PATIENTS WITH TUBERCULOSIS AND HUMAN IMMUNODEFICIENCY VIRUS
HIV infection is the strongest known risk factor for tuberculosis, and the incidence of tuberculosis in HIV-positive patients is much higher than in the general population. Patients with a new diagnosis of tuberculosis are almost 20 times more likely to have HIV, and HIV patients are 20 to 30 times more likely to develop tuberculosis. Tuberculosis (pulmonary and extrapulmonary) often can be the initial clinical manifestation of immunodeficiency and is a defining event in the acquired immunodeficiency syndrome. Once active tuberculosis has developed, the risk of rapid progression and drug resistance is much higher in the HIV patient. Successful treatment with antiretroviral therapy lowers the rate of tuberculosis and reduces the incidence of extrapulmonary involvement.17 For these reasons, physicians considering a diagnosis of tuberculosis should obtain HIV testing to provide early diagnosis and therapy.
Treatment of tuberculosis in HIV-positive patients is generally effective and not markedly different from others with the infection. However, due to the number of medications taken by patients with HIV, potential drug interactions are common, and compliance may become an issue. There is no consensus statement on the timing of antiretroviral therapy when treating both diseases. Recent studies support early antiretroviral therapy in combination with antituberculous medications, especially in those who are severely immunocompromised.1,18
Immune reconstitution inflammatory syndrome or paradoxical reaction (see Treatment of Active Tuberculosis) is a condition in which HIV patients clinically worsen as the immune system recovers after the initiation of antiretroviral therapy or antituberculous medications. The ideal timing of antiretroviral therapy in those with active tuberculosis is uncertain.1,18 See chapter 154, Human Immunodeficiency Virus Infection.
Multidrug-resistant tuberculosis is defined as tuberculosis with isolates that demonstrate resistance to at least INH and RIF. M. tuberculosis becomes resistant by spontaneous genetic mutation, often as a result of inadequate drug therapy or noncompliance with initial treatment. While resistance is usually not confirmed until culture and sensitivity data are available, certain historical and clinical features raise the level of suspicion for multidrug-resistant tuberculosis. These include a history of tuberculosis treatment in the past, exposure to multidrug-resistant tuberculosis, known INH resistance in the community above 4%, and persistent symptoms or persistently positive sputum cultures despite 4 months of standard treatment.19
Extensive drug-resistant tuberculosis is a more intense worldwide threat to public health and tuberculosis control. Extensive drug-resistant tuberculosis is defined as disease resistant to INH and RIF, plus resistance to any fluoroquinolone, and resistance to at least one injectable second-line medication. It is associated with poor outcomes and higher mortality.
Treatment of multidrug-resistant tuberculosis depends on sensitivity patterns from culture. Some countries may use standardized regimens based on known local resistance patterns. Usually a combination therapy with four to six medications, including the more toxic and less potent second-line medications, is administered for up to 2 years. Success rates rarely exceed 75%.20 In refractory cases, resectional surgery may be necessary in addition to ongoing medical therapy.19
The "Global Plan to Stop Tuberculosis" calls for new medications to fight against the problem of multidrug-resistant tuberculosis. In addition to testing and better current therapy compliance, new medications show promise, especially delamanid.20
Tuberculosis in children occurs in the same risk groups as in the adult population (see Table 67-1). The clinical course and disease manifestations in children have several unique aspects. Although children are at greater risk for developing rapidly progressive and disseminated disease, their presenting signs and symptoms can be subtle. Primary tuberculosis in children is often asymptomatic and only identified through screening programs or contact tracing.21 Children may be asymptomatic even with abnormal radiographs. Or, children may present with fever, cough, wheezing, poor feeding, and fatigue. The classic symptoms of fever, night sweats, and weight loss may be seen in older children; however, in those younger than 5 years, presentation may be that of miliary tuberculosis (see below), meningitis, or a pneumonia that does not respond to therapy. The most common extrapulmonary presentation is cervical lymphadenitis, but other regions may be involved including the meninges, pericardium, abdomen, bone, joints, kidneys, skin, and eyes.
The yield of sputum smears and cultures is lower in children because of difficulty in obtaining adequate samples in addition to the lower incidence of cavitary disease.22,23 Traditionally, obtaining three early morning consecutive gastric lavage or gastric aspirate samples has been standard procedure. However, this is invasive, unpleasant, and often requires an overnight admission and trained staff. Sputum induction using bronchodilators, followed by nebulized saline and expectoration of mucus, can improve sampling.23
The diagnosis of tuberculosis in children is confirmed by culture in only 30% to 40% of cases.13 The newer tests, IGRA and NAAT, are not recommended for children less than 5 years old. The immune response differs in this age group, making the tests less reliable.11 Often, treatment is initiated based on a skin test or on clinical grounds (symptoms, a history of exposure, or abnormal radiographs), and the diagnosis is presumed based on response to treatment.22 Multidrug therapy is currently recommended for all children considered to have active disease, whereas monotherapy is used for latent infections.
Miliary tuberculosis is a historic term used in reference to the gross appearance of the lung during disseminated tuberculosis. In such cases, the lung is often covered with multiple small lesions resembling millet seeds. Classic miliary tuberculosis shows diffuse nodules on radiographs (1 to 3 mm) in a patient with positive laboratory testing or by demonstration of mycobacteria in multiple organs. The classic radiographic findings may not appear on films until the disease has progressed over time. A miliary pattern on radiographs can be found in conditions other than tuberculosis including histoplasmosis, malignancy, siderosis, and sarcoidosis.24
Today, miliary tuberculosis refers to wide hematogenous spread during the primary or reactivation disease, and it is associated with higher mortality. Children, the elderly, and immunocompromised patients are all at increased risk of developing miliary disease.
Miliary disease during primary tuberculosis is generally more rapid and severe, often presenting with multiorgan failure, shock, and acute respiratory distress syndrome. Conversely, miliary reactivation often manifests with a chronic, nonspecific clinical course affecting any number of organ systems. Fever, anorexia, night sweats, cough, weight loss, splenomegaly, lymphadenopathy, and signs of multisystem illness should cause one to suspect miliary disease. Cutaneous involvement, seen more often in HIV patients, manifests as papules or vesiculopapules (tuberculosis cutis miliaris disseminata or tuberculosis cutis acuta generalisata). Choroidal tubercles found on ocular exam are pathognomonic for miliary tuberculosis.
Tuberculous meningitis is often seen in children, although those with HIV or others who are immunocompromised may also be afflicted. The challenge is the subtle and subacute presentation over days to weeks, with gradual fever, headache, and cognition or sensorium changes that often are not accompanied by neck stiffness or irritation, in contrast with those seen in other forms of bacterial meningitis. Focal neurologic deficits or cranial nerve palsies may also be evident. Suspecting the infection and requesting tuberculosis cultures and smear are key to making a diagnosis, because other diagnostics are not helpful.25 Long-term neurologic dysfunction is common, with ventriculoperitoneal shunting needed in 25% of patients for hydrocephalus. Tuberculous meningitis often seeds after a miliary infection. Treatment parallels other forms of tuberculosis.