Thehistopathologichallmarkofhostreactiontotuberculosisinimmunocompetentindividualsisthepresenceofgranulomas,usuallywithcaseousnecrosis.
Primarypulmonarytuberculosisinimmunocompetentindividualsisasymptomaticandresultsonlyinhealedlesions,typicallyinasub-pleuralfocusandadraininglymphnode.
Secondary(reactivation)tuberculosisarisesinpreviouslyexposedindividualswhenhostimmunedefensesarecompromised,andusuallymanifestsascavitarylesionsinthelungapices.
Bothprogressiveprimarytuberculosisandsecondarytuberculosiscanresultinsystemicseeding,causinglife-threateningformsofdiseasesuchasmiliarytuberculosisandtuberculousmeningitis.
HIV-seropositivestatusisanimportantriskfactorfordevelopmentorrecrudescenceofactivetuberculosis.
Nontuberculous mycobacteria most commonly cause chronic, localized pulmonary disease in immunocompetent individuals. In the United States, strains implicated most frequently include Mycobacterium avium-intracellulare (also called M. avium complex), Mycobacterium kansasii, and Mycobacterium abscessus. It is not uncommon for nontuberculous mycobacterial infection to manifest as upper-lobe cavitary disease, mimicking tuberculosis, especially in patients with a long history of smoking or alcohol abuse. Concomitant chronic pulmonary disease (COPD, cystic fibrosis, pneumoconiosis) is often present.
In immunosuppressed individuals (primarily HIVseropositive patients), M. avium complex infection manifests as a disseminated disease associated with systemic signs and symptoms (fever, night sweats, weight loss). Hepatosplenomegaly and lymphadenopathy, signifying involvement of the mononuclear phagocyte system by the opportunistic pathogen, is common, as are gastrointestinal symptoms such as diarrhea and malabsorption. Pulmonary involvement is often indistinguishable from tuberculosis in patients with AIDS. Disseminated M. avium complex infection in patients with AIDS tends to occur late in the clinical course, when CD4+ T cell counts have fallen below 100 cells/µL. Hence, tissue examination usually does not reveal granulomas; instead, foamy macrophages “stuffed” with atypical mycobacteria typically are seen.
Histoplasmosis,Coccidioidomycosis,andBlastomycosis
Infections caused by dimorphic fungi, which include Histoplasma capsulatum, Coccidioides immitis, and Blastomyces dermatitidis, manifest either with isolated pulmonary involvement, as commonly seen in infected immunocompetent individuals, or with disseminated disease in immunocompromised individuals. T cell–mediated immune responses are critical for containing the infection, so individuals with compromised cell-mediated immunity, such as those with HIV, are prone to systemic disease. In part because of the overlap in clinical presentations, infectious diseases due to all three dimorphic fungi are considered together in this section.
Each of the dimorphic fungi has a typical geographic distribution, as follows:
H. capsulatum is endemic in the Ohio and central Mississippi River valleys and along the Appalachian Mountains in the southeastern United States. Warm, moist soil containing droppings from bats and birds provides an ideal medium for the growth of the mycelial form, which produces infectious spores.
C. immitis is endemic in the southwestern and far western regions of the United States, particularly in California’s San Joaquin Valley, where coccidial infection is known as “valley fever.”
B. dermatitidis has a distribution in the United States that overlaps with those in which histoplasmosis is found.
MORPHOLOGYTheyeastformsarefairlydistinctive,whichhelpsintheidenti ficationofindividualfungiintissuesections: