Ebola virus disease.

Ebolaviruses are pathogenic agents associated with a severe, potentially fatal, systemic disease in man and great apes. Four species of ebolaviruses have been identified in west or equatorial Africa. Once the more virulent forms enter the human population, transmission occurs primarily through contact with infected body fluids and can result in major epidemics in under-resourced settings. These viruses cause a disease characterised by systemic viral replication, immune suppression, abnormal inflammatory responses, major fluid and electrolyte losses, and high mortality. Despite recent progress on vaccines, and with no licensed prophylaxis or treatment available, case management is essentially supportive with management of severe multiple organ failure resulting from immune-mediated cell damage. The 2013-16 outbreak was classified by WHO as a Public Health Emergency of International Concern, which drew attention to the challenges of diseases caused by infections with ebolaviruses and questioned scientific, clinical, and societal preparation to handle future epidemics.

Severe malaria in Europe: an 8-year multi-centre observational study.

BACKGROUND: Malaria remains one of the most serious infections for travellers to tropical countries. Due to the lack of harmonized guidelines a large variety of treatment regimens is used in Europe to treat severe malaria. METHODS: The European Network for Tropical Medicine and Travel Health (TropNet) conducted an 8-year, multicentre, observational study to analyse epidemiology, treatment practices and outcomes of severe malaria in its member sites across Europe. Physicians at participating TropNet centres were asked to report pseudonymized retrospective data from all patients treated at their centre for microscopically confirmed severe Plasmodium falciparum malaria according to the 2006 WHO criteria. RESULTS: From 2006 to 2014 a total of 185 patients with severe malaria treated in 12 European countries were included. Three patients died, resulting in a 28-day survival rate of 98.4%. The majority of infections were acquired in West Africa (109/185, 59%). The proportion of patients treated with intravenous artesunate increased from 27% in 2006 to 60% in 2013. Altogether, 56 different combinations of intravenous and oral drugs were used across 28 study centres. The risk of acute renal failure (36 vs 17% p = 0.04) or cerebral malaria (54 vs 20%, p = 0.001) was significantly higher in patients ≥60 years than in younger patients. Respiratory distress with the need for mechanical ventilation was significantly associated with the risk of death in the study population (13 vs 0%, p = 0.001). Post-artemisinin delayed haemolysis was reported in 19/70 (27%) patients treated with intravenous artesunate. CONCLUSION: The majority of patients with severe malaria in this study were tourists or migrants acquiring the infection in West Africa. Intravenous artesunate is increasingly used for treatment of severe malaria in many European treatment centres and can be given safely to European patients with severe malaria. Patients treated with intravenous artesunate should be followed up to detect and manage late haemolytic events.

Acceptability and feasibility of home and hospital follow-up in Burkina Faso and Guinea: A mixed-method study among patients of the COVID-19 Coverage-Africa clinical trial.

Patient experiences and perspectives on trial participation and follow-up may influence their compliance with research procedures or negatively impact their well-being. We aimed to explore the acceptability and feasibility of home-based and hospital-based follow-up modalities among COVID-19 patients enrolled in the ANTICOV ANRS COV33 Coverage-Africa trial in Burkina Faso and Guinea. The trial (2021-2022) evaluated the efficacy of treatments to prevent clinical worsening among COVID-19 patients with mild to moderate symptoms. Patients were either based at home or hospitalized, as per national recommendations, and followed-up through face-to-face visits and phone calls. We conducted a mixed-methods sub-study administering a questionnaire to all consenting participants and individually interviewing purposively selected participants. We performed descriptive analyses of Likert scale questions for the questionnaires and thematic analysis for the interviews. We conducted framework analysis and interpretation. Of the 400 trial patients, 220 completed the questionnaire (n = 182 in Burkina Faso, n = 38 in Guinea) and 24 were interviewed (n = 16 and n = 8, respectively). Participants were mostly followed-up at home in Burkina Faso; all patients from Guinea were first hospitalized, then followed-up at home. Over 90% of participants were satisfied with follow-up. Home follow-up was considered acceptable if (i) participants perceived they were not severely ill, (ii) it was combined with telemedicine, and (iii) the risk of stigma could be avoided. Hospital-based follow-up was viewed as a way to prevent contamination of family members, but could be badly experienced when mandatory and conflicting with family responsibilities and commitments. Phone calls were seen as reassuring and as a way to ensure continuity of care. These overall positive findings support the development of home-based follow-up for mildly ill patients in West-Africa, provided that both emotional and cognitive factors at individual, familial/inter-relational, healthcare and national levels be addressed when planning the implementation of a trial, or developing any public health strategy.

Inhaled ciclesonide for outpatient treatment of COVID-19 in adults at risk of adverse outcomes: a randomised controlled trial (COVERAGE).

OBJECTIVES: To assess the efficacy of inhaled ciclesonide in reducing the risk of adverse outcomes in COVID-19 outpatients at risk of developing severe illness. METHODS: COVERAGE is an open-label, randomized controlled trial. Outpatients with documented COVID-19, risk factors for aggravation, symptoms for ≤7 days, and absence of criteria for hospitalization are randomly allocated to either a control arm or one of several experimental arms, including inhaled ciclesonide. The primary efficacy endpoint is COVID-19 worsening (hospitalization, oxygen therapy at home, or death) by Day 14. Other endpoints are adverse events, maximal follow-up score on the WHO Ordinal Scale for Clinical Improvement, sustained alleviation of symptoms, cure, and RT-PCR and blood parameter evolution at Day 7. The trial's Safety Monitoring Board reviewed the first interim analysis of the ciclesonide arm and recommended halting it for futility. The results of this analysis are reported here. RESULTS: The analysis involved 217 participants (control 107, ciclesonide 110), including 111 women and 106 men. Their median age was 63 years (interquartile range 59-68), and 157 of 217 (72.4%) had at least one comorbidity. The median time since first symptom was 4 days (interquartile range 3-5). During the 28-day follow-up, 2 participants died (control 2/107 [1.9%], ciclesonide 0), 4 received oxygen therapy at home and were not hospitalized (control 2/107 [1.9%], ciclesonide 2/110 [1.8%]), and 24 were hospitalized (control 10/107 [9.3%], ciclesonide 14/110 [12.7%]). In intent-to-treat analysis of observed data, 26 participants reached the composite primary endpoint by Day 14, including 12 of 106 (11.3%, 95% CI: 6.0%-18.9%) in the control arm and 14 of 106 (13.2%; 95% CI: 7.4-21.2%) in the ciclesonide arm. Secondary outcomes were similar for both arms. DISCUSSION: Our findings are consistent with the European Medicines Agency's COVID-19 task force statement that there is currently insufficient evidence that inhaled corticosteroids are beneficial for patients with COVID-19.

Post-exposure prophylaxis following high-risk contact with Ebola virus, using immunotherapies with monoclonal antibodies, in the eastern Democratic Republic of the Congo: an emergency use program.

INTRODUCTION: With the development of therapeutics and vaccine against Ebola virus disease (EVD), the question of post-exposure prophylaxis for high-risk contact has emerged. Immunotherapies (monoclonal antibodies [mAbs]) recently validated for treating infected patients appear to be a good candidate for protecting contacts. DESIGN: During the tenth EVD outbreak in the Democratic Republic of the Congo, we have administrated mAbs (Mab114 or REGN-EB3) to high and intermediate-risk contacts of EVD patients. RESULTS: Overall, 23 non-vaccinated contacts received mAbs after a median delay between contact and post-exposure prophylaxis of 1 day (interquartile range 1-2). All contacts were free of symptoms, and all had negative reverse transcriptase-polymerase chain reaction 14 days after the contact. CONCLUSION: Immunotherapies appear to be promising candidates to protect EVD contacts. Interaction with vaccine needs to be analyzed and a larger study on efficacy conducted.

An imported case of Chikungunya fever from Madagascar: use of the sentinel traveller for detecting emerging arboviral infections in tropical and European countries.

A major Chikungunya virus (CHIKV) epidemic affected the South-Western Indian Ocean islands in 2005. This major outbreak raised concerns about the possibility of the emergence of CHIKV infections in Europe as an autochthonous CHIKV outbreak occurred in the Ravenna region of Italy during the summer of 2007 and was linked to a viraemic index case originating in Kerala, India. This report highlights the need for surveillance in countries where such emerging infections could be introduced by returning travellers.

[Epidemic and emerging prone-infectious diseases: Lessons learned and ways forward]. / Qu'apprend-t-on de nouveau des épidémies émergentes ?

Africa along side with south-east Asia are the epicentres of emerging and epidemic prone-infectious diseases and megacity biosecurity threat scenarios. Massive mobility and reluctance in the populations exposed to epidemic and emerging prone-infectious diseases coupled by a weak health system made disease alert and control measures difficult to implement. The investigation of virus detection and persistence in semen across a range of emerging viruses is useful for clinical and public health reasons, in particular for viruses that lead to high mortality or morbidity rates or to epidemics. Innovating built facility to safely treat patients with highly pathogenic infectious diseases is urgently need, not only to prevent the spread of infection from patients to healthcare workers but also to offer provision of relatively invasive organ support, whenever considered appropriate, without posing additional risk to staff. Despite multiple challenges, the need to conduct research during epidemics is inevitable, and candidate products must continue undergoing rigorous trials. Preparedness including management of complex humanitarian crises with community distrust is a cornerstone in response to high consequence emerging infectious disease outbreaks and imposes strengthening of the public health response infrastructure and emergency outbreak systems in high-risk regions.

Reimbursement of malaria chemoprophylaxis for travellers from Europe to Sub-Saharan Africa: Cost-effectiveness analysis from the perspective of the French national health insurance system.

Among Western countries, France has the highest incidence of imported malaria cases, mostly from travellers visiting Sub-Saharan Africa (SSA). Despite related high costs of imported malaria assumed by the public French national health insurance system (FHS), the latter does not reimburse travellers for malaria chemoprophylaxis (MC). This study aims to analyzes, from the FHS perspective, the cost-effectiveness of a 65% reimbursement of MC costs (MC 65%) for French resident travellers, under the assumption that this reimbursement would lead to increased recourse to MC. For that purpose, a decision tree model was developed with variables obtained from the literature, including incidence of malaria among travellers in the absence of MC, probabilities of recourse to MC, MC effectiveness and costs and medical expenses for a case of imported malaria. Data analysis of 1,434,675 travellers to SSA in 2005 estimated, for MC 65% vs. MC 0%, incidence of malaria cases to be 3836 malaria cases (21 deaths)/year vs. 6321 cases (34 deaths)/year, respectively, and cost of Euro 47,071,687/year vs. Euro 17,416,955/year. Incremental cost of MC 65% related to MC 0% was Euro 11,933 per malaria case prevented and Euro 2,281,133 per malaria-related death prevented. Results generated by this model, which can be adapted for other European countries, should be an incentive for the FHS to favourably consider MC 65% for French residents travelling to SSA.

Haemoglobinuria in a 38-year-old French expatriate man living in Cameroon following artemisinin-based antimalarial treatment.

Massive haemoglobinuria is encountered rarely during the course of malaria. It is usually considered a diagnostic criterion for severe malaria, together with anaemia, acute renal failure and jaundice. Haemoglobinuria can also present among expatriates travelling to endemic areas following repeated exposure to quinoline or arylaminoalcohol drugs. A case is described of haemoglobinuria developing in a 38-year-old French expatriate diagnosed concurrently with numerous tropical infections, and treated on presumptive basis with an antimalarial regimen containing artemisinin derivatives. Haemoglobinuria resolved spontaneously within a few days. Although this case does not definitely indicate a causal link between haemoglobinuria and artemisinin derivatives, the risk of such infrequent side-effects should be taken into account in pharmacovigilance monitoring. Moreover, the patient illustrates the multifaceted pathology that can be encountered with tropical infections.

[Integrating clinical research into epidemic response: the field perspective in the Ebola experience]. / Intégrer la recherche clinique dans la réponse aux épidémies - Les leçons de l'expérience d'Ebola.

During the 2013-2016 west African Ebola outbreak that affected West Africa, accelerated clinical trials, testing unproven but promising and potentially lifesaving experimental interventions emerged as a key component of the global outbreak. In 2017, no Ebola medical countermeasures had proven antiviral efficacy in patients. However, in September 2014, the World Health Organization inventoried a list of potential drug candidates developed or repurposed with demonstrated antiviral efficacy in vitro or in animal models. Numerous therapeutics were considered or explored during the outbreak, including nucleoside and nucleotide analogues, nucleic acid-based drugs and immunotherapeutics. Drugs in clinical trials were tested within the framework of optimized supportive care with fluids and electrolytes and management of severe compromise of multiple organs resulting from viral cytopathology and immune-mediated cell damage. Assessment of those therapeutics with encouraging preliminary efficacy or safety profile, like the repurposed direct antiviral agent favipiravir or the combination of antibodies ZMapp requires further investigation to confirm their efficacy in humans, propose appropriate doses and evaluate the possibility of treatment combinations. During the lull before the next epidemic, major challenges for managing future Ebola epidemics include scientific, clinical and public health preparedness with establishment of innovative patient care and clinical research support in remote poor areas where Ebola and other deadly infectious diseases typically reemerge.

Onchocerciasis-associated limb swelling in a traveler returning from Cameroon.

Travelers to West Central Africa are at risk for infection with Onchocerca volvulus. We describe the case of an adventurous traveler who became infected with O volvulus after a 10-day stay in rural Cameroon. Two years after his return, he was diagnosed with a 3-month history of limb swelling with pruritus and fixed edema of the right arm. He was successfully treated by a single dose of ivermectin, with an additional treatment with doxycycline. The patient was followed-up during 1 year after therapy without relapse. Such travelers experiencing unusual dermatitis syndromes should prompt evaluation for onchocerciasis.

[Retrospective analysis of 107 imported adult cases of malaria. Experience report of uncomplicated falciparum malaria treatment in adults with oral atovaquone-proguanil]. / Analyse rétrospective de 107 cas de paludisme d'importation chez l'adulte. Intérêt de l'association orale atovaquone-proguanil dans le traitement de l'accès simple à Plasmodium falciparum.

OBJECTIVES: The principal aim of this study was to assess the efficacy of the combination of oral atovaquone and proguanil (AP) in routine treatment of uncomplicated falciparum malaria in recent visitors to the tropics. We also analyzed the epidemiologic, clinical and hematologic characteristics of these patients with imported malaria. METHODS: This retrospective study reviewed the records of 107 cases of imported malaria, treated in the Tropical Disease Unit of Bordeaux University Hospital (France). RESULTS: More than 75% had uncomplicated falciparum malaria; 10 developed complications, and one died. Average time from fever onset to first medical consultation was 4.8 days. Less than 10% had used physical measures of prevention against mosquito bites, and nearly 65% had not used chemoprophylaxis. The most frequent hematologic abnormalities were eosinopenia (84%) and thrombocytopenia (75%). In more than 30% of cases, another disease was also present. The oral AP combination was administered to more than 86% of patients with uncomplicated falciparum malaria (n=72). Tolerance was excellent and only one treatment failure was observed, associated with digestive disorders. CONCLUSION: Better information for travelers and general practitioners is required to reduce the number of cases of imported malaria and to shorten the delay between symptom onset and specific treatment. The oral AP combination appears to be a safe and effective treatment for uncomplicated imported falciparum malaria.

Atovaquone-proguanil versus chloroquine-proguanil for malaria prophylaxis in nonimmune pediatric travelers: results of an international, randomized, open-label study.

Atovaquone-proguanil has been shown to be effective and well tolerated for malaria prophylaxis in residents of countries of endemicity and in nonimmune adult travelers, but data about traveling children are limited. In a randomized, open-label, multicenter prophylaxis trial, 221 nonimmune pediatric travelers (age, 2-17 years) received either atovaquone-proguanil or chloroquine-proguanil. Safety and clinical outcome were evaluated 7, 28, and 60 days after travel. By posttravel day 7, a total of 39 (35%) of 110 atovaquone-proguanil and 41 (37%) of 111 chloroquine-proguanil recipients reported > or =1 adverse event. The data indicate that, over the course of treatment, fewer atovaquone-proguanil recipients had treatment-related adverse events (8% vs. 14%), including gastrointestinal complaints (5% vs. 10%). Two subjects discontinued prophylaxis because of drug-related adverse events; both had received chloroquine-proguanil. Observed compliance with prophylaxis was similar before and during travel, but it was higher for atovaquone-proguanil in the posttravel period. No study participant developed malaria. Atovaquone-proguanil was well tolerated and is an important addition to the limited arsenal of prophylactic agents available to children.