A Comparative Study of the Interactions of Two Calcium Phosphates, PEO/PBT Copolymer (Polyactive) and a Silicone Rubber with Bone and Fibrous Tissue

In this study, hydroxyapatite, tetracalcium phosphate, HPEO/PBT 55145 copolymer, PEO/PBT 55!45 copolymer (Polyactive) and silicone rubber were implanted as dense blocks, subcutaneously and. into the tibia of rats. Biocompatibility and degradation were investigated but most attention was directed to .the bone/biomaterial interactions. None of the materials showed any significant adverse tissue reactions. With exception of the silicone rubber, all materials sho~ed bone bonding phenomena based on both morphological and mechanical evaluations. (H)PEO/PBT 55145 copolymer is the first polymer reported to be bonded by bone and thus widens the spectrum of bone bonding materials with a low modulus, degradable, elastomer in contrast to the high modulus glasses and ceramics that are available to date. The possible associated bone-bonding mechanism is briefly discussed

The frequencies of IFNγ+IL2+TNFα+ PPD-specific CD4+CD45RO+ T-cells correlate with the magnitude of the QuantiFERON® gold in-tube response in a prospective study of healthy Indian adolescents

Background: QuantiFERON-TB Gold In-Tube (QFT) is an IFNγ-release assay used in the diagnosis of Mycobacterium tuberculosis (MTB) infection. The risk of TB progression increases with the magnitude of the MTB-specific IFNγ-response. QFT reversion, also associated with low Tuberculin Skin Test responses, may therefore represent a transient immune response with control of M. tuberculosis infection. However, studies at the single cell level have suggested that the quality (polyfunctionality) of the T-cell response is more important than the quantity of cytokines produced. Objective: To explore the quality and/or magnitude of mycobacteria-specific T-cell responses associated with QFT reversion and persistent QFT-positivity. Methods: Multi-color flowcytometry on prospectively collected peripheral blood mononuclear cells was applied to assess mycobacteria-specific T-cell responses in 42 QFT positive Indian adolescents of whom 21 became QFT negative (reverters) within one year. Ten QFT consistent negatives were also included as controls. Results: There was no difference in the qualitative PPD-specific CD4+ T-cell response between QFT consistent positives and reverters. However, compared with QFT consistent positives, reverters displayed lower absolute frequencies of polyfunctional (IFNγ+IL2+TNFα+) CD4+ T-cells at baseline, which were further reduced to the point where they were not different to QFT negative controls one year later. Moreover, absolute frequencies of these cells correlated well with the magnitude of the QFT-response. Conclusion: Whereas specific polyfunctional CD4+ T-cells have been suggested to protect against TB progression, our data do not support that higher relative or absolute frequencies of PPD-specific polyfunctional CD4+ T-cells in peripheral blood can explain the reduced risk of TB progression observed in QFT reverters. On the contrary, absolute frequencies of these cells correlated with the QFT-response, suggesting that this readout reflects antigenic load

Challenges in recruiting children to a multidrug-resistant TB prevention trial

BACKGROUND: Recruitment to randomised clinical trials can be challenging and slow recruitment has serious consequences. This study aimed to summarise and reflect on the challenges in enrolling young children to a multidrug-resistant TB (MDR-TB) prevention trial in South Africa. METHODS: Recruitment to the Tuberculosis Child Multidrug-resistant Preventive Therapy Trial (TB-CHAMP) was tracked using an electronic recruiting platform, which was used to generate a recruiting flow diagram. Structured personnel questionnaires, meeting minutes and workshop notes were thematically analysed to elucidate barriers and solutions. RESULT: Of 3,682 (85.3%) adult rifampicin (RIF) resistant index cases with pre-screening outcomes, 1597 (43.4%) reported having no children under 5 years in the household and 562 (15.3%) were RIF-monoresistant. More than nine index cases were pre-screened for each child enrolled. Numerous barriers to recruitment were identified. Thorough recruitment planning, customised tracking data systems, a dedicated recruiting team with strong leadership, adequate resources to recruit across large geographic areas, and excellent relationships with routine TB services emerged as key factors to ensure successful recruitment. CONCLUSION: Recruitment of children into MDR-TB prevention trials can be difficult. Several MDR-TB prevention trials are underway, and lessons learnt from TB-CHAMP will be relevant to these and other TB prevention studies

Routine programmatic delivery of isoniazid preventive therapy to children in Cape Town, South Africa

Setting: Fourteen primary health care facilities in Cape Town, South Africa. Objective: To determine the proportion and characteristics of infectious adult tuberculosis (TB) cases that identify children aged <5 years who qualify for isoniazid preventive therapy (IPT), and to determine the proportion of children who initiate and complete IPT. Design: A retrospective clinical record review conducted as a stratified cluster survey. Results: Of 1179 records of infectious adult cases, 33.3% had no documentation of contacts. Of the remaining 786 records, 525 contacts aged <5 years were identified, representing 0.7 child contacts per infectious adult case. Older age, male, human immunodeficiency virus (HIV) positive, smear-negative and retreatment TB cases were all associated with no documentation of contacts. Of the 525 child contacts identified, less than half were screened for TB, 141 initiated IPT and 19 completed it. Conclusion: Less than 67% of infectious TB case records had documentation of contacts. Younger, female, HIVnegative and new smear-positive TB cases were more likely to have had contacts identified. Less than 14% of children already initiated on IPT completed 6 months of treatment

High prevalence of childhood multi-drug resistant tuberculosis in Johannesburg, South Africa: a cross sectional study

<p>Abstract</p> <p>Background</p> <p>There are limited data on the prevalence of multi-drug resistant tuberculosis (MDR-TB), estimated at 0.6-6.7%, in African children with tuberculosis. We undertook a retrospective analysis of the prevalence of MDR-TB in children with <it>Mycobacterium tuberculosis </it>(MTB) at two hospitals in Johannesburg, South Africa.</p> <p>Methods</p> <p>Culture-confirmed cases of MTB in children under 14 years, attending two academic hospitals in Johannesburg, South Africa during 2008 were identified and hospital records of children diagnosed with drug-resistant TB were reviewed, including clinical and radiological outcomes at 6 and 12 months post-diagnosis. Culture of <it>Mycobacterium tuberculosis </it>complex (MTB) was performed using the automated liquid broth MGIT™ 960 method. Drug susceptibility testing (DST) was performed using the MGIT™ 960 method for both first and second-line anti-TB drugs.</p> <p>Results</p> <p>1317 children were treated for tuberculosis in 2008 between the two hospitals where the study was conducted. Drug susceptibility testing was undertaken in 148 (72.5%) of the 204 children who had culture-confirmed tuberculosis. The prevalence of isoniazid-resistance was 14.2% (n = 21) (95%CI, 9.0-20.9%) and the prevalence of MDR-TB 8.8% (n = 13) (95%CI, 4.8-14.6%). The prevalence of HIV co-infection was 52.1% in children with drug susceptible-TB and 53.9% in children with MDR-TB. Ten (76.9%) of the 13 children with MDR-TB received appropriate treatment and four (30.8%) died at a median of 2.8 months (range 0.1-4.0 months) after the date of tuberculosis investigation.</p> <p>Conclusions</p> <p>There is a high prevalence of drug-resistant tuberculosis in children in Johannesburg in a setting with a high prevalence of HIV co-infection, although no association between HIV infection and MDR-TB was found in this study. Routine HIV and drug-susceptibility testing is warranted to optimize the management of childhood tuberculosis in settings such as ours.</p

TB programme stakeholder views on lessons from the COVID-19 response in South Africa

BACKGROUND: The global COVID-19 pandemic has reversed many of the hard-won gains made in TB programmes and the associated reduction in the number of TB deaths, case notifications and incidence over the last three decades. Modelling estimates show that the impact will be lasting. There are global calls to recover the shortfalls along the TB care cascade that have resulted from COVID-19, with the recognition that the COVID-19 response holds lessons to inform more robust and comprehensive TB programmes and services. OBJECTIVE: To explore lessons from response measures to the COVID-19 pandemic in two high TB burden South African provinces. DESIGN: This was an exploratory qualitative study. We conducted interviews with TB programme stakeholders (managers and facility-level staff: n = 35) between February and June 2022. RESULTS: We identified eight facilitators of the COVID-19 response, including political will, rapid policy development, multi-sectoral collaboration, patient-centred models of care delivery, community engagement, mHealth and telehealth technologies, rigorous contact tracing and widespread mask wearing. Political will was singled out as a critical driver of the response. CONCLUSION: Leveraging COVID-19 inspired collaborations, technologies and avenues for health service delivery is an opportunity to maximise benefits for the TB programme. Reinvestment in national TB programmes and political prioritisation of TB are critical

Closing the reporting gap for childhood tuberculosis in South Africa : improving hospital referrals and linkages

CITATION: Du Preez, K., et al. 2020. Closing the reporting gap for childhood tuberculosis in South Africa : improving hospital referrals and linkages. Public Health Action, 10(1):38-46. doi:10.5588/pha.19.0053.The original publication is available at https://theunion.org/our-work/journals/public-health-actionSetting: A referral hospital in Cape Town, Western Cape Province, Republic of South Africa. Objective: To measure the impact of a hospital-based referral service (intervention) to reduce initial loss to follow-up among children with tuberculosis (TB) and ensure the completeness of routine TB surveillance data. Design: A dedicated TB referral service was established in the paediatric wards at Tygerberg Hospital, Cape Town, in 2012. Allocated personnel provided TB education and counselling, TB referral support and weekly telephonic follow-up after hospital discharge. All children identified with TB were matched to electronic TB treatment registers (ETR.Net/EDRWeb). Multivariable logistic regression was used to compare reporting of culture-confirmed and drug-susceptible TB cases before (2007–2009) and during (2012) the intervention. Results: Successful referral with linkage to care was confirmed in 267/272 (98%) and successful reporting in 227/272 (84%) children. Children with drug-susceptible, culture-confirmed TB were significantly more likely to be reported during the intervention period than in the pre-intervention period (OR 2.52, 95%CI 1.33–4.77). The intervention effect remained consistent in multivariable analysis (adjusted OR 2.62; 95%CI 1.31–5.25) after adjusting for age, sex, human immunodeficiency virus status and the presence of TB meningitis. Conclusions: A simple hospital-based TB referral service can reduce initial loss to follow-up and improve recording and reporting of childhood TB in settings with decentralised TB services.https://www.ingentaconnect.com/content/iuatld/pha/2020/00000010/00000001/art00010Publisher's versio

Prophylactic Effect of a Therapeutic Vaccine against TB Based on Fragments of Mycobacterium tuberculosis

The prophylactic capacity of the RUTI® vaccine, based on fragmented cells of Mycobacterium tuberculosis, has been evaluated in respect to aerosol challenge with virulent bacilli. Subcutaneous vaccination significantly reduced viable bacterial counts in both lungs and spleens of C57Bl mice, when challenged 4 weeks after vaccination. RUTI® protected the spleen less than BCG. Following a 9 month vaccination-challenge interval, protection was observed for the lungs, but not for the spleen. Survival of infected guinea pigs was prolonged by vaccination given 5 weeks before challenge. Inoculations of RUTI® shortly after infection significantly reduced the viable bacterial counts in the lungs, when compared with infected control mice. Thus, vaccination by RUTI® has potential for both the prophylaxis and immunotherapy of tuberculosis

Bacille Calmette-Guerin (BCG) vaccine and the COVID-19 pandemic : responsible stewardship is needed

CITATION: Schaaf, H. S. et al. 2020. Bacille Calmette-Guerin (BCG) vaccine and the COVID-19 pandemic : responsible stewardship is needed. International Journal of Tuberculosis and Lung Disease, 4(7):732-734, doi:10.5588/ijtld.20.0267.The original publication is available at https://www.theunion.org/what-we-do/journals/ijtldWe believe that responsible stewardship of the bacille Calmette-Guérin (BCG) vaccine in the context of the COVID-19 epidemic is urgently needed. Live attenuated BCG is currently the only licensed vaccine to protect against tuberculosis (TB). Neonatal BCG vaccination has proven efficacy in protecting infants and young children against life-threatening disseminated forms of TB, including TB meningitis and miliary TB.Post-prin