A household-level score to predict the risk of tuberculosis among contacts of patients with tuberculosis: a derivation and external validation prospective cohort study.

BACKGROUND: The epidemiological impact and cost-effectiveness of social protection and biomedical interventions for tuberculosis-affected households might be improved by risk stratification. We therefore derived and externally validated a household-level risk score to predict tuberculosis among contacts of patients with tuberculosis. METHODS: In this prospective cohort study, we recruited tuberculosis-affected households from 15 desert shanty towns in Ventanilla and 17 urban communities in Callao, Lima, Peru. Tuberculosis-affected households included index patients with a new diagnosis of tuberculosis and their contacts who reported being in the same house as the index patient for more than 6 h per week in the 2 weeks preceding index patient diagnosis. Tuberculosis-affected households were not included if the index patient had no eligible contacts or lived alone. We followed contacts until 2018 and defined household tuberculosis, the primary outcome, as any contact having any form of tuberculosis within 3 years. We used logistic regression to identify characteristics of index patients, contacts, and households that were predictive of household tuberculosis, and used these to derive and externally validate a household-level score. FINDINGS: Between Dec 12, 2007, and Dec 31, 2015, 16 505 contacts from 3 301 households in Ventanilla were included in a derivation cohort. During the 3-year follow-up, tuberculosis occurred in contacts of index patients in 430 (13%, 95% CI 12-14) households. Index patient predictors were pulmonary tuberculosis and sputum smear grade, age, and the maximum number of hours any contact had spent with the index patient while they had any cough. Household predictors were drug use, schooling of the female head of a household, and lower food spending. Contact predictors were if any of the contacts were children, number of lower-weight (body-mass index [BMI] <20·0 kg/m2) adult contacts, number of normal-weight (BMI 20·0-24·9 kg/m2) adult contacts, and number of past or present household members who previously had tuberculosis. In this derivation cohort, the score c statistic was 0·77 and the risk of household tuberculosis in the highest scoring quintile was 31% (95% CI 25-38; 65 of 211) versus 2% (95% CI 0-4; four of 231) in the lowest scoring quintile. We externally validated the risk score in a cohort of 4248 contacts from 924 households in Callao recruited between April 23, 2014, and Dec 31, 2015. During follow-up, tuberculosis occurred in contacts of index patients in 120 (13%, 95% CI 11-15) households. The score c statistic in this cohort was 0·75 and the risk of household tuberculosis in the highest scoring quintile was 28% (95% CI 21-36; 43 of 154) versus 1% (95% CI 0-5; two of 148) in the lowest scoring quintile. The highest-scoring third of households captured around 70% of all tuberculosis among contacts. A simplified risk score including only five variables performed similarly, with only a small reduction in performance. INTERPRETATION: This externally validated score will enable comprehensive biosocial, household-level interventions to be targeted to tuberculosis-affected households that are most likely to benefit. FUNDING: Wellcome Trust, Medical Research Council, Department of Health and Social Care, Department for International Development, Joint Global Health Trials consortium, Bill & Melinda Gates Foundation, Innovation for Health and Development.

Active and passive case-finding in tuberculosis-affected households in Peru: a 10-year prospective cohort study.

BACKGROUND: Active case-finding among contacts of patients with tuberculosis is a global health priority, but the effects of active versus passive case-finding are poorly characterised. We assessed the contribution of active versus passive case-finding to tuberculosis detection among contacts and compared sex and disease characteristics between contacts diagnosed through these strategies. METHODS: In shanty towns in Callao, Peru, we identified index patients with tuberculosis and followed up contacts aged 15 years or older for tuberculosis. All patients and contacts were offered free programmatic active case-finding entailing sputum smear microscopy and clinical assessment. Additionally, all contacts were offered intensified active case-finding with sputum smear and culture testing monthly for 6 months and then once every 4 years. Passive case-finding at local health facilities was ongoing throughout follow-up. FINDINGS: Between Oct 23, 2002, and May 26, 2006, we identified 2666 contacts, who were followed up until March 1, 2016. Median follow-up was 10·0 years (IQR 7·5-11·0). 232 (9%) of 2666 contacts were diagnosed with tuberculosis. The 2-year cumulative risk of tuberculosis was 4·6% (95% CI 3·5-5·5), and overall incidence was 0·98 cases (95% CI 0·86-1·10) per 100 person-years. 53 (23%) of 232 contacts with tuberculosis were diagnosed through active case-finding and 179 (77%) were identified through passive case-finding. During the first 6 months of the study, 23 (45%) of 51 contacts were diagnosed through active case-finding and 28 (55%) were identified through passive case-finding. Contacts diagnosed through active versus passive case-finding were more frequently female (36 [68%] of 53 vs 85 [47%] of 179; p=0·009), had a symptom duration of less than 15 days (nine [25%] of 36 vs ten [8%] of 127; p=0·03), and were more likely to be sputum smear-negative (33 [62%] of 53 vs 62 [35%] of 179; p=0·0003). INTERPRETATION: Although active case-finding made an important contribution to tuberculosis detection among contacts, passive case-finding detected most of the tuberculosis burden. Compared with passive case-finding, active case-finding was equitable, helped to diagnose tuberculosis earlier and usually before a positive result on sputum smear microscopy, and showed a high burden of undetected tuberculosis among women. FUNDING: Wellcome Trust, Department for International Development Civil Society Challenge Fund, Joint Global Health Trials consortium, Bill & Melinda Gates Foundation, Imperial College National Institutes of Health Research Biomedical Research Centre, Foundation for Innovative New Diagnostics, Sir Halley Stewart Trust, WHO, TB REACH, and IFHAD: Innovation for Health and Development.

Mobile phone interventions for tuberculosis should ensure access to mobile phones to enhance equity - a prospective, observational cohort study in Peruvian shantytowns.

OBJECTIVES: Mobile phone interventions have been advocated for tuberculosis care, but little is known about access of target populations to mobile phones. We studied mobile phone access among patients with tuberculosis, focusing on vulnerable patients and patients who later had adverse treatment outcomes. METHODS: In a prospective cohort study in Callao, Peru, we recruited and interviewed 2584 patients with tuberculosis between 2007 and 2013 and followed them until 2016 for adverse treatment outcomes using national treatment registers. Subsequently, we recruited a further 622 patients between 2016 and 2017. Data were analysed using logistic regression and by calculating relative risks (RR). RESULTS: Between 2007 and 2013, the proportion of the general population of Peru without mobile phone access averaged 7.8% but for patients with tuberculosis was 18% (P < 0.001). Patients without access were more likely to hold a lower socioeconomic position, suffer from food insecurity and be older than 50 years (all P < 0.01). Compared to patients with mobile phone access, patients without access at recruitment were more likely to subsequently have incomplete treatment (20% vs. 13%, RR = 1.5; P = 0.001) or an adverse treatment outcome (29% vs. 23% RR = 1.3; P = 0.006). Between 2016 and 2017, the proportion of patients without access dropped to 8.9% overall, but remained the same (18%) as in 2012 among the poorest third. CONCLUSION: Access to mobile phones among patients with tuberculosis is insufficient, and rarest in patients who are poorer and later have adverse treatment outcomes. Thus, mobile phone interventions to improve tuberculosis care may be least accessed by the priority populations for whom they are intended. Such interventions should ensure access to mobile phones to enhance equity.

Socioeconomic and Behavioral Factors Associated with Tuberculosis Diagnostic Delay in Lima, Peru.

Early detection and diagnosis of tuberculosis (TB) is a global priority. Prolonged symptom duration before TB diagnosis is associated with increased morbidity, mortality, and risk of transmission. We aimed to determine socioeconomic and behavioral factors associated with diagnostic delays among patients with TB. Data were collected from 105 patients with TB using a semi-structured interview guide in Lima, Peru. Factors associated with diagnostic delay were analyzed using negative binomial regression. The median delay from when symptoms commenced and the first positive diagnostic sample in public health facilities was 57 days (interquartile range: 28-126). In multivariable analysis, greater diagnostic delay was independently associated with patient older age, female gender, lower personal income before diagnosis, living with fewer people, and having more visits to professional health facilities before diagnosis (all P < 0.05). Patients who first sought care at a private health facility had more visits overall to professional health facilities before diagnosis than those who first sought care from public or insured employee health facilities and had longer diagnostic delay in analysis adjusted for age and gender. Patients with TB were significantly more likely to first self-medicate than to visit professional health facilities before diagnosis (P = 0.003). Thus, diagnostic delay was prolonged, greatest among older, low-income women, and varied according to the type of care sought by individuals when their symptoms commenced. These findings suggest that TB case-finding initiatives should target vulnerable groups in informal and private health facilities, where many patients with TB first seek health care.

A score to predict and stratify risk of tuberculosis in adult contacts of tuberculosis index cases: a prospective derivation and external validation cohort study.

BACKGROUND: Contacts of tuberculosis index cases are at increased risk of developing tuberculosis. Screening, preventive therapy, and surveillance for tuberculosis are underused interventions in contacts, particularly adults. We developed a score to predict risk of tuberculosis in adult contacts of tuberculosis index cases. METHODS: In 2002-06, we recruited contacts aged 15 years or older of index cases with pulmonary tuberculosis who lived in desert shanty towns in Ventanilla, Peru. We followed up contacts for tuberculosis until February, 2016. We used a Cox proportional hazards model to identify index case, contact, and household risk factors for tuberculosis from which to derive a score and classify contacts as low, medium, or high risk. We validated the score in an urban community recruited in Callao, Peru, in 2014-15. FINDINGS: In the derivation cohort, we identified 2017 contacts of 715 index cases, and median follow-up was 10·7 years (IQR 9·5-11·8). 178 (9%) of 2017 contacts developed tuberculosis during 19 147 person-years of follow-up (incidence 0·93 per 100 person-years, 95% CI 0·80-1·08). Risk factors for tuberculosis were body-mass index, previous tuberculosis, age, sustained exposure to the index case, the index case being in a male patient, lower community household socioeconomic position, indoor air pollution, previous tuberculosis among household members, and living in a household with a low number of windows per room. The 10-year risks of tuberculosis in the low-risk, medium-risk, and high-risk groups were, respectively, 2·8% (95% CI 1·7-4·4), 6·2% (4·8-8·1), and 20·6% (17·3-24·4). The 535 (27%) contacts classified as high risk accounted for 60% of the tuberculosis identified during follow-up. The score predicted tuberculosis independently of tuberculin skin test and index-case drug sensitivity results. In the external validation cohort, 65 (3%) of 1910 contacts developed tuberculosis during 3771 person-years of follow-up (incidence 1·7 per 100 person-years, 95% CI 1·4-2·2). The 2·5-year risks of tuberculosis in the low-risk, medium-risk, and high-risk groups were, respectively, 1·4% (95% CI 0·7-2·8), 3·9% (2·5-5·9), and 8·6%· (5·9-12·6). INTERPRETATION: Our externally validated risk score could predict and stratify 10-year risk of developing tuberculosis in adult contacts, and could be used to prioritise tuberculosis control interventions for people most likely to benefit. FUNDING: Wellcome Trust, Department for International Development Civil Society Challenge Fund, Joint Global Health Trials consortium, Bill & Melinda Gates Foundation, Imperial College National Institutes of Health Research Biomedical Research Centre, Foundation for Innovative New Diagnostics, Sir Halley Stewart Trust, WHO, TB REACH, and Innovation for Health and Development.

A randomized controlled study of socioeconomic support to enhance tuberculosis prevention and treatment, Peru.

OBJECTIVE: To evaluate the impact of socioeconomic support on tuberculosis preventive therapy initiation in household contacts of tuberculosis patients and on treatment success in patients. METHODS: A non-blinded, household-randomized, controlled study was performed between February 2014 and June 2015 in 32 shanty towns in Peru. It included patients being treated for tuberculosis and their household contacts. Households were randomly assigned to either the standard of care provided by Peru's national tuberculosis programme (control arm) or the same standard of care plus socioeconomic support (intervention arm). Socioeconomic support comprised conditional cash transfers up to 230 United States dollars per household, community meetings and household visits. Rates of tuberculosis preventive therapy initiation and treatment success (i.e. cure or treatment completion) were compared in intervention and control arms. FINDINGS: Overall, 282 of 312 (90%) households agreed to participate: 135 in the intervention arm and 147 in the control arm. There were 410 contacts younger than 20 years: 43% in the intervention arm initiated tuberculosis preventive therapy versus 25% in the control arm (adjusted odds ratio, aOR: 2.2; 95% confidence interval, CI: 1.1-4.1). An intention-to-treat analysis showed that treatment was successful in 64% (87/135) of patients in the intervention arm versus 53% (78/147) in the control arm (unadjusted OR: 1.6; 95% CI: 1.0-2.6). These improvements were equitable, being independent of household poverty. CONCLUSION: A tuberculosis-specific, socioeconomic support intervention increased uptake of tuberculosis preventive therapy and tuberculosis treatment success and is being evaluated in the Community Randomized Evaluation of a Socioeconomic Intervention to Prevent TB (CRESIPT) project.