Recent advances in diagnosis and treatment of tuberculosis

1. RECENT ADVANCES IN DIAGNOSIS AND
TREATMENT OF TUBERCULOSIS
SEMINAR PRESENTATION
TO
THE
DEPARTMENT OF MICROBIOLOGY
ADELEKE UNIVERSITY, OSUN STATE, NIGERIA
SUPERVISED BY DR. OLADIPO KOLAWOLE
18 AUGUST, 2020
BY
ABIOSUN OLANIKE MOYOLOYE
MATRIC NUMBER: 17/1077

2. OVERVIEW OF TUBERCULOSIS
According to the World Health Organization (WHO),
9.6 million new incident cases of tuberculosis and 1.5
million deaths are estimated to have occurred in 2016,
with Africa and Asia continents carrying the greatest
burden (WHO, 2020)
A persistent non-remitting cough is the most
frequently reported symptom (95%) while typical triad
of:
 Fever,
 Night-sweats and
 Weight-loss are present in roughly 75%, 45% and 55
% of patients respectively (Heemskerk D, Caws M,
and Marais B, 2015).
(WHO, 2016)

3. TRANSMISSION
TB is an airborne infectious disease, spread when a
person with TB disease
 coughs,
 speaks, or
 sings.
When a person is diagnosed with TB disease, a contact
investigation is done to find and test people (like family
members) who may have been exposed to TB.
This is done to prevent community spreading and to
actualize the vision to eradicate the causative agent in
the affected zone.
Cell.com

4. DIAGNOSTIC OF TUBERCULOSIS
Diagnosis of TB crudely started as been an hereditary plague
before the discovery of Mycobacterium tuberculosis, the
causative agent.
On March 24, 1882, Dr. Robert Koch announced the
discovery of Mycobacterium tuberculosis, the bacteria that
causes tuberculosis (TB) in his presentation “Die
Aetiologie der Tuberculose” at the Berlin Physiological
Society conference.
In 1907, Clemens von Pirquet developed a skin test that
put a small amount of tuberculin that was developed
by Koch under the skin and measured the body’s
reaction.
CLEMENS VON PIRQUET
ROBERT KOCH

5. DIAGNOSIS OF TB (CNTD)
1908, Charles Mantoux updated the skin test method by using a needle and
syringe to inject the tuberculin.
In the 1930s, American Florence Seibert PhD developed a process to create a
purified protein derivative of tuberculin (PPD) for the TB skin test.
Today, both TB skin tests and TB blood tests are both used to diagnose TB
infection. Additional tests, like chest x-rays, are needed to diagnose TB disease.
Charles Mantoux

6. DIAGNOSTIC ADVANCEMENT OF TUBERCULOSIS
While conventional culture systems requires several weeks, diagnosis of
TB has entered an era of molecular detection that provides faster and
more cost-effective methods to diagnose and confirm drug resistance
in TB cases.
Diagnosis by New advances in the molecular detection of TB, including
the faster and simpler:
Nucleic acid amplification test (NAAT) and
Whole-genome sequencing (WGS),
(Nurwidya, Handayani, Burhan and Yunus, 2018).
The Xpert MTB/RIF assay is a nucleic acid amplification-based test
using a cartridge based on the GeneXpert Instrument System.
The basis of the Xpert MTB/RIF assay is a real-time PCR that can be
used to detect DNA sequences specific to the MTB in sputum samples
(Friedrich et al., 2013).
GENEXPERT

7. (NURWIDYA, HANDAYANI, BURHAN AND YUNUS, 2018).
Workflow of whole-genome sequencing from specimen processing until diagnostic
report

8. CHALLENGES IN THE DIAGNOSIS OF TB
Discrepant reports between clinical findings, laboratory reports and treatment
outcomes were found in 58.53% cases.
A long delay in diagnosing TB that is mostly related to the time from first medical visit to
diagnosis is a problem of effective diagnosis.
Errors in the diagnostic process were identified in 97.5% of patients in a study carried
out by Neshati.
The most common type of error in diagnosing TB were
failure in hypothesis generation (72%), followed by
History taking and
Physical examination of the patients aside of resources limitation
(Neshati et al., 2018).

9. TREATMENT OF TUBERCULOSIS
Until the discovery of antibiotics, treatment for TB was
limited to provision of warmth, rest, and good food
In the Middle Ages, treatment for scofula (TB of the
lymph nodes and neck) was the “royal touch.” People
lined up for the royal touch of English and French kings
and queens, hoping a touch from the sovereign would
result in a cure.
Cod liver oil, vinegar massages, and inhaling hemlock
or turpentine were all treatments for TB in the early
1800s.
ROYAL TOUCH

10. ANTIBIOTICS ADVANCEMENT
Antibiotics became a major breakthrough in TB treatment.
In 1943, Selman Waksman, Elizabeth Bugie, and Albert Schatz developed
streptomycin. Waksman later received the 1952 Nobel Prize for Physiology
and Medicine for this discovery (CDC, 2020).
Subsequently, it was noted that some patients who received streptomycin
improved only to become ill again because the tubercle bacillus had
developed resistance to the drug.
SELMAN WAKSMAN

11. ANTIBIOTICS ADVANCEMENT (CTND)
A chemical related to aspirin, para-aminosalicylate or PAS, another chemical isonicotinic
acid hydrazide or INH, and a compound released by a fungus-like microbe to inhibit
other organisms from competing with it in the soil (streptomycin), were all discovered
between 1943 and 1951.
By the late 1950s it was observed that if all three drugs were given to TB patients, cure
rates of 80-90% could be achieved. However, the side effects and toxicity were
formidable and required 18-24 months treatment (Nationaljewish, 2020).

12. REGULATION OF TB TREATMENT
The World Health Organization in its first edition on the treatment of
tuberculosis recommended the discontinuation of regimen based on just 2
months of rifampicin (2HRZE/6HE) and change to the regimen based on a
full 6 months of rifampicin (2HRZE/4HR).
 Also, prior recommendations for supervised treatment, as well as the use
of fixed-dose combinations of anti-TB drugs and patient kits as further
measures for preventing the acquisition of drug resistance (WHO, 2020).
Drug cocktail is still the most common treatment for drug-susceptible TB. In
addition to treating TB disease, we can treat latent TB infection to prevent
the development of TB disease in the future.

13. MODE OF ACTIONS OF COMMONLY USED ANTIBIOTICS
Rifampicin (Immunopedia, 2020) Pyrazinamide (PZA) (Zhang, Y., Shi, W.,
Zhang, W., & Mitchison, D. 2014).
Isoniazid (Timmins, Master,
Rusnak and Deretic, 2004)

14. CHALLENGES IN THE TREATMENT OF TB
The major challenges hindering the success of these search are:
High rate of the emergence of resistant strains of Mycobacterium tuberculosis, and
Complexities related to other associated infections and disease conditions, there is
a desperate need for further research input in the treatment options for TB (Nema,
2012).
The resistance of M. tuberculosis to anti-TB drugs is as a result of chromosomal
mutations in genes coding drug targets
CHROMOSOMAL MUTATION

15. VISUAL DETECTION OF RPOB MUTATIONS IN RIFAMPIN RESISTANT MYCOBACTERIUM
TUBERCULOSIS STRAINS BY USE OF AN ASYMMETRICALLY SPLIT PEROXIDASE DNAZYME
(Deng et al., 2012)

16. CONCLUSION
Tuberculosis (TB) is prominent infectious killers of adults and children all over the world.
Many paper review and research studies had been done to probe recent advances and
comprehension of the epidemiology, diagnosis, and management of the disease.
There is lack of consistency with clinical manifestation of the diseases and laboratory
reports due to the reasons discussed earlier.
The growing frequency of resistance of Mycobacterium tuberculosis strains to the most-
effective anti-TB drugs is a significant factor leading to the current TB epidemic.
Drug-resistant strains have evolved majorly due to incomplete treatment of TB patients.
The resistance of M. tuberculosis to anti-TB drugs is as a result of chromosomal mutations
in genes coding drug targets.

17. REFERENCES
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