Active Case Finding Interventions Research Articles

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.

Islands of Tuberculosis Elimination: An Evaluation of Community-Based Active Case Finding in North Sumatra, Indonesia.

Community-based active case finding (ACF) is needed to reach key/vulnerable populations with limited access to tuberculosis (TB) care. Published reports of ACF interventions in Indonesia are scarce. We conducted an evaluation of a multicomponent community-based ACF intervention as it scaled from one district to nine in Nias and mainland North Sumatra. Community and health system support measures including laboratory strengthening, political advocacy, sputum transport, and community awareness were instituted. ACF was conducted in three phases: pilot (18 months, 1 district), intervention (12 months, 4 districts) and scale-up (9 months, 9 districts). The pilot phase identified 215 individuals with bacteriologically positive (B+) TB, representing 42% of B+ TB notifications. The intervention phase yielded 509, representing 54% of B+ notifications and the scale-up phase identified 1345 individuals with B+ TB (56% of notifications). We observed large increases in B+ notifications on Nias, but no overall change on the mainland despite district variation. Overall, community health workers screened 377,304 individuals of whom 1547 tested positive, and 95% were initiated on treatment. Our evaluation shows that multicomponent community-based ACF can reduce the number of people missed by TB programs. Community-based organizations are best placed for accessing and engaging hard to reach populations and providing integrated support which can have a large positive effect on TB notifications.

Children as sentinels of tuberculosis transmission: disease mapping of programmatic data

BackgroundIdentifying hotspots of tuberculosis transmission can inform spatially targeted active case-finding interventions. While national tuberculosis programs maintain notification registers which represent a potential source of data to investigate transmission patterns, high local tuberculosis incidence may not provide a reliable signal for transmission because the population distribution of covariates affecting susceptibility and disease progression may confound the relationship between tuberculosis incidence and transmission. Child cases of tuberculosis and other endemic infectious disease have been observed to provide a signal of their transmission intensity. We assessed whether local overrepresentation of child cases in tuberculosis notification data corresponds to areas where recent transmission events are concentrated.MethodsWe visualized spatial clustering of children < 5 years old notified to Peru’s National Tuberculosis Program from two districts of Lima, Peru, from 2005 to 2007 using a log-Gaussian Cox process to model the intensity of the point-referenced child cases. To identify where clustering of child cases was more extreme than expected by chance alone, we mapped all cases from the notification data onto a grid and used a hierarchical Bayesian spatial model to identify grid cells where the proportion of cases among children < 5 years old is greater than expected. Modeling the proportion of child cases allowed us to use the spatial distribution of adult cases to control for unobserved factors that may explain the spatial variability in the distribution of child cases. We compare where young children are overrepresented in case notification data to areas identified as transmission hotspots using molecular epidemiological methods during a prospective study of tuberculosis transmission conducted from 2009 to 2012 in the same setting.ResultsAreas in which childhood tuberculosis cases are overrepresented align with areas of spatial concentration of transmission revealed by molecular epidemiologic methods.ConclusionsAge-disaggregated notification data can be used to identify hotspots of tuberculosis transmission and suggest local force of infection, providing an easily accessible source of data to target active case-finding intervention.

Tuberculosis active case-finding interventions and approaches for prisoners in sub-Saharan Africa: a systematic scoping review

BackgroundIn sub-Saharan Africa (SSA), most prisons are overcrowded with poor ventilation and put prisoners disproportionally at risk of exposure to Mycobacterium tuberculosis (TB) and developing TB infection but are mostly missed due to poor access to healthcare. Active case-finding (ACF) of TB in prisons facilitates early diagnosis and treatment of inmates and prevent the spread. We explored literature and described evidence on TB ACF interventions and approaches for prisoners in SSA prisons.MethodsGuided by the Arksey and O’Malley framework, we searched PubMed, Google Scholar, SCOPUS, Academic search complete, CINAHL and MEDLINE with full text via EBSCOhost for articles on prisoners and ACF from 2000 to May 2019 with no language restriction. Two investigators independently screened the articles at the abstract and full-text stages in parallel guided by the eligibility criteria as well as performed the methodological quality appraisal of the included studies using the latest mixed-method appraisal tool. We extracted all relevant data, organized them into themes and sub-themes, and presented a narrative summary of the results.ResultsOf the 391 eligible articles found, 31 met the inclusion criteria. All 31 articles were published between 2006 and 2019 with the highest six (19.4%) in 2015. We found evidence in 11 countries. That is, Burkina Faso, Cameroon, Coˆte d’Ivoire, the Democratic Republic of the Congo, Ethiopia, Ghana, Malawi, Nigeria, South Africa, Uganda, and Zambia with most 41.9% (13/31) recorded in Ethiopia. These intervention studies were conducted in 134 prisons between 2001 and 2018 using either a single or combination of mass, facility-led, entry, peer educators for routine screening, and exit ACF approaches. The majority (74%) of the studies utilized only a mass screening approach. The most (68%) reported study outcome was smear-positive TB cases only (68%). We found no evidence in 16 SSA countries although they are classified among the three high-burden country lists for TB TB/HIV and Multidrug resistant-TB group.ConclusionOur review highlights a dearth of evidence on TB ACF interventions in most SSA countries prisons. Hence, there is the need to scaling-up ACF interventions in SSA prisons, particularly countries included in the three high-burden country lists for TB, TB/HIV, and MDR-TB.

Spatial distribution of people diagnosed with tuberculosis through routine and active case finding: a community-based study in Kampala, Uganda

BackgroundRoutine tuberculosis (TB) notifications are geographically heterogeneous, but their utility in predicting the location of undiagnosed TB cases is unclear. We aimed to identify small-scale geographic areas with high TB notification rates based on routinely collected data and to evaluate whether these areas have a correspondingly high rate of undiagnosed prevalent TB.MethodsWe used routinely collected data to identify geographic areas with high TB notification rates and evaluated the extent to which these areas correlated with the location of undiagnosed cases during a subsequent community-wide active case finding intervention in Kampala, Uganda. We first enrolled all adults who lived within 35 contiguous zones and were diagnosed through routine care at four local TB Diagnosis and Treatment Units. We calculated average monthly TB notification rates in each zone and defined geographic areas of “high risk” as zones that constituted the 20% of the population with highest notification rates. We compared the observed proportion of TB notifications among residents of these high-risk zones to the expected proportion, using simulated estimates based on population size and random variation alone. We then evaluated the extent to which these high-risk zones identified areas with high burdens of undiagnosed TB during a subsequent community-based active case finding campaign using a chi-square test.ResultsWe enrolled 45 adults diagnosed with TB through routine practices and who lived within the study area (estimated population of 49 527). Eighteen zones reported no TB cases in the 9-month period; among the remaining zones, monthly TB notification rates ranged from 3.9 to 39.4 per 100 000 population. The five zones with the highest notification rates constituted 62% (95% CI: 47–75%) of TB cases and 22% of the population–significantly higher than would be expected if population size and random chance were the only determinants of zone-to-zone variation (48%, 95% simulation interval: 40–59%). These five high-risk zones accounted for 42% (95% CI: 34–51%) of the 128 cases detected during the subsequent community-based case finding intervention, which was significantly higher than the 22% expected by chance (P < 0.001) but lower than the 62% of cases notified from those zones during the pre-intervention period (P = 0.02).ConclusionsThere is substantial heterogeneity in routine TB notification rates at the zone level. Using facility-based TB notification rates to prioritize high-yield areas for active case finding could double the yield of such case-finding interventions.

Patient predictors of health-seeking behaviour for persons coughing for more than two weeks in high-burden tuberculosis communities: the case of the Western Cape, South Africa

BackgroundThis study aimed to analyse the patient predictors of health-seeking behaviour for persons coughing for more than 2 weeks to better understand this vulnerable and important population.MethodsThe study analysed data from a cohort study (SOCS - Secondary Outcome Cohort Study) embedded in a community randomised trial ZAMSTAR (Zambia and South Africa TB and AIDS Reduction Study) in eight high-burden TB communities in the Western Cape, South Africa. These datasets are unique as they contain TB-related data as well as data on health, health-seeking behaviour, lifestyle choices, employment, socio-economic status, education and stigma. We use uni- and multivariate logistic regressions to estimate the odds ratios of consulting for a cough (of more than 2 weeks duration) for a range of relevant patient predictors.ResultsThree hundred and forty persons consulted someone about their cough and this represents 37% of the 922 participants who reported coughing for more than 2 weeks. In the multivariate analysis, respondents of black ethnic origin (OR 1.99, 95% CI 1.28–3.12, P < 0.01), those with higher levels of education (OR 1.05 per year of education, 95% CI 1.00–1.10, P = 0.05), and older respondents (OR 1.02 per year, 95% CI 1.01–1.04, P < 0.01) had a higher likelihood of consulting for their chronic cough. Individuals who smoked (OR 0.63, 95% CI 0.45–0.88, P < 0.01) and those with higher levels of socio-economic status (OR 0.81, 95% CI 0.71–0.92, P < 0.01) were less likely to consult. We find no evidence of stigma playing a role in health-seeking decisions, but caution that this may be due to the difficulty of accurately and reliably capturing stigma due to, amongst other factors, social desirability bias.ConclusionsThe low levels of consultation for a cough of more than 2 weeks suggest that there are opportunities to improve case-finding. These findings on health-seeking behaviour can assist policymakers in designing TB screening and active case-finding interventions that are targeted to the characteristics of those with a chronic cough who do not seek care.

The Effect of Health Education on Tuberculosis Case-Finding Based on Advocacy, Communication and Social Mobilization (ACSM) Movement in Majene District, West Sulawesi, Indonesia

This research aimed to determine the effect of tuberculosis (TB) active case-finding interventions based on Advocacy, communication and social mobilization (ACSM) movement toward housewives’ knowledge at the work area of Banggae I Community Health Center, Majene District, West Sulawesi, Indonesia. Quasi-experimental one group pretest and posttest design was used in this research. Participants of the research were selected by inclusive criterias. The data were analyzed by paired T-test with significancy level 0.05. There was a decrease on several questions related to advocacy efforts in TB control. The paired T-test’s result showed that there was association between the intervention activities and knowledge of TB information, advocacy efforts, as well as communication and social mobilization related to TB case-finding and prevention (p = 0,005). The housewives’ knowledge significantly rise after the TB active case-finding interventions. It was recommended to do the further training focusing on advocacy and communication skills as well as initiate a group that concern to TB control.

Improving TB case notification in northern Uganda: evidence of a quality improvement-guided active case finding intervention

BackgroundStrategies to identify and treat undiagnosed prevalent cases that have not sought diagnostic services on their own, are necessary to treat TB in patients earlier and interrupt transmission. Late presentation for medical services of symptomatic patients require special efforts to detect early and notify TB in high risk populations. An intervention that combined quality improvement with facility-led active case finding (QI-ACF) was implemented in 10 districts of Northern Uganda with the highest TB burden to improve case notification among populations at highest risk of TB.MethodsUsing QI-ACF intervention approach in 48 facilities, we; 1) targeted key vulnerable populations, 2) engaged district and facility teams in TB systems strengthening, 3) conducted systematic screening and diagnosis in vulnerable groups (people living with HIV, fishing communities, and prisoners), and 4) trained health workers on national x-ray diagnosis guidelines for smear-negative patients. Facility-led QI-ACF meant that health care providers identified the target population, mobilized and massively screened suspects, and addressed gaps in documentation. Chest X-ray diagnosis was promoted for smear-negative TB among those suspects whose sputum examination was negative. The effect of the intervention on case notification was then assessed separately over the post intervention period.ResultsOver all TB case notification in the intervention districts increased from 171 to 223 per 100,000 population between the baseline months of October–December 2016 and end line month of April–June 2017. TB patient contacts had the majority of TB positive cases identified during active case finding (40, 6.1%). Fishing communities had the highest TB positivity rate at 6.8%. Prisoners accounted for the lowest number of TB positive cases at 34 (2.3%).ConclusionTargeting should be applied at all levels of TB intervention to improve yield: targeting districts and facilities with the lowest rates of case notification and targeting index patient contacts, HIV clients, and fishing communities. Screening tools are useful to guide health workers to identify presumptive cases. Efforts to improve availability of x-ray for TB diagnosis contributed to almost half of the new cases identified. Having all HIV patients who were eligible for viral load provide sputum for TB screening proved easy to implement.

Results from a roving, active case finding initiative to improve tuberculosis detection among older people in rural cambodia using the Xpert MTB/RIF assay and chest X-ray

BackgroundCambodia has one of the highest tuberculosis (TB) prevalence rates in the world. People aged 55 years and over account for an estimated 50% of the country's TB burden, yet this group has a low notification rate owing to specific barriers in accessing health services. One-off active case finding (ACF) days with mobile GeneXpert and X-ray systems were organized at 75 government health facilities in four operational districts. Symptomatic community members with an abnormal chest X-ray were tested using the Xpert MTB/RIF assay. People with TB were then treated at health facilities after screening services moved onto the next site. MethodsDe-identified project data were analysed to produce descriptive statistics about the people tested on Xpert and those diagnosed with TB. A linear regression was fit through the 12 quarters of National TB Program (NTP) TB case notification data immediately prior to ACF. The regression was used to calculate trend-expected notifications during and after the ACF quarters. Notifications from the ACF quarters were then compared to actual notifications from the previous year and to the trend-expected notifications during the ACF quarter by age group and type of TB. Finally, NTP TB treatment outcomes for the patients started on treatment during the ACF quarter were compared to those from a year prior. Results2068 individuals submitted sputum for Xpert MTB/RIF testing, resulting in the identification of 319 (15.4%) bacteriologically-positive TB patients and an additional 574 people who were clinically diagnosed with TB. In the ACF quarters, new bacteriologically-positive notifications increased +119.2% for all ages and +262.7% for people aged 55 and over compared with trend-expected notifications. Treatment initiation figures remained above trend-expected notifications for three full quarters after ACF. The treatment success rate across all operational districts was significantly higher for patients detected in the ACF quarters (88.8% vs 94.5%, p = 0.012). ConclusionA series of roving, one-off ACF days at government health facilities were able to increase TB diagnosis, treatment initiation and treatment outcomes in a key population with high TB prevalence. Targeted ACF interventions such as this could be used to reduce a backlog of untreated, prevalent TB.

Active Case Finding for Communicable Diseases in Prison Settings: Increasing Testing Coverage and Uptake Among the Prison Population in the European Union/European Economic Area.

Prison populations are disproportionally affected by communicable diseases when compared with the general community because of a complex mix of socioeconomic determinants and environmental factors. Tailored and adequate health care provision in prisons has the potential to reach vulnerable and underserved groups and address their complex needs. We investigated the available evidence on modalities and effectiveness of active case-finding interventions in prisons by searching PubMed, Embase, and the Cochrane Library for records on prison and active case finding with no language limit. Conference abstracts and unpublished research reports also were retrieved. We analyzed the findings by testing modality, outcomes, and study quality. The included 90 records—63 peer-reviewed, 26 from gray literature, and 1 systematic review—reported variously on viral hepatitis, human immunodeficiency virus, sexually transmitted infections, and tuberculosis. No records were retrieved for other communicable diseases. Provider-initiated opt-in testing was the most frequently investigated modality. Testing at entry and provider-initiated testing were reported to result in comparatively higher uptake ranges. However, no comparative studies were identified that reported statistically significant differences between testing modalities. Positivity rates among tested inmates ranged broadly but were generally high for all diseases. The evidence on active case finding in correctional facilities is limited, heterogeneous, and of low quality, making it challenging to draw conclusions on the effect of different testing modalities. Scale-up of provider-initiated testing in European correctional facilities could substantially reduce the undiagnosed fraction and, hence, prevent additional disease transmission in both prison settings and the community at large.

Evaluation of a tuberculosis active case finding project in peri-urban areas, Myanmar: 2014-2016

ObjectivesWe assessed the effect of an active case finding (ACF) project on tuberculosis (TB) case notification and the yields from a household and neigbourhood intervention (screening contacts of historical index TB patients diagnosed >24months ago) and a community intervention (screening attendants of health education sessions/mobile clinics). DesignCross-sectional analysis of project records, township TB registers and annual TB reports. ResultsIn the household and neigbourhood intervention, of 56,709 people screened, 1,076 were presumptive TB and 74 patients were treated for active TB with a screening yield of 0.1% and a yield from presumptive cases of 6.9%. In the community intervention, of 162,881 people screened, 4,497 were presumptive TB and 984 were treated for active TB with a screening yield of 0.6% and yield from presumptive cases of 21.9%. Of active TB cases, 94% were new, 89% were pulmonary, 44% were bacteriologically-confirmed and 5% had HIV. Case notification rates per 100,000 in project townships increased from 142 during baseline (2011-2013) to 148 during intervention (2014-2016) periods. ConclusionsThe yield from household and neigbourhood intervention was lower than community intervention. This finding highlights reconsidering the strategy of screening of contacts from historical index cases. Strategies to reach high-risk groups should be explored for future ACF interventions to increase yield of TB.

Mathematical Modeling of "Chronic" Infectious Diseases: Unpacking the Black Box.

BackgroundMathematical models are increasingly used to understand the dynamics of infectious diseases, including “chronic” infections with long generation times. Such models include features that are obscure to most clinicians and decision-makers.MethodsUsing a model of a hypothetical active case-finding intervention for tuberculosis in India as an example, we illustrate the effects on model results of different choices for model structure, input parameters, and calibration process.ResultsUsing the same underlying data, different transmission models produced different estimates of the projected intervention impact on tuberculosis incidence by 2030 with different corresponding uncertainty ranges. We illustrate the reasons for these differences and present a simple guide for clinicians and decision-makers to evaluate models of infectious diseases.ConclusionsMathematical models of chronic infectious diseases must be understood to properly inform policy decisions. Improved communication between modelers and consumers is critical if model results are to improve the health of populations.

An evaluation of innovative community-based approaches and systematic tuberculosis screening to improve tuberculosis case detection in Ebonyi State, Nigeria

National tuberculosis (TB) programmes globally rely heavily on passive case finding for detecting TB in the community as advocated by the World Health Organization (WHO). TB case detection is low in Nigeria despite improvement in TB services and coverage. A retrospective evaluation of an active case-finding intervention utilizing community-based approaches and targeted systematic TB screening in Ebonyi State, Nigeria was done. The analysis was performed using Epi Info. Using community-based and health-facility-based systematic screening strategies, 218,751 persons were screened, with 19.7% of them being presumptive TB cases. Among these, 23,729 (55.1%) submitted sputum samples for microscopy, and 764 (3.2%) had smear-positive TB. In addition, 683 individuals were diagnosed with other forms of TB using X-ray and clinical evaluation giving a total of 1447 all forms of TB cases. The overall number needed to screen (NNS) to find one person with all forms of TB through the project was 151. The NNS was 53 for general outpatients, 88 through contact tracing, and 110 among HIV-infected persons. Active case-finding strategies achieved good yields though early loss to follow-up was high. Active case finding is recommended for integration into national TB control policy and practice.

A Data-Driven Evaluation of the Stop TB Global Partnership Strategy of Targeting Key Populations at Greater Risk for Tuberculosis.

ObjectiveIdentifying those infected with tuberculosis (TB) is an important component of any strategy for reducing TB transmission and population prevalence. The Stop TB Global Partnership recently launched an initiative with a focus on key populations at greater risk for TB infection or poor clinical outcomes, due to housing and working conditions, incarceration, low household income, malnutrition, co-morbidities, exposure to tobacco and silica dust, or barriers to accessing medical care. To achieve operational targets, the global health community needs effective, low cost, and large-scale strategies for identifying key populations. Using South Africa as a test case, we assess the feasibility and effectiveness of targeting active case finding to populations with TB risk factors identified from regularly collected sources of data. Our approach is applicable to all countries with TB testing and census data. It allows countries to tailor their outreach activities to the particular risk factors of greatest significance in their national context.MethodsWe use a national database of TB test results to estimate municipality-level TB infection prevalence, and link it to Census data to measure population risk factors for TB including rates of urban households, informal settlements, household income, unemployment, and mobile phone ownership. To examine the relationship between TB prevalence and risk factors, we perform linear regression analysis and plot the set of population characteristics against TB prevalence and TB testing rate by municipality. We overlay lines of best fit and smoothed curves of best fit from locally weighted scatter plot smoothing.FindingsHigher TB prevalence is statistically significantly associated with more urban municipalities (slope coefficient β1 = 0.129, p < 0.0001, R2 = 0.133), lower mobile phone access (β1 = -0.053, p < 0.001, R2 = 0.089), lower unemployment rates (β1 = -0.020, p = 0.003, R2 = 0.048), and a lower proportion of low-income households (β1 = -0.048, p < 0.0001, R2 = 0.084). Municipalities with more low-income households also have marginally higher TB testing rates, however, this association is not statistically significant (β1 = -0.025, p = 0.676, R2 = 0.001). There is no relationship between TB prevalence and the proportion of informal settlement households (β1 = 0.021, p = 0.136, R2 = 0.014).ConclusionsThese analyses reveal that the set of characteristics identified by the Global Plan as defining key populations do not adequately predict populations with high TB burden. For example, we find that higher TB prevalence is correlated with more urbanized municipalities but not with informal settlements. We highlight several factors that are counter-intuitively those most associated with high TB burdens and which should therefore play a large role in any effective targeting strategy. Targeting active case finding to key populations at higher risk of infection or poor clinical outcomes may prove more cost effective than broad efforts. However, these results should increase caution in current targeting of active case finding interventions.

Implementation of a stepped-wedge cluster randomized design in routine public health practice: design and application for a tuberculosis (TB) household contact study in a high burden area of Lima, Peru.

BackgroundWe designed a pragmatic stepped-wedge cluster randomized controlled trial in order to evaluate provider-initiated evaluation of household contacts (HCs) of smear positive tuberculosis (TB) cases within a routine TB program in Lima, Peru.Methods/DesignNational TB program (NTP) officers of San Juan de Lurigancho District (Lima, Peru) and university-based researchers jointly designed a pragmatic stepped-wedge cluster randomized trial design in order to evaluate a planned active case finding (ACF) program for all HCs of smear-positive TB cases in 34 district healthcare centres. Randomization of time to intervention initiation was stratified by health centre TB case rate. The ACF intervention included provider-initiated home visits of all new sputum smear positive TB patients in order to evaluate household contacts for active TB. Active TB was diagnosed using symptom screening, sputum screening, chest x-ray and clinical evaluation. Once initiated, ACF was provided by NTP staff and integrated into the routine DOTS TB program activities.DiscussionThis study protocol describes the pragmatic stepped-wedge cluster randomized trial of active household contact evaluations within an NTP. The stepped-wedge design met overlapping needs of local TB programmers and researchers to adequately evaluate the large-scale roll out of a new control program in a TB endemic setting. Multiple planning meetings were required to develop the necessary networks and in order to understand the operations, needs and goals of the NTP staff and researchers collaborating on this project. The advantages and challenges of using this study design in practice and within existing routine TB programs in a middle-income country context are discussed.Trial registrationClinicalTrials.gov NCT02174380. Registered 24 Jun 2014