In healthy young children and adults, the disease is nearly always asymptomatic. In surveys around the world, 50% to 100% of adults demonstrate anti-CMV antibodies in the serum, indicating previous exposure. The most common clinical manifestation of CMV infection in immunocompetent hosts beyond the neonatal period is an infectious mononucleosis–like illness marked by fever, atypical lymphocytosis, lymphadenopathy, and hepatomegaly accompanied by abnormal liver function test results, suggesting mild hepatitis. Most patients recover from CMV mononucleosis without any sequelae, although excretion of the virus may occur in body fluids for months to years. Irrespective of the presence or absence of symptoms after infection, an individual who is once infected becomes seropositive for life. The virus remains latent within leukocytes, which are the major reservoirs.
Immunosuppression-related CMV infection occurs most commonly in recipients of transplants (such as heart, liver, kidney, lung, or hematopoietic stem cell) and in patients with AIDS. This can be either primary infection or reactivation of a latent infection. CMV is the most common opportunistic viral pathogen in AIDS.
In all of these settings, serious disseminated CMV infections primarily affect the lungs (pneumonitis), gastrointestinal tract (colitis), and retina (retinitis); the central nervous system usually is spared. In the lung, infection is associated with typical cytomegalic changes, mononculear infiltrates, and foci of necrosis, which may progress to acute respiratory distress syndrome. Intestinal necrosis and ulceration can develop and may be extensive, leading to the formation of “pseudomembranes” (Chapter 15) and debilitating diarrhea. CMV retinitis, by far the most common form of opportunistic CMV disease, can occur either alone or in combination with involvement of the lungs and intestinal tract. Diagnosis of CMV infection is made by demonstration of characteristic viral inclusions in tissue sections, successful viral culture, rising anti-viral antibody titer, and qualitative or quantitative PCR assay–based detection of CMV DNA. The latter has revolutionized the approach to monitoring patients after transplantation.
P. jiroveci (previously P. carinii), an opportunistic infectious agent formerly considered to be a protozoan, is now classified as a fungus. Serologic evidence indicates that virtually all individuals are exposed to Pneumocystis during the first few years of life, but in most the infection remains latent. Reactivation with development of clinical disease occurs almost exclusively in immunocompromised individuals. Indeed, patients with AIDS are extremely susceptible to infection with P. jiroveci, and it also may infect severely malnourished infants and immunosuppressed individuals (especially after organ transplantation or in individuals receiving cytotoxic chemotherapy or corticosteroids). In patients with AIDS, the risk for acquiring P. jiroveci infections increases in inverse proportion to the CD4+ T cell count, with counts less than 200 cells/µL having a strong predictive value. Pneumocystis infection is largely confined to the lung, where it produces an interstitial pneumonitis.
MORPHOLOGYInvolvedareasofthelungcontainacharacteristicintraalveolar foamy, pink-staining exudate withhematoxylin-eosin(H&E)stain(“cottoncandy”exudate)(
Fig.13.41A ).Theseptaarethickenedbyedemaandaminimalmononuclearinfiltrate.Specialstainsarerequiredtovisualizetheorganism.Silverstainoftissuesectionsrevealsroundto cup-shaped cysts (4to10µmindiameter)withinthealveolarexudates(see
Fig.13.41B