Journal Article > Meta-AnalysisFull Text
Eur Respir J. 2020 March 20; Volume 55 (Issue 3); 1901467.; DOI:10.1183/13993003.01467-2019
Abidi S, Achar J, Assao Neino MM, Bang D, Benedetti A, et al.
Eur Respir J. 2020 March 20; Volume 55 (Issue 3); 1901467.; DOI:10.1183/13993003.01467-2019
We sought to compare the effectiveness of two World Health Organization (WHO)-recommended regimens for the treatment of rifampin- or multidrug-resistant (RR/MDR) tuberculosis (TB): a standardised regimen of 9-12 months (the "shorter regimen") and individualised regimens of ≥20 months ("longer regimens").
We collected individual patient data from observational studies identified through systematic reviews and a public call for data. We included patients meeting WHO eligibility criteria for the shorter regimen: not previously treated with second-line drugs, and with fluoroquinolone- and second-line injectable agent-susceptible RR/MDR-TB. We used propensity score matched, mixed effects meta-regression to calculate adjusted odds ratios and adjusted risk differences (aRDs) for failure or relapse, death within 12 months of treatment initiation and loss to follow-up.
We included 2625 out of 3378 (77.7%) individuals from nine studies of shorter regimens and 2717 out of 13 104 (20.7%) individuals from 53 studies of longer regimens. Treatment success was higher with the shorter regimen than with longer regimens (pooled proportions 80.0% versus 75.3%), due to less loss to follow-up with the former (aRD -0.15, 95% CI -0.17- -0.12). The risk difference for failure or relapse was slightly higher with the shorter regimen overall (aRD 0.02, 95% CI 0-0.05) and greater in magnitude with baseline resistance to pyrazinamide (aRD 0.12, 95% CI 0.07-0.16), prothionamide/ethionamide (aRD 0.07, 95% CI -0.01-0.16) or ethambutol (aRD 0.09, 95% CI 0.04-0.13).
In patients meeting WHO criteria for its use, the standardised shorter regimen was associated with substantially less loss to follow-up during treatment compared with individualised longer regimens and with more failure or relapse in the presence of resistance to component medications. Our findings support the need to improve access to reliable drug susceptibility testing.
We collected individual patient data from observational studies identified through systematic reviews and a public call for data. We included patients meeting WHO eligibility criteria for the shorter regimen: not previously treated with second-line drugs, and with fluoroquinolone- and second-line injectable agent-susceptible RR/MDR-TB. We used propensity score matched, mixed effects meta-regression to calculate adjusted odds ratios and adjusted risk differences (aRDs) for failure or relapse, death within 12 months of treatment initiation and loss to follow-up.
We included 2625 out of 3378 (77.7%) individuals from nine studies of shorter regimens and 2717 out of 13 104 (20.7%) individuals from 53 studies of longer regimens. Treatment success was higher with the shorter regimen than with longer regimens (pooled proportions 80.0% versus 75.3%), due to less loss to follow-up with the former (aRD -0.15, 95% CI -0.17- -0.12). The risk difference for failure or relapse was slightly higher with the shorter regimen overall (aRD 0.02, 95% CI 0-0.05) and greater in magnitude with baseline resistance to pyrazinamide (aRD 0.12, 95% CI 0.07-0.16), prothionamide/ethionamide (aRD 0.07, 95% CI -0.01-0.16) or ethambutol (aRD 0.09, 95% CI 0.04-0.13).
In patients meeting WHO criteria for its use, the standardised shorter regimen was associated with substantially less loss to follow-up during treatment compared with individualised longer regimens and with more failure or relapse in the presence of resistance to component medications. Our findings support the need to improve access to reliable drug susceptibility testing.
Journal Article > CommentaryFull Text
Int J Tuberc Lung Dis. 2012 June 16 (Issue 6)
Zachariah R, Harries AD, Srinath S, Ram S, Viney K, et al.
Int J Tuberc Lung Dis. 2012 June 16 (Issue 6)
The words 'defaulter', 'suspect' and 'control' have been part of the language of tuberculosis (TB) services for many decades, and they continue to be used in international guidelines and in published literature. From a patient perspective, it is our opinion that these terms are at best inappropriate, coercive and disempowering, and at worst they could be perceived as judgmental and criminalising, tending to place the blame of the disease or responsibility for adverse treatment outcomes on one side-that of the patients. In this article, which brings together a wide range of authors and institutions from Africa, Asia, Latin America, Europe and the Pacific, we discuss the use of the words 'defaulter', 'suspect' and 'control' and argue why it is detrimental to continue using them in the context of TB. We propose that 'defaulter' be replaced with 'person lost to follow-up'; that 'TB suspect' be replaced by 'person with presumptive TB' or 'person to be evaluated for TB'; and that the term 'control' be replaced with 'prevention and care' or simply deleted. These terms are non-judgmental and patient-centred. We appeal to the global Stop TB Partnership to lead discussions on this issue and to make concrete steps towards changing the current paradigm.
Journal Article > Short ReportFull Text
Public Health Action. 2014 June 21; Volume 4 (Issue 1); DOI:10.5588/pha.13.0071
Harries AD, Marais BJ, Kool B, Ram S, Kumar AMV, et al.
Public Health Action. 2014 June 21; Volume 4 (Issue 1); DOI:10.5588/pha.13.0071
Journal Article > ResearchAbstract Only
Transcult Psychiatry. 2018 March 19; Volume 55 (Issue 3); 361-383.; DOI:10.1177/1363461518764487
Housen TSS, Lenglet AD, Ariti C, Ara S, Shah SK, et al.
Transcult Psychiatry. 2018 March 19; Volume 55 (Issue 3); 361-383.; DOI:10.1177/1363461518764487
The present study aimed to culturally adapt, translate, and validate the Hopkins Symptom Checklist-25 (HSCL-25) and the Harvard Trauma Questionnaire-Posttraumatic Stress Symptoms Checklist (HTQ-16) prior to use in a cross-sectional mental health population survey in the Kashmir Valley. Cultural adaptation and translation of the HSCL-25 and the HTQ-16 employed multiple forms of transcultural validity check. The HSCL-25 and HTQ-16 were compared against a "gold standard" structured psychiatric interview, the Mini International Neuropsychiatric Interview (MINI). Interviews were conducted with 290 respondents recruited using consecutive sampling from general medical outpatient departments in five districts of the Kashmir Valley. Receiver operating characteristics (ROC) analysis was used to estimate the cut point with optimal discriminatory power based on sensitivity and specificity. Internal reliability of the HSCL-25 was high, Cronbach's alpha (a) = .92, intraclass correlation coefficient (ICC) = 0.75, with an estimated optimal cut point of 1.50, lower than the conventional cut point of 1.75. Separation of the instruments into subscales demonstrated a difference in the estimated cut point for the anxiety subscale and the depression subscale, 1.75 and 1.57, respectively. Too few respondents were diagnosed with posttraumatic stress disorder (PTSD) during structured psychiatric interview, and therefore the HTQ-16 could not be validated despite the fact that high internal reliability was demonstrated (a = .90). This study verified the importance of culturally adapting and validating screening instruments in particular contexts. The use of the conventional cut point of 1.75 would likely have misclassified depression in our survey, leading to an underestimate of this condition.
Journal Article > ReviewFull Text
Public Health Action. 2014 June 21; Volume 4; DOI:10.5588/pha.13.0091
Bissel K, Viney K, Brostom R, Gounder S, Khogali MA, et al.
Public Health Action. 2014 June 21; Volume 4; DOI:10.5588/pha.13.0091
Operational research (OR) in public health aims to investigate strategies, interventions, tools or knowledge that can enhance the quality, coverage, effectiveness or performance of health systems. Attention has recently been drawn to the lack of OR capacity in public health programmes throughout the Pacific Islands, despite considerable investment in implementation. This lack of ongoing and critical reflection may prevent health programme staff from understanding why programme objectives are not being fully achieved, and hinder long-term gains in public health. The International Union Against Tuberculosis and Lung Disease (The Union) has been collaborating with Pacific agencies to conduct OR courses based on the training model developed by The Union and Médecins Sans Frontières Brussels-Luxembourg in 2009. The first of these commenced in 2011 in collaboration with the Fiji National University, the Fiji Ministry of Health, the World Health Organization and other partners. The Union and the Secretariat of the Pacific Community organised a second course for participants from other Pacific Island countries and territories in 2012, and an additional course for Fijian participants commenced in 2013. Twelve participants enrolled in each of the three courses. Of the two courses completed by end 2013, 18 of 24 participants completed their OR and submitted papers by the course deadline, and 17 papers have been published to date. This article describes the context, process and outputs of the Pacific courses, as well as innovations, adaptations and challenges.
Journal Article > ResearchFull Text
Lancet Child Adolesc Health. 2023 March 13; Online ahead of print; DOI:10.1016/S2352-4642(23)00004-4
Gunasekera KS, Marcy O, Muñoz J, Lopez-Varela E, Sekadde MP, et al.
Lancet Child Adolesc Health. 2023 March 13; Online ahead of print; DOI:10.1016/S2352-4642(23)00004-4
BACKGROUND
Many children with pulmonary tuberculosis remain undiagnosed and untreated with related high morbidity and mortality. Recent advances in childhood tuberculosis algorithm development have incorporated prediction modelling, but studies so far have been small and localised, with limited generalisability. We aimed to evaluate the performance of currently used diagnostic algorithms and to use prediction modelling to develop evidence-based algorithms to assist in tuberculosis treatment decision making for children presenting to primary health-care centres.
METHODS
For this meta-analysis, we identified individual participant data from a WHO public call for data on the management of tuberculosis in children and adolescents and referral from childhood tuberculosis experts. We included studies that prospectively recruited consecutive participants younger than 10 years attending health-care centres in countries with a high tuberculosis incidence for clinical evaluation of pulmonary tuberculosis. We collated individual participant data including clinical, bacteriological, and radiological information and a standardised reference classification of pulmonary tuberculosis. Using this dataset, we first retrospectively evaluated the performance of several existing treatment-decision algorithms. We then used the data to develop two multivariable prediction models that included features used in clinical evaluation of pulmonary tuberculosis-one with chest x-ray features and one without-and we investigated each model's generalisability using internal-external cross-validation. The parameter coefficient estimates of the two models were scaled into two scoring systems to classify tuberculosis with a prespecified sensitivity target. The two scoring systems were used to develop two pragmatic, treatment-decision algorithms for use in primary health-care settings.
FINDINGS
Of 4718 children from 13 studies from 12 countries, 1811 (38·4%) were classified as having pulmonary tuberculosis: 541 (29·9%) bacteriologically confirmed and 1270 (70·1%) unconfirmed. Existing treatment-decision algorithms had highly variable diagnostic performance. The scoring system derived from the prediction model that included clinical features and features from chest x-ray had a combined sensitivity of 0·86 [95% CI 0·68-0·94] and specificity of 0·37 [0·15-0·66] against a composite reference standard. The scoring system derived from the model that included only clinical features had a combined sensitivity of 0·84 [95% CI 0·66-0·93] and specificity of 0·30 [0·13-0·56] against a composite reference standard. The scoring system from each model was placed after triage steps, including assessment of illness acuity and risk of poor tuberculosis-related outcomes, to develop treatment-decision algorithms.
INTERPRETATION
We adopted an evidence-based approach to develop pragmatic algorithms to guide tuberculosis treatment decisions in children, irrespective of the resources locally available. This approach will empower health workers in primary health-care settings with high tuberculosis incidence and limited resources to initiate tuberculosis treatment in children to improve access to care and reduce tuberculosis-related mortality. These algorithms have been included in the operational handbook accompanying the latest WHO guidelines on the management of tuberculosis in children and adolescents. Future prospective evaluation of algorithms, including those developed in this work, is necessary to investigate clinical performance.
Many children with pulmonary tuberculosis remain undiagnosed and untreated with related high morbidity and mortality. Recent advances in childhood tuberculosis algorithm development have incorporated prediction modelling, but studies so far have been small and localised, with limited generalisability. We aimed to evaluate the performance of currently used diagnostic algorithms and to use prediction modelling to develop evidence-based algorithms to assist in tuberculosis treatment decision making for children presenting to primary health-care centres.
METHODS
For this meta-analysis, we identified individual participant data from a WHO public call for data on the management of tuberculosis in children and adolescents and referral from childhood tuberculosis experts. We included studies that prospectively recruited consecutive participants younger than 10 years attending health-care centres in countries with a high tuberculosis incidence for clinical evaluation of pulmonary tuberculosis. We collated individual participant data including clinical, bacteriological, and radiological information and a standardised reference classification of pulmonary tuberculosis. Using this dataset, we first retrospectively evaluated the performance of several existing treatment-decision algorithms. We then used the data to develop two multivariable prediction models that included features used in clinical evaluation of pulmonary tuberculosis-one with chest x-ray features and one without-and we investigated each model's generalisability using internal-external cross-validation. The parameter coefficient estimates of the two models were scaled into two scoring systems to classify tuberculosis with a prespecified sensitivity target. The two scoring systems were used to develop two pragmatic, treatment-decision algorithms for use in primary health-care settings.
FINDINGS
Of 4718 children from 13 studies from 12 countries, 1811 (38·4%) were classified as having pulmonary tuberculosis: 541 (29·9%) bacteriologically confirmed and 1270 (70·1%) unconfirmed. Existing treatment-decision algorithms had highly variable diagnostic performance. The scoring system derived from the prediction model that included clinical features and features from chest x-ray had a combined sensitivity of 0·86 [95% CI 0·68-0·94] and specificity of 0·37 [0·15-0·66] against a composite reference standard. The scoring system derived from the model that included only clinical features had a combined sensitivity of 0·84 [95% CI 0·66-0·93] and specificity of 0·30 [0·13-0·56] against a composite reference standard. The scoring system from each model was placed after triage steps, including assessment of illness acuity and risk of poor tuberculosis-related outcomes, to develop treatment-decision algorithms.
INTERPRETATION
We adopted an evidence-based approach to develop pragmatic algorithms to guide tuberculosis treatment decisions in children, irrespective of the resources locally available. This approach will empower health workers in primary health-care settings with high tuberculosis incidence and limited resources to initiate tuberculosis treatment in children to improve access to care and reduce tuberculosis-related mortality. These algorithms have been included in the operational handbook accompanying the latest WHO guidelines on the management of tuberculosis in children and adolescents. Future prospective evaluation of algorithms, including those developed in this work, is necessary to investigate clinical performance.
Journal Article > ResearchFull Text
Int J Tuberc Lung Dis. 2014 August 1; Volume 18 (Issue 8); 899-904.; DOI:10.5588/ijtld.14.0007
Hill P, Dye C, Viney K, Tabutoa K, Kienene T, et al.
Int J Tuberc Lung Dis. 2014 August 1; Volume 18 (Issue 8); 899-904.; DOI:10.5588/ijtld.14.0007
SETTING
The global target of tuberculosis (TB) elimination by 2050 requires new approaches. Active case finding plus mass prophylactic treatment has been disappointing. We consider mass full anti-tuberculosis treatment as an approach to TB elimination in Kiribati, a Pacific Island nation, with a persistent epidemic of high TB incidence.
OBJECTIVE
To construct a mathematical model to predict whether mass treatment with a full course of anti-tuberculosis drugs might eliminate TB from the defined population of the Republic of Kiribati.
METHODS
We constructed a seven-state compartmental model of the life cycle of Mycobacterium tuberculosis in which active TB disease arises from the progression of infection, reinfection, reactivation and relapse, while distinguishing infectious from non-infectious disease. We evaluated the effects of 5-yearly mass treatment using a range of parameter values to generate outcomes in uncertainty analysis.
RESULTS
Assuming population-wide treatment effectiveness for latent tuberculous infection and active TB of ⩾90%, annual TB incidence is expected to fall sharply at each 5-yearly round of treatment, approaching elimination in two decades. The model showed that the incidence rate is sensitive to the relapse rate after successful treatment of TB.
CONCLUSION
Mass treatment may help to eliminate TB, at least for discrete or geographically isolated populations.
The global target of tuberculosis (TB) elimination by 2050 requires new approaches. Active case finding plus mass prophylactic treatment has been disappointing. We consider mass full anti-tuberculosis treatment as an approach to TB elimination in Kiribati, a Pacific Island nation, with a persistent epidemic of high TB incidence.
OBJECTIVE
To construct a mathematical model to predict whether mass treatment with a full course of anti-tuberculosis drugs might eliminate TB from the defined population of the Republic of Kiribati.
METHODS
We constructed a seven-state compartmental model of the life cycle of Mycobacterium tuberculosis in which active TB disease arises from the progression of infection, reinfection, reactivation and relapse, while distinguishing infectious from non-infectious disease. We evaluated the effects of 5-yearly mass treatment using a range of parameter values to generate outcomes in uncertainty analysis.
RESULTS
Assuming population-wide treatment effectiveness for latent tuberculous infection and active TB of ⩾90%, annual TB incidence is expected to fall sharply at each 5-yearly round of treatment, approaching elimination in two decades. The model showed that the incidence rate is sensitive to the relapse rate after successful treatment of TB.
CONCLUSION
Mass treatment may help to eliminate TB, at least for discrete or geographically isolated populations.
Journal Article > ResearchFull Text
Oxford Medical Journal. 2024 November 6; Online ahead of print; DOI:10.1093/inthealth/ihae066
Harrison RE, Shyleika V, Vishneuski R, Leonovich O, Vetushko D, et al.
Oxford Medical Journal. 2024 November 6; Online ahead of print; DOI:10.1093/inthealth/ihae066
BACKGROUND
TB is concentrated in populations with complex health and social issues, including alcohol use disorders (AUD). We describe treatment adherence and outcomes in a person-centred, multidisciplinary, psychosocial support and harm reduction intervention for people with multidrug-resistant or rifampicin-resistant TB (MDR/RR-TB) with harmful alcohol use.
METHODS
An observational cohort study, including multilevel mixed-effects logistic regression and survival analysis with people living in Minsk admitted with MDR/RR-TB and AUD during January 2019–November 2021 who received this person-centred, multidisciplinary, psychosocial support and harm reduction intervention, was conducted.
RESULTS
There were 89 participants enrolled in the intervention, with a median follow-up of 12.2 (IQR: 8.1–20.5) mo. The majority (n=80; 89.9%) of participants had AUD, 11 (12.4%) also had a dependence on other substances, six (6.7%) a dependence on opioids and three (3.4%) a personality disorder. Fifty-eight had a history of past incarceration (65.2%), homelessness (n=9; 10.1%) or unemployment (n=55; 61.8%). Median adherence was 95.4% (IQR: 90.4–99.6%) and outpatient adherence was 91.2% (IQR: 65.1–97.0%). Lower adherence was associated with hepatitis C, alcohol plus other substance use and outpatient facility-based treatment, rather than video-observed treatment, home-based or inpatient treatment support.
CONCLUSIONS
This intervention led to good adherence to MDR/RR-TB treatment in people with harmful use of alcohol, a group usually at risk of poor outcomes. Poor outcomes were associated with hepatitis C, other substance misuse and outpatient facility-based treatment support.
Journal Article > ResearchFull Text
BMJ Glob Health. 2017 October 15; Volume 2 (Issue 4); e000419.; DOI:10.1136/bmjgh-2017-000419
Housen TSS, Lenglet AD, Ariti C, Shah SK, Shah H, et al.
BMJ Glob Health. 2017 October 15; Volume 2 (Issue 4); e000419.; DOI:10.1136/bmjgh-2017-000419
BACKGROUND
Following the partition of India in 1947, the Kashmir Valley has been subject to continual political insecurity and ongoing conflict, the region remains highly militarised. We conducted a representative cross-sectional population-based survey of adults to estimate the prevalence and predictors of anxiety, depression and post-traumatic stress disorder (PTSD) in the 10 districts of the Kashmir Valley.
METHODS
Between October and December 2015, we interviewed 5519 out of 5600 invited participants, ≥18 years of age, randomly sampled using a probability proportional to size cluster sampling design. We estimated the prevalence of a probable psychological disorder using the Hopkins Symptom Checklist (HSCL-25) and the Harvard Trauma Questionnaire (HTQ-16). Both screening instruments had been culturally adapted and translated. Data were weighted to account for the sampling design and multivariate logistic regression analysis was conducted to identify risk factors for developing symptoms of psychological distress.
FINDINGS
The estimated prevalence of mental distress in adults in the Kashmir Valley was 45% (95% CI 42.6 to 47.0). We identified 41% (95% CI 39.2 to 43.4) of adults with probable depression, 26% (95% CI 23.8 to 27.5) with probable anxiety and 19% (95% CI 17.5 to 21.2) with probable PTSD. The three disorders were associated with the following characteristics: being female, over 55 years of age, having had no formal education, living in a rural area and being widowed/divorced or separated. A dose-response association was found between the number of traumatic events experienced or witnessed and all three mental disorders.
INTERPRETATION
The implementation of mental health awareness programmes, interventions aimed at high risk groups and addressing trauma-related symptoms from all causes are needed in the Kashmir Valley.
Following the partition of India in 1947, the Kashmir Valley has been subject to continual political insecurity and ongoing conflict, the region remains highly militarised. We conducted a representative cross-sectional population-based survey of adults to estimate the prevalence and predictors of anxiety, depression and post-traumatic stress disorder (PTSD) in the 10 districts of the Kashmir Valley.
METHODS
Between October and December 2015, we interviewed 5519 out of 5600 invited participants, ≥18 years of age, randomly sampled using a probability proportional to size cluster sampling design. We estimated the prevalence of a probable psychological disorder using the Hopkins Symptom Checklist (HSCL-25) and the Harvard Trauma Questionnaire (HTQ-16). Both screening instruments had been culturally adapted and translated. Data were weighted to account for the sampling design and multivariate logistic regression analysis was conducted to identify risk factors for developing symptoms of psychological distress.
FINDINGS
The estimated prevalence of mental distress in adults in the Kashmir Valley was 45% (95% CI 42.6 to 47.0). We identified 41% (95% CI 39.2 to 43.4) of adults with probable depression, 26% (95% CI 23.8 to 27.5) with probable anxiety and 19% (95% CI 17.5 to 21.2) with probable PTSD. The three disorders were associated with the following characteristics: being female, over 55 years of age, having had no formal education, living in a rural area and being widowed/divorced or separated. A dose-response association was found between the number of traumatic events experienced or witnessed and all three mental disorders.
INTERPRETATION
The implementation of mental health awareness programmes, interventions aimed at high risk groups and addressing trauma-related symptoms from all causes are needed in the Kashmir Valley.