a new cluster of EVD in Guinea and Liberia.

Perspectives on West Africa Ebola Virus Disease Outbreak, 2013-2016.

The variety of factors that contributed to the initial undetected spread of Ebola virus disease in West Africa during 2013-2016 and the difficulty controlling the outbreak once the etiology was identified highlight priorities for disease prevention, detection, and response. These factors include occurrence in a region recovering from civil instability and lacking experience with Ebola response; inadequate surveillance, recognition of suspected cases, and Ebola diagnosis; mobile populations and extensive urban transmission; and the community's insufficient general understanding about the disease. The magnitude of the outbreak was not attributable to a substantial change of the virus. Continued efforts during the outbreak and in preparation for future outbreak response should involve identifying the reservoir, improving in-country detection and response capacity, conducting survivor studies and supporting survivors, engaging in culturally appropriate public education and risk communication, building productive interagency relationships, and continuing support for basic research.