Quantitative Polymerase Chain Reaction in Diagnosis of Pneumocystis Pneumonia
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Quantitative Polymerase Chain Reaction in Diagnosis of Pneumocystis Pneumonia , Quantitative Polymerase Chain Reaction in Diagnosis of Pneumocystis Pneumonia , کتابخانه دیجیتال دانشگاه علوم پزشکی اصفهانKeywords:
Pneumocystis pneumonia
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Pneumocystis pneumonia is a major cause of illness and death in immunocompromised hosts. The numbers of pneumocystis pneumonia cases in Thailand have increased each year from 1992 to 2000 and peaked in 2000 at 6,255 cases. The microbe that causes pneumocystis pneumonia in humans is called Pneumocystis jirovecii. Pneumocystis sp. was discovered nearly a century ago, but the knowledge of Pneumocystis sp. remained poorly understood, until the molecular biology techniques help scientists verify it fungus nature. In the past, Pneumocystis sp. was misclassified as protozoan due to its morphologic features. Later, it was reclassified as fungus due to DNA analysis. Cotrimaxazole, the combination of trimethoprim-sulfamethoxazole, is the drug of choice for treatment and prophylaxis of pneumocystis pneumonia. However, increasing evidence of mutations in the enzyme dihydropteroate synthase (DHPS), the target of sulfa drugs represent emergence of sulfa resistance.
Pneumocystis pneumonia
Dihydropteroate synthase
DHPS
Trimethoprim
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Pneumocystis pneumonia (PCP) is the most frequent fungal opportunistic infection defining AIDS in HIV-infected patients, and is of growing importance in HIV-negative patients. In this latter category of patients, the diagnosis mainly relies on real-time polymerase chain reaction (qPCR) detection of Pneumocystis jirovecii (Pj) on respiratory samples. The PneumoGenius® kit (PathoNostics) allows the simultaneous detection of Pj mitochondrial large subunit (mtLSU) and dihydropteroate synthase (DHPS) polymorphisms, which could be of interest to anticipate therapeutic failure. This study aimed at evaluating its clinical performance on 251 respiratory specimens (239 patients), (i) for P. jirovecii detection in clinical samples, and (ii) for DHPS polymorphisms detection in circulating strains. Patients were classified according to modified European Organization for Research and Treatment of Cancer/Invasive Fungal Infections Cooperative Group and the National Institute of Allergy and Infectious Diseases Mycoses Study Group (EORTC/MSG) criteria, as having proven PCP (n = 62), probable PCP (n = 87), Pneumocystis colonization (n = 37), and no PCP (n = 53). Compared with in-house qPCR, the sensitivity of PneumoGenius® assay for P. jirovecii detection reached 91.9% (182/198), the specificity was excellent (100%, 53/53) and the global concordance was 93.6% (235/253). A total of four diagnoses of proven/probable PCP were missed by the PneumoGenius® assay, reaching a 97.5% sensitivity (157/161) in this sub-group. The 12 other 'false-negative' results were obtained in patients diagnosed as colonized using the in-house PCR. DHPS genotyping was successful for 147/182 samples with PneumoGenius® and revealed dhps mutation in 8 samples, which were all confirmed by sequencing. In conclusion, PneumoGenius® assay missed the detection of low-burden PCP. This lower sensitivity for PCP diagnosis can be balanced by a higher specificity (P. jirovecii colonization less frequently detected) and the efficient detection of DHPS hot spot mutations.The diagnosis of Pneumocystis pneumonia (PCP) relies on DNA detection of P. jirovecii in respiratory samples. In this study, we show that the commercial assay PneumoGenius® has a lower sensitivity than our in-house qPCR for PCP diagnosis, but provides accurate results for DHPS genotyping.
Dihydropteroate synthase
DHPS
Pneumocystis pneumonia
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2009 marks the 100th anniversary of the first description of Pneumocystis, an organism that was ignored for much of its first 50 years but that has subsequently been recognized as an important pathogen of immunocompromised patients, especially patients infected with human immunodeficiency virus (HIV). We present a patient with chronic lymphocytic leukemia who died from Pneumocystis pneumonia (PCP) despite appropriate anti-Pneumocystis therapy. Although substantial advances in diagnosis, treatment, and prevention of PCP have decreased its frequency and improved prognosis, PCP continues to be seen in both HIV-infected patients and patients receiving immunosuppressive medications. Pneumocystis species comprise a family of fungi, each of which appears to be able to infect only 1 host species. Pneumocystis has a worldwide distribution. Immunocompetent hosts clear infection without obvious clinical consequences. Pneumocystis has been identified in patients with other diseases such as chronic obstructive pulmonary disease, although its clinical impact is uncertain. Immunocompromised patients develop disease as a consequence of reinfection and possibly reactivation of latent infection. In patients with HIV infection, the CD4 count is predictive of the risk for developing PCP, but such reliable markers are not available for other immunocompromised populations. In the majority of patients with PCP, multiple Pneumocystis strains can be identified using recently developed typing techniques. Because Pneumocystis cannot be cultured, diagnosis relies on detection of the organism by colorimetric or immunofluorescent stains or by polymerase chain reaction. Trimethoprim-sulfamethoxazole is the preferred drug regimen for both treatment and prevention of PCP, although a number of alternatives are also available. Corticosteroids are an important adjunct for hypoxemic patients.
Pneumocystis pneumonia
Opportunistic infection
Pneumocystosis
Trimethoprim
AIDS-Related Opportunistic Infections
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Elevation of levels of serum (1→3) beta-d-glucan (BDG), an important cell wall component of most fungi, including Pneumocystis jirovecii, have been observed in adult patients with Pneumocystis jirovecii pneumonia (PCP), usually at levels exceeding 500 pg/ml ([4][1], [6][2], [10][3]). However,
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The immune responses to Pneumocystis jirovecii major surface glycoprotein (Msg) in individuals with human immunodeficiency virus (HIV) infection are poorly understood.We examined the sequential serologic responses to recombinant Msg carboxyl terminus fragments (MsgC1, MsgC3, MsgC8, and MsgC9) by enzyme-linked immunosorbent assay in a cohort of individuals with HIV infection for the 5.5 years before death and autopsy. Analyses included mean antibody levels by status at death (Pneumocystis pneumonia, P. jirovecii colonization, or neither), factors associated with high antibody levels, and antibody responses before and after active Pneumocystis pneumonia.Patients who died from Pneumocystis pneumonia had higher levels of antibody to MsgC8 than did patients who died from other causes. Previous episode of Pneumocystis pneumonia, geographic location, and age were independent predictors of high levels of anitbodies to most or all Msgs. Failure to take Pneumocystis pneumonia prophylaxis was associated with high levels of antibody to MsgC1. Patients who developed and recovered from active Pneumocystis pneumonia during the study exhibited an increase in serum antibody levels that persisted for months after the infection, whereas patients who developed another acquired immunodeficiency syndrome-defining illness did not.Serum antibodies to Msgs are important markers of P. jirovecii infection in patients with HIV infection and are influenced by host and environmental factors in complex ways.
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