The document discusses concerns with the current tuberculosis vaccine BCG and the need for an improved vaccine. BCG provides unreliable protection against pulmonary TB and has not impacted the growing global TB epidemic. It is not recommended for use in HIV-infected infants due to increased risk of complications. While it reduces risk of severe pediatric TB, a better TB vaccine is needed that can eliminate TB as a public health threat in line with global targets. The document outlines the desired characteristics of an improved TB vaccine.

1. A GREAT HUMAN CONCERN

4.  BCG provides unreliable protection against BCG introduced in 1921
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

5.  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

6.  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

7. 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

12.  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.

16.  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.

22.  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.

23.  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.

24.  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.

25.  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.

27. • Can be cured with first line
TB drugs
• Treatable with second line
MDR drugs
• Treatment options strictly
XDR restricted

28. • Complete drug resistant TB??
DR-TB • So what's next???????
• Are we going back to PRE-
??? ANTIBIOTIC era!!!!!!!!!!!!!!!!
• Let us put some efforts..............
GOAL

29.  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