Management of Latent Tuberculosis Infections in Australia and New Zealand: A Review of Current Practice

Aim: To survey practices in the diagnosis and management of latent tuberculosis infection (LTBI) in Australia and New Zealand. Methods: Infectious diseases and respiratory physicians and trainees were invited to complete an online questionnaire concerning various aspects of LTBI management. Results: The questionnaire was completed by 126 clinicians self-reporting regular management of LTBI. Respondents were experienced physicians, with 95/126 (75.4%) having managed LTBI for more than 5 years. Forty-seven (37.3%) reported seeing more than 5 patients per month for assessment of LTBI. Substantial variation among clinicians was reported in relation to a number of common clinical scenarios. For instance, while 52/126 (43.7%) informed patients that the incidence of severe hepatotoxicity related to isoniazid monotherapy was 0.1–0.5%, 21/126 (15.7%) thought it was >5%. 36/126 (28.6%) clinicians would proceed with TNF-αtherapy following an indeterminate screening: interferon-γassay, while 78/126 (61.9%) would perform further investigations and 12/126 (9.5%) would initiate isoniazid therapy. Follow-up intervals during therapy varied from 1–3 monthly, with liver function testing performed routinely by 89/126 (70.6%). Conclusion: This study demonstrated a large degree of variation in clinical practice of LTBI management in Australia and New Zealand. Strategies for increasing uniformity of practice are required, including improved guidelines and physician education

The use of anti-tuberculosis therapy for latent TB infection

Tuberculosis infection is of global public health significance, with millions of incident cases each year. Many cases, particularly in low-prevalence settings, result from the reactivation of latent tuberculosis infection (LTBI); potentially acquired years prior to active disease. Up to one-third of the world’s population has been infected with LTBI, and so may be at risk for future active TB disease. A variety of antituberculosis medications and treatment regimens have now been evaluated in the management of LTBI, with the aim of eradicating tuberculosis bacilli and reducing the likelihood of subsequent reactivation disease. This article reviews LTBI therapies and their use in clinical contexts, and considers future directions for individual and population-based strategies in LTBI management

Management of Latent Tuberculosis Infections in Australia and New Zealand: A Review of Current Practice

Aim: To survey practices in the diagnosis and management of latent tuberculosis infection (LTBI) in Australia and New Zealand. Methods: Infectious diseases and respiratory physicians and trainees were invited to complete an online questionnaire concerning various aspects of LTBI management. Results: The questionnaire was completed by 126 clinicians self-reporting regular management of LTBI. Respondents were experienced physicians, with 95/126 (75.4%) having managed LTBI for more than 5 years. Forty-seven (37.3%) reported seeing more than 5 patients per month for assessment of LTBI. Substantial variation among clinicians was reported in relation to a number of common clinical scenarios. For instance, while 52/126 (43.7%) informed patients that the incidence of severe hepatotoxicity related to isoniazid monotherapy was 0.1–0.5%, 21/126 (15.7%) thought it was >5%. 36/126 (28.6%) clinicians would proceed with TNF-αtherapy following an indeterminate screening: interferon-γassay, while 78/126 (61.9%) would perform further investigations and 12/126 (9.5%) would initiate isoniazid therapy. Follow-up intervals during therapy varied from 1–3 monthly, with liver function testing performed routinely by 89/126 (70.6%). Conclusion: This study demonstrated a large degree of variation in clinical practice of LTBI management in Australia and New Zealand. Strategies for increasing uniformity of practice are required, including improved guidelines and physician education

Management of Tuberculosis: a handbook for clinicians

This handbook, a distillation of recommendations from international TB guidelines and the accumulated clinical experience of its authors, provides practical information for clinicians involved in the care of patients with tuberculosis (TB) and other mycobacterial diseases. Topics covered are: management of drug-sensitive and drug-resistant TB; latent TB infection; pregnancy and TB; HIV and TB; nontuberculous mycobacterial infections; BCG vaccination and BCG installation for bladder cancer. The emphasis is on presenting a practical approach to the many clinical issues, common and uncommon, that arise in the day-to-day management of patients with mycobacterial infections. The handbook is primarily intended for specialists and trainee specialists working in the ward and in the outpatient clinic, but it should also appeal to pharmacists and nurses involved with TB care, and to students

Clinical standards for the management of adverse effects during treatment for TB

BACKGROUND: Adverse effects (AE) to TB treatment cause morbidity, mortality and treatment interruption. The aim of these clinical standards is to encourage best practise for the diagnosis and management of AE.METHODS: 65/81 invited experts participated in a Delphi process using a 5-point Likert scale to score draft standards.RESULTS: We identified eight clinical standards. Each person commencing treatment for TB should: Standard 1, be counselled regarding AE before and during treatment; Standard 2, be evaluated for factors that might increase AE risk with regular review to actively identify and manage these; Standard 3, when AE occur, carefully assessed and possible allergic or hypersensitivity reactions considered; Standard 4, receive appropriate care to minimise morbidity and mortality associated with AE; Standard 5, be restarted on TB drugs after a serious AE according to a standardised protocol that includes active drug safety monitoring. In addition: Standard 6, healthcare workers should be trained on AE including how to counsel people undertaking TB treatment, as well as active AE monitoring and management; Standard 7, there should be active AE monitoring and reporting for all new TB drugs and regimens; and Standard 8, knowledge gaps identified from active AE monitoring should be systematically addressed through clinical research.CONCLUSION: These standards provide a person-centred, consensus-based approach to minimise the impact of AE during TB treatment.CONTEXTE : Les effets indésirables (AE) du traitement de la TB sont une cause de morbidité, de mortalité et d’interruption du traitement. L’objectif de ces normes cliniques est d’encourager une meilleure pratique en matière de diagnostic et de prise en charge des AE. MÉTHODES : Ont participé 65/81 experts invités à un processus Delphi utilisant une échelle de Likert en 5 points pour évaluer des ébauches de normes. RÉSULTATS : Nous avons identifié huit normes cliniques. Chaque personne commençant un traitement antituberculeux devrait : Norme 1, être informée des AE avant et pendant le traitement ; Norme 2, être évaluée afin de détecter tout facteur susceptible d’augmenter le risque d’AE et faire l’objet d’un examen régulier afin d’identifier et de prendre en charge ces facteurs de manière proactive ; Norme 3, en cas d’AE, être évaluée avec soin et tenir compte d’éventuelles réactions allergiques ou d’hypersensibilité ; Norme 4, recevoir des soins appropriés pour minimiser la morbidité et la mortalité associées aux AE ; Norme 5, reprendre les médicaments antituberculeux après un AE grave selon un protocole standardisé avec une surveillance active de l’innocuité des médicaments ; Norme 6, les agents de santé doivent être formés aux AE, y compris à la manière de conseiller les personnes qui suivent un traitement antituberculeux, ainsi qu’à la surveillance et à la prise en charge actives des AE ; Norme 7 : tous les nouveaux médicaments et schémas antituberculeux doivent faire l’objet d’une surveillance active des AE et d’une notification ; et Norme 8 : les lacunes en matière de connaissances identifiées grâce à la surveillance active des AE doivent être systématiquement comblées par la recherche clinique. CONCLUSION : Ces normes fournissent une approche centrée sur la personne et fondée sur le consensus afin de minimiser l’impact des AE pendant le traitement de la TB

Estimating the prevalence of latent tuberculosis in a low-incidence setting: Australia.

Migration is a key driver of tuberculosis (TB) in many low-incidence settings, with the majority of TB cases attributed to reactivation of latent TB (LTBI) acquired overseas. A greater understanding of LTBI risk in heterogeneous migrant populations would aid health planning. We aimed to estimate the LTBI prevalence and distribution among locally born and overseas-born Australians.Annual risks of TB infection estimates were applied to population cohorts (by country of birth, year of arrival and age) in Australian census data in 2006, 2011 and 2016.Both the absolute number and proportion of Australian residents with LTBI increased from 4.6% (interquartile range (IQR) 4.2-5.2%) in 2006 to 5.1% (IQR 4.7-5.5%) in 2016, due to the increasing proportion of the population born overseas (23.8% in 2006 to 28.3% in 2016). Of all residents estimated to have LTBI in 2016; 93.2% were overseas born, 21.6% were aged <35 years and 34.4% had migrated to Australia since 2007.The overall prevalence of LTBI in Australia is low. Some residents, particularly migrants from high-incidence settings, may have considerably higher risk of LTBI, and these findings allow for tailored public health interventions to reduce the risk and impact of future TB disease

Critical Consideration of Tuberculosis Management of Papua New Guinea Nationals and Cross-Border Health Issues in the Remote Torres Strait Islands, Australia

The international border between Australia and Papua New Guinea (PNG) serves as a gateway for the delivery of primary and tertiary healthcare for PNG patients presenting to Australian health facilities with presumptive tuberculosis (TB). An audit of all PNG nationals with presumptive TB who presented to clinics in the Torres Strait between 2016 and 2019 was conducted to evaluate outcomes for PNG patients and to consider the consistency and equity of decision-making regarding aeromedical evacuation. We also reviewed the current aeromedical retrieval policy and the outcomes of patients referred back to Daru General Hospital in PNG. During the study period, 213 PNG nationals presented with presumptive TB to primary health centres (PHC) in the Torres Strait. In total, 44 (21%) patients were medically evacuated to Australian hospitals; 26 met the evacuation criteria of whom 3 died, and 18 did not meet the criteria of whom 1 died. A further 22 patients who met the medical evacuation criteria into Australia were referred to Daru General Hospital of whom 2 died and 10 were lost to follow-up. The cross-border movement of people from PNG into Australia is associated with an emergent duty of care. Ongoing monitoring and evaluation of patient outcomes are necessary for transparency and justice

Empirical ways to identify novel Bedaquiline resistance mutations in AtpE.

Clinical resistance against Bedaquiline, the first new anti-tuberculosis compound with a novel mechanism of action in over 40 years, has already been detected in Mycobacterium tuberculosis. As a new drug, however, there is currently insufficient clinical data to facilitate reliable and timely identification of genomic determinants of resistance. Here we investigate the structural basis for M. tuberculosis associated bedaquiline resistance in the drug target, AtpE. Together with the 9 previously identified resistance-associated variants in AtpE, 54 non-resistance-associated mutations were identified through comparisons of bedaquiline susceptibility across 23 different mycobacterial species. Computational analysis of the structural and functional consequences of these variants revealed that resistance associated variants were mainly localized at the drug binding site, disrupting key interactions with bedaquiline leading to reduced binding affinity. This was used to train a supervised predictive algorithm, which accurately identified likely resistance mutations (93.3% accuracy). Application of this model to circulating variants present in the Asia-Pacific region suggests that current circulating variants are likely to be susceptible to bedaquiline. We have made this model freely available through a user-friendly web interface called SUSPECT-BDQ, StrUctural Susceptibility PrEdiCTion for bedaquiline (http://biosig.unimelb.edu.au/suspect_bdq/). This tool could be useful for the rapid characterization of novel clinical variants, to help guide the effective use of bedaquiline, and to minimize the spread of clinical resistance.M.K was funded by the Melbourne Research Scholarship. D.B.A was funded by a Newton Fund RCUK-CONFAP Grant awarded by The Medical Research Council (MRC) and Fundação de Amparo à Pesquisa do Estado de Minas Gerais (FAPEMIG) (MR/M026302/1), the Jack Brockhoff Foundation (JBF 4186, 2016), and a C. J. Martin Research Fellowship from the National Health and Medical Research Council (NHMRC) of Australia (APP1072476). The Vietnam genomic dataset was funded by a NHMRC Australia grant (APP1056689) to SJD and KEH. Supported in part by the Victorian Government's OIS Program