Last data update: Apr 18, 2025. (Total: 49119 publications since 2009)
Records 1-30 (of 117 Records) |
Query Trace: Rollin D[original query] |
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Revisiting the minimum incubation period of Zaire ebolavirus
Kofman AD , Haberling DL , Mbuyi G , Martel LD , Whitesell AN , Van Herp M , Makaya G , Corvil S , Abedi AA , Ngoma PM , Mbuyi F , Mossoko M , Koivogui E , Soke N , Gbamou N , Fonjungo PN , Keita L , Keita S , Shoemaker TR , Richards GA , Montgomery JM , Breman JG , Geisbert TW , Choi MJ , Rollin PE . Lancet Infect Dis 2023 23 (10) 1111-1112 Ebola virus disease (EVD) caused by Ebola virus species Zaire ebolavirus (EBOV) is a major global health challenge causing sporadic outbreaks with high mortality. The minimum incubation period of EBOV, or the time from infection with the virus to the development of first symptoms, is thought to be 2 days and was initially established during the first EVD investigation in 1976.1 A published observation from the investigation noted that, “in one case of the disease, the only possible source of infection was contact with a probable case 48 hours before the latter developed symptoms”, and this observation was restated in another publication.2, 3 However, concluding that the minimum incubation period for EBOV is 2 days based on these reports is flawed for several reasons. First, the presumed source of the infection was a probable case of EVD and was not laboratory-confirmed; it is therefore uncertain whether the source truly had EVD. Second, since the report describes the contact between the source and the case occurring before the source developed symptoms, this implies asymptomatic transmission, which has been established to not occur with EBOV.4, 5, 6 Finally, the report's description of 48 h refers to the time between the case's contact with the alleged source and the source's onset of symptoms, which is itself not an incubation period. |
New Lineage of Lassa Virus, Togo, 2016.
Whitmer SLM , Strecker T , Cadar D , Dienes HP , Faber K , Patel K , Brown SM , Davis WG , Klena JD , Rollin PE , Schmidt-Chanasit J , Fichet-Calvet E , Noack B , Emmerich P , Rieger T , Wolff S , Fehling SK , Eickmann M , Mengel JP , Schultze T , Hain T , Ampofo W , Bonney K , Aryeequaye JND , Ribner B , Varkey JB , Mehta AK , Lyon GM 3rd , Kann G , De Leuw P , Schuettfort G , Stephan C , Wieland U , Fries JWU , Kochanek M , Kraft CS , Wolf T , Nichol ST , Becker S , Ströher U , Günther S . Emerg Infect Dis 2018 24 (3) 599-602 ![]() ![]() 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. |
Risk Factors for Ebola Virus Persistence in Semen of Survivors - Liberia.
Dyal J , Kofman A , Kollie JZ , Fankhauser J , Orone R , Soka MJ , Glaybo U , Kiawu A , Freeman E , Giah G , Tony HD , Faikai M , Jawara M , Kamara K , Kamara S , Flowers B , Kromah ML , Desamu-Thorpe R , Graziano J , Brown S , Morales-Betoulle ME , Cannon DL , Su K , Linderman SL , Plucinski M , Rogier E , Bradbury RS , Secor WE , Bowden KE , Phillips C , Carrington MN , Park YH , Martin MP , Del Pilar Aguinaga M , Mushi R , Haberling DL , Ervin ED , Klena JD , Massaquoi M , Nyenswah T , Nichol ST , Chiriboga DE , Williams DE , Hinrichs SH , Ahmed R , Vonhm BT , Rollin PE , Purpura LJ , Choi MJ . Clin Infect Dis 2022 76 (3) e849-e856 ![]() ![]() 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 two consecutive negative EBOV semen tests by real-time reverse transcriptase polymerase chain reaction (rRT-PCR) at least two weeks apart within 1 year after discharge from the Ebola Treatment Unit (ETU) or acute EVD. "Late clearers" had detectable EBOV RNA by rRT-PCR over one year following ETU discharge or acute EVD. Retrospective histories of their EVD clinical course were collected by questionnaire, followed by complete physical exams and blood work. RESULTS: Compared to early clearers, late clearers were older (median 42.5 years, p = 0.0001) and experienced fewer severe clinical symptoms (median 2, p = 0.006). Late clearers had more lens opacifications (OR 3.9, 95%CI 1.1-13.3, p = 0.03), after accounting for age, higher total serum IgG3 titers (p = 0.007) and increased expression of the HLA-C*03:04 allele (OR 0.14, 95% CI 0.02-0.70, p = 0.007). 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
Shieh WJ , Demby A , Jones T , Goldsmith CS , Rollin PE , Ksiazek TG , Peters CJ , Zaki SR . Clin Infect Dis 2021 74 (10) 1821-1830 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 three 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 LF is multifactorial and additional studies are needed. |
Use of Ebola vaccine: Recommendations of the Advisory Committee on Immunization Practices, United States, 2020
Choi MJ , Cossaboom CM , Whitesell AN , Dyal JW , Joyce A , Morgan RL , Campos-Outcalt D , Person M , Ervin E , Yu YC , Rollin PE , Harcourt BH , Atmar RL , Bell BP , Helfand R , Damon IK , Frey SE . MMWR Recomm Rep 2021 70 (1) 1-12 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 RT-PCR
Kofman A , Linderman S , Su K , Purpura LJ , Ervin E , Brown S , Morales-Betoulle M , Graziano J , Cannon DL , Klena JD , Desamu-Thorpe R , Fankhauser J , Orone R , Soka M , Glaybo U , Massaquoi M , Nysenswah T , Nichol ST , Kollie J , Kiawu A , Freeman E , Giah G , Tony H , Faikai M , Jawara M , Kamara K , Kamara S , Flowers B , Mohammed K , Chiriboga D , Williams DE , Hinrichs SH , Ahmed R , Vonhm B , Rollin PE , Choi MJ . Clin Infect Dis 2020 73 (11) e3641-e3646 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 qRT-PCR, and for anti-EBOV-specific IgM and IgG antibodies by enzyme-linked immunosorbent assay (ELISA) for 126 study participants. We performed peripheral blood mononuclear cell (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 which produced anti-EBOV-specific IgG antibodies upon stimulation with EBOV-specific GP and NP antigens. DISCUSSION: 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 one IgM/IgG negative participant who had PBMCs which 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. |
A retrospective cohort investigation of seroprevalence of Marburg virus and ebolaviruses in two different ecological zones in Uganda
Nyakarahuka L , Schafer IJ , Balinandi S , Mulei S , Tumusiime A , Kyondo J , Knust B , Lutwama J , Rollin P , Nichol S , Shoemaker T . BMC Infect Dis 2020 20 (1) 461 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. |
Seoul virus infection and spread in US home-based ratteries-rat and human testing results from a multistate outbreak investigation.
Knust B , Brown S , de St Maurice A , Whitmer S , Koske SE , Ervin E , Patel K , Graziano J , Morales-Betoulle ME , House J , Cannon D , Kerins J , Holzbauer S , Austin C , Gibbons-Burgener S , Colton L , Dunn J , Zufan S , Choi MJ , Davis WR , Chiang CF , Manning CR , Roesch L , Shoemaker T , Purpura L , McQuiston J , Peterson D , Radcliffe R , Garvey A , Christel E , Morgan L , Scheftel J , Kazmierczak J , Klena JD , Nichol ST , Rollin PE . J Infect Dis 2020 222 (8) 1311-1319 ![]() ![]() BACKGROUND: During 2017, a multi-state outbreak investigation occurred following 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 IgG and IgM serology and traditional 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; seven reported symptoms and three 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 lab-confirmed cases were significantly associated with rat IgG positivity and RT-PCR positivity (p=0.03 and p=0.006, 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. |
Culture cell block controls as a tool to the biomolecular diagnosis of infectious diseases
Jose Tadeu de Araujo L , Salas-Gomez D , Midori Kimura L , Fernandes Possatto Takahashi J , de Souza Barrel J , Rollin DC , Mariotti Guerra J . Appl Immunohistochem Mol Morphol 2019 28 (6) 484-487 The cell block (CB) technique has allowed easy obtainment of samples such as cellular and culture suspensions, to perform specific molecular tests such as immunohistochemistry and in situ hybridization. It has been improved along time, accuracy, and quality of the diagnoses, however, the cost of a commercial gel matrix for the preparation of CB is high and not suitable depending on the situation. The objective of this study is to test agarose as an alternative to the commercial gel matrix in the preparation of Aspergillus fumigatus' CB. |
Lassa virus circulating in Liberia: a retrospective genomic characterisation.
Wiley MR , Fakoli L , Letizia AG , Welch SR , Ladner JT , Prieto K , Reyes D , Espy N , Chitty JA , Pratt CB , Di Paola N , Taweh F , Williams D , Saindon J , Davis WG , Patel K , Holland M , Negron D , Stroher U , Nichol ST , Sozhamannan S , Rollin PE , Dogba J , Nyenswah T , Bolay F , Albarino CG , Fallah M , Palacios G . Lancet Infect Dis 2019 19 (12) 1371-1378 ![]() ![]() BACKGROUND: An alarming rise in reported Lassa fever cases continues in west Africa. Liberia has the largest reported per capita incidence of Lassa fever cases in the region, but genomic information on the circulating strains is scarce. The aim of this study was to substantially increase the available pool of data to help foster the generation of targeted diagnostics and therapeutics. METHODS: Clinical serum samples collected from 17 positive Lassa fever cases originating from Liberia (16 cases) and Guinea (one case) within the past decade were processed at the Liberian Institute for Biomedical Research using a targeted-enrichment sequencing approach, producing 17 near-complete genomes. An additional 17 Lassa virus sequences (two from Guinea, seven from Liberia, four from Nigeria, and four from Sierra Leone) were generated from viral stocks at the US Centers for Disease Control and Prevention (Atlanta, GA) from samples originating from the Mano River Union (Guinea, Liberia, and Sierra Leone) region and Nigeria. Sequences were compared with existing Lassa virus genomes and published Lassa virus assays. FINDINGS: The 23 new Liberian Lassa virus genomes grouped within two clades (IV.A and IV.B) and were genetically divergent from those circulating elsewhere in west Africa. A time-calibrated phylogeographic analysis incorporating the new genomes suggests Liberia was the entry point of Lassa virus into the Mano River Union region and estimates the introduction to have occurred between 300-350 years ago. A high level of diversity exists between the Liberian Lassa virus genomes. Nucleotide percent difference between Liberian Lassa virus genomes ranged up to 27% in the L segment and 18% in the S segment. The commonly used Lassa Josiah-MGB assay was up to 25% divergent across the target sites when aligned to the Liberian Lassa virus genomes. INTERPRETATION: The large amount of novel genomic diversity of Lassa virus observed in the Liberian cases emphasises the need to match deployed diagnostic capabilities with locally circulating strains and underscores the importance of evaluating cross-lineage protection in the development of vaccines and therapeutics. FUNDING: Defense Biological Product Assurance Office of the US Department of Defense and the Armed Forces Health Surveillance Branch and its Global Emerging Infections Surveillance and Response Section. |
Marburg virus disease outbreak in Kween District Uganda, 2017: Epidemiological and laboratory findings
Nyakarahuka L , Shoemaker TR , Balinandi S , Chemos G , Kwesiga B , Mulei S , Kyondo J , Tumusiime A , Kofman A , Masiira B , Whitmer S , Brown S , Cannon D , Chiang CF , Graziano J , Morales-Betoulle M , Patel K , Zufan S , Komakech I , Natseri N , Chepkwurui PM , Lubwama B , Okiria J , Kayiwa J , Nkonwa IH , Eyu P , Nakiire L , Okarikod EC , Cheptoyek L , Wangila BE , Wanje M , Tusiime P , Bulage L , Mwebesa HG , Ario AR , Makumbi I , Nakinsige A , Muruta A , Nanyunja M , Homsy J , Zhu BP , Nelson L , Kaleebu P , Rollin PE , Nichol ST , Klena JD , Lutwama JJ . PLoS Negl Trop Dis 2019 13 (3) e0007257 ![]() INTRODUCTION: In October 2017, a blood sample from a resident of Kween District, Eastern Uganda, tested positive for Marburg virus. Within 24 hour of confirmation, a rapid outbreak response was initiated. Here, we present results of epidemiological and laboratory investigations. METHODS: A district task force was activated consisting of specialised teams to conduct case finding, case management and isolation, contact listing and follow up, sample collection and testing, and community engagement. An ecological investigation was also carried out to identify the potential source of infection. Virus isolation and Next Generation sequencing were performed to identify the strain of Marburg virus. RESULTS: Seventy individuals (34 MVD suspected cases and 36 close contacts of confirmed cases) were epidemiologically investigated, with blood samples tested for MVD. Only four cases met the MVD case definition; one was categorized as a probable case while the other three were confirmed cases. A total of 299 contacts were identified; during follow- up, two were confirmed as MVD. Of the four confirmed and probable MVD cases, three died, yielding a case fatality rate of 75%. All four cases belonged to a single family and 50% (2/4) of the MVD cases were female. All confirmed cases had clinical symptoms of fever, vomiting, abdominal pain and bleeding from body orifices. Viral sequences indicated that the Marburg virus strain responsible for this outbreak was closely related to virus strains previously shown to be circulating in Uganda. CONCLUSION: This outbreak of MVD occurred as a family cluster with no additional transmission outside of the four related cases. Rapid case detection, prompt laboratory testing at the Uganda National VHF Reference Laboratory and presence of pre-trained, well-prepared national and district rapid response teams facilitated the containment and control of this outbreak within one month, preventing nationwide and global transmission of the disease. |
Lassa fever in travelers from West Africa, 1969-2016
Kofman A , Choi MJ , Rollin PE . Emerg Infect Dis 2019 25 (2) 245-248 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. |
First Laboratory-Confirmed Outbreak of Human and Animal Rift Valley Fever Virus in Uganda in 48 Years.
Shoemaker TR , Nyakarahuka L , Balinandi S , Ojwang J , Tumusiime A , Mulei S , Kyondo J , Lubwama B , Sekematte M , Namutebi A , Tusiime P , Monje F , Mayanja M , Ssendagire S , Dahlke M , Kyazze S , Wetaka M , Makumbi I , Borchert J , Zufan S , Patel K , Whitmer S , Brown S , Davis WG , Klena JD , Nichol ST , Rollin PE , Lutwama J . Am J Trop Med Hyg 2019 100 (3) 659-671 ![]() ![]() In March 2016, an outbreak of Rift Valley fever (RVF) was identified in Kabale district, southwestern Uganda. A comprehensive outbreak investigation was initiated, including human, livestock, and mosquito vector investigations. Overall, four cases of acute, nonfatal human disease were identified, three by RVF virus (RVFV) reverse transcriptase polymerase chain reaction (RT-PCR), and one by IgM and IgG serology. Investigations of cattle, sheep, and goat samples from homes and villages of confirmed and probable RVF cases and the Kabale central abattoir found that eight of 83 (10%) animals were positive for RVFV by IgG serology; one goat from the home of a confirmed case tested positive by RT-PCR. Whole genome sequencing from three clinical specimens was performed and phylogenetic analysis inferred the relatedness of 2016 RVFV with the 2006-2007 Kenya-2 clade, suggesting previous introduction of RVFV into southwestern Uganda. An entomological survey identified three of 298 pools (1%) of Aedes and Coquillettidia species that were RVFV positive by RT-PCR. This was the first identification of RVFV in Uganda in 48 years and the 10(th) independent viral hemorrhagic fever outbreak to be confirmed in Uganda since 2010. |
Complete Genome Sequences of Monongahela Hantavirus from Pennsylvania, USA.
Albarino CG , Guerrero LW , Chakrabarti AK , Rollin PE , Nichol ST . Microbiol Resour Announc 2018 7 (11) ![]() ![]() Monongahela hantavirus was first identified in deer mice and was later found responsible for hantavirus pulmonary syndrome cases in Pennsylvania and West Virginia in the United States. Here, we report the complete sequences of Monongahela virus S, M, and L genomic segments obtained from a fatal clinical case reported in 1997. Copyright © 2018 Microbiology Resource Announcements. All rights reserved. |
Care of Ebola survivors and factors associated with clinical sequelae - Monrovia, Liberia
de St Maurice A , Ervin E , Orone R , Choi M , Dokubo EK , Rollin PE , Nichol ST , Williams D , Brown J , Sacra R , Fankhauser J , Knust B . Open Forum Infect Dis 2018 5 (10) ofy239 Background: The Eternal Love Winning Africa (ELWA) Clinic was the first clinic to provide free, comprehensive care to Ebola virus disease (EVD) survivors in Liberia. The objectives of this analysis were to describe the demographics and symptoms of EVD survivors at ELWA from January 2015 through March 2017 and to identify risk factors for development of sequelae. Methods: Patients' demographic and clinical information was collected by chart review in June 2016 and March 2017. Associations with clinical sequelae were analyzed using the chi-square test, t test, and multivariate logistic regression. Results: From January 2015 to March 2017, 329 EVD survivors were evaluated at ELWA. Most survivors experienced myalgia/arthralgia (73%; n = 239) and headache (53%; n = 173). The length of time from Ebola Treatment Unit (ETU) discharge to first clinic visit ranged from 0 to 30 months. Many visits (30%) occurred 24 or more months after ETU discharge. The proportion of visits for headache, weight loss, joint pain, visual problems, insomnia, fatigue, memory loss, decreased libido, depression, and uveitis decreased over time. More men than women had visits for depression; however, these differences were not significant. Symptom prevalence differed in adults and children; significantly more adults experienced myalgia/arthralgia (77% vs 44%), visual problems (41% vs 12%), post-EVD-related musculoskeletal pain (42% vs 15%), and insomnia (17% vs 2%). Conclusions: EVD survivors frequented ELWA for EVD-related symptoms many months after ETU discharge, indicating a long-term need for care. Reported symptoms changed over time, which may reflect eventual resolution of some sequelae. |
Notes from the Field: Contact tracing investigation after first case of Andes virus in the United States - Delaware, February 2018
Kofman A , Eggers P , Kjemtrup A , Hall R , Brown SM , Morales-Betoulle M , Graziano J , Zufan SE , Whitmer SLM , Cannon DL , Chiang CF , Choi MJ , Rollin PE , Cetron MS , Yaglom HD , Duwell M , Kuhar DT , Kretschmer M , Knust B , Klena JD , Alvarado-Ramy F , Shoemaker T , Towner JS , Nichol ST . MMWR Morb Mortal Wkly Rep 2018 67 (41) 1162-1163 In January 2018, a woman admitted to a Delaware hospital tested positive for New World hantavirus immunoglobulin M (IgM) and immunoglobulin G (IgG) by enzyme-linked immunosorbent assay (ELISA). Subsequent testing by CDC’s Viral Special Pathogens Branch detected New World hantavirus by nested reverse transcription–polymerase chain reaction (RT-PCR) and Andes virus by nucleic acid sequencing. This case represents the first confirmed importation of Andes virus infection into the United States; two imported cases have also been reported in Switzerland (1). Before her illness, the patient had traveled to the Andes region of Argentina and Chile from December 20, 2017, to January 3, 2018. She stayed in cabins and youth hostels in reportedly poor condition. No rodent exposures were reported. After returning to the United States on January 10, she developed fever, malaise, and myalgias on January 14. On January 17, while ill, she traveled on two commercial domestic flights. She was hospitalized during January 20–25 in Delaware and discharged to her home after clinical recovery. |
New tools in the Ebola arsenal
Damon IK , Rollin PE , Choi MJ , Arthur RR , Redfield RR . N Engl J Med 2018 379 (21) 1981-1983 ![]() Human Ebola virus disease can be caused by four viruses: Sudan virus, Tai Forest virus, Bundibugyo virus, and Ebola virus (EBOV, species Zaire ebolavirus). The 2014 outbreak of EBOV in West Africa was the worst ever, with more than 28,000 cases and more than 11,000 deaths in Liberia, Guinea, Sierra Leone, Nigeria, and Mali. Investigational studies undertaken during the latter stages of the response, however, have led to progress in the development and use of biologic and chemical compounds to treat EBOV and Ebola virus disease (EVD). Recommendations to study vaccines and therapeutics and evaluate their benefit in the context of Ebola responses have been issued by a panel of the National Academies of Sciences, Engineering, and Medicine and by the World Health Organization (WHO) in the form of an EVD Blueprint.1,2 |
Case report: Imported case of Lassa fever - New Jersey, May 2015
Kulkarni PA , Chew D , Youssef-Bessler M , Hamdi HA , Montoya LA , Cervantes KB , Mazur NL , Lucas D , Wells JW , Cennimo D , Sutherland A , Di Domenico LM , Miller LP , Pierre-Louis F , Rokosz G , Nazir A , de Perio MA , Lowe L , Manning C , Mead KR , Christensen BE , Albarino CG , Stroher U , Glover M , Lifshitz EI , Tan CG , Rollin PE , Semple S . Am J Trop Med Hyg 2018 99 (4) 1062-1065 We report a fatal case of Lassa fever diagnosed in the United States in a Liberian traveler. We describe infection control protocols and public health response. One contact at high risk became symptomatic, but her samples tested negative for Lassa virus; no secondary cases occurred among health care, family, and community contacts. |
A case of Lassa fever diagnosed at a community hospital - Minnesota 2014
Choi MJ , Worku S , Knust B , Vang A , Lynfield R , Mount MR , Objio T , Brown S , Griffith J , Hulbert D , Lippold S , Ervin E , Stroher U , Holzbauer S , Slattery W , Washburn F , Harper J , Koeck M , Uher C , Rollin P , Nichol S , Else R , DeVries A . Open Forum Infect Dis 2018 5 (7) ofy131 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. |
Prevalence and risk factors of Rift Valley fever in humans and animals from Kabale district in Southwestern Uganda, 2016
Nyakarahuka L , de St Maurice A , Purpura L , Ervin E , Balinandi S , Tumusiime A , Kyondo J , Mulei S , Tusiime P , Lutwama J , Klena J , Brown S , Knust B , Rollin PE , Nichol ST , Shoemaker TR . PLoS Negl Trop Dis 2018 12 (5) e0006412 BACKGROUND: Rift Valley fever (RVF) is a zoonotic disease caused by Rift Valley fever virus (RVFV) found in Africa and the Middle East. Outbreaks can cause extensive morbidity and mortality in humans and livestock. Following the diagnosis of two acute human RVF cases in Kabale district, Uganda, we conducted a serosurvey to estimate RVFV seroprevalence in humans and livestock and to identify associated risk factors. METHODS: Humans and animals at abattoirs and villages in Kabale district were sampled. Persons were interviewed about RVFV exposure risk factors. Human blood was tested for anti-RVFV IgM and IgG, and animal blood for anti-RVFV IgG. PRINCIPAL FINDINGS: 655 human and 1051 animal blood samples were collected. Anti-RVFV IgG was detected in 78 (12%) human samples; 3 human samples (0.5%) had detectable IgM only, and 7 (1%) had both IgM and IgG. Of the 10 IgM-positive persons, 2 samples were positive for RVFV by PCR, confirming recent infection. Odds of RVFV seropositivity were greater in participants who were butchers (odds ratio [OR] 5.1; 95% confidence interval [95% CI]: 1.7-15.1) and those who reported handling raw meat (OR 3.4; 95% CI 1.2-9.8). No persons under age 20 were RVFV seropositive. The overall animal seropositivity was 13%, with 27% of cattle, 7% of goats, and 4% of sheep seropositive. In a multivariate logistic regression, cattle species (OR 9.1; 95% CI 4.1-20.5), adult age (OR 3.0; 95% CI 1.6-5.6), and female sex (OR 2.1; 95%CI 1.0-4.3) were significantly associated with animal seropositivity. Individual human seropositivity was significantly associated with animal seropositivity by subcounty after adjusting for sex, age, and occupation (p < 0.05). CONCLUSIONS: Although no RVF cases had been detected in Uganda from 1968 to March 2016, our study suggests that RVFV has been circulating undetected in both humans and animals living in and around Kabale district. RVFV seropositivity in humans was associated with occupation, suggesting that the primary mode of RVFV transmission to humans in Kabale district could be through contact with animal blood or body fluids. |
Impact of enhanced viral haemorrhagic fever surveillance on outbreak detection and response in Uganda
Shoemaker TR , Balinandi S , Tumusiime A , Nyakarahuka L , Lutwama J , Mbidde E , Kofman A , Klena JD , Stroher U , Rollin PE , Nichol ST . Lancet Infect Dis 2018 18 (4) 373-375 The recent outbreak of Marburg virus disease in Kween District, eastern Uganda, reported in The Lancet Infectious Diseases,1 marks the 13th independent viral haemorrhagic fever outbreak identified and confirmed via laboratory test by the Uganda Virus Research Institute (UVRI)’s viral haemorrhagic fever surveillance and laboratory programme since 2010. This Marburg virus disease outbreak was followed closely by three independent confirmations of human Rift Valley fever virus infection in three districts in central Uganda, and now brings the total viral haemorrhagic fever outbreak detections to 16. This exceptional number of early detections and subsequent outbreak responses has led to a significant decrease in the overall intensity (p=0·001) and duration (p<0·0001) of viral haemorrhagic fever outbreaks in Uganda, and serves as a role model for detecting and responding to public health threats of international concern. |
Rift Valley Fever: A survey of knowledge, attitudes, and practice of slaughterhouse workers and community members in Kabale District, Uganda
de St Maurice A , Nyakarahuka L , Purpura L , Ervin E , Tumusiime A , Balinandi S , Kyondo J , Mulei S , Tusiime P , Manning C , Rollin PE , Knust B , Shoemaker T . PLoS Negl Trop Dis 2018 12 (3) e0006175 BACKGROUND: Rift Valley Fever virus (RVF) is a zoonotic virus in the Phenuiviridae family. RVF outbreaks can cause significant morbidity and mortality in humans and animals. Following the diagnosis of two RVF cases in March 2016 in southern Kabale district, Uganda, we conducted a knowledge, attitudes and practice (KAP) survey to identify knowledge gaps and at-risk behaviors related to RVF. METHODOLOGY/PRINCIPAL FINDINGS: A multidisciplinary team interviewed 657 community members, including abattoir workers, in and around Kabale District, Uganda. Most participants (90%) had knowledge of RVF and most (77%) cited radio as their primary information source. Greater proportions of farmers (68%), herdsmen (79%) and butchers (88%) thought they were at risk of contracting RVF compared to persons in other occupations (60%, p<0.01). Participants most frequently identified bleeding as a symptom of RVF. Less than half of all participants reported fever, vomiting, and diarrhea as common RVF symptoms in either humans or animals. The level of knowledge about human RVF symptoms did not vary by occupation; however more farmers and butchers (36% and 51%, respectively) had knowledge of RVF symptoms in animals compared to those in other occupations (30%, p<0.01). The use of personal protective equipment (PPE) when handling animals varied by occupation, with 77% of butchers using some PPE and 12% of farmers using PPE. Although most butchers said that they used PPE, most used gumboots (73%) and aprons (60%) and less than 20% of butchers used gloves or eye protection when slaughtering. CONCLUSIONS: Overall, knowledge, attitudes and practice regarding RVF in Kabale District Uganda could be improved through educational efforts targeting specific populations. |
Genome Sequences of Crimean-Congo Hemorrhagic Fever Virus Strains Isolated in South Africa, Namibia, and Turkey.
Zivcec M , Albarino CG , Guerrero LIW , Ksiazek TG , Nichol ST , Swanepoel R , Rollin PE , Spiropoulou CF . Genome Announc 2017 5 (42) ![]() We report here the full-length sequences of 16 historical isolates of Crimean-Congo hemorrhagic fever orthonairovirus (CCHFV) obtained in Turkey, Namibia, and South Africa. The strains may be useful for future work to develop molecular diagnostics or viral evolution studies. |
Favipiravir and ribavirin treatment of epidemiologically linked cases of Lassa fever
Raabe VN , Kann G , Ribner BS , Morales A , Varkey JB , Mehta AK , Lyon GM , Vanairsdale S , Faber K , Becker S , Eickmann M , Strecker T , Brown S , Patel K , De Leuw P , Schuettfort G , Stephan C , Rabenau H , Klena JD , Rollin PE , McElroy A , Stroher U , Nichol S , Kraft CS , Wolf T . Clin Infect Dis 2017 65 (5) 855-859 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. |
What we are watching-top global infectious disease threats, 2013-2016: An update from CDC's Global Disease Detection Operations Center
Christian KA , Iuliano AD , Uyeki TM , Mintz ED , Nichol ST , Rollin P , Staples JE , Arthur RR . Health Secur 2017 15 (5) 453-462 To better track public health events in areas where the public health system is unable or unwilling to report the event to appropriate public health authorities, agencies can conduct event-based surveillance, which is defined as the organized collection, monitoring, assessment, and interpretation of unstructured information regarding public health events that may represent an acute risk to public health. The US Centers for Disease Control and Prevention's (CDC's) Global Disease Detection Operations Center (GDDOC) was created in 2007 to serve as CDC's platform dedicated to conducting worldwide event-based surveillance, which is now highlighted as part of the "detect" element of the Global Health Security Agenda (GHSA). The GHSA works toward making the world more safe and secure from disease threats through building capacity to better "Prevent, Detect, and Respond" to those threats. The GDDOC monitors approximately 30 to 40 public health events each day. In this article, we describe the top threats to public health monitored during 2012 to 2016: avian influenza, cholera, Ebola virus disease, and the vector-borne diseases yellow fever, chikungunya virus, and Zika virus, with updates to the previously described threats from Middle East respiratory syndrome-coronavirus (MERS-CoV) and poliomyelitis. |
Clinical management of Ebola virus disease patients in low-resource settings
Sprecher A , Van Herp M , Rollin PE . Curr Top Microbiol Immunol 2017 411 93-113 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. |
Seoul virus infection in humans, France, 2014-2016
Reynes JM , Carli D , Bour JB , Boudjeltia S , Dewilde A , Gerbier G , Nussbaumer T , Jacomo V , Rapt MP , Rollin PE , Septfons A . Emerg Infect Dis 2017 23 (6) 973-977 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
Nyakarahuka L , Ojwang J , Tumusiime A , Balinandi S , Whitmer S , Kyazze S , Kasozi S , Wetaka M , Makumbi I , Dahlke M , Borchert J , Lutwama J , Stroher U , Rollin PE , Nichol ST , Shoemaker TR . Emerg Infect Dis 2017 23 (6) 1001-1004 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. |
Insights into Reston virus spillovers and adaption from virus whole genome sequences.
Albarino CG , Wiggleton Guerrero L , Jenks HM , Chakrabarti AK , Ksiazek TG , Rollin PE , Nichol ST . PLoS One 2017 12 (5) e0178224 ![]() Reston virus (family Filoviridae) is unique among the viruses of the Ebolavirus genus in that it is considered non-pathogenic in humans, in contrast to the other members which are highly virulent. The virus has however, been associated with several outbreaks of highly lethal hemorrhagic fever in non-human primates (NHPs), specifically cynomolgus monkeys (Macaca fascicularis) originating in the Philippines. In addition, Reston virus has been isolated from domestic pigs in the Philippines. To better understand virus spillover events and potential adaption to new hosts, the whole genome sequences of representative Reston virus isolates were obtained using a next generation sequencing (NGS) approach and comparative genomic analysis and virus fitness analyses were performed. Nine virus genome sequences were completed for novel and previously described isolates obtained from a variety of hosts including a human case, non-human primates and pigs. Results of phylogenetic analysis of the sequence differences are consistent with multiple independent introductions of RESTV from a still unknown natural reservoir into non-human primates and swine farming operations. No consistent virus genetic markers were found specific for viruses associated with primate or pig infections, but similar to what had been seen with some Ebola viruses detected in the large Western Africa outbreak in 2014-2016, a truncated version of VP30 was identified in a subgroup of Reston viruses obtained from an outbreak in pigs 2008-2009. Finally, the genetic comparison of two closely related viruses, one isolated from a human case and one from an NHP, showed amino acid differences in the viral polymerase and detectable differences were found in competitive growth assays on human and NHP cell lines. |
Exposure characteristics of hantavirus pulmonary syndrome patients, United States, 1993-2015
de St Maurice A , Ervin E , Schumacher M , Yaglom H , VinHatton E , Melman S , Komatsu K , House J , Peterson D , Buttke D , Ryan A , Yazzie D , Manning C , Ettestad P , Rollin P , Knust B . Emerg Infect Dis 2017 23 (5) 733-739 Those at highest risk are persons in occupations with potential for rodent exposure and American Indian women 40--64 years of age. |
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