Interns Seminar

Here, we shall share with you from time to time, some of the interesting seminar presentations by our interns. What we share here are the power point slides which represent the summary of each seminar presentation. Enjoy!

A SEMINAR PRESENTATION

BY:

ORISAKWE, ONYEKACHI TIMOTHY

AND

ANYAKORA , IFEOMA LILIAN

TOPIC:

MULTI-DRUG RESISTANT TUBERCULOSIS (MDR-TB).

INTRODUCTION

• Tuberculosis , MTB, or TB (short for tubercle bacillus ), in the past also called phthisis, phthisis pulmonalis, or consumption , is a widespread, and in many cases fatal, infectious disease caused by various strains of mycobacteria.
• Multidrug-resistant (MDR) tuberculosis (TB), defined as resistance to at least isoniazid (INH) and rifampicin (RFP). Significant high rates of MDR-TB were observed in some parts of the world, not only among previously treated TB patients, due to poor case management, but also among new cases due to transmission in the community.

CAUSES

•Inadequate treatment administration

•Use of substandard drugs
•Irregular drug supply or intake

•Interruption of chemotherapy
•Non-adherence to treatment norms
•Wrong prescription giving incorrect doses of medicine
•Massive bacillary load
•Illiteracy and ignorance (Rajesh, 2008).

TRANSMISSION

•    When people with active pulmonary TB cough, sneeze, speak, sing, or spit, they expel infectious aerosol droplets 0.5 to 5.0 µm in diameter.

•      A single sneeze can release up to 40,000 droplet (Cole and Cook, 1998).

•      The infectious dose of tuberculosis is very small (the inhalation of fewer than 10 bacteria may cause an infection) (Nicas et al., 2005).This makes contact without infection nearly impossible.

•     Those with latent infection are not thought to be contagious (Kumar et al., 2007).

•    If someone does become infected, it typically takes three to four weeks before the newly infected person becomes infectious enough to transmit the disease to others (Mayo, 2006).  
•      Only the extracellular form can be aerosolized.

EPIDEMIOLOGY

*Roughly one-third of the world's population has been infected with M. tuberculosis, with new infections occurring in about 1% of the population each year (WHO, 2002).

*Most infections with M. tuberculosis do not cause TB disease, (CDC , 2011) and 90–95% of infections remain asymptomatic (Skolnik and Richard, 2011).

*Tuberculosis is the second-most common cause of death from infectious disease (after those due to HIV/ AIDS) (Dolin, 2010).

PATHOGENESIS

qM. tuberculosis has a thick, waxy mycolic acid capsule that protects it from  toxic substances.
qM. tuberculosis actually reproduces inside the macrophage and will eventually kill the immune cell.
qLeads to the formation of granuloma which often undergo necrosis.
qForms tubercles which can break off and travel through the blood stream, leading to extra-pulmonary tuberculosis.
qIn a small percentage of hosts the tubercles liquefy, creating bacteria-rich environment and thickening the host’s sputum.

MOLECULAR MECHANISM OF DRUG RESISTANCE

•ISONIAZID(INH)ØResistance results from mutation in KatG gene which codes for catalase-peroxidase haemoprotein KatG.
ØBetween 40% and 95% of INH resistant clinical isolates result from blocking pro-drug activation through deletions or frame shifts in katG gene.
Ø. Most mutations are found in region comprising codons 138 and 328,  with the most commonly observed gene alteration (75% to  90% frequency) being at codon 315 of the katG gene (Hazbon, 2006).

Resistance also results from mutation in the inhA gene  encodes  a mycobacterial  enoyl-ACP  reductase  enzyme  that  is  probably  involved  in  the biosynthesis of mycobacterial cell wall fatty acids.

§RIFAMPICIN(RMP)

ØInhibits RNA synthesis by binding to the β subunit of RNA polymerase and prevents elongation.

ØResistance results from mutation in rpoB gene which codes for RNA polymerase.

ØThe mutation results in loss of target for rifampicin hence resistance.

Ø Mutations at positions 531, 526 and 516 are among the most frequent mutations in RMP-resistant strains.

DIAGNOSIS OF MDR-TB

vIn vitro Drug Susceptibility Test (DST) plays a key role in diagnosis of MDR-TB.v vthe use of gene xpert mtb/rif assay.•This is based on the princple of  nucleic acid amplification test(NAAT)

Only detects rifampicin resistance- serogate marker for MDR-TB.

MANAGEMENT OF MDR-TB

•Sustained government commitment• Accurate, timely diagnosis through quality assured culture and drug       susceptibility testing;•Appropriate treatment utilising second-line drugs under strict supervision;• Uninterrupted supply of quality assured second-line drugs; and

•Standardised recording and reporting system. 

PREVENTION

•Standardised First-line Regimens for New and Re-Treatment Patients•Compliance to Treatment Protocols•Patient Adherence and Supervision of Therapy

Drug Supply

CONCLUSION

•Prevention is the key to effective control of DR-TB. DR-TB is a laboratory diagnosis and therefore quality-assured laboratory services are of paramount importance. Uninterrupted supply of appropriate drugs, treatment under direct supervision with proper education and counselling of patients are also required.

•THANKS FOR LISTENING