Adaptation and validation of a TB stigma scale for adolescents in Lima, Peru.

BACKGROUND: TB-related stigma contributes to poor clinical outcomes and reduced wellbeing for affected individuals. Adolescents may be particularly susceptible to TB-related stigma due to their heightened sensitivity to peer acceptance, yet few studies have evaluated TB-related stigma in this group. Without a validated scale, it remains challenging to measure TB-related stigma in adolescents.METHODS: We adapted and validated the Van Rie TB Stigma Scale (VTSS) for adolescents on treatment for rifampicin-susceptible TB in Lima, Peru. The modified stigma scale was administered within a larger survey, which measured other psychosocial factors, including depression, adverse childhood experiences (ACEs), and social support. Data analysis included factor analysis, internal consistency, and convergent validity.RESULTS: From October 2020 to September 2021, 249 adolescents (individuals aged 10-19 years) completed the survey. Preliminary confirmatory factor analysis led to removal of two items. The final 10-item scale demonstrated good internal consistency (Cronbach's α = 0.82) and adequate model fit (χ²/df = 2.0; root mean square error of approximation: 0.06; comparative fit index: 0.94; Tucker-Lewis Index: 0.92: standardized root mean square residual: 0.05). Stigma was positively correlated with ACEs (γ = 0.13), depression (γ = 0.39), and suicidal ideation (γ = 0.27), and negatively correlated with social support (γ = -0.19).CONCLUSION: This adolescent TB stigma scale may serve as a practical tool to measure TB-related stigma and evaluate the impact of stigma-reduction interventions in adolescents.

Outcomes of WHO-conforming, longer, all-oral multidrug-resistant TB regimens and analysis implications.

BACKGROUND: Evidence of the effectiveness of the WHO-recommended design of longer individualized regimens for multidrug- or rifampicin-resistant TB (MDR/RR-TB) is limited.OBJECTIVES: To report end-of-treatment outcomes for MDR/RR-TB patients from a 2015-2018 multi-country cohort that received a regimen consistent with current 2022 WHO updated recommendations and describe the complexities of comparing regimens.METHODS: We analyzed a subset of participants from the endTB Observational Study who initiated a longer MDR/RR-TB regimen that was consistent with subsequent 2022 WHO guidance on regimen design for longer treatments. We excluded individuals who received an injectable agent or who received fewer than four likely effective drugs.RESULTS: Of the 759 participants analyzed, 607 (80.0%, 95% CI 77.0-82.7) experienced successful end-of-treatment outcomes. The frequency of success was high across groups, whether stratified on number of Group A drugs or fluoroquinolone resistance, and ranged from 72.1% to 90.0%. Regimens were highly variable regarding composition and the duration of individual drugs.CONCLUSIONS: Longer, all-oral, individualized regimens that were consistent with 2022 WHO guidance on regimen design had high frequencies of treatment success. Heterogeneous regimen compositions and drug durations precluded meaningful comparisons. Future research should examine which combinations of drugs maximize safety/tolerability and effectiveness.

Concordance of three approaches for operationalizing outcome definitions for multidrug-resistant TB.

BACKGROUND: The WHO provides standardized outcome definitions for rifampicin-resistant (RR) and multidrug-resistant (MDR) TB. However, operationalizing these definitions can be challenging in some clinical settings, and incorrect classification may generate bias in reporting and research. Outcomes calculated by algorithms can increase standardization and be adapted to suit the research question. We evaluated concordance between clinician-assigned treatment outcomes and outcomes calculated based on one of two standardized algorithms, one which identified failure at its earliest possible recurrence (i.e., failure-dominant algorithm), and one which calculated the outcome based on culture results at the end of treatment, regardless of early occurrence of failure (i.e., success-dominant algorithm).METHODS: Among 2,525 patients enrolled in the multi-country endTB observational study, we calculated the frequencies of concordance using cross-tabulations of clinician-assigned and algorithm-assigned outcomes. We summarized the common discrepancies.RESULTS: Treatment success calculated by algorithms had high concordance with treatment success assigned by clinicians (95.8 and 97.7% for failure-dominant and success-dominant algorithms, respectively). The frequency and pattern of the most common discrepancies varied by country.CONCLUSION: High concordance was found between clinician-assigned and algorithm-assigned outcomes. Heterogeneity in discrepancies across settings suggests that using algorithms to calculate outcomes may minimize bias.

Uncovering reasons for treatment initiation delays among children with TB in Lima, Peru.

BACKGROUND: Timely diagnosis and treatment of pediatric tuberculosis (TB) is critical to reducing mortality but remains challenging in the absence of adequate diagnostic tools. Even once a TB diagnosis is made, delays in treatment initiation are common, but for reasons that are not well understood.METHODS: To examine reasons for delay post-diagnosis, we conducted semi-structured interviews with Ministry of Health (MoH) physicians and field workers affiliated with a pediatric TB diagnostic study, and caregivers of children aged 0-14 years who were diagnosed with pulmonary TB in Lima, Peru. Interviews were analyzed using systematic comparative and descriptive content analysis.RESULTS: We interviewed five physicians, five field workers and 26 caregivers with children who initiated TB treatment < 7 days after diagnosis (n = 15) or who experienced a delay of ≥7 days (n = 11). Median time in delay from diagnosis to treatment initiation was 26 days (range 7-117). Reasons for delay included: health systems challenges (administrative hurdles, medication stock, clinic hours), burden of care on families and caregiver perceptions of disease severity.CONCLUSION: Reasons for delay in treatment initiation are complex. Interventions to streamline administrative processes and tools to identify and support families at risk for delays in treatment initiation are urgently needed.

Time for a change: considering regimen changes in analyses of observational drug-resistant TB treatment cohort data.

Randomized clinical trials represent the gold standard in therapeutic research. Nevertheless, observational cohorts of patients treated for multidrug-resistant TB (MDR-TB) or rifampin-resistant TB (RR-TB) also play an important role in generating evidence to guide drug-resistant TB care. Generally, summary exposure classifications (e.g., 'ever vs. never´, 'exposed at baseline´) have been used to characterize drug exposure in the absence of detailed longitudinal data on MDR-TB regimen changes. These summary classifications, along with an absence of data on covariates that change throughout the course of treatment, constrain researchers´ ability to answer the most relevant questions while accounting for known biases. In this paper, we highlight the importance of regimen changes in improving inference from observational studies of longer MDR-TB treatment regimens, and offer an overview of the data and analytic strategies required to do so.

Introducing new and repurposed TB drugs: the endTB experience.

In 2015, the initiative Expand New Drug Markets for TB (endTB) began, with the objective of reducing barriers to access to the new and repurposed TB drugs. Here we describe the major implementation challenges encountered in 17 endTB countries. We provide insights on how national TB programmes and other stakeholders can scale-up the programmatic use of new and repurposed TB drugs, while building scientific evidence about their safety and efficacy. For any new drug or diagnostic, multiple market barriers can slow the pace of scale-up. During 2015-2019, endTB was successful in increasing the number of patients receiving new and repurposed TB drugs in 17 countries. The endTB experience has many lessons, which are relevant to country level introduction of new TB drugs, as well as non-TB drugs and diagnostics. For example: the importation of TB drugs is possible even in the absence of registration; emphasis on good clinical monitoring is more important than pharmacovigilance reporting; national guidelines and expert committees can both facilitate and hinder innovative practice; clinicians use new and repurposed TB drugs when they are available; data collection to generate scientific evidence requires financial and human resources; pilot projects can drive national scale-up.

Increasing isoniazid preventive therapy uptake in an HIV program in rural Papua New Guinea.

Setting: Tuberculosis (TB) is the leading cause of death among people living with the human immunodeficiency virus (PLHIV) in Papua New Guinea. Despite a policy for isoniazid preventive therapy (IPT) among PLHIV, implementation has been slow. Objective: We prospectively evaluated a standardized guided screening process, including TB diagnostic support, to increase IPT initiation in adult PLHIV on antiretro-viral treatment. Design: The guided process included a paper-based IPT screening tool that prompted review of patient history and TB symptoms and sputum analysis by smear microscopy and Xpert® MTB/RIF. Chest X-ray was performed at the provider's discretion. We quantified the yield of this guided process on IPT initiation and detection of TB and rifampicin resistance, and examined the contributions of each diagnostic modality. Results: Among 532 patients, TB was ruled out and IPT initiated in 450 (84%). TB was diagnosed and treatment was started in 82 (15%) patients. Xpert detected rifampicin resistance in one of 21 patients (5%, 95%CI 0.24-21.3) with a positive Xpert result. All TB cases were diagnosed by chest X-ray and/or Xpert. No cases were diagnosed by sputum smear alone. Conclusion: A standardized guided process, including TB diagnostic support, successfully enabled IPT initiation and identified a large burden of undetected TB.

Contexte : La tuberculose (TB) est la première cause de décès parmi les personnes vivant avec le VIH (PVVIH) en Papouasie Nouvelle Guinée. En dépit d'une politique en faveur du traitement préventif par isoniazide (TPI) parmi les PVVIH, la mise en oeuvre a été lente.Objectif : Nous avons prospectivement évalué un processus de dépistage standardisé guidé, incluant le soutien au diagnostic de la TB, pour augmenter la mise en route du TPI chez les adultes PVVIH sous traitement antirétroviral.Schéma : Le processus guidé a inclus un outil de dépistage sur support papier du TPI qui a suscité la revue des antécédents des patients, les symptômes de TB et l'analyse des crachats par microscopie de frottis et Xpert® MTB/RIF. Une radiographie pulmonaire a été réalisée à la discrétion du prestataire de soins. Nous avons quantifié le rendement de ce processus guidé relatif à la mise en route du TPI et à la détection de la TB et de la résistance à la rifampicine et examiné les contributions de chaque modalité de diagnostic.Résultats : Parmi 532 patients, la TB a été éliminée et le TPI a été initié chez 450 (84%) patients. Une TB a été diagnostiquée et le traitement a été mis en œuvre chez 82 (15%) patients. L'Xpert a détecté la résistance à la rifampicine chez un des 21 patients (5% ; IC95% 0,24­21,3) avec un résultat d'Xpert positif. Tous les cas de TB ont été diagnostiqués par radiographie pulmonaire et/ou Xpert. Aucun cas n'a été diagnostiqué par frottis de crachats seul.Conclusion : Un processus guidé standardisé, incluant la soutien au diagnostic de la TB, a permis la mise en route du TPI et identifié une large charge de TB non détectée.

Marco de referencia: La tuberculosis (TB) es la principal causa de muerte en las personas infectadas por el virus de la inmunodeficiencia humana (VIH) en Papua Nueva Guinea. Pese a las políticas vigentes en materia de tratamiento preventivo con isoniazida (TPI) en las personas afectadas por el VIH, su aplicación ha sido lenta.Objetivo: Se evaluó de manera prospectiva un procedimiento normalizado dirigido de detección sistemática, que comprendía el apoyo al diagnóstico de la TB, con el objeto de aumentar la tasa de iniciación del TPI en los adultos aquejados de infección por el VIH que recibían tratamiento antirretrovírico.Método: El procedimiento dirigido comportaba un instrumento impreso de detección para el TPI, que incitaba la evaluación de los antecedentes del paciente, los síntomas de TB y un análisis del esputo mediante la baciloscopia y la prueba Xpert® MTB/RIF. La radiografía de tórax se practicó según el criterio del profesional de salud. Se cuantificó el efecto de este método dirigido sobre la iniciación del TPI, la detección de la TB y la resistencia a rifampicina y se examinaron además las contribuciones de cada modalidad diagnóstica.Resultados: De los 532 pacientes, en 450 se descartó el diagnóstico de TB y se inició el TPI (84%). Se diagnosticó la TB y se inició el tratamiento a 82 personas (15%). Mediante la prueba Xpert se detectó la resistencia a rifampicina en uno de los 21 pacientes con resultado positivo a esta prueba (5%; intervalo de confianza del 95% de 0,24 a 21,3). Todos los casos de TB se diagnosticaron mediante la radiografía de tórax, la prueba Xpert o ambas. La baciloscopia por sí sola no permitió el diagnostico de ningún caso.Conclusión: Un procedimiento normalizado dirigido, que comportaba apoyo al diagnóstico de la TB, hizo posible la iniciación del TPI y favoreció el reconocimiento de una gran carga de morbilidad por TB no detectada.

Presumptive treatment of multidrug-resistant tuberculosis in household contacts.

SETTING: Multidrug-resistant tuberculosis (MDR-TB) is a growing global health threat that often requires presumptive treatment in the absence of drug susceptibility testing (DST) results. OBJECTIVE: To compare two approaches to the treatment of MDR-TB contacts with no DST results who develop TB disease. DESIGN: We conducted a retrospective cohort study of adults treated for TB disease who were contacts of patients living with MDR-TB. Subjects had been treated according to one of two presumptive treatment strategies: 1) regimens containing exclusively first-line drugs, and 2) regimens that included both first- and second-line drugs that were adjusted if and when DST results became available. The primary endpoint was a composite of death and treatment failure. RESULTS: Household contacts of MDR-TB patients who developed TB disease and were treated with first-line regimens were significantly more likely to experience unfavorable end-of-treatment outcomes than those treated with presumptive MDR-TB regimens (RR 2.88, 95%CI 1.24-6.68). CONCLUSION: Household contacts of MDR-TB patients who develop TB disease but have no DST results should receive regimens containing second-line drugs selected based on the infecting strain of the index patient. Regimens containing only first-line anti-tuberculosis drugs significantly increase the risk of unfavorable outcomes.

Concordance of Mycobacterium tuberculosis fluoroquinolone resistance testing: implications for treatment.

Fluoroquinolone (FQ) drug susceptibility testing (DST) is an important step in the design of effective treatment regimens for multidrug-resistant tuberculosis. Here we compare ciprofloxacin, ofloxacin and moxifloxacin (MFX) resistance results from 226 multidrug-resistant samples. The low level of concordance observed suggests that DST should be performed for the specific FQ planned for clinical use. The results also support the new World Health Organization recommendation for testing MFX at a critical concentration of 2.0 µg/ml.