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Pneumocystis jirovecii infection
  1. R Miller1,
  2. L Huang2
  1. 1Centre for Sexual Health and HIV Research, Department of Primary Care and Population Sciences, Royal Free and University College Medical School, University College London, London WC1E 6AU, UK
  2. 2Positive Health Programme and Division of Pulmonary and Critical Care Medicine, San Francisco General Hospital, Department of Medicine, University of California San Francisco, San Francisco, CA 94110, USA
  1. Correspondence to:
    Dr R Miller
    Centre for Sexual Health and HIV Research, Department of Primary Care and Population Sciences, Royal Free and University College Medical School, University College London, London WC1E 6AU, UK;

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A review of Pneumocystis and the rationale for renaming it

The organism Pneumocystis causes severe pneumonia in individuals with immune systems impaired by HIV, transplantation, malignancy, connective tissue disease, and the treatment thereof. In HIV infected patients it remains a major pathogen in those who are unaware of their HIV serostatus, or who decline to take or are intolerant of highly active antiretroviral therapy. Pneumocystis also infects a wide variety of mammals and causes pneumonia in those that are immunosuppressed or immunodeficient. Originally Pneumocystis was thought to be a single species of protozoa. Study of the organism has been severely hampered by the fact that it cannot be cultured in vitro. Over the last 20 years, using molecular biological, immunological and other techniques, Pneumocystis has been shown to be a fungus, to be genetically diverse, host species specific, transmissible from animal to animal, to colonise individuals with minor degrees of immunosuppression, and to cause clinical disease by “new” infection in addition to reactivation of latent childhood acquired infection. More recently the organism causing disease in humans has been renamed Pneumocystis jirovecii. This article highlights some of these recent developments and provides a rationale for the renaming of the organism.


Chagas first identified Pneumocystis organisms in humans in 1909, but they were mistaken for a new stage of the life cycle of the protozoan Trypanosoma cruzi.1 Within a very short time it became apparent that the organism infected other host species, was not a trypanosome, and was named Pneumocystis carinii in honour of Carini, a colleague of Chagas.2 For many years the organism continued to be widely viewed as a protozoan, based on the observations that it had morphological features of protozoa and lacked some phenotypic features typical of fungi, and that antiprotozoal but not antifungal drugs were effective. In 1988 DNA sequence analysis showed that Pneumocystis was a fungus.3,4 Subsequently, additional DNA analysis at many loci has shown that Pneumocystis organisms from different mammalian hosts are quite different.5–7 It is also apparent that Pneumocystis shows strong host species specificity—for example, it is not possible to cross infect a mouse with Pneumocystis from a rat8 yet, if Pneumocystis obtained from the lungs of one rat is transferred to another rat, it will cause severe pneumonia. One explanation for these observations is that Pneumocystis is an obligate parasite which has co-evolved in a particular host in order to survive.9 The above data further indicate that human Pneumocystis infection is not a zoonosis. DNA sequence analysis of human Pneumocystis at several different loci has demonstrated genetic diversity in the organism7,10,11 and has shown that two or more types of organism infect some patients with Pneumocystis pneumonia.7,11


It was originally thought that Pneumocystis organisms were acquired during childhood and persisted in the lungs in adult life in a dormant phase. Immunosuppression of the individual—for example, by transplantation or by HIV infection—allowed the organism to propagate and cause pneumonia. The finding of antibodies to Pneumocystis in the majority of healthy children12 and the strong association of disease with immunosuppression support this “latency” hypothesis. This hypothesis has been challenged by studies showing a lack of Pneumocystis in the lungs of healthy individuals13 and by studies which showed that Pneumocystis organisms are frequently acquired and cleared by the immune system of immune competent humans.14 Animal studies also challenge the “latency” hypothesis. In rat and severe combined immunodeficiency (SCID) mice models of infection, Pneumocystis organisms are eliminated from the lungs after Pneumocystis pneumonia and persistence of latent organisms is limited.15,16 Limited asymptomatic carriage of Pneumocystis has been demonstrated in some HIV immunosuppressed adults; during carriage a change in genotype was observed, strongly supporting a hypothesis of “recent infection”.17 Further support for the “recent infection” model comes from studies of patients with recurrent episodes of Pneumocystis pneumonia in which a different genotype of Pneumocystis was associated with each episode.18,19 Recent infection is suggested by the finding that allelic variation patterns in isolates of Pneumocystis are correlated with patient’s place of diagnosis and not their place of birth.20 The target enzyme for sulpha drugs (sulphamethoxazole, dapsone, etc) is dihydropteroate synthase (DHPS). In many organisms, including protozoa such as Plasmodium falciparum and bacteria such as Streptococcus pneumoniae, mutations in the DHPS gene confer resistance to sulpha drugs. Several studies have shown a significant association between patients’ receipt of sulpha drug prophylaxis and the presence of mutations in the DHPS gene of Pneumocystis.21,22 These mutations also correlate with geographical location22,23 and may additionally be found in Pneumocystis from patients who have not received sulpha drug prophylaxis, suggesting that recent transmission has occurred, either directly person to person or via a common environmental source.23–25

In animal models airborne transmission of Pneumocystis has been demonstrated26 but the route of transmission of human Pneumocystis is unclear. Human Pneumocystis DNA has been identified in air spores from both rural27 and hospital environments,28 and it is likely that transmission between humans occurs via the airborne route. This hypothesis is supported by reports of case clusters of Pneumocystis pneumonia among immunosuppressed patients,29 transmission of Pneumocystis DNA from immunosuppressed patients to immune competent healthcare workers,14,30 and mother to child transmission of Pneumocystis infection.31


Increasingly sensitive techniques have been developed for detecting Pneumocystis DNA in human respiratory samples (bronchoscopic alveolar lavage fluid, induced sputum, and oropharyngeal washes) using the polymerase chain reaction.11,13,14,32 This sensitivity has enabled detection of very low levels of Pneumocystis, not detectable by conventional histochemical staining, in respiratory samples from individuals in whom it was not expected. Molecular detection techniques have shown that Pneumocystis is carried in the lungs of asymptomatic individuals with mild immunosuppression induced by HIV or malignancy,33–36 in immune competent patients37 with primary pulmonary disorders,38 in patients receiving long term corticosteroid therapy for malignancy or connective tissue disorders,39,40 and in pregnant women.41 It is thought that detection of Pneumocystis in respiratory samples from these asymptomatic patient groups represents colonisation with the organism. It is further hypothesised that these groups of patients may be important in the person to person transmission of Pneumocystis and that they may be a reservoir for future Pneumocystis infection in other susceptible (immunosuppressed) individuals.17


In 1994, in response to the accumulation of molecular biological data demonstrating genetic diversity among isolates of Pneumocystis from different host species together with data from cross infection studies suggesting host species specificity, an interim renaming of Pneumocystis carinii occurred using a trinomial system.42 Thus the organism causing infection in humans was named Pneumocystis carinii f. sp. hominis and that causing infection in rats was called Pneumocystis carinii f. sp. carinii. In 1999 a binomial system was proposed for naming the organism.43 The organism producing human disease is now known as Pneumocystis jirovecii (pronounced “yee-row-vetsee”) in honour of the Czech parasitologist Otto Jírovec who was one of the first researchers to study Pneumocystis in humans.44,45 This renaming not only recognises the host specificity of different species of Pneumocystis for different mammalian hosts, but also the significant differences that exist among different species of Pneumocystis at a DNA sequence level. Pneumocystis carinii is now the name used to describe infection in rats and is not infectious to humans.44,45 The acronym “PCP” which is used to describe the clinical syndrome of pneumonia in both humans and other mammals is still used, but it now represents PneumoCystis Pneumonia. Physicians and patients will be reassured by the knowledge that human infection does not arise in—nor can it be transmitted to—domestic animals, and by the fact that, despite the name change, the clinical disease remains “PCP”.

A review of Pneumocystis and the rationale for renaming it


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  • Dr Miller is supported by Camden PCT, UK and Dr Huang is supported by the National Institutes of Health, USA, grant no K23 HL072117.

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