Tuberculous meningitis (TBM) is the most lethal and disabling form of tuberculosis. In 2017, approximately 10 million people developed TB worldwide, of whom more than 100,000 new cases of TBM are ...estimated to occur per year. In patients who are co-infected with HIV-1, TBM has a mortality approaching 50%. Diagnosis of TBM is often delayed by the insensitive and lengthy culture technique required for disease confirmation. GeneXpert represents the most significant advance in TBM diagnostics over the past decade, but it lacks sensitivity and cannot be used to rule out the diagnosis. Higher volume of cerebrospinal fluid (CSF) seems to be interesting to improve the diagnosis performances. New rapid and accurate diagnostic tools are necessary. Better advances have been made concerning the anti-tuberculosis chemotherapy of TBM, with the publication of clinical trials and pharmacokinetic studies exploring the use of higher rifampicin doses and fluoroquinolones. The rise of drug-resistant TBM is another challenge for management because TBM caused by multidrug resistant organisms results in death or severe disability in almost all sufferers.
The incidence of tuberculosis (TB) is currently increasing in HIV-infected patients living in Africa and Asia, where TB endemicity is high, reflecting the susceptibility of this group of patients to ...mycobacteria belonging to the TB group. In this population, extension of multiple resistance to anti-tuberculous drugs is also a matter of anxiety. HIV-induced immunosuppression modifies the clinical presentation of TB, resulting in atypical signs and symptoms, and more frequent extrapulmonary dissemination. The treatment of TB is also more difficult to manage in HIV-infected patients, particularly with regard to pharmacological interactions secondary to inhibition or induction of cytochrome P450 enzymes by protease inhibitors with rifampicin or rifabutin, respectively. Finally, immune restoration induced by highly active anti-retroviral therapy (HAART) in developed countries may be responsible for a paradoxical worsening of TB manifestations.
In this placebo-controlled phase II randomized clinical trial, 103 human immunodeficiency virus type 1 (HIV-1)-infected patients under cART (combined antiretroviral treatment) were randomized 2:1 to ...receive either 3 doses of DNA GTU-MultiHIV B (coding for Rev, Nef, Tat, Gag, and gp160) at week 0 (W0), W4, and W12, followed by 2 doses of LIPO-5 vaccine containing long peptides from Gag, Pol, and Nef at W20 and W24, or placebo. Analytical treatment interruption (ATI) was performed between W36 to W48. At W28, vaccinees experienced an increase in functional CD4
T-cell responses (
< 0.001 for each cytokine compared to W0) measured, predominantly against Gag and Pol/Env, and an increase in HIV-specific CD8
T cells producing interleukin 2 (IL-2) and tumor necrosis factor alpha (TNF-α) (
= 0.001 and 0.013, respectively), predominantly against Pol/Env and Nef. However, analysis of T-cell subsets by mass cytometry in a subpopulation showed an increase in the W28/W0 ratio for memory CD8
T cells coexpressing exhaustion and senescence markers such as PD-1/TIGIT (
= 0.004) and CD27/CD57 (
= 0.044) in vaccinees compared to the placebo group. During ATI, all patients experienced viral rebound, with the maximum observed HIV RNA level at W42 (median, 4.63 log
copies cp/ml; interquartile range IQR, 4.00 to 5.09), without any difference between arms. No patient resumed cART for CD4 cell count drop. Globally, the vaccine strategy was safe. However, a secondary HIV transmission during ATI was observed. These data show that the prime-boost combination of DNA and LIPO-5 vaccines elicited broad and polyfunctional T cells. The contrast between the quality of immune responses and the lack of potent viral control underscores the need for combined immunomodulatory strategies. (This study has been registered at ClinicalTrials.gov under registration no. NCT01492985.)
In this placebo-controlled phase II randomized clinical trial, we evaluated the safety and immunogenicity of a therapeutic prime-boost vaccine strategy using a recombinant DNA vaccine (GTU-MultiHIV B clade) followed by a boost vaccination with a lipopeptide vaccine (HIV-LIPO-5) in HIV-infected patients on combined antiretroviral therapy. We show here that this prime-boost strategy is well tolerated, consistently with previous studies in HIV-1-infected individuals and healthy volunteers who received each vaccine component individually. Compared to the placebo group, vaccinees elicited strong and polyfunctional HIV-specific CD4
and CD8
T-cell responses. However, these immune responses presented some qualitative defects and were not able to control viremia following antiretroviral treatment interruption, as no difference in HIV viral rebound was observed in the vaccine and placebo groups. Several lessons were learned from these results, pointing out the urgent need to combine vaccine strategies with other immune-based interventions.
Staphylococcus aureus
(SA) is the leading cause of bloodstream infection (BSI). The incidence of methicillin-resistant SA (MRSA) has decreased in France and Europe since one decade. Early and precise ...prediction of methicillin susceptibility is needed to improve probabilistic antibiotic therapy of MRSA-BSI. The aim of this study was to identify MRSA-BSI risk factors at admission and evaluate which patients need costly rapid diagnostic tests. A single-center retrospective descriptive study of all diagnosed SA-BSI was conducted in a French University Hospital between January 2015 and December 2016. All medical charts were reviewed. Univariate and multivariate analyses by a logistic regression model were performed on the data. We then build a prediction score of MRSA-BSI by assigning one point for each of the risk factor identified. During the study period, 151 SA-BSI were identified including 32 (21%) MRSA-BSI. In multivariate analysis, three factors were associated with MRSA-BSI: coming from long-term care facility, known previous MRSA colonization and/or infection, and chronic renal disease. Among our population, respectively, 5% and 100% had a MRSA-BSI when no or three risk factors were identified. Therefore, among the PCR performed, 43 (96%) could be avoided according to our clinical score. In our study, methicillin-susceptible SA and MRSA-BSI can be predictable by counting MRSA risk factors. This prediction rule could avoid the use of expensive rapid diagnostic tests. Prospective studies and prediction rules could help physicians to predict SA-BSI susceptibility to improve appropriate empiric therapy choice.
Data on the microbiological epidemiology of Intra-Abdominal Abscesses (IAAs) are very scarce. We aimed to study the microbiological epidemiology of these infections in order to optimize empirical ...antibiotic therapy.
Between January 2015 and December 2020, we retrospectively analyzed all IAAs files in our hospital. Clinical and microbiological data such as antibiotic susceptibilities were collected.
We studied 243 IAA cases. All in all, 139 (57.2%) IAAs were healthcare-associated and 201 (82.7%) were drained. The highest risk situations for IAAs were appendicitis (n = 69) and diverticulitis (n = 37). Out of the 163 microbiologically documented infections, 136 (81.9%) were polymicrobial. Enterobacterales (n = 192, 36.1%), Enterococcus sp. (n = 84, 17.6%) and anaerobes (n = 66, 16.1%) were the most frequently identified bacteria. Gram-negative bacteria were susceptible to amoxicillin-acid clavulanic, piperacillin-tazobactam, cefotaxime, meropenem in 55.2%, 84.9%, 77.6% and 99.5% of cases, respectively. Concerning Gram-positive bacteria, the susceptibility rate was 81.8% for amoxicillin-clavulanic acid, piperacillin-tazobactam and meropenem, and decreased to 63.4% for cefotaxime.
This study highlights the polymicrobial profile of IAAs and their low susceptibility to amoxicillin and clavulanic acid. The piperacillin-tazobactam association remained the most appropriate empirical antibiotic therapy.
Recommendations for improving traveler adherence address both the content of the advice given and the structure of the consultation. The objective of this article is to describe how travel health ...consultations are structured in France.
A questionnaire based on both theoretical foundations and recommendations in the literature was sent to health professionals who practice in travel clinics, all of them members of France's Société de Médecine des Voyages.
The response rate was 78.5% (176/224). One hundred thirty nine respondents (78.9%) reported that treatment (vaccinations, in particular) and advising were done at separate times in the consultation. The majority of respondents questioned the traveler on his wishes, difficulties, expectations, experiences, and previous knowledge. A third explored the traveler's perceptions regarding the seriousness of diseases, the effectiveness of prevention measures and the latter's adverse effects with a difference when health professionals were practicing >5 years and/or had received specific training ( P < 0.05). At the end of the consultation, 92% of the respondents asked the traveler whether he understood the advice given. One hundred thirty seven respondents (77.8%) gave travelers a booklet with additional advice, and 66.5% gave them a website where they could find health advice on their destination. Travelers were almost never offered group consultations or the opportunity to work on real-life situations. When there were language barriers, the respondents were more likely to seek help from a French-speaking member of the traveler's entourage (48.9%) than from an interpreter (22.7%).
While the majority of practitioners follow most of the recommendations regarding the structure of travel health consultations, some of the factors that enhance traveler learning are underutilized, reducing the likelihood that travelers will apply the advice given. The study illustrates the need to develop more educational intervention methods and to evaluate their impact on travelers.
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.
To estimate rates and identify correlates of HIV disclosure in migrants from sub-Saharan Africa (SSA) successfully treated, a sub-analysis was conducted in HIV-1 native SSA migrants, living in France ...with undetectable viral load on antiretroviral, included in the VIHVO adherence study. Logistic regression models assessed factors associated with HIV disclosure. Among 246 individuals (40 % male, median age 41), 79 % of those in a steady heterosexual partnership (n = 167) had disclosed their status to their partner, 55 % of the total 246 to a relative, and 33 % to (an)other person(s). Disclosure to one’s steady partner was associated with a follow-up duration since HIV diagnosis of more than 5 years, a higher literacy level, a better social context and marital status. Women were more likely to disclose their HIV status to relatives. Interventions targeting this population should be provided to improve disclosure which in turn ensures better social support, testing of the partner and lower rates of undiagnosed HIV.
To evaluate isolation practices and management of sputum smear-positive tuberculosis (TB) in France.
A survey was conducted using a questionnaire e-mailed in 2011 and 2012 to physicians of the French ...Society of Infectious Diseases, the French Respiratory Society and the French National Society of Internal Medicine.
Of 311 responders, a quarter stated they treated more than 25 TB cases per year. A total of 87.8% declared they routinely used a four-drug regimen in the initial intensive phase. Of the 311 physicians who responded, 31.9% removed isolation precautions after three negative acid-fast bacilli (AFB) sputum results, 19.0% after 15 days of treatment and 34.1% only in case of clinical improvement. According to 71% of the responders, discharge from hospital despite positive AFB sputum smear results was 'possible'. A routine AFB sputum smear was performed after 2 months of treatment by only 21% of the responders.
Despite recent national guidelines, the management of isolation precautions for sputum smear-positive TB remains heterogeneous, and a significant proportion of physicians use a three-drug regimen. Further efforts should be made to implement TB guidelines, mainly by raising awareness through national scientific institutions, but also by obtaining better evidence.
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