Desmond Tutu TB Centre (Tygerberg)

Has universal screening with Xpert® MTB/RIF increased the proportion of multidrugresistant tuberculosis cases diagnosed in a routine operational setting?

2017-03-15T10:00:38Z

Has universal screening with Xpert® MTB/RIF increased the proportion of multidrugresistant tuberculosis cases diagnosed in a routine operational setting? Naidoo, Pren; Dunbar, Rory; Caldwell, Judy; Lombard, Carl; Beyers, Nulda Setting: Primary health services in Cape Town, South Africa where the introduction of Xpert® MTB/RIF (Xpert) enabled simultaneous screening for tuberculosis (TB) and drug susceptibility in all presumptive cases. Study aim: To compare the proportion of TB cases with drug susceptibility tests undertaken and multidrug-resistant tuberculosis (MDR-TB) diagnosed pre-treatment and during the course of 1st line treatment in the previous smear/culture and the newly introduced Xpert-based algorithms. Methods: TB cases identified in a previous stepped-wedge study of TB yield in five sub-districts over seven one-month time-points prior to, during and after the introduction of the Xpert-based algorithm were analysed. We used a combination of patient identifiers to identify all drug susceptibility tests undertaken from electronic laboratory records. Differences in the proportions of DST undertaken and MDR-TB cases diagnosed between algorithms were estimated using a binomial regression model. Results: Pre-treatment, the probability of having a DST undertaken (RR = 1.82)(p<0.001) and being diagnosed with MDR-TB (RR = 1.42)(p<0.001) was higher in the Xpert-based algorithm than in the smear/culture-based algorithm. For cases evaluated during the course of 1st-line TB treatment, there was no significant difference in the proportion with DST undertaken (RR = 1.02)(p = 0.848) or MDR-TB diagnosed (RR = 1.12)(p = 0.678) between algorithms. Conclusion: Universal screening for drug susceptibility in all presumptive TB cases in the Xpert-based algorithm resulted in a higher overall proportion of MDR-TB cases being diagnosed and is an important strategy in reducing transmission. The previous strategy of only screening new TB cases when 1st line treatment failed did not compensate for cases missed pre-treatment. CITATION: Naidoo, P. et al. 2017. Has universal screening with Xpert® MTB/RIF increased the proportion of multidrugresistant tuberculosis cases diagnosed in a routine operational setting? PLoS ONE, E 12(2):e0172143, doi:10.1371/journal.pone.0172143.; The original publication is available at http://journals.plos.org/plosone

Effect of non-tuberculous mycobacteria on host biomarkers potentially relevant for tuberculosis management

2016-03-10T10:36:04Z

Effect of non-tuberculous mycobacteria on host biomarkers potentially relevant for tuberculosis management Dhanasekaran, S.; Jenum, Synne; Stavrum, Ruth; Wiker, Harald G.; Kenneth, John; Vaz, Mario; Doherty, T. Mark; Grewal, Harleen M. S.; Hesseling, A. C. Background: Non-tuberculous mycobacteria (NTM) are different from Mycobacterium tuberculosis (MTB) both in their ubiquitous environmental distribution and in their reduced capacity to cause disease. While often neglected in favour of other infectious diseases, NTM may interfere with important aspects of TB control and management, namely the efficacy of new anti-tuberculosis (TB) vaccines; the immuno-diagnostic Tuberculin skin test (TST) and QuantiFERON TB Gold In Tube assay (QFTGIT); and immune biomarkers explored for their diagnostic and/or predictive potential. Our objective was therefore to explore host immune biomarkers in children who had NTM isolated from respiratory and/or gastric specimens. Methodology and Principle Findings: The present study was nested within a prospective cohort study of BCG-vaccinated neonates in Southern India. In this setting, immune biomarkers from peripheral blood were analyzed in 210 children aged , 3 years evaluated for TB using dual-colour-Reverse-Transcriptase-Multiple-Ligation-dependent-Probe-Amplification (dcRTMLPA) and Bio-Plex assays. The children were classified based on clinical examination, chest X-rays and mycobacterial culture reports as either: 1) TB disease, 2) NTM present and 3) controls. The study shows a down-regulation of RAB33A (p, 0.001) and up-regulation of TGFb1, IL-2 and IL-6 (all p,0.05) in children with TB disease, and that RAB33A, TGFBR2 and IL-10 (all p,0.05) were differentially expressed in children with NTM present when compared to children that were culture negative for MTB and NTM (controls). Conclusions and Significance: Carriage of NTM may reduce the specificity of future diagnostic and predictive immune biomarkers relevant to TB management. Please cite as follows: Dhanasekaran, S. et al. 2014. Effect of non-tuberculous mycobacteria on host biomarkers potentially relevant for tuberculosis management. PLoS Neglected Tropical Diseases, 8(10):e3243., doi:10.1371/journal.pntd.0003243.; The original publication is available at http://journals.plos.org/plosntds

HPTN 071 (PopART) : a cluster-randomized trial of the population impact of an HIV combination prevention intervention including universal testing and treatment : mathematical model

2016-03-09T09:18:54Z

HPTN 071 (PopART) : a cluster-randomized trial of the population impact of an HIV combination prevention intervention including universal testing and treatment : mathematical model Cori, Anne; Ayles, Helen; Beyers, Nulda; Schaap, Ab; Floyd, Sian; Sabapathy, Kalpana; Eaton, Jeffrey W.; Hauck, Katharina; Smith, Peter; Griffith, Sam; Moore, Ayana; Donnell, Deborah; Vermund, Sten H.; Fidler, Sarah; Hayes, Richard; Fraser, Christophe Background: The HPTN 052 trial confirmed that antiretroviral therapy (ART) can nearly eliminate HIV transmission from successfully treated HIV-infected individuals within couples. Here, we present the mathematical modeling used to inform the design and monitoring of a new trial aiming to test whether widespread provision of ART is feasible and can substantially reduce population-level HIV incidence. Methods and Findings: The HPTN 071 (PopART) trial is a three-arm cluster-randomized trial of 21 large population clusters in Zambia and South Africa, starting in 2013. A combination prevention package including home-based voluntary testing and counseling, and ART for HIV positive individuals, will be delivered in arms A and B, with ART offered universally in arm A and according to national guidelines in arm B. Arm C will be the control arm. The primary endpoint is the cumulative three-year HIV incidence. We developed a mathematical model of heterosexual HIV transmission, informed by recent data on HIV-1 natural history. We focused on realistically modeling the intervention package. Parameters were calibrated to data previously collected in these communities and national surveillance data. We predict that, if targets are reached, HIV incidence over three years will drop by >60% in arm A and >25% in arm B, relative to arm C. The considerable uncertainty in the predicted reduction in incidence justifies the need for a trial. The main drivers of this uncertainty are possible community-level behavioral changes associated with the intervention, uptake of testing and treatment, as well as ART retention and adherence. Conclusions: The HPTN 071 (PopART) trial intervention could reduce HIV population-level incidence by >60% over three years. This intervention could serve as a paradigm for national or supra-national implementation. Our analysis highlights the role mathematical modeling can play in trial development and monitoring, and more widely in evaluating the impact of treatment as prevention. Please cite as follows: Cori, A. et al. 2014. HPTN 071 (PopART) : a cluster-randomized trial of the population impact of an HIV combination prevention intervention including universal testing and treatment : mathematical model. PLoS ONE, 9(1):e84511, doi:10.1371/journal.pone.0084511.; The original publication is available at http://journals.plos.org/plosone

A comparison of multidrug-resistant tuberculosis treatment commencement times in MDRTBPlus line probe assay and XpertH MTB/RIF-based algorithms in a routine operational setting in Cape Town

2016-03-09T09:42:04Z

A comparison of multidrug-resistant tuberculosis treatment commencement times in MDRTBPlus line probe assay and XpertH MTB/RIF-based algorithms in a routine operational setting in Cape Town Naidoo, Pren; Du Toit, Elizabeth; Rory Dunbar, Rory; Lombard, Carl; Caldwell, Judy; Detjen, Anne; Squire, S. Bertel; Enarson, Donald A.; Beyers, Nulda Background: Xpert MTB/RIF was introduced as a screening test for all presumptive tuberculosis cases in primary health services in Cape Town, South Africa. Study Aim: To compare multidrug-resistant tuberculosis (MDR-TB) treatment commencement times in MDRTBPlus Line Probe Assay and Xpert MTB/RIF-based algorithms in a routine operational setting. Methods: The study was undertaken in 10 of 29 high tuberculosis burden primary health facilities, selected through stratified random sampling. An observational study was undertaken as facilities transitioned to the Xpert MTB/RIF-based algorithm. MDR-TB diagnostic data were collected from electronic laboratory records and treatment data from clinical records and registers. Kaplan Meier time-to-event analysis was used to compare treatment commencement time, laboratory turnaround time and action delay between algorithms. A facility-level paired analysis was done: the median time-to-event was estimated per facility in each algorithm and mean differences between algorithms compared using a paired t-test. Cox proportional hazards regression was used to assess the effect of patient-level variables on treatment commencement time. The difference between algorithms was compared using the hazard ratio. Results: The median treatment commencement time in the Xpert MTB/RIF-based algorithm was 17 days (95% CI 13 to 22 days), with a median laboratory turnaround time (to result available in the laboratory) of <1 day (95% CI<1 to 1 day). There was a decrease of 25 days (95% CI 17 to 32 days, p<0.001) in median MDR-TB treatment commencement time in the Xpert MTB/RIF-based algorithm. We found no significant effect on treatment commencement times for the patient-level variables assessed. Conclusion: MDR-TB treatment commencement time was significantly reduced in the Xpert MTB/RIF-based algorithm. Changes in the health system may have contributed. However, an unacceptable level of delay remains. Health system and patient factors contributing to delay need to be evaluated and addressed to optimise test benefits. Please cite as follows: Naidoo, P. et al. 2014. A comparison of multidrug-resistant tuberculosis treatment commencement times in MDRTBPlus line probe assay and XpertH MTB/RIF-based algorithms in a routine operational setting in Cape Town. PLoS ONE, 9(7):e103328, doi:10.1371/journal.pone.0103328.; The original publication is available at http://journals.plos.org/plosone

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

2016-03-11T08:04:28Z

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 Jenum, Synne; Grewal, Harleen M. S.; Hokey, David A.; Kenneth, John; Vaz, Mario; Doherty, Timothy Mark; Jahnsen, Frode Lars; Hesseling, A. C. 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. Please cite as follows: Jenum, S. et al. 2014. 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. PLoS ONE, 9(7):e101224, doi:10.1371/journal.pone.0101224.; The original publication is available at http://journals.plos.org/plosone

Reducing deaths from severe pneumonia in children in Malawi by improving delivery of pneumonia case management

2016-03-11T09:10:21Z

Reducing deaths from severe pneumonia in children in Malawi by improving delivery of pneumonia case management Enarson, Penelope M.; Gie, Robert P.; Mwansambo, Charles C.; Maganga, Ellubey R.; Lombard, Carl J.; Enarson, Donald A.; Graham, Stephen M. Objective: To evaluate the pneumonia specific case fatality rate over time following the implementation of a Child Lung Health Programme (CLHP) within the existing government health services in Malawi to improve delivery of pneumonia case management. Methods: A prospective, nationwide public health intervention was studied to evaluate the impact on pneumonia specific case fatality rate (CFR) in infants and young children (0 to 59 months of age) following the implementation of the CLHP. The implementation was step-wise from October 1st 2000 until 31st December 2005 within paediatric inpatient wards in 24 of 25 district hospitals in Malawi. Data analysis compared recorded outcomes in the first three months of the intervention (the control period) to the period after that, looking at trend over time and variation by calendar month, age group, severity of disease and region of the country. The analysis was repeated standardizing the follow-up period by using only the first 15 months after implementation at each district hospital. Findings: Following implementation, 47,228 children were admitted to hospital for severe/very severe pneumonia with an overall CFR of 9•8%. In both analyses, the highest CFR was in the children 2 to 11 months, and those with very severe pneumonia. The majority (64%) of cases, 2–59 months, had severe pneumonia. In this group there was a significant effect of the intervention Odds Ratio (OR) 0•70 (95%CI: 0•50–0•98); p = 0•036), while in the same age group children treated for very severe pneumonia there was no interventional benefit (OR 0•97 (95%CI: 0•72–1•30); p = 0•8). No benefit was observed for neonates (OR 0•83 (95%CI: 0•56–1•22); p = 0•335). Conclusions: The nationwide implementation of the CLHP significantly reduced CFR in Malawian infants and children (2–59 months) treated for severe pneumonia. Reasons for the lack of benefit for neonates, infants and children with very severe pneumonia requires further research. Please cite as follows: Enarson, P. M. et al. 2014. Reducing deaths from severe pneumonia in children in Malawi by improving delivery of pneumonia case management. PLoS ONE, 9(7):e102955, doi:10.1371/journal.pone.0102955.; The original publication is available at http://journals.plos.org/plosone

Vitamin D levels in Indian children with intrathoracic tuberculosis

2016-02-09T06:30:19Z

Vitamin D levels in Indian children with intrathoracic tuberculosis Khandelwal, Deepchand; Gupta, Nandita; Mukherjee, Aparna; Lodha, Rakesh; Singh, Varinder; Grewal, Harleen M. S.; Bhatnagar, Shinjini; Singh, Sarman; Kabra, S. K.; Delhi Pediatric TB study group; Hesseling, A. C. Background & objectives: Deficiency of vitamin D, an immunomodulator agent, is associated with increased susceptibility to tuberculosis in adults, but only limited studies are available in the paediatric age group, especially regarding association of vitamin D with type and outcome of tuberculosis. We conducted this study to determine the baseline 25-hydroxy vitamin D levels in children suffering from intrathoracic tuberculosis and its association with type and outcome of tuberculosis. Methods: Children with intrathoracic tuberculosis, diagnosed on the basis of clinico-radiological criteria, were enrolled as part of a randomized controlled trial on micronutrient supplementation in paediatric tuberculosis patients. Levels of 25-hydroxy vitamin D were measured in serum samples collected prior to starting antitubercular therapy by chemiluminescent immunoassay technology. Results: Two hundred sixty six children (mean age of 106.9 ± 43.7 months; 57.1% girls) were enrolled. Chest X-ray was suggestive of primary pulmonary complex, progressive disease and pleural effusion in 81 (30.5%), 149 (56%) and 36 (13.5%) subjects, respectively. Median serum 25-hydroxy vitamin D level was 8 ng/ml (IQR 5, 12). One hundred and eighty six (69.9%) children were vitamin D deficient (serum 25-hydroxy vitamin D <12 ng/ml), 55 (20.7%) were insufficient (12 to <20 ng/ml) and 25 (9.4%) were vitamin D sufficient (≥ 20 ng/ml). Levels of 25-hydroxy vitamin D were similar in all three types of intrathoracic tuberculosis, and in microbiologically confirmed and probable cases. Levels of 25-hydroxy vitamin D did not significantly affect outcome of the disease. Children who were deficient or insufficient were less likely to convert (become smear/culture negative) at two months as compared to those who were 25-hydroxy vitamin D sufficient ( p <0.05). Interpretation & conclusions: Majority of Indian children with newly diagnosed intrathoracic tuberculosis were deficient in vitamin D. Type of disease or outcome was not affected by 25-hydroxy vitamin D levels in these children. However, children who did not demonstrate sputum conversion after intensive phase of antitubercular therapy had lower baseline 25-hydroxy vitamin D levels as compared to those who did. Please cite as follows: Khandelwal, D. et al. 2014. Vitamin D levels in Indian children with intrathoracic tuberculosis. Indian Journal of Medical Research, 140(4):531-537.; The original publication is available at http://www.ijmr.org.in/

Tuberculosis control in South Africa : successes, challenges and recommendations

2016-02-11T07:50:30Z

Tuberculosis control in South Africa : successes, challenges and recommendations Churchyard, G. J.; Mametja, L. D.; Mvusi, L.; Ndjeka, N.; Hesseling, A. C.; Reid, A.; Babatunde, S.; Pillay, Y. Tuberculosis (TB) remains a global health threat, and South Africa (SA) has one of the world’s worst TB epidemics driven by HIV. Among the 22 countries with the highest burden of TB, SA has the highest estimated incidence and prevalence of TB, the second highest number of diagnosed multidrug-resistant TB cases, and the largest number of HIV-associated TB cases. Although SA has made notable progress in reducing TB prevalence and deaths and improving treatment outcomes for new smear-positive TB cases, the burden of TB remains enormous. SA has the means to overcome this situation. In addition to better implementing the basics of TB diagnosis and treatment, scaling up the use of Xpert MTB/RIF as a replacement for sputum smear microscopy, strengthening case finding in and beyond healthcare facilities and a greater focus on TB prevention for people living with HIV, particularly earlier initiation of and scaling up antiretroviral therapy and scaling up continuous isoniazid preventive therapy, will have a substantial impact on TB control. New TB drugs, diagnostics and vaccines are required to further accelerate progress towards improved TB control in SA and beyond. Please cite as follows: Churchyard, G. J. et al. 2014. Tuberculosis control in South Africa: successes, challenges and recommendations. South African Medical Journal, 104(3 Suppl 1):244-248, doi:10.7196/SAMJ.7689.; The original publication is available at http://www.samj.org.za

Integration of TB and ART services fails to improve TB treatment outcomes : comparison of ART/TB primary healthcare services in Cape Town, South Africa

2016-02-11T08:27:38Z

Integration of TB and ART services fails to improve TB treatment outcomes : comparison of ART/TB primary healthcare services in Cape Town, South Africa Kaplan, R.; Caldwell, J.; Bekker, L-G.; Jennings, K.; Lombard, C.; Enarson, D. A.; Wood, R.; Beyers, N. Background. The combined tuberculosis (TB) and HIV epidemics in South Africa (SA) have created enormous operational challenges for a health service that has traditionally run vertical programmes for TB treatment and antiretroviral therapy (ART) in separate facilities. This is particularly problematic for TB/HIV co-infected patients who need to access both services. Objective. To determine whether integrated TB facilities had better TB treatment outcomes than single-service facilities in Cape Town, SA. Methods. TB treatment outcomes were determined for newly registered, adult TB patients (aged ≥18 years) at 13 integrated ART/TB primary healthcare (PHC) facilities and four single-service PHC facilities from 1 January 2009 to 30 June 2010. A χ2 test adjusted for a cluster sample design was used to compare outcomes by type of facility. Results. Of 13 542 newly registered patients, 10 030 received TB treatment in integrated facilities and 3 512 in single-service facilities. There was no difference in baseline characteristics between the two groups with HIV status determined for 9 351 (93.2%) and 3 227 (91.9%) patients, of whom 6 649 (66.3%) and 2 213 (63%) were HIV-positive in integrated facilities and single-service facilities, respectively. The median CD4+ count of HIV-positive patients was 152 cells/μl (interquartile range (IQR) 71 - 277) for integrated facilities and 148 cells/μl (IQR 67 - 260) for single-service facilities. There was no statistical difference in the TB treatment outcome profile between integrated and single-service facilities for all TB patients (p=0.56) or for the sub-set of HIV-positive TB patients (p=0.58) Conclusion. This study did not demonstrate improved TB treatment outcomes in integrated PHC facilities and showed that the provision of ART in the same facility as TB services was not associated with lower TB death and default rates. Please cite as follows: Kaplan, R. et al. 2014. Integration of TB and ART services fails to improve TB treatment outcomes: comparison of ART/TB primary healthcare services in Cape Town, South Africa. South African Medical Journal, 104(3):204-209, doi:10.7196/SAMJ.7696.; The original publication is available at http://www.samj.org.za

Tuberculosis in healthcare workers and infections control measures at primary healthcare facilities in South Africa

2017-04-13T10:01:33Z

Tuberculosis in healthcare workers and infections control measures at primary healthcare facilities in South Africa Claassens, Mareli M.; Van Schalkwyk, Cari; Du Toit, Elizabeth; Roest, Eline; Lombard, Carl J.; Enarson, Donald A.; Beyers, Nulda; Borgdorff, Martien W. Background Challenges exist regarding TB infection control and TB in hospital-based healthcare workers in South Africa. However, few studies report on TB in non-hospital based healthcare workers such as primary or community healthcare workers. Our objectives were to investigate the implementation of TB infection control measures at primary healthcare facilities, the smear positive TB incidence rate amongst primary healthcare workers and the association between TB infection control measures and all types of TB in healthcare workers. Methods One hundred and thirty three primary healthcare facilities were visited in five provinces of South Africa in 2009. At each facility, a TB infection control audit and facility questionnaire were completed. The number of healthcare workers who had had TB during the past three years was obtained. Results The standardised incidence ratio of smear positive TB in primary healthcare workers indicated an incidence rate of more than double that of the general population. In a univariable logistic regression, the infection control audit score was significantly associated with reported cases of TB in healthcare workers (OR=1.04, 95%CI 1.01-1.08, p=0.02) as was the number of staff (OR=3.78, 95%CI 1.77-8.08). In the multivariable analysis, the number of staff remained significantly associated with TB in healthcare workers (OR=3.33, 95%CI 1.37-8.08). Conclusion The high rate of TB in healthcare workers suggests a substantial nosocomial transmission risk, but the infection control audit tool which was used did not perform adequately as a measure of this risk. Infection control measures should be monitored by validated tools developed and tested locally. Different strategies, such as routine surveillance systems, could be used to evaluate the burden of TB in healthcare workers in order to calculate TB incidence, monitor trends and implement interventions to decrease occupational TB. CITATION: Claassens, M. M. et al. 2013. Tuberculosis in healthcare workers and infections control measures at primary healthcare facilities in South Africa. PLoS ONE, 8(10): e76272, doi:10.1371/journal.pone.0076272.; The original publication is available at http://journals.plos.org

Comparing same day sputum microscopy with conventional sputum microscopy for the diagnosis of tuberculosis : Chhattisgarh, India

2017-04-12T08:01:20Z

Comparing same day sputum microscopy with conventional sputum microscopy for the diagnosis of tuberculosis : Chhattisgarh, India Nayak, Priyakanta; Kumar, Ajay M. V.; Claassens, Mareli; Enarson, Donald A.; Satyanarayana, Srinath; Kundu, Debashish; Khaparde, Kshitij; Agrawal, Tarun K.; Dapkekar, Shankar; Chandraker, Sachin; Nair, Sreenivas Achuthan Background The World Health Organization (WHO) recommends same day sputum microscopy (spot-spot) in preference to conventional strategy (spot-morning) for the diagnosis of smear positive tuberculosis with the view that completing diagnosis on a single day may be more convenient to the patients and reduce pre-treatment losses to follow-up. Methods We conducted a cross-sectional study in seven selected district level hospitals of Chhattisgarh State, India. During October 2012 – March 2013, two sputum specimens (spot-early morning) were collected from consecutively enrolled adult (≥18 years) presumptive TB patients as per current national guidelines. In addition, a second sample was collected (one hour after the collection of first spot sample) from the same patients. All the samples were examined by ziehl-Neelsen (ZN) microscopy. McNemar’s test was used to compare statistical differences in the proportion smear positive between the two approaches (spot-spot versus spot-morning). Results Of 2551 presumptive TB patients, 69% were male. All patients provided the first spot specimen, 2361 (93%) provided the second spot specimen, and 2435 (96%) provided an early morning specimen. 72% of specimens were mucopurulent in conventional strategy as compared to 60% in same day strategy. The proportion of smear-positive patients diagnosed by same day microscopy was 14%, as compared to 17% by the conventional method (p<0.001). A total of 73 (16.9%) potential cases were missed by the same day method compared to only 2 (0.5%) by the conventional method. Conclusion Same-day microscopy method missed 17% of smear-positive cases and contrary to prior perception, did not increase the proportion of suspects providing the second sample. These findings call for an urgent need to revisit the WHO recommendation of switching to same-day diagnosis over the current policy. CITATION: Nayak, P. et al. 2013. Comparing same day sputum microscopy with conventional sputum microscopy for the diagnosis of tuberculosis : Chhattisgarh, India. PLoS ONE, 8(9): e74964, doi:10.1371/journal.pone.0074964.; The original publication is available at http://journals.plos.org/plosone

HPTN 071 (PopART) : rationale and design of a cluster-randomised trial of the population impact of an HIV combination prevention intervention including universal testing and treatment - a study protocol for a cluster randomised trial

2015-06-30T10:50:53Z

HPTN 071 (PopART) : rationale and design of a cluster-randomised trial of the population impact of an HIV combination prevention intervention including universal testing and treatment - a study protocol for a cluster randomised trial Hayes, Richard; Ayles, Helen; Beyers, Nulda; Sabapathy, Kalpana; Floyd, Sian; Shanaube, Kwame; Bock, Peter; Griffith, Sam; Moore, Ayana; Watson-Jones, Deborah; Fraser, Christophe; Vermund, Sten H.; Fidler, Sarah; The HPTN 071 (PopART) Study Team Abstract Background Effective interventions to reduce HIV incidence in sub-Saharan Africa are urgently needed. Mathematical modelling and the HIV Prevention Trials Network (HPTN) 052 trial results suggest that universal HIV testing combined with immediate antiretroviral treatment (ART) should substantially reduce incidence and may eliminate HIV as a public health problem. We describe the rationale and design of a trial to evaluate this hypothesis. Methods/Design A rigorously-designed trial of universal testing and treatment (UTT) interventions is needed because: i) it is unknown whether these interventions can be delivered to scale with adequate uptake; ii) there are many uncertainties in the models such that the population-level impact of these interventions is unknown; and ii) there are potential adverse effects including sexual risk disinhibition, HIV-related stigma, over-burdening of health systems, poor adherence, toxicity, and drug resistance.In the HPTN 071 (PopART) trial, 21 communities in Zambia and South Africa (total population 1.2 m) will be randomly allocated to three arms. Arm A will receive the full PopART combination HIV prevention package including annual home-based HIV testing, promotion of medical male circumcision for HIV-negative men, and offer of immediate ART for those testing HIV-positive; Arm B will receive the full package except that ART initiation will follow current national guidelines; Arm C will receive standard of care. A Population Cohort of 2,500 adults will be randomly selected in each community and followed for 3 years to measure the primary outcome of HIV incidence. Based on model projections, the trial will be well-powered to detect predicted effects on HIV incidence and secondary outcomes. Discussion Trial results, combined with modelling and cost data, will provide short-term and long-term estimates of cost-effectiveness of UTT interventions. Importantly, the three-arm design will enable assessment of how much could be achieved by optimal delivery of current policies and the costs and benefits of extending this to UTT. Trial registration ClinicalTrials.gov NCT01900977. Please site as follows:; Hayes, R. et al. 2014. HPTN 071 (PopART) : rationale and design of a cluster-randomised trial of the population impact of an HIV combination prevention intervention including universal testing and treatment - a study protocol for a cluster randomised trial. Trials, 15(1):57, doi:10.1186/1745-6215-15-57.; The original publication is available athttp://www.trialsjournal.com/content/15/1/57

The rate of sputum smear-positive tuberculosis after treatment default in a high-burden setting : a retrospective cohort study

2015-07-01T12:26:32Z

The rate of sputum smear-positive tuberculosis after treatment default in a high-burden setting : a retrospective cohort study Marx, Florian M.; Dunbar, Rory; Enarson, Donald A.; Beyers, Nulda Rationale: High rates of recurrent tuberculosis after successful treatment have been reported from different high burden settings in Sub-Saharan Africa. However, little is known about the rate of smear-positive tuberculosis after treatment default. In particular, it is not known whether or not treatment defaulters continue to be or become again smear-positive and thus pose a potential for transmission of infection to others. Objective: To investigate, in a high tuberculosis burden setting, the rate of re-treatment for smear-positive tuberculosis among cases defaulting from standardized treatment compared to successfully treated cases. Methods: Retrospective cohort study among smear-positive tuberculosis cases treated between 1996 and 2008 in two urban communities in Cape Town, South Africa. Episodes of re-treatment for smear-positive tuberculosis were ascertained via probabilistic record linkage. Survival analysis and Poisson regression were used to compare the rate of smear-positive tuberculosis after treatment default to that after successful treatment. Results: A total of 2,136 smear-positive tuberculosis cases were included in the study. After treatment default, the rate of retreatment for smear-positive tuberculosis was 6.86 (95% confidence interval [CI]: 5.59–8.41) per 100 person-years compared to 2.09 (95% CI: 1.81–2.41) after cure (adjusted Hazard Ratio [aHR]: 3.97; 95% CI: 3.00–5.26). Among defaulters, the rate was inversely associated with treatment duration and sputum conversion prior to defaulting. Smear grade at start of the index treatment episode (Smear3+: aHR 1.61; 95%CI 1.11–2.33) was independently associated with smear-positive tuberculosis retreatment, regardless of treatment outcome. Conclusions: In this high-burden setting, there is a high rate of subsequent smear-positive tuberculosis after treatment default. Treatment defaulters are therefore likely to contribute to the pool of infectious source cases in the community. Our findings underscore the importance of preventing treatment default, as a means of successful tuberculosis control in highburden settings. Publication of this article was funded by the Stellenbosch University Open Access Fund.; The original publication is available at http://www.plosone.org/; 9 p. : ill.; Bibliography

Hearing loss in patients on treatment for drug-resistant tuberculosis

2016-08-08T09:09:59Z

Hearing loss in patients on treatment for drug-resistant tuberculosis Seddon, James A.; Godfrey-Faussett, Peter; Jacobs, Kayleen; Ebrahim, Adam; Hesseling, Anneke C.; Schaaf, H. Simon The treatment of drug‐resistant (DR) tuberculosis (TB) necessitates the use of second‐line injectable anti‐TB drugs which are associated with hearing loss. Hearing loss affects communication and for children the development of language and social skills. This article describes the pathophysiology of hearing loss and the testing methodologies that can be employed. It is the first paper to systematically review the literature regarding hearing loss in those treated for DR‐TB. In the studies identified, the methodology used to test for and to classify hearing loss is inconsistent and children and those with HIV are poorly represented. The review describes existing guidelines and suggests management strategies when hearing loss is found. It describes the challenges of testing hearing in the developing world contexts where the majority of patients with DR‐TB are treated. Finally it makes the recommendation that a standardised testing methodology and classification system be used. The original publication is available at http://erj.ersjournals.com/; Published ahead of print on 14 June 2012, as a manuscript, for the June publication. Indicated on the Website as ERJ in press the copyediting, typesetting, and proofreading, has not been performed.; Bibliography; Publication of this article was funded by the Stellenbosch University Open Access Fund.

Airway involvement in pulmonary tuberculosis

2016-03-23T09:27:10Z

Airway involvement in pulmonary tuberculosis Goussard, P.; Gie, R. [No abstract available] The original publication is available at http://www.samj.org.za; Please cite as follows: Goussard, P. & Gie, R. 2007. Airway involvement in pulmonary tuberculosis. South African Medical Journal, 97(10):986-988.

Pediatric tuberculosis : clinical and epidemiological reflections from a highly endemic setting

2015-07-01T12:28:00Z

Pediatric tuberculosis : clinical and epidemiological reflections from a highly endemic setting Hesseling, Anneke Pediatric TB provides unique opportunities to study TB disease epidemiology. Improved diagnostics are of key importance in order to address many of the challenges posed by TB in children. In the Western Cape Province in South Africa, the TB notification rate was more than 600 out of 100,000 for children aged 0-14 years in 2007; the maternal HIV prevalence was 15%, with a good vertical preventative program. The HIV transmission rate was 4-5%; 99% of neonates routinely receive BCG vaccination at birth. Isoniazid prophylaxis, shown to be effective in the prevention of TB in young children, is seldom initiated and many missed opportunities for preventive therapy exist. In children admitted to hospital, mycobacterial culture is routinely done for TB in children less than five years of age through gastric aspiration of stomach contents in this setting; the culture yield is 30-40% in children with clinically suspected TB.