Journal Article > ResearchFull Text
PLoS Negl Trop Dis. 2022 January 6; Volume 16 (Issue 1); E0010089.; DOI:10.1371/journal.pntd.0010089
Olayinka A, Bourner J, Akpede GO, Okoeguale J, Abejegah C, et al.
PLoS Negl Trop Dis. 2022 January 6; Volume 16 (Issue 1); E0010089.; DOI:10.1371/journal.pntd.0010089
BACKGROUND
Only one recommendation currently exists for the treatment of Lassa fever (LF), which is ribavirin administered in conjunction with supportive care. This recommendation is primarily based on evidence generated from a single clinical trial that was conducted more than 30 years ago-the methodology and results of which have recently come under scrutiny. The requirement for novel therapeutics and reassessment of ribavirin is therefore urgent. However, a significant amount of work now needs to be undertaken to ensure that future trials for LF can be conducted consistently and reliably to facilitate the efficient generation of evidence.
METHODOLOGY
We convened a consultation group to establish the position of clinicians and researchers on the core components of future trials. A Core Eligibility Criteria (CEC), Core Case Definition (CCD), Core Outcome Set (COS) and Core Data Variables (CDV) were developed through the process of a multi-stakeholder consultation that took place using a modified-Delphi methodology.
RESULTS
A consensus position was achieved for each aspect of the framework, which accounts for the inclusion of pregnant women and children in future LF clinical trials. The framework consists of 8 core criteria, as well as additional considerations for trial protocols.
CONCLUSIONS
This project represents the first step towards delineating the clinical development pathway for new Lassa fever therapeutics, following a period of 40 years without advancement. Future planned projects will bolster the work initiated here to continue the advancement of LF clinical research through a regionally-centred, collaborative methodology, with the aim of delineating a clear pathway through which LF clinical trials can progress efficiently and ensure sustainable investments are made in research capacity at a regional level.
Only one recommendation currently exists for the treatment of Lassa fever (LF), which is ribavirin administered in conjunction with supportive care. This recommendation is primarily based on evidence generated from a single clinical trial that was conducted more than 30 years ago-the methodology and results of which have recently come under scrutiny. The requirement for novel therapeutics and reassessment of ribavirin is therefore urgent. However, a significant amount of work now needs to be undertaken to ensure that future trials for LF can be conducted consistently and reliably to facilitate the efficient generation of evidence.
METHODOLOGY
We convened a consultation group to establish the position of clinicians and researchers on the core components of future trials. A Core Eligibility Criteria (CEC), Core Case Definition (CCD), Core Outcome Set (COS) and Core Data Variables (CDV) were developed through the process of a multi-stakeholder consultation that took place using a modified-Delphi methodology.
RESULTS
A consensus position was achieved for each aspect of the framework, which accounts for the inclusion of pregnant women and children in future LF clinical trials. The framework consists of 8 core criteria, as well as additional considerations for trial protocols.
CONCLUSIONS
This project represents the first step towards delineating the clinical development pathway for new Lassa fever therapeutics, following a period of 40 years without advancement. Future planned projects will bolster the work initiated here to continue the advancement of LF clinical research through a regionally-centred, collaborative methodology, with the aim of delineating a clear pathway through which LF clinical trials can progress efficiently and ensure sustainable investments are made in research capacity at a regional level.
Journal Article > ReviewFull Text
Lancet Infect Dis. 2016 June 10; Volume 16 (Issue 7); DOI:10.1016/S1473-3099(16)30063-9
Cnops L, van Griensven J, Honko AN, Bausch DG, Sprecher A, et al.
Lancet Infect Dis. 2016 June 10; Volume 16 (Issue 7); DOI:10.1016/S1473-3099(16)30063-9
Quantitative measurement of viral load is an important parameter in the management of filovirus disease outbreaks because viral load correlates with severity of disease, survival, and infectivity. During the ongoing Ebola virus disease outbreak in parts of Western Africa, most assays used in the detection of Ebola virus disease by more than 44 diagnostic laboratories yielded qualitative results. Regulatory hurdles involved in validating quantitative assays and the urgent need for a rapid Ebola virus disease diagnosis precluded development of validated quantitative assays during the outbreak. Because of sparse quantitative data obtained from these outbreaks, opportunities for study of correlations between patient outcome, changes in viral load during the course of an outbreak, disease course in asymptomatic individuals, and the potential for virus transmission between infected patients and contacts have been limited. We strongly urge the continued development of quantitative viral load assays to carefully evaluate these parameters in future outbreaks of filovirus disease.
Journal Article > CommentaryFull Text
Lancet Infect Dis. 2016 September 19; Volume 16 (Issue 10); DOI:10.1016/S1473-3099(16)30339-5
Cnops L, van Griensven J, Honko AN, Bausch DG, Sprecher A, et al.
Lancet Infect Dis. 2016 September 19; Volume 16 (Issue 10); DOI:10.1016/S1473-3099(16)30339-5
Journal Article > ResearchFull Text
PLoS Negl Trop Dis. 2011 May 24; 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. 2011 May 24; 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 > ResearchFull Text
J Infect Dis. 2019 April 3; Volume 221 (Issue 5); 701-706.; DOI:10.1093/infdis/jiz107
Nsio JM, Kapteshi K, Makiala S, Raymond F, Tshapenda G, et al.
J Infect Dis. 2019 April 3; Volume 221 (Issue 5); 701-706.; DOI:10.1093/infdis/jiz107
BACKGROUND
In 2017, the Democratic Republic of the Congo (DRC) recorded its eighth Ebola virus disease (EVD) outbreak, approximately 3 years after the previous outbreak.
METHODS
Suspect cases of EVD were identified on the basis of clinical and epidemiological information. Reverse transcription–polymerase chain reaction (RT-PCR) analysis or serological testing was used to confirm Ebola virus infection in suspected cases. The causative virus was later sequenced from a RT-PCR–positive individual and assessed using phylogenetic analysis.
RESULTS
Three probable and 5 laboratory-confirmed cases of EVD were recorded between 27 March and 1 July 2017 in the DRC. Fifty percent of cases died from the infection. EVD cases were detected in 4 separate areas, resulting in > 270 contacts monitored. The complete genome of the causative agent, a variant from the Zaireebolavirus species, denoted Ebola virus Muyembe, was obtained using next-generation sequencing. This variant is genetically closest, with 98.73% homology, to the Ebola virus Mayinga variant isolated from the first DRC outbreaks in 1976–1977.
CONCLUSION
A single spillover event into the human population is responsible for this DRC outbreak. Human-to-human transmission resulted in limited dissemination of the causative agent, a novel Ebola virus variant closely related to the initial Mayinga variant isolated in 1976–1977 in the DRC.
In 2017, the Democratic Republic of the Congo (DRC) recorded its eighth Ebola virus disease (EVD) outbreak, approximately 3 years after the previous outbreak.
METHODS
Suspect cases of EVD were identified on the basis of clinical and epidemiological information. Reverse transcription–polymerase chain reaction (RT-PCR) analysis or serological testing was used to confirm Ebola virus infection in suspected cases. The causative virus was later sequenced from a RT-PCR–positive individual and assessed using phylogenetic analysis.
RESULTS
Three probable and 5 laboratory-confirmed cases of EVD were recorded between 27 March and 1 July 2017 in the DRC. Fifty percent of cases died from the infection. EVD cases were detected in 4 separate areas, resulting in > 270 contacts monitored. The complete genome of the causative agent, a variant from the Zaireebolavirus species, denoted Ebola virus Muyembe, was obtained using next-generation sequencing. This variant is genetically closest, with 98.73% homology, to the Ebola virus Mayinga variant isolated from the first DRC outbreaks in 1976–1977.
CONCLUSION
A single spillover event into the human population is responsible for this DRC outbreak. Human-to-human transmission resulted in limited dissemination of the causative agent, a novel Ebola virus variant closely related to the initial Mayinga variant isolated in 1976–1977 in the DRC.
Journal Article > Short ReportFull Text
MMWR Morb Mortal Wkly Rep. 2007 February 2; Volume 56 (Issue 4); 73-76.
Nguku PM, Sharif S, Omar A, Nzioka C, Muthoka P, et al.
MMWR Morb Mortal Wkly Rep. 2007 February 2; 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 > CommentaryFull Text
J Infect Dis. 2016 October 15; Volume 214 (Issue suppl 3); S294-S296.; DOI:10.1093/infdis/jiw257
Wong G, Qiu X, Bi Y, Formenty P, Sprecher A, et al.
J Infect Dis. 2016 October 15; Volume 214 (Issue suppl 3); S294-S296.; DOI:10.1093/infdis/jiw257
Cases of relapsed Ebola virus disease involving symptoms in the central nervous system are reminiscent of our past observations with some nonhuman primates (NHPs) that survived acute Ebola virus infection. We document our findings in detail here and suggest that this phenomenon can be further investigated in NHPs.
Journal Article > LetterFull Text
N Engl J Med. 2022 June 30; Volume 386 (Issue 26); 2528-2530.; DOI:10.1056/NEJMc2120183
Koundouno FR, Kafetzopoulou LE, Faye M, Renevey A, Soropogui B, et al.
N Engl J Med. 2022 June 30; Volume 386 (Issue 26); 2528-2530.; DOI:10.1056/NEJMc2120183
Journal Article > ResearchFull Text
Nature. 2016 May 4; Volume 533 (Issue 7601); 100-104.; DOI:10.1038/nature17949
Ruibal P, Oestereich L, Ludtke A, Becker-Ziaja B, Wozniak DM, et al.
Nature. 2016 May 4; Volume 533 (Issue 7601); 100-104.; DOI:10.1038/nature17949
Despite the magnitude of the Ebola virus disease (EVD) outbreak in West Africa, there is still a fundamental lack of knowledge about the pathophysiology of EVD. In particular, very little is known about human immune responses to Ebola virus. Here we evaluate the physiology of the human T cell immune response in EVD patients at the time of admission to the Ebola Treatment Center in Guinea, and longitudinally until discharge or death. Through the use of multiparametric flow cytometry established by the European Mobile Laboratory in the field, we identify an immune signature that is unique in EVD fatalities. Fatal EVD was characterized by a high percentage of CD4(+) and CD8(+) T cells expressing the inhibitory molecules CTLA-4 and PD-1, which correlated with elevated inflammatory markers and high virus load. Conversely, surviving individuals showed significantly lower expression of CTLA-4 and PD-1 as well as lower inflammation, despite comparable overall T cell activation. Concomitant with virus clearance, survivors mounted a robust Ebola-virus-specific T cell response. Our findings suggest that dysregulation of the T cell response is a key component of EVD pathophysiology.
Journal Article > ReviewFull Text
Emerg Infect Dis. 2011 May 5; Volume 17 (Issue 5); DOI:10.3201/eid1705.100029
Bertherat E, Thullier P, Shako JC, England K, Kone ML, et al.
Emerg Infect Dis. 2011 May 5; Volume 17 (Issue 5); DOI:10.3201/eid1705.100029