Challenges and Progress with Diagnosing Pulmonary Tuberculosis in Low- and Middle-Income Countries

Case finding and the diagnosis of tuberculosis (TB) are key activities to reach the World Health Organization’s End TB targets by 2030. This paper focuses on the diagnosis of pulmonary TB (PTB) in low- and middle-income countries. Sputum smear microscopy, despite its many limitations, remains the primary diagnostic tool in peripheral health facilities; however, this is being replaced by molecular diagnostic techniques, particularly Xpert MTB/RIF, which allows a bacteriologically confirmed diagnosis of TB along with information about whether or not the organism is resistant to rifampicin within two hours. Other useful diagnostic tools at peripheral facilities include chest radiography, urine lipoarabinomannan (TB-LAM) in HIV-infected patients with advanced immunodeficiency, and the loop-mediated isothermal amplification (TB-LAMP) test which may be superior to smear microscopy. National Reference Laboratories work at a higher level, largely performing culture and phenotypic drug susceptibility testing which is complemented by genotypic methods such as line probe assays for detecting resistance to isoniazid, rifampicin, and second-line drugs. Tuberculin skin testing, interferon gamma release assays, and commercial serological tests are not recommended for the diagnosis of active TB. Linking diagnosis to treatment and care is often poor, and this aspect of TB management needs far more attention than it currently receives.

[1]  Jingtao Gao,et al.  WHO treatment guidelines for isoniazid-resistant tuberculosis: supplement to the WHO treatment guidelines for drug-resistant tuberculosis , 2018 .

[2]  A. Harries,et al.  Has the utilisation of Xpert® MTB/RIF in Manicaland Province, Zimbabwe, improved with new guidance on whom to test? , 2018, Public health action.

[3]  Alimuddin Zumla,et al.  Advancing global tuberculosis control after the UNGA-HLM , 2018, The Lancet.

[4]  A. Harries,et al.  What can National TB Control Programmes in low- and middle-income countries do to end tuberculosis by 2030? , 2018, F1000Research.

[5]  S. Lawn,et al.  Rapid urine-based screening for tuberculosis in HIV-positive patients admitted to hospital in Africa (STAMP): a pragmatic, multicentre, parallel-group, double-blind, randomised controlled trial , 2018, The Lancet.

[6]  H. Ait Benhassou,et al.  Rapid molecular assays for detection of tuberculosis , 2018, Pneumonia.

[7]  K. K. K. Htet,et al.  Rifampicin-resistant tuberculosis patients in Myanmar in 2016: how many are lost on the path to treatment? , 2018, The international journal of tuberculosis and lung disease : the official journal of the International Union against Tuberculosis and Lung Disease.

[8]  C. Kuaban,et al.  Pre-treatment loss to follow-up of pulmonary tuberculosis patients in two regions of Cameroon. , 2018, The international journal of tuberculosis and lung disease : the official journal of the International Union against Tuberculosis and Lung Disease.

[9]  A. Medina-Marino,et al.  Estimating the magnitude of pulmonary tuberculosis patients missed by primary health care clinics in South Africa. , 2018, The international journal of tuberculosis and lung disease : the official journal of the International Union against Tuberculosis and Lung Disease.

[10]  Y. Manabe,et al.  Performance of loop-mediated isothermal amplification assay in the diagnosis of pulmonary tuberculosis in a high prevalence TB/HIV rural setting in Uganda , 2018, BMC Infectious Diseases.

[11]  A. Harries,et al.  Impact of Laboratory Practice Changes on the Diagnosis of Tuberculosis with the Introduction of Xpert MTB/RIF in Kiribati. , 2018, Hawai'i journal of medicine & public health : a journal of Asia Pacific Medicine & Public Health.

[12]  Irene N Njuguna,et al.  Stool Xpert MTB/RIF and urine lipoarabinomannan for the diagnosis of tuberculosis in hospitalized HIV-infected children , 2018, AIDS.

[13]  C. Arnold,et al.  Mycobacterium tuberculosis and whole-genome sequencing: how close are we to unleashing its full potential? , 2017, Clinical microbiology and infection : the official publication of the European Society of Clinical Microbiology and Infectious Diseases.

[14]  G. Marks,et al.  Evaluation of Loopamp™MTBC detection kit for diagnosis of pulmonary tuberculosis at a peripheral laboratory in a high burden setting. , 2017, Diagnostic microbiology and infectious disease.

[15]  P. Kiepiela,et al.  Detecting Mycobacterium tuberculosis using the loop-mediated isothermal amplification test in South Africa. , 2017, The international journal of tuberculosis and lung disease : the official journal of the International Union against Tuberculosis and Lung Disease.

[16]  S. Dorman,et al.  Evaluation of a Rapid Molecular Drug‐Susceptibility Test for Tuberculosis , 2017, The New England journal of medicine.

[17]  T. Thomas Tuberculosis in Children. , 2017, Pediatric clinics of North America.

[18]  T. Sterling,et al.  Isoniazid-monoresistant tuberculosis is associated with poor treatment outcomes in Durban, South Africa. , 2017, The international journal of tuberculosis and lung disease : the official journal of the International Union against Tuberculosis and Lung Disease.

[19]  F. Cobelens,et al.  Delays and loss to follow-up before treatment of drug-resistant tuberculosis following implementation of Xpert MTB/RIF in South Africa: A retrospective cohort study , 2017, PLoS medicine.

[20]  R. Ferrand,et al.  Stool Xpert® MTB/RIF test for the diagnosis of childhood pulmonary tuberculosis at primary clinics in Zimbabwe , 2016, The international journal of tuberculosis and lung disease : the official journal of the International Union against Tuberculosis and Lung Disease.

[21]  G. Fox,et al.  Passive case finding for tuberculosis is not enough , 2016, International journal of mycobacteriology.

[22]  S. Lawn,et al.  Xpert MTB/RIF - why the lack of morbidity and mortality impact in intervention trials? , 2016, Transactions of the Royal Society of Tropical Medicine and Hygiene.

[23]  K. Dheda,et al.  Effect on mortality of point-of-care, urine-based lipoarabinomannan testing to guide tuberculosis treatment initiation in HIV-positive hospital inpatients: a pragmatic, parallel-group, multicountry, open-label, randomised controlled trial , 2016, The Lancet.

[24]  S. Lawn,et al.  Detection of lipoarabinomannan (LAM) in urine is indicative of disseminated TB with renal involvement in patients living with HIV and advanced immunodeficiency: evidence and implications , 2016, Transactions of the Royal Society of Tropical Medicine and Hygiene.

[25]  Y. Boum,et al.  Detection Yield and Tolerability of String Test for Diagnosis of Childhood Intrathoracic Tuberculosis , 2016, The Pediatric infectious disease journal.

[26]  Anne-Laure Page,et al.  Implementing the Xpert® MTB/RIF Diagnostic Test for Tuberculosis and Rifampicin Resistance: Outcomes and Lessons Learned in 18 Countries , 2015, PloS one.

[27]  S. Lawn,et al.  Prevalence of tuberculosis in post-mortem studies of HIV-infected adults and children in resource-limited settings: a systematic review and meta-analysis , 2015, AIDS.

[28]  S. Lawn,et al.  Rapid microbiological screening for tuberculosis in HIV-positive patients on the first day of acute hospital admission by systematic testing of urine samples using Xpert MTB/RIF: a prospective cohort in South Africa , 2015, BMC Medicine.

[29]  Christopher Dye,et al.  Xpert MTB/RIF versus sputum microscopy as the initial diagnostic test for tuberculosis: a cluster-randomised trial embedded in South African roll-out of Xpert MTB/RIF. , 2015, The Lancet. Global health.

[30]  A. Harries,et al.  Countrywide roll-out of Xpert(®) MTB/RIF in Swaziland: the first three years of implementation. , 2015, Public health action.

[31]  M. Nicol,et al.  Impact of Xpert MTB/RIF for TB Diagnosis in a Primary Care Clinic with High TB and HIV Prevalence in South Africa: A Pragmatic Randomised Trial , 2014, PLoS medicine.

[32]  Ben J Marais,et al.  Tuberculosis in children. , 2014, Cold Spring Harbor perspectives in medicine.

[33]  Grant Theron,et al.  Feasibility, accuracy, and clinical effect of point-of-care Xpert MTB/RIF testing for tuberculosis in primary-care settings in Africa: a multicentre, randomised, controlled trial , 2014, The Lancet.

[34]  J. Glynn,et al.  Pre-treatment loss to follow-up in tuberculosis patients in low- and lower-middle-income countries and high-burden countries: a systematic review and meta-analysis. , 2014, Bulletin of the World Health Organization.

[35]  Keertan Dheda,et al.  Determine TB-LAM lateral flow urine antigen assay for HIV-associated tuberculosis: recommendations on the design and reporting of clinical studies , 2013, BMC Infectious Diseases.

[36]  S. Egwaga,et al.  Are sputum samples of retreatment tuberculosis reaching the reference laboratories? A 9-year audit in Tanzania. , 2013, Public health action.

[37]  Alimuddin Zumla,et al.  Advances in tuberculosis diagnostics: the Xpert MTB/RIF assay and future prospects for a point-of-care test. , 2013, The Lancet. Infectious diseases.

[38]  S. Lawn,et al.  Diagnostic accuracy of a low-cost, urine antigen, point-of-care screening assay for HIV-associated pulmonary tuberculosis before antiretroviral therapy: a descriptive study , 2012, The Lancet. Infectious diseases.

[39]  S. Lawn,et al.  Tuberculosis in Antiretroviral Treatment Services in Resource-Limited Settings: Addressing the Challenges of Screening and Diagnosis , 2011, The Journal of infectious diseases.

[40]  A. Harries,et al.  Operational Challenges in Diagnosing Multi-Drug Resistant TB and Initiating Treatment in Andhra Pradesh, India , 2011, PloS one.

[41]  H. Zar,et al.  Accuracy of the Xpert MTB/RIF test for the diagnosis of pulmonary tuberculosis in children admitted to hospital in Cape Town, South Africa: a descriptive study. , 2011, The Lancet. Infectious diseases.

[42]  A. Van Deun,et al.  Xpert® MTB/RIF for national tuberculosis programmes in low-income countries: when, where and how? , 2011, The international journal of tuberculosis and lung disease : the official journal of the International Union against Tuberculosis and Lung Disease.

[43]  Eduardo Gotuzzo,et al.  Feasibility, diagnostic accuracy, and effectiveness of decentralised use of the Xpert MTB/RIF test for diagnosis of tuberculosis and multidrug resistance: a multicentre implementation study , 2011, The Lancet.

[44]  D. Havlir,et al.  Significant variation in presentation of pulmonary tuberculosis across a high resolution of CD4 strata. , 2010, The international journal of tuberculosis and lung disease : the official journal of the International Union against Tuberculosis and Lung Disease.

[45]  Eduardo Gotuzzo,et al.  Rapid molecular detection of tuberculosis and rifampin resistance. , 2010, The New England journal of medicine.

[46]  P. Phanuphak,et al.  An algorithm for tuberculosis screening and diagnosis in people with HIV. , 2010, The New England journal of medicine.

[47]  N. Dendukuri,et al.  Performance of Purified Antigens for Serodiagnosis of Pulmonary Tuberculosis: a Meta-Analysis , 2008, Clinical and Vaccine Immunology.

[48]  K. Steingart,et al.  Commercial Serological Antibody Detection Tests for the Diagnosis of Pulmonary Tuberculosis: A Systematic Review , 2007, PLoS medicine.

[49]  S. Rüsch-Gerdes,et al.  Evaluation of the GenoType MTBDRplus Assay for Rifampin and Isoniazid Susceptibility Testing of Mycobacterium tuberculosis Strains and Clinical Specimens , 2007, Journal of Clinical Microbiology.

[50]  M. Perkins,et al.  Sputum processing methods to improve the sensitivity of smear microscopy for tuberculosis: a systematic review. , 2006, The Lancet. Infectious diseases.

[51]  A. Ramsay,et al.  Using a bus service for transporting sputum specimens to the Central Reference Laboratory: effect on the routine TB culture service in Malawi. , 2004, The international journal of tuberculosis and lung disease : the official journal of the International Union against Tuberculosis and Lung Disease.

[52]  B. Barrell,et al.  Deciphering the biology of Mycobacterium tuberculosis from the complete genome sequence , 1998, Nature.

[53]  C. Dolea,et al.  World Health Organization , 1949, International Organization.

[54]  D. van Soolingen,et al.  Performance of Xpert MTB/RIF Ultra: a matter of dead or alive. , 2018, The Lancet. Infectious diseases.

[55]  M. Grzemska,et al.  Roadmap towards ending TB in children and adolescents. , 2018 .

[56]  A. Harries,et al.  Performance of culture and drug susceptibility testing in pulmonary tuberculosis patients in northern China. , 2011, The international journal of tuberculosis and lung disease : the official journal of the International Union against Tuberculosis and Lung Disease.