Tuberculosis

Etiology and pathogenesis

The pathogen belongs to the family Mycobacteriaceae. Its key generic feature is resistance to acids, alcohols, and alkalis, which is due to the high content of mycolic acids in the cell wall.

The basis of pathogenesis is the ability of mycobacteria to persist inside macrophages for a long time. This incomplete phagocytosis triggers a delayed-type hypersensitivity reaction (DTH, type IV).

Active tuberculosis acts as a catalyst accelerating the progression of HIV infection. In turn, increasing immunosuppression leads either to the reactivation of old (endogenous latent) infection or to the rapid development of a primary process upon new (exogenous) transmission.

Clinical presentation in HIV

The specifics of the clinical and radiological manifestations of pulmonary tuberculosis strictly correlate with the severity of immunodeficiency:

• With preserved immunity (CD4+ > 350 cells/µL): the disease proceeds typically. Infiltrates form in the upper lobes of the lungs, often with destruction of lung tissue and the formation of cavities.
• With pronounced immunodeficiency (CD4+ < 50 cells/µL): infiltrates are localized in the lower and middle lobes. Multiple miliary lesions are common, and cavity formation is atypical.

In HIV-infected patients, the risk of generalization with the development of extrapulmonary forms is extremely high. Most commonly affected are the pleura (pleurisy), pericardium, CNS (meningitis, cerebral tuberculoma), GI tract, liver, and musculoskeletal system. Kidneys, adrenal glands, skin, and genital organs are involved less frequently.

Comprehensive diagnostics

A multidisciplinary approach is used for accurate diagnosis and selection of therapy:

• Sputum examination: the standard algorithm includes a threefold collection of the morning portion over three days for smear microscopy and culture. Culture on liquid and solid media is mandatory to determine drug susceptibility.
• PCR diagnostics: allows rapid detection of M. tuberculosis DNA and identification of resistance mutations (e.g., to rifampicin and isoniazid).
• Instrumental methods: CT of the chest and abdominal cavity for an accurate assessment of parenchymal and mesenteric/intrathoracic lymph node involvement.
• General clinical tests: blood biochemistry (transaminases, bilirubin, creatinine) to assess liver and kidney function before starting hepato- and nephrotoxic therapy.

Important feature: in miliary tuberculosis, sputum examination is of low informativeness (cultures are positive in only 25% of cases). To increase detection rates up to 50–60%, collection of other biological fluids and biopsy specimens is required.

Medical tactics and treatment

Patients with bacterial excretion and a severe condition are subject to hospitalization in a specialized inpatient facility (tuberculosis department for HIV patients). Tuberculosis treatment is carried out in two phases: intensive (2–3 months) and continuation (4–5 months).

Problem of simultaneous therapy initiation: Simultaneous initiation of antiretroviral therapy (ART) and anti-tuberculosis therapy (ATT) is strictly contraindicated due to overlapping toxic effects and the risk of immune reconstitution inflammatory syndrome (IRIS).

• If the patient has not received ART, empiric tuberculosis treatment is initiated first, and HIV drugs are added with a delay of 4–8 weeks.
• If the patient is already taking ART, the regimen is continued with the addition of ATT.
• With a high immune status (CD4+ > 350 cells/µL), the start of ART can be delayed to a later date.

HIV-infected individuals with preserved immunity and a positive tuberculin skin test (papule greater than 5 mm) are indicated for chemoprophylaxis with isoniazid (5 mg/kg, maximum 300 mg/day) for 6 months.

Atypical mycobacterioses (NTM)

In the late stages of HIV infection with a profound drop in CD4+, lesions caused by nontuberculous mycobacteria, most commonly Mycobacterium avium complex (MAC infection), frequently develop. Morphologically, the process is characterized by the presence of macrophages engorged with mycobacteria, histologically resembling leprosy.

MAC infection is characterized by a typical triad: fever, profuse night sweats, and marked weight loss. A severe course is accompanied by hematogenous dissemination.

The baseline treatment regimen includes clarithromycin and ethambutol. In profound immunosuppression (CD4+ < 50 cells/µL), a third drug, rifabutin, is added to the therapy. An alternative regimen involves replacing clarithromycin with azithromycin.

Class and exam questions

What else to study on this topic

• Differential diagnosis of tuberculosis and MAC infection
• Mechanisms of development of immune reconstitution inflammatory syndrome (IRIS)
• Algorithm for chemoprophylaxis of opportunistic infections (Pneumocystis pneumonia, toxoplasmosis)
• Interpretation of tuberculin skin test results against the background of immunosuppression
• Features of CNS involvement in tuberculosis (meningitis, tuberculomas)

Other topics in the section "Viral Hepatitis and HIV"

Prepared by WhiteCoat Pro faculty in accordance with the medical school curriculum. For educational purposes only.