1. Tuberculosis

2. 1882 March 24– Robert Koch – “one seventh of all human beings die of tuberculosis and… if one considers only the productive middle-age groups, tuberculosis carries away one-third and often more of these…”

3. M tuberculosis as causative agent for tuberculosis
Robert Koch
1886

4. TB – A Multi-system Infection

5. Global burden of TB
200 crore infected, i.e. 1 in 3 of global population
90 lakh (139/lakh) new cases in 2013, 80% in 22 high-burden countries
40 lakh new sm+ve PTB (61/lakh) cases in 2008
Global incidence of TB has peaked in 2004 and is declining.
1.5m deaths in 2013, 98% in low-income countries
MDR-TB -prevalence in new cases around 3.6%
Source of information (2006 report) 06 3

6. Estimated TB incidence rate, 2007
:Source: WHO Geneva; WHO Report 2009: Global Tuberculosis Control; Surveillance, Planning and Financing

7. Magnitude of the Problem
Global annual incidence = 9.1 million
India annual incidence = 1.9 million
India is 17th among 22 High Burden Countries (in terms of TB incidence rate)
In 2008, there were estimated 9.4 million new cases equivalents to 139 cases per 100,000 population of TB globally. In 2008, out of the estimated global
annual incidence of 9.4 million TB cases, 1.98 million were estimated to have occurred in India, of whom 0.87 million were infectious cases, thus catering to a fifth of the global burden of TB. About 40% of Indian population is infected with TB bacillus. The incidence of TB in India is estimated based on findings of the nationwide annual risk of tuberculosis infection (ARTI) study conducted in
The national ARTI being 1.5%, the incidence on smear positive TB cases in the country is estimated as 75 new smear positive cases per 100,000 population
Source: WHO Geneva; WHO Report 2008: Global Tuberculosis Control; Surveillance, Planning and Financing
Dr. KANUPRIYA CHATURVEDI
4/17/2019

8. Problem of TB in India Estimated incidence
171 per lakh in 2013
Estimated prevalence of TB disease
211 per lakh in 2013
Estimated mortality
19/lakh in 2013
240,000 deaths due to TB each year
Divide into two slides

9. Natural History of TB Infection
Exposure to TB
No infection
(70-90%)
Infection
(10-30%)
Latent TB
(90%)
Active TB
(10%)
Never develop
Active disease
Untreated
Treated
Die within 2 years
Survive
Die
Cured

10. Latent TB vs. Active TB
Latent TB (LTBI) (Goal = prevent future active disease) = TB Infection = No Disease = NOT SICK = NOT INFECTIOUS Active TB (Goal = treat to cure, prevent transmission) = TB Infection which has progressed to TB Disease = SICK (usually) = INFECTIOUS if PULMONARY (usually) = NOT INFECTIOUS if not PULMONARY (usually)

11. Agent-Mycobacterium tuberculosis

12. TB Invades/Infects the Lung
Effective immune
response
Infection limited
to small area of lung
Immune response
insufficient

14. Source of infection
Human source- Sputum smear positive case can infect 15 person per year if untreated
Bovine source- infected milk

15. Factors associated with TB
Host factors
Age- affect all ages, but more in productive age group
Males are more affected than females
Nutrition status
Immunity
Social factors
Poor housing
Over crowding
Smoking , alcoholism
poverty

16. Classification of tuberculosis
Pulmonary – affecting lung or tracheobronchial tree
Extra pulmonary- involving
Pleura or pericardium
Lymphnodes
Abdomen
Genitourinary tract
Skin
Joints
Bones
meninges

17. Bacteriological confirmed TB and clinical tuberculosis
Drug resistant tubeculosis

18. Pulmonary tuberculosis
The most common symptom of PTB is a persistent cough of two weeks or more, with or without expectoration.
It may be accompanied by one or more of the following symptoms:-
• Fever, night sweats, weight loss
• Chest pain, hemoptysis, shortness of breath, tiredness and loss of appetite

19. Extra pulmonary tuberculosis
A person with extra-pulmonary TB may have symptoms related to the organs affected along with constitutional symptoms stated above.
Enlarged cervical lymph nodes with or without discharging sinuses (TB Lymphadenitis)
Chest pain with or without dyspnoea in pleural TB
Pain and swelling of the joints in bone tuberculosis (fever, backache, deformity in spinal TB)
Signs of raised intra-cranial tension like irritability, headache, vomiting, fever, stiffness of the neck and mental confusion in TB meningitis
Painless haematuria or sterile pyuria in renal tuberculosis and infertility in genito-urinary TB.

20. Control of tuberculosis
Has 2 component
Preventive –
BCG vaccination,
INH prophylaxis for children
Curative
Case finding and treatment

21. BCG Vaccination Danish 1331 strain
Dose 0.1 ml intra dermal (0.05 ml in < 4 weeks)
Effective in reducing pediatric tuberculosis and mortality
Contraindicated in those with eczema, immunodeficiency states

22. Evolution of TB Control in India
1950s-60s Important TB research at TRC and NTI
National TB Programme (NTP)
Programme Review
only 30% of patients diagnosed;
of these, only 30% treated successfully
RNTCP pilot began
RNTCP scale-up
million population covered
>80% of country covered
2006 Entire country covered by RNTCP
4/17/2019

23. Program performance and evolution of RNTCP
Despite a nationwide network of facilities , NTCP failed to yield satisfactory results. The situation did not change much.
The case finding efficiency was only 30 of the expected level although the mortality rate decreased to 53/100,00 population
Government of India launched the Revised National Tuberculosis Control Program(RNTCP) in 1997 encouraged by the results of Pilot studies were tested in
4/17/2019

24. Case finding tools Sputum microscopy X ray Sputum culture
Light microscopy
Fluorescent microscopy
X ray
Sputum culture
Genotypic method
Phenotypic method

25. Sputum microscopy
Sputum smear microscopy is the most widely used and acceptable testing tool for diagnosing smear positive pulmonary TB.
Ziehl-Neelsen staining technique is used in RNTCP.
Sputum microscopy has the following advantages:-
• Simple, inexpensive, requires minimum training
• High specificity
• High reliability with low inter-reader variation
• Can be used for diagnosis, monitoring and defining cure
• Results are available quickly
• Feasible at peripheral health institutions
• Correlates with infectivity in pulmonary TB cases

26. X ray
Chest x-ray as a diagnostic tool is more sensitive but less specific with higher inter and intra reader variation.
It should always be preceded by a repeat sputum smear examination following treatment with
It is also useful for diagnosing extra pulmonary TB like pleural effusion,pericardial effusion, mediastinal adenopathy and miliary TB.
The following are the limitations of the chest x-ray as a diagnostic tool
High inter and intra-reader variation
No shadow is characteristic of TB

27. Diagnostic tools for MDR-TB / XDR TB:
Drug resistant TB (MDR/XDR and other types) is a laboratory based diagnosis either
phenotypically i.e., growing the bacteria (culture) and demonstrating the ability of bacteria to grow in the presence of the anti-TB drugs (drug sensitivity testing - DST)
genotypically by demonstrating the presence of resistance genes using molecular methods.

28. Culture The conventional and newer rapid tools used for diagnosis are:
Solid culture medium - (Egg-based Lowenstein Jensen) or agar based 7H11/10medium
Liquid culture medium – Commercial automated MGIT 960

29. Molecular Assays
PCR based technologies resistance genes (rpoβ for rifampicin, katG and inhA for INH etc).
Line Probe Assays (LPA) which
GeneXpert – a completely closed automated system using real-time PCR which has a sensitivity of 70-90% even for smear negative cases and can also detect the presence of rifampicin resistance

30. Process of diagnosis of Pulmonary TB
Referral of Presumptive TB cases to DMC
Collection of 2 sputum samples

31. Algorithm for case detection

34. Diagnosis of extra pulmonary tuberculosis
(a) Fine Needle Aspiration Cytology (FNAC) and direct smear examination (b) Excision / Biopsy of specimen for histopathological examination (c) Fluid for cytology , biochemical analysis and smear examination (d) X-ray of the involved region (e) Ultra Sonography for Abdominal Tuberculosis (f) Culture for Mycobacterium tuberculosis (M.Tb)

36. Chemotherapy First line drugs Bacteriocidal Bacteriostatic
Rifampicin (R)
Isoniazide (H)
Pyrazinamide (P)
Streptomycin (S)
Bacteriostatic
Ethambutol (E)

37. Chemotherapy Second line drugs Fluroquinalones Ethionamide Capreomycin
Cycloserine
Thioactetazone
Para amino salicilic acid
Macrolides
NEW DRUG-
BEUDAQUALINE

38. Category of treatment in RNTCP

39. Sputum examination
Category 1
2 months -
start continuation phase. Repeat sputum at 4 th and 6th month +
Continue intensive phase for one more month.
If sputum positive in 5th month then considered as failure
Category 2
3 months
Start continuation phase.
Test sputum at 5 months, 6 months and completion of tratment
Continue intensive phase for one more month
Test sputum at 4 months, if positive send for culture and drug sensitivity

42. Non-DOTS (ND) treatment regimen under RNTCP
Given to
Those with adverse reactions to rifampicin and/or pyrazinamide
“New” patients who refuse DOTS despite all efforts
12-month duration, comprising 2 months of SHE and 10 months of HE (2SHE / 10HE).
Dosages administered per day in the regimen are:
Isoniazid mg
Ethambutol mg
Streptomycin mg (500 mg for those >50 years of age).

43. Treatment Related Information
Importance of DOT
Role of rest, special diet and isolation
Cough hygiene and sputum disposal
Referral for HIV counseling and testing
Diabetes screening and control
Adherence to follow-up schedules:
Sensitization on adverse reactions:
Smoking
Alcohol abuse
Importance of screening symptomatic contacts and children below 6 years

46. Drug resistant tuberculosis
Multi Drug resistant tuberculosis:
resistance to isoniazide and rifampicin
Poly drug resisitance
Resistance to more than one first line drugs (otherthan INH and rifampicin)
Extensive drug resistance
Resistance to any fluroquinalones and at least one of the second line injectables ( capreomycin, kanamycin,and amikacine)

47. Drug resistance tuberculosis
Drug resistant TB is seen in 2.2 % of new cases and 15 % or retretment cases
Diagnosed at intermediate reference laboratory (IRL) by culture, and drug sensitivity test
Rapid diagnosis by gene Xpert is avaliable

48. Multi Drug resistance tuberculosis
Treatment is initiated at DOTS plus site
Given as single daily dose under DOT
Phase
Duration
drugs
Intensive phase
6-9 months
Kanamycin
Levofloxacin
Ethionamide
Pyrazinamide
Ethambutol
cycloserine
Continuation phase
18 months
Levofloxacine
Cycloserine
Reserve drugs
PAS
Capreomycin
moxifloxacin

49. Regimen of XDR TB Phase Duration Intensive phase 6-12 months
Capreomycin
PAS
Moxifloxacin
INH high dose
Clofazamine
Linezolid
amoxyclav
Continuation phase
18 months
Reserve drugs
Clarithromycin, thioacetazone

50. TB in pregnant women
IP with Isoniazide, refampicin and ethambutol for 2 months
CP with INH and rifampicin for 7 months
Ethambutol can be stopped after one month if found sensitive to R and H
Vitamin B6 25 mg Od to pevent peripheral neuropathy

51. TB and HIV All TB cases should be tested for HIV in ICTC
All HIV positives should be referred for sputum microscopy

52. TB and Diabetes Diabetes accounts for 15 % of tuberculosis
All tuberculosis cases should be screened for diabetes
Blood sugar level of Diabetic TB patients should be checked regularly to asses control

53. TB notification

54. Thank you