Tuberculosis Diagnostics Research Articles

Recent advances in tuberculosis diagnostics in resource-limited settings.

Smear-negative and drug-resistant cases of tuberculosis (TB) disease necessitate the development of new diagnostic methods, especially in resource-limited settings. To improve the current TB situations, sensitive and specific TB point-of-care tests (POCTs) should be developed. This review addresses the current status of TB, novel diagnostic methodologies for TB, and the impact of those new diagnostics on TB control in such situations. Moreover, the perspective of TB management based on laboratory examinations is described. Smear microscopy with sputum samples is the only laboratory examination available in many resource-limited settings and is still used globally. Several nucleic acid amplification tests (NATs) have been developed. The World Health Organization (WHO) endorsed novel diagnostics based on NATs and updated their definition of a bacteriologically confirmed case requiring the biological specimen to be positive by smear microscopy, culture, or the WHO-recommended rapid diagnostic protocols. The use of new diagnostics increased the number of bacteriologically confirmed TB cases. Novel diagnostics are now available, but their sensitivity is still lower than that of conventional liquid culture method. To address the increasing incidence of TB, more resources including novel diagnostics as POCTs with higher sensitivity must be allocated to healthcare systems.

ОЦЕНКА ЭФФЕКТИВНОСТИ МОДИФИЦИРОВАННОГО ИФА-МЕТОДА ИДЕНТИФИКАЦИИ ПРОТИВОТУБЕРКУЛЕЗНЫХ АНТИТЕЛ ДЛЯ ПРОГНОЗА РАЗВИТИЯ И ДИАГНОСТИКИ ТУБЕРКУЛЕЗА У БОЛЬНЫХ ВИЧ-ИНФЕКЦИЕЙ

The objective of the study: modification of the standard IFA method aimed to detect antibodies against tuberculosis, assessment of its efficiency as a screening tool for prediction and diagnostics of tuberculosis in HIV patients. Subjects and methods. The modification of the standard IFA method aimed to assess the intensity of humoral anti-tuberculosis immune response included measurement of operational dilution of tested sera in order to enhance its diagnostic value. The modified method was used for the examination in the following groups: 85 active tuberculosis cases, 92 HIV patients with no clinical signs of tuberculosis, and 30 healthy donors. Results: it is possible to use the modified method in HIV positive people in order to detect those with the highest risk of tuberculosis among them; to provide early diagnostics of active tuberculosis, which is especially crucial at the advanced stages of HIV infection. This method cannot replace the classic methods of tuberculosis diagnostics and it is not recommended for mass screening in HIV negative persons.

Which attributes within target product profiles for tuberculosis diagnostics are the most important to focus on?

New diagnostic tools for tuberculosis (TB) are urgently needed. To guide investment decisions, sufficient information regarding which test attributes are the most important for users and decision makers interested in introducing TB diagnostics should be made available. To rank test attributes in a target product profile (TPP) in order of importance for a sputum smear replacement test for TB. An online survey was administered among 33 participants representing 14 of the 22 TB high-burden countries. Respondents included laboratory personnel, national TB program managers, donors, technical experts, patients and researchers. Participants were asked to rank 21 TPP test attributes in order of importance using a maximum-differential method that required ranking of relative trade-offs. Sensitivity was ranked as the most important test attribute, followed by maintenance/calibration, reagent kit storage/stability, sample preparation steps and time to results. Consulting widely regarding which TPP attributes are valued most by users and decision-makers involved in introducing TB diagnostics can assist TB test developers to prioritize their investments, and guide decision making if trade-offs are necessary.

The evolution of methods of diagnostics of male genitals tuberculosis

Мета дослідження: вивчення еволюції методів діагностики туберкульозу статевих органів чоловіків за останні десятиріччя. Матеріал і методи дослідження. Обстежено 467 чоловіків на туберкульоз статевих органів віком від 16 до 82 років (середній вік склав 49±14 року). Оцінювали симптоматику, дані анамнезу, клінічних, біохімічних і бактеріологічних аналізів, полімеразної ланцюгової реакції на ДНК мікобактерій туберкульозу, імунологічних досліджень, променевої діагностики: (сонографії, рентгенографії, мультиспіральної комп’ютерної томографії, магнітно-резонансної томографії, радіоізотопних) і ендоскопічних методів дослідження, з прицільною аспірацією і біопсією для здобуття біологічного матеріалу. Результати. У 372 (79,7%) пацієнтів з туберкульозом органів мошонки, у 305 (65,3%) діагностовано туберкульоз передміхурової залози та у 280 (59,9%) – сім’яних міхурців. У 94 (20,1%) виявлено туберкульоз внутрішньотазових статевих органів без залучання в процес органів мошонки, простатит діагностовано у 93 (19,9%) спостереженнях, а везикуліт – у 74 (15,8%) хворих. У 2 (2,2%) пацієнтів виявлено туберкульоз статевого члена. Алгоритм діагностики туберкульозу статевих органів чоловіків за останні десятиріччя зазнав змін: замість очищеного туберкуліну застосовували алерген туберкульозний рекомбінантний. З імунологічних методів використовували: визначення в крові протитуберкульозних антитіл по моноклональних антитілах до мікобактерій туберкульозу за допомогою ІФА і методи імунофенотипування з визначенням кількості CD4, CD8 клітин. Також досліджували інші поверхневі маркери Т-лімфоцитів за наявності у пацієнтів поєднання ТБ і ВІЛ інфекції. Провідне місце для візуалізації анатомії статевих органів чоловіків зайняли сонографічні дослідження з проведенням прицільної аспірації біологічних матеріалів і біопсії тканин. На перше місце серед методів верифікації мікобактерій туберкульозу вийшли молекулярно-генетичні дослідження біологічних матеріалів за допомогою ПЛР. Вивчення біоптатів тканин проводиться не лише з використанням класичної гістології, але і мікроскопії тканин на наявність кислотостійких бактерій і ПЛР. Також застосовували фіброуретроцистоскопію з катетеризацією сім’явиприскуючих проток і сім’яних міхурців. Висновки. Ці еволюційні зміни методів діагностики дозволили більш швидко, безпечно і точно обстежувати всі статеві органи чоловіків і виявляти ураження їх туберкульозом.

АБДОМИНАЛЬНЫЙ ТУБЕРКУЛЕЗ В РАБОТЕ ВРАЧА ОБЩЕЙ ПРАКТИКИ

Last years are marked by the increased number of cases of extra pulmonary localizations of tubercular process that are proved by the numerous publications. The diagnostics of these forms of tuberculosis is not easy because it requires a detailed examination of the patient. Cases of abdominal tuberculosis are among them. The article contains the data of modern medical literature on extra pulmonary forms of tuberculosis and information of clinical cases of posthumous diagnostics of tuberculosis of serous membranes of abdominal cavity and lungs.

Cost analysis of rapid diagnostics for drug-resistant tuberculosis

BackgroundGrowth-based drug susceptibility testing (DST) is the reference standard for diagnosing drug-resistant tuberculosis (TB), but standard time to result (TTR) is typically ≥ 3 weeks. Rapid tests can reduce that TTR to days or hours, but accuracy may be lowered.In addition to the TTR and test accuracy, the cost of a diagnostic test may affect whether it is adopted in clinical settings. We examine the cost-effectiveness of rapid diagnostics for extremely drug-resistant TB (XDR-TB) in three different high-prevalence settings.Methods1128 patients with confirmed TB were enrolled at clinics in Mumbai, India; Chisinau, Moldova; and Port Elizabeth, South Africa. Patient sputum samples underwent DST for first and second line TB drugs using 2 growth-based (MGIT, MODS) and 2 molecular (Pyrosequencing [PSQ], line-probe assays [LPA]) assays. TTR was the primary measure of effectiveness. Sensitivity and specificity were also evaluated. The cost to perform each test at each site was recorded and included test-specific materials, personnel, and equipment costs. Incremental cost-effectiveness ratios were calculated in terms of $/day saved. Sensitivity analyses examine the impact of batch size, equipment, and personnel costs.ResultsOur prior results indicated that the LPA and PSQ returned results in a little over 1 day. Mean cost per sample without equipment or overhead was $23, $28, $33, and $41 for the MODS, MGIT, PSQ, and LPA, respectively. For diagnosing XDR-TB, MODS was the most accurate, followed by PSQ, and LPA. MODS was quicker and less costly than MGIT. PSQ and LPA were considerably faster but cost more than MODS. Batch size and personnel costs were the main drivers of cost variation.ConclusionsMultiple factors must be weighed when selecting a test for diagnosis of XDR-TB. Rapid tests can greatly improve the time required to diagnose drug-resistant TB, potentially improving treatment success, and preventing the spread of XDR-TB. Faster time to result must be weighed against the potential for reduced accuracy, and increased costs.Trial registrationClinicalTrials.gov Identifier: NCT02170441.

Point of care diagnostics for tuberculosis

The goals of the End TB strategy, which aims to achieve a 90% reduction in tuberculosis (TB) incidence and a 95% reduction in TB mortality by 2035, will not be achieved without new tools to fight TB. These include improved point of care (POC) diagnostic tests that are meant to be delivered at the most decentralised levels of care where the patients make the initial contact with the health system, as well as within the community. These tests should be able to be performed on an easily accessible sample and provide results in a timely manner, allowing a quick treatment turnaround time of a few minutes or hours (in a single clinical encounter), hence avoiding patient loss-to-follow-up. There have been exciting developments in recent years, including the WHO endorsement of Xpert MTB/RIF, Xpert MTB/RIF Ultra, loop-mediated isothermal amplification (TB-LAMP) and lateral flow lipoarabinomannan (LAM). However, these tests have limitations that must be overcome before they can be optimally applied at the POC. Furthermore, worrying short- to medium-term gaps exist in the POC diagnostic test development pipeline. Thus, not only is better implementation of existing tools and algorithms needed, but new research is required to develop new POC tests that allow the TB community to truly make an impact and find the “missed TB cases”.

Potential Application of Digitally Linked Tuberculosis Diagnostics for Real-Time Surveillance of Drug-Resistant Tuberculosis Transmission: Validation and Analysis of Test Results.

BackgroundTuberculosis (TB) is the highest-mortality infectious disease in the world and the main cause of death related to antimicrobial resistance, yet its surveillance is still paper-based. Rifampicin-resistant TB (RR-TB) is an urgent public health crisis. The World Health Organization has, since 2010, endorsed a series of rapid diagnostic tests (RDTs) that enable rapid detection of drug-resistant strains and produce large volumes of data. In parallel, most high-burden countries have adopted connectivity solutions that allow linking of diagnostics, real-time capture, and shared repository of these test results. However, these connected diagnostics and readily available test results are not used to their full capacity, as we have yet to capitalize on fully understanding the relationship between test results and specific rpoB mutations to elucidate its potential application to real-time surveillance.ObjectiveWe aimed to validate and analyze RDT data in detail, and propose the potential use of connected diagnostics and associated test results for real-time evaluation of RR-TB transmission.MethodsWe selected 107 RR-TB strains harboring 34 unique rpoB mutations, including 30 within the rifampicin resistance–determining region (RRDR), from the Belgian Coordinated Collections of Microorganisms, Antwerp, Belgium. We subjected these strains to Xpert MTB/RIF, GenoType MTBDRplus v2.0, and Genoscholar NTM + MDRTB II, the results of which were validated against the strains’ available rpoB gene sequences. We determined the reproducibility of the results, analyzed and visualized the probe reactions, and proposed these for potential use in evaluating transmission.ResultsThe RDT probe reactions detected most RRDR mutations tested, although we found a few critical discrepancies between observed results and manufacturers’ claims. Based on published frequencies of probe reactions and RRDR mutations, we found specific probe reactions with high potential use in transmission studies: Xpert MTB/RIF probes A, Bdelayed, C, and Edelayed; Genotype MTBDRplus v2.0 WT2, WT5, and WT6; and Genoscholar NTM + MDRTB II S1 and S3. Inspection of probe reactions of disputed mutations may potentially resolve discordance between genotypic and phenotypic test results.ConclusionsWe propose a novel approach for potential real-time detection of RR-TB transmission through fully using digitally linked TB diagnostics and shared repository of test results. To our knowledge, this is the first pragmatic and scalable work in response to the consensus of world-renowned TB experts in 2016 on the potential of diagnostic connectivity to accelerate efforts to eliminate TB. This is evidenced by the ability of our proposed approach to facilitate comparison of probe reactions between different RDTs used in the same setting. Integrating this proposed approach as a plug-in module to a connectivity platform will increase usefulness of connected TB diagnostics for RR-TB outbreak detection through real-time investigation of suspected RR-TB transmission cases based on epidemiologic linking.

Genotypic drug resistance using whole-genome sequencing of Mycobacterium tuberculosis clinical isolates from North-western Tanzania

BackgroundDrug resistant Tuberculosis (TB) is considered a global public health threat. Whole-genome sequencing (WGS) is a new technology for tuberculosis (TB) diagnostics and is capable of providing rapid drug resistance profiles and genotypes for epidemiologic surveillance. Therefore, we used WGS to determine genotypic drug resistance profiles and genetic diversity of drug resistant Mycobacterium tuberculosis isolates from Mwanza, North-western Tanzania. MethodsA cross-sectional study was conducted at the Bugando Medical Center (BMC) from September 2014 to June 2015. Consecutively, smear-positive newly diagnosed TB patients aged ≥18 years were enrolled. Sputum samples were cultured on Löwenstein-Jensen (LJ) slants. Mycobacterial genomic DNA was extracted for WGS to determine drug resistant mutations for first and second line drugs as well as the spoligotypes. ResultsA total of 78 newly diagnosed patients with pulmonary TB with a median age of 37 [IQR: 30–46] years were enrolled. Of these, 57.8% (45/74) were males and 34.6% (27/78) were HIV positive. Mycobacterium tuberculosis genomic DNA for WGS was obtained from isolates in 74 (94.9%) patients. Of the 74 isolates, six (8.1%) isolates harbored mutations for resistance to at least one drug. The resistance to the drugs was isoniazid 3/74 (4.1%), rifampicin mono-resistant 2/74 (2.7%), ethambutol 2/74 (2.7%) and streptomycin 1/74 (1.4%). None was isoniazid mono-resistant. Of the 74 only one (1.4%) patient had MDR-TB. The resistance to ethionamide, the second line drug, was detected in one patient (1.4%). None was resistant to pyrazinamide, fluoroquinolones, kanamycin, amikacin, or capreomycin. The mutations detected were mabA-inhA promoter region C(-15)T and katG Ser513Thr for isoniazid; rpoB His526Leu and rpoB Ser531Leu for rifampicin; embB Met306Val and embB Met306Ile for ethambutol; rpsL Lys43Arg for streptomycin; and mabA-inhA promoter region C(-15)T for ethionamide. The spoligotypes of the drug resistant Mycobacterium tuberculosis were distinct to all six isolates and belonged to T1, T2, T3-ETH, CAS1-DELHI, EAI5 and LAM11-ZWE lineages. ConclusionThe genetic drug resistance profile of Mycobacterium tuberculosis isolates from North-western Tanzania comprises of the common previously reported mutations. The prevalence of resistance to first and second line drugs including MDR-TB is low. Six drug resistant strains exhibited different spoligotypes, suggesting limited transmission of drug resistant strains in the region.

TB diagnosis from the Dark Ages to fluorescence.

Effective treatment and eradication of tuberculosis requires highly sensitive and specific, easy-to-use detection methods. New advances in molecular tools and technology are driving improved tuberculosis diagnostics, including ways to rapidly identify highly drug-resistant infections.

Tuberculosis diagnostics in 2018

The National Tuberculosis Advisory Committee (NTAC) is publishing revised guidelines for Australian laboratories performing mycobacteriology testing. This revision has been through an extensive consultative peer-review process involving the Mycobacterium Reference Laboratory (MRL) network, the Mycobacterium Special Interest Group (SIG) of the Australian Society for Microbiology (ASM), the Royal College of Pathologists of Australasia (RCPA) and other relevant national bodies.

Striving for increased sensitivity by repeat testing – Why repeat testing is not always the answer

Introduction: Molecular methods reduce turn-around times in Mycobacterium tuberculosis (MTB) diagnostics. Our laboratory performs an in-house MTB assay testing 2 targets in duplicate (IS6110 and HSP).

Empiric tuberculosis treatment in South African primary health care facilities - for whom, where, when and why: Implications for the development of tuberculosis diagnostic tests.

BackgroundThe extent and circumstances under which empiric tuberculosis (TB) treatment (treatment without microbiological confirmation at treatment initiation) is administered in primary health care settings in South Africa are not well described.MethodsWe used data from a pragmatic evaluation of Xpert MTB/RIF in which persons undergoing TB investigations by PHC nurses were followed for six months. Following Xpert or smear-microscopy at enrolment, investigations for tuberculosis were undertaken at the discretion of health care workers. We identified persons whose TB treatment was initiated empirically (no microbiological confirmation at time of treatment initiation at a primary health care facility) and describe pathways to treatment initiation.ResultsOf 4665 evaluable participants, 541 persons were initiated on treatment of whom 167 (31%) had negative sputum tests at enrolment. Amongst these 167, the median number of participant visits to health care providers prior to treatment initiation was 3 (interquartile range [IQR] 2–4). Chest radiography, sputum culture or hospital referral was done in 106/167 (63%). Reasons for TB treatment start were: 1) empiric (n = 82, 49%); 2) a positive laboratory test (n = 49, 29%); 3) referral and treatment start at a higher level of care (n = 28, 17%); and 4) indeterminable (n = 8, 5%). Empiric treatment accounted for 15% (82/541) of all TB treatment initiations and 1.7% (82/4665) of all persons undergoing TB investigations. Chest radiography findings compatible with TB (63/82 [77%]) were the basis for treatment initiation amongst the majority of empirically treated participants. Microbiological confirmation of TB was subsequently obtained for 11/82 (13%) empirically-treated participants. Median time to empiric treatment start was 3.9 weeks (IQR 1.4–11 weeks) after enrolment.ConclusionUncommon prescription of empiric TB treatment with reliance on chest radiography in a nurse-managed programme underscores the need for highly sensitive TB diagnostics suitable for point-of-care, and strong health systems to support TB diagnosis in this setting.

The Evolution of Methods of Diagnostics of Male Genitals Tuberculosis

The Evolution of Methods of Diagnostics of Male Genitals Tuberculosis

Detection of tuberculosis in patients with the use of portable SPR device

Tuberculosis (TB) is still one of the important causes of death worldwide. Its detection is challenging and new tools for TB diagnostics are highly needed. In this work, we investigated a possibility of using surface plasmon resonance (SPR) phenomenon in detection of TB bacteria in sputum. For this purpose we designed a portable SPR apparatus. We compared its performance with a standard desktop SPR platform designed to work in laboratory by measuring response to Ag85 – TB secretory protein. We examined samples of suspended Mycobacterium tuberculosis cultures and sputum samples of TB patients. The device was able to detect M. tuberculosis secretory protein (Ag85) in concentration of 10 ng/ml which was comparable to the desktop SPR equipment. It has been also able to detect TB bacteria cultures in concentration of 1*104 cfu/ml with no significant interfering response from two other bacteria species. Finally, detection of bacteria in sputum of confirmed tuberculosis patients has been demonstrated.

OMNIgene.SPUTUM suppresses contaminants while maintaining Mycobacterium tuberculosis viability and obviates cold-chain transport.

Tuberculosis (TB) diagnostics are centralised, requiring long-distance transportation of specimens in most resource-limited settings. We evaluated the ability of OMNIgene.SPUTUM (OM-S) to obviate cold-chain transport of TB specimens.A two-arm (same-day and after 5 days sample processing) study was conducted to assess contamination rates and Mycobacterium tuberculosis viability in OM-S-treated samples against the standard decontamination procedure (SDP) in Mozambique, using Lowenstein Jensen (LJ) and mycobacterial growth indicator tube (MGIT) culture and molecular bacterial load assay.270 specimens were processed using OM-S and SDP in same-day and 5-day arms. Contamination was lower in OM-S-treated than SDP-treated cultures: 12% versus 15% and 2% versus 27% in the same-day and 5-day arms, respectively. M. tuberculosis recovery in OM-S-treated LJ cultures was 10% and 56% higher in the same-day and 5-day arms, respectively, than SDP-treated cultures, but lower in MGIT (52% and 28% lower in the same-day and 5-day arms, respectively). M. tuberculosis viable count was 1log estimated CFU·mL−1 lower in 5-day OM-S-treated sputa. OM-S was more effective at liquefying sputum with a shorter sample processing time: 22 min for culture.OM-S is simple to use and has demonstrated a high potency to suppress contaminants, maintenance of viability at ambient temperatures and higher M. tuberculosis recovery, particularly in the solid LJ cultures. Optimisation of OM-S to achieve higher MGIT culture positivity and shorter time to result will increase its application and utility in the clinical management of TB.

Tuberkulózissal összefüggésbe hozható endocranialis csontelváltozások vizsgálata a Robert J. Terry Anatomical Skeletal Collection-ben (Washington, DC, USA)

Despite significant advances in the fight against tuberculosis (TB), it still presents a global health emergency. Therefore, a renewed interest and funding to the research of the disease and of its aetiological agents, including the palaeopathological diagnostics for TB, has sparked since the late 20th century to eliminate or at least control TB in the future. Traditionally, the palaeopathological diagnosis of TB relies on the identification of pathological lesions in the skeleton. Although a number of endocranial bony alterations, namely abnormally pronounced digital impressions (APDIs), periosteal appositions (PAs), abnormal blood vessel impressions (ABVIs), and granular impressions (GIs) have been attributed to TB in the palaeopathological literature, the diagnostic value of these lesions has more recently been questioned, as their precise aetiology is still a matter of controversy, and similar or even the same morphological features can be found in non-TB-related cases. In the last three decades, the Terry Collection has been used to define and refine palaeopathological diagnostic criteria for TB, however, the possible TB-associated endocranial alteration types were beyond the scope of the aforementioned research projects.
 To expand our knowledge and understanding about the development of the four probable TB-related endocranial alteration types and to improve their palaeopathological interpretation, as well as to contribute to strengthening their diagnostic value in the identification of TB in human osteoarchaeological material, a detailed investigation was performed on all individuals recorded to have died of TB in the Terry Collection (TB group), and on a control group consisting of randomly selected specimens from the remaining skeletons of the Terry Collection, identified to have died of causes other than TB (NTB group). The evaluation of the selected skeletons focused on the macromorphological characteristics and on the frequencies of the possible TB-associated endocranial alteration types, as well as of their co-occurrence with each other and with non-endocranial bony changes probably related to TB.
 All the examined endocranial alteration types, as well as their association with each other and with non-endocranial lesions occurred significantly more frequently in the TB group compared to the NTB group; therefore, all of them can be used as diagnostic criteria for TB in the palaeopathological practice, especially when they simultaneously occur with each other and/or with probable TB-related non-endocranial bony changes. Our findings fit in with those of previous studies concerning the specificity of the examined lesions: APDIs, PAs, and ABVIs cannot be considered as pathognomonic features of TB and have a weaker diagnostic value compared to GIs, which are TB-specific alterations. In summary, our results contribute to facilitating the establishment of a more reliable and accurate palaeopathological diagnosis of TB.

Optimization of the present-day diagnostics of tuberculosis of the upper respiratory tract and ears

This study included a total of 365 patients presenting with tuberculosis of the respiratory organs followed up based at the the Republican TB dispensary. All the patients underwent the comprehensive clinical and laboratory examination with the use of the diagnostic algorithm designed for the otorhinolaryngological examination of the patients suffering from respiratory tuberculosis. The upper respiratory tract tuberculosis was diagnosed in 46 (12.6%) of the examined patients. Laryngeal tuberculosis was documented in 44 (12.1%) patients and middle ear tuberculosis in 2 (0.5%) patients. The most informative method for the diagnostics of tuberculosis of the upper respiratory tract and the ears was a histological study that allowed to reveal more than 70% of the total number of the cases. However, this method of does not reliably confirm or exclude the diagnosis of tuberculous of the upper respiratory tract and ears in all the patients. The accurate diagnostics with the elucidation of the specific character of the pathological process is possible only on the basis of a thorough investigation and comprehensive examination of the suspected patients.

Tuberculous Spondylitis, 14 Years’ Experience of a Tertiary Care Center in Saudi Arabia

Background: Spinal Tuberculosis is the most common and dangerous form of skeletal tuberculosis. It has the potential for serious morbidity, including permanent neurologic deficits and severe deformity. The aim of this study is to review spinal Tuberculosis (TB) cases in our tertiary care center and evaluate it from different aspects, which may provide great support to the clinical decisions of this disease. Methods: The study was a retrospective charts review of all adult spinal TB patients who were evaluated at King Abdulaziz Medical City, Riyadh, from January 2001 to March 2015. The inclusion of cases will need to meet a specific case definition. Patients demography, presenting symptoms and signs, and radiological and microbiological data for all the patients were collected and reviewed. Results: A total of 61 cases screened charts were included according to the case definition. 59% were female, and the mean age was 51.3 years. The most presenting symptom was back pain (85%), followed by lower limbs weakness and lower limbs pain. The average duration of symptoms was 170 days. The average hospital stay was 41.4 days. On physical examination, about half of the patients had bilateral lower limbs weakness. Acute phase reactants like C-reactive protein (CRP) and Erythrocyte sedimentation rate (ESR) were elevated, 97% and 92% respectively, however leukocytosis was not common. Out of all the patients who had a biopsy done (59 patients), 51 patients (86%) had positive AFB culture. MTB PCR was done from spine biopsy in 16 patients, and 81% were positive. Out of 53 tissue specimens, histopathology showed 45% necrotizing granuloma, 21% non-necrotizing granuloma, and 34% non-specific inflammation. Imaging (either CT scan or MRI) was performed on the patients at the time of presentation, and the most common signs seen in both were vertebral bone destruction (95%, 80%) and perivertebral collections (70%, 84%). The thoracic and lumbar vertebrae were the most common involved locations. Thirty-one patients had both modalities done (CT and MRI), and spinal compression was seen on MRI in 68% of the cases compared to 36% on the CT scan. All the patients received the first line therapy with some individual adjustment and only 39% (27 patients) underwent surgery. Conclusion: Spinal Tuberculosis is a chronic presentation illness with a non-specific clinical picture. Interventional diagnostics is the best current modality to reach a confirmatory diagnosis. The gold standard for confirming TB diagnosis probably will remain cultures in addition to early utilization of molecular TB diagnostics. Time for diagnosis of Spinal Tuberculosis is delayed despite improvement in diagnostics tests. Medical treatment is the major solution of uncomplicated spinal TB.

Evaluation of a Urine-Based Rapid Molecular Diagnostic Test with Potential to Be Used at Point-of-Care for Pulmonary Tuberculosis: Cape Town Cohort

Tuberculosis (TB) diagnosis among sputum-scarce patients is time consuming. Thus, a nonsputum diagnostic alternative is urgently needed. The Mycobacterium tuberculosis-specific transrenal (Tr) DNA from urine is a potential target for TB diagnostics. In this study, a new urine-based Tr-DNA molecular assay was evaluated for diagnosis of pulmonary tuberculosis among 428 adults suspected of having pulmonary TB (164 HIV positive, 263 HIV negative) from Cape Town, South Africa. Tr-DNA was isolated from 4 mL of EDTA urine, and a rapid, double-stranded, primer-based PCR method was performed targeting the Mycobacterium tuberculosis-specific direct repeat region. Each Tr-DNA eluate was tested in triplicate using an automated molecular analyzer with controls included in each test. With liquid culture used as the gold standard, the Tr-DNA assay showed sensitivity of 42.9% (n = 75/175; 95% CI, 35.4%-50.5%) and specificity of 88.6% (n = 210/237; 95% CI, 83.9%-92.4%). Among HIV-infected patients with TB, sensitivity and specificity were 45.2% and 89.0%, respectively. The combination of smear microscopy and Tr-DNA increased the sensitivity to 83.8% (smear microscopy alone, 75.1%), with 96.6% specificity. This study indicates that Tr-DNA has a moderate specificity with low sensitivity for diagnosis of pulmonary TB. Despite low sensitivity, this diagnostic test may have potential in combination with smear microscopy to support TB diagnosis in HIV-endemic regions, where sputum-scarce patients are common.