Cost-effectiveness in the diagnosis of tuberculosis: choices in developing countries

Tuberculosis remains one of the major causes of global death from a single infectious agent. This situation is worsened by the HIV/AIDS pandemic because one-third of HIV/AIDS patients are co-infected with Mycobacterium tuberculosis. Failure to control the spread of tuberculosis is largely due to our inability to detect and treat all infectious cases of pulmonary tuberculosis in a timely manner, allowing continued M. tuberculosis transmission within communities. Diagnosis of tuberculosis can be made using indirect and direct methods. The indirect tests, such as interferon-gamma release assays, provide a new diagnostic method for M. tuberculosis infection, but do not discriminate between infection and active disease. The most common direct method for diagnosing TB worldwide is sputum smear microscopy (developed more than 100 years ago), where bacteria are observed in sputum samples examined under a microscope. In countries with more developed laboratory capacities, cases of tuberculosis may also be diagnosed using culture methods (the current gold standard) or, increasingly, using rapid molecular tests. In this review, we discuss the traditional methods for the diagnosis of tuberculosis. We also discuss other inexpensive assays that can be used to detect the presence of M. tuberculosis.

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Improved Diagnosis of Pulmonary Tuberculosis using Bleach (Sodium hypochlorite) Concentration Technique at Tertiary Care Hospital

Nepal Journal of Health Sciences ◽

10.3126/njhs.v1i2.42371 ◽

2021 ◽

Vol 1 (2) ◽

pp. 15-22

Author(s):

Saroj Kumar Thakur ◽

Vishvesh Prakashchandra Bansal ◽

Jyotsna Mishra ◽

M.P. Bansal ◽

Iswari Sapkota ◽

...

Keyword(s):

Pulmonary Tuberculosis ◽

Sodium Hypochlorite ◽

Direct Method ◽

Tertiary Care ◽

Sputum Smear ◽

Smear Microscopy ◽

Care Hospital ◽

Case Detection ◽

Acid Fast Bacilli ◽

Concentration Method

Introduction: In the Revised National Tuberculosis Control Program (RNTCP), microscopic examination of sputum for acid-fast bacilli (AFB) is currently the backbone for the diagnosis of pulmonary tuberculosis. Studies have shown liquefaction and concentration of sputum by 5% sodium hypochlorite is useful in providing increased sensitivity and safety for the handling of specimens. Objective: To assess the utility of the 5% Sodium hypochlorite concentration method in increasing the sensitivity of smear microscopy for detection of AFB for diagnosis of pulmonary tuberculosis. Methods: The study included a total of 1000 sputum samples from 500 patients with suspected pulmonary tuberculosis. Direct smears were prepared from the sputum samples as per RNTCP guidelines. The remaining sputum was used for bleach concentration and smears prepared from the concentrated material. Both smears were stained by Ziehl-Neelsen staining and screened for acid-fast bacilli and graded according to the RNTCP guidelines. Results: A total of 158 samples (15.8%) from 89 patients were positive by a routine direct method whereas by concentration method 236 samples (23.6%) from 143 patients were found positive diagnosing additional 54 patients. The gain in sputum smear positivity of 7.8% over the routine method is highly significant (p=0.0000, χ2= 270) with a 10.8% increase in case detection. Conclusions: Improvement in the sensitivity of smears microscopy will be useful in case detection of tuberculosis especially in resource-poor countries. The increased positivity of microscopy by bleach method indicates that would prove useful if included in the RNTCP to improve case detection. Keywords: Concentration; smear positivity; sodium hypochlorite; tuberculosis.

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Aptamer-Based Diagnostic Systems for the Rapid Screening of TB at the Point-of-Care

Diagnostics ◽

10.3390/diagnostics11081352 ◽

2021 ◽

Vol 11 (8) ◽

pp. 1352

Author(s):

Darius Riziki Martin ◽

Nicole Remaliah Sibuyi ◽

Phumuzile Dube ◽

Adewale Oluwaseun Fadaka ◽

Ruben Cloete ◽

...

Keyword(s):

Low Income ◽

Point Of Care ◽

Health Care Systems ◽

Cost Effective ◽

Rapid Screening ◽

Low Income Countries ◽

Sputum Smear ◽

Diagnostic Systems ◽

Molecular Tests ◽

Rapid Tests

The transmission of Tuberculosis (TB) is very rapid and the burden it places on health care systems is felt globally. The effective management and prevention of this disease requires that it is detected early. Current TB diagnostic approaches, such as the culture, sputum smear, skin tuberculin, and molecular tests are time-consuming, and some are unaffordable for low-income countries. Rapid tests for disease biomarker detection are mostly based on immunological assays that use antibodies which are costly to produce, have low sensitivity and stability. Aptamers can replace antibodies in these diagnostic tests for the development of new rapid tests that are more cost effective; more stable at high temperatures and therefore have a better shelf life; do not have batch-to-batch variations, and thus more consistently bind to a specific target with similar or higher specificity and selectivity and are therefore more reliable. Advancements in TB research, in particular the application of proteomics to identify TB specific biomarkers, led to the identification of a number of biomarker proteins, that can be used to develop aptamer-based diagnostic assays able to screen individuals at the point-of-care (POC) more efficiently in resource-limited settings.

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A Retrospective Cross-Sectional Study of the Utility of Cartridge-Based Nucleic Acid Amplification Test in Diagnosis of Pulmonary and Extrapulmonary Tuberculosis in People Living with HIV in Second Highest HIV Prevalent State in India

International Journal of Recent Surgical and Medical Sciences ◽

10.1055/s-0041-1730242 ◽

2021 ◽

Author(s):

Tade Bagbi ◽

Ningthoukhongjam Reema ◽

S. Bhagyabati Devi ◽

Thangjam Gautam Singh ◽

Mohammad Jaleel ◽

...

Keyword(s):

Nucleic Acid ◽

Cross Sectional Study ◽

Nucleic Acid Amplification Test ◽

Nucleic Acid Amplification ◽

Rifampicin Resistance ◽

Sputum Smear ◽

Smear Microscopy ◽

Sectional Study ◽

Cross Sectional ◽

Smear Negative

Abstract Introduction Tuberculosis (TB) in people living with human immunodeficiency virus (PLHIV) is difficult to diagnose due to fewer organisms in sputum and extrapulmonary samples. Sputum culture takes 4 to 8 weeks for growth of the mycobacteria. Delayed treatment for TB in PLHIV leads to increased mortality. This study evaluated cartridge-based nucleic acid amplification test (CBNAAT) as a diagnostic tool for diagnosis of pulmonary TB (PTB) and extrapulmonary TB (EPTB) in PLHIV in the second most HIV prevalent state in India and for comparing its efficacy between Ziehl–Neelsen (ZN) staining sputum smear–positive and sputum smear–negative TB. Methods This cross-sectional study was conducted in RIMS, Imphal, with 167 PLHIV patients, age 15 years or older, having signs and symptoms of TB. Appropriate samples for sputum microscopy and CBNAAT were sent. Conclusion The overall sensitivity of sputum smear for acid-fast bacillus (AFB) was found to be 30.71% and that of CBNAAT was 38.57%. Sensitivity of CBNAAT for sputum smear–positive and sputum smear–negative TB was 100 and 11.3%, respectively. Sensitivity of ZN smear for AFB of EPTB sample was 48.1% and that of CBNAAT was 59.25%. In both PTB and EPTB, CBNAAT showed an increase in diagnosis of microbiologically confirmed PTB cases by 7.8 and 11.1%, respectively, over and above the cases diagnosed by ZN smear microscopy. Rifampicin resistance was detected in five patients. We conclude that CBNAAT is a rapid test with better sensitivity in diagnosis of PTB and EPTB in PLHIV, compared with ZN smear microscopy. It detects rifampicin resistance for multidrug-resistant TB and helps in early treatment intervention.

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Characterization of Drug-Resistant Lipid-Dependent Differentially Detectable Mycobacterium tuberculosis

Journal of Clinical Medicine ◽

10.3390/jcm10153249 ◽

2021 ◽

Vol 10 (15) ◽

pp. 3249

Author(s):

Annelies W. Mesman ◽

Seung-Hun Baek ◽

Chuan-Chin Huang ◽

Young-Mi Kim ◽

Sang-Nae Cho ◽

...

Keyword(s):

Mycobacterium Tuberculosis ◽

Culture Media ◽

Multidrug Resistant ◽

Culture Conditions ◽

Sputum Smear ◽

Smear Microscopy ◽

Solid Culture ◽

Lowenstein Jensen ◽

Genetic Mechanisms ◽

Lipid Resuscitation

An estimated 15–20% of patients who are treated for pulmonary tuberculosis (TB) are culture-negative at the time of diagnosis. Recent work has focused on the existence of differentially detectable Mycobacterium tuberculosis (Mtb) bacilli that do not grow under routine solid culture conditions without the addition of supplementary stimuli. We identified a cohort of TB patients in Lima, Peru, in whom acid-fast bacilli could be detected by sputum smear microscopy, but from whom Mtb could not be grown in standard solid culture media. When we attempted to re-grow Mtb from the frozen sputum samples of these patients, we found that 10 out of 15 could be grown in a glycerol-poor/lipid-rich medium. These fell into the following two groups: a subset that could be regrown in glycerol after “lipid-resuscitation”, and a group that displayed a heritable glycerol-sensitive phenotype that were unable to grow in the presence of this carbon source. Notably, all of the glycerol-sensitive strains were found to be multidrug resistant. Although whole-genome sequencing of the lipid-resuscitated strains identified 20 unique mutations compared to closely related strains, no single genetic lesion could be associated with this phenotype. In summary, we found that lipid-based media effectively fostered the growth of Mtb from a series of sputum smear-positive samples that were not culturable in glycerol-based Lowenstein–Jensen or 7H9 media, which is consistent with Mtb’s known preference for non-glycolytic sources during infection. Analysis of the recovered strains demonstrated that both genetic and non-genetic mechanisms contribute to the observed differential capturability, and suggested that this phenotype may be associated with drug resistance.

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Impact of Xpert MTB/RIF on Antiretroviral Therapy-Associated Tuberculosis and Mortality: A Pragmatic Randomized Controlled Trial

Open Forum Infectious Diseases ◽

10.1093/ofid/ofu038 ◽

2014 ◽

Vol 1 (1) ◽

Cited By ~ 30

Author(s):

L. Mupfumi ◽

B. Makamure ◽

M. Chirehwa ◽

T. Sagonda ◽

S. Zinyowera ◽

...

Keyword(s):

Randomized Controlled Trial ◽

Controlled Trial ◽

Limited Resource ◽

Hiv Treatment ◽

Treatment Programs ◽

Sputum Smear ◽

Smear Microscopy ◽

Pragmatic Randomized Controlled Trial ◽

Randomized Controlled ◽

Art Initiation

Abstract Introduction. GeneXpert® MTB/RIF (Xpert) is now widely distributed in high human immunodeficiency virus (HIV)/tuberculosis (TB)-burden countries. Yet, whether the test improves patient-important outcomes within HIV treatment programs in limited resource settings is unknown. Methods. To investigate whether use of Xpert for TB screening prior to initiation of antiretroviral treatment (ART) improves patient-important outcomes, in a pragmatic randomized controlled trial we assigned 424 patients to Xpert or fluorescence sputum smear microscopy (FM) at ART initiation. The primary endpoint was a composite of 3-month mortality and ART-associated TB. Results. There was no difference in overall TB diagnosis at ART initiation (20% [n = 43] Xpert vs 21% [n = 45] FM; P = .80), with most patients in both groups treated empirically. There was no difference in time to TB treatment initiation {5 days (interquartile range [IQR], 3–13) vs 8 days [IQR, 3–23; P = .26]} or loss to follow-up (32 [15%] vs 38 [18%]; P = 0.38). Although a nonsignificant reduction in mortality occurred in the Xpert group (11 [6%] vs 17 [10%]; 95% CI, −9% to 2%; P = .19), there was no difference in the composite outcome (9% [n = 17] Xpert vs 12% [n = 21] FM; difference −3%; 95% CI, −9% to 4%). Conclusions. Among HIV-infected initiating ART, centralized TB screening with Xpert did not reduce the rate of ART-associated TB and mortality, compared with fluorescence microscopy.

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What a difference a day makes: same-day vs. 2-day sputum smear microscopy for diagnosing tuberculosis

Public Health Action ◽

10.5588/pha.16.0062 ◽

2016 ◽

Vol 6 (4) ◽

pp. 232-236 ◽

Cited By ~ 5

Author(s):

D. J. Deka ◽

B. Choudhury ◽

P. Talukdar ◽

T. Q. Lo ◽

B. Das ◽

...

Keyword(s):

Sputum Smear ◽

Smear Microscopy ◽

Sputum Smear Microscopy

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Ziehl–Neelsen sputum smear microscopy image database: a resource to facilitate automated bacilli detection for tuberculosis diagnosis

Journal of Medical Imaging ◽

10.1117/1.jmi.4.2.027503 ◽

2017 ◽

Vol 4 (2) ◽

pp. 027503 ◽

Cited By ~ 15

Author(s):

Mohammad Imran Shah ◽

Smriti Mishra ◽

Vinod Kumar Yadav ◽

Arun Chauhan ◽

Malay Sarkar ◽

...

Keyword(s):

Image Database ◽

Sputum Smear ◽

Smear Microscopy ◽

Sputum Smear Microscopy ◽

Microscopy Image ◽

Tuberculosis Diagnosis

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Clinical impact and cost analysis of the use of either the Xpert MTB Rif test or sputum smear microscopy in the diagnosis of pulmonary tuberculosis in Rio de Janeiro, Brazil

Revista da Sociedade Brasileira de Medicina Tropical ◽

10.1590/0037-8682-0082-2018 ◽

2018 ◽

Vol 51 (5) ◽

pp. 631-637

Author(s):

Anália Zuleika de Castro ◽

Adriana Rezende Moreira ◽

Jaqueline Oliveira ◽

Paulo Albuquerque Costa ◽

Carolyne Lalucha Alves Lima Da Graça ◽

...

Keyword(s):

Pulmonary Tuberculosis ◽

Cost Analysis ◽

Rio De Janeiro ◽

Clinical Impact ◽

Sputum Smear ◽

Smear Microscopy ◽

Sputum Smear Microscopy

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Previremic Identification of Ebola or Marburg Virus Infection Using Integrated Host-Transcriptome and Viral Genome Detection

mBio ◽

10.1128/mbio.01157-20 ◽

2020 ◽

Vol 11 (3) ◽

Author(s):

Emily Speranza ◽

Ignacio Caballero ◽

Anna N. Honko ◽

Joshua C. Johnson ◽

J. Kyle Bohannon ◽

...

Keyword(s):

Host Response ◽

Nonhuman Primates ◽

Ebola Virus ◽

Clinical Symptoms ◽

Infectious Agent ◽

Marburg Virus ◽

Viral Rna ◽

Molecular Tests ◽

Early Replication ◽

Host Infection

ABSTRACT Outbreaks of filoviruses, such as those caused by the Ebola (EBOV) and Marburg (MARV) virus, are difficult to detect and control. The initial clinical symptoms of these diseases are nonspecific and can mimic other endemic pathogens. This makes confident diagnosis based on clinical symptoms alone impossible. Molecular diagnostics for these diseases that rely on the detection of viral RNA in the blood are only effective after significant disease progression. As an approach to identify these infections earlier in the disease course, we tested the effectiveness of viral RNA detection combined with an assessment of sentinel host mRNAs that are upregulated following filovirus infection. RNAseq analysis of EBOV-infected nonhuman primates identified host RNAs that are upregulated at early stages of infection. NanoString probes that recognized these host-response RNAs were combined with probes that recognized viral RNA and were used to classify viral infection both prior to viremia and postviremia. This approach was highly successful at identifying samples from nonhuman primate subjects and correctly distinguished the causative agent in a previremic stage in 10 EBOV and 5 MARV samples. This work suggests that unified host response/viral fingerprint assays can enable diagnosis of disease earlier than testing for viral nucleic acid alone, which could decrease transmission events and increase therapeutic effectiveness. IMPORTANCE Current molecular tests that identify infection with high-consequence viruses such as Ebola virus and Marburg virus are based on the detection of virus material in the blood. These viruses do not undergo significant early replication in the blood and, instead, replicate in organs such as the liver and spleen. Thus, virus begins to accumulate in the blood only after significant replication has already occurred in those organs, making viremia an indicator of infection only after initial stages have become established. Here, we show that a multianalyte assay can correctly identify the infectious agent in nonhuman primates (NHPs) prior to viremia through tracking host infection response transcripts. This illustrates that a single-tube, sample-to-answer format assay could be used to advance the time at which the type of infection can be determined and thereby improve outcomes.

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Factors associated with unfavorable outcome of tuberculosis treatment in people deprived of liberty: a systematic review

Revista da Escola de Enfermagem da USP ◽

10.1590/1980-220x-reeusp-2020-0583 ◽

2021 ◽

Vol 55 ◽

Author(s):

Nanci Michele Saita ◽

Rubia Laine de Paula Andrade ◽

Pedro Augusto Bossonario ◽

Rafaele Oliveira Bonfim ◽

Paula Hino ◽

...

Keyword(s):

Systematic Review ◽

Selection Process ◽

Data Extraction ◽

Previous History ◽

Unfavorable Outcome ◽

Tuberculosis Treatment ◽

Sputum Smear ◽

Smear Microscopy ◽

Sputum Smear Microscopy ◽

Factors Associated

ABSTRACT Objective: to analyze factors associated with unfavorable outcome of tuberculosis treatment in people deprived of liberty. Method: systematic review, carried out in March 2021 in seven databases, with no delimitation of period of publication. The selection process of publications and data extraction was carried out by two independent reviewers. Results: a total of 1,448 publications was identified and nine were included in the study. Unfavorable outcome was higher among those who were men; had low level of education; were living in a rural area before detention; had longer prison time; received occasional visits; had been transferred between prisons; with no sputum smear microscopy or with a positive result at the diagnosis; with no follow-up sputum smear microscopy, previous history of tuberculosis; having both clinical forms of the disease, HIV/AIDS; alcoholics; smokers; low body weight; and self-administered treatment. Treatment default was associated with young people and death with older people. Conclusion: prison health managers and professionals are expected to establish mechanisms of surveillance and health actions innovation aimed at the population deprived of liberty, making efforts to reduce the unfavorable outcomes of tuberculosis treatment.

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