Low tuberculosis treatment initiation after positive tuberculosis lipoarabinomannan results.

A positive urine TB-LAM result should lead to TB treatment initiation. TB treatment uptake was low after a positive TB-LAM but negative Xpert test. A lack of trust in TB-LAM results by clinicians and false-positive results may contribute to these results. https://bit.ly/3VGHekC.

Understanding male circumcision: insights from a peri-urban community in Maputo City, Mozambique.

BACKGROUND: Circumcision is a protective measure against sexually transmitted infections (STIs), reducing the risk of HIV infection. This study reported coverage of male circumcision and assessed the factors associated with male uncircumcision in a peri-urban area in Maputo City, Mozambique. METHODS: This cross-sectional study of the Health Demographic Surveillance System in the Polana Caniço neighborhood investigated the sociodemographic and behavioral factors associated with uncircumcised males aged 15-49 y from October 2019 to June 2021. Data were collected from an HIV risk factors questionnaire and descriptive analyses conducted comparing self-reported male circumcision status by sociodemographic factors and sexual behaviors. The association was assessed via χ2 tests, and a multivariable logistic regression model was constructed. Adjusted ORs and 95% CIs were reported for factors associated with uncircumcised status. RESULTS: Of the 3481 males aged 15-49 y who responded to the questionnaire, 79.5% (2766) self-reported being circumcised. The percentage of uncircumcised men steadily increased with age, ranging from 12.4% (95) among males aged 15-19 y to 34.5% (148) of men aged 40-49 y. Men without education or with primary education, as well as those not practicing Islam, were 3-4 times more likely to be uncircumcised. Uncircumcised men were more likely to self-report an STI and a lack of condom use. CONCLUSIONS: Being uncircumcised was associated with not using condoms and having STIs, highlighting the need to further emphasize combination HIV-prevention programs and regular HIV/STI screening. Targeting males with lower education and across religions can help reach those with lower coverage of this effective prevention intervention.

Relapse after treatment with standardized all-oral short regimens for rifampicin-resistant tuberculosis (RR-TB): A systematic review and meta-analysis.

Background: Treatment for rifampicin-resistant tuberculosis (RR-TB) has been shortened to 12 months or less, with duration depending on the regimen used and treatment response. Treatment shortening has the potential to increase the risk of relapse, with a new episode of RR-TB after cure or completion. The proportion of relapses after standardized all-oral short (12 months or less) RR-TB regimens has not yet been systematically reviewed, which is the main objective of this review. Methods: This is a systematic review and meta-analysis. PubMed, Web of Science and Google scholar databases were systematically investigated to identify studies published between January 2018 and November 2023. Characteristics of studies, demographic data, baseline clinical condition, resistance profile, and definitions used for relapse, failure, and end-of-treatment outcomes are summarized in tables and graphs. Pooled proportions are estimated for relapse. Results: A total of ten studies were included in this review and meta-analysis, representing 1792 participants. Seven studies were clinical trials and two were cohorts. Five studies investigated all-oral six-month regimens composed of bedaquiline, pretomanid, and linezolid (BPaL). The remaining studies assessed other standardized all-oral short regimens, with treatment duration between 6 and 12 months. Post-treatment follow-up (PTFU) duration ranged from 6 to 30 months. The pooled proportion estimate of relapse was 2·0% (95 % CI, 1·0-3·0%) for all and BPaL-based regimens. Treatment extension due to poor treatment response was poorly documented. Conclusion: This review showed that the proportion of relapse in RR-TB patients treated with standardized short all-oral regimens was low. The low relapse proportion is similar to what was achieved for drug-susceptible Tuberculosis patients treated with first-line rifampicin-containing regimens. However, most data came from trial settings, and in some studies the post-treatment follow-up was short. Studies of large programmatic cohorts with longer post-treatment follow-up periods are needed to confirm the low relapse rate shown in the clinical trials.

Uptake and challenges with daily oral pre-exposure prophylaxis among men who have sex with men and transgender women, suburban Yangon, Myanmar.

BACKGROUND: Pre-exposure prophylaxis (PrEP) is effective for human immunodeficiency virus (HIV) prevention in risk groups. We assessed PrEP uptake and 12-month retention among men who have sex with men (MSM) and transgender women (TGW) in Myanmar during the coronavirus disease 2019 pandemic and a political crisis. METHODS: Using prospectively collected data, we assessed the proportion of persons eligible, initiated and retained 12 months on PrEP. We calculated HIV and syphilis incidence among those initiated on PrEP. Predictors of compliance to scheduled visits were assessed with fractional logistic regression. RESULTS: Among 652 persons screened between July and December 2020, 85.3% were eligible and 38.8% initiated PrEP. The daily pill burden was the main reason (86.5%) for refusing PrEP. A history of HIV post-exposure prophylaxis (PEP) and having an HIV-positive partner not on anti-retroviral therapy (ART) was associated with PrEP uptake (p<0.05). The 12-month retention among those initiating PrEP was 43.0%. Age ≥25 y, a history of PEP and having an HIV-positive partner not on ART predicted better compliance with scheduled visits (p<0.05). HIV incidence among PrEP initiators was 3.1 per 100 person-years (95% confidence interval [CI] 1.3 to 7.4) and syphilis incidence was 17.6 per 100 person-years (95% CI 12.3 to 25.1). CONCLUSIONS: A PrEP program for MSM and TGW in Myanmar was implemented successfully under difficult circumstances. Alternative strategies are needed addressing PrEP uptake and retention.

Correction: How to bring residents' psychosocial well-being to the heart of the fight against Covid-19 in Belgian nursing homes-A qualitative study.

[This corrects the article DOI: 10.1371/journal.pone.0249098.].

Correction: Viraemic-time predicts mortality among people living with HIV on second-line antiretroviral treatment in Myanmar: A retrospective cohort study.

[This corrects the article DOI: 10.1371/journal.pone.0271910.].

Refined understanding of the impact of the Mycobacterium tuberculosis complex diversity on the intrinsic susceptibility to pretomanid.

Previous work reported unprecedented differences in the intrinsic in vitro susceptibility of the Mycobacterium tuberculosis complex (MTBC) to pretomanid (Pa) using the Mycobacteria Growth Indicator Tube (MGIT) system. We tested 125 phylogenetically diverse strains from all known MTBC lineages (1-9) without known Pa resistance mutations and four strains with known resistance mutations as controls. This confirmed that MTBC, unlike most bacteria-antimicrobial combinations, displayed substantial differences in the intrinsic susceptibility relative to the technical variation of Pa MIC testing. This was also the case for the Middlebrook 7H11 (7H11) medium, demonstrating that these differences were not specific to MGIT. Notably, lineage 1 was confirmed to have intrinsically elevated MICs compared with lineages 2, 3, 4, and 7 (L2-4/7), underlining the urgent need for WHO to publish its decision of whether lineage 1 should be deemed treatable by BPaL(M), the now preferred all-oral regimen for treating rifampin-resistant tuberculosis. Lineages 5 and 6, which are most frequent in West Africa, responded differently to Pa, with lineage 5 being more similar to L2-4/7 and lineage 6 being more susceptible. More data are needed to determine whether 7H11 MICs are systematically lower than those in MGIT. IMPORTANCE: This study confirmed that the Mycobacterium tuberculosis complex lineage 1, responsible for 28% of global tuberculosis cases, is less susceptible to pretomanid (Pa). It also refined the understanding of the intrinsic susceptibilities of lineages 5 and 6, most frequent in West Africa, and lineages 8 and 9. Regulators must review whether these in vitro differences affect the clinical efficacy of the WHO-recommended BPaL(M) regimen and set breakpoints for antimicrobial susceptibility testing accordingly. Notably, regulators should provide detailed justifications for their decisions to facilitate public scrutiny.

Correction: Translating drug resistant tuberculosis treatment guidelines to reality in war-torn Kandahar, Afghanistan: A retrospective cohort study.

[This corrects the article DOI: 10.1371/journal.pone.0237787.].

Development of antepartum risk prediction model for postpartum hemorrhage in Lagos, Nigeria: A prospective cohort study (Predict-PPH study).

OBJECTIVES: There is currently a limited ability to accurately identify women at risk of postpartum hemorrhage (PPH). We conducted the "Predict-PPH" study to develop and evaluate an antepartum prediction model and its derived risk-scoring system. METHODS: This was a prospective cohort study of healthy pregnant women who registered and gave birth in five hospitals in Lagos, Nigeria, from January to June 2023. Maternal antepartum characteristics were compared between women with and without PPH. A predictive multivariable model was estimated using binary logistic regression with a backward stepwise approach eliminating variables when P was greater than 0.10. Statistically significant associations in the final model were reported when P was less than 0.05. RESULTS: The prevalence of PPH in the enrolled cohort was 37.1%. Independent predictors of PPH such as maternal obesity (adjusted odds ratio [aOR] 3.25, 95% confidence interval [CI] 2.47-4.26), maternal anemia (aOR 1.32, 95% CI 1.02-1.72), previous history of cesarean delivery (aOR 4.24, 95% CI 3.13-5.73), and previous PPH (aOR 2.65, 95% CI 1.07-6.56) were incorporated to develop a risk-scoring system. The area under the receiver operating characteristic curve (AUROC) for the prediction model and risk scoring system was 0.72 (95% CI 0.69-0.75). CONCLUSION: We recorded a relatively high prevalence of PPH. Our model performance was satisfactory in identifying women at risk of PPH. Therefore, the derived risk-scoring system could be a useful tool to screen and identify pregnant women at risk of PPH during their routine antenatal assessment for birth preparedness and complication readiness.

Management of rifampicin-resistant tuberculosis in conflict-affected areas: The case of Iraq.

Since December 2019, the World Health Organization (WHO) has encouraged National Tuberculosis Programs to deprioritize the use of injectable-containing regimens and roll-out all-oral bedaquiline-containing regimens for rifampicin-resistant tuberculosis (RR-TB) treatment. Consequently, Iraq gradually replaced the injectable-containing regimen with an all-oral regimen, including bedaquiline. To assess treatment enrolment and outcomes of both regimens during a transitioning phase in Iraq, where health system services are recovering from decades of war, we conducted a nationwide retrospective cohort study using routinely collected programmatic data for patients enrolled between 2019-2021. We describe treatment enrolment and use logistic regression to identify predictors of unfavorable treatment outcomes (failure, death, or lost to follow-up), including regimen type. Nationwide, a total of 301 RR-TB patients started treatment, of whom 167 concluded treatment. The proportion of patients enrolled on the all-oral regimen increased from 53.2% (50/94) in 2020, to 75.5% (80/106) in 2021. Successful treatment was achieved in 82.1% (32/39) and 63.3% (81/128), for all-oral and injectable-containing regimens respectively. Moreover, the proportion of lost to follow-up was lower among those treated with the all-oral versus the long injectable-containing regimen; respectively 2.6% (1/39) versus 17.9% (23/128: p = 0.02). Unfavorable treatment outcome was associated with male gender (aOR 2.12, 95%CI:1.02-4.43) and age <15 years (vs 30-49 years, aOR 5.80, 95%CI:1.30-25.86). Regimen type (aOR 2.37, 95%CI: 0.91-6.13) was not significantly associated with having an unfavorable treatment outcome. In Iraq, the use of bedaquiline-containing all-oral regimen resulted in a high treatment success and reduced lost to follow-up.

Effect of dolutegravir-based versus efavirenz-based antiretroviral therapy on excessive weight gain in adult treatment-naïve HIV patients at Matsanjeni health center, Eswatini: a retrospective cohort study.

BACKGROUND: There is limited data on dolutegravir (DTG)-associated weight gain from settings with a dual burden of HIV and overnutrition. METHODS: In Eswatini (at Matsanjeni), among 156 and 160 adult patients on DTG-based and EFV-based antiretroviral therapy (ART), respectively, we studied excessive weight gain (BMI at 24 months ART greater than baseline and ≥25 kg/m2). RESULTS: The median BMI increase in DTG-based patients was 1.09 (IQR:-0.28,3.28) kg/m2 compared to 0.20 (IQR:-0.85,2.18) kg/m2 in EFV-based patients (p value = 0.001). DTG-based ART predicted excessive weight gain (aOR 2.61;95% CI:1.39-4.93). CONCLUSION: Practitioners should consider DTG-based regimens as one of the risk factors for overweight/obesity.

Correction: Psychiatric comorbidities among patients with complex drug-resistant tuberculosis in Mumbai, India.

[This corrects the article DOI: 10.1371/journal.pone.0263759.].

Challenges and knowledge gaps in the management of non-tuberculous mycobacterial pulmonary disease in sub-Saharan African countries with a high tuberculosis burden: a scoping review.

INTRODUCTION: In sub-Saharan African (SSA) countries endemic for tuberculosis (TB), previous TB is a significant risk factor for non-tuberculous mycobacterial pulmonary disease (NTM-PD). The deployment of GeneXpert MTB/RIF in pulmonary TB diagnostic work-up regularly identifies symptomatic patients with a positive smear microscopy but negative GeneXpert, indicative of NTM presence. This scoping review outlines recent evidence for NTM-PD diagnosis and management in SSA. OBJECTIVE: The review's objective was to outline the risk factors, available diagnostics, management options and outcomes of NTM-PD in high-burden TB settings in SSA using the population-concept-context framework. DESIGN AND DATA SOURCES: We searched existing literature from PubMed, Web of Science, African Journals Online, Google Scholar and grey literature. Studies published between January 2005 and December 2022 were retained. Data were extracted into Rayyan software and Mendeley and summarised using Excel. RESULTS: We identified 785 potential articles, of which 105 were included in the full-text review, with 7 papers retained. Included articles used international criteria for diagnosing NTM-PD. Multiple papers were excluded due to non-application of the criteria, suggesting challenging application in the SSA setting. Identified risk factors include previous TB, smoking and mining. Most commonly, chest radiography and not CT was used for the radiological diagnosis of PD, which may miss early changes related to NTM-PD. Molecular methods for NTM species identification were employed in research settings, usually at referral centres, but were unavailable for routine care. Most studies did not report a standardised approach to treatment and they were not offered treatment for the specific disease, marking a lack of guidance in treatment decision-making. When treatment was provided, the outcome was often not reported due to the lack of implementation of standardised outcome definitions. CONCLUSIONS: These outlined challenges present a unique opportunity for researchers to undertake further studies in NTM-PD and proffer solutions more applicable to SSA.

A four-drug standardized short regimen for highly resistant TB in South-West Nigeria.

BACKGROUND: Patients with TB resistant to rifampicin (Rr-TB), and those with additional resistance to fluoroquinolones (pre-XDR-TB), should be treated with bedaquiline-pretomanid-linezolid-moxifloxacin and bedaquiline-pretomanid-linezolid, respectively. However, pretomanid is not yet widely available. METHODS: This is a pragmatic prospective single-arm study investigating the efficacy and safety of 9 mo of bedaquiline-delamanid-linezolid-clofazimine in patients with pre-XDR-TB or Rr-TB unresponsive to Rr-TB treatment in Nigeria. RESULTS: From January 2020 to June 2022, 14 of 20 patients (70%) successfully completed treatment, five died and one was lost-to-follow-up. No one experienced a treatment-emergent grade three/four event. Treatment success was higher compared with global pre-XDR-TB treatment outcomes. CONCLUSIONS: While pretomanid is unavailable, highly resistant TB can be treated with bedaquiline-delamanid-linezolid-clofazimine.

Implementation of the advanced HIV disease care package with point-of-care CD4 testing during tuberculosis case finding: A mixed-methods evaluation.

During TB-case finding, we assessed the feasibility of implementing the advanced HIV disease (AHD) care package, including VISITECT CD4 Advanced Disease (VISITECT), a semiquantitative test to identify a CD4≤200cells/µl. Adult participants with tuberculosis symptoms, recruited near-facility in Lesotho and South-Africa between 2021-2022, were offered HIV testing (capillary blood), Xpert MTB/RIF and Ultra, and MGIT culture (sputum). People living with HIV (PLHIV) were offered VISITECT (venous blood) and Alere tuberculosis-lipoarabinomannan (AlereLAM, urine) testing. AHD was defined as a CD4≤200cells/µl on VISITECT or a positive tuberculosis test. A CD4≤200cells/µl on VISITECT triggered Immy cryptococcal antigen (Immy CrAg, plasma) testing. Participants were referred with test results. To evaluate feasibility, we assessed i) acceptability and ii) intervention delivery of point-of-care diagnostics among study staff using questionnaires and group discussions, iii) process compliance, and iv) early effectiveness (12-week survival and treatment status) in PLHIV. Predictors for 12-week survival were assessed with logistic regression. Thematic content analysis and triangulation were performed. Among PLHIV (N = 676, 48.6% of 1392 participants), 7.8% were newly diagnosed, 81.8% on ART, and 10.4% knew their HIV status but were not on ART. Among 676 PLHIV, 41.7% had AHD, 29.9% a CD4≤200cells/µl and 20.6% a tuberculosis diagnosis. Among 200 PLHIV tested with Immy CrAg, 4.0% were positive. The procedures were acceptable for study staff, despite intervention delivery challenges related to supply and the long procedural duration (median: 73 minutes). At 12 weeks, among 276 PLHIV with AHD and 328 without, 3.3% and 0.9% had died, 84.8% and 92.1% were alive and 12.0% and 7.0% had an unknown status, respectively. Neither AHD nor tuberculosis status were associated with survival. Implementing AHD care package diagnostics was feasible during tuberculosis-case finding. AHD was prevalent, and not associated with survival, which is likely explained by the low specificity of VISITECT. Challenges with CD4 testing and preventive treatment uptake require addressing.

Community-supported self-administered tuberculosis treatment combined with active tuberculosis screening: a pilot experience in Conakry, Guinea.

Directly observed treatment (DOT) for tuberculosis (TB) is recommended by the World Health Organization. However, DOT does not always meet patients' preferences, burdens health facilities, and is hard to implement in settings where access to healthcare services is regularly interrupted. A model addressing these limitations of DOT is community-supported self-administered treatment (CS-SAT), in which patients who self-administer TB treatment receive regular visits from community members. Guinea is a country with a high TB burden, recurrent epidemics, and periodic socio-political unrest. We piloted a CS-SAT model for drug-susceptible TB patients in Conakry, led by community volunteers, who also conducted active TB case finding among household contacts and referrals for isoniazid preventive treatment (IPT) in children below 5 years old. We aimed to assess TB treatment outcomes of patients on CS-SAT and describe the number of patients identified with TB case finding and IPT provision. Prospectively enrolled bacteriologically confirmed TB patients, presenting to two facilities, received monthly TB medication. Community volunteers performed bi-weekly (initiation phase) and later monthly (continuation phase) home visits to verify treatment adherence, screen household contacts for TB, and assess IPT uptake in children under five. Among 359 enrolled TB patients, 237 (66.0%) were male, and 37 (10.3%) were HIV-positive. Three hundred forty (94.7%) participants had treatment success, seven (1.9%) died, seven (1.9%) experienced treatment failure, and five (1.4%) were lost-to-follow-up. Among 1585 household contacts screened for TB, 26 (1.6%) had TB symptoms, of whom five (19.2%) were diagnosed with pulmonary TB. IPT referral was done for 376 children from 198 households. In a challenging setting, where DOT is often not feasible, CS-SAT led to successful TB treatment outcomes and created an opportunity for active TB case finding and IPT referral. We recommend the Guinean CS-SAT model for implementation in similar settings.

Systematic review on cumulative HIV viraemia among people living with HIV receiving antiretroviral treatment and its association with mortality and morbidity.

BACKGROUND: We performed a systematic review to generate evidence on the association between cumulative human immunodeficiency virus (HIV) viraemia and health outcomes. METHODS: Quantitative studies reporting on HIV cumulative viraemia (CV) and its association with health outcomes among people living with HIV (PLHIV) on antiretroviral treatment (ART) were included. We searched MEDLINE via PubMed, Embase, Scopus and Web of Science and conference abstracts from 1 January 2008 to 1 August 2022. RESULTS: The systematic review included 26 studies. The association between CV and mortality depended on the study population, methods used to calculate CV and its level. Higher CV was not consistently associated with greater risk of acquire immunodeficiency syndrome-defining clinical conditions. However, four studies present a strong relationship between CV and cardiovascular disease. The risk was not confirmed in relation of increased hazards of stroke. Studies that assessed the effect of CV on the risk of cancer reported a positive association between CV and malignancy, although the effect may differ for different types of cancer. CONCLUSIONS: CV is associated with adverse health outcomes in PLHIV on ART, especially at higher levels. However, its role in clinical and programmatic monitoring and management of PLHIV on ART is yet to be established.

Face mask sampling (FMS) for tuberculosis shows lower diagnostic sensitivity than sputum sampling in Guinea.

BACKGROUND: Pulmonary tuberculosis (PTB) diagnosis relies on sputum examination, a challenge in sputum-scarce patients. Alternative non-invasive sampling methods such as face mask sampling (FMS) have been proposed. OBJECTIVE: To evaluate the value of FMS for PTB diagnosis by assessing its agreement with sputum samples processed by GeneXpert MTB/RIF (Ultra)(Xpert) testing, and describe FMS sensitivity and specificity. METHODS: This was a prospective study conducted at the Carrière TB clinic in Guinea. Presumptive TB patients willing to participate were asked to wear a surgical mask containing a polyvinyl alcohol (PVA) strip for thirty minutes. Subsequently, two spot sputum samples were collected, of which one was processed by microscopy on site and the other by Xpert in Guinea's National Reference Laboratory of Mycobacteriology (LNRM). The first 30 FMS were processed at the Supranational Reference Laboratory in Antwerp, Belgium, and the following 118 FMS in the LNRM. RESULTS: One hundred fifty patients participated, of whom 148 had valid results for both mask and sputum. Sputum smear microscopy was positive for 47 (31.8%) patients while sputum-Xpert detected MTB in 54 (36.5%) patients. Among the 54 patients testing sputum-Xpert positive, 26 (48.1%) yielded a positive FMS-Xpert result, while four sputum-Xpert negative patients tested positive for FMS and 90 patients were Xpert-negative for both sputum and mask samples, suggesting a moderate level of agreement (k-value of 0.47). The overall mask sensitivity was 48.1%, with 95.7% specificity. CONCLUSION: In our setting, Xpert testing on FMS did not yield a high level of agreement to sputum sample.