Association Between Increased Linezolid Plasma Concentrations and the Development of Severe Toxicity in Multidrug-Resistant Tuberculosis Treatment.

BACKGROUND: Treatment of multidrug-resistant (MDR) tuberculosis with linezolid is characterized by high rates of adverse events. Evidence on therapeutic drug monitoring to predict drug toxicity is scarce. This study aimed to evaluate the association of linezolid trough concentrations with severe toxicity. METHODS: We retrospectively assessed consecutive patients started on linezolid for MDR tuberculosis between 2011 and 2017. The primary outcome was severe mitochondrial toxicity (SMT) due to linezolid, defined as neurotoxicity or myelotoxicity leading to drug discontinuation. The impact of plasma linezolid trough concentrations >2 mg/L was assessed in multivariate Cox proportional hazards models including time-varying covariates. RESULTS: SMT occurred in 57 of 146 included patients (39%) at an incidence rate of 0.38 per person-year (95% confidence interval, .30-.49). A maximum linezolid trough concentration >2 mg/L was detected in 52 patients (35.6%), while the mean trough concentration was >2 mg/L in 22 (15%). The adjusted hazard ratio for SMT was 2.35 (95% confidence interval, 1.26-4.38; P = .01) in patients with a mean trough concentration >2 mg/L and 2.63 (1.55-4.47; P < .01) for SMT after the first detection of a trough concentration >2 mg/L. In an exploratory analysis, higher maximum trough concentrations were dose-dependently associated with toxicity, while lowering elevated trough concentrations did not restore baseline risk. CONCLUSIONS: Linezolid trough concentrations >2 mg/L are strongly associated with the development of severe treatment-emergent toxicity in patients treated for MDR tuberculosis. Pending further prospective evidence, an individual risk-benefit assessment on the continuation of linezolid treatment is warranted in any patient with trough concentrations >2 mg/L.

Positive intrathecal anti-Borrelia antibody synthesis: what are the implications for clinical practice? Clinical features and outcomes of 138 patients in a French multicenter cohort study.

We aimed to describe the clinical characteristics, management, and residual symptoms (RS) in patients with definite and possible Lyme neuroborreliosis (LNB). We conducted a retrospective French multicenter cohort study (2010-2020). Cases of LNB were defined as clinical manifestations attributed to LNB and a positive Borrelia-specific intrathecal antibody index (AI) ("possible" LNB) and with pleocytosis ("definite" LNB). Risk factors of RS were determined using a logistic regression model. We included 138 adult patients with a positive AI. Mean age was 59.5 years (± 14.7). The median duration of symptoms before diagnosis was 1.0 [0.5-4.0] months. The most frequent manifestation was radicular pain (n = 79, 57%). Complete cerebrospinal fluid (CSF) leukocyte analysis was available in 131 patients, of whom 72 (55%) had pleocytosis. Patients with definite LNB had a shorter duration of symptoms (median 1.0 [0.5-2.6] vs. 3.0 [0.6-7.0] months, p < 0.01) and more radicular pain (74% vs 44%, p < 0.01) than patients with possible LNB. At the last visit (median duration of follow-up: 70 [30-175] days), 74/124 patients (59.7%) reported RS, mostly radicular pain (n = 31, 25%). In multivariate analysis, definite LNB (OR = 0.21 [0.05-0.931], p = 0.039) and duration of symptoms less than 3 months (OR = 0.04 [0.01-0.37], p = 0.005) were protective factors against RS at last follow-up. Our study highlights the challenges of LNB management, especially for patients with a positive AI without pleocytosis, questioning whether LB is still ongoing or not. Early diagnosis and treatment are important to improve outcomes and to lower potential RS.

Intravenous Artesunate for the Treatment of Severe Imported Malaria: Implementation, Efficacy, and Safety in 1391 Patients.

BACKGROUND: Intravenous artesunate is the World Health Organization-recommended first-line treatment for severe malaria worldwide, but it is still not fully licensed in Europe. Observational studies documenting its safety and efficacy in imported malaria are thus essential. METHODS: We prospectively collected clinical and epidemiological features of 1391 artesunate-treated patients among 110 participant centers during the first 7 years (2011-2017) of a national program implemented by the French Drug Agency. RESULTS: Artesunate became the most frequent treatment for severe malaria in France, rising from 9.9% in 2011 to 71.4% in 2017. Mortality was estimated at 4.1%. Treatment failure was recorded in 27 patients, but mutations in the Kelch-13 gene were not observed. Main reported adverse events (AEs) were anemia (136 cases), cardiac events (24, including 20 episodes of conduction disorders and/or arrhythmia), and liver enzyme elevation (23). Mortality and AEs were similar in the general population and in people with human immunodeficiency virus, who were overweight, or were pregnant, but the only pregnant woman treated in the first trimester experimented a hemorrhagic miscarriage. The incidence of post-artesunate-delayed hemolysis (PADH) was 42.8% when specifically assessed in a 98-patient subgroup, but was not associated with fatal outcomes or sequelae. PADH was twice as frequent in patients of European compared with African origin. CONCLUSIONS: Artesunate was rapidly deployed and displayed a robust clinical benefit in patients with severe imported malaria, despite a high frequency of mild to moderate PADH. Further explorations in the context of importation should assess outcomes during the first trimester of pregnancy and collect rare but potentially severe cardiac AEs.

Compassionate Use of Hydroxychloroquine in Clinical Practice for Patients With Mild to Severe COVID-19 in a French University Hospital.

BACKGROUND: Data from nonrandomized studies have suggested that hydroxychloroquine could be an effective therapeutic agent against coronavirus disease 2019 (COVID-19). METHODS: We conducted an observational, retrospective cohort study involving hospitalized adult patients with confirmed, mild to severe COVID-19 in a French university hospital. Patients who received hydroxychloroquine (200 mg 3 times daily dosage for 10 days) on a compassionate basis in addition to standard of care (SOC) were compared with patients without contraindications to hydroxychloroquine who received SOC alone. A propensity score-weighted analysis was performed to control for confounders: age, sex, time between symptom onset and admission ≤ 7 days, Charlson comorbidity index, medical history of arterial hypertension, obesity, National Early Warning Score 2 (NEWS2) score at admission, and pneumonia severity. The primary endpoint was time to unfavorable outcome, defined as: death, admission to an intensive care unit, or decision to withdraw or withhold life-sustaining treatments, whichever came first. RESULTS: Data from 89 patients with laboratory-confirmed COVID-19 were analyzed, 84 of whom were considered in the primary analysis; 38 patients treated with hydroxychloroquine and 46 patients treated with SOC alone. At admission, the mean age of patients was 66 years, the median Charlson comorbidity index was 3, and the median NEWS2 severity score was 3. After propensity score weighting, treatment with hydroxychloroquine was not associated with a significantly reduced risk of unfavorable outcome (hazard ratio, 0.90 [95% confidence interval, .38-2.1], P = .81). Overall survival was not significantly different between the 2 groups (hazard ratio, 0.89 [0.23; 3.47], P = 1). CONCLUSION: In hospitalized adults with COVID-19, no significant reduction of the risk of unfavorable outcomes was observed with hydroxychloroquine in comparison to SOC. Unmeasured confounders may have persisted however, despite careful propensity-weighted analysis and the study might be underpowered. Ongoing controlled trials in patients with varying degrees of initial severity on a larger scale will help determine whether there is a place for hydroxychloroquine in the treatment of COVID-19. In hospitalized adults with COVID-19, no significant reduction of the risk of unfavorable outcomes was observed with hydroxychloroquine in comparison to SOC.

Initial Failure of Pristinamycin Treatment in a Case of Multidrug-Resistant Mycoplasma genitalium Urethritis Eventually Treated by Sequential Therapy.

ABSTRACT: We present a case of persistent Mycoplasma genitalium urethritis with documented macrolide and fluoroquinolone resistance, and we describe the A2062T mutation in the 23S rRNA gene, possibly associated with pristinamycin resistance. After several treatment failures and loss of the A2062T mutation, M. genitalium urethritis was finally cured by a sequential antibiotic treatment including minocycline.

Prevalence of hyposmia and hypogeusia in 390 COVID-19 hospitalized patients and outpatients: a cross-sectional study.

Anecdotal evidence rapidly accumulated during March 2020 from sites around the world that sudden hyposmia and hypogeusia are significant symptoms associated with the SARS-CoV-2 pandemic. Our objective was to describe the prevalence of hyposmia and hypogeusia and compare it in hospitalized and non-hospitalized COVID-19 patients to evaluate an association of these symptoms with disease severity. We performed a cross-sectional survey during 5 consecutive days in March 2020, within a tertiary referral center, associated outpatient clinic, and two primary care outpatient facilities in Paris. All SARS-CoV-2-positive patients hospitalized during the study period and able to be interviewed (n = 198), hospital outpatients seen during the previous month (n = 129), and all COVID-19-highly suspect patients in two primary health centers (n = 63) were included. Hospitalized patients were significantly more often male (64 vs 40%) and older (66 vs 43 years old in median) and had significantly more comorbidities than outpatients. Hyposmia and hypogeusia were reported by 33% of patients and occurred significantly less frequently in hospitalized patients (12% and 13%, respectively) than in the health centers' outpatients (33% and 43%, respectively) and in the hospital outpatients (65% and 60%, respectively). Hyposmia and hypogeusia appeared more frequently after other COVID-19 symptoms. Patients with hyposmia and/or hypogeusia were significantly younger and had significantly less respiratory severity criteria than patients without these symptoms. Olfactory and gustatory dysfunction occurs frequently in COVID-19, especially in young, non-severe patients. These symptoms might be a useful tool for initial diagnostic work-up in patients with suspected COVID-19.

Propensity Score Analysis of Artesunate Versus Quinine for Severe Imported Plasmodium falciparum Malaria in France.

BACKGROUND: Little is known on the use of artesunate compared with quinine for the treatment of imported malaria cases in nonendemic countries with a high level of care. Therefore, we compared the 2 treatments in terms of mortality and hospital and intensive care unit (ICU) discharge rates. METHODS: We analyzed the cohort of all severe imported malaria patients reported to the French National Reference Center from 2011 to 2017. After controlling for differences between quinine- and artesunate-treated individuals using the inverse probability of treatment weighting method, 28-day mortality rate was compared between the groups as well as hospital and ICU discharge rates using Kaplan-Meier estimation and weighted Cox proportional hazard models. RESULTS: Overall, 1544 patients were enrolled. Fifty patients died, 18 in the quinine group (n = 460) and 32 in the artesunate group (n = 1084), corresponding to death rates of 3.9% and 2.9%, respectively. No difference was evident between quinine and artesunate either in mortality or in hospital discharge rate, with hazard ratios (HRs) of 1.03 (95% confidence interval [CI], 0.47-2.25) and 1.12 (95% CI, 0.94-1.34), respectively. Artesunate was associated with a faster ICU discharge rate (HR, 1.18. 95% CI, 1.02-1.36). CONCLUSIONS: In a country with a high level of care, artesunate was associated with a shorter length of stay in the ICU, which supports the actual therapeutic transition; however, no difference was found in terms of mortality or in hospital discharge rates between artesunate- and quinine-treated patients.

Linezolid-Associated Neurologic Adverse Events in Patients with Multidrug-Resistant Tuberculosis, France.

Linezolid is one of the most effective drugs for treating multidrug-resistant tuberculosis (MDR TB), but adverse effects remain problematic. We evaluated 57 MDR TB patients who had received >1 dose of linezolid during 2011-2016. Overall, patients received 600 mg/day of linezolid for a median of 13 months. In 33 (58%) patients, neurologic or ophthalmologic signs developed, and 18 (32%) had confirmed peripheral neuropathy, which for 78% was irreversible at 12 months after the end of TB treatment despite linezolid withdrawal. Among the 19 patients who underwent ophthalmologic evaluation, 14 patients had optic neuropathy that fully reversed for 2. A total of 16 (33%) of 49 patients had a linezolid trough concentration >2 mg/L, and among these, 14 (88%) experienced adverse effects. No significant association was found between trough concentration and neurologic toxicity. These findings suggest the need to closely monitor patients for neurologic signs and discuss optimal duration of linezolid treatment.

Epidemiological and Clinical Characteristics of International Travelers with Enteric Fever and Antibiotic Resistance Profiles of Their Isolates: a GeoSentinel Analysis.

Enteric fever, caused by Salmonella enterica serovar Typhi (S Typhi) and S. enterica serovar Paratyphi (S Paratyphi), is a common travel-related illness. Limited data are available on the antimicrobial resistance (AMR) patterns of these serovars among travelers. Records of travelers with a culture-confirmed diagnosis seen during or after travel from January 2007 to December 2018 were obtained from GeoSentinel. Traveler demographics and antimicrobial susceptibility data were analyzed. Isolates were classified as nonsusceptible if intermediate or resistant or as susceptible in accordance with the participating site's national guidelines. A total of 889 travelers (S Typhi infections, n = 474; S Paratyphi infections, n = 414; coinfection, n = 1) were included; 114 (13%) were children of <18 years old. Most individuals (41%) traveled to visit friends and relatives (VFRs) and acquired the infection in South Asia (71%). Child travelers with S Typhi infection were most frequently VFRs (77%). The median trip duration was 31 days (interquartile range, 18 to 61 days), and 448 of 691 travelers (65%) had no pretravel consultation. Of 143 S Typhi and 75 S Paratyphi isolates for which there were susceptibility data, nonsusceptibility to antibiotics varied (fluoroquinolones, 65% and 56%, respectively; co-trimoxazole, 13% and 0%; macrolides, 8% and 16%). Two S Typhi isolates (1.5%) from India were nonsusceptible to third-generation cephalosporins. S Typhi fluoroquinolone nonsusceptibility was highest when infection was acquired in South Asia (70 of 90 isolates; 78%) and sub-Saharan Africa (6 of 10 isolates; 60%). Enteric fever is an important travel-associated illness complicated by AMR. Our data contribute to a better understanding of region-specific AMR, helping to inform empirical treatment options. Prevention measures need to focus on high-risk travelers including VFRs and children.

Imported loiasis in France: a retrospective analysis of 167 cases with comparison between sub-Saharan and non sub-Saharan African patients.

BACKGROUND: Imported loiasis is a rare cause of consultation at the return of stay in central Africa, which often poses difficult diagnostic and therapeutic questions to practitioners especially those who are unaccustomed to tropical medicine. These difficulties can lead to risks for the patients especially if inappropriate treatment is given. Large series of imported loiasis are scarce. METHODS: We retrospectively studied the data including outcome in patients diagnosed with imported loiasis between 1993 and 2013 in the Paris area on the basis of a parasitological diagnosis (microfilaremia > 1/ml and/or serologic tests). We compared sub-Saharan and non sub-Saharan African patients. RESULTS: Of the 177 identified cases, 167 could be analysed. Sex ratio was 1, mean age 41 years and 83% were sub-Saharan Africans. Cameroon was the main country of exposure (62%). Incubation time may be long (up to 18 months). Of the 167 cases, 57% presented with characteristic symptoms (Calabar swellings, creeping dermatitis, eyeworm) whereas 43% were diagnosed fortuitously. Microfilaremia was evidenced in 105 patients (63%), and specific antibodies in 53%. Compared to sub-Saharan Africans, other patients were presenting less frequently with eyeworm migration and microfilaremia whereas they had higher eosinophilia and positive serology. Prevalence of Calabar swellings was not significantly different between the two groups. Cure rates were 52% with ivermectin alone, and 77% with ivermectin followed by diethylcarbamazine. No severe adverse event was reported. CONCLUSIONS: Presentation of imported loiasis varies according to ethnicity. A systematic screening should be recommended in patients with potential exposure in endemic country. Treatment with ivermectin followed by diethylcarbamazine could be a valuable option.

Unusual subdural empyema in a homeless patient diagnosed by molecular approach: a case report.

BACKGROUND: We report a case of subdural empyema in a homeless patient caused by Bartonella quintana. B. quintana is a facultative intracellular bacteria for which bacterial growth is fastidious. The molecular biology approach has been a real help in establishing the diagnosis. CASE REPORT: A 59-years old homeless patient, with a history of chronic alcohol abuse, was brought to the emergency department with a massive subdural empyema. Extensive microbiological evaluation didn't reveal any pathogen in the pus collected before antibiotic treatment. B. quintana was detected in the pus from the empyema using a 16S rRNA-based PCR. Histology of intraoperative samples was consistent with the diagnosis and a serological assay was positive. The patient responded well to a treatment that included craniectomy with drainage of the loculated pus, total removal of the infected capsule and a combination of antibiotics. CONCLUSION: This unique case of B. quintana-related empyema illustrates the risk of secondary infection of subdural hematoma with B. quintana since such infections have recently reemerged, predominantly among the homeless populations. Patients with subdural empyema in at-risk populations should be systematically evaluated for B. quintana with an appropriate diagnostic approach involving molecular biology.

Mortality from malaria in France, 2005 to 2014.

IntroductionMalaria is a notifiable disease in all European Union and European Economic Area countries except Belgium and France, where only autochthonous malaria is notifiable. Although morbidity caused by malaria has been assessed, little is known about mortality incidence.ObjectiveOur aim was to estimate the number of imported malaria-related deaths in hospital in metropolitan France.MethodsWe matched individual deaths reported between 1 January 2005 and 31 December 2014 to the French National Reference Centre for malaria (FNRCm) with malaria-related deaths from two other sources: the French National Registry on medical causes of death and the French national hospital discharge database. A capture-recapture method with log-linear modelling was used. Age, sex and place of death stratification were applied to remove heterogeneity.ResultsThe estimated malaria-related deaths in metropolitan France during the study period were 205 (95% confidence interval (CI): 191-219). The annual mean number of malaria-related deaths was estimated at 21 (95% CI: 19-22). The FNRCm malaria-related deaths surveillance had a 38% sensitivity (95% CI: 32-44). Among 161 in-hospital individual malaria-related deaths reported from three data sources, the sex ratio (male to female) was 2.6. Median age of the patients was 57 years, ranging from 1 to 89 years.ConclusionThe pertinent finding of this report is that malaria-related death records were significantly less complete [corrected] than case records. Therefore, data comparison of imported malaria morbidity and mortality between countries should imperatively be assessed using standard indicators weighted according to the completeness of health surveillance systems.

Holistic Approach in Patients With Presumed Lyme Borreliosis Leads to Less Than 10% of Confirmation and More Than 80% of Antibiotic Failures.

BACKGROUND: There is no precise idea whether patients with chronic symptoms attributed to Lyme borreliosis (LB) have LB or another disease. METHODS: We evaluated patients consulting for a presumed LB with a holistic approach including presumptive treatment. We included symptomatic patients consulting for presumed LB. They were classified as confirmed LB when they met four criteria, and possible LB if three with a positive clinical response to presumptive treatment. RESULTS: Amongst the 301 patients, 275 (91%) were exposed to tick bites, and 165 (54%) were bitten by a tick. At presentation, 151 patients (50.1%) had already been treated with a median of one (1-22) course of antimicrobials, during 34 (28-730) days. Median number of symptoms was three (1-12) with a median duration of 16 (1-68) months. Median number of signs was zero (0-2). ELISA was positive in 84/295 (28.4%) for IgM and 86/295 (29.1%) for IgG, and immunoblot was positive in 21/191 (10.9%) for IgM and 50/191 (26.1 %) for IgG. Presumptive treatment after presentation failed in 46/88 patients (52%). Diagnosis of LB was confirmed in 29 patients (9.6%), and possible in 9 (2.9%). Of the 243 patients with non-LB diagnosis, diseases were psychological, musculoskeletal, neurological or other origin in 76 (31.2%), 48 (19.7%), 37 (15.2%) and 82 (33.7%) patients respectively. Patients with other diseases were significantly younger, having more symptoms, longest duration of symptoms, less clinical signs and less frequent LB positive serologies. CONCLUSIONS: Overdiagnosis and overtreatment of LB is worsening. Health authorities should investigate this phenomenon.

Outcomes of Bedaquiline Treatment in Patients with Multidrug-Resistant Tuberculosis.

Bedaquiline is recommended by the World Health Organization for the treatment of multidrug-resistant (MDR) and extensively drug-resistant (XDR) tuberculosis (TB). We pooled data from 5 cohorts of patients treated with bedaquiline in France, Georgia, Armenia, and South Africa and in a multicountry study. The rate of culture conversion to negative at 6 months (by the end of 6 months of treatment) was 78% (95% CI 73.5%-81.9%), and the treatment success rate was 65.8% (95% CI 59.9%-71.3%). Death rate was 11.7% (95% CI 7.0%-19.1%). Up to 91.1% (95% CI 82.2%-95.8%) of the patients experienced >1 adverse event, and 11.2% (95% CI 5.0%-23.2%) experienced a serious adverse event. Lung cavitations were consistently associated with unfavorable outcomes. The use of bedaquiline in MDR and XDR TB treatment regimens appears to be effective and safe across different settings, although the certainty of evidence was assessed as very low.

Treatment correlates of successful outcomes in pulmonary multidrug-resistant tuberculosis: an individual patient data meta-analysis.

BACKGROUND: Treatment outcomes for multidrug-resistant tuberculosis remain poor. We aimed to estimate the association of treatment success and death with the use of individual drugs, and the optimal number and duration of treatment with those drugs in patients with multidrug-resistant tuberculosis. METHODS: In this individual patient data meta-analysis, we searched MEDLINE, Embase, and the Cochrane Library to identify potentially eligible observational and experimental studies published between Jan 1, 2009, and April 30, 2016. We also searched reference lists from all systematic reviews of treatment of multidrug-resistant tuberculosis published since 2009. To be eligible, studies had to report original results, with end of treatment outcomes (treatment completion [success], failure, or relapse) in cohorts of at least 25 adults (aged >18 years). We used anonymised individual patient data from eligible studies, provided by study investigators, regarding clinical characteristics, treatment, and outcomes. Using propensity score-matched generalised mixed effects logistic, or linear regression, we calculated adjusted odds ratios and adjusted risk differences for success or death during treatment, for specific drugs currently used to treat multidrug-resistant tuberculosis, as well as the number of drugs used and treatment duration. FINDINGS: Of 12 030 patients from 25 countries in 50 studies, 7346 (61%) had treatment success, 1017 (8%) had failure or relapse, and 1729 (14%) died. Compared with failure or relapse, treatment success was positively associated with the use of linezolid (adjusted risk difference 0·15, 95% CI 0·11 to 0·18), levofloxacin (0·15, 0·13 to 0·18), carbapenems (0·14, 0·06 to 0·21), moxifloxacin (0·11, 0·08 to 0·14), bedaquiline (0·10, 0·05 to 0·14), and clofazimine (0·06, 0·01 to 0·10). There was a significant association between reduced mortality and use of linezolid (-0·20, -0·23 to -0·16), levofloxacin (-0·06, -0·09 to -0·04), moxifloxacin (-0·07, -0·10 to -0·04), or bedaquiline (-0·14, -0·19 to -0·10). Compared with regimens without any injectable drug, amikacin provided modest benefits, but kanamycin and capreomycin were associated with worse outcomes. The remaining drugs were associated with slight or no improvements in outcomes. Treatment outcomes were significantly worse for most drugs if they were used despite in-vitro resistance. The optimal number of effective drugs seemed to be five in the initial phase, and four in the continuation phase. In these adjusted analyses, heterogeneity, based on a simulated I2 method, was high for approximately half the estimates for specific drugs, although relatively low for number of drugs and durations analyses. INTERPRETATION: Although inferences are limited by the observational nature of these data, treatment outcomes were significantly better with use of linezolid, later generation fluoroquinolones, bedaquiline, clofazimine, and carbapenems for treatment of multidrug-resistant tuberculosis. These findings emphasise the need for trials to ascertain the optimal combination and duration of these drugs for treatment of this condition. FUNDING: American Thoracic Society, Canadian Institutes of Health Research, US Centers for Disease Control and Prevention, European Respiratory Society, Infectious Diseases Society of America.

Fatal Yellow Fever in Travelers to Brazil, 2018.

Yellow fever virus is a mosquito-borne flavivirus that causes yellow fever, an acute infectious disease that occurs in South America and sub-Saharan Africa. Most patients with yellow fever are asymptomatic, but among the 15% who develop severe illness, the case fatality rate is 20%-60%. Effective live-attenuated virus vaccines are available that protect against yellow fever (1). An outbreak of yellow fever began in Brazil in December 2016; since July 2017, cases in both humans and nonhuman primates have been reported from the states of São Paulo, Minas Gerais, and Rio de Janeiro, including cases occurring near large urban centers in these states (2). On January 16, 2018, the World Health Organization updated yellow fever vaccination recommendations for Brazil to include all persons traveling to or living in Espírito Santo, São Paulo, and Rio de Janeiro states, and certain cities in Bahia state, in addition to areas where vaccination had been recommended before the recent outbreak (3). Since January 2018, 10 travel-related cases of yellow fever, including four deaths, have been reported in international travelers returning from Brazil. None of the 10 travelers had received yellow fever vaccination.

Post-malaria neurological syndrome: four cases, review of the literature and clarification of the nosological framework.

BACKGROUND: Post-malaria neurological syndrome (PMNS) is a debated entity, defined by neurological complications following a post-malaria symptom-free period and a negative blood smear. Four cases of PMNS are hereby reported and a review the literature performed to clarify the nosological framework of this syndrome. METHODS: A French teaching hospital infectious diseases database was investigated for all PMNS cases occurring between 1999 and 2016 and the PubMed database for cases reported by other institutions after 1997. A case was defined by the de novo appearance of neurological signs following a post-malaria symptom-free period, a negative blood smear, and no bacterial or viral differential diagnoses. RESULTS: Four patients from the database and 48 from PubMed, including 4 following Plasmodium vivax infection were found matching the definition. In the institution, the estimated PMNS incidence rate was 1.7 per 1000 malaria cases overall. Of the 52 patients (mean age 33 years), 65% were men. Malaria was severe in 85% of cases, showed neurological involvement in 53%, and treated with quinine in 60%, mefloquine in 46%, artemisinin derivatives in 41%, antifolic drugs in 30%, doxycycline in 8% and other types in 8%. The mean symptom-free period was 15 days. PMNS signs were confusion (72%), fever (46%), seizures (35%), cerebellar impairment (28%), psychosis (26%), and motor disorders (13%). Cerebrospinal fluid analyses showed high protein levels in 77% (mean 1.88 g/L) and lymphocytic meningitis in 59.5% (mean 48 WBC/mm3) of cases. Electroencephalograms were pathological in 93% (14/15) of cases, and brain MRIs showed abnormalities in 43% (9/21) of cases with white matter involvement in 100%. Fourteen patients were treated with steroids. The 18 patients with follow-up data showed no sequelae. The mean time to recovery was 17.4 days. CONCLUSION: PMNS is a rare entity englobing neurological signs after severe or non-severe malaria. It appears after a symptom-free period. PMNS occurred following treatment of malaria with a wide range of anti-malarials. The disease is self-limiting and associated with good outcome. MRI patterns underline a possible link with acute disseminated encephalomyelitis (ADEM) or auto-immune encephalitis. Plasmodium falciparum and Plasmodium vivax should be added to the list of pathogens causing ADEM.

Travel-Associated Zika Virus Disease Acquired in the Americas Through February 2016: A GeoSentinel Analysis.

Background: Zika virus has spread rapidly in the Americas and has been imported into many nonendemic countries by travelers. Objective: To describe clinical manifestations and epidemiology of Zika virus disease in travelers exposed in the Americas. Design: Descriptive, using GeoSentinel records. Setting: 63 travel and tropical medicine clinics in 30 countries. Patients: Ill returned travelers with a confirmed, probable, or clinically suspected diagnosis of Zika virus disease seen between January 2013 and 29 February 2016. Measurements: Frequencies of demographic, trip, and clinical characteristics and complications. Results: Starting in May 2015, 93 cases of Zika virus disease were reported. Common symptoms included exanthema (88%), fever (76%), and arthralgia (72%). Fifty-nine percent of patients were exposed in South America; 71% were diagnosed in Europe. Case status was established most commonly by polymerase chain reaction (PCR) testing of blood and less often by PCR testing of other body fluids or serology and plaque-reduction neutralization testing. Two patients developed Guillain-Barré syndrome, and 3 of 4 pregnancies had adverse outcomes (microcephaly, major fetal neurologic abnormalities, and intrauterine fetal death). Limitation: Surveillance data collected by specialized clinics may not be representative of all ill returned travelers, and denominator data are unavailable. Conclusion: These surveillance data help characterize the clinical manifestations and adverse outcomes of Zika virus disease among travelers infected in the Americas and show a need for global standardization of diagnostic testing. The serious fetal complications observed in this study highlight the importance of travel advisories and prevention measures for pregnant women and their partners. Travelers are sentinels for global Zika virus circulation and may facilitate further transmission. Primary Funding Source: Centers for Disease Control and Prevention, International Society of Travel Medicine, and Public Health Agency of Canada.

Yellow fever in two unvaccinated French tourists to Brazil, January and March, 2018.

We report two yellow fever cases in unvaccinated French travellers in Brazil in January and March 2018, respectively; one exposed during an excursion in Minas Gerais and the other in Ilha Grande. Both presented with fever, hepatitis, thrombocytopenia and leucopenia. Yellow fever diagnosis was based on RT-PCR and serological tests. Both patients recovered within a few days. The increasing occurrence of cases in unvaccinated travellers highlights the need to reinforce vaccination recommendation for travellers at-risk.

[Syphilis: what's new?] / Syphilis : quoi de nouveau ?

Syphilis : what's new ? Syphilis is a sexually transmitted disease caused by Treponema pallidum. It is strongly resurgent since the end of the 1990s especially in the MSM community. The diagnosis is serological, sometimes confirmed by the direct examination of a mucocutaneous lesion. Neurological and ophthalmological localizations may be early and involve functional prognosis. Treatment normally relies on intramuscular benzathine penicillin or oral doxycycline. The effectiveness of the treatment is judged on the decrease of the quantitative VDRL.

Syphilis : quoi de nouveau ? La syphilis est une infection sexuellement transmissible (IST) due à une bactérie, Treponema pallidum. Elle est en forte recrudescence depuis la fin des années 1990, notamment dans la communauté homosexuelle. Le diagnostic est sérologique parfois confirmé par l'examen direct d'une lésion cutanéo-muqueuse. Les localisations neurologiques et ophtalmologiques peuvent être précoces et mettre en jeu le pronostic fonctionnel. Le traitement repose normalement sur la benzathine pénicilline retard par voie intramusculaire ou la doxycycline per os. L'efficacité du traitement se juge sur la décroissance du VDRL quantitatif.