DESCRIPTION

Pneumocystis jirovecii is an opportunistic organism that has some features of a protozoan but morphologically is closer to a fungus and is currently considered a fungus based on DNA sequence analysis. Asymptomatic infection is widespread and occurs early in life. Pneumocystis pneumonia (PCP) occurs in immune compromised hosts, and infection is typically localized to the lungs.

• Previously known as Pneumocystis carinii pneumonia (PCP), the acronym PCP is still in use and refers to Pneumocystis pneumonia.
• Children with acute leukemia, severe combined immune deficiency (SCID), organ or stem cell transplant are at high risk for infection.
• PCP is an AIDS-defining illness in both children and adults with HIV and remains a leading cause of opportunistic infection, particularly among the persons with undiagnosed HIV.
• Chemoprophylaxis against PCP is highly effective and is recommended for all at-risk populations.

EPIDEMIOLOGY

• Pneumocystis species are ubiquitous worldwide and found in mammals, predominantly in the respiratory tract epithelium.
• Mode of transmission is unclear.
  • Airborne animal-to-animal transmission has been demonstrated.
  • Human-to-human airborne transmission is suggested by hospital outbreaks, molecular epidemiology, and clusters of cases.
  • Vertical transmission is postulated but not proven.
• Asymptomatic infection occurs early in life with antibody positivity in 85% of children by 2 years of age.
• Cell-mediated immunity is the single most important factor in disease.
  • In resource-limited areas, famine and malnourishment lead to outbreaks of the endemic infantile form of PCP.
  • In industrialized nations, PCP occurs only in patients with deficient cell-mediated immunity such as HIV/AIDS, hematologic malignancy, and recipients of stem cell or solid organ transplant.
• Endemic infantile form of PCP in infants is likely from primary infection.
• Disease occurring later in life in immune compromised patients is almost certainly from reinfection as there is no evidence for latent infection with Pneumocystis.
• Incubation period is unknown, but the average in hospital outbreaks is about 53 days.
• PCP occurs in 40–60% of untreated infants with AIDS or SCID typically by 3 to 6 months of age.
• In children with leukemia not on prophylaxis, PCP incidence is 12% and can occur during remission or relapse.

RISK FACTORS

• Patients with cancer—mainly hematologic malignancies
• Hematopoietic stem cell transplant or solid organ transplant
• Certain treatments for inflammatory or rheumatologic conditions, such as chronic steroids alone or in combination with other immunosuppressive therapies.
• Defects in cell-mediated immunity including HIV/AIDS and SCID.
• Epidemics of PCP may occur in premature and malnourished infants in resource-limited countries and during times of famine.

GENERAL PREVENTION

• PCP is prevented by antimicrobial prophylaxis in high-risk hosts. Chemoprophylaxis is recommended in the following situations.
  • HIV-infected patients with stage III disease as defined by CD4 count by age, rapidly declining CD4 counts, infants <1 year of age with HIV, or HIV-exposed infants until proven HIV negative
  • Children undergoing chemotherapy
  • Children with hematopoietic stem cell transplants from engraftment and administered for 6 months.
  • Patients with solid organ transplant while on significant immunosuppression
  • Patients on long-term glucocorticoid therapy
  • Patients with cell-mediated immune deficiency
  • Consider in patients on high-dose long-term immune suppression.
• Drug regimen for prophylaxis
  • Trimethoprim-sulfamethoxazole (TMP-SMX) is the drug of choice.
    • 150 mg/m² body surface area per 24 hours of TMP or 5 mg/kg/24 h orally divided into 1 or 2 doses on 2 to 3 consecutive days per week. Maximum daily dose is 320 mg TMP or 2 double-strength tablets per day.
    • TMP-SMX can also be given 7 days a week when prevention against other bacterial infections is sought or to aid in compliance.
  • For patients who cannot tolerate TMP-SMX, alternatives include dapsone 2 mg/kg/24 h with a maximum dose 100 mg/24 h or atovaquone (30 mg/kg/24 h for children 1 to 3 months or >2 years of age and 45 mg/kg/24 h for infant 4 to 24 months of age, maximum dose 1,500 mg/24 h). Inhaled pentamidine is an alternative for children >5 years of age who can tolerate the required nebulizer. Intravenous pentamidine is less effective and generally not recommended.

PATHOPHYSIOLOGY

• Pneumocystis species are biologically and morphologically similar to protozoa; however, DNA analysis is closer to a fungus, so classified as an ascomycetous or sac fungus.
• P. jirovecii, which infects humans, is one of several species of Pneumocystis.
• Two morphologic forms exist:
  • Cyst form with 5 to 7 µm cysts containing sporozoites.
  • Trophozoite form
• Trophozoites attach to the type I alveolar epithelium and transition to larger cystic form.
• Host immune response to infection causes most of the lung damage and leads to hypoxia and respiratory failure.
• In severely immune compromised individuals, disseminated disease is a rare occurrence and involve the liver, spleen, thyroid, eyes, ears, and/or skin.

HISTORY

• PCP presents as a respiratory illness with shortness of breath, nonproductive cough, chills, fatigue, tachypnea, and fever.
• Initial presentation can be indolent and progress slowly over several weeks or occur more abruptly with hypoxemia and respiratory distress or failure.
• Malnourished infants and persons with late-stage HIV/AIDS typically have a subacute onset and will progress to hypoxia and respiratory distress over 1 to 2 weeks.
• Patients with severe immune compromise have a more rapid onset with fevers, cough, and hypoxic respiratory failure.
• Fatigue, weight loss, myalgia/arthralgia, rash, and headache may be signs of an undiagnosed HIV infection.
• A history of immune suppressing medications particularly recent or long-term use of glucocorticoids.

PHYSICAL EXAM

• Physical exam findings are typical for any pneumonia and may include fever, tachycardia, dyspnea, tachypnea, crackles, and/or rhonchi on pulmonary auscultation.
• 50% of cases will have a clear lung exam.
• Hypoxemia out of proportion to the exam findings is characteristic.
• Clinical findings of other opportunistic infections like plaques of oral/esophageal thrush may be present.

DIFFERENTIAL DIAGNOSIS

• Acute respiratory distress syndrome (ARDS)
• Viral or bacterial causes of pneumonia including:
  • COVID-19
  • Mycoplasma
  • Legionella
  • C. pneumoniae
  • Cytomegalovirus
• Tuberculosis
• Fungal infection
  • Candidiasis
  • Histoplasmosis
  • Coccidioidomycosis
  • Cryptosporidium

DIAGNOSTIC TESTS & INTERPRETATION

• Initial tests
  • PCP is suggested by these findings on routine evaluation in an appropriate host and further testing should be considered.
    • Chest radiographs with diffuse bilateral alveolar infiltrates. Infection starts in the perihilar area and then spreads peripherally. Apices are generally spared.
    • Chest CT scans show diffuse ground glass opacities. Nodules, cysts, or areas of consolidation may be present.
    • In moderate to severe disease, arterial blood gases show an alveolar-arterial oxygen gradient >35 mm Hg and an arterial oxygen pressure (Pao ₂) <70 mm Hg.
    • Serum 1,3-β-D-glucan, a nonspecific marker for invasive fungal infection, may be elevated.
• Confirmatory testing
  • Definitive diagnosis is made by visualization of Pneumocystis cysts in lung tissue or respiratory tract secretions. Special stains are used to visualize cysts, sporozoites within cysts, and the trophozoite form.
    • Cyst form can be visualized with methenamine silver stain, toluidine blue stain, or fluorescent monoclonal antibodies.
    • Sporozoites and trophozoites are seen with Giemsa or modified Wright stains.
    • Sputum either expectorated or induced samples can be used to make diagnosis but may have a lower yield.
    • Bronchoalveolar lavage is the primary diagnostic test as sputum can be collected directly and transbronchial lung biopsies can be performed.
    • Polymerase chain reaction (PCR) assays for Pneumocystis are more readily available and can be performed on either sputum or lavage specimens. These tests are not currently approved by the U.S. Food and Drug Administration (FDA), and there is a risk that they could detect colonization over true disease so should be interpreted with care.

GENERAL MEASURES

• Hospitalization is typically required.
• Supportive care including respiratory support is essential and may necessitate intensive care.
• Coinfection with other opportunistic organisms like cytomegalovirus can occur and may cause more severe disease or require additional care.
• Standard precautions are recommended. Due to a theoretical risk of transmission, some experts suggest that patients with PCP should avoid room sharing with other immunodeficient patients.

MEDICATION

FOLLOW-UP RECOMMENDATIONS

• Patients who do not improve after 5 to 7 days of therapy should be reassessed and therapy changed typically from TMP-SMX to pentamidine. Search for other opportunistic infections should also be sought.
• Medical treatment course is typically 21 days and should consist of both antimicrobial agent and steroid taper.
• PCP prophylaxis should be instituted after the completion of therapy.

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.
• Prior episodes of PCP, coinfection with cytomegalovirus (CMV), elevated lactate dehydrogenase (LDH), and low CD4 counts are risk factors for worse prognosis in patients with HIV.

COMPLICATIONS

• Complications include heart failure, pleural effusion, pneumothorax, and respiratory failure necessitating intubation with mechanical ventilation.
• Adverse reactions to the treatment primarily TMP-SMX are common. Mild reactions like vomiting do not necessitate medication changes.

ICD 10

B59 Pneumocystosis