tb diagnostics
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Biosensors ◽  
2022 ◽  
Vol 12 (1) ◽  
pp. 29
Author(s):  
Cristina Gordillo-Marroquín ◽  
Héctor J. Sánchez-Pérez ◽  
Anaximandro Gómez-Velasco ◽  
Miguel Martín ◽  
Karina Guillén-Navarro ◽  
...  

Despite its reduced sensitivity, sputum smear microscopy (SSM) remains the main diagnostic test for detecting tuberculosis in many parts of the world. A new diagnostic technique, the magnetic nanoparticle-based colorimetric biosensing assay (NCBA) was optimized by evaluating different concentrations of glycan-functionalized magnetic nanoparticles (GMNP) and Tween 80 to improve the acid-fast bacilli (AFB) count. Comparative analysis was performed on 225 sputum smears: 30 with SSM, 107 with NCBA at different GMNP concentrations, and 88 with NCBA-Tween 80 at various concentrations and incubation times. AFB quantification was performed by adding the total number of AFB in all fields per smear and classified according to standard guidelines (scanty, 1+, 2+ and 3+). Smears by NCBA with low GMNP concentrations (≤1.5 mg/mL) showed higher AFB quantification compared to SSM. Cell enrichment of sputum samples by combining NCBA-GMNP, incubated with Tween 80 (5%) for three minutes, improved capture efficiency and increased AFB detection up to 445% over SSM. NCBA with Tween 80 offers the opportunity to improve TB diagnostics, mainly in paucibacillary cases. As this method provides biosafety with a simple and inexpensive methodology that obtains results in a short time, it might be considered as a point-of-care TB diagnostic method in regions where resources are limited.


2022 ◽  
Vol 26 (1) ◽  
pp. 57-64
Author(s):  
M. Chipinduro ◽  
C. Timire ◽  
J. Chirenda ◽  
R. Matambo ◽  
E. Munemo ◽  
...  

BACKGROUND: We conducted the first national TB prevalence survey to provide accurate estimates of bacteriologically confirmed pulmonary TB disease among adults aged ≥15 years in 2014.METHODS: A TB symptoms screen and chest X-ray (CXR) were used to identify presumptive TB cases who submitted two sputum samples for smear microscopy, liquid and solid culture. Bacteriological confirmation included acid-fast bacilli smear positivity confirmed using Xpert® MTB/RIF and/or culture. Prevalence estimates were calculated using random effects logistic regression with multiple imputations and inverse probability weighting.RESULTS: Of 43,478 eligible participants, 33,736 (78%) were screened; of these 5,820 (17%) presumptive cases were identified. There were 107 (1.9%) bacteriologically confirmed TB cases, of which 23 (21%) were smear-positive. The adjusted prevalences of smear-positive and bacteriologically confirmed TB disease were respectively 82/100,000 population (95% CI 47–118/100,000) and 344/100,000 (95% CI 268–420/100,000), with an overall all-ages, all-forms TB prevalence of 275/100,000 population (95% CI 217–334/100,000). TB prevalence was higher in males, and age groups 35–44 and ≥65 years. CXR identified 93/107 (87%) cases vs. 39/107 (36%) using the symptom screen.CONCLUSION: Zimbabwe TB disease prevalence has decreased relative to prior estimates, possibly due to increased antiretroviral therapy coverage and successful national TB control strategies. Continued investments in TB diagnostics for improved case detection are required.


2021 ◽  
Vol 11 (4) ◽  
pp. 196-201
Author(s):  
K. Zvinoera ◽  
I. D. Olaru ◽  
P. Khan ◽  
J. Mutsvangwa ◽  
C. M. Denkinger ◽  
...  

SETTING: Governmental health facilities performing TB diagnostics in Manicaland, Zimbabwe.OBJECTIVE: To investigate the effect of making Xpert® MTB/RIF the primary TB diagnostic for all patients presenting with presumptive TB on 1) the number of samples investigated for TB, 2) the proportion testing TB-positive, and 3) the proportion of unsuccessful results over time.DESIGN: This retrospective study used data from GeneX-pert downloads, laboratory registers and quality assurance reports between 1 January 2017 and 31 December 2018.RESULTS: The total number of Xpert tests performed in Manicaland increased from 3,967 in the first quarter of 2017 to 7,011 in the last quarter of 2018. Mycobacterium tuberculosis DNA was detected in 4.9–8.6% of the samples investigated using Xpert, with a higher yield in 2017 than in 2018. The overall proportion of unsuccessful Xpert assays due to “no results”, errors and invalid results was 6.3%, and highly variable across sites.CONCLUSION: Roll out of more sensitive TB diagnostics does not necessarily result in an increase of microbiologically confirmed TB diagnosis. While the number of samples tested using Xpert increased, the proportion of TB-positive tests decreased. GeneXpert soft- and hardware infrastructure needs to be strengthened to reduce the rate of unsuccessful assays and therefore, costs and staff time.


2021 ◽  
Vol 17 (12) ◽  
pp. e1010061
Author(s):  
Laura Olbrich ◽  
Lisa Stockdale ◽  
Robindra Basu Roy ◽  
Rinn Song ◽  
Luka Cicin-Sain ◽  
...  

Over 1 million children develop tuberculosis (TB) each year, with a quarter dying. Multiple factors impact the risk of a child being exposed to Mycobacterium tuberculosis (Mtb), the risk of progressing to TB disease, and the risk of dying. However, an emerging body of evidence suggests that coinfection with cytomegalovirus (CMV), a ubiquitous herpes virus, impacts the host response to Mtb, potentially influencing the probability of disease progression, type of TB disease, performance of TB diagnostics, and disease outcome. It is also likely that infection with Mtb impacts CMV pathogenesis. Our current understanding of the burden of these 2 diseases in children, their immunological interactions, and the clinical consequence of coinfection is incomplete. It is also unclear how potential interventions might affect disease progression and outcome for TB or CMV. This article reviews the epidemiological, clinical, and immunological literature on CMV and TB in children and explores how the 2 pathogens interact, while also considering the impact of HIV on this relationship. It outlines areas of research uncertainty and makes practical suggestions as to potential studies that might address these gaps. Current research is hampered by inconsistent definitions, study designs, and laboratory practices, and more consistency and collaboration between researchers would lead to greater clarity. The ambitious targets outlined in the World Health Organization End TB Strategy will only be met through a better understanding of all aspects of child TB, including the substantial impact of coinfections.


2021 ◽  
Vol 25 (12) ◽  
pp. 1019-1027
Author(s):  
I. Chikovani ◽  
N. Shengelia ◽  
N. Marjanishvili ◽  
T. Gabunia ◽  
I. Khonelidze ◽  
...  

BACKGROUND: Patient-centred care along with optimal financing of inpatient and outpatient services are the main priorities of the Georgia National TB Programme (NTP). This paper presents TB diagnostics and treatment unit cost, their comparison with NTP tariffs and how the study findings informed TB financing policy.METHODS: Top-down (TD) and bottom-up (BU) mean unit costs for TB interventions by episode of care were calculated. TD costs were compared with NTP tariffs, and variations in these and the unit costs cost composition between public and private facilities was assessed.RESULTS: Outpatient interventions costs exceeded NTP tariffs. Unit costs in private facilities were higher compared with public providers. There was very little difference between per-day costs for drug-susceptible treatment and NTP tariffs in case of inpatient services. Treatment day financing exceeded actual costs in the capital (public facility) for drug-resistant TB, and this was lower in the regions.CONCLUSION: Use of reliable unit costs for TB services at policy discussions led to a shift from per-day payment to a diagnosis-related group model in TB inpatient financing in 2020. A next step will be informing policy decisions on outpatient TB care financing to reduce the existing gap between funding and costs.


Author(s):  
Derek T. Armstrong ◽  
Erin A. Tacheny ◽  
Gene Olinger ◽  
Ryan Howard ◽  
M. Megan Lemmon ◽  
...  

The SARS-CoV-2 pandemic has strained manufacturing capacity worldwide resulting in significant shortages of laboratory supplies both directly and indirectly. Such shortages include probe-based kits for detection of the M. tuberculosis complex from positive liquid broth cultures. These shortages and possible loss of this particular assay have consequences for laboratory testing algorithms and public health in the United States. As there are no FDA approved, commercially available options that currently exist which could immediately fill this gap, laboratories must identify alternatives and plan for modifying current testing algorithms to accommodate this change.


2021 ◽  
Vol 6 (8) ◽  
pp. e005357
Author(s):  
Nyanda Elias Ntinginya ◽  
Davis Kuchaka ◽  
Fred Orina ◽  
Ivan Mwebaza ◽  
Alphonce Liyoyo ◽  
...  

BackgroundEarly access to diagnosis is crucial for effective management of any disease including tuberculosis (TB). We investigated the barriers and opportunities to maximise uptake and utilisation of molecular diagnostics in routine healthcare settings.MethodsUsing the implementation of WHO approved TB diagnostics, Xpert Mycobacterium tuberculosis/rifampicin (MTB/RIF) and Line Probe Assay (LPA) as a benchmark, we evaluated the barriers and how they could be unlocked to maximise uptake and utilisation of molecular diagnostics.ResultsHealth officers representing 190 districts/counties participated in the survey across Kenya, Tanzania and Uganda. The survey findings were corroborated by 145 healthcare facility (HCF) audits and 11 policy-maker engagement workshops. Xpert MTB/RIF coverage was 66%, falling behind microscopy and clinical diagnosis by 33% and 1%, respectively. Stratified by HCF type, Xpert MTB/RIF implementation was 56%, 96% and 95% at district, regional and national referral hospital levels. LPA coverage was 4%, 3% below culture across the three countries. Out of 111 HCFs with Xpert MTB/RIF, 37 (33%) used it to full capacity, performing ≥8 tests per day of which 51% of these were level five (zonal consultant and national referral) HCFs. Likewise, 75% of LPA was available at level five HCFs. Underutilisation of Xpert MTB/RIF and LPA was mainly attributed to inadequate—utilities, 26% and human resource, 22%. Underfinancing was the main reason underlying failure to acquire molecular diagnostics. Second to underfinancing was lack of awareness with 33% healthcare administrators and 49% practitioners were unaware of LPA as TB diagnostic. Creation of a national health tax and decentralising its management was proposed by policy-makers as a booster of domestic financing needed to increase access to diagnostics.ConclusionOur findings suggest higher uptake and utilisation of molecular diagnostics at tertiary level HCFs contrary to the WHO recommendation. Country-led solutions are crucial for unlocking barriers to increase access to diagnostics.


Author(s):  
Shruti Srivastava ◽  
Philip Raj Abraham ◽  
Sangita Mukhopadhyay

Tuberculosis (TB) has been plaguing human civilization for centuries, and currently around one-third of the global population is affected with TB. Development of novel intervention tools for early diagnosis and therapeutics against Mycobacterium tuberculosis (M.tb) is the main thrust area in today’s scenario. In this direction global efforts were made to use aptamers, the chemical antibodies as tool for TB diagnostics and therapeutics. This review describes the various aptamers introduced for targeting M.tb and highlights the need for development of novel aptamers to selectively target virulent proteins of M.tb for vaccine and anti-TB drugs. The objective of this review is to highlight the diagnostic and therapeutic application of aptamers used for tuberculosis. The discovery of aptamers, SELEX technology, different types of SELEX development processes, DNA and RNA aptamers reported for diseases and pathogenic agents as well have also been described in detail. But the emphasis of this review is on the development of aptamers which can block the function of virulent mycobacterial components for developing newer TB vaccine candidates and/or drug targets. Aptamers designed to target M.tb cell wall proteins, virulent factors, secretory proteins, or combination could orchestrate advanced diagnosis and therapeutic measures for tuberculosis.


Author(s):  
Emily MacLean ◽  
Ruvandhi R. Nathavitharana

A highly accurate, non-sputum based test for tuberculosis (TB) detection is a key priority for the field of TB diagnostics. A recent study in Journal of Clinical Microbiology by Oreskovic and colleagues (J Clin Microbiol 59:e00074-21, 2021, https://doi.org/10.1128/JCM.00074-21) reports the performance of an optimized urine cell-free DNA (cfDNA) using sequence-specific purification combined with short-target PCR to improve the accuracy of TB detection. Their retrospective clinical study utilized frozen urine samples (n=73) from study participants diagnosed with active pulmonary TB in South Africa and the USA in an early phase validation study. Overall, this cfDNA technique detected TB with sensitivity of 83.7% (95% CI:71.0-91.5) and specificity of 100% (95% CI:86.2-100), which meet the World Health Organization’s published performance criteria. Sensitivity was 73.3% in people without HIV (95% CI:48.1-89.1) and 76% in people with smear negative TB (95% CI:56.5-88.5). In this commentary, we discuss the results of this optimized urine TB cfDNA assay within the larger context of TB diagnostics and pose additional questions for further research.


Author(s):  
Ji Young Hong ◽  
Ahreum Kim ◽  
So Yeong Park ◽  
Sang-Nae Cho ◽  
Hazel M. Dockrell ◽  
...  

BackgroundThe Beijing strain of Mycobacterium tuberculosis (M. tb) has been most frequently isolated from TB patients in South Korea, and the hyper-virulent Beijing/K genotype is associated with TB outbreaks. To examine the diagnostic potential of Beijing/K-specific peptides, we performed IFN-γ release assays (IGRA) using a MTBK antigen tube containing Beijing/K MTBK_24800, ESAT-6, and CFP-10 peptides in a cohort studied during a school TB outbreak.MethodsA total of 758 contacts were investigated for M. tb infection, and 43 contacts with latent TB infection (LTBI) and 25 active TB patients were enrolled based on serial screening with QuantiFERON-TB Gold In-Tube tests followed by clinical examinations. Blood collected in MTBK antigen tubes was utilized for IGRA and multiplex cytokine bead arrays. Immune responses were retested in 24 patients after TB treatment, and disease progression was investigated in subjects with LTBI.ResultsTotal proportions of active disease and LTBI during the outbreak were 3.7% (28/758) and 9.2% (70/758), respectively. All clinical isolates had a Beijing/K M. tb genotype. IFN-γ responses to the MTBK antigen identified M. tb infection and distinguished between active disease and LTBI. After anti-TB treatment, IFN-γ responses to the MTBK antigen were significantly reduced, and strong TNF-α responses at diagnosis were dramatically decreased.ConclusionsMTBK antigen-specific IFN-γ has diagnostic potential for differentiating M. tb infection from healthy controls, and between active TB and LTBI as well. In addition, TNF-α is a promising marker for monitoring therapeutic responses. These data provide informative readouts for TB diagnostics and vaccine studies in regions where the Beijing/K strain is endemic.


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