Int J Infect. 2014 September: 1(3): e21116.

Review Article

Published online 2014 September 10.

Pulmonary Tuberculosis in Children

1

Maryam Keshtkar Jahromi ; Batool Sharifi-Mood

2,*

1Division of Infectious Diseases, Pennsylvania State University, Hershey, PA, USA

2Infectious Diseases and Tropical Medicine Research Center, Zahedan University of Medical Sciences, Zahedan, IR Iran

*Corresponding author: Batool Sharifi-Mood, Infectious Diseases and Tropical Medicine Research Center, Boo-Ali Hospital, Zahedan University of Medical Sciences, IR Iran. Tel: +985413228101, Fax: +98-5413236722, E-mail: [email protected]

Received: June 11, 2014; Revised: June 24, 2014; Accepted: July 26, 2014

Tuberculosis (TB) is the most common cause of infection-related death worldwide. Children represent 5 to 15% of all TB cases around
the world and are more frequently infected and more easily affected by the most severe forms of the disease such as meningitis and
disseminated form .Here, we reviewed TB in children with impact on the routes of transmission, clinical manifestations, treatment,
control, and prophylaxis.
Electronic databases (PubMed, Scopus) were searched from June1995 to May 2014 by using key words (pulmonaryTB,epidemiology,transm
ission,clinical manifestations,treatment,control, and prophylaxis) .
Pulmonary tuberculosis may manifest in several forms, including endobronchial TB with focal lymphadenopathy, progressive pulmonary
disease, pleural involvement, and reactivated pulmonary disease . Symptoms of primary pulmonary disease in the pediatric population
are often insignificant. Gastric aspirates are used instead of sputum in children younger than 6 years. BCG vaccination is used in many
parts of the world and the major role of vaccination is the prevention of life-threatening illness such as disseminated TB and meningitis in
children.Treatment is the same as for adults.
Most people infected with M .tuberculosis do not develop active disease. In healthy individuals, the lifetime risk of developing infection to
disease is 5-10%. Reactivation of TB often occurs in older children and adolescent and is more common in patients who acquire TB at age 7
years and older.
Keywords: Children; Prevention; Pulmonary Tuberculosis; Treatment

1. Context
Most children with TB infection develop no signs or
symptoms at any time. Sometimes, the beginning of infection is stated by several days of low grade fever and a
mild cough. Rarely, the child presents a clinically important disease with high fever, cough, and flul ike symptoms that ameliorate approximately within a week (1-5).
The majority of children who develop tuberculosis disease experience pulmonary manifestations, but 25 to 35
% of children have an extra pulmonary (EPTB) presentation. The most common extra pulmonary form of tuberculosis is lymphatic which accounting for about two
thirds of all cases of EPTB. The second most common
form is meningeal form arising in 13% of children with
TB (1, 2). The clinical and physical manifestations of disease tend to be different by the age of onset of disease.
Pre-school children and adolescents are more likely to
have significant signs or symptoms, whereas school-age
children often have clinically silent disease (1, 4-10). Half
of young children with radiographically moderate to
severe pulmonary TB dont have any symptoms or physical findings and, mainly, are detected by contact tracing
of an adult with pulmonary TB. Infants also, are more
likely to experience clinical manifestations of TB, maybe

due to small airway diameters. Non-productive cough

and mild dyspnea are the most common symptoms in
this age group. Systemic complaints such as anorexia, fever, and night sweats occur less common. Some infants
have difficulty in getting weight and growing up. Some
infants and young children with bronchial obstruction
show localized wheezing or decreased breath sounds
that may be accompanied by tachypnea or respiratory
distress (1, 4-9). In pediatric pulmonary tuberculosis,
the radiographic hallmark is the relatively large size and
importance of lymphadenopathy compared with the
less significant size of the parenchymal infiltration. The
best specimen for diagnosis of pulmonary TB in a child
is the early morning gastric lavage (11, 12). Unfortunately, three gastric aspirates detect M. tuberculosis in less
than 50% of cases and a negative culture never excludes
the diagnosis of PTB in a child. Fortunately, the need
for culture confirmation is usually low. If the child has
a positive tuberculin skin test, clinical or radiographic
findings suggestive of tuberculosis, and known contact
with an smear positive pulmonary tuberculosis, the
child should be treated for tuberculosis disease (1, 13-16).
Treatment methods are like adults and in any patient
with HIV drug susceptibility test should be carried out.

Copyright 2014, Infectious Diseases and Tropical Medicine Research Center. This is an open-access article distributed under the terms of the Creative Commons
Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Keshtkar Jahromi M et al.

2. Evidence Acquisition
Electronic databases (PubMed, scopus) were searched
from June1995 to May 2014 by using key words (pulmonaryTB, epidemiology, transmission, clinical manifestations, treatment, control, and prophylaxis).

3. Results

We found major risk factors, transmission and prevention routes, clinical manifestations, diagnosis methods
and treatment as below:

3. 2. Transmission

Tuberculosis is transmitted from an infected person

to a child and a susceptible person by airborne particles
(droplet nuclei). These are 15 microns in diameter. These
infectious droplet nuclei are released when persons with
pulmonary or laryngeal tuberculosis cough, sneeze, or
laugh, Droplet nuclei remain suspended in the air for
up to several hours (1, 2, 6-10). Patients with high loads
of bacteria in their sputums are more likely to transmit
the infection than those with a low numbers of bacteria.
Persons who show presence of cavities in the lungs on
chest-X rays, or have a positive sputum test and have a
cough lasting two to three weeks or more, are more likely
to transmit the infection to others (1, 12). Also, patients
with laryngyal involvement, those who fail to cover their
mouth and nose while coughing or sneezing and those
are not on appropriate and inadequate medication can
transmit the infection more to susceptible close contacts.
Young children with pulmonary and laryngeal tuberculosis are less likely than adults to be infectious (1, 6, 9, 12).

3. 3. Clinical Manifestations

TB in children is a direct consequence of adult TB and

is a good marker of current transmission in the community. The two main factors detecting the risk of progression to disease are patients age and immune status (4-9).
Neonates are at higher risk of progression of infection to
disease, with higher rate of military TB and meningeal involvement. Children between 5 to 10 years are less likely
to develop disease than other age groups, and adolescent
patients can present with progressive primary pulmonary tuberculosis or cavitary disease (1, 3, 9). Children
with AIDS and TB most frequently present with an atypical presentation. The majority of children with tuberculosis infection develop no signs or symptoms at any time.
Occasionally, the initiation of the infection is marked by
several days of low grade fever and mild cough. Rarely,
the child experiences a clinically significant disease with
high fever, cough, malaise, and flulike symptoms that resolve within a week.

3. 4. Diagnosis

A major challenge of pediatric TB is making an accurate diagnosis. Less than 15% of children with TB have
2

a positive sputum smear and mycobacterial culture

detects the bacilli in 30%40% (1, 2, 6). In the absence of
bacteriological confirmation, the diagnosis of childhood TB in countries where TB is endemic is based on
close contact with an infectious patient, a positive tuberculin skin test, presence of suggestive clinical signs
and syptoms, and or abnormalities on a chest-X ray
(17-20). Chest radiograph findings may be normal for
a significant proportion of children with confirmed
pulmonary TB. Collecting an adequate sample for microbiological studies feces with a significant challenge,
particularly about children less than 6 years who cannot produce a good sputum specimen (9, 10, 12). The
best specimen for diagnosis of pulmonary TB in a child
is the early morning gastric lavage which obtained before the child has uparisen and peristalsis has emptied
the stomach of the pooled secretions that have been
swallowed within night. Unfortunately, less than 15%
of children with TB have a positive sputum smear and
three gastric aspirates detect M. tuberculosis in less
than 50% of cases on culture medium. Bacteriologic
confirmation is common in adolescents and in infants
and children with extensive parenchymal involvement
(14-16). Although, culture on Lowenstein-Jensen medium is considered to be the gold standard, but,liquid
culture systems can give more rapid and more sensitive diagnosis of active TB and drug susceptibility. This
method is not widely available in poor countries where
the TB rate is high (8, 9, 12). Serum-based antibody also
is an easy and rapid way for diagnosis, but, none of the
currently available serologic tests are sensitive or specific enough for clinical use. Polymerase chain reaction
(PCR) has shown variable sensitivity in various studies,
and a negative result does not rule out TB. Conversely, a
positive test could occur from cross-contamination of
specimens when high standards of laboratory biosafety
are not observed. Today, PCR is useful for species identification, molecular epidemiology, and rapid detection of drug resistance (1, 12). The tuberculin skin test
(TST) is a widely used as a diagnostic test for evaluation
of patients who have symptoms of tuberculosis or in
those infections with M tuberculosis is suspected. The
sensitivity and the specificity of the TST is about 90% .Efforts are making to develop tests based on detection
of antigens, such as lipoarabinomannan in urine or
serum samples, and detection of interferon- production by sensitized mononuclear cells on stimulation by
specific M. tuberculosis antigens ESAT-6 and CFP-10 is an
alternative to TST (12-18). This test (interferon- release
assays) has not been detected to have a major advantages over the TST in terms of sensitivity or specificity
and is more expensive; although, it does not require a
second patient visit, and they reduce the chances of human error in interpretation. New tests such as antigen
detection could mainly play a role in detection of TB in
HIV-infected or malnourished children, however, they
require to further evaluation (12, 18, 19).
Int J Infect. 2014;1(3):e21116

Keshtkar Jahromi M et al.

3. 5.Treatment
Two treatment categories recommend for the treatment of pulmonary TB in children (1, 3, 8, 9) are as fllows:
1- A 6-month course of isoniazid (INH) and rifampin
(RIF), supplemented during the first 2 months with pyrazinamide (PZA). Ethambutol (ETB) or streptomycin (STM)
(in children who are too young to be monitored for visual
acuity) may need to be included in the initial regimen until the results of drug susceptibility are available.
2-Another treatment option is a 2-month regimen of
INH, rifampin, and pyrazinamide daily, followed by 4
months of high dose of INH and rifampin twice a week.
Drug susceptibility is not required if the risk of drug
resistance is not hight. Significant risk factors for drug resistatce include; residence in an area with greater than 4%
primary resistance to INH, history of previous treatment
with anti-TB drugs, history of exposure to a drug-resistant
patient, and origin in a country with a high prevalence
of drug resistance (2-6). Drug-resistant organisms occur
approximately 10-6; however, individual resistance may
be different. The resistance to streptomycin is 10-5, INH
is 10-6, and rifampin is 10-8. Therefore, chance that an organism is naturally resistant to both INH and rifampin is
on the order of 10-14. Some people have a poor adherence
to their regimens and it has a major role in treatment failure, so directly observed therapy (DOT) is recommended
for treatment of TB. DOT means a responsible person like
as health care provider must watch the patient taking the
medications. DOTS-plus strategy, is based on finding suitable strategies for treatment of MDR TB (resistant to INH
and RIF) and drug susceptibility testing, as well as judicious usage of second-line drugs (9, 10).

3. 6. Prevention
The key method of preventing tuberculosis (TB) is
prompt identification and treatment of patients with TB.
Other strategies include patient education, treatment of
latent infection, and vaccination.
Patient education; Patients should be educated regarding compliance to therapy, drugs side effects, and followup care.
Treatment of latent TB infection
The risk of acquisition of TB following primary infection is high in very young children (< 5 y) and in the adolescent population. Thus, patients in these age groups
with a positive TST especially when they are in close contact with a smear positive PTB and no other clinical manifestations should receive INH prophylaxis (21, 22). Active
TB should be excluded before the initiation of preventive
therapy. Adults with a positive TST and no other clinical or
radiographic manifestations who are receiving INH therapy have been reported to have 54-88% protection against
the development of infection to the disease, whereas
children have been shown to have 100% protection (1, 3, 4,
23, 24). When you are faced with MDR-TB (Multiple drug
resistance), observation is recommended, because these
Int J Infect. 2014;1(3):e21116

drugs are not effective for this kind of infection (3, 4, 2427). Several drugs have been tried in these circumstances,
including PZA, fluoroquinolones, and ETB, depending
on the susceptibility patterns. For recent contacts of
patients with contagious TB (in the last 3 months), INH
therapy is indicated even if the TST result is negative. This
is especially true for contacts who are infected with HIV
or for household contacts younger than 5 years (4-7, 25,
28).Some countries have an especial guidelines for preventin, For example, in Iran all children younger than
6 years with a TST more than 6 mm and a history with a
contagious case should receive INH for 6 months if they
do not have the disease. Also, all HIV patients and IVDUs
with a TST more than 5 mm with a history of close contact
with a patient with contagious form should receive INH
for 9 months (26).

3.7. Vaccination
The bacille Calmette-Gurin vaccine (BCG) is available
for the prevention of disseminated TB. BCG is a live vaccine prepared from attenuated strains of Mycobacterium. bovis. The important role of BCG vaccination is
the prevention of serious disease such as disseminated
TB and meningitis among children(26-29). BCG vaccine
does not prevent infection with M tuberculosis. From
birth time to age 2 months, administration of BCG does
not require a previous TST. Thereafter, a TST is mandatory before vaccination. Contraindications for the vaccine include immunosuppressed conditions such as
primary or secondary immunodeficiency, high dose
steroid use and HIV infection(29-31). However, in the
countries of the world where the risk of TB is very high,
WHO recommends using BCG vaccine in children who
have asymptomatic HIV infection.Adverse reactions due
to the vaccine include subcutaneous abscess formation and lymphadenopathy. Rare complications, such
as osteitis of the long bones and disseminated TB, may
necessitate administration of anti-TB therapy, except for
PZA because M,bovis has an natural resistance to this
drug(31-35).

3.8. Prevention in Especial Situations

3.8.1. Mother has Current Disease but is Noncontagious at Delivery

In this situation, separation of the mother and infant is
not necessary, and the mother can breastfeed her baby.
Evaluation of the infant includes chest radiography and
TST at age 4-6 weeks is recommended. INH should be
administered even if the TST result and chest radiography do not suggest TB, because cell-mediated immunity
(CMI) is not enough until age 6 months to prevent progressive disease (26, 31-34). According Iranian guid-line,
vaccination is recommended in this child and separation
of the mother and infant is not necessary and mother can
breastfeed her baby.
3

Keshtkar Jahromi M et al.

3.8.2. Mother has Current Disease and is Contagious at Delivery

Separation of the mother and infant is recommended
until the mother is noncontagious. The rest of the management is the same as for the mother with current disease but who is noncontagious at delivery. According to
guid- line in Iran, separation of the mother and infant is
not necessary, and the mother can breastfeed her baby.
But, in this situation the child should receive INH for 6
months (26).

15.

16.
17.

4. Conclusions

18.

The results of the present review suggest the utility of

the systematic study of household pediatric contacts for
early detection and suitable prevention of infection by
Mycobacterium.TB. Development in new vaccines, better
diagnostics methods, and shorter duration of treatment,
can be improved the tuberculosis outcomes in the world.

19.

Authors Contribution
Maryam Keshtkar Jahromi and Batool Sharifi-Mood
wrote the manuscript.Two authors had an equal role in
the writing of paper.

20.
21.
22.

23.

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