Active case finding in tuberculosis-affected households: time to scale up

In 2017, 10 million people developed tuberculosis, of whom approximately 4 million were not diagnosed, treated, or notified to national tuberculosis programmes (NTP).1WHOGlobal Tuberculosis Report 2018. World Health Organization, Geneva2018Google Scholar Of the remaining 6 million, many experienced substantial delays in accessing and receiving appropriate care.1WHOGlobal Tuberculosis Report 2018. World Health Organization, Geneva2018Google Scholar This unacceptable situation leads to unnecessary disability and loss of life, and impedes tuberculosis control because of onward transmission at a household and community level. To rectify these shortcomings and eliminate tuberculosis, new strategies are urgently required to enhance tuberculosis case detection. WHO endorses two complementary approaches to improve tuberculosis case detection: active case finding (ACF) and systematic screening of household contacts.2WHOSystematic screening for active tuberculosis: principles and recommendations. World Health Organization, Geneva2013Google Scholar, 3WHORecommendations for investigating contacts of persons with infectious tuberculosis in low- and middle-income countries. World Health Organization, Geneva2012Google Scholar Household contacts of people with tuberculosis are a group at high risk of acquisition of tuberculosis infection and development of tuberculosis disease. Most incident tuberculosis cases within the household occur in the first 2 years following the diagnosis of the index patient.4Saunders MJ Wingfield T Tovar MA et al.A score to predict and stratify risk of tuberculosis in adult contacts of tuberculosis index cases: a prospective derivation and external validation cohort study.Lancet Infect Dis. 2017; 17: 1190-1199Summary Full Text Full Text PDF PubMed Scopus (62) Google Scholar Household-level interventions that identify contacts with latent tuberculosis infection and tuberculosis disease and provide appropriate preventive therapy or treatment can break the chain of onward transmission.5Saunders MJ Tovar MA Datta S Evans BEW Wingfield T Evans CA Pragmatic tuberculosis prevention policies for primary care in low- and middle-income countries.Eur Respir J. 2018; 51: 1800315Crossref PubMed Scopus (5) Google Scholar Thus, such interventions have the potential to reduce the prevalence of tuberculosis at a community level, especially in low-income and middle-income countries with a high tuberculosis burden.6Fair E Miller CR Ottmani SE Fox GJ Hopewell PC Tuberculosis contact investigation in low- and middle-income countries: standardized definitions and indicators.Int J Tuberc Lung Dis. 2015; 19: 269-272Crossref PubMed Scopus (28) Google Scholar In The Lancet Global Health, Thomas Lung and colleagues7Lung T Marks GB Nhung NV et al.Household contact investigation for the detection of tuberculosis in Vietnam: economic evaluation of a cluster-randomised trial.Lancet Glob Health. 2019; 9: e376-e384Google Scholar report the findings of an economic evaluation conducted alongside a large trial of an ACF intervention in Vietnam. ACT2 was a large, cluster randomised trial8Fox GJ Nhung NV Marks GB Household-contact investigation for detection of tuberculosis in Vietnam.N Engl J Med. 2018; 378: 221-229Crossref PubMed Scopus (112) Google Scholar that recruited 25 707 household contacts of 10 964 patients with tuberculosis in 70 districts of Vietnam. Household contacts in intervention districts were invited to be screened for tuberculosis (consisting of physical examination, chest radiograph, and symptom questionnaire) at a local clinic at enrolment, then at 6 months, 12 months, and 24 months. Household contacts in control districts received standard care. Lung and colleagues estimated the number of disability-adjusted life years (DALYs) averted in the intervention group over 24 months.8Fox GJ Nhung NV Marks GB Household-contact investigation for detection of tuberculosis in Vietnam.N Engl J Med. 2018; 378: 221-229Crossref PubMed Scopus (112) Google Scholar The trial results showed that, in the study sites, an additional 1084 registered tuberculosis cases (95% CI 721–1410) and 1154 (776–1495) smear positive tuberculosis contacts per 100 000 people were identified over the 24-month follow-up period in the intervention group compared with the control group, respectively. The estimated incremental cost-effectiveness ratio was US$544 (95% CI 330–1375) per DALY averted and the investigators conducted several sensitivity analyses around model inputs. Although these findings might not be generalisable to other settings—especially to low-income countries or those with high rates of HIV and tuberculosis co-prevalence—the findings, nonetheless, remain important. ACT2 is one of the first rigorous trials to show that an ACF intervention integrated into NTP activities not only increased tuberculosis case detection and reduced all-cause mortality8Fox GJ Nhung NV Marks GB Household-contact investigation for detection of tuberculosis in Vietnam.N Engl J Med. 2018; 378: 221-229Crossref PubMed Scopus (112) Google Scholar but was also cost-effective. The authors conclude that ACF in tuberculosis-affected households should be considered for wider implementation and scale-up in Vietnam. Despite proven benefits and endorsement by WHO, ACF interventions tailored towards tuberculosis-affected households have not been widely adopted or integrated into NTP activities in high-burden settings.9Ho J Fox GJ Marais BJ Passive case finding for tuberculosis is not enough.Int J Mycobacteriol. 2016; 5: 374-378Crossref PubMed Scopus (60) Google Scholar The reasons behind this low implementation are complex and include health systems that have restricted, overstretched resources; NTPs that work mainly within a static model of health-care provision in clinics and hospitals; and tuberculosis care and prevention that occurs predominantly through passive case finding rather than active case finding, community engagement, and outreach. Another important factor underlying the gap between global policy and national-level implementation of ACF and systematic household screening interventions is the lack of robust economic data available to NTPs to support them to make the most locally-appropriate decisions concerning allocation of resources.10Wingfield T MacPherson P Ormerod LP Squire SB Cleary P Cost-effectiveness and tuberculosis elimination: never the twain shall meet. Aug 31, 2018.https://thorax.bmj.com/content/early/2018/08/18/thoraxjnl-2018-211662.responses?versioned=true#cost-effectiveness-and-tuberculosis-elimination-never-the-twain-shall-meet-Date: 2018Date accessed: January 29, 2019Google Scholar Indeed, most extant data supporting ACF interventions was derived from non-randomised observational and modelling studies, rather than being empirical data from pragmatic trials. Lung and colleagues' research7Lung T Marks GB Nhung NV et al.Household contact investigation for the detection of tuberculosis in Vietnam: economic evaluation of a cluster-randomised trial.Lancet Glob Health. 2019; 9: e376-e384Google Scholar highlights the wider importance of incorporating well planned, economic evaluation into the design of randomised trials, both in the field of tuberculosis and more widely.11Wingfield T Mitigating the financial effects of tuberculosis requires more than expansion of services.Lancet Glob Health. 2017; 5: e1056-e1057Summary Full Text Full Text PDF PubMed Scopus (1) Google Scholar Building on this research, innovative developments in health economic evaluations should be assimilated into the planning and design of randomised trials addressing tuberculosis. First, analyses should go beyond the standard, narrow evaluation of the effect of interventions on health outcomes only (eg, disease-related deaths or cases averted) and examine the effect on non-health outcomes. Extended cost-effectiveness analysis (ECEA) takes into account the effect of an intervention on both health and non-health outcomes, including out-of-pocket expenditures averted, financial risk protection provided, and distributional consequences across socioeconomic strata.12Verguet S Laxminarayan R Jamison DT Universal public finance of tuberculosis treatment in India: an extended cost-effectiveness analysis.Health Econ. 2015; 24: 318-332Crossref PubMed Scopus (99) Google Scholar, 13Verguet S Riumallo-Herl C Gomez GB et al.Catastrophic costs potentially averted by tuberculosis control in India and South Africa: a modelling study.Lancet Glob Health. 2017; 5: e1123-e1132Summary Full Text Full Text PDF PubMed Scopus (33) Google Scholar ECEA is highly pertinent to tuberculosis given that poorer people are often underserved by health and social services and disproportionately affected by tuberculosis infection, disease, catastrophic tuberculosis-related costs, and adverse treatment outcomes.14Wingfield T Boccia D Tovar M et al.Defining catastrophic costs and comparing their importance for adverse tuberculosis outcome with multi-drug resistance: a prospective cohort study, Peru.PLoS Med. 2014; 11: e1001675Crossref PubMed Scopus (146) Google Scholar, 15Wingfield T Tovar MA Huff D et al.The economic effects of supporting tuberculosis-affected households in Peru.Eur Respir J. 2016; 48: 1396-1410Crossref PubMed Scopus (43) Google Scholar Developing simple, user-friendly scores to estimate individual or household risk of tuberculosis, adverse tuberculosis clinical outcomes, or financial shock could ensure that potential interventions reach those most in need and offer the best value for money.16Lönnroth K Glaziou P Weil D Floyd K Uplekar M Raviglione M Beyond UHC: monitoring health and social protection coverage in the context of tuberculosis care and prevention.PLoS Med. 2014; 11: e1001693Crossref PubMed Scopus (96) Google Scholar Second, existing economic evaluations of interventions targeted at tuberculosis-affected households often underestimate their cost-effectiveness. This is mainly because health outcomes are estimated at a patient or individual level rather than at a household level, despite the household being either the unit of randomisation in the trial or the expressed target of an intervention. Other reasons for this underestimation are that rates of onward transmission of tuberculosis (either intra-household or extra-household) are not incorporated into calculations; duration of data collection or time to final follow-up is often insufficient; and, as in Lung and colleagues' study,7Lung T Marks GB Nhung NV et al.Household contact investigation for the detection of tuberculosis in Vietnam: economic evaluation of a cluster-randomised trial.Lancet Glob Health. 2019; 9: e376-e384Google Scholar data on household contacts' rates of tuberculosis preventive therapy or tuberculosis treatment completion are not frequently included in analyses. More accurate and representative estimates of household-level rather than individual-level health and non-health outcomes are required. Finally, ongoing community-based studies are now evaluating the broader economic consequences of ACF interventions from both a health system and a societal perspective, including mitigation of catastrophic costs of tuberculosis-affected households (eg, the EU-funded IMPACT-TB project in Nepal and Vietnam) and the role of innovations to complement ACF, including socioeconomic support, empowerment, and stigma reduction for tuberculosis-affected households (eg, the CRESIPT trial in Peru17Wingfield T Tovar MA Huff D et al.A randomized controlled study of socioeconomic support to enhance tuberculosis prevention and treatment, Peru.Bull World Health Organ. 2017; 95: 270-280Crossref PubMed Scopus (50) Google Scholar). In Vietnam, Lung and colleagues7Lung T Marks GB Nhung NV et al.Household contact investigation for the detection of tuberculosis in Vietnam: economic evaluation of a cluster-randomised trial.Lancet Glob Health. 2019; 9: e376-e384Google Scholar have shown that an NTP-delivered ACF intervention targeted to tuberculosis-affected households was not only clinically impactful but also cost-effective. This evidence highlights the importance of economic evaluation in trials and supports the potential scale-up of ACF in Vietnam. These findings should motivate researchers, implementers, and policy makers to evaluate similar ACF models in diverse settings. We declare no competing interests. TW is supported by grants from the Wellcome Trust (209075/Z/17/Z), the Academy of Medical Sciences, the Liverpool Glasgow Wellcome Trust Centre for Global Health Research, the Swedish Health Research Council, Stockholm, and the National Institute for Health Research. Household contact investigation for the detection of tuberculosis in Vietnam: economic evaluation of a cluster-randomised trialActive case finding was shown to be highly cost-effective in a setting with a high prevalence of tuberculosis. Investment in the wide-scale implementation of this programme in Vietnam should be strongly supported. Full-Text PDF Open Access