An optimized strategy triggered at the 2nd immunization visit to prevent HIV acquisition by breastfeeding: a phase 2 trial in Burkina Faso (PREVENIR-PEV).

BACKGROUND: Mother-to-child transmission of HIV during breastfeeding remains a challenge in low- and middle-income countries (LMIC). A prevention package was initiated during the highly attended 2nd visit of the Expanded Program of Immunisation (EPI-2) to identify the undiagnosed infants living with HIV and reduce the postnatal transmission of infant exposed to HIV. METHODS: PREVENIR-PEV is a non-randomized phase II clinical trial conducted at two health centres in Bobo Dioulasso (Burkina Faso). The study recruited mothers living with HIV aged 15 years and older with their singleton breastfed infants. During EPI-2 (at 8 weeks) and upon signature of the informed consent, a point-of-care early infant diagnosis (EID) was performed. HIV exposed uninfected (HEU) infants were followed-up until 12 months of age. High risk HEU infants (i.e., whose maternal viral load ≥ 1000 cp/mL at EPI-2 or M6) received an extended postnatal prophylaxis (PNP) with lamivudine until end of follow-up or the end of breastfeeding. RESULTS: Between 4 December 2019 and 4 December 2020, 118 mothers living with HIV-1 were identified, and 102 eligible mother/infant pairs had their infants tested for HIV EID. Six infants were newly diagnosed with HIV, and 96 HEU infants were followed-up for 10 months. Among the participants followed-up, all mothers were prescribed antiretrovirals. All 18 infants eligible for PNP at either EPI-2 or 6 months (M6) were initiated on lamivudine. No HIV transmission occurred, and no serious adverse events were reported in infants receiving lamivudine. CONCLUSIONS: The PREVENIR-PEV prevention package integrated into existing care is safe and its implementation is feasible in a LMIC with a low HIV prevalence. More research is needed to target mother/infant pairs not adhering to the intervention proposed in this trial. TRIAL REGISTRATION: NCT03869944; first registered on 11/03/2019.

Using adult care visits to diagnose HIV infection in children, Burkina Faso.

Objective: To estimate the feasibility, positivity rate and cost of offering child testing for human immunodeficiency virus (HIV) to mothers living with HIV attending outpatient clinics in Burkina Faso. Methods: We conducted this implementation study in nine outpatient clinics between October 2021 and June 2022. We identified all women ≤ 45 years who were attending these clinics for their routine HIV care and who had at least one living child aged between 18 months and 5 years whose HIV status was not known. We offered these mothers an HIV test for their child at their next outpatient visit. We calculated intervention uptake, HIV positivity rate and costs. Findings: Of 799 eligible children, we tested 663 (83.0%) and identified 16 new HIV infections: 2.5% (95% confidence interval, CI: 1.5-4.1). Compared with HIV-negative children, significantly more HIV-infected children were breastfed beyond 12 months (P-value: 0.003) and they had not been tested before (P-value: 0.003). A significantly greater proportion of mothers of HIV-infected children were unaware of the availability of child testing at 18 months (P-value: < 0.001) and had more recently learnt their HIV status (P-value: 0.01) than mothers of HIV-negative children. The intervention cost 98.1 United States dollars for one child testing HIV-positive. Barriers to implementing this strategy included shortages of HIV tests, increased workload for health-care workers and difficulty accessing children not living with their mothers. Conclusion: Testing HIV-exposed children through their mothers in outpatient clinics is feasible and effective in a low HIV-prevalence setting such as Burkina Faso. Implementation of this strategy to detect undiagnosed HIV-infected children is recommended.

Long-Term Persistence of Mitochondrial DNA Instability among HCV-Cured People Who Inject Drugs.

People who inject drugs (PWID) are a population exposed to many genotoxicants and with a high prevalence of HCV infection. Direct-acting antiviral (DAA) regimens are now widely used to treat chronic HCV infection. Although side effects to treatment are currently rare, the long-term effects such as suspicions of de novo hepatocellular carcinoma (HCC) occurrence or HCC recurrence and cardiac defects are still up for debate. Given the structure of DAAs, the molecules have a potential mitochondrial DNA (mtDNA) genotoxicity. We have previously reported acute mtDNA toxicity of three DAA regimens among PWID with a strong impact on the rate of mtDNA deletion, less on the quantity of mtDNA copy per cell at sustained viral response at 12 weeks (SVR12). Herein, we report the mtDNA parameters nine months after drug discontinuation. We observed that the percentage of the deleted mtDNA genome increased over time. No exposure to any other genotoxicants during this period was associated with a high deletion percentage, suggesting that the replicative advantage of the deleted molecules outweighed their elimination processes. Such observation calls for longer-term follow-up and may contribute to the molecular basis of subclinical side effects of DAA treatments.

Mental Disorders Are Associated With Leukocytes Telomere Shortening Among People Who Inject Drugs.

Premature biological aging, assessed by shorter telomere length (TL) and mitochondrial DNA (mtDNA) alterations, has been reported among people with major depressive disorders or psychotic disorders. However, these markers have never been assessed together among people who inject drugs (PWIDs), although mental disorders are highly prevalent in this population, which, in addition, is subject to other aggravating exposures. Diagnosis of mental disorders was performed by a psychiatrist using the Mini International Neuropsychiatric Interview test among active PWIDs in Haiphong, Vietnam. mtDNA copy number (MCN), mtDNA deletion, and TL were assessed by quantitative PCR and compared to those without any mental disorder. We next performed a multivariate analysis to identify risk factors associated with being diagnosed with a major depressive episode (MDE) or a psychotic syndrome (PS). In total, 130 and 136 PWIDs with and without psychiatric conditions were analyzed. Among PWIDs with mental disorders, 110 and 74 were diagnosed with MDE and PS, respectively. TL attrition was significantly associated with hepatitis C virus-infected PWIDs with MDE or PS (adjusted odds ratio [OR]: 0.53 [0.36; 0.80] and 0.59 [0.39; 0.88], respectively). TL attrition was even stronger when PWIDs cumulated at least two episodes of major depressive disorders. On the other hand, no difference was observed in mtDNA alterations between groups. The telomeric age difference with drug users without a diagnosis of psychiatric condition was estimated during 4.2-12.8 years according to the number of MDEs, making this group more prone to age-related diseases.

Magnetic field-enhanced agglutination as a readout for rapid serologic assays with human plasma.

Recent virus outbreaks have revealed a critical need for large scale serological assays. However, many available tests either require a cumbersome, costly apparatus or lack the availability of full automation. In order to address these limitations, we describe a homogeneous assay for antibody detection via measurement of superparamagnetic particles agglutination. Application of a magnetic field permits to overcome the limitations governed by Brownian translational diffusion in conventional assays and results in an important acceleration of the aggregation process as well as an improvement of the limit of detection. Furthermore, the use of protein-concentrated fluid such as 5 times-diluted human plasma does not impair the performances of the method. Screening of human plasma samples shows a strict discrimination between seropositive and seronegative samples in an assay duration as short as 14 s. The sensitivity of this method, combined with its quickness and simplicity, makes it a promising diagnostic tool.

Diagnostic Performance of a Magnetic Field-Enhanced Agglutination Readout in Detecting Either Viral Genomes or Host Antibodies in Arbovirus Infection.

Arbovirus diagnostics on blood from donors and travelers returning from endemic areas is increasingly important for better patient management and epidemiological surveillance. We developed a flexible approach based on a magnetic field-enhanced agglutination (MFEA) readout to detect either genomes or host-derived antibodies. Dengue viruses (DENVs) were selected as models. For genome detection, a pan-flavivirus amplification was performed before capture of biotinylated amplicons between magnetic nanoparticles (MNPs) grafted with DENV probes and anti-biotin antibodies. Magnetization cycles accelerated this chaining process to within 5 min while simple turbidimetry measured the signal. This molecular MFEA readout was evaluated on 43 DENV RNA(+) and 32 DENV RNA(-) samples previously screened by real-time RT-PCR. The sensitivity and the specificity were 88.37% (95% CI, 78.76%-97.95%) and 96.87% (95% CI, 90.84%-100%), respectively. For anti-DENV antibody detection, 103 plasma samples from donors were first screened using ELISA assays. An immunological MFEA readout was then performed by adding MNPs grafted with viral antigens to the samples. Anti-DENV antibodies were detected with a sensitivity and specificity of 90.62% (95% CI, 83.50%-97.76%) and 97.44% (95% CI, 92.48%-100%), respectively. This adaptable approach offers flexibility to platforms dedicated to the screening of emerging infections.

Large Stem/Progenitor-Like Cell Subsets can Also be Identified in the CD45- and CD45+/High Populations in Early Human Milk.

BACKGROUND: Stem/progenitor cells have been identified in human milk. However, characterization and percentages of cell subsets in human milk using hematopoietic stem and progenitor cell markers according to the differential expression of CD45, i.e., as CD45dim/+ (mainly hematopoietic stem/progenitor cells) and CD45- (mainly non-hematopoietic stem/progenitor cells), have not been assessed to date. RESEARCH AIM: To characterize stem/progenitor-like cell phenotypes in human milk and to report the percentages of these cells at two different lactation stages compared to peripheral blood. METHODS: Human milk samples paired with peripheral blood samples (N = 10) were analyzed by flow cytometry using CD45, CD34, CD133, CD38, and lineage-negative markers. The percentage of cell subsets was analyzed in colostrum (Day 3 postpartum) and transitional milk (Day 5/6 postpartum) and compared with the peripheral blood counterpart. RESULTS: The percentage of CD45-CD34+ cells was predominant in both colostrum and transitional milk. The percentage of CD45+/highCD133+ cells was high in colostrum while the percentage of CD45-CD133+ cells was high in transitional milk. Furthermore, the median percentages of the CD45-CD34+, CD45-CD133+, and CD45dimCD133+ cell subsets were higher in colostrum than its peripheral blood counterpart (0.11% vs. 0.002%; 0.17% vs. 0.0005%; 0.09% vs. 0.05%, p = .04, respectively); also CD45-CD34-CD133+ and CD45dimCD34-CD133+ cell subsets were higher in colostrum than peripheral blood (1.32% vs. 0.0% and 2.4% vs. 0.06%, p = .04), respectively). CONCLUSION: Early human milk is an abundant reservoir of hematopoietic stem/progenitor-like cells in the CD45+/high population and non-hematopoietic stem/progenitor-like cells in the CD45- population.

[Usutu virus: the phantom menace]. / Le virus Usutu : la menace fantôme.

Usutu virus, an arbovirus discovered in Africa in 1959, has spread over a large part of Europe over the last twenty years causing significant bird mortality as reported in France since 2015. The zoonotic risk, associated with this succession of avian epizootics in Europe, deserves to be taken into account even if human cases remain rare to date. Human infections are most often asymptomatic or present a benign clinical expression. However, neurological complications such as encephalitis or meningoencephalitis have been described. In addition, the recent description of an atypical case of facial paralysis in France suggests that the clinical spectrum of infections caused by Usutu virus is not fully characterized. Finally, the recent history of other arboviral outbreaks invites the scientific community to be extremely vigilant.

Sacroiliitis secondary to catheter-related bacteremia due to Mycobacterium abscessus (sensu stricto).

We describe a case of sacroiliitis secondary to catheter-related bacteremia due to Mycobacterium abscessus (sensu stricto). This case confirms that MultiLocus sequence typing and variable-number tandem-repeat methods are very robust techniques to identify the pathogen species and to validate molecular epidemiological links among complex M. abscessus isolates.