SUMMARYIn April 2005, an outbreak of Chikungunya fever occurred on the island of Re´union in the Indian Ocean. During winter 2005, six patients developed meningoencephalitis and acute hepatitis due to Chikungunya virus. Our objectives were to determine the incidence and mortality of atypical Chikungunya viral infections and to identify risk factors for severe disease. A hospital-based surveillance system was established to collect data on atypical Chikungunya cases. Case reports, medical records and laboratory results were reviewed and analysed. We defined an atypical case as one in which a patient with laboratory-confirmed Chikungunya virus infection developed symptoms other than fever and arthralgia. We defined a severe atypical case as one which required maintenance of at least one vital function. We recorded 610 atypical cases of Chikungunya fever : 222 were severe cases, 65 affected patients died. Five hundred and forty-six cases had underlying medical conditions (of which 226 suffered from cardiovascular, 147 from neurological and 150 from respiratory disorders). Clinical features that had never been associated with Chikungunya fever were recorded, such as bullous dermatosis, pneumonia, and diabetes mellitus. Hypertension, and underlying respiratory or cardiological conditions were independent risk factors for disease severity. The overall mortality rate was 10 . 6 % and it increased with age. This is the first time that severe cases and deaths due to Chikungunya fever have been documented. The information presented in this article may assist clinicians in identifying the disease, selecting the treatment strategy, and anticipating the course of illness.

In January 2005, an epidemic of chikungunya fever broke out in the Comoro Islands and lasted until May 2005. In April, cases were also reported in Mayotte and Mauritius. On Réunion Island, the first cases were reported at the end of April. Surveillance of this epidemic required an adaptive system, which at first was based on active and retrospective case detection around the cases reported, then relied on a sentinel network when the incidence increased. Emerging and severe forms of infection were investigated. Death certificates were monitored. By April 2006, the surveillance estimate was 244,000 cases of chikungunya virus infection, including 123 severe cases and 41 of maternoneonatal transmission, with an overall attack rate of 35%. Chikungunya infection was mentioned on 203 death certificates and significant mortality was observed. This epidemic highlighted the need for a mutual strategy of providing information on arboviral diseases and their prevention and control between countries in the southwestern Indian Ocean.

BackgroundEbola 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 FindingsInclusion 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 i...

Although the acute manifestations of Chikungunya virus (CHIKV) illness are well-documented, few data exist about the long-term rheumatic outcomes of CHIKV-infected patients. We undertook between June and September 2006 a retrospective cohort study aimed at assessing the course of late rheumatic manifestations and investigating potential risk factors associated with the persistence of these rheumatic manifestations over 15 months. 147 participants (>16 yrs) with laboratory-confirmed CHIKV disease diagnosed between March 1 and June 30, 2005, were identified through a surveillance database and interviewed by telephone. At the 15-month-period evaluation after diagnosis, 84 of 147 participants (57%) self-reported rheumatic symptoms. Of these 84 patients, 53 (63%) reported permanent trouble while 31 (37%) had recurrent symptoms. Age ≥45 years (OR = 3.9, 95% CI 1.7–9.7), severe initial joint pain (OR = 4.8, 95% CI 1.9–12.1), and presence of underlying osteoarthritis comorbidity (OR = 2.9, 95% CI 1.1–7.4) were predictors of nonrecovery. Our findings suggest that long-term CHIKV rheumatic manifestations seem to be a frequent underlying post-epidemic condition. Three independent risk factors that may aid in early recognition of patients with the highest risk of presenting prolonged CHIKV illness were identified. Such findings may be particularly useful in the development of future prevention and care strategies for this emerging virus infection.

BackgroundIn 2014, Western Africa experienced an unanticipated explosion of Ebola virus infections. What distinguishes fatal from non-fatal outcomes remains largely unknown, yet is key to optimising personalised treatment strategies. We used transcriptome data for peripheral blood taken from infected and convalescent recovering patients to identify early stage host factors that are associated with acute illness and those that differentiate patient survival from fatality.ResultsThe data demonstrate that individuals who succumbed to the disease show stronger upregulation of interferon signalling and acute phase responses compared to survivors during the acute phase of infection. Particularly notable is the strong upregulation of albumin and fibrinogen genes, which suggest significant liver pathology. Cell subtype prediction using messenger RNA expression patterns indicated that NK-cell populations increase in patients who survive infection. By selecting genes whose expression properties discriminated between fatal cases and survivors, we identify a small panel of responding genes that act as strong predictors of patient outcome, independent of viral load.ConclusionsTranscriptomic analysis of the host response to pathogen infection using blood samples taken during an outbreak situation can provide multiple levels of information on both disease state and mechanisms of pathogenesis. Host biomarkers were identified that provide high predictive value under conditions where other predictors, such as viral load, are poor prognostic indicators. The data suggested that rapid analysis of the host response to infection in an outbreak situation can provide valuable information to guide an understanding of disease outcome and mechanisms of disease.Electronic supplementary materialThe online version of this article (doi:10.1186/s13059-016-1137-3) contains supplementary material, which is available to authorized users.