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Amsterdam-Zuidoost, Netherlands

Vinkeles Melchers N.V.S.,University of Amsterdam | van Elsland S.L.,VU University Amsterdam | Lange J.M.A.,University of Amsterdam | Borgdorff M.W.,Public Health Service GGD Amsterdam | van den Hombergh J.,PharmAccess International
PLoS ONE | Year: 2013

Background: Prisoners are at high risk of developing tuberculosis (TB), causing morbidity and mortality. Prison facilities encounter many challenges in TB screening procedures and TB control. This review explores screening practices for detection of TB and describes limitations of TB control in prison facilities worldwide. Methods: A systematic search of online databases (e.g., PubMed and Embase) and conference abstracts was carried out. Research papers describing screening and diagnostic practices among prisoners were included. A total of 52 articles met the inclusion criteria. A meta-analysis of TB prevalence in prison facilities by screening and diagnostic tools was performed. Results: The most common screening tool was symptom questionnaires (63·5%), mostly reporting presence of cough. Microscopy of sputum with Ziehl-Neelsen staining and solid culture were the most frequently combined diagnostic methods (21·2%). Chest X-ray and tuberculin skin tests were used by 73·1% and 50%, respectively, as either a screening and/or diagnostic tool. Median TB prevalence among prisoners of all included studies was 1,913 cases of TB per 100,000 prisoners (interquartile range [IQR]: 332-3,517). The overall annual median TB incidence was 7·0 cases per 1000 person-years (IQR: 2·7-30·0). Major limitations for successful TB control were inaccuracy of diagnostic algorithms and the lack of adequate laboratory facilities reported by 61·5% of studies. The most frequent recommendation for improving TB control and case detection was to increase screening frequency (73·1%). Discussion: TB screening algorithms differ by income area and should be adapted to local contexts. In order to control TB, prison facilities must improve laboratory capacity and frequent use of effective screening and diagnostic tools. Sustainable political will and funding are critical to achieve this. © 2013 Vinkeles Melchers et al.

Breuninger M.,Swiss Tropical and Public Health Institute | Breuninger M.,Ifakara Health Institute | Breuninger M.,University Hospital Freiburg | Van Ginneken B.,Radboud University Nijmegen | And 14 more authors.
PLoS ONE | Year: 2014

Background: Chest radiography to diagnose and screen for pulmonary tuberculosis has limitations, especially due to interreader variability. Automating the interpretation has the potential to overcome this drawback and to deliver objective and reproducible results. The CAD4TB software is a computer-aided detection system that has shown promising preliminary findings. Evaluation studies in different settings are needed to assess diagnostic accuracy and practicability of use. Methods: CAD4TB was evaluated on chest radiographs of patients with symptoms suggestive of pulmonary tuberculosis enrolled in two cohort studies in Tanzania. All patients were characterized by sputum smear microscopy and culture including subsequent antigen or molecular confirmation of Mycobacterium tuberculosis (M.tb) to determine the reference standard. Chest radiographs were read by the software and two human readers, one expert reader and one clinical officer. The sensitivity and specificity of CAD4TB was depicted using receiver operating characteristic (ROC) curves, the area under the curve calculated and the performance of the software compared to the results of human readers. Results: Of 861 study participants, 194 (23%) were culture-positive for M.tb. The area under the ROC curve of CAD4TB for the detection of culture-positive pulmonary tuberculosis was 0.84 (95% CI 0.80-0.88). CAD4TB was significantly more accurate for the discrimination of smear-positive cases against non TB patients than for smear-negative cases (p-value<0.01). It differentiated better between TB cases and non TB patients among HIV-negative compared to HIV-positive individuals (p<0.01). CAD4TB significantly outperformed the clinical officer, but did not reach the accuracy of the expert reader (p = 0.02), for a tuberculosis specific reading threshold. Conclusion: CAD4TB accurately distinguished between the chest radiographs of culture-positive TB cases and controls. Further studies on cost-effectiveness, operational and ethical aspects should determine its place in diagnostic and screening algorithms. © 2014 Breuninger et al.

Aitken S.C.,University Utrecht | Wallis C.L.,Lancet Laboratories | Stevens W.,University of Witwatersrand | Stevens W.,National Health Laboratory Services | And 3 more authors.
PLoS ONE | Year: 2015

Dried blood spots (DBS) are an easy to collect sample-type that can stabilize biological material at ambient temperature for transport and storage, making them ideal for use in resource-limited settings (RLS). We investigated the effect of storage temperature and duration on ability to detect mixed HIV-1 viral RNA populations, and subsequently viral RNA populations in a background of proviral DNA. Part one of the study used DBS samples of whole blood spiked with specific quantities of HIV-1 subtype-B and -C RNA to study mixed virus population detection. Part two used DBS comprising of HIV-1 subtype-B proviral DNA containing U1 cells combined with HIV-1 subtype-C RNA to mimic HIV-1 infected clinical samples as a model system to study the relative stability of HIV-1 RNA and DNA in DBS. Prepared DBS were stored at -20°C and +30°C for periods of one day, one, two, and four weeks. Samples were genotyped to determine changes in the detection of mixtures in the sample over time. From two weeks onwards, storage at +30°C resulted in gradual, time-related reduction in the detection of mixed virus population at log10 VL 4.0 but not at log10 5.0. Proviral DNA and viral RNA were both stable for at least 52 weeks when stored at -20°C, compared to progressive RNA decay over time at +30°C. DBS storage conditions and duration had a significant effect on HIV-1 RNA amplification. Our results demonstrate that DBS storage at ambient temperature (+30°C) should not exceed two weeks, with longterm storage at -20°C or lower. © 2015 Aitken et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Balinda S.N.,Joint Clinical Research Center | Ondoa P.,Amsterdam Institute for Global Health and Development | Obuku E.A.,Joint Clinical Research Center | Kliphuis A.,PharmAccess International | And 7 more authors.
PLoS ONE | Year: 2016

Background: WHO recommends regular viral load (VL) monitoring of patients on antiretroviral therapy (ART) for timely detection of virological failure, prevention of acquired HIV drug resistance (HIVDR) and avoiding unnecessary switching to second-line ART. However, the cost and complexity of routine VL testing remains prohibitive in most resource limited settings (RLS). We evaluated a simple, low-cost, qualitative viral-failure assay (VFA) on dried blood spots (DBS) in three clinical settings in Uganda. Methods: We conducted a cross-sectional diagnostic accuracy study in three HIV/AIDS treatment centres at the Joint Clinical Research Centre in Uganda. The VFA employs semi-quantitative detection of HIV-1 RNA amplified from the LTR gene. We used paired dry blood spot (DBS) and plasma with the COBASAmpliPrep/COBASTaqMan, Roche version 2 (VLref) as the reference assay. We used the VFA at two thresholds of viral load, (>5,000 or >1,000 copies/ml). Results: 496 paired VFA and VLref results were available for comparative analysis. Overall, VFA demonstrated 78.4%sensitivity, (95% CI: 69.7%-87.1%), 93% specificity (95% CI: 89.7%- 96.4%), 89.3% accuracy (95% CI: 85%-92%) and an agreement kappa = 0.72 as compared to the VLref. The predictive values of positivity and negativity among patients on ART for >12 months were 72.7%and 99.3%, respectively. Conclusions: VFA allowed 89%of correct classification of VF. Only 11%of the patients weremisclassified with the potential of unnecessary or late switch to second-line ART. Our findings present an opportunity to roll out simple and affordable VLmonitoring for HIV-1 treatment in RLS. © 2016 Balinda et al.This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Aitken S.C.,University Utrecht | Aitken S.C.,University of Witwatersrand | Kliphuis A.,University Utrecht | Wallis C.L.,University of Witwatersrand | And 8 more authors.
Journal of Clinical Virology | Year: 2012

Background: High cost and varying sensitivity for non-B HIV-1 subtypes limits application of current commercial kits for HIV-1 drug resistance genotyping of all major HIV-1 group-M subtypes. Objectives: Our research aimed to develop and validate an assay specific for all major HIV-1 group-M subtypes for use as an alternative to commercial assays for HIV-1 protease (PR) and reverse transcriptase (RT) drug resistance genotyping. Study design: A nested RT-PCR encompassing the entire PR and RT up to amino acid 321 of HIV-1 was designed to detect HIV-1 group-M subtypes. Primers compatible with group-M subtypes were defined and analytical sensitivity of the assay evaluated using a panel of reference viruses for subtypes A-H and CRF01_AE. The assay was subsequently evaluated on 246 plasma samples from HIV-1 infected individuals harboring various group-M subtypes and viral loads (VLs). Results: All major group-M HIV-1 subtypes were detected with an overall analytical sensitivity of 1.00E+03 RNA copies/ml. Application of the genotyping assay on 246 primarily African clinical samples comprising subtypes A (n= 52; 21.7%), B (n= 12; 5.0%), C (n= 127; 52.9%), D (n= 25; 10.4%), CRF01_AE (n= 10; 4.2%), and CRF02_AG (n= 10; 4.2%), and unassigned variants (n= 10; 4.2%), VL range 4.32E+02-8.63E+06 (median 2.66E+04) RNA copies/ml, was ∼98% successful. Conclusions: A group-M subtype-independent genotyping assay for detection of HIV-1 drug resistance was developed. The described assay can serve as an alternative to commercial assays for HIV-1 drug resistance genotyping in routine diagnostics, and for surveillance and monitoring of drug resistance in resource-limited settings (RLS). © 2012 Elsevier B.V.

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