INCREASING IMMUNITY Primary infection Spreading lesions,little caseation Localized lesions,more caseation (localized caseation) Caseation Caseation in lymph node PRIMARY COMPLEX Massive hematogenous dissemination Liver Spleen Reactivation Reinfection Scar Caseation CaseationCavity (organisms dormant; pulmonary or extrapulmonary) PROGRESSIVE PRIMARY TB MILIARY TB SECONDARY TUBERCULOSIS LATENT LESIONS (organisms not viable) Scar Scar HEALED LESIONS Massive hematogenous dissemination PROGRESSIVE SECONDARY TB MILIARY TB LOCALIZED CASEATING DESTRUCTIVE LESIONS (pulmonary or extrapulmonary)
Fig. 13.38 Thenaturalhistoryandspectrumoftuberculosis.(Adapted from a sketch provided by Dr. R.K. Kumar,The University of New South Wales, School of Pathology, Sydney, Australia.) is present in about half of all cases of pulmonary tuberculosis. Pleuritic pain may result from extension of the infection to the pleural surfaces. Extrapulmonary manifestations of tuberculosis are legion and depend on the organ system involved (e.g., tuberculous salpingitis may present as infertility, tuberculous meningitis with headache and neurologic deficits, Pott disease with back pain and paraplegia). The diagnosis of pulmonary disease is based in part on the history and on physical and radiographic findings of consolidation or cavitation in the apices of the lungs. Ultimately, however, tubercle bacilli must be identified.
The most common methodology for diagnosis of tuberculosis remains demonstration of acid-fast organisms in sputum by staining or by use of fluorescent auramine rhodamine. Conventional cultures for mycobacteria require up to 10 weeks, but liquid media–based radiometric assays that detect mycobacterial metabolism are able to provide an answer within 2 weeks. PCR amplification can be performed on liquid media with growth, as well as on tissue sections, to identify the mycobacterium. However, culture remains the standard diagnostic modality because it can identify the occasional PCR-negative case and also allows testing of drug susceptibility. Of concern, multidrug resistance (MDR), defined as resistance of mycobacteria to two or more of the primary drugs used for treatment of tuberculosis, is becoming more common, and the WHO estimated that 500,000 individuals were newly infected with multidrug-resistant tuberculosis in 2014. This represents approximately 3% of new cases and 20% of previously treated cases. The epicenter of this troubling epidemic lies in Eastern Europe and Russia, where in some locales up to 20% of new infections are with multidrug-resistant strains. Of even greater concern, approximately 5% to 10% of such cases exhibit extensive multidrug resistance, defined by resistance to a broad spectrum of antibiotics in current use against tuberculosis.
The prognosis is determined by the extent of the infection (localized versus widespread), the immune status of the host, and the antibiotic sensitivity of the organism. Understandably, the prognosis is guarded in those with multidrug-resistant tuberculosis. Amyloidosis may develop in persistent cases.
TuberculosisisachronicgranulomatousdiseasecausedbyM. tuberculosis, usuallyaffectingthelungs,butvirtuallyanyextra-pulmonaryorgancanbeinvolved.
Initialexposuretomycobacteriaresultsindevelopmentofacellularimmuneresponsethatconfersresistanceandleadstohypersensitivity(asdeterminedbyapositiveresultonthetuberculinskintest).
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TheTH1subsetofCD4+ Tcellshasacrucialroleincell-mediatedimmunityagainstmycobacteria;mediatorsofinflammationandbacterialcontainmentincludeIFN-γ,TNF,andnitricoxide.