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.