Tuberculosis is a chronic, wasting, communicable disease, which made a huge comeback with the HIV pandemic, making it an opportunistic infection, and and an AID-defining infection. This presentation explores the different types of tuberculosis in terms of their locations (pulmonary and extra-pulmonary) as well as in terms of their drug susceptibility. It also addresses the approach to the management of each one of these.

2. TUBERCULOSIS
PRESENTED BY: DR KD DELE
DEPARTMENT OF FAMILY MEDICINE
DORA NGINZA HOSPITAL

4. CONTENT
• Overview of Tuberculosis
• Epidemiology
• Risk Factors
• Classification
• Clinical Presentation & Diagnosis
• Laboratory Diagnosis of Tuberculosis
• Case Definition of Tuberculosis
• Extra Pulmonary Tuberculosis (EPTB)
• Drug Resistant Tuberculosis
• MDR-TB & XDR-TB Regimen

5. INTRODUCTION & OVERVIEW OF
TUBERCULOSIS

6. OVERVIEW OF TUBERCULOSIS
• Tuberculosis (TB) is a potentially fatal contagious disease that can
affect almost any part of the body but is mainly an infection of the
lungs.
• Neo-latin word :
• “Tubercle” - Round nodule/Swelling
• “Osis” - Condition

7. OVERVIEW CONT.
• It is an airborne disease caused by the bacterium “Mycobacterium spp”
• …whch is expelled when a person with infectious TB coughs, sneezes,
shouts, or sings etcetera
• Transmission occurs when droplet nuclei (airborne particle about 1-5
microns) are inhaled and reach the alveoli of the lungs, via nasal
passages, respiratory tract, and bronchi

8. CAUSATIVE ORGANISMS
• Tuberculosis (TB) is caused by one of several genetically related group
of mycobacterial species that belong to the Mycobacterium
tuberculosis complex
• The human pathogens are M. tuberculosis, M. africanum, and M. bovis .
• The other member of the complex, M. microti, is a rodent pathogen.
• Mycobacterium tuberculosis – Humans
• Mycobacterium Bovis – Animals / cattle

9. OTHER CAUSATIVE ORGANISMS
• Mycobacterium africanum
• Mycobacterium microti
• Non-Mycobacterium Genus
• Mycobacterium leprae
• Mycobacterium avium
• Mycobacterium asiaticum

10. MYCOBACTERIUM TUBERCULOSIS
• Gram positive
• Obligate aerobe
• Non-spore-forming
• Non-motile rods / bacilli
• Mesophile
• 0.2 – 0.6 um3

11. MYCOBACTERIUM TUBERCULOSIS…
• Slow generation time 15 – 20 hours – may contribute to virulence)
• Lipid-rich cell wall contains mycolytic acids – 50% of dead weight
• Responsible for many of the bacteria’s characteristics
• Acid- fast (retains acidic substances)
• Confers resistance e.g. detergents and antibiotics

12. EPIDEMIOLOGY

13. EPIDEMIOLOGY
• In 2011,there were an estimated 8.7million incidence cases of TB globally –
equivalent to 125 cases in 1,00,000 population.
• In 2015, figure rose to 9.6million
• Asian : 59%
• African : 26%
• Eastern Mediterranean Region: 7.7%
• The European Region : 4.3%
• Region of the America : 3%

14. TB IS A GLOBAL DISEASE

17. WHO TB REPORT 2015
• 90% in developing world
• 75% in economically active people
• 22 high burden countries – Cambodia has managed to stem the tide
and is managing a turn around.
• 74% of patients with TB and HIV co infection are in the African region!

18. WHO TB REPORT 2015
• 9.6million people globally, 12% of these HIV +ve
• 1.5 Million deaths
• Of these 890 000 men, 480 000 women, 140 000 children.
• 1.1 million in HIV negative patients, 400 000 deaths in HIV positive
patients
• 480 000 estimated MDR patients but <25% diagnosed

19. WHO TB REPORT 2015
• African region estimates 281 cases of TB per 100 000 popln i.e. double
the world average of 133/100 000
• However, Indian, Indonesia, China are the top 3 countries
• Halving mortality target only met by one African country i.e. Uganda
• MDR estimated to be 3.3% of all new cases and 20% of all retreatment
cases
• SA has world’s 2nd highest TB prevalence rates!

20. SA TUBERCULOSIS EPIDEMIC
• Spread by airborne droplet nuclei – poor cough hygiene among
patients
• Increase in population, poverty, unemployment, lack of services,
urbanization
• Poor management of TB control programmes – NDOH working hard to
reverse this.
• 60-80% of new TB cases in SA are co-infected with HIV

21. RISK FACTORS

22. WHO IS MORE PRONE TO DEVELOP ACTIVE
TUBERCULOSIS?
• Diseases, conditions or drugs that weaken the immune system:
• Cancer
• Transplantation
• Malnutrition
• Diabetes
• Alcoholism
• Patients on immunosuppressive medications

23. WHO IS MORE PRONE TO DEVELOP ACTIVE
TUBERCULOSIS?
• HIV infection
• TB is the leading cause of death worldwide in HIV infected individuals
• 10% lifetime risk for developing active TB among HIV uninfected
• 10% annual risk for developing active TB among HIV infected

24. WHO IS MORE PRONE TO DEVELOP ACTIVE
TUBERCULOSIS?
• Infants and children < 3 years
• Kidney failure
• COPD
• Transplant patients
• Genetics
• Silicosis
• Low socioeconomic status
• Homelessness
• Major surgical procedures may
occasionally trigger
dissemination

25. RISK FACTORS FOR TB INFECTION
• Sharing air space with someone sick with TB disease (e.g., live, work, or
play together)
• Crowded living conditions
• Residency or travel in a country with a high-incidence of TB disease
• High risk occupations including laboratory and health care jobs

26. PREVENTION OF SPREAD
• Cough etiquette
• Adequate early diagnosis and treatment
• Plenty of sunlight and good ventilation in any spaces with close
proximity with infectious patients

27. CLASSIFICATION

28. CLASSIFICATION
• Pulmonary and Extra-pulmonary
• PULMONARY
• Primary Disease
• Secondary Disease

29. EXTRA PULMONARY
• i. Lymph node TB
• ii. Pleural TB
• iii. TB of upper airways
• iv. Skeletal TB
• v. Genitourinary TB
• vi. Miliary TB
• vii. Pericardial TB
• viii. Gastrointestinal TB
• ix. Tuberculous Meningitis
• x. Less common forms
• 20% of patients of TB Patient are extrapulmonary

30. A. PULMONARY TUBERCULOSIS

31. A. PULMONARY TB
1. Primary Tuberculosis :-
• The infection of an individual who has not been previously infected or
immunised is called Primary tuberculosis or Ghon’s complex or
childhood tuberculosis.
• Lesions forming after infection is peripheral and accompanied by hilar
which may not be detectable on chest radiography.

32. A. PULMONARY TB
2. Secondary Tuberculosis :
• The infection that individual who has been previously infected or
sensitized is called secondary or post primary or reinfection or chronic
tuberculosis.

33. POST-PRIMARY DISEASE
• Occurs after a latent period of months or years
• Reactivation occurs when dormant bacilli start to multiply
• It can result from re-infection
• Only a small fraction of all infected people ever progress to disease
• TB disease often as a result of depressed immunity

34. RISK OF PROGRESSION TO TB DISEASE
• Untreated, 5% of infected persons with normal immunity develop TB in
first 1–2 years post infection, another 5% later in life
• Thus, about 10% of infected persons with normal immunity will develop
TB at some point in life if not treated

35. B. EXTRA PULMONARY TB
1) Lymph node TB ( tuberculuous lymphadenitis):-
• Seen frequently in HIV infected patients.
• Symptoms :- Painless swelling of lymph nodes most commonly at
cervical and Supraclavical (Scrofula)
• Systemic systems are limited to HIV infected patients.
2) Pleural TB :-
• Involvement of pleura is common in Primary TB and results from
penetration of tubercle bacilli into pleural space.

36. B. EXTRA PULMONARY TB
3) TB of Upper airways :-
• Involvement of larynx, pharynx and epiglottis.
• Symptoms :- Dysphagia, chronic productive cough
4) Genitourinary TB :-
• Any part of the genitourinary tract get infected.
• Symptoms :- Urinary frequency, Dysuria, Hematuria.

37. B. EXTRA PULMONARY TB
5) Skeletal TB :-
• Involvement of weight bearing parts like spine, hip, knee.
• Symptoms :- Pain in hip joints n knees, swelling of knees, trauma.
6) Gastrointestinal TB :-
• Involvement of any part of GI Tract.
• Symptoms :- Abdominal pain, diarrhoea, weight loss

38. B. EXTRA PULMONARY TB
• 7) TB Meningitis & Tuberculoma :-
• 5% of All Extra pulmonary TB
• Results from Hematogenous spread of 10 & 20 TB.
• 8) TB Pericarditis :-
• 1- 8% of All Extra pulmonary TB cases.
• Spreads mainly in mediastinal or hilar nodes or from lungs.

39. B. EXTRA PULMONARY TB
• 9) Milliary or disseminated TB :-
• Results from hematogenous spread of Tubercle Bacilli.
• Spread is due to entry of infection into pulmonary vein producing
lesions in different extra pulmonary sites.
• 10) Less common Extra Pulmonary TB
• uveitis, pan-ophthalmitis, painful hypersensitivity related phlyctenular
conjunctivitis.

40. CLINICAL PRESENTATION &
DIAGNOSIS OF TUBERCULOSIS

41. DIAGNOSIS
• Clinicians need a high index of suspicion first!
• Insidious development
• Patients tend to ignore symptoms
• Can occur in any site
• Often associated with other diseases.

42. DIAGNOSIS
• Most cases can be identified by taking thorough history (*screening
questions)
• Do sputum smear microscopy and GXP
• Counselling and testing for HIV
• Send for X-rays and TB culture if smears are negative
• Investigate for extrapulmonary TB
• In children tuberculin skin test

43. SYMPTOMS
• *Cough – any duration
• *Weight loss and anorexia
• *Chills and night sweats
• *Pyrexia of unknown origin
• Chest pain
• Dyspnoea
• Haemoptysis
• Malaise and tiredness

44. CLINICAL SIGNS
• Patient is thin and pale
• Rapid pulse
• Fast respiratory rate
• Nasal flaring
• May have increased temperature
• Chest - crackles, dullness, bronchial breathing, amphoric breathing, use
of accessory muscles for breathing…

45. EXTRA-PULMONARY TB
• Lymphadenopathy
• Milliary TB
• Pleural and pericardial effusion
• Ascites
• Upper respiratory ie larynx
• TB Meningitis
• TB spine / bone
• Hepatic / Renal / Adrenal
• Male / female genital tract

46. BASED ON TYPES OF TB

47. LABORATORY DIAGNOSIS OF
TUBERCULOSIS

48. LAB CHARACTERISTICS OF TB
• Microscopic thin and rod like
• Occur singly or in clusters
• Complex thick waxy cell wall (Mycolic acids)
• need special antibiotics
• special staining methods needed Ziehl- Niehlsen (ZN) or Auramine
stain (acid and alcohol fast)
• survive for long periods in the dark, cool places
• Destroyed by heat, UV light, pasteurisation

49. DIRECT/ ZN SMEAR FOR AFB

50. AURAMINE/ FLUOROCHROME STAINING

51. SPUTUM COLLECTION
• Good specimens
• Bronchial secretions and not saliva
• Ideally 3-5 ml
• When to collect?
• On the spot

52. SPUTUM COLLECTION : WHEN SHOULD SPUTUM
BE COLLECTED?
• Pre-treatment
• One specimen to diagnose
• After intensive treatment phase
• One specimen to monitor progress and smear conversion
• At end of treatment
• to prove cure
• identify treatment failure

53. SPUTUM COLLECTION CONT.
• Sensitivity of microscopy depends on:
• quality of sputum
• quality of laboratory processing and
• quality of staining and microscopy
• Saliva or nasal secretions give false negative results
• Health care workers and other patients should be protected from
potential nosocomial transmission of aerosolised bacilli

54. LABORATORY DIAGNOSIS OF
TUBERCULOSIS…
GENERAL LABORATORY DIAGNOSIS OF TUBERCULOSIS

55. GENERAL LABORATORY DIAGNOSIS OF
TUBERCULOSIS
• 1. Microscopy:
• Mainstay of NTP (id transmitters of TB, posing a ↑ infection risk)
• Essential for diagnosis and/or management of drug susceptible and
resistant strains of TB

56. GENERAL LABORATORY DIAGNOSIS OF
TUBERCULOSIS
• 2. Culture:
• Adds sensitivity to diagnosis of TB in sputum specimens with lower
bacillary load (e.g. extra-pulmonary TB, HIV co-infected patients),
regardless of drug susceptibility

57. GENERAL LABORATORY DIAGNOSIS OF
TUBERCULOSIS
• 3. Culture and drug susceptibility testing (DST)
• Essential for diagnosis and surveillance of drug resistance (e.g. M(X)DR-
TB)
• 4. Molecular techniques (e.g. Line probe assay, GeneXpert)
• Rapid diagnosis of DR TB
• Identification of mycobacterial species

58. 1. AFB SMEAR MICROSCOPY:
• Advantages
• Identifies patients most likely to transmit TB (i.e. with high pulmonary
bacillary load,5,000- 10 000 bacilli per millilitre of sputum)
• can be done at point-of care, with short turn around time of 24 - 48 hrs
(no need for advanced infrastructure)
• it is accessible to most patients (even in resource limited settings)
• instrumental in monitoring treatment success (patient follow up /
smear conversions)

59. AFB SMEAR MICROSCOPY:
• Limitations
• low sensitivity
• requires presence of at least 5,000 or more AFB/ml of sputum
• worsened by non-cavitary disease as in HIV coinfected patients
• does not distinguish tubercle bacilli from other mycobacteria (most
mycobacteria are acid-fast)
• does not distinguish live bacilli from dead bacilli
• cannot detect drug resistance

60. 2. CULTURES & SENSITIVITIES
• Done for:
• All re-treatment cases
• All symptomatic contacts of MDR TB cases
• Cases who remain positive at end of intensive phase or at end of
treatment
• If drug susceptibility is required

61. CULTURE ADVANTAGES
• more sensitive than microscopy (can detect as few as 10 bacilli per
millilitre of sputum vs >5,000 required for AFB smear microscopy
• very useful in diagnosis of HIV infected TB patients and children, with
normally low sputum bacillary load
• Allows for further identification to distinguish between tubercle bacilli
and other mycobacteria (species identification)

62. CULTURE ADVANTAGES
• allows for drug susceptibility testing (diagnosis of mono-, poly-, multi-,
and extensively-drug resistant TB)
• allows for epidemiological studies (e.g community outbreaks,
nosocomial infections, etc)
• Live vs. dead bacilli
• Culture is the gold-standard for the diagnosis of TB

63. CULTURE LIMITATIONS
• long TAT due to slow growth of tubercle bacilli – Culture takes 2-6
weeks
• requires advanced infrastructure and highly trained personnel
• reagents are expensive
• limited facilities (culture coverage) in the country
• poses higher biohazard risk than microscopy to lab personnel, hence
need for higher level safety measures and quality management.

64. CULTURE RESULTS INTERPRETATION
• A positive culture means that Mycobacteria are present, and the patient needs TB
treatment if MTB cultured.
• A negative culture means that MTB is absent in the sample
• False negative cultures may occur when MTB is killed by decontamination or if a poor
specimen is sent
• A contaminated culture means that normal bacterial flora present in the sputum over-
grew in the MGIT tube. Even if MTB was present, it could not be detected
• False positive cultures are uncommon but can occur

65. 3. DRUG SUSCEPTIBILITY TESTING (DST)
• DST is required to make a definitive diagnosis of drug-resistant TB (DR-
TB)
• It is the Gold standard in the diagnosis of drug resistant TB
• DST is required to make a definitive diagnosis of DR-TB

66. DRUG SUSCEPTIBILITY TESTING (DST)
• 1st line DST:
• well studied and established; reliable and reproducible (INH & Rif);
high correlation with clinical outcome
• Drugs currently tested (NHLS): STP, INH, RMP, EMB, PZA*

67. DRUG SUSCEPTIBILITY TESTING (DST)
• 2nd line DST
• inadequate knowledge on mechanisms of resistance
• lower reproducibility (exceptions: aminoglycosides, fluoroquinolones)
• correlation of laboratory resistance to clinical outcome not well studied
• Drugs currently tested (NHLS): ETH, OFLX, KM, CAP*

68. LIMITATIONS OF DST
• Intrinsic accuracy of DST varies with the drug tested - or first line drugs, DST (FLD) is most
accurate for rifampicin and isoniazid and less so for streptomycin andethambutol
• Testing of second-line drugs is not as simple as DST for the first-line drugs
• Proficiency testing results similar to those obtained for first-line drugs are not available for
any of the second-line agents
• SLD has not been standardized internationally due to in vitro drug instability
• Good reproducibility are for aminoglycosides, fluoroquinolones and polypeptides
• Reproducibility and reliability of DST is much less reliable for PAS, terizidone, ethionamide
and cycloserine

69. 4. LINE PROBE ASSAY (LPA)
• It is a test that diagnoses TB and simultaneously detects resistance to
RIF and INH.
• It does this by detecting the presence of the DNA of Mycobacterium
tuberculosis in the sputum and also identifies any changes/ mutations in
the DNA that may cause rifampicin and/or isoniazid resistance.
• presence of mutations is interpreted as resistance to the antibiotic in
question (e.g. RIF and/or INH)

70. ADVANTAGES OF LPA (GENOTYPE MTBDRPLUS)
• It detects MTB and resistance to RIF & INH at the same time
• – From the same specimen, within the same test.
• Short turnaround time for diagnosis of MDR-TB
• – Processing time for the test itself is approx. 8 hours.
• – minimum TAT is expected to be a week.
• It is specific for MTB complex (i.e. it can differentiate MTB from other mycobacteria).
• – The test is designed to specifically detect MTB complex DNA, and not other mycobacteria

71. LIMITATIONS OF LPA (GENOTYPE MTBDRPLUS)
• Cannot be used for monitoring treatment
• It is dependent on smear results (hence smear TAT)
• The test is done on smear positive specimens or smear-negative culture-positive samples
• NB! 2ND generation tests able to detect MTB DNA even in smear negative samples
• Prone to contamination and human error
• The test is multi-stepped and only partially automated (lab intensive)
• it requires at least 3 separate rooms for different steps
• False positive RIF / INH resistance

72. INTERPRETATION OF LPA RESULTS
• MTB complex positive = positive for MTB
• RIF sensitive OR resistant
• INH sensitive OR resistant
• If both RIF and INH are sensitive → susceptible MTB
• If only RIF or INH is resistant → mono-resistant MTB
• If both RIF and INH are resistant → MDR-TB
• MTB not detected = negative for MTB.This result does not exclude TB

73. 5. GENEXPERT
• What is GeneXpert?
• It is an instrument that is used to conduct rapid diagnosis of
tuberculosis and detection of rifampicin resistance.
• It does this by detecting the presence of the DNA of Mycobacterium
tuberculosis in the sputum and also identifies any changes in the DNA
that may cause rifampicin resistance.

74. GENEXPERT…
• The test is called Xpert MTB/RIF
• This test shares fundamental principles with the LPA
• both are PCR-based;
• detect presence of MTB complex DNA;
• detect changes in the DNA that may cause RIF resistance.

75. ADVANTAGES OF GENE XPERT
• It detects MTB and RIF resistance at the same time.
• From the same specimen, within the same test.
• Short turnaround time.
• Processing time for the test itself is approx. 2 hours.
• minimum turnaround time is expected to be the same or less than that of
smear microscopy.

76. ADVANTAGES OF GENE XPERT
• It is specific for MTB complex,
• i.e. it can differentiate MTB from other mycobacteria.
• Can be used on :
• CSF, aspirates (e.g. gastric and lymph nodes) and tissue (e.g. pleural biopsy)
• Less prone to contamination and human error.
• The test for each specimen is carried out in a closed system (cartridge), so
there is a reduced risk of cross-contamination from other specimens.

77. LIMITATIONS OF GENEXPERT
• Cannot be used for monitoring treatment
• limited to diagnosis largely
• False positive RIF resistant
• a small fraction of resistance detected may not correlate with
physiological resistance
• this leading to discordance between Gene-Xpert and DST results or clinical
outcome)

78. ALGORITHM RECOMMENDED FOR GXP
• In all contacts or symptomatic patients – collect one sputum sample
under supervision
• GXP +ve or GXP –ve or unsuccessful
• Rif susceptible treat as TB. Send 2nd sputum for microscopy
• Rif resistant treat as MDR TB refer to treating unit, collect sputum
for M/C/DST for R/H/a/F
• Rif unsuccessful – Start on regimen 1, send sputum for M&C / DST or
LPA

79. GXP POSITIVE/ RIF SENSITIVE
• MTB is present, and sensitive to Rifampicin
• XPert MTB/RIF is sensitive and specific for detection of TB and
Rifampicin resistance
• However this result does not exclude possibility of resistance to other
drugs.

80. GXP POSITIVE/ RIF RESISTANT
• MTB present
• Rifampicin resistance may be falsely positive (10%)
• Second sputum specimen must be sent for confirmatory culture and
DST

81. GXP POSITIVE/ RIF INDETERMINATE
• MTB present
• Rifampicin resistance could not be assessed
• Repeat GXP
• A second sputum may be sent for TB culture and DST to confirm
susceptibility/ LPA
• Treat the patient as if they have drug-sensitive TB

82. ERROR
• The test failed
• Caused by problem with the cartridge, e.g. food particles
• Submit a second specimen for Xpert MTB/RIF

83. 6. CHEST X-RAY
• Common CXR findings:
• Cavitation
• Focal infiltrates in upper and hilar regions
• Hilar adenopathy
• Pleural or pericardial effusion

84. CHEST X-RAY IN DISSEMINATED TB
• The CXR is abnormal in most, but not all, cases of disseminated TB.
• Grieco & Chmel: 50% had “miliary” pattern
• Munt: 90% reported “miliary” pattern
• Overall, it appears that at the time of diagnosis, 85% of patients have
the characteristic radiographic findings of miliary tuberculosis

85. CHEST X-RAY IN DISSEMINATED TB

86. CHEST X-RAY IN DISSEMINATED TB

87. CHEST X-RAY IN DISSEMINATED TB

88. CHEST X-RAY IN DISSEMINATED TB

89. CHEST X-RAY IN DISSEMINATED TB

90. 7. TUBERCULIN SKIN TEST (PPD)
• Positive test
• TB infection
• Not necessarily active disease
• Negative test
• No TB
• Malnutrition
• HIV
• Severe viral infection
• Disseminated tuberculosis

91. CORRECT
Only the induration is
being measured.
INCORRECT
The erythema is being
measured.

92. 8. OTHER INVESTIGATIONS
• Adenosine Deaminase (ADA): especially in CSF, and other body fluids
such as in pleural effusion and ascites.
• Interferon gamma release assay (IGRA): unable to distinguish between
active & latent infection. Can be performed on a single visit.
• Polymerase chain reaction (PCR): GeneXpert system, Sputum LPA
• Antigen detection assays: poor sensitivity, based on detection of M.
lipoarabinomannan in urine of patients
• Antibody tests: difficult to tell between latent & active infection

93. CASE DEFINITION OF
TUBERCULOSIS

94. CASE DEFINITION
• Based on
• Anatomical site
• Bacteriological results (including MDR, XDR)
• Hx of previous treatment
• HIV status of the patient

95. OLD CASE DEFINITION
• TB suspect
• Persons who present with symptoms of TB or contacts of TB /DR-TB
patients
• TB case
• Definite case of TB or patient in which HCW has decided to treat for TB
• Definite case of TB
• patient with M.TB isolated from a clinical specimen

96. NEW CASE DEFINITION
• Presumptive TB
• previously known as TB suspect
• Bacteriologically confirmed TB case
• i.e. GXP / Auramine stain/ TB culture positive results
• Clinically Diagnosed TB
• i.e. no bacteriological confirmation received, patient has features
suggestive of active TB and clinician decides to treat as TB.
• This includes patients diagnosed with CXR.

97. NEW CASE DEFINITION
• Smear positive patients
• Patient is smear +ve if one or more sputum samples +ve for AFB
• more likely to spread disease.
• Smear negative patients
• especially in PLWHA
• associated with higher mortality

98. DIAGNOSIS OF TB IN HIV-POSITIVE INDIVIDUALS
• Protocol for diagnosis of TB in HIV follows the same principles,
irrespective of whether the patient is HIV infected or not
• In HIV+ patients a higher degree of attention will be required
• Diagnosis of TB in HIV+ persons more difficult:
• There is increased frequency of sputum smear negative disease
(pulmonary or extra-pulmonary)
• There is increased atypical radiological manifestations

99. PRESENTATION OF TB IN HIV+ VS HIV-
• Extrapulmonary TB more common
• CXR atypical
• More commonly smear negative
• More rapid clinical deterioration

100. PULMONARY TUBERCULOSIS
CD4 > 200 CD4 < 200

101. EXTRA PULMONARY TUBERCULOSIS
(EPTB)

102. EXTRA PULMONARY TUBERCULOSIS (EPTB)
• More of a diagnostic problem than PTB.
• ? Less common
• ? Less familiar to clinicians
• EPTB involves relatively inaccessible sites
• Bacteriological confirmation of diagnosis more difficult
• Invasive procedures are required often

103. MOST COMMON SITES OF EXTRAPULMONARY TB
• Lymphadenitis
• Pleural
• Pericardial
• Abdominal
• Miliary / Disseminated
• CNS
• TBM
• Tuberculomas

104. DISSEMINATED TUBERCULOSIS
• Because of multisystem involvement, the clinical manifestations are
varied.
• Are usually non-specific and are dominated by systemic effects: fever,
weight loss, night sweats, anorexia and “weakness”.
• Productive cough ±
• Headache and changes in mental status ±

105. TB LYMPHADENITIS

106. TB LYMPHADENITIS

107. TB ABDOMEN

108. CHOROIDAL GRANULOMA

109. RENAL TB

110. TB DACTYLITIS

111. SPINAL TB

112. TB Arthritis
SKELETAL TB

113. TB MASTITIS

114. DRUG RESISTANT TUBERCULOSIS

115. DRUG RESISTANT TB
• MDR TB is TB disease where there is in vitro resistance to both INH &
RIF with or without resistance to other TB drugs
• XDR TB is MDR TB and in vitro resistance to any of the
fluoroquinolones and any injectable i.e. Kanamycin OR Amikacin OR
Capreomycin
• TDR …. Total drug resistant TB!!

116. DRUG RESISTANT TUBERCULOSIS
• Mono Resistance : Resistance to one first line anti TB drug ONLY.
• Poly Resistance : Resistance to more than 1 first line anti TB drug
• Multidrug Resistance : Resistance to Rifampicin and Isoniazid
• Extensive DR (XDR) TB : MDR + R to any fluoroquinolone and at least
one of the 3 injectables i.e. Capreomycin (Polypeptide), Amikacin and
Kanamycin (Aminoglycosides)

117. MDR TB STATS
• Global epidemiology ~ 650 000 patients diagnosed worldwide in WHO
report of 2011, only 46000 ~7% started on therapy
• SA high burden country for both MDR TB and TB, ranking 5th & 3rd
respectively
• In 2010 report, 7386 lab diagnoses of MDR TB, 5313 patients treated.
• In 2008 cohort study, success rate of MDR TB therapy ~48% - causes for
this multifactorial.

118. XDR TB STATS
• 741 patients diagnosed in 2010, 615 started on therapy
• In April 2011, 2500 beds available for in hospital care of all DR TB
patients.
• Needless to say SA struggling with escalating burden of DR TB

119. CHALLENGES IDENTIFIED BY NDOH
• Not enough beds in TB facilities
• High default rate
• Half of newly diagnosed DR TB patients not started on therapy or delay to start therapy
• Long waiting lists to start admissions
• Socioeconomic impact of diagnosis
• Clinicians outside of facilities often ignorant of treatment guidelines
• Poor infection control measures
• Poor outcome

120. LOGIC FOR DECENTRALISED CARE
• Start therapy as soon as diagnosis made by clinician
• Patient to be managed closer to home, more likely to improve
adherence to therapy and improve outcome
• Guidelines provided by NDOH on management of these patients in
community
• Training of clinicians in the community

121. DECENTRALISATION OF SERVICES IN DR TB SINCE 2011
(I.E. AMBULATORY RX
• MDR-TB smear negative patients: can be started on ambulatory
treatment
• MDR-TB smear positive, stable patient without extensive disease:
admit in the decentralised MDR TB unit until 2 smear neg sputa
• Sick MDR TB with extensive disease & XDR TB patients: admit in
central MDR TB unit until 2 successive sputum cultures are neg.

122. DECENTRALISATION OF SERVICES IN DR TB SINCE 2011
(I.E. AMBULATORY RX)
• Every unit needs to adopt a policy to prevent the spread of any TB
(possibly MDR TB) among ambulatory patients or patients admitted
into hospital on an open medical or surgical ward.
• The resources are often spread very thin but we still need to be pro
active in preventing the spread of disease since a lot of patients are
being managed from home

123. REFERRAL OF THE MDR TB PATIENT
• Initiate therapy ASAP after baseline tests to review for comorbid states
CUE,LFT, etc
• Telephonic discussion with Empilweni or Jose Pearson for inpatient
admission and a registration number if patient requires protracted
admission in DNH.
• Ensure samples are taken for culture to confirm diagnosis.
• Patient with R&H resistance will have DST for 2nd line drugs i.e. F & A

124. MDR-TB & XDR-TB REGIMEN

125. OLD MDR REGIMEN
• Group A (Fluoroquinolones): Levofloxacin, Moxifloxacin, Gatifloxacin
• Group B (2nd line Injectable agents): Amikacin, Capreomycin, Kanamycin (streptomycin)
• Group C (Other core 2nd line agents): Ethionamide/prothionamide,
Cycloserine/Terizodone, Linezoid, Clofazimine
• Group D (Add-on agents)
• D1: Pyrazinamide/Ethambutol/high dose Isoniazide
• D2: Bedaquiline/ Delaminid
• D3: Imipenem, Meropenem, Augmentin

126. OLD STANDARD MDR REGIMEN
• (A + B + 2C + D1)
• Moxifloxacin 400mg (children 7.5mg – 10mg/kg)
• Kanamycin 750mg to 1g IMI (15 – 20mg/kg)
• Terizidone 750mg to 1000mg (15-20mg/kg)
• Ethionamide 500mg to 750mg (15 – 20mg/kg)
• Pyrazinamide 1750mg to 2500mg (30-40mg/kg)

127. NEW (SHORT) BEDAQUILINE REGIMEN FOR DR-TB
• Bedaquiline (Group D2 – previously an add-on, now forms the bedrock of the new
regimen)
• Levofloxacin (Group A drugs – fluoroquinolones are still vital parts of the regimen)
• Clofazimine & Ethionamide (Both group C drugs)
• Isoniazid HD, Ethambutol & Pyrazinamide (Previously from the group D1. 3 drugs now
used instead of 1)
• NB!! No room for injectables or aminoglycosides in this new regimen

128. NEW (SHORT) BEDAQUILINE REGIMEN FOR DR-TB
ADVANTAGES
• Short course
• 4 – 6 months of intensive phase and 5 months of continuation phase
• Bedaquiline is used for a minimum of 6 months
• No injectables in the new regimen
• Better adherence and less loss to follow up
• Higher cure rates and greater success in the roll out phases

129. NEW (SHORT) BEDAQUILINE REGIMEN FOR DR-TB
MEDICINE WEIGHT
<33 kg 33 – 50 kg > 50 kg
BEDAQUILINE 400mg daily for 2 weeks, then 200mg 3 times per week
LEVOFLOXACIN 750 mg 750 mg 1000 mg
ETHIONAMIDE 250 mg 500 mg 750 mg
ISONIAZID (HD) 600 mg 600 mg 900 mg
CLOFAZIMINE 50 mg 100 mg 100 mg
ETHAMBUTOL 800 mg 800 mg 1200 mg
PYRAZINAMIDE 1500 mg 1500 mg 2000 mg

130. NEW (SHORT) BEDAQUILINE REGIMEN FOR DR-TB
INTENSIVE PHASE
4 – 6 MONTHS
• BEDAQUILINE
• Levofloxacin
• Ethionamide
• Isoniazid (HD)
• Clofazimine
• Ethambutol
• Pyrazinamide
CONTINUATION PHASE
5 MONTHS
• Levofloxacin
• Clofazimine
• Pyrazinamide
• Ethambutol

131. XDR TB REGIMEN
• Bedaquiline 400 mg daily for 2 weeks
• Then Bedaquiline 200 mg 3 times
weekly for 22 weeks
• Levofloxacin 1000 mg daily
• Linezolid 600 mg daily
• PAS 8 g daily
• Terizidone 750 mg daily
• Then
• +/- high dose Isoniazid 600 mg daily
• Ethambutol 1200 mg daily
• Pyrazinamide 1759 mg daily

132. THANK YOU FOR YOUR PATIENCE