PULMONARY TUBERCULOSIS AS A

DIFFERENTIAL DIAGNOSIS OF PNEUMONIA

A Case Report

Presented by:
Kadek Ayu Atrie Swarita, dr.

Consultants:

Retno Asih, dr., Sp. A (K)

Department of Child Health

Medical School – Airlangga University
Dr. Soetomo General Hospital Surabaya
2017
INTRODUCTION
Pneumonia is one of the most common global childhood illnesses, and it
is the most common cause of childhood mortality.1 Despite advances in childhood
pneumonia management, it remains a major killer of children worldwide.2 Use of
empiric antibiotic therapy based on these guidelines has been estimated to reduce
pneumonia-specific mortality by 35-40% and overall mortality by 24% in children
of 0-4 years of age.3 Some of children with pneumonia do not respond to proper
management, this condition show that the management of pneumonia remains a
problem.4 Follow-up should be obtained in patients with complicated pneumonia
with worsening respiratory distress or clinical instability, or in those with
persistent fever that is not responding to therapy over 48-72 hours. 5
The incidence of pneumonia varies by age groups and between
developing and developed countries. Worldwide, the overall annual incidence of
pneumonia in children younger than 5 years is 150 million to 156 million cases,
leading to an estimated 2 million deaths per year, most of which occur in
developing countries.6.7 In Indonesia, pneumonia is estimated to occur in 3.55%
of children in 2015, with mortality rate 0.15% in children younger than 5 years.8
Children without significant clinical improvement with empirical
pneumonia therapy, should be considered of other cause of pneumonia including
differential diagnosis of pneumonia, also any comorbid present or a complication
of pneumonia itself.2 Studies have emphasized the potential importance of
Mycobacterium tuberculosis in acute severe pneumonia in children as a primary
cause or underlying comorbidity.10 A research done in Uganda by Nantongo et al
showed the incident ratio of pulmonary TB in children admitted with severe
pneumonia was 18.9%. These data highlight the need for considering TB as
differential diagnosis of children presenting with pneumonia, especially in high-
burden country.9 The diagnosis of TB in children relies on history physical
examination as well as any relevant investigations e.g. tuberculin skin test/TST
(Mantoux test), chest x-ray, acid-fast-bacilli smear microscopy and Xpert
MTB/RIF assay. 11,12
The prognosis of primary tuberculosis in children is excellent.
Tuberculosis therapy is close to 100% effective in children for preventing future
disease if adherence is excellent. 13 Commonly in a child has little
microorganism, so the recommendation of four kinds tuberculosis drug in
intensive phase only given to the child with positive acid fast bacilli. Tuberculosis
treatment in a child with negative acid fast bacilli using composition INH,
Rifampisin, Pirazinamid at initial phase (early 2 months) folowed by Rifampisin
and INH at maintenance phase (4 months) 14
The objective of this case was to report the case of pulmonary
tuberculosis, focusing on diagnosis.
In this case, initial treatment pneumonia with empirical antibiotics
(ampicillin) was given. Clinical evaluation after 3 days empirical antibiotic did
not show significant improvement, other differential diagnosis was considered.
Based on clinical manifestation and poor treatment response, atypical pneumonia
was suspected and started macrolide while waiting the result of blood culture.
CASE REPORT
F, a 2-year-and-2-month-old girl, came to emergency department of Dr.
Soetomo Hospital with chief complaint of worsening dyspnea in the last 10 days
before admission. Her dyspnea was not worsening with activity, not reduced by
positional changes, and no history of cyanosis during dyspnea. She also had
productive cough in the last 5 days before admission, especially at night, no
hemoptysis, no additional breath sound like wheezing, and cough was not
triggered by environment or certain food. She had fever since 5 days before
admission, with body temperature 390 C. Her temperature remains above normal
throughout the day and does not fluctuate more than 1 °C in 24 hours. Her weight
also reduced from 11.5 kg to 10 kg in 2 weeks.
She was delivered full term with birth weight 3400 grams, by cesarean
section, cry immediately after birth, and no history of cyanosis or jaundice. Her
history of immunization was on schedule. She lived in a house together with five
other members of her family in a crowded settlement. History of infectious
disease, genetic disease, and congenital disease in the big family were denied.
There was no family member or neighbors who were diagnosed with TB.
Physical examination on admission revealed a weak child with body
weight 10.5 kg, body length 90 cm, and head circumference 49 cm. Her
nutritional status was moderate malnutrition (Weight for height Z score was
-3<WHZ<-2). She looked anemic and breathlessness with respiratory rate 35
breaths per minute, heart rate 120 beats per minute, and temperature 37.80C.
Pallor on conjunctiva and nasal flaring were noted. Chest examination revealed
symmetrical chest movement with retractions on subcostal and intercostal spaces.
On auscultation, fine moist rales were found in upper region of both lungs, no
wheezing, and normal heart sound. Abdominal examination revealed normal
bowel sound, with no liver or spleen enlargement. There was no lymphadenopathy
on the neck, axilla, or inguinal region. Edema was not noted on the extremities.
BCG scar was visible on her right arm. Central nervous system examinations
revealed no abnormality.
Figure 1. The patient’s anthropometric examination on first admission based on WHO Growth
Chart revealed moderate malnutrition status, a. Weight for age Z score (-2<WAZ<0), b. Height for
age Z score (-2<HAZ<0), c. Weight for height Z score ( -3<WHZ<-2).
 Figure 2. Head circumference was 49 cm (HC/A=1)

Figure 3. Chest X-ray of patient’s

The laboratory examination revealed iron deficiency anemia (Hb 9.7g/dl,

serum iron 13mg/dl, total iron binding capacity 159 mg/dl, transferin saturation
less than 20%), leukocytosis (white blood count 25.360/cm3) and neutrophil
dominant (67%), increased CRP level (258.99 mg/dl). Chest x-ray in AP position
revealed uniform opacity with air-bronchogram on right upper lobe consistent
with lobar pneumonia.
Based on history taking, physical, laboratory, and chest x-ray
examination, we assessed this patient with lobar pneumonia in superior right lobe
differential diagnose atypical pneumonia, iron deficiency anemia, and moderate
malnutrition. O2 support with O2 nasal cannula 2 liters per minute, iron
supplementation, thermoregulation, and empirical antibiotics (ampicilin injection
and clarithromycin) was started. Culture of blood also evaluated for possible
infection. On the fifth day of treatment, her cough and dyspnea were improved,
but the fever still present with temperature 390C. Laboratory evaluation revealed
anemia (Hb 9.1 g/dl), leukocytosis (white blood count 21.500/cm 3) and neutrophil
dominant (66.1%), and improved CRP level 15.4 mg/dl. Both antibiotics were
decided to continue while waiting the blood culture result.

Figure 4. Chest X-ray of patient's on 5th day of admission after got five days antibiotic reveal lobar
pneumonia right lobe superior

Figure 5. Temperature curve during hospitalization

After optimal pneumonia treatment, she still had fever with temperature 38.5 oC.
Blood culture revealed no bacteria. Due to lack of improvement on patient’s condition, a
decision was taken to do an evaluation of probable other infection such as tuberculosis.
Mantoux test revealed 10 mm induration, and first AFB smear was negative. Second AFB
smear microscopy was positive one and Xpert MTB/RIF assay result was positive with
rifampicin suseptibility detected. Four-drug antituberculous therapy (rifampicin,
isoniazid, pyrazinamide, and ethambutol) was started. After 2 days four-drug
antituberculous therapy, her fever decreased, and after afebrile for 48 hours, she was
discharge. Antituberculous treatment was continued for intensive phase using 4-drug
fixed-dose combination (FDC) and sent the patient to respirology outpatient clinic for
next evaluation.
 DISCUSSION
Patients 2-year-and-2-month-old girl. Patient came with chief complaint
dyspnea in the last 10 days before admission, cough in the last 5 days before
admission, and fever until 390 C. Physical examination on admission revealed a
weak child and fine moist rales in upper region of both lungs. According to the
anamnesis and physical examination this patient was diagnosed pneumonia.
In pneumonia, the symptomps were cough or difficult breathing of less
than 14 days, and fever. Absence of fever makes pneumonia less likely. 15,16
Auscultation of all lung fields should be performed, listening for crackles (rales)
or crepitations, the presence of which correlates with pneumonia.15
Children aged 2–24 months are at increased risk for infections. 17 The
etiologic agents of pneumonia depend on the patient’s age. In children ages 3
months to 5 years, 50% to 60% of cases are associated with viral respiratory
infections. In school-aged children (>5 years), atypical organisms. 6,7,15
Predispositions to pneumonia such as acquired immunodeficiency have been
reported in 40–92% of the children.16,18,19
Children with pneumonia have body temperature ≥38.0oC, leukocytosis
(WBC count ≥ 10,500/mL) and infiltrate on chest radiograph.15 Laboratory
examination from this patient revealed leukocytosis (white blood count
25.360/cm3) and neutrophil dominant (67%), increased CRP level (258.99 mg/dl)
and chest x-ray in AP position revealed uniform opacity with air-bronchogram on
right upper lobe consistent with lobar pneumonia. In our cases, this patient was
aged 2 years 2 months old, so it could be included to the risk of viral infection.
But from laboratory examination this patient revealed bacterial infection.
Pneumonia can be caused by many pathogens, mainly bacterial and
viruses. 15 Bacteria are the most common cause of pneumonia. Streptococcus
pneumoniae are the most common cause of bacterial pneumonia in the United
States.20,21 Streptococcus pneumoniae, classically associated with a cough
productive of rust-colored sputum. Staphylococcus aureus is known to be an
important cause of pneumonia. There is no doubt that the organism can cause
pneumoniae, often very severe pneumoniae with abscesses and pneumatocoeles
within the lung. 16 Mycoplasma pneumoniae is a major etiologic agent behind
community-acquired pneumonia.21 Clinical manifestation of atypical pneumonia
shows gradual symptoms from days to weeks, dominated by constitutional
symptoms such as myalgia, malaise, severe headache, non-productive cough, and
low-grade fever. 20 The bacterial pneumonia score (BPS) is a clinical assessment
comprised of several investigations: age, assessment of axillary temperature,
absolute neutrophil count, band neutrophil percentage, and interpretation of
radiological examination. The score will use to differentiate the etiology of
pneumonia.21,22
Initial treatment antibiotic empirically was recommended to all patient
with pneumonia. All patients with pneumonia are at risk to be infected by typical
or atypical pathogens.23 In our case, initial treatment pneumonia evaluation did
not respond well.
Clinical improvement should be evaluated as early respond to initial
treatment. The clinical picture should show decrease of respiratory rate, decrease
of fever, and better appetite. Evaluation done within 48-72 hours after empirical
treatment started. Children with unresponsive to initial treatment should be
considered of other cause of pneumonia including differential diagnosis such as
heart defect or foreign substance aspiration. History taking, physical examination,
and chest x-ray should be reevaluated, and do other diagnostic test based on
indication. Other possible etiologies of unresponsive to initial treatment of
pneumonia are viral, atypical pneumonia, tuberculosis. 16 In our cases, we
suggested this patient suffered atypical pneumonia.
On average, a virus can be found in 40-50% of acute lower respiratory
tract infections (ALRI) cases seen at clinics or hospitals. Respiratory syncytial
virus (RSV) is the leading cause of viral ALRI, followed by parainfluenza virus,
influenza virus, adenovirus. In earlier years’ measles also played a major role in
childhood pneumonia. Where measles control activities have broken down this
can be expected to return as a major cause of pneumoniae. 16
Atypical pneumonia is pneumonia caused by atypical organism that are
not detectable by standard diagnostic of pneumonia and generally do not respond
to beta-lactam antibiotics. Atypical pneumonia can be diagnosed from history,
physical, laboratory, and radiologic examination. Radiologic examination in
atypical pneumonia does not show a specific sign. Infection caused by M.
pneumonia usually only affect one lobe of lung, radiology examination show
reticular consolidation.23 On laboratory examination, atypical pneumonia does
not show a specific sign.24 In our cases, according to the laboratory and
radiological examination this patient was diagnoses atypical pneumonia.
Atypical pneumonia incidence quite high and not all center has facilities
to diagnose atypical pathogen. Experts consider starting antibiotic treatment
empirically to all patients with pneumonia who still able to be treated as atypical
pneumonia. There are 3 classes of empirical antibiotic for atypical pneumonia;
they are macrolide, quinolone, and tetracycline.23 In this case we give macrolide,
but the antibiotic therapy did not respond well. So we suggested probably other
disease such as pulmonary tuberculosis.
Tuberculosis (TB) is a global health concern for both developing and
developed countries and has recently become more complex due to persistence in
aging populations and the rise of drug-resistant strains. In clinical practice, rapid
TB diagnosis can be difficult, and early pulmonary TB detection continues to be
challenging for clinicians. Prompt diagnosis of active pulmonary TB is a priority
for TB control, both for treating the individual and for public health intervention
to reduce further spread in the community.25
Table 1. Sign and Symptom Tuberculosis.6
Clinical Feature or Disease Type Infants Children Adolescents

Symptom
Fever Common Uncommon Common
Night sweats Rare Rare Uncommon
Cough Common Common Common
Productive cough Hemoptysis Rare Rare Common
Dyspnea Never Rare Rare
Common Rare Rare
Sign
Rales Common Uncommon Rare
Wheezing Common Uncommon Uncommon
Decreased breath sounds Common Rare Uncommon
Location of Disease
Pulmonary Common Common Common
Pulmonary + Extrapulmonary Common Uncommon Uncommon

Gejala sistemik yang didapatkan pada TB yaitu berat badan turun atau
tidak naik dalam 2 bulan sebelumnya atau gagal tumbuh (failure to thrive)
meskipun telah diberikan upaya perbaikan gizi yang baik dala waktu 1-2 bulan,
demam lebih dari 2 minggu dan atau berulang tanpa sebab yang jelas, batuk lama
lebih dari 2 minggu dan bersifat non remitting dan sebab lain batuk telah dapat
disingkirkan, batuk tidak membaik dengan pemberian antibiotika atau obat asma,
malaise, anak kurang aktif bermain. Gejala TB ekstraparu dapat dijumpai gejala
dan tanda klinis yang khas pada organ yang terkena. Tuberkulosis kelenjar
biasanya di daerah leher (regio colli), pembesaran PKG tidak nyeri, konsistensi
kenyal, multiple, dan kadang saling melekat (konfluens), ukuran besar terlihat
jelas bukan hanya teraba, tidak berespon terhadap pemberian antibiotika, bisa
terbentuk rongga dan discharge. Tuberkulosis sistem saraf pusat seperti gejala
pada pasien meningitis. Tuberkulosis sistem skeletal, spondilitis didapatkan
gibbus, koksitis tanda peradangan di daerah panggul, gonitis bengkak pada lutut
tanpa sebab yang jelas. TB kulit (skrofuloderma) ditandai adanya ulkus dengan
jembatan kulit antar tepi ulkus (skin bridge). 14 Pada kasus ini didapatkan anak
demam lebih dari 14 hari termasuk selama perawatan di RS, batuk lebih dari 14
hari termasuk selama perawatan di RS, dan penurunan berat badan 1.5 kg dalam 2
minggu sehingga dugaan kearah pulmonary TB.
The diagnosis of TB in children relies on history physical examination as
well as any relevant investigations tuberculin skin test (TST) or Mantoux test,
acid-fast-bacilli (AFB), Xpert MTB/RIF assay and chest x-ray. Even though
microbiological diagnosis is not always feasible, all efforts should be made to do
sputum microscopy where possible in children with suspected pulmonary
tuberculosis. A trial treatment with anti-TB drugs is not recommended as a
method of diagnosing TB in children.26 In this case, mantoux test revealed 10
mm induration, and AFB smear I was negative. Second AFB smear microscopy
was positive one and X-pert MTB/RIF assay result was positive with rifampicin
susceptibility detected. So we assessment the patient as pulmonary tuberculosis.

Figure 6. Mantoux Tuberculin Test and its Reading in 48–72 h.26

Figure 7. A and B showing Myctobacterim Bacilli in Sputum and Slide Smear. 26

Table 2. Reaction Size of Tuberculin Skin Test Considered Positive. 13

Reaction Size Risk Factors
≥ 5 mm Human immunodeficiency virus infection or other
immunocompromising conditions
Abnormal chest radiograph consistent with tuberculosis
Contact with an infectious case
≥ 10 mm Age <4 years
Birth or residence in high-prevalence country
Residence in a correctional or long-term care facility
Certain medical conditions (eg, diabetes, renal failure, silicosis)
Health-care workers exposed to patients who have tuberculosis
Any child who is a close contact of an adult who has any of the
previously noted high-risk factors
≥ 15 mm No risk factors

Table 3. Showing the Count of Mycobacterium Bacilli in per Fields of 100x.26

Count on Ziehl-Neelsen/Kinyoun stain (1000x) Report

0 Non AFB observed

1–9/100 fields Exact count

10–99/100 fields 1+

1–10/field 2+

>10/field 3+

Foto toraks merupakan pemeriksaan penunjang untuk menegakkan

diagnosa TB pada anak. Namun gambaran foto toraks pada TB tidak khas kecuali
gambaran TB milier. Secara umum, gambaran radiologis yang menunjang TB
adalah sebagai berikut pembesaran kelenjar hilus atau paratrakeal dengan atau
tanpa infiltrat, konsolidasi segmental/lobar, efusi pleura, milier, atelektasis,
kavitas, kalsifikasi dengan infiltrat, tuberkulom14,26 Pada pasien chest x-ray in
AP position revealed uniform opacity with air-bronchogram on right upper lobe
consistent with lobar pneumonia, sesuai dengan gambaran pulmonary TB.
Secara umum penegakan diagnosis TB pada anak didasarkan pada 4 hal
yaitu konfirmas bakteriologis TB, gejala klinis yang khas, adanya bukti infeksi TB
(hasil uji tuberkulin positif atau kontak erat dengan pasien TB, gambaran foto
toraks sygestif TB.14
Indonesia telah menyusun sistem skoring membantu menegakkan
diagnosis TB pada anak. Sistem skoring ini membantu tenga kesehatan agak tidak
terlewat dalam mengumpulkan data klinismaupun pemeriksaan penunjang
sederhana sehingga mengurangi terjadinya underdiagnosis maupun overdiagnosis
TB. Jika skor total ≥ 6 adalah diagnosis TB dan obati dengan OAT, jika skor total
<6 dengan uji tuberkulin positif atau ada kontak erat maka akan didiagnosis TB
dan diobati dengan OAT. Jika skor total < 6 dan uji tuberkulin negatif atau tidak
ada kontak erat, maka observasi sela 2-4 minggu, bila menetap evaluasi ulang
kemungkinan diagnosis TB atau rujuk ke fasilitas pelayanan kesehatan yang lebih
tinggi.14
tabel 4 disalin sambil cocokin tabel di juknis

Commonly in a child has little microorganism, so the recommendation of

four kinds tuberculosis drug in intensive phase only given to the child with
positive acid fast bacilli. Tuberculosis treatment in a child with negative acid fast
bacilli using composition INH, Rifampisin, Pirazinamid at initial phase (early 2
months) folowed by Rifampisin and INH at maintenance phase (4 months) 14
Untuk mempermudah pemberian OAT dan meningkatkan keteraturan
minum obat, paduan OAT disediakan dalam bentuk paket KDT/FDC. Satu paket
dibuat untuk satu pasien untuk satu masa pengobatan. Paket KDT untuk anak
berisi obat fase intensif, yaitu Rifampisisn (R) 75 mg, INH (H) 50 mg,
pirazinamid (Z) 150 mg, serta obat fase lanjutan, yaitu R75 mg dan H 50 mg
dalam satu paket. Dosis yang dianjurkan dapat dilihat pada tabel berikut. 14

Tabel 5. Recommended doses of essential tuberculosis drugs.14,27

Tuberculosis drug Mode of action Recommended dose (and range) (mg/kg)

daily maximal dose (mg/day)

Isoniazid (H) Bactericidal 10 (7-15) 300

Rifampicin (R) Bactericidal 15 (10-20) 600

Pyrazinamide Bactericidal 35 (30–40) -

Ethambutol Bacteriostatic 20 (15–25) -

Tabel6 6. Dosis OAT KDT pada anak14

Body Weight (kg) Intesive phase Maintenance Phase
(2 months) (4 months)
RHZ (75/50/150) RH (75/50)
5-7 1 tablet 1 tablet
8-11 2 tablet 2 tablet
12-16 3 tablet 3 tablet
17-22 4 tablet 4 tablet
23-30 5 tablet 5 tablet
>30 Adult OAT

Bayi di bawah 5 kg OAT diberikan secara terpisah tidak dalam bentuk

KDT dan sebaiknya dirujuk ke RS, apabila kenaikan berat badan maka dosis atau
jumlah tablet yang diberikan disesuaikan berat badan saat itu, untuk anak dengan
obesitas dosis KDT berdasarkan berat badan ideal sesuai umur, obat KDT harus
diberikan secara utuh (tidak boleh dibelah, digerus), obat dapat diberikan dengan
cara ditelan utuh/dikunyah (chewable) atau dimasukan air dalam sendok
(dispersable), obat diberikan pada saat perut kosong atau paling cepat 1 jam
setelah makan, bila INH dikombinasi dengan rifampisin, dosis INH tidak boleh
melebihi 10mg/kgBB/hari, apabila OAT lepas diberikan dalam bentuk puyer maka
semua obat tidak boleh digerus bersama dan dicampur dalam satu puyer. 14 In this
case, on one months treatment with tuberculosis drug recovery soon. The
symptomps was decreased and the nutritional status was increased. So we
conclude that this patient with pulmonary tuberculosis.
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