Systems analysis and improvement approach to optimize tuberculosis (SAIA-TB) screening, treatment, and prevention in South Africa: a stepped-wedge cluster randomized trial.

BACKGROUND: The use of systems engineering tools, including the development and use of care cascades using routinely collected data, process mapping, and continuous quality improvement, is used for frontline healthcare workers to devise systems level change. South Africa experiences high rates of tuberculosis (TB) infection and disease as well as HIV co-infection. The Department of Health has made significant gains in HIV services over the last two decades, reaching their set "90-90-90" targets for HIV. However, TB services, although robust, have lagged in comparison for both disease and infection. The Systems Analysis and Improvement Approach (SAIA) is a five-step implementation science method, drawn from systems engineering, to identify, define, and implement workflow modifications using cascade analysis, process mapping, and repeated quality improvement cycles within healthcare facilities. METHODS: This stepped-wedge cluster randomized trial will evaluate the effectiveness of SAIA on TB (SAIA-TB) cascade optimization for patients with TB and high-risk contacts across 16 clinics in four local municipalities in the Sarah Baartman district, Eastern Cape, South Africa. We hypothesize that SAIA-TB implementation will lead to a 20% increase in each of: TB screening, TB preventive treatment initiation, and TB disease treatment initiation during the 18-month intervention period. Focus group discussions and key informant interviews with clinic staff will also be conducted to determine drivers of implementation variability across clinics. DISCUSSION: This study has the potential to improve TB screening, treatment initiation, and completion for both active disease and preventive measures among individuals with and without HIV in a high burden setting. SAIA-TB provides frontline health care workers with a systems-level view of their care delivery system with the aim of sustainable systems-level improvements. TRIAL REGISTRATION: Clinicaltrials.gov, NCT06314386. Registered 18 March 2024, https://clinicaltrials.gov/study/NCT06314386 . NCT06314386.

Healthcare worker perceived barriers and facilitators to implementing a tuberculosis preventive therapy program in rural South Africa: a content analysis using the consolidated framework for implementation research.

BACKGROUND: South African national tuberculosis (TB) guidelines, in accordance with the World Health Organization, recommend conducting routine household TB contact investigation with provision of TB preventive therapy (TPT) for those who qualify. However, implementation of TPT has been suboptimal in rural South Africa. We sought to identify barriers and facilitators to TB contact investigations and TPT management in rural Eastern Cape, South Africa, to inform the development of an implementation strategy to launch a comprehensive TB program. METHODS: We collected qualitative data through individual semi-structured interviews with 19 healthcare workers at a district hospital and four surrounding primary-care clinics referring to the hospital. The consolidated framework for implementation research (CFIR) was used to develop interview questions as well as guide deductive content analysis to determine potential drivers of implementation success or failure. RESULTS: A total of 19 healthcare workers were interviewed. Identified common barriers included lack of provider knowledge regarding efficacy of TPT, lack of TPT documentation workflows for clinicians, and widespread community resource constraints. Facilitators identified included healthcare workers high interest to learn more about the effectiveness of TPT, interest in problem-solving logistical barriers in provision of comprehensive TB care (including TPT), and desire for clinic and nurse-led TB prevention efforts. CONCLUSION: The use of the CFIR, a validated implementation determinants framework, provided a systematic approach to identify barriers and facilitators to TB household contact investigation, specifically the provision and management of TPT in this rural, high TB burden setting. Specific resources-time, trainings, and evidence-are necessary to ensure healthcare providers feel knowledgeable and competent about TPT prior to prescribing it more broadly. Tangible resources such as improved data systems coupled with political coordination and funding for TPT programming are essential for sustainability.

Treatment Outcomes Among Pregnant Patients With Multidrug-Resistant Tuberculosis: A Systematic Review and Meta-analysis.

Importance: The management of multidrug-resistant tuberculosis (MDR-TB) during pregnancy is challenging, yet no systematic synthesis of evidence has accurately measured treatment outcomes. Objective: To systematically synthesize treatment outcomes and adverse events among pregnant patients with MDR-TB. Data Sources: PubMed, Scopus, Web of Science, and ProQuest were searched from the inception of each database through August 31, 2021. Study Selection: Studies containing cohorts of pregnant patients with a defined treatment outcome were eligible. Data Extraction and Synthesis: Independent reviewers screened studies and assessed the risk of bias. The study followed the Preferring Reporting Items for Systematic Review and Meta-analyses reporting guideline. Meta-analysis was performed using random-effects models. The sources of heterogeneity were explored through metaregression. Main Outcomes and Measures: The primary outcome was the proportion of patients with each treatment outcome (including treatment success, death, loss to follow-up, and treatment failure), and the secondary outcomes included the proportion of patients experiencing adverse events during pregnancy. Results: In this systematic review and meta-analysis, 10 studies containing 275 pregnant patients with available data on treatment outcomes were included. The pooled estimate was 72.5% (95% CI, 63.3%-81.0%) for treatment success, 6.8% (95% CI, 2.6%-12.4%) for death, 18.4% (95% CI, 13.1%-24.2%) for loss to follow-up, and 0.6% (95% CI, 0.0%-2.9%) for treatment failure. Treatment success was significantly higher in studies in which the proportion of patients taking linezolid was greater than the median (20.1%) compared with studies in which this proportion was lower than the median (odds ratio, 1.22; 95% CI, 1.05-1.42). More than half of the pregnant patients (54.7%; 95% CI, 43.5%-65.4%) experienced at least 1 type of adverse event, most commonly liver function impairment (30.4%; 95% CI, 17.7%-45.7%), kidney function impairment (14.9%; 95% CI, 6.2%-28.3%), hypokalemia (11.9%; 95% CI, 3.9%-25.6%), hearing loss (11.8%; 95% CI, 5.5%-21.3%), gastrointestinal disorders (11.8%; 95% CI, 5.2%-21.8%), psychiatric disorders (9.1%; 95% CI, 2.5%-21.6%), or anemia (8.9%; 95% CI, 3.6%-17.4%). The pooled proportion of favorable pregnancy outcomes was 73.2% (95% CI, 49.4%-92.1%). The most common types of adverse pregnancy outcomes were preterm birth (9.5%; 95% CI, 0.0%-29.0%), pregnancy loss (6.0%; 95% CI, 1.3%-12.9%), low birth weight (3.9%; 95% CI, 0.0%-18.7%), and stillbirth (1.9%; 95% CI, 0.1%-5.1%). Most of the studies had low-quality (3 studies) or medium-quality (4 studies) scores. Conclusions and Relevance: In this systematic review and meta-analysis, high treatment success and favorable pregnancy outcomes were reported among pregnant patients with MDR-TB. Further research is needed to design shorter, more effective, and safer treatment regimens for pregnant patients with MDR-TB.

Association of HIV infection and antiretroviral therapy with the occurrence of an unfavorable TB treatment outcome in a rural district hospital in Eastern Cape, South Africa: A retrospective cohort study.

BACKGROUND: Our objective was to assess differences in TB treatment outcomes between individuals who were HIV negative, HIV positive on anti-retroviral treatment (ART) and HIV positive not on ART, at TB treatment initiation at a rural district hospital in Eastern Cape, South Africa. METHODS: This was a retrospective cohort study of individuals diagnosed with TB between January 2017 and April 2020 at a district hospital. Adults 15 years and over with reported HIV status and treatment outcome were included (N = 711). A categorical outcome with three levels was considered: unfavorable, down referral, and success. We report descriptive statistics for the association between HIV and ART status and treatment outcome using Chi-square and Fisher's exact tests. A multinomial baseline logit model was used to estimate odds ratios for treatment outcomes. RESULTS: Overall, 59% of included patients were HIV positive with 75% on ART. Eighty-eight patients 12% had an unfavorable outcome. Half of all patients were down referred with an additional 37% having a successful outcome. Individuals without HIV were more likely to be down referred (versus unfavorable) compared to individuals with untreated HIV (2.90 OR, 1.36, 6.17 95% CI). There was a greater likelihood for individuals without HIV having a successful TB treatment outcome compared to individuals with untreated HIV (4.98 OR, 2.07, 11.25 95% CI). CONCLUSION: The majority of individuals had positive TB treatment outcomes (down referred or success). However, people without HIV had nearly five times greater odds of having successful outcomes than those with untreated HIV.

Concordance of Drug-resistance Profiles Between Persons With Drug-resistant Tuberculosis and Their Household Contacts: A Systematic Review and Meta-analysis.

BACKGROUND: Household contacts of patients with drug-resistant tuberculosis (TB) are at high risk for being infected with Mycobacterium tuberculosis and for developing TB disease. To guide regimen composition for the empirical treatment of TB infection and disease in these household contacts, we estimated drug-resistance profile concordance between index patients with drug-resistant TB and their household contacts. METHODS: We performed a systematic review and meta-analysis of studies published through 24 July 2018 that reported resistance profiles of drug-resistant TB index cases and secondary cases within their households. Using a random-effects meta-analysis, we estimated resistance profile concordance, defined as the percentage of secondary cases whose M. tuberculosis strains were resistant to the same drugs as strains from their index cases. We also estimated isoniazid/rifampin concordance, defined as whether index and secondary cases had identical susceptibilities for isoniazid and rifampin only. RESULTS: We identified 33 eligible studies that evaluated resistance profile concordance between 484 secondary cases and their household index cases. Pooled resistance profile concordance was 54.3% (95% confidence interval [CI], 40.7-67.6%; I2 = 85%). Pooled isoniazid/rifampin concordance was 82.6% (95% CI, 72.3-90.9%; I2 = 73%). Concordance estimates were similar in a subanalysis of 16 studies from high-TB-burden countries. There were insufficient data to perform a subanalysis among pediatric secondary cases. CONCLUSIONS: Household contacts of patients with drug-resistant TB should receive treatment for TB infection and disease that assumes that they, too, are infected with a drug-resistant M. tuberculosis strain. Whenever possible, drug susceptibility testing should be performed for secondary cases to optimize regimen composition.

Perceived barriers and supports to accessing community-based services for Uganda's pediatric post-surgical population.

BACKGROUND: Access to pediatric surgical intervention in low-income countries is expanding, but investments in post-surgical care have received less attention. This study explored the barriers and supports for school-aged children to access post-surgical, community-based follow-up care in Uganda as perceived by community stakeholders. MATERIALS AND METHODS: This qualitative exploratory case study used in-depth, semi-structured interviews and in-country site visits among Ugandan organizations providing follow-up care to school-aged children in Uganda after surgery. Data from eight interviews and eight site visits were coded, analyzed, and cross-tabulated with a modified grounded theory approach. RESULTS: Four key barriers to community-based follow-up care were identified: discrimination, financial barriers, geographical barriers (including transportation), and caregiver limitations to support recovery. Three key supports to successful access to and participation in community-based post-surgical recovery were identified: disability awareness, the provision of sustained follow-up care, and caregiver supports for reintegration. CONCLUSIONS: Increasing awareness of disability across local Ugandan communities, educating caregivers with accessible and culturally aware approaches, and funding sustainable follow-up care programming provide promising avenues for pediatric post-surgical recovery and community reintegration in contemporary Uganda.Implications for rehabilitationMultiple, intersecting factors prevent or promote access to post-surgical community-based services among school-aged children in Uganda.The most prominent barriers to pediatric community reintegration in Uganda include discrimination, lack of financial resources, geographical factors, and caregiver limitations.Community and interprofessional alliances must address disability awareness and sources of stigma in local contexts to promote optimal recovery and reintegration after surgery.Collaborative efforts are needed to develop sustainable funding for community-based care programs that specifically support pediatric post-surgical recovery and reintegration.Efforts to provide appropriate and empowering caregiver education are critical, particularly in geographical regions where ongoing access to rehabilitation professionals is minimal.

Tuberculosis clinical presentation and treatment outcomes in pregnancy: a prospective cohort study.

BACKGROUND: There is limited research to guide TB treatment specifically in pregnant women and few studies have described the presentation of TB in pregnant women. We aimed to understand TB presentation and treatment outcomes in pregnant women in a low HIV burden setting. We describe a cohort of women of childbearing age treated for TB disease in Lima, Peru, and compare clinical presentation and treatment outcomes among pregnant and non-pregnant women between 2009 and 2012, including 36 pregnant women. METHODS: This is a prospective cohort study. Subjects were recruited from across 106 public health centers in Lima, Peru. Baseline demographic, medical history, and drug-susceptibility test results were collected. We used descriptive statistics to describe demographic and clinical characteristics of the women using Pearson chi-squared, Fisher's exact tests, or Kruskal-Wallis. RESULTS: Among 4500 individuals with pulmonary TB disease, 1334 women were included in analysis with 36 (2.69%) pregnant women. Pregnant women had similar demographics, past medical histories, and clinical presentation to non-pregnant women, except being more likely to be married (p = 0.01) and have cardiac disease (p = 0.04) and less likely to have weight loss (p = 0.05). Twenty (71.4%) pregnant women had pan-susceptible TB compared with 616 (63.1%) non-pregnant women; four (14.3%) pregnant women had mono-resistant TB compared with 154 (15.8%) non-pregnant women; and four (14.3%) pregnant women had multi-drug-resistant TB compared with 140 (14.3%) of non-pregnant women (p = 0.53). Twenty-eight (96.6%) pregnant women had a successful outcome (cure, completed treatment, treatment ended early by clinical team) while one (3.4%) had an unsuccessful outcome (treatment failed) and 1074 (97.3%) non-pregnant women had a successful outcome while 30 (2.7%) had an unsuccessful outcome (p = 0.56). CONCLUSION: In this cohort with low HIV co-infection, we found high TB treatment success rates in both pregnant and non-pregnant women, irrespective of drug-susceptibility profiles. If treated appropriately, pregnant women with TB disease can have successful outcomes.

Provision of guideline-based care for drug-resistant tuberculosis in South Africa: Level of concordance between prescribing practices and guidelines.

TITLE: Provision of guideline-based care for drug-resistant tuberculosis in South Africa: Level of concordance between prescribing practices and guidelines. OBJECTIVE: We examined the influence of individual and site characteristics on the concordance between prescribed treatment regimens and recommended standardized regimen according to national guidelines for patients with drug-resistant tuberculosis (DR-TB) in South Africa. METHODS: Participants were 337 youth and adults treated for DR-TB between November 2014 and August 2016 at ten DR-TB treatment sites in Eastern Cape and KwaZulu Natal provinces, South Africa. Logistic regression was used to determine individual and system characteristics related to concordance at treatment initiation between the prescribed treatment regimens in terms of medication composition, dosage, and frequency and guideline-based standardized regimen that included four oral and one injectable medications. RESULTS: The sample was 19% (n = 64) youth (15-24 years), 53% (n = 179) male, 73% (n = 243) HIV coinfected, and 51% (n = 169) with prior history of TB treatment. Guideline medications were correctly prescribed for 88% (n = 295) of patients, but only 33% (n = 103) received the correct medications and doses. Complete guideline adherence to medications, doses, and frequency was achieved for 30% (n = 95) of patients. Younger age, HIV coinfection, and rural treatment setting were associated with the prescription of correct medications. CONCLUSION: Most individuals are prescribed the correct DR-TB medications, yet few individuals receive correct medications, dosages, and frequencies. Further study is needed to examine the root causes for treatment guideline deviations and opportunities for improvement.

Availability of post-hospital services supporting community reintegration for children with identified surgical need in Uganda.

BACKGROUND: Community services and supports are essential for children transitioning home to recover from the hospital after surgery. This study assessed the availability and geographic capacity of rehabilitation, assistive devices, familial support, and school reintegration programs for school-aged children in Uganda with identified surgical need. METHODS: This study assessed the geographic epidemiology and spatial analysis of resource availability in communities in Uganda. Participants were children with identified surgical need using the Surgeons OverSeas Assessment of Surgical need (SOSAS). Community-based resources available to children and adolescents after surgery in Uganda were identified using publicly available data sources and searching for resources through consultation with in-country collaborators We sought resources available in all geographic regions for a variety of services. RESULTS: Of 1082 individuals surveyed aged 5 to 14 yearsr, 6.2% had identified surgical needs. Pediatric surgical conditions were most prevalent in the Northern and Central regions of Uganda. Of the 151 community-based services identified, availability was greatest in the Central region and least in the Northern region, regardless of type. Assuming 30% of children with surgical needs will need services, a maximum of 50.1% of these children would have access to the needed services in the extensive capacity estimates, while only 10.0% would have access in the minimal capacity estimates. The capacity varied dramatically by region with the Northern region having much lower capacity in all scenarios as compared to the Central, Eastern, or Western regions. CONCLUSIONS: Our study found that beyond the city of Kampala in the Central region, community-based services were severely lacking for school-aged children in Uganda. Increased pediatric surgical capacity to additional hospitals in Uganda will need to be met with increased availability and access to community-based services to support recovery and community re-integration.

Time to Drug-Resistant Tuberculosis Treatment in a Prospective South African Cohort.

This study examined time to treatment initiation by age among a prospective cohort with drug-resistant tuberculosis (DR-TB). Participants aged 13 years or older nested within a cluster-randomized trial in 2 South African provinces were evaluated. Outcomes were treatment initiation within 5 days of DR-TB diagnosis (National Tuberculosis Program guidelines) and days from diagnosis to treatment. A total of 521 participants met inclusion criteria. Eighty-two patients (16%) met national guidelines; median time to treatment was 11 days (range = 0-180). No patient (age, sex, prior TB history, HIV status) or health system characteristics (geographic urban/rural location, province) were associated with treatment initiation per guidelines except geographic location (t = 3.64, degrees of freedom = 1, P = .0003). One in 6 individuals with DR-TB received treatment per guidelines, and average time to treatment was 11 days. Strategies are needed to decrease treatment delays and meet the recommended guidelines for treatment for patients of all ages.