Concomitant bedaquiline and delamanid therapy in patients with drug-resistant extra-pulmonary tuberculosis in Mumbai, India.

Background: World Health Organization suggests concurrent bedaquiline-delamanid (BDQ-DLM) as part of individualised regimens for eligible patients with pulmonary drug-resistant tuberculosis (DR-TB); however, data for patients with drug-resistant extrapulmonary tuberculosis (EPTB) is extremely limited. This study documents the treatment outcomes and adverse events associated with concurrent BDQ-DLM-based regimens in patients with drug-resistant EPTB at a Médecins Sans Frontières clinic in Mumbai, India. Methods: Retrospective cohort study based on routinely collected programmatic data. Individualised regimens were based on drug-susceptibility testing and previous drug exposure. Drug-resistant EPTB patients initiated on regimens containing concurrent BDQ and DLM from April 2016 to October 2019 were included. Patients who completed treatment were followed up at 12 months. Results: Of 17 patients, median age was 23 years (IQR = 21-30 years) and 12/17 (71 %) were female. Pre-extensively drug-resistant tuberculosis and extensively drug-resistant TB was reported in 13/17 (76.4 %) and 2/17 (11.7 %) patients respectively. Microbiological reports were unavailable for two patients with central nervous system TB. Lymph node TB was the commonest form of EPTB in 9/17 (53 %) of patients. Median duration of treatment was 18.9 months. At least one grade three or four severe adverse event (SAE) was reported by 13/17 (76.4 %) patients. Thirteen (76.4 %) patients had favourable outcomes. None of the patients relapsed or died in the one-year period of post-treatment follow-up. Conclusion: Concurrent BDQ-DLM-based regimens in drug-resistant EPTB were effective and associated with manageable adverse events.

Supporting re-engagement with HIV services after treatment interruption in South Africa: a mixed method program evaluation of MSF's Welcome Service.

Psychosocial challenges impact patients' ability to remain on antiretroviral therapy lifelong, magnified by disorganized health-systems and healthcare worker (HCW) attitudes. To address this, Médecins Sans Frontières and the Department of Health developed the Welcome Service intervention, to provide person-centered care at re-engagement after HIV treatment interruption. Implemented in Khayelitsha, South Africa, between August 2020 and February 2021, the intervention aimed to reorganize triage, optimize clinical and counselling services and address HCW attitudes. The study used a mixed-methods design, incorporating in-depth interviews, and analyses of programmatic and routine health data. Interviews demonstrated positive patient care experiences. HCWs understood the potential impact of attitudes on patient engagement, however, some continued to demonstrate judgmental attitude. Clinical objectives were variably met at re-engagement: 98% were re-initiated the same day, 50% had a CD4 done, and 45% received tuberculosis prevention. Nevertheless, 4-month retention was 66%, and 88% had a VL < 1000 c/mL. Despite HCWs' understanding of person-centered care not translating into supportive behaviors, patients had positive care experiences and the intervention ended with a high rate of VL suppression. More efforts are needed to design interventions building on Welcome Service principles to provide person-centered care and sustain retention after re-engagement.

Correction: Retention on ART and viral suppression among patients in alternative models of differentiated HIV service delivery in KwaZulu-Natal, South Africa.

[This corrects the article DOI: 10.1371/journal.pgph.0000336.].

Correction: Access to health services for men who have sex with men and transgender women in Beira, Mozambique: A qualitative study.

[This corrects the article DOI: 10.1371/journal.pone.0228307.].

Correction: Ambulatory management of pre- and extensively drug resistant tuberculosis patients with imipenem delivered through port-a-cath: A mixed methods study on treatment outcomes and challenges.

[This corrects the article DOI: 10.1371/journal.pone.0234651.].

Correction: Challenging drug-resistant TB treatment journey for children, adolescents and their care-givers: A qualitative study.

[This corrects the article DOI: 10.1371/journal.pone.0248408.].

Correction: Acceptability of unsupervised peer-based distribution of HIV oral self-testing for the hard-to-reach in rural KwaZulu Natal, South Africa: Results from a demonstration study.

[This corrects the article DOI: 10.1371/journal.pone.0264442.].

Correction: Prevalence and risk factors for hepatitis C virus infection in an informal settlement in Karachi, Pakistan.

[This corrects the article DOI: 10.1371/journal.pgph.0002076.].

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

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

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.

Prevalence and risk factors for hepatitis C virus infection in an informal settlement in Karachi, Pakistan.

The burden of hepatitis C virus (HCV) infection in Pakistan is amongst the highest in the world. People living in slums are likely to be at high risk of infection. Here, we describe the results of a cross-sectional survey conducted in March 2022 that aimed to quantify the prevalence of HCV infection in Machar Colony, one of the largest and oldest slum settlements in Karachi. Risk factors for HCV seropositivity were identified using multi-level logistic regression. We recruited 1,303 individuals in a random selection of 441 households from Machar Colony. The survey-adjusted HCV-seroprevalence was 13.5% (95% Confidence Interval (CI) 11.1-15.8) and survey-adjusted viraemic prevalence was 4.1% (95% CI 3.1-5.4) with a viraemic ratio of 32% (95% CI 24.3-40.5). Of 162 seropositive people, 71 (44%) reported receiving previous treatment for chronic hepatitis C. The odds of HCV seropositivity were found to increase with each additional reported therapeutic injection in the past 12 months (OR = 1.07 (95% Credible Interval (CrI) 1.00-1.13)). We found weaker evidence for a positive association between HCV seropositivity and a reported history of receiving a blood transfusion (OR = 1.72 (95% CrI 0.90-3.21)). The seroprevalence was more than double the previously reported seroprevalence in Sindh Province. The overall proportion of seropositive people that were viraemic was lower than expected. This may reflect the long-term impacts of a non-governmental clinic providing free of cost and easily accessible hepatitis C diagnosis and treatment to the population since 2015. Reuse of needles and syringes is likely to be an important driver of HCV transmission in this setting. Future public health interventions should address the expected risks associated with iatrogenic HCV transmission in this community.

Tuberculosis Diagnosis and Preventive Monotherapy Among Children and Adolescents Exposed to Rifampicin-Resistant Tuberculosis in the Household.

Background: Children and adolescents with household exposure to multidrug- or rifampicin-resistant tuberculosis (MDR/RR-TB) are at high risk of developing TB disease. Tuberculosis preventive therapy (TPT) is recommended, but programmatic experience is limited, particularly for adolescents. Methods: We conducted a prospective cohort study to describe MDR/RR-TB diagnosis and TPT provision for individuals aged <18 years with MDR/RR-TB exposure. Participants were assessed for TB either in homes or health facilities, with referral for chest x-ray or specimen collection at clinician discretion. The TPT regimens included levofloxacin, isoniazid, or delamanid monotherapy for 6 months, based on source patient drug-resistance profile. Results: Between March 1, 2020 and July 31, 2021, 112 participants were enrolled; median age was 8.5 years, 57 (51%) were female, and 6 (5%) had human immunodeficiency virus. On screening, 11 (10%) were diagnosed with TB: 10 presumptive MDR/RR-TB and 1 drug-susceptible TB. Overall, 95 (94% of 101) participants started TPT: 79 with levofloxacin, 9 with isoniazid, and 7 with delamanid. Seventy-six (80%) completed TPT, 12 (13%) were lost to follow up, and 7 (7%) stopped TPT early due to adverse events. Potential adverse events were reported for 12 (13%) participants; none were serious. There were no further TB diagnoses (200 days median follow up). Conclusions: Post-MDR/RR-TB exposure management for children and adolescents resulted in significant MDR/RR-TB detection and both high TPT initiation and completion. Tuberculosis preventive monotherapy was well tolerated and there were no further TB diagnoses after initial assessment. Key factors supporting these outcomes included use of pediatric formulations for young children, monotherapy, and community-based options for assessment and follow up.

Provider-initiated HIV testing uptake and socio-economic status among women in a conflict zone in the Central African Republic: a mixed-methods cross-sectional study.

INTRODUCTION: In the Central African Republic (CAR), HIV/AIDS is the main cause of death in women aged 15-49 years. Increased testing coverage is essential in prevention of HIV/AIDS, especially in areas where conflict hinders access to health care. Socio-economic status (SES) has been shown to be associated with HIV testing uptake. We investigated whether "Provider-initiated HIV testing and counselling" (PITC) could be implemented in a family planning clinic in an active conflict zone in the Central African Republic to reach women of reproductive age and assessed whether socioeconomic status was associated with testing uptake. METHODS: Women aged 15-49 years were recruited from a free family planning clinic run by Médecins Sans Frontières in the capital Bangui. An asset-based measurement tool was created based on analysis of qualitative in-depth interviews. Measures of socioeconomic status were constructed from the tool, also by using factor analysis. Logistic regression was used to quantify the association between SES and HIV testing uptake (yes/no), while controlling for potential confounders: age, marital status, number of children, education level and head of household. RESULTS: A total of 1419 women were recruited during the study period, where 87.7% consented to HIV testing, and 95.5% consented to contraception use. A total of 11.9% had never been tested for HIV previously. Factors negatively associated with HIV testing uptake were: being married (OR = 0.4, 95% CI 0.3-0.5); living in a household headed by the husband as opposed to by another person (OR = 0.4, 95% CI 0.3-0.6), and lower age (OR = 0.96, 95% CI 0.93-0.99). Higher level of education (OR = 1.0, 95% CI 0.97-1.1) and having more children aged under 15 (OR = 0.92, 95% CI 0.81-1.1) was not associated with testing uptake. In multivariable regression, testing uptake was lower in the higher SES groups, but the differences were not significant (OR = 0.80, 95% CI 0.55-1.18). CONCLUSIONS: The findings show that PITC can be successfully implemented in the patient flow in a family planning clinic, without compromising contraception uptake. Within the PITC framework in a conflict setting, socioeconomic status was not found to be associated with testing uptake in women of reproductive age.

Poor outcomes among critically ill HIV-positive patients at hospital discharge and post-discharge in Guinea, Conakry: A retrospective cohort study.

INTRODUCTION: Optimal management of critically ill HIV-positive patients during hospitalization and after discharge is not fully understood. This study describes patient characteristics and outcomes of critically ill HIV-positive patients hospitalized in Conakry, Guinea between August 2017 and April 2018 at discharge and 6 months post-discharge. METHODS: We carried out a retrospective observational cohort study using routine clinical data. Analytic statistics were used to describe characteristics and outcomes. RESULTS: 401 patients were hospitalized during the study period, 230 (57%) were female, median age was 36 (IQR: 28-45). At admission, 229 patients (57%) were on ART, median CD4 was 64 cells/mm3, 166 (41%) had a VL >1000 copies/ml, and 97 (24%) had interrupted treatment. 143 (36%) patients died during hospitalisation. Tuberculosis was the major cause of death for 102 (71%) patients. Of 194 patients that were followed after hospitalization a further 57 (29%) were lost-to-follow-up (LTFU) and 35 (18%) died, 31 (89%) of which had a TB diagnosis. Of all patients who survived a first hospitalisation, 194 (46%) were re-hospitalised at least once more. Amongst those LTFU, 34 (59%) occurred immediately after hospital discharge. CONCLUSION: Outcomes for critically ill HIV-positive patients in our cohort were poor. We estimate that 1-in-3 patients remained alive and in care 6 months after their hospital admission. This study shows the burden of disease on a contemporary cohort of patients with advanced HIV in a low prevalence, resource limited setting and identifies multiple challenges in their care both during hospitalisation as well as during and after re-transitioning to ambulatory care.

Acceptability of unsupervised peer-based distribution of HIV oral self-testing for the hard-to-reach in rural KwaZulu Natal, South Africa: Results from a demonstration study.

BACKGROUND: Innovative models to distribute oral HIV self-tests (HIVST) provide an opportunity to increase access to HIV testing, especially for hard-to-reach populations. This study aimed to describe the acceptability of unsupervised peer-distribution of HIVST as a method to scale-up HIV testing. METHODS: In this study, lay counsellors or community health workers provided HIVST kits to primary recipients (PRs) for distribution to their sexual partners, anyone in their social network (termed secondary recipients) or for self-testing, from September 2018 to March 2020. The study was conducted in Eshowe and Mbongolwane areas in KwaZulu-Natal, South Africa. A structured questionnaire was administered during the recruitment and passive follow-up, when people came for confirmatory HIV testing. Electronic records were retrospectively examined to determine initiation of antiretroviral treatment (ART) for all HIVST users and non-users. RESULTS: Among 36,708 people approached to be primary recipients, 9,891 (26.9%) accepted; 31,341 HIVST kits were distributed with a median of three (IQR: 2-4) per peer. PRs were predominately recruited at primary health clinics (PHCs). However, acceptability of HIVST was thrice as high at community-based testing sites compared to PHCs (64.5% vs. 21.0%; p<0.001). During the study period, 34,715 adults were tested for HIV at both PHCs and community-based testing sites; of these, 1,089 individuals reported HIVST use. Among HIVST users, 893 (82.0%) returned to the clinic for confirmatory testing after testing negative on HIVST; 196 (17.9%) were confirmed HIV positive following a positive HIVST. After excluding 36/196 (18.4%) participants for whom clinical records could not be found in electronic register and 25/160 (15.6%) who were already on ART before receiving HIVST, 129/135 (95.5%) initiated ART, whereas 2,362/2685 (88%) of HIV positive HIVST non-users-initiated ART. CONCLUSION: Unsupervised peer-distribution of HIVST was feasible and acceptable, with more than 25% accepting to be peer-distributors. Acceptability of HIVST was thrice as high in community sites compared to clinics.

Implementing a Substance-Use Screening and Intervention Program for People Living with Rifampicin-Resistant Tuberculosis: Pragmatic Experience from Khayelitsha, South Africa.

Substance use (SU) is associated with poor rifampicin-resistant tuberculosis (RR-TB) treatment outcomes. In 2017, a SBIRT (SU screening-brief intervention-referral to treatment) was integrated into routine RR-TB care in Khayelitsha, South Africa. This was a retrospective study of persons with RR-TB who were screened for SU between 1 July 2018 and 30 September 2020 using the ASSIST (Alcohol, Smoking and Substance Involvement Screening Test). Here we describe outcomes from this program. Persons scoring moderate/high risk received a brief intervention and referral to treatment. Overall, 333 persons were initiated on RR-TB treatment; 38% (n = 128) were screened for SU. Of those, 88% (n = 113/128) reported SU; 65% (n = 83/128) had moderate/high risk SU. Eighty percent (n = 103/128) reported alcohol use, of whom 52% (n = 54/103) reported moderate/high risk alcohol use. Seventy-seven persons were screened for SU within ≤2 months of RR-TB treatment initiation, of whom 69%, 12%, and 12% had outcomes of treatment success, loss to follow-up and death, respectively. Outcomes did not differ between persons with no/low risk and moderate/high risk SU or based on the receipt of naltrexone (p > 0.05). SU was common among persons with RR-TB; there is a need for interventions to address this co-morbidity as part of "person-centered care". Integrated, holistic care is needed at the community level to address unique challenges of persons with RR-TB and SU.

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

BACKGROUND: People with drug-resistant tuberculosis (DR-TB) are known to suffer from many mental-health disorders. This study aims to describe the proportion of patients diagnosed with psychiatric comorbidities, the different psychiatric diagnoses made, and treatment outcomes among DR-TB patients with or without psychiatric comorbidity and initiated on DR-TB treatment between January 2012 and March 2019 at Médecins Sans Frontières independent clinic in Mumbai, India. METHODS: This is a retrospective study using routinely collected clinical data. DR-TB care included individualised treatment, psychosocial support, and integrated psychiatric care. RESULTS: During the study period, 341 DR-TB patients were enrolled, with a median age of 25 years (IQR:20.0-36.5 years), 185 (54.2%) females, 143 (41.9%) with PreXDR-TB, and 140 (41.0%) with XDR-TB. All 341 patients were screened by a counsellor, 119 (34.9%) were referred for psychiatric evaluation, and 102 (29.9% of 341) were diagnosed with a psychiatric comorbidity. Among 102 diagnosed with a psychiatric comorbidity, 48 (47.0%) were diagnosed at baseline, and 86 (84.3%), or 25.2% of all 341 patients enrolled, were treated with psychotropic drugs. Depressive disorders were diagnosed in 49 (48.0%), mixed anxiety and depression in 24 (23.5%), neurocognitive disorders and anxiety in five (4.9%), and medication induced psychosis in two (2.0%). No anti-TB drugs were significantly associated with psychiatric comorbidities developed during treatment. Of 102 DR-TB patients with a psychiatric comorbidity, 75.5% (77) had successful DR-TB treatment outcomes, compared to 61.1% (146/239) not diagnosed with a psychiatric comorbidity (p = 0.014). CONCLUSION: In our setting, among people started on DR-TB treatment, and with a complex TB resistance profile, about one in three patients experienced a psychiatric comorbidity, of which half developed this comorbidity during treatment. With comprehensive psychiatric care integrated into DR-TB care delivery, treatment outcomes were at least as good among those with psychiatric comorbidities compared to those without such comorbidities.

An analysis of the HIV testing cascade of a group of HIV-exposed infants from birth to 18 months in peri-urban Khayelitsha, South Africa.

BACKGROUND: Despite the reduction of HIV mother-to-child transmission, there are concerns regarding transmission rate in the breastfeeding period. We describe the routine uptake of 6 or 10 (6/10) weeks, 9 months and 18 months testing, with and without tracing, in a cohort of infants who received HIV PCR testing at birth (birth PCR) (with and without point of care (POC) testing) in a peri-urban primary health care setting in Khayelitsha, South Africa. METHODS: In this cohort study conducted between November 2014 and February 2018, HIV-positive mothers and their HIV-exposed babies were recruited at birth and all babies were tested with birth PCR. Results of routine 6/10 weeks PCR, 9 months and 18 months testing were followed up by a patient tracer. We compared testing at 6/10 weeks with a subgroup from historical cohort who was not tested with birth PCR. RESULTS: We found that the uptake of 6/10 weeks testing was 77%, compared to 82% with tracing. When including all infants in the cascade and comparing to a historical cohort without birth testing, we found that infants who tested a birth were 22% more likely to have a 6/10 weeks test compared to those not tested at birth. There was no significant difference between the uptake of 6/10 weeks testing after birth PCR POC versus birth PCR testing without POC. Uptake of 9 months and 18 months testing was 39% and 24% respectively. With intense tracing efforts, uptake increased to 45% and 34% respectively. CONCLUSION: Uptake of HIV testing for HIV-exposed uninfected infants in the first 18 months of life shows good completion of the 6/10 weeks PCR but suboptimal uptake of HIV testing at 9 months and 18 months, despite tracing efforts. Birth PCR testing did not negatively affect uptake of the 6/10 weeks HIV test compared to no birth PCR testing.