The World Health Organization (WHO) estimates that 600,000 children develop tuberculosis (TB) disease a year, causing 74,000 deaths in HIV-uninfected children.
TB infection is determined through use of either the Mantoux tuberculin skin test (TST) or an interferon gamma release assay (IGRA).
True congenital TB with transmission from the mother to the fetus in utero is quite rare but can occur in several ways: hematogenous spread through the umbilical vein, aspiration of infected amniotic fluid, or ingestion of other infected materials.
The clinical signs and symptoms of congenital TB vary in relation to the intensity of transmission as well as the site of disease.
I. EPIDEMIOLOGY AND INCIDENCE.Mycobacterium tuberculosis is the etiologic agent that cases tuberculosis (TB). The organism produces a spectrum of clinical entities that have differing diagnostic and management approaches. Prior to any discussion about TB, it is helpful to define these entities at the outset (Table 52.1).
Over one-third of the world’s population is infected with M. tuberculosis. Each year, at least 9 million people develop TB disease, and almost 2 million people die as a result. The World Health Organization (WHO) estimates that 600,000 children develop TB disease a year, causing 74,000 deaths in HIV-uninfected children (there are no estimates for HIV-infected children, who likely have the majority of the deaths).
In the early 20th century, TB was a common entity in the United States. The advent of effective anti-TB medications in the 1950s resulted in a declining TB prevalence until the mid-1980s. At that time, a decline in public health services, the HIV epidemic, an increase in immigration from high-prevalence countries, and increased transmission in congregate settings caused a sudden upsurge in cases (20% increase overall and 40% increase among children). This surge peaked in 1992 at 26,673 reported annual cases. Once increased strategic public health were enacted in the early 1990s, the incidence subsequently decreased to only 9,582 cases in 2013.
In the United States, most TB-infected patients are found in certain highrisk groups, as listed in Table 52.2. Over 60% of TB cases in the United States occur in foreign-born individuals. Foreign-born individuals are screened and treated only for TB disease before they immigrate; treatment of TB infection requires that they enter into care after arrival in the United States, which can be difficult due to lack of insurance and a medical home. Persons traveling to the United States on visitors’ visas receive no TB screening. Thus, many foreign-born women are at risk for developing TB disease after arrival in the United States. For many young women, their first health care visit after arrival is during their pregnancy or at labor and delivery, and this may be the best opportunity to diagnose and manage their TB infection or disease.
Table 52.1. Definitions
Tuberculosis exposure
Occurs when an individual has had contact with a case of contagious tuberculosis disease in the past 3 months. An exposed individual may or may not have infection or disease.
Tuberculosis infection
Occurs when an individual has a positive tuberculin skin test result (defined in Table 52.2) or a positive interferon gamma release assay result (defined in the text), a normal physical exam, and a chest radiograph that is either normal or shows evidence of healed calcifications. An untreated infected individual can develop tuberculosis disease in the near or distant future.
Tuberculosis disease
Occurs when an evident illness (signs, symptoms, and/or radiographic changes) is caused by Mycobacterium tuberculosis.
Congenital tuberculosis disease
Occurs when a neonate is infected with M. tuberculosis in utero or during delivery and develops disease afterward. This is determined by having a positive acid-fast bacillus stain or culture from the neonate, with exclusion of possible postnatal transmission, and either lesions in the first week of life, primary hepatic complex or caseating hepatic granulomas, or tuberculosis infection of the placenta or maternal genital tract.
Postnatally acquired tuberculosis disease
Occurs when an infant is infected after delivery, either through inhalation of M. tuberculosis from a contagious caregiver or ingestion of M. tuberculosis via infected breast or cow milk, and develops signs, symptoms, and/or radiographic evidence of tuberculosis disease.
Table 52.2. Groups at High Risk for Tuberculosis Infection
Foreign-born person from high-prevalence countries
Individuals who travel to high-prevalence countries
Inmates of correctional facilities
Illicit drug users
Migrant families
Homeless persons
II. TRANSMISSION AND PATHOGENESIS. Transmission of M. tuberculosis most commonly occurs when an individual expectorates infectious droplet nuclei, which may remain airborne for hours. An individual whose sputum is acid-fast bacillus (AFB) smear positive is the most likely to be infectious. Individuals who are AFB smear negative but culture positive are less infectious than those who are AFB smear positive, but many can still transmit the organism. Fomites and other secretions rarely cause transmission.
Children with pulmonary TB usually do not produce a cough effective enough to expectorate the droplet nuclei necessary to spread the disease, and they usually have a low burden of organisms; hence, childhood TB is often called “pauci-bacillary disease.” As a result, children rarely infect others. However, adolescents with reactivation pulmonary disease or children who have hallmarks of adult-type disease (cavitary lung lesions with an effective cough) may be contagious. In addition, children with true congenital TB often have a large pulmonary burden of organisms and may transmit infection to health care workers, especially if they are intubated. Within 2 weeks of starting effective treatment, a patient of any age with drug-susceptible TB usually becomes noncontagious, but a patient with multidrug-resistant TB (MDR-TB) may remain infectious for weeks to months after starting treatment.
Once the droplet nuclei are inhaled, M. tuberculosis bacilli land in the alveoli where they multiply freely or are consumed by alveolar macrophages. In some individuals, the immune system is able to clear the infection without treatment. In others, M. tuberculosis subverts the alveolar macrophages’ attempts at its degradation and instead replicates inside macrophages for several weeks. As the bacilli multiply, they frequently are carried into regional lymph nodes by alveolar macrophages and can spread hematogenously to other sites, including but not limited to the vertebrae, peritoneum, meninges, liver, spleen, lymph nodes, and genitourinary tract. Most patients are asymptomatic during this time and usually have no radiologic evidence of disease. The exception to this occurs in infants, who are at much higher risk for progressing rapidly to symptomatic disease due to their immature immune system. Although healthy adults infected with M. tuberculosis have a 5% to 10% of developing TB disease within their lifetime, the majority who do so—including pregnant women—develop disease within the first 1 to 2 years after infection. Infants and toddlers who are infected but untreated have a 40% chance of developing disease within 6 to 9 months. The risk to both the mother and the child is greatest when the mother has been infected recently. Any condition that depresses cell-mediated immunity (HIV infection, diabetes mellitus, poor nutritional status, or high-dose corticosteroids) increases the risk of progression to from infection to disease in adults and children.
In young children, the organisms tend to spread to the regional hilar and mediastinal lymph nodes, which then enlarge if inflammation is intense. The lymph nodes can compress or erode into the bronchi, frequently resulting in a distal atelectasis or parenchymal infection, causing the so-called “collapseconsolidation” lesion. However, the hallmark of childhood TB is intrathoracic lymphadenopathy with or without subsequent parenchymal disease.
A. Tuberculosis infection. TB infection is defined as having evidence of an immune response to M. tuberculosis-related antigens. TB infection is determined through use of either the Mantoux tuberculin skin test (TST) or an interferon gamma release assay (IGRA).
1. The TST is a delayed-type hypersensitivity test to determine if the patient reacts to a purified protein derivative (PPD) of M. tuberculosis. The delayed-type hypersensitivity typically develops 3 to 9 weeks after the TB infection occurs; the TST will be negative before this time. The PPD is placed subcutaneously, typically on the left volar forearm. After 48 to 72 hours, the area is examined for any induration and the amount of induration is measured and recorded. A TST is interpreted as positive depending on the measurement of the induration as well as risk factors that the patient may have (see Table 52.3).
2. IGRAs are blood tests that detect the production of interferon-gamma, a chemical routinely released by immune cells as they combat TB organisms. The IGRAs include positive and negative controls, and because there is no “gold standard” for TB infection, their thresholds for positivity have been determined from studies in adults who have culture-positive TB disease. These tests help to determine if someone has been infected with M. tuberculosis, but they do not differentiate between infection and disease. There are two IGRAs approved for clinical use in the United States: QuantiFERON Gold-TB test (QIA-GEN, Germantown, Maryland) and the T-SPOT.TB test (Oxford Immunotec, Abingdon, United Kingdom). Although PPD contains hundreds of mycobacterial antigens, the IGRA tests utilize only two or three that are specific for M. tuberculosis. The IGRAs do not cross-react with Mycobacterium bovis-BCG (the organism used in TB vaccines) or Mycobacterium avium complex, the most common environmental nontuberculous mycobacterium. Because these two organisms are responsible for most false-positive TST results, the IGRAs are more specific than the TST. An additional advantage of the IGRAs is that they require only one provider visit to take blood. However, they require specific laboratory capacities and are more expensive than the TST. Although the IGRAs are more specific for infection by M. tuberculosis than TSTs, they appear to offer no increased sensitivity. IGRAs can be used to diagnose TB infection in both adults and children, except in children <2 years of age; the American Academy of Pediatrics currently recommends against using IGRAs in children under 2 years of age because there are limited data regarding reliability of a negative test result, and a false-negative result has important implications because these children are more prone to rapidly advance to severe disease.
III. MATERNAL TUBERCULOSIS. There are few studies in the modern era that examine the impact of pregnancy on TB and of TB on pregnancy. The majority of literature predates the 1960s. Prior to the availability of anti-TB medications, TB disease had a poor prognosis for both the fetus and the mother. Now, with effective therapy, the mother with TB can be cured and the fetus or child spared from disease. Providers should screen all pregnant women for risk factors of TB infection or disease at an early prenatal visit, and questionnaires have been developed to aid this screening. Women belonging to high-risk groups, such as those listed in Table 52.2, or contacts to a current or previous TB case, should be tested with a TST or an IGRA. There is strong evidence that pregnancy does not alter the response to the TST and that the TST does not adversely affect the woman or the fetus. Similarly, the IGRA results do not appear to be affected by pregnancy.
Table 52.3. Definitions of Positive Tuberculin Skin Test
≥5 mm Induration
10 mm-14 mm Induration
≥15 mm Induration
HIV-positive persons
Persons who immigrated from a high-prevalence country in the past 5 years
Persons with no risk factors for tuberculosis disease
Recent contacts of contagious tuberculosis disease cases
Injection drug users
Individuals with chest radiographic changes suggestive of prior tuberculosis disease
Residents and employees of the following high-risk congregate settings:
▪ Prisons/jails
▪ Nursing homes/long-term care facilities for the elderly
▪ Hospitals and other health care facilities
▪ Residential facilities for HIV/AIDS patients
▪ Homeless shelters
Organ transplant or otherwise immunosuppressed patients (receiving the equivalent of 15 mg/day of prednisone or more)
Mycobacteriology laboratory personnel
Persons with any of the following high-risk clinical conditions:
▪ Silicosis
▪ Diabetes mellitus
▪ Chronic renal failure
▪ Hematologic disorders (e.g., leukemia and lymphoma)
▪ Carcinoma of the head, neck, or lung
▪ Weight loss (>10% ideal body weight)
▪ Gastrectomy/jejunoileal bypass
▪ Children <4 years old
▪ Any infant, child, or adolescent in contact with a highrisk adult
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