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ABSTRACT Introduction Pediatric Hydrocephalus is a common disease in sub-Saharan Africa. In Mali, 350-400 new cases are diagnosed in our center yearly. With a total land mass of 1.241.000 km2, patients in remote areas must travel up to 1500km to access neurosurgical care. Hence, treatment and follow-ups of “shunted” patients are difficult. In this context, endoscopic third ventriculostomy with choroid plexus cauterization (ETV/CPC) provides an opportunity for an affordable and less-constraining treatment for hydrocephalus children under 12 months of age. Methods We performed a retrospective analysis of ETV/CPC performed on infants from July 2013 to January 2015. Patients were followed post operatively on Day 15, Month 6 and Month 12. Statistical analysis was conducted using Prism 9 GraphPad software. ETV successes were categorized according to the patient’s age in 03 groups: < 3 months, 3 - 6 months, and 6 - 12 months. Statistical significance was defined at p

Introduction: Intracranial suppurations are neoformed purulent collections including, in decreasing order, cerebral abscesses, subdural empyemas and extradural empyemas. Otorhinolaryngologic infections are one of the main causes, especially in older children and adolescents. We report 3 clinical cases of endocranial suppurations treated at the Mali Hospital. Clinical Cases: 1) Observation 1. IK was a 14-year-old boy, who was hospitalized in our department for fever, headache and left hemiplegia. The emergency brain scan showed a right frontal and interhemispheric subdural empyema associated with multifocal sinusitis. Surgical drainage associated with ceftriaxone: 100 mg/Kg/d in direct intravenous (DI), metronidazole: 10 mg/Kgs/12hours in slow intravenous (SI) for 15 days, gentamycin: 3 mg/Kgs/d in SI for 3 days, paracetamol 15 mg/Kgs/6hours in SI, 10% glucose serum: 100 ml/Kg/d were given. The bacteriological analysis of the pus came back sterile. The postoperative period was calm. 2) Observation 2. This was a 14-year-old boy with a history of headaches who was admitted to our department for left hemiplegia. An emergency brain scan showed a right pre-suppurative encephalitis associated with a right fronto-ethmoidal and maxillary sinusitis. He was put on ceftriaxone 100 mg/kg/d in DI for 21 days, gentamycin: 3 mg/Kg/d in SI for 3 days; metronidazole: 10 mg/kg/12hours in SI for 21 days, paracetamol: 15 mg/kg/6hours in SI. After 3 weeks of medical treatment, a follow-up brain scan revealed an interhemispheric and right subdural empyema. Surgical drainage was associated with the triple antibiotic therapy initially instituted. The bacteriological analysis of the pus was sterile. The postoperative course was calm. 3) Observation 3. N.M was an 11-year-old boy, who was admitted with fever and left hemiplegia. An emergency brain scan revealed a right hemispheric subdural empyema associated with an intracerebral abscess and pansinusitis. Surgical drainage associated with ceftriaxone 100 mg/kg/d in DI for 15 days, gentamycin; 3 mg/kg/d in SI for 3 days, metronidazole: 10 mg/kg/12hours in SI for 15 days and paracetamol: 15 mg/kg/6hours in SI were instituted. Staphylococcus aureus was isolated in the pus of the abscess. The postoperative course was calm. Conclusion: Endocranial suppurations of sinus origin are serious and frequent infections in children in developing countries. Its diagnosis must be evoked in front of any hemiplegia associated with a fever or headache and confirmed by a cerebral scanner.

Background: Reported cases of knife injuries to the head in children are rare. Here we describe a case of pediatric penetrating brain injury by knife (PPBIK) and review literature. The patient’s parents were informed that non-identifying information from the case would be submitted for publication, and they provided consent. Case Presentation: A 3-year-old boy presented to our emergency department with a knife penetrating the front of his head during play. Neurologic examination was normal. Radiograph in lateral view demonstrated a metallic knife entering frontal bone. Computed tomography (CT) scan showed small hemorrhage around the foreign body recognized, accompanied by small pneumocephalus. The knife was surgically removed and the dura was closed. He was discharged home after the surgery with normal neurological status. Conclusion: Only four cases of PPBIK have been reported in the literature. The adequate management of these types of injuries requires a correct neuroradiological evaluation.

Context: Cerebellar syndrome caused by disturbances of balance and coordination is not an uncommon neurological disorder. It has varied etiologies usually caused by tumor processes or suppurative collections. Vascular causes remain very rare, especially when it is a giant aneurysm of PICA representing 1% of intracranial aneurysms. Treating giant PICA aneurysms is a very difficult task for neurosurgeons because the surgical dissection can lead to severe damage due to the intimate relationship of PICA with the brainstem or nerve structures. We report a case of giant PICA aneurysm responsible for cerebellar syndrome successfully treated with surgery. The objective of this work is to draw the attention of practitioners to this unusual cause which can lead to diagnosis wandering and a lack of planning at the time of management. Case report: A 65 years old hypertensive patient was seen for a progressive disturbance of balance and walking disorder, but worsened in the last three months with no notion of fever. On admission, the patient was lucid, oriented in time and space and presented with static and kinetic cerebellar syndrome. Brain CT-scan without and with contrast revealed a tissular mass in the posterior fossa suggesting a tumor process, however, CT angiography showed a giant aneurysm of the PICA after reconstruction. A careful microdissection by a sub-occipital approach was decided. Opening the large cistern made it possible to visualize the aneurysm sack surrounded by a yellowish gliosis. The reclining and microdissection revealed the neck of the aneurysm, which was clipped to exclude the giant aneurysm in block. Postoperative follow-up was simple with progressive improvement in the cerebellar syndrome and walking over three months. Conclusion: Giant aneurysm of the PICA is rare. The localization in the posterior cerebral fossa can be confusing. Microsurgery gives a good result.

International audience

Introduction: Gold panning is the research and artisanal exploitation of gold in the auriferous areas (rivers or others). Traumatisms arising from these activities are due to severe spinal cord injury and generally affect young people in full activity. They constitute a real social handicap in Mali and even in Africa. The aim of our study is to share our expertise in the management of these vertebro-medullary traumasin these miners who currently escape to all controls in Mali. Material and Methods: From 2013 to 2016, 76 Traumatic Spine Cord Injuries (TSCI) were treated in the department of Neurosurgery of “Hopital du Mali”. There were 73 males (96.05%) versus 03 Females (3.95%), aged between 21 - 43 years old. Results: All of our patients were admitted with deficit differing from paraparesis to tetraplegia. According to Frankel scale, we found 59 patients with complete deficits (A grade, 77.63%), and incomplete deficits in 17 cases (12 grade B, 04 grade C, 01 grade D). The X-ray standard radiographies were done in 24 cases (31.58%) from which 02 patients had been operated with these data. CT scan centered on the injured spinal segment was performed in 74 cases (97.37%). The lumbar spine was affected in 39 cases, followed by thoracolumbar junction in 19 cases and thoracic spine in 16 cases. The cervical spine was only interested in two cases. Fractures dislocations are the most frequently lesions encountered in our series. The surgical approach was performed in 74 patients and 02 patients received conservative treatment. Conclusion: Traumatic Spinal Cord Injuries (TSCI) among miners are a real disaster in Mali and continue to plague thousands of families or increase the number of disabled people in our society. It is the only work, where the person concerned is making of his own grave. And according to witnesses, several miners remained at the bottom of the wells. Their prevention must first involve users by raising the awareness of local residents and traditional therapists, but also the country that must participate in regional development and ensure strict enforcement of regulatory measures. Our structure must have enough resources to acquire and treat these patients at any time.

International audience; Background: The pathophysiology of Ebola virus disease (EVD) is still poorly understood. This study aimed at identifying soluble biomarkers that inform on disease mechanisms.Methods: Fifty-four soluble mediators of the immune, coagulation, and endothelial system were measured in baseline and follow-up samples from hospitalized patients with EVD, using Luminex technology. Cross-sectional expression levels and changes over time were correlated with outcome. Results: Levels of circulating proinflammatory cytokines and chemokines, as well as markers of endothelial dysfunction and coagulopathy, were elevated on admission to hospital in patients who died from EVD as compared to survivors. These markers further increased in patients who died and/or decreased over time in survivors. In contrast, markers of gut integrity and T-cell response were higher in survivors and increased until discharge.Conclusions: Inflammatory response, endothelial integrity, gastric tissue protection, and T cell immunity play a role in EVD pathophysiology.

The purpose of the study was to weigh the community burden of chikungunya determinants on Reunion island. Risk factors were investigated within a subset of 2101 adult persons from a population-based cross-sectional serosurvey, using Poisson regression models for dichotomous outcomes. Design-based risk ratios and population attributable fractions (PAF) were generated distinguishing individual and contextual (i.e. that affect individuals collectively) determinants. The disease burden attributable to contextual determinants was twice that of individual determinants (overall PAF value 89.5% vs. 44.1%). In a model regrouping both categories of determinants, the independent risk factors were by decreasing PAF values: an interaction term between the reporting of a chikungunya history in the neighbourhood and individual house (PAF 45.9%), a maximal temperature of the month preceding the infection higher than 28.5 °C (PAF 25.7%), a socio-economically disadvantaged neighbourhood (PAF 19.0%), altitude of dwelling (PAF 13.1%), cumulated rainfalls of the month preceding the infection higher than 65 mm (PAF 12.6%), occupational inactivity (PAF 11.6%), poor knowledge on chikungunya transmission (PAF 7.3%) and obesity/overweight (PAF 5.2%). Taken together, these covariates and their underlying causative factors uncovered 80.8% of chikungunya at population level. Our findings lend support to a major role of contextual risk factors in chikungunya virus outbreaks.

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.

In 2015, favipiravir was administered on a compassionate-use basis to patients with Ebola virus disease in Guinea. This study reveals a trend toward improved survival in favipiravir-treated patients; however, the effect of treatment was not statistically significant, except for its influence on survival time., Background In 2015, the laboratory at the Ebola treatment center in Coyah, Guinea, confirmed Ebola virus disease (EVD) in 286 patients. The cycle threshold (Ct) of an Ebola virus–specific reverse transcription–polymerase chain reaction assay and 13 blood chemistry parameters were measured on admission and during hospitalization. Favipiravir treatment was offered to patients with EVD on a compassionate-use basis. Methods To reduce biases in the raw field data, we carefully selected 163 of 286 patients with EVD for a retrospective study to assess associations between potential risk factors, alterations in blood chemistry findings, favipiravir treatment, and outcome. Results The case-fatality rate in favipiravir-treated patients was lower than in untreated patients (42.5% [31 of 73] vs 57.8% [52 of 90]; P = .053 by univariate analysis). In multivariate regression analysis, a higher Ct and a younger age were associated with survival (P < .001), while favipiravir treatment showed no statistically significant effect (P = .11). However, Kaplan-Meier analysis indicated a longer survival time in the favipiravir-treated group (P = .015). The study also showed characteristic changes in blood chemistry findings in patients who died, compared with survivors. Conclusions Consistent with the JIKI trial, this retrospective study revealed a trend toward improved survival in favipiravir- treated patients; however, the effect of treatment was not statistically significant, except for its influence on survival time.

We present our experience of microsurgical treatment of pericallosal artery aneurysms (PCAA) in three neurosurgical centers in Abidjan (Ivory Coast) from 1990 to 2016. This present study aimed to evaluate characteristics of 6 patients with PCAA treated during a 26-year period and to establish the rate, clinical nuances, anatomical variations and respective microsurgical approaches of PCAA in Abidjan. We analyzed medical files of all 93 patients admitted for an intracranial aneurysm between 1990 and 2016 and focused on the 6 patients who were treated for a PCCA. The mean age of patients was 37 years, half of whom were less than 30 years old. They were 3 men and 3 women. The time from first symptom to admission was more than 3 days, but less than 16 days. Five out of six patients had ruptured aneurysms and the clinical condition on admission was WFNS grade 0 one patient (16.67%) and WFNS I-III five patients (83.33%). Analysis of radiological data revealed Fischer grade IV three patients and Fischer grade I-II three patients. A total of 7 PCCA were recorded and they accounted for 6.19% of all intracranial aneurysms and 9.72% of all anterior circulation aneurysms. Six out of seven aneurysms (85.71%) were either smaller (2 - 6 mm) or middle sized (6 - 15 mm). There was only one (14.29%) giant PCA aneurysm (>25 mm). According to the location, two aneurysms (28.57%) were located on the A2 segment of the pericallosal artery (PCA) and five (71.43%) on the A3 segment of the artery. We found 4 cases of saccular aneurysms (57.14%) and 3 cases of fusiform aneurysms (42.86%), two of which were located on A2 segments of the 2 PCA on the same patient (16.67%). We didn’t find any PCA anatomical variation associated with any of the 7 aneurysms. Two patients developed perioperative rebleeding and in 1 case a severe preoperative hydrocephalus was diagnosed. The median time from rupture to surgery was 59.5 days with a range of 14 to 180 days. Treatment techniques included 4 clipping (57.14%) and 3 wrapping (42.86%). In 2 cases there was premature perioperative rupture of the aneurysm (33.33%). One patient (16.67%) had postoperative persistent anosmia and, we didn’t record any fatal outcome in our series. PCAA remain rare anterior circulation aneurysms, located in the vast majority of cases, on the A3 segment of the PCA and, are mostly smaller in size even when ruptured. Microsurgical clipping remains a safe and effective treatment option despite their complex surgical approaches and the risk of premature rupture.

Background: By January, 2016, all known transmission chains of the Ebola virus disease (EVD) outbreak in west Africa had been stopped. However, there is concern about persistence of Ebola virus in the reproductive tract of men who have survived EVD. We aimed to use biostatistical modelling to describe the dynamics of Ebola virus RNA load in seminal fluid, including clearance parameters.Methods: In this longitudinal study, we recruited men who had been discharged from three Ebola treatment units in Guinea between January and July, 2015. Participants provided samples of seminal fluid at follow-up every 3–6 weeks, which we tested for Ebola virus RNA using quantitative real-time RT-PCR. Representative specimens from eight participants were then inoculated into immunodeficient mice to test for infectivity. We used a linear mixed-effect model to analyse the dynamics of virus persistence in seminal fluid over time.Findings: We enrolled 26 participants and tested 130 seminal fluid specimens; median follow up was 197 days (IQR 187–209 days) after enrolment, which corresponded to 255 days (228–287) after disease onset. Ebola virus RNA was detected in 86 semen specimens from 19 (73%) participants. Median duration of Ebola virus RNA detection was 158 days after onset (73–181; maximum 407 days at end of follow-up). Mathematical modelling of the quantitative time-series data showed a mean clearance rate of Ebola virus RNA from seminal fluid of −0·58 log units per month, although the clearance kinetic varied greatly between participants. Using our biostatistical model, we predict that 50% and 90% of male survivors clear Ebola virus RNA from seminal fluid at 115 days (90% prediction interval 72–160) and 294 days (212–399) after disease onset, respectively. We also predicted that the number of men positive for Ebola virus RNA in affected countries would decrease from about 50 in January 2016, to fewer than 1 person by July, 2016. Infectious virus was detected in 15 of 26 (58%) specimens tested in mice.Interpretation: Time to clearance of Ebola virus RNA from seminal fluid varies greatly between individuals and could be more than 13 months. Our predictions will assist in decision-making about surveillance and preventive measures in EVD outbreaks.Funding: This study was funded by European Union's Horizon 2020 research and innovation programme, Directorate-General for International Cooperation and Development of the European Commission, Institut national de la santé et de la recherche médicale (INSERM), German Research Foundation (DFG), and Innovative Medicines Initiative 2 Joint Undertaking.

Morel-Lavallee Lesions (MLL), described in 1863 by French surgeon Victor-Auguste-Francois Morel-Lavallee, are rare posttraumatic closed degloving injuries, occurring as a result of tangential sheer forces, in which the skin and subcutaneous tissue separate abruptly from the underlying deep fascia, causing fluid collection with liquefied fat. A 31-year-old policeman involved in a road traffic accident, presented with a gradually expanding lumbar swelling, which was soft, fluctuant and painful with contused skinon examination. Computed Tomography (CT) scan of the lumbar spine revealed a large subcutaneous hematoma on axial view, extending from the 12th thoracic vertebra down to the first sacral vertebra. There was no skeletal lesion. The treatment consisted of surgical excision/drainage of the collection followed by continuous suction with drainage tubes for two days. The collection is completely resolved; the patient made a full recovery and has been asymptomatic. Since there was a history of blunt trauma and given the nature and the location of the collection over osseous prominences, we report this rare case of a large posttraumatic lumbar hematoma diagnosed on clinical and CT scanning grounds as a Morel-Lavallee lesion. The patient was informed that non-identifying information from the case would be submitted for publication, and he provided consent.

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.

Our results highlight the identification of an array of pathogens in the blood of patients with Ebola virus disease (EVD). This has not been done before, and the data have important implications for the treatment of patients with EVD, particularly considering antibiotic stewardship. We show that EVD patients who were also infected with Plasmodium, particularly at higher loads, had more adverse outcomes than patients with lower levels of Plasmodium. However, the presence of Plasmodium did not influence the innate immune response, and it is likely that the presence of EBOV dominated this response. Several viruses other than EBOV were identified, and bacteria associated with sepsis were also identified. These findings were indicative of bacterial translocation across the gut during the acute phase of EVD., In this study, samples from the 2013–2016 West African Ebola virus outbreak from patients in Guinea with Ebola virus disease (EVD) were analyzed to discover and classify what other pathogens were present. Throat swabs were taken from deceased EVD patients, and peripheral blood samples were analyzed that had been taken from patients when they presented at the treatment center with acute illness. High-throughput RNA sequencing (RNA-seq) and bioinformatics were used to identify the potential microorganisms. This approach confirmed Ebola virus (EBOV) in all samples from patients diagnosed as acute positive for the virus by quantitative reverse transcription-PCR in deployed field laboratories. Nucleic acid mapping to Plasmodium was also used on the patient samples, confirming results obtained with an antigen-based rapid diagnostic test (RDT) conducted in the field laboratories. The data suggested that a high Plasmodium load, as determined by sequence read depth, was associated with mortality and influenced the host response, whereas a lower parasite load did not appear to affect outcome. The identifications of selected bacteria from throat swabs via RNA-seq were confirmed by culture. The data indicated that the potential pathogens identified in the blood samples were associated with translocation from the gut, suggesting the presence of bacteremia, which transcriptome data suggested may induce or aggravate the acute-phase response observed during EVD. Transcripts mapping to different viruses were also identified, including those indicative of lytic infections. The development of high-resolution analysis of samples from patients with EVD will help inform care pathways and the most appropriate general antimicrobial therapy to be used in a resource-poor setting. IMPORTANCE Our results highlight the identification of an array of pathogens in the blood of patients with Ebola virus disease (EVD). This has not been done before, and the data have important implications for the treatment of patients with EVD, particularly considering antibiotic stewardship. We show that EVD patients who were also infected with Plasmodium, particularly at higher loads, had more adverse outcomes than patients with lower levels of Plasmodium. However, the presence of Plasmodium did not influence the innate immune response, and it is likely that the presence of EBOV dominated this response. Several viruses other than EBOV were identified, and bacteria associated with sepsis were also identified. These findings were indicative of bacterial translocation across the gut during the acute phase of EVD.

During the large Ebola outbreak that affected West Africa in 2014 and 2015, studies were launched to evaluate potential treatments for the disease. A clinical trial to evaluate the effectiveness of the antiviral drug favipiravir was conducted in Guinea. This paper describes the main challenges of the implementation of the trial in the Ebola treatment center of Guéckédou. Following the principles of the Good Clinical Research Practices, we explored the aspects of the community's communication and engagement, ethical conduct, trial protocol compliance, informed consent of participants, ongoing benefit/risk assessment, record keeping, confidentiality of patients and study data, and roles and responsibilities of the actors involved. We concluded that several challenges have to be addressed to successfully implement a clinical trial during an international medical emergency but that the potential for collaboration between research teams and humanitarian organizations needs to be highlighted. ispartof: PLoS Neglected Tropical Diseases vol:11 issue:6 ispartof: location:United States status: published

Les medecins generalistes sont des acteurs majeurs dans la surveillance des maladies infectieuses, notamment a caractere epidemique. Une enquete a ete conduite a La Reunion deux ans apres l’epidemie de chikungunya (CHIK) de 2006 aupres de 100 medecins generalistes selectionnes a partir d’un echantillonnage aleatoire par choix raisonne. L’objectif de cette etude est de decrire et analyser les facteurs associes a l’implication des medecins dans la notification des cas de CHIK pendant la crise sanitaire. Le questionnaire a ete conduit en face a face, et une analyse uni-et multivariee des facteurs associes a la notification a ete executee. Soixante pour cent des participants ont declare ne pas avoir adhere a la notification des cas pendant l’epidemie. Le principal obstacle rapporte etait represente par la contrainte de disponibilite liee a l’afflux massif des patients affectes par l’epidemie. A l’inverse, l’exercice en cabinet de groupe etait en faveur de la notification. La majorite des repondants ont adhere aux recommandations officielles de prevention et de prise en charge, malgre une perception d’efficacite limitee. L’implication des medecins generalistes dans la surveillance des maladies a caractere epidemique doit etre renforcee par un partenariat preetabli construit sur des reseaux permettant une demarche proactive et volontaire. Cet objectif comprend la mobilisation et l’offre de formation continue en veille sanitaire.

The reported case fatality ratios (CFR) of Ebola virus disease (EVD) have been as high as 90% in previous outbreaks. While the cumulative CFR among patients medically evacuated and treated in Western countries was inferior to 20%, it peaked to approximately 75% between September and December 2014 in West Africa, thereafter decreasing to less than 40% (May 2015) without current evidence of major virus mutations capable to alter virus pathogenicity over the course of the epidemic. Therefore, the observed diminution of CFR is likely to reflect improvement of EVD patient care. Here, we summarize major lessons learned, that is, progresses and knowledge gaps, about the clinical management of patients in West African settings during the 2014-2016 outbreak.

We report on an Ebola virus disease (EVD) survivor who showed Ebola virus (EBOV) in seminal fluid 531 days after onset of disease. The persisting virus was sexually transmitted in February 2016, about 470 days after onset of symptoms, and caused a new cluster of EVD in Guinea and Liberia.

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, In the context the recent Ebola outbreak, Xavier Anglaret and colleagues test an experimental treatment, favipiravir, for Ebola virus disease in a multicenter non-randomized trial., Editors' Summary Background In 2014 and 2015, an Ebola virus outbreak larger than any known before occurred in West Africa. Ebola virus disease (EVD) is highly contagious, and many infected people die. Central to the emergency response to the recent outbreak were local Ebola treatment centers where patients were diagnosed, were isolated, and received supportive care. With thousands of patients dying and many health workers contracting the disease, fear was ubiquitous and distrust abundant. While conducting research in this environment was extremely challenging, the urgent need for treatments and the opportunity to conduct studies that could bring such treatments closer to reality was also recognized. In September 2014, WHO released a short list of existing drugs that were candidates for clinical trials among patients infected in the outbreak. Favipiravir, an antiviral drug developed in Japan for patients with severe influenza, was on the list. Why Was This Study Done? Because of the urgent need to find drugs that could reduce deaths caused by Ebola, the researchers decided to conduct a clinical trial using favipiravir in patients with EVD in Guinea. In view of the circumstances, they decided against a randomized controlled trial and instead designed a study where all participants would receive the same treatment. In randomized controlled trials only some participants receive the treatment in addition to standard care, while others serve as a control group and receive standard care only, or standard care plus a placebo. Such studies allow stronger conclusions to be drawn about whether a treatment is safe and whether it works or not. The researchers had two main reasons for this decision. First, patients from the same family or village often sought EVD treatment at the same time, and the researchers felt that it was ethically unacceptable to randomize such groups, with only some of them receiving the experimental drug. Second, the strict isolation procedures imposed to interrupt virus transmission had intensified fear in affected communities and fueled rumors of illicit drug experimentation and organ theft at the treatment centers. In this context, the researchers worried that a randomized study might increase distrust among the community and the reluctance of patients to seek care. Rather than seeking definitive answers about the safety and efficacy of favipiravir in patients with EVD, the objectives of the study as it was designed were to test the feasibility and acceptability of an emergency trial in the context of a large Ebola outbreak and to learn lessons from the experience. In addition, the researchers planned to collect data on the safety and effectiveness of favipiravir in reducing mortality and viral load in patients with EVD in the hope that their preliminary findings could improve the design of subsequent trials and the chance to provide conclusive answers. What Did the Researchers Do and Find? After 13 weeks of preparation, the trial took place from December 2014 to April 2015 at four separate Ebola treatment centers, three in rural areas and one in an urban setting. In addition to standard care (which included rehydration, antimalarial and antibacterial therapies, and medication to reduce fever, pain, and nausea), all participants were given favipiravir by mouth for ten days, at doses substantially higher than those recommended for patients with influenza. Outcomes measured were mortality, viral load changes over time (based on blood samples), and adverse events. EVD was confirmed with an assay that used patient blood and provided an estimate of the viral load, that is, of how much virus the blood contained. Because viral load was known to influence the course of EVD, the researchers analyzed the participants in two groups, namely, those with a viral load estimate above a certain threshold and those with viral load estimate below the threshold. They also used existing data from Guinean patients diagnosed with Ebola earlier in the outbreak who had received only standard care and calculated an expected mortality rate for patients above and below the viral load threshold. The researchers were able to enroll 126 participants in the trial. Of these, 111 were included in the final analysis. Of 99 adult and adolescent participants 13 years and older, 55 were in the lower viral load group and 44 in the higher viral load group. Mortality was 20% in the former and 91% in the latter. Neither mortality rate was significantly different from that of earlier patients who had received only standard care. The researchers also found that favipiravir was well tolerated. None of the patients stopped the course of treatment, vomiting following drug intake was rare, and no severe adverse events were attributed to the drug. The researchers did not see a difference in mortality between patients who reported onset of symptoms less than three days before the start of treatment and those whose symptoms had started more than three days the start of treatment. What Do these Findings Mean? The report shows that it is possible to conduct an emergency trial during an outbreak in a low-resource setting. In fact, at the time of its acceptance, this paper reported on an Ebola treatment trial larger than any other yet published. The experience described should be useful for similar undertakings in the future. The following conditions contributed to the success of the trial: close collaboration between researchers, local health officials, and affected communities on one hand, and flexibility in design, conduct, and analysis based on close monitoring and interim assessments on the other. Besides using interim results to influence the conduct and analysis of their own trial, the researchers also shared these results with the scientific community in real time, and this feedback influenced other research during the outbreak. The trial could not answer definitively whether favipiravir treatment was safe or reduced mortality in patients with EVD. The results suggest that the drug is unlikely to be beneficial for patients with very high viral loads, at least when given by itself. They also suggest that favipiravir is safe in patients with lower viral loads, and that in such patients additional efficacy studies are warranted. Intermediate analysis of various measurements in trial participants showed that the estimate of viral load from the field EVD diagnosis test is a good proxy for the actual viral load (determined after the samples were shipped to and analyzed in a reference laboratory in France) and suitable as a surrogate marker. The results also confirm that viral load is a strong predictor of mortality. Additional Information This list of resources contains links that can be accessed when viewing the PDF on a device or via the online version of the article at http://dx.doi.org/10.1371/journal.pmed.1001967. The World Health Organization has pages on Ebola virus disease, trials of Ebola treatments and vaccines, and the current update of the list of suitable drugs for testing or use in patients infected with Ebola (originally compiled in September 2014) US Centers for Disease Control and Prevention has information on the Ebola outbreak in West Africa The European Centre for Disease Prevention and Control also has information on the Ebola outbreak in West Africa

Malaria, which was eliminated first from Metropolitan France (mainland and Corsica), then in the French West Indies and the Reunion Island during the 20(th) century, remains endemic in two French territories: French Guiana and the Indian Ocean Mayotte island. Despite differences in the dominating plasmodial species and epidemiological patterns, these two territories have achieved marked quantitative improvements (in the reported number of cases and severe cases) thanks to efforts undertaken over the past decade. The situation, however, remains a concern from a qualitative standpoint with the emergence of resistance to antimalarial drugs and logistical and administrative issues which hinder access to treatment. Although malaria was eradicated in Metropolitan France half a century ago, competent vectors remain present in part or all of these territories and can give rise to limited outbreaks.

After a long period of endemicity until the 1950s, the World Health Organization considered autochthonous malaria eliminated from Reunion in 1979. To prevent secondary transmission and re-emergence of autochthonous malaria, permanent epidemiologic and entomological surveillance and vector control measures are conducted. The objective of this study is to report sociodemographic characteristics of imported malaria patients and incidence rates from 2003-2008 using mandatory notification with the aim of identifying risk groups and destinations. During this period, 684 imported malaria cases were reported. Median age of patients was 34.4 years and 22.1% were children

Resume Objectifs Une epidemie de rougeole est survenue en 2005–2006 a Mayotte. L’objectif de cette etude etait de decrire l’epidemie, d’analyser les caracteristiques epidemiologiques et sociodemographiques des cas et de proposer des recommandations pour la surveillance et la prevention de la rougeole. Patients et methode Une investigation epidemiologique autour des cas a ete realisee et un systeme de surveillance passif renforce des cas incidents a ete mis en place. Resultats Mille deux cent soixante-neuf cas cliniques dont 156 (12,3 %) cas confirmes biologiquement ont ete rapportes. Le taux d’attaque etait de 0,71 % et aucun deces par rougeole n’a ete signale. L’âge median des malades etait de 12 ans et le sex-ratio homme/femme de 1,1. La classe d’âge la plus representee etait celle des 10–19 ans avec 44,4 % des cas et les enfants de moins d’un an representaient 21,6 % des cas. Parmi les 1269 cas de rougeole, 27,3 % malades avaient eu au moins une dose de vaccin antirougeole avant l’epidemie. La couverture vaccinale a la fin de la campagne de vaccination realisee chez les enfants scolarises entre le 16 janvier et le 15 fevrier 2006 etait de 59,1 %. Conclusion A l’avenir, cette couverture vaccinale doit etre amelioree pour prevenir ces foyers epidemiques, notamment chez les groupes vulnerables de migrants. La detection d’eventuelles epidemies de rougeole survenant a Mayotte necessite egalement la mise en place d’un systeme de surveillance reposant sur le signalement precoce systematique et la confirmation biologique de tous les cas.

In an effort to evaluate the potential of non-specific immunotherapy in restoring global immunity, we have examined the clinical tolerance and biological effects of a 6 week administration of the immunomodulator, murabutide, in chronically infected HIV-1 patients. Forty-two subjects, presenting weak immune reconstitution and ineffective virus suppression following long-term highly active antiretroviral therapy (HAART), were randomized to receive, or not, murabutide 7 mg/day on five consecutive days/week. Clinical and immunological parameters were monitored before and after the immunotherapy period. Administration of murabutide was generally well tolerated, although some grade III adverse events, reversible on treatment cessation, were observed. Interestingly, in comparison with pre-inclusion levels, at 1 week after the immunotherapy cycle, only murabutide recipients presented a significant increase in CD4 cells, platelet counts, and in the percentage of patients with undetectable viral loads (

Objectifs : la double dispensation des antiretroviraux en France est possible depuis octobre 1997. Un an plus tard, nous avons mene une enquete aupres de patients et de pharmaciens de la metropole lilloise pour decrire l’impact de cette mesure. Materiels et methodes : interview d’un echantillon representatif de pharmaciens d’officine et de personnes infectees par le VIH de la region lilloise. Resultats : un echantillon de 100 pharmaciens d’officine a ete interviewe. La plupart sont installes dans une zone urbaine avec une clientele plutot de quartier. La majorite d’entre eux ressentent l’infection a VIH comme une maladie commune et considerent la delivrance des antiretroviraux comme une mission de sante publique, malgre des benefices financiers tres faibles. Deux tiers d’entre eux ont suivi une formation sur l’infection par le VIH et la plupart reconnaissent l’importance d’une bonne adhesion au traitement. Cependant, le nombre d’antiretroviraux et de classes d’antiretroviraux disponibles est mal connu.Parmi les 97 patients interroges suivis dans le Service des Maladies Infectieuses du Centre Hospitalier de Tourcoing, 22 % vont chercher leurs medicaments en officine de ville, 62 % a la pharmacie de l’hopital et 16 % aux deux endroits. Cependant, 39 % recoivent au moins une molecule uniquement disponible a l’hopital. Les patients allant en officine de ville soulignent une amelioration de leur qualite de vie. En ville, ils choisissent la plupart du temps leur pharmacie habituelle et preferent etre servis normalement plutot que secretement. La majorite de ceux allant en pharmacie hospitaliere expliquent leur choix en raison d ’une meilleure confidentialite. Le manque de confidentialite en ville est egalement ressenti par les pharmaciens d’officine. L’accueil en ville est considere comme meilleur, l’attente moins longue mais les competences du pharmacien d’officine sont jugees legerement inferieures a celles du pharmacien hospitalier. Enfin, la notion d’adhesion au traitement est peu abordee en officine de ville.Les patients et les pharmaciens d’officine apprecient la possibilite de double dispensation. L’impact est limite par l’impossibilite de trouver en ville certains antiretroviraux, disponibles uniquement a l’hopital. L’adhesion au traitement n’est pas souvent evoquee par le pharmacien d’officine et des progres pourraient etre faits en ce domaine.

A 9-month-old infant died from Ebola virus (EBOV) disease with unknown epidemiological link. While her parents did not report previous illness, laboratory investigations revealed persisting EBOV RNA in the mother’s breast milk and the father’s seminal fluid. Genomic analysis strongly suggests EBOV transmission to the child through breastfeeding.

BackgroundAlthough Dengue virus (DENV) circulation had been documented in neighbouring South-western Indian Ocean Islands, its presence in Mayotte is poorly characterised. To address this issue, we aimed to assess the seroprevalence of dengue IgG antibodies (DENV-IgG Ab) among the population and to investigate potential associations with individual and household characteristics.Methods/principal findingsIn November-December 2006 we conducted a cross-sectional serologic survey in Mayotte among 1,154 inhabitants aged≥2 years by using a multistage cluster random sampling method. The overall prevalence of DENV-specific IgG antibodies (ELISA) was 22.73% (95% CI, 18.16-27.31). The age-specific seroprevalence increased with age (χ2 for trend=11.86, PConclusionsThese findings document substantial prior exposure of the population of Mayotte to DENV and highlight the risk of severe illness due to the possibility of sequential DENV infections. Further investigations characterizing current DENV circulation patterns and associated serotypes are needed.

Aim Mayotte, a French overseas territory located in the Indian Ocean, has never had a previous estimate of diabetes prevalence, but has recently undergone socioeconomic changes leading to lifestyle modifications. For this reason, a survey was carried out in 2008 to estimate the prevalence of diabetes and cardiovascular risk factors in the island's population. Methods A three-step, randomized sample of 1268 individuals, aged 30–69 years, was home-screened, using capillary blood glucose and capillary HbA 1c , weight, height, waist circumference and two blood-pressure measurements. Those with a history of diabetes, glucose ≥1g/L (fasting) or ≥1.40g/L (non-fasting), or HbA 1c ≥6%, and a subgroup of those with normal results were examined at a healthcare centre to measure venous HbA 1c and glucose, and to diagnose diabetes, using an oral glucose tolerance test. Results The weighted prevalence of diabetes (venous plasma glucose ≥1.26g/L at fasting and/or ≥2g/L at 2h, or treatment with oral hypoglycaemic agents or insulin) was 10.5% (95% CI: 8.2–13.4%). This increased with age from 3% at age 30–39 years to 26% at age 60–69 years, with no gender differences. Also, more than 50% of those with diabetes were unaware of it, while half of those treated for diabetes still had HbA 1c levels >7%. The prevalence of overweight (BMI: 25–29kg/m 2 ) was estimated to be 35% in men and 32% in women, while obesity (≥30kg/m 2 ) was estimated to be 17% in men and 47% in women. Conclusion The high prevalence of obesity combined with a high prevalence of diabetes indicates a potential for further increases in the prevalence of diabetes and cardiovascular disease in Mayotte. Preventative action against obesity, diabetes and hypertension is required now, as well as plans for appropriate healthcare delivery in the island.

Summary Background To record and assess the clinical features of chikungunya fever (CHIKF), with a view to enable diagnosis based on clinical criteria rather than costly laboratory procedures in field conditions. Methods As part of a cross-sectional serologic survey conducted in Mayotte after a massive chikungunya outbreak in 2006, we collected data on clinical features of chikungunya infection and assessed the performance and accuracy of clinical case definition criteria combining different symptoms. Results Of 1154 participants included, 440 (38.1%) had chikungunya-specific IgM or IgG antibodies by enzyme-linked immunosorbent assay (ELISA). Of symptomatic participants, 318 (72.3%) had confirmed chikungunya, the dominant symptoms reported were incapacitating polyarthralgia (98.7%), myalgia (93.1%), backache (86%), fever of abrupt onset (85%) and headache (81.4%). There was a strong linear association between symptomatic infection and age (χ2 for trend = 9.85, P

Background In 2005–2006, a major epidemic of CHIKV infection occurred in the Islands of the south-western Indian Ocean, and longstanding manifestations seemed to be more frequent than described before. Objectives To describe the frequency and related factors of late clinical manifestations of CHIKV infection among imported cases living in Aquitaine area, France. Study design All patients recruited through the travel clinic and tropical medicine unit of the University Hospital Centre of Bordeaux with possible CHIKV infection were prospectively recorded, and confirmed cases of CHIKV infection were interviewed 2 years after infection. Factors associated with the persistence of symptoms were determined by multivariate logistic regression. Results Among the 29 cases followed, 17 still suffered from arthralgia 2 years after infection, and most of them had never recovered from the initial phase of the condition. The risk of persistent arthralgia tended to be higher among subjects with low educational level, subjects infected in the Reunion Island, and when initial phase lasted 30 days or more and was characterised by a severe pain. Conclusions Consistent with previous studies, our findings showed worsened late manifestations among patients returning from Indian Ocean area. Persistence of symptoms tended to be linked with clinical burden during the acute phase, which can be informative for early recognition and management of patients at risk for developing persistent rheumatic symptoms. Cryoglobulins failed to be identified in seronegative patients with invalidating dengue-like syndrome.

After the 2006–2007 epidemic wave of Rift Valley fever (RVF) in East Africa and its circulation in the Comoros, laboratory case-finding of RVF was conducted in Mayotte from September 2007 through May 2008. Ten recent human RVF cases were detected, which confirms the indigenous transmission of RFV virus in Mayotte.

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., Author Summary Transmitted by day-biting mosquitoes, Chikungunya virus (CHIKV), causing febrile illness and joint pain, is widespread in Africa and Asia. Recent outbreaks in the Indian Ocean islands, its rapid expansion across continents, and its unusual clinical acute pattern have shed light on and brought awareness of this re-emerging virus. However, late rheumatic manifestations of this infection remain poorly examined. Thus, we have evaluated over a 15-month period the evolution and assessed potential risk factors of CHIKV-related rheumatic manifestations in a cohort of Reunion Island residents infected with CHIKV during the initial phase of the epidemic in 2005. Eligible adult patients were identified through a surveillance database. We found that rheumatic symptoms lasted for at least 15 months in 57% of the participants. Of these, 63% reported permanent trouble while 37% had recurrent symptoms. Factors such as age ≥45 years, severe initial joint pain, and presence of underlying osteoarthritis comorbidity were associated with nonrecovery over the 15-month period. Our findings suggest that long-term CHIKV rheumatic manifestations seem to be a hidden, frequent, post-epidemic condition. These findings should be considered in the development of preventive measures.

SUMMARYIn April 2005, an outbreak of Chikungunya fever occurred on the island of Réunion 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.