Beruflich Dokumente
Kultur Dokumente
SUMMARY
About one million children develop tuberculosis (TB) an- Specifically regarding the diagnosis of TB in children,
nually worldwide, accounting for about 11% of all TB this relies on a careful and thorough assessment of all the
cases. Children with TB differ from adults in their immu- evidence derived from a careful history, clinical examina-
nological and pathophysiological response in ways that tion and relevant investigations, e.g., tuberculin skin test,
may have important implications for the prevention, di- chest radiograph and sputum smear microscopy. Although
agnosis and treatment of TB in children. There is an urgent bacteriological confirmation of TB is not always pos-
need to improve the diagnosis and management of chil- sible, it should be sought whenever possible, e.g., by spu-
dren with TB, and the prevention of TB in children, by tum microscopy in children with suspected pulmonary
ensuring their inclusion under the implementation of the TB who are old enough to produce a sputum sample. A
Stop TB strategy by National TB Programmes. Critical trial of treatment with TB medications is not generally
areas for further research include a better understanding recommended as a method to diagnose TB in children.
of the epidemiology of childhood TB, vaccine develop- New, improved diagnostic tests are urgently needed.
ment, the development of better diagnostic techniques, K E Y W O R D S : tuberculosis; children; diagnosis
new drug development, and the optimal formulations
and dosing of first- and second-line TB drugs in children.
IT IS ESTIMATED that one third of the worlds pop- (Ghon focus) in the lung with spread to the regional
ulation is infected with Mycobacterium tuberculosis lymph node(s). In the majority of cases, the resultant
(the bacterium that causes tuberculosis, or TB), and that cell-mediated immunity contains the disease process
each year, about 9 million people develop TB, of whom at this stage. Risk of disease progression is increased
about 2 million die. Of the 9 million cases of TB world- in the very young (3 years old) and in immune com-
wide that occur annually, about 1 million cases (11%) promised children. Progression of disease occurs by 1)
occur in children 15 years of age. Seventy-five per extension of the primary focus with or without cavi-
cent of these childhood cases occur annually in 22 tation; 2) the effects of pathological processes caused
high-burden countries that together account for 80% by the enlarging lymph nodes or by 3) lymphatic and/
of the worlds estimated incident cases. The reported or haematogenous spread.
percentage of all TB cases occurring in children varies Implementation of the Stop TB Strategy1 (see Table
from 3% to more than 25% in different countries. 1), which builds on the DOTS strategy2 developed by
Infection with M. tuberculosis usually results from the World Health Organization (WHO) and the Inter-
inhalation into the lungs of infected droplets pro- national Union Against Tuberculosis and Lung Disease
duced by someone who is coughing and who has pul- (The Union), has a critical role to play in reducing the
monary TB disease. The source of infection of most worldwide burden of disease and thus in protecting
children is an infectious adult in their close environ- children from infection and disease. The management
ment (usually the household). This exposure leads to of children with TB should be in line with the Stop TB
the development of a primary parenchymal lesion Strategy, taking into consideration the particular epi-
demiology and clinical presentation of TB in children.
Adapted from: World Health Organization. Guidance for national
The International Standards for TB Care,3 WHOs
tuberculosis programmes on the management of tuberculosis in chil- TB treatment guidelines4 and WHOs TB/HIV clinical
dren. WHO/HTM/TB/2006.371. Geneva, Switzerland: WHO, 2006. manual5 provide useful guidance for patients of all
Correspondence to: Dermot Maher, Stop TB Department, World Health Organization, Geneva, Switzerland. Tel: (41) 22
791 2655. Fax: (41) 22 791 4268. e-mail: maherd@who.int
[A version in French of this article is available from the Editorial Office in Paris and from the Union website www.iuatld.org]
1092 The International Journal of Tuberculosis and Lung Disease
Table 1 Components of the Stop TB Strategy and Table 2 Recommended approach to diagnose TB in children
implementation approaches
1 Careful history (including history of TB contact and symptoms
1 Pursue high-quality DOTS expansion and enhancement consistent with TB)
Political commitment with increased and sustained financing 2 Clinical examination (including growth assessment)
Case detection through quality-assured bacteriology 3 Tuberculin skin testing (TST)
Standardised treatment with supervision and patient support 4 Bacteriological confirmation whenever possible
An effective drug supply and management system 5 Investigations relevant for suspected 1) pulmonary TB, and
Monitoring and evaluation system, and impact measurement 2) extra-pulmonary TB
2 Address TB-HIV, MDR-TB and other challenges 6 HIV testing (in high HIV prevalence areas)
Implement collaborative TB-HIV activities TB tuberculosis; HIV human immunodeficiency virus.
Prevent and control multidrug-resistant TB
Addressing prisoners, refugees and other high-risk groups and
special situations ther research include a better understanding of the ep-
3 Contribute to health system strengthening idemiology of childhood TB, vaccine development,
Actively participate in efforts to improve system-wide policy,
human resources, financing, management, service delivery the development of better diagnostic techniques, new
and information systems drug development and the optimal formulations and
Share innovations that strengthen systems, including the dosing of first- and second-line TB drugs in children.
Practical Approach to Lung Health
Adapting innovations from other fields
4 Engage all care providers DIAGNOSIS OF TUBERCULOSIS IN CHILDREN
Public-public and public-private mix (PPM) approaches
International Standards for TB Care (ISTC) The diagnosis of TB in children relies on careful and
5 Empower people with TB and communities thorough assessment of all the evidence derived from
Advocacy, communication and social mobilisation a careful history, clinical examination and relevant in-
Community participation in TB care
Patients Charter for Tuberculosis Care vestigations, e.g., the tuberculin skin test (TST), chest
6 Enable and promote research radiograph (CXR) and sputum smear microscopy. Al-
Programme-based operational research though bacteriological confirmation of TB is not al-
Research to develop new diagnostics, drugs and vaccines ways possible, it should be sought whenever possible,
TB tuberculosis; HIV human immunodeficiency virus; MDR-TB multi- e.g., by sputum microscopy in children with suspected
drug-resistant tuberculosis. pulmonary TB who are old enough to produce a spu-
tum sample. A trial of treatment with TB medications
ages. The guidelines developed by the childhood TB is not recommended as a method of diagnosing TB in
subgroup are designed to complement current na- children. The decision to treat a child should be care-
tional and international guidelines on the implemen- fully considered, and once such a decision is made, the
tation of the Stop TB Strategy and existing guidelines, child should be treated with a full course of therapy.
but also to fill existing gaps to ensure that children Most children with TB have pulmonary TB. The
with M. tuberculosis infection and TB disease are proposed approach to the diagnosis of TB in children
identified early and managed effectively. (see Table 2) is based on limited published evidence
The human immunodeficiency virus (HIV) epidemic and rests heavily on expert opinion.
threatens TB control efforts, particularly in Africa. In most immunocompetent children, TB presents
Children are at risk of HIV, and HIV-infected children with symptoms of a chronic disease after they have
are at risk of TB. These guidelines thus also include rec- been in contact with an infectious source case. Infec-
ommendations for HIV-infected children. tion with M. tuberculosis can be demonstrated by a
For National TB Programmes (NTPs) to success- TST, and CXR changes typical of TB are usually
fully manage TB in children, standardised approaches present. The presentation in infants may be more acute,
based on the best available evidence are required. The resembling acute severe pneumonia, and should be
engagement of all who provide care to children (in- suspected when there is poor response to antibiotics.
cluding paediatricians and other clinicians) is crucial. There is often an identifiable contact, usually the in-
These standardised approaches need to be incorpo- fants mother, in this situation. Table 3 shows key fea-
rated into existing guidelines and strategies that have tures suggestive of TB, and Table 4 key risk factors.
been developed by NTPs. Reducing the burden of TB Existing diagnostic tests for TB in children have
in children will require changing and improving many shortcomings, and the full range of tests (including
existing practices, such as those that relate to contact bacteriology and TST) may not be readily accessible
investigations. in settings where the vast majority of TB cases are di-
These guidelines are based on the best available ev- agnosed. The development of affordable diagnostic
idence. However, epidemiological data on TB in chil- tests for TB in children in low-resource settings should
dren in high-burden countries are scarce. Children with be a priority for researchers and policy makers.
TB differ from adults in their immunological and Some countries and NTPs use score charts for the
pathophysiological response in ways that may have diagnosis of TB in children, although these have
important implications for the prevention, diagnosis rarely been evaluated and validated against a gold
and treatment of TB in children. Critical areas for fur- standard. They should therefore be used as screening
Diagnosis of tuberculosis in children 1093
Table 3 Key features suggestive of TB Fever: of 38C for 14 days after common
causes such as malaria or pneumonia have been
The presence of three or more of the following should strongly
suggest the diagnosis of TB excluded.
Chronic symptoms suggestive of TB Weight loss or failure to thrive: always ask about
Physical signs highly of suggestive of TB weight loss or failure to thrive and look at the
A positive tuberculin skin test
Chest radiograph suggestive of TB childs growth chart.
TB tuberculosis.
Clinical examination
(including growth assessment)
Table 4 Key risk factors for TB
There are no specific features on clinical examination
Household contact with a newly diagnosed smear-positive case that can confirm that the presenting illness is due to
Age 5 years pulmonary TB. Some signs, although uncommon, are
HIV infection
Severe malnutrition highly suggestive of extra-pulmonary TB and the
threshold to initiate treatment should be lower. Other
TB tuberculosis; HIV human immunodeficiency virus.
signs are common and should initiate investigation as
to the possibility of childhood TB.
tools and not as a means of making a firm diagnosis.
1 Physical signs highly suggestive of extra-pulmonary
Score charts perform particularly poorly in children
TB:
suspected of pulmonary TB (the most common form)
and in children who are also HIV-infected. Gibbus, especially of recent onset (vertebral TB)
Non-painful enlarged cervical lymphadenopathy
Recommended approach to diagnose TB in children with fistula formation.
Careful history (including history of TB contact
2 Physical signs requiring investigation to exclude
and symptoms consistent with TB)
extra-pulmonary TB:
1 Contact: A close contact is defined as living in the
same household or in frequent contact with a Meningitis not responding to antibiotic treat-
source case (e.g., care giver) with sputum smear- ment, with a sub-acute onset or raised intracra-
positive TB. Source cases who are sputum smear- nial pressure
negative but culture-positive are also infectious, Pleural effusion
but to a much lesser degree. Pericardial effusion
The following points concerning contact are of Distended abdomen with ascites
importance for children: Non-painful enlarged lymph nodes without fis-
tula formation
Children (especially those 5 years of age) who Non-painful enlarged joint
have been in close contact with a case of smear- Signs of tuberculin hypersensitivity: phlyctenu-
positive TB must be screened for TB (see Chapter lar conjunctivitis, erythema nodosum.
4 of this series: Childhood contact screening and
managementto appear January 2007). Documented weight loss or failure to gain weight,
After TB is diagnosed in a child or adolescent, an especially after being treated in a nutritional rehabili-
effort should be made to detect the adult source tation programme, is a good indicator of chronic dis-
cases, and especially other undiagnosed house- ease in children, and TB may be the cause.
hold cases.
If a child presents with infectious TB, then child- Tuberculin skin test
hood contacts must be sought and screened as for A positive TST occurs when a child is infected with
any smear-positive source case. Children should M. tuberculosis. However, in children, TST can also
be regarded as infectious if they are sputum smear- be used as an adjunct in diagnosing TB disease, when
positive or have a cavity visible on CXR. it is used in conjunction with signs and symptoms
2 Symptoms: Children with symptomatic disease of TB and other diagnostic tests. There are a number of
develop chronic symptoms in most cases. The com- TSTs available, but the Mantoux skin test is the rec-
monest symptoms are chronic, unremitting cough, ommended test.
fever and weight loss. The specificity of symptoms
1 Using the test: The TST should be standardised for
for the diagnosis of TB depends on how strict the
each country using either 5TU (tuberculin units) of
definitions of the symptoms are.
tuberculin purified protein derivative (PPD) S or 2
Chronic cough: an unremitting cough that is not TU of tuberculin PPD RT23, as these give similar
improving and has been present for 21 days (3 reactions in infected children. Health care workers
weeks). must be trained in performing and reading a TST
1094 The International Journal of Tuberculosis and Lung Disease
* Appendix A (Placement and interpretation of tuberculin skin Appendix B (Procedures for obtaining sputum specimens) can be
test) is available on request from the corresponding author. obtained on request from the corresponding author.
Diagnosis of tuberculosis in children 1095
Table 5 Common forms of extra-pulmonary TB in children conditions, and in TB patients with a history sugges-
tive of high risk of HIV exposure.
Site Practical approach to diagnosis
Peripheral lymph nodes Lymph node biopsy or fine needle
(especially cervical) aspiration (FNA) Standardised case definitions of TB in children
Miliary TB CXR The diagnosis of TB refers to the recognition of an
(e.g., disseminated)
TB meningitis Lumbar puncture (and CT where active case, i.e., a patient with symptomatic disease
available) due to M. tuberculosis. Beyond the diagnosis of TB
Pleural effusion (older Chest radiograph, pleural tap for disease, the type of TB case should also be defined
children and adolescents) chemistry and culture
Abdominal TB Abdominal ultrasound and ascitic tap to enable appropriate treatment to be given and the
(e.g., peritoneal) outcome of treatment evaluated. The case defini-
Osteoarticular Radiograph, joint tap or synovial tion is determined by: 1) site of disease, 2) result of
biopsy
Pericardial TB Ultrasound and pericardial tap any bacteriology, 3) severity of TB disease, and 4)
history of previous TB treatment. All children with
TB tuberculosis; CXR chest X-ray; CT computed tomography.
TB should be registered with the NTP as smear-
positive pulmonary, smear-negative pulmonary TB,
Adolescent patients with TB have CXR changes or extra-pulmonary TB, and as a new case or a previ-
similar to adult patients, with large pleural effusions ously treated case. The standard case definitions are
and apical infiltrates with cavity formation being the following:
the most common forms of presentation. Adoles-
cents may also develop primary disease, with hilar 1 Pulmonary tuberculosis, sputum smear-positive:
adenopathy and collapse lesions visible on CXR.
Two or more initial sputum smear examinations
Chest radiography is useful in the diagnosis of
positive for AFB, or
TB in children, and CXRs should preferably be read
One sputum smear examination positive for AFB
by a radiologist or a health care worker trained in
plus radiographic abnormalities consistent with
their reading. Good quality CXRs are essential for
active pulmonary tuberculosis as determined by
proper evaluation. A practical guide for interpret-
a clinician, or
ing CXRs has been developed (available at www.
One sputum smear positive for AFB plus sputum
iuatld.org).6
culture positive for M. tuberculosis.
2 Relevant for suspected extra-pulmonary TB: Table 5
Children with smear-positive disease are more
shows the usual investigations used to diagnose the
likely to be adolescent patients or children of any
common forms of extra-pulmonary TB. In most of
age with severe intrathoracic disease.
these cases, TB will be suspected from the clinical
picture and confirmed by histology or other special 2 Pulmonary tuberculosis, sputum smear-negative: A
investigations. case of pulmonary TB that does not meet the above
definition for smear-positive TB. This group in-
3 Other tests: Serological and nucleic acid amplifica-
cludes cases without smear result, which should be
tion (e.g., polymerase chain reaction [PCR]) tests
exceptional in adults but are relatively more fre-
are not currently recommended for the routine
quent in children.
diagnosis of childhood TB, as they have been inad-
In keeping with good clinical and public health
equately studied in children and they have per-
practice, diagnostic criteria for pulmonary TB should
formed poorly in the few studies that have been
include:
done. However, this is an area that requires further
research, as they may prove to be useful in the At least three sputum specimens negative for AFB,
future. and
Other specialised tests, such as computerised Radiographic abnormalities consistent with active
chest tomography and bronchoscopy, are not pulmonary TB, and
recommended for the routine diagnosis of TB in No response to a course of broad spectrum anti-
children. biotics, and
Decision by a clinician to treat with a full course
HIV testing of tuberculosis chemotherapy.
In areas with a high prevalence of HIV infection in
the general population where TB and HIV infection 3 Extra-pulmonary TB: Children with only extra-
are likely to co-exist, HIV counselling and testing is pulmonary TB (i.e., TB of organs other than the
indicated for all TB patients as part of their routine lungs) should be classified under this case defini-
management. In areas with lower prevalence rates of tion. Children who have both pulmonary and
HIV, HIV counselling and testing is indicated for TB extra-pulmonary TB should be classified under the
patients with symptoms and/or signs of HIV-related case definition of pulmonary TB.
1096 The International Journal of Tuberculosis and Lung Disease
RSUM
Environ un million denfants dveloppent une tubercu- En ce qui concerne spcifiquement le diagnostic de la
lose (TB) chaque anne dans le monde, ce qui reprsente TB chez les enfants, celui-ci repose sur une valuation
environ prs de 11% de tous les cas de TB. Les enfants soigneuse et approfondie de toutes les donnes prove-
atteints de TB diffrent des adultes dans leurs rponses nant dune anamnse soigneuse, dun examen clinique et
immunologique et pathophysiologique de manire telle dinvestigations utiles, par exemple le test cutan tubercu-
quelle puisse avoir dimportantes implications pour la linique, le clich thoracique et lexamen microscopique
prvention, le diagnostic et le traitement de la TB chez des frottis dexpectoration. Quoique la confirmation
les enfants. Il est ncessaire durgence damliorer le di- bactriologique de la TB ne soit pas toujours possible,
agnostic et la prise en charge des enfants atteints de TB elle devrait tre cherche lorsque cest possible par exem-
ainsi que la prvention de la TB infantile en sassurant ple par lexamen microscopique des expectorations chez
de leur inclusion dans la mise en uvre de la stratgie les enfants suspects de TB pulmonaire et qui sont suf-
Stop TB par les programmes nationaux TB. Les zones fisamment gs pour produire un chantillon dexpecto-
critiques pour les recherches ultrieures comportent une ration. On ne recommande pas en gnral un traitement
meilleure comprhension de lpidmiologie de la TB in- dessai antituberculeux comme moyen de diagnostic de
fantile, le dveloppement de vaccins, le dveloppement la TB chez les enfants. Il existe un besoin urgent de nou-
de meilleures techniques de diagnostic, celui de nou- veaux tests diagnostiques amliors.
veaux mdicaments, et de formulations et dosages opti-
maux des mdicaments TB de premire et de seconde
ligne pour les enfants.
Diagnosis of tuberculosis in children 1097
RESUMEN
Cerca de un milln de nios contraen tuberculosis (TB) de los medicamentos antituberculosos de primera y se-
cada ao en el mundo y representan el 11% de todos los gunda lnea en los nios.
casos de TB. Los nios con TB difieren de los adultos en En relacin con el diagnstico de la TB en nios, este
su respuesta inmunitaria y fisiopatolgica, en aspectos se basa en una evaluacin exhaustiva y metdica de toda
que pueden tener implicaciones importantes para la pre- la informacin obtenida a travs de la historia clnica, el
vencin, el diagnstico y el tratamiento de la enferme- examen fsico y los exmenes pertinentes como la prueba
dad. Existe una necesidad urgente de mejorar el diagn- cutnea de la tuberculina, la radiografa de trax y la ba-
stico y el tratamiento de los nios con TB y la prevencin ciloscopia del esputo. Si bien no siempre se obtiene la
de la TB en la infancia, mediante su inclusin en la confirmacin bacteriolgica, esta debe buscarse cuando
ejecucin de la estrategia Alto a la TB por parte de los sea posible mediante la baciloscopia del esputo, en nios
Programas Nacionales de Tuberculosis. Entre los aspec- con presuncin diagnstica de TB pulmonar y que tienen
tos primordiales que requieren mayor investigacin se edad suficiente para suministrar una muestra de esputo.
encuentran una mejor comprensin de las caractersticas En general, no se recomienda un tratamiento de ensayo
epidemiolgicas de la TB en la infancia, el desarrollo de con medicamentos antituberculosos como mtodo diag-
vacunas, el diseo de mejores tcnicas diagnsticas, la nstico de la TB en los nios. Necesita pruebas diagn-
formulacin de nuevos medicamentos y la definicin de sticas nuevas y mejoradas.
ptimas formas farmacuticas y pautas de administracin