Wallach's Interpretation of Diagnostic Tests: Pathways to Arriving at a Clinical Diagnosis (581 page)

Non–HIV-infected patients
: These patients typically present with acute onset of respiratory failure, fever, and nonproductive cough. Glucocorticoid use and defects in cell-mediated immunity are the most common predisposing factors for infection. Conditions associated with increased risk for PCP in patients without HIV infection include

   Immunosuppressive drug therapy

   Malignancy (usually hematologic)

   Organ transplantation (hematopoietic or solid organ)

   Primary immunodeficiency

   Rheumatologic or inflammatory diseases

The risk of PCP is reduced in patients taking effective prophylactic therapy.

   Diagnostic Testing

Definitive diagnosis of
P. jirovecii
depends on the demonstration of organisms in respiratory specimens taken from patients at risk for PCP with typical signs, symptoms, and radiographic findings.

Specimens
: It is critical to sample alveolar contents or lung tissue for sensitive diagnosis of PCP. Induced sputum (IS) samples are relatively noninvasive and sensitive (50–90%). The sensitivity of bronchoalveolar lavage (BAL) for PCP diagnosis approaches 100%. The sensitivity of lung biopsy is very high, but biopsy is rarely needed for diagnosis. Lung biopsy may be collected for diagnosis of other infections (e.g., fungi) or diseases (e.g., lymphoma) that may be in the differential diagnosis. Organisms are rarely detected in routine expectorated sputum or bronchial wash specimens. The sensitivity of detection may be reduced in non-HIV patients or patients on antifungal prophylaxis.

Direct detection
: Definitive diagnosis is achieved by microscopic demonstration of organism in respiratory secretions or lung tissue. A variety of stains may be used to demonstrate characteristic cyst forms (like calcofluor white, Gomori silver, toluidine blue) or troph forms (like Wright-Giemsa or Papanicolaou) of
Pneumocystis
. A commercially available fluorescein-conjugated monoclonal antibody is available that provides sensitive detections of both cyst and troph forms.

Nucleic acid amplification
: Methods have been developed for PCP diagnosis, but none are FDA approved. The increased sensitivity of PCR testing may allow for sensitive detection using noninvasively collected specimens, like saliva. However, the increased cost and turnaround time for PCR, and small (if any) incremental sensitivity compared to visual detection, are likely to limit wide implementation of PCR for PCP diagnosis. In addition, false-positive results have been reported for PCR.

Culture
: Effective in vitro culture techniques are not available.

Serum beta-
D
-glucan assay
: May be used as a sensitive test to screen for PCP in HIV-infected patients. The performance of the assay depends on the definition used for a positive result as well as the population studied, but sensitivity >90% for detection of PCP has been demonstrated. The specificity is limited by reactivity in infections caused by other fungi.

Serology
: Testing does not play a role in PCP diagnosis.

Core laboratory
: Elevated LDH is typical; the degree of LDH elevation and increasing LDH despite therapy are poor prognostic signs.

Suggested Readings

Azoulay E, Bergeron A, Chevret S, et al. Polymerase chain reaction for diagnosing pneumocystis pneumonia in non-HIV immunocompromised patients with pulmonary infiltrates.
Chest.
2009;135:655–661.

Fischer S, Gill VJ, Kovacs J, et al. The use of oral washes to diagnose
Pneumocystis carinii
pneumonia: a blinded prospective study using a polymerase chain reaction-based detection system.
J Infect Dis.
2001;184:1485–1488.

Sax PE, Komarow L, Finkelman MA, et al. Blood (1->3)-beta-D-glucan as a diagnostic test for HIV-related
Pneumocystis jiroveci
pneumonia.
Clin Infect Dis.
2011;53:197–202.

Stringer JR.
Pneumocystis carinii
: what is it, exactly?
Clin Microbiol Rev.
1996;9:489–498.

Thomas CF, Limper AH. Pneumocystis pneumonia.
N Engl J Med.
2004;350:2487–2498.

VIRAL PNEUMONIA

   Definition

Viral pneumonia is characterized by the development of abnormal alveolar gas exchange and inflammation of the lung tissue. May be caused by a number of viral respiratory pathogens. Pneumonia is often preceded by nonspecific symptoms of URI. The etiology depends somewhat on the age and the patient’s state of immunocompetence. In children, viral pneumonia is most important in patients younger than 5 years. Clinically significant, purely viral pneumonia is uncommon in immunocompetent older children and adults. The parainfluenza viruses, RSV, and human metapneumoviruses are relatively more common causes of viral pneumonia in children and infants compared to older children and adults. In older children and adults, influenza viruses, especially type A, are responsible for most cases of pneumonia. CMV is the most common, clinically significant cause of viral pneumonia in immunocompromised patients.

   Etiology and Diagnosis

   Specific identification may be required for optimal management of severely ill patients. Because the clinical and laboratory presentation of viral pneumonia is not specific, other etiologies, like bacteria, mycoplasmas,
P. jirovecii
, must be considered and ruled out by relevant laboratory and other evaluations.