Pneumocystis jirovecii infection
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《胸》
1 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
2 Positive 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
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; rmiller@gum.ucl.ac.uk
A review of Pneumocystis and the rationale for renaming it
Keywords: Pneumocystis carinii; Pneumocystis jirovecii; nomenclature
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.
WHAT IS PNEUMOCYSTIS?
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
HOW DOES HUMAN INFECTION ARISE?
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
COLONISATION AND THE HUMAN RESERVOIR OF INFECTION
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
WHY RENAME PNEUMOCYSTIS CARINII?
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".
FOOTNOTES
Dr Miller is supported by Camden PCT, UK and Dr Huang is supported by the National Institutes of Health, USA, grant no K23 HL072117.
REFERENCES
Chagas C. Uber eine neue Typanosomiasis des Menschen. Mem Inst Oswaldo Cruz 1909;3:1–218.
Delano? P, Delano? M. Sur les rapports des kystes de Carini du poumon des rats avec le Trypanosoma lewisi. C R Acad Sci 1912;155:658–61.
Edman JC, Kovacs JA, Masur H, et al. Ribosomal RNA sequence shows Pneumocystis carinii to be a member of the fungi. Nature 1988;334:519–22.
Stringer SL, Stringer JR, Blase MA, et al. Pneumocystis carinii: sequence from ribosomal RNA implies a close relationship with fungi. Exp Parasitol 1989;68:450–61.
Sinclair K, Wakefield AE, Banerji S, et al. Pneumocystis carinii organisms derived from rat and human hosts are genetically distinct. Mol Biochem Parasitol 1991;45:183–4.
Mazars E, Odberg-Ferragut C, Dei-Cas E, et al. Polymorphism of the thymidylate synthase gene of Pneumocystis carinii from different host species. J Eukaryot Microbiol 1995;42:26–32.
Banerji S, Lugli EB, Miller RF, et al. Analysis of genetic diversity at the arom locus in isolates of Pneumocystis carinii. J Eukaryot Microbiol 1995;42:675–9.
Aliouat EM, Mazars E, Dei-Cas E, et al. Pneumocystis cross infection experiments using SCID mice and nude rats as recipient host showed strong host-species specificity. J Eukarot Microbiol 1994;41:71S.
Demanche C, Berthelemy M, Petit T, et al. Phylogeny of Pneumocystis carinii from 18 primate species confirms host specificity and suggests co-evolution. J Clin Microbiol 2001;39:2126–33.
Tsolaki AG, Beckers P, Wakefield AE. Pre-AIDS isolates of Pneumocystis carinii f. sp. hominis: high genotypic similarity with contemporary isolates, J Clin Microbiol 1998;36:90–3.
Miller RF, Lindley AR, Ambrose HE, et al. Multilocus genotyping of Pneumocystis jiroveci from adult patients with Pneumocystis pneumonia. J Eukaryot Microbiol 2003;50:654–5S.
Wakefield AE, Stewart TJ, Moxon ER, et al. Infection with Pneumocystis carinii is prevalent in healthy Gambian children. Trans R Soc Trop Med Hyg 1990;84:800–2.
Wakefield AE, Pixley FJ, Banerji S, et al. Detection of Pneumocystis carinii with DNA detection. Lancet 1990;336:451–3.
Miller RF, Ambrose HE, Wakefield AE. Pneumocystis carinii f. sp. hominis DNA in immunocompetent health care workers in contact with patients with Pneumocystis carinii pneumonia. J Clin Microbiol 2001;39:3877–82.
Vargas S, Hughes WT, Wakefield AE, et al. Limited persistence in and subsequent elimination of Pneumocystis carinii from the lungs after P carinii pneumonia. J Infect Dis 1995;172:506–10.
Chen W, Gigliotti F, Harmsen AG. Latency is not an inevitable outcome of infection with Pneumocystis carinii. Infect Immun 1993;61:5406–9.
Wakefield AE, Lindley AR, Ambrose HE, et al. Limited asymptomatic carriage of Pneumocystis jiroveci in human immunodeficiency virus-infected patients. J Infect Dis 2003;187:901–8.
Keely SP, Stringer JR, Baughman RP, et al. Genetic variation among Pneumocystis carinii hominis isolates in recurrent pneumocystosis. J Infect Dis 1995;172:595–8.
Tsolaki AG, Miller RF, Underwood AP, et al. Genetic diversity at the internal transcribed spacer regions of the rRNA operon among isolates of Pneumocystis carinii from AIDS patients with recurrent pneumonia. J Infect Dis 1996;174:141–56.
Beard CB, Carter JL, Keely SP, et al. Genetic variation in Pneumocystis carinii isolates from different geographic regions: implications for transmission. Emerg Infect Dis 2000;6:265–72.
Kazanjian P, Armstrong W, Hossler PA, et al. Pneumocystis carinii mutations are associated with duration of sulfa or sulfone prophylaxis exposure in AIDS patients. J Infect Dis 2000;182:551–7.
Huang L, Beard CB, Creasman J, et al. Sulfa or sulfone prophylaxis and geographic region predict mutations in the Pneumocystis carinii dihydropteroate synthase gene. J Infect Dis 2000;182:1192–8.
Huang L, Friedly J, Morris AM, et al. Pneumocystis carinii dihydropteroate synthase genotypes in HIV-infected persons residing in San Francisco: possible implications for disease transmission. J Eukaryot Microbiol 2001;48:137S–8S.
Miller RF, Lindley AR, Ambrose HE, et al. Genotypes of Pneumocystis jiroveci isolates obtained in Harare, Zimbabwe and London, United Kingdom. Antimicrob Agents Chemother 2003;47:3979–81.
Crothers K, Huang L, Morris A, et al. Pneumocystis dihydropteroate synthase mutations in patients with Pneumocystis pneumonia who are newly diagnosed with HIV infection. J Eukaryot Microbiol 2003;50:609S–10S.
Dumoulin A, Mazars E, Seguy N, et al. Transmission of Pneumocystis carinii disease from immunocompetent contacts of infected hosts to susceptible hosts. Eur J Clin Microbiol Infect Dis 2000;19:671–8.
Wakefield AE. DNA sequences identical to Pneumocystis carinii f. sp. carinii and Pneumocystis carinii f. sp. hominis in samples of air spora. J Clin Microbiol 1996;34:1754–9.
Bartlett MS, Vermund SH, Jacobs R, et al. Detection of Pneumocystis carinii DNA in air samples: likely environmental risk to susceptible persons. J Clin Microbiol 1997;31:2511–3.
Helweg-Larsen J, Tsolaki AG, Miller RF, et al. Clusters of Pneumocystis carinii pneumonia: analysis of person to person transmission by genotyping. Q J Med 1998;91:813–20.
Vargas SL, Ponce CA, Gigliotti F, et al. Transmission of Pneumocystis carinii DNA from a patient with P carinii pneumonia to immunocompetent health care workers. J Clin Microbiol 2000;38:1536–8.
Miller RF, Ambrose HE, Novelli V, et al. Probable mother-to-infant transmission of Pneumocystis carinii f. sp. hominis infection. J Clin Microbiol 2002;40:1555–7.
Tsolaki AG, Miller RF, Wakefield AE. Oropharyngeal samples for genotyping and monitoring of response to treatment in AIDS patients with Pneumocystis carinii pneumonia. J Med Microbiol 1999;48:897–905.
Leigh TR, Kangro HO, Gazzard BG, et al. DNA amplification by the polymerase chain reaction to detect sub-clinical Pneumocystis carinii colonization in HIV-positive and HIV-negative homosexuals with and without respiratory symptoms. Respir Med 1993;87:525–9.
Nevez G, Raccurt C, Jounieaux V, et al. Pneumocystosis versus pulmonary Pneumocystis carinii colonization in HIV-negative and HIV-positive patients. AIDS 1999;13:535–6.
Huang L, Crothers K, Morris A, et al. Pneumocystis colonization in HIV-infected patients. J Eukaryot Microbiol 2003;50:616–7S.
Morris A, Kingsley LA, Groner G, et al. Prevalence and clinical predictors of Pneumocystis colonization among HIV-infected men. AIDS 2004;18:793–8.
Armbruster C, Hassl A, Kriwanek S. Pneumocystis carinii colonization in the absence of immunosuppression. Scand J Infect Dis 1997;29:591–3.
Sing A, Roggenkamp A, Autenrieth IB, et al. Pneumocystis carinii carriage in immunocompetent patients with primary pulmonary disorders as detected by single or nested PCR. J Clin Microbiol 1999;37:3409–10.
Maskell NA, Waine DJ, Lindley A, et al. Asymptomatic carriage of Pneumocystis jiroveci in subjects undergoing bronchoscopy: a prospective study. Thorax 2003;58:594–7.
Helweg-Larsen J, Jensen JS, Dohn B, et al. Detection of Pneumocystis DNA in samples from patients suspected of bacterial pneumonia: a case-control study. BMC Infect Dis 2002;2:28.
Vargas SL, Ponce CA, Sanchez CA, et al. Pregnancy and asymptomatic carriage of Pneumocystis jiroveci. Emerg Infect Dis 2003;9:605–6.
The Pneumocystis Workshop. Revised nomenclature for Pneumocystis carinii. J Eukaryot Microbiol 1994;41:121–2S.
Frenkel JK. Pneumocystis pneumonia, an immunodeficiency dependent disease (IDD): a critical historical overview. J Eukaryot Microbiol 1999;46:89–92S.
Stringer JR, Cushion MT, Wakefield AE. New nomenclature for Pneumocystis carinii. Proceedings of the Seventh International Workshops on Opportunistic Protists. J Eukaryot Microbiol 2001;48:184–9S.
Stringer JR, Beard CB, Miller RF, et al. A new name (Pneumocystis jiroveci) for Pneumocystis from humans. Emerg Infect Dis 2002;8:891–6.(R Miller1 and L Huang2)
2 Positive 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
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; rmiller@gum.ucl.ac.uk
A review of Pneumocystis and the rationale for renaming it
Keywords: Pneumocystis carinii; Pneumocystis jirovecii; nomenclature
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.
WHAT IS PNEUMOCYSTIS?
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
HOW DOES HUMAN INFECTION ARISE?
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
COLONISATION AND THE HUMAN RESERVOIR OF INFECTION
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
WHY RENAME PNEUMOCYSTIS CARINII?
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".
FOOTNOTES
Dr Miller is supported by Camden PCT, UK and Dr Huang is supported by the National Institutes of Health, USA, grant no K23 HL072117.
REFERENCES
Chagas C. Uber eine neue Typanosomiasis des Menschen. Mem Inst Oswaldo Cruz 1909;3:1–218.
Delano? P, Delano? M. Sur les rapports des kystes de Carini du poumon des rats avec le Trypanosoma lewisi. C R Acad Sci 1912;155:658–61.
Edman JC, Kovacs JA, Masur H, et al. Ribosomal RNA sequence shows Pneumocystis carinii to be a member of the fungi. Nature 1988;334:519–22.
Stringer SL, Stringer JR, Blase MA, et al. Pneumocystis carinii: sequence from ribosomal RNA implies a close relationship with fungi. Exp Parasitol 1989;68:450–61.
Sinclair K, Wakefield AE, Banerji S, et al. Pneumocystis carinii organisms derived from rat and human hosts are genetically distinct. Mol Biochem Parasitol 1991;45:183–4.
Mazars E, Odberg-Ferragut C, Dei-Cas E, et al. Polymorphism of the thymidylate synthase gene of Pneumocystis carinii from different host species. J Eukaryot Microbiol 1995;42:26–32.
Banerji S, Lugli EB, Miller RF, et al. Analysis of genetic diversity at the arom locus in isolates of Pneumocystis carinii. J Eukaryot Microbiol 1995;42:675–9.
Aliouat EM, Mazars E, Dei-Cas E, et al. Pneumocystis cross infection experiments using SCID mice and nude rats as recipient host showed strong host-species specificity. J Eukarot Microbiol 1994;41:71S.
Demanche C, Berthelemy M, Petit T, et al. Phylogeny of Pneumocystis carinii from 18 primate species confirms host specificity and suggests co-evolution. J Clin Microbiol 2001;39:2126–33.
Tsolaki AG, Beckers P, Wakefield AE. Pre-AIDS isolates of Pneumocystis carinii f. sp. hominis: high genotypic similarity with contemporary isolates, J Clin Microbiol 1998;36:90–3.
Miller RF, Lindley AR, Ambrose HE, et al. Multilocus genotyping of Pneumocystis jiroveci from adult patients with Pneumocystis pneumonia. J Eukaryot Microbiol 2003;50:654–5S.
Wakefield AE, Stewart TJ, Moxon ER, et al. Infection with Pneumocystis carinii is prevalent in healthy Gambian children. Trans R Soc Trop Med Hyg 1990;84:800–2.
Wakefield AE, Pixley FJ, Banerji S, et al. Detection of Pneumocystis carinii with DNA detection. Lancet 1990;336:451–3.
Miller RF, Ambrose HE, Wakefield AE. Pneumocystis carinii f. sp. hominis DNA in immunocompetent health care workers in contact with patients with Pneumocystis carinii pneumonia. J Clin Microbiol 2001;39:3877–82.
Vargas S, Hughes WT, Wakefield AE, et al. Limited persistence in and subsequent elimination of Pneumocystis carinii from the lungs after P carinii pneumonia. J Infect Dis 1995;172:506–10.
Chen W, Gigliotti F, Harmsen AG. Latency is not an inevitable outcome of infection with Pneumocystis carinii. Infect Immun 1993;61:5406–9.
Wakefield AE, Lindley AR, Ambrose HE, et al. Limited asymptomatic carriage of Pneumocystis jiroveci in human immunodeficiency virus-infected patients. J Infect Dis 2003;187:901–8.
Keely SP, Stringer JR, Baughman RP, et al. Genetic variation among Pneumocystis carinii hominis isolates in recurrent pneumocystosis. J Infect Dis 1995;172:595–8.
Tsolaki AG, Miller RF, Underwood AP, et al. Genetic diversity at the internal transcribed spacer regions of the rRNA operon among isolates of Pneumocystis carinii from AIDS patients with recurrent pneumonia. J Infect Dis 1996;174:141–56.
Beard CB, Carter JL, Keely SP, et al. Genetic variation in Pneumocystis carinii isolates from different geographic regions: implications for transmission. Emerg Infect Dis 2000;6:265–72.
Kazanjian P, Armstrong W, Hossler PA, et al. Pneumocystis carinii mutations are associated with duration of sulfa or sulfone prophylaxis exposure in AIDS patients. J Infect Dis 2000;182:551–7.
Huang L, Beard CB, Creasman J, et al. Sulfa or sulfone prophylaxis and geographic region predict mutations in the Pneumocystis carinii dihydropteroate synthase gene. J Infect Dis 2000;182:1192–8.
Huang L, Friedly J, Morris AM, et al. Pneumocystis carinii dihydropteroate synthase genotypes in HIV-infected persons residing in San Francisco: possible implications for disease transmission. J Eukaryot Microbiol 2001;48:137S–8S.
Miller RF, Lindley AR, Ambrose HE, et al. Genotypes of Pneumocystis jiroveci isolates obtained in Harare, Zimbabwe and London, United Kingdom. Antimicrob Agents Chemother 2003;47:3979–81.
Crothers K, Huang L, Morris A, et al. Pneumocystis dihydropteroate synthase mutations in patients with Pneumocystis pneumonia who are newly diagnosed with HIV infection. J Eukaryot Microbiol 2003;50:609S–10S.
Dumoulin A, Mazars E, Seguy N, et al. Transmission of Pneumocystis carinii disease from immunocompetent contacts of infected hosts to susceptible hosts. Eur J Clin Microbiol Infect Dis 2000;19:671–8.
Wakefield AE. DNA sequences identical to Pneumocystis carinii f. sp. carinii and Pneumocystis carinii f. sp. hominis in samples of air spora. J Clin Microbiol 1996;34:1754–9.
Bartlett MS, Vermund SH, Jacobs R, et al. Detection of Pneumocystis carinii DNA in air samples: likely environmental risk to susceptible persons. J Clin Microbiol 1997;31:2511–3.
Helweg-Larsen J, Tsolaki AG, Miller RF, et al. Clusters of Pneumocystis carinii pneumonia: analysis of person to person transmission by genotyping. Q J Med 1998;91:813–20.
Vargas SL, Ponce CA, Gigliotti F, et al. Transmission of Pneumocystis carinii DNA from a patient with P carinii pneumonia to immunocompetent health care workers. J Clin Microbiol 2000;38:1536–8.
Miller RF, Ambrose HE, Novelli V, et al. Probable mother-to-infant transmission of Pneumocystis carinii f. sp. hominis infection. J Clin Microbiol 2002;40:1555–7.
Tsolaki AG, Miller RF, Wakefield AE. Oropharyngeal samples for genotyping and monitoring of response to treatment in AIDS patients with Pneumocystis carinii pneumonia. J Med Microbiol 1999;48:897–905.
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