1

Chapter 1
THE PROBLEM AND ITS BACKGROUND
Introduction
At the beginning, the extensive majority of people suffering from tuberculosis
(TB) extend from the poorer and most susceptible division of society, global TB control
targets cannot be met unless this group of people is reached with essential health
services. Early diagnosis and effective treatment are important aspects that help reduce
the adverse social and financial consequences of the disease for TB patients and their
families. Consequently, all influential policy documents on TB control always highlight
the importance of developing strategies that ensure global access to essential health
services for all TB patients.
Despite the successes achieved by the adoption of the Directly Observed
Therapy, short course (DOTS) strategy in countries such as Philippines, the recent
emergence of multidrug resistant (MDR) TB and extremely drug resistant (XDR) TB has
slowed down the progress toward the ultimate goal of TB control and elimination.
Originally named after one of the components of the strategy, DOTS comprises
four other critical components including: government commitment, case detection by
sputum smear microscopy, uninterrupted drug supply and standardized reporting and
recording. Given this new understanding, a fast, simple and cost-effective tool to assess
anti-TB treatment efficacy becomes a paramount aspect of this goal.

Furthermore, tuberculosis (TB) has traditionally been one of the principal causes
of pleural disease and, up until the past decades of the earlier century, held as a

2
foremost paradigm of "pleuritis". Undeniably in the presence of a noticeably exudative
effusion and a compatible clinical presentation the widely used term "pleuritis exudativa"
insinuated a tuberculous aetiology and has therefore been understood to be
synonymous with "pleuritis exudativa tuberculosa". At the same time as in the era of TBdecline the term "pleuritis exudativa" has largely survived but may be simply mistaken
for exudative effusion in general, the full and precise term is required when addressing
the possibility of TB. Otherwise the term "tuberculous pleurisy" is used to depict this
entity. Separately from pleuritis exudativa tuberculosa, TB of the pleura may
occasionally also present as caseous pleurisy or specific (tuberculous) empyema
respectively. The following chapter reviews on tuberculosis, the different features and
mechanisms of tuberculous pleural involvement as well as their diagnostic and
therapeutic implications.

Background of the Study

An Era of Tuberculosis
Tuberculosis is one of the oldest documented infectious diseases and remains a
major public health problem today. The evolutionary origin of the causative organism,
Mycobacterium tuberculosis, is uncertain. It was believed to have originated in
prehistoric humans as a zoonotic infection transmitted from tuberculous animals most
probably cattle, between 8000 and 4000 BC (Bloom, 1994). However, a recent analysis
of genetic data based on tubercle bacilli from East Africa has shown that M.
tuberculosis, as a progenitor species about 3 million years old (Gutierrez et al., 2005).

3
Indeed, signs of tuberculosis have been identified in the spines of Egyptians and South
American mummies dated over 6000 years old (McKinney et al., 1998).
Various names have been used to depict tuberculosis. The Greek poet Homer
described it as a grievous consumption that separates soul and body (Gallagher, 1969
p.167). Hippocrates (470-376 BC) called it phthisis; English speaking people called it
consumption, and later the Captain of all the Men of Death, and The Great White
Plague. The enlarged cervical lymph nodes were called Scrofula or The Kings Evil
(Myers, 1970 p.10). The disease also had significant social impact in history and was
prominent in arts and politics. For instance, Botticellis Venus is a popular painting
depicting a pale beauty to signify the disease that would take her life at the age of 23
and the self-entrusted power of 18th century English royalty to heal the disease by the
touch of their hands (McCray et al., 1997).
The cause of the disease was shrouded in mystery and it was believed to be an
inherited disease for a very long time (McKinney et al., 1998). A few people, however,
suspected the contagious nature of tuberculosis. Italy and Spain, for example, had
regulations to prevent its spread as early as 1699. Patients so afflicted were strictly
isolated, and when they died, their bedding and the doors to their rooms were burned
and their rooms were re-plastered (Dowling, 1977).
In 1722 Benjamin Marten, an English physician, explicitly said that the disease
might arise from a micro-organism, which may be an airborne contagion. His idea of
germ theory was mocked at that time (McKinney et al., 1998). In 1865, Jean-Antoine
Villemin went on to demonstrate that the disease could be transmitted using sputum or
caseous tissue from a patient to animal. This was widely discredited at that time

4
(McKinney et al., 1998). In 1882, Robert Koch, a German physician and microbiologist
was able to identify and isolate the causative organism M. tuberculosis (McKinney et al.,
1998).
Antonin Marfan suggested the existence of acquired immunity to tuberculosis as
early as 1886, but it was not until 1919 that Calmette and Guerin succeeded in making
a stable vaccine (BCG) against the disease. Benjamin Weill-Halle and Raymond Turpin
used this vaccine for the first time in 1921 (McKinney et al., 1998). Following the initial
success, its use spread throughout Europe and to other continents in the world. In the
1940s, the WHO started promoting mass vaccination with BCG in its campaign to
control the disease (Raviglione and Pio, 2002).
Drugs that were used in the treatment of other diseases were also tried on
tuberculosis. For example, cod liver oil, prescribed for rheumatism in the late eighteenth
century, was later given for tuberculosis (Dowling, 1977).
In the absence of effective drugs, other measures were tried, including urging
patients to move to warmer climates. A movement towards high altitude, where the air
was believed to be beneficial, began in 1859 with establishment of a sanatorium for
patients suffering from pulmonary tuberculosis by a German physician, Herman
Brehmer (Dowling, 1977). Later, surgical resection of the affected parts of the lung
became the predominant practice in most parts of the world (Dowling, 1977).
In 1939, Selman Waksman attended a congress of microbiologists in New York
City, where he was intrigued by Alexander Fleming`s description of his experiments.
Although he had made earlier observation that avian tubercles were inhibited or killed in
septic soils, he failed to follow this up (McKinney et al., 1998). In 1943, Albert Schatz, a

5
student of Selman Waksman, extracted streptomycin from soil fungus and showed it to
be active against the tubercle bacilli in vitro, leading to its administration for the first time
to a human patient on November 20, 1944 (McKinney et al., 1998). Around the same
period, Jorgan Lehman, noticed that synthetic para-aminosalicylic acid (PAS) inhibited
the growth of the tubercle bacilli in vitro and used it to treat tuberculosis in guinea pigs.
It was first successfully used in the treatment of tuberculosis in a human patient in 1944
(McKinney et al., 1998).
In an era of 1940s, the discovery of anti-TB drugs and combination of
chemotherapy made TB a curable disease. The treatment of tuberculosis began in
1946, when streptomycin was demonstrated to be efficacious against the disease
(McKinney et al., 1998). In 1952, isoniazid became available, and in 1965, rifampicin
was also found to be as effective as isoniazid, making tuberculosis curable in the
majority of patients (Mandell and Bennett, 2000). The discovery of these drugs ushered
in the concept of combination chemotherapy, dubbed, short course with duration of not
less than 6 months (Harries and Dye, 2006). In the developed countries, it was hoped to
eradicate this disease because of its effective treatment.

The Threat
The Philippines ranks ninth on the list of 22 high-burden tuberculosis (TB)
countries in the world, according to the World Health Organizations (WHOs) Global TB
Report 2009. After China, it had the second highest number of cases in the WHO
Western Pacific Region in 2007, and TB is the sixth greatest cause of morbidity and
mortality in the country. In 2007, approximately 100 Filipinos died each day from the

6
disease, but significant strides have been made in increasing case detection and
treatment. In 2004, the country achieved a TB case detection rate of 72 percent,
exceeding WHOs target of 70 percent, and reached 75 percent in 2007. The DOTS (the
internationally recommended strategy for TB control) treatment success rate reached
WHOs target of 85 percent in 1999 and has remained around 88 percent since then.
Nowadays, with its recent emerging of population growth in cities and quickening
development arising from globalization, today's urban settings are focusing on the field
of public health. Diseases at this time vary and much more become a threat. Such in a
case of tuberculosis, is now out of control and increasing at an alarming rate across
most of the poorest regions of the world.
Nearly one third of the global population i.e. two billion people are infected with
mycobacteria tuberculosis and are at risk of developing the disease. Pleural effusion is
one of the common complications of pulmonary tuberculosis.
The first step in the evaluation of patients with pleural effusion is to determine
whether the effusion is a transudate or an exudate. An exudative effusion is diagnosed if
the patient meets Lights criteria. The serum to pleural fluid protein or albumin gradients
may help better categorize the occasional transudate misidentified as an exudate by
these criteria. If the patient has a transudative effusion, therapy should be directed
toward the underlying heart failure or cirrhosis. If the patient has an exudative effusion,
attempts should be made to define the etiology. Pneumonia, cancer, tuberculosis, and
pulmonary embolism account for most exudative effusions. Many pleural fluid tests are
useful in the differential diagnosis of exudative effusions. Other tests helpful for
diagnosis include helical computed tomography and thoracoscopy.

7
Pleural effusion develops when morel fluid enters the pleural space than is
removed. Potential mechanisms of fluid increased interstitial fluid in the lungs secondary
to increased pulmonary capillary pressure (i.e., heart failure) or permeability (i.e.,
pneumonia); decreased intrapleural pressure (i.e., atelectasis); decreased plasma
oncotic pressure (i.e., hypoalbuminemia); increased pleural membrane permeability and
obstructed lymphatic flow (e.g., pleural malignancy or infection); diaphragmatic defects
(i.e., hepatic hydrothorax); and thoracic duct rupture (i.e., chylothorax). Although many
different diseases may cause pleural effusion, the most common causes in adults are
heart failure, malignancy, pneumonia, tuberculosis, and pulmonary embolism, whereas
pneumonia is the leading etiology in children (Light RW, 2002).
Need for Study
Tuberculosis is still a great threat to our community and remains a major health
problem despite laudable efforts of the National TB Program after the implementation of
DOTS in 1996. While the initiation and preservation of DOTS in the public sector, and
the consequent development concerning the private sector, several accomplishments
have been reported.
In spite of the significant achievements, several issues and concerns related to
TB control have been recognized. Different problems linked to factors attributable to the
patient, the health care provider, and the program contributes to the persistence of
tuberculosis in the country.
This study entitled, Retrospective Analysis of Pleural Fluid: Patients
Demographics, AFB Pleural Stain and MTB Culture in Relation to Medical
Treatment of Pulmonary Tuberculosis in Santo Tomas University Hospital from

8
January 2011- October 2011 is an attempt to describe conditions of tuberculous
pleural effusion and its impact to present protocol specifically thoracentesis. The study
also aims to give us further awareness on medical treatment of tuberculosis and ways
to manage it.

Study Objectives
General Objective

The goal of this study is to review the efficiency of pleural fluid AFB staining and
to discuss thoracenthesis and its role in PTB to pleural effusion among patients. It would
also highlight the current medical treatment and management practices/protocols
towards in combating this infectious disease.

Specific Objectives
1. To determine the efficiency of AFB staining as a tool in the diagnosis of
tuberculous effusion.
2. To understand on how pleural effusion in TB can be properly managed with its
practices and protocols.
3. To impart better insights of ways to fight this disease with appropriate
recommendations.

Significance of the Study

There is a need to supervise and evaluate treatment outcomes so as to make
comparisons with standard protocols in managing this disease. Identification and

9
tackling of managing TB protocols will enable optimal hospitalization to reconsider
appropriate and concise protocols to help patients in a comfortable manner. This
research report will describe the management practices. Such a study targeting
hospitalized TB protocols at Santo Tomas Hospital has not been done since the
introduction of standardized TB treatment regimens. The outcomes of the study will be
valuable in assessing past performance and informing situation-specific operational
planning at the hospital.
Furthermore, this study seeks to provide further understanding in determining
several ways of its medical treatment to have better options in seeking for its cure. This
information, however, is vital to the proper management of TB cases.
Understanding the current conditions of the medical treatments provided for the
patients, we hope, will help public health and government officials to fight the disease
more astutely and to take greater programs toward eliminating it without delay and
proficiently as possible.

Theoretical Framework
A health system has been defined by WHO (2007) to consist of all organizations,
people and actions whose primary intent is to promote, restore or maintain health.
Considerably, a health system consists of six components imparted to as health system
building blocks and they include: leadership and governance, health financing,
information system, health workforce, medical technologies and service delivery (WHO,
2009). Several relationships and interactions between these six components result in
four functions of the health system, namely: stewardship (oversight), creating resources

10
(investment and training), financing (collecting, pooling and purchasing), and delivering
services (provision) (WHO, 2007). Generally, health system goals (Figure 1) are to
improve health and health equity, in ways that are responsive, financially fair, and make
the best, or most efficient, use of available resources (WHO, 2007-2009). There are
also important intermediate goals which are to achieve greater access to and coverage
for effective health interventions, without compromising efforts to ensure provider quality
and safety. Worthy of note is that the people are at the centre of the health system
because they play important roles including serving as key factors driving the
components of the building blocks in various capacities, and as beneficiaries of the
health system (WHO, 2009).

Figure 1. The health system building blocks and its overall goals/outcomes
This thesis uses the health system framework depicted in Figure 1 to address
research objectives. The system building blocks which composed of six categories
address the objectives of the study. As leadership/governance, it pertains to an accurate

11
strategic plan to combat the prevalence of this infectious disease. In service delivery,
pertains to ways on how to properly execute the plan for combating TB. Health
workforce, as to broaden their knowledge on ways to manage and have a better grasp
of protocols. Financing, coming from the partnership of DOH and Global funds to
provide treatments and awareness on the current status of tuberculosis locally and
worldwide. Medical products, vaccines, information and technology, for enhanced
knowledge to reduce or as well to eliminate this infectious disease.

Scope and Limitation

The study presents a model of Retrospective Analysis of Pleural Fluid: Patients
Demographics, AFB Pleural Stain and MTB Culture in Relation to Medical Treatment of
Pulmonary Tuberculosis in Santo Tomas University Hospital from

January 2011-

October 2011 is based on descriptive retrospective approach. This approach would be

discussed extensively in Chapter 3, on the studys research methodology.
The study performed at Santo Tomas University Hospital, Manila, of study period
from January 2011 through October 2011. A total of 47 patients were included.
Exempted from the study are other diseases not mentioned in this research.

Definition of Terms
Pleura a delicate membrane that encloses the lungs. The pleurae are divided
into two areas separated by fluid: the visceral pleura, which cover the lungs, and the
parietal pleura, which line the chest wall and cover the diaphragm.

12
Pleural effusion is excess fluid that accumulates between the two pleural
layers, the fluid-filled space that surrounds the lungs. Excessive amounts of such fluid
can impair breathing by limiting the expansion of the lungs during ventilation.
Thoracentesis also known as thoracocentesis or pleural tap, is an invasive
procedure to remove fluid or air from the pleural space for diagnostic or therapeutic
purposes.
Tuberculosis (TB) is a potentially fatal contagious disease that can affect
almost any part of the body but is mainly an infection of the lungs. It is caused by a
bacterial microorganism, the tubercle bacillus or Mycobacterium tuberculosis

Chapter 2
REVIEW OF RELATED LITERATURE AND STUDIES

13
This chapter provides background information on TB and control activities. A brief
history of TB, the natural course of infection, clinical presentation, and diagnosis, with a
focus on developing countries, pleural effusion and the role of thoracenthesis in PTB
are outlined.

Natural history of TB infection

Patients with open pulmonary tuberculosis (PTB) are the most important source
of infection, the risk of infection being determined by how infectious the source is, the
closeness of the contact, and the immune state of the host (Harries and Dye, 2006).
The initial infection occurs by the inhalation of droplets containing the bacilli when a
PTB patient coughs, sneezes, spits or speaks. These infectious particles are generated
in large numbers and can remain suspended in the air for long periods. The small sizes
of the droplets allow them to bypass the protective barriers in the throat and reach the
alveoli where they get deposited. The infectivity of a patient depends on the number of
viable bacilli produced during coughing or sneezing. When the patient produces
sufficient bacilli to be visible on microscopic examination of sputum, it is referred to as a
smear positive case (Enarson et al., 2000). Such patients are most important in the
spread of the infection.
As with many infectious diseases, the events following such infection vary from
person to person. Local multiplication of the bacilli at the site of implantation leads to the
formation of a small lesion termed the Ghon focus. From this focus bacilli are carried
through the lymphatic systems to adjacent lymph nodes where multiplication of the

14
bacilli continues. The resulting lesion consisting of the Ghon focus and the enlarged
regional lymph nodes is termed the primary focus (Collins, 1997).
The presence of bacilli in the lungs usually stimulates a cell-mediated protective
immune response, which is due to activation of macrophages by chemical mediators
called lymphokines released by T-lymphocytes attracted to the site of infection.
Activated macrophages and lymphocytes form a compact aggregate around the bacilli
thereby creating the histological structure termed the granuloma (Collins, 1997).
Of those who become infected, 80-90% will never become ill with tuberculosis
unless their immunity is seriously compromised later in life. The bacilli remain dormant
within the body and their presence is indicated by a significant size of reaction to a
tuberculin skin test (Collins, 1997). In this group of infected individuals, there may
eventually be reactivation of such dormant lesions in about 5% of them, leading to postprimary tuberculosis several years or even decades after the initial infection.
Alternatively, post-primary tuberculosis may be due to exogenous re-infection
(McKinney et al., 1998).
However, in the remainder of those infected, the disease process may progress
in one or more ways to give rise to overt primary tuberculosis. In these individuals,
bacilli may spread from the primary complex to other sites by the lymphatic or blood
streams. This may lead to tuberculous meningitis, which may occur about three months
after infection, or to progressive lesions in bones, joints or the kidney, which are usually
detected a year or more after infection (Collins, 1997).
About two-thirds of all untreated smear-positive cases of PTB will die within 5-8
years of developing the disease (Harries and Dye, 2006). Most of those who survive

15
beyond 8 years develop dormant TB, whilst a few continue to excrete the tubercle bacilli
in their sputum (Harries and Dye, 2006, Enarson et al., 2000).

Aetiology of tuberculosis

The causative organism of tuberculosis, M. tuberculosis, belongs to the family

Mycobacteriaceae, and the order Actinomycetales. The bacillus is aerobic, non-spore
forming and non-motile, with a high cell wall content of high molecular weight lipids. It
measures between 1m to 4m in length and 0.3m to 0.6m in diameter (Brooks and
Jawetz, 1995).
Mycobacteria are classified as Acid and Alcohol Fast (AAFBs), because they
cannot be decolourised by acid or alcohol after using basic dyes to stain them. This
property depends on the integrity of the waxy envelope. They grow very slowly, with
generation time of about 18 hours. They tend to be more resistant to chemical agents
than other bacteria because of the hydrophobic nature of the cell surface. The cell walls
can induce delayed hypersensitivity (Brooks and Jawetz, 1995). The Ziehl-Neilsen
technique of staining is employed for the identification of acid-fast bacteria.

Clinical presentation of TB

Tuberculosis can affect any organ in the body and hence can present in different
ways. The diagnosis of the disease is based on clinical presentation and the use of

16
certain investigative tools. The clinical presentation can be broadly grouped into
constitutional, pulmonary and other symptoms (Grange, 1996).

Constitutional symptoms

Common symptoms of tuberculosis include fatigue, loss of appetite, irritability

and weight loss. There is usually a low-grade fever, which persists for weeks and
becomes marked as the disease progresses. Night sweats may accompany the fever. It
should be noted that the absence of fever or other symptoms does not however mean
the absence of the disease.

Pulmonary manifestation
In pulmonary tuberculosis, there is usually a progressive cough with production
of sputum, which may be blood stained in 8% of adults with active disease (Lutwick,
1995). There may be localised or generalised chest pain and breathlessness when a
massive amount of lung tissue is involved.

Other symptoms
The disease may present in many other forms because it can affect virtually any
organ in the body. Under such circumstances, the manifestation will depend on the
organ involved.

17
Investigation of TB
Table 1 summarises some of the investigative methods used in the diagnosis of
tuberculosis and identifies the advantages and disadvantages of each, emphasizing
methods that are relevant to developing countries.

TABLE 1. Investigative methods used in the diagnosis of tuberculosis

Type(s) of Test
Sputum
microscopy

Advantages
Disadvantages
smear Smear microscopy is the May
be
problematic
only means by which the depending

on

the

of

the

diagnosis of PTB can be competence

confirmed

in

developing
efficiently

most laboratory staff. No bacilli

countries.
identifies

It may be found in the sputum

the of advanced HIV positive

most infectious cases. It is patients. Cannot be used in

cheap and affordable and children since they cannot
can

be

performed

minimal skill.
Sputum culture

with produce sputum. It is not

sensitive

and

may

pick

other mycobacteria species

This is the definitive way of It needs skilled laboratory
making a diagnosis of TB. facilities, which may not be
When sputum smear is available

in

most

negative, culture may be developing countries. It is

positive. It is commonly very slow and takes 4-8
used in monitoring drug weeks to get results. It is

18
sensitivity

patterns

recurrent

TB,

in very expensive and may

and not be affordable to most

community prevalence of developing countries. Only

drug-resistant TB.

in 50% (higher in good

laboratories) of cases is it
possible

to

isolate

the

bacilli from the sputum.

Radiological test

Very

efficient

in

the It

is

unreliable;

diagnosis of TB when used abnormalities identified on

by trained medical officer. It a chest radiograph may be
identifies sputum negative due to TB or a variety of
cases missed by sputum other conditions. Individuals
microscopy. Very useful in previously treated for TB
the

diagnosis

tuberculosis

in

of may show signs of the

children disease

on

radiographic

since they cannot produce examination.

Advanced

sputum.

individuals

HIV-positive

may not show the classical

pattern of TB on chest
radiograph.

19
Tuberculin test

Very useful in measuring A positive test may not be

the prevalence of TB in the caused

by

TB

and

community, especially if not negative

test

does

not

vaccinated with BCG. Very always

rule

it

out,

valuable

in

making especially in HIV positive. It

diagnosis in a young child may

be

negative

at an age when fewer malnutrition

or

in
other

children in the community diseases even though the

will

normally

positive

test.

have
A

a person may have TB. Its

strong use is very limited in high-

positive test is a point in prevalence countries where

favour of tuberculosis.

about 50% of the adult

population are infected with
TB.

It

is

available

not

routinely

in

many

peripheral

health

institutions; it is expensive,
has a very short expiry
date,

must

be

kept

protected from light and

heat and requires some
technical

skills

in

its

administration and reading.

20
Others-Biopsies

of These tests are very useful Most

of

the

tests

are

lymph nodes, laryngeal in skilled hands since they expensive and cannot be
swabs,

and are very fast and specific. afforded

immunological tests etc.

Immunological

tests,

by

for developing

most
countries.

example, are very useful in Technical skills are needed

patients

who

cannot in their performance and

produce sputum. They are this may not readily be

very

useful

work on TB

in

research available
countries.

in

low-income
Expensive

equipments are needed for

most of these tests and this
limits their use developing
countries.
Since the vast majority of people suffering from tuberculosis (TB) come from the
poorer and most vulnerable segments of society, global TB control targets cannot be
met unless this group of people is reached with essential health services.

Early

diagnosis and effective treatment are important aspects that help reduce the adverse
social and financial consequences of the disease for TB patients and their families.
Consequently, all influential policy documents on TB control always highlight the
importance of developing strategies that ensure global access to Despite the successes
achieved by the adoption of the Directly Observed Therapy, short course (DOTS)
strategy in countries such as Philippines, the recent emergence of Latent and Multiple
Drug Resistant Tuberculosis has slowed down the progress toward the ultimate goal of

21
TB control and elimination. Originally named after one of the components of the
strategy, DOTS comprises four other critical components including: government
commitment, case detection by sputum smear microscopy, uninterrupted drug supply
and standardized reporting and recording.

Given this new understanding, a fast,

simple and cost-effective tool to assess anti-TB treatment efficacy becomes a

paramount aspect of this goal.

Initial Evaluation of Pleural Effusion

The history and physical examination are critical in guiding the evaluation of
pleural effusion (Table 2). Signs and symptoms of an effusion vary depending on the
underlying disease, but dyspnea, cough, and pleuritic chest pain are common. Chest
examination of a patient with pleural effusion is notable for dullness to percussion,
decreased or absent tactile fremitus, decreased breath sounds, and no voice
transmission (Light RW, (2001), Porcel JM, Light RW, (2004), and Sahn SA, Heffner JE
(2003).

TABLE 2. Causes of Pleural Effusions: History, Signs, and Symptoms

Condition
History

Potential causes of the pleural effusion

Abdominal surgical procedures

Postoperative pleural effusion, subphrenic

22
Condition

Potential causes of the pleural effusion

abscess, pulmonary embolism

Alcohol abuse or pancreatic disease

Pancreatic effusion

Artificial pneumothorax therapy

Tuberculous

empyema,

pyothorax-

associated lymphoma, trapped lung

Asbestos exposure

Mesothelioma,

benign

asbestos

pleural

effusion
Cancer

Malignancy

Cardiac surgery or myocardial injury

Pleural effusion secondary to coronary artery

bypass graft surgery or Dresslers syndrome

Chronic hemodialysis

Heart failure, uremic pleuritis

Cirrhosis

Hepatic hydrothorax, spontaneous bacterial

empyema

Childbirth

Postpartum pleural effusion

Esophageal dilatation or endoscopy

Pleural effusion secondary to esophageal

perforation

Human immunodeficiency virus infection

Pneumonia, tuberculosis, primary effusion

lymphoma, Kaposi sarcoma

Medication use

Medication-induced pleural disease

Remote inflammatory pleural process

Trapped lung

Rheumatoid arthritis

Rheumatoid pleuritis, pseudochylothorax

Superovulation with gonadotrophins

Pleural

effusion

secondary

to

ovarian

hyperstimulation syndrome
Systemic lupus erythematosus

Lupus

pleuritis,

pneumonia,

pulmonary

23
Condition

Potential causes of the pleural effusion

embolism

Trauma

Hemothorax, chylothorax, duropleural fistula

Signs
Ascites

Hepatic hydrothorax, ovarian cancer, Meigs

syndrome

Dyspnea on exertion, orthopnea,

Heart failure, constrictive pericarditis

peripheral edema, elevated jugular venous

pressure
Pericardial friction rub

Pericarditis

Unilateral lower extremity swelling

Pulmonary embolism

Yellowish nails, lymphedema

Pleural effusion secondary to yellow nail

syndrome*

Symptoms
Fever

Pneumonia, empyema, tuberculosis

Hemoptysis

Lung

cancer,

pulmonary

embolism,

tuberculosis
Weight loss

Malignancy, tuberculosis, anaerobic bacterial

pneumonia

*Yellow nail syndrome results from an abnormality of lymphatics and consists of the
triad of yellow nails, lymphedema, and pleural effusion.

24
Thoracentesis
Except for patients with obvious heart failure, thoracentesis should be performed
in all patients with more than a minimal pleural effusion (i.e., larger than 1 cm height on
lateral decubitus radiograph, ultrasound, or CT) of unknown origin (Porcel JM and Light
RW, 2004). In the context of heart failure, diagnostic thoracentesis is only indicated if
any of the following atypical circumstances is present: According to their study, (1) the
patient is febrile or has pleuritic chest pain; (2) the patient has a unilateral effusion or
effusions of markedly disparate size; (3) the effusion is not associated with
cardiomegaly, or (4) the effusion fails to respond to management of the heart failure.
Thoracentesis is urgent when it is suspected that blood (i.e., hemothorax) or pus
(i.e., empyema) is in the pleural space, because immediate tube thoracostomy is
indicated in these situations. If difficulty in obtaining pleural fluid is encountered because
the effusion is small or loculated, ultrasound-guided thoracentesis minimizes the risk for
iatrogenic pneumothorax (Jones PW et al., 2003). In most instances, analysis of the
pleural fluid yields valuable diagnostic information or definitively establishes the cause
of the pleural effusion. This is the case when malignant cells, microorganisms, or chyle
are found, or when a transudative effusion is found in the setting of heart failure or
cirrhosis. Although common, chest radiography is not necessary after thoracentesis
unless air is obtained during the procedure; the patient develops symptoms such as
dyspnea, cough, or chest pain; or tactile fremitus is lost over the upper part of the
aspirated hemithorax.
Should a thoracentesis be performed?

25
Most patients who have a pleural effusion should undergo a diagnostic
thoracentesis. There are, however, two situations in which a diagnostic thoracentesis is
not recommended. Firstly, if the effusion is very small, the risk/benefit ratio of a
thoracentesis increases. The amount of pleural fluid can be semiquantitated by
obtaining a decubitus chest radiograph with the side of the effusion down, and
measuring the distance between the outer border of the lung and the inner border of the
chest wall. If this distance is less than 10 mm, a diagnostic thoracentesis is not
recommended (Light RW, 1995). The use of ultrasound to facilitate the performance of
the thoracentesis is recommended in patients with relatively small effusions (1015 mm
thickness on the decubitus radiograph). Secondly, if the patient has congestive heart
failure, a thoracentesis is recommended only if the patient meets one of the following
three conditions: 1) the effusions are not bilateral and comparably sized; 2) the patient
has pleuritic chest pain; or 3) the patient is febrile. If none of these three conditions is
met, then treatment of the congestive heart failure is initiated. If the pleural effusions do
not rapidly disappear, a diagnostic thoracentesis is performed several days later. It
should be noted that, with diuresis, the characteristics of the pleural fluid may
occasionally change from those of a transudate to those of an exudates (Shinto RA,
Light RW, 1993). However, in such patients, the serum to pleural fluid albumin gradient
usually remains above 1.2 gdL-1; in this situation, this gradient can be used to assess
when the patient has a transudative or an exudative pleural effusion (Mlika-Cabanne N,
Brauner M, Magusi F, et al, 1995.)
Analysis of Pleural Fluid

26
Furthermore, pleural effusions are either transudates or exudates based on the
biochemical characteristics of the fluid, which usually reflect the physiologic mechanism
of its formation. 1) A transudative pleural effusion is one producing a clear fluid. This is
not a disease in the pleura itself, but rather an imbalance in the removal and intake of
pleural fluid. Forty percent of the time, congestive heart failure is the known main cause
of pleural effusion. As a result, a bilateral type of effusion is usually observed. For a onesided effusion, the right part of the lungs is frequently the one affected because people
tend to lie on the right side. 2) Exudative pleural effusion comes about when the pleura
itself is diseased. The causes are several and varying, most common of which are
infections due to bacterial pneumonia and tuberculosis (Jones PW et al., 2003).
Consequently, pleural effusions are commonly seen in a variety of diseases. In
order to identify which disease is involved, the pleural fluid is usually subjected to
several examinations. These are the tests for chemical characteristics like specific
gravity, ph, protein and glucose; tests for changes of its components like the total
leukocyte and differential cell counts and determinations of other elements like gram
and AFB staining and culture (Table 3). Light et al have shown that two groups of
patients can be separated as initial part of the diagnostic work-up by measuring the
protein and lactate dehydrogenase (LDH) in the serum and in the pleural fluid 5 in to
the exudative and transudative effusions (Table 4).
TABLE 3. Routine tests on pleural fluid
Chemistries
Ph
centrifuged cell sediment
Glucose
Lactate dehydrogenase Protein

Bacteriologic Studies
Culture of
Aerobes
Anaerobes

27
Amylase
Bacteriologic Studies Fungi
Stains of centrifuged cell sediment
sediment
Gram stain
Acid-fast stain
stains
Silver or PAS stain
differential count

Acid fast bacilli

Cytologic studies of centrifuged
Papanicolaou's stain
Romanovsky-type
Complete cell and

TABLE 4. Values distinguishing transudative from exudative pleural effusion

Value

Transudate

Exudate
Total protein (pleural fluid)
< 3 gm%
Lactate dehydrogenase (LDH)
< 200 IU
Pleura1fluid total protein/Serum total < 0.5
protein
Pleural fluid LDH/Serum LDH
< 0.6
Specific gravity by hydrometer
< 1.016

>3 gm%
> 200 IU
> 0.5
> 0.6
> 1.016

Another study, conducted by Tantongco (1987), in his thesis entitled, Pleural

Fluid AFB Staining: Useful or Not? A 5-Year CVGH Experience, found the following:
The 5 year review of patients admitted at Cebu Velez General Hospital and
diagnosed to have tuberculous pleural effusion, revealed that AFB staining of the
pleural fluid is not an efficacious tool in the initial work-up. The result is in
accordance with the proposed pathophysiologic mechanism for pleural effusion
based on hypersensitivity reaction to tuberculous protein. Although foreign
reports have shown the possibility of a positive AFB smear, it was generally
considered insignificant, attributed to other pathophysiologic mechanisms of less
practical value. Omission of AFB smear may lessen the cost of diagnosis which
ultimately rests on other tests used to demonstrate the organism and other
supportive evidences of the disease.

28
Hence in our locality, whenever a patient is found to have exudative effusion, a
diagnosis of tuberculous pleuritis is considered. The obvious explanation to this
is the continued high incidence of tuberculosis in the Philippines. In the desire to
establish the diagnosis, AFB staining of the pleural fluid is one of the most
commonly ordered laboratory examination. A review of foreign literature has
consistently shown that this procedure is not an efficacious tool in the diagnosis
of tuberculous effusion.

Treatment Protocols of PTB

The World Health Organization (2009) procured a standard regimen for the
treatment of tuberculosis with regards to new and previously treated patients,
recommended doses for the first-line anti-TB drugs and considerations in selecting a
regimen for defined patient groups. It aims to cure the disease and to restore the quality
of life of the patient, prevent death and avoid possible complications of the disease,
prevent relapse, reduce transmission to others and avoid the development of drug
resistance.

Directly Observed Treatment Short Course was started by the World Health
Organization in order to effectively diagnose, give standard treatment under direct
observation, and systematic monitoring and evaluation of patients undergoing
treatment. The five principles of the DOTS program as recommended by the World
Health Organization include effective political and administrative commitment, case

29
finding primarily by microscopic examination of sputum of patients presenting to health
facilities, short-course therapy given under direct observation, adequate drug supply,
and systematic monitoring accountability for every patient diagnosed (ICMR Bulletin,
2001). In the Philippines, TB-DOTS Program in still being currently implemented. As of
2004, the case detection rate (CDR) improved from 53% in 2003 to 68% and the cure
rate increased from 75% in 2003 to80.6%. Both are however still below global targets of
70% and 85% respectively.
As of the present study of WHO (200), case detection and treatment success
rates have exceeded the global targets since 2004. PPM initiatives have been further
expanded, and their contribution to the national case detection rate reached 9% in
2007, with only 40% population coverage. The country is now scaling up programmatic
management of drug-resistant TB to include areas beyond Metro Manila, expanding
services for TB in children and addressing TB in high-risk groups including among the
HIV-infected, the urban poor and the prison population. The third prevalence survey in
2007 showed a 34% decrease in bacteriologically-confirmed TB compared with the
1997 survey. The survey results will help re-estimate the burden of TB in the Philippines
and improve understanding of risk factors. Government commitment is strong, and the
increases in funding from domestic sources and the Global Fund grant have helped to
reduce funding gaps.

Synthesis
The present study - Retrospective Analysis of Pleural Fluid: Patients
Demographics, AFB Pleural Stain and MTB Culture in Relation to Medical Treatment of

30
Pulmonary Tuberculosis in Santo Tomas University Hospital from
October 2011 basically

January 2011-

differs from the aforementioned related studies published in

books and journals for the following reasons. First, this study attempts to describe the
over-all aspects of pleural effusion in tuberculosis. Second, it raises awareness and
consciousness of the diagnostic approach, specifically using thoracentesis. Third, the
study provides more in-depth knowledge on the treatments of PTB in our country.
Currently, no study has taken into consideration of pleural fluid AFB staining as
one of the procedures of evaluating pleural effusion in PTB among Santo Tomas
Hospital. This study will bridge this gap in the literature.

Chapter 3
RESEARCH METHODLOGY

This chapter describes the methodology used in the study. It is divided into the
following sections: research design, data collection methods, inclusion criteria,
exclusion criteria, and data analysis. The methodology is based on the research
objectives of the study.

Research Design
A retrospective analysis with descriptive study was done. The study entailed a
detailed retrospective review of medical census from Junior Interns Batch 2012 of UST

31
Faculty of Medicine and Surgery. Medical censuses of 47 patients, who were admitted
and underwent thoracentesis at Santo Tomas University Hospital from January 2011
December 2011.

Data Collection Methods

The method used to address the objectives of the study was done by collecting
all the medical censuses made by the Junior Interns Batch 2012 of admitted patients.
The records include name, age, gender, and admitting diagnosis. Results of
thoracenteses done are also included.

Inclusion Criteria
All patients admitted at the Medicine Ward of the Clinical Division of Santo
Tomas University Hospital, presenting with pleural effusion and subsequently underwent
thoracentesis from January 2011 December 2011.

Exclusion criteria
Patients who have proven malignancies, on pub treatment, have other primary
considerations for cause of pleural effusion other than PTB.

Research Setting
The study was conducted at Santo Tomas University Hospital, Clinical Division.

32

Chapter 4
RESULTS AND CONCLUSIONS

This chapter presents the results and discussion of data gathered based on the
main research goal of the study.

Patients Demographics
In these patients, the diagnosis of tuberculous effusion was made through either
of the following criteria:
1. The demographic of patients diagnosed with tuberculous effusion along with
age and sex shown in Table 5. The clinical history, physical examination findings, pleural

33
fluid analysis, pleural biopsy results and response to treatment were suggestive of
tuberculous effusion and sufficient to rule out other diseases like congestive heart
failure, liver cirrhosis, nephrosis, malignancy, parapneumonic effusion or effusion
associated with connective tissue diseases.

Table 5. Demographics based on criteria No. 1

Demographics
Age
<25
25-50
50-75
>75

6
22
17
2

Sex
Male
Female

25
22

Demonstration of AFB Staining

2. The demonstration of acid fast bacilli in the sputum examination on PTB and
the diagnosis of the patients, Table 6.

Table 6. Distribution of AFB staining based on criteria No. 2

AFB Pleural fluid

Stain

(+)

MTB Culture
(-)

11

15

(+)
(-)
Tally patients scoring system

NIL(culture)

34
Diagnosis
Pneumonia
Malignancy
Hypoalbuminemia
Parapneumonic effusion
Unknown

No. of Patients
11
1
7
2

Not sent: 10
Total Respondents population (47)

Results
Population (N) 47 Forty-seven patients were included in the study. All underwent
thoracentesis from January 2011- December 2011 at the UST Hospital Clinical Division. Of the
forty-seven (47) patients, twenty-six (26) patients were diagnosed to have Pulmonary
Tuberculosis, eleven (11) with Malignancy, one (1) with Hypoalbuminemia, seven (7) with
Parapneumonic effusion and two (2) with unknown diagnosis. Twenty-two (22) patients were
female while twenty-five (25) were male. Patients who were included in the study belong to
different age group. Six (6) were aged twenty-five and below (<25), twenty-two (22) were aged
twenty-five to fifty (25-50), seventeen (17) were fifty to seventy-five (50-75) and two (2) were
seventy-five and above (>75).

In the twenty-six patients who were diagnosed to have PTB, all were able to send their
pleural fluid for AFB staining and culture. All the patients had negative results for AFB staining.
Eleven (11) patients had positive culture while fifteen (15) had negative results.

There were a total of ten (10) patients who were not able to send their pleural fluids for
AFB or culture studies.

35

Discussion

1. Pleural fluid analysis is used to aid in analyzing the cause of inflammation of

the pleura (pleuritis)

and/or

accumulation

of

fluid

in

the

pleural

space

(pleural effusion). make short paragraph about pleural fluid analysis. discuss each
parameter then narrow it down to the importance of culture as a gold standard and AFB
staining.

Light (2001) has theorized that rupture of the pleuralcaseous foci often

detected by pleural biopsy into the pleural space allow tuberculous protein to enter and
generate the hypersensitivity reaction. This is further supported by Sallach, et al (2002)
in their study, which demonstrated the presence of T-lymphocytes in the pleural fluid
specifically sensitized to tuberculous protein. The ensuing reaction caused increased
permeability of the pleural capillaries to protein and the increased protein levels in the
pleural fluid then lead to the accumulation of pleural fluid. Such is probably the
pathophysiologic explanation for the low or zero recovery rate of the AFB smear. As
shown by this study, there were 26 cases with negative AFB staining of the pleural fluid
where TB effusion was the subsequent diagnosis. The technique of AFB staining
adopted by the SantoTomas University Hospital, was universally accepted or
recognized. This was used not only during the period covered by this study but also in
preceding years.
2. In a study by Tantongco (1987), he pointed out that the probability of a positive AFB
stain in exudates of unknown cause to be low, e.g. 7%, in subsequently proven cases of
tuberculosis as to render the test virtually useless. This further supports the idea that
mechanisms other than hypersensitivity reaction play a negligible role in the

36
development of tuberculous pleural effusion. It was even mentioned the role of multiple
pleural fluid cultures as a means of increasing diagnostic yield. Though this may sound
ideal, we question its practical usefulness in the local setting. As far as our experience
with AFB smear is concerned, the test was useless. Physicians should therefore not rely
strongly on the diagnostic reliability of AFB staining and should make use of other tests
for the diagnosis of tuberculous effusion. One still has to maximize the benefits of a
good history, physical examination, supportive evidences obtained from pleural fluid
analysis, chest x-ray, response to treatment, and more definitely, the isolation of the
3.

organism from specimens.

Currently, several authors have endorsed the use of histopathologic examinations and
culture for AFB of pleural tissue obtained by closed pleural biopsy. Added to the fact that
the AFB stain costs 410 pesos and one culture for 1480 pesos. In a practical sense, the

patients could use this money for medicines.

4. The other 10 patients whom did not go through AFB staining are most likely having
insufficient funds to continue this test.

Conclusion

The review of patients by medical censuses who were admitted and underwent
thoracentesis at Santo Tomas University, revealed that AFB staining of the pleural flu id is not
an effective tool in the preliminary set up. The result is in arrangement with the proposed
pathophysiologic mechanism for pleural effusion based on hypersensitivity reaction to
tuberculous protein. As much as overseas information have shown the chance of a positive
AFB smear, it was generally considered irrelevant, attributed to other pathophysiologic

37
mechanisms of less practical value. Exclusion of AFB smear may lessen the cost of diagnosis
which ultimately rests on other tests used to demonstrate the organism and other supportive
evidences of the disease.

Recommendation

More subjects, more parameters, more tertiary hospitals

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