Directly Observed Therapy for Tuberculosis In Filipino Patients:

Preliminary Experience With a Largely Twice-Weekly Intermittent

Treatment Regimen*
Rodrigo L. C. Romulo, M.D., Maribeth Villena, R.N. and Angelic S. Mesina, R.N.

(*Tuberculosis Clinic, Santo Tomas University Hospital, Manila, Philippines)

ABSTRACT

In order to determine the feasibility of performing clinic-based directly observed therapy (DOT) for
tuberculosis in the Philippine setting a largely twice-weekly intermittent therapy regimen was used to treat consecutive
TB cases seen at a TB Clinic in Manila. The regimen consisted of a two-week daily dose initial phase with INH (H),
Rifampicin (R), Pyrazinamide (Z) and Ethambutol (E) or Streptomycin (S) followed by twice weekly HRZE or S for
six weeks then twice weekly HR for the remainder of the six months. All doses were to be ingested at the clinic under
the supervision of the TB Clinic nurse. Failure to report to clinic for a scheduled dose prompted a home visit by the
clinic nurse in which the missed dose was administered.
A total of 74 patients were enrolled in the DOT program in the period beginning August 1995 until the end of
August 1996. Fifty-three (72%) agreed to treatment, by DOT. Twenty-one patients were treated with a self-
administered treatment regimen using the 2HRZE4HR short course chemotherapy. Preliminary outcome information
was available for only 64 patients.
Rates of completion of therapy appeared similar in the DOT (63%) and non-DOT (61%) groups but
percentage of patients lost were three-fold higher in the non-DOT group (33.3%). A large percentage of patients (20%)
transferred out of treatment in the DOT group leading to lower completion rates. Adverse drug effects were reported
frequently (31.1%) but were mostly mild and did not require alteration of the treatment regimen.
Clinic-based DOT with an intermittent treatment regimen appears to be feasible in the urban Philippine
setting with a high acceptance among Filipino TB patients and reasonable toxicity profile. (Phil J Microbiol Infect Dis
1997; 26(1):17-23)

Key words: directly observed therapy, tuberculosis

INTRODUCTION

When effective chemotherapy for tuberculosis (TB) first became available all patients
were treated under close supervision during a protracted inpatient course. With the advent of
domiciliary or ambulatory care for TB, self-administered therapy emerged as the standard method
for TB treatment. In the 1990's, after three decades of experience with self-administered therapy
for TB, it has become clear that ensuring completion of the six-month short course chemotherapy
using self-administered therapy is extremely difficult. Patient education regarding the importance
of regular medication intake and methods for checking adherence to the recommended regimen
such as pill counts and urine examinations fail to ensure that all patients will complete the
treatment. Directly observed therapy (DOT) in which all doses of medications are ingested under
the observation of a physician or health worker, has become the only way of ensuring that
treatment will be completed.
In the 1960's, DOT using daily treatment regimens was shown to be too inconvenient for
both health worker and patient. When higher dose, intermittent treatment regimens were proven
to be effective, DOT became a more viable method for treating TB patients. Recent experience in
such disparate sites as Tanzania, China and New York City1-5 has shown that DOT can improve
treatment completion rates tremendously. The World Health Organization now recommends what
they call DOTS (Directly Observed Therapy, Short-course) as the preferred strategy for TB
control.
In the Philippines, where self-administered treatment for TB is the practice, no
infrastructure for the implementation of DOT is in place. In order to determine the feasibility of
performing DOT in an urban Philippine setting, the University of Santo Tomas TB Clinic began a
pilot project in August 1995 using an intermittent regimen and direct observation. Would Filipino
TB patients accept DOT as a method of treatment and would they tolerate the higher dose
prescribed in intermittent therapy? This paper reports the preliminary results after one year of
experience.

METHODS

Patients. Consecutive patients presenting to the UST TB Clinic with a diagnosis of TB were
invited to participate in the DOT program. The merits of DOT and the requirements of the
program were explained and if the patient agreed to participate in the DOT program the first dose
was immediately administered. Patients who were unable or unwilling to participate in the DOT
program were entered in a parallel treatment tract using self-administered therapy.

Criteria for diagnosis of TB and classification of cases.

1. TB symptomatic - a person, aged 10 years or older, who presents with cough of two or more
weeks duration and one or more of the other cardinal signs and symptoms of TB such as fever,
progressive weight loss, hemoptysis, or recurrent blood-streaked sputum and chest and/or back
pains not referable to musculoskeletal disorder, and others (tiredness, night sweats, shortness of
breath, loss of appetite).
2. Pulmonary smear positive TB – a TB symptomatic with at least two sputum specimens positive
for acid-fast bacilli by microscopy, with or without radiographic abnormalities consistent with
active pulmonary TB, or a patient with one sputum examination positive for AFB with
radiographic abnormalities consistent with active TB.
3. Pulmonary smear negative TB – a TB symptomatic with radiographic abnormalities consistent
with active pulmonary TB in whom sputum examination was negative on three occasions, and for
whom there is a decision by a physician to treat with anti-TB chemotherapy.
4. Extra-pulmonary TB - a patient with one mycobacterial culture positive specimen from an
extrapulmonary site; TB of organs other than the lungs (TB of the pleura, lymph glands,
abdomen, genito-urinary tract, skin, joints and bones, meninges, intestines and peritoneum,
pericardium) or a patient with histological and/or clinical evidence consistent with active
tuberculosis and decision by a physician to treat the patient with anti-tuberculosis chemotherapy.
5. New case-tuberculosis in a patient who has never taken anti-tuberculosis drugs for more than
one month.
6. Relapse - tuberculosis in a patient who has been declared cured in the past by a physician.
7. Treatment failure - tuberculosis in a patient who remains smear positive 5 months or more after
the start of chemotherapy.
8. Incompletely treated - tuberculosis in a patient who had been treated previously with anti-
tuberculosis drugs for more than one month but less than four months ending one month or more
before the start of the present treatment.

Treatment Regimen. New cases, relapses and incompletely treated cases were all treated
empirically with short course chemotherapy using INH (H), Rifampicin (R), Pyrazinamide (Z),
and Ethambutol (E) or Streptomycin (S). All anti-tuberculosis medications were provided free of
charge. Source of the medications was the TB Control Service, Department of Health (H, R, Z, E,
S) and Duncan Pharmaceuticals for supplementary 150 mg R capsules (Rifadin).
The DOT program used the following treatment regimen: First two weeks - daily H 10 -
20 mg/kg (max 300 mg), R 10-20 mg/kg (max 600 mg), Z 15-30 mg/kg (max 2 g), E 15-25
mg/kg or S 20-40 mg/kg (max 1 g); Next six weeks - twice weekly H 15 mg/kg (max 900mg),
R10 mg/kg (max 600 mg), Z 50-70 mg/kg (max 4 g), E 50 mg/kg or S 25-30 mg/kg (max 1.5 g);
Next sixteen weeks - twice weekly H 15 mg/kg (max 900 mg), R 10 mg/kg (max 600 mg). This
regimen is one of the treatment options for empiric therapy of TB recommended by the American
Thoracic Society. Patients in the DOT program were required to report to clinic for the ingestion
of all doses. Failure to report for a scheduled dose prompted a home visit by the clinic nurse
during which the missed dose was administered, the reason for the missed dose was ascertained
and the patient encouraged not to miss any more doses in the future.
Patients in the non-DOT group were treated with the standard short course chemotherapy
(2HRZE4HR): First two months - daily H 10 -20 mg/kg (max 300 mg), R 10-20 mg/kg (max. 600
mg), Z 15-30 mg/kg (max 2 g), E 15-25 mg/kg or S 2040 mg/kg (max. 1 g); Next four months -
daily H 10 -20 mg/kg (max 300 mg), R 10-20 mg/kg (max. 600 mg). Patients in this group
reported to clinic once a week for pick-up of their free medications.

Sputum examinations. All patients were required to submit three sputum specimens for AFB
smear prior to initiating therapy. Several sputum specimens were submitted for mycobacterial
culture and susceptibility testing, which was available, free of charge as part of a separate
research project. Lowenstein-Jenssen method of mycobacterial culture and susceptibility testing
by the proportion method was performed at the Research Institute for Tropical Medicine in
Alabang, Muntinlupa. Susceptibility of isolates to INH, Rifampicin, Ethambutol, Streptomycin,
Amikacin, Kanamycin, Ciprofloxacin and Ofloxacin was done. If the patient was still
expectorating by the end of the second and sixth months, follow-up sputum AFB smears were
performed.

Chest Radiographs. All patients had a chest radiograph done at or prior to the start of therapy.
Those who could afford were requested to have follow-up chest films done at the end of the
second and sixth months of treatment.

Monitoring. Patients in the DOT group were seen twice weekly and those in the non-DOT group
once weekly. Assessment of patients as to progress of symptoms or development of adverse drug
effects was conducted by the TB Clinic nurse with referral to the TB Clinic physician as needed.
All patients were seen by the clinic physician at least upon entry and at the end of the second and
sixth months.

Catchment Area. Anticipating an increasing patient load, the TB Clinic delineated an arbitrary
catchment area called North Manila. This includes the areas of city of Manila north of the Pasig
river (Quiapo, Binondo, San Miguel, Tondo, Sta. Cruz, Sampaloc and Sta. Mesa). It was intended
that when the patient load became too excessive for the TB Clinic nurses, patients accepted for
DOT would be limited to those residing or working in the North Manila area.

Outcomes. At the end of six months the patient could be classified as cured, completed treatment,
treatment failure, transferred out or lost. Patients declared cured but later found to have recurrent
TB could be classified as relapse. Definitions used are as follows:

1. Cured - with documented sputum conversion to negative at the end of therapy.

2. Completed treatment - took the entire course of anti-tuberculosis medications.
3. Relapse - declared cured by a physician but subsequently developed active tuberculosis.
4. Treatment Failure - remains sputum smear positive after five months of therapy.
5. Transferred Out - informed the TB Clinic of desire to continue treatment elsewhere due to
relocation or other reason.
6. Lost - ceased reporting to TB Clinic and not found at submitted residence address.

RESULTS
Patients. From August of 1995 until end of August 1996,74 TB cases were started on treatment at
the UST TB Clinic. All patients except 2 (97.3%) had pulmonary TB. The 2 extrapulmonary
cases were both TB lymphadenitis. One of the pulmonary TB cases also had lymph node TB.
There were 36 males (48.6%) and 38 females (51.4%) with ages ranging from 17 to 69 years.
Forty-two (56.8%) of the 74 cases were classified as new, 21/74 (28.4%) had received incomplete
anti-tuberculosis treatment, 7/74 (9.6%) were relapses, and none were treatment failures.

Symptoms. The most common symptoms reported by the 72 patients with pulmonary TB were
cough in 59 (81.9%), fever in 28 (38.8%), weight loss in 19 (26.4%), hemoptysis in 14 (19.4%),
back pain in 13 (18,1%) and easy fatigability in 10 (13.9%). Other symptoms included anorexia
in 8 (11.1%), night sweats in 6 (8.3%), difficulty of breathing in 3 (4.2%), chest pain and malaise
with 2 (2.8%) each, and chills, weakness and shoulder pain with 1 (1.4%) each. There was one
patient who was asymptomatic but had new chest x-ray findings compatible with TB found on a
routine employment x-ray. These findings were not present in the previous years radiograph.

Radiographic and AFB Smear Findings, Twenty-two (30.5%) of the 72 pulmonary TB cases
were smear positive while 48 (66.7%) were smear negative. Thirty-eight (52.8%) had cavitary
lesions on chest x-ray, while 34 (47.2%) had non-cavitary lesions compatible with pulmonary TB.
Of the 38 with cavitary lesions, 23 (60.5%) were smear positive compared with 9/34 (26.5%)
smear positives among patients with non-cavitary lesions. Two patients who presented with TB
symptoms and cavitary chest x-ray lesions were immediately started on treatment but were lost to
follow-up even before sputum smears were submitted. One of these two was enrolled in the DOT
group but could not be located as a fake address was given.

Treatment Groups. Fifty-three of the 74 patients (71.6%) agreed to participate in the Directly
Observed Therapy (DOT) program. In this DOT group, 43 (81.1%) resided within the UST TB
Clinic catchment area (North Manila) and 10 (18.9%) were from outside.

Outcomes. Preliminary outcome data were available for 64 of the 74 patients as 10 were still
undergoing treatment as of this writing. This is summarized in Table 2. Although majority of the
patients had a favorable clinical response to therapy, none could be classified as "cured" based on
the established criteria of sputum conversion to negative at the end of therapy. With the exception
of 2 treatment failures, all patients who completed the 6-month short course chemotherapy were
no longer expectorating sputum by the end of therapy. These 40 patients, although probably
cured, were classified merely as "completed treatment." These included 29/45 (63.0%) from the
DOT group and 11/18 (61.1%) from the non-DOT group. Of the 29 who completed treatment
under DOT 23 were from within the North Manila catchment area and 6 were from outside. All
11 who completed treatment under self-administered therapy (non-DOT) were from outside the
North Manila area.
There were two treatment failures, one each in the DOT and non-DOT groups. The
patient that failed treatment in the DOT group was a relapse case who eventually had multidrug-
resistant M. tuberculosis isolated from his sputum. This isolate was resistant to INH, Rifampicin
and Ethambutol. The treatment failure in the non-DOT group had received incomplete treatment
in the past. A fully susceptible organism was isolated on mycobacterial culture of sputum but the
patient persisted to be smear positive and developed debilitating Pott's disease while on therapy.
There has been one relapse so far among those completing therapy. This case had received
incomplete therapy before being treated at the UST TB Clinic. She had become asymptomatic at
the end of therapy but developed smear-positive pulmonary TB several months after. Review' of
initial sputum culture revealed M. tuberculosis resistant to Rifampicin and Ethambutol. This
particular isolate required sub-culturing during processing which led to a delay in transmission of
susceptibility data to the clinician. One patient with smear-negative pulmonary TB also had
severe underlying liver disease and died of massive hematemesis.
Table 1. Preliminary outcome of patients treated at the USTTB Clinic, August 1995 to August 31, 1996

Cases W/Out Com Fai Rel Tra Los Exp Ong

DOT 53(71.6) 29 (63.0) 1 (2.2) 1 (2.2) 9 (20.0) 5(11.1) 1 (2.2) 7 (15.2)
In 43 (81.1) 35 (76.0) 23 (79.3) 0 (0.0) 0 (0.0) 8 (88.9) 4 (80.0) 0 (0.0) 7 (100)
Out 10 (18.9) 10 (21.7) 6 (20.6) 1 (100) 1 (100) 1 (11.1) 1 (20.0) 1 (100) 0. (0.0)
Non-
DOT 21(28.4) 18 (85.7) 11 (61.1) 1 (5.6) 0 (0.0) 0 (0.0) 6 (33.3) 0 (0.0) 3 (14.3)
In 0 (0.0) 0 (0.0) 0 (0.0) 0 (0.0) 0 (00) 0 (0.0) 0(0.0) 0 (0.0) 0 (0.0)
Out 21 (100) 18 (100) 11 (100) 1 (100) 0 (0.0) 0 (0.0) 6(100) 0 (0.0) 3 (100)
Total 74 (100) 64 (86.5) 40 (54.1) 2 (2.7) 1 (1.4) 9 (13.5) 11 (14.9) 1 (1.4) 10 (13.5)
DOT - Directly Observed Therapy; Non-DOT - Self-administered therapy; W/ Out - with preliminary outcome data;
Com - Completed Treatment; Fai - Failed Treatment; Rel - Relapse; Tra - transferred out; Los - Lost; Exp - expired;
Ong - Ongoing Treatment; In - inside North Manila area; Out - outside North Manila area

There were 9/45 (20.0%) patients on DOT who transferred to other areas for continuation
of treatment. Five of these patients returned to their home provinces while four relocated in
neighboring cities of Metro Manila. Five of the 45 (11.1%) DOT patients were classified as lost.
Three of these defaulted during the first two weeks of therapy and could not be located by the TB
Clinic nurse due to incorrect addresses. One patient was rehired at her previous job in Quezon
City and preferred to continue treatment on her own by self-administered therapy. The other
patient classified as lost simply refused to continue treatment after the first two weeks of DOT
despite several visits by the clinic nurse. No explanation for refusal was given. Six out of 18
(33.3%) patients with preliminary outcome data in the non-DOT group were classified as lost.
These patients simply stopped reporting to clinic for pick-up of medications.

Culture and Susceptibility Testing, There were 27 specimens processed for mycobacterial culture
and susceptibility testing. The number of specimens processed depended on the availability of the
TB Clinic medical technologist for transport and processing of the specimens at the Research
Institute for Tropical Medicine. The TB Clinic medical technologist resigned in April 1996 and
was replaced only in November 1996.
Of the 27 specimens submitted for culture, 16 (59.2%) grew Mycobacterium tuberculosis.
Seven (43.8%) of these 16 specimens had been initially AFB smear negative. Only 4 (25%) of the
16 isolates were susceptible to all anti-tuberculosis agents tested. Twelve (75%) had resistance to
at least one drug, only one (6.3%) was resistant to a single drug (H), 4 (25%) had 2-drug
resistance, 4 (25%) had 3-drug resistance, 1 (6.3%) had 5-drug resistance, 1 (6.3%) had 6-drug
resistance and 1 (6.3%) was resistant to all eight drugs tested. Six (37.5%) isolates were resistant
to at least H and R. Three (18.8%) of the isolates exhibited resistance to fluoroquinolones. These
results are summarized in Table 2.

Adverse Drug Effects. Twenty-three of the 74 patients (31.1%) treated reported adverse drug
effects. The most frequently reported symptoms were dizziness, which was reported in 9 (12.2%),
nausea in 9 (12.2%), vomiting in 8 (10.8%) and weakness in 5 (6.7%). Other reported adverse
effects were anorexia, numbness, epigastric pain, lightheadedness, headache, tinnitus, blurred
vision and itching. Earlier, patients enrolled in the DOT program had trouble ingesting the large
volume of pills during the third to eighth weeks. This would amount to up to 19 pills for a 60 kg
individual. Nausea and vomiting would occur if these were ingested rapidly but could be avoided
by having the patient ingest the pills slowly, one at a time. In no patient was the adverse effect
severe enough to cause an alteration in the treatment regimen. Adverse drug effects are
summarized in Table 3.
Table 2. AFB smears, susceptibility results and outcomes in 16 patients with M. tuberculosis isolated on culture, UST
TB Clinic, August 1995-August 1996

Pt. Type at
Susceptibility Pattern Start of Rx AFS H R E S C O A K Out
Fully Susceptible (4/16; 25.0%) Rel + S S S S S S S S Los
Rel - S S S S S S S S Los
Inc + S S S S S S S S Fai
Inc - S S S S S S S S Com
One-drug Resistance (1/16; 6.3%) New + R S S S S S S S Com
Two-drug Resistance (4/16; 25.0%) Inc + S R R S S S S S Rel
Rel + R S R S S S S S Com
New + S S R S R S S S Com
Rel + R S S R S S S S Com
Three-drug Resistance (4/16; 25.0%) Rel + R R R S S S S S Fai
Inc - R S S S R R S S Com
New - R R R S S S S S Com
Rel + R R S R S S S S Ong
Five-drug Resistance (1/16; 6.3%) Inc - R R R R S S S R Com
Six-drug Resistance (1/16; 6.3%) New - R R R R S S R R Com
Eight-drug Resistance (1/16; 6.3%) Inc - R R R R R R R R Com
Total Resistance 10 7 8 5 3 2 2 3
AFS - Acid-fast Smear; H - INH; R - Rifamficin; E – Ethambutol; C – Ciprofloxacin; O - - Ofloxacin; A- Amikacin;
K – Kanamycin; Out – Outcome; New – New patient; Rel - Relapse; Inc - Incompletely treated: Los – Lost;
Com – Completed treatment; Ong - Ongoing treatment; Fai – Failed treatment

This corrected table appeared as an erratum in PJMID 1997, 26(2):88

Table 2. AFB smears, susceptibility results and outcomes in 16 patients with M. tuberculosis isolated on culture, UST
TB Clinic, August 1995-August 1996

No. Species (Concomitant isolate) Pt. Type at

Start of Rx AFS Ri E H S C O A K Out
001 M. tuberculosis Rel + R R R S S S S S Fai
005 M. tuberculosis + S S S S S S S S
002 M. tuberculosis Rel + S S S S S S S S Los
004 M. tuberculosis Rel - S S S S S S S S Los
007 M. tuberculosis New + S S S S S S S S Com
015 M. tuberculosis +++ S R R S S S S S
010 M. tuberculosis Rel ++ R S R R S S S S Ong
012 M. tuberculosis +++ R R R R R S S S
011 M. tuberculosis (011) Inc + R S S S S S S S Fai
014 M. tuberculosis +++ S R R R S R S S
021 M. tuberculosis (019) Rel ++ * * * * * * * * Com
026 M. tuberculosis (026) New +++ S S S S R S S S Com
027 M. tuberculosis New +++ S R S S R S S S Com
030 M. tuberculosis New ++ S S R S S S S S Com
033 M. tuberculosis Rel +++ S S R S S S S S Com
MOTT
006 M. chelonei Inc - R R R R S S S S Com
011 M. chelonei (011) Inc + S R R R R R S S Fai
017 M. flavescens New - R R R R S S R R Com
019 M. terrae complex Rel ++ S R R R S S S S Com
022 M. gordonae Inc - S R R S S S S S Com
024 M. terrae complex - R R R R R R R R
025 M. scrofulaceum Inc - R R R S S S S S Exp
026 M. scrofulaceum New +++ * * * * * * * * Com
M. terrae complex * * * * * * * *
034 M. terrae complex New ++ S S R S S S S S Tra
AFS - Acid-fast Smear; H - INH; R - Rifamficin; E – Ethambutol; C – Ciprofloxacin; O - - Ofloxacin; A- Amikacin;
K – Kanamycin; Out – Outcome; New – New patient; Rel - Relapse; Inc - Incompletely treated: Los – Lost;
Com – Completed treatment; Ong - Ongoing treatment; Fai – Failed treatment
*Insufficient growth for susceptibility testing
Table 3. Adverse Drug Effects Among Patients Treated at UST TB Clinic
August 1, 1995 to August 31,1996.

Adverse Effect Number

Dizziness 9
Nausea 9
Vomiting 8
Weakness 5
Joint pains 3
Numbness 2
Anorexia 2
Epigastric pain 2
Light headedness 1
Tinnitus 1
Blurred vision 1
Headache 1
Itching 1

DISCUSSION

In the Philippines, when a physician diagnoses TB he or she will prescribe anti-TB

medications and often explain to the patient the importance of strict compliance with the
instructions given. In the private setting, the physician hands the prescription to the patient
leaving the patient the responsibility of purchasing the medications and ingesting them as
directed. In the public or government health system, the diagnosed TB case is entered into a
treatment program in which he or she is expected to return weekly to the health center to pick-up
the free anti-TB medications. The patient is then expected to take these medications daily as
directed. In both these settings using self-administered therapy, the responsibility of ingesting the
drugs and completing the course of treatment rests mainly on the patient's shoulders. It is not
surprising, therefore, that patients often discontinue therapy on their own when they feel better,
when they relocate to a different area, when they experience adverse drug effects or when they
can no longer afford to purchase the medications. Although many patients do comply with the
treatment regimen, there is ample evidence in the medical literature showing that a physician or
health worker cannot identify in advance the patient who will fail to adhere to the prescribed
treatment.
Directly Observed Therapy (DOT) is the strategy in which all doses of anti-tuberculosis
medications are ingested under the direct supervision of a health care worker until the patient is
cured. This strategy, adapted by the World Health Organization as DOTS (Directly Observed
Therapy, Short-course), is promoted as "the only viable method for reducing TB transmissions
and deaths worldwide, and preventing the emergence of multi-drug resistant TB bacteria."3 In the
Philippines, no mechanism or infrastructure for the delivery of DOT has been established thus far.
In this initial attempt to routinely use DOT in treating its patients, the UST TB Clinic
hired a full-time DOT nurse to supervise all doses of anti-TB medications and pursue defaulting
patients in their homes. Great difficulty was anticipated in performing DOT using a daily
treatment regimen so a proven intermittent regimen for tuberculosis was chosen. Thrice-weekly
(Hong Kong) and every other day (China) treatment regimens have been shown to be effective in
treating tuberculosis but it was felt that a twice-weekly regimen may be more practical in the
urban Philippine setting. The chosen regimen was a largely twice-weekly, intermittent regimen
using four drugs (HRZE) in the intensive phase. This regimen is one of the treatment options
offered by the American Thoracic Society for the empiric treatment of tuberculosis.6
The cases of pulmonary TB seen at the UST TB Clinic presented in the typical fashion
with cough, fever, weight loss, hemoptysis and back pain as the most common symptoms. There
were 22 (30.5%) pulmonary smear-positive cases and 48 (66.7%) pulmonary smear-negative
cases.
Of the 74 patients treated during the study period, majority (71.6%) agreed to participate
in the DOT program. The 21 cases who chose to be treated in the non-DOT program were all
from outside the North Manila catchment area. These data seem to indicate that DOT using an
intermittent regimen is indeed acceptable to the Filipino TB patients particularly if the treatment
center is located near the patients' area of residence. One may speculate that if a network of DOT
centers were established, bringing DOT closer to patients' homes, that acceptance of DOT may
rise even further.
Sixty-four patients had preliminary outcome data. The overall rate of completion of
therapy among these patients appeared similar in both treatment groups with 63% completion in
the DOT group and 61.1% in the non-DOT group. However, the percentage of patients lost in the
non-DOT group (33.3%) was three-fold higher than the DOT group (11.1%) implying a stronger
case-holding ability in the DOT group. There was a large percentage (20%) of patients in the
DOT group that transferred out to a different treatment center in another city or province thereby
lowering the completion rate significantly. This reflects the transient nature of TB patients in the
urban setting and suggests that safeguards against accepting such transients into a DOT program
should be developed. Such safeguards may include a written agreement or contract indicating that
the patient will remain in the DOT area for the duration of treatment.
Of the 5 patients classified as Lost in the DOT group, three had given false addresses.
This identifies another point for improvement in the current DOT program of UST. Rather than
being over-eager to enroll patients as was the case early in the course of the project, verification
of the patients address prior to initiation of therapy may be important in improving completion
rates.
Not surprisingly, one of the two treatment failures turned out to be infected with M.
tuberculosis resistant to H, R and E. What was surprising was the second treatment failure who
developed Pott's Disease while on therapy. This patient's initial isolate was fully susceptible M.
tuberculosis. Potential explanations for this are non-compliance as this patient was in the non-
DOT group, a gastrointestinal disturbance interfering with absorption of the drugs or problems
with bioavailability of the drugs used. The one relapse so far had an M. tuberculosis isolate from
the start of therapy that was resistant to R and E.
Mycobacterial cultures and susceptibility were not done routinely. Depending on the
availability of the UST TB Clinic medical technologist, specimens were transported to and
processed at the Research Institute for Tropical Medicine as part of another research project.
Most of the specimens that were cultured were collected between January to April 1996. A total
of 27 specimens were processed for culture and 16 grew M. tuberculosis. Hardly representative of
The TB cases in the community, these 16 cases do serve as a grim reminder of the ominous
presence of drug resistant TB in the Philippines. Another worrisome finding in this group of
isolates was the presence of quinolone resistance in three. This may be a result of the current
rampant use of quinolones by medical practitioners. Quinolones used as empiric therapy for
respiratory infections may be tantamount to monotherapy if the condition turns out to be
undiagnosed tuberculosis. As many second-line drugs for the treatment of MDR-TB are not
available in the Philippines, quinolones are valuable alternatives. Should the incidence of
quinolone resistant TB rise as a result of the continued indiscriminate use of quinolones in
respiratory infections, an important class of drugs in the treatment of MDR-TB will be lost. For
this reason, we argue that quinolones, though proven efficacious in the treatment of respiratory
infections in other countries, should not be used for this indication in countries with a high
prevalence for tuberculosis such as the Philippines as this may promote the development of
quinolone resistant TB. This class of drugs should be reserved for the treatment of proven
multidrug-resistant TB.
 Adverse drug effects were reported in a significant percentage of patients treated (31.1%)
but none of these were severe enough to cause a change in the treatment regimen. This important
finding indicates that most Filipino patients can tolerate the higher doses of anti-TB medications
used in intermittent therapy. Ingesting the medications slowly and one at a time was important in
preventing subsequent nausea and vomiting particularly during the intensive phase of treatment
when large numbers of pills had to be taken.

SUMMARY

In this initial attempt to routinely treat TB patients with clinic -based DOT, acceptability
of DOT among Filipino TB patients was found to be high (72%). This is likely to be increased if
DOT service is offered mainly to patients living in the vicinity of the treatment center. Although
the completion rates appeared similar in the DOT and non-DOT treatment groups, the percentage
of patients lost was much higher in the non-DOT group. The high transfer rate out of the DOT
group suggests that more stringent residence criteria be applied to entrants in a DOT program.
The frequency of adverse drug effects was significant at 31.1% but all of the adverse effects were
tolerable and required no alteration in the treatment regimen. Majority of the M. tuberculosis
isolates obtained in this project were drug resistant with 68% being resistant to two or more drugs
suggesting a high prevalence of drug-resistant cases in the community. The presence of
quinolone-resistant M. tuberculosis argues against the use of these drugs in the empiric treatment
of respiratory infections. The feasibility of performing clin ic-based DOT for TB in the
Philippines is good particularly with the use of an intermittent regimen. The high doses of
medications used in this largely twice-weekly, intermittent regimen were reasonably tolerated.
Refinements in the model used at the UST TB Clinic should lead to improvement in the
completion rates. Larger scale trials of clinic -based DOT are now warranted.

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