Professional Documents
Culture Documents
OLEH :
Dr EMMA NOVITA MKes
UNIVERSITAS SRIWIJAYA
MONOGRAF
EFECTIVITY OF TREATMENT, NUTRIONAL GAIN,
AND ASSOCIATION FACTORS IN CLINICAL
SYMPTOMS ON TB PATIENT
Penulis
Dr EMMA NOVITA MKes
ISBN:………..
Penerbit
Universitas Sriwijaya
Palembang
Sumatera Selatan
1
Kata Pengantar
Daftar Singkatan
2
HIV : Human Immunodeficiency Virus
INH : Isoniazid
OAT : Obat Anti Tuberkulosis
IMT : Indeks Massa Tubuh
OHO : Obat Hipoglikemik Oral
HSP : Heat Shock Protein
M.TB : Mycobacterium Tuberculosis
TB : Tuberkulosis
Th1 : T Helper 1
TIGO : Tes Toleransi Glukosa Oral
TNFα : Tumor Necrosis Factor Alpha
CONTENTS
CHAPTER I INTRODUCTION.......................................................................................................1
CHAPTER II STATEMENT OF PROBLEM, RESEARCH PURPOSE, STRATEGIC
PLANNING, & ROAD MAP OF RESEARCH...............................................................................3
2.1. Statement of Problem............................................................................................................3
2.2. Research Purpose...................................................................................................................3
2.3. Strategic Planning and Road Map of Research.....................................................................4
2.3.1. Strategic Planning..........................................................................................................4
2.3.2. Road Map of Research...................................................................................................4
CHAPTER III LITERATURE REVIEW........................................................................................6
3.1. Tuberculosis...........................................................................................................................6
3.1.1. Definition.......................................................................................................................6
3.1.2. Epidemiology.................................................................................................................6
3.1.3. Etiology..........................................................................................................................8
3.1.4. Pathogenesis...................................................................................................................9
3.1.5. Clinical Symptoms.........................................................................................................9
3.1.6. Diagnose.......................................................................................................................10
3.1.7. Treatment.....................................................................................................................13
3.1.8. Prognose.......................................................................................................................16
3
3.2. Tuberculosis Treatment in Indonesia..................................................................................16
3.2.1. Tuberculosis Treatment Based on WHO.....................................................................16
3.2.2. Tuberculosis Treatment and Mitigation in Indonesia..................................................19
3.3. Factors that are Affecting Tuberculosis Recovery..............................................................22
CHAPTER IV METHODS.............................................................................................................27
4.1. Types of research.................................................................................................................27
4.2. Research Location and Time...............................................................................................27
4.3. Inclusion and Exclusion Criteria.........................................................................................27
4.4. Ethics...................................................................................................................................28
4.5. Dependent and Independent Variable..................................................................................28
4.6. Data Processing and Analysis Methods...............................................................................28
4.6.1. Data processing............................................................................................................28
4.6.2. Data Analysis...............................................................................................................30
CHAPTER V RESULT AND DISCUSSION................................................................................31
5.1. Result...................................................................................................................................31
5.2. Discussion............................................................................................................................35
REFERENCES.................................................................................................................................40
4
CHAPTER I
INTRODUCTION
2
CHAPTER II
STATEMENT OF PROBLEM, RESEARCH PURPOSE, STRATEGIC
PLANNING, & ROAD MAP OF RESEARCH
3
8. Analysing the relationship between smoke exposure and clinical symptoms
on the Pulmonary Tuberculosis patient who did treatments between 3 and 6
months in Palembang Health Care Centre;
9. Analysing the relationship between alcohol consumption and clinical
symptoms on the Pulmonary Tuberculosis patient who did treatments
between 3 and 6 months in Palembang Health Care Centre;
10.Analysing the relationship between regular treatment and clinical symptoms
on the Pulmonary Tuberculosis patient who did treatments between 3 and 6
months in Palembang Health Care Centre;
11.Analysing the relationship between degree of control in taking medication
and clinical symptoms on the Pulmonary Tuberculosis patient who did
treatments between 3 and 6 months in Palembang Health Care Centre;
12.Analysing the most affecting risk factor in clinical symptoms on the
Pulmonary Tuberculosis patient who did treatments between 3 and 6
months in Palembang Health Care Centre.
4
2017
Tuberculosis Patient Treatment
Compliance
(Emma Novita, Zata Ismah)
2017
The Effect of Education Level on the
Tuberculosis Patient' Nutrition Status
(Emma Novita, Zata Ismah, Pariyana)
2017
Characteristic of Tuberculosis Patient on
Seberang Ulu 1 Palembang Health Care
(Emma Novita, Zata Ismah)
2018
Efectivity of Treatment, Nutrional Gain,
and Association Factors in Clinical
Sumptoms on Tuberculosis Patient
Treatment 3-6 Months
(Emma Novita, Mariana, Zata Ismah,
Agitha Diora Fitri)
Graphic 2.1. Road Map of Research
5
CHAPTER III
LITERATURE REVIEW
3.1. Tuberculosis
3.1.1. Definition
Tuberculosis (TB) is an infectious disease caused by Mycobacterium
tuberculosis who can attack many organs, mainly pulmonary. The condition can
attack everyone, especially for low immunity, older people, immunosuppressive
drugs user, and HIV/AIDS people. Tuberculosis is becoming the most dangerous
infectious disease in the world (Irianti et al, 2016). It occurs because more than 9.6
million people are suspected of Tuberculosis and 1.5 million people died because of
the disease (Kemenkes RI, 2016; Sulis G, 2014).
3.1.2. Epidemiology
World Health Organization (WHO) stated that there were 8.6 million
Tuberculosis cases in 2012, to be more specific, 2.9 million tuberculosis affected in
the woman. Most of the cases occurred in Asia (58%) and Africa (27%) with the
highest occurrences in India (around 2-2.4 million cases) and China (around 0.9 - 1.1
million cases). There was a slight decrease from 1997 to 2001, and however in 2001,
there was an increasing HIV case in Africa. In 2002, there was a reducing in
tuberculosis case ,and it continued 1.3% every year until reaching 2.2% in 2010 and
2011 (WHO, 2013). In 2014, WHO stated that there was 58% of new Tuberculosis
cases in South East Asia and Western Pacific with India (23%), Indonesia (10%), and
China (10%) became the highest Tuberculosis country in the world. Indonesia and
China became the second-largest Tuberculosis country, with 1 million new cases
every year (WHO, 2015).
For a year, treatment for infectious diseases such as tuberculosis disease can be
treated by Rifampicin (RIF), Isoniazid (INH), Ethambutol (EMB), Streptomycin, and
Pyrazinamide (PZA) antibiotic as anti-Tuberculosis (TB). However, there was a
resistance to those first-line drugs. There was an increasing tuberculosis case in the
world after the occurrence Multi-drug Resistant Tuberculosis (MDR-TB) since 1980
(Cheng et al, 2002) MDR-TB is caused by strain M bacteria tuberculosis who
resistant to anti-Tuberculosis (TB) drugs first line such as Isoniazid and Rifampicin.
MDR-TB accelerates Tuberculosis drugs’ second- line, which is more toxic, namely
ethionamide, ciclosporin, kanamycin, and capreomycin (Tripathi et al, 2005).
6
However, extensively drug-resistant tuberculosis (XDR-TB) occurred and caused
Tuberculosis bacteria resistant to drugs second line (WHO, 2010).
In 2013, WHO predicted 9 million new Tuberculosis cases globally and 480
thousand cases were Multi-drug resistant Tuberculosis (MDR-TB). Only a quarter of
MDR cases (123 thousand) in 2015 are detected and reported, while XDR-TB
occurred in 105 countries (WHO, 2015). Historically, Indonesia is a tropical country
who infected quickly with infectious diseases in comparing with the sub tropic
countries. The main factor is an environmental factor where a tropical country has
high humidity and biological development as supporting for massive biodiversity,
including pathogen, vector, and host. This condition worsens since the level of public
awareness, and infectious or tropical disease management are minimum (Skolnik,
2010). One of the tropical diseases is tuberculosis.
Indonesia is known as the highest Tuberculosis prevalence in the world, with
591 thousand cases. In 2001, The National Health Survey announced that
Tuberculosis was the third-highest cause of death in Indonesia. Also, Basic Health
Research (Riskesdas) showed that more than 45 years old group has a higher
prevalence than other aged groups in Tuberculosis case (Kementerian Kesehatan RI,
2013). Higher prevalence in Tuberculosis also found on the low education level and
socio-economy. In 2015, the halving reduction rate of infection and death caused by
tuberculosis occurred in Indonesia. However, the notification rate of the new cases,
which describes the scope of a new case between Tuberculosis and Acid Resistant
Bacteria (BTA), shows positive signs for a new instance and there was an increase
from year to year in Indonesia’ all cases (Kemenkes RI, 2016).
Data for Tuberculosis prevalence rate in 2014 (describing the frequency of old
and the new patients who found in a specific time and group) were 647 per 100.000
people. There was an increasing number from the previous year, which reached 272
per 100.000 people. Furthermore, the incidence rate (describing the frequency of new
patient), and mortality rate raised. Incidence rate in 2014 was 399 per 100.000 people
and the previous year was 183 per 100.000 people. While mortality rate in 2014 was
41 per 100.000 people, and the previous year was 25 per 100.000 people (WHO,
2015).
In 2015, the Tuberculosis case detected around 330.910 cases. Those numbers
increased from the previous year with 324.539 cases. The highest number of
tuberculosis cases are reported in West Java, East Java, and Central Java who have
the highest number of societies in Indonesia (38% of all the cases in Indonesia).
According to gender preference, the number of cases in the male is 1.5 times bigger
7
than female. Also, in the aged group, there was 18.65% patients in 25-34 age groups,
17.33% patients in 45-54 aged group, and 17.18% patient in 35-44 age group. Graph
1 described tuberculosis cases proportion based on the aged group.
3.1.3. Etiology
Tuberculosis is a disease which caused by Mycobacterium tuberculosis
bacteria. Mycobacterium tuberculosis has a straight bar shape or curve, without
spores, and without capsule. The width of bacteria is 0.3 – 0.6 μm, and the length of
bacteria is 1 - 4 μm. The cellulose cell wall in Mycobacterium tuberculosis is
complex, where lipid layers (60%) dominate the composition. It is arranged by
micolat acid, complex-waxes, trehalosadimicolat (cord factor), and mycobacterial
sulfolipids who conduct as a virulence. Micolat acid is lipid acid with a long-chain
(C60-C90) who connected to arabinogalactan with the glycolipid bond and to
peptidoglycan with fosfodiester bridge. Another element in the cellulose cell wall is
polisacarida, such as arabinogalactan and arabinomanan. It caused the acidity of
Mycobacterium tuberculosis bacteria, if it colors then stands with the dye removal in
the alcohol acid solution (Herchline, TE, 2017).
The spreading of Mycobacterium tuberculosis transmitted through the air
medium, not surface contact. When people with active pulmonary tuberculosis (Acid
Resistant Bacteria and Rontgen Result are positive) cough, sneeze, scream or even
sing, bacteria will be carried out of the lungs into the air. The bacteria will inside a
bubble called a droplet nuclei. It stays in the air for several hours and cannot be seen
with the eyes since it has 1-5 μm diameter (CDC, 2016; WHO, 2014).
Tuberculosis transmission occurs when a person breathes in droplet nuclei, as
illustrated in Figure 16. Droplet nuclei will pass through the mouth or nasal passages,
upper respiratory tract, bronchus, and then towards the alveolus (CDC, 2016). After
the tubercle bacillus reaches the lung tissue, they begin to multiply. Eventually, they
spread to the lymph nodes. This process is referred to the primary tuberculosis
infection. A person is suspected to be a primary tuberculosis infection when the
tubercle bacillus is inside in that person’s body. A person with primary tuberculosis
infection cannot spread the disease to other people. Also, the symptoms of
tuberculosis do not appear (WHO, 2004).
Transmission doses of droplet nuclei are reported between 1 to 200 bacilli per
person, where one droplet contains 1 to 400 bacilli, but the assumption about the
relevant dose remains unclear (Sakamoto, 2012). Although tuberculosis is not
transmitted in short contact, sharing the air with tuberculosis patients in the infectious
phase will increase the risk of transmission (CDC, 1999).
8
3.1.4. Pathogenesis
After the primary infection, Macrophages (defense cell) will move to the area
of infection and persecute the bacilli. Since the cell wall of bacilli structure is very
strong, tubercle bacilli survive even though macrophages persecute them. The next
stage is the bacilli infects the macrophages and live inside the macrophages who
grow as usual.
The immunity system attempts another defense strategy after the macrophages
are conquered. The number of defense cells reaches the lymph nodes and surrounding
the area of infection. The cell forms clumps of hard cells known as a tubercle. It helps
to kill bacilli through the formation of the wall in order to prevent the spread of
infection. In some cases, defense cell damage permanently all bacilli tubercle.
In some cases, defense cells are unable to damage all of the tubercle bacilli.
The surviving tubercle bacilli enter dormant status and long last time. During the
time, bacteria fall asleep. The patient is asymptomatic and cannot pass it on to others.
The condition is known as latent tuberculosis. Dormant bacteria can rebuild and
damage the cell wall of defense in a process. The process is known as secondary
tuberculosis infection. Secondary tuberculosis infection occurs when the immune
system weakens and unable to fight bacteria or when bacteria begin to multiply and
overflow. Secondary tuberculosis infection occurs within five years of primary
infection. Secondary tuberculosis infection is considered to be the onset of active
tuberculosis disease (a condition when bacteria begin to win resistance to the body’s
defense system and cause symptoms) (WHO, 2014). The pathogenesis of LTBI and
tuberculosis disease can be seen in Figure 19.
3.1.5. Clinical Symptoms
a. Fever
The patient usually complains about low fever, such as influenza fever. For
a moment, the fever attack can recover and show up again until the patient
cannot be released by a fever attack. It occurs because fever is affected by a
patient’s immunity system and the degree of tuberculosis infection in the
body (Sudoyo AW, 2014).
b. Cough or Haemoptysis
Cough or haemoptysis is the most complaint in tuberculosis patients.
Cough occurs because of the irritation in the bronchus. Cough can be
occurred after the development of disease in the lung tissue, which started
in weeks or months after the inflammation. A cough begins in dry cough
form and transformed into a productive cough (sputum) after the
9
inflammation. The difficult situation is haemoptysis because the blood
vessels are broken. Almost of haemoptysis in tuberculosis patient occur in
cavities (Sudoyo, 2014).
c. Dyspnoea, Chest Pain and Malaise
Dyspnoea usually complains of advance diseases that infiltrate is already
covering half of the lungs. Meanwhile, chest pain found when the infiltrate
reached the pleura, and formed pleuritis. Tuberculosis is a chronic
inflammation disease. The next stage is malaise, which occurs in the form
of anorexia, no appetite, weight loss, headaches, muscle aches, night
sweats and others. When these symptoms worsen, the occurrence disappear
irregularly (Sudoyo, 2014)
d. Loss of Appetite
Clinical symptoms often found in tuberculosis are in the form of anorexia
or no appetite, thin body, chest pain, dyspnoea, fever, headache, miliaria,
and others. These symptoms felt more severe and occur dissipated
irregularly. Also, the occurrence of clinical symptoms depends on the
severity of the patient and the individual (Christine, 2014).
During the treatment, clinical symptoms can improve and disappear. The
degree of disappearing symptoms is determined by many factors such as
drugs, disease, and individual. Drug factors consist of inadequate drug
guidelines, inadequate doses, irregular of taking medication, duration of
drug consumption, and drug resistance. Disease factors are caused by
extensive lesions, the presence of comorbidities, and immunity disorders.
The individual problem occurs because lack of knowledge about
tuberculosis, financial barriers, lazy treatment, and feel healed. In Manado,
there was an association between medication compliance and the
disappearance of clinical symptoms of pulmonary tuberculosis in Lung
Hospital Prof. Dr. R. D. Kandaou (Christine, 2014).
3.1.6. Diagnose
The diagnosis of pulmonary tuberculosis is made through examination of
clinical symptoms, microbiology, radiology, and clinical pathology. A primary
diagnosis is the discovery of acid-resistant bacteria through microscopic sputum
examination. Other tests can be utilized to support the diagnosis, namely radiology,
culture, and sensitivity tests (Sudoyo, 2014).
Suspect TB Paru
10
Microscopic sputum examination - Sewaktu, Pagi, Sewaktu (SPS)
BTA:
+++ BTA: BTA:
++- +-- ---
Non-OAT antibiotics
No Improvement
Improvement
BTA:
+++ BTA:
++- ---
+--
TB NOT TB
Figure 3.1 Diagnosis of Pulmonary Tuberculosis
Information: In certain circumstances with special medical and emergency
considerations, the flow can be used more flexibly (Kemenkes, 2009).
a. Physical examination
The signs on the physical examination depend on the wide and the
abnormalities of lung structure. In minimal lesi, physical examination can
11
be normal, or lung consolidation sign can be obtained mainly apex of
lungs. Those signs of physical examination in the lungs are increasing
focal fremitus, dim percussion, signs of bronchovesicular breathing or the
presence of rocks, especially at the apex of lungs. In the wide lesion, the
signs such as tracea deviation to the infection pulmonary, consolidation
sign, amphoric breath of sound in cavitas, and thickening of pleura can be
obtained (Sudoyo, 2014).
b. Supporting observation
1. Sputum
Sputum examination utilizes to establish the diagnosis, assess the
successes of treatment, and determines the transmission potential. Sputum
examination for diagnosing is carried out by collecting three sputum
specimens, which is collected in two consecutive days of morning visit
(SPS) (Sudoyo, 2014).
S (Sewaktu): Phlegm is collected when tuberculosis suspect visits at the
first time. When returning home, Suspect brought a sputum pot to collect
phlegm on the second morning.
P (Pagi): Phlegm is collected at home on the second morning, immediately
after waking up. The pot was brought and handed over to the officers
themselves.
S (Sewaktu): Phlegm is collected on the second day and the time to submit
the phlegm is in the morning.
Microscopic examination can be divided into two, namely ordinary
microscopic examination where the staining is done by Ziehls Nielsen and
fluorescent microscopic examination is done by auramine-rhodamine
(Especially for screening).
2. Laboratory (Blood)
The results of a routine blood tests describe less specific indicators for
pulmonary tuberculosis. Blood sediment rate (LED) in the first hour and
second hour are the requirement in the blood test. The data can be utilized
as an indicator of the stability state of the patient’s balance number. Hence,
it can be used for the response to the treatment of the patient as well as the
possibility of detection in the patient’s recovery rate. Also, lymphocyte
levels describe the patient’s immune system. LEDs often increase in the
active process, but having normal LED’s does not exclude any
Tuberculosis diagnoses.
12
3. Radiology
Standard examination is thorax photography Postero-Anterior (PA).
Other examinations are a lateral photo, lordotic top, oblique, and CT-scan.
When the sputum SPS examination shows a positive result, Thorax
photography is not necessary to do. In some cases, with the positive blood
smears result, thorax photography must be done if there are suspicions of
complication e.g. pleural effusion and pneumothorax, recurrent
hemoptysis, and there is at least one positive acid-resistant bacteria (BTA)
in the specimen.
Thorax photography examination illustrates various forms. The
suspected active tuberculosis lesion in radiology can be formed as shadows
or nodular cloudy in the apical segments, the upper lobe superior, and the
lower lobe superior in the lung, having more than one cavity, surrounded
by cloudy or nodular opaque shadows, miliary shadows, and pleural
effusions.
3.1.7. Treatment
Tuberculosis treatments are divided into two phases, namely the intensive
phase (2-3 months), and advanced phase (4-7 months). Medication guidelines consist
of main medication and supporting medication (PDPI, 2014).
Tabel 3.1 Anti-Tuberculosis Drug’s Group
First Line Anti- Group 1
Tuberculosis Drugs Oral : Isoniazid (INH/H), rifampisin/rifampin
(RIF/R), pirazinamid (PZA/Z), etambutol (EMB/E).
Rifapentin (RPT/P) and rifabutin (RFB).
Second Line Anti- Group 2
Tuberculosis Drugs Aminoglycosides injection: Streptomisin
(STM/S), kanamycin (Km), amikacin (Amk).
Polypeptida injection: Capreomisin (Cm),
Viomisin (Vim).
Group 3
Fluoroquinolon oral and injection :
Ciprofloxacin (Cfx), levofloxacin (Lfx),
moxifloxacin (Mfx), ofloxacin (Ofx), gatifloxacin
(Gfx).
Group 4
Oral : Para-aminosalicylate acid (Pas),
13
ciclocerin (Dcs), terizidon (Trd), etionamid (Eto),
protionamid (Pto).
Third Line Anti- Group 5
Tuberculosis Drugs Clofazimin (Cfz), linezoid (Lzd), amoxycicilyn
plus clavulanat (Amx/Clv), imipenem plus
cilastatin (Ipm/Cln), Claritomicyn (Clr).
3.1.8. Prognose
Some studies state that the recurrence rate of tuberculosis patients in taking
DOTS treatment is 0 – 14%. In the low rate of tuberculosis occurrance countries,
recurrence usually occurs 12 months after treatment and it occurs due to relapse.
While in the high rate tuberculosis occurance countries, after treatment is the most
recurrence case due to reinfection. The prognosis worse when there are
15
extrapulmonary tuberculosis, immunocompromised patient, older people, and a
history of tuberculosis disease (Sudoyo, 2014).
16
WHO released the tuberculosis world report and stated the newest
recommendation about tuberculosis management, which can be a guideline for the
country in arranging the tuberculosis policy. The purpose of tuberculosis treatment
which is emphasized by WHO are :
a. To cure the patient and to restore the quality of life and productivity;
b. To prevent death causality due to active tuberculosis or late side effects of
tuberculosis;
c. To prevent the recurrence;
d. To eliminate tuberculosis infection to other people;
e. To prevent development and drug resistancy transmission.
WHO suggests Fixed Dosed Combination (FDC) system in tuberculosis treatment
to advert the drugs resistance due to monotherapy, which will occur in the common
treatment. A patient who utilizes FDC cannot choice the drugs to ingest selectively.
The opportunity to error recipe tends to decrease because of the user-friendly dosage.
Dosage adjustment is more comfortable because it is based on the patient’s weight.
Also, a little number of intake tablet in FDC supports the patient’ compliance.
WHO recommends that every tuberculosis patient is given a special kit with the
complete drug. Also, the kit provides the information to health officer about the
compulsory drug with the precise dosage and precise amount. This method tries to
eliminate confusion and dissipation and to create the easiness of supervision.
Furthermore, the success of avoiding drug depletion in a patient maintains the trust
issue on the health system. The patient assures about the kit ownership and increases
the motivation to complete the treatment. However, the kit ownership in the patient is
not eliminating the direct supervision treatment (DOT).
All the patients should be monitored to assess the response to therapy. The
response assessment is carried out based on the predetermined schedule and done by
sputum examination. Radiology examination is not recommended by WHO to asses
the response to therapy. Also, routine monitoring of patients helps the completion of
treatment and allows the identification and management of adverse drug reactions.
Health care workers for each patient should be instructed to report perseverance or
recurrency of tuberculosis symptoms (including weight loss), symptoms of adverse
drug reactions, or treatment interruptions. The patient’s body weight must be
monitored every month, and the dosage of drugs should be adjusted to the body
weight. The report contains the given drugs, bacteriological responses, and adverse
reactions that should be maintained on the tuberculosis treatment card in each
tuberculosis patient.
17
A positive sputum test at the end of the intensive phase shows the following
result:
a. The initial phase of therapy is monitored poorly and the noncompliance patient to
the treatment;
b. Low quality of anti-tuberculosis drugs;
c. The doses of anti-tuberculosis drugs are under the recommendation range;
d. The slow resolution since the patient has extensive cavitas and a heavy initial
bacillary burden;
e. There are co-morbid conditions that interfere with compliance or response;
f. Patient has mycobacteria tuberculosis resistance on the drugs that are not
responding on the first-line treatment;
g. Unsurvival bacteria can be seen on microscopy.
There are many reasons why WHO recommends to culture tuberculosis bacteria
on the patient who get the positive result on the sputum test after the intensive phase
therapy. It intended to detect the drugs resistance without waiting until the fifth
month if the therapy should be changed. If one country has not had the adequate
laboratory capacity, the additional monitoring that using sputum microscopic
observation in the fifth month and after the last therapy is adequate to the patient that
suspects positive tuberculosis. If the additional monitoring shows the positive result,
the treatment failed and the patient can be re-referenced to start the new therapy.
In the last treatment phase, tuberculosis officers write the treatment result in
tuberculosis register district book. Tuberculosis officers in district or city should do
the cohort analysis to the treatment result quarterly and annually. New patient and
treated patient must be analyzed as a different cohort because they have different
characteristics and treatment results. Evaluation of the last treatment result should be
done immediately after the last patient finishes the treatment.
3.2.2. Tuberculosis Treatment and Mitigation in Indonesia
Tuberculosis is an infectious disease which remains the health problem in
Indonesia and the world. In Indonesia, the tuberculosis guidelines and mitigation had
fully stated on the Minister of Health Regulation Number 67 in 2006. The
tuberculosis mitigation intended in protecting public health, reducing the illness,
disability, and death rates, resolving the infection, preventing the drug resistance,
and reducing the negative effect of tuberculosis. Therefore, the national tuberculosis
mitigation target program is achieved based on the global elimination target, namely
Tuberculosis elimination in 2035 and Indonesia free tuberculosis in 2050.
18
Tuberculosis elimination is the achievement of tuberculosis case scope per million
people (Kemenkes RI, 2016).
TB control policies in Indonesia are regulated in Decree of the Minister of
Health of the Republic of Indonesia Number 364/MENKES/SK/V/2009, is:
a. TB control is carried out in accordance with the principle of decentralization,
namely districts / cities as the focus of program management which includes:
planning, implementation, monitoring and evaluation as well as ensuring the
availability of human resources, facilities and infrastructure;
b. TB control is carried out using the DOTS strategy;
c. Strengthening policies to increase regional commitment to TB control programs;
d. Development of a DOTS strategy to improve service quality, easy access,
discovery and treatment so as to break the chain of transmission and prevent the
occurrence of MDR-TB;
e. TB control is carried out by all health service facilities, including Puskesmas,
Public and Private Public Hospitals, Lung Hospitals (RSP), Community Lung
Health Centers (BBKPM), Community Lung Health Centers (BKPM), Lung
Disease Treatment Centers (BP4), and other Medical Clinics and Private
Practitioners (DPS);
f. Development of implementing TB control programs at workplaces (TB in
workplaces), Penitentiaries and Detention Centers (TB in prison), the Indonesian
National Army and the Republic of Indonesia Police;
g. TB control programs using the DOTS Plus (MDR) program, TB-HIV
Collaboration, PAL (Practical Approach to Lung Health), and HDL (Hospital
DOTS Linkages);
h. TB control is carried out through promotion, collaboration / partnership with
cross programs and related sectors, the government and the private sector in the
framework of the National Integrated TB Control Movement (Gerdunas TB);
i. TB laboratory capacity building at various service levels is aimed at improving
service quality and networking;
j. Guaranteeing the availability of Anti-TB Drugs (OAT) for TB control and given
to patients for free;
k. Ensuring the availability of competent human resources in sufficient quantities to
improve and maintain program performance;
l. TB control is prioritized for the poor and vulnerable groups for TB;
m. Eliminating community stigma against TB patients from being excluded from
their families, communities and jobs;
19
n. Pay attention to the international commitments contained in the MDGs.
Anti-tuberculosis drugs (OAT) is the main component in tuberculosis
treatment. Tuberculosis treatment is the most efficient effort to prevent the spreading
of advanced tuberculosis bacteria. Adequate treatment must be followed by the
principle as follows (Kemenkes RI, 2016):
a. The given treatment on the anti-tuberculosis drugs (OAT) guideline contains at
least four drugs to prevent the resistance;
b. Given the precise dosage;
c. Ingesting regularly and monitoring directly by Drug Ingest Supervision (PMO)
until the last treatment;
d. The treatment should be given in an adequate time divided into two phases,
namely intensive phase and advanced phase, as an adequate treatment to prevent
the reccurence.
The main points of TB program activities with the DOTS strategy are as follows:
1. Management of TB Patients
a. Discovery of TB suspects;
b. Diagnosis;
c. Treatment.
2. Program Management
a. Planning;
b. Implementation;
c. Recording and Reporting;
d. Training;
e. Technical guidance (supervision);
f. Strengthening laboratory quality;
g. Logistics management;
h. Monitoring and Evaluation (Surveillance).
3. Supporting activities
a. Promotion;
b. Partnership;
c. Research.
Tuberculosis treatment phase (Kemenkes RI, 2016):
A tuberculosis treatment phase is divided into intensive phase, and advanced
phase The intensive treatment phase is given in two months effectively to decrease
the number of resistant microbe in the body’s patient and to minimize the effect of
resistant germ in the body’s patient before the treatment. In general, the infection
20
term decreased slightly after two weeks of treatment with a regular treatment and
without any complication. On the other hand, the advanced treatment phase intended
to kill the rest of bacteria in the body’s patient, especially persister germ until the
patient is recovering and to prevent the reccurence.
Implementation organizations for TB control in Indonesia are:
a. Central level
TB prevention efforts are carried out through the National Integrated TB Control
Movement (Gerdunas-TB) which is a cross-sectoral forum under the coordination
of the Coordinating Minister for People's Welfare and the Minister of Health as
the technical responsible for TB control efforts. In the implementation of the TB
program nationally carried out by the Directorate of Controlling Disease Control,
cq. TB Sub Directorate.
b. Provincial Level
At the provincial level a Provincial Gerdunas-TB was formed consisting of a
Steering Team and a Technical Team. The shape and structure of the organization
is adapted to the needs of the region. In implementing the TB program at the
provincial level, the Provincial Health Office was implemented.
c. Regency / City Level
At the regency / city level a regency / city Gerdunas-TB was formed consisting of
a Steering Team and a Technical Team. The shape and structure of the
organization is adjusted to the needs of the district / city. In implementing the TB
program at the District / City level, it is carried out by the District / City Health
Office.
d. Level of Health Service Facilities
Implemented by Puskesmas, Hospitals, BP4 / Clinics and Private Doctor
Practices.
1. The Community Health Center (CHC) was formed by the Implementing
Puskesmas (KPP) group consisting of the Microscopic Reference Health
Center (PRM), surrounded by approximately 5 (five) Satellite Puskesmas
(PS). In difficult geographical conditions, an Independent Implementing
Community Health Center (PPM) can be formed which is equipped with BTA
sputum examination facilities and personnel.
2. Public and Private Public Hospitals, Lung Hospitals (RSP), Center for
Community Lung Health (BBKPM), Community Lung Health Centers
(BKPM), Lung Disease Treatment Centers (BP4), and other Treatment
21
Clinics and Private Practitioners (DPS) can carry out all management
activities of TB patients.
25
CHAPTER IV
METHODS
26
Figure 4.1. Seven Community Health Centres (CHC) in Palembang City
4.4. Ethics
This study was approved from the Research Ethics Committee of Mohammad
Hoesin Central Hospital and Faculty of Medicine Sriwijaya University Palembang
Indonesia. The ID number of ethical Approval Certificate is
360/keprsmhfkunsri/2018.
27
4.6. Data Processing and Analysis Methods
4.6.1. Data processing
Research data obtained, will then be processed and further analyzed. There are
4 stages in data processing, namely:
a. Cleaning
At the cleaning stage, data cleaning is performed so that the data collected does
not have missing data so errors in the analysis can be avoided. The cleaning phase
begins with cleaning data from respondents who have exclusion criteria. After the
cleaning process was carried out, data obtained in accordance with the research
criteria were 101 people in seven Community Health Centers (CHC).
b. Editing
At the editing stage, the data that has been collected is then checked again whether
it is complete, relevant, clear, and consistent in accordance with this research. In this
study, the data obtained after cleaning meet these criteria, namely the data is
complete, relevant, clear, and consistent in accordance with this study.
c. Coding
At the coding stage, the data that has been cleaned and edited will then be given a
code (recode) in accordance with the research variables. This stage is needed to
facilitate researchers when conducting data analysis. The coding data is explained in
the following table:
d. Processing
At the processing stage, the data that has been coded is entered into a computer
program application for further data analysis.
CHAPTER V
RESULT AND DISCUSSION
5.1. Result
Table 5.1. Distribution of Pulmonary TB Patients Under General Characteristics (n =
101)
General Characteristics N %
Age
Productive (>15–45 years) 80 85.1
Not Productive (>45 years) 21 14.9
Sex
Man 50 49.5
Women 51 50.5
Education
Primary School (Kindergarten, ES) 47 46.5
Secondary School (JHS, SHS) 54 53.4
High School (University) 13 12.9
Employment Status
Employed 58 57.4
30
General Characteristics N %
Unemployed 43 42.6
Nutritional Status
Malnutrition (IMT < 16) 38 37.6
Good Nutrition (IMT ≥ 16) 63 62.4
Smoking
Yes 22 21.8
No 79 78.2
Exposure to Cigarette Smoke
Yes 46 45.5
No 55 54.5
Alcohol Consumption
Yes 6 4.9
No 95 94.1
Contact History
Yes 32 31.7
No 69 68.3
Regularity of Treatment
Regular 95 94.1
Not Regular 6 5.9
Activity of Supervisors
Active 83 82.2
Not Active 18 17.8
After conducting the study, 101 pulmonary tuberculosis patients were fulfilled
the criteria as the study sample. Table 1 presents the general characteristics of
research respondents consisting of age, sex, education, occupation, nutritional status,
smoking, exposure to cigarette smoke, alcohol consumption, and contact history.
Distribution of tuberculosis patients based on age, found that TB patients who
were undergoing with treatment, the most in the productive age group. More sexes
are men. The dominating level of education is low education. The sample is
dominated by pulmonary TB patients still working with adequate nutritional status.
Patients are still dominated by non-smokers even though there are still many who are
exposed to cigarette smoke. The sample is almost entirely dominated by alcohol
consumption. More than half of the patients had never had a contact history with
pulmonary TB patients. More patients were treated regularly and supervisors ate
regular, active drugs.
Information:
A: Symptoms of cough with phlegm ≥2 weeks D: Weight loss symptoms
B: Symptoms of cough mixed with blood E: Decreased appetite symptoms
C: Shortness of breath F: prolonged fever symptoms
According to the table above, it is known that the clinical symptoms of cough
with phlegm ≥ 2 weeks had a significant or meaningful relationship with two
variables, namely the nutritional status (p value = 0.000) and the regularity of taking
medications (p value = 0.028). While the clinical symptoms of cough with blood do
not have any p value with the value ≤0,05. This means that there is no significant
relationship between clinical symptoms of coughing blood mixed with any variable.
Clinical symptoms of shortness of breath had significant relation with 3
variables. The three variables were the nutritional status, contact history, and the
regularity of taking medication with p value are respectively 0,049, 0,014, and 0,012.
For the clinical symptoms of weight loss also has results (p value <0.05) with
multiple variables. Variables such variables are age, nutritional status and contact
history. P values were obtained for the variables of age and contact history is 0.001
while for the variable nutritional status is 0.011.
The clinical symptoms decreased appetite had a significance with regularity of
taking medicine and the activeness of Drugs Consumption Controller (DCC)
variable. P value of regularity of taking medicine and the activeness of DCC are
respectively 0.034 and 0.017. As for the clinical symptoms of prolonged fever had
significance with the alcohol consumption variable (p value = 0.008).
5.2. Discussion
Positive tuberculosis patients diagnosed with TB or are being treated for most
(81%) in the productive age group. One of the clinical symptoms of pulmonary
tuberculosis are coughing up phlegm ≥ 2 weeks. Differences sputum TB and other
lung diseases cannot be seen with the eye directly. To determine whether the sputum
produced the symptoms of TB or not it is necessary to test sputum.
In this study, found that 54.5% of respondents experiencing clinical symptoms
of cough with phlegm ≥ 2 weeks. Based on test results obtained statistics which were
significant relationship between clinical symptoms of cough with phlegm ≥ 2 weeks
34
with nutritional status (p value = 0.000) and the regularity of taking medications (p
value = 0.028). This means that clinical symptoms are influenced by two factors of
nutritional status and order a drink drug. In this study the nutritional status of
respondents categorized by BMI numbers, where respondents who have a BMI <16,
otherwise the status of malnutrition and respondents who have a BMI ≥ 16 declared
sufficient nutritional status. Respondents who have nourished more experienced
coughing up phlegm ≥ 2 weeks compared to respondents who have less nutrition.
Malnutrition are common in patients suffering from tuberculosis. Prevalence of
malnutrition among adult TB patients is still high, especially in developing countries,
including Indonesia (Nurkumalasari, 2013). Based on the theory it is appropriate
because it is known that the appearance of clinical symptoms of TB patients is
influenced by several factors: patient factors and factors of tuberculosis germs that
infect body. Patient factors is very associated with the immune system or the body's
immunity and nutritional status of a person greatly affect the immune system (Pare,
2012).
The study also showed that 53 samples (54.5%) had clinical symptoms of
cough with phlegm ≥ 2 weeks, while 48 samples (45.5%) didn’t. Based on statistical
tests performed, the clinical symptoms of cough with phlegm ≥ 2 weeks had a
significant or meaningful relationship with the regularity of treatment with OR =
0,495, which means the variable regularity drugs have protective properties against
clinical symptoms of cough with phlegm ≥ 2 weeks. Regularity of TB patients take
medication will help optimize the treatment so as to prevent the appearance of
clinical symptoms when treatment.
In addition, the clinical symptoms of pulmonary TB disease are coughing with
blood. The blood that comes out when cough normally associated with phlegm.
However, the cause of cough with blood not only for the bacteria that causes
tuberculosis infection. Coughing up blood can be caused by several conditions such
as bronchitis, tuberculosis, pulmonary embolism, lung cancer, throat cancer, the side
effects of drugs, pneumonia and others. In this study, the clinical symptoms of cough
with blood have no significance or relationship with any risk factors. This is because
there may be other variables cause bloody cough in addition to the variables included
in the study (Katzung, 2007).
Shortness of breath is the clinical symptoms of pulmonary TB disease. It is
known that shortness of breath is one of the disorders of the respiratory system. In
this study, the clinical symptoms of shortness of breath significance or relationship
35
with nutritional status (p value = 0.049), history of contact (p value = 0.014), and the
regularity of taking medications (p value = 0.012).
3 variables of the study included nutritional status, contact history and
regularity of taking medications play a role in causing the clinical symptoms of
shortness of breath in patients with TB treatment. The relationship between
malnutrition and diseases of the respiratory system have been known for a long time.
Malnutrition a negative effect on the structure, elasticity and lung function, muscle
mass, strength and durability of respiration, immunity mechanisms of lung and
respiratory control. Malnutrition interfere with the immune system thereby increasing
the risk of airway problems. One of the environmental factors causing the increasing
spread of the tuberculosis bacteria that appear clinical symptoms of shortness of
breath is a history of contact with tuberculosis. Contact history are distinguished
based on the duration, frequency and proximity of physical exposure to the patient,
the longer, often and close to the patient, the risk of transmission until the appearance
of clinical symptoms will be higher (Korua, 2014).
Statistical analysis for the variable contact history with clinical symptoms of
pulmonary TB, obtained significant results in clinical symptoms shortness of breath
with p value is 0,011. Frequent contact with active tuberculosis will cause infection
or exposure to healthy people. Risk of contact with adult patients can be caused due
to pulmonary TB transmission through person to person and repeatedly over the air
directly by means of coughing, sneezing and talking, infection from exposure to
active TB can easily occur in the home. Infections caused by Mycobacterium
tuberculosis is transmitted through droplets (droplet) from tuberculosis to vulnerable
individuals. The highest risk for a person infected with the bacteria of tuberculosis is
the most distantly related to tuberculosis. The risk also increases if the person has a
cough does not cover the mouth using handkerchief (Christine, 2014).
Shortness of breath has a significance or a meaningful relationship with the
regularity of taking medications (p value = 0.012). Regularity of TB patients take
medication will help optimize the treatment so as to prevent the appearance of
clinical symptoms when treatment include shortness of breath.
Based on bivariate analysis with the characteristic clinical symptoms of
pulmonary TB obtained significant results between clinical symptoms body weight
decreased with age (p value = 0.001), nutritional status (p value = 0.011) and a
history of contact (p value = 0.001).
At this study, age of the respondents was categorized into productive and non-
productive age in which respondents had a productive age category aged ≤45 years
36
with non-productive age category has aged> 45 years. Positive tuberculosis patients
diagnosed with pulmonary tuberculosis or are undergoing treatment (80%) were in
the productive age group. This is consistent with the theory that the incidence of
pulmonary TB is most common in young age or productive age 15-55 years. This is
probably because of childbearing age more often located outside the home so that the
transmission of tuberculosis is more vulnerable than non-productive age. Research
conducted at the Regional Hospital Noongan obtained much risk of tuberculosis
patients of childbearing age than non-productive age.
Age has a significant relevance to clinical symptoms of pulmonary TB because
the older will be changes in physiological function, pathological and a decrease in the
body's defense system that would affect the body's ability to handle the bacteria that
cause the symptoms of pulmonary TB that is generally displayed can be more severe
(Katzung, 2007). Based on bivariate analysis obtained a significant association
between clinical symptoms of body weight decreased with age (p value = 0,001) with
OR = 15.36, which means the TB patients non-productive age category who received
treatment had 15.36 times the risk of experiencing clinical symptoms of weight loss
compared with TB patients of childbearing age category. Clinical symptoms of
weight loss have a significant association with nutritional status (p value = 0.011) and
the value of OR = 3.195.
In this study, showed a significant relationship between clinical symptoms
decreased appetite and regularity of taking medications (p value = 0.034) with OR =
0.537, which means the variable regularity of treatment have protective properties
against clinical symptoms decreased appetite in patients with pulmonary tuberculosis.
So, based on statistical tests in this study showed that the consumption of tuberculosis
medication regularly can improve the patient's appetite. This can improve the
nutritional status of patients. Pulmonary TB patients should not be to the extent of
malnutrition, particularly protein and calories. Malnutrition will make pulmonary
tuberculosis disease getting worse, because the body does not have enough energy to
be able to fight the infection completely. Malnutrition in patients with pulmonary TB
can make the healing process run longer, ineffective treatment and a higher mortality
rate than patients with an adequate nutritional status. A study of tuberculosis showed
that the nutritional status of TB patients during treatment is 38 samples (37.6%)
patients with malnutrition and 63 samples (62.4%) with status adequate nutrition. It
can be said that not many pulmonary TB patients who have malnutrition, pulmonary
TB treatment means having an impact on changes in the nutritional status of TB in
line with clinical improvement. Prayitami (2011) mentioned that, the effect of
37
treatment on TB impact improvement at nutritional status in the continuation phase as
compared to the nutritional status before treatment. compared with a nutritionist
before treatment.
This study shows that the nutritional status of TB patients during treatment is
38 samples (37.6%) patients with malnutrition and 63 samples (62.4%) with
sufficient nutritional status. It can be said that not many pulmonary TB patients who
have malnutrition, pulmonary TB treatment means having an impact on changes in
the nutritional status of TB in line with clinical improvement.(Prayitami (2011)
mentioned that, the effect of treatment on TB impact change in nutritional status is
better in the continuation phase as compared to the nutritional status before treatment.
compared with a nutritionist before treatment.
Of the 101 patients more active PMO that 83 patients (82.2%), this result is
consistent with research on Biological et al (2014) that 100% of patients with
pulmonary tuberculosis were cured performance baik. PMO analysis of bivariate
activeness drug watchdog meal-related symptoms decreased appetite clinical p value
= 0.017. In Jumaelah study (2013) that there is a significant relationship between the
performance of the PMO with the successful treatment of the patient so that the
disappearance of the clinical symptoms of pulmonary tuberculosis in Kariadi
Hospital Semarang.
Of the 101 patients with pulmonary tuberculosis in table 7 can be seen that
there is no significant relationship between the variables of the smoking habit with
any clinical symptoms of pulmonary TB. In theory, the smoke would trigger a cough
and other symptoms that correspond with pulmonary TB and will affect the results of
pulmonary TB treatment becomes ineffective. According to the WHO in 2015,
globally more than 20% of patients with TB are smokers, even in South Africa with
observational studies it is known that 56% of patients with active tuberculosis are
smokers. Smoking will worsen airway mucus formation and lowering movement of
the cilia. In addition, the substances contained in cigarettes affects the body's immune
system that serves as protection against infection (Kalandadze, 2015).
Persistent fever is one of the clinical symptoms of pulmonary TB disease. In
this research, clinical symptoms of prolonged fever has significant or a meaningful
relationship with alcohol consumption. Excessive alcohol consumption can weaken
the immune system. Decreased levels of immunity characterized by the emergence of
symptoms of fever. Fever is a condition when the body temperature exceeds 37
degrees Celsius due to a disease or inflammation. Fever indicates that cells of human
antibodies that leukocytes were against a virus or bacteria. Effects of alcohol
38
consumption immune system is complex, in this case the function of the immune
system in most tissues is inhibited, one of which is in the lung tissue, thereby
increasing the risk of progression to active tuberculosis. But it is different from the
research conducted Shetty at al (2006) that an evaluation of the risk factors of
tuberculosis in South India. In the study found that alcohol is not a significant risk
factor for tuberculosis. However, in two other studies by Imtiaz et al (2017) in
European countries found that alcohol consumption of more than 40g is an important
risk factor to the onset of active tuberculosis and reactivation of infection.
REFERENCES
Amin, Z. dan A. B. (2014). Tuberkulosis Paru. Dalam Buku Ajar Ilmu Penyakit
Dalam Jilis I Edisi VI. Jakarta: Interna Publishing.
Budiarto, E. (2003). Pengantar Epidemiologi. Jakarta: EGC.
CDC. (1999). Tuberculosis Elimination Revisited: Obstacles, Opportunities, and a
Renewed Commitment. Atlanta, Georgia.
CDC. (2016). Guidelines Tuberculosis (TB). Retrieved March 9, 2017, from
https://www.cdc.gov/tb/publication/guidelines/default.htm
Cheng VC, Ho PL, Lee RA, Chan KS, Chan KK, Woo PC, Lau SK, Y. K. (2002).
Clinical spectrum of paradoxical deterioration during antituberculosis therapy in
39
non-HIV-infected patients. Eur J Clin Microbio. Infect Dis, 21(1), 803–9.
Christine M, Yudi A, dan K. V. (2014). Hubungan kepatuhan pengobatan dengan
hilangnya gejala klinis pasien tuberkulosis paru di poli paru RSUPProf. Dr. R.
D. Kandou Manado. Universitas Sam Ratulangi.
Christine M, Yudi A, K. V. (2014). Hubungan kepatuhan pengobatan dengan
hilangnya gejala klinis pasien tuberkulosis paru di poli paru RSUPProf. Dr. R.
D. Kandou Manado. Universitas Sam Ratulangi.
Depkes RI. (2011a). Pedoman Nasional Pengendalian Tuberkulosis. Jakarta.
Depkes RI. (2011b). TBC Masalah Kesehatan Dunia. Jakarta.
Herchline, TE, B. M. (2017). Tuberculosis. Retrieved January 14, 2017, from NCBI
website: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4235436/
Hoagland, D.T., Liu, J., Lee, R.B. & Lee., R. E. (2016). New Agents for the
Treatment of Drug-Resistant Mycobacterium tuberculosis. Advanced Drug
Delivery Reviews, 102(1), 55–72.
Imtiaz, SK, Shield, M Roerecke, AV, Samokhvalov, K, Lönnroth and Rehm, J.
(2017). Alcohol consumption as a risk factor for tuberculosis: meta-analyzes and
burden of disease. The European Respiratory Journal, 50(1). Retrieved from
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5540679
Irianti, T., Kuswandi., Yasin, M.N., & Kusumaningtyas, A. . (2016). Mengenal Anti-
Tuberkulosis. Yogyakarta: UGM.
Jumaelah. (2013). Hubungan Kinerja Pengawas Menelan Obat terhadap Keberhasilan
Pengobatan TB Parudengan DOTS di RSUP Dr. Kariadi Semarang. Medika
Hospitalia, 2(1).
Kalandadze, T. Chakhaia, Golub JE, and H. B. (2015). Tobacco smoking and
tuberculosis treatment outcomes: a prospective cohort study in Georgia Bulletin
of the World Health Organization. Retrieved from WHO website:
http://www.who.int/bulletin/volumes/93/6/14-147439/en/
Katzung, B. (2007). Basic and Clinical Pharmacology (10th ed.). USA: The
McGraw-Hill Companies, Inc.
Kemenkes RI. (2016). InfoDatin Tuberkulosis. Retrieved from
http://www.depkes.go.id/download.php?file=download/pusdatin/infodatin/Inf
oDatin-2016-TB.pdf
Kementerian Kesehatan RI. (2013). Laporan Riset Kesehatan Dasar. Jakarta: Badan
Penelitian dan Pengembangan Kesehatan.
Korua, ES, Kapantow NH, K. P. (2014). Hubungan antara umur, jenis kelamin, dan
kepadatan hunian dengan kejadian TB paru pada pasien rawatjalan di Rumah
Sakit Umum Daerah Noogan.
Kurniawan, Nurmasadi Siti Rahmalia HD, G. I. (2015). Faktor-faktor yang
Mempengaruhi Keberhasilan Pengobatan Tuberkulosis Paru. UNRI, 2(1).
Lewrence, M. (2002). Diagnosis dan Terapi Kedokteran Ilmu Penyakit Dalam.
Jakarta: Salemba Medika.
Lonnroth K, Williams S, Stadlin E, J. C. (2008). Alkohol use as a risk factor for
tuberculosis. BMC Public Health, 8(1), 289.
McKenna, L. (2019). The Tuberculosis Treatment Pipeline: PIPELINE REPORT
40
2019. New York.
Muttaqin, A. (2008). Buku Ajar Gangguan Sistem Pernapasan. Jakarta: Salemba
Medika.
Nurkumalasari, Wahyuni, N. (2013). Hubungan karakteristik Penderita Tuberkulosis
Paru dengan Hasil Pemeriksaan Dahak di Kabupaten Ogan Ilir. Unsri, 3(2).
Pare, A. L. , R. Amiruddin, I. L. (2012). Hubungan Antara Pekerjaan, PMO,
Pelayanan Kesehatan, Dukungan Keluarga dan Diskriminasi dengan Perilaku
Berobat Pasien TB Paru.
PDPI. (2014). Pedoman Penatalaksanaan TB (Konsensus TB). Jakarta: Perhimpunan
Dokter Paru Indonesia.
Prayitami, S.p., L. D. dan A. R. (2011). Hubungan Fase Pengobatan dengan Status
Gizi Tuberkulosis Anak di Rumah Sakit Umum Daerah Dr. H. Soewondo Kendal
Periode Januari 2011 - Semptember 2011. Kedokteran, 1(1).
Sakamoto. (2012). the Pathology of Mycobacterium Tuberculosis Infection. Vet
Pathol, 49(1), 423–439.
Shetty, N, Shemko, M, Vaz, M, Souza, G. (2006). An Epidemiological Evaluation Of
Risk Faktors For Tuberculosis In South India: A Matched Case Control Study.
Int J Tuberc Lung Dis, 10(1), 80–86.
Skolnik, Richard, dan A. A. (2010). Ending the Neglect of Neglected Tropical
Disease. Retrieved October 20, 2016, from PRB website:
http://www.prb.org/pdf10/neglectedtropicaldiseases.pdf
Sudoyo, Setiohadi B, Alwi I, Simadibrata M, S. S. (2014). Buku Ajar Ilmu Penyakit
Dalam Jilid 1 (6th ed.). Jakarta: Interna Publishing.
Sulis G, Roggi A, Matteelli A, dan R. M. (2014). No Title. Tuberculosis:
Epidemiology and Control, 6(1). https://doi.org/e2014070
Tripathi, R.P, Tewari, N, Dwivedi, N, Tiwari, V. . (2005). Fighting tuberculosis: an
old disease with new challenges. Fighting Tuberculosis: An Old Disease with
New Challenges, 25(1), 93–131.
Tsani, Rosy Mutiara, K. (2012). Gambaran Klinis Tuberkulosis Paru di RSUP Dr.
Kariadi Semarang Periode Januari – Juni 2011. Semarang.
WHO. (2001). Guidelines for Drug Susceptibility Testing for Second-Line Anti-
Tuberculosis Drugs for DOTS-Plus. Geneva.
WHO. (2004). Global Tuberculosis Control: Surveillance, Planning, Financing.
Geneva.
WHO. (2010). Guidelines for Treatment of Tuberculosis (4th ed.). Geneva: WHO.
WHO. (2013). Nutritional Care and Support for Patients with Tuberculosis. Geneva.
WHO. (2014). Global Tuberculosis Report 2014. Geneva.
WHO. (2015). Global Tuberculosis Report 2015. Switzerland.
Wijaya. (2012). Merokok dan tuberkulosis. Tuberkulosis Indonesia, 8(1), 18–23.
Zumla, A., Nahid, P. & Cole, S. T. (2013). Advances in the Development of New
Tuberculosis Drugs And Treatment Regimens. Nature Reviews, Drug Discovery,
12(1), 388–404.
41