Optimal Detection of Latent Mycobacterium tuberculosis Infection by Combined Heparin-Binding Hemagglutinin (HBHA) and Early Secreted Antigenic Target 6 (ESAT-6) Whole-Blood Interferon Gamma Release Assays.

Optimal detection of latent tuberculosis (TB) infection (LTBI) remains a challenge, although it is essential to reach the goal of TB elimination. Our objective was to develop and clinically evaluate a user-friendly, 24-h, whole-blood (WB) interferon gamma (IFN-γ) release assay (IGRA) improving the detection of LTBI, compared to available tests. One milliliter of blood was divided into four aliquots and in vitro stimulated for 24 h with two different stage-specific mycobacterial antigens, i.e., heparin-binding hemagglutinin (HBHA) and early secreted antigenic target 6 (ESAT-6), a latency-associated antigen and a bacterial replication-related antigen, respectively, in addition to positive and negative controls. Clinical evaluation was performed on two independent cohorts of carefully selected subjects, i.e., a training cohort of 83 individuals and a validation cohort of 69 individuals. Both cohorts comprised LTBI subjects (asymptomatic people with a positive tuberculin skin test result and potential exposure to TB index cases), patients with active TB (aTB), and noninfected controls. The sensitivity and specificity of the WB-HBHA-IGRA to identify LTBI subjects among asymptomatic individuals were 93%. Combining the results in response to HBHA and ESAT-6 allowed us to identify LTBI subgroups. One group, with IFN-γ responses to HBHA only, was easily differentiated from patients with aTB. The other group, responding to both antigens like the aTB group, is likely at risk to reactivate the infection and should be prioritized for prophylactic anti-TB treatment. The combined WB-IGRA may be offered to clinicians for the selection of LTBI subjects to benefit from prophylactic treatment.

[Societal impact of vaccination : beyond individual protection. Renewed interest following COVID-19 pandemic ?] / Impact sociétal de la vaccination : au-delà de la protection individuelle. Regain d'intérêt face à la pandémie COVID-19 ?

Vaccine hesitancy is growing worldwide and hampering efforts to control vaccine-preventable diseases. Healthcare professionals have a critical role in the acceptance of vaccination by patients. Increased awareness about the benefits of vaccination is one of the recommended strategy to counter vaccine hesitancy. Beyond protection of individuals against specific pathogens, vaccination have broad benefits at multiple levels of society, partly mediated by community protection. These benefits include improved access to education, increased productivity and positive fiscal impact, limitation of gender inequalities, control and prevention of antibiotic resistant pathogens. In this narrative review, those benefits are summarized and relevant studies reviewed. The broad benefits of immunization should contribute to better communication about the impact of immunization and could be part of educational programs of future health-care workers. The COVID-19 pandemic has a tremendous socio-economic impact and is the illustration of a world without vaccine. Nevertheless, recent surveys indicate that the acceptance of a future SARS-CoV-2 vaccine will not be universal, illustrating the importance of communication centered on safety and tolerability of future vaccines.

L'hésitation vaccinale est croissante dans le monde, nuisant aux efforts de contrôle des maladies infectieuses. Les professionnels de la santé jouent un rôle important dans l'acceptation de la vaccination. Une conscientisation sur les effets bénéfiques de la vaccination est une des stratégies conseillées par l'OMS afin de contrer l'hésitation vaccinale. Au-delà de la protection individuelle vis-à-vis d'un pathogène, la vaccination est associée à une protection au niveau de la communauté. Dans cette revue narrative de la littérature, les effets sociétaux de la vaccination, au sens large, sont résumés. Les bénéfices incluent une meilleure probabilité de profiter d'une éducation complète, une augmentation de la productivité et un impact fiscal positif, la limitation des inégalités hommes-femmes et la prévention d'épidémies coûteuses. Les bénéfices larges de la vaccination doivent faire partie de la communication au sujet de l'impact de la vaccination et intégrer les programmes éducationnels destinés aux futurs professionnels de la santé. La pandémie liée à la COVID-19 a un impact social et économique sévère et est l'illustration paroxystique d'un monde sans vaccin. Malgré cela, des enquêtes récentes ont montré que l'acceptation d'un futur vaccin prévenant le SARS-CoV-2 ne sera pas automatique et illustrent l'importance d'une communication également axée sur la sécurité et la tolérance d'un futur vaccin.

Prevalence and risk factors of measles seronegativity in a cohort of HIV-positive subjects: a retrospective study.

OBJECTIVES: Measles infection is a vaccine-preventable disease currently resurging in Europe. HIV-infected subjects are at higher risk of complications following measles infection. We investigated the risk factors associated with being seronegative in a cohort of HIV-infected subjects. METHODS: All HIV-infected subjects in our cohort who had a measles serological test performed between December 2005 and May 2017 were retrospectively identified. A measles immunoglobulin G (IgG) titre > 275 mIU/mL was considered protective. Risk factors were analysed using logistic regression. RESULTS: Measles serology was available in 273 of 3124 subjects in active follow-up (8.7%). The prevalence of measles seronegativity was 21.6% (59 of 273). In the univariate analysis, being born after 1970 and HIV infection by vertical transmission were both associated with a higher risk of measles seronegativity, while a nadir CD4 T-cell count < 200 cells/µL was associated with a lower risk of measles seronegativity. In the multivariate analysis, only being born after 1970 [odds ratio (OR) 4.9; 95% confidence interval (CI) 1.3-18.7] and vertical transmission (OR 7.7; 95% CI 3.3-18.3) were significantly associated with seronegativity. Among the vertically infected subjects with measles-mumps-rubella (MMR) immunization documentation, the median number of doses of vaccine received before testing was 2 (range 1-3). CONCLUSIONS: HIV-infected subjects born after 1970 and vertically infected subjects should be screened for measles seropositivity.

Hepatitis E virus (HEV): seroprevalence and HEV RNA detection in subjects attending a sexually transmitted infection clinic in Brussels, Belgium.

Men who have sex with men (MSM) have an increased incidence of pathogens transmitted by the oro-fecal route. Hepatitis E virus (HEV) is an emerging cause of acute hepatitis and fecal shedding is observed during primary infection. We investigated whether MSM are at increased risk of HEV infection. Subjects who attended a sexually transmitted infection clinic in Brussels and had an HIV test performed between 1 June 2014 and 15 January 2016 were identified. A total of 576 samples were retrospectively screened for both total HEV IgG and HEV RNA. Samples positive for IgG were tested for IgM. MSM proportion was 31·1% (179/576). Overall HEV IgG prevalence was 9·03% (52/576) and was identical in MSM and heterosexual subjects. Among the IgG positive samples, 2/52 (3·84%) samples (both women) were positive for anti-HEV IgM. No sample was positive for HEV RNA. Age over 35 was the only risk factor significantly associated with HEV seropositivity (OR 2·07; 95% CI 1·16-3·67). In conclusion, MSM were not found to have an increased prevalence of HEV as previously reported in other European countries suggesting distinct dynamics of HEV infection in this group across Europe and increased age was associated with a higher risk of seropositivity.

Antimicrobial susceptibility testing determined by Alfred 60/AST (Alifax®) in a multi-sites lab: performance's evaluation and optimization of workflow.

PURPOSE: New techniques are needed to speed-up the identification and antimicrobial susceptibility testing (AST) of bacteria associated with bloodstream infections. Alfred 60/AST (Alifax®, Polverara, Italy) performs AST by light scattering directly from positive blood cultures. METHODS: We evaluated Alfred 60/AST performances for 4 months. Each new episode of bacteraemia was included and AST were compared to either our rapid automated AST (Vitek® 2) or disk diffusion method. The discrepancies were investigated using Etest®. The time-to-result (TTR) was evaluated by comparing the blood volume inserted into Alfred 60/AST, i.e. 2 versus 7 blood drops. Taking into account the TTR, the workflow of positive blood cultures and the availability of AST results was studied in order to optimize the implementation of Alfred 60/AST. RESULTS: A total of 249 samples and 1108 antibiotics for AST were tested. After exclusion of unavailable results, 1008 antibiotics were analysed. 94.9% (n = 957/1008) of the antibiotics showed categorical agreement. There were 14 very major errors (VME), 24 major errors (ME) and 13 minor errors (mE). The VME were mostly related to clindamycin (64.3%) whereas meropenem and piperacillin-tazobactam constituted the major part (37.5% and 61.5%) of ME and mE respectively. Results were highly reliable for Enterobacterales and enterococci. The mean TTR ranged between 4.3 and 6.3 h and was statistically 20 min faster when applying the 7 blood drops protocol. We showed that Alfred 60/AST could give relievable results within working hours for positive blood culture which are flagged the same day between 12:00 am and 12:00 pm. CONCLUSION: Our study confirmed that Alfred 60/AST gives reliable AST results in a short period of time, especially for Enterobacterales and enterococci. AST could thus be easily obtained the same day of a positive blood culture. Clinical impact studies are mandatory to validate a 24/24 working.

Saccharomyces cerevisiae fungemia: Risk factors, outcome and links with S. boulardii-containing probiotic administration.

Saccharomyces cerevisiae fungemia: risk factors, outcome and links with S. boulardii-containing probiotic administration. OBJECTIVE: The aim of our study was to review cases of S. cerevisiae fungemia along with the corresponding risk factors (including S. boulardii probiotic intake), treatment and outcomes. PATIENTS AND METHODS: Retrospective study (2005-2017) of S. cerevisiae fungemia. All the data were extracted from medical files. RESULTS: We identified 10 patients with S. cerevisiae fungemia. Mean age was 59.4 years (range 21-88). Four fifths (80%) were on total parenteral or enteral nutrition, 70% had a central venous line, and 30% were admitted in an Intensive Care Unit (ICU). S. boulardii-containing probiotic prescription was identified in 6 subjects. Three patients with no risk factors such as ICU or central venous catheter were 80 years old or more. Mortality rate was 50%. CONCLUSION: S. cerevisiae fungemia is a rare but life-threatening infection, associated with intake of probiotics containing S. boulardii. Besides classical risk factors, older age should be a contraindication for these probiotics.

Staggered enforcement of infection control and prevention measures following four consecutive potential laboratory exposures to imported Brucella melitensis.

From 2015 until 2020, Brucella melitensis was isolated four times in our microbiology laboratory. All patients had travelled in endemic-areas. Immediately after the first occurrence, all laboratory staff were risk-stratified and preventive and protective measures were applied according to CDC guidelines. Nineteen workers were exposed and needed chemoprophylaxis and follow-up. At each subsequent occurrence, risk analysis was performed, and additional measures were implemented accordingly, leading to a progressive reduction of exposed staff members to none the fourth time. We describe here the additional measures that permitted this important exposure reduction.

Dynamics of SARS-CoV-2 RT-PCR positivity and seroprevalence among high-risk healthcare workers and hospital staff.

Staff working in units that were highly exposed to coronavirus disease 2019 were invited to participate in a 6-month study on the carriage and seroprevalence of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2). The results from visits on Day 1 and Day 15 show that 41 cases of SARS-CoV-2 infection were confirmed by reverse transcriptase polymerase chain reaction and/or serology in 326 participants (overall infection rate 12.6%). The presence of comorbidities or symptoms at the time of sample collection was a risk factor for infection, but working as a physician/nurse was not a risk factor. Universal screening in high-risk units, irrespective of symptoms, allowed the identification of asymptomatic and potentially contagious infected workers, enabling them to self-isolate for 7 days.

First case of Desulfovibrio desulfuricans bacteraemia successfully identified using MALDI-TOF MS.

Desulfovibrio species are anaerobic Gram-negative bacilli that make up part of the human gastrointestinal and vaginal flora. Infection with these bacteria is usually secondary to an intra-abdominal source. Identification of these bacteria is possible using available contemporary methods. We report the first case of Desulfovibrio desulfuricans bacteraemia identified using matrix-assisted laser desorption ionization time-of-flight mass spectrometry (MALDI-TOF MS).

First case of Campylobacter rectus and Solobacterium moorei mixed bacteraemia successfully identified by MALDI TOF-MS.

Campylobacter rectus and Solobacterium moorei are anaerobic Gram-negative and Gram-positive rods, respectively, that are occasionally members of the human oral flora. Bacteraemia has rarely been reported. We present the first case of mixed C. rectus-S. moorei bacteraemia in an individual with diabetes and human immunodeficiency virus infection. Both bacteria were successfully identified by MALDI-TOF MS.

Contribution of the FilmArray Respiratory Panel in the management of adult and pediatric patients attending the emergency room during 2015-2016 influenza epidemics: An interventional study.

AIM: To evaluate the contribution of a multiplex PCR for respiratory viruses on antibiotic and antiviral prescription, ancillary test prescription, admission and length of stay of patients. METHODS: Two hundred ninety-one adult and pediatric patients visiting the emergency department during the 2015-2016 influenza epidemic were prospectively included and immediately tested 24/7 using the FilmArray Respiratory Panel. The results were communicated to the practitioner in charge as soon as they became available. Clinical and biological data were gathered and analyzed. FINDINGS: Results from the FilmArray Respiratory Panel do not appear to impact admission or antibiotic prescription, with the exception of a lower admission rate for children who tested positive for influenza B. Parameters that account for the clinical decisions evaluated are CRP level, white blood cell count, suspected or proven bacterial infection and, for adult patients only, signs of respiratory distress. Length of stay is also not significantly different between patients with a positive and a negative result. A rapid influenza test result permits a more appropriate prescription of oseltamivir.

Prospective evaluation of diagnostic tools for respiratory viruses in children and adults.

AIM: To compare the performances of molecular and non-molecular tests to diagnose respiratory viral infections and to evaluate the pros and contras of each technique. METHODS: Two hundred ninety-nine respiratory samples were prospectively explored using multiplex molecular techniques (FilmArray Respiratory Panel, Clart Pneumovir), immunological techniques (direct fluorescent assay, lateral flow chromatography) and cell cultures. FINDINGS: Molecular techniques permitted the recovery of up to 50% more respiratory pathogens in comparison to non-molecular methods. FilmArray detected at least 30% more pathogens than Clart Pneumovir which could be explained by the differences in their technical designs. The turnaround time under 2 hours for the FilmArray permitted delivery of results when patients were still in the emergency room.

MALDI-TOF MS contribution to the diagnosis of Campylobacter rectus multiple skull base and brain abscesses.

Campylobacter rectus is rarely associated with invasive infection. Both the isolation and the identification requirements of C. rectus are fastidious, probably contributing to an underestimation of its burden. We report the case of a 66-year-old man who developed several skull base and intracerebral abscesses after dental intervention. Campylobacter rectus was isolated from the brain biopsy. Within 45 minutes of reading the bacterial plate, the strain was accurately identified by MALDI-TOF MS. This rapid identification avoided the extra costs and delays present with 16S rRNA gene sequencing and allowed for a rapid confirmation of the adequacy of the empirical antibiotic treatment.

Probable hypersensitivity reaction to vancomycin associating rash, fever and neutropenia.

We describe the case of a 54-year old woman with breast cancer who was treated by vancomycin for febrile neutropenia due to a methicillin-resistant Staphyloccocus epidermidis infection of a surgically implanted catheter. She developed an hypersensitivity reaction to vancomycin associating neutropenia, fever, skin rash and elevated liver enzymes following re-challenge with vancomycin after having been misdiagnosed with septic thrombophlebitis. Following this re-challenge, neutrophils count fell dramatically but promptly resolved after cessation of vancomycin.