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Introduction: HIV replication leads to a change in lymphocyte phenotypes that impairs immune protection against opportunistic infections. We examined current HIV replication as an independent risk factor for tuberculosis (TB)., Methods: We included people living with HIV from 25 European cohorts 1983-2015. Individuals <16 years or with previous TB were excluded. Person-time was calculated from enrolment (baseline) to the date of TB diagnosis or last follow-up information. We used adjusted Poisson regression and general additive regression models., Results: We included 272,548 people with a median follow-up of 5.9 years (interquartile range [IQR] 2.3-10.9). At baseline, the median CD4 cell count was 355 cells/μL (IQR 193-540) and the median HIV-RNA level 22,000 copies/mL (IQR 1,300-103,000). During 1,923,441 person-years of follow-up, 5,956 (2.2%) people developed TB. Overall, TB incidence was 3.1 per 1,000 person-years (95% confidence interval [CI] 3.02-3.18) and was four times higher in patients with HIV-RNA levels of 10,000 compared with levels <400 copies/mL in any CD4 stratum. CD4 and HIV-RNA time-updated analyses showed that the association between HIV-RNA and TB incidence was independent of CD4. The TB incidence rate ratio for people born in TB-endemic countries compared with those born in Europe was 1.8 (95% CI 1.5-2.2)., Conclusions: Our results indicate that ongoing HIV replication (suboptimal HIV control) is an important risk factor for TB, independent of CD4 count. Those at highest risk of TB are people from TB-endemic countries. Close monitoring and TB preventive therapy for people with suboptimal HIV control is important., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Atkinson et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Melioidosis is a life-threatening tropical disease caused by an intracellular gram-negative bacterium Burkholderia pseudomallei. B. pseudomallei polymerizes the host cell actin through autotransporters, BimA, and BimC, to facilitate intracellular motility. Two variations of BimA in B. pseudomallei have been reported previously: BimA Bp and BimA B. mallei-like (BimA Bm ). However, little is known about genetic sequence variations within BimA and BimC, and their potential effect on the virulence of B. pseudomallei. This study analyzed 1,294 genomes from clinical isolates of patients admitted to nine hospitals in northeast Thailand between 2015 and 2018 and performed 3D structural analysis and plaque-forming efficiency assay. The genomic analysis identified 10 BimA Bp and 5 major BimC types, in the dominant and non-dominant lineages of the B. pseudomallei population structure. Our protein prediction analysis of all BimA Bp and major BimC variants revealed that their 3D structures were conserved compared to those of B. pseudomallei K96243. Sixteen representative strains of the most distant BimA Bp types were tested for plaque formation and the development of polar actin tails in A549 epithelial cells. We found that all isolates retained these functions. These findings enhance our understanding of the prevalence of BimA Bp and BimC variants and their implications for B. pseudomallei virulence., (© 2024. The Author(s).)

Background: Burkholderia thailandensis is an environmental bacteria closely related to Burkholderia pseudomallei that rarely causes infection in humans. Some environmental isolates have shown to express a capsular polysaccharide known as B. thailandensis capsular variant (BTCV), but human infection has not previously been reported. Although B. thailandednisis has been identified in environmental samples in Laos before, there have not been any human cases reported., Case: A 44-year-old man presented to a district hospital in Laos with a short history of fever and pain in his left foot. Physical examination identified a deep soft-tissue abscess in his left foot and an elevated white blood count. A deep pus sample was taken and melioidosis was suspected from preliminary laboratory tests. The patient was initially started on cloxacillin, ceftriaxone and metronidazole, and was then changed to ceftazidime treatment following local melioidosis treatment guidelines., Laboratory Methods: A deep pus sample was sent to Mahosot Hospital microbiology laboratory where a mixed infection was identified including Burkholderia sp. Conventional identification tests and API 20NE were inconclusive, and the B. pseudomallei -specific latex agglutination was positive. The isolate then underwent a Burkholderia species specific PCR which identified the isolate as B. thailandensis. The isolate was sent for sequencing on the Illumina NovaSeq 6000 system and multi-locus sequence typing analysis identified the isolate had the same sequence type (ST696) as B. thailandensis E555, a strain which expresses a B. pseudomallei -like capsular polysaccharide., Conclusion: This is the first report of human infection with B. thailandensis in Laos, and the first report of any human infection with the B. thailandensis capsular variant. Due to the potential for laboratory tests to incorrectly identify this bacteria, staff in endemic areas for B. thailandensis and B. pseudomallei should be aware and ensure that appropriate confirmatory methods are used to differentiate between the species., Competing Interests: No competing interests were disclosed., (Copyright: © 2024 Vannachone S et al.)

Melioidosis is an often-fatal neglected tropical disease caused by an environmental bacterium Burkholderia pseudomallei. However, our understanding of the disease-causing bacterial lineages, their dissemination, and adaptive mechanisms remains limited. To address this, we conduct a comprehensive genomic analysis of 1,391 B. pseudomallei isolates collected from nine hospitals in northeast Thailand between 2015 and 2018, and contemporaneous isolates from neighbouring countries, representing the most densely sampled collection to date. Our study identifies three dominant lineages, each with unique gene sets potentially enhancing bacterial fitness in the environment. We find that recombination drives lineage-specific gene flow. Transcriptome analyses of representative clinical isolates from each dominant lineage reveal increased expression of lineage-specific genes under environmental conditions in two out of three lineages. This underscores the potential importance of environmental persistence for these dominant lineages. The study also highlights the influence of environmental factors such as terrain slope, altitude, and river direction on the geographical dispersal of B. pseudomallei. Collectively, our findings suggest that environmental persistence may play a role in facilitating the spread of B. pseudomallei, and as a prerequisite for exposure and infection, thereby providing useful insights for informing melioidosis prevention and control strategies., (© 2024. The Author(s).)

Introduction: The national malaria programme of Cambodia targets the rapid elimination of all human malaria by 2025. As clinical cases decline to near-elimination levels, a key strategy is the rapid identification of malaria outbreaks triggering effective action to interrupt local transmission. We report a comprehensive, multipronged management approach in response to a  2022 Plasmodium falciparum outbreak in Kravanh district, western Cambodia., Methods: The provincial health department of Pursat in conjunction with the Center for Parasitology, Entomology and Malaria Control (CNM) identified villages where transmission was occurring using clinical records, and initiated various interventions, including the distribution of insecticide-treated bed nets, running awareness campaigns, and implementing fever screening with targeted drug administration. Health stations were set up at forest entry points, and later, targeted drug administrations with artesunate-pyronaridine (Pyramax) and intermittent preventive treatment for forest goers (IPTf) were implemented in specific village foci. Data related to adherence and adverse events from IPTf and TDA were collected. The coverage rates of interventions were calculated, and local malaria infections were monitored., Results: A total of 942 individuals were screened through active fever surveillance in villages where IPTf and TDA were conducted. The study demonstrated high coverage and adherence rates in the targeted villages, with 92% (553/600) coverage in round one and 65% (387/600) in round two. Adherence rate was 99% (551/553) in round one and 98% (377/387) in round two. The study found that forest goers preferred taking Pyramax over repeated testing consistent with the coverage rates: 92% in round one compared to 65% in round two. All individuals reachable through health stations or mobile teams reported complete IPTf uptake. No severe adverse events were reported. Only six individuals reported mild adverse events, such as loss of energy, fever, abdominal pain, diarrhoea, and muscle aches. Two individuals attributed their symptoms to heavy alcohol intake following prophylaxis., Conclusions: The targeted malaria outbreak response demonstrated high acceptability, safety, and feasibility of the selected interventions. Malaria transmission was rapidly controlled using the available community resources. This experience suggests the effectiveness of the programmatic response for future outbreaks., (© 2024. The Author(s).)

Background: No study has compared the virological and immunological status of young people with perinatally-acquired HIV infection (P-HIV) with that of people with HIV adulthood (A-HIV) having a similar duration of infection., Methods: 5 French cohorts of P-HIV and A-HIV patients with a known date of HIV-infection and receiving antiretroviral treatment (ART), were used to compare the following proportions of: virological failure (VF) defined as plasma HIV RNA ≥ 50 copies/mL, CD4 cell percentages and CD4:CD8 ratios, at the time of the most recent visit since 2012. The analysis was stratified on time since infection, and multivariate models were adjusted for demographics and treatment history., Findings: 310 P-HIV were compared to 1515 A-HIV (median current ages 20.9 [IQR:14.4-25.5] and 45.9 [IQR:37.9-53.5] respectively). VF at the time of the most recent evaluation was significantly higher among P-HIV (22.6%, 69/306) than A-HIV (3.3%, 50/1514); p ≤ 0.0001. The risk of VF was particularly high among the youngest children (2-5 years), adolescents (13-17 years) and young adults (18-24 years), compared to A-HIV with a similar duration of infection: adjusted Odds-Ratio (aOR) 7.0 [95% CI: 1.7; 30.0], 11.4 [4.2; 31.2] and 3.3 [1.0; 10.8] respectively. The level of CD4 cell percentages did not differ between P-HIV and A-HIV. P-HIV aged 6-12 and 13-17 were more likely than A-HIV to have a CD4:CD8 ratio ≥ 1: 84.1% vs. 58.8% (aOR = 3.5 [1.5; 8.3]), and 60.9% vs. 54.7% (aOR = 1.9 [0.9; 4.2]) respectively., Interpretation: P-HIV were at a higher risk of VF than A-HIV with a similar duration of infection, even after adjusting for treatment history, whereas they were not at a higher risk of immunological impairment. Exposure to viral replication among young patients living with HIV since birth or a very early age, probably because of lower adherence, could have an impact on health, raising major concerns about the selection of resistance mutations and the risk of HIV transmission., Funding: Inserm - ANRS MIE., Competing Interests: LM has received grants from ANRS-MIE, SIDACTION, all of which were paid to her institution. PF has received grants from ANRS-MIE which were paid to his institution, personal fees from MSD France, ViiV Healthcare, Janssen Cilag Gilead Sciences, support for attending meetings/and or travel from MSD France, Gilead Sciences, ViiV Healthcare. PF reports to be EACS Panel member. RS has received grants from ANRS-MIE which were paid to her institution. JW has received grants from ANRS-MIE and Region Ile de France, all of which were paid to her institution. All other authors declare no competing interests., (© 2024 Published by Elsevier Ltd.)

Introduction: In a context of declining condom use and high sexually transmitted infection (STI) incidence, the diffusion of "treatment as prevention" (Tasp) and more recently pre-exposure prophylaxis (PrEP) may have changed the sexual behaviour of newly diagnosed men who have sex with men (MSM) with HIV., Methods: Six hundred and nine MSM were enrolled and followed annually between 2014 and 2021 in the ANRS PRIMO Cohort (ClinicalTrials.gov:NCT03148964) from the time of HIV seroconversion. We studied changes over calendar time in sexual behaviour before and after HIV diagnosis. Factors associated with inconsistent condom use (ICU) after HIV diagnosis, PrEP use by partner(s) and bacterial STI acquisition were studied in random-effects models., Results: In the 6 months preceding HIV diagnosis, the number of sexual partners decreased from a median of 10 (IQR: 4-19) in 2014 to 6 (3-11) in 2021. After HIV diagnosis, ICU increased from 57.1% (16/28) of visits in 2014 up to 84.2% (229/272) in 2020-2021. Up to 25% (63/229) of MSM with HIV in recent years reported the use of PrEP by their partner(s) as the reason for ICU; these MSM were less frequently in a stable relationship, had a higher number of sexual partners and higher education level than those who did not report the use of PrEP by their partner(s). STI incidence after HIV diagnosis increased between 2014 and 2016 and remained high afterwards. STI risk was no longer associated with PrEP use by partners after adjustment for the number of partners and calendar period. ICU, age below 35 years, not being in a stable relationship, higher number of sexual partners were independently associated with an increased risk of STI., Conclusions: Implementation of TasP and more recently PrEP has led to major changes in the sexual behaviour of MSM with HIV. ICU has become overwhelmingly prevalent, PrEP use by the partner increasingly being the reported reason for ICU, behind TasP, which remains the main reason. Characteristics of MSM at the time of diagnosis of HIV have changed, with fewer number of sexual partners today than in 2014, which must lead to broaden the indications for PrEP prescription. STIs incidence remains high in MSM with HIV and requires improvements in screening and prevention methods such as pre- or post-exposition antibiotics or vaccines., (© 2024 The Authors. Journal of the International AIDS Society published by John Wiley & Sons Ltd on behalf of International AIDS Society.)