Description

Opportunistic lung infection caused by Pneumocystis jiroveci. This organism is currently considered a primitive fungus based on DNA sequence analysis. It has two developmental forms (the cysts contain sporozoites that become trophozoites when excised).

• Although previously known as Pneumocystis carinii pneumonia (PCP), the acronym PCP is still in use and refers to Pneumocystis pneumonia.
• PCP occurs almost exclusively in the immunocompromised host.
• PCP is an AIDS-defining illness. It is the most common opportunistic life-threatening lung infection in infants with perinatally acquired HIV disease.
• P. jiroveci causes a diffuse pneumonitis characterized by fever, dyspnea at rest, tachypnea, hypoxemia, nonproductive cough, and bilateral diffuse infiltrates in the roentgenogram. It is a severe condition frequently leading to respiratory failure, necessitating intubation and mechanical ventilation.
• Chemoprophylaxis against this microorganism has proven successful. Therefore, early identification of the HIV-infected mother becomes essential.
• Despite advances in therapy, the infection continues to be associated with significant morbidity and mortality.

Epidemiology

• Ubiquitous in mammals worldwide, particularly rodents
• Growth on respiratory tract surfaces
• Mode of transmission is unknown:
  • Airborne person-to-person transmission is possible, but case contacts are rarely identified.
  • Environmentally acquired
• Asymptomatic infection appears early in life; >70% of healthy individuals have antibodies by age 4 years.
• Primary infection is likely to be the mechanism in infants. Reactivation of latent disease with immunosuppression was proposed as an explanation for disease later in childhood; however, animal models of PCP do not support this proposition.
• PCP in the HIV patient can occur at any time but usually presents during the 1st year of life. The highest incidence is between 3 and 6 months of age.

Risk Factors

Immunocompromised host

• Children with congenital or acquired AIDS and recipients of suppressive therapy in the treatment of malignancies or after organ transplantation are at high risk.
• In leukemic patients, the incidence of PCP has been directly related to the degree of immunodeficiency resulting from chemotherapy.
• Epidemics of PCP were reported in premature and malnourished infants and children in resource-limited countries and during times of famine.

General Prevention

• Chemoprophylaxis indications: During high-risk periods, PCP can be effectively prevented in the immunodeficient host by chemoprophylaxis in the following groups:
  • HIV exposed: 4 to 6 weeks to 4 months
  • HIV infected or indeterminate: 4 to 12 months
  • HIV infected: 1 to 5 years if CD4⁺ T-lymphocyte count is <500 cells/μL or <15%
  • HIV infected: ≥6 years if CD4⁺ T-lymphocyte count is <200 cells/μL or <15%
  • Severely symptomatic HIV patients or those with rapidly declining CD4 counts
  • HIV patients who have had previous PCP illness
  • Children who have received hematopoietic stem cell transplants (HSCTs)
  • All HSCT recipients with hematologic malignancies (e.g., leukemia, lymphoma)
  • All HSCT recipients receiving intense conditioning regimens or graft manipulation
    • Prophylaxis is initiated at engraftment and administered for 6 months; longer than 6 months in children receiving immunosuppressive therapy or with chronic graft-versus-host disease
• Drug regimen for prophylaxis
  • Trimethoprim-sulfamethoxazole (TMP-SMX) is the drug of choice.
    • 150 mg/m² body surface area per day of TMP or 750 mg/m² body surface area per day of SMX PO divided into 2 doses on 3 consecutive days per week
    • TMP-SMX can also be given 7 days a week when prevention against other bacterial infections is sought.
  • For patients who cannot tolerate TMP-SMX
    • Dapsone (>1 month of age): 2 mg/kg (maximum 100 mg) PO daily or 4 mg/kg (maximum 200 mg) PO weekly
    • Aerosolized pentamidine (>5 years of age): 300 mg via Respirgard II nebulizer inhaled monthly
    • Atovaquone at age 1 to 3 months and >24 months: 30 mg/kg (maximum 1,500 mg/dose) PO daily; at age 4 to 24 months: 45 mg/kg (maximum 1,500 mg/dose) PO daily

Pathophysiology

• In the immunodeficient child, the pathologic changes occur predominantly in the alveoli. Cysts and trophozoites are seen adhering to the alveolar lining cells or in the cytoplasm of macrophages.
• As infection progresses, the alveolar spaces are filled with a pink, foamy exudate containing fibrin, abundant desquamative cells, and a large number of organisms. Alveolar septal thickening with mononuclear cell infiltration is also seen.

History

• In malnourished host
  • Subacute onset with nonspecific manifestations
    • Poor feeding, weight loss, and restlessness
    • Chronic diarrhea
    • Usually without fever
    • After 1 to 2 weeks, the patient develops progressive tachypnea, respiratory distress, and cough.
• In sporadic or immunocompromised host
  • This form has a more abrupt onset, sometimes even fulminant:
    • Fever (>38.5°C)
    • Nonproductive cough
    • Dyspnea at rest
• These subtypes are characterized by general clinical guidelines. Symptoms may be superimposed and can be seen in infants, children, and adolescents.

Physical Exam

• Fever and significant tachypnea are characteristic.
• Hypoxemia: early in the course of disease and disproportionate to the auscultatory findings
• Rapidly progressive respiratory distress with cyanosis: respiratory failure early in course
• Absence of crackles is a common initial finding.
• Chest auscultation can reveal decreased breath sounds, crackles, and rhonchi.
• Coryza and wheezing have infrequently been reported.

Differential Diagnosis

• Viral infections
  • Common viral respiratory pathogens
  • Cytomegalovirus
  • Epstein-Barr virus
• Bacterial infections
  • Mycobacterium tuberculosis
  • Mycobacterium avium-intracellulare
• Other
  • Lymphocytic interstitial pneumonitis

Diagnostic Tests and Interpretation

• Arterial blood gas
  • pH is usually increased.
  • Reduced Pao₂ in room air (<70 mm Hg)
  • Alveolar–arterial oxygen gradient (>35 mm Hg)
• Chest radiograph
  • Most common radiologic presentation is diffuse bilateral alveolar infiltrates:
    • Initially a perihilar distribution that spreads to the periphery
    • Apices are the least affected.
    • Interstitial infiltrates and air bronchograms can be seen.
    • Rapid progression to whole lung consolidation
• Presence of hilar or mediastinal adenopathy may indicate another process such as M. tuberculosis, M. avium-intracellulare, fungal infections, cytomegalovirus, or lymphoma.
• Other tests
  • Lactate dehydrogenase (LDH) can be elevated in patients with AIDS and PCP, but this finding is nonspecific.
  • White blood cell (WBC) count is usually normal.
• Pathologic findings
  • Definitive diagnosis can be obtained by demonstration of P. jiroveci in pulmonary specimens:
    • Induced sputum
    • Bronchoalveolar lavage (BAL) usually through flexible bronchoscopy (90% sensitivity)
    • Open lung or transbronchial biopsy
  • Staining
    • Cysts stain with methenamine-silver, toluidine blue-O stains, calcofluor white, and fluorescein monoclonal antibody
    • Sporozoites and trophozoites are identified with Giemsa stain, modified Wright-Giemsa stain, and fluorescein-conjugated monoclonal antibody stain.
    • Polymerase chain reaction assays of BAL fluid or induced sputum is available and more sensitive for detecting P. jiroveci than microscopic methods but is not approved for diagnosis by the U.S. Food and Drug Administration (FDA).

General Measures

• Supply oxygen as necessary to keep Pao₂ >70 mm Hg.
• Mechanical ventilation must be considered if Pao₂ is <60 mm Hg on FiO₂ of 0.5.

Medication (Drugs)

Additional Therapies

Corticosteroids

• May be beneficial in HIV patients with moderate to severe PCP
• Not systematically evaluated in children
• Consider when Pao₂ is <70 mm Hg or the alveolar–arterial oxygen gradient is >35 mm Hg.
• In patients >13 years of age, suggested dose is prednisone 40 mg PO b.i.d. for days 1 to 5, 40 mg PO once daily for days 6 to 10, and 20 mg PO once daily for days 11 to 21 with tapering. Doses of methylprednisolone or prednisone at 1 mg/kg given b.i.d.–q.i.d. for 5 to 7 days with a taper over the next 5 days have been suggested.

Follow-Up Recommendations

• After 5 to 7 days of treatment
• If no improvement, TMP-SMX should be replaced with pentamidine.
• Standard precautions are required. Isolation from other immunodeficient patients is recommended.

Prognosis

• 5–40% mortality in treated patients
• Near 100% mortality if patient is untreated
• ~35% of patients will have recurrence unless lifetime prophylaxis is instituted.

Complications

• High rate of respiratory failure necessitating intubation and mechanical ventilation (~60%)
• HIV-infected patients have a higher rate (40%) of adverse reactions to TMP-SMX than the general population. Rash is most common, with fever, neutropenia, anemia, renal dysfunction, nausea, vomiting, and diarrhea occurring as well.
• Prophylactic medication protects the patient as long as the drug is administered. However, this does not eradicate P. jiroveci.

ICD-9

136.3 Pneumocystosis

ICD-10

B59 Pneumocystosis

SNOMED

• 75549005 Infection by Pneumocystis jiroveci
• 420403001 Pneumocystosis associated with AIDS
• 415125002 Pneumocystosis jiroveci pneumonia (disorder)