Tuberculosis in the Philippines

Tuberculosis is the third leading cause of death in the Philippines, and it is the sixth leading cause
of morbidity (1). At any one time approximately 450,000 Filipinos have active tuberculosis infection. The
disease kills 36,000 Filipinos each year (2).

Tuberculosis in the Philippines

Total population of the Philippines2 90 million

# active tuberculosis cases, 20072 440,000

# deaths due to tuberculosis in one year2 36,000

% of new TB cases that are multi-drug resistant in 20072 4%

% of new TB patients in Western Pacific region who are

7%
HIV+3

% of previously treated cases that are multi-drug

21%
resistant2

TB case detection rate in 20074 75%

Directly observed treatment, short course (DOTS)

88%
success rate in 20074

# of people to whom an infected person spreads TB in

10-15 people
one year5

Multi-drug resistance is resistance to the first-line drugs isoniazid, rifampin, pyrazinamide, and
ethambutol.

Health and Nutrition in the Philippines6

Children receiving Vitamin A supplementation 86%

Houses consuming iodized salt 45%

Urban dwellers consuming improved drinking water 96%

Under-fives underweight, moderate or severe

28%
(WHO)

Under-fives wasted, moderate or severe (WHO) 6%

Under-fives stunted, moderate or severe (WHO) 34%

Children receiving BCG vaccine 93%

Underweight means a child’s weight-for-age is less than two standard deviations below the median
weight-for-age of the reference population. Wasted means a child’s weight-for-height is less than two
standard deviations below the mean weight-for-height of the reference population (6).
Figure: Number of TB cases per 100,000 population

Outcomes of untreated pulmonary tuberculosis9

Spontaneous resolution by body’s immune system 30%

Death within 2 years 50%

Continued contagiousness and eventual death many years

20%
later

Testing for TB

Sputum smear microscopy is the primary method used to diagnose active tuberculosis in the
Philippines and other parts of the developing world. A patient coughs up one or more sputum samples
from the lungs, and using staining or a fluorescent dye, the discovery of acid-fast bacteria in at least one
sample indicates active tuberculosis infection (7). However, MSF reports that in its field work sputum
smear microscopy “is not a very sensitive test and detects less than half of all active TB cases. In
addition, people with extra-pulmonary TB (infection outside the lungs) and children go undetected by
this method” (8). According to the WHO, sputum smear microscopy detects 66% of positive cases using
one sample. On the other hand, the WHO reports that the most contagious patients, those with cavitary
pulmonary TB, will be smear positive (9).

Pulmonary TB detection11

% of cases detected with % of cases detected with

# of samples
sputum smear microscopy bacterial culture

1 66% 93%

2 76% 97%
 3 84% 99%

4 85% 100%

Further testing for pulmonary TB involves cell culture. Cell culture is slow: mycobacterial colonies
are only visible after 3 weeks of culture. Chest x-rays are not used for diagnosis, but they reveal
abnormalities in the lungs (which could be due to pneumonia, lung abscesses, carcinoma, sarcoidosis
(inflammation of any organ), pneumoconiosis (lung disease due to inhalation of coal, graphite, or man-
made carbon)) and can be used to rule out TB in the case of a negative sputum smear.

the Organism: Mycobacterium tuberculosis

Mycobacteria are aerobic bacteria with waxy cell walls made of mycolic acid. Because of the cell
wall, mycobacteria are resistant to drying, to strong acids, and to strongly basic salts (alkalis) (5).
However, mycobacteria are quickly destroyed by UV light (9). Mycobacteria grow slowly: 8-24 hours
lapse between the birth of a mycobacterial cell and its division (average 20 hour doubling time).
Detecting mycobacterial growth using fluid media and an automated detection system requires 1-2
weeks (5).

BCG vaccine

99% of Filipino children are vaccinated with BCG.

The World Health Organization launched the Expanded Program on Immunization in the
Philippines in 1979. In this program, children received oral polio, diptheria-pertussis-tetanus, BCG,
Hepatitis B, and measles vaccines. However, BCG does not prevent primary tuberculosis infection. It is
intended to prevent disseminated infection, but studies show its efficacy ranges from 0 to 80%. BCG
does not prevent reactivation of latent TB (5). Revaccination with BCG confers no protection.

Spread of TB

A person infected with TB spreads the disease to an average of 10-15 persons per year. A person
becomes infected by inhalation of aerosol mycobacteria (<10 microns in diameter) (5).

Onset of TB

Bacteria are phagocytosed by alveolar macrophages in the lung, where the bacteria replicate
inside macrophage vacuoles at primary loci. Immune cells arrive at the site of infection and release
cytokines that recruit and activate monocytes to form follicles around the infected cells. Two kinds of
follicles form: those with and those without “central caseating necrosis.”

Follicles without central caseating necrosis:

Monocytes fuse to form giant cells due to cytokines released by lymphocytes recruited to the infection.
Lymphocytes encase the giant cell follicles. This follicle can become entirely calcified over time.

Follicles with central caseating necrosis:

On the other hand, monocytes can form a granuloma, or a follicle inside which bacteria grow slowly and
ultimately die. The granuloma contains dead macrophages and bacteria (scar tissue) as well as 1000-
10,000 bacteria that grow and divide more and more slowly in a process known as caseating (“cheese-
like”) necrosis. Bacteria can survive for years in granulomas in the lungs, lymph nodes, bones, liver, and
kidneys; however, these caseating areas usually fibrose and calcify on their own. Resolution of primary
infection by the body’s immune system is primarily achieved by CD4 and CD8 T-cells, or cell-mediated
immunity. Humoral immunity (antibodies) is not as effective because antibodies cannot penetrate the
encased granuloma (9).

If the bacteria do not die but remain limited to isolated follicles, a person has latent tuberculosis.
Latent tuberculosis can be reactivated years later if a person becomes immunocompromised, for
example if he/she becomes infected with HIV (9).

If the tuberculosis is not treated and the bacteria are not contained within isolated granuloma(s)
by the immune system, a person develops active tuberculosis.

Risk factors for developing active tuberculosis infection10

Overcrowded housing Stress

Poorly ventilated housing Diabetes

Immunodeficiency (such as HIV infection)* Head and neck cancer

Silicosis
Immunosuppressant drugs
(inhalation of silica crystals in the workplace, causing
(corticosteroids, TNF inhibitors)
lung abrasion)

Renal insufficiency Adolescence

Weight loss Age >70 years

Malnutrition

*The lifetime risk of active tuberculosis in an HIV-positive person is 50%, whereas the lifetime risk of
active tuberculosis in an HIV-negative person is 5%.

Anti-tuberculosis drugs

Four first line drugs: isoniazid, rifampin, pyrazinamide, ethambutol

1. Isoniazid (INH)

Isoniazid Summary: Isoniazid is bactericidal. It is administered as a

prodrug that is coupled to NADH by the KatG enzyme. INH-NAD is a
competitive inhibitor of the fatty acid synthase, thereby blocking mycolic
acid production. Isoniazid is metabolized in the liver by acetylation. Most
Asians are slow acetylators, meaning the drug has a 1-2 hour ½ life and
they excrete 10% in the urine. The drug is safe in pregnant women,
although breast milk can contain 5-20% of a child’s dose of isoniazid.
Isoniazid competes with pyridoxine (vitamin B6), a coenzyme in
2. Rifampin

Rifampin Summary: Rifampin is bactericidal. It inhibits the DNA-primed

RNA polymerase in mycobacteria, and therefore acts at an early stage of
replication. It is active against rapidly dividing bacteria as well as semi-
dormant bacteria. Rifampin is lipophilic; it can cross the blood-brain barrier
and reach tuberculosis meningitis (5,13).
3. Pyrazinamide

Pyrazinamide Summary: Pyrazinamidase converts pyrazinamide to

pyrazinoic acid, and the specific drug action is unknown beyond that it is
bacteriostatic. Pyrazinamide is active at low pH in macrophages and is most
active against dormant bacteria. Pyrazinamide increases and quickens the
effects of isoniazid and rifampin (14).
4. Ethambutol

Ethambutol Summary: Ethambutol inhibits arabinosyl transferase, a

polymerizing enzyme for the mycobacterial cell wall (15).