Biochemical testing in a laboratory tent and semi-intensive care of Ebola patients on-site in a remote part of Guinea: a paradigm shift based on a bleach-sensitive point-of-care device.

BACKGROUND: During the West Africa Ebola virus disease (EVD) outbreak, a Belgian laboratory was deployed for supporting the Ebola treatment unit (ETU) of N'Zerekore, Guinea. Besides diagnosis of EVD and malaria, biochemical parameters were tested and used to guide supportive treatment of EVD. METHODS: To preserve analytes stability, lithium-heparin blood samples were analyzed using the i-STAT® point-of-care testing (POCT) handheld device without the viral inactivation step. To mitigate the risk of Ebola virus transmission, assays were performed inside a portable glovebox with strict biosafety procedures. RESULTS: Providing the medical staff with real-time biochemical data modified their therapeutic attitude, shifting from empiric to a semi-intensive laboratory-guided treatment of hydro-electrolytic disturbances, metabolic acidosis and/or impaired kidney function. As illustrated with representative EVD cases (n=8), optimized supportive treatment with intravenous fluid therapy and electrolyte replacement often helped correct these abnormalities. However, the harsh operating conditions, especially the use of bleach decontamination inside the glovebox, caused several technical failures and the final breakdown of the POCT device. CONCLUSIONS: POCT availability resulted in a paradigm shift in laboratory practice and care delivery at the N'Zerekore ETU. We conclude that there is urgent need for novel well-designed and validated POCT devices usable by non-expert operators in high ambient temperature and limited space. These devices should withstand regular and thorough decontamination by the personnel working on-site with life-threatening pathogens and be compatible with high biosafety level procedures. Such specific users' requirements need a European validation and standardization process of proposed solutions led by the EU Standardization Committee (CEN).

Aerial medical evacuation of health workers with suspected Ebola virus disease in Guinea Conakry-interest of a negative pressure isolation pod-a case series.

We report 4 cases of Health Workers (HW) suspected of having contracted Ebola Virus Disease (EVD), transported from the Alliance for International Medical Action (ALIMA) Ebola Treatment Centre (ETC) in N'Zerekore, Guinea to the Treatment Centre for Carers run by the medical corps of the French army in Conakry, the capital of Guinea, which was established on 17 January 2015 and closed on 7 July 2015. In total more than 500 HWs have died from EVD since the epidemic began. This mortality has had significant effects on the ability of local services to respond appropriately to the disaster. The HWs were transported by air in the "Human Stretcher Transit Isolator-Total Containment (Oxford) Limited" (HSTI-TCOL) negative pressure isolation pod. Medical evacuation of patients with suspected, potentially fatal, infectious diseases is feasible with the use of a light isolator for patients without critical dysfunctions.

Correction: Experimental Treatment with Favipiravir for Ebola Virus Disease (the JIKI Trial): A Historically Controlled, Single-Arm Proof-of-Concept Trial in Guinea.

[This corrects the article DOI: 10.1371/journal.pmed.1001967.].

Experimental Treatment with Favipiravir for Ebola Virus Disease (the JIKI Trial): A Historically Controlled, Single-Arm Proof-of-Concept Trial in Guinea.

BACKGROUND: Ebola virus disease (EVD) is a highly lethal condition for which no specific treatment has proven efficacy. In September 2014, while the Ebola outbreak was at its peak, the World Health Organization released a short list of drugs suitable for EVD research. Favipiravir, an antiviral developed for the treatment of severe influenza, was one of these. In late 2014, the conditions for starting a randomized Ebola trial were not fulfilled for two reasons. One was the perception that, given the high number of patients presenting simultaneously and the very high mortality rate of the disease, it was ethically unacceptable to allocate patients from within the same family or village to receive or not receive an experimental drug, using a randomization process impossible to understand by very sick patients. The other was that, in the context of rumors and distrust of Ebola treatment centers, using a randomized design at the outset might lead even more patients to refuse to seek care. Therefore, we chose to conduct a multicenter non-randomized trial, in which all patients would receive favipiravir along with standardized care. The objectives of the trial were to test the feasibility and acceptability of an emergency trial in the context of a large Ebola outbreak, and to collect data on the safety and effectiveness of favipiravir in reducing mortality and viral load in patients with EVD. The trial was not aimed at directly informing future guidelines on Ebola treatment but at quickly gathering standardized preliminary data to optimize the design of future studies. METHODS AND FINDINGS: Inclusion criteria were positive Ebola virus reverse transcription PCR (RT-PCR) test, age ≥ 1 y, weight ≥ 10 kg, ability to take oral drugs, and informed consent. All participants received oral favipiravir (day 0: 6,000 mg; day 1 to day 9: 2,400 mg/d). Semi-quantitative Ebola virus RT-PCR (results expressed in "cycle threshold" [Ct]) and biochemistry tests were performed at day 0, day 2, day 4, end of symptoms, day 14, and day 30. Frozen samples were shipped to a reference biosafety level 4 laboratory for RNA viral load measurement using a quantitative reference technique (genome copies/milliliter). Outcomes were mortality, viral load evolution, and adverse events. The analysis was stratified by age and Ct value. A "target value" of mortality was defined a priori for each stratum, to guide the interpretation of interim and final analysis. Between 17 December 2014 and 8 April 2015, 126 patients were included, of whom 111 were analyzed (adults and adolescents, ≥13 y, n = 99; young children, ≤6 y, n = 12). Here we present the results obtained in the 99 adults and adolescents. Of these, 55 had a baseline Ct value ≥ 20 (Group A Ct ≥ 20), and 44 had a baseline Ct value < 20 (Group A Ct < 20). Ct values and RNA viral loads were well correlated, with Ct = 20 corresponding to RNA viral load = 7.7 log10 genome copies/ml. Mortality was 20% (95% CI 11.6%-32.4%) in Group A Ct ≥ 20 and 91% (95% CI 78.8%-91.1%) in Group A Ct < 20. Both mortality 95% CIs included the predefined target value (30% and 85%, respectively). Baseline serum creatinine was ≥110 µmol/l in 48% of patients in Group A Ct ≥ 20 (≥300 µmol/l in 14%) and in 90% of patients in Group A Ct < 20 (≥300 µmol/l in 44%). In Group A Ct ≥ 20, 17% of patients with baseline creatinine ≥110 µmol/l died, versus 97% in Group A Ct < 20. In patients who survived, the mean decrease in viral load was 0.33 log10 copies/ml per day of follow-up. RNA viral load values and mortality were not significantly different between adults starting favipiravir within <72 h of symptoms compared to others. Favipiravir was well tolerated. CONCLUSIONS: In the context of an outbreak at its peak, with crowded care centers, randomizing patients to receive either standard care or standard care plus an experimental drug was not felt to be appropriate. We did a non-randomized trial. This trial reaches nuanced conclusions. On the one hand, we do not conclude on the efficacy of the drug, and our conclusions on tolerance, although encouraging, are not as firm as they could have been if we had used randomization. On the other hand, we learned about how to quickly set up and run an Ebola trial, in close relationship with the community and non-governmental organizations; we integrated research into care so that it improved care; and we generated knowledge on EVD that is useful to further research. Our data illustrate the frequency of renal dysfunction and the powerful prognostic value of low Ct values. They suggest that drug trials in EVD should systematically stratify analyses by baseline Ct value, as a surrogate of viral load. They also suggest that favipiravir monotherapy merits further study in patients with medium to high viremia, but not in those with very high viremia. TRIAL REGISTRATION: ClinicalTrials.gov NCT02329054.

Use of the intubating laryngeal mask airway in emergency pre-hospital difficult intubation.

AIM OF THE STUDY: While several techniques are used for the management of difficult intubation (DI) in planned conditions in the operating theatre, they are not always suitable or usable in pre-hospital emergencies. We decided to assess the intubating laryngeal mask airway (ILMA) after failure of tracheal intubation (TI) under direct laryngoscopy. MATERIAL AND METHODS: After emergency physicians of the mobile intensive care unit were trained (theory and training on manikin) in using the ILMA (Fastrach), prospective data were collected after each use from March 2002 to December 2005. Data included patient's age, clinical status, number of direct laryngoscopies before using ILMA, Cormack and Lehane grade, subjective and objective evaluation of ease of ILMA insertion and TI (analogue scale from 1 to 10, attempts required, failure rate). RESULTS: Over 46 months, the ILMA was used 45 times (24: cardio-respiratory arrest, 21: anaesthesia with rapid sequence induction). Median age was 59 years [range 20-86]. The number of direct laryngoscopy attempts was 3 [0-4] (76% Cormack 4). The success of ILMA insertion and TI were 96 and 91%, respectively. CONCLUSION: Emergency physicians were satisfied with using the ILMA. It allowed TI in 91% of cases of DI. The ILMA can be recommended to be included in the algorithm of DI in pre-hospital emergencies after initial training.