TUBERCULOSIS IN ADULT FILIPINOS

LIFTED FROM CLINICAL PRACTICE GUIDELINES

2016
IN THE GENERAL POPULATION, HOW IS PRESUMPTIVE PTB IDENTIFIED? 




QUESTION/ ISSUE 2016 CPG

Identifying Presumptive
PTB 

Cough of at least 2-weeks duration (Strong recommendation, low quality evidence)

Unexplained cough of any duration in a close contact of a known

Presumptive TB replaces active TB case (Strong recommendation, low quality evidence)
the term TB Symptomatic or
TB Suspect Chest x-ray findings suggestive of PTB, with or without
symptoms
(Strong recommendation, low quality evidence)
ANY of the following symptoms:

cough of any duration,

significant and unintentional weight loss,

fever,

bloody sputum or hemoptysis,

chest pains not referable to any musculoskeletal disorders,

easy fatigability or malaise,

night sweats,

shortness of breath or difficulty of breathing

(Weak recommendation, low quality evidence)

WHAT EXAMINATIONS SHOULD BE PERFORMED TO
BACTERIOLOGICALLY CONFIRM PTB? 


• smear microscopy,

• culture or

• WHO-approved rapid diagnostic test (WRD), such as Xpert®MTB/ Rif

WHEN SHOULD TB CULTURE BE REQUESTED? 


• TB culture remains the gold standard for TB diagnosis.

• TB culture should be performed preferably in quality assured culture centers

recommended by the National TB Program

• If culture-positive for Mycobacterium tuberculosis (MTB), case is bacteriologically-

confirmed PTB.
WHAT ARE THE INDICATIONS FOR PERFORMING SPUTUM TB
CULTURE WITH DRUG SUSCEPTIBILITY TESTING (DST)? 


should be performed for the following:

• Retreatment cases
• Treatment failure
• Contacts of known drug-resistant TB

Drug Susceptibility Test (DST) should not be routinely performed among new cases of PTB.
(Strong recommendation, high quality evidence)
WHEN SHOULD XPERT® MTB/RIF BE REQUESTED? 



HOW ACCURATE IS XPERT® MTB/RIF IN CONFIRMING PTB? 


Can be requested in the following clinical situations:

•As initial diagnostic test in adults with presumptive TB (Weak recommendation, high quality evidence) with
a pooled sensitivity of 89%, specificity 99%. (Strong recommendation, high quality evidence)

•As follow-on test to smear-negative patients with chest x-ray findings suggestive of
active PTB (Weak recommendation, high quality evidence) with a pooled sensitivity of 67%, specificity of
99%. (Strong recommendation, high quality evidence)
• As initial diagnostic test for presumptive drug-resistant TB (Strong recommendation, high quality
evidence), with a pooled sensitivity of 95% and specificity of 99% for rifampicin

resistance detection. (Strong recommendation, high quality evidence)

• In comparison with smear microscopy, Xpert® MTB/Rif increased TB detection

among culture-confirmed cases by 23% (Strong recommendation, high quality evidence).

• For smear-positive, culture-positive TB, Xpert ® MTB/Rif pooled sensitivity was

98% and specificity was not reported (all smear positive considered TB positive).
(Strong recommendation, high quality evidence).
WHAT ARE THE REQUIREMENTS FOR SPUTUM SPECIMENS FOR
XPERT® MTB/RIF? 

REVISED IMPLEMENTATION OF XPERT® MTB/RIF 



DOH – OCTOBER 2018

• National TB Control Program (NTP) and Philippine Strategic TB Elimination Plan

Phase I
• As of June 30, 2018, only 3,486 (38%) of the 9,137 drug-resistant TB patients
(DR-TB) have been notified to NTP.

• Key strategy: expand use of rapid TB diagnostic test

XPERT® MTB/RIF

• Shall now be the primary diagnostic tool for all presumptive TB in Regions III,
IV-A and NCR, in addition to presumptive drug-resistant TB
 FOR REGIONS III, IV-A AND NCR, THE PROGRAM
WOULD LIKE TO REITERATE THE FF:
1) For adults (>15y/old) a presumptive TB presents as any of the following:
• Cough of 2weeks duration with or without other signs/symptoms
• Cough of any duration among:
• Close contact of known TB case
• DM
• People living with HIV with any of the ff: cough of any duration, fever, weight loss
or night sweats
• Elderly (>60y/old)
• Persons deprived of liberty
• 2) for children (<15y/old) a presumptive TB presents as any of the following:
• With at least three (3) of the following:
• Coughing or wheezing of 2 weeks or more especially if unexplained
• Unexplained fever of 2 weeks or more after common causes such as malaria or pneumonia
have been excluded
• Loss of weight/failure to gain weight/ weight faltering/ loss of appetite
• Failure to respond to 2 weeks of appropriate antibiotic therapy for LRTI
• Failure to regain state of health 2 weeks after a viral infection or exanthem (e.g. measles)
• Fatigue, reduced playfulness or lethargy
• Any of the above who is a close contact of known active TB case
XPERT® MTB/RIF

• 3) CXR findings suggestive of TB, with or without symptoms, regardless of age

• 4) with signs/symptoms suggestive of extra-pulmonary TB

• Once a patient has been identified as presumptive TB, Xpert MTB/RIF test
shall be requested and performed without undergoing smear microscopy.
FOR OTHER REGIONS, THE INDICATION FOR
USE OF RAPID TB TEST SHALL BE THE FF:

• 1) as the primary diagnostic tool (replacing smear microscopy) among:

• Presumptive drug-resistant TB
• All retreatment cases (with history of TB treatment for > 1 month
• Contacts of drug-resistant TB
• Non-converter of Category I

• Presumptive drug-susceptible TB among the vulnerable groups

• Cough of any duration among:
• Persons deprived of liberty
• Elderly (>60y/old)
• DM
• People living with HIV with any of the ff: cough of any duration, fever, weight loss or night sweat
• for children (<15y/old) a presumptive TB presents as any of the following:
• With at least three (3) of the following:
• Coughing or wheezing of 2 weeks or more especially if unexplained
• Unexplained fever of 2 weeks or more after common causes such as malaria or pneumonia have
been excluded
• Loss of weight/failure to gain weight/ weight faltering/ loss of appetite
• Failure to respond to 2 weeks of appropriate antibiotic therapy for LRTI
• Failure to regain state of health 2 weeks after a viral infection or exanthem (e.g. measles)
• Fatigue, reduced playfulness or lethargy
• Any of the above who is a close contact of known active TB case
• Presumptive extrapulmonary TB specimen
• All patients with CXR finding suggestive of TB regardless of symptoms, age, co-
morbidity, and indication for CXR

Xpert® MTB/Rif
• Shall be requested and performed for all patients with CXR finding suggestive
of TB without undergoing smear microscopy, and for all new TB patients with
positive smear microscopy result.
• Regions CAR, I, II, MIMAROPA, V, VI, VII, VII, IX, X, XI, XII, XIII and ARMM.
TREATMENT
WHAT PRE-TREATMENT CLINICAL EVALUATION SHOULD BE DONE
TO PATIENTS WITH TB DISEASE? 


HISTORY AND PHYSICAL LIVER RISK FACTORS

EXAMINATION

• History should include past • chronic alcohol Baseline testing of visual

medical history consumption acuity (Snellen and color
• • perception charts) are advised
• (previous TB treatment, risk • viral hepatitis when ethambutol is to be
factors for hepatic, renal • used.
and ocular toxicity), • pre-existing liver diseases
• •
• Sexual history • exposure to hepatotoxic
• agents
• Personal and social history •
• • previous abnormal results
• Occupation of ALT/AST/bilirubin
•
• HIV infection (Strong recommendation, moderate quality
evidence)
WHAT BASELINE LABORATORY EXAMINATIONS SHOULD ROUTINELY
BE REQUESTED BEFORE STARTING ANTI-TB TREATMENT? 


• Serum alanine aminotransferase (ALT) and serum creatinine (Strong recommendation,

moderate quality evidence)

• All patients should be taught how to recognize symptoms of common adverse

effects and to consult if they develop such symptoms.

• All patients with TB with history of high-risk behavior for HIV and coming from
areas with high prevalence of HIV should be offered provider initiated counseling
and testing (PICT) for HIV. (Strong recommendation, moderate quality evidence)
HIV testing
•TB and HIV/AIDS display a lethal bidirectional interaction, with major epidemic
overlap
•The Philippines is one of the 22 high TB burden countries, with incidence of
290/100,000 in 2013
• In a cross- sectional study of 101 TB patients in PGH in 2012, 3 patients (3%)
tested positive for HIV. This is much higher than the 0.1% cutoff recommended
for universal screening of a population at risk, and very much higher than
the general population prevalence of 0.01%. This study provides data to
support universal HIV screening for TB patients in the Philippines

• TB is the most common opportunistic infection.

Screening for Diabetes Mellitus (DM)

•A systematic review showed that treatment outcomes differ between TB patients

with DM as compared to non-diabetics with greater relapse, treatment failure and
death among patients with both DM and TB (Baker, Harries, Jeon, Hart, & Kapur, 2011).

•Another study showed that patients with both DM and TB have higher
mycobacterial load compared to TB patients without DM (Alisjahbana, Sahiratmadja, Nelwan, Purwa, &
Ahmad, 2007).
• DM increases the risk of TB three-fold and poor glycemic control increases the
risk of poorer outcomes among those with TB

• higher risk for

relapse (RR=3.89, 95% CI 2.43 to 6.23)
death (RR=1.89, 95% CI 1.52 to 2.36)
treatment failure and death combined

• In 2011, WHO recommended that all patients with TB should be screened for DM.
Hyperuricemia
•not a significant side effect of PZA
•uric acid levels always return to normal after PZA is withdrawn (Combs, O’Brien, & Geiter, 1990).

•is common among patients on PZA and no intervention is required unless frank
gout has developed.
•Serum uric acid testing is not recommended.
REGISTRATION CATEGORIES OF TB CASES 


New no or less than 1 month of previous treatment for TB

Retreatment
 patient who has received 1 month or more of anti-TB drugs in the past
(excluding prophylaxis or treatment for latent TB infection

Relapse patient has previously been declared cured or treatment completed at the

end of most recent course of treatment, and is now diagnosed with
bacteriologically confirmed or clinically diagnosed TB
Treatment after lost to patient has previously been declared lost to follow-up after
follow-up (TALF) interruption of at least 2 consecutive months at the end of
most recent course of treatment and is now bacteriologically
confirmed or clinically diagnosed TB (previously known as
Return After Default)

Treatment after Failure patient has previously been treated for TB and has been
declared failed at the end of most recent course of treatment

Previous Treatment patient has previously been treated for TB but outcome after
Outcome Unknown (PTOU) their most recent course of treatment is unknown or
undocumented

Other patients who do not fit in any of the above categories

WHAT IS THE EFFECTIVE TREATMENT REGIMEN FOR NEW PTB
CASES? 


intensive phase continuation phase

2 months 4 months Category I (2HRZE/4HR)

regardless of bacteriologic
isoniazid, rifampicin, isoniazid and rifampicin status. (Strong recommendation, high
quality evidence
pyrazinamide, and (4HR)
ethambutol (2HRZE)

• For the six-month treatment duration to be maximally effective, the regimen must
include PZA during the two-month intensive phase and RIF must be included
throughout the six months.
WHEN IS A PATIENT ON TB TREATMENT CONSIDERED NON-
INFECTIOUS? 


• Patients who are bacteriologically-confirmed and do not have risk factors for
drug-resistance are considered non-infectious when they have received at least
14 daily doses of treatment with sputum conversion and clinical improvement.
(Strong recommendation, high quality evidence)

• Patients who are clinically diagnosed and do not have risk factors for drug-
resistance are considered non-infectious when they have received at least 5
daily doses of treatment with clinical improvement. (Strong recommendation, high quality evidence)
HOW SHOULD PTB PATIENTS WHO HAVE INTERRUPTED
TREATMENT BE MANAGED? 


• Patients who fail to

follow-up as
scheduled should
be immediately
traced through:
telephone call, text
message or home/
workplace visit.
HOW SHOULD RETREATMENT CASES BE MANAGED? 


• Category II regimen (2HRZES/1HRZE/5HRE) should only be given among confirmed

Rifampicin-sensitive retreatment cases or in circumstances where Xpert® MTB/Rif
services cannot be performed (i.e. no access or no sputum specimen). (Strong recommendation,
moderate quality evidence)

• All retreatment cases should immediately be referred to the nearest Xpert® MTB/Rif
facility for rifampicin susceptibility testing.
(Strong recommendation, high quality evidence)

• Rifampicin-resistant cases should immediately be referred to a PMDT facility for further

management
HOW SHOULD WE MONITOR TREATMENT RESPONSE? 


• Clinically diagnosed and bacteriologically-confirmed cases treated with first-line

drugs:
• DO at least one sputum smear microscopy at the end of the intensive phase of
treatment (end of 2 months for new cases and end of 3 months for retreatment
cases)
Clinically diagnosed whose sputum smears are no further sputum monitoring
cases negative at end of intensive
phase
New patients - if specimen obtained at the end repeat DSSM at the end of the
of 2 months is smear-positive, third month.

New and Retreatment If specimen obtained at the end do Xpert®MTB/Rif,

patients of third month is still smear- sputum culture and drug
positive susceptibility test (DST)
• Patients found to be harboring a drug-resistant strain at any point during treatment
should be referred to a PMDT (Programmatic Management of Drug-resistant TB)
center.

• All PTB and EPTB patients should also be monitored clinically. Body weight is a
useful progress indicator that should be monitored and medication doses adjusted
according to weight (Strong recommendation, low quality evidence)
• Rapid diagnostic tests (such as Interferon Gamma Release Assay, Xpert® MTB/
Rif, Antiphopholipid Antibody tests) are NOT recommended for monitoring
treatment response pending further studies. (Strong recommendation, low quality evidence)

• CXR is NOT a substitute for microbiological monitoring. It may be used in

monitoring complications, identifying co-existing conditions. (Strong recommendation, low
quality evidence)
ADVERSE EFFECT OF ANTI-TB DRUGS

• Drug-induced hepatitis is the most serious and common adverse effect.

• Isoniazid
• Pyrazinamide
• Rifampicin - can cause asymptomatic jaundice without evidence of hepatitis.

most common adverse effects most common systemic manifestation

pruritus and exanthem (54.4%) transaminitis (10.5%)

nausea and/or vomiting (24.1%) jaundice (9.6%)

hepatitis (9.7%) nausea, vomiting and other abdominal

symptoms (14% )
headache (8.3%)
 WHAT ARE THE COMMON ADVERSE REACTIONS TO ANTI-TB
DRUGS? 

MINOR Adverse Reactions
Gastrointestinal intolerance
Mild or localized skin reactions
Orange/red-colored urine
Pain at the injection site
Burning sensation in the feet due to peripheral
neuropathy
Arthralgia due to hyperuricemia
Flu-like symptoms (fever, muscle pains,
inflammation of the respiratory tract)
MAJOR Adverse Reactions
Severe skin rash due to hypersensitivity
Jaundice due to hepatitis
Impairment of visual acuity and color vision due
to optic neuritis
Hearing impairment, ringing of the ears, dizziness
due to damage of the eighth cranial nerve
Oliguria or albuminuria due to renal disorder
Psychosis and convulsion
Thrombocytopenia, anemia, shock
HOW SHOULD THE MOST COMMON ADVERSE REACTIONS DUE TO
ANTI-TB DRUGS (HRZES) BE MONITORED AND MANAGED? 


• General principles in the management of adverse reactions due to anti-TB drugs

are as follows:
• Minor adverse reactions can be managed with symptomatic therapy. First-line
drugs should not be stopped without adequate justification.

• Major adverse reactions, all drugs must be discontinued. Switching to single

drug formulations may be needed. Referral to a specialist is warranted
HOW SHOULD DRUG-INDUCED HEPATOTOXICITY BE MONITORED
AND MANAGED? 


• Routine liver function monitoring is NOT needed among asymptomatic patients.

(Strong recommendation, moderate quality evidence)

(Strong recommendation, moderate quality evidence)

Serum ALT (SGPT) should only be
requested for:

(1) individuals who exhibit symptoms of hepatotoxicity

such as jaundice, anorexia, nausea, vomiting, or abdominal pain
(2) monitoring of patients with baseline risk factors for hepatotoxicity or
abnormal baseline LFTs (2-4 weeks after the start of anti-TB medications).
• Hepatotoxicity: serum ALT level >3x the upper limit of normal in the presence of
symptoms, or >5x the upper limit of normal in the absence of symptoms. ALL
medications should be stopped immediately. (Strong recommendation, moderate quality evidence)
• After normalization of ALT to less than twice the ULN and resolution of clinical
symptoms, step-wise reintroduction of potentially hepatotoxic anti-TB drugs
may be started with Rifampicin (with or without Ethambutol), followed by INH
after 3 to 7 days, subsequently rechecking transaminases.

• Pyrazinamide should be permanently discontinued in patients who have

experienced prolonged or severe hepatotoxicity. (Strong recommendation, low quality evidence)
MANAGEMENT OF HEPATOTOXICITY AND ALTERNATIVE REGIMENS 


The WHO (2010) recommends shifting of implicated medication

Rifampicin alternative regimen of 2HES/10HE
Isoniazid regimen can be shifted to 6 to 9 months of RZE
Pyrazinamide extend HR for 9 months total duration
(if discontinued before
completion of intensive
phase)

If there are no single-drug formulations (SDFs), replace

pyrazinamide with streptomycin during the intensive phase;

during continuation phase, restart HR to complete 4 months

DIAGNOSIS AND TREATMENT OF DRUG-RESISTANT
TUBERCULOSIS IN ADULT FILIPINOS 


Drug-resistant resistance of the TB bacilli to one or more anti-TB

tuberculosis (DR-TB) drugs based on drug susceptibility test (DST) results.

Mono-resistant TB resistance to one first-line anti-TB drug only

Polydrug-resistant TB resistance to more than one first-line anti-TB drug,

other than both Isoniazid and Rifampicin

Multidrug-resistant TB resistance to at least both

(MDR-TB) Isoniazid and Rifampicin
Extensively drug-resistant multidrug-resistant TB plus
TB resistance to any fluoroquinolone and at least one of
(XDR-TB) three second- line injectable drugs
(Capreomycin, Kanamycin and Amikacin)

Rifampicin-resistant TB resistance to Rifampicin detected using Xpert® MTB/Rif

(RR-TB) test or conventional DST, with or without resistance to
other anti-TB drugs.

It includes any resistance to Rifampicin, whether mono-

resistance, multidrug resistance, polydrug
resistance or extensive drug resistance
For questions and clarifications, you
may consult the guideline itself.
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