Active Case Finding Interventions Research Articles

Effectiveness of Using AI-Driven Hotspot Mapping for Active Case Finding of Tuberculosis in Southwestern Nigeria.

Background: Nigeria is among the top five countries that have the highest gap between people reported as diagnosed and estimated to have developed tuberculosis (TB). To bridge this gap, there is a need for innovative approaches to identify geographical areas at high risk of TB transmission and targeted active case finding (ACF) interventions. Leveraging community-level data together with granular sociodemographic contextual information can unmask local hotspots that could be otherwise missed. This work evaluated whether this approach helps to reach communities with higher numbers of undiagnosed TB. Methodology: A retrospective analysis of the data generated from an ACF intervention program in four southwestern states in Nigeria was conducted. Wards (the smallest administrative level in Nigeria) were further subdivided into smaller population clusters. ACF sites and their respective TB screening outputs were mapped to these population clusters. This data were then combined with open-source high-resolution contextual data to train a Bayesian inference model. The model predicted TB positivity rates on the community level (population cluster level), and these were visualised on a customised geoportal for use by the local teams to identify communities at high risk of TB transmission and plan ACF interventions. The TB positivity yield (proportion) observed at model-predicted hotspots was compared with the yield obtained at other sites identified based on aggregated notification data. Results: The yield in population clusters that were predicted to have high TB positivity rates by the model was at least 1.75 times higher (p-value < 0.001) than the yield in other locations in all four states. Conclusions: The community-level Bayesian predictive model has the potential to guide ACF implementers to high-TB-positivity areas for finding undiagnosed TB in the communities, thus improving the efficiency of interventions.

Improving tuberculosis case detection through contact risk stratification by Xpert MTB/RIF Ultra and spatial parameters: Evaluation of an innovative active case finding strategy in Mozambique (Xpatial-TB)

Prompt diagnosis is critical for tuberculosis (TB) control, as it enables early treatment which in turn, reduces transmission and improves treatment outcomes. We investigated the impact on TB diagnosis of introducing Xpert Ultra as the frontline diagnostic test, combined with an innovative active-case finding (ACF) strategy (based on Xpert Ultra semi-quantitative results and spatial parameters), in a semi-rural district of Southern Mozambique. From January-December 2018 we recruited incident TB-cases (index cases, ICs) and their household contacts (HCs). Recruitment of close community contacts (CCs) depended on IC´s Xpert Ultra results, and the population density of their area. TB-contacts, either symptomatic or people living with HIV, were asked to provide a spot sputum for lab-testing. Trends on TB case notification were compared to the previous years and to those of two districts in the south of the Maputo province (control area), using an interrupted time series analysis with and without control (CITS/ITS). A total of 1010 TB ICs (37.1% laboratory-confirmed) were recruited; 3165 HCs and 4730 CCs were screened for TB. Eighty-nine additional TB cases were identified through the ACF intervention (52.8% laboratory-confirmed). The intervention increased by 8.2% all forms of TB cases detected in 2018. Xpert Ultra trace positive results accounted for a high proportion of laboratory confirmations in the ACF cohort (51.1% vs 13.7% of those passively diagnosed). The Number Needed to Screen to find a TB case differed widely among HCs (55) and CCs (153). During the intervention period, a reversal of the previous negative trend in lab-confirmed case notifications was observed in the district. However, the CITS model did not show any statistically significant difference compared to the control area. Paediatric population benefited the most from the ACF strategy and HCs screening seemed an effective intervention to find microbiological confirmed cases in early stages of the disease.

Comparative assessment of the cost-effectiveness of Tuberculosis (TB) active case-finding interventions: A systematic analysis of TB REACH wave 5 projects.

Interventions that can help streamline and reduce gaps in the tuberculosis (TB) care cascade can play crucial roles in TB prevention and care, but are often operationally complex and resource intensive, given the heterogenous settings in which they are implemented. In this study, we present a comparative analysis on cost-effectiveness of TB REACH Wave 5 projects with diverse programmatic objectives to inform future decisions regarding funding, strategic adoption, and scale-up. We comprehensively reviewed project reports and financial statements from TB REACH Wave 5, a funding mechanism for interventions that aimed to strengthen the TB care cascade in diverse settings. Two independent reviewers abstracted cost (in 2017 US dollars) and key programmatic data, including project type (case-finding only; case-finding and linkage-to-care; or case-finding, linkage-to-care and patient support), operational setting (urban or rural), and project outputs (numbers of people with TB diagnosed, started on treatment, and successfully completing treatment). Cost-effectiveness ratios for each project were calculated as ratios of apportioned programmatic expenditures to corresponding project outputs. Of 32 case finding and patient support projects funded through TB REACH Wave 5, 29 were included for analysis (11 case-finding only; 9 case-finding and linkage-to-care; and 9 case-finding, linkage-to-care and patient support). 21 projects (72%) were implemented in either Africa or Southeast Asia, and 19 (66%) focused on serving urban areas. Average cost-effectiveness was $184 per case diagnosed (range: $30-$10,497), $332 per diagnosis and treatment initiation ($123-$10,608), and $40 per patient treatment supported ($8-$160). Cost per case diagnosed was lower for case-finding-only projects ($132) than projects including linkage-to-care ($342) or linkage-to-care and patient support ($254), and generally increased with the corresponding country's per-capita GDP ($543 per $1000 increase, 95% confidence interval: -$53, $1138). The costs and cost-effectiveness of interventions to strengthen the TB care cascade were heterogenous, reflecting differences in context and programmatic objective. Nevertheless, many such interventions are likely to offer good value for money. Systematic collection and analysis of cost-effectiveness data can help improve comparability, monitoring, and evaluation.

Population benefits of addressing programmatic and social determinants of gender disparities in tuberculosis in Viet Nam: A modelling study.

High prevalence of infectious tuberculosis among men suggests potential population-wide benefits from addressing programmatic and social determinants of gender disparities. Utilising a sex-stratified compartmental transmission model calibrated to tuberculosis burden estimates for Viet Nam, we modelled interventions to increase active case finding, to reduce tobacco smoking, and to reduce alcohol consumption by 2025 in line with national and global targets. For each intervention, we examined scenarios differentially targeting men and women and evaluated impact on tuberculosis morbidity and mortality in men, women, and children in 2035. Active case finding interventions targeting men projected greater reductions in tuberculosis incidence in men, women, and children (16.2%, uncertainty interval, UI, 11.4-23.0%, 11.8%, UI 8.0-18.6%, and 21.5%, UI 16.9-28.5%, respectively) than those targeting women (5.2%, UI 3.8-7.1%, 5.4%, UI 3.9-7.3%, and 8.6%, UI 6.9-10.7%, respectively). Projected reductions in tuberculosis incidence for interventions to reduce male tobacco smoking and alcohol consumption were greatest for men (17.4%, UI 11.8-24.7%, and 11.0%, UI 5.4-19.4%, respectively), but still substantial for women (6.9%, UI 3.8-12.5%, and 4.4%, UI 1.9-10.6%, respectively) and children (12.7%, UI 8.4-19.0%, and 8.0%, UI 3.9-15.0%, respectively). Comparable interventions targeting women projected limited impact, with declines of 0.3% (UI 0.2%-0.3%) and 0.1% (UI 0.0%-0.1%), respectively. Addressing programmatic and social determinants of men's tuberculosis burden has population-wide benefits. Future interventions to increase active case finding, to reduce tobacco smoking, and to reduce harmful alcohol consumption, whilst not ignoring women, should focus on men to most effectively reduce tuberculosis morbidity and mortality in men, women, and children.

Number needed to screen for TB in clinical, structural or occupational risk groups.

BACKGROUND: Screening for active TB using active case-finding (ACF) may reduce TB incidence, prevalence, and mortality; however, yield of ACF interventions varies substantially across populations. We systematically reviewed studies reporting on ACF to calculate the number needed to screen (NNS) for groups at high risk for TB.METHODS: We conducted a literature search for studies reporting ACF for adults published between November 2010 and February 2020. We determined active TB prevalence detected through various screening strategies and calculated crude NNS for - TB confirmed using culture or Xpert® MTB/RIF, and weighted mean NNS stratified by screening strategy, risk group, and country-level TB incidence.RESULTS: We screened 27,223 abstracts; 90 studies were included (41 in low/moderate and 49 in medium/high TB incidence settings). High-risk groups included inpatients, outpatients, people living with diabetes (PLWD), migrants, prison inmates, persons experiencing homelessness (PEH), healthcare workers, and miners. Screening strategies included symptom-based screening, chest X-ray and Xpert testing. NNS varied widely across and within incidence settings based on risk groups and screening methods. Screening tools with higher sensitivity (e.g., Xpert, CXR) were associated with lower NNS estimates.CONCLUSIONS: NNS for ACF strategies varies substantially between adult risk groups. Specific interventions should be tailored based on local epidemiology and costs.

Digital Storytelling and Community Engagement to Find Missing TB Cases in Rural Nuh, India.

Nuh, Haryana, is one of India’s least developed districts. To improve TB case notifications, ZMQ carried out an active case-finding (ACF) intervention conducted by community health workers (MIRAs) using a digital TB storytelling platform to create TB awareness in the community. The combined storytelling and ACF intervention were conducted house-to-house or in community group settings. Steps included (A) the development of digital TB awareness-raising stories using a participatory approach called Story Labs; (B) the implementation of the intervention; and (C) process, outcome, and impact evaluation of these activities. Six digital stories were created and used during ACF in which 19,345 people were screened and 255 people were diagnosed with TB. Of 731 participants surveyed, the stories were well received and resulted in an increase in TB knowledge. ACF activities resulted in a 56% increase in bacteriologically confirmed TB and an 8% decrease in all forms of TB compared to baseline. All form notifications may have been impacted by COVID-19 lockdowns. Digital TB storytelling can improve TB awareness and knowledge, particularly for low-literacy populations. The use of these tools may benefit ACF campaigns and improve TB case finding.

Reaching 95-95-95 targets: The role of private sector health facilities in closing the HIV detection gap-Kisumu Kenya, 2018.

HIV testing efficiency could be improved by focusing on high yield populations and identifying types of health facilities where people with undiagnosed HIV infection are more likely to attend. A retrospective cohort analysis of data collected during an integrated TB/HIV active case-finding intervention in Western Kenya. Data were analyzed from health facilities' registers on individuals who reported TB-suggestive symptoms between 1 July and 31 December 2018 and who had an HIV test result within one month following symptom screening. We used logistic regression with general estimating equations adjusting for sub-county level data to identify health facility-level predictors of new HIV diagnoses. Of 11,376 adults with presumptive TB identified in 143 health facilities, 1038 (9%) tested HIV positive. The median HIV positivity per health facility was 6% (IQR = 2-15%). Patients with TB symptoms were over three times as likely to have a new HIV diagnosis in private not-for-profit facilities compared to those in government facilities (adjusted odds ratio (aOR) 3.40; 95% CI = 1.96-5.90). Patients tested in hospitals were over two times as likely to have a new HIV diagnosis as those tested in smaller facilities (i.e., health centers and dispensaries) (aOR 2.26; 95% CI = 1.60-3.21). Individuals with presumptive TB who attended larger health facilities and private not-for-profit facilities had a higher likelihood of being newly diagnosed with HIV. Strengthening HIV services at these facilities and outreach to populations that use them could help to close the HIV diagnosis gap.

Do community-based active case-finding interventions have indirect impacts on wider TB case detection and determinants of subsequent TB testing behaviour? A systematic review.

Community-based active case-finding (ACF) may have important impacts on routine TB case-detection and subsequent patient-initiated diagnosis pathways, contributing "indirectly" to infectious diseases prevention and care. We investigated the impact of ACF beyond directly diagnosed patients for TB, using routine case-notification rate (CNR) ratios as a measure of indirect effect. We systematically searched for publications 01-Jan-1980 to 13-Apr-2020 reporting on community-based ACF interventions compared to a comparison group, together with review of linked manuscripts reporting knowledge, attitudes, and practices (KAP) outcomes or qualitative data on TB testing behaviour. We calculated CNR ratios of routine case-notifications (i.e. excluding cases identified directly through ACF) and compared proxy behavioural outcomes for both ACF and comparator communities. Full text manuscripts from 988 of 23,883 abstracts were screened for inclusion; 36 were eligible. Of these, 12 reported routine notification rates separately from ACF intervention-attributed rates, and one reported any proxy behavioural outcomes. Two further studies were identified from screening 1121 abstracts for linked KAP/qualitative manuscripts. 8/12 case-notification studies were considered at critical or serious risk of bias. 8/11 non-randomised studies reported bacteriologically-confirmed CNR ratios between 0.47 (95% CI:0.41-0.53) and 0.96 (95% CI:0.94-0.97), with 7/11 reporting all-form CNR ratios between 0.96 (95% CI:0.88-1.05) and 1.09 (95% CI:1.02-1.16). One high-quality randomised-controlled trial reported a ratio of 1.14 (95% CI 0.91-1.43). KAP/qualitative manuscripts provided insufficient evidence to establish the impact of ACF on subsequent TB testing behaviour. ACF interventions with routine CNR ratios >1 suggest an indirect effect on wider TB case-detection, potentially due to impact on subsequent TB testing behaviour through follow-up after a negative ACF test or increased TB knowledge. However, data on this type of impact are rarely collected. Evaluation of routine case-notification, testing and proxy behavioural outcomes in intervention and comparator communities should be included as standard methodology in future ACF campaign study designs.

Economic Evaluation of Community Tuberculosis Active Case-Finding Approaches in Cambodia: A Quasi-Experimental Study.

This study aimed to estimate the costs and incremental cost-effectiveness of two community-based tuberculosis (TB) active case-finding (ACF) strategies in Cambodia. We also assessed the number needed to screen and test to find one TB case. Program and national TB notification data from a quasi-experimental study of a cohort of people with TB in 12 intervention operational districts (ODs) and 12 control ODs between November 2018 and December 2019 were analyzed. Two ACF interventions (ACF seed-and-recruit (ACF SAR) model and one-off roving (one-off) ACF) were implemented concurrently. The matched control sites included PCF only. We estimated costs using the program and published data in Cambodia. The primary outcome was disability-adjusted life years (DALY) averted over 14 months. We considered the gross domestic product per capita of Cambodia in 2018 as the cost-effectiveness threshold. ACF SAR needed to test 7.7 people with presumptive TB to identify one all-forms TB, while one-off ACF needed to test 22.4. The costs to diagnose one all-forms TB were USD 458 (ACF SAR) and USD 191 (one-off ACF). The incremental cost per DALY averted was USD 257 for ACF SAR and USD 204 for one-off ACF. Community-based ACF interventions that targeted key populations for TB in Cambodia were highly cost-effective.

Durations of asymptomatic, symptomatic, and care-seeking phases of tuberculosis disease with a Bayesian analysis of prevalence survey and notification data

BackgroundRatios of bacteriologically positive tuberculosis (TB) prevalence to notification rates are used to characterise typical durations of TB disease. However, this ignores the clinical spectrum of tuberculosis disease and potentially long infectious periods with minimal or no symptoms prior to care-seeking.MethodsWe developed novel statistical models to estimate progression from initial bacteriological positivity including smear conversion, symptom onset and initial care-seeking. Case-detection ratios, TB incidence, durations, and other parameters were estimated by fitting the model to tuberculosis prevalence survey and notification data (one subnational and 11 national datasets) within a Bayesian framework using Markov chain Monte Carlo methods.ResultsAnalysis across 11 national datasets found asymptomatic tuberculosis durations in the range 4–8 months for African countries; three countries in Asia (Cambodia, Lao PDR, and Philippines) showed longer durations of > 1 year. For the six countries with relevant data, care-seeking typically began half-way between symptom onset and notification. For Kenya and Blantyre, Malawi, individual-level data were available. The sex-specific durations of asymptomatic bacteriologically-positive tuberculosis were 9.0 months (95% credible interval [CrI]: 7.2–11.2) for men and 8.1 months (95% CrI: 6.2–10.3) for women in Kenya, and 4.9 months (95% CrI: 2.6–7.9) for men and 3.5 months (95% CrI: 1.3–6.2) for women in Blantyre. Age-stratified analysis of data for Kenya showed no strong age-dependence in durations. For Blantyre, HIV-stratified analysis estimated an asymptomatic duration of 1.3 months (95% CrI: 0.3–3.0) for HIV-positive people, shorter than the 8.5 months (95% CrI: 5.0–12.7) for HIV-negative people. Additionally, case-detection ratios were higher for people living with HIV than HIV-negative people (93% vs 71%).ConclusionAsymptomatic TB disease typically lasts around 6 months. We found no evidence of age-dependence, but much shorter durations among people living with HIV, and longer durations in some Asian settings. To eradicate TB transmission, greater gains may be achieved by proactively screening people without symptoms through active case finding interventions

Engaging Private Health Care Providers to Identify Individuals with TB in Nepal.

In Nepal, 47% of individuals who fell ill with TB were not reported to the National TB Program in 2018. Approximately 60% of persons with TB initially seek care in the private sector. From November 2018 to January 2020, we implemented an active case finding intervention in the Parsa and Dhanusha districts targeting private provider facilities. To evaluate the impact of the intervention, we reported on crude intervention results. We further compared case notification during the implementation to baseline and control population (Bara and Siraha) notifications. We screened 203,332 individuals; 11,266 (5.5%) were identified as presumptive for TB and 8077 (71.7%) were tested for TB. Approximately 8% had a TB diagnosis, of whom 383 (56.2%) were bacteriologically confirmed (Bac+). In total, 653 (95.7%) individuals were initiated on treatment at DOTS facilities. For the intervention districts, there was a 17%increase for bacteriologically positive TB and 10% for all forms TB compared to baseline. In comparison, the change in notifications in the control population were 4% for bacteriologically positive, and −2% all forms. Through engagement of private sector facilities, our intervention was able to increase the number of individuals identified with TB by over 10% in the Parsa and Dhanusha districts.

Socio-protective effects of active case finding on catastrophic costs from tuberculosis in Ho Chi Minh City, Viet Nam: a longitudinal patient cost survey

BackgroundMany tuberculosis (TB) patients incur catastrophic costs. Active case finding (ACF) may have socio-protective properties that could contribute to the WHO End TB Strategy target of zero TB-affected families suffering catastrophic costs, but available evidence remains limited. This study measured catastrophic cost incurrence and socioeconomic impact of an episode of TB and compared those socioeconomic burdens in patients detected by ACF versus passive case finding (PCF).MethodsThis cross-sectional study fielded a longitudinal adaptation of the WHO TB patient cost survey alongside an ACF intervention from March 2018 to March 2019. The study was conducted in six intervention (ACF) districts and six comparison (PCF) districts of Ho Chi Minh City, Viet Nam. Fifty-two TB patients detected through ACF and 46 TB patients in the PCF cohort were surveyed within two weeks of treatment initiation, at the end of the intensive phase of treatment, and after treatment concluded. The survey measured income, direct and indirect costs, and socioeconomic impact based on which we calculated catastrophic cost as the primary outcome. Local currency was converted into US$ using the average exchange rates reported by OANDA for the study period (VNĐ1 = US$0.0000436, 2018–2019). We fitted logistic regressions for comparisons between the ACF and PCF cohorts as the primary exposures and used generalized estimating equations to adjust for autocorrelation.ResultsACF patients were poorer than PCF patients (multidimensional poverty ratio: 16 % vs. 7 %; p = 0.033), but incurred lower median pre-treatment costs (US$18 vs. US$80; p < 0.001) and lower median total costs (US$279 vs. US$894; p < 0.001). Fewer ACF patients incurred catastrophic costs (15 % vs. 30 %) and had lower odds of catastrophic cost (aOR = 0.17; 95 % CI: [0.05, 0.67]; p = 0.011), especially during the intensive phase (OR = 0.32; 95 % CI: [0.12, 0.90]; p = 0.030). ACF patient experienced less social exclusion (OR = 0.41; 95 % CI: [0.18, 0.91]; p = 0.030), but more often resorted to financial coping mechanisms (OR = 5.12; 95 % CI: [1.73, 15.14]; p = 0.003).ConclusionsACF can be effective in reaching vulnerable populations and mitigating the socioeconomic burden of TB, and can contribute to achieving the WHO End TB Strategy goals. Nevertheless, as TB remains a catastrophic life event, social protection efforts must extend beyond ACF.

Factors Affecting Motivation among Key Populations to Engage with Tuberculosis Screening and Testing Services in Northwest Tanzania: A Mixed-Methods Analysis.

In northwest Tanzania, many artisanal small-scale miners (ASMs) and female sex workers (FSWs) live in informal communities surrounding mines where tuberculosis (TB) is highly prevalent. An active case finding (ACF) intervention to increase TB case notification was undertaken in two districts. Alongside this, a study was implemented to understand engagement with the intervention through: (1) quantitative questionnaires to 128 ASMs and FSWs, who either engaged or did not engage in the ACF intervention, to assess their views on TB; (2) qualitative interviews with 41 ASMs and FSWs, 36 community health workers (CHWs) and 30 community stakeholders. The mean perceived severity of TB score was higher in the engaged than in the non-engaged group (p = 0.01). Thematic analysis showed that health-seeking behaviour was similar across both groups but that individuals in the non-engaged group were more reluctant to give sputum samples, often because they did not understand the purpose. CHWs feared contracting TB on the job, and many noted that mining areas were difficult to access without transportation. Community stakeholders provided various recommendations to increase engagement. This study highlights reasons for engagement with a large-scale ACF intervention targeting key populations and presents insights from implementers and stakeholders on the implementation of the intervention.

COVID-19 control strategies and intervention effects in resource limited settings: A modeling study.

IntroductionMany countries with weaker health systems are struggling to put together a coherent strategy against the COVID-19 epidemic. We explored COVID-19 control strategies that could offer the greatest benefit in resource limited settings.MethodsUsing an age-structured SEIR model, we explored the effects of COVID-19 control interventions–a lockdown, physical distancing measures, and active case finding (testing and isolation, contact tracing and quarantine)–implemented individually and in combination to control a hypothetical COVID-19 epidemic in Kathmandu (population 2.6 million), Nepal.ResultsA month-long lockdown will delay peak demand for hospital beds by 36 days, as compared to a base scenario of no intervention (peak demand at 108 days (IQR 97-119); a 2 month long lockdown will delay it by 74 days, without any difference in annual mortality, or healthcare demand volume. Year-long physical distancing measures will reduce peak demand to 36% (IQR 23%-46%) and annual morality to 67% (IQR 48%-77%) of base scenario. Following a month long lockdown with ongoing physical distancing measures and an active case finding intervention that detects 5% of the daily infection burden could reduce projected morality and peak demand by more than 99%.ConclusionLimited resource settings are best served by a combination of early and aggressive case finding with ongoing physical distancing measures to control the COVID-19 epidemic. A lockdown may be helpful until combination interventions can be put in place but is unlikely to reduce annual mortality or healthcare demand.

Active case finding of pulmonary TB in a European refugee camp: lessons learnt from Oinofyta hosting site in Greece.

To report on an active case finding (ACF) intervention that took place in the migrant camp of Oinofyta, Greece, upon suspicion of active TB transmission. Upon diagnosis of 3TB cases among camp residents, an ACF intervention among contacts was implemented. All camp residents were offered two-step screening, that is tuberculin skin testing (TST) followed by chest X-ray in case of positive TST (defined as ≥5mm). 336 of 379 (89%) camp residents underwent TST testing, of whom 110 (33%) exhibited a positive skin reaction. The rate of positive TST results was particularly high in the elderly and significantly higher in adults than in children. Differences by sex or nationality were not observed. Of the 110 cases with positive TST, only 75 underwent chest X-ray, resulting in the detection of one pulmonary TB case in an adult woman. In the given intervention context, two-step ACF proved to be operationally cumbersome, with many residents lost to follow-up and a high Number Needed to Screen. Simpler ACF designs should be pilot-tested in similar settings in the future, and blanket screening of all camp residents should be reconsidered. Conclusions drawn by these exercises should pave the way for adopting a comprehensive, context-specific and evidence-based national strategy on TB in migrants.

Comparative Yield of Tuberculosis during Active Case Finding Using GeneXpert or Smear Microscopy for Diagnostic Testing in Nepal: A Cross-Sectional Study.

This study compared the yield of tuberculosis (TB) active case finding (ACF) interventions applied under TB REACH funding. Between June 2017 to November 2018, Birat Nepal Medical Trust identified presumptive cases using simple verbal screening from three interventions: door-to-door screening of social contacts of known index cases, TB camps in remote areas, and screening for hospital out-patient department (OPD) attendees. Symptomatic individuals were then tested using smear microscopy or GeneXpert MTB/RIF as first diagnostic test. Yield rates were compared for each intervention and diagnostic method. We evaluated additional cases notified from ACF interventions by comparing case notifications of the intervention and control districts using standard TB REACH methodology. The project identified 1092 TB cases. The highest yield was obtained from OPD screening at hospitals (n = 566/1092; 52%). The proportion of positive tests using GeneXpert (5.5%, n = 859/15,637) was significantly higher than from microscopy testing 2% (n = 120/6309). (OR = 1.4; 95%CI = 1.12–1.72; p = 0.0026). The project achieved 29% additionality in case notifications in the intervention districts demonstrating that GeneXpert achieved substantially higher case-finding yields. Therefore, to increase national case notification for TB, Nepal should integrate OPD screening using GeneXpert testing in every district hospital and scale up of community-based ACF of TB patient contacts nationally.

Community-based active case-finding interventions for tuberculosis: a systematic review

SummaryBackgroundCommunity-based active case-finding interventions might identify and treat more people with tuberculosis disease than standard case detection. We aimed to assess whether active case-finding interventions can affect tuberculosis epidemiology in the wider community.MethodsWe did a systematic review by searching PubMed, Embase, Scopus, and Cochrane Library for studies that compared tuberculosis case notification rates, tuberculosis disease prevalence, or tuberculosis infection prevalence or incidence in children, between populations exposed and unexposed to active case-finding interventions. We included studies published in English between Jan 1, 1980, and April 13, 2020. Studies of active case-finding in the general population, in populations perceived to be at high risk for tuberculosis, and in closed settings were included, whereas studies of tuberculosis screening at health-care facilities, among household contacts, or among children only, and studies that screened fewer than 1000 people were excluded. To estimate effectiveness, we extracted or calculated case notification rates, prevalence of tuberculosis disease, and incidence or prevalence of tuberculosis infection in children, and compared ratios of these outcomes between groups that were exposed or not exposed to active case-finding interventions.Results27 883 abstracts were screened and 988 articles underwent full text review. 28 studies contributed data for analysis of tuberculosis case notifications, nine for prevalence of tuberculosis disease, and two for incidence or prevalence of tuberculosis infection in children. In one cluster-randomised trial in South Africa and Zambia, an active case-finding intervention based on community mobilisation and sputum drop-off did not affect tuberculosis prevalence, whereas, in a cluster-randomised trial in Vietnam, an active case-finding intervention based on sputum tuberculosis tests for everyone reduced tuberculosis prevalence in the community. We found inconsistent, low-quality evidence that active case-finding might increase the number of cases of tuberculosis notified in populations with structural risk factors for tuberculosis.InterpretationCommunity-based active case-finding for tuberculosis might be effective in changing tuberculosis epidemiology and thereby improving population health if delivered with high coverage and intensity. If possible, active case-finding projects should incorporate a well designed, robust evaluation to contribute to the evidence base and help elucidate which delivery methods and diagnostic strategies are most effective.FundingWHO Global TB Programme.

Determining the value of TB active case-finding: current evidence and methodological considerations.

Active case-finding (ACF) is an important component of the End TB Strategy. However, ACF is resource-intensive, and the economics of ACF are not well-understood. Data on the costs of ACF are limited, with little consistency in the units and methods used to estimate and report costs. Mathematical models to forecast the long-term effects of ACF require empirical measurements of the yield, timing and costs of case detection. Pragmatic trials offer an opportunity to assess the cost-effectiveness of ACF interventions within a 'real-world´ context. However, such analyses generally require early introduction of economic evaluations to enable prospective data collection on resource requirements. Closing the global case-detection gap will require substantial additional resources, including continued investment in innovative technologies. Research is essential to the optimal implementation, cost-effectiveness, and affordability of ACF in high-burden settings. To assess the value of ACF, we must prioritize the collection of high-quality data regarding costs and effectiveness, and link those data to analytical models that are adapted to local settings.

Diagnostic Performance of Xpert MTB/RIF Ultra for Tuberculosis Diagnosis in the Context of Passive and Active Case Finding Strategies in Rural Mozambique

Background: Xpert MTB/RIF Ultra (Ultra) is a novel molecular assay which is replacing Xpert MTB/RIF (Xpert) as a front-line test for tuberculosis (TB) diagnosis. We conducted a field evaluation of the diagnostic accuracy of Ultra using two cohorts of participants (from passive and active case finding interventions) in a high TB/HIV burden area in Southern Mozambique. Methods: Respiratory specimens obtained from symptomatic adults accessing health care services (passive case finding (PCF) cohort), and from household and community close contacts (active case finding (ACF) cohort), were tested for smear microscopy, culture, Xpert and Ultra (same specimen). Liquid and solid culture results served as a composite reference standard. We also explored trace results’ impact on test specificity by their recategorization to negative (in all cases or just in previously treated individuals) and active follow-up. Findings: A total of 1419 and 252 participants were enrolled in the ACF and PCF cohorts respectively. For the PCF cohort, Ultra showed higher sensitivity compared to Xpert, overall (0·95 (95% CI: 0·90, 0·98) vs 0·88 (0·82, 0·93); p<0·001) and among smear negative patients (0·84 (95% CI: 0·71, 0·93) vs 0·63 (95% CI: 0·48, 0·76) p<0·001). Conversely, specificity of Ultra was lower and similar than Xpert’s (0·98 (0·97, 0·99) vs 0·96 (0·95, 0·97); p= 0·008). In the ACF-group, sensitivity and specificity for both tests were the same (0·67 (95% CI: 0·22,0·96), although Ultra doubled Xpert in the number of microbiologically confirmed samples (4·7% (12/252) vs 2·7% (7/252)). Conditional recategorization of trace results, maintained differences in specificity in the PCF cohort. Interpretation: Our results add evidence on the improved sensitivity of Ultra and suggest that overall differences in specificity among assays might be driven by misclassification of true-positive results. These findings support the use of Ultra as initial front-line test for diagnosis in health care settings, and advocate for a comprehensive clinical and epidemiological evaluation of patients with single trace results in order to inform treatment initiation. Funding Statement: We acknowledge support from the Spanish Ministry of Science, Innovation and Universities through the “Centro de Excelencia Severo Ochoa 2019-2023” Program (CEX2018-000806-S), and support from the Generalitat de Catalunya through the CERCA Program. B.S receives a pre-doctoral fellowship from the Secretariat of Universities and Research, Ministry of Enterprise and Knowledge of the Government of Catalonia and co-funded by European Social Fund (AGAUR). This project has received consumables donations from Cepheid. Cepheid was not involved in the data analysis or decision to submit this manuscript for publication. Declaration of Interests: The authors have no conflicts of interest to disclose. Ethics Approval Statement: The protocol was approved by CISM’s Internal Scientific Committee, CISM’s Internal Bioethics Committee (CIBS – Comite Institucional de Bioetica para a Saude) and the National Bioethics Committee (CNBS - Comite Nacional de Bioetica para a Saude, reference 369/CNBS/17).

Economic Evaluation of Community Tuberculosis Active Case Finding Approaches in Cambodia

Background: We conducted an economic evaluation of two community tuberculosis (TB) active case finding (ACF) strategies in Cambodia by assessing the cost per disability-adjusted life years (DALY) averted among people with TB. Methods: We analyzed program and national TB notification data from a cohort of people with TB in 12 intervention operational districts (ODs) and 12 control ODs between November 2018 and February 2020. The interventions comprised—1) ACF using a seed-and-recruit model and 2) one-off roving ACF that were implemented concurrently. Passive case finding, a default setup in the health system, was continuously present in both the intervention and control areas. We estimated costs using the program and previously published primary cost data in Cambodia. The primary outcome was the cost per DALY averted among people with TB in the intervention sites compared to the control sites. We considered an intervention to be cost-effective if the cost per DALY averted was lower than the gross domestic product per capita of Cambodia (US$ 1643 in 2018). Findings: In total, 12074 were screened and tested via the seed-and-recruit model and 51636 via the one-off roving ACF model. The former needed to test 7·7 presumptive TB to identify 1577 all-forms TB, while the latter needed to test 22·4 to identify 2303 all-forms TB. The cost per DALY averted was US$ 237 for ACF using a seed-and-recruit model, US$ 164 for one-off roving ACF. Interpretation: Community-based ACF interventions that targeted engagements with key populations for TB in Cambodia were highly cost-effective. Funding Statement: This study was funded by the Stop TB Partnership TB REACH Grant. Declaration of Interests: We declare no competing interests. Ethics Approval Statement: This study was approved by the National Ethics Committee for Health Research Cambodia (112/NECHR). A waiver of consent was granted due to the retrospective nature of this study, the minimal risk to rights and welfare of the participants, and the lack of practicality to obtain consent.