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BackgroundHousehold contact investigations are effective for finding tuberculosis (TB) cases but are hindered by low referral uptake for clinic-based evaluation and testing. We assessed the acceptability and feasibility of in-home testing of household contacts (HHC) using the GeneXpert Edge platform.MethodsWe conducted a 2-arm, randomized study in Eastern Cape, South Africa. HHCs were verbally assessed using the World Health Organization-recommended 4-symptom screen. Households with ≥1 eligible symptomatic contact were randomized. Intervention households received in-home GeneXpert MTB/RIF molecular testing. GeneXpert-positive HHCs were referred for clinic-based treatment. Standard-of-care households were referred for clinic-based sputum collection and testing. We defined acceptability as agreeing to in-home testing and feasibility as generation of valid Xpert MTB/RIF results. The proportion and timeliness of test results received was compared between groups.ResultsEighty-four households were randomized (n = 42 per arm). Of 100 eligible HHCs identified, 98/100 (98%) provided consent. Of 51 HHCs allocated to the intervention arm, all accepted in-home testing; of those, 24/51 (47%) were sputum productive and 23/24 (96%) received their test results. Of 47 HCCs allocated to standard-of-care, 7 (15%) presented for clinic-based TB evaluation, 6/47 (13%) were tested, and 4/6 (67%) returned for their results. The median (interquartile range) number of days from screening to receiving test results was 0 (0) and 16.5 (11-15) in the intervention and standard-of-care arms, respectively.ConclusionsIn-home testing for TB was acceptable, feasible, and increased HHCs with a molecular test result. In-home testing mitigates a major limitation of household contact investigations (dependency on clinic-based referral), revealing new strategies for enhancing early case detection.

Active case finding (ACF) of individuals with tuberculosis (TB) is a key intervention to find the 30% of people missed every year. However, ACF requires screening large numbers of individuals who have a low probability of positive results, typically <5%, which makes using the recommended molecular tests expensive. We conducted two ACF surveys (in 2020 and 2021) in high TB burden areas of Lao PDR. Participants were screened for TB symptoms and received a chest X-ray. Sputum samples of four consecutive individuals were pooled and tested with Xpert Mycobacterium tuberculosis (MTB)/rifampicin (RIF) (Xpert-MTB/RIF) (2020) or Xpert-Ultra (2021). The agreement of the individual and pooled samples was compared and the reasons for discrepant results and potential cartridge savings were assessed. Each survey included 436 participants, which were tested in 109 pools. In the Xpert-MTB/RIF survey, 25 (sensitivity 89%, 95% CI 72.8% to 96.3%) of 28 pools containing MTB-positive samples tested positive and 81 pools containing only MTB-negative samples tested negative (specificity 100%, 95% CI 95.5% to 100%). In the Xpert-Ultra survey, all 32 (sensitivity 100%, 95% CI 89.3% to 100%) pools containing MTB-positive samples tested positive and all 77 (specificity 100%, 95% CI 95.3% to 100%) containing only MTB-negative samples tested negative. Pooling with Xpert-MTB/RIF and Xpert-Ultra saved 52% and 46% (227/436 and 199/436, respectively) of cartridge costs alone. Testing single and pooled specimens had a high level of agreement, with complete concordance when using Xpert-Ultra. Pooling samples could generate significant cartridge savings during ACF campaigns.

I n pursuit of Sustainable Development Goal 3 “Ensure healthy lives and promote well-being for all at all ages,” considerable global effort is directed toward elimination of infectious diseases in general and Neglected Tropical Diseases in particular. For various such diseases, the deployment of mobile screening teams forms an important instrument to reduce prevalence toward elimination targets. There is considerable variety in planning methods for the deployment of these mobile teams in practice, but little understanding of their effectiveness. Moreover, there appears to be little understanding of the relationship between the number of mobile teams and progress toward the goals. This research considers capacity planning and deployment of mobile screening teams for one such neglected tropical disease: Human African trypanosomiasis (HAT, or sleeping sickness). We prove that the deployment problem is strongly NP-Hard and propose three approaches to find (near) optimal screening plans. For the purpose of practical implementation in remote rural areas, we also develop four simple policies. The performance of these methods and their robustness is benchmarked for a HAT region in the Democratic Republic of Congo (DRC). Two of the four simple practical policies yield near optimal solutions, one of which also appears robust against parameter impreciseness. We also present a simple approximation of prevalence as a function of screening capacity, which appears rather accurate for the case study. While the results may serve to more effectively allocate funding and deploy mobile screening capacity, they also indicate that mobile screening may not suffice to achieve HAT elimination

ObjectiveThe effectiveness of household contact investigations is limited by low referral uptake for clinic-based TB testing by symptomatic household contacts. We qualitatively investigated the acceptability and perceived benefits of home-based TB testing using a portable GeneXpert-I instrument (GX-I) in an urban South African township.MethodsIn-depth interviews were conducted with household contacts tested and those that observed testing. Semi-structured interviews explored household contact's understanding of TB, perceptions of the GX-I device and testing procedures, confidentiality, willingness to refer others, and views on home- vs. clinic-based testing. Focus group discussions with home-based TB testing implementing staff assessed operational considerations for scale-up. Data were analysed using a constant comparison approach to qualitatively evaluate the acceptability and feasibility of home-based TB testing.ResultsThirty in-depth interviews and two focus group discussions were conducted. Observing one's own sputum being tested resulted in an emergent trust in home-based TB testing, the GX-I device and one's test results. Home-based TB testing was considered convenient, helped to overcome apathy towards testing and mitigated barriers to clinic-based testing. Perceptions that home-based TB testing contributes to improved household and community health resulted in an emergent theme of alleviation of health insecurities. Operational concerns regarding inadvertent disclosure of one's diagnosis to household members and time spent in people's homes were identified.ConclusionsHome-based TB testing was acceptable and feasible. Individuals expressed belief in the machine by being able to witness the testing process. Though most themes mirrored qualitative studies of home-based HIV testing, the alleviation of health insecurities theme is unique to home-based TB testing. Future research must evaluate the impact of home-based TB testing on case finding yield, time-to-trea

Diabetes Mellitus (DM) is a non-communicable disease that contributes to the cause of death. Based on the analysis of the situation in Kawengen Village, Semarang Regency, there were several problems related to the incidence of DM, including the Non-Communicable Disease Integrated Guidance Post Program (Posbindu PTM), which was not running optimally. Based on these problems, it is necessary to form a movement called the Anti-Diabetes Mellitus Community Alert Movement (SIMANIS). Active case finding and detection of pre-DM cases aim to capture people who already have pre-DM symptoms, but they do not know. Furthermore, if caught, they can be followed up so that they are willing to go to the health service unit before complications occur. The implementation of this community service activity is carried out in four stages, namely the formation of SIMANIS cadres, education on prevention and control of DM to SIMANIS cadres and the community, ToT on how to fill in and use the SIDIA Card (pre-diabetes screening) to SIMANIS cadres, and use of the SIDIA Card for early detection active case finding pre-DM. There was an increase in the pre-post education knowledge score from 7.59 + 1.5 to 8.93 + 0.9 and an increase in the pre-post education attitude score from 7.96 + 1.22 to 9.07 + 0.78. SIMANIS through the use of the SIDIA Card can be used to increase public awareness in prevention, early detection, and case finding of DM.

Background: Chest x-ray is central in screening and diagnosis of tuberculosis. However, sputum culture remains gold standard for diagnosis. Aim: To establish the rate of normal chest x-rays in tuberculosis patients found by spot sputum culture screening, and compare them to a group identified through passive case finding. Method: Chest x-rays from 39 culture-positive patients, identified by spot sputum culture screening in Copenhagen from 2012 to 2014, were included in the study (spot sputum culture group(SSC)). 39 normal chest x-rays from persons screened by mobile x-ray, and 39 chest x-rays from tuberculosis-patients identified through passive case finding(PCF) were anonymised and randomised. Two respiratory physicians and two radiologists assessed the chest x-rays. Results: The normal chest x-ray rate was higher in the non-tuberculosis control group (median = 32 (82.1%), range = 74.4% – 100%), compared to the SSC group (median = 7 (17.9%), range = 10.3% – 33.3%), and the PCF controls (median = 3(7.7%), range = 2.6% – 15.4%). In the SSC group 14 (35.9%) were categorized as normal by at least one study participant. Conclusion: A substantial minority of patients diagnosed with tuberculosis by spot sputum culture screening, and through passive case finding would not have been identified with chest x-ray alone, highlighting that a normal chest x-ray does not exclude pulmonary tuberculosis.

Tuberculosis (TB) and human immunodeficiency Virus (HIV) are considered as major global health concerns. According to the World Health Organization (WHO), TB and HIV are the two infectious diseases causing more deaths worldwide. In 2017 10.0 and 1.8 million people were newly infected by TB and HIV respectively. In the same year 2.1 million people died from these diseases worldwide. In particular, Mozambique is one of the world's regions more hardly affected by these epidemics, with 163,000 new TB cases and 150,000 new HIV infections in 2017. Interdependence between both diseases is high, with 40% of the people living with TB in Mozambique also being HIV positive. One of the major challenges in these regions remains as the low-case detection rates for both pathogens. Active case finding (ACF) strategies have often been used to reduce the number of undetected people living in the community. However, these strategies often fail in their capacity to effectively deploy their interventions in an integrated and cost-effective manner. Innovative strategies are needed to identify these diseases early in the community and improve outcomes of people living with HIV (PLHIV) and TB in sub-Saharan Africa. In 2018 a TB ACF study was implemented in the Manhiça district, Mozambique (population ~180,000). Through this intervention community health workers reached all household and community contacts of every new TB case reported in any of the health centres of the district. Participants were tested for HIV and for TB (Xpert® MTB/RIF Ultra in induced sputum). Participants newly detected with TB were referred to the National Tuberculosis Control Program for clinical evaluation and timely TB treatment initiation. All PLHIV identified to be on treatment received a nonadherence questionnaire, those who reported poor antiretroviral therapy (ART)-adherence or who were ART-naïve were invited to be referred to the Manhiça District Hospital to receive screening of advanced HIV disease (AHD). P

Tuberculosis (TB) remains a major global health problem. The World Health Organization (WHO) has set ambitious targets to eliminate TB by 2035. To achieve this, dramatic reductions in TB incidence must be achieved worldwide. Strategies to achieve these targets include the early detection and treatment of all patients with TB, and preventative treatment to reduce the burden of infection sustaining this epidemic. Intensified research and innovation to develop new methods and approaches are crucial to achieve these elimination targets.The research in this thesis encompasses novel strategies that directly align with the plan for TB elimination set by the WHO. The two main themes of this research revolve around active case finding for TB and diagnostic and prognostic biomarkers for TB infection and disease.The research setting is a large cluster randomised controlled trial (RCT) of community-wide active case finding for TB in an endemic region – Ca Mau Province, Vietnam. This study uses a simple automated polymerase chain reaction test, Xpert MTB/RIF, performed on spontaneously expectorated sputum as the primary screening tool. This test has been endorsed by the WHO and is in widespread use as a diagnostic tool in symptomatic individuals in many TB endemic countries. However, it’s use as a screening tool in the community is novel. As part of the research in this thesis, I assessed the performance of Xpert in the setting of community-wide active case finding. Due to the large number of Xpert tests performed, I was able to precisely estimate the positive predictive value and specificity of this test, and to show that both these are substantially higher than previously estimated (in a Cochrane review and by WHO).I also explore novel strategies to improve the feasibility and cost effectiveness of large scale sputum testing in the setting of TB screening. These strategies are: using sputum quality as a predictor of the presence or absence of Mycobacterium tuberculosis in sput

SETTING: The objective of tuberculosis (TB) screening in low-incidence countries is to identify TB patients earlier, ideally to improve health outcomes and reduce Mycobacterium tuberculosis transmission. In this retrospective study, we compare hospitalisation (morbidity) and smear positivity rates (infectiousness) in TB patients identified through active case finding (ACF) with patients identified through passive case finding (PCF). METHODS : ACF patients were identified by screening socially marginalised persons or through contact investigation. Logistic regression was used to model the associations between case-finding group (ACF/PCF) and hospitalisation, and between case-finding group and smear positivity rates. RESULT S : A total of 108 patients were identified through ACF and 332 through PCF. Thirty (27.8%) ACF patients and 153 (46.1%) PCF patients were hospitalised. In the adjusted models, ACF patients (OR 0.24, P < 0.001) and ACF subgroups identified using mobile X-ray screening, spot sputum culture screening and contact investigation were significantly less likely to be hospitalised than PCF patients. Thirty-one (34.4%) ACF patients and 127 (50.4%) PCF patients were smearpositive. ACF patients (OR 0.30, P < 0.001) and ACF subgroups identified through contact investigation and spot sputum culture screening were less likely to be smear-positive than PCF patients. CONCLUS IONS : These findings suggest that ACF reduces morbidity and infectiousness among TB patients, thereby potentially improving health outcomes and reducing transmission of M. tuberculosis.

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.