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Background: Efficient contact investigation strategies are needed for the early diagnosis of tuberculosis (TB) disease and treatment of latent TB infections., Methods: Between September 2009 and August 2012, we conducted a prospective cohort study in Lima, Peru, in which we enrolled and followed 14 044 household contacts of adults with pulmonary TB. We used information from a subset of this cohort to derive 2 clinical prediction tools that identify contacts of TB patients at elevated risk of progressing to active disease by training multivariable models that predict (1) coprevalent TB among all household contacts and (2) 1-year incident TB among adult contacts. We validated the models in a geographically distinct subcohort and compared the relative utilities of clinical decisions based on these tools to existing strategies., Results: In our cohort, 296 (2.1%) household contacts had coprevalent TB and 145 (1.9%) adult contacts developed incident TB within 1 year of index patient diagnosis. We predicted coprevalent disease using information that could be readily obtained at the time an index patient was diagnosed and predicted 1-year incident TB by including additional contact-specific characteristics. The area under the receiver operating characteristic curves for coprevalent TB and incident TB were 0.86 (95% confidence interval [CI], .83-.89]) and 0.72 (95% CI, .67-.77), respectively. These clinical tools give 5%-10% higher relative utilities than existing methods., Conclusions: We present 2 tools that identify household contacts at high risk for TB disease based on reportable information from patient and contacts alone. The performance of these tools is comparable to biomarkers that are both more costly and less feasible than this approach., (© The Author(s) 2020. Published by Oxford University Press for the Infectious Diseases Society of America.)

Rationale: The World Health Organization recommends the use of isoniazid (INH) alone or in combination with rifapentine to treat latent tuberculosis infections. The recent rise of drug-resistant tuberculosis has complicated the choice of treatment regimen for latent tuberculosis infection. Objectives: To evaluate the effects of INH preventive therapy on the contacts of patients with multidrug-resistant tuberculosis. Methods: In a prospective cohort study conducted between September 2009 and August 2012, we identified 4,500 index patients with tuberculosis and 14,044 tuberculosis-exposed household contacts who we followed for 1 year for the occurrence of incident tuberculosis disease. Although Peruvian national guidelines specify that INH preventive therapy should be provided to contacts aged 19 years old or younger, only half this group received INH preventive therapy. Measurements and Main Results: Among 4,216 contacts under 19 years of age, 2,106 contacts (50%) initiated INH preventive therapy at enrollment. The protective effect of INH was more extreme in contacts exposed to drug-sensitive tuberculosis (adjusted hazard ratio, 0.30; 95% confidence interval, 0.18-0.48) and to multidrug-resistant tuberculosis (adjusted hazard ratio, 0.19; 95% confidence interval, 0.05-0.66) compared with those exposed to mono-INH-resistant tuberculosis (adjusted hazard ratio, 0.80; 95% confidence interval, 0.23-2.80). In the second independent study, tuberculosis occurred in none of the 76 household contacts who received INH preventive therapy compared with 3% (8 of 273) of those who did not. Conclusions: Household contacts who received INH preventive therapy had a lower incidence of tuberculosis disease even when they had been exposed to an index patient with multidrug-resistant tuberculosis. INH may have a role in the management of latent multidrug-resistant tuberculosis infection.

Background: Appropriate management of people exposed in the home to tuberculosis is essential to prevent morbidity. These household contacts, particularly children, should receive preventive therapy to prevent them from falling ill. However, few people receive preventive therapy worldwide. We sought to determine whether a community-based accompaniment intervention could improve tuberculosis contact management., Methods: We conducted a prospective cohort study of household contacts of tuberculosis patients who initiated treatment during September 2015-June 2016 in Lima, Peru. Enrolled households received an intervention comprising home visits, transport vouchers, assistance coordinating evaluation procedures, and adherence support during preventive therapy. To evaluate the impact of the intervention, we conducted retrospective chart reviews of all patients initiating treatment during 6-month baseline and intervention periods., Results: We enrolled 314 household contacts of 109 index patients. Of these, 283 (90%) completed evaluation, and 4 (1%) were diagnosed with tuberculosis. Preventive therapy was prescribed for 35/38 (92%) contacts 0-19 years old who were eligible under Peruvian guidelines. Preventive therapy was also prescribed for 6/26 (23%) contacts with unknown eligibility due to lack of a tuberculin skin test (TST), and 20/69 (29%) who were ineligible either because of a negative TST result or exposure to a drug-resistant or extrapulmonary case. Of the 61 contacts who were prescribed preventive therapy, 57 (93%) initiated treatment, and 51 (91%) completed treatment. The proportion of contacts who completed evaluation increased from 42% during the baseline period to 71% during the evaluation period (risk ratio [RR] = 1.73, 95% confidence interval [95% CI]: 1.41-2.13). The proportion of contacts who initiated preventive therapy increased from 15% to 40% (RR = 2.45, 95% CI: 1.42-4.22)., Conclusion: Accompaniment of TB patient households greatly improved the evaluation of household contacts for TB and increased the use of preventive therapy., Competing Interests: The authors have declared that no competing interests exist.

Rationale: Individuals living with patients with tuberculosis (TB) are at elevated risk of infection and disease, with children at greatest risk. The World Health Organization recommends isoniazid preventive therapy (IPT) for HIV-positive contacts and those younger than 5 years. Despite these recommendations, household-level IPT programs are rarely implemented in high TB burden settings. Evidence is scarce about the age-specific efficacy of interventions, such as IPT and bacillus Calmette-Guérin (BCG) vaccination for preventing TB disease among exposed contacts., Objectives: We estimate the age-specific efficacy of IPT and BCG for preventing TB disease using data from a large observational prospective cohort study of household contacts of patients with TB in Lima, Peru., Methods: We identified all adults (>15 yr) with incident pulmonary TB (index cases) diagnosed at 106 public health centers in Lima from September 2009 to August 2012. Among 14,041 household contacts (of 3,446 index cases) assessed for infection and disease during the year-long follow-up period, we identified 462 additional TB cases. We estimate risk ratios (RR) for pulmonary TB associated with BCG, IPT, and latent TB infection., Measurements and Main Results: BCG confers protection against coprevalent and incident TB among HIV-negative children younger than 10 years (RR, 0.35; 95% confidence interval, 0.19-0.66). IPT confers protection against incident TB among HIV-negative contacts younger than 30 years (RR, 0.33; 95% confidence interval, 0.20-0.54). Risk of incident TB associated with latent TB infection is greatest for children younger than 5 years and decreases with age., Conclusions: These findings support the use of IPT in older children and young-adult household contacts, in addition to children younger than 5 years.

Contact investigations among individuals living with drug-susceptible tuberculosis patients (source cases) have shown a high yield of tuberculosis disease and latent tuberculosis, but the yield of such investigations in households of drug-resistant tuberculosis source cases is unknown. In this systematic review and meta-analysis, we found 25 studies that evaluated a median of 111 (interquartile range, 21-302) household contacts of drug-resistant tuberculosis source cases. The pooled yield was 7.8% (95% CI, 5.6%-10.0%) for active tuberculosis and 47.2% (95% CI, 30.0%-61.4%) for latent tuberculosis, although there was significant statistical heterogeneity (P < .0001). More than 50% of secondary cases with drug susceptibility test results were concordant with those of the source case. Among studies that followed household members, the majority of secondary cases were detected within 1 year of the source case's diagnosis. Household contact investigation around drug-resistant tuberculosis patients is a high-yield intervention for detection of drug-resistant tuberculosis and prevention of ongoing transmission.

Background: Multidrug-resistant (MDR) and extensively drug-resistant (XDR) tuberculosis have emerged as major global health threats. WHO recommends contact investigation in close contacts of patients with MDR and XDR tuberculosis. We aimed to assess the burden of tuberculosis disease in household contacts of such patients., Methods: We undertook a retrospective cohort study of household contacts of patients treated for MDR or XDR tuberculosis in Lima, Peru, in 1996-2003. The primary outcome was active tuberculosis in household contacts at the time the index patient began MDR tuberculosis treatment and during the 4-year follow-up. We examined whether the occurrence of active tuberculosis in the household contacts differed by resistance pattern of the index patient: either MDR or XDR tuberculosis., Findings: 693 households of index patients with MDR tuberculosis were enrolled in the study. In 48 households, the Mycobacterium tuberculosis isolate from the index patient was XDR. Of the 4503 household contacts, 117 (2·60%) had active tuberculosis at the time the index patient began MDR tuberculosis treatment-there was no difference in prevalence between XDR and MDR tuberculosis households. During the 4-year follow-up, 242 contacts developed active tuberculosis-the frequency of active tuberculosis was nearly two times higher in contacts of patients with XDR tuberculosis than it was in contacts of patients with MDR tuberculosis (hazard ratio 1·88, 95% CI 1·10-3·21). In the 359 contacts with active tuberculosis, 142 (40%) had had isolates tested for resistance against first-line drugs, of whom 129 (90·9%, 95% CI 85·0-94·6) had MDR tuberculosis., Interpretation: In view of the high risk of disease recorded in household contacts of patients with MDR or XDR tuberculosis, tuberculosis programmes should implement systematic household contact investigations for all patients identified as having MDR or XDR tuberculosis. If shown to have active tuberculosis, these household contacts should be suspected as having MDR tuberculosis until proven otherwise., Funding: The Charles H Hood Foundation, the David Rockefeller Center for Latin American Studies at Harvard University, and the Bill & Melinda Gates Foundation., (Copyright © 2011 Elsevier Ltd. All rights reserved.)

Objectives: Tuberculosis (TB) case detection remains low in many countries, compromising the efficacy of TB control efforts. Current global TB control policy emphasizes case finding through sputum smear microscopy for patients who self-report to primary health centers. Our objective was to assess the feasibility and yield of a simple active case finding strategy in a high incidence population in northern Lima, Peru., Methods: We implemented this pilot strategy in one health center's catchment area. Health workers visited household contacts of new TB case subjects to identify symptomatic individuals and collect sputum for screening. Neighboring households were screened in the same manner. Secondary analyses measured risk of TB by (1) sputum smear status of the index case subject, (2) compliance with testing, and (3) risk factors for disease detected through active contact tracing in contrast to self-report., Results: The TB prevalence detected through combined active and passive case finding among 1,094 household contacts was 0.91% (914 per 100,000), much higher than with passive case finding alone (0.18%; 183 per 100,000; p=0.02). Among 2,258 neighbors, the combined strategy detected a TB prevalence of 0.22% (221 per 100,000) in contrast to 0.08% (80 per 100,000) detected through passive case finding alone (p=0.25). Risk factors for being diagnosed through active case finding in contrast with self-report included age >55 years (odds ratio [OR]=5.5; 95% confidence interval [CI] 1.2, 22.8) and female gender (OR=3.9; 95% CI 0.99, 22.3)., Conclusions: Risk of active TB among symptomatic household contacts of active case subjects in this community is very high. Results suggest that contact tracing in such settings may be a powerful means of improving case detection rates for active TB disease.

Rationale: The persistent burden of tuberculosis (TB) disease emphasizes the need to identify individuals with TB for treatment and those at a high risk of incident TB for prevention. Targeting interventions toward those at high risk of developing and transmitting TB is a public health priority. Objectives: We aimed to identify characteristics of individuals involved in TB transmission in a community setting, which may guide the prioritization of targeted interventions. Methods: We collected clinical and sociodemographic data from a cohort of patients with TB in Lima, Peru. We used whole-genome sequencing data to assess the genetic distance between all possible pairs of patients; we considered pairs to be the result of a direct transmission event if they differed by three or fewer SNPs, and we assumed that the first diagnosed patient in a pair was the transmitter and the second was the recipient. We used logistic regression to examine the association between host factors and the likelihood of direct TB transmission. Measurements and Main Results: Analyzing data from 2,518 index patients with TB, we identified 1,447 direct transmission pairs. Regardless of recipient attributes, individuals less than 34 years old, males, and those with a history of incarceration had a higher likelihood of being transmitters in direct transmission pairs. Direct transmission was more likely when both patients were drinkers or smokers. Conclusions: This study identifies men, young adults, former prisoners, alcohol consumers, and smokers as priority groups for targeted interventions. Innovative strategies are needed to extend TB screening to social groups such as young adults and prisoners with limited access to routine preventive care. [ABSTRACT FROM AUTHOR]

Mathematical models have suggested that spatially-targeted screening interventions for tuberculosis may efficiently accelerate disease control, but empirical data supporting these findings are limited. Previous models demonstrating substantial impacts of these interventions have typically simulated large-scale screening efforts and have not attempted to capture the spatial distribution of tuberculosis in households and communities at a high resolution. Here, we calibrate an individual-based model to the locations of case notifications in one district of Lima, Peru. We estimate the incremental efficiency and impact of a spatially-targeted interventions used in combination with household contact tracing (HHCT). Our analysis reveals that HHCT is relatively efficient with a median of 40 (Interquartile Range: 31.7 to 49.9) household contacts required to be screened to detect a single case of active tuberculosis. However, HHCT has limited population impact, producing a median incidence reduction of only 3.7% (Interquartile Range: 5.8% to 1.9%) over 5 years. In comparison, spatially targeted screening (which we modeled as active case finding within high tuberculosis prevalence areas 100 m2 grid cell) is far less efficient, requiring evaluation of ≈12 times the number of individuals as HHCT to find a single individual with active tuberculosis. Furthermore, the addition of the spatially targeted screening effort produced only modest additional reductions in tuberculosis incidence over the 5 year period (≈1.3%) in tuberculosis incidence. In summary, we found that HHCT is an efficient approach for tuberculosis case finding, but has limited population impact. Other screening approaches which target areas of high tuberculosis prevalence are less efficient, and may have limited impact unless very large numbers of individuals can be screened. [ABSTRACT FROM AUTHOR]

Background Scaling up a shorter preventive regimen such as weekly isoniazid and rifapentine (3HP) for 3 months is a priority for tuberculosis (TB) preventive treatment (TPT). However, there are limited data on 3HP acceptability and completion from high-burden-TB countries. Methods We scaled up 3HP from 2018 to 2021 in 2 cities in Pakistan. Eligible participants were household contacts of persons diagnosed with TB disease. Participants were prescribed 3HP after ruling out TB disease. Treatment was self-administered. We analyzed the proportion who completed 3HP. Results In Karachi, we verbally screened 22 054 household contacts of all ages. Of these, 83% were clinically evaluated and 3% were diagnosed with TB. Of household contacts without TB disease, 59% initiated the 3HP regimen, of which 69% completed treatment. In Peshawar, we verbally screened 6389 household contacts of all ages. We evaluated 95% of household contacts, of whom 2% were diagnosed with TB disease. Among those without TB disease, 65% initiated 3HP, of which 93% completed. Factors associated with higher 3HP completion included residence in Peshawar (risk ratio [RR], 1.35 [95% confidence interval {CI}: 1.32–1.37]), index patient being a male (RR, 1.03 [95% CI: 1.01–1.05]), and index patient with extrapulmonary TB compared to bacteriologically positive pulmonary TB (RR, 1.10 [95% CI: 1.06–1.14]). The age of the index patient was inversely associated with completion. Conclusions We observed a high level of acceptance and completion of 3HP in programs implemented in 2 cities in Pakistan, with differences observed across the cities. These findings suggest that 3HP can be effectively scaled up in urban settings to improve the reach and impact of TPT. [ABSTRACT FROM AUTHOR]

Background There is a dearth of research to understand which children, among those who are exposed at home to tuberculosis (TB), are at the highest risk of TB disease, to tailor care. We sought to identify predictors of TB progression in children. Methods We conducted a prospective cohort study of children living with adults with pulmonary TB in Lima, Peru (2009–2012). We applied classification and regression tree analysis to examine potential predictors of incident TB disease during 12 months in 3 age groups (0–4, 5–9, and 10–14 years). We calculated the relative risk (RR) for top predictors in each age group. Results Among 4545 children 0–14 years old, 156 (3.4%) were diagnosed with TB within 1 year of household exposure to TB (3.4%, 2.3%, and 4.7% in children 0–4, 5–9, and 10–14 years old, respectively). The most important predictor of TB was having a positive tuberculin skin test (TST) result, with RRs of 6.6 (95% CI, 4.0–10.7), 6.6 (95% CI, 3.2–13.6), and 5.2 (95% CI, 3.0–9.0) in the age groups 0–4, 5–9, and 10–14 years, respectively. In young children with a positive TST, not using isoniazid preventive treatment further increased risk of disease (RR, 12.2 [95% CI, 3.8–39.2]). Conclusions We present a tool that identifies child household contacts at high risk of TB disease progression based on data collected during contact tracing. In addition to the use of TB preventive therapy for all children exposed at home to TB, those children at highest risk of progressing to TB disease may benefit from more frequent follow-up. [ABSTRACT FROM AUTHOR]

Background While previous studies have shown that cigarette smoking increases the infectiousness of tuberculosis patients, the impact of smoking cessation on tuberculosis transmissibility has not been evaluated. Methods Between 2009 and 2012, we enrolled 4500 tuberculosis patients and followed 14 044 household contacts in Lima, Peru. Tuberculosis patients were classified into 4 categories: never smoked, quit in the distant past (stopped smoking >2 months prior to time of diagnosis), recently quit (stopped smoking ≤2 months prior to time of diagnosis), and active smokers. We used a modified Poisson generalized estimating equation to assess the risk of tuberculosis infection of child contacts at enrollment and by 6 months of follow-up. Results In total, 1371 (76.8%) child contacts were exposed to patients who had never smoked, 211 (11.8%) were exposed to distant quitters, 155 (8.7%) were exposed to recent quitters, and 49 (2.7%) were exposed to active smokers. Compared with child contacts of index patients who had never smoked, child contacts of recent quitters had a similar risk of tuberculosis infection at enrollment (adjusted risk ratio, 95% confidence intervals [0.81, 0.50–1.32]) and by six months of follow-up (0.76, 0.51–1.13); and by 6 months of follow-up (aRR, 0.76; 95% CI,.51–1.13); child contacts of recent quitters had a significantly reduced risk of tuberculosis infection compared with contacts of active smokers (enrollment 0.45, 0.24–0.87; 6-month follow-up 0.48, 0.29–0.79). Conclusions Our results show that the adverse effects of smoking on the transmissibility of tuberculosis are significantly reduced shortly after quitting smoking, reinforcing the importance of smoking cessation interventions in tuberculosis control. [ABSTRACT FROM AUTHOR]

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%; I 2 = 85%). Pooled isoniazid/rifampin concordance was 82.6% (95% CI, 72.3–90.9%; I 2 = 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. [ABSTRACT FROM AUTHOR]

Background: Targeted testing and treatment of TB infection to prevent disease is a pillar of TB elimination. Despite recent global commitments to greatly expand access to preventive treatment for TB infection, there remains a lack of research on how best to expand preventive treatment programs in settings with high TB burdens. Methods: We conducted implementation research in Lima, Peru, around a multifaceted intervention to deliver TB preventive treatment to close contacts of all ages, health care workers, and people in congregate settings. Key interventions included use of the interferon gamma release assay (IGRA), specialist support for generalist physicians at primary-level health facilities, and treatment support by community health workers. We applied a convergent mixed methods approach to evaluate feasibility and acceptability based on a care cascade framework. Findings: During April 2019-January 2020, we enrolled 1,002 household contacts, 148 non-household contacts, 107 residents and staff of congregate settings, and 357 health care workers. Cumulative completion of the TB preventive care cascade was 34% for contacts <5 years old, 28% for contacts 5–19 years old, 18% for contacts ≥20 years old, 0% for people in congregate settings, and 4% of health care workers. IGRA testing was acceptable to adults exposed to TB. Preventive treatment was acceptable to contacts, but less acceptable to physicians, who frequently had doubts about prescribing preventive treatment for adults. Community-based treatment support was both acceptable and feasible, and periodic home-visits or calls were identified as facilitators of adherence. Conclusions: We attempted to close the gap in TB preventive treatment in Peru by expanding preventive services to adult contacts and other risk groups. While suboptimal, care cascade completion for adult contacts was consistent with what has been observed in high-income settings. The major losses in the care cascade occurred in completing evaluations and having doctors prescribe preventive treatment. [ABSTRACT FROM AUTHOR]

We analyzed data from a large population-based prospective cohort study of household contacts of tuberculosis patients in Lima, Peru, to estimate the importance of within-household transmission relative to community-based transmission. We identified all adults (older than 15 years of age) who had incident pulmonary tuberculosis diagnosed at any of 106 public health centers in Lima from September 2009 to August 2012. A total of 14,041 household contacts of 3,446 index patients were assessed for tuberculosis infection and disease. We compared the prevalence of latent tuberculosis infection (LTBI) among persons who had received the Bacillus Calmette–Guérin vaccine in households with and without a microbiologically confirmed index case to estimate the age-specific risk of infection and excess risk of LTBI from household and community exposures. We found that the risk of infection from household and community sources increased from birth until 20 years of age. However, a large proportion of infections among child and young-adult household contacts could have been the result of household exposure. Excess infection risk associated with household exposure accounted for 58% (95% confidence interval: 47, 66) of LTBI prevalence among exposed children younger than 1 year of age, 48% (95% confidence interval: 39, 57) among 10-year-old children, and 44% (95% confidence interval: 34, 51) among 15-year-old adolescents. These findings suggest that expanded access to preventive therapy for older children and young-adult household contacts of known tuberculosis cases may be beneficial. [ABSTRACT FROM PUBLISHER]