How much is tuberculosis screening worth? Estimating the value of active case finding for tuberculosis in South Africa, China, and India

BACKGROUND: Current approaches are unlikely to achieve the aggressive global tuberculosis (TB) control targets set for 2035 and beyond. Active case finding (ACF) may be an important tool for augmenting existing strategies, but the cost-effectiveness of ACF remains uncertain. Program evaluators can often measure the cost of ACF per TB case detected, but how this accessible measure translates into traditional metrics of cost-effectiveness, such as the cost per disability-adjusted life year (DALY), remains unclear. METHODS: We constructed dynamic models of TB in India, China, and South Africa to explore the medium-term impact and cost-effectiveness of generic ACF activities, conceptualized separately as discrete (2-year) campaigns and as continuous activities integrated into ongoing TB control programs. Our primary outcome was the cost per DALY, measured in relationship to the cost per TB case actively detected and started on treatment. RESULTS: Discrete campaigns costing up to $1,200 (95$3,800 (95% UR 2,706–6,392) in China, and $9,400 (95$1,000 to detect and initiate treatment for each extra case of active TB. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12916-014-0216-0) contains supplementary material, which is available to authorized users

Reply to “At the crossroads between early or delayed antiretroviral therapy initiation during TB/HIV coinfection”

La digitalització dels textos, iniciada en la dècada dels setanta, ha originat sistemes i productes diversos que poden ser molt útils en la investigació literària. Un dels més coneguts, lâhipertext, és un bon exemple de les possibilitats de la lectura no seqüencial que caracteritza les obres de referència o determinades recerques en lâàmbit de la filologia, com ara lâedició de textos. La digitalització destaca les característiques tant hipertextuals com intertextuals de la literatura i ajuda a entendre, així, alguns dels seus trets constitutius. Dâaltra banda, la publicació en línia de textos de molt difícil abast proposada per comunitats científiques molt presents a Internet és una oferta plena de possibilitats i suggereix un camí a seguir per comunitats encara poc implantades, com ara la filologia catalana. | Digitisation of text, begun in the 1970s, has produced a diversity of systems and products that could be very useful for literary research. One of the better known examples, hypertext, demonstrates the potential for non-sequential reading that characterises the use made of reference works or specific searches performed in the field of philology, such as for text publishing. Digitisation highlights both | La digitalización de textos, iniciada en la década de los años setenta, ha dado lugar a sistemas y productos diversos que pueden ser muy útiles en la investigación literaria. Uno de los más conocidos, el hipertexto, constituye un buen ejemplo de las posibilidades de la lectura secuencial que caracteriza las obras de referencia o determinadas investigaciones en el ámbito de la Filología, como, por ejemplo, la edición de textos. La digitalización destaca las características tanto hipertextuales como intertextuales de la literatura facilitando, por tanto, su comprensión. Por otro lado, la publicación en línea de textos de muy difícil acceso, propuesta por comunidades científicas muy presentes en Internet, es una oferta llena de posibilidades y abre un camino a seguir por parte de comunidades poco implantadas todavía como es el caso de la Filología catalana

Tobacco Smoking and Tuberculosis Treatment Outcomes: A Prospective Cohort Study in Georgia

Objective To assess the effect of tobacco smoking on the outcome of tuberculosis treatment in Tbilisi, Georgia. Methods We conducted a prospective cohort study of adults with laboratory-confirmed tuberculosis from May 2011 to November 2013. History of tobacco smoking was collected using a standardized questionnaire adapted from the global adult tobacco survey. We considered tuberculosis therapy to have a poor outcome if participants defaulted, failed treatment or died. We used multivariable regressions to estimate the risk of a poor treatment outcome. Findings Of the 591 tuberculosis patients enrolled, 188 (31.8%) were past smokers and 271 (45.9%) were current smokers. Ninety (33.2%) of the current smokers and 24 (18.2%) of the participants who had never smoked had previously been treated for tuberculosis (P \u3c 0.01). Treatment outcome data were available for 524 of the participants, of whom 128 (24.4%) – including 80 (32.9%) of the 243 current smokers and 21 (17.2%) of the 122 individuals who had never smoked – had a poor treatment outcome. Compared with those who had never smoked, current smokers had an increased risk of poor treatment outcome (adjusted relative risk, aRR: 1.70; 95% confidence interval, CI: 1.00–2.90). Those who had ceased smoking more than two months before enrolment did not have such an increased risk (aRR: 1.01; 95% CI: 0.51–1.99). Conclusion There is a high prevalence of smoking among patients with tuberculosis in Georgia and smoking increases the risk of a poor treatment outcome

Adherence to isoniazid prophylaxis among HIV-infected children: a randomized controlled trial comparing two dosing schedules

<p>Abstract</p> <p>Background</p> <p>Tuberculosis contributes significantly to morbidity and mortality among HIV-infected children in sub-Saharan Africa. Isoniazid prophylaxis can reduce tuberculosis incidence in this population. However, for the treatment to be effective, adherence to the medication must be optimized. We investigated adherence to isoniazid prophylaxis administered daily, compared to three times a week, and predictors of adherence amongst HIV-infected children.</p> <p>Methods</p> <p>We investigated adherence to study medication in a two centre, randomized trial comparing daily to three times a week dosing of isoniazid. The study was conducted at two tertiary paediatric care centres in Cape Town, South Africa. Over a 5 year period, we followed 324 HIV-infected children aged ≥ 8 weeks. Adherence information based on pill counts was available for 276 children. Percentage adherence was calculated by counting the number of pills returned. Adherence ≥ 90% was considered to be optimal. Analysis was done using summary and repeated measures, comparing adherence to the two dosing schedules. Mean percentage adherence (per child during follow-up time) was used to compare the mean of each group as well as the proportion of children achieving an adherence of ≥ 90% in each group. For repeated measures, percentage adherence (per child per visit) was dichotomized at 90%. A logistic regression model with generalized estimating equations, to account for within-individual correlation, was used to evaluate the impact of the dosing schedule. Adjustments were made for potential confounders and we assessed potential baseline and time-varying adherence determinants.</p> <p>Results</p> <p>The overall adherence to isoniazid was excellent, with a mean adherence of 94.7% (95% confidence interval [CI] 93.5-95.9); similar mean adherence was achieved by the group taking daily medication (93.8%; 95% CI 92.1-95.6) and by the three times a week group (95.5%; 95% CI 93.8-97.2). Two-hundred and seventeen (78.6%) children achieved a mean adherence of ≥ 90%. Adherence was similar for daily and three times a week dosing schedules in univariate (odds ratio [OR] 0.88; 95% CI 0.66-1.17; <it>P </it>= 0.38) and multivariate (adjusted OR 0.85; 95% CI 0.64-1.11; <it>P </it>= 0.23) models. Children from overcrowded homes were less adherent (adjusted OR 0.71; 95% CI 0.54-0.95; <it>P </it>= 0.02). Age at study visit was predictive of adherence, with better adherence achieved in children older than 4 years (adjusted OR 1.96; 95% CI 1.16-3.32; <it>P </it>= 0.01).</p> <p>Conclusion</p> <p>Adherence to isoniazid was excellent regardless of the dosing schedule used. Intermittent dosing of isoniazid prophylaxis can be considered as an alternative to daily dosing, without compromising adherence or efficacy.</p> <p>Trial registration</p> <p>Clinical Trials NCT00330304</p

The Impact of Expanded Testing for Multidrug Resistant Tuberculosis Using Geontype MTBDRplus in South Africa: An Observational Cohort Study

Globally, multidrug resistant tuberculosis (MDR-TB) remains underdiagnosed. The Genotype MTBDRplus®, a rapid drug susceptibility testing (DST) assay used to detect resistance to isoniazid and rifampicin in the diagnosis of MDR-TB, has good diagnostic accuracy, but its impact on patient outcomes in routine practice is unproven. We assessed the clinical impact of routine DST using MTBDRplus in a single health district in South Africa

Prevalence and risk factors for latent tuberculosis infection among household contacts of index cases in two South African provinces: Analysis of baseline data from a cluster-randomised trial.

INTRODUCTION: Household contacts of patients with active pulmonary tuberculosis (TB) often have latent TB infection, and are at risk of progression to disease. We set out to investigate whether index TB case HIV status was linked to a higher probability of latent TB infection among household contacts. MATERIALS AND METHODS: Data were collected prospectively from participants in the intervention arm of a household cluster-randomised trial in two South Africa provinces (Mangaung, Free State, and Capricorn, Limpopo). In intervention group households, TB contacts underwent HIV testing and tuberculin skin testing (TST). TST induration was estimated at two cut-offs (≥5mm, ≥10mm). Multilevel Bayesian regression models estimated posterior distributions of the percentage of household contacts with TST induration ≥5mm and ≥10mm by age group, and compared the odds of latent TB infection by key risk factors including HIV status index case age and study province. RESULTS: A total of 2,985 household contacts of 924 index cases were assessed, with most 2,725 (91.3%) undergoing TST. HIV prevalence in household contacts was 14% and 10% in Mangaung and Capricorn respectively. Overall, 16.8% (458/2,725) had TST induration of ≥5mm and 13.1% (359/2,725) ≥10mm. In Mangaung, children aged 0-4 years had a high TST positivity prevalence compared to their peers in Capricorn (22.0% vs. 7.6%, and 20.5% vs. 2.3%, using TST thresholds of ≥5mm and ≥10mm respectively). Compared to contacts from Capricorn, household contacts living in Mangaung were more likely to have TST induration ≥5mm (odds ratio [OR]: 3.08, 95% credibility interval [CI]: 2.13-4.58) and ≥10mm (OR: 4.52, 95% CI: 3.03-6.97). There was a 90% and 92% posterior probability that the odds of TST induration ≥5mm (OR: 0.79, 95% CI: 0.56-1.14) and ≥10mm (OR: 0.77, 95% CI: 0.53-1.10) respectively were lower in household contacts of HIV-positive compared to HIV-negative index cases. CONCLUSIONS: High TST induration positivity, especially among young children and people living in Mangaung indicates considerable TB transmission despite high antiretroviral therapy coverage. Household contact of HIV-positive index TB cases were less likely to have evidence of latent TB infection than contacts of HIV-negative index cases

Loop Evolution Observed with AIA and Hi-C

In the past decade, the evolution of EUV loops has been used to infer the loop substructure. With the recent launch of High Resolution Coronal Imager (Hi-C), this inference can be validated. In this presentation we discuss the first results of loop analysis comparing AIA and Hi-C data. In the past decade, the evolution of EUV loops has been used to infer the loop substructure. With the recent launch of High Resolution Coronal Imager (Hi-C), this inference can be validated. In this presentation we discuss the first results of loop analysis comparing AIA and Hi-C data

Nonlinear intensity dependence of ratchet currents induced by terahertz laser radiation in bilayer graphene with asymmetric periodic grating gates

We report on the observation of a nonlinear intensity dependence of the terahertz radiation induced ratchet effects in bilayer graphene with asymmetric dual grating gate lateral lattices. These nonlinear ratchet currents are studied in structures of two designs with dual grating gate fabricated on top of encapsulated bilayer graphene and beneath it. The strength and sign of the photocurrent can be controllably varied by changing the bias voltages applied to individual dual grating subgates and the back gate. The current consists of contributions insensitive to the radiation's polarization state, defined by the orientation of the radiation electric field vector with respect to the dual grating gate metal stripes, and the circular ratchet sensitive to the radiation helicity. We show that intense terahertz radiation results in a nonlinear intensity dependence caused by electron gas heating. At room temperature the ratchet current saturates at high intensities of the order of hundreds to several hundreds of kWcm$^{-2}$. At $T = 4 {\rm K}$, the nonlinearity manifests itself at intensities that are one or two orders of magnitude lower, moreover, the photoresponse exhibits a complex dependence on the intensity, including a saturation and even a change of sign with increasing intensity. This complexity is attributed to the interplay of the Seebeck ratchet and the dynamic carrier density redistribution, which feature different intensity dependencies and a nonlinear behavior of the sample's conductivity induced by electron gas heating. Our study demonstrates that graphene-based asymmetric dual grating gate devices can be used as terahertz detectors at room temperature over a wide dynamic range, spanning many orders of magnitude of terahertz radiation power. Therefore, their integration together with current-driven read-out electronics is attractive for the operation with high-power pulsed sources.Comment: 11 pages, 13 figure

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

This work was made possible through grants provided by the WHO Global TB Programme. RMB, ELC, and PM hold Wellcome fellowships: 203905/Z/16/Z (RMB), 200901/Z/16/Z (ELC), and 206575/Z/17/Z (PM). MR, LT, and HA are funded by part of the European and Developing Countries Clinical Trials Partnership 2 programme supported by the EU (grant number RIA2016S-1632-TREATS). AES is supported by a National Institutes of Health (NIH) grant K23AI140918.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. Methods We 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.Peer reviewe

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

Funding: This work was made possible through grants provided by the WHO Global TB Programme. RMB, ELC, and PM hold Wellcome fellowships: 203905/Z/16/Z (RMB), 200901/Z/16/Z (ELC), and 206575/Z/17/Z (PM). MR, LT, and HA are funded by part of the European and Developing Countries Clinical Trials Partnership 2 programme supported by the EU (grant number RIA2016S-1632-TREATS). AES is supported by a National Institutes of Health (NIH) grant K23AI140918. WHO facilitated discussions among authors at the design stage and contributed to this manuscript but had no role in the conduct or writing of the WHO 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.Peer reviewe