Chapare Hemorrhagic Fever and Virus Detection in Rodents in Bolivia in 2019.

BACKGROUND: In June 2019, the Bolivian Ministry of Health reported a cluster of cases of hemorrhagic fever that started in the municipality of Caranavi and expanded to La Paz. The cause of these cases was unknown. METHODS: We obtained samples for next-generation sequencing and virus isolation. Human and rodent specimens were tested by means of virus-specific real-time quantitative reverse-transcriptase-polymerase-chain-reaction assays, next-generation sequencing, and virus isolation. RESULTS: Nine cases of hemorrhagic fever were identified; four of the patients with this illness died. The etiologic agent was identified as Mammarenavirus Chapare mammarenavirus, or Chapare virus (CHAPV), which causes Chapare hemorrhagic fever (CHHF). Probable nosocomial transmission among health care workers was identified. Some patients with CHHF had neurologic manifestations, and those who survived had a prolonged recovery period. CHAPV RNA was detected in a variety of human body fluids (including blood; urine; nasopharyngeal, oropharyngeal, and bronchoalveolar-lavage fluid; conjunctiva; and semen) and in specimens obtained from captured small-eared pygmy rice rats (Oligoryzomys microtis). In survivors of CHHF, viral RNA was detected up to 170 days after symptom onset; CHAPV was isolated from a semen sample obtained 86 days after symptom onset. CONCLUSIONS: M. Chapare mammarenavirus was identified as the etiologic agent of CHHF. Both spillover from a zoonotic reservoir and possible person-to-person transmission were identified. This virus was detected in a rodent species, O. microtis. (Funded by the Bolivian Ministry of Health and others.).

A public, cross-reactive glycoprotein epitope confounds Ebola virus serology.

Ebola disease (EBOD) in humans is a severe disease caused by at least four related viruses in the genus Orthoebolavirus, most often by the eponymous Ebola virus. Due to human-to-human transmission and incomplete success in treating cases despite promising therapeutic development, EBOD is a high priority in public health research. Yet despite almost 50 years since EBOD was first described, the sources of these viruses remain undefined and much remains to be understood about the disease epidemiology and virus emergence and spread. One important approach to improve our understanding is detection of antibodies that can reveal past human infections. However, serosurveys routinely describe seroprevalences that imply infection rates much higher than those clinically observed. Proposed hypotheses to explain this difference include existence of common but less pathogenic strains or relatives of these viruses, misidentification of EBOD as something else, and a higher proportion of subclinical infections than currently appreciated. The work presented here maps B-cell epitopes in the spike protein of Ebola virus and describes a single epitope that is cross-reactive with an antigen seemingly unrelated to orthoebolaviruses. Antibodies against this epitope appear to explain most of the unexpected reactivity towards the spike, arguing against common but unidentified infections in the population. Importantly, antibodies of cross-reactive donors from within and outside the known EBOD geographic range bound the same epitope. In light of this finding, it is plausible that epitope mapping enables broadly applicable specificity improvements in the field of serology.

Use of Ebola Vaccines - Worldwide, 2021-2023.

Ebola virus disease (Ebola) is a rare but severe illness in humans, with an average case fatality rate of approximately 50%. Two licensed vaccines are currently available against Orthoebolavirus zairense, the virus that causes Ebola: the 1-dose rVSVΔG-ZEBOV-GP (ERVEBO [Merck]) and the 2-dose regimen of Ad26.ZEBOV and MVA-BN-Filo (Zabdeno/Mvabea [Johnson & Johnson]). The Strategic Advisory Group of Experts on Immunization recommends the use of 1-dose ERVEBO during Ebola outbreaks, and in 2021, a global stockpile of ERVEBO was established to ensure equitable, timely, and targeted access to vaccine doses for future Ebola outbreaks. This report describes the use of Ebola vaccines and the role of the stockpile developed and managed by the International Coordinating Group (ICG) on Vaccine Provision during 2021-2023. A total of 145,690 doses have been shipped from the ICG stockpile since 2021. However, because outbreaks since 2021 have been limited and rapidly contained, most doses (139,120; 95%) shipped from the ICG stockpile have been repurposed for preventive vaccination of high-risk groups, compared with 6,570 (5%) used for outbreak response. Repurposing doses for preventive vaccination could be prioritized in the absence of Ebola outbreaks to prevent transmission and maximize the cost-efficiency and benefits of the stockpile.

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.

Detection of Hantavirus during the COVID-19 Pandemic, Arizona, USA, 2020.

We identified 2 fatal cases of persons infected with hantavirus in Arizona, USA, 2020; 1 person was co-infected with SARS-CoV-2. Delayed identification of the cause of death led to a public health investigation that lasted ≈9 months after their deaths, which complicated the identification of a vector or exposure.

Postmortem Surveillance for Ebola Virus Using OraQuick Ebola Rapid Diagnostic Tests, Eastern Democratic Republic of the Congo, 2019-2020.

After a pilot study, we tested 443 cadavers using OraQuick Ebola rapid diagnostic tests during surveillance after the 10th Ebola outbreak in the Democratic Republic of the Congo. No false negative and 2% false-positive results were reported. Quickly returning results and engaging the community enabled timely public health actions.

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.

Use of Ebola Vaccine: Expansion of Recommendations of the Advisory Committee on Immunization Practices To Include Two Additional Populations - United States, 2021.

On December 19, 2019, the Food and Drug Administration (FDA) approved rVSVΔG-ZEBOV-GP Ebola vaccine (ERVEBO, Merck) for the prevention of Ebola virus disease (EVD) caused by infection with Ebola virus, species Zaire ebolavirus, in adults aged ≥18 years. In February 2020, the Advisory Committee on Immunization Practices (ACIP) recommended preexposure vaccination with ERVEBO for adults aged ≥18 years in the United States who are at highest risk for potential occupational exposure to Ebola virus 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 members at biosafety level 4 facilities in the United States (1).

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.

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.

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.

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.

Implementation of a National Semen Testing and Counseling Program for Male Ebola Survivors - Liberia, 2015-2016.

According to World Health Organization (WHO) data, the Ebola virus disease (Ebola) outbreak that began in West Africa in 2014 has resulted in 28,603 cases and 11,301 deaths (1). In March 2015, epidemiologic investigation and genetic sequencing in Liberia implicated sexual transmission from a male Ebola survivor, with Ebola virus detected by reverse transcription-polymerase chain reaction (RT-PCR) 199 days after symptom onset (2,3), far exceeding the 101 days reported from an earlier Ebola outbreak (4). In response, WHO released interim guidelines recommending that all male survivors, in addition to receiving condoms and sexual risk reduction counseling at discharge from an Ebola treatment unit (ETU), be offered semen testing for Ebola virus RNA by RT-PCR 3 months after disease onset, and every month thereafter until two consecutive semen specimens collected at least 1 week apart test negative for Ebola virus RNA (5). Male Ebola survivors should also receive counseling to promote safe sexual practices until their semen twice tests negative. When these recommendations were released, testing of semen was not widely available in Liberia. Challenges in establishing and operating the first nationwide semen testing and counseling program for male Ebola survivors included securing sufficient resources for the program, managing a public health semen testing program in the context of ongoing research studies that were also collecting and screening semen, identification of adequate numbers of trained counselors and appropriate health communication messages for the program, overcoming Ebola survivor-associated stigma, identification and recruitment of male Ebola survivors, and operation of mobile teams.

Live Animal Markets in Minnesota: A Potential Source for Emergence of Novel Influenza A Viruses and Interspecies Transmission.

BACKGROUND: Live animal markets have been implicated in transmission of influenza A viruses (IAVs) from animals to people. We sought to characterize IAVs at 2 live animal markets in Minnesota to assess potential routes of occupational exposure and risk for interspecies transmission. METHODS: We implemented surveillance for IAVs among employees, swine, and environment (air and surfaces) during a 12-week period (October 2012-January 2013) at 2 markets epidemiologically associated with persons with swine-origin IAV (variant) infections. Real-time reverse transcription polymerase chain reaction (rRT-PCR), viral culture, and whole-genome sequencing were performed on respiratory and environmental specimens, and serology on sera from employees at beginning and end of surveillance. RESULTS: Nasal swabs from 11 of 17 (65%) employees tested positive for IAVs by rRT-PCR; 7 employees tested positive on multiple occasions and 1 employee reported influenza-like illness. Eleven of 15 (73%) employees had baseline hemagglutination inhibition antibody titers ≥40 to swine-origin IAVs, but only 1 demonstrated a 4-fold titer increase to both swine-origin and pandemic A/Mexico/4108/2009 IAVs. IAVs were isolated from swine (72/84), air (30/45), and pen railings (5/21). Whole-genome sequencing of 122 IAVs isolated from swine and environmental specimens revealed multiple strains and subtype codetections. Multiple gene segment exchanges among and within subtypes were observed, resulting in new genetic constellations and reassortant viruses. Genetic sequence similarities of 99%-100% among IAVs of 1 market customer and swine indicated interspecies transmission. CONCLUSIONS: At markets where swine and persons are in close contact, swine-origin IAVs are prevalent and potentially provide conditions for novel IAV emergence.

Notes from the field: multistate outbreak of listeriosis linked to soft-ripened cheese--United States, 2013.

On June 27, 2013, the Minnesota Department of Health notified CDC of two patients with invasive Listeria monocytogenes infections (listeriosis) whose clinical isolates had indistinguishable pulsed-field gel electrophoresis (PFGE) patterns. A query of PulseNet, the national molecular subtyping network for foodborne disease surveillance, identified clinical and environmental isolates from other states. On June 28, CDC learned from the Food and Drug Administration's Coordinated Outbreak Response and Evaluation Network that environmental isolates indistinguishable from those of the two patients had been collected from Crave Brothers Farmstead Cheese during 2010-2011. An outbreak-related case was defined as isolation of L. monocytogenes with the outbreak PFGE pattern from an anatomic site that is normally sterile (e.g., blood or cerebrospinal fluid), or from a product of conception, with an isolate upload date during May 20-June 28, 2013. As of June 28, five cases were identified in four states (Minnesota, two cases; Illinois, Indiana, and Ohio, one each). Median age of the five patients was 58 years (range: 31-67 years). Four patients were female, including one who was pregnant at the time of infection. All five were hospitalized. One death and one miscarriage were reported.

Recombinant Sudan virus and evaluation of humoral cross-reactivity between Ebola and Sudan virus glycoproteins after infection or rVSV-ΔG-ZEBOV-GP vaccination.

Ebola disease outbreaks are major public health events because of human-to-human transmission and high mortality. These outbreaks are most often caused by Ebola virus, but at least three related viruses can also cause the disease. In 2022, Sudan virus re-emerged causing more than 160 confirmed and probable cases. This report describes generation of a recombinant Sudan virus and demonstrates its utility by quantifying antibody cross-reactivity between Ebola and Sudan virus glycoproteins after human infection or vaccination with a licensed Ebola virus vaccine.