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Global Health Econ Sustain MDR-TB and the road ahead

2. Epidemiology of MDR-TB suitable treatment, monitoring, and public health
measures. Several factors contribute to diagnostic delays,
Globally, approximately 500,000 cases of MDR-TB occur including poor healthcare access (geographical and
each year, likely a significant underestimate, with only 25% stigma-related), patient unawareness of TB symptoms,
of cases reported to the WHO in 2016. This underestimation, HIV positivity, negative sputum smear results, and low
coupled with the fact that only a minority of diagnosed patient education status (Storla et al., 2008). Moreover,
cases are managed appropriately, raises the potential for reduced laboratory capacity and availability to perform
further resistance development and onward transmission phenotypic/genotypic resistance testing often result in
(Molla et al., 2022; United Nations, 2018; Fitzpatrick &
Floyd, 2012). At present, Russia, China, India, and South the initiation of empirical DS-TB treatment erroneously,
Africa represent over 60% of all global MDR-TB cases; while insufficient patient support fosters non-
compliance to treatments. Indeed, MDR-TB compliance
however, due to migration, the epidemiology of MDR-TB is historically challenging due to associated toxicity,
is evolving (Ou et al., 2021). If current trends persist,
MDR-TB is poised to become the predominant form of parenteral routes of administration, and significantly
TB in Eastern Europe, Australasia, and Africa, as well as prolonged treatment durations (18 – 24 months) (Jang &
overall in low- and middle-income countries (Ou et al., Chung, 2020; Monedero & Caminero, 2013).
2021; Bu et al., 2023). MDR-TB accounts for approximately While cure rates in MDR-TB are lower than in DS-TB
3.6% of new TB cases and 21% of previously treated TB (59% vs. 85%) (Nyang’wa et al., 2022; Rockwood et al.,
cases, with over 75% of MDR-TB cases occurring in 2016), accompanied by higher loss to follow-up rates
patients with no prior TB treatment exposure, highlighting (16% vs. 6%) (Van den Hof et al., 2016; Jiang et al., 2023),
the significant contribution of community transmission newer all-oral regimes now advocated by the WHO, such
(Molla et al., 2022; Fitzpatrick & Floyd, 2012). While as 6-month BPaL/BPaLM (bedaquiline, pretomanid,
exposure to an MDR-TB case is an obvious risk factor linezolid ± moxifloxacin) (Labuda et al., 2024), have
for acquisition, several other risk factors are implicated, revolutionized MDR-TB treatment. These regimens have
including house overcrowding, smoking, alcohol misuse, achieved high treatment success rates (75 – 89%), culture
prison exposure, low socioeconomic status, diabetes, conversion rates at 2 months (Sinha et al., 2023), low
and human immunodeficiency virus (HIV) infection. In relapse rates (~3%), heightened compliance rates, and
developing countries, where these factors often coexist, the improved tolerability, except for high-dose linezolid use,
development, propagation, and maintenance of MDR-TB which may pose issues (Nyang’wa et al., 2022). As such,
within communities are possible, necessitating multimodal BPaL/BPaLM is now recommended for all MDR-TB
approaches to achieve control (Molla et al., 2022; Xi patients, irrespective of HIV status, provided they have
et al., 2022; Iradukunda et al., 2021). In 2021, the WHO had less than 1 month of prior exposure to associated
published a revised global list of high-burden countries for drugs, are at least 14 years old, and have no central nervous
TB, MDR-TB, and HIV, demonstrating their clear overlap system or osteoarticular involvement (WHO, 2022).
and the urgent need to improve HIV testing in TB cases, By 2026, 78% of global MDR-TB cases will be treated
currently at only 60%. Therefore, there is a real need to utilizing BPaL/BPaLM, with real-world data suggesting
redesign, integrate, and coordinate HIV and TB national that BPaL can reduce national TB service budgets by
programs, thereby reducing their respective transmission, 15 – 32%. However, achieving this global reach requires
reactivation (e.g., isoniazid preventive therapy), and drug security, enhanced patient engagement, and the local
negative effects on their respective disease progressions availability of appropriate monitoring (Gupta et al., 2024;
and outcomes (United Nations, 2018; WHO, 2021; Assebe Mulder et al., 2022). Importantly, primary bedaquiline
et al., 2015; Sultana et al., 2021). resistance is not uncommon, observed in approximately
3. Existing issues with the management of 3.8% of TB isolates from South Africa between 2015 and
2019, and is associated with poorer outcomes (Ismail et al.,
MDR-TB 2022). Therefore, it is imperative to conduct confirmatory
3.1. MDR-TB management options resistance testing against any proposed treatments

Diagnosing MDR-TB involves several critical steps. alongside appropriate follow-up, as the WHO suggests that
First, affected individuals must recognize their illness susceptibility testing should not delay treatment initiation
and seek care at a health-care facility. Second, health- (Van Rie et al., 2022).
care professionals must accurately assess and identify The WHO’s End TB strategy aims to achieve a 95%
the individual’s TB risk and order relevant diagnostic reduction in TB-related mortality and a 90% reduction
and resistance testing. Third, on diagnosis, provide in TB incidence by 2035, based on a 2015 baseline

Volume 2 Issue 2 (2024) 2 https://doi.org/10.36922/ghes.2876