Acute severe asthma requiring invasive mechanical ventilation in the era of modern resuscitation techniques: A 10-year bicentric retrospective study.

PURPOSE: Patients with acute severe asthma (ASA) may in rare cases require invasive mechanical ventilation (IMV). However, recent data on this issue are lacking. MATERIALS AND METHODS: In this retrospective and bicentric study conducted on a 10 year period, we investigate the in-hospital mortality in patients with ASA requiring IMV. We compare this mortality to that of patients with other types of respiratory distress using a standardized mortality ratio (SMR) model. RESULTS: Eighty-one episodes of ASA requiring IMV were evaluated. Factors significantly associated with in-hospital mortality were cardiac arrest on day of admission, cardiac arrest as the reason for intubation, absence of decompensation risk factors, need for renal replacement therapy on day of admission, and intubation in pre-hospital setting. Non-survivors had higher SAPS II, SOFA, creatinine and lactate levels as well as lower blood pressure, pH, and HCO3 on day of admission. In-hospital mortality was 15% (n = 12). Compared to a reference population of 2,670 patients, the SMR relative to the SAPS II was very low at 0.48 (95% CI, 0.25-0.84). The only factor independently associated with in-hospital mortality was cardiac arrest on day of admission. In-hospital mortality was 69% in patients with cardiac arrest on day of admission and 4% in others (p < 0.01). Salvage therapies were given to 7 patients, sometimes in combination with each other: ECMO (n = 6), halogenated gas (n = 1) and anti-IL5 antibody (n = 1). Death occurred in only 2 of these 7 patients, both of whom had cardiac arrest on day of admission. CONCLUSION: Nowadays, the mortality of patients with ASA requiring IMV is low. Death is due to multi-organ failure, with cardiac arrest on day of admission being the most important risk factor. In patients who did not have cardiac arrest on day of admission the mortality is even lower (4%) which allows an aggressive management.

Chikungunya virus-associated encephalitis: A cohort study on La Réunion Island, 2005-2009.

OBJECTIVE: To estimate the cumulative incidence rate (CIR) of Chikungunya virus (CHIKV)-associated CNS disease during the La Réunion outbreak, and assess the disease burden and patient outcome after 3 years. METHODS: CHIKV-associated CNS disease was characterized retrospectively in a cohort of patients with positive CHIKV reverse transcriptase PCR or anti-CHIKV immunoglobulin M antibodies in the CSF and fulfilling International Encephalitis Consortium criteria for encephalitis or encephalopathy. Neurologic sequelae were assessed after 3 years. RESULTS: Between September 2005 and June 2006, 57 patients were diagnosed with CHIKV-associated CNS disease, including 24 with CHIKV-associated encephalitis, the latter corresponding to a CIR of 8.6 per 100,000 persons. Patients with encephalitis were observed at both extremes of age categories. CIR per 100,000 persons were 187 and 37 in patients below 1 year and over 65 years, respectively, both far superior to those of cumulated causes of encephalitis in the United States in these age categories. The case-fatality rate of CHIKV-associated encephalitis was 16.6% and the proportion of children discharged with persistent disabilities estimated between 30% and 45%. Beyond the neonatal period, the clinical presentation and outcomes were less severe in infants than in adults. CONCLUSIONS: In the context of a large outbreak, CHIKV is a significant cause of CNS disease. As with other etiologies, CHIKV-associated encephalitis case distribution by age follows a U-shaped parabolic curve.

Chikungunya fever: a clinical and virological investigation of outpatients on Reunion Island, South-West Indian Ocean.

BACKGROUND: Chikungunya virus (CHIKV) is responsible for acute febrile polyarthralgia and, in a proportion of cases, severe complications including chronic arthritis. CHIKV has spread recently in East Africa, South-West Indian Ocean, South-Asia and autochthonous cases have been reported in Europe. Although almost all patients are outpatients, medical investigations mainly focused on hospitalised patients. METHODOLOGY/PRINCIPAL FINDINGS: Here, we detail clinico-biological characteristics of Chikungunya (CHIK) outpatients in Reunion Island (2006). 76 outpatients with febrile arthralgia diagnosed within less than 48 hours were included by general practitioners during the CuraChik clinical trial. CHIK was confirmed in 54 patients and excluded in 22. A detailed clinical and biological follow-up was organised, that included analysis of viral intrahost diversity and telephone survey until day 300. The evolution of acute CHIK included 2 stages: the 'viral stage' (day 1-day 4) was associated with rapid decrease of viraemia and improvement of clinical presentation; the 'convalescent stage' (day 5-day 14) was associated with no detectable viraemia but a slower clinical improvement. Women and elderly had a significantly higher number of arthralgia at inclusion and at day 300. Based on the study clinico-biological dataset, scores for CHIK diagnosis in patients with recent febrile acute polyarthralgia were elaborated using arthralgia on hands and wrists, a minor or absent myalgia and the presence of lymphopenia (<1G/L) as major orientation criteria. Finally, we observed that CHIKV intra-host genetic diversity increased over time and that a higher viral amino-acid complexity at the acute stage was associated with increased number of arthralgia and intensity of sequelae at day 300. CONCLUSIONS/SIGNIFICANCE: This study provided a detailed picture of clinico-biological CHIK evolution at the acute phase of the disease, allowed the elaboration of scores to assist CHIK diagnosis and investigated for the first time the impact of viral intra-host genetic diversity on the disease course.

Serious acute chikungunya virus infection requiring intensive care during the Reunion Island outbreak in 2005-2006.

OBJECTIVE: To report the clinical and laboratory findings of adults with serious chikungunya virus acute infection hospitalized in an intensive care unit. DESIGN: Case series study from August 2005 to May 2006. SETTING: Medical intensive care unit, South Reunion Hospital. PATIENTS: We observed 33 episodes of confirmed acute chikungunya virus infection (chikungunya virus-IgM or reverse transcription-polymerase chain reaction positive in the serum) admitted to the intensive care unit. INTERVENTIONS: We collected cerebrospinal fluid, serum, and sometimes tissue samples from patients with suspected chikungunya fever in our intensive care unit. These samples underwent viral testing for evidence of acute chikungunya virus infection. MEASUREMENTS AND MAIN RESULTS: Of the 33 patients, 19 (58%) had chikungunya virus specific manifestations, 8 (24%) had associated acute infectious disease and 6 (18%) exacerbations of previous complaints. Among the chikungunya virus specific manifestations, we identified 14 cases of encephalopathy, one case each of myocarditis, hepatitis and Guillain Barré syndrome. Eighty-five percent of patients had a McCabe score = 1 (for nonfatal or no underlying disease). Mortality was 48%. CONCLUSIONS: Chikungunya virus infection may be responsible for very severe clinical presentation, including young patients with unremarkable medical histories. Chikungunya virus infection is strongly suspected to have neurologic, hepatic, and myocardial tropism leading to dramatic complications and high mortality rate.

On chikungunya acute infection and chloroquine treatment.

In recent issues, the efficacy of chloroquine (and the dosage that may be used) in the treatment of acute chikungunya infections was discussed. We have conducted a double-blind placebo-controlled randomized trial on the French Reunion Island (Indian Ocean), in which 27 patients received chloroquine and 27 patients received a placebo treatment. The chloroquine treatment consisted of 600 mg at day 1, 600 mg at days 2 and 3, and 300 mg at days 4 and 5. No significant difference between groups could be identified regarding the duration of febrile arthralgia or the decrease of viremia between day 1 and day 3. However, at day 200, patients who received chloroquine complained more frequently of arthralgia than those who received placebo (p < 0.01). In conclusion, our results suggest that there is currently no justification for the use of chloroquine to treat acute chikungunya infections.

[Chikungunya, La Réunion and Mayotte, 2005-2006: an epidemic without a story?]. / Chikungunya, La Réunion et Mayotte, 2005-2006: une epidémie sans histoire?

Many triggering factors for onset of emerging infectious diseases are now recognised, such as: globalisation, demographic increase, population movements, international trade, urbanisation, forest destruction, climate changes, loss in biodiversity, and extreme life conditions such as poverty, famine and war. Epidemic burden is often leading to disasters, in terms of human losses, as well as economic, political or social consequences. These outbreaks may jeopardize within a few weeks or months, industry, trade, or tourism. While dengue and its most severe forms (hemorrhagic and shock syndrome) is spreading all over the tropical world, another arbovirosis, chikungunya disease dramatically spread in Indian Ocean islands where 30 to 75% of population were infected in 2005 and 2006, and then extended its progression towards India, Sri Lanka, Indonesia, Malaysia, Maldives islands with more than a million people infected with the East-African strain, replacing the former Asian strain which was known to prevail more than 30 years ago in India. Patients experience sequelae with disability, work loss, and rarely severe outcome recently identified in La Réunion and Mayotte (French overseas territories). No country, no part of the world may consider itself as protected against such events. However, consequences of emerging or re-emerging diseases are more and more unacceptable when they impact the poorest countries of the world. Viruses, bacteria, as well as wild animals, birds, or arthropods are not stopped by borders. It is time now to promote barriers against infectious diseases, including prevention, anticipation, disease surveillance and research. This is not only for humanitarian reasons, but also for contributing to a sustainable development with equity for worldwide population. This report presents comprehensive actions taken in 2006 for tracing the epidemic and mobilise research, as requested to the task force set up by the Prime Minister by March 20, 2006.