Review
Diagnosis and treatment of tuberculosis in children

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Summary

There has been a recent global resurgence of tuberculosis in both resource—limited and some resource—rich countries. Several factors have contributed to this resurgence, including HIV infection, overcrowding, and immigration. Childhood tuberculosis represents a sentinel event in the community suggesting recent transmission from an infectious adult. The diagnosis of tuberculosis in children is traditionally based on chest radiography, tuberculin skin testing, and mycobacterial staining/culture although these investigations may not always be positive in children with tuberculosis. Newer diagnostic methods, such as PCR and immune-based methods, are increasingly being used although they are not widely available and have a limited role in routine clinical practice. Diagnostic approaches have been developed for use in resource—limited settings; however, these diagnostic methods have not been standardised and few have been validated. Short—course, multidrug treatment has been adopted as standard therapy for adults and children with tuberculosis, with or without directly observed therapy. Compliance is a major determinant of the success of drug treatment. Although uncommon in children, multidrug—resistant tuberculosis is also increasing and treatment will often involve longer courses of therapy with second—line antituberculosis drugs. Treatment of latent infection and chemoprophylaxis of young household contacts is also recommended for tuberculosis prevention, although this may not always be carried out, particularly in high incidence areas.

Section snippets

Natural history of tuberculosis and clinical spectrum of disease

It has been traditionally useful to distinguish between “infection” and “disease” in the natural history of tuberculosis. Following initial exposure to a case of transmissible tuberculosis, the hallmark of tuberculosis infection is conversion of the tuberculin skin test (TST). Subsequent tuberculosis disease is characterised by the development of signs and symptoms and/or radiographical changes. Without hemoprophylaxis, 40–50% of infants and 15% of older children with infection will develop

Microscopy and culture

Early and timely diagnosis of tuberculosis relies heavily on microscopic examination of clinical samples for acid-fast bacilli using the Ziehl-Neelsen (ZN) stain. Microscopy can detect 60–70% of culture positive samples with a lower limit of detection of 5×103 organisms/mL. Newer fluorochromes stains, such as the auramine and rhodamine, are superior to the ZN stain.15 These tests are easy to perform and are cheap and rapid. However, younger children with pulmonary tuberculosis rarely produce

PCR

Due to the slow growth of most pathogenic bacteria, tests have been developed for the detection of mycobacteria directly from clinical specimens. Most have involved amplification of small amounts of bacterial nucleic acid using techniques such as PCR. PCR has been used successfully in identifying many infectious agents, allowing early diagnosis and institution of therapy. Although the specificity of a well-developed PCR can be high, the sensitivity is significantly less than that of the use of

Treatment

Treatment of children can be divided broadly into treatment of tuberculosis infection and treatment of tuberculosis disease. As mentioned above, the distinction between these different categories may be unclear in some patients.

Treatment schedules, policies, and drug doses as advocated by a number of national and international bodies often differ. Table 2, Table 3 compare drug regimens and dosages recommended by the BTS, American Thoracic Society (ATS), and WHO.28, 29, 30, 50 Traditionally,

Multidrug-resistant tuberculosis

Single, multiple, and multidrug resistance has been on the increase. Isoniazid-resistance has been found in 6·8–7·2% of isolates in children less than 15 years old in England and Wales from 1995–1999. Multidrug resistance (defined as resistance to both isoniazid and rifampicin) over the same period was 0·5–0·7%. Higher levels of resistance occur in ethnic minority groups, especially those from the Indian subcontinent and sub-Saharan Africa. As children have lower rates of tuberculosis

Treatment of tuberculosis Infection

Treatment of tuberculosis infection, rather than the disease, involves the use of one or two antituberculosis agents to prevent the future development of tuberculosis disease. Many studies have shown that isoniazid for 12 months is highly effective, as well as shorter courses of between 6 and 9 months' duration. A 6-month regimen of isoniazid is generally recommended in the UK28 although ATS/CDC recommends a 9-month course.31 Regimens of rifampicin and isoniazid lasting for 3 months have been

Management of young children who are close contacts of smear-positive adults

Young children who are exposed to a household contact with smear-positive pulmonary tuberculosis are at high-risk of developing both infection and disease. Young children (less than 2 years for BTS, less than 4 years for ATS/CDC and less than 5 years for WHO) who are thus exposed should begin isoniazid chemoprophylaxis irrespective of the TST at baseline. TST is repeated at 6 weeks (12 weeks for ATS/CDC). If the TST is positive at baseline or becomes positive on re-testing, then the duration of

Conclusions

Tuberculosis continues to cause considerable mortality and morbidity in adults and children worldwide. The global resurgence of tuberculosis has been fuelled by several factors including HIV infection, breakdown of tuberculosis control programmes, overcrowding and MDR tuberculosis. Childhood tuberculosis represents a sentinel event within a community suggesting recent transmission from an infectious adult. The early diagnosis and adequate treatment of adults and children with tuberculosis

Search strategy and selection criteria

Data for this review were identified by searches of PubMed and references from relevant articles. Search terms were “tuberculosis”, “children/child”, “diagnosis”, and “treatment” used in various combinations. The search was limited to articles in the English language. Additionally, websites from various organisations including those of the WHO, the International Union Against Tuberculosis and Lung Disease, the US Centres for Disease Control and Prevention, the American Thoracic Society,

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