Journal Reading #14 - Tuberculosis

Tuberculosis: Pathogenesis, Current Treatment Regimens
and New Drug Targets
A Journal Reading Presented to

Lendell Kelly B. Ytac, RN
Faculty, FNAHS BSN-Program
Davao Oriental State University
_____________________________________________________
In Partial Fulfillment
of the requirements
for NCM 118
CARE OF CLIENTS WITH LIFE THREATENING CONDITIONS
(ACUTE AND CHRONIC)
By
SANTOS, MIKE LUTHONY G.

Student Nurse, BSN-4A
Journal Reading#14
Tuberculosis: Pathogenesis, Current Treatment Regimens
and New Drug Targets
A Study by Alsayed, S. et al. (2023)
SUMMARY
Tuberculosis (TB), caused by Mycobacterium tuberculosis (M. tb),

remains a pervasive global health threat. Despite Robert Koch's 1882
discovery, TB continues to affect 2 billion people worldwide, with 10 million
cases and 1.5 million deaths annually. TB typically targets lungs (pulmonary
TB) but can spread to other body parts (extrapulmonary TB). M. tb's ability to
remain dormant and reactivate, especially in immunocompromised
individuals, complicates treatment.
Current treatments involve first-line drugs (isoniazid, rifampicin,

pyrazinamide and ethambutol) for drug-susceptible TB. However, multidrug-
resistant TB (MDR-TB) and extensively drug-resistant TB (XDR-TB) pose
significant challenges. MDR-TB requires lengthy (18-20 month) treatment
regimens with second-line drugs like bedaquiline, moxifloxacin and
clofazimine. Shorter (9-11 month) all-oral regimens offer hope, but treatment
adherence and side effects remain concerns. HIV co-infection, COVID-19 and
suboptimal approaches exacerbate TB control efforts.
Recent research focuses on novel drug targets, including GyrA/B, ATP

synthase, QcrB, DprE1, FadD32, Pks13 and MmpL3. Inhibitors targeting
these pathways show promise against drug-susceptible and drug-resistant M.
tb strains. Host-directed therapies, immunomodulation and anti-inflammatory
strategies also merit investigation. Advancements in whole-genome
sequencing and high-throughput screening facilitate identification of potent
anti-TB molecules. However, toxicity, efficacy and pharmacokinetic issues
must be addressed.
Despite progress, TB treatment development faces challenges. Only

three new drugs with novel mechanisms have been approved since 2013.
Serious side effects and limited efficacy hinder treatment outcomes. To
combat TB, it's essential to: (1) discover new drugs with improved safety
profiles, (2) develop personalized medicine approaches, (3) enhance
diagnostic capabilities, and (4) address socioeconomic determinants and
healthcare infrastructure disparities.
TB's persistence underscores the need for sustained research,
innovative treatments and collaborative efforts. The interplay between M. tb
pathogenesis, host immunity and treatment strategies must be better
understood. By exploring new drug targets, improving existing regimens and
addressing global health disparities, we can combat TB's relentless spread.
PERSONAL INSIGHTS AND REFLECTION
Reflecting on my studies of tuberculosis (TB), I am struck by the

complexity of its pathogenesis. TB's causative agent, Mycobacterium
tuberculosis (M. tuberculosis), employs multiple strategies to evade the host
immune response. The bacterium's cell wall components, particularly cord
factor, facilitate intracellular survival and replication within macrophages.
Additionally, M. tuberculosis's ability to form biofilms and granulomas enables
persistent infection. This intricate interplay between host and pathogen
underscores the challenges in developing effective treatments.
Current TB treatment regimens, consisting of isoniazid, rifampicin,

pyrazinamide, and ethambutol, have limitations. The lengthy treatment
duration (6-9 months) and potential side effects (hepatotoxicity, neuropathy)
often lead to poor adherence. Multidrug-resistant TB (MDR-TB) and
extensively drug-resistant TB (XDR-TB) pose significant concerns. The
emergence of resistance underscores the need for novel therapeutic
approaches. I wonder if personalized medicine strategies could improve
treatment outcomes.
Recent research highlights promising new drug targets for TB. Inhibitors
targeting M. tuberculosis's enzymatic pathways, such as DNA gyrase and
topoisomerase IV, show potential. Additionally, compounds disrupting the
bacterium's cell wall synthesis, like beta- lactam antibiotics, demonstrate
efficacy. Host-directed therapies, focusing on immunomodulation and anti-
inflammatory strategies, also merit investigation. The development of novel
drugs and regimens will be crucial in combating TB.
TB's global burden is staggering, with 10 million cases and 1.5 million
deaths annually. The disease disproportionately affects vulnerable
populations, exacerbating health disparities. Effective TB control requires
addressing socioeconomic determinants, improving healthcare infrastructure,
and enhancing diagnostic capabilities. I'm reminded of the critical role
healthcare professionals play in advocating for policy changes and public
health initiatives.
Despite challenges, advancements in TB research offer hope. The

development of vaccine candidates, like M72/AS01E, and innovative
diagnostic tools, such as GeneXpert, demonstrate progress. Moreover,
repurposing existing drugs and exploring host-directed therapies may
accelerate treatment development. Collaborative efforts between researchers,
policymakers, and healthcare professionals will be essential in combating TB.
I'm inspired to contribute to this global effort.
REFERENCE/S
Alsayed, S. et.al (2023). Tuberculosis: Pathogenesis, Current Treatment

Regimens and New Drug Targets. International Journal of Molecular
Sciences, 24(6), 5202. https://doi.org/10.3390/ijms24065202
Luies, L. & du Preez, I (2020). The Echo of Pulmonary Tuberculosis:

Mechanisms of Clinical Symptoms and Other Disease-Induced Systemic
Complications. Clin. Microbiol. 33, e00036-20. [Google Scholar] [CrossRef]
[PubMed]

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Tuberculosis: Pathogenesis, Current Treatment Regimens

and New Drug Targets

A Journal Reading Presented to

SANTOS, MIKE LUTHONY G.

Tuberculosis (TB), caused by Mycobacterium tuberculosis (M. tb),

Current treatments involve first-line drugs (isoniazid, rifampicin,

Recent research focuses on novel drug targets, including GyrA/B, ATP

Despite progress, TB treatment development faces challenges. Only

PERSONAL INSIGHTS AND REFLECTION

Reflecting on my studies of tuberculosis (TB), I am struck by the

Current TB treatment regimens, consisting of isoniazid, rifampicin,

Despite challenges, advancements in TB research offer hope. The

Alsayed, S. et.al (2023). Tuberculosis: Pathogenesis, Current Treatment

Luies, L. & du Preez, I (2020). The Echo of Pulmonary Tuberculosis:

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