Research Article: A Systematic Review of Clinical Diagnostic Systems Used in the Diagnosis of Tuberculosis in Children

Date Published: July 17, 2012

Publisher: Hindawi Publishing Corporation

Author(s): Emily C. Pearce, Jason F. Woodward, Winstone M. Nyandiko, Rachel C. Vreeman, Samuel O. Ayaya.


Background. Tuberculosis (TB) is difficult to diagnose in children due to lack of a gold standard, especially in resource-limited settings. Scoring systems and diagnostic criteria are often used to assist in diagnosis; however their validity, especially in areas with high HIV prevalence, remains unclear. Methods. We searched online bibliographic databases, including MEDLINE and EMBASE. We selected all studies involving scoring systems or diagnostic criteria used to aid in the diagnosis of tuberculosis in children and extracted data from these studies. Results. The search yielded 2261 titles, of which 40 met selection criteria. Eighteen studies used point-based scoring systems. Eighteen studies used diagnostic criteria. Validation of these scoring systems yielded varying sensitivities as gold standards used ranged widely. Four studies evaluated and compared multiple scoring criteria. Ten studies selected for pulmonary tuberculosis. Five studies specifically evaluated the use of scoring systems in HIV-positive children, generally finding the specificity to be lower. Conclusions. Though scoring systems and diagnostic criteria remain widely used in the diagnosis of tuberculosis in children, validation has been difficult due to lack of an established and accessible gold standard. Estimates of sensitivity and specificity vary widely, especially in populations with high HIV co-infection.

Partial Text

Tuberculosis (TB) remains one of the most important causes of pediatric mortality worldwide, especially in areas with high HIV prevalence. There are approximately nine million new TB cases each year, with ten percent of those occurring in children, equaling almost one million new pediatric cases each year. Seventy-five percent of those are in twenty-two high-burden countries, which also tend to have fewer resources for diagnosis. Accurate and timely diagnosis of pediatric TB remains crucial because children are more likely than adults to progress from latent infection to active TB disease [1].

We searched several bibliographic databases, including MEDLINE (through October 19, 2009), EMBASE, and relevant websites such as those for the World Health Organization. We used the following strategy: (tuberculosis/diagnosis) [MeSH heading] AND (criteria* OR screen* OR guideline* OR scor*). Three authors (S. O. Ayaya, J. F. Woodward, and E. C. Pearce) reviewed all returned titles and excluded articles that obviously did not involve children or tuberculosis. These authors then reviewed abstracts of remaining articles to determine which studies examined scoring systems or diagnostic criteria used in the diagnosis of pediatric tuberculosis. The bibliographies of all relevant articles were also reviewed for potential articles.

The systematic literature search identified 2261 articles. The online search of MEDLINE yielded 2011 articles, and the search of EMBASE yielded 250 articles, many of which were also found by the MEDLINE search. Additional potential studies were identified through searches of bibliographies. After articles that did not address the diagnosis of tuberculosis in children were excluded, 408 articles remained. Further articles were excluded upon closer review because they did not include pediatric patients, did not include a scoring system or diagnostic criteria, or focused only on screening for latent tuberculosis. Articles that briefly mentioned a scoring system but did not give details or include how it was used in the study were also excluded. Forty articles met the general study criteria.

We identified and reviewed forty different studies of twenty-two unique scoring systems or diagnostic criteria that were developed from five original scoring systems and five original diagnostic criteria. These diagnostic approaches varied in the types of clinical signs and symptoms included in the criteria, the inclusion or exclusion of laboratory testing, and even their diagnostic focus (i.e., pulmonary TB alone or pulmonary and extrapulmonary TB). Studies designed to validate the various diagnostic systems varied significantly in the gold standard chosen for comparison. Because the publication dates of the articles range over the last fifty years, some criteria were developed and evaluated prior to the HIV epidemic, while other studies focused specifically on coinfected children.

Clinical diagnostic systems in use for many years (e.g., the original Kenneth Jones criteria) and those more recently developed (e.g., the Brazil MOH criteria) have generally been developed, and subsequently adapted, in an attempt to accurately and reliably diagnose tuberculosis in children. As more continues to be learned about the disease and newer, more accurate tests are developed, methods of diagnosis will likely be altered further. It remains crucial that these methods remain applicable to resource-limited settings where the majority of children with TB are still most likely to be found. Although the studies included in this paper are heterogeneous and difficult to compare, the Brazil MOH criteria seems to emerge as the best validated in children with TB alone as well as those coinfected with TB and HIV. Due to the difficulty with obtaining cultures and the expense of the newer diagnostic tests, clinical scoring systems and diagnostic criteria will likely continue to be necessary in resource-limited settings for some time. However, unless additional studies identify refined diagnostic systems with improved sensitivity and specificity, they will likely mainly be utilized as initial screening tools or adjuncts to support clinical diagnosis. Improving the accuracy of diagnosis of pediatric TB is needed to ensure appropriate and timely treatment of those with active disease and to prevent unnecessary morbidity and mortality. Validated clinical diagnostic systems that can be implemented in resource limited settings can improve the accuracy and timeliness of tuberculosis in children; however, additional well-designed studies are needed to validate the accuracy and reliability of current scoring systems and diagnostic criteria.




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