1. Epidemiology and Control Maria Liaqat-1042 Mahad Javaid-1056
Tuberculosis
Epidemiology and Control
Maria Liaqat-1042
Mahad Javaid-1056

2. Scenario:
A 16 years old girl presented in OPD with H/O of low grade fever, anorexia and weight loss for one month. She complains of productive cough and chest pain.
A 25 years old male complained of evening rise of temperature, weight loss. When presented to OPD for checkup, he coughed up blood(bloody phlegm/hemoptysis) which fell on the desk and in attempt to muffle his cough, his hands were too contaminated by the blood. Cervical lymph nodal swelling was also present. FNA(fine needle aspiration) was performed which showed granuloma formation.

3. Objectives Natural History of Tuberculosis Epidemiological Indices
Burden of Disease
Control and Treatment

4. Tuberculosis
Tuberculosis is an infectious disease that is caused by Mycobacterium tuberculosis.
The disease primarily affects lungs causing pulmonary tuberculosis but it can also affect intestines, bones, joints, lymph nodes, skin and various other tissues.

5. Source Of Infection
There are two sources of infection: Human source & Bovine source.
The most common source of infection are humans whose sputum is positive for tubercle bacilli and who has either not received any treatment or has not been treated fully. On average persons contract infection from one case of TB.
The second source of infection is infected milk but it is not a major problem because of the practice of boiling milk before consumption.

6. Burden Of Disease
Tuberculosis is curable but kills 5000 people daily worldwide.
98% of the deaths are in developing world affecting mostly young adults in their most productive years.
Quarter of a million Tuberculosis deaths are HIV associated in individuals with reduced immunity.
If left unchecked within 20 years Tuberculosis will kill a further 35 million people worldwide.
About 2 billion people, equal to one third of world’s population, are infected with Tuberculosis bacilli. 1 in 10 people worldwide are infected with Tuberculosis bacilli will become sick with bacilli.

7. Clinical Presentation
Productive cough for more than two weeks
Fever
Night sweats
Weight loss
Chest pain
Modes Of Transmission
The disease is transmitted by droplet infection via coughing or sneezing.
The incubation period of the disease is from 3 to 6 weeks.

8. Pathogenesis
Mycobacterium tuberculosis is the agent responsible for causing tuberculosis. It is readily ingested by phagocytes and is resistant to intracellular killing. It produces Exported Repetitive Proteins that protect the bacterium from enzymes of lysosomes. Two types of lesions are Exudative lesions and Granulomatous lesions.
Exudative lesion is acute inflammatory response at the initial site of infection. Exudative lesion with draining lymph node is called Ghon complex. Granulomatous lesion consists of central area of giant cells of Langhans with tubercle bacilli surrounded by epithelioid cells. Tubercle is a granuloma surrounded by fibrous tissue with central caseous necrosis.

9. Factors
Host
Age: TB affects all age groups from children to elderly people. Mostly working age/productive age males
Sex: It is more prevalent in males than in females.
Heredity: TB is not a hereditary disease however latest studies have shown inherited susceptibility is an important risk factor.
Nutrition: Malnutrition is the most important host factor that affects the individuals more in the developing countries where malnutrition is highly prevalent.
Immunity: There is no inherited immunity against TB however immunity develops as a result of infection of BCG vaccination(Artificially acquired active immunity)
Social
Poor quality of life, population explosion, over crowding, malnutrition, lack of knowledge and large families
Related to quality of life (No less than 70,000 people die from TB and it is highest in people of low socioeconomic class)

10. (INH, Rifampicin , Fluoroquinolone Resistance)
(MDR, 2nd-line drug Resistance)
WHO defines XDR-TB as MDR-TB that is resistant to at least one fluoroquinolone and a second-line injectable drug (amikacin, capreomycin, or kanamycin) Source:1.2

11. Epidemiological Indices International and National
10 million new cases of TB emerged globally in 2018
96% cases reported were from Asian countries and only 6% from the Western World
Around 510,000 new cases of TB emerge annually including children. This accounts for about 61% of TB burden in WHO East Mediterranean Region
Pakistan is now 5th on the list of highest cases of TB and 4th on drug resistant TB globally (350 cases in 100,000 population at any given time)

12. Incidence of tuberculosis per 100,000 in Pakistan
Source:1.1

13. Current International and National efforts
In MDGs to be halted by 2015 resulted in endorsed partnership to ‘Stop Tuberculosis’
By 2050, eliminate Tuberculosis as a public health problem(<1 case per million population)

14. Control Of Tuberculosis

15. Immunization BCG (Bacillus Calmette-Guérin) Vaccine Storage:
Live attenuated bacterial vaccine
Attenuated M. bovis
Types: 1) Freeze-dried 2) Fresh Liquid
Storage:
At a < 10° C
Away from direct sunlight
ADMINISTRATION
Intradermal
Tuberculin syringe(Omega microstat syringe)
Site of Injection: Above the insertion of the deltoid muscle.
95% of BCG vaccine recipients experience a reaction at the injection site that heals within 2-5 months leaving a superficial scar.

16. WHO Recommendations
Recommended in countries or settings with high incidence of TB
A single dose should be given to all healthy neonates at birth or earliest available opportunity.
Safely co-administered with other routine childhood vaccinations.
Revaccination is not recommended.
Contraindicated in immunocompromised persons and those undergoing immunosuppressive therapy.
Dosage:
Adults = 0.1 mg in 0.1 mL volume
Infants ≤ 1 year = mL

17. Case Finding The Case Target Group
(Diagnosing cases)
The Case
Target Group
Intensified Case Finding(Mass Screening)

19. Case Finding Methods (Diagnostic Techniques) Direct Techniques
Indirect Techniques

20. Direct Techniques Culturing Methods(Gold Standard)
BACTEC 460: Pakistani inventor, radiation hazard, expensive, solid medium
MODS: New, prevalent in developing countries, cheap(3$), give drug susceptibility results too, risk of exposure, liquid culture medium
Thin Layer Agar Method: complicated technique, very effective, cheap
MGIT 960: Successor to BACTEC 460, gives drug sensitivity results as well, expensive, liquid culture(2007 WHO recommended)

21. Lowenstein-Jenson Medium: (AFB culture) easy, risk of exposure, cheap, GOLD STANDARD in our country , long detection time(4 – 8 weeks)
Source: 1.5

22. Staining/Microscopy Methods
Ziehl-Neelson(Z-N) Staining: cheap, easy, risk of exposure as sputum for smear is taken
Fluorescence(Luciferase Antibody Assay) Staining: costly, easy

23. Molecular Methods
Xpert MTB/RIF(Gene Xpert): Detects resistance to Rifampicin, can be done of soft tissue as well as bone tissue, WRD (December 2010, extended 2013 endorsed by WHO, as Initial test for adults and children with symptoms of T.B, favoured over culturing and microscopy)
PCR: not recommended with blood sample, rapid detection method

24. Indirect Techniques X-ray (very important in our clinical setup)
Histopathology
Tuberculin Skin Test/Mantoux Test
Quantiferon Gold Test(not the gold standard)
IGRA
ADA Test
Serology

26. CASE DEFINITIONS
Bacteriologically Confirmed TB Case: Biological sample diagnosed with TB via Direct Techniques/Methods i.e Xpert MTB/RIF , Microscopy, Culture
Clinically Diagnosed TB Case: Practitioner diagnosed it as TB via Indirect Techniques/Methods i.e X-ray, Histopathology
New Patient: never been treated or treatment < 1 month
Previously Treated Patient: Treatment > 1 month

27. Relapse Patient: Treated, Cured, Reinfection or true relapse
Treatment After Failure Patients: treated, failed
Treatment After Loss To Follow-Up Patients: treated, lost to follow-up
Other Previously Treated Patients: treated, no info on course of treatment and results

28. TREATMENT First line Anti-TB Drugs:
Isoniazid/INH(most commonly used for chemoprophylaxis), Rifampin/Rifampicin, Ethambutol, Pyrazinamide, Streptomycin(contraindicated in pregnancy), causes deafness in the fetus)
Second line Anti-TB Drugs:
Amikacin, Ciprofloxacin, Ofloxacin, Ethionamide, PAS, Capreomycin, Cycloserine

29. REGIMENS Standard Regimen: Alternative Regimen:
Rifampin, pyrazinamide and ethambutol. Pyrazinamide can be discontinued after 2 months, and the remaining 2-drug regimen continued for 4 months.
Alternative Regimen:
INH + Rifampin for 9 months
INH + Ethambutol for 18 months
Regimen for INH Resistance Strains:
Rifampin, Pyrazinamide , Ethambutol for 6 months
MDR-TB Regimen:
3 or more drugs to which the organism is susceptible, for 18 months(upto 2 years)
XDR-TB Regimen:
Same as MDR, atleast three susceptible drugs(including a fluoroquinolone) upto 2 years

30. HIV & TUBERCULOSIS Treatment Of TB in HIV+ Adults
HIV+ patients are times more likely to develop TB disease.
Out of all the TB cases globally, 11% (1.2 million) are people living with HIV aka HIV Postive TB cases (tip of the iceberg)
57% of HIV positive TB cases were not diagnosed or treated, and resulted in  in 2015
HIV-positive TB cases in Source: 1.3
Treatment Of TB in HIV+ Adults
6-month daily regimen consisting of:
An intensive phase of isoniazid (INH), a rifamycin (see Drug Interactions below), pyrazinamide (PZA), and ethambutol (EMB) for the first 2 months.
A continuation phase of INH and a rifamycin for the last 4 months.
Source: 1.4

32. Future Goals and Steps(National TB Control Program Pakistan)
To reduce by 50% the prevalence of TB in the general population by 2025 in comparison with 2012.
To increase the number of notified TB cases from 298,981 in 2013 to at least 420,000 by 2020 while maintaining the treatment success rate at 91%.
To reduce by at least 5% per year by 2020 the prevalence of MDR-TB among TB patients who have never received any TB treatment.
Strengthen programmatic and operational management capacity of the TB Control Program while enhancing public sector support for TB control by 2020.
Source: 1.0

33. Sources & References: 1.0: https://www.ntp.gov.pk/
1.1: people-wb-data.html
1.2: resistant_tuberculosis#cite_note-:0-2
1.3:
1.4:
1.5: 1/An%20Update%20on%20the%20Laboratory%20Diagnosis%20of%20Tuberculosis.pdf