Current Diagnosis of Infant Tuberculosis Infection

Of the 9.2 million new tuberculosis cases occurring each year, about 10% are in children less than 15-years old. Since childhood tuberculosis is usually non-infectious and non-fatal, management programs often do not prioritize diagnosis and treatment. Experts in childhood tuberculosis believe that children have been neglected in the worldwide effort to control this disease. Many reasons account for this apathy towards the disease in the young: The majority of children with tuberculosis are not infectious and consequently not considered to be as essential as adults with contagious tuberculosis, the lack of a microbiological diagnosis of tuberculosis in children, and the relative neglect of pediatricians and researchers in studying childhood tuberculosis. In fact, there is a rich scientific literature base regarding childhood tuberculosis supporting simple practices, which, if adequately put into place, would greatly improve the ability to diagnose and treat children with tuberculosis. This chapter will focus on historical aspects of this ancient disease plus parameters related to childhood tuberculosis, including the tubercle vaccine discovery and its first use in a French child. However, it does not focus on children and in particular on infants as we intend to introduce tuberculosis as a whole to students and professionals that are not familiar to the disease.

Tuberculosis in children should be confronted as a seminal event in public health, as it refers to recent infections supported by direct contact with infected people, mostly adults. However, due to children seldom constituting an important source of infectiousness thanks to the small ratio of bacilli released or spread, they have a limited epidemiology impact at a global perspective. Furthermore only those cases with larynx commitment plus those ones with lung cavity are at risk for contagiousness. There are three pathways that lead to illness: the progression of the primary infection, the exogenous reinfection, and the endogenous reactivation, (which is usually the basis for the post-primary or secondary tuberculosis in adults). Indeed, the possibility that persons previously infected with Mycobacterium tuberculosis can be exogenously re-infected has been debated for decades. Frequently, children can present both the primary form and the typical post-primary tuberculosis form of the adult. Primary Tuberculosis predominates early in life, predominantly in highly endemic countries, since children are constantly exposed to the infectious sources. In contrast, within developed countries, the risk of infection is lower and individuals can expect to reach adolescence or adulthood without M. tuberculosis infection.

Tuberculosis remains one of the major diseases afflicting children throughout the world. The World Health Organization (WHO) recommends tuberculosis disease screening in children who live in the household of a smear-positive case, but lack effective measures for this management in high-burden countries to perform this routinely. WHO has recently called for more studies to define the global epidemiology of childhood tuberculosis, because the literature remains scant, dominated primarily by studies from industrialized countries and South Africa, but few epidemiologic studies of pediatric tuberculosis have been published from Asia. Children account for 10-15% of all new cases of tuberculosis worldwide. For a long time, childhood tuberculosis was neglected because of the paucibacillary characteristic of the disease in pediatric population. However, recent works have reinforced the role of childhood tuberculosis as an indicator of the effectiveness of control-programmes and also in the dissemination of the disease, since prevalent cases may persist for a long time. This chapter will focus on epidemiologic parameters related to childhood tuberculosis, including risk factors associated to disease development, the extrapulmonary tuberculosis epidemiology and the limitations in children tuberculosis diagnosis, which impairs the correct evaluation of the impact of tuberculosis in childhood community.

It is estimated that the lifetime risk of developing active disease after infection with Mycobacterium tuberculosis in childhood is about 10%. Therefore, the human immune response to M. tuberculosis infection prevents the development of illness in most people. Tuberculosis is contagious and spreads through the air. Bacilli can subsequently enter the blood stream where they spread hematogenously throughout the body. If not treated, each person with active tuberculosis disease can infect on average 10 to 15 people per year. The factors that allow for progression to active disease among infected persons are not fully understood, however, they are likely immunologic, based on the increased rates of disease in persons with varying forms of immune response. The source of infection for most children is an infectious adult in a closed environment. This exposure leads to the development of a primary lesion in the lung witch spreads to the regional lymph nodes. In the majority of cases, the resultant cell-mediated immunity controls the disease at this stage. Risk of disease progression is higher in the very young (< 3 years-old) and in immune compromised children. However, children with tuberculosis differ from adults in their immunological and pathophysiological response in ways that may have important implications for the prevention, diagnosis and treatment of this disease in the pediatric population.

The diagnosis of children tuberculosis involves the clinical, epidemiology and image methods, as well as the results of a tuberculin skin test. Tuberculosis can mimic many common childhood diseases, including pneumonia, generalized bacterial and viral infections, malnutrition and HIV. The main impediment to the accurate diagnosis of active tuberculosis is the paucibacillary nature of the disease in children. Although the diagnosis of tuberculosis disease in adults is mainly bacteriologic, in children it is usually epidemiologic and, therefore, indirect. In the absence of accurate diagnostic tools for tuberculosis in children, both underdiagnosis and overdiagnosis are common. The overdiagnosis is exacerbated in areas with a high prevalence of HIV and tuberculosis because both share many clinical features, often making it impossible to exclude tuberculosis in HIV-infected children. Many adults who develop infectious reactivation of tuberculosis acquired the infection during childhood. Given the effectiveness of isoniazid preventive therapy to stop progression of active tuberculosis, accurate diagnosis and treatment of M. tuberculosis infection in children would reduce many cases of contagious, adult, tuberculosis in the future.

Pulmonary tuberculosis is a common worldwide infection, causing high mortality and morbidity, especially in developing countries. Despite advances in diagnosis of tuberculosis, chest imaging, combined with the clinical history, remain the basis in the diagnosis, staging and follow-up of pulmonary tuberculosis. Typical radiological patterns of pulmonary tuberculosis help clinicians in management of the disease. Upper zone shadows, frequently bilateral and often associated with cavitation, are typical, as are miliary lesions. However, these findings are uncommon in childhood thoracic tuberculosis. The diagnosis of childhood intrathoracic tuberculosis depends on a constellation of symptoms, signs, and tuberculin skin test and chest radiograph results. Paratracheal, mediastinal, and hilar lymphadenopathy are frequent in childhood tuberculosis. In HIV-infected patients the radiological appearances are less specific, just as symptoms and signs may not be typical and sputum is often negative on direct smear. However chest computed tomography (CT) is frequently necessary to establish the need of additional tests. CT is more sensitive than chest X-ray in the detection and characterization of both slight localized or disseminated parenchymal disease and mediastinal lymphadenopathy. Eventually, nuclear medicine can be necessary since it provides tools for diagnosis and monitoring tuberculosis mainly in children, HIV immunecompromised individuals, tuberculosis sequel and suspected reactivation.

New diagnostic tools for active and latent tuberculosis have been proposed in the last decades, but real progress in disease management is still lacking. Many recent reviews have addressed the subject, with special interest in comparing the performance of the different methods. In this chapter, some of the new strategies that are currently in the market will be discussed. Presented will be the principles underlying those strategies, and stress their present value in the diagnosis of pediatric tuberculosis disease. Combining methods maybe necessary to address the diagnosis of tuberculosis in its multiplicity of forms, while the testing of different combinations might yield promising diagnostic trees that could be used with the necessary accuracy and reproducibility in the field.

Despite the lack of attention paid by effective control programs, childhood tuberculosis still remains an important public health problem. Identifying and treating tuberculosis infection and disease in children can also provide long-term benefits to tuberculosis control, preventing future cases due to reactivation. Rates of childhood tuberculosis appear to be rising, particularly in countries with generalized HIV epidemics. Data on childhood tuberculosis treatment outcomes is scarce. Unfortunately, measuring the true burden of childhood tuberculosis in any country is extremely difficult, because no diagnostic test performs well in childhood tuberculosis. Thus, in 25%-50% of childhood tuberculosis the tuberculin skin test may be invariably negative and, hence, much more progress needs to be made in obtaining better and faster diagnostic methods. Thus, perspectives at a management level are briefly described in this chapter in order to provide an update regarding recent advances in diagnosing tuberculosis.

Full text available