1. National Tuberculosis Program NTP

2. WHAT IS TUBERCULOSIS

3. Tuberculosis is an infectious disease caused mainly by Mycobacterium tuberculosis.
It can affect most organs in the body, but the lung is the main organ affected.
If left untreated, each person with smear-positive pulmonary TB will infect, on average, between 10 and 15 persons in each year.
Those who will be infected with TB will not necessarily get the disease. The immune system “walls off” the TB bacilli, which can lie dormant for years.
On average, 10 percent of the infected individuals develop the disease during their lifetime.
When someone’s immune system is weakened, chances of developing TB are increased.

4. History of TB

5. 2400 BC Spinal columns of Egyptian mummies show definite Evidence of tubercular decay

6. 460 BC HIPPOCRATE: Most widespread disease, almost always fatal
1702 MANGET explained miliary TB
1720 BENJAMIN MARTIN (a new theory of consumption) TB could be caused by wonderfully minute living creature
1854 HERMANN BREHMER (TB is a curable disease) Established
first sanatorium in Germany , Beginning of sanatorium era.
1882 ROBERT KOCH, discovered the micro-organisms responsible
for TB

7. History of anti-TB drugs

8. 1944 STREPTOMYCIN 1949 P A S 1952 ISONIAZID 1954 PYRIZINAMIDE
CYCLOSERINE
ETHAMBUTOL
RIFAMPICIN
OTHER DRUGS USED
ETHIONAMIDE,THIACETAZONE, QUINILONES

9. TB Infection

10. Source of Infection: The source of infection can be either:
human: Mycobacterium Tuberculosis
animal: Mycobacterium Bovis

11. Mode of Infection: Exogenous: Endogenous:
Inhalation: droplet nuclei, 1-5 microns, consisting of two to three viable bacteria surrounded by a layer of moisture.
Ingestion: usually contaminated milk
Cutaneous transmission: very rare, the organism gain entrance either through broken skin.
Congenital transmission: also very rare, the fetus acquires the infection either transplacentally from the diseased mother through umbilical vein, or by aspirating amniotic fluid that contains viable mycobacteria.
Endogenous:
Activation of a dormant focus.

12. Natural history of untreated TB
Without treatment, after 5 years.
50% of pulmonary TB patients will be dead.
25% will be healthy (self-cured by strong immune defense).
25% will remain ill with chronic, infectious TB.

13. TB evolution

14. Primary infection
Phenomena that take place when an individual comes into contact with the tubercle bacillus for the first time.
95% of all affected individuals remain asymptomatic or present with minimal clinical manifestations similar to those of common cold.
Only 5% develop manifest disease.
This phenomenon typically takes place in childhood.
As a result of which primary infection is often associated with childhood TB.

15. Primary infection, cont.
Upon arrival in the alveolar region, the bacteria encounter three types of cells that potentially oppose infection:
the alveolar macrophages within the alveolar lumen, the key cell
the natural killer cells, and
the / T lymphocytes.

16. Primary infection, cont.
The initial interaction between M. tuberculosis and alveolar Macrophages involves Non-specific phagocytosis of the bacilli.
This phase concludes with destruction of the alveolar macrophages by proliferating intracellular bacilli.
Attracted blood monocytes ingest the released bacilli.
The monocytes have not been activated yet. The tubercle bacilli increase in number, killing host cells and spread locally.
In the lung, intense alveolitis takes place at the expense of the young cells of the mononuclear phagocyte system.

17. Primary infection, cont.
Then Mycobacterial spread via lymphatics towards the regional lymph nodes.
In this region, the host immune response to tuberculous infection takes place.
In some instances, this immune response is sufficient to arrest the progression of infection.
In more often times the bacilli escape towards the lymphatic duct and penetrate the pulmonary bloodstream, from where there is hematogenous spreading of the bacilli to the other organs.

18. Primary infection, cont.
The main target zones of such bacterial dissemination are the highly irrigated organs and tissues—the central nervous system, spongy bone, liver, kidneys, and genitals.
In each of these zones, the arriving bacilli are phagocytosed by the local cells of the mononuclear phagocyte system.
In most cases, this period implies immunologic control of the infection as a result of two mechanisms: cell-mediated immunity and delayed hypersensitivity.

19. Primary infection, cont.
Delayed hypersensitivity is the phenomenon responsible for the destruction of macrophages that contain intracytoplasmic bacteria, thereby forming a characteristic focus of caseous necrosis.
Although the bacteria may survive within this necrotic focus for years, they are unable to reproduce due to the prevalent acidosis, the lack of oxygen, and the presence of inhibitory fatty acids.
From the clinical point of view, immunocompetent individuals develop a balance between themselves and the mycobacteria, which persists throughout life until some predisposing event is able to reactivate the infectious focus.

20. Progressive pulmonary component:
Primary TB:
Pulmonary: Ghon’s focus
Glandular: hilar lymph node, draining lymphangitis
The infection develops as interplay between virulence of the organism, and immunity of the host.
In 80-90% of infected individuals, immunity takes the upper hand leads to spontaneous healing, resolution, fibrosis and calcification.
In 10-20% of infected individuals, virulence takes the upper hand (progressive primary =childhood tuberculosis)
Progressive pulmonary component:
pneumonic
bronchopneumonia
cavitation
pleural effusion
Progressive glandular component:
hilar lymph node  other lymph nodes
atelectasis: middle lobe syndrome
haematogenous spread

21. Adulthood Tuberculosis
Post-primary:
Haematogenous: dissemination by blood stream leads to multiple organs affection
Intra-thoracic: miliary, idiopathic effusion, tuberculoma, punched out cavity.
Extra-thoracic: meningeal, glandular, renal, bone and joint, etc.
Bronchogenic: spread, to other part or other lung
Adulthood Tuberculosis
minimal, advanced or far advanced lung lesion
exceptional extra-pulmonary: laryngitis and enteritis
late haematogenous dissemination

22. TB epidemiology

23. Global Burden of Tuberculosis:
In 1993 WHO declared TB a global emergency.
It is estimated by WHO worldwide that:
A nine million new cases of TB occurred/year
Three million TB deaths/year.
Tuberculosis poses a major problem for developing countries.
Deaths from TB comprise 25 % of all avoidable deaths in developing countries.
95 % of all TB cases occur in developing countries
98 % of TB deaths occur in developing countries.
75 % of TB cases in developing countries are in the economically productive age group ( years).

24. 22 high-burden countries: 80% of all new cases10
100
1000
10000
India
China
Indonesia
Bangladesh
Nigeria
Pakistan
Philippines
South Africa
Russian Federation
Ethiopia
DR Congo
Viet Nam
Kenya
UR Tanzania
Brazil
Thailand
Myanmar
Zimbabwe
Uganda
Cambodia
Afghanistan
Mozambique
Estimated new TB cases ('000s)

25. Why Does the Global Burden of TB Increase?
Inadequate health services.
Improper management practices resulting in poor case detection, diagnosis and treatment.
Demographic changes: increasing world population and changing age structure.
Impact of HIV.
The emergence of resistance to the first line drugs used to treat TB.

26. The pulmonary form of tuberculosis (smear positive and smear negative) represents roughly 80 to 85 percent of all cases.
The remaining 15 to 20 percent is made up by cases of extra-pulmonary tuberculosis.
The expected number of new smear positive cases in Egypt currently about 10,000 per year.
For every new smear-positive pulmonary tuberculosis case usually a case of smear-negative pulmonary or extra-pulmonary tuberculosis will also be present.

27. Magnitude Of TB Problem in Egypt

28. In terms of incidence of tuberculosis, Egypt is ranked among the mid-level incidence countries.
Tuberculosis in Egypt is considered an important public health problem.

30. Indicators

31. Case Detection Indicators
SS+ case detection rate:
No. of detected new SS+ cases = >70%
Estimated No of new SS+ cases
SS+ cases in relation to all pulmonary cases
No. of detected new SS+ cases = 50 – 70%
Total No. of new pulmonary cases
SS+ cases in relation to all TB cases
No. of detected new SS+ cases = 50 – 60%
Total No. of TB cases detected

32. Treatment Outcome

33. Treatment success
No. of patient cured + No. of patient completed treatment = > 85%
No. of patient registered

34. Diagnosis of tuberculosis refers to the recognition of an active case, i.e. a patient with symptomatic disease due to lesions caused by Mycobacterium tuberculosis.
According to the site of the lesion, TB can be classified to Pulmonary or Extra-Pulmonary Tuberculosis.
Pulmonary TB can further be classified to smear positive or smear negative types.

35. Identifying TB suspects

36. What is TB suspect
A TB suspect is any person, who presents with symptoms or signs suggestive of tuberculosis, in particular cough of long duration.

37. When to Suspect Pulmonary Tuberculosis?
Persistent cough for more than two weeks.
Blood tinged sputum.
Breathlessness and chest pain.
General symptoms such as: loss of appetite; loss of weight; malaise and tiredness; night sweats and fever.
A history of contact with a TB patient .

38. What to do when you suspect a case?
1) List the TB suspect in the Suspect Register
The Register of TB Suspects is a record of all patients identified as TB suspects at the health facility,
all sputum samples sent to the laboratory & their results.

40. 2) Collect sputum for smear examination.
3) When the laboratory results are received, record results in the Register.
4) Decide on appropriate action in response to the laboratory results.

41. Diagnosis of TB

42. Diagnosis of Pulmonary TB is A bacteriological one.
Microscopic Direct Smear Examination
is an easy and quick procedure. A minimum of three samples must be examined.
Cultures:
To confirm the diagnosis even in smear negative.
To detect drug susceptibility and resistance.
To detect the bacilli in any specimen in extra-pulmonary tuberculosis.

43. Sensitivity of sputum smear microscopy
Collection of sputum samples
A PTB suspect should submit 3 sputum samples for microscopy.
The chances of finding tubercle bacilli are greater with 3 sputum samples than with 2 samples or 1 sample.
Secretions build up in the airways overnight.
So an early morning sputum sample is more likely than a sample later in the day to contain tubercle bacilli.
Sensitivity of sputum smear microscopy
Sputum smear microscopy for tubercle bacilli is positive when there are at least 10,000 organisms present per 1 ml of sputum.

44. False positive results of sputum smear microscopy
A false positive result means that the sputum smear result is positive even though the patient does not really have sputum smear-positive PTB.
This may arise because of the following:
red stain retained by scratches on the slide;
contamination of the slide
various particles that are acid-fast (e.g. food particles, dye precipitates, other micro-organisms).

45. Causes of false negative results of sputum smear microscopy
EXAMPLE
TYPE OF PROBLEM
patient provides inadequate sample
sputum stored too long before smear microscopy
sputum collection
faulty smear preparation and staining
sputum processing
inadequate time spent examining slide
inadequate attention during examination
sputum smear examination
incorrect labeling of sample
mistakes in documentation
administrative errors

46. TUBERCULIN SKIN TEST
Tuberculin is a purified protein derived from tubercle bacilli. Thus, another name for tuberculin is PPD (Purified Protein Derivative).
Following infection with M. tuberculosis, a person develops hypersensitivity to tuberculin.
Tuberculin injected into the skin of an infected person produces a delayed local reaction after hours. We quantify this reaction by measuring the diameter of skin induration (thickening) at the site of the reaction.
Various conditions may suppress this reaction.
The reaction only shows that the person has at some time had infection with M. tuberculosis

47. Tuberculin Skin Test, cont.
A positive test (induration of 10 mm or more) is suggestive for tuberculous infection in children who are not vaccinated with BCG or 5 years or more after vaccination.
A positive test (induration of 15 mm or more) is suggestive for tuberculous infection in children who are vaccinated with BCG.
A negative test in adults may be suggestive of absence of tuberculous infection.
False negative test may be obtained in immunosuppressed individuals.

48. CONDITIONS WHICH MAY SUPPRESS THE TUBERCULIN SKIN TEST
HIV infection
Malnutrition
Severe bacterial infections, including TB itself
Viral infections, e.g. measles, chickenpox, glandular fever
Cancer
Immunosuppressive drugs, e.g. steroids

49. Tuberculin Testing

50. Chest X-rays in diagnosis
No certain x-ray pattern is specific to TB
INDICATIONS FOR CHEST X-RAY
Positive sputum smear
The first screening test for PTB suspects is sputum smear microscopy.
In most cases of sputum smear-positive PTB a chest X-ray is un-necessary.
In those few cases of sputum smear-positive PTB when a chest X-ray is necessary, the indications are as follows:

51. a) suspected complications in the breathless patient, needing specific treatment, e.g. pneumothorax, (pericardial effusion or pleural effusion - positive sputum smear is rare);
b) frequent or severe haemoptysis (to exclude bronchiectasis or aspergilloma);
c) only 1 sputum smear positive out of 3 (in this case, an abnormal chest X-ray is a necessary additional criterion for the diagnosis of sputum smear-positive PTB).

52. Radiological Examination

53. Other methods of diagnosis
Biopsies
PCR

54. Childhood Tuberculosis

55. History: Chronic cough
Longer than 2 weeks not improving with ordinary treatment and getting worse
Fever
Longer than 7 days not responding to antibiotics and treatment of common conditions
Antibiotics to be given in such cases
Weight loss
documented weight loss or failure to thrive.
failure to gain weight if on feeding scheme after 1month.

56. SCORE SYSTEM FOR THE DIAGNOSIS OF TB IN CHILDREN
A score system is one way of trying to improve the diagnosis of childhood TB.
The basis of a score system is the careful and systematic collection of diagnostic information.
A score of 7 or more indicates a high likelihood of TB.

57. No response to nonspecific treatment
score 4 3 2 1
feature
General
4w<
2-4w
2w>
Duration
of illness
60%>
60-80%
80%<
Weight for
age
Proved
+VE
Reported
-VE
Family
history
positive
Tuberculin
test
Not
improving
After 4 w
Malnutrition
No response to nonspecific treatment
Unexplained
fever and night sweats

58. Angle deformity of the spine
Local
Lymph
nodes
Joint or bone swelling
Abd.
mass or
ascites
CNS findings
Angle deformity of the spine
Total score

59. Case definitions

60. A smear-positive pulmonary TB
A patient with at least two sputum specimens positive for AFB; or,
A patient with at least one sputum specimen positive for AFB, with culture positive for M. tuberculosis, or with radiological abnormalities consistent with pulmonary TB.
A smear-negative pulmonary TB
A patient with two sets (taken at least two weeks apart) of at least three sputum specimens that are negative for AFB, radiological abnormalities consistent with pulmonary TB and a lack of clinical response to at least two weeks of a broad spectrum antibiotic Or,
A patient who is severely ill with at least three sputum specimens negative for AFB and radiological abnormalities consistent with extensive pulmonary TB
N.B. a patient whose initial sputum-specimens were negative and who did have sputum sent for culture initially should be considered a sputum-negative pulmonary TB even if the sputum culture result is positive.

61. New case A patient who has never had treatment for TB or who has taken drugs for less than one month
Relapse A patient who is declared cured by a physician, after one full course of chemotherapy, and has become sputum smear-positive
Treatment failure
A patient who, while on treatment, remained or became again smear-positive 5 months or later after commencing treatment;
or,
A patient who was initially smear-negative before starting treatment and became smear-positive after the second month of treatment

62. Treatment after interruption
A patient who interrupts his treatment for 2 months or more (defaulter) and returns with smear positive sputum
Others
A patient who was either smear-negative pulmonary TB or extra-pulmonary TB, completed treatment and returned with symptoms and active disease or chronic cases.
chronic case:
A patient who remained or became again smear-positive after completing a fully supervised retreatment regimen.

63. TB treatment

64. TB chemotherapy should be based on two important microbiological considerations:
The combination of drugs to avoid the development of resistance.
The need for prolonged chemotherapy to prevent disease relapse.

65. All mono-therapeutic regimens (real or masked by combination with drugs to which bacilli are resistant) lead to treatment failure and to the development of resistance.
When three or more drugs are administered, the risk of resistance is practically zero.

66. Phases of treatment: The intensive phase The continuation phase
usually covers the first 2 months of treatment.
During this phase, most of the bacilli will be killed.
The sputum converts from positive to negative in more than 80 % of the new patients within the first 2 months of treatment.
The continuation phase
usually lasts 4-6 months, depending on the treatment regimen.
This phase is intended to eliminate the remaining dormant bacilli.
These dormant bacilli decrease constantly as treatment intake progresses.
Since it is not possible to identify which patients still have dormant bacilli, all patients should continue their treatment until the end of the prescribed period, to limit the number of relapses.

67. First-line anti-tuberculosis drugs, action and side effects

68. RECOMMENDED DAILY DOSAGE (DOSE RANGE),mg/kg
DRUG
RECOMMENDED DAILY DOSAGE (DOSE RANGE),mg/kg
Isoniazide (H)
5 (4–6)
Rifampicin (R)
10 (8–12)
Pirazinamide (Z)
25 (20–30)
Streptomycin (S)
15 (12–18)
Ethambutol (E)
15 (15–20)

70. Treatment regimens Continuation Initial Patient Category
Treatment category
4/HR
2/SHRZ OR
2/EHRZ
New smear +ve PTB.
New smear –ve
New forms of extra-Pulmonary TB. I

71. Treatment regimens, cont
Continuation
Initial
Patient Category
Treatment category
5/HRE
2/SHRZE
then
1/HRZE
Sputum smear +ve
Relapse.
Treatment after failure.
Treatment after interruption. II

72. TREATMENT OUTCOME Cure
A patient who is smear-negative in the month of treatment and on at least one previous occasion
Treatment completed
A patient who has completed treatment but who does not meet the criteria to be classified as a cure or a failure
Treatment failure
A patient who remains or becomes again smear-positive at five months or later during treatment*
Died
A patient who dies for any reason during the course of treatment
Default
A patient whose treatment was interrupted for two months or more
Transfer out
A patient who has been transferred to another reporting unit outside the Governorate and for whom the treatment outcome is not known

73. DOTS means directly observed treatment with short course chemotherapy
DOTS strategy
DOTS means directly observed treatment with short course chemotherapy
Principles of DOTS strategy
Government commitment to TB control
Case detection through sputum-smear microscopy in the general health services
Standardized short-course chemotherapy to, at least, all smear-positive TB cases under proper case management conditions
Regular, uninterrupted supply of all essential anti-tuberculous drugs
Monitoring system for programme supervision and evaluation

74. Role of PHC in DOTS implementation
Provide TB patients with daily supervised treatment with anti-TB drugs according to prescribed regimen, dosage and duration
Provide patients, who are unable to attend at the PHC centre on a daily basis (e.g. handicapped patients) with supervised treatment at the patient’s home.
DOT at the patient’s home, if necessary
Retrieve patients who did not attend the PHC centre for their daily treatment
Record daily attendance and anti-TB drug intake in the TB treatment card
Health education and counseling to TB patients, their contacts and the community
Timely referral of TB patients to the chest clinic for follow up sputum examination
Order and collect the required quantity of anti-TB drugs for TB patients
Ensure that the anti-TB drugs present in the unit are not expired
Refer contacts of TB patients to chest clinic
Refer TB suspects to chest clinic

75. DR-Tuberculosis

76. Causes of drug-resistant tuberculosis:
From a microbiological perspective, resistance is caused by a genetic mutation.
An inadequate or poorly administered treatment regimen allows a drug-resistant strain to become the dominant strain; hence, TB is essentially a man-made phenomenon.

78. Factors That May Lead To Developing Resistance

79. Factors may include: HEALTH-CARE PROVIDERS through
- INADEQUATE REGIMENS:
- Poorly organized or funded TB control programs.
- Inappropriate, Absence of or Noncompliance with guidelines
- Poor training
- No monitoring of treatment.

80. - Lack of information, poor health education - Adverse effects.
2- PATIENTS through INADEQUATE DRUG INTAKE (patient incompliance):
- Poor adherence
- Lack of information, poor health education
- Adverse effects.
- Social barriers.
- Malabsorption.

81. 3- DRUGS through: Poor quality Stock-outs or delivery disruptions.
Wrong dose.
Poor storage conditions

82. Different resistance patterns

83. Mono-resistance, Poly-resistance,
colonies are resistant to only one of the first-line anti-TB drugs.
Poly-resistance,
colonies are resistant to more than one of the first line anti-TB drugs but do not combine resistance to both Isoniazid and Rifampicin. Examples of poly-resistance may include Streptomycin, Isoniazid and Ethambutol or Streptomycin, Rifampicin and Ethambutol.

84. Multiple drug resistant,
colonies combine resistance to at least Isoniazid and Rifampicin.
Extensively Drug Resistant TB (XDR-TB):
Colonies are resistant to:
1st Line drugs , at least Rifampicin and Isoniazid, (MDR-TB)
A fluoroquinolone
One or more of the following injectable drugs:
kanamycin
Amikacin
Capreomycin

85. Primary resistance and acquired resistance:
“Primary resistance” means that the patient was infected with already resistant bacilli.
“Acquired resistance” means that patient was initially infected with sensitive bacilli but developed resistance of any pattern during the course of treatment because of any or a combination of the previously mentioned causes

86. Treatment regimens for DR-TB in Egypt

87. Treatment regimen
Patient resistant to
Regimen I
3 months: canamycin daily + Ofloxacin + Cycloserine + Ethionamide + PAS then:
6 months canamycin 5 times a week + previous drugs then:
12 months Ofloxacin + Cycloserine + Ethionamide + PAS
RHSE
Regimen II
3 months: canamycin + Ofloxacin + Ethambutol + Ethionamide + Cycloserine then:
6 months: canamycin 5 times a week + previous drugs then:
12 months: Ofloxacin + Ethambutol + Ethionamide + Cycloserine
RHS
Regimen III
3 months streptomycin daily + Ethambutol + Pyrazinamide + Ofloxacin + PAS then:
6 months streptomycin 5 times a week + previous drugs then:
12 months: Ethambutol + Pyrazinamide + Ofloxacin + PAS RH