Case discussion

Pulmonary tuberculosis

• Etiologic agent: Myocobacterium Tuberculosis

• Rod-shaped, non-spore forming, thin, aerobic bacterium
measuring 0.5um by 3um

• Mode of transmission: Airborne spread of droplet nuclei

produced by patients with infectious pulmonary tuberculosis,
which are aerosolized by coughing, sneezing or speaking.
 Pathogenesis

• Inhaled droplet -> alveoli -> phagocytosis -> bacterial cell

wall + macrophage cell surface molecule -> post-
phagocytic events -> phagosome forms -> generated by:
Bacterial cell wall lipoglycan lipoarabinomannan
(ManLam) -> arrest in phagosome maturation ->:
replication begins and macrophages ruptures -> release
of bacillary contents
 Clinical manifestation

•Classified as:
•Pulmonary
•extrapulmonary
 Clinical manifestation

Pulmonary TB
1. Primary
2. Secondary (Post-primary, adult type)
 Clinical manifestation

Primary TB
- Asymptomatic
- Fever
- Pleuritic chest pain
- Ghon focus
 Clinical manifestation

Secondary TB
- Diurnal fever
- Night sweats
- Weight loss
- Anorexia
- General body malaise
- Weakness
- hemoptysis
DIAGNOSIS OF TUBERCULOSIS
IN ADULT FILIPINOS
Based on clinical practice guidelines for PTB 2016
 Diagnosis of Tuberculosis in adult Filipinos

For patients 15 years old and above, a presumptive TB has any of the following:

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

- Unexplained cough of any duration in a close contact of a known active TB case (Strong recommendation, low
quality evidence)

- 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)
 Diagnosis of Tuberculosis in adult Filipinos

Bacteriologic confirmation of PTB:

- SMEAR POSITIVE:
A patient with at least one (1) sputum specimen positive for AFB, with or
without radiologic abnormalities consistent with active TB
- CULTURE POSITIVE:
- A patient with positive sputum culture for MTB complex, with or without
radiographic abnormalities consistent with active TB
- RAPID DIAGNOSTIC TEST POSITIVE
- A patient with sputum positive for MTB complex using rapid diagnostic
modalities such as Xpert® MTB/Rif, with or without radiographic
abnormalities consistent with active TB
 Diagnosis of Tuberculosis in adult Filipinos

Clinical diagnosis

- A patient with 2 sputum specimens negative for AFB or MTB, smear

not done due to specified conditions but with radiographic
abnormalities consistent with active TB, and there has been no
response to empiric antibiotics and/or symptomatic medications, and
who has been decided to have TB disease requiring full course of anti-
TB chemotherapy
TREATMENT OF PULMONARY AND EXTRA-
PULMONARY TUBERCULOSIS IN ADULTS
Based on the Clinical Practice Guidelines of 2016
Treatment of Pulmonary and
Extra-Pulmonary Tuberculosis in Adults
It is crucial to understand that once treatment is initiated for TB,
whether bacteriologically confirmed or clinically diagnosed, clinicians
assume a public health responsibility both to the individual patient and
to the community at large. Evaluation of TB patients before and during
treatment should not only be clinical, it should also involve assessment
of risk factors leading to disruption of treatment.
Pre-Treatment Evaluation
1. What pre-treatment clinical evaluation should be done to patients
with TB disease?

Thorough history and physical examination should be done on all patients with TB disease. History
should include past medical history (previous TB treatment, risk factors for hepatic, renal and ocular toxicity),
sexual history, personal and social history, and occupation.

The liver risk factors that should be identified include chronic alcohol consumption, viral hepatitis, pre-
existing liver diseases, exposure to hepatotoxic agents, previous abnormal results of ALT/AST/bilirubin and HIV
infection.

Baseline testing of visual acuity using Snellen and color perception charts are advised when
ethambutol is to be used.
Pre-Treatment Evaluation
2. What baseline laboratory examinations should routinely be
requested before starting anti-TB treatment?
Baseline testing for serum alanine aminotransferase (ALT) and
serum creatinine are recommended before starting anti-TB treatment.
In resource-limited settings, baseline ALT and serum creatinine,
at the least, should be requested for patients older than 60
years old, and those with risk factors for liver or kidney disease
before starting TB treatment.
Pre-Treatment Evaluation
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.
Screening for diabetes mellitus using Fasting Blood Sugar (FBS),
Random Blood Sugar (RBS), or 75g Oral Glucose Tolerance Test (OGTT) is
recommended for all patients with TB.
What is the effective treatment regimen for new PTB
cases?

The effective treatment regimen for new PTB cases (without risk
factors for drug resistance) is 2 months of Isoniazid, Rifampicin,
Pyrazinamide, and Ethambutol (2HRZE) as intensive phase followed by 4
months of Isoniazid and Rifampicin (4HR) as continuation phase or
Category I (2HRZE/4HR) regardless of bacteriologic status.
DRUG TARGET MECHANISM OF ACTION MECHANISM OF
RESISTANCE
Isoniazid (H) Cell wall Inhibits mycolic acid Mutations in KAtG gene
synthesis. producing catalase
peroxidase enzyme
needed for its activation
Mutation in inhA gene that
binds with activated INH to
inhibit mycolic acid
Rifampicin (R) Nucleic acid Inhibits transcription by Mutation in rpoB gene
interfering with preventing its interaction
DNAdependent with Rifampicin
RNA polymerase
Pyrazinamide (Z) Intracellular Targets essential Mutations in pncA gene
membrane transport, in
fatty acid synthesis
Ethambutol (E) Cell wall Affects lipid and cell Mutation of embCAB
wall metabolism operon
Inhibits RNA synthesis
Streptomycin (S) Ribosome Inhibits translation during Mutations of ribosomes
protein synthesis target binding site.
CATEGORY CLASSIFICATION INITIAL PHASE CONTINUATION PHASE
Treatment Categories
I • New PTB ( bacteriologically confirmed or 2 HRZE 4HR
clinically diagnosed)
• New EPTB ( bacteriologically confirmed or
clinically diagnosed), except CNS and
Bones or joints

Ia • New EPTB (CNS/bones or joints) 2HRZE 10HR

II • Previously treated drug susceptible PTB or 2HRZES and 1HRZE 5HRE
EPTB ( bacteriologically confirmed or
clinically diagnosed) ), except CNS and
Bones or joints.
 Relapse
 Treatment after failure
 Treatment after lost to follow up
 Previous treatment outcome unknown

IIa • Previously treated, drug susceptible EPTB 2HRZES and 1HRZE 9HRE
in CNS/bones or joints ( bacteriologically
confirmed or clinically diagnosed)
Drug-Resistant TB
• Standard Regimen Drug-Resistant (SRDR): Rifampicin-resistant TB or
multi-drug resistant TB
• XDR TB Regimen: Extensively Drug-Resistant TB
Treatment:
Individualized based on previous treatment courses and
sensitivity testing.
OUTCOME DEFINITION

CURED • Bacteriologically – confirmed TB patient(sputum-positive at the beginning of treatment)

and is smear- (or culture-) negative in the last month of treatment and on at least1
previous occasion in the continuation phase
TREATMENT COMPLETED • A patient completes treatment, but does not meet the criteria of “cured” or “failure” –
includes:
 Bacteriologically confirmed patient who completed treatment but without DSSM follow
up in the last month pf treatment & on at least one previous occasion.
 Clinically diagnosed patient who has completed treatment.
TREATMENT FAILED • For bacteriologically confirmed TB: patient who is sputum smear positive at five months
or later during the treatment, or
• For clinically diagnosed TB: patient for whom sputum examination cannot be done& who
does not show clinical improvement during treatment.
TREATMENT SUCCESS • Sum of “cured’ and “treatment completed”

DIED • Patient who dies for any reason during the course of the treatment.

LOST TO FOLLOW-UP • Patient whose treatment was interrupted for > 2 consecutive months
THANK YOU!