71

JOURNAL OF PREVENTIVE MEDICINE AND HYGIENE 2002; 43: 71-74

REVIEW
Tuberculosis in children
R. GIACCHINO, G. LOSURDO
Infectious Diseases Unit. Giannina Gaslini Childrens Hospital. Genoa, Italy
Key words
tubercolosis children
Introduction
From the second half of the 80s, the cases of tuberculo-
sis (TBC) in Italy have been constantly increasing, with
an incidence of 15-25:100,000 people. TBC infection,
expressed as positivity to tuberculin test in index popu-
lations as students and soldiers, increased from 5% in
1987 to 13% in 1995
1
. This increase in TBC cases in de-
veloped countries is related to different factors, inclu-
ding HIVepidemic and increased number of immigrants
from countries with high TBC incidence and important
socio-economic problems.
These observations were confirmed by an epidemiologic
study carried out from December 2000 to November
2001 in the Infectious Diseases Department of Gaslini In-
stitute of Genoa, Italy
2
, in order to evaluate the impact of
TBC infection in immigrant children. Mantoux test (5 IU)
was performed in 60 of 114 immigrant children hospitali-
zed or followed at Gaslini Institute. They included 40 ma-
les and 20 females, mean age 4 years (range 1 month to
15 years). Thirty-four (57%) patients came from South
America, especially from Ecuador (88%), 11 from Ea-
stern Europe (18%), 9 from Middle East and North Afri-
ca (15%), 4 from equatorial Africa (7%), 2 from Far East
(3%). In 50 (83%) out of 60 children was Mantoux test
negative, while in 10 cases (17%) it was positive. Among
these latter, 5 had tuberculous disease with pulmonary lo-
calization and one of them associated with cervical ade-
nopathy, whereas another 5 were infected. In the study
period, among children admitted to our Department, the
prevalence of tuberculous disease was 4.3% in immigrant
children compared 0.4% in native children.
Methods
The following international classification (3, 4, 5) was
used to evaluate TBC even in the pediatric patient:
TBC exposure: significant contact with a suspected
or confirmed case of contagious pulmonary TBC. At
this stage, skin test, chest X-ray, and clinical picture
are negative or normal;
TBC infection: positive reaction to tuberculin skin
test (Mantoux), with no radiographic evidence of
TBC, and/or negative bacteriologic studies;
TBC disease: clinical and/or radiographic evidence
of TBC disease or presence of positive culture for M.
tuberculosis.
Mantoux skin test (5 IU) remains the standard method to
identify M. tuberculosis infection even in children, whe-
reas tine test is not sensitive enough for evaluation of in-
fection in pediatric patients. The interpretation of Man-
toux test misuring diameter of the induration, depends
on the different clinical and epidemiologic conditions.
In particular, a reaction > 5 mm is classified as positive
for the following groups:
contact with suspected or known TBC patients;
children with suspected TBC disease:
chest X-ray compatible with TBC;
clinical signs of TBC;
immunocompromised children for therapy or disease
(HIV infection, diabetes, cancer, chronic renal failure,
malnutrition, etc.);
Areaction of 10 mm is classified as positive in all the
other children.
increased risk of environmental exposure to TBC:
children born in (or with parents coming from) highly
endemic regions;
frequent exposure to adults with HIV infection, home-
less, intravenous drug addicts, nursing home residents,
prisoners or institute residents, seasonal farm labourers;
traveling and/or exposure in world areas with high
prevalence.
In case of contact with contagious or suspected subjects,
the diagnostic and therapeutic procedures to perform are
reported in Table I.
Summary
The increase in TBC casesi n developed countries is related to
different factors, including HIV epidemic and increased num-
ber of immigrants from countries with high TBC incidence and
important socio-economic problems. An epidemiologic study
was carried out from December 2000 to November 2001 in the
infectious diseases department of Gaslini Childrens Hospital.
Mantoux test was performed in 60 of 114 immigrant children hos-
pitalized or followed at Gaslini Institute.
The prevalence of tuberculosis disease was 4.3% in immigrant
children compared to 0.4 in native children.
R. GIACCHINO, ET AL.
72
Clinical aspects
Pediatric TBC presents some peculiar microbiologic
and clinical features. TBC presents a lower contagiou-
sness in pediatric age: children are less likely to cough
and produce sputum and cavity in lung is unusual.
Evolution of TBC infection towards disease is more fre-
quent and clinical course is more rapid, especially in
children aged less than 5 years.
There is a higher incidence of severe extrapulmonary
forms, whereas the radiological picture of lung disease
often does not show the specific features of adult pa-
tients.
The majority of infected children with positive reaction
to tuberculin are asymptomatic.
The most frequent manifestations differ according to
age (Table II).
Children aged less than 1 year, often presenting negati-
ve Mantoux test (60% of cases), are at higher risk of de-
veloping severe and extrapulmonary forms.
In particular, different clinical pictures can be observed
at that age:
miliary: cough, fever, malaise, weight loss, hepato-
splenomegaly, lymphadenopathy, respiratory di-
stress with typical chest X-ray picture (miliary
90%);
meningitis: fever, headache, irritability, vomiting,
lethargy, nucal rigidity, seizures, meningeal irrita-
tion with typical results of cerebrospinal fluid
(CSF) analysis: clear CSF, leukocyte count: 50-
500/mmc, increased proteins, low glucose (19-35%
of cases);
encephalitis: rare but severe (exitus 15-30% of ca-
ses);
lymphadenitis: superficial associated with paratra-
cheal and supraclavicular lymphadenitis. The
lymph nodes not painful, unilateral progressively
increase in size and evolve to colliquation and fi-
stulization.
In the older child lung TBC infections are most fre-
quent. The most common radiologic aspects are the fol-
lowing: Hilar adenopathy, Obstructive emphysema, Pe-
rifocal infiltrate, Focal bronchial pneumonia, Bronchial
obstruction, Adenobronchial fistula, Atelectasis, Pleuri-
tis, Lobar pneumonia, Acute pulmonary miliary.
Other less frequent localizations, that can appear even
12 months or more after initial infection, include midd-
le ears, mastoids, bones, and joints. Renal tuberculosis
and post-primary pulmonary tuberculosis are rare in
children, but can appear in adolescents
6
.
Diagnostic aspects
Diagnosis of TBC disease is based on different parame-
ters, namely:
family history (contact with suspected or known
TBC cases);
compatible clinical picture;
Tab. I. Management of tuberculosis in pediatric age
Mantoux test 5 IU positivity with reaction > 5 mm
YES NO
Chest X-ray Chest X-ray
Negative Positive Negative
Preventive chemotherapy Diagnosis and treatment
for 6 months Preventive chemotherapy
Mantoux test 5 IU After 3 months
POSITIVE NEGATIVE
Chest X-ray
Negative Positive Suspension of therapy
Preventive chemotherapy Diagnosis and
for overall 6-9 months treatment Vaccine when necessary
Tab. II. Tubercolosis in children: age and disease localization
SITE CASES (%) MEAN AGE (YRS)
Pulmonary 77.5 6
Lymphatic 13.3 5
Pleural 3.1 16
Meningeal 1.9 2
Bone/Joint 1.2 8
Other 1.0 12
Miliary 0.9 1
Genitourinary 0.8 16
Peritoneal 0.3 13
Modified by Starke JR. J Pediatr, 1989
73
TUBERCULOSIS AND HIV INFECTION
imaging diagnosis (chest X-ray, chest CT, broncho-
scopy);
skin tuberculin reaction;
identification of Mycobacterium tuberculosis by mi-
croscopic examination (Ziehl-Neelsen method), cul-
ture test or DNA probes.
In the young child and in the frequent case of absent or
non productive cough, the sample of choice for culture
is gastric aspirate obtained early in the morning for th-
ree consecutive days. Aspirates should be obtained th-
rough nasogastric tube on child awakening, before get-
ting up and having breakfast, in order to use bronchial
secretions swallowed during the night.
Bronchial secretions can also be sampled by bronchoal-
veolar lavage
6
.
Therapeutic aspects
Therapy is correlated with different clinical and epide-
miological situations:
exposed children, especially when aged less than 5
years, should immediately undergo prophylaxis, sin-
ce TBC incubation period during preschool age can
be very short (6-8 weeks). In our country, characteri-
zed by low resistance levels, Isoniazid remains the
drug of choice. Duration of prophylaxis should be 3
months from the last contact with the index case. If
Mantoux test remains negative after this period,
prophylaxis should be suspended. Conversely, in ca-
se of positivity, the child should be reevaluated and
treated as an infected patient;
Tab. III. Therapy of pediatric tuberculosis
DISEASE REGIMENTS
Pulmonary
6 months
Extrapulmonary (except for miliary, meningeal
and Osteoarticular 2 months: Isoniazid + Rifampin + Pyrazinamide
4 months: Isoniazid + Rifampin
Meningeal 9-12 months
Miliary 2-3 months: Isoniazid + Rifampin + Pyrazinamide + Streptomycin
Osteoarticular 7-10 months: Isoniazid + Rifampin
Suspected drug resistence: add Etambutol and/or Streptomycin
Further treatment period according to clinical, radiologic and laboratory data
Tab. IV. Pediatric doses of antituberculosis drugs
DRUG DOSAGE (mg/kg/die) MAX DOSE SIDE EFFECTS
Isoniazid 5-10 300 mg Liver Toxicity
Peripheral neuropathy
Hypersensitivity
Seizures, psychosi
Rifampin 15-20 600 mg Liver Toxicity
Thrombocytopenia
Drugs interaction
Pyrazinamide 15-30 2 g Liver Toxicity
Hyperuricemia
Streptomycin 20-25 1 g Ototoxicity
Nephrotoxicity
Ethambutol 15-25 2.5 g Optic neuritis
Red/green discrimination
Gastrointestinal disorders
Hypersensitivity
R. GIACCHINO, ET AL.
74
infected children, following the classification men-
tioned above, should undergo preventive chemothe-
rapy. In fact the child infections are supposed to be
recent and adequate treatment can reduce the risk of
TBC disease evolution in 90% of cases. To this pro-
posal Isoniazid therapy should be administered for 6-
9 months. In case of documented or suspected resi-
stance, Rifampin or Rifampin plus Isoniazid should
be administered for 6 months;
children with TBC disease should follow the treat-
ment program classically validated in the general ex-
perience and in the literature (Table III). Dosage
should be scrupulously followed and side effects
should be evaluated (Table IV).
Accurate epidemiologic monitoring, further clinical stu-
dies aimed at highlighting TBC peculiar aspects in chil-
dren, and adequate therapy can lead to TBC control in
the child
3 5 7-9
.
References
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I Correspondence: Dr. Raffaella Giacchino, MD, Infectious Disea-
ses Unit, G. Gaslini Childrens Hospital, Largo G. Gaslini 5,
16147 Genoa (Italy) - Tel. +39 010 5636220 - Fax +39 010
3776590 - E-mail: raffaellagiacchino@ospedale-gaslini.ge.it