Journal Article > CommentaryFull Text
J Infect Dis. 19 August 2023; online ahead of print; jiad354.; DOI:10.1093/infdis/jiad354
Sprecher A, Cross RW, Marzi A, Martins KA, Wolfe D, et al.
J Infect Dis. 19 August 2023; online ahead of print; jiad354.; DOI:10.1093/infdis/jiad354
Although there are now approved treatments and vaccines for Ebola virus disease (EVD), the case fatality of EVD remains unacceptably high even when treated with the newly approved therapeutics; furthermore, these countermeasures are not expected to be effective against disease caused by other filoviruses. A meeting of subject matter experts from public health, research, and countermeasure development agencies and manufacturers was held during the 10th International Filovirus Symposium to discuss strategies to address these gaps, including how newer countermeasures could be advanced for field readiness. Several investigational therapeutics, vaccine candidates, and combination strategies were presented. In all, a common theme emerged: the greatest challenge to completing development was the implementation of well-designed clinical trials of safety and efficacy during filovirus disease outbreaks. These outbreaks are usually of short duration, providing but a brief opportunity for trials to be launched, and have too few cases to allow for full enrollment during a single outbreak, so clinical trials will necessarily need to span multiple outbreaks which may occur in a number of at-risk countries. Preparing for this will require agreed-upon common protocols for trials intended to bridge multiple outbreaks across all at-risk countries. A multi-national research consortium including, and led by, at-risk countries would be an ideal mechanism to negotiate agreement on protocol design and coordinate preparation. Discussion participants recommended a follow-up meeting be held in Africa with national public health and research agencies from at-risk countries to establish such a consortium.
Journal Article > ResearchFull Text
Clin Infect Dis. 15 August 2016; Volume 63 (Issue 8); 1026-1033.; DOI:10.1093/cid/ciw452
Rosenke K, Adjemian J, Munster VJ, Marzi A, Falzarano D, et al.
Clin Infect Dis. 15 August 2016; Volume 63 (Issue 8); 1026-1033.; DOI:10.1093/cid/ciw452
BACKGROUND
The ongoing Ebola outbreak in West Africa has resulted in 28 646 suspected, probable, and confirmed Ebola virus infections. Nevertheless, malaria remains a large public health burden in the region affected by the outbreak. A joint Centers for Disease Control and Prevention/National Institutes of Health diagnostic laboratory was established in Monrovia, Liberia, in August 2014, to provide laboratory diagnostics for Ebola virus.
METHODS
All blood samples from suspected Ebola virus-infected patients admitted to the Médecins Sans Frontières ELWA3 Ebola treatment unit in Monrovia were tested by quantitative real-time polymerase chain reaction for the presence of Ebola virus and Plasmodium species RNA. Clinical outcome in laboratory-confirmed Ebola virus-infected patients was analyzed as a function of age, sex, Ebola viremia, and Plasmodium species parasitemia.
RESULTS
The case fatality rate of 1182 patients with laboratory-confirmed Ebola virus infections was 52%. The probability of surviving decreased with increasing age and decreased with increasing Ebola viral load. Ebola virus-infected patients were 20% more likely to survive when Plasmodium species parasitemia was detected, even after controlling for Ebola viral load and age; those with the highest levels of parasitemia had a survival rate of 83%. This effect was independent of treatment with antimalarials, as this was provided to all patients. Moreover, treatment with antimalarials did not affect survival in the Ebola virus mouse model.
CONCLUSIONS
Plasmodium species parasitemia is associated with an increase in the probability of surviving Ebola virus infection. More research is needed to understand the molecular mechanism underlying this remarkable phenomenon and translate it into treatment options for Ebola virus infection.
The ongoing Ebola outbreak in West Africa has resulted in 28 646 suspected, probable, and confirmed Ebola virus infections. Nevertheless, malaria remains a large public health burden in the region affected by the outbreak. A joint Centers for Disease Control and Prevention/National Institutes of Health diagnostic laboratory was established in Monrovia, Liberia, in August 2014, to provide laboratory diagnostics for Ebola virus.
METHODS
All blood samples from suspected Ebola virus-infected patients admitted to the Médecins Sans Frontières ELWA3 Ebola treatment unit in Monrovia were tested by quantitative real-time polymerase chain reaction for the presence of Ebola virus and Plasmodium species RNA. Clinical outcome in laboratory-confirmed Ebola virus-infected patients was analyzed as a function of age, sex, Ebola viremia, and Plasmodium species parasitemia.
RESULTS
The case fatality rate of 1182 patients with laboratory-confirmed Ebola virus infections was 52%. The probability of surviving decreased with increasing age and decreased with increasing Ebola viral load. Ebola virus-infected patients were 20% more likely to survive when Plasmodium species parasitemia was detected, even after controlling for Ebola viral load and age; those with the highest levels of parasitemia had a survival rate of 83%. This effect was independent of treatment with antimalarials, as this was provided to all patients. Moreover, treatment with antimalarials did not affect survival in the Ebola virus mouse model.
CONCLUSIONS
Plasmodium species parasitemia is associated with an increase in the probability of surviving Ebola virus infection. More research is needed to understand the molecular mechanism underlying this remarkable phenomenon and translate it into treatment options for Ebola virus infection.
Journal Article > ResearchFull Text
J Infect Dis. 28 July 2016; Volume 214 (Issue suppl 3); S303-S307.; DOI:10.1093/infdis/jiw187
de Wit E, Kramer S, Prescott JB, Rosenke K, Falzarano D, et al.
J Infect Dis. 28 July 2016; Volume 214 (Issue suppl 3); S303-S307.; DOI:10.1093/infdis/jiw187
The development of point-of-care clinical chemistry analyzers has enabled the implementation of these ancillary tests in field laboratories in resource-limited outbreak areas. The Eternal Love Winning Africa (ELWA) outbreak diagnostic laboratory, established in Monrovia, Liberia, to provide Ebola virus and Plasmodium spp. diagnostics during the Ebola epidemic, implemented clinical chemistry analyzers in December 2014. Clinical chemistry testing was performed for 68 patients in triage, including 12 patients infected with Ebola virus and 18 infected with Plasmodium spp. The main distinguishing feature in clinical chemistry of Ebola virus-infected patients was the elevation in alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase, and γ-glutamyltransferase levels and the decrease in calcium. The implementation of clinical chemistry is probably most helpful when the medical supportive care implemented at the Ebola treatment unit allows for correction of biochemistry derangements and on-site clinical chemistry analyzers can be used to monitor electrolyte balance.
Journal Article > ResearchFull Text
PLoS Negl Trop Dis. 24 May 2011; Volume 5 (Issue 5); DOI:10.1371/journal.pntd.0001183
Grolla A, Jones SM, Fernando L, Strong JE, Stroher U, et al.
PLoS Negl Trop Dis. 24 May 2011; Volume 5 (Issue 5); DOI:10.1371/journal.pntd.0001183
Background: Marburg virus (MARV), a zoonotic pathogen causing severe hemorrhagic fever in man, has emerged in Angola resulting in the largest outbreak of Marburg hemorrhagic fever (MHF) with the highest case fatality rate to date. Methodology/Principal Findings: A mobile laboratory unit (MLU) was deployed as part of the World Health Organization outbreak response. Utilizing quantitative real-time PCR assays, this laboratory provided specific MARV diagnostics in Uige, the epicentre of the outbreak. The MLU operated over a period of 88 days and tested 620 specimens from 388 individuals. Specimens included mainly oral swabs and EDTA blood. Following establishing on site, the MLU operation allowed a diagnostic response in ,4 hours from sample receiving. Most cases were found among females in the child-bearing age and in children less than five years of age. The outbreak had a high number of paediatric cases and breastfeeding may have been a factor in MARV transmission as indicated by the epidemiology and MARV positive breast milk specimens. Oral swabs were a useful alternative specimen source to whole blood/serum allowing testing of patients in circumstances of resistance to invasive procedures but limited diagnostic testing to molecular approaches. There was a high concordance in test results between the MLU and the reference laboratory in Luanda operated by the US Centers for Disease Control and Prevention. Conclusions/Significance: The MLU was an important outbreak response asset providing support in patient management and epidemiological surveillance. Field laboratory capacity should be expanded and made an essential part of any future outbreak investigation.
Journal Article > Short ReportFull Text
MMWR Morb Mortal Wkly Rep. 2 February 2007; Volume 56 (Issue 4); 73-76.
Nguku PM, Sharif S, Omar A, Nzioka C, Muthoka P, et al.
MMWR Morb Mortal Wkly Rep. 2 February 2007; Volume 56 (Issue 4); 73-76.
In mid-December 2006, several unexplained fatalities associated with fever and generalized bleeding were reported to the Kenya Ministry of Health (KMOH) from Garissa District in North Eastern Province (NEP). By December 20, a total of 11 deaths had been reported. Of serum samples collected from the first 19 patients, Rift Valley fever (RVF) virus RNA or immunoglobulin M (IgM) antibodies against RVF virus were found in samples from 10 patients; all serum specimens were negative for yellow fever, Ebola, Crimean-Congo hemorrhagic fever, and dengue viruses. The outbreak was confirmed by isolation of RVF virus from six of the specimens. Humans can be infected with RVF virus from bites of mosquitoes or other arthropod vectors that have fed on animals infected with RVF virus, or through contact with viremic animals, particularly livestock. Reports of livestock deaths and unexplained animal abortions in NEP provided further evidence of an RVF outbreak. On December 20, an investigation was launched by KMOH, the Kenya Field Epidemiology and Laboratory Training Program (FELTP), the Kenya Medical Research Institute (KEMRI), the Walter Reed Project of the U.S. Army Medical Research Unit, CDC-Kenya's Global Disease Detection Center, and other partners, including the World Health Organization (WHO) and Médecins Sans Frontières (MSF). This report describes the findings from that initial investigation and the control measures taken in response to the RVF outbreak, which spread to multiple additional provinces and districts, resulting in 404 cases with 118 deaths as of January 25, 2007.
Journal Article > ResearchFull Text
Emerg Infect Dis. 1 February 2016; Volume 22 (Issue 2); 323-326.; DOI:10.3201/eid2202.151656
de Wit E, Falzarano D, Onyango C, Rosenke K, Marzi A, et al.
Emerg Infect Dis. 1 February 2016; Volume 22 (Issue 2); 323-326.; DOI:10.3201/eid2202.151656
Malaria is a major public health concern in the countries affected by the Ebola virus disease epidemic in West Africa. We determined the feasibility of using molecular malaria diagnostics during an Ebola virus disease outbreak and report the incidence of Plasmodium spp. parasitemia in persons with suspected Ebola virus infection.
Journal Article > LetterFull Text
Clin Infect Dis. 15 December 2016; Volume 64 (Issue 2); 232.; DOI:10.1093/cid/ciw734
Rosenke K, Adjemian J, Munster VJ, Strong JE, Sprecher A, et al.
Clin Infect Dis. 15 December 2016; Volume 64 (Issue 2); 232.; DOI:10.1093/cid/ciw734
Journal Article > CommentaryFull Text
J Infect Dis. 27 March 2015; Volume 212 (Issue suppl 2); DOI:10.1093/infdis/jiv153
Sprecher A, Caluwaerts C, Draper M, Feldmann H, Frey C, et al.
J Infect Dis. 27 March 2015; Volume 212 (Issue suppl 2); DOI:10.1093/infdis/jiv153
Personal protective equipment (PPE) is an important part of worker protection during filovirus outbreaks. The need to protect against a highly virulent fluid-borne pathogen in the tropical environment imposes a heat stress on the wearer that is itself a safety risk. No evidence supports the choice of PPE employed in recent outbreaks, and standard testing procedures employed by the protective garment industry do not well simulate filovirus exposure. Further research is needed to determine the appropriate PPE for filoviruses and the heat stress that it imposes.
Journal Article > ResearchFull Text
Nat Commun. 27 July 2020; Volume 11; DOI:10.1038/s41467-020-17446-4
Cross RW, Bornholdt ZA, Prasad AN, Geisbert JB, Borisevich V, et al.
Nat Commun. 27 July 2020; Volume 11; DOI:10.1038/s41467-020-17446-4
A replication-competent vesicular stomatitis virus vaccine expressing the Ebola virus (EBOV) glycoprotein (GP) (rVSV-ZEBOV) was successfully used during the 2013-16 EBOV epidemic. Additionally, chimeric and human monoclonal antibodies (mAb) against the EBOV GP have shown promise in animals and humans when administered therapeutically. Uncertainty exists regarding the efficacy of postexposure antibody treatments in the event of a known exposure of a recent rVSV-ZEBOV vaccinee. Here, we model a worst-case scenario using rhesus monkeys vaccinated or unvaccinated with the rVSV-ZEBOV vaccine. We demonstrate that animals challenged with a uniformly lethal dose of EBOV one day following vaccination, and then treated with the anti-EBOV GP mAb MIL77 starting 3 days postexposure show no evidence of clinical illness and survive challenge. In contrast, animals receiving only vaccination or only mAb-based therapy become ill, with decreased survival compared to animals vaccinated and subsequently treated with MIL77. These results suggest that rVSV-ZEBOV augments immunotherapy.
Journal Article > ReviewFull Text
N Engl J Med. 7 May 2020; Volume 382 (Issue 19); 1832-1842.; DOI:10.1056/NEJMra1901594
Feldmann H, Sprecher A, Geisbert TW
N Engl J Med. 7 May 2020; Volume 382 (Issue 19); 1832-1842.; DOI:10.1056/NEJMra1901594