Tuberculosis

PGI: Mikhail Jude L. Opay

Tuberculosis
 is caused by a bacteria (Mycobacterium
tuberculosis) that most often affect the lungs.
Tuberculosis is curable and preventable
 spread from person to person through the air
 one-quarter of the world's population has latent
TB, which means people have been infected by
TB bacteria but are not (yet) ill with the disease
and cannot transmit the disease.
 People infected with TB bacteria have a 5–15%
lifetime risk of falling ill with TB
 persons with compromised immune systems,
such as people living with HIV, malnutrition or
diabetes, or people who use tobacco, have a much
higher risk of falling ill.
 symptoms (such as cough, fever, night sweats, or
weight loss) may be mild for many months.
 Without proper treatment, 45% of HIV-negative
people with TB on average
 nearly all HIV-positive people with TB will die.
Global impact of TB
 the largest number of new TB cases occurred in
Asia, with 45% of new cases, followed by Africa,
with 25% of new cases
 The Philippines is one of the top seven countries
with the highest number of new TB cases for the
year 2016
Diagnosis
 symptoms active lung TB
 cough with sputum and blood
 chest pains
 Weakness
 weight loss
 Fever
 night sweats
Diagnosis
 Direct sputum smear
 TB culture
 Xpert
Diagnosis
 Presumptive TB
 Bacteriologically confirmed case of TB
 Clinically diagnosed case of TB
Presumptive TB
 Cough of at least 2-weeks duration
 Unexplained cough of any duration in a close
contact of a known active TB case
 Chest x-ray findings suggestive of PTB, with or
without symptoms
 Cough, weight loss, fever, body malaise,
hemoptysis, chest pain, night sweats, SOB, DOB
Bacteriologically Confirmed TB
 positive by smear microscopy, culture or
WHO-approved rapid diagnostic test (WRD),
such as Xpert®MTB/Rif
Clinically Diagnosed TB
 Patients with 2 sputum specimens negative for
AFB or MTB, smear not done due to specified
conditions
 Radiographic abnormalities
 No response to empiric antibiotics or
symptomatic medications
Xpert
 As initial diagnostic test in adults with
presumptive TB
 As follow-on test to smear-negative patients with
chest x-ray findings suggestive of active PTB
 As initial diagnostic test for presumptive drug-
resistant TB
Smear Negative
 chest x-ray should be performed for all smear-
negative presumptive PTB
 If available, Xpert® MTB/Rif should be
requested among smearnegative presumptive TB
cases with radiologic fndings suggestive of
PTB
Treatment
 New Case
 Retreatment Case
 Relapse
 Treatment after failure
 Treatment after lost to follow-up (TALF)
 Previous Treatment Outcome Unknown
(PTOU)
 Other
Pre treatment evaluation
 liver risk factors
 Baseline testing of visual acuity using Snellen and
color perception charts
 Serum Creatinine
 Screening for DM
Treatment
Treatment
 Category 1
 Intensive phase – 2 months HRZE
 Continuation phase - 4 months HR
 Category 2
 Refer for Xpert
 for rifampicin sensitive
 2HRZES/1HRZE/5HRE
Monitoring Treatment Response
 DO at least one sputum smear microscopy at
the end of the intensive phase of treatment
 New patients - if the specimen obtained at the
end of 2 months is smear-positive, repeat DSSM
at the end of the third month
 New and Retreatment patients - if the specimen obtained at
the end of third month is still smear-positive, do
Xpert®MTB/Rif, sputum culture and DST
 Clinically diagnosed cases whose sputum smears are negative
at end of intensive phase need no further sputum
monitoring.
 Patients found to be harboring a drug-resistant strain at any
point during treatment should be referred to a PMDT
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
Non-infectious
 Bacteriologically confirmed, no risk factors for
drug resistance – 14 daily doses
 Clinically diagnosed – 5 daily doses with clinical
improvement
Drug resistance
 Drug-resistant tuberculosis (DR-TB) – resistance
of the TB bacilli to one or more anti-TB drugs
based on drug susceptibility test (DST) results.
 Mono-resistant TB
 Polydrug-resistant TB
 Multidrug-resistant TB (MDR-TB)
 Extensively drug-resistant TB (XDR-TB)
 Rifampicin-resistant TB (RR-TB)
Suspect for DRTB
 All retreatment cases
 Contacts of confirmed DR-TB cases
 People living with HIV (PLHIV)
Diagnosis
 Drug Susceptibility test
 Genotypic DST, endorsed by WHO
° Xpert® MTB/Rif
 Treatment
 Shorter MDR-TB treatment regimen
 Longer MDR-TB treatment regimen
 Drug Target Mode of action Adverse reactions
Fluoroquinolones Protein synthesis Inhibits bacterial DNA QT prolongation
topoisomerase 4 subunit
A, DNA topoisomerase2-
a and DNA gyrase
Aminoglycosides Protein syntheis Inhibits 30s ribosomal Hearing loss,
protein and 16s rRNA nephrotoxicity, skin rash,
hypersensitivity,
peripheral neuropathy

Ethionamide Cell wall Inhibits enoyl reductase GI disturbances,

hypothyroidism
Cycloserine Cell wall Alanine ligase and alanine Neuropsychiatric effects
racemose
Linezolid Protein synthesis Targets bacterial 23S Lactic acidosis,
ribosomal RNA of the thrombocytopenia,
50s subunit anemia, optic neuropathy
Clofazamine DNA synthesis Prevents completion of QT prolongation, skin
cell cycle discoloration

Delamanid Cell wall Inhibits wall components, QT prolongation, GI

methoxy mycolic acid disturbances
and ketomycolic acid
 Drug Target Mode of action Adverse reactions

Bedaquilline Cell energy Blocks the proton pump QT prolongation,

for ATP synthase of Hepatotoxicity
mycobacteria
PAS Folic acid synthesis generates a hydroxyl GI disturbances,
dihydrofolate hypothyroidism
antimetabolite, which in
turn inhibits
dihydrofolate reductase
(DHFR) enzymatic
activity
Carbapenems Cell wall Inhibits penicillin SJS, GI disturbances
bindings proteins
B-lactam/b-lactamase Cell wall Inhibits penicillinase, GI disturbances,
inhibitor inhibits penicillin-binding hypersensitivity
protein 1A
Thioacetazone Cell wall remains unknown, SJS, GI disturbances
although it is thought to
interfere with mycolic
acid synthesis.
Shorter MDR-TB regimen
 Patients with RR-TB or MDR-TB who are not
previous treatment with second line drugs
 Resistance to fluoroquinolones and second line
injectable agents were excluded or is considered
highly unlikely
Shorter MDR-TB regimen
 Intensive phase of 4 months(extended up to a maximum
of six months in case of lack of conversion)
 Drugs included:
 Gatifloxacin(or moxifloxacin)
 Kanamycin
 Prothionamide
 Clofamizine
 High dose isoniazide
 Pyrazinamide
 ethambutol
Shorter MDR-TB regimen
 Continuation phase of 5 to 6 months
 Drugs included:
 Gatifloxacin(moxifloxacin)
 Clofazimine
 Pyrazinamide
 ethambutol
Subgroup considerations
 Rifampicin-resistant TB without MDR-TB – may
be treated with the shorter MDR-TB regimen
 Resistance additional to MDR-TB – it is
recommended not to use the shorter regimen
Longer Treatment regimen
 A regimen with at least five effective TB medications
during the intensive phase is recommended
 Pyrazinamide
 Four core second line TB medicines
 one group A
 One group b
 Two group c
 If the minimum number of medicines cannot be
composed, an agent from group D2 and D3 to bring
the total to 5
 Pyrazinamide is added routinely unless there is
confirmed resistance
 Other agents from Group d1 are included if they
are considered to add benefit
Effect of delay in starting treatment
 Increased disease progression
 Higher bacillary load in sputum
 More lung damage
 Continued transmission

 Adequate treatment regimen within four weeks

of diagnosis was associated with positive
outcome
Prevention and Control
 observance of proper cough etiquette
 Surgical face masks should be used among
patients presumed or confirmed to have
infectious PTB until they are deemed non-
infectious
 There is no evidence that the use of 2 or more
surgical face masks in layers provide additional
protection
 Exposed health care workers should use fIltering
face-piece respirator masks (i.e., N95 or FFP2)
when performing procedures with high risk of
aerosolization
 Surgical masks do not offer signifIcant protection
on personnel performing aerosol-producing
procedure
 Household contacts of active TB cases are at
increased risk of infection and disease, contacts
should be screened for disease activity according
to CPG recommendations
References
 Clinical Practice Guidelines For The Diagnosis,
Treatment, Prevention and Control of
Tuberculosis in Adult Filipinos 2016 update
 WHO treatment guidelines for drug resistant
tuberculosis 2016
THANK YOU