The World Health Organization (WHO) estimates that one-third of the world’s population is infected by the acid-fast bacillus (AFB) Mycobacterium tuberculosis, with 9.2 million (139 per 100, 000 population) new cases and 1.7 million deaths reported in 2006 (1). Between 1985 and 1992, there was a 20% increase in the reported cases of tuberculosis (TB) in the United States (2, 3). This increase was greatest in young adults and children and has been attributed to four factors: (i) the human immunodeficiency virus (HIV) co-epidemic; (ii) recent immigration to the United States from areas with a high prevalence of TB; (iii) increased transmission in high-risk facilities (prisons, hospitals, nursing homes, and homeless shelters); and (iv) the decrease in public health TB services and lack of access to care in persons of low socioeconomic status (4).

Intensified strategic measures initiated in 1989 have steadily reduced the incidence of TB in the United States. Indeed, there were only 11,540 cases reported in the United States in 2009, the lowest recorded since reporting was initiated in 1953 (3). However, the Centers for Disease Control and Prevention’s (CDC) goal of eliminating TB from the United States by 2010 failed, in part, to deceleration in the decline of TB from 7.3% per year from 1993 to 2000 to 3.8% per year from 2000 to 2008 (of note, from 2008 to 2009, a record high decrease of 11.4% was observed). Although the rate of TB has declined among all racial and ethnic groups in the United States, the foreign-born persons remain most affected with a rate of almost 11 times higher compared to those born in the United States; among those born in the United States, blacks have the highest number of cases (3). The number of multidrug-resistant TB cases in the United States has remained low, at just over 1%, with a disproportionate burden among foreign-born persons who accounted for 81.6% of the cases in 2007 (3, 5). The increasing proportion of TB among foreign-born persons is due to emigration from countries with higher rates of TB, coupled with falling rates of TB in U.S.-born persons (5). Indeed, foreign-born children younger than 5 years had the highest rate of TB between 1993 and 1998 among different age groups (5). Because the highest risk group for mortality from TB are patients < 5 years of age, and untreated TB in the newborn is fatal in approximately 30% to 40% of cases (6), pediatricians and neonatologists should maintain a high index of suspicion for this disease.

TB is transmitted most commonly by respiratory droplet nuclei, which can remain suspended in the air for several hours. Under normal conditions, M. tuberculosis organisms are only transmissible from disease sites in the respiratory system: larynx, bronchi, and pulmonary parenchyma. The risk of infectivity from pulmonary TB increases if the sputum is smear positive for AFB in addition to being culture positive. In primary TB, the chest radiograph may show hilar lymphadenopathy, often with focal infiltrates, but may be normal if the focus of infection is small. In contrast, the chest radiograph in adult type reactivation disease often shows pulmonary cavities in the upper lung zones. Primary TB may have
mild or nonspecific symptoms, so in some cases, there may be a prolonged period of symptoms before a diagnosis of TB is made (4, 6, 7). In other cases, there may be significant fever or cough, the latter often related to impingement of bronchi by enlarged lymph nodes. Extrapulmonary TB can act as a source of transmission only rarely, which is related to medical/surgical procedures that create aerosols from infected tissue. One rare but critical exception is congenital transmission, which can arise from maternal blood-borne or occult genitourinary TB (8).

The incubation stage occurs after a person has become infected after exposure to a person with contagious pulmonary TB (9). Usually, exposure has to be close (e.g., in an enclosed room) for an extended period. After being inspired by a new host, the respiratory droplets may travel to the alveoli, where they are ingested by alveolar macrophages. For the first several days, there is relatively unrestricted bacterial replication, and the organisms can spread to the regional lymph nodes and the bloodstream (6). During this incubation stage, the tuberculin skin test with purified protein derivative (PPD) remains negative (if the person had not been previously sensitized), and the chest x-ray (CXR) is normal. Acquired immunity typically develops within 2 to 8 weeks, at which point the individual will react to the tuberculin skin test. Sensitivity to tuberculin may take longer to evolve in neonates and young children (9). In all age groups, after the infection is established, the CXR may be normal or minimally abnormal because of enlarged lymph nodes or focal infiltrates (9).

The initial infection can then progress directly to TB disease. The likelihood of direct progression to disease is increased by weakened cellular immunity (HIV infection, prolonged courses of corticosteroids or other immunosuppressive therapies, substance abuse, neonatal period, chronic malabsorption syndromes, and low body weight defined as less than 10% or more below ideal weight). In the majority of infected individuals, the infection is controlled and remains asymptomatic (latent). When infection progresses to TB disease, it may occur within weeks from 1 to 2 years following infection. The reactivation of latent infection is more likely in individuals with specific underlying illnesses such as pneumosilicosis, diabetes, end-stage renal disease, and cancer of the head and neck or any form of immune suppression. In any individual who has been infected, TB disease can emerge after a quiescent (latent) period. Ten percent of those with normal immune systems and latent tuberculosis infection (LTBI) will convert to TB disease at some point during their lifetime. Approximately half of those cases occur within 2 years. Therefore, the treatment of latent infection is appropriate for individuals with LTBI, as demonstrated by diagnosis of infection after recent known exposure or by a skin test conversion. The disease can take decades to emerge, presumably after intercurrent declines in immunity (6). Although TB disease involves only the lungs in two-thirds of cases, it can also affect any organ system. Extrapulmonary manifestations of TB are more common in immunosuppressed patients and occur in 25% to 35% of infants and young children with disease (4).

Clear distinctions must be made between LTBI and TB disease because the diagnosis, treatment, and health implications are different. LTBI is common in populations that are at risk for exposure, and it is not an immediate threat to the mother, the fetus or newborn, or the wider community. Diagnosing LTBI creates opportunities for preventing future TB disease. Public health departments often take an active role in the diagnosis and treatment of LTBI, for example, in the setting of contact investigations, or they can provide consultation. In contrast with LTBI, TB disease is uncommon, but it is an immediate threat to the
mother and the fetus or newborn, and it creates an infection-control hazard in the health care setting and the wider community.