Tuberculosis is a chronic infectious disease caused by the bacterium Mycobacterium tuberculosis that primarily affects the lungs. It is one of the top 10 causes of death worldwide. In 2017, 10 million people fell ill with TB and 1.6 million died from the disease. TB is a global problem, with high rates in Africa where 13 of the 15 most affected countries are located. Zimbabwe has one of the highest burdens of TB, with incidence increasing in the 1990s-2000s due to the HIV epidemic. TB is transmitted via airborne droplets when people with active pulmonary TB cough, sneeze or speak. Most infections are asymptomatic and latent, but active disease can develop when the immune system is compromised. Active

1. Tuberculosis

2. Tuberculosis
• Chronic (sometimes acute or sub acute),
debilitating and notifiable disease
characterized by formation of tubercles in
lungs and other tissues of the body

4. Distribution - global
• Tuberculosis (TB) is one of the top 10 causes of death worldwide.
• In 2017, 10 million people fell ill with TB, and 1.6 million died from the disease
(including 0.3 million among people with HIV).
• TB is a leading killer of HIV-positive people.
• In 2017, an estimated 1 million children became ill with TB and 230 000 children
died of TB (including children with HIV associated TB).
• Multidrug-resistant TB (MDR-TB) remains a public health crisis and a health
security threat. WHO estimates that there were 558 000 new cases with resistance
to rifampicin – the most effective first-line drug, of which - 82% had MDR-TB.
• Globally, TB incidence is falling at about 2% per year. This needs to accelerate to a
4–5% annual decline to reach the 2020 milestones of the End TB Strategy.
• An estimated 54 million lives were saved through TB diagnosis and treatment
between 2000 and 2017.
• Ending the TB epidemic by 2030 is among the health targets of the Sustainable
Development Goals.

6. Distribution - Africa
• Has 12% of world population but 31% of TB
cases are in Africa. 13/15 very high burden
countries are in Africa. (Swaziland highest). In
South Africa it is the 2nd cause of death after
HIV/AIDS

7. Distribution - Zimbabwe
• 17/22 high burden countries. Incidence increasing (1990-
2007) due to HIV/AIDS. Most cases in Mashonaland East,
Matebeleland North and South. 78% PLWHA have TB. TB
one of the top 5 causes of illness (morbidity) and death
(mortality)
 Incidence increased due to HIVfrom 96.9/100,000 in 1990
to 1136/100,000 in 2007 (who,2008)
 TB/HIV co-infection rates estimated to be 72%
 TB among top 5 leading causes of hospital admission and
outpatient visits
 Affects -more men than women
-The reproductive, economically
productive age group

8. Causative organism
• Mycobacterium tuberculosis [90%]and mycobacterium bovis [5%].
• M. tuberculosis complex: M. tuberculosis (MTB)
• TB-causing mycobacteria
– M. africanum is not widespread, but in parts of Africa it is a significant cause of
tuberculosis.
– M. bovis was once a common cause of tuberculosis, but the introduction of pasteurized
milk has largely eliminated this public health problem in developed countries
– M. canetti is rare and seems to be limited to Africa, although a few cases have been
seen in African emigrants.
– M. microti is mostly seen in immunodeficient people
• Other known pathogenic mycobacteria
• M.leprae (Leprosy)
• M. avium, and M. kansasii (non-tuberculosis mycobacteria – NTM) (seen in severe COPD or
immune compromise AIDS)
• Aerobic, alcohol acid fast Bacilli with active and inactive phases.
• Cannot be digested by macrophages
• Resistant to many disinfectants, alkali, drying agents
Reservoir
• Humans, cattle, pigs, dust.

9. M. tuberculosis

10. M. Tuberculosis
• Rod shaped
• 2-4 µm in length and 0.2-0.5 µm in
width
• Gram positive (lacks a phospholipid
outer membrane)
• Lipid/waxy walled coating (mycolic
acid) thus impervious to gram
staining
• Acid Fast - Ziehl Neelsen Stain used
• aerobic requires high levels of
oxygen
– Lungs
– Vascular organs

11. Mode of Transmission and Spread
• droplet infection when an infected person coughs, sneezes,
speaks or sings close to a vulnerable person
• airborne through inhalation of infected dust
• ingestion of unpasteurised infected milk
• inoculation during birth if contaminated equipment is used
• during post mortem of someone who died from TB
• transplacental if mother has TB
• NB: TB becomes non-infectious 2-4 weeks after starting
treatment. It is not highly infectious and cannot be spread
by hands, books, glasses, dishes or formites
• Incubation period : 2-10 weeks. May be latent for several
decades

13. Risk factors
• Close contact
• Immunocompromised status e.g. pregnant mothers,
HIV/AIDS, Immunosuppressant drugs, chronic illness, DM
• Recent TB infection
• Substance abuse, smoking, alcohol
• Overcrowding/substandard housing
• Institutionalization
• Immigration
• Malnutrition
• Extremes of age [< 5 years and >60 years]
• Health care workers
• Inadequate health care

14. Public Health Agency of Canada | Agence de la santé publique du Canada 14
Social Determinants of TB
Source: Lönnroth K et al. Soc Sci Med 2009;68:2240-6
Determinant Prevalence
Relative
Risk
PAF (%)
Malnutrition 16.7% 3.2 27
Indoor air pollution 71.2% 1.4 22
Active smoking 26.0% 2.0 21
HIV infection 0.8% 20.6-26.7 16
Alcohol abuse 8.1% 2.9 13
Diabetes mellitus 5.4% 3.1 10
Newly landed immigrants increased risk in 1st 4 years
? Stressor of immigration, ? Environment/nutrition/Vit D exposure

15. Pathophysiology TB
• Phase 1: Transmission
• Phase 2: Initiation of infection, proliferation &
dissemination
• Phase 3: Evolution of the host immune response
& latent Infection
• Phase 4: Liquefaction and accelerated bacillary
proliferation (Active TB disease)
• Retransmission again

16. Phase 1: Transmission

17. Diseased Person Generates Aerosol
• Airborne droplet
• Fluid source (sputum)
• Force aerosolization (cough,
sneeze, medical procedures)
• ~103 – 104 bacilli needed
• Infected tissue also infectious
– issue for lab work/surgical
only
• GI tract (M bovis) consuming
contaminated milk/bovine
products

18. Host Inhales Aerosol
• Dehydrated droplet nuclei are
inhaled
• Most of the bacillus is
trapped and expelled by the
ciliated epithelium
• Few mycobacteria reach
the lungs where they lodge
in well aerated areas (lower
part of upper lobe or upper
part of lower lobe
• Travel to bronchial tree 25
generations progressively
smaller airways (1st carina)
• deposit in alveolus

19. Contagious?
• Factors Influencing Transmission
(organism/host):
– Hardiness of bacilli (survive the journey)
– virulence
– ventilation, environment
– duration of exposure
– Immunity of host
– Resident macrophage (present or
compromised)
• Protect with N95 mask

20. Resident Alveolar Macrophage (RM) Engulf TB
Bacilli

21. Phase #2: Proliferation & Spread
• In the lungs, mycobacteria are ingested
(phagocytosed) by macrophages and neutrophils.
• Most are destroyed by the phagocytes resulting
in an exudative response which causes a non-
specific pneumonitis/bronchopneumonia
• A few multiply in the phagocytes and are released
upon death of the phagocytes to subsequently
infect other cells

22. Phase #2: Proliferation & Spread
Option #1
RM is able to kill TB
Option #2
TB bacilli proliferate
Alveolus
Resident (Non-immune) Macrophage (RM)
Engullfed TB

23. Perfect Place for Bacilli to Multiply
Slide #13 Virulent M.TB side
• TB organism promotes
macrophage uptake “come and
get me”
• Proliferate intracellularly
• Slow replication 15 -18 hrs
• Geometric replication = 1 bacilli
q 16 hrs =540,000 bacilli in 20
days
• Replicates/destroys the cell
• Now that’s a party!!

24. Journey Begins: Bacilli (free/intracellular)
transport to hilar lymph nodes to seed organs

25. Phase 3: Evolution of Cellular Immunity and
Delayed-Type Hypersensitivity
DELAYED -TYPE HYPERSENSITIVITY
Distruction of incompetent macrophage
Tuberculosis Skin Test
10% lifetime chance of progressing to active TB
Unless Immune compromised % higher
CELLULAR MEDIATED IMMUNITY
LATENT TUBERCULOSIS
Cutail proliferation/kill bacilli
Option #1
HALT PROLIFERATION
Takes up to 3 month
Asymptomatic/Non-infectious
PROGRESSION TO ACTIVE DISEASE
Phase #4
Option #2
INSUFFICIENT IMMUNE RESPONSE
Infants, HIV/AIDS, vulnerable hosts
Immune War Rages On
Intracellular & Extracellular TB
All organs are being seeded

26. Sound the Immune Alarm:
Acquired Cellular Immunity
• Humeral or antibody responses -
play very little roles (unlike other
infections)
• Struggle/lysis of the cell =
cytokines and chemokines
• Set off the alarm system in the
immune response to send back
up (additional macrophages,
dendritic cells, peripheral blood
monocytes (PBM), lymphocytes
and neutrophil)
• Incompetent macrophage
continue to gobble providing
place to multiply

27. Immune Response
• Alveolar macrophage present TB antigens to T- lymphocytes
(), CD4, CD8,
• T cells release cytokines, IL1, IL12
• These recruit activated “Big Strong” macrophage (AM)
– TNF- (kills incompetent resident macrophage),
– Vit D (1,25, 25-OH vitamin D) builds “big stronger” AM
• AM limits proliferation and/or kills bacilli
• Protect cellular and tissue damage
• AM result in involution (builds a shell = granuloma/ Ghon)
around bacilli (in and out of cells) at the primary lung lesion
and extra-pulmonary sites.

29. Ghon complex

31. Old Sanitarium Treatment
Sunbathing and Vitamin D Reflects This
Immune Pathway
• Before the availability of drugs a
widely accepted treatment was
sunbathing.
• Sunbathing: exposure to
moderately hot temperatures for
extended periods of time.
• Skin converted the sun’s UV rays
into vitamin D, which was
thought to do further damage to
the TB bacilli acting as a
bactericide
• Sunlamps were often used to
replace natural sunlight in sun-
therapy, or "heliotherapy"

32. Option 1 Latent Infection:
Halting Proliferation/Granuloma (Fibrocalcific
Residua, Ghon Complex)
• Asymptomatic 99%
<1% may have erythema nodosum
(cutaneous immune response) or
conjuctivitis (Hypersensitivity reaction)
• Not contagious
• No prophylaxis: 90% will stay asleep
(latent) but 10% will activate (5% in first 2
years after infection, then 5% over
lifetime) – assuming immune competent
• Immune compromised higher risk
• Many factors interfere with delicate
balance
• With prophylaxis (INH) <1% risk of going
on to active disease

33. TST: What does it tell you?
• Mantoux/PPD test for Purified Protein Derivative
• A standard dose of 5 Tuberculin units (0.1 mL)
• Read 48-72 hr by measuring the diameter of induration (palpable raised hardened area) across
the forearm (perpendicular to the long axis) in millimeters
• If there is no induration, the result should be recorded as "0 mm"
• Erythema (redness) should NOT be measured.
• WHO estimates 1/3 worlds population has (positive TST) or TB infection

34. Negative = No Infection
Except….
False Negative Results
• <3 month from last exposure
• Planted to deep
• Immune suppressed (anergy)
• Active TB disease 60% will have a
negative skin test!!!
(Serial testing)
• Long duration waned immunity
(Two Step - Booster Phenomenon)

35. Positive = TB Infection
ONLY INDICATES INFECTION NOT ACTIVE
TB
• > 10 mm induration
• Contacts/HIV (5mm)
• False positives
– Contact with other
Mycobacterium (see Slide #3 All in
the family)
– BCG vaccine (see Slide # 14 & 23)
• Treatment INH 6-9 months
• OR Rifampin 4 months
• Children (contacts – tx if TST
negative until 3m test)
• Pregnancy Issues (Tx if close contact
otherwise defer)

36. TST Reading & BCG Vaccine
WHEN READING TST IGNORE
BCG VACCINE
MUST ASSUME INFECTION!
• Endemic (high TB rates)
– Aboriginal
– Foreign Borne
• High TB risk populations
– Contacts
– Abnormal x-rays
– HIV infection

37. Option #2: Active TB Disease: Progression
primary infection or Activation of Latent
Infection

38. Inhalation of bacilli
No active case of TB.
Only x-ray evidence of
TB infection is a
calcified nodule
(Gohn tubercle)
PREVIOUS
EXPOSURE
Inflammation within Alveoli
Calcification
Liquefaction
Necrosis of Tubercle
(Caseation Necrosis)
A small, firm, white nodule is
produced (Primary tubercle)
NO PREVIOUS
EXPOSURE
Natural body defence attempt
to counteract infection
Expectoration
and Cavitation

39. Phase 4:Progression to Active
Disease (Soupy Mess)
• Active TB disease can occur:
– During initial infection phases OR
– When delicate balance of latent TB granuloma is upset after X years
• If battle continues or delicate balance of latent TB granuloma upset:
– In battle cells, macrophage, leukocytes are destroyed
– When destroyed they release potent proteolytic enzyme as well as
cytokines and TNF-
– Tumour necrosis factor (TNF) promote thrombosis of local blood
vessels/tissue breakdown
– liquefies (tissue into soupy detritus) cavitations/ hemoptysis/bleeding
– Bacilli love the soup and feed off it promoting a robust muliplication
extracellularly
– Macrophage don’t survive in acidic environment & rendered useless
– Bronchi are invaded/ irritated by “soup”/bacilli and provide the perfect
transport to the next host TRANSMISSION AGAIN

41. HIV Co-infection
• T-Cell destruction
• CD4 < 500
• 100 X more risk of
activation the latent
infection
• All HIV + test for TB &
offer preventive Tx
• All active TB test for
HIV
• TB is an AIDS defining
diagnosis

42. Clinical features
• 75% cases have pulmonary TB, the remainder 25% have extra pulmonary
TB
• TB Suspects present with a cough of at least 2 weeks plus one of:
– Sputum production – usually purulent but may be blood stained
– Night sweats
– Fever
– Loss of weight
– Shortness of breast
– Chest pain
– Loss of appetite
– General feeling of being unwell
– Other features include:fatigue, loss of appetite, dyspnea, hoarseness of voice,
amenorrhea,
– NB: features are less clear in HIV/AIDS
– ALWAYS do functional Inquiry that include s/s from extra pulmonary sites

43. Extrapulmonary tuberculosis
• Can affect any body part. May involve painless
swelling of local lymph nodes, lassitude, loss
of appetite, loss of weight, anaemia, pyrexia,
night sweats, tachycardia and local features:

44. Extrapulmonary tuberculosis
• TB pericarditis tachycardia, distended neck
veins, swelling of lower limps, pericardial
friction rub, pulsus paradoxicus, carotid
shadow on x-ray, pericardial effusion
• TB Meningitis: headache, meningism, palsies,
reduced mental status due to cerebral
oedema

45. • TB Spine: Local back pain, gibbus/kyphosis,
paraplegia, paraplegia if it affects thoracic
spine, cold abscess
• TB abdomen: abdominal distension, pain,
diarrhea, ascites,
• Other: TB pleura, tongue, larynx, peritoneum,
kidneys, testes, bones, skin, eyes, etc

46. Tuberculosis in children
• has non specific features e.g. weight loss
(FTT), fever, diarrhea, enlarged glands, fits,
chronic cough/wheeze which does not
respond to antibiotics
• TB is suspected in children with a history of
contact with a sputum positive patient

47. Latent TB and TB disease

49. TB screening tool

50. Diagnosis
1. Direct smear microscopy of sputum for AAFBs -
through either DSM (direct smear microscopy) or
Gene Xpert MTB/Rif. Gene Xpert MTB/Rif is done for
all HIV positive patients [results in 3 hours]
2. DST – Drug susceptibility testing at any one of the
National Tuberculosis Reference Laboratories (NTRLs)
– Harare (northern region), Bulawayo (Southern
region).
3. Chest x-ray
4. Tuberculin test - (Mantoux test) – [Purified tuberculin
1:1000 0.1ml (ID) stat]. Check after 24-48 hours.
5. Biopsy

51. Mantoux test

52. Sputum specimen collection
• All TB presumptive clients should have 2
sputum samples taken:
– “On the spot” sample
• Taken at the health facility after identified as a TB
suspect
– Early morning sample
• Done at patient’s home upon waking the next day
• 2 sputum samples can be collected 2 hours apart on
the same day if necessary

55. Indications for chest x-ray
• A child suspected of TB
• Adult with body mass index less than 17 kg/m2),
• HIV positive patient who is sputum negative
• Non-response to broad-spectrum antibiotics for correct duration in
sputum negative and HIV negative patient
• Non-response to broad spectrum antibiotics in a sputum negative
patient.
• When suspecting complications, e.g., pneumothorax, or pleural
effusion
• When frequent and severe haemoptysis occurs
• When other lung diseases are suspected by the medical officer
• Pericardial effusion

56. Tuberculosis radiograph

58. TB Chest X-ray
• Cavitations
• Infiltrate can occur
• Permanent scars
can impact gas
exchange,
decrease lung
compliance and
perfusion

59. Atypical X-rays & Miliary TB
• Primary Infection
– Lower Lobes
• HIV
– Normal film
– Hilar fullness
– Miliary (millet seeds)
– Lower Lobes
• Children
– Same

60. Sputum Smear
• Scarce = 1,000 to 10,000 bacilli/ml
• Moderate
• Numerous (cavity)
• All infectious including negative
smears !!!
• False positives
– Atypical Mycobacterium
– AMTB (97% sensitivity/specificity
on positive smears) will solve this
question of TB ribosomal RNA

61. Culture & Sensitivity

62. Other TB Tests
• PCR testing (aspirate,
tissue biopsy)
• DNA Fingerprinting
• Gastric Aspirate
(Children)
• Other sampling

63. Special populations
• Due to concern for drug resistance the following cases
should submit samples for Gene Xpert MTB/Rif
– All relapses
– Patients on category 1 treatment who are sputum positive at
3/5 months
– Patients on category 2 treatment who are sputum positive at
3/4 months (at end of prolonged intensive phase).
– Patients on category 2 treatment who are sputum positive at
the end of treatment
– Patients who are sputum-smear positive and have been in
contact with MDR-TB case.
– Gene-Xpert screening for all HIV positive patients
– Residence in DRTB high burden zones
– Return after treatment default

64. Management
• Most TB drug regiments are given under
DOTS (direct observation of treatment),
which means that a treatment supervisor
watches the patient actually swallowing the
tablets.

65. National TB Policy - Zimbabwe
1. Sputum microscopy for diagnosis and follow up
provided free of charge in the public health sector
2. Short-course chemotherapy provided free of charge
in the public health sector
3. Treatment of Drug Resistant TB(DRTB) provided for
free of charge in the public sector
4. TB services available at all levels of the health
delivery system, being integrated into the primary
health care system to ensure efficient case finding,
particularly for sputum smear positive patients
5. Collaborative TB/HIV activities at all levels

66. 1st Line Active TB Treatment

68. TB treatment categories

69. Category I
– All new cases
– 2HRZE (DOT) [intensive phase] + 4HR (DOT)
[continuation phase] – it can be extended to 6HR
(DOT) in adults or 10HR(DOT) in children TB of
meninges, bone, joint, pericardium, disseminated
spinal disease)
– Test sputum at 2 and 3 months or 5 and 6 months. If
still AAFB positive after 3, 5 or 6 months, sent for MCS
at reference laboratory (Mpilo and Harare)
– If still sputum positive after 5 months start category II

70. Patient’s
weight
(kg)
HRZE
(75mg/150m
g/400mg/27
5mg)
Number of
tablets in
intensive
phase
Dosage of
streptomyci
n in
Category II
HR
(150mg/150
mg)
Number of
tablets in
continuatio
n phase
HRE
(75mg/150m
g/275mg) –
Category II
continuatio
n phase
30-39 2 0.5g 1.5 2
40-54 3 0.75g 2 3
55-70 4 1g 3 4
70+ 5 1g 3 5
Adult dosages:

71. Category II
– All retreatment of TB forms
– Adults >12years: 2SHRZE + 1HRZE = 5HRE (DOT)
– Children: 3HRZE = 5HRZ (DOT)
– Take sputum for AAFB at 3 months and Start
continuation phase regardless of AAFB results
– If still sputum smear positive after 4 months stop
all anti TB drugs for 3 days and collect sputum for
M/C/S. then start continuation phase

72. Type of TB patient Definition
New Any individual who has received no or < 1 month of anti-TB treatment
Previously
treated
Relapse
Any individual whose most recent anti-TB treatment outcome was
“cured” or “treatment completed”, and who is afterwards diagnosed with
TB (sputum smear microscopy and/or culture positivity)
Treatment after failure of
category I
Any individual treated with category I anti-TB treatment, which failed (i.e.
sputum smear positive at 5 months or later during treatment)
Treatment after failure of
category II
Any individual treated with category II anti-TB treatment, which failed
(i.e. sputum smear positive at 5 months or later during treatment)
Treatment after default
Any individual who restart anti-TB treatment, after an interruption of at
least 2 consecutive months and is smear and/or culture positive
Transfer in
Any individual transferred in from another register for treatment of DR-
TB to continue category IV treatment
Other
Any individual not fitting into the above-mentioned groups. They can be
sub-classified as follows:
a) sputum smear and/or culture positive cases whose previous anti-TB
treatment outcome is unknown;
b) sputum smear and/or culture positive cases whose previous anti-TB
treatment was not category I nor II;
c) cases treated with numerous ineffective anti-TB treatments, were
deemed not curable and who have lived with TB with no or
inadequate treatment for a period of time until category IV regimen
became available (“chronic” or “back-log” patients).

73. Drug resistance
• Mono resistance – resistance to one anti-TB
drug usually INH
• Poly resistant – resistance to more than one
anti-TB but not a combination of RIFA and INH
• MDR TB – resistance to at least INHand RIFA
• XDR TB (extensively resistant) – resistance to
INH, RIFA, a fluoroquinolone and at least 1 of
the 3 injectable anti-TB drug (amikacin,
capreomycin, Kanamycin)

76. Health care worker and
programmatic factors
Anti-TB medicine
related factors
Patient related
factors
-Inappropriate or absent
guidelines
-Non- compliance with
guidelines
-Poor training and
supervision of HCWs
-Lack of anti- TB
treatment monitoring
-Poorly organised and/or
funded NTP
-Poor quality
-Unavailability
-Poor storage
-Wrong dose or
inadequate
combination
-Poor adherence (poor
DOT)
-Lack of information
on treatment
-Adverse events on
treatment
- Social barriers
(stigma, restrictions)
-Malabsorption due to
other causes
-Substance addiction
Mental disorder
•Causes of Drug Resistant TB

77. People at risk of developing drug
resistant TB
• Failure of Category I regimen (new case);
• Failure of Category 2 regimen (retreatment);
• Exposure to a known case of drug-resistant TB;
• Patients (new or previously treated) who remain sputum
smear +ve at month 2 or 3 while on TB treatment;
• Return after default;
• Exposure in institutions that have a high DR-TB prevalence
(for example: prisons, squatter camps, hospitals, refugee
camps);
• Relapses;
• Patients from high burden DR-TB countries.

78. Drugs used in the management of DR
TB
• group 1 – first-line oral anti-TB agents;
• group 2 – injectable anti-TB agents;
• group 3 – fluoroquinolones;
• group 4 – oral bacteriostatic second-line anti-
TB medicines;
• group 5 – anti-TB agents with unclear efficacy
(these are not recommended by WHO for
routine use in DR-TB patients).

79. MDR-TB Treatment Options

81. XDR-TB
WHO confirmed in 58 countries

82. Group
Medicines
(abbreviati
on)
Principles
Group 1 –
first-line
oral anti-TB
agents
isoniazid
(H);b
rifampicin
(R); b
ethambutol
(E);
pyrazinamid
e (Z)
Begin with any first-line agents that
have certain, or almost certain,
efficacy. If the patient’s TB is highly
likely to be resistant to a first-line agent
, do not use it. (For example, most DR-
TB regimens used for patients in whom
a retreatment regimen has failed do not
include ethambutol because the
patient’s disease is likely to be
resistant to ethambutol.)

83. Group 2 –
injectable TB
agents
kanamycin
(Km);
amikacin
(Am);
capreomycin
(Cm);
streptomycin
(S)
One injectable agent should be given to every
patient. Add an injectable agent based on DST
and treatment history. Don’t give streptomycin,
even if DST suggests susceptibility, because
of high rates of resistance among drug-
resistant TB strains and higher incidence of
ototoxicity. Kanamycin is generally selected
given its lower cost and good experiences with
use. Kanamycin and amikacin are similar (both
are aminoglycosides) and have close to 100%
cross-resistance: if an isolate is resistant to
kanamycin or amikacin, then capreomycin
should be used.

84. Group 3 –
fluoroquinolo
nes
ofloxacin
(Ofx);
levofloxacin
(Lfx);
moxifloxacin
(Mfx)
Add a fluoroquinolone based on DST and
treatment history. While levofloxacin or
moxifloxacin are considered to be more
effective against M. tuberculosis than ofloxacin,
according to data from animal and early
bactericidal activity( EBA )studies, levofloxacin
is the fluoroquinolone of choice until more data
confirm the long-term safety of moxifloxacin. In
resource-constrained areas, ofloxacin is an
acceptable choice for ofloxacin-susceptible
drug-resistant TB. In cases where resistance to
ofloxacin or extensively drug-resistant TB is
suspected, use levofloxacin or moxifloxacin,
but do not rely upon it as one of the four core
medicines.

85. Group 4
– oral
bacterio
static
second-
line anti-
TB
agents
ethionamide
(Eto);
prothionamide
(Pto);
cycloserine
(Cs)c ;
Terizedone(Tr
d)d para-
aminosalicylic
acid (PAS)
Add these agents according to the estimated susceptibility of
the strain, the patient’s treatment history, efficacy, profile of
adverse effects and cost.
 If only one of these agents is needed, ethionamide or
prothionamide is often added because of their proven
efficacy and low cost.
 If two agents are needed, cycloserine is commonly used in
conjunction with ethionamide or prothionamide.
 Ethionamide or prothionamide should be started at a low
dose (250 mg) for a few days and then gradually increased
until the full dose is reached.
 Since the combination of ethionamide or prothionamide
with para-aminosalicylic acid causes a high incidence of
adverse gastrointestinal effects, these two agents are
commonly used together only when all three agents in
group 4 are needed.
 If it is necessary to add a third agent, para-aminosalicylic
acid should be used. It is costly, has significant adverse
gastrointestinal effects, and the microgranules require a
cold-chain for storage, all of which make this medicine less
convenient to use.

86. Group 5 –
Anti-TB
agents with
unclear
efficacy
(not
recommend
ed by WHO
for routine
use in DR-
TB patients)
clofazimine
(Cfz);
amoxicillin/cla
vulanate
(Amx/Clv);
clarithromycin
(Clr); linezolid
(Lzd)
thioacetazone
(Th)
Consider adding medicines from
group 5 after consulting with an
expert in DR-TB if there are not four
medicines that are likely to be
effective from groups 1–4. If
medicines are needed from this
group,each medicine counts as half
therefore two drugs.

87. Shorter regimens
• Contraindicated in the following circumstances
– Confirmed resistance, or suspected ineffectiveness, to
a SLID or FQ
– Previous exposure for more than one month to a SLID
or FQ
– A contraindication to any medicines in the shorter
MDR-TB regimen or increased risk of toxicity
– Pregnancy
– Close contact with a patient that has resistance to FQ/
SLID.

89. DR treatment regimen
• The standard shorter DR-TB treatment
regimen for Zimbabwe is:
– 4-6 months (Km-Mfxhd-Eto-Cfz-Hhd-Z-E)
plus
– 5 months (Mfxhd-Cfz-Z-E)

90. X-DR treatment regimen
• 6 months (Cm-LZD-BDQ-Lfx-Cfz-Amx/clv- Hhd)
plus
• 12 months (LZD-BDQ-Lfx-Cfz-Amx/clv-Hhd)
• LZD=Linezolid, BDQ=Bedaquiline

91. Prevention and control of TB
• BCG at birth or first contact in first 1 year of
life(not to symptomatic HIVor children born to
sputum positive mothers)
• INH 10mg/kg to children born to sputum positive
mothers. After 2 months do the Mantoux test. If
positive give full TB treatment, if negative
continue INH prophylaxis for 4 more months.
Then BCG
• Contact tracing and investigation
• Active case finding

92. • Reducing overcrowding, stress, alcoholism
• Infection control – keeping windows open,
waiting n positive pressure ventilation, cough
etiquette, prompt health services to TB suspects,
separating TB cases and suspects from other
patients into a well ventilated area.
• Personal protection – N95 masks
• Health education
• Treatment of cases

93. Stop TB strategy
• Pursue DOTS:
– Political commitment with consistent financing
– Case detection through quality bacteriology
– Standardized treatment with supervision and support
– Effective drug supply and management system
– Monitoring and evaluation of the program
• Address TB/HIV, MDR-TB and other challenges
• Strengthen the health system
• Engage all care providers
• Empower people to fight TB through health education and
community participation – including patient’s charter for TB care
• Facilitate and promote research for new diagnostics, drugs and
vaccines

94. Complications
• Pleural effusion/empyema
• Pneumothorax
• Chronic obstructive pulmonary disease
• Cor pulmonale
• Extra pulmonary TB
Prognosis
• Good if PTB patient complies with treatment.
Fatal if untreated. Cure rate of MDR TB is 50-60%
at its best