[Pneumocystis pneumonia (PCP)--Pneumocystis carinii pneumonia (Syn. Pneumocystis jirovecii pneumonia)].
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Pneumocystis pneumonia (PCP) caused by the opportunistic fungal agent Pneumocystis jirovecii (formerly P. carinii) continues to cause illness and death in HIV-infected patients. In the absence of a culture system to isolate and maintain live organisms, efforts to type and characterize the organism have relied on polymerase chain reaction-based approaches. Studies using these methods have improved understanding of PCP epidemiology, shedding light on sources of infection, transmission patterns, and potential emergence of antimicrobial resistance. One concern, however, is the lack of guidance regarding the appropriateness of different methods and standardization of these methods, which would facilitate comparing results reported by different laboratories.
Pneumocystis pneumonia (PCP) has historically been one of the leading causes of disease among persons with AIDS. The introduction of highly active antiretroviral therapy in industrialized nations has brought about dramatic declines in the incidence of AIDS-associated complications, including PCP. In the adult population, the incidence of PCP has significantly decreased, but it remains among the most common AIDS-defining infections. Similar declines have been documented in the pediatric population. In much of the developing world, PCP remains a significant health problem, although its incidence among adults in sub-Saharan Africa has been debated. This review discusses the epidemiology of PCP during the current era of the AIDS epidemic. Although fewer cases of PCP occur in industrialized countries, increasing drug-resistant HIV infections, possible drug-resistant PCP, and the tremendous number of AIDS cases in developing countries make this disease of continued public health importance.
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Pneumocystis carinii pneumonia is often difficult to diagnose in an ambulatory care setting. Previous reports have identified elements of the clinical history, physical examination, and clinical testing that are useful predictors of P carinii pneumonia. We analyzed published data on these predictors and measured them against methodologic standards for clinical prediction rules. Variables with high negative or positive predictive value for P carinii pneumonia, low error rates, or compelling biologic credibility were then selected to develop an untested clinical prediction rule for P carinii pneumonia. We suggest that dyspnea, oral lesions, chest roentgenographic examination, and pulse oximetry may be used to select patients requiring sputum testing and/or bronchoscopy for the diagnosis of P carinii pneumonia. The role of pulse oximetry in the diagnosis of P carinii pneumonia merits further study.
Pneumocystis f. sp. hominis causes pneumonia in immunocompromised persons. In order to determine the types and distribution of P. carinii organisms within a single human lung, multiple samples were obtained from the lung of a child who died of P. carinii pneumonia. P. carinii DNA was detected in all of the samples and 2 different genotypes of P. carinii were identified, with uneven distribution in the lung, demonstrating that infection of the human lung is not necessarily clonal, and that different P. carinii genotypes may predominate in different areas of the lung.
BACKGROUND: The impact of Pneumocystis jirovecii (formerly P. carinii) dihydropteroate synthase (DHPS) gene mutations on morbidity and mortality of Pneumocystis pneumonia (PCP) in HIV-positive patients is unclear. OBJECTIVE: To determine whether severity and outcome of HIV-associated PCP differs according to DHPS genotype. SETTING: A prospective, observational study in a university-affiliated county hospital. PATIENTS: The study included 197 patients with 215 microscopically confirmed PCP episodes and successfully sequenced DHPS genotypes; 175 (81%) episodes displayed mutant genotypes. MAIN OUTCOME MEASURE: All-cause mortality within 60 days. RESULTS: The majority of patients (86%) with PCP containing Pneumocystis DHPS mutations survived. Although severity of PCP was comparable, there was a trend for more patients with mutant genotypes than patients with wild-type to require mechanical ventilation (14.3% versus 2.5%; P = 0.056) and to die (14.3% versus 7.5%, P = 0.31). Independent predictors of mortality at baseline were low serum albumin levels [odds ratio (OR), 4.62; 95% confidence interval (CI), 1.63-13.1; P = 0.004] and requiring intensive care within 72 h of hospitalization (OR, 5.06; 95% CI, 1.43-18.0; P = 0.012). CONCLUSION: The majority of HIV-infected patients with PCP containing mutant Pneumocystis DHPS genotypes survived. Mortality was related primarily to the underlying severity of illness. However, a trend towards increased mortality in episodes of PCP containing mutant DHPS genotypes was observed and this warrants further study.
Pneumocystis jiroveci is a common cause of pneumonia in South African patients with AIDS. Sulphonamide resistance may become a problem in South Africa, as patients are treated with prophylactic co-trimoxazole when their CD4 counts fall below 200 cells/microliter. Failure of prophylaxis and treatment has been observed, possibly due to infection with sulphonamide-resistant strains. Sulphonamide resistance has been reported elsewhere, and is due to point mutations at codons 55 and 57 of the dihydropteroate synthase gene. Strain typing is useful for molecular epidemiological purposes.
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We performed an analysis of the value of repeat bronchoalveolar lavage (BAL) at 21 days to identify patients at risk for early relapse with Pneumocystis carinii pneumonia. Patients with P. carinii pneumonia and the acquired immunodeficiency syndrome (AIDS) were asked to participate in this study. All patients had P. carinii identified on methenamine silver stain of BAL fluid. BAL fluid was also stained with a modified Wright-Giemsa technique. The Wright-Giemsa stain was done to determine the cell differential count, and the number of P. carinii clusters associated with 500 nucleated cells was used as an estimate of P. carinii burden in the BAL. Initial and follow-up lavage was performed in 56 patients. Patients were classified based on their clinical response to anti-P. carinii therapy at 21 days. Nonresponders were patients with persistent or worsening symptoms. Responders were patients who improved and had therapy discontinued. Responders were further classified as responders with relapse if P. carinii pneumonia recurred within 6 months of the initial episode or responders without relapse if they remained disease free during the follow-up period. Responders without relapse reduced P. carinii cluster counts more than 50% in 24 of 25 cases. In responders with relapse P. carinii cluster counts were unchanged. The responders as a group had a significant decrease in the percentage of neutrophils in the BAL, with only 2 of 32 still having increased neutrophils in the follow-up lavage compared to 17 of 24 nonresponders (p less than 0.0001).(ABSTRACT TRUNCATED AT 250 WORDS)
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Pneumocystis pneumonia (PCP) is a major cause of morbidity and mortality among immunocompromised persons, and it remains a leading acquired immune deficiency syndrome (AIDS)-defining opportunistic infection in human immunodeficiency virus (HIV)-infected individuals throughout the world. Pneumocystis has proven difficult to study, in part due to the lack of a reliable culture system for the organism. With the development of molecular techniques, significant advances in our understanding of the organism and the disease have been made over the past several years. These advances include an improved understanding of host-organism interactions and host defense, the development of noninvasive polymerase chain reaction (PCR)-based diagnostic assays, and the emerging data regarding the possible development of trimethoprim-sulfamethoxazole-resistant Pneumocystis. In addition, the recognition that patients without PCP may nevertheless be carriers of or colonized with Pneumocystis, and observations that suggest a role for Pneumocystis in the progression of pulmonary disease, combine to signal the need for a comprehensive and accessible review. In May 2005, the American Thoracic Society sponsored a one-day workshop, "Recent Advances and Future Directions in Pneumocystis Pneumonia (PCP)," which brought together 45 Pneumocystis researchers. The workshop included 21 presentations on diverse topics, which are summarized in this report. The workshop participants identified priorities for future research, which are summarized in this document.
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.
INTRODUCTION: Granulomatous pneumocystis pneumonia (PCP) is a rarity whose presentation may be misleading. CASE REPORT: We report the case of a patient suffering from chronic lymphatic leukaemia presenting with acute respiratory insufficiency, with a fatal outcome, due to granulomatous PCP. Broncho-alveolar lavage (BAL) remained negative and the diagnosis could only be made later by open lung biopsy. CONCLUSION: Although infrequent, granulomatous PCP should be recognised because in this situation the standard investigation (BAL) may be negative. New, more sensitive, methods of investigation such as the polymerase chain reaction (PCR) may permit earlier diagnosis.
Pneumocystis jirovecii is an atypical fungus that causes Pneumocystis pneumonia in immunocompromised patients. Underlying diseases associated with Pneumocystis pneumonia mainly consist of hematologic malignancies, solid tumors, organ transplant recipients and inflammatory disorders. Currently, inflammatory disorders represent 20% of underlying diseases. Corticosteroids are considered as a major risk factor. Recently introduced immunosuppressive drugs, such as antitumor necrosis factor monoclonal antibodies, could enhance the risk of Pneumocystis pneumonia. In patients with inflammatory disorders, lymphopenia is probably a determining factor but CD4+ T-cell count associated with the risk of Pneumocystis pneumonia remains unassessed. The diagnosis is based upon clinical, radiologic and biologic data. The identification of P. jirovecii usually requires a lower respiratory tract specimen, even if oral washes samples seem to be promising. According to recent data, immunofluorescent stains should be considered as the new gold standard, and specialized techniques such as PCR should be applied for sputum samples or oral washes. Recommendations on prophylaxis remains controversial except in patients with Wegener's granulomatosis and systemic lupus erythematosus. Cotrimoxazole is the preferred agent for prophylaxis as well as for treatment. An adjunctive corticosteroid therapy is usually prescribed despite the lack of evidence for utility in patients with inflammatory disorders. As person-to-person transmission is the most likely mode of acquiring P. jirovecii, isolation precautions should be advised.
Serum concentrations of immunoglobulin G (IgG), IgM, and IgA were measured in 9 Cavalier King Charles Spaniels with pneumonia caused by Pneumocystis sp that were examined at 4 veterinary surgeries in the United Kingdom (UK) between September 2001 and November 2002. Pneumocystis pneumonia was confirmed in all dogs by visualization of the organism in bronchoalveolar lavage fluid or a transthoracic lung aspirate. Two dogs had a history of demodicosis. Immunoglobulin concentrations also were measured in breed-and age-matched dogs sampled over the same period. IgG concentrations were significantly (P = .000) lower in the affected dogs (median 3.2 mg/mL) than in the control dogs (median 8.5 mg/mL). IgM concentrations were significantly (P = .002) higher in the affected dogs (median 1.95 mg/mL) than in the control dogs (median 1.12 mg/mL). One affected dog had no change in IgG concentration more than 3 months after resolution of infection or vaccination, but did have reduction in IgM concentration after resolution of infection and vaccination. Control dogs had low serum IgG and IgM concentrations, compared with the reference interval for all dogs. Lymphocyte count in blood was normal or high in 7 of 8 affected dogs. The results of this study suggest that there is a defect in immunity in Cavalier King Charles Spaniels that underlies the susceptibility of these dogs to pneumocystosis. Further studies are indicated to elucidate the mechanisms behind the defect, the prevalence within the breed, and the potential mode of inheritance of the problem.
The detection of Pneumocystis DNA in clinical specimens by using PCR assays is leading to important advances in Pneumocystis pneumonia (PcP) clinical diagnosis, therapy and epidemiology. Highly sensitive and specific PCR tools improved the clinical diagnosis of PcP allowing an accurate, early diagnosis of Pneumocystis infection, which should lead to a decreased duration from onset of symptoms to treatment, a period with recognized impact on prognosis. This aspect has marked importance in HIV-negative immunocompromised patients, who develop often PcP with lower parasite rates than AIDS patients. The specific amplification of selected polymorphous sequences of Pneumocystis jirovecii genome, especially of internal transcribed spacer regions of the nuclear rRNA operon, has led to the identification of specific parasite genotypes which might be associated with PcP severity. Moreover, multi-locus genotyping revealed to be a useful tool to explore person-to-person transmission. Furthermore, PCR was recently used for detecting P. jirovecii dihydropteroate synthase gene mutations, which are apparently associated with sulfa drug resistance. PCR assays detected Pneumocystis-DNA in bronchoalveolar lavage fluid or biopsy specimens, but also in oropharyngeal washings obtained by rinsing of the mouth. This non-invasive procedure may reach 90%-sensitivity and has been used for monitoring the response to treatment in AIDS patients and for typing Pneumocystis isolates.
Linear opacities are generally regarded as uncommon in pneumocystis pneumonia. The authors' experience suggests this is not so, and that such opacities may have diagnostic value. Chest radiographs of 22 episodes of uncomplicated pneumocystis pneumonia were reviewed and linear opacities were present in nine episodes (41%). Similar opacities were present in 11 out of 121 cases of other pneumonias (9%). Characteristically the opacities are related to the acute illness, usually one to three in number, predominantly basal, 1-4 cm long and less than 2 mm thick. Other radiographic signs of pneumocystis pneumonia were present in all cases. The pathogenesis of these linear opacities is uncertain, but it is possible that they result from areas of sub-segmental atelectasis. The frequency of such linear opacities is much greater in pneumocystis pneumonia (four times) than in other pneumonias and they therefore have some diagnostic value.