Journal Article > ReviewFull Text
Lancet Infect Dis. 12 December 2024; Volume S1473-3099 (Issue 24); 00727-8.; DOI:10.1016/S1473-3099(24)00727-8
Rojek A, Fieggen J, Paterson A, Byakika-Kibwika P, Camara M, et al.
Lancet Infect Dis. 12 December 2024; Volume S1473-3099 (Issue 24); 00727-8.; DOI:10.1016/S1473-3099(24)00727-8
Journal Article > ResearchFull Text
mSphere. 30 August 2017; Volume 2 (Issue 4); DOI:10.1128/mSphereDirect.00325-17
Carroll MW, Haldenby S, Rickett NY, Palyi B, Garcia-Dorival I, et al.
mSphere. 30 August 2017; Volume 2 (Issue 4); DOI:10.1128/mSphereDirect.00325-17
In this study, samples from the 2013-2016 West African Ebola virus outbreak from patients in Guinea with Ebola virus disease (EVD) were analyzed to discover and classify what other pathogens were present. Throat swabs were taken from deceased EVD patients, and peripheral blood samples were analyzed that had been taken from patients when they presented at the treatment center with acute illness. High-throughput RNA sequencing (RNA-seq) and bioinformatics were used to identify the potential microorganisms. This approach confirmed Ebola virus (EBOV) in all samples from patients diagnosed as acute positive for the virus by quantitative reverse transcription-PCR in deployed field laboratories. Nucleic acid mapping to Plasmodium was also used on the patient samples, confirming results obtained with an antigen-based rapid diagnostic test (RDT) conducted in the field laboratories. The data suggested that a high Plasmodium load, as determined by sequence read depth, was associated with mortality and influenced the host response, whereas a lower parasite load did not appear to affect outcome. The identifications of selected bacteria from throat swabs via RNA-seq were confirmed by culture. The data indicated that the potential pathogens identified in the blood samples were associated with translocation from the gut, suggesting the presence of bacteremia, which transcriptome data suggested may induce or aggravate the acute-phase response observed during EVD. Transcripts mapping to different viruses were also identified, including those indicative of lytic infections. The development of high-resolution analysis of samples from patients with EVD will help inform care pathways and the most appropriate general antimicrobial therapy to be used in a resource-poor setting.
IMPORTANCE
Our results highlight the identification of an array of pathogens in the blood of patients with Ebola virus disease (EVD). This has not been done before, and the data have important implications for the treatment of patients with EVD, particularly considering antibiotic stewardship. We show that EVD patients who were also infected with Plasmodium, particularly at higher loads, had more adverse outcomes than patients with lower levels of Plasmodium. However, the presence of Plasmodium did not influence the innate immune response, and it is likely that the presence of EBOV dominated this response. Several viruses other than EBOV were identified, and bacteria associated with sepsis were also identified. These findings were indicative of bacterial translocation across the gut during the acute phase of EVD.
IMPORTANCE
Our results highlight the identification of an array of pathogens in the blood of patients with Ebola virus disease (EVD). This has not been done before, and the data have important implications for the treatment of patients with EVD, particularly considering antibiotic stewardship. We show that EVD patients who were also infected with Plasmodium, particularly at higher loads, had more adverse outcomes than patients with lower levels of Plasmodium. However, the presence of Plasmodium did not influence the innate immune response, and it is likely that the presence of EBOV dominated this response. Several viruses other than EBOV were identified, and bacteria associated with sepsis were also identified. These findings were indicative of bacterial translocation across the gut during the acute phase of EVD.
Journal Article > ResearchFull Text
N Engl J Med. 5 November 2014; Volume 372 (Issue 1); DOI:10.1056/NEJMoa1411249
Brah E, Lamah MC, Fletcher TE, Jacob S, Brett-Major D, et al.
N Engl J Med. 5 November 2014; Volume 372 (Issue 1); DOI:10.1056/NEJMoa1411249
Background In March 2014, the World Health Organization was notified of an outbreak of Zaire ebolavirus in a remote area of Guinea. The outbreak then spread to the capital, Conakry, and to neighboring countries and has subsequently become the largest epidemic of Ebola virus disease (EVD) to date. Methods From March 25 to April 26, 2014, we performed a study of all patients with laboratory-confirmed EVD in Conakry. Mortality was the primary outcome. Secondary outcomes included patient characteristics, complications, treatments, and comparisons between survivors and nonsurvivors. Results Of 80 patients who presented with symptoms, 37 had laboratory-confirmed EVD. Among confirmed cases, the median age was 38 years (interquartile range, 28 to 46), 24 patients (65%) were men, and 14 (38%) were health care workers; among the health care workers, nosocomial transmission was implicated in 12 patients (32%). Patients with confirmed EVD presented to the hospital a median of 5 days (interquartile range, 3 to 7) after the onset of symptoms, most commonly with fever (in 84% of the patients; mean temperature, 38.6°C), fatigue (in 65%), diarrhea (in 62%), and tachycardia (mean heart rate, >93 beats per minute). Of these patients, 28 (76%) were treated with intravenous fluids and 37 (100%) with antibiotics. Sixteen patients (43%) died, with a median time from symptom onset to death of 8 days (interquartile range, 7 to 11). Patients who were 40 years of age or older, as compared with those under the age of 40 years, had a relative risk of death of 3.49 (95% confidence interval, 1.42 to 8.59; P=0.007). Conclusions Patients with EVD presented with evidence of dehydration associated with vomiting and severe diarrhea. Despite attempts at volume repletion, antimicrobial therapy, and limited laboratory services, the rate of death was 43%.
Journal Article > LetterFull Text
Lancet. 17 October 2017; Volume 391 (Issue 10121); 700-708.; DOI:10.1016/S0140-6736(17)31795-6
Lamontagne F, Fowler RA, Adhikari NK, Murthy S, Brett-Major D, et al.
Lancet. 17 October 2017; Volume 391 (Issue 10121); 700-708.; DOI:10.1016/S0140-6736(17)31795-6
The 2013-16 Ebola virus disease outbreak in west Africa was associated with unprecedented challenges in the provision of care to patients with Ebola virus disease, including absence of pre-existing isolation and treatment facilities, patients' reluctance to present for medical care, and limitations in the provision of supportive medical care. Case fatality rates in west Africa were initially greater than 70%, but decreased with improvements in supportive care. To inform optimal care in a future outbreak of Ebola virus disease, we employed the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) methodology to develop evidence-based guidelines for the delivery of supportive care to patients admitted to Ebola treatment units. Key recommendations include administration of oral and, as necessary, intravenous hydration; systematic monitoring of vital signs and volume status; availability of key biochemical testing; adequate staffing ratios; and availability of analgesics, including opioids, for pain relief.