Pneumocystis jirovecii Pneumonia
Section snippets
Historical background of Pneumocystis spp
Members of the fungal genus now known as Pneumocystis were first identified in 1909 by Chagas in the lung of guinea pigs that had been experimentally infected with Trypanosoma cruzi. Chagas thought he had identified a new trypanosomal life form. In 1910, Carini noted morphologically similar organisms in the lung of rats infected with Trypanosoma lewisi, and likewise thought they were a new type of trypanosome. In 1912, Delanoe and Delanoe, working at the Institut Pasteur, Paris, reviewed
Taxonomy
Pneumocystis organisms were considered to form a unique taxonomic entity (designated as P carinii). Recent research has demonstrated that the genus Pneumocystis is in fact a complex group with numerous species. Based on morphologic criteria and response of the infection to treatment with the antiprotozoan drug pentamidine, it was initially thought that P carinii was a protozoan. In 1988, Edman and Stringer independently showed that the ribosomal RNA sequences of P carinii were related to those
Life Cycle
Many investigators have attempted to cultivate Pneumocystis using a variety of techniques, but have had limited success, impeding studies of Pneumocystis. Studies of the life cycle of Pneumocystis have been based mainly on light and electron microscopic analysis of forms seen in infected lungs or short-term culture.36 There are 2 predominant life cycle forms, the trophic form and the cyst form. The trophic form is small (1–4 μm) and predominate over the cyst form during infection by
Epidemiology
In this section the possible reservoirs of Pneumocystis spp and data on human colonization are discussed, and groups at risk of PCP are addressed.
Although Pneumocystis DNA has been identified in the air surrounding apple orchards and the surface of pond water, the existence of an environmental niche for Pneumocystis is uncertain.57, 58, 59, 60 However, exposure to P jirovecii is common early during life, as demonstrated by a high seroprevalence of anti-Pneumocystis antibodies in immunocompetent
HIV Infection
During HIV infection, the level and percentage of circulating CD4+ cells and the control of viral replication have been found to be predictive of the risk of pneumocystosis. Indeed, PCP develops predominantly in persons whose CD4+ cell count is less than 200 cells/μL or 15% of T cells, and whose viral replication is not controlled.114, 115, 116 Early in the epidemic, the incidence of PCP was almost 20 cases per 100 person-years among HIV-infected patients with CD4+ cell counts of less than 200
Clinical presentation
PCP classically presents with fever, cough, and dyspnea. Physical examination is nonspecific, and the pulmonary auscultation is often normal, even in the presence of significant disease and hypoxemia. Discrete crackles may be present. Acute dyspnea with pleuritic chest pain may indicate the development of a pneumothorax, which has been described in 2% to 4% of patients.186, 187 In general, HIV-infected persons present with a subacute course and longer symptom duration than other
Radiological presentation
On chest radiograph, PCP usually presents with bilateral, diffuse, reticular, or granular opacities. Chest radiograph may be normal at diagnosis in as many as 39% of cases.189 High-resolution computed tomography (CT) scanning is more sensitive than chest radiograph for detection of PCP (Fig. 1; for a review, see Boiselle and colleagues.189). A CT scan typically shows ground-glass opacities with patchy distribution, predominating in perihilar regions of lungs. Thickened septal lines and areas of
Microbiological diagnosis
As Pneumocystis cannot readily be cultured in the laboratory, the diagnosis of PCP continues to mostly rely on the microscopic demonstration of the characteristic organisms in respiratory specimens such as BAL fluid or induced sputum. Trophic forms can be detected with the use of certain stains, such as modified Papanicolaou, Giemsa, or Gram-Weigert. Cysts can be stained with Gomori-methenamine silver, cresyl echt violet, and toluidine blue O or Calcofluor white (Fig. 2).192 Fluorescein-labeled
Treatment
Because of high efficacy and the availability of oral and parenteral forms, trimethoprim-sulfamethoxazole (TMP-SMX) is the first-line agent for the treatment of mild to severe PCP either in HIV and non-HIV-infected patients. Adverse reactions usually begin during the second week of treatment. These reactions are more frequent in HIV-infected patients. First-line and alternative therapies are summarized in Table 1. Parenteral pentamidine is the most studied drug as an alternative to TMP-SMX.
Prognosis
Despite treatment, mortality of PCP still remains high. Some early studies showed similar poor survival between AIDS and non-AIDS patients of 50% to 64%.11, 123, 139 However, most studies demonstrate a better survival (86%–92%) in AIDS patients118, 222, 223 in comparison with non-AIDS patients with various underlying conditions (survival 51%–80%).125, 140, 141, 154, 224, 225, 226 As PCP is a severe infection with a high mortality rate, prevention is essential in the groups at risk.
Prevention of Nosocomial Transmission
As nosocomial acquisition of Pneumocystis infection has been demonstrated in some of the PCP outbreaks,80, 81, 82 prevention of air transmission from hospitalized patients with PCP should be considered to avoid secondary cases. As person-to-person transmission has not been demonstrated, respiratory isolation is not currently recommended in national guidelines. However, mice-to-mice transmission has been demonstrated.69, 70, 71 In the authors' practice, patients with PCP are hospitalized in
Recommendation for HIV-Infected Patients
The Infectious Disease Society of America and the US Public Health Service had published guidelines for the prevention of opportunistic infection including PCP.227 HIV-infected adults and adolescents, including pregnant women and those on HAART, should receive chemoprophylaxis against PCP if they have a CD4+ T-cell count of less than 200/μL or oropharyngeal candidiasis. Persons who have a CD4+ T-cell percentage of less than 14% should be considered for prophylaxis. Primary and secondary PCP
Summary
PCP still remains a severe opportunistic infection, associated with a high mortality rate. Despite a growing knowledge base on PCP, progress is desired in many directions. First, one is still not able to measure the level of risk of PCP in the non-HIV immunocompromised host. Biologic markers of immunodeficiency, such as CD4 levels in HIV-infected patients, are needed. It is hoped that such tools will exist in the future. Factors influencing colonization, such as previous lung disease or smoking
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2023, Journal of the American Society of CytopathologyCitation Excerpt :While initially believed to be a protozoan, ribosomal RNA sequencing in the late 1980s revealed it to be more closely related to fungi.54,55 Interestingly, Pneumocystis displays features that are atypical of most fungi including that it is unable to be grown in vitro in fungal culture media, it responds to some antiparasitic agents, and its cell wall contains cholesterol rather than ergosterol which is a property that makes amphotericin and some other fungal agents ineffective toward it.56 Today, despite prior controversies, it is accepted that Pneumocystis belongs to the fungal kingdom with Pneumocystis jirovecii chosen to refer to the form that infects humans and Pneumocystis carinii, the form that infects rats.56-60
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