INFECTIOUS DISEASES

Topic: Tuberculosis (Adults, Childhood and Infancy)

Lecturer: Dr. Sy, Celia

If a person has a positive skin test (TST) and had no symptoms, his chest CXR
is normal, he is classified as:
A. Latent Tuberculosis Infection (LTBI)
B. TB disease

DEFINITIONS
 Asymptomatic or Latent Tuberculosis Infection (LTBI)
o Infection associated with tuberculin hypersensitivity as shown
by a POSITIVE TUBERCULIN SKIN TEST(TST) with no striking
clinical or roentgenographic manifestations
Example: If the doctor has done a PPD test or TST and the
patient became positive but with no symptoms  then it is Lecture Discussion: Primary Complex
a case of latent TB infection
The first thing the TB bacilli will do is to lodge into the adjacent lymph nodes
 creates lymphadenopathy. So in the CXR, you will see enlarged LNs. Now,
o Mycobacterium tuberculosis complex infection in a person
the TB bacilli may travel through lymphatic spread to the adjacent lung (this
who has POSITIVE TUBERCULIN SKIN TEST (or IGRA) results,
is what we called as a primary focus). The 3 elements: primary focus,
with no clinical manifestations of disease and chest lymphangitis, and regional adenitis  all of these consists the Ghon’s
radiographic findings that are normal complex (Primary complex)

INCUBATION PERIOD In children, we usually request for PA or AP and Lateral CXR. On the lateral
 Time interval from the exposure to mycobacterium to the development CXR  we would like to look for any enlarged LNs
of delayed hypersensitivity reaction as manifested by a POSITIVE TST (or
IGRA) DIAGNOSTIC TESTS
o This is approximately around 3-4 weeks. By the time you inhale
CASE: P.T. 16 y/o male, cough >2 weeks, blood streak sputum
or ingest an M. TB bacilli  it goes to the lungs, lymph nodes
or other organs  body creates a reaction to the bacteria as You want to test if he has tuberculosis?
manifested by a (+) TST
 For TB infection
o TST (Tuberculin Skin Test)
o IGRA (gamma interferon release assay)
 For TB disease
o DSSM (direct sputum smear microscopy)
o Gene Xpert
o Culture and sensitivity

Mantoux Test
 Current standard for TST
 A skin test for tuberculosis infection
 0.1 ml of solution containing:
o 0.1 ug of 5 tuberculin units (5”TU”) of PPD-S
o or 2 TU of PPD-RT 23 with Tween 80
 IGRA  also a test to check for TB infection but instead of using a What is the difference between the 2 solutions?
tuberculin test, they use blood 5”TU” PPD-S  is readily available; this is the one that we are using
 Incubation period depends on the bacilli load and it usually ranges from in the clinical practice
7 days to 3 months 2 TU of PPD-RT 23  usually used by large organizations (e.g. WHO,
 So if you inhaled a M. tuberculosis, it can get into your lungs and it is DOH) for clinical or epidemiologic surveillance
where it will lodge into the adjacent lung tissues or lymph node (this is
what we called the primary complex). Later on, these TB bacilli may  Intradermal/intracutaneous
travel through hematogenous spread into the different organs or if the  Positive result read as INDURATION between 48 to 72 hours of
patient has a ↓ immune system (e.g. HIV patient), the TB bacilli may go injection
directly to the lungs as a progressive cavitary TB Remember that it is an INDURATION! It is NOT a wheal or redness
 In some individuals who are immunocompromised, 5-10% of infected Induration  raised portion (“Tambok”)
persons upon lodging of TB bacilli on the lungs directly goes into the
lung parenchyma

PRIMARY COMPLEX (GHON)

 The first “landing” or “encounter’ of TB bacilli on the lungs is what we
called Primary Complex (Ghon’s Complex). Common in children
 Initial lung lesion of primary TB (ghon focus)
 Composed of :
o Primary focus
o Lymphangitis Image Above: A positive tuberculin skin test (TST) =/> 10 mm induration
Site: Volar surface of the forearm
o Localized pleural effusion
o Regional lymphadenitis

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 INFECTIOUS DISEASES
Topic: Tuberculosis (Adults, Childhood and Infancy)
Lecturer: Dr. Sy, Celia

 10 mm induration is considered as positive generally Gene Xpert MTB/RIF Assay

 If your patient is immunocompromised (e.g. HIV patient or patient  Real time PCR based molecular test
taking corticosteroid for a long time)  5 mm induration is already  It can detect TB bacteria and rifampicin resistance in less than 2 hours
positive  More sensitive and specific than smear microscopy for detecting MTB
 If a patient is living in an endemic area to TB (e.g. Neighborhood or
Barangay has many cases of TB)  5 mm induration is already positive Recommended by WHO as replacement for conventional microscopy
(DSSM), culture and drug susceptibility testing as initial diagnostic test in
Interferon Gamma Release Assays (IGRA) both Adults and children with PTB and suspected at risk for drug
 Whole blood specimen resistance TB or have HIV-associated TB
 Measure person’s immune system reactivity to MTB
 Cellular immune response  In Gene Xpert, you also have a bonus exam which is RIF Assay  checks
 QuantiFERON TB Gold if the patient is resistant to Rifampicin. It has been shown in many
studies that if they are resistant to Rifampicin, the chances of him/her
 Recommended by WHO either IGRA or TST can be used to test for latent
TB infection (LTBI) being resistant to other anti-TB drugs is high
 It detects TB infection, NOT TB disease

TST
 2 visits required (minimum)
 Method: injection into skin
 Results affected by BCG
 Results in 48-72 hours
 Subjective results
 Can cause booster
phenomenon
 This test are sometimes free in
some institutions; Price for this
test is cheaper compared to
IGRA
IGRAs
 1 visit required
 Method: blood draw
 Results not affected by BCG
 Next-day results
 Objective results
 Does not cause booster
phenomenon
 Drawbacks: Not available in
most institutions; Price is higher
compared with TST (5k-6k pesos)

 MTB detected, RIF Resistance not detected (T)  treat with drug
sensitive or DS-TB regimen
Diagnostic Tests  MTB detected, RIF Resistance detected (RR)  can be high DR-TB risk
 If the patient is already coughing out blood and has positive exposure or low DR-TB risk
to TB, aside from doing TST or IGRA you can also do diagnostic tests o High DR-TB risk  do further testing and revise regimen
o Low DR-TB risk  repeat test and treat accordingly based on
Sputum (DSSM) the second result
 2 sputum specimens in 2 different days  MTB detected, RR Indeterminate (TI)  Collect new specimen and
o Get 1 specimen once the patient wakes up in the morning repeat test; treat accordingly based on the second result
 Minimum volume — 3 ml  Error/Invalid (I)  Collect new specimen and repeat test; treat
 Transport asap, if delayed more than 1 hr, must be stored and accordingly based on the second result
refrigerated
NOTE: If you see a letter “I”  automatic that you have to repeat the
If the patient is a child  since they do not know how to cough out testing
sputum (“dahak”) then you can do gastric aspiration
 MTB not detected (N)  if patient is coughing and is highly suspicious
Gastric Aspirate
of TB, reassess the patient
 Done in children who are usually admitted in the hospital
 5 ml to 10 ml
WHAT IS THE BEST DIAGNOSTIC TEST/PROCEDURE FOR TB?
 Collect it on 2 consecutive days  Chest x ray
 Patient should be on NPO first before doing the gastric aspirate  TST Answer: No single laboratory test should
 Ask the patient to lie down on the bed upon waking up and put an NGT  IGRA be used in diagnosing TB, it depends on
or OGT then get the aspirate of about 5-10 mL (for 2 consecutive days) the age of the patient, immunologic
 DSSM
 Gene Xpert status, and financial status

 Community that has only CXR machine  then use it as a test for TB
 Hospital has all the lab tests needed but patient has no money  use
TST because it is the least expensive
 2 important test to use: DSSM and Gene Xpert

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 INFECTIOUS DISEASES
Topic: Tuberculosis (Adults, Childhood and Infancy)
Lecturer: Dr. Sy, Celia

Lecture Discussion:
If you have a patient suspected of TB, Do a Gene Xpert and DSSM
 Gene Xpert – for diagnosis
 DSSM – for screening
 If these are (+)  patient is bacteriologically confirmed TB

If patient clinically has fever >2 weeks, coughed blood-streak sputum, weight
loss, (+) contact from household member with TB. CXR shows cavitary lesion
 If you did not do any of the tests but has the signs and symptoms of
TB  Clinically-diagnosed TB

TB Disease based on History of Previous Treatment

 A patient who has NEVER had treatment for TB or who
has taken anti-TB drugs for less than one (<1) month
New Case
 INH preventive therapy (IPT) is not considered as previous
TB treatment
 A patient who has been previously treated with anti-TB
Retreatment Case
drugs for at least one (1) month in the past
 If a patient presents at least one of the signs and symptoms for >2
weeks  it is a Presumptive TB case TB Disease based on HIV Status
o You collect a sputum sample for Gene Xpert (Smear or TB  HIV-negative
LAMP  alternative if Xpert not available) o Bacteriologically-confirmed or clinically-diagnosed case of TB
 If a patient has presents the symptoms but <2 weeks (e.g. 5 days cough) who has a negative results from HIV testing at the time of TB
 request for CXR if CXR is suggestive of TB  Presumptive TB case diagnosis
o If CXR is not suggestive of TB  check for other diseases  HIV-positive

CLASSIFICATION AND PRESUMPTIVE DIAGNOSIS OF TUBERCULOSIS TB Disease based on Drug Susceptibility Testing
 Anatomic Site
Mono-resistant TB  Resistance to one first-line anti-TB drug only
 Bacteriologic Status
 Resistance to more than one first-line anti-TB drug
 History of Previous Medication Polydrug-resistant TB
(other than Isoniazid and Rifampicin)
 Drug susceptibility testing Multidrug-resistant TB
 Resistance to at least both Isoniazid and Rifampicin
(MDRTB)
TB Disease based on Anatomic Site and Bacteriologic Status  Resistance to any fluoroquinolones and to at least one of
Extensively drug- three second-line injectable drugs (Capreomycin,
ANATOMIC SITE BACTERIOLOGIC STATUS DEFINITION OF TERMS resistant TB (XDR-TB) Kanamycin, and Amikacin), in addition to multidrug
 Smear-positive resistance
Bacteriologically-confirmed  Culture-positive  Resistance to Rifampicin detected using phenotypic or
Rifampicin-resistant
 Rapid diagnostic test-positive genotypic methods, with or without resistance to other
TB (RR-TB)
 Patient with 2 DSSM (-) with anti-TB drugs
CXR consistent with active TB
 Child with 2 DSSM (-) but  Studies have shown that if a person is RR-TB  most likely they are also
PTB fulfills 3 out of 5 criteria for
resistant to other anti-TB drugs
TB disease
Clinically-diagnosed  HIV/AIDS patient with 2
DSSM (-) regardless of CXR is TB CASE CLASSIFICATION/DEFINITION
decided by MD (attending
physician) or TBDC (TB
Disease Control Committee)
to have TB disease
 Patient with smear / culture/
rapid diagnostic test from a
Bacteriologically-confirmed biological specimen in an
extra-pulmonary site positive
for AFB or MTB complex
EPTB  Patient with histological
and/or clinical or radiological
evidence consistent with
Clinically-diagnosed
active EPTB and there is
decision by MD to treat
patient with anti-TB drugs

 Histologically-diagnosed EPTB through biopsy of appropriate site will be

considered clinically-diagnosed TB. Laryngeal TB, though likely to be
sputum smear (+), is considered an EPTB in the absence of lung infiltrate
on CXR

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 INFECTIOUS DISEASES
Topic: Tuberculosis (Adults, Childhood and Infancy)
Lecturer: Dr. Sy, Celia

CLINICAL DIAGNOSIS OF TB TREATMENT

 Presumptive diagnosis based on signs and symptoms Treatment Regimen for Tuberculosis
 Laboratory diagnosis  Standard Therapy – 6 months treatment
 Radiologic diagnosis o Intensive Phase
 Special considerations  To rapidly eliminate the majority of organisms and
 Diagnostic algorithm prevent emergence of drug resistance (hence the
greater number of drugs)
IDENTIFICATION OF PRESUMPTIVE TB  2 months
 HRZE
Patient 15 years old and above:
o Continuation Phase
 Cough of at LEAST 2 WEEKS duration with or without the ff:  To eradicate dormant organisms (fewer drugs used as
o Significant and unintentional weight loss risk of acquiring drug resistance is low as most have
o Fever been eradicated)
o Bloody sputum (hemoptysis)  4 months
o Chest/back pains not referable to any musculoskeletal  HR
disorders
o Easy fatigability or malaise
Basis for Treatment Regimen
o Shortness of breath or difficulty of breathing
1. Anti-TB treatment regimen shall be based from:
o Night sweats
o a. Anatomical site
 Unexplained cough of any duration in: o b. Bacteriologic status
o Close contact of a known active TB case o c. Drug resistance
o High risk clinical groups (HIV/AIDS, diabetes, ESRD, cancer, CT o d. History or prior treatment
disease, autoimmune disease, silicosis, postgastrectomy or 2. Treatment may be modified in special circumstances
solid organ transplantation, and on prolonged systemic
steroids)
Goals of Treatment
o High risk populations (e.g. elderly, urban poor, inmates and
 To cure the patient (by rapidly eliminating most bacteria)
other congregate settings)
 To prevent death from active TB
 To prevent relapse (by eliminating dormant bacteria)
Patient below 15 years old:
 To prevent drug resistance (by using a combination of drugs)
 At least 3 of the following clinical criteria:
 To decrease TB transmission
o Coughing/wheezing of 2 weeks or more, esp. unexplained
 To achieve minimal toxicity
o Unexplained fever of 2 weeks or more after causes such as
malaria or pneumonia is excluded
o Loss of weight/ failure to gain weight/ weight faltering/ loss of
appetite
o Failure to respond to 2 weeks of appropriate antibiotics for
LRTI
o Failure to regain previous state of health 2 weeks after a viral
infection (measles)
o Fatigue, reduced playfulness, or lethargy
 Any one of the above signs and symptoms (Clinical criteria) in a child
who is a close contact of a known active TB case

Chest X-ray suggestive of PTB

 Dosage for children are higher since there are more metabolizing
enzymes among children than adults leading to faster metabolism

Key Points
 The primary goal in the treatment of TB is to cure the patient
 Different drugs are used to treat a child with TB to effect cure and
prevent resistance
 Anti-TB treatment regimen shall be based on:
o Anatomic site, bacteriologic status, drug resistance, history of
prior treatment
 HRZE remain to be the mainstay in the treatment of a child with TB

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 INFECTIOUS DISEASES
Topic: Tuberculosis (Adults, Childhood and Infancy)
Lecturer: Dr. Sy, Celia
SPECIAL CONDITIONS
A. Pregnancy
 When a woman is pregnant, she can be given anti-TB drugs
 Ascertain whether or not a woman is pregnant before she starts TB
treatment
 Most anti-tuberculosis drugs are safe for pregnant women, except
Streptomycin, which is ototoxic to the fetus.
 Recommended standardized treatment regimen 2HRZE/4HR
 Pregnant women taking isoniazid should be given pyridoxine (Vitamin
B6) at 25 mg/day
o Some obstetricians say that it is better to give anti-TB drugs at
the 2nd trimester of pregnancy
 The risk of the baby being infected with TB is highest if a mother was
diagnosed of TB at the time of delivery or shortly thereafter
 Separation from mother not advised for resource-limited settings
 Mother should wear mask during infectious stage for 2 weeks
 In this case, it is very important that health workers should assess the
newborn at once
B. Baby born to a mother with PTB
 Isoniazid can be given to a newborn infant born to a mother with active
TB
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C. Breastfeeding
 A breastfeeding woman afflicted with TB should receive a full course of
TB treatment
 Timely and properly applied chemotherapy is the best way to prevent
transmission of tubercle bacilli to the baby.
 In lactating mothers on treatment, effects of such exposure on infants
have not been established.
 Most anti-tuberculosis drugs will be found in the breastmilk in
concentrations equal to only a small fraction of the therapeutic dose in
infants.
 It is recommended that lactating mothers feed their infants before
taking medications
 Supplemental Pyridoxine should be given at 5-10mg/day to the infant
who is taking INH or whose breastfeeding mother is taking INH
WHEN TO INTERRUPT TREATMENT IN PATIENT WITH LIVER DISEASE?
 SGPT/ALT level >3x the upper limit of normal + symptoms (nausea,
vomiting and abdominal pain) and or
 SGPT/ALT >5x the upper limit WITHOUT symptoms
 If it is not possible to perform liver function tests, it is advisable to wait
an extra 2 weeks after resolution of jaundice and upper abdominal
tenderness before restarting TB treatment
ADDITIONAL INFORMATION
If you have a patient on TB treatment, at what month do you have to check for
the progress of treatment? What is the diagnostic test will you request?
 After 2 months by the end of the patient’s treatment
 Request for DSSM only
o No Gene Xpert because it may still be positive for M.
tuberculosis due to presence of the dead bacteria
 If the patient is still (+) for TB (DS-TB case)  continue treatment
o At what month are you going to repeat the test? 5th month of
treatment
o If still it is (+) at the 5th month of treatment  treatment failed
It is hard to get sputum on pediatric patients and the parents do not allow
gastric aspiration. What will you do?
 Just go by clinical diagnosis
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