TB Test Research Articles

Prevalence of Hepatitis B Virus and Latent Tuberculosis Coinfection in the United States.

Underlying chronic hepatitis B virus (HBV) infection increases the risk of drug-induced liver injury (DILI) when receiving tuberculosis therapies. Prevalence of HBV and latent tuberculosis infection (LTBI) coinfection is not well reported and no studies have evaluated testing patterns for and prevalence of HBV-LTBI coinfection in the United States. To evaluate patterns of HBV and LTBI testing and prevalence of HBV-LTBI coinfection in the United States. Retrospective cohort study. Quest Diagnostics clinical laboratory data, 2014-2020. Chronic HBV infection was defined as any combination of 2 positive HBV surface antigen, HBV e antigen, or detectable HBV DNA tests at least 6 months apart. LTBI was defined as a positive QuantiFERON-TB or T-SPOT.TB test without evidence of active tuberculosis infection. Testing patterns for chronic HBV infection and LTBI and prevalence of HBV-LTBI coinfection were evaluated from 2016 through 2020 and stratified by age, sex, and race and ethnicity. Among 89 259 patients with chronic HBV infection, 9508 (10.7%) were tested for LTBI, among whom prevalence of HBV-LTBI coinfection was 19.6%, more than twice the observed prevalence of LTBI in patients with no chronic HBV infection in our cohort. Among 394 817 LTBI patients, 127 414 (32.3%) were tested for HBV, among whom prevalence of HBV-LTBI coinfection was 1.5%, approximately 3 times higher than prevalence of HBV infection in patients with no LTBI. The HBV-LTBI coinfection prevalence was highest among Asian Americans and older individuals. The HBV-LTBI coinfection prevalence was likely underestimated because of suboptimal awareness and testing among at-risk populations. Among US individuals with chronic HBV infection or LTBI, prevalence of HBV-LTBI coinfection is substantial and highlights the need of testing for HBV-LTBI coinfection to mitigate risk of DILI associated with tuberculosis medications in patients with chronic HBV infection.

Uptake of the lateral flow urine LAM test in Europe and Central Asia.

SUMMARYINTRODUCTION:Since 2015 (updated in 2019), the WHO has recommended to include the commercial lateral flow urine lipoarabinomannan TB test (LF-LAM), AlereLAM, in the diagnostic toolkit for severely ill people living with HIV.METHODS:To assess the current use and barriers to the implementation of the test, we conducted an electronic survey among national focal points and managers of TB and HIV programmes in the 53 Member States of the WHO European Region and a European network of clinicians working in TB and HIV medicine.RESULTS:In all, 45 individual responses (37 countries) were received from programme managers and focal points and 17 responses (14 countries) from clinicians. Only eight countries reported adopting LF-LAM policies, with only four currently using the AlereLAM (Armenia, Belarus, Ukraine and Uzbekistan). The most commonly reported barriers to implementing the test were the small number of eligible patients (with HIV-TB co-infections), the test not being included in the TB or HIV programme’s mandate and lack of budget allocation.CONCLUSION:Consistent with findings from high TB burden countries in Africa and Asia, the survey demonstrated that uptake of AlereLAM is almost non-existent. Addressing the identified barriers and the intrinsic limitations of the test could help to increase the use of the test.

Infectious disease surveillance in U.S. jails: Findings from a national survey.

While infectious diseases (ID) are a well-documented public health issue in carceral settings, research on ID screening and treatment in jails is lacking. A survey was sent to 1,126 jails in the United States to identify the prevalence of health screenings at intake and characteristics of care for ID; 371 surveys were completed correctly and analyzed. Despite conflicting Centers for Disease Control (CDC) guidance, only seven percent of surveyed jails test individuals for HIV at admission. In 46% of jails, non-healthcare personnel perform ID screenings. Jails in less urban areas were more likely to report healthcare screenings performed by correctional officers. Survey findings indicate that HIV, HCV and TB testing during jail admissions and access to PrEP are severely lacking in less urban jails in particular. Recommendations are provided to improve ID surveillance and address the burden of ID in correctional facilities.

Rapid Diagnosis of XDR and Pre-XDR TB: A Systematic Review of Available Tools

IntroductionNo previous systematic reviews have comprehensively investigated the features of Xpert MTB/XDR and other rapid tests to diagnose pre-XDR/XDR-TB. The aim of this systematic review is to assess existing rapid diagnostics for pre-XDR/XDR-TB from a point-of-care perspective and describe their technical characteristics (i.e., sensitivity, specificity, positive and negative predictive values). MethodsEmbase, PubMed, Scopus, and Web of Science were searched to detect the articles focused on the accuracy of commercially available rapid molecular diagnostic tests for XDR-TB according to PRISMA guidelines. The analysis compared the diagnostic techniques and approaches in terms of sensitivity, specificity, laboratory complexity, time to confirmed diagnosis. ResultsOf 1298 records identified, after valuating article titles and abstracts, 97 (7.5%) records underwent full-text evaluation and 38 records met the inclusion criteria.Two rapid World Health Organization (WHO)-endorsed tests are available: Xpert MTB/XDR and GenoType MTBDRsl (VER1.0 and VER 2.0). Both tests had similar performance, slightly favouring Xpert, although only 2 studies were available (sensitivity 91.4–94; specificity 98.5–99; accuracy 97.2–97.7; PPV 88.9–99.1; NPV 95.8–98.9). ConclusionsXpert MTB/XDR could be suggested at near-point-of-care settings to be used primarily as a follow-on test for laboratory-confirmed TB, complementing existing rapid tests detecting at least rifampicin-resistance.Both Xpert MTB/XDR and GenoType MTBDRsl are presently diagnosing what WHO defined, in 2021, as pre-XDR-TB.

Adaptations to the first wave of the COVID-19 pandemic by private sector tuberculosis care providers in India

BackgroundIndia’s dominant private healthcare sector is the destination for 60–85% of initial tuberculosis care-seeking. The COVID-19 pandemic in India drastically affected TB case notifications in the first half of 2020. In this survey, we assessed the impact of the first wave of COVID-19 in India on private providers, and changes they adopted in their practice due to the pandemic. MethodsThe Joint Effort for Elimination of TB (JEET) is a nationwide Global Fund project implemented across 406 districts in 23 states to extend quality TB services to patients seeking care in private sector. We conducted a rapid survey of 11% (2,750) of active providers engaged under JEET’s intense Patient Provider Support Agency (PPSA) model across 15 Indian states in Q1 (February–March) of 2021. Providers were contacted in person or telephonically, and consenting participants were interviewed using a web-based survey tool. Responses from participants were elicited on their practice before COVID-19, during the 2020 lockdowns (March–April 2020) and currently (Q1 2021). Data were adjusted for survey design and non-response, and results were summarised using descriptive statistics and logistic regression. ResultsOf the 2,750 providers sampled, 2,011 consented and were surveyed (73 % response). Nearly 50 % were between 30 and 45 years of age, and 51 % were from Uttar Pradesh, Maharashtra and Gujarat. Seventy percent of providers reported reduced daily out-patient numbers in Q1 2021 compared to pre-COVID times. During the lockdown, 898 (40 %) of providers said their facilities were closed, while 323 (11 %) offered limited services including teleconsultation. In Q1 2021, 88 % of provider facilities were fully open, with 10 % providing adjusted services, and 4 % using teleconsultation. Only 2 % remained completely closed. Majority of the providers (92 %) reported not experiencing any delays in TB testing in Q1 2021 compared to pre-COVID times. Only 6 % reported raising costs at their clinic, mostly to cover personal protective equipment (PPE) and other infection control measures, although 60–90 % implemented various infection control measures. Thirty-three percent of TB providers were ordering COVID-19 testing, in addition to TB testing.To adapt, 82% of survey providers implemented social distancing and increased timing between appointments and 83% started conducting temperature checks, with variation by state and provider type, while 89% adopted additional sanitation measures in their facilities. Furthermore, 62% of providers started using PPE, and 13% made physical changes (air filters, isolation of patient areas) to their clinic to prevent infection. Seventy percent of providers stated that infection control measures could decrease TB transmission. ConclusionAlthough COVID-19 restrictions resulted in significant declines in patient turn-out at private facilities, our analysis showed that most providers were open and costs for TB care remained mostly the same in Q1 2021. As result of the COVID-19 pandemic, several positive strategies have been adapted by the private sector TB care providers. Since the subsequent COVID-19 waves were more severe or widespread, additional work is needed to assess the impact of the pandemic on the private health sector.

A call to action to reclaim focus on testing and early treatment for HIV, viral hepatitis, sexually transmitted infections and tuberculosis.

We present the outcomes of the HepHIV 2021 Lisbon & virtual conference held on 5-7 May 2021, including a Call to Action addressing policy and practice implications in the field of earlier and integrated testing for HIV, viral hepatitis, STI and TB and in light of lessons learned from the COVID-19 pandemic. Conference presentations showed that combination prevention and integrated testing and care models for multiple infectious diseases are necessary and feasible in diverse settings. Successful examples of service and system adaptations developed to mitigate impact of the pandemic were shared. Aiming to ensure greater equity in health in current and future health policies and programmes and address the adverse effects of COVID-19, we must learn from the many innovative approaches to service delivery developed in response to the pandemic, many of which have the potential to reach people whose needs were not met by existing models.

Accelerating TB diagnosis during the COVID-19 pandemic.

SETTING: The COVID-19 pandemic has caused significant disruption worldwide to economies and healthcare systems, even those with well-developed infrastructure.OBJECTIVE: To examine the effects of COVID-19 on TB diagnosis in Singapore, and to identify any factors that could facilitate early detection of TB among persons screened.DESIGN: To assess the impact of testing and diagnosis of the pandemic on TB, the number of TB-related tests from January 2018 to December 2020 were collected. We also conducted a retrospective case-control study of all adult patients admitted for COVID-19, TB or coinfection from 23 January to 31 May 2020.RESULTS: Nationwide testing for TB from 2018 to 2020 increased by 24.2%. We analysed 253 adult inpatients, of whom 107 (42.3%) were diagnosed with COVID-19, 134 (53.0%) had TB, while 12 (4.7%) had co-infection. Patients with TB were more likely to have chest X-ray abnormalities than those with COVID-19 (89.9% vs. 76.0%; P < 0.01). Patients with TB were more likely to have prolonged cough vs. those with COVID-19 infection (28 vs. 5 days; P < 0.01).CONCLUSION: Early screening for TB, even among patients with COVID-19, could lead to earlier diagnosis and treatment, thereby breaking the chain of transmission.

AN UNUSUAL CASE OF BRONCHIECTASIS IN A PATIENT WITH DERMATOMYOSITIS

TYPE: Case Report TOPIC: Diffuse Lung Disease INTRODUCTION: Bronchiectasis is a progressive lung disease defined by dilatation of the bronchi in the setting of chronic airway infection and/or inflammation. It is common pulmonary manifestation in certain rhumatologic disorders, however, it has never been reported in association with inflammatory myopathies. Here we present a case of bronchiectasis in a patient with dermatomyositis. CASE PRESENTATION: A 71 year old African American woman with history of dermatomyositis presented with productive cough for two years. She was diagnosed with dermatomyositis 20 years prior, treated with immunosuppressives and no current active disease. She had no history of smoking, recurrent respiratory infection or occupational exposure. Her Chest CT demonstrated bibasilar and upper lobes cylindrical bronchiectasis (figure). Labratory tests indicated normal CBC, CMP, Muscle enzyms, Serum IgE levels to Aspergillus, Alpha-1antitrypsin and negative ANA, RF, Anti-CCP and TB tests. Patient was started on acapella therapy and albuterol as needed with improvement in her symptoms. DISCUSSION: Bronchiectasis often develops in the setting of infections, ciliary clearance impairment, immunodeficiencies, allergic bronchopulmonary aspergillosis and Alpha1-antitrypsin deficiency. It is an unusual manifestation in inflammatory myopathies where Interstitial Lung Diseases (ILDs) are the most common pattern of lung involvement. ILDs often present with dyspnea, dry cough and CT findings of basal reticular abnormalities or honeycombing, as oppose to our patient's presentation and CT findings of diffuse cylindrical bronchiectasis without reticular abnormalities. With all other etiologies ruled out, it was suspected her dermatomyositis to be the underlying etiology of bronchiectasis. CONCLUSIONS: It is important to recognize and suspect atypical lung presentations in patients with inflammatory myopathies. DISCLOSURE: Nothing to declare. KEYWORD: Bronchiectasis

The impact of COVID-19 on essential health service provision for endemic infectious diseases in the South-East Asia region: A systematic review.

SummaryBackgroundThere is increasing evidence that the COVID-19 pandemic has impacted adversely on the provision of essential health services. The South East Asia region (SEAR) has experienced extremely high rates of COVID-19 infection, and continues to bear a significant proportion of communicable disease burden worldwide.MethodsWe conducted a systematic literature review of quantitative evidence to estimate the impact of COVID-19 on the provision of essential prevention, detection, treatment, and management services for five high-burden infectious diseases across the SEAR.FindingsA total of 2338 studies were reviewed, and 12 studies were included in our analysis, covering six countries across the SEAR (Bhutan, Sri Lanka, Nepal, Myanmar, Thailand, and India) for three conditions of interest (HIV, TB, dengue fever). We identified significant disruption to TB testing (range=25% to 77.9%) and diagnoses (range=50% to 58%) in India, Nepal, and Indonesia; and similar disruptions were observed for screening, new diagnoses and commencing HIV treatment in India and Thailand. There was also drastically reduced case detection for dengue fever (range=75% to 90% disrupted) in Bhutan and Sri Lanka. No studies were identified for malaria nor hepatitis in any country, and nor for any service in the remaining six SEAR countries.InterpretationWe identified evidence of significant disruption to the prevention, diagnoses, treatment, and management of TB, HIV, and dengue fever due to the COVID-19 pandemic across multiple SEAR country settings. This has the potential to set back hard-fought gains in infectious disease control across the region. The lack of evidence for the impact of the pandemic on malaria and hepatitis services, and in the remaining six SEAR countries, is an important evidence gap that should be addressed in order to inform future policy for service protection and pandemic preparedness.FundingThis work was supported by the WHO Sri Lanka Country office.

Screening for tuberculosis of patients with HIV-infection. New possibilities

Background. Tuberculosis associated with HIV infection is becoming almost a new disease, where not only new approaches to treatment are being formed, but there is also a need to improve the quality and search for new means of early diagnosis of tuberculosis infection.The aim. To evaluate the diagnostic performance of the T-SPOT.TB test for the detection of latent tuberculosis infection and clinical forms of tuberculosis in patients with HIV infection.Materials and methods. 396 patients registered at the AIDS Center for more than a year were examined. Everyone underwent standard examinations for pulmonary tuberculosis using sputum bacterioscopy techniques with Ziehl – Neelsen staining; a molecular genetic method based on hybridization technology – HAIN-GenoType MTBDRplus; crops on liquid media in the automated BACTEC MGIT 960 system and on Löwenstein–Jensen dense medium. T-SPOT.TB was conducted as a screening for everyone. With positive T-SPOT.TB results, negative results of the MBT search, absence of specific changes on the X-ray a conclusion was made about latent tuberculosis infection. Statistical data processing was carried out using the software package Statistica 10 (StatSoft Inc., USA).Results. According to the results of a comprehensive examination, tuberculosis was diagnosed in 174 patients, verified using various methods of searching for Mycobacterium tuberculosis in 116 patients (66.6 %). Infiltrative (63.8 %) and disseminated (24.7 %) tuberculosis were more often diagnosed. Latent tuberculosis infection was diagnosed in 52 patients, 170 HIV-infected patients have no data for tuberculosis at this stage.Conclusions. T-SPOT.TB can be used in the diagnostic complex of monitoring patients with HIV infections – as a screening method to detect latent tuberculosis, for preventive chemotherapy.

Diagnosis of Mycobacterium tuberculosis using GeneXpert MTB / RIF and TB-LAMP techniques from pulmonary and extra-pulmonary TB patients in Iraq

Tuberculosis is considered one globally public health problem, particularly in unindustrialized countries. The disease has an increasing threat to public health, causing high morbidity and mortality rates. So, rapid diagnosis is critical to diminish the death and interfere with transmission. In this study, GeneXpert MTB/RIF and Loop-Mediated Isothermal Amplification (TB-LAMP) assays were utilized for the rapid molecular diagnosis of Mycobacterium tuberculosis bacteria and compared sensitivity and specificity of Mycobacterium tuberculosis bacteria; these tests with acid-fast bacilli staining in pulmonary and extra-pulmonary clinical specimens from Iraqi patients in Baghdad capital. 141 pulmonary and extra-pulmonary samples were collected and tested for tuberculosis detection. Acid-fast bacilli, TB-LAMP and GeneXpert MTB/RIF methods were used to diagnose tuberculosis. Of 141 tuberculosis specimens, 58 were acid-fast bacilli smear-positive, while 90 samples were positive for Mycobacterium tuberculosis by GeneXpert MTB/RIF assay and 78 by TB-LAMP assay. The results reported a high sensitivity rate of GeneXpert MTB/RIF assay compared to the TB-LAMP and bacilli staining method. The sensitivity of GeneXpert was 63.83%, specificity 50%; positive and negative predictive values were 58.36% to 68.96% and 42.73% to 57.27%, respectively. TB-LAMP sensitivity was 55.32%, specificity 50%; positive and negative predictive values were 49.61% to 60.89% and 43.70% to 56.30%, respectively, while the sensitivity of bacilli staining was 41.13%, specificity 50%; positive and negative predictive values were 35.26% to 47.27% and 44.88% to 55.12%, respectively, these values are dependent on disease prevalence. We concluded that the GeneXpert MTB/RIF test is more sensitive and specific than the TB-LAMP and both techniques are more sensitive and specific than the conventional acid-fast staining method for both pulmonary and extra-pulmonary specimens. Despite culture remaining the gold standard for laboratory confirmation of TB, GeneXpert MTB/RIF and TB-LAMP should become standard practice for patients with suspected TB, and all clinicians and public health programs for TB control should have access to molecular testing for TB to shorten diagnosis time. Keywords. Mycobacterium tuberculosis; Pulmonary TB; Extrapulmonary TB; GeneXpert MTB/RIF; TB-LAMP; A.F.B

Xpert MTB/RIF on urine samples to increase diagnosis of TB in people living with HIV in Guinea-Bissau

ObjectivesWe investigated if Xpert MTB/RIF (Xpert) testing on urine samples among newly diagnosed HIV-patients as an adjunctive test to Xpert testing on sputum increases diagnosis. We sought to define subgroups of patients, for whom testing with either test is especially advantageous. MethodsWe included patients >15 years, newly diagnosed with HIV, that delivered a urine sample on the day of HIV-diagnosis at the biggest HIV-clinic in Guinea-Bissau between September 5, 2016 and October 13, 2017 into a cross-sectional study. Patients were asked for a sputum sample, which was Xpert tested if returned within 30 days. A questionnaire and physical examination were completed on day of inclusion. ResultsWe included 390 patients. TB prevalence was 12.6%. Adding Xpert urine test to all newly diagnosed HIV-patients increased diagnostic yield of TB by 58% compared with testing on sputum alone. Patients who tested positive by Xpert on urine samples were clinically similar to those tested with sputum, except that the sputum positives reported more cough (p=0.03). ConclusionsIndiscriminate Xpert urine testing in newly diagnosed HIV-patients with advanced disease increased diagnostic yield. Xpert testing for TB on urine and sputum should be offered as screening in Guinea-Bissau and possibly in similar settings.

Integrated screening and testing for TB and COVID-19 in Peru.

We describe the experience of integrating COVID-19 screening and testing into a mobile TB screening unit in Lima, Peru. All attendees received chest radiographs, which were analysed using CAD4TB and CAD4COVID; Xpert MTB/RIF Ultra was used to test for TB, and antibody and polymerase chain reaction (PCR) for SARS-CoV-2. One Xpert-positive TB case was diagnosed per 168 people screened, one person with SARS-CoV-2 antibodies per 3 people screened, and one PCR-confirmed SARS-CoV-2 infection per 8 people screened. Integrated screening can help to avoid delays in the diagnosis of both TB and COVID-19.

A real-world, single-center experience and the immediate impact of granulocyte and monocyte adsorption apheresis on generalized pustular psoriasis

To the Editor: Generalized pustular psoriasis (GPP) often requires urgent treatment such as biologics.1 However, the safe administration of a biologic typically requires laboratory testing, which presents a timeliness issue because most tests take a few days to return results (eg, 4 business days for the commercial T-Spot.TB test). Granulocyte and monocyte adsorption apheresis (GMA) is an extracorporeal circulation therapy that removes activated granulocytes and monocytes, which can be easily introduced in clinics and hospitals where hemodialysis is performed.

World Tuberculosis Day 2022: aligning COVID-19 and tuberculosis innovations to save lives and to end tuberculosis

World Tuberculosis Day 2022: aligning COVID-19 and tuberculosis innovations to save lives and to end tuberculosis

TB testing in HIV-positive patients prior to antiretroviral treatment.

BACKGROUND :TB diagnosis in patients with HIV is challenging due to the lower sensitivities across tests. Molecular tests are preferred and the Xpert® MTB/RIF assay has limitations in lower-income settings. We evaluated the performance of loop-mediated isothermal amplification (LAMP) and the lipoarabinomannan (LAM) test in HIV-positive, ART-naïve clinic patients.METHODS :A total of 783 eligible patients were enrolled; three spot sputum samples of 646 patients were tested using TB-LAMP, Xpert, smear microscopy and culture, while 649 patients had TB-LAM testing. Sensitivity, specificity, and negative and positive predictive values were estimated with 95% confidence intervals.RESULTS :Sensitivities for smear microscopy, TB-LAMP and Xpert were respectively 50%, 63% and 74% compared to culture, with specificities of respectively 99.2%, 98.5% and 97.5%. An additional eight were positive on TB-LAM alone. Seventy TB patients (9%) were detected using standard-of-care testing, an additional 27 (3%) were detected using study testing. Treatment was initiated in 57/70 (81%) clinic patients, but only in 56% (57/97) of all those with positive TB tests; 4/8 multidrug-resistant samples were detected using Xpert.CONCLUSION :TB diagnostics continue to miss cases in this high-burden setting. TB-LAMP was more sensitive than smear microscopy, and if followed by culture and drug susceptibility testing as required, can diagnose TB in HIV-positive patients. TB-LAM is a useful add-in test and both tests at the point-of-care would maximise yield.

Integrated testing for TB and COVID-19

Integrated testing for TB and COVID-19 may help find those TB patients who are not accessing care in the context of the COVID-19 pandemic. Some molecular platforms with assays for both diseases are already commercially available; however, integrated testing approaches need to be systematically evaluated to ensure their appropriate implementation.

Assessing the diagnostic accuracy of the Xpert MTB/RIF assay in detecting epididymal tuberculosis.

We analyzed 84 samples from patients with suspected epididymal TB or chronic epididymitis who received surgical treatment (epididymal resection or epididymis-testicular resection) at our hospital between July 1, 2016 and July 1, 2020. A composite reference standard (CRS) was used in this study. We determined the sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and area under the curve (AUC) of the Xpert MTB/RIF assay for epididymal TB and compared its diagnostic accuracy with that of the Mycobacterium tuberculosis (MTB) culture test in detecting epididymal TB. Three patients were excluded because of incomplete data. Comparing with the composite reference standard, the sensitivity, specificity, PPV, NPV, and AUC of Xpert MTB/RIF assay for epididymal TB were 80.95% (69.09-89.75%); 94.44% (72.71-99.86%); 98.08% (89.74-99.95%); and 58.62% (38.94-76.48%), respectively, with an AUC of 0.88 (95% confidence interval: 0.79-0.94). The diagnostic sensitivity of the Xpert MTB/RIF assay was significantly higher than that of the MTB culture test for epididymal TB. We recommend the Xpert MTB/RIF assay as a diagnostic method for the detection of epididymal TB.

Latent Tuberculosis Infection Treatment Outcomes in an At-Risk Underserved Population in Rhode Island.

Objectives:Within the United States (US), significant racial and ethnic disparities exist in the rates of latent TB infection (LTBI) and active TB disease. A disproportionate number of TB disease cases result from untreated LTBI among individuals born outside the US. This study evaluates LTBI treatment outcomes among an underserved, at-risk population in Rhode Island.Methods:A quantitative retrospective chart review of adult patients with a positive screening test assessed LTBI care cascade outcomes including referral, treatment initiation, and completion.Results:Seventy-four percent of patients found to have positive screening TB tests were born outside of the US; 80% identified as Hispanic or Black and 45% spoke a preferred language other than English. Twenty-one percent of potential candidates for LTBI treatment initiated treatment.Conclusions:Major gaps were identified in referral success and treatment initiation. Expanding LTBI treatment access into primary care settings could be a solution to improve outcomes and decrease health inequities among at-risk communities.

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.