Multidrug-Resistant Tuberculosis: A Global Threat

This assignment delves into the complex issue of Multidrug-Resistant Tuberculosis (MDR-TB), examining its causes, transmission, and global implications. It analyzes the challenges associated with diagnosing, treating, and preventing MDR-TB, highlighting factors contributing to treatment failure and patient mortality. The assignment also explores potential solutions, including improved diagnostic tools, novel drug development, and enhanced public health interventions.

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Tuberculosis (TB) is one of the major causes of morbidity and mortality affecting
humankind worldwide. It is caused by bacterium, Mycobacterium tuberculosis that spreads
through air from one person to another. It affects lungs and in extreme cases, affects other body
parts and cause symptom like chest pain, chronic cough, fatigue, weakness, fever or weight loss.
TB deaths are widespread contributing to 7% of most common deaths and first infectious disease
becoming a major public health issue. There are also problems of late diagnosis and interrupted
treatment being the cornerstone for TB widespread affecting millions of people. Control and
prevention of TB are the priority areas to curb this major health issue. This essay aims to
examine the causes of MDR-TB and genetic resistance and mismanagement of TB as the key
contributing factors to high morbidity and mortality rates worldwide, and then asses the two
effects, side effects of drug-resistant TB treatment, high Tb transmission rates, emergence and
major public health issue.
TB is one of the major causes of death worldwide and greatly contributing to burden of
disease due to mismanagement of TB medications and bacterial resistance to drugs. In 2015, 1.8
million people died from TB majorly in low and middle-income countries (95%). In addition,
10.4 people In addition, 10.4 million people fell ill with TB and estimated 480,000 cases
developed MDR-TB. This shows that TB incidence has accelerated to four to 5% annually and
likely to increase by 2020 (Zumla, George, Sharma, 2015). This evidence shows that TB Is going
to be epidemic taking a heavy toll of life by 2030. It is important to study the causes of MDR-TB
resistance to mitigate this major public health issue. There is an ineffective use of formulation of
drugs, poor quality medicines, single drug usage, or bad storage conditions causing drug
resistance. An also premature treatment interruption is causing this drug resistance and
transmission to the population. It is difficult to treat MDR TB resistance as the treatment options

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are expensive and limited and the recommended medicines are not always available. People face
adverse drug reactions that is difficult to be treated and as a result, MDR TB is developed. it has
been reported that apart from multidrug resistant TB there is additional anti TB drug resistance
that respond to few medicines in around 117 countries worldwide.
Rifampicin and Isoniazid are considered powerful first line drugs for treating TB and
MDR TB is treatable only with second line drugs, however, they are expensive, limited and
highly toxic and genetic mutations. The main mechanism of this drug resistance is due to genetic
mutation at the bacteria loses the ability to transfer genes through plasmids between organisms
by horizontal transfer. There are other mechanisms of drug resistance where M. tuberculosis
(TB) cell wall consisting of complex liquid molecules act as barriers and stop drugs from
entering the cell. There are also inactivating and drug modifying enzymes TB genome that code
for protein and has the ability to inactive drug molecules (Augustine & Jain, 2014). These
enzymes are acetylate, adenylate or phosphorylate drug compounds. There are also drug efflux
systems in TB cell consisting of molecular systems that pump drug molecules actively out of the
cell. There are also instances of spontaneous mutations that can occur in TB genome altering the
proteins of the target cells by the drugs which make the drug of the bacteria resistant.
The mutation takes place in the genes of the bacteria, changes conformation and as a
result, unable to prevent the infection spread due to bacterial resistance. Mutation takes place in
rpoB gene that code for bacterial RNA polymerase beta subunit (Prammananan, 2017). In TB,
which are non-resistant rifampins binds to the RNA polymerase beta subunit and there is
disruption of elongation step in transcription. When mutation takes place in the rpoB gene there
is change in the Amino acid sequence and eventually beta subunit conformation changes.
Therefore, rifampin is no longer able to prevent or bind transcription and bacteria become

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resistant. There are other mutations that occur in isoniazid (INH) that includes inhA, ahpC or
katG genes (Van Deun, Aung, Hossain, 2015). In this mutation, there is apparent replacement of
amino acid in the NADH binding site of InhA resulting in INH resistance that prevents the
mycolid acid biosynthesis from which the bacterium uses for its cell wall. The mutation that
occurs in katG gene results in the inability of enzyme catalase peroxidase to convert to INH that
is the biologically active form. Therefore, INH becomes ineffective and as a result, the bacteria
become resistant (Salinas, Armstrong, Silk, 2017). MDR-TB or RR -TB can occur in two main
ways (Kasapo, Chimzizi, Simwanza, 2017). Firstly, the patient does not take my medicines as
exactly as prescribed by the Healthcare professional. It can also happen if the patient is not
taking the current drugs and make the bacteria resistant to more variety of drugs that is not
recognized by the healthcare provider. In this condition, the resistance remains undiagnosed and
referred to as acquired TB.
Another reason of MDR-TB is the misuse of the drugs by the patients, as they do not
complete the course or inefficiency of drug supply. MDR-TB resistance also occurs when there
is mismanagement or misuse of anti TB drugs (Kåhrström, 2014). In this cases, those patients are
included who do not complete their full drugs course or treatment or healthcare professionals
prescribe the wrong treatment, dose or duration for taking drugs. There are also instances when
drug supply is not in ample amount or of poor quality. This resistance causes high burden for TB
resistance and a public health issue where around 30 countries are labeled as high burden. Apart
from long treatment duration, limited treatment options, side effects and toxicity, there are
psychosocial issues that affect patients and challenge the MDR-TB (Thomas, Shanmugam,
Malaisamy, 2016). The systematic review results depicted that there are economic and
psychosocial issues that challenges MDR patients. Therefore, there is requirement of innovative,

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feasible economic and psychosocial interventions that help the patients to cope up with MDR-TB
with the illness, improve treatment outcomes and adherence and improve their quality of life.
From the above discussion, it can be inferred that the main causes of MDR-TB are non-
adherence to prescribed drugs and treatment, poor management, unavailability or lack of national
programme. Apart from long treatment duration, limited treatment options, side effects and
toxicity, there are psychosocial issues that affect patients and challenge the MDR-TB. There is
also person-to-person transmission of TB. In most cases, TB is cured through a strict procedure
that is six-month drug treatment regimen provided to TB patients with strict supervision and
support. However, MDR-TB becomes resistant and gives least response to rifampicin and
isoniazid being the most powerful anti-TB drugs. There is high burden of MDR-TB in around 30
countries developing resistance to two major drugs-rifampicin or isoniazid that causes resistance.
Therefore, there is need for treatment compliance, national programme and monitoring of
patients response to taking medications.

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References
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