Review

12 pages, 967 KiB

Open AccessReview

The Global Expansion of LTBI Screening and Treatment Programs: Exploring Gaps in the Supporting Economic Evidence

by Nokwanda Thandeka Kota, Suvesh Shrestha, Abdulhameed Kashkary, Pushpita Samina and Alice Zwerling

Pathogens 2023, 12(3), 500; https://doi.org/10.3390/pathogens12030500 - 22 Mar 2023

Cited by 3 | Viewed by 1658

Abstract

The global burden of latent TB infection (LTBI) and the progression of LTBI to active TB disease are important drivers of ongoing TB incidence. Addressing LTBI through screening and TB preventive treatment (TPT) is critical in order to end the TB epidemic by [...] Read more.

The global burden of latent TB infection (LTBI) and the progression of LTBI to active TB disease are important drivers of ongoing TB incidence. Addressing LTBI through screening and TB preventive treatment (TPT) is critical in order to end the TB epidemic by 2035. Given the limited resources available to health ministries around the world in the fight against TB, we must consider economic evidence for LTBI screening and treatment strategies to ensure that limited resources are used to achieve the biggest health impact. In this narrative review, we explore key economic evidence around LTBI screening and TPT strategies in different populations to summarize our current understanding and highlight gaps in existing knowledge. When considering economic evidence supporting LTBI screening or evaluating different testing approaches, a disproportionate number of economic studies have been conducted in high-income countries (HICs), despite the vast majority of TB burden being borne in low- and middle-income countries (LMICs). Recent years have seen a temporal shift, with increasing data from low- and middle-income countries (LMICs), particularly with regard to targeting high-risk groups for TB prevention. While LTBI screening and prevention programs can come with extensive costs, targeting LTBI screening among high-risk populations, such as people living with HIV (PLHIV), children, household contacts (HHC) and immigrants from high-TB-burden countries, has been shown to consistently improve the cost effectiveness of screening programs. Further, the cost effectiveness of different LTBI screening algorithms and diagnostic approaches varies widely across settings, leading to different national TB screening policies. Novel shortened regimens for TPT have also consistently been shown to be cost effective across a range of settings. These economic evaluations highlight key implementation considerations such as the critical nature of ensuring high rates of adherence and completion, despite the costs associated with adherence programs not being routinely assessed and included. Digital and other adherence support approaches are now being assessed for their utility and cost effectiveness in conjunction with novel shortened TPT regimens, but more economic evidence is needed to understand the potential cost savings, particularly in settings where directly observed preventive therapy (DOPT) is routinely conducted. Despite the growth of the economic evidence base for LTBI screening and TPT recently, there are still significant gaps in the economic evidence around the scale-up and implementation of expanded LTBI screening and treatment programs, particularly among traditionally hard-to-reach populations. Full article

(This article belongs to the Special Issue Mycobacterium tuberculosis Infection: Policy Gaps and Research Breakthroughs)

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15 pages, 523 KiB

Open AccessReview

Management of Tuberculosis Infection: Current Situation, Recent Developments and Operational Challenges

by Gino Agbota, Maryline Bonnet and Christian Lienhardt

Pathogens 2023, 12(3), 362; https://doi.org/10.3390/pathogens12030362 - 21 Feb 2023

Cited by 7 | Viewed by 1855

Abstract

Tuberculosis infection (TBI) is defined as a state of infection in which individuals host live Mycobacterium tuberculosis with or without clinical signs of active TB. It is now understood as a dynamic process covering a spectrum of responses to infection resulting from the [...] Read more.

Tuberculosis infection (TBI) is defined as a state of infection in which individuals host live Mycobacterium tuberculosis with or without clinical signs of active TB. It is now understood as a dynamic process covering a spectrum of responses to infection resulting from the interaction between the TB bacilli and the host immune system. The global burden of TBI is about one-quarter of the world’s population, representing a reservoir of approximately 2 billion people. On average, 5–10% of people who are infected will develop TB disease over the course of their lives, but this risk is enhanced in a series of conditions, such as co-infection with HIV. The End-TB strategy promotes the programmatic management of TBI as a crucial endeavor to achieving global targets to end the TB epidemic. The current development of new diagnostic tests capable of discriminating between simple TBI and active TB, combined with novel short-course preventive treatments, will help achieve this goal. In this paper, we present the current situation and recent developments of management of TBI and the operational challenges. Full article

(This article belongs to the Special Issue Mycobacterium tuberculosis Infection: Policy Gaps and Research Breakthroughs)

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14 pages, 297 KiB

Open AccessReview

Landscape of TB Infection and Prevention among People Living with HIV

by Anca Vasiliu, Rebecca Abelman, Yousra Kherabi, Antonia Morita Iswari Saktiawati and Alexander Kay

Pathogens 2022, 11(12), 1552; https://doi.org/10.3390/pathogens11121552 - 16 Dec 2022

Cited by 2 | Viewed by 1565

Abstract

Tuberculosis (TB) is one of the leading causes of mortality in people living with HIV (PLHIV) and contributes to up to a third of deaths in this population. The World Health Organization guidelines aim to target early detection and treatment of TB among [...] Read more.

Tuberculosis (TB) is one of the leading causes of mortality in people living with HIV (PLHIV) and contributes to up to a third of deaths in this population. The World Health Organization guidelines aim to target early detection and treatment of TB among PLHIV, particularly in high-prevalence and low-resource settings. Prevention plays a key role in the fight against TB among PLHIV. This review explores TB screening tools available for PLHIV, including symptom-based screening, chest radiography, tuberculin skin tests, interferon gamma release assays, and serum biomarkers. We then review TB Preventive Treatment (TPT), shown to reduce the progression to active TB and mortality among PLHIV, and available TPT regimens. Last, we highlight policy-practice gaps and barriers to implementation as well as ongoing research needs to lower the burden of TB and HIV coinfection through preventive activities, innovative diagnostic tests, and cost-effectiveness studies. Full article

(This article belongs to the Special Issue Mycobacterium tuberculosis Infection: Policy Gaps and Research Breakthroughs)

14 pages, 336 KiB

Open AccessReview

Tuberculosis Infection in Children and Adolescents

by Boris Tchakounte Youngui, Boris Kevin Tchounga, Stephen M. Graham and Maryline Bonnet

Pathogens 2022, 11(12), 1512; https://doi.org/10.3390/pathogens11121512 - 09 Dec 2022

Cited by 5 | Viewed by 2157

Abstract

The burden of tuberculosis (TB) in children and adolescents remains very significant. Several million children and adolescents are infected with TB each year worldwide following exposure to an infectious TB case and the risk of progression from TB infection to tuberculosis disease is [...] Read more.

The burden of tuberculosis (TB) in children and adolescents remains very significant. Several million children and adolescents are infected with TB each year worldwide following exposure to an infectious TB case and the risk of progression from TB infection to tuberculosis disease is higher in this group compared to adults. This review describes the risk factors for TB infection in children and adolescents. Following TB exposure, the risk of TB infection is determined by a combination of index case characteristics, contact features, and environmental determinants. We also present the recently recommended approaches to diagnose and treat TB infection as well as novel tests for infection. The tests for TB infection have limitations and diagnosis still relies on an indirect immunological assessment of cellular immune response to Mycobacterium tuberculosis antigens using immunodiagnostic testing. It is recommended that TB exposed children and adolescents and those living with HIV receive TB preventive treatment (TPT) to reduce the risk of progression to TB disease. Several TPT regimens of similar effectiveness and safety are now available and recommended by the World Health Organisation. Full article

(This article belongs to the Special Issue Mycobacterium tuberculosis Infection: Policy Gaps and Research Breakthroughs)

18 pages, 328 KiB

Open AccessReview

Tuberculosis Infection in Pregnant People: Current Practices and Research Priorities

by Jyoti S. Mathad, Sharan Yadav, Arthi Vaidyanathan, Amita Gupta and Sylvia M. LaCourse

Pathogens 2022, 11(12), 1481; https://doi.org/10.3390/pathogens11121481 - 06 Dec 2022

Cited by 6 | Viewed by 1622

Abstract

Women are significantly more likely to develop tuberculosis (TB) disease within the first 90 days after pregnancy than any other time in their lives. Whether pregnancy increases risk of progression from TB infection (TBI) to TB disease is unknown and is an active [...] Read more.

Women are significantly more likely to develop tuberculosis (TB) disease within the first 90 days after pregnancy than any other time in their lives. Whether pregnancy increases risk of progression from TB infection (TBI) to TB disease is unknown and is an active area of investigation. In this review, we discuss the epidemiology of TB and TBI in pregnancy, TBI diagnostics, and prevalence in pregnancy. We also review TBI treatment and highlight research priorities, such as short-course TB prevention regimens, drug-resistant TB prevention, and additional considerations for safety, tolerability, and pharmacokinetics that are unique to pregnant and postpartum people. Full article

(This article belongs to the Special Issue Mycobacterium tuberculosis Infection: Policy Gaps and Research Breakthroughs)

9 pages, 1105 KiB

Open AccessReview

High Throughput Sequencing for Clinical Tuberculosis: An Overview

by Tara E. Ness, Andrew DiNardo and Maha R. Farhat

Pathogens 2022, 11(11), 1343; https://doi.org/10.3390/pathogens11111343 - 14 Nov 2022

Cited by 3 | Viewed by 2314

Abstract

High throughput sequencing (HTS) can identify the presence of Mycobacterium tuberculosis DNA in a clinical sample while also providing information on drug susceptibility. Multiple studies have provided a context for exploring the clinical application of HTS for TB diagnosis. The workflow challenges, strengths [...] Read more.

High throughput sequencing (HTS) can identify the presence of Mycobacterium tuberculosis DNA in a clinical sample while also providing information on drug susceptibility. Multiple studies have provided a context for exploring the clinical application of HTS for TB diagnosis. The workflow challenges, strengths and limitations of the various sequencing platforms, and tools used for analysis are presented to provide a framework for further innovations in the field. Full article

(This article belongs to the Special Issue Mycobacterium tuberculosis Infection: Policy Gaps and Research Breakthroughs)

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13 pages, 1129 KiB

Open AccessReview

Preventive Treatment for Household Contacts of Drug-Susceptible Tuberculosis Patients

by Nicole Salazar-Austin, Christiaan Mulder, Graeme Hoddinott, Theresa Ryckman, Colleen F. Hanrahan, Kavindhran Velen, Lucy Chimoyi, Salome Charalambous and Violet N Chihota

Pathogens 2022, 11(11), 1258; https://doi.org/10.3390/pathogens11111258 - 29 Oct 2022

Cited by 2 | Viewed by 2337

Abstract

People who live in the household of someone with infectious pulmonary tuberculosis are at a high risk of tuberculosis infection and subsequent progression to tuberculosis disease. These individuals are prioritized for contact investigation and tuberculosis preventive treatment (TPT). The treatment of TB infection [...] Read more.

People who live in the household of someone with infectious pulmonary tuberculosis are at a high risk of tuberculosis infection and subsequent progression to tuberculosis disease. These individuals are prioritized for contact investigation and tuberculosis preventive treatment (TPT). The treatment of TB infection is critical to prevent the progression of infection to disease and is prioritized in household contacts. Despite the availability of TPT, uptake in household contacts is poor. Multiple barriers prevent the optimal implementation of these policies. This manuscript lays out potential next steps for closing the policy-to-implementation gap in household contacts of all ages. Full article

(This article belongs to the Special Issue Mycobacterium tuberculosis Infection: Policy Gaps and Research Breakthroughs)

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20 pages, 2266 KiB

Open AccessReview

Mycobacterium tuberculosis Transmission in High-Incidence Settings—New Paradigms and Insights

by Mikaela Coleman, Leonardo Martinez, Grant Theron, Robin Wood and Ben Marais

Pathogens 2022, 11(11), 1228; https://doi.org/10.3390/pathogens11111228 - 25 Oct 2022

Cited by 11 | Viewed by 6006

Abstract

Tuberculosis has affected humankind for thousands of years, but a deeper understanding of its cause and transmission only arose after Robert Koch discovered Mycobacterium tuberculosis in 1882. Valuable insight has been gained since, but the accumulation of knowledge has been frustratingly slow and [...] Read more.

Tuberculosis has affected humankind for thousands of years, but a deeper understanding of its cause and transmission only arose after Robert Koch discovered Mycobacterium tuberculosis in 1882. Valuable insight has been gained since, but the accumulation of knowledge has been frustratingly slow and incomplete for a pathogen that remains the number one infectious disease killer on the planet. Contrast that to the rapid progress that has been made in our understanding SARS-CoV-2 (the cause of COVID-19) aerobiology and transmission. In this Review, we discuss important historical and contemporary insights into M. tuberculosis transmission. Historical insights describing the principles of aerosol transmission, as well as relevant pathogen, host and environment factors are described. Furthermore, novel insights into asymptomatic and subclinical tuberculosis, and the potential role this may play in population-level transmission is discussed. Progress towards understanding the full spectrum of M. tuberculosis transmission in high-burden settings has been hampered by sub-optimal diagnostic tools, limited basic science exploration and inadequate study designs. We propose that, as a tuberculosis field, we must learn from and capitalize on the novel insights and methods that have been developed to investigate SARS-CoV-2 transmission to limit ongoing tuberculosis transmission, which sustains the global pandemic. Full article

(This article belongs to the Special Issue Mycobacterium tuberculosis Infection: Policy Gaps and Research Breakthroughs)

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11 pages, 258 KiB

Open AccessReview

Preventive Therapy for Contacts of Drug-Resistant Tuberculosis

by Yousra Kherabi, Simone Tunesi, Alexander Kay and Lorenzo Guglielmetti

Pathogens 2022, 11(10), 1189; https://doi.org/10.3390/pathogens11101189 - 15 Oct 2022

Cited by 7 | Viewed by 2603

Abstract

Preventing the progression of a drug-resistant tuberculosis (DR-TB) infection to disease is an important pillar of the DR-TB elimination strategy. International guidelines have recently proposed fluoroquinolones for tuberculosis preventive therapy (TPT) in DR-TB contacts, although the available evidence is low quality. The pooled [...] Read more.

Preventing the progression of a drug-resistant tuberculosis (DR-TB) infection to disease is an important pillar of the DR-TB elimination strategy. International guidelines have recently proposed fluoroquinolones for tuberculosis preventive therapy (TPT) in DR-TB contacts, although the available evidence is low quality. The pooled data from small observational studies suggest that a fluoroquinolone-based TPT is safe, effective and cost-effective as a preventive treatment in DR-TB contacts. Three clinical trials are currently ongoing to generate higher quality evidence on the efficacy of levofloxacin and delamanid as a DR-TB preventive therapy. Additional evidence is also needed, regarding TPT treatment in fluoroquinolone-resistant-TB contacts, patient and health care worker perceptions on DR-TB preventive therapy for contacts, and the service delivery models to increase DR-TPT access. This state-of-the-art review presents the current literature on TPT for contacts of DR-TB cases, focusing on the available evidence and international guidelines. Full article

(This article belongs to the Special Issue Mycobacterium tuberculosis Infection: Policy Gaps and Research Breakthroughs)

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