Why are people still dying of drug-susceptible TB in Paris in the 21st century?

BACKGROUND: Although the burden of TB is lower in France than in low-income countries, patients continue to die from TB in Paris. Our goal was to describe TB-related deaths and to identify associated risk factors.METHODS: We conducted a retrospective cohort study in two hospitals in Paris between 2013 and 2018. All patients with drug-susceptible TB were included and followed until end of treatment. The primary outcome was death. We performed univariate and multivariate analysis using Cox proportional hazard model.RESULTS: Of the 523 patients included, 362 were men (median age 37 years), of whom 24 patients died (4.5%). The final survival model concluded that age (HR 1.1 for each additional year), not living in one´s own accommodation (HR 5.9), being born in France (HR 8.0), being alcoholic (HR 4.2), having a history of cancer (HR 7.1) or meningeal or miliary TB (HR 8.2) were associated with a higher risk of death.CONCLUSION: The rate of TB-associated death is unacceptably high for a curable disease. To note, patients born in France were much more at risk of death than immigrants. We believe raising awareness among healthcare professionals is a potentially easy and efficient lever for improving care.

High performance of a novel antigen detection test on nasopharyngeal specimens for diagnosing SARS-CoV-2 infection.

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic has become a major public health issue worldwide. Developing and evaluating rapid and easy-to-perform diagnostic tests is a high priority. The current study was designed to assess the diagnostic performance of an antigen-based rapid detection test (COVID-VIRO®) in a real-life setting. Two nasopharyngeal specimens of symptomatic or asymptomatic adult patients hospitalized in the Infectious Diseases Department or voluntarily accessing the COVID-19 Screening Department of the Regional Hospital of Orléans, France, were concurrently collected. The diagnostic specificity and sensitivity of COVID VIRO® results were compared to those of real-time reverse-transcriptase quantitative polymerase chain reaction (RT-qPCR) results. A subset of patients underwent an additional oropharyngeal and/or saliva swab for rapid testing. A total of 121 patients confirmed to be infected and 127 patients having no evidence of recent or ongoing infection were enrolled for a total of 248 nasopharyngeal swab specimens. Overall, the COVID-VIRO® sensitivity was 96.7% (CI, 93.5%-99.9%). In asymptomatic patients, symptomatic patients having symptoms for more than 4 days and those with an RT-qPCR cycle threshold value ≥ 32, the sensitivities were 100%, 95.8%, and 91.9%, respectively. The concordance between RT-qPCR and COVID VIRO® rapid test results was 100% for the 127 patients with no SARS-CoV-2 infection. The COVID-VIRO® test had 100% specificity and sensitivity greater than 95%, which are better than the recommendations set forth by the WHO (specificity ≥ 97%-100%, sensitivity ≥ 80%). These rapid tests may be particularly useful for large-scale screening in emergency departments, low-resource settings, and airports.

First year of pre-exposure prophylaxis implementation in France with daily or on-demand tenofovir disoproxil fumarate/emtricitabine.

BACKGROUND: In January 2016, the French Medicine Agency initiated a Temporary Recommendation for Use (TRU) to allow the use of oral intake of tenofovir disoproxil fumarate and emtricitabine for pre-exposure prophylaxis (PrEP) in adults at high risk of HIV. We report the results of the first year of PrEP implementation in France. METHODS: Data were collected by physicians using a secured web subject-monitoring interface, with two forms: an initiation form, with patients' baseline characteristics, and an HIV seroconversion form. Univariate and adjusted multivariate analysis using a logistic regression model were performed to identify baseline factors associated with on-demand PrEP regimen prescription. RESULTS: From 4 January 2016 to 28 February 2017, 3405 subjects were enrolled, with 2774 initiation forms completed; 98.1% were male and 96.9% were MSM. An on-demand regimen was prescribed to 57% of subjects. Older age (OR for participants older than 50 years = 1.76, 95% CI 1.35-2.3, P < 0.001) and site of prescription (OR of former IPERGAY sites = 2.28, 95% CI 1.84-2.83, P < 0.001) were associated with on-demand prescription. Those reporting sexually transmitted infection (STI) and condomless anal sex with at least two different partners were less likely to receive on-demand PrEP (OR = 0.68, 95% CI 0.57-0.82 and 0.75, 95% CI 0.57-0.98, respectively; P < 0.05 for all). Four breakthrough HIV infections were reported during the study, in the context of PrEP interruption or acute infection at the time of PrEP initiation. CONCLUSIONS: In a real-life setting in France, PrEP was used, either daily or on-demand, mostly by MSM, with breakthrough infections being rare.

Imported malaria in pregnant women: report from a French University Centre.

OBJECTIVE: To describe malaria during pregnancy outside endemic areas. MATERIALS AND METHODS: We retrospectively reviewed all cases of imported malaria during pregnancy, diagnosed over a 11-year period in a French hospital. RESULTS AND CONCLUSION: We recovered 18 cases, all from sub-Saharan countries. The infection could appear distantly from arrival in France (up to 36 months), was asymptomatic in 3 cases, with anemia being the most common marker of infection (n = 14). The adverse consequences for the fetus (n = 3) or the newborn (n = 4) were frequent. Physicians should be aware of these atypical presentations in order to anticipate the diagnosis and improve the maternal and fetal prognosis.

Risk of HIV transmission during combined ART initiation for HIV-infected persons with severe immunosuppression.

BACKGROUND: Individuals presenting for care with severe immunosuppression typically have high plasma HIV viral load (pVL) and may transmit HIV before and after initiation of combination antiretroviral therapies (cART). PATIENTS AND METHODS: Using risk equations and data collected in the IMEA 040 DATA trial on sexual behaviour and pVL level of 84 HIV-infected patients (23 women), we estimated monthly rates of HIV transmission for each virologically unsuppressed participant (pVL >50 copies/mL) who reported sex with HIV-negative or unknown serostatus (HNUS) partners at cART initiation, 24 weeks (W24) and W48 after; rates were considered negligible for other participants. RESULTS: At cART initiation, median pVL was 5.4 log10 copies/mL. The percentage of virologically unsuppressed patients decreased, from 100% at cART initiation to 27% (95% CI 16%-43%) for heterosexuals and 8% (95% CI 2%-22%) for MSM at W48 (P < 0.001). The percentage of patients reporting sex with HNUS partners increased between cART initiation and W48, from 23% (95% CI 10%-42%) to 42% (95% CI 25%-61%) for heterosexuals (P = 0.042) and from 41% (95% CI 21%-64%) to 73% (95% CI 52%-88%) for MSM (P = 0.004). Median monthly HIV transmission rates were 0.0540 (IQR 0.0339-0.0742) for MSM and 0.0018 (IQR 0.0014-0.0191) for heterosexuals at cART initiation, and were reduced by 95% (95% CI 87%-100%) for heterosexuals and 98% (95% CI 95%-100%) for MSM as early as W24. CONCLUSIONS: Risk of onward transmission for severely immunosuppressed individuals is high before and within the first weeks of cART, and persists, at a substantially reduced level, beyond 24 weeks of cART for some individuals. Earlier cART and protecting HIV-negative partners until full viral suppression is achieved could reduce HIV transmission.

Bacterial chondritis complications following ear piercing.

BACKGROUND: Body piercing has become widespread and is associated with increased complications. Post-piercing chondritis may lead to severe residual deformity. We aimed to report case patients presenting with post-piercing chondritis in our department and to describe clinical features and treatment. PATIENTS AND METHODS: We conducted a retrospective study of patients presenting with post-piercing chondritis in the infectious disease department of Tenon Hospital, Paris, France. RESULTS: We included 21 patients. Fifteen bacteriological cultures were positive (7 Pseudomonas aeruginosa, 5 Staphylococcus aureus, and three other). Dual intravenous antibiotic therapy was administered to 13 patients for a median duration of six days [2-8], replaced by an oral antibiotic therapy for a median duration of 15 days [7-40]. Eight patients received oral antibiotic monotherapy for 10 days [7-30]. Median duration of antibiotic therapy was 16 days. Earring removal was performed for 18 patients. No ear deformity or general complication was reported. CONCLUSION: Transcartilaginous ear piercing may lead to infectious complications or deformity. In case of chondritis, early administration of an antibiotic therapy active against P. aeruginosa and S. aureus is recommended. Specific guidelines are needed.

Pre-exposure prophylaxis: a useful tool to prevent human immunodeficiency virus infection?

The aim of preventive measures against human immunodeficiency virus (HIV) is to reduce the incidence of HIV infection in the general population and in high-risk groups, such as men having sex with men (MSM), and to reduce the risk that a given individual will contract or spread the virus. Male and female condoms, post-exposure prophylaxis and circumcision are preventive methods currently recognized or promoted worldwide. Although modest success has been reported in a phase-III vaccine trial, other methods are being evaluated, such as vaginal and rectal microbicides, and pre-exposure prophylaxis (PrEP). Herein, we discuss results from prevention trials, especially those focusing on PrEP and particularly on recent results from 'on-demand' PrEP regimens. The efficacy of PrEP (rates of 0%-86%) is strongly correlated with adherence and plasma concentrations of antiretrovirals. Adverse events are rare. Selection of emtricitabine-resistant strains is mainly reported in individuals with an undiagnosed HIV infection using PrEP. PrEP is now strongly recommended in WHO prevention programmes for individuals at substantial risk for HIV with a view to controlling this epidemic by 2030.

Pharmacokinetics of dolutegravir in a premature neonate after HIV treatment intensification during pregnancy.

We describe the pharmacokinetics of dolutegravir (DTG) in a premature neonate after maternal intensification of an antiretroviral (ARV) regimen by adding DTG. During the last 2 weeks of pregnancy, the ARV was tenofovir-emtricitabine, atazanavir-ritonavir, and DTG (50 mg once daily). From the interaction between atazanavir and DTG via CYP3A4 and UGT1A1 and placental efflux transporter inhibition and considering the infant's probable enzymatic immaturity, the DTG elimination half-life was estimated to be 4-fold longer in neonates than in adults.

Acquisition of carbapenemase-producing Enterobacteriaceae by healthy travellers to India, France, February 2012 to March 2013.

Healthy travellers to countries where carbapenemases-producing Enterobacteriaceae (CPE) are endemic might be at risk for their acquisition, even without contact with the local healthcare system. Here, we report the acquisition of CPE (two OXA-181, one New Delhi metallo-beta-lactamase 1 (NDM-1)) in three healthy travellers returning from India. The duration of CPE intestinal carriage was less than one month. The results indicate that healthy travellers recently returning from India might be considered as at risk for CPE carriage.

Peg-IFNα/ribavirin/protease inhibitor combination in hepatitis C virus associated mixed cryoglobulinemia vasculitis: results at week 24.

BACKGROUND: The standard-of-care treatment of patients with hepatitis C virus (HCV)-mixed cryoglobulinemia (MC) vasculitis includes pegylated interferon α (PegIFN)-α plus ribavirin and/or rituximab. About 30-40% of patients are non-responders or relapsers to such combination. OBJECTIVE: To analyse the safety and efficacy of Peg-IFNα/ribavirin/protease inhibitor combination in HCV-MC vasculitis. PATIENTS AND METHODS: Open-label, prospective, cohort study including 23 patients with HCV-MC vasculitis. Peg-IFNα/ribavirin was associated to telaprevir (375 mg three times daily, for 12 weeks, (n=15)) or boceprevir (800 mg three times daily, for 44 weeks, (n=8)) for 48 weeks. RESULTS: The median age was 59 (52.5-66) years, with 48.8% women. Thirteen patients (56.5%) were complete clinical responders, and 10 (43.5%) were partial responders at week 24. The virological response (ie, HCV RNA negativation) was of 69.6% at week 24 (p=0.005). The cryoglobulin level decreased from 0.44 to 0.06 g/l (p=0.0006) and the C4 level increased from 0.09 to 0.15 g/l (p=0.045). Grades 3 and 4 adverse events (mainly anaemia, neutropenia and thrombocytopenia) were observed in 10 cases (43.5%). Twenty patients (87%) received erythropoietin, 9 (39.1%) had red cell transfusion, and 2 (8.7%) had granulocyte stimulating agents. Antiviral therapy discontinuation was required in 8 (34.7%) patients for virological non-response (n=5), virological relapse (n=2) and depression (n=1). CONCLUSIONS: Peg-IFNα/ribavirin/protease inhibitor combination seems highly effective in HCV-MC. Such therapeutic regimen should be administered cautiously considering the high rate of side effects.

Liver stiffness values in HIV-infected patients with isolated anti-hepatitis B core antibodies.

BACKGROUND: Hepatitis B reactivation has been observed in HIV-infected patients with isolated anti-HBc. However, the impact of isolated anti-HBc on liver fibrosis is not known in this population. METHODS: We investigated liver stiffness values (LSV) in a population of HIV-infected patients with isolated anti-HBc, and attempted to identify risk factors for high values. RESULTS: Fifty-one out of 69 patients (74%) had low LSV (≤7.1 kPa). In univariate analysis, high LSV (>7.1 kPa) were associated with HCV coinfection, the duration of HIV infection, the duration of antiretroviral therapy and lipodystrophy. In age-adjusted multivariate analysis, HCV coinfection (OR 11.5; 95% CI, 3.0-62.9; P=0.001) and lipodystrophy (OR 4.6; 95% CI, 1.1-20.7; P=0.031) remained associated with high liver stiffness values. CONCLUSIONS: Lipodystrophy was the only factor associated with high liver stiffness values in our population of HIV-infected patients with isolated anti-Hbc and extensive exposure to antiretroviral drugs active on HBV, apart from HCV coinfection Our study correlates to recent studies the results of which have shown that lipodystrophy, and more generally mitochondrial toxicity, was associated with advanced liver fibrosis in HIV/HCV co-infected patients.

[Malaria among immigrants, experience of a Parisian hospital (2006-2010)]. / Paludisme chez les migrants, expérience d'un hôpital parisien (2006-2010).

In recent days immigrants represent the main risk group for imported malaria in northern countries. Most of them are migrants returning to their country of origin to visit friends and relatives (VFR). We retrospectively examined the main clinical, biological, and therapeutic data of all malaria cases in immigrants from 2006 to 2010 in Tenon hospital, Paris. The hospital is situated in a Paris district with an important African community. During the study period 239 imported malaria cases were observed in adults of which 199 were immigrants, 186 VFR, and 13 recently arrived. Most cases were from sub-Saharan Africa and Comoro islands. Chimioprophylaxis was not taken in 81.2% of VFR. It was inadequate in 43.7% and not taken correctly in 84.4%. Plasmodium falciparum was the most frequent species identified: 190/199 (95.5%). Severe P. falciparum malaria was observed in 25 cases (13.2%); two of them were recently arrived. One patient, African VFR, died. In this series two high-risk groups were represented: HIV-infected patients and pregnant women. Six of the HIV patients had severe malaria and all pregnant women had anemia. Our results are similar to those observed recently in other European countries. Mean age of VFR is increasing and the risk for severe P. falciparum malaria became identical to the one observed in non-immune travelers. Protection measures remain still insufficient in this population of travelers.

The risk of going abroad in sickle cell disease: a study of 148 adults.

Going abroad is considered to be a risk for acute complications in patients with sickle cell disease (SCD). Our objective was to describe the risk in our cohort of adult SCD patients. Complications occurring during a trip were recorded from adults with SCD seen at a routine visit in a referral centre and during hospitalizations for acute complications. One hundred and eight patients participated; mean age=26.8 (± SD 7.3; range 18-56) years. Eighty-two patients travelled in the previous year, half of them in Africa. Among patients going to endemic areas, 68% of patients received chemoprophylaxis against malaria. Health problems occurred in 53 (65%) travellers: vaso-occlusive crisis (VOC) (68%), fever (19%), diarrhoea (19%), broncho-pulmonary symptoms (11%), headaches (8%), vomiting (6%), and cutaneous wound (4%). Sixteen patients required hospitalization; no specific infection was diagnosed. The prevalence of VOC during the trip was higher than the frequency of VOC during the year before. Patients who developed severe complications were not the most symptomatic patients from SCD. Our study showed that going abroad is associated with a large number of acute complications in adults with SCD. Complications were mostly VOC, and severity was unpredictable. Prevention should be improved.