Hilde De Clerck

Emergence of Zaire Ebola Virus Disease in Guinea

In March 2014, the World Health Organization was notified of an outbreak of a communicable disease characterized by fever, severe diarrhea, vomiting, and a high fatality rate in Guinea. Virologic investigation identified Zaire ebolavirus (EBOV) as the causative agent. Full-length genome sequencing and phylogenetic analysis showed that EBOV from Guinea forms a separate clade in relationship to the known EBOV strains from the Democratic Republic of Congo and Gabon. Epidemiologic investigation linked the laboratory-confirmed cases with the presumed first fatality of the outbreak in December 2013. This study demonstrates the emergence of a new EBOV strain in Guinea.

The Contribution of Ebola Viral Load at Admission and Other Patient Characteristics to Mortality in a Médecins Sans Frontières Ebola Case Management Centre, Kailahun, Sierra Leone, June–October 2014

This paper describes patient characteristics, including Ebola viral load, associated with mortality in a Médecins Sans Frontières Ebola case management centre (CMC). Out of 780 admissions between June and October 2014, 525 (67%) were positive for Ebola with a known outcome. The crude mortality rate was 51% (270/525). Ebola viral load (whole-blood sample) data were available on 76% (397/525) of patients. Univariate analysis indicated viral load at admission, age, symptom duration prior to admission, and distance traveled to the CMC were associated with mortality (P < .05). The multivariable model predicted mortality in those with a viral load at admission greater than 10 million copies per milliliter (P < .05, odds ratio >10), aged ≥50 years (P = .08, odds ratio = 2) and symptom duration prior to admission less than 5 days (P = .14). The presence of confusion, diarrhea, and conjunctivitis were significantly higher (P < .05) in Ebola patients who died. These findings highlight the importance viral load at admission has on mortality outcomes and could be used to cohort cases with viral loads greater than 10 million copies into dedicated wards with more intensive medical support to further reduce mortality.

Unique human immune signature of Ebola virus disease in Guinea

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.

First Newborn Baby to Receive Experimental Therapies Survives Ebola Virus Disease

Abstract A neonate born to an Ebola virus–positive woman was diagnosed with Ebola virus infection on her first day of life. The patient was treated with monoclonal antibodies (ZMapp), a buffy coat transfusion from an Ebola survivor, and the broad-spectrum antiviral GS-5734. On day 20, a venous blood specimen tested negative for Ebola virus by quantitative reverse-transcription polymerase chain reaction. The patient was discharged in good health on day 33 of life. Further follow-up consultations showed age-appropriate weight gain and neurodevelopment at the age of 12 months. This patient is the first neonate documented to have survived congenital infection with Ebola virus.

Field evaluation of capillary blood samples as a collection specimen for the rapid diagnosis of Ebola virus infection during an outbreak emergency

This study demonstrated the applicability of capillary blood samples as clinical specimens for field diagnosis of Ebola virus infection in an outbreak emergency.

Risk of Misinterpretation of Ebola Virus PCR Results After rVSV ZEBOV–GP Vaccination

TO THE EDITOR—We would like to report on a recent false-positive Ebola polymerase chain reaction (PCR) result after postexposure prophylaxis (PEP) with the recombinant vesicular stomatitis virus (rVSV) Zaire Ebola virus–glycoprotein (ZEBOV–GP) vaccine. We believe this observation is important in light of ongoing vaccine and diagnostic developments sparked by the recent Ebola virus disease (EVD) epidemic. A physician working for Médecins Sans Frontières (MSF) was evacuated from Monrovia, Liberia, to Belgium on 4 December 2014. Two days earlier, she had accidentally pricked herself with an unused needle through 2 gloves that had been in contact with the skin of a patient confirmedwithEVD.Upon arrival inBrussels, she was asymptomatic but nonetheless immediately hospitalized at the SaintPierre University Hospital. The MSFOperational Center Brussels occupational physicians and the Belgian clinical Ebola expert team performed a risk assessment. Considering the limited options available for PEP in humans, the experience with post-exposure vaccination using a live-attenuated rVSV ZEBOV–GP in nonhuman primates [1], and a single report of PEP with this vaccine in a human [2], it was decided that a single dose (titer ≥1 × 10 pfu/mL) of the rVSV ZEBOV–GP vaccine (NewLink Genetics, Canada) would be administered. The next morning, the patient developed fever. Although the fever was likely attributable to an adverse reaction to the vaccine, the expert group agreed to immediately performmolecular testing for EVD. Blood samples collected immediately prior to and 16 hours after vaccination were sent to the Belgian National Reference Laboratory for Infectious and Tropical Diseases (Institute of Tropical Medicine, Antwerp) for analysis using 2 real-time (RT)-PCRs targeting different EBOV genes, according to the European guidelines [3]. An in-house RT-PCR (adapted from [4]), targeting EBOV–GP, and the commercially available RealStar filovirus RT-PCR (Altona Diagnostics GmbH, Hamburg, Germany), targeting the large polymerase gene, were used [5].The commercial PCR test was negative in both samples, while the in-house test was positive in the sample after vaccination (Figure 1A). Based on these results, the patient was considered as not infected. The patient fully recovered the following day. Subsequent PCR testing revealed that the in-house RT-PCR remained positive for up to 5 days after vaccination, which is longer than the 2 days previously reported [2] and most likely the result of the higher vaccine dose given. At day 6

Analysis of Diagnostic Findings From the European Mobile Laboratory in Guéckédou, Guinea, March 2014 Through March 2015

Background. A unit of the European Mobile Laboratory (EMLab) consortium was deployed to the Ebola virus disease (EVD) treatment unit in Guéckédou, Guinea, from March 2014 through March 2015. Methods. The unit diagnosed EVD and malaria, using the RealStar Filovirus Screen reverse transcription–polymerase chain reaction (RT-PCR) kit and a malaria rapid diagnostic test, respectively. Results. The cleaned EMLab database comprised 4719 samples from 2741 cases of suspected EVD from Guinea. EVD was diagnosed in 1231 of 2178 hospitalized patients (57%) and in 281 of 563 who died in the community (50%). Children aged <15 years had the highest proportion of Ebola virus–malaria parasite coinfections. The case-fatality ratio was high in patients aged <5 years (80%) and those aged >74 years (90%) and low in patients aged 10–19 years (40%). On admission, RT-PCR analysis of blood specimens from patients who died in the hospital yielded a lower median cycle threshold (Ct) than analysis of blood specimens from survivors (18.1 vs 23.2). Individuals who died in the community had a median Ct of 21.5 for throat swabs. Multivariate logistic regression on 1047 data sets revealed that low Ct values, ages of <5 and ≥45 years, and, among children aged 5–14 years, malaria parasite coinfection were independent determinants of a poor EVD outcome. Conclusions. Virus load, age, and malaria parasite coinfection play a role in the outcome of EVD.

Emerging Filoviral Disease in Uganda: Proposed Explanations and Research Directions

Outbreaks of Ebola and Marburg virus diseases have recently increased in frequency in Uganda. This increase is probably caused by a combination of improved surveillance and laboratory capacity, increased contact between humans and the natural reservoir of the viruses, and fluctuations in viral load and prevalence within this reservoir. The roles of these proposed explanations must be investigated in order to guide appropriate responses to the changing epidemiological profile. Other African settings in which multiple filoviral outbreaks have occurred could also benefit from such information.

Electrolyte and Metabolic Disturbances in Ebola Patients during a Clinical Trial, Guinea, 2015

Such abnormalities were common during infection and enabled accurate stratification of the risk for death. Electrolyte and Metabolic Disturbances in Ebola