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short description about tb todayTRANSCRIPT
TUBERCLUOSIS
A GREAT HUMAN CONCERN
Discoverer of M.tubercluosis-Robert Koch
Existing TB Vaccine Ineffective
BCG provides unreliable protection against pulmonary TB, which accounts for most TB disease worldwide
BCG is not know to protect against latent TB
BCG is not recommended for use in infants infected with HIV due to increased risk for severe BCG-related complications
Despite wide use, particularly in high burden countries, BCG has had no apparent impact on the growing global TB epidemic
BCG does reduce risk of severe pediatric TB disease, so it should continue to be used until a better TB vaccine is available
BCG introduced in 1921
Goals for Better TB Vaccines Eliminate TB as a public health
threat, in line with global targets (<1 case/million), in conjunction with new drugs and diagnostics
Safe and effective in preventing TB in children, adolescents and adults, including people with HIV (for whom BCG is unsafe)
Protect against all forms of TB – including MDR and XDR
Drug Resistance
WHO estimates 490,000 MDR-TB cases emerge every year, with more than 110,000 deaths
Extensively drug-resistant (XDR) TB has been identified in 57 countries as of November 2009
Treatment for drug-resistant TB is much longer, more complex and more expensive - with much lower success rates
TB -India
370,000 people die of TB in India every year (~ 1000 deaths per day, 2deaths every 3mins)
The estimated incidence of TB in India is 1.8 million new cases annually.India accounts for approximately one fifth of the global TB incidence.
Of world's estimated 450,000 MDR-TB patients 15700 MDR-TB suspects are from India in the past years
Selman Waksman Discoverer of streptomycine - first antibiotic (TB)
1/3 of AIDS patients die due to TB
And many more.........
Aims of Treatment TB
Cure the patient
Prevent Death
Prevent Relapse
Prevent Transmission
Prevent development of drug resistant
TB Drugs First line Drugs: More effective, less toxic. Second line Drugs: less effective than the
first-line drugs but more toxic. Third line drugs: either because they are
not very effective or because their efficacy has not been proven (e.g., linezolid, R207910). Rifabutin is effective, but is not included on the WHO list because for most developing countries, it is impractically expensive.
First line Drugs
Second line Drugs-Aminoglycosides& polypeptides
Second line Drugs:Fluoroquinolones & thioamides
Third line drugs
Other drugs that may be useful, but are not on the WHO list of SLDs:
rifabutin macrolides: e.g., clarithromycin (CLR); linezolid (LZD); thioacetazone (T); thioridazine; arginine; vitamin D; R207910.
Drugs acting at different parts of micobacterium
Current Drugs and limitations
Poor absorbance and toxic
Toxic to liver
CNS side effects
Current Drugs and limitations
Rifampicine and its derivatives showed Decrease in white blood platelet count
Compounds under clinical trail
Compounds under clinical trail
F3C
NO2
S
N
O
N
O
O
BTZ
"Directly Observed Treatment, Short-course"
The DOTS strategy focuses on five main points of action.
These include government commitment to control TB,
diagnosis based on sputum-smear microscopy tests done on patients who actively report TB symptoms,
direct observation short-course chemotherapy treatments,
a definite supply of drugs, and standardized reporting and recording of
cases and treatment outcomes.
MDR-TUBERCLUOSIS MDR-TB is TB that is resistant to at
least two of the best anti-TB drugs, isoniazid and rifampicin. These drugs are considered first-line drugs and are used to treat all persons with TB disease.
XDR-Tubercluosis Extensively drug resistant TB (XDR
TB) is which -resistant to isoniazid and rifampicin, plus resistant to any fluoroquinolone and at least one of three injectable 2nd line drugs, i.e amikacin, kanamycin or capreomycin.
XDR-TB in South Africa August 2006
53 of 544 patients defined as XDR-TB cases.
52 of the 53 patients died within 25 days
XDR-TB likely in bordering in afro-asian countries.
The first XDR-TB case in India is reported in King Georg Medical University, Lucknow September 2007.
New Chemical Entities
TB •Can be cured with first line drugs
MDR •Treatable with second line drugs
XDR •Treatment options strictly restricted
DR-TB •Complete drug resistant TB??•So what's next???????
??? •Are we going back to PRE-ANTIBIOTIC era!!!!!!!!!!!!!!!!
GOAL •Let us put some efforts..............
What we can do.......... As an organic chemist synthesize few
libraries and check for the in vivo. If you got reasonable activity, do some
SAR. Pick a candidate do pharmacokinetic
studies.... You may get a lead molecule If you didn't get try again.... Because your efforts will definitely help
them.......see next slide
ALL LIVES HAVE EQUAL VALUE
Thank you