Background Community-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.Results 27 883 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.Interpretation Community-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.Funding WHO Global TB Programme.

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Background To eliminate trachoma as a public health problem, countries must achieve a district-level prevalence of trachomatous inflammation—follicular (TF) <5% in children ages 1–9 years. Re-emergence of TF could trigger additional rounds of mass drug/antibiotic administration (MDA), so accurate tools for use in surveys assessing trachoma prevalence are essential. Methodology & principal findings We surveyed 2401 children ages 1–9 years from 50 villages in Kongwa, Tanzania, 2 years post-MDA and 1.5 years after an impact survey found TF <5% in the same villages. Our survey included multiple tools: clinical determination of TF, Cepheid testing for Chlamydia trachomatis infection, and testing for anti-pgp3 antibodies via multiplex bead array. Photographs of the upper tarsal conjunctiva were taken in a subset of children to corroborate the field grades. Overall TF prevalence in 1–9 year olds was 7.1% (95% CI: 5.6%-8.9%), which decreased with age (p = <0.0001). TF prevalence by village was heterogeneous, with 19 villages having TF <5% and 16 villages having TF >10%. There was a strong correlation between field and photo grading of TF (kappa = 0.69; 95% CI: 0.60–0.78) and between TF and infection, with 21.5% of TF-positive children also testing positive for infection, as compared to only 1.6% of TF-negative children (p = 0.0010). Overall seroprevalence was 18.2% (95% CI: 14.8%-22.1%), which increased with age (p = <0.0001). Notably, 1–2 year olds, who were born after the cessation of MDA and theoretically should not have had exposure to C. trachomatis in the absence of transmission, had an average seroprevalence of 6.7%. Conclusions & significance Field TF prevalence, supported by photographic review and infection data, suggested re-emergence of trachoma in Kongwa. Moreover, seropositivity in the children born after cessation of MDA indicated exposure to C. trachomatis despite a previous survey finding of TF <5%. Examining seropositivity in specific age groups expected to have limited exposure to C. trachomatis can be used to detect re-emergence.

Background As the prevalence of trachoma declines worldwide, it is becoming increasingly expensive and challenging to standardize graders in the field for surveys to document elimination. Photography of the tarsal conjunctiva and remote interpretation may help alleviate these challenges. The purpose of this study was to develop, and field test an Image Capture and Processing System (ICAPS) to acquire hands-free images of the tarsal conjunctiva for upload to a virtual reading center for remote grading. Methodology/Principal findings This observational study was conducted during a district-level prevalence survey for trachomatous inflammation—follicular (TF) in Chamwino, Tanzania. The ICAPS was developed using a Samsung Galaxy S8 smartphone, a Samsung Gear VR headset, a foot pedal trigger and customized software allowing for hands-free photography. After a one-day training course, three trachoma graders used the ICAPS to collect images from 1305 children ages 1–9 years, which were expert-graded remotely for comparison with field grades. In our experience, the ICAPS was successful at scanning and assigning barcodes to images, focusing on the everted eyelid with adequate examiner hand visualization, and capturing images with sufficient detail to grade TF. The percentage of children with TF by photos and by field grade was 5%. Agreement between grading of the images compared to the field grades at the child level was kappa = 0.53 (95%CI = 0.40–0.66). There were ungradable images for at least one eye in 199 children (9.1%), with more occurring in children ages 1–3 (18.5%) than older children ages 4–9 (4.2%) (χ2 = 145.3, p<0.001). Conclusions/Significance The prototype ICAPS device was robust, able to image 1305 children in a district level survey and transmit images from rural Tanzania to an online grading platform. More work is needed to improve the percentage of ungradable images and to better understand the causes of disagreement between field and photo grading.

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.

BACKGROUND: Systematic screening for active TB is recommended for all people living with HIV (PLWH); however, case detection remains poor globally. We investigated the yield of active case finding (ACF) by calculating the number needed to screen (NNS) to detect a case of active TB among PLWH.METHODS: We identified studies reporting ACF for TB among PLWH published from November 2010 to February 2020. We calculated crude NNS for Xpert- or culture-confirmed TB and weighted mean NNS stratified by screening approach, population/risk group, and country TB burden.RESULTS: Of the 27,221 abstracts screened, we identified 58 studies eligible for inclusion, including 5 in low/moderate TB incidence settings and 53 in medium/high incidence settings. Populations screened for TB included inpatients, outpatients not receiving antiretroviral therapy (ART), outpatients receiving ART, those with CD4 < 200 cells/µL, children aged ≤15 years, pregnant PLWH, and PLWH in prisons. Screening tools included symptom-based screening, chest X-ray, C-reactive protein levels, and Xpert. The weighted mean NNS varied across groups but was consistently low, ranging from 4 among inpatients in moderate/high TB burden settings to 137 among pregnant PLWH in moderate/high TB burden settings.CONCLUSIONS: ACF is a high yield intervention among PLWH. Approaches to screening should be tailored to local epidemiological and health-system contexts, and sensitive screening tools such as Xpert should be implemented where feasible.

Background: To determine if tuberculosis (TB) screening improves patient outcomes, we conducted two systematic reviews to investigate the effect of TB screening on diagnosis, treatment outcomes, deaths (clinical review assessing 23 outcome indicators); and patient costs (economic review). Methods: Pubmed, EMBASE, Scopus and the Cochrane Library were searched between 1/1/1980-13/4/2020 (clinical review) and 1/1/2010-14/8/2020 (economic review). As studies were heterogeneous, data synthesis was narrative. Findings: Clinical review: of 27,270 articles, 18 (n=3 trials) were eligible. Nine involved general populations. Compared to passive case finding (PCF), studies showed lower smear grade (n=2/3) and time to diagnosis (n=2/3); higher pre-treatment losses to follow-up (screened 23% and 29% vs PCF 15% and 14%; n=2/2); and similar treatment success (range 68-81%; n=4) and case fatality (range 3-11%; n=5) in the screened group. Nine reported on risk groups. Compared to PCF, studies showed lower smear positivity among those cultureconfirmed (n=3/4) and time to diagnosis (n=2/2); and similar (range 80-90%; n=2/2) treatment success in the screened group. Case fatality was lower in n=2/3 observational studies; both reported on established screening programmes. A neonatal trial and post-hoc analysis of a household contacts trial found screening was associated with lower all-cause mortality. Economic review: From 2841 articles, six observational studies were eligible. Total costs (n=6) and catastrophic cost prevalence (n=4; range screened 9-45% vs PCF 12-61%) was lower among those screened. Interpretation: We found very limited patient outcome data. Collecting and reporting this data must be prioritised to inform policy and practice. Funding: WHO and EDCTP.