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.

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.

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.

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.

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.).

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).

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.

Tick-borne encephalitis among US travellers, 2010-20.

BACKGROUND: Tick-borne encephalitis (TBE) is an arboviral disease that is focally endemic in parts of Europe and Asia. TBE cases among US travellers are rare, with previous reports of only six cases among civilian travellers through 2009 and nine military-related cases through 2020. A TBE vaccine was licenced in the USA in August 2021. Understanding TBE epidemiology and risks among US travellers can help with the counselling of travellers going to TBE-endemic areas. METHODS: Diagnostic testing for TBE in the USA is typically performed at the Centers for Disease Control and Prevention (CDC) because no commercial testing is available. Diagnostic testing for TBE at CDC since 2010 was reviewed. For individuals with evidence of TBE virus infection, information was gathered on demographics, clinical presentations and risk factors for infection. RESULTS: From 2010-20, six patients with TBE were identified. Cases occurred among both paediatric and adult travellers and all were male. Patients were diagnosed with meningitis (n = 2) or encephalitis (n = 4); none died. Cases had travelled to various countries in Europe or Russia. Three cases reported visiting friends or relatives. Activities reported included hiking, camping, trail running, or working outdoors, and two cases had a recognized tick bite. CONCLUSIONS: TBE cases among US travellers are uncommon, with these six cases being the only known TBE cases among civilian travellers during this 11-year period. Nonetheless, given potential disease severity, pre-travel counselling for travellers to TBE-endemic areas should include information on measures to reduce the risk for TBE and other tick-borne diseases, including possible TBE vaccine use if a traveller's itinerary puts them at higher risk for infection. Clinicians should consider the diagnosis of TBE in a patient with a neurologic or febrile illness recently returned from a TBE-endemic country, particularly if a tick bite or possible tick exposure is reported.

Hantavirus Disease and COVID-19.

OBJECTIVES: Navajo Nation is disproportionately affected by hantavirus cardiopulmonary syndrome (HCPS), a severe respiratory disease that can quickly progress to respiratory failure and cardiogenic shock. The initial signs and symptoms of HCPS are indistinguishable from coronavirus disease 2019 (COVID-19). However, this distinction is critical, as the disease course differs greatly, with most patients with COVID-19 experiencing mild to moderate illness. We set out to determine if the evaluation of peripheral blood smears for five hematopathologic criteria previously identified as hallmarks of hantavirus infection, or "the hantavirus 5-point screen," could distinguish between COVID-19 and HCPS. METHODS: The hantavirus 5-point screen was performed on peripheral blood smears from 139 patients positive for COVID-19 seeking treatment from Tséhootsooí Medical Center and two Emory University hospitals. RESULTS: Of these 139 individuals, 136 (98%) received a score of 3/5 or below, indicating low suspicion for HCPS. While thrombocytopenia, one of the key signs of HCPS, was seen in the patients with COVID-19, it was generally mild and remained stable on repeat specimens collected 12 to 24 hours later. CONCLUSIONS: Given these findings, the 5-point screen remains a useful rapid screening tool for potential HCPS cases and may be useful to distinguish early HCPS from COVID-19 in HCPS endemic regions.

Successful Implementation of a Rapid Screening Tool for Hantavirus Cardiopulmonary Syndrome: 5 Years of Experience From a Community Hospital in an Endemic Region.

OBJECTIVES: Hantavirus is endemic in the Four Corners region of Arizona, Colorado, New Mexico, and Utah, and hantavirus cardiopulmonary syndrome (HCPS) disproportionately affects the Navajo Nation. We describe the application of a rapid screening tool for identification of HCPS. METHODS: A rapid screening tool for HCPS was implemented at Tséhootsooí Medical Center (TMC) in collaboration with academic partners. RESULTS: Since its implementation in 2016, 20 TMC staff members have been trained to perform this test, and 189 screens for HCPS have been reported. Although hantavirus infection is rare even in high-risk areas, use of this tool resulted in the identification of 4 acute cases of hantavirus infection. CONCLUSIONS: The results demonstrate the successful implementation of a 5-point screening tool for hantavirus infection in an endemic setting by a laboratory in a small community hospital.

Ebola virus disease nosocomial infections in the Democratic Republic of the Congo: a descriptive study of cases during the 2018-2020 outbreak.

OBJECTIVES: To describe the characteristics of nosocomial cases of Ebola virus disease (EVD) in the Democratic Republic of the Congo between July 2018 and May 2020 in order to inform future interventions. METHODS: Nosocomial cases of EVD were identified during outbreak response surveillance, and a retrospective analysis of cases was conducted according to demographic characteristics and type of health facility (HF). RESULTS: Of 3481 cases of EVD, 579 (16.6%) were nosocomial. Of these, 332 cases occurred in women (57.3%). Patients and visitors accounted for 419 cases (72.4%), of which 79 (18.9%) were aged 6-≤18 years and 108 (25.8%) were aged ≤5 years. Health workers (HWs) accounted for the remaining 160 (27.6%) nosocomial cases. The case fatality rate (CFR) for HWs (66/160, 41.3%) was significantly lower than the CFR for patients and visitors (292/419, 69.7%) (P<0.001). The CFR was higher among cases aged 6-≤18 years (54/79, 68.4%) and ≤5 years (89/108, 82.4%). Referral HFs (>39 beds) had the highest prevalence of nosocomial EVD (148/579, 25.6%). Among HFs with at least one case of nosocomial infection, 50.0% (98/196) were privately owned. CONCLUSIONS: Nurses and traditional healers should be targeted for infection prevention and control training, and supportive supervision should be provided to HFs to mitigate EVD transmission.

Development and implementation of the Ebola Exposure Window Calculator: A tool for Ebola virus disease outbreak field investigations.

During an Ebola virus disease (EVD) outbreak, calculating the exposure window of a confirmed case can assist field investigators in identifying the source of infection and establishing chains of transmission. However, field investigators often have difficulty calculating this window. We developed a bilingual (English/French), smartphone-based field application to assist field investigators in determining the exposure window of an EVD case. The calculator only requires the reported date of symptoms onset and the type of symptoms present at onset or the date of death. Prior to the release of this application, there was no similar electronic capability to enable consistent calculation of EVD exposure windows for field investigators. The Democratic Republic of the Congo Ministry of Health endorsed the application and incorporated it into trainings for field staff. Available for Apple and Android devices, the calculator continues to be downloaded even as the eastern DRC outbreak resolved. We rapidly developed and implemented a smartphone application to estimate the exposure window for EVD cases in an outbreak setting.

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.

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.

A Case of Lassa Fever Diagnosed at a Community Hospital-Minnesota 2014.

BACKGROUND: In April 2014, a 46-year-old returning traveler from Liberia was transported by emergency medical services to a community hospital in Minnesota with fever and altered mental status. Twenty-four hours later, he developed gingival bleeding. Blood samples tested positive for Lassa fever RNA by reverse transcriptase polymerase chain reaction. METHODS: Blood and urine samples were obtained from the patient and tested for evidence of Lassa fever virus infection. Hospital infection control personnel and health department personnel reviewed infection control practices with health care personnel. In addition to standard precautions, infection control measures were upgraded to include contact, droplet, and airborne precautions. State and federal public health officials conducted contract tracing activities among family contacts, health care personnel, and fellow airline travelers. RESULTS: The patient was discharged from the hospital after 14 days. However, his recovery was complicated by the development of near complete bilateral sensorineural hearing loss. Lassa virus RNA continued to be detected in his urine for several weeks after hospital discharge. State and federal public health authorities identified and monitored individuals who had contact with the patient while he was ill. No secondary cases of Lassa fever were identified among 75 contacts. CONCLUSIONS: Given the nonspecific presentation of viral hemorrhagic fevers, isolation of ill travelers and consistent implementation of basic infection control measures are key to preventing secondary transmission. When consistently applied, these measures can prevent secondary transmission even if travel history information is not obtained, not immediately available, or the diagnosis of a viral hemorrhagic fever is delayed.