Tuberculosis Diagnostics Research Articles

Generalized tuberculosis and multifetal pregnancy

The article describes a clinical case of successful treatment of generalized tuberculosis in a young immunocompetent woman with multifetal pregnancy (triplets) and multiple localizations of tuberculosis: tuberculosis meningitis, disseminated pulmonary tuberculosis, and uterine tuberculosis. Specific parameters of tuberculosis diagnostics in the pregnant are presented.

A clinical score has utility in tuberculosis case-finding among patients with HIV: A feasibility study from Bissau

BackgroundClinical scores are promising case-finding tools for tuberculosis (TB) among HIV-infected patients. The Bandim TBscore has been shown to increase the diagnostic yield among patients with presumed TB in general, but has not previously been tested among newly diagnosed HIV patients at high risk of TB. MethodsHIV-infected patients were included in this cross-sectional study. A pre–post-intervention study design was used to assess the outcome of a change in practice, i.e. the application of a clinical score (TBscore) consisting of 13 signs and symptoms to assess the need for further TB diagnostics. Patients with a TBscore ≥2 were evaluated using smear microscopy and Xpert MTB/RIF. A TB diagnosis was made based on microbiology or clinical evaluation. The sensitivity and specificity of the TBscore were compared with those of World Health Organization symptoms. ResultsThe TB prevalence among newly enrolled HIV-infected patients during the study period was 13.4% (22/164). Using the TBscore and a diagnostic algorithm, it was possible to increase the proportion of patients started on TB treatment from 2.7% (10/367) the year before the study to 10.4% (17/164) during the study period. Five patients diagnosed with TB were not started on TB treatment as they were lost to follow-up or died. With a cut-off value of 2, the TBscore had a sensitivity, specificity, positive predictive value, and negative predictive value of 95.5% (21/22), 36.9% (41/111), 23.1% (22/118), and 97.6% (41/42), respectively. ConclusionThe TBscore is useful for standardized TB screening among HIV-infected individuals and may be a valuable tool to prioritize patients at high risk of TB.

Tuberculosis screening during the 2015 European refugee crisis

BackgroundThe purpose of our study was to describe and evaluate management, performance and results of Tuberculosis (TB)-screening among refugees and asylum seekers in a rural area in Germany in 2015.MethodsRefugees or asylum seekers, staying in shared-accommodation are obligated to participate on screening chest X-ray (CXR) in order to screen for signs of potentially infectious pulmonary TB (German Protection against Infection Act and German Asylum Procedure Act). n = 705 individuals underwent screening chest X-ray (CXR) to detect pulmonary TB in September and October 2015 on site. One experienced radiologist interpreted and reported each CXR within 24 h after the enrollment in the screening program and results were sent to the local Public Health Department for potential further medical care. Image abnormalities suggestive for TB were defined according to established radiographic criteria such as pleural effusion, cavitation, consolidation, fibrous scarring or calcification. Only in case of TB-suggestive findings on CXR, further diagnostics were arranged (pulmonological examination, follow-up CXR, sputum culture, interferon-gamma release assay, bronchoscopy). Follow-up data was collected in collaboration with the local Public Health Department. Descriptive statistics were calculated using GraphPad Prism software.Resultsn = 637 CXR examinations (90%) did not show abnormal findings, n = 54 CXR (8%) showed incidental findings, and n = 14 CXR (2%) were suspicious for acute TB. Of these, n = 14 individuals, eight underwent further TB diagnostics. Active TB was confirmed in one individual (0.001% of the screening cohort).ConclusionsOur cohort reflects current immigrations statistics in Europe and illustrates an overall low TB prevalence amongst individuals entering Germany in 2015. However, our findings support the improvement of diagnostic algorithms.

Improving the design of studies evaluating the impact of diagnostic tests for tuberculosis on health outcomes: a qualitative study of perspectives of diverse stakeholders

Background: Studies evaluating the impact of Xpert MTB/RIF testing for tuberculosis (TB) have demonstrated varied effects on health outcomes with many studies showing inconclusive results. We explored perceptions among diverse stakeholders about studies evaluating the impact of TB diagnostic tests, and identified suggestions for improving these studies. Methods: We used purposive sampling with consideration for differing expertise and geographical balance and conducted in depth semi-structured interviews. We interviewed English-speaking participants, including TB patients, and others involved in research, care or decision-making about TB diagnostics. We used the thematic approach to code and analyse the interview transcripts. Results: We interviewed 31 participants. Our study showed that stakeholders had different expectations with regard to test impact and how it is measured. TB test impact studies were perceived to be important for supporting implementation of tests but there were concerns about the unrealistic expectations placed on tests to improve outcomes in health systems with many influencing factors. To improve TB test impact studies, respondents suggested conducting health system assessments prior to the study; developing clear guidance on the study methodology and interpretation; improving study design by describing questions and interventions that consider the influences of the health-care ecosystem on the diagnostic test; selecting the target population at the health-care level most likely to benefit from the test; setting realistic targets for effect sizes in the sample size calculations; and interpreting study results carefully and avoiding categorisation and interpretation of results based on statistical significance alone. Researchers should involve multiple stakeholders in the design of studies. Advocating for more funding to support robust studies is essential. Conclusion: TB test impact studies were perceived to be important to support implementation of tests but there were concerns about their complexity. Process evaluations of their health system context and guidance for their design and interpretation are recommended.

Enablers and Challenges in the Implementation of Active Case Findings in a Selected District of Karnataka, South India: A Qualitative Study.

Background Active case finding (ACF) for tuberculosis (TB) is a promising tool to enhance early case detection among marginalized populations. As opposed to passive case finding, it involves systematically searching for TB in individuals who would not spontaneously present for care. The National TB Program (NTP) of India has initiated ACF for TB through the existing general health system since the end of 2017. However, prior to scale-up, there is need for exploring the implementation challenges and solutions to improve the efficiency of this program. Objectives (1) To explore the enablers and challenges in the implementation of ACF for TB by NTP in the Bengaluru rural district of Karnataka, South India, and (2) to explore the perceived solutions to improve the efficiency of ACF activity. Methods A qualitative descriptive study was conducted in the Bengaluru rural district during July 2018. In-depth interviews using purposively selected health care providers involved in active case finding (n = 9) and presumptive TB patients (n = 9) and presumptive TB patients (Results The challenges in conduct of ACF were as follows: inadequate training of health care workers, shortage of staff, indifferent attitude of community due to stigma, lack of awareness about TB, illiteracy, inability to convince patients for sputum test, and delay in getting CBNAAT results. The field staff recommended the installation of mobile CBNAAT machine, involvement of general health staff in activity, training of health workers on counseling of patients, and issue of identity cards for community health workers/volunteers so that people recognize them. Conclusion The health system challenges in conduct of ACF need to be addressed by training the health staff involved in activity and also improving the access to TB diagnostics.

Aligning in the dark: Variable and shifting (user-) settings in developing point-of-care diagnostics for tuberculosis and HIV.

To be effective, healthcare technologies should be attuned to particular contexts of use. This article examines how such attuning is articulated in global innovation practices for tuberculosis and HIV diagnostics, and to what effect. It examines the development of point-of-care (POC) diagnostics - promised to be designed for users outside laboratories or in resource constrained settings - to study what developers and implementers do to align diagnostic technologies to the POC. Fieldwork among global health actors involved in diagnostic development, including manufacturers, donors, industry consultants, international organizations, policymakers, regulators and researchers, is combined with fieldwork among users of diagnostics in India, including decision-makers, NGOs, program officers, laboratory technicians and nurses. The article adds to STS's theory of alignment and user interaction, where the setting and user to which developers and implementers of global health diagnostics align are multiple, varied, emerging and keep shifting. The characteristics of a local user setting include multiple engaged and imagined user settings, but also the settings of developers, of global intermediaries, competitors and diseases. As such, alignment is happening across multiple dimensions and scales and has an important temporal dimension. The results reveal how alignment happens to some extent in the dark, characterized by uncertainty about the elements that should align. Standardizing elements, politics and scarce resources cause frictions in the temporalities of aligning and over what constitutes a well-aligned diagnostic.

Evaluation of an Ag85B Immunosensor with Potential for Electrochemical Mycobacterium Tuberculosis Diagnostics

Tuberculosis remains a major global health concern, especially in the developing world, and monitoring/early detection of the disease relies on low cost technologies that provide rapid and accurate results. Mycobacterium tuberculosis is the responsible bacterial pathogen and it is currently estimated by the World Health Organisation (WHO), that one quarter of the world’s population, mainly in the developing world, is infected with TB. The overall aim of this work was to advance a screening electrochemical sensor for label free detection of Ag85B, a member of the Antigen 85 complex—major secretary protein of M. tuberculosis and biomarker for disease. An indirect ELISA Ag85B assay was optimised with capture antibody and antigen levels determined via a checkerboard titration (0.625 μg ml−1 and 2.5 μg ml−1 respectively). Following assay development, crosslinking of the bioreceptor Anti-Ag85B onto electrochemically deposited gold nanoparticle (AuNP) modified carbon electrodes was achieved and Ag85B binding successfully evaluated electrochemically via cyclic voltammetry. Following each modification step, ΔEp of a redox probe was monitored and overall results show that GCE/AuNP/anti-Ag85B electrochemical transducers are a viable method for Ag85B detection, capable of measuring antigen levels <2.5 μg ml−1.

A public-private model to scale up diabetes mellitus screening among people accessing tuberculosis diagnostics in Dhaka, Bangladesh

BackgroundData are scarce regarding the prevalence of diabetes mellitus (DM) among tuberculosis (TB) patients in Bangladesh. This study was undertaken to estimate the number needed to screen (NNS) to identify a case of DM among those with TB symptoms and those with confirmed TB disease, and to identify factors predicting treatment outcomes of TB patients with and without DM. MethodsPersons attending public–private model screening centres in urban Dhaka for the evaluation of TB were offered free blood glucose testing in addition to computer-aided chest X-ray and sputum Xpert MTB/RIF. ResultsAmong 7647 people evaluated for both TB and DM, the NNS was 35 (95% confidence interval (CI) 31–40) to diagnose one new case of DM; among those diagnosed with TB, the NNS was 21 (95% CI 17–29). Among those with diagnosed TB, patients with DM were more likely to have cavitation on chest X-ray compared to those without DM (31% vs 22%). Treatment failure (odds ratio (OR) 18.9, 95% CI 5.43–65.9) and death (OR 2.08, 95% CI 1.11–3.90) were more common among TB patients with DM than among TB patients without DM. DM was the most important predictor of a poor treatment outcome in the classification analysis for TB patients aged 39 years and above. ConclusionsA considerable burden of DM was found among patients accessing TB diagnostics through a public–private model in urban Bangladesh, and DM was associated with advanced TB disease and a high rate of poor treatment outcome.

Multicenter feasibility study to assess external quality panels for molecular diagnostics for tuberculosis in China.

The roll-out of molecular diagnostic tools continues to be the most important shift in the tuberculosis diagnostic landscape. The aim of this study was to develop a novel external quality assessment (EQA) panels for molecular TB diagnostics. In addition, we also assessed the performance of the laboratories with the EQA panels in China. Dried Mycobacterium tuberculosis (MTB) DNA in the chelex resin was designed as part of an EQA program. The storage of genomic DNA in the chelex resin layer had no effect on the stability of genomic DNA, even after 12 weeks of storage. Seventy-one laboratories have participated in EQA of molecular diagnostics for TB diagnosis in 2018. GeneXpert (74.6%, 53/71) was the most predominant molecular method, followed by GeneChip (32.3%, 23/71), MeltPro (22.5%, 16/71), and TB-LAMP (7.0%, 5/71). Out of 105 EQA panels, 103 EQA results (98.1%) achieved perfect scores, whereas the other two (1.9%) had satisfactory scores. There were a total of two false-negative results reported from two laboratories with local LAMP, respectively. In conclusion, we firstly develop feasible EQA panels for molecular diagnostics for tuberculosis in China. Our data demonstrate that a majority of participating laboratories are able to produce perfect results with molecular diagnostics in China, giving us important hints for the implementation of molecular diagnostics.

Diagnostic Potential of a PPE Protein Derived from Mycobacterium tuberculosis Beijing/K Strain.

PurposeThe prevalence of Mycobacterium tuberculosis (M. tb) and the status of M. bovis BCG vaccination may affect host immune responses to M. tb antigens. Understanding of the predominant local M. tb strain and immune signatures induced by its strain-specific antigens may contribute to an improved diagnosis of tuberculosis (TB). The aim of this study was to determine immune responses to M. tb antigen which was identified from the hyper-virulent Beijing/K strain in South Korea.Materials and MethodsPulmonary TB patients (n=52) and healthy subjects (n=92) including individuals with latent TB infection (n=31) were recruited, and QuantiFERON-TB Gold In-Tube tests were performed. The Beijing/K-antigen specific immune signatures were examined by diluted whole blood assays and multiplex bead arrays in a setting where nationwide BCG vaccination is employed.ResultsStatistical analyses demonstrated that three [C-X-C motif chemokine (CXCL10), interleukin (IL)-6, interferon (IFN)-α] of 17 cytokines/chemokines distinguished active cases from healthy controls following stimulation with the Beijing/K-specific antigen. IFN-α also differentiated between active diseases and latent TB infection (p<0.01), and the detection rate of TB was dramatically increased in combination with IL-6 and CXCL10 at the highest levels of specificity (95–100%).ConclusionOur data indicate that immune signatures to the M. tb Beijing/K-specific antigen can provide useful information for improved TB diagnostics. The antigen may be developed as a diagnostic marker or a vaccine candidate, particularly in regions where the M. tb Beijing/K strain is endemic.

Developing and Implementing new TB Technologies: Key Informants' Perspectives on the Ethical Challenges.

To identify the ethical challenges associated with the development and implementation of new tuberculosis (TB) drugs and diagnostics. Twenty-three semi-structured qualitative interviews conducted between December 2015 and September 2016 with programme administrators, healthcare workers, advocates, policymakers, and funders based in the Americas, Europe, and Africa. Interviews were analysed using thematic analysis. Divergent interests and responsibilities, coupled with power imbalances, are a primary source of ethical challenges; the uncertain risk profiles of new drugs present an additional one. Although this challenge can be partially mitigated through stringent pharmacovigilance, respondents highlighted that high-burden countries tend to lack the resources to facilitate safe implementation. Increased advocacy and community engagement are considered an ethical imperative for future TB development and implementation. This project helps identify some of the ethical challenges of new TB technologies. It demonstrates that investigating ethical challenges through qualitative research is one way to apprehend the difficulty of implementing new TB technologies. Addressing this difficulty will require that those in positions of power reconsider their interests in relation to disempowered communities. Efforts to build consensus regarding what values should underpin the global governance of TB research, prevention, and care are essential to facilitate the ethical implementation of new TB technologies.

Realizing the "40 by 2022" Commitment from the United Nations High-Level Meeting on the Fight to End Tuberculosis: What Will It Take to Meet Rapid Diagnostic Testing Needs?

The potential gains from full adoption of World Health Organization (WHO)-recommended rapid diagnostics (WRDs) for tuberculosis (TB) are significant, but there is no current analysis of the additional investment needed to reach this goal. We sought to estimate the necessary investment in instruments, tests, and money, using Xpert MTB/RIF (Xpert), which detects Mycobacterium tuberculosis (MTB) and tests for resistance to rifampicin (RIF), as an example. An existing calculator for TB diagnostic needs was adapted to estimate the Xpert needs for a group of 24 countries with high TB burdens. This analysis assumed that countries will achieve the case-finding commitments agreed to at the recent United Nations High-Level Meeting on the Fight to End Tuberculosis, and that countries would adopt the WHO-recommended algorithm in which all people with signs and symptoms of TB receive an Xpert test. When compared to the current investments in these countries, this baseline model revealed that countries would require a 4-fold increase in the number of Xpert modules and a 6-fold increase in the number of Xpert test cartridges per year to meet their full testing needs. The incremental cost of the additional instruments for these countries would total approximately US$474 million, plus an incremental cost each year of cartridges of approximately $586 million, or a 5-fold increase over current investments. A sensitivity analysis revealed a variety of possible changes under alternative scenarios, but most of these changes either do not meet the global goals, are unrealistic, or would result in even greater investment needs. These findings suggest that a major investment is needed in WRD capacity to implement the recommended diagnostic algorithm for TB and reach the case-finding commitments by 2022.

Gene-based diagnosis of tuberculosis with a new-generation pathogen enrichment technique

While the Xpert MTB/RIF assay (Cepheid Sunnyvale, CA, USA) has greater than 95% sensitivity for identifying acid-fast bacilli (AFB) smear-positive tuberculosis (TB) cases, for smear-negative pulmonary tuberculosis (PTB) the sensitivity was as low as 60% [1, 2]. To address the low sensitivity of current TB diagnostics for AFB smear-negative cases, we developed a simple and label-free pathogen enrichment using homobifunctional imidoesters (HIs) using a microfluidic (SLIM) platform followed by conventional MTB PCR to extract low amounts of pathogens from clinical samples [3]. In this study, we compared the diagnostic performance of the SLIM assay with the Xpert MTB/RIF for PTB diagnosis in a country with an intermediate TB burden and a low human immunodeficiency virus burden. The SLIM assay were performed by using 1 mL and 2 mL aliquots of sputum, respectively. Footnotes This manuscript has recently been accepted for publication in the European Respiratory Journal . It is published here in its accepted form prior to copyediting and typesetting by our production team. After these production processes are complete and the authors have approved the resulting proofs, the article will move to the latest issue of the ERJ online. Please open or download the PDF to view this article. Conflict of interest: None Conflict of interest: None Conflict of interest: None Conflict of interest: None Conflict of interest: None Conflict of interest: None Conflict of interest: None Conflict of interest: None Conflict of interest: None Conflict of interest: None

Implementation science to improve the quality of tuberculosis diagnostic services in Uganda

Nucleic acid amplification tests such as Xpert MTB/RIF (Xpert) have the potential to revolutionize tuberculosis (TB) diagnostics and improve case finding in resource-poor settings. However, since its introduction over a decade ago in Uganda, there remain significant gaps along the cascade of care for patients undergoing TB diagnostic evaluation at peripheral health centers. We utilized a systematic, implementation science-based approach to identify key reasons at multiple levels for attrition along the TB diagnostic evaluation cascade of care. Provider- and health system-level barriers fit into four key thematic areas: human resources, material resources, service implementation, and service coordination. Patient-level barriers included the considerable costs and time required to complete health center visits. We developed a theory-informed strategy using the PRECEDE framework to target key barriers by streamlining TB diagnostic evaluation and facilitating continuous quality improvement. The resulting SIMPLE TB strategy involve four key components: 1) Single-sample LED fluorescence microscopy; 2) Daily sputum transport to Xpert testing sites; 3) Text message communication of Xpert results to health centers and patients; and 4) Performance feedback to health centers using a quality improvement framework. This combination of interventions was feasible to implement and significantly improved the provision of high-quality care for patients undergoing TB diagnostic evaluation. We conclude that achieving high coverage of Xpert testing services is not enough. Xpert scale-up should be accompanied by health system co-interventions to facilitate effective implementation and ensure that high quality care is delivered to patients.

Improving the design of studies evaluating the impact of diagnostic tests for tuberculosis on health outcomes: a qualitative study of perspectives of diverse stakeholders.

Background: Studies evaluating the impact of Xpert MTB/RIF testing for tuberculosis (TB) have demonstrated varied effects on health outcomes with many studies showing inconclusive results. We explored perceptions among diverse stakeholders about studies evaluating the impact of TB diagnostic tests, and identified suggestions for improving these studies. Methods: We used purposive sampling with consideration for differing expertise and geographical balance and conducted in depth semi-structured interviews. We interviewed English-speaking participants, including TB patients, and others involved in research, care or decision-making about TB diagnostics. We used the thematic approach to code and analyse the interview transcripts. Results: We interviewed 31 participants. Our study showed that stakeholders had different expectations with regard to test impact and how it is measured. TB test impact studies were perceived to be important for supporting implementation of tests but there were concerns about the unrealistic expectations placed on tests to improve outcomes in health systems with many influencing factors. To improve TB test impact studies, respondents suggested conducting health system assessments prior to the study; developing clear guidance on the study methodology and interpretation; improving study design by describing questions and interventions that consider the influences of the health-care ecosystem on the diagnostic test; selecting the target population at the health-care level most likely to benefit from the test; setting realistic targets for effect sizes in the sample size calculations; and interpreting study results carefully and avoiding categorisation and interpretation of results based on statistical significance alone. Researchers should involve multiple stakeholders in the design of studies. Advocating for more funding to support robust studies is essential. Conclusion: TB test impact studies were perceived to be important to support implementation of tests but there were concerns about their complexity. Process evaluations of their health system context and guidance for their design and interpretation are recommended.

Biomarkers of iron metabolism facilitate clinical diagnosis in Mycobacterium tuberculosis infection

BackgroundPerturbed iron homeostasis is a risk factor for tuberculosis (TB) progression and an indicator of TB treatment failure and mortality. Few studies have evaluated iron homeostasis as a TB diagnostic...

Bacillus Calmette–Guérin strains with defined resistance mutations: a new tool for tuberculosis laboratory quality control

ObjectiveLaboratory quality control (QC) is essential to assess the reliability of tuberculosis diagnostic testing. To provide safe QC reagents for the detection of drug-resistant Mycobacterium tuberculosis, we generated antibiotic-resistant mycobacterial strains of attenuated virulence (M. bovis bacillus Calmette–Guérin (BCG)). MethodsSeven mono-resistant BCG strains were developed by introducing resistance-conferring mutations into wild-type BCG strains. Mutations were confirmed by dideoxynucleotide sequencing. Phenotypic resistance was quantified by microbroth dilution to determine the MIC90. The capacity of two commercial tests (GeneXpert TB/RIF and Genotype MTBDRplus) to detect resistance-conferring mutations was evaluated independently. ResultsOur panel included BCG strains with mutations in rpoB (S450L, I491F), katG (deletion at AA428), gyrA (D94G), rpsL (K43R) and Rv0678c (S63R). These mutations translated respectively into phenotypic resistance to rifampin (MIC ≥8 mg/L), isoniazid (MIC ≥8 mg/L), moxifloxacin (MIC 4 mg/L) and streptomycin (MIC ≥8 mg/L); the Rv0678c mutant showed decreased susceptibility to both clofazimine (MIC 4 mg/L) and bedaqualine (MIC 1 mg/L). GeneXpert (Cepheid) and Genotype MTBDRplus (Hain Lifesciences) both called the rpoB S450L strain rifampin-resistant and the I491F mutant rifampin-susceptible, as expected based on single nucleotide polymorphism positions. Likewise, MTBDRplus called the novel katG deletion mutant isoniazid susceptible despite phenotypic resistance. ConclusionBCG strains engineered to be mono-resistant to anti-tuberculosis drugs can be used as safe QC reagents for tuberculosis diagnostics and drug susceptibility testing.

Tuberculosis: Diagnostic Challenges in Rural Africa.

Tuberculosis (TB) remains among the top 10 infectious diseases with highest mortality globally since the 1990s despite effective chemotherapy. Among 10 million patients that fell ill with tuberculosis in the year 2017, 36 % were undiagnosed or detected and not reported; the number goes as high as 55 % in Tanzania, showing that the diagnosis of TB is a big challenge in the developing countries. There have been great advancements in TB diagnostics with introduction of the molecular tests such as Xpert MTB/RIF, loop-mediated isothermal amplification, lipoarabinomannan urine strip test, and molecular line-probe assays. However, most of the hospitals in Tanzania still rely on the TB score chart in children, the WHO screening questions in adults, acid-fast bacilli and chest x-ray for the diagnosis of TB. Xpert MTB/RIF has been rolled-out but remains a challenge in settings where the samples for testing must be transported over many kilometers. Imaging by sonography - nowadays widely available even in rural settings of Tanzania - has been shown to be a useful tool in the diagnosis of extrapulmonary tuberculosis. Despite all the efforts and new diagnostics, 30-50 % of patients in high-burden TB countries are still empirically treated for tuberculosis. More efforts need to be placed if we are to reduce the death toll by 90 % until 2030.

A modular paper-and-plastic device for tuberculosis nucleic acid amplification testing in limited-resource settings

We present a prototype for conducting rapid, inexpensive and point-of-care-compatible nucleic acid amplification tests (NAATs) for tuberculosis (TB). The fluorescent isothermal paper-and-plastic NAAT (FLIPP-NAAT) uses paper-based loop mediated isothermal amplification (LAMP) for DNA detection. The cost of materials required to build a 12-test-zone device is $0.88 and the cost of reagents per reaction is $0.43. An inexpensive imaging platform enables filter-free fluorescence detection of amplified DNA using a cell-phone camera. FLIPP-NAAT can be operated by an untrained user and only requires a regular laboratory incubator as ancillary equipment. All reagents can be dry-stored in the device, facilitating storage and transportation without cold chains. The device design is modular and the assay demonstrated high specificity to Mycobacterium tuberculosis (Mtb), analytical sensitivity of the order of 10 copies of Mtb gDNA, and tolerance to complex samples. The clinical sensitivity and specificity of sputum-based FLIPP NAAT tests were 100% (zero false negatives) and 68.75% (five false positives), respectively (N = 30), using Xpert MTB/RIF assay as the reference standard. FLIPP-NAAT has the potential to provide affordable and accessible molecular diagnostics for TB in low- and middle-income countries, when used in conjunction with an appropriate sample preparation technique. Although demonstrated for the detection of TB, FLIPP-NAAT is a platform technology for amplification of any nucleic acid sequence.

Tuberculosis and HIV co-infection in inpatients of phthisio-pulmonological profile: frequency, form of lesion, diagnostic features (according to data of highly specialized institution)

Objective — to clarify the prevalence of tuberculosis infection in HIV-positive inpatients of the TB hospital for 2014—2018 and features of its diagnosis in the affection of the chest cavity organs.Materials and methods. The method of retrospective analysis was used to process medical records of the Institute’s clinic for the period 2014—2018. A database has been formed that includes all patients with HIV infection treated in the hospital, from which a group of patients with a final clinical diagnosis of co-infection tuberculosis and HIV was subsequently selected.Among them were 195 (68.9 %) men and 88 (31.1 %) women. The average age of men was (37.0 ± 0.5), women — (38.0 ± 1.2) years. Separate subgroups of patients were selected, taking into account the localization of the tuberculous process in the chest cavity. The general clinical data of patients, the presence of comorbidities, diagnostic methods, localization and prevalence of the tuberculous process were taken into account.Results and discussion. Among 496 hospitalized HIV-positive patients with various pathologies of the chest cavity, the diagnosis of tuberculosis, that is, the presence of HIV-TB co-infection, was established in 283 (57.1 %) cases. In 46 (16.3 %) cases the diagnosis of HIV infection was established for the first time during hospitalization. Comorbid pathology was present in 184 (65.0 %) patients.Specific lung damage prevailed, 123 (44 %) cases, most often infiltrative tuberculosis (48.8 %). In 33 % of cases, there was a widespread tuberculous lesion — pulmonary and extrapulmonary (pleura or lymph nodes were involved). Isolated pleural lesion was diagnosed in 13 % of cases. The main methods of laboratory diagnostics were classical bacteriological methods — simple direct light microscopy and MBT culture, the positive results of which were obtained in only half of all studies, as well as molecular-genotypic tests. Prevalence of multidrug-resistant MBT strains was found (66.7 %).In about half of the cases, (44.9 %), additional mini-invasive procedures or surgical interventions with therapeutic and diagnostic purposes were performed. Histological examination confirmed the diagnosis of tuberculosis in 92 % of cases, whereas in the absence of signs of tuberculosis, diagnoses of other opportunistic diseases were most often specified/established.Conclusions. In HIV-positive inpatients of a phthisiopulmonary profile, tuberculosis infection prevails in the structure of opportunistic morbidity, 57.1 %. The largest proportion of patients consist cases with pulmonary tuberculosis (44 %), is also a large group (33 %), formed by patients with the extended lesion of the organs of the chest cavity.Positive results of traditional bacteriological studies were obtained in approximately half of the cases, which required an expansion of the diagnostic algorithm with the implementation of mini-invasive diagnostic procedures with biopsy of the affected tissues and subsequent histological examination.Analysis of the results of laboratory diagnostics of tuberculosis in cases of TB/HIV co-infection showed that the use of not only different microbiological research methods is most effective, but an important component in the diagnostic search is the histological examination of biopsy material.