Tuberculosis preventive therapy: An underutilised strategy to reduce individual risk of TB and contribute to TB control

Churchyard, Gavin J.; Chaisson, Richard E.; Maartens, Gary; Getahun, Haileyesus

doi:10.7196/samj.8290

Cited by 21 publications

(21 citation statements)

References 46 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…As with any model, we have made several simplifying assumptions which may affect the conclusions. Uptake and completion of preventive therapy among HIV-infected individuals has been challenging in South Africa 25 , and similar challenges are likely to be experienced in targeted use of 3HP among HIV-uninfected populations. We assumed uptake of 3HP following a positive COR or IGRA would be the same as initiation of treatment among those diagnosed with active TB which may overestimate the potential impact.…”

Section: Discussionmentioning

confidence: 99%

Potential population level impact on tuberculosis incidence of using an mRNA expression signature correlate-of-risk test to target tuberculosis preventive therapy

Sumner

Scriba

Penn-Nicholson

et al. 2019

Sci Rep

View full text Add to dashboard Cite

Achieving the WHo end-tuberculosis (tB) targets requires approaches to prevent progression to tB among individuals with Mycobacterium tuberculosis (M.tb) infection. Effective preventive therapy (PT) exists, but current tests have low specificity for identifying who, among those infected, is at risk of developing tB. Using mathematical models, we assessed the potential population-level impact on TB incidence of using a new more specific mRNA expression signature (COR) to target PT among HiV-uninfected adults in South Africa. We compared the results to the use of the existing interferon-γ release assay (IGRA). With annual screening coverage of 30% COR-targeted PT could reduce TB incidence in 2035 by 20% (95% CI 15-27). With the same coverage, IGRA-targeted PT could reduce TB incidence by 39% (31-48) but would require greater use of PT resulting in a higher number needed to treat per TB case averted (COR: 49 (29-77); IGRA: 84 (59-123)). The relative differences between COR and iGRA were not sensitive to screening coverage. coR-targeted pt could contribute to reducing total TB burden in high incidence countries like South Africa by allowing more efficient targeting of treatment. to maximise impact, coR-like tests may be best utilised in the highest burden regions, or sub-populations, within these countries. Achieving the World Health Organisation (WHO) End-Tuberculosis (TB) strategy targets (reducing TB deaths by 95% and TB cases by 90%) 1 , and ultimately eliminating the disease, will not be possible without tools to prevent progression to TB among individuals with Mycobacterium tuberculosis (M.tb) infection 2. Effective regimens for preventive therapy exist 3,4 but treating the quarter of the global population estimated to be infected with M.tb 5 is unlikely to be feasible, especially given the relatively low lifetime risk of developing disease and the rare, yet potential, adverse effects of prophylactic treatment. Existing tests for M.tb infection, such as the tuberculin skin test (TST) and interferon-γ release assay (IGRA), have poor specificity for predicting who will progress to disease. New, more specific tests, which could more accurately identify those individuals at greatest risk of developing TB, and therefore allow better targeted preventive therapy, are needed. Several such tests are currently under development 6,7 and the WHO have recently released a target product profile (TPP) outlining the desired characteristics of such a test 8. The TPP identified those with increased likelihood of recent exposure (such as household contacts) or those with risk factors for developing TB (such as people living with HIV) as the primary target groups for such a test, especially in low-risk settings. However, in high incidence settings such tests may have value for screening the general population 8. An 11-gene version of a previously validated blood 16-gene mRNA expression signature 9 is currently being evaluated in a proof-of-concept study in South Africa (Correlate of Risk (COR) Targeted Intervention Study

show abstract

Section: Discussionmentioning

confidence: 99%

Potential population level impact on tuberculosis incidence of using an mRNA expression signature correlate-of-risk test to target tuberculosis preventive therapy

Sumner

Scriba

Penn-Nicholson

et al. 2019

Sci Rep

View full text Add to dashboard Cite

show abstract

“…63 Large population-based studies of tuberculosis preventive therapy and mathematical models both suggest that preventive treatment of tuberculosis infection-as part of a comprehensive approach that includes active case-finding and prompt, effective treatment-can sufficiently reduce population-level transmission to interrupt the cycle of infection, illness, and death. 64,65 Unfortunately, despite abundant evidence of its efficacy, the use of preventive therapy globally has been limited, 66 because tuberculosis control programmes in low-income and middle-income countries (LMICs) have focused almost exclusively on detection and treatment of individuals with active tuberculosis disease.…”

Section: Neglect Of Tuberculosis Control Strategiesmentioning

confidence: 99%

Building a tuberculosis-free world: The Lancet Commission on tuberculosis

et al. 2019

View full text Add to dashboard Cite

growing political momentum to definitively address tuberculosis, could all make ending the pandemic within a generation more feasible than ever before. Moving forward with bold, comprehensive strategies Globally, the priority must be to deliver person-centred and family-centred services to all individuals with tuberculosis who present to care. This approach means ensuring that high-quality diagnostics, treatment, and prevention modalities are available to all, wherever they seek care. Improving quality of tuberculosis care in the private sector is crucial to end tuberculosis in high incidence countries such as India, the country with the highest tuberculosis burden. Modelling shows that optimising private sector engagement in India could avert 8 million deaths from tuberculosis between 2019 and 2045 (appendix p 3). In high drug-resistant tuberculosis burden countries, access to rapid drug susceptibility testing (DST) and second-line drugs is essential to success. In Moldova, where more than 25% of all tuberculosis cases are drug-resistant, improving access to DST and second-line drugs would reduce mortality from drug-resistant tuberculosis by 44% in the coming generation (appendix p 3). Secondly, tuberculosis programme budgets must increase to enable reaching these people and populations at high risk of tuberculosis. In Kenya, for example, where the proportions of HIV and tuberculosis coinfection are high, scaling up access to both antiretroviral therapy and tuberculosis preventive therapy can help save an additional 3 million lives over the next generation (appendix p 3). However, ultimately, the fight against tuberculosis will not be won unless countries also ensure that everyone, not just high-risk groups, can access essential health Key messages The Commission recommends five priority investments to achieve a tuberculosis-free world within a generation. These investments are designed to fulfil the mandate of the UN High Level Meeting on tuberculosis. In addition, they answer the question of how countries with high-burden tuberculosis and their development partners should target their future investments to ensure that ending tuberculosis is achievable. Invest first to ensure that high quality rapid diagnostics and treatment are provided to all individuals receiving care for tuberculosis, wherever they seek care This priority includes rapid drug susceptibility testing and second-line treatment for resistant forms of tuberculosis. Achieving universal, high-quality person-centred and family-centred care-including sustained improvement in the performance of private sector providers-usually should be the top policy and budget priority. Reach people and populations at high risk for tuberculosis (such as household and other close contacts of people with tuberculosis, and people with HIV) and bring them into care Active case-finding and treatment in high-risk populations demands adequate resources to reach and care for these populations. At the same time, reaching certain high-risk populations, such as people co-infec...

show abstract

“…[1] In this edition we present the opinion from the Aurum Institute [2] that it may substantially improve TB control, particularly for populations at high risk. As we reported in Izindaba, [3] picking up on the mining indaba recently held in Cape Town, the moment a TB carrier (i.e.…”

Section: Isoniazid Prophylaxis -The Prosmentioning

confidence: 99%

Editor's Choice

Seggie

2014

S Afr Med J

View full text Add to dashboard Cite

This month's CME deals with the topic of breast cancer, a common cancer that consequently receives a lot of publicity. In women who have easy access to screening and medical care, and are aware of the significance of changes in the breast, this cancer presents early and can often be managed very successfully. However, for the majority of our population -and indeed elsewhere in Africa and the developing world -the situation is very different. The cancer presents late, has often already spread, is difficult to manage and has a low cure rate. Jenny Edge and her team concentrate on this aspect of breast cancer. Articles take in the situation in a population of women presenting to Baragwanath Hospital in Soweto, for whom distance to the clinic was a factor in late presentation, as well as management of locally advanced disease, side-effects of systemic therapy, and management of a common post-treatment complication, lymphoedema. These articles should be particularly useful for those who work in the public sector and in private practice in less affluent areas.

show abstract

Tuberculosis preventive therapy: An underutilised strategy to reduce individual risk of TB and contribute to TB control

Cited by 21 publications

References 46 publications

Potential population level impact on tuberculosis incidence of using an mRNA expression signature correlate-of-risk test to target tuberculosis preventive therapy

Potential population level impact on tuberculosis incidence of using an mRNA expression signature correlate-of-risk test to target tuberculosis preventive therapy

Building a tuberculosis-free world: The Lancet Commission on tuberculosis

Editor's Choice

Contact Info

Product

Resources

About