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Background This meta-analysis examines the comparative diagnostic performance of polymerase chain reaction (PCR) for the diagnosis of Pneumocystis pneumonia (PCP) on different respiratory tract samples, in both human immunodeficiency virus (HIV) and non-HIV populations. Methods A total of 55 articles met inclusion criteria, including 11 434 PCR assays on respiratory specimens from 7835 patients at risk of PCP. QUADAS-2 tool indicated low risk of bias across all studies. Using a bivariate and random-effects meta-regression analysis, the diagnostic performance of PCR against the European Organisation for Research and Treatment of Cancer–Mycoses Study Group definition of proven PCP was examined. Results Quantitative PCR (qPCR) on bronchoalveolar lavage fluid provided the highest pooled sensitivity of 98.7% (95% confidence interval [CI], 96.8%–99.5%), adequate specificity of 89.3% (95% CI, 84.4%–92.7%), negative likelihood ratio (LR−) of 0.014, and positive likelihood ratio (LR+) of 9.19. qPCR on induced sputum provided similarly high sensitivity of 99.0% (95% CI, 94.4%–99.3%) but a reduced specificity of 81.5% (95% CI, 72.1%–88.3%), LR− of 0.024, and LR+ of 5.30. qPCR on upper respiratory tract samples provided lower sensitivity of 89.2% (95% CI, 71.0%–96.5%), high specificity of 90.5% (95% CI, 80.9%–95.5%), LR− of 0.120, and LR+ of 9.34. There was no significant difference in sensitivity and specificity of PCR according to HIV status of patients. Conclusions On deeper respiratory tract specimens, PCR negativity can be used to confidently exclude PCP, but PCR positivity will likely require clinical interpretation to distinguish between colonization and active infection, partially dependent on the strength of the PCR signal (indicative of fungal burden), the specimen type, and patient population tested. [ABSTRACT FROM AUTHOR]

Background Recent studies have reported that reduced-dose trimethoprim-sulfamethoxazole (TMP-SMX) may be effective in the treatment of Pneumocystis jirovecii pneumonia (PJP), but data are lacking for patients with hematologic malignancies. Methods This retrospective study included all adult hematologic patients with PJP between 2013 and 2017 at 6 Swedish university hospitals. Treatment with 7.5–15 mg TMP/kg/day (reduced dose) was compared with >15–20 mg TMP/kg/day (standard dose), after correction for renal function. The primary outcome was the change in respiratory function (Δpartial pressure of oxygen [PaO2]/fraction of inspired oxygen [FiO2]) between baseline and day 8. Secondary outcomes were clinical failure and/or death at day 8 and death at day 30. Results Of a total of 113 included patients, 80 patients received reduced dose and 33 patients received standard dose. The overall 30-day mortality in the whole cohort was 14%. There were no clinically relevant differences in ΔPaO2/FiO2 at day 8 between the treatment groups, either before or after controlling for potential confounders in an adjusted regression model (−13.6 mm Hg [95% confidence interval {CI}, −56.7 to 29.5 mm Hg] and −9.4 mm Hg [95% CI, −50.5 to 31.7 mm Hg], respectively). Clinical failure and/or death at day 8 and 30-day mortality did not differ significantly between the groups (18% vs 21% and 14% vs 15%, respectively). Among patients with mild to moderate pneumonia, defined as PaO2/FiO2 >200 mm Hg, all 44 patients receiving the reduced dose were alive at day 30. Conclusions In this cohort of 113 patients with hematologic malignancies, reduced-dose TMP-SMX was effective and safe for treating mild to moderate PJP. [ABSTRACT FROM AUTHOR]

The article focuses on the risks of opportunistic infections (OIs) associated with long-term glucocorticoid therapies in adults, examining factors influencing infection risk and proposing preventive strategies. Topics include the impact of glucocorticoids on immunity; challenges in quantifying infection risk; and strategies for preventing OIs through screening, prophylaxis and immunizations, applicable to various patient populations receiving glucocorticoids.

Background Pneumocystis jirovecii is an opportunistic fungus that causes Pneumocystis pneumonia (PCP) in immunocompromised hosts. Over an 11-month period, we observed a rise in cases of PCP among kidney-transplant recipients (KTR), prompting an outbreak investigation. Methods Clinical and epidemiologic data were collected for KTR diagnosed with PCP between July 2019 and May 2020. Pneumocystis strain typing was performed using restriction fragment length polymorphism analyses and multilocus sequence typing in combination with next-generation sequencing. A transmission map was drawn, and a case-control analysis was performed to determine risk factors associated with PCP. Results Nineteen cases of PCP in KTR were diagnosed at a median of 79 months post-transplantation; 8 received monthly belatacept infusions. Baseline characteristics were similar for KTR on belatacept versus other regimens; the number of clinic visits was numerically higher for the belatacept group during the study period (median 7.5 vs 3). Molecular typing of respiratory specimens from 9 patients revealed coinfection with up to 7 P. jirovecii strains per patient. A transmission map suggested multiple clusters of interhuman transmission. In a case-control univariate analysis, belatacept, lower absolute lymphocyte count, non-White race, and more transplant clinic visits were associated with an increased risk of PCP. In multivariate and prediction power estimate analyses, frequent clinic visits was the strongest risk factor for PCP. Conclusions Increased clinic exposure appeared to facilitate multiple clusters of nosocomial PCP transmission among KTR. Belatacept was a risk factor for PCP, possibly by increasing clinic exposure through the need for frequent visits for monthly infusions. [ABSTRACT FROM AUTHOR]

Background Available information on the causes of death among people living with human immunodeficiency virus (PLHIV) in low- and middle-income countries (LMICs) remains scarce. We aimed to provide data on causes of death in PLHIV from two LMICs, Brazil and Mozambique, to assess the impact of clinical misdiagnosis on mortality rates and to evaluate the accuracy of minimally invasive tissue sampling (MITS) in determining the cause of death in PLHIV. Methods We performed coupled MITS and complete autopsy on 164 deceased PLHIV (18 children, 36 maternal deaths, and 110 adults). HIV antibody levels and HIV RNA viral loads were determined from postmortem serum samples. Results Tuberculosis (22.7%), toxoplasmosis (13.9%), bacterial infections (13.9%), and cryptococcosis (10.9%) were the leading causes of death in adults. In maternal deaths, tuberculosis (13.9%), bacterial infections (13.9%), cryptococcosis (11.1%), and cerebral malaria (8.3%) were the most frequent infections, whereas viral infections, particularly cytomegalovirus (38.9%), bacterial infections (27.8%), pneumocystosis (11.1%), and HIV-associated malignant neoplasms (11.1%) were the leading cause among children. Agreement between the MITS and the complete autopsy was 100% in children, 91% in adults, and 78% in maternal deaths. The MITS correctly identified the microorganism causing death in 89% of cases. Conclusions Postmortem studies provide highly granular data on the causes of death in PLHIV. The inaccuracy of clinical diagnosis may play a significant role in the high mortality rates observed among PLHIV in LMICs. MITS might be helpful in monitoring the causes of death in PLHIV and in highlighting the gaps in the management of the infections. [ABSTRACT FROM AUTHOR]

A case study of a 31-year-old male who is human immunodeficiency virus (HIV) seropositive and on stable antiretroviral therapy (ART) of abacavir, lamivudine, and dolutegravir was admitted to our hospital for investigation of dyspnea associated with progressive mediastinal lymphadenopathy and new pulmonary nodules. It mentions that Mycobacterium avium complex (MAC) disseminated infection and Pneumocystis jirovecii pneumonia.

Background Using data from the COHERE collaboration, we investigated whether primary prophylaxis for pneumocystis pneumonia (PcP) might be withheld in all patients on antiretroviral therapy (ART) with suppressed plasma human immunodeficiency virus (HIV) RNA (≤400 copies/mL), irrespective of CD4 count. Methods We implemented an established causal inference approach whereby observational data are used to emulate a randomized trial. Patients taking PcP prophylaxis were eligible for the emulated trial if their CD4 count was ≤200 cells/µL in line with existing recommendations. We compared the following 2 strategies for stopping prophylaxis: (1) when CD4 count was >200 cells/µL for >3 months or (2) when the patient was virologically suppressed (2 consecutive HIV RNA ≤400 copies/mL). Patients were artificially censored if they did not comply with these stopping rules. We estimated the risk of primary PcP in patients on ART, using the hazard ratio (HR) to compare the stopping strategies by fitting a pooled logistic model, including inverse probability weights to adjust for the selection bias introduced by the artificial censoring. Results A total of 4813 patients (10 324 person-years) complied with eligibility conditions for the emulated trial. With primary PcP diagnosis as an endpoint, the adjusted HR (aHR) indicated a slightly lower, but not statistically significant, different risk for the strategy based on viral suppression alone compared with the existing guidelines (aHR,.8; 95% confidence interval,.6–1.1; P  = .2). Conclusions This study suggests that primary PcP prophylaxis might be safely withheld in confirmed virologically suppressed patients on ART, regardless of their CD4 count. [ABSTRACT FROM AUTHOR]

Background The majority of pediatric human immunodeficiency virus (HIV) cases in Africa reflect maternal-to-child transmission. HIV exposed but uninfected (HEU) children have increased rates of morbidity and mortality when compared to HIV unexposed and uninfected (HUU) children. The mechanisms behind these unexpected trends are only partially understood but could be explained by the differences in the immune response to infections triggered by an altered immune system state. Methods Using quantitative reverse transcription polymerase chain reaction, we compared the nasopharyngeal carriage prevalence and density of Streptococcus pneumoniae (SP) and Pneumocystis jirovecii (PJ) between children living with HIV and HEU or HUU cases (pneumonia) and controls (without pneumonia). Results The cohort included 1154 children (555 cases and 599 matched controls). The SP carriage prevalence rates were similar between cases and controls. Among SP carriers with pneumonia, carriage density was increased among children living with HIV, versus HEU or HUU children (15.8, 4.7, and 3.6 × 105 copies/mL, respectively). The rate of PJ carriage was significantly higher among children living with HIV than among HEU and HUU children (31%, 15%, and 10%, respectively; P  < .05), as was carriage density (63.9, 20.9, and 4.8 × 103 copies/mL, respectively; P  < .05). Conclusions Carriage prevalences and densities for SP and PJ show different kinetics in terms of their relationship with HIV exposure and clinical status, particularly for Pneumocystis jirovecii. This supports the theory that the increased morbidity and mortality observed among HEU children may reflect deficits not just in humoral immunity but in cell-mediated immunity as well. [ABSTRACT FROM AUTHOR]

The burden of nosocomial Pneumocystis infections in transplantation units in France was evaluated through a retrospective survey. Over 12 years, 16 outbreaks occurred, including 13 among renal transplant recipients (RTRs). We performed Pneumocystis jirovecii genotyping in 5 outbreaks, which suggested that specific strains may have been selected by RTRs. [ABSTRACT FROM AUTHOR]

Background There are limited data on the etiology of respiratory infections in human immunodeficiency virus (HIV)–infected patients in resource-limited settings. Methods We performed quantitative multiplex real-time polymerase chain reaction (PCR) for Pneumocystis jirovecii and common bacterial and viral respiratory pathogens on sputum samples (spontaneous or induced) from a prospective cohort study of HIV-infected inpatients with World Health Organization danger signs and cough. Mycobacterial culture was done on 2 sputum samples, blood cultures, and relevant extrapulmonary samples. Results We enrolled 284 participants from 2 secondary-level hospitals in Cape Town, South Africa: median CD4 count was 97 cells/μL, 64% were women, and 38% were on antiretroviral therapy. One hundred forty-eight had culture-positive tuberculosis, 100 had community-acquired pneumonia (CAP), 26 had P. jirovecii pneumonia (PJP), and 64 had other diagnoses. Probable bacterial infection (>105 copies/mL) was detected in 133 participants; the prevalence was highest in those with CAP (52%). Haemophilus influenzae and Streptococcus pneumoniae were the commonest bacterial pathogens detected; atypical bacteria were uncommon. Viruses were detected in 203 participants; the prevalence was highest in those with PJP (85%). Human metapneumovirus was the commonest virus detected. Multiple coinfections were commonly detected. Conclusions Sputum multiplex PCR could become a useful diagnostic tool for bacterial respiratory infections in HIV-infected inpatients, but its value is limited as quantitative cutoffs have only been established for a few bacterial pathogens and validation has not been done in this patient population. We found a high prevalence of respiratory viruses, but it is unclear whether these viruses were causing infection as there are no accepted quantitative PCR cutoffs for diagnosing respiratory viral infections. [ABSTRACT FROM AUTHOR]

Background Serum (1,3)-beta-D glucan (BDG) is increasingly used to guide the management of suspected Pneumocystis pneumonia (PCP). BDG lacks specificity for PCP, and its clinical performance in high-risk cancer patients has not been fully assessed. Polymerase chain reaction (PCR) for PCP detection is highly sensitive, but cannot differentiate between colonization and infection. We evaluated the diagnostic performance of serum BDG in conjunction with PCP PCR on respiratory samples in patients with cancer and unexplained lung infiltrates. Methods We performed a retrospective analysis of adult patients evaluated for PCP at our institution from 2012 to 2015, using serum BDG and PCP PCR. The sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of the serum BDG at different thresholds were evaluated using PCP PCR alone or in conjunction with clinical presentation in PCP PCR–positive patients. Results With PCP PCR alone as the reference method, BDG (≥80 pg/mL) had a sensitivity of 69.8%, specificity of 81.2%, PPV of 34.6%, and NPV of 95.2% for PCP. At ≥200 pg/mL in patients with a positive PCR and a compatible PCP clinical syndrome, BDG had a sensitivity of 70%, specificity of 100%, PPV of 100%, and NPV of 52.0% for PCP. Conclusions Patients negative by both BDG and PCR were unlikely to have PCP. In patients with a compatible clinical syndrome for PCP, higher BDG values (>200 pg/mL) were consistently associated with clinically-significant PCP infections among PCP PCR–positive oncology patients. [ABSTRACT FROM AUTHOR]

In this retrospective study, (1–>3)-β- d -glucan (B-glucan) was an unreliable marker for AIDS-related Pneumocystis jirovecii pneumonia (PCP) because a high percentage of participants with progressive disseminated histoplasmosis and respiratory symptoms had a positive B-glucan result. Where histoplasmosis is common, attributing B-glucan positivity to PCP without further testing risks misdiagnosis. [ABSTRACT FROM AUTHOR]

In the article, the authors present a case of a 52-year-old male who was rushed to the emergency unit of a hospital due to high fever, cough and shortness of breath. His condition worsened and he underwent endotracheal intubation. He later developed acute respiratory failure due to COVID-19, Pneumocystis jirovecii pneumonia (PJP), and stage 3 human immunodeficiency (HIV) while at the intensive care unit (ICU).

Background Pneumocystis pneumonia (PCP) is associated with morbidity and mortality in solid organ transplant (SOT) recipients. In this case-control study, we determined the association between posttransplant PCP and 3 variables: cytomegalovirus (CMV) infection, allograft rejection, and prophylaxis. Methods Eight transplant centers participated. For each case (SOT recipient with PCP), 3–5 controls (SOT recipients without PCP) were included. Controls were matched to the cases based on transplant center, type of allograft, and date of transplantation (±6 months). Results We enrolled 53 cases and 209 controls. Transplant types included kidney (n = 198), heart (n = 30), liver (n = 15), kidney-pancreas (n = 14), and lung (n = 5). PCP occurred beyond 12 months after transplantation in 43 (81.1%) cases. Thirty-four cases (64.1%) required admission to the intensive care unit, and 28 (52.8%) had mechanical ventilation. Allograft failure occurred in 20 (37.7%) cases, and 14 (26.9%) died. No patient developed PCP prophylaxis breakthrough. The proportion of female sex (P =.009), kidney dysfunction (P =.001), cardiac diseases (P =.005), diabetes mellitus (P =.03), allograft rejection (P =.001), CMV infection (P =.001), and severe lymphopenia (P =.001) were significantly higher in cases. In the logistic regression model, CMV infection (adjusted odds ratio [aOR], 4.6 [95% confidence interval {CI}, 2.0–10.5]) and allograft rejection (aOR, 3.0 [95% CI, 1.5–6.1]) significantly increased the likelihood of PCP. Conclusions PCP was mostly a late-onset disease occurring after complete course of prophylaxis, particularly among patients with CMV infection or allograft rejection. PCP is associated with significant allograft loss. Extended prophylaxis targeting recipients with allograft rejection or CMV infection may reduce the risk of PCP. [ABSTRACT FROM AUTHOR]

The article discusses the use of elevated (1,3)-β-d- Glucan levels to distinguish causation from colonization in Pneumocystis jirovecii polymerase chain reaction–positive (PJP) cancer patients. Topics discussed include ways =in which P. jirovecii has necessitated reevaluation of clinical practices and optimization of detection methods; benefits of Molecular diagnostic assays for detection of P. jirovecii; and ways to enhance performance of the novel PJP risk assessment model.

Background Although trimethoprim-sulfamethoxazole is the more efficient drug for prophylactic and curative treatment of pneumocystosis, atovaquone is considered a second-line prophylactic treatment in immunocompromised patients. Variations in atovaquone absorption and mutant fungi selection after atovaquone exposure have been associated with atovaquone prophylactic failure. We report here a Pneumocystis jirovecii cytochrome b (cyt b) mutation (A144V) associated with such prophylactic failure during a pneumocystosis outbreak among heart transplant recipients. Methods Analyses of clinical data, serum drug dosage, and molecular modeling of the P. jirovecii Rieske–cyt b complex were performed to investigate these prophylactic failures. Results The cyt b A144V mutation was detected in all infected, heart transplant recipient patients exposed to atovaquone prophylaxis but in none of 11 other immunocompromised, infected control patients not treated with atovaquone. Serum atovaquone concentrations associated with these prophylactic failures were similar than those found in noninfected exposed control patients under a similar prophylactic regimen. Computational modeling of the P. jirovecii Rieske–cyt b complex and in silico mutagenesis indicated that the cyt b A144V mutation might alter the volume of the atovaquone-binding pocket, which could decrease atovaquone binding. Conclusions These data suggest that the cyt b A144V mutation confers diminished sensitivity to atovaquone, resulting in spread of Pneumocystis pneumonia among heart transplant recipients submitted to atovaquone prophylaxis. Potential selection and interhuman transmission of resistant P. jirovecii strain during atovaquone prophylactic treatment has to be considered and could limit its extended large-scale use in immucompromised patients. [ABSTRACT FROM AUTHOR]

Background. An outbreak of Pneumocystis jirovecii pneumonia (PCP) occurred among heart transplant recipients (HTR) at the outpatient clinic of a university hospital, from March to September 2015. Clinical, therapeutic, biological, and molecular data were analyzed to determine its origin and control the outbreak. Methods. Clinical and biological data regarding all HTR followed in the outpatient clinic were collected. PCP diagnosis was based on microscopy and real-time polymerase chain reaction (PCR). Investigations were performed by building a transmission map, completed by genotyping Pneumocystis isolates and by a control of chemoprophylaxis observance. Asymptomatic exposed patients were screened for colonization using real-time PCR. Results. Among 124 HTR, 7 PCP cases were confirmed. Screening identified 3 additional patients colonized by P. jirovecii. All patients were cured, and no further cases were identified after trimethoprim-sulfamethoxazole prophylaxis was introduced in the entire cohort. Genotyping demonstrated the same strain in all PCP cases and colonized patients. All cases were linked with possible transmission chains from 2 possible index patients. Interhuman transmission was significantly associated with more frequent visits in the outpatient clinic. Six cases were receiving atovaquone as a prophylaxis. The occurrence of PCP was significantly associated with atovaquone prophylaxis. Conclusions. This is the first outbreak with detailed molecular analysis in HTR so far. Genotyping and transmission chain confirmed interhuman transmission in all colonized/infected PCP cases. Outpatient clinic layout and high encounters probably caused this PCP cluster, which was controlled after systematic trimethoprim-sulfamethoxazole prophylaxis in exposed patients. [ABSTRACT FROM AUTHOR]

Background. Pneumocystis pneumonia is a well-recognized lung disease of premature and malnourished babies. Even though serologic studies have shown that children are exposed to Pneumocystis jirovecii early in life, the epidemiology of human P. jirovecii infection and the host–microorganism relationship in infancy remain poorly understood. The aim of the present study was to investigate the prevalence of P. jirovecii colonization in preterm infants and its possible association with medical complications. Methods. A prospective observational study of preterm infants (birth weight <1500 g and/or gestational age <32 weeks) was carried out. Identification of P. jirovecii colonization was performed by means of molecular techniques in nasal aspirated samples at birth. Results. A total of 128 preterm infants were included during the study period. Pneumocystis DNA was identified in 25.7% (95% confidence interval [CI], 17.8%–33.7%) of newborns studied. A significant increase of respiratory distress syndrome in colonized group, even after adjusting for confounding factors (odds ratio, 2.7 [95% CI, 1.0–7.5]; P = .04), was observed. No differences were observed in other medical conditions between the 2 groups. Conclusions. Pneumocystis jirovecii colonization is frequent in preterm births and could be a risk factor to develop respiratory distress syndrome among preterm infants. [ABSTRACT FROM AUTHOR]

This report identifies both climatological and air pollution constituents as independent risk factors for hospitalization of HIV-positive patients with Pneumocystis pneumonia (PcP). These findings may lead to new insights about the epidemiology and pathogenesis of PcP.Background. Pneumocystis pneumonia (PcP) is the second leading cause of morbidity and mortality in human immunodeficiency virus (HIV)–infected patients in the United States. Although the host risk factors for the development of PcP are well established, the environmental (climatological, air pollution) risk factors are poorly understood. The major goal of this study was to determine the environmental risk factors for admissions of HIV-positive patients with PcP to a single medical center.Methods. Between 1997 and 2008, 457 HIV-positive patients with microscopically confirmed PcP were admitted to the San Francisco General Hospital. A case-crossover design was applied to identify environmental risk factors for PcP hospitalizations. Climatological and air pollution data were collected from the Environmental Protection Agency and Weather Warehouse databases. Conditional logistic regression was used to evaluate the association of each environmental factor and PcP hospital admission.Results. Hospital admissions were significantly more common in the summer than in the other seasons. Increases in temperature and sulfur dioxide levels were independently associated with hospital admissions for PcP, but the effects of sulfur dioxide were modified by increasing carbon monoxide levels.Conclusions. This study identifies both climatological and air pollution constituents as independent risk factors for hospitalization of HIV-positive patients with PcP in San Francisco. Thus, the environmental effects on PcP are more likely complex than previously thought. Further studies are needed to understand how these factors exert their effects and to determine if these factors are associated with PcP in other geographic locations. [ABSTRACT FROM AUTHOR]

By restriction fragment length polymorphism analysis, 2 outbreaks of Pneumocystis pneumonia in renal transplant patients in Europe were shown to be caused by the same strain of Pneumocystis; another outbreak in Japan was caused by a different strain.Background. There have been numerous reports of clustered outbreaks of Pneumocystis pneumonia (PCP) at renal transplant centers over the past 2 decades. It has been unclear whether these outbreaks were linked epidemiologically to 1 or several unique strains, which could have implications for transmission patterns or strain virulence.Methods. Restriction fragment length polymorphism (RFLP) analysis was used to compare Pneumocystis isolates from 3 outbreaks of PCP in renal transplant patients in Germany, Switzerland, and Japan, as well as nontransplant isolates from both human immunodeficiency virus (HIV)–infected and uninfected patients.Results. Based on RFLP analysis, a single Pneumocystis strain caused pneumonia in transplant patients in Switzerland (7 patients) and Germany (14 patients). This strain was different from the strain that caused an outbreak in transplant patients in Japan, as well as strains causing sporadic cases of PCP in nontransplant patients with or without HIV infection.Conclusions. Two geographically distinct clusters of PCP in Europe were due to a single strain of Pneumocystis. This suggests either enhanced virulence of this strain in transplant patients or a common, but unidentified, source of transmission. Outbreaks of PCP can be better understood by enhanced knowledge of transmission patterns and strain variation. [ABSTRACT FROM PUBLISHER]

Background. Eighteen renal transplant recipients (RTRs) developed Pneumocystis jirovecii infections at the renal transplantation unit of Brest University Hospital (Brest, Brittany, France) from May 2008 through April 2010, whereas no cases of P. jirovecii infection had been diagnosed in this unit since 2002. This outbreak was investigated by identifying P. jirovecii types and analyzing patient encounters. Methods. The identification of P. jirovecii internal transcribed spacer (ITS) types was performed on P. jirovecii isolates from the 18 RTRs (12 patients with Pneumocystis pneumonia [PCP], 6 colonized patients), 22 unlinked control patients (18 patients with PCP, 4 colonized patients), and 69 patients (34 patients with PCP, 35 colonized patients) with contemporaneously diagnosed P. jirovecii infections in the Brest geographic area. A transmission map was drawn up. Its analysis was combined with the results of P. jirovecii typing. Results. P. jirovecii ITS type identification was successful in 14 of 18 RTRs, 15 of 22 control patients, and 48 of the 69 patients. Type Eg was the most frequent type in the 3 patient groups. However, its frequency was significantly higher in the first patient group than in the 2 other groups (P <.05 and P < .01, respectively). Fourteen encounters between RTRs who harbored an identical type were observed. Ten patients were considered as possible index patients, of whom 3 were colonized by the fungus, and 7 presented PCP. Conclusions. The results provide to our knowledge the first data on the role of colonized patients as potential sources of P. jirovecii in a context of nosocomial acquisition of the fungus. [ABSTRACT FROM AUTHOR]

Background. Current guidelines suggest that primary prophylaxis for Pneumocystis jiroveci pneumonia (PcP) can be safely stopped in human immunodeficiency virus (HIV)-infected patients who are receiving combined antiretroviral therapy (cART) and who have a CD4 cell count 1200 cells/μL. There are few data regarding the incidence of PcP or safety of stopping prophylaxis in virologically suppressed patients with CD4 cell counts of 101-200 cells/μL. Methods. The Opportunistic Infections Project Team of the Collaboration of Observational HIV Epidemiological Research in Europe (COHERE) included data from 23,412 patients from 12 European cohorts who started taking cART after 1997. Poisson regression was used to model incidence rate ratios (IRRs) of primary PcP. Results. There were 253 PcP cases during 107,016 person-years of follow-up (PYFU). Prophylaxis significantly reduced the incidence of PcP among patients with current CD4 cell counts -100 cells/mL (adjusted IRR, 0.41; 95% confidence interval [CI], 0.27-0.60) but not significantly among those with current CD4 cell counts of 101-200 cells/μL (adjusted IRR, 0.63; 95% CI, 0.34-1.17). The incidence of PcP among patients who had a current CD4 cell count of 100-200 cells/μL, who had a viral load <400 copies/mL, and who were receiving prophylaxis was 2.1 cases per 1000 PYFU (95% CI, 0.8-4.3 cases per 1000 PYFU; 7 events occurred during 3363 PYFU), whereas 1.2 cases per 1000 PYFU (95% CI, 0.2-4.5 cases per 1000 PYFU; 2 events occurred during 1614 PYFU) occurred among persons who were not receiving prophylaxis (adjusted IRR, 1.65; 95% CI, 0.33-8.15). Among patients who discontinued PcP prophylaxis after starting cART, the incidence of primary PcP was 0 cases per 1000 PYFU (95% CI, 0.0-2.7 cases per 1000 PYFU; 0 events occurred during 1363 PYFU) for patients who had a current CD4 cell count of 101-200 cells/μL and who were receiving cART. Conclusions. The incidence of primary PcP among patients who had virologically suppressed HIV infection, were receiving cART, and who had CD4 cell counts 1100 cells/μL was low irrespective of prophylaxis use. Discontinuation of prophylaxis may be safe in patients with CD4 counts of 101-200 cells/μL and suppressed viral load. [ABSTRACT FROM AUTHOR]

Background. Pneumocystis jirovecii dihydropteroate synthase (DHPS) mutations are associated with failure of prophylaxis with sulfa drugs. This retrospective study sought to better understand the geographical variation in the prevalence of these mutations. Methods. DHPS polymorphisms in 394 clinical specimens from immunosuppressed patients who received a diagnosis of P. jirovecii pneumonia and who were hospitalized in 3 European cities were examined using polymerase chain reaction (PCR) single-strand conformation polymorphism. Demographic and clinical characteristics were obtained from patients' medical charts. Results. Of the 394 patients, 79 (20%) were infected with a P. jirovecii strain harboring one or both of the previously reported DHPS mutations. The prevalence of DHPS mutations was significantly higher in Lyon than in Switzerland (33.0% vs 7.5%; P < .001). The proportion of patients with no evidence of sulfa exposure who harbored a mutant P. jirovecii DHPS genotype was significantly higher in Lyon than in Switzerland (29.7% vs 3.0%; P < .001). During the study period in Lyon, in contrast to the Swiss hospitals, measures to prevent dissemination of P. jirovecii from patients with P. jirovecii pneumonia were generally not implemented, and most patients received suboptimal prophylaxis, the failure of which was strictly associated with mutated P. jirovecii. Thus, nosocomial interhuman transmission of mutated strains directly or indirectly from other individuals in whom selection of mutants occurred may explain the high proportion of mutations without sulfa exposure in Lyon. Conclusions. Interhuman transmission of P. jirovecii, rather than selection pressure by sulfa prophylaxis, may play a predominant role in the geographical variation in the prevalence in the P. jirovecii DHPS mutations. [ABSTRACT FROM AUTHOR]

Background. Airborne transmission of Pneumocystis has been demonstrated in animal models and is highly probable in humans. However, information concerning burdens of Pneumocystis jirovecii (human-derived Pneumocystis) in exhaled air from infected patients is lacking. Our objective is to evaluate P. jirovecii air diffusion in patients with Pneumocystis pneumonia. Methods. Patients admitted with Pneumocystis pneumonia were prospectively enrolled from 9 January 2008 to 21 July 2009. Air samples (1.5 m³) were collected on liquid medium with a commercial sampler at 1-, 3-, 5-, and 8-m distances from patients' heads. Air control samples were collected away from Pneumocystis pneumonia patient wards and outdoors. Samples were examined for P. jirovecii detection and quantification using a real-time polymerase chain reaction assay targeting the mitochondrial large subunit ribosomal RNA gene. Results. Forty patients were diagnosed as having Pneumocystis pneumonia. Air sampling was performed in the environment for 19 of them. At a 1-m distance from patients' heads, P. jirovecii DNA was detected in 15 (79.8%) of 19 patients, with fungal burdens ranging from 7.5 x 10³to 4.5 x 106 gene copies/m³. These levels decreased with distance from the patients (P < .002). Nevertheless, 4 (33.3%) of the 12 samples taken at 8 m, in the corridor adjacent to their room, were still positive. Forty control samples were collected and remained negative. Conclusion. This study provides the first quantitative data on the spread of P. jirovecii in exhaled air from infected patients. It sustains the risk of P. jirovecii direct transmission in close contact with patients with Pneumocystis pneumonia and leads the way for initiating a quantitative risk assessment for airborne transmission of P. jirovecii. [ABSTRACT FROM AUTHOR]

Background. Increasing reports of Pneumocystis DNA in noninvasive respiratory specimens from immunocompetent asymptomatic adults and the characteristic lung tropism of Pneumocystis suggest that asymptomatic pulmonary infections with Pneumocystis occur after primary infection. However, studies searching for Pneumocystis in the autopsied lungs of healthy immunocompetent adults have not met with success. Methods. Lungs of people who died of violent causes (accidents, homicide, and suicide) and of nonviolent causes (diseases causing a rapid demise in the street) in Santiago, Chile-for whom an autopsy was legally required- were examined for Pneumocystis by nested polymerase chain reaction (PCR) DNA amplification of the mitochondrial large subunit ribosomal RNA-specific P. jirovecii gene and immunofluorescent microscopic analysis. Lung tissue concentration methods and analysis of ∼3% of the weight of the right upper lobe (RUL) were needed to reach the sensitivity threshold of the assays. Individuals determined to be P. jirovecii negative after analysis of 3% of the RUL weight in the violent death group were confirmed to be negative by analyzing additional tissue, totaling 6%-7% of the RUL weight. Results. P. jirovecii was identified by nested PCR in 50 (64.9%) of 77 individuals (34 [61.8%] of 55 in the violent death group and 15 [78.9%] of 19 in the nonviolent death group; P > .05) and additionally by microscopic analysis in all individuals who tested positive for P. jirovecii DNA in the violent death group. Analysis of tissue beyond 3.0% of the RUL weight for the individuals who tested negative yielded consistently negative results. Conclusions. A mild P. jirovecii pulmonary infection is prevalent in more than half of the general adult population. Our results strengthen the concept that immunocompetent adults develop frequent self-limited reinfections throughout life and participate in the circulation of P. jirovecii as an infective reservoir for susceptible individuals. [ABSTRACT FROM AUTHOR]

High serum (1→3) β-D-glucan levels are described in patients with Pneumocystis pneumonia (PCP). We evaluated the diagnostic value of β-D-glucan in 111 patients with AIDS who had PCP and confirmed its usefulness. However, it does not correlate with disease severity and is not suitable for monitoring response to treatment. [ABSTRACT FROM AUTHOR]

Antilymphocyte therapies are widely used for immunosuppression in solid organ transplantation. These agents have varied mechanisms of action, with resulting differences in the intensity and duration of immunosuppression and in associated infectious complications. Induction therapy with antithymocyte globulins is associated with a greater incidence of cytomegalovirus, Epstein-Barr virus, and BK polyomavirus infections, compared with therapy with interleukin (IL)-2a receptor antagonists. However, long-term experience with the IL-2a receptor antagonists is lacking. By contrast, the treatment of graft rejection with T cell-depleting antibodies is associated with an increased risk of opportunistic infections. This is likely a reflection of the intensification of immunosuppression in the treatment of graft rejection and, often, a failure to link the use of antilymphocyte agents to prophylaxis for infection. The use of T cell-depleting agents, especially in the treatment of acute graft rejection, must be linked to monitoring and risk-adjusted prophylaxis for Pneumocystis, other fungi, Epstein-Barr virus, BK polyomavirus, and cytomegalovirus infection. [ABSTRACT FROM AUTHOR]

Background. Pneumocystis jirovecii pneumonia (PCP) remains the leading cause of opportunistic infection among human immunodeficiency virus (HIV)-infected persons. Previous studies of PCP that identified case-fatality risk factors involved small numbers of patients, were performed over few years, and often focused on patients who were admitted to the intensive care unit. Objective. The objective of this study was to identify case-fatality risk factors present at or soon after hospitalization among adult HIV-infected patients admitted to University College London Hospitals (London, United Kingdom) from June 1985 through June 2006. Patients and Methods. We performed a review of case notes for 494 consecutive patients with 547 episodes of laboratory-confirmed PCP. Results. Overall mortality was 13.5%. Mortality was 10.1% for the period from 1985 through 1989, 16.9% for the period from 1990 through June 1996, and 9.7% for the period from July 1996 through 2006 (P = .142). Multivariate analysis identified factors associated with risk of death, including increasing patient age (adjusted odds ratio [AOR], 1.54; 95% confidence interval [CI], 1.11-2.23; P = .011), subsequent episode of PCP (AOR, 2.27; 95% CI, 1.14-4.52; P = .019), low hemoglobin level at hospital admission (AOR, 0.70; 95% CI, 0.60-0.83; P< .001), low partial pressure of oxygen breathing room air at hospital admission (AOR, 0.70; 95% CI, 0.60-0.8 1; P<.001), presence of medical comorbidity (AOR, 3.93; 95% CI, 1.77-8.72; P = .001), and pulmonary Kaposi sarcoma (AOR, 6.95; 95% CI, 2.26-21.37; P = .001). Patients with a first episode of PCP were sicker (mean partial pressure of oxygen at admission ± standard deviation, 9.3 ± 2.0 kPa) than those with a second or third episode of PCP (mean partial pressure of oxygen at admission ± standard deviation,9.9 ± 1.9 kPa; P = .008), but mortality among patients with a first episode of PCP (12.5%) was lower than mortality among patients with subsequent episodes of PCP (22.5%) (P = .019). No patient was receiving highly active antiretroviral therapy before presentation with PCP, and none began highly active antiretroviral therapy during treatment of PCP. Conclusions. Mortality risk factors for PCP were identifiable at or soon after hospitalization. The trend towards improved outcome after June 1996 occurred in the absence of highly active antiretroviral therapy. [ABSTRACT FROM AUTHOR]

Background. An outbreak of Pneumocystis jiroveci pneumonia (PCP) occurred among renal transplant recipients attending the outpatient department at the Leiden University Medical Centre (Leiden, The Netherlands) from 1 March 2005 through 1 February 2006. Clinical, epidemiological, and molecular data were analyzed to trace the outbreak's origin. Methods. Renal transplant recipients with a clinical suspected diagnosis of PCP were included in the study. The diagnosis had to be confirmed by direct microscopy or real-time polymerase chain reaction of the dihydropteroate synthase gene in a bronchoalveolar fluid specimen. To detect contacts between patients, a transmission map was constructed. A case-control analysis was performed to asses whether infection was associated with certain wardrooms. Genotyping of Pneumocystis isolates was performed by sequence analysis of the internal transcribed spacer (ITS) number 1 and 2 gene regions. Results. Twenty-two confirmed PCP cases were identified; approximately 0-1 would have been expected over the same time period. No risk factor was predominantly present, and standard immunosuppressive regimens had not changed. Liver transplant recipients who used the same outpatient facilities had not acquired PCP. The transmission map findings were compatible with interhuman transmission on multiple occasions. The case-control study did not point to wardrooms as a common source. Genotyping by sequencing of the ITS1 and ITS2 gene regions revealed type Ne in 12 of 16 successfully typed samples. Genotype Ne was found in only 2 of 12 reference samples. Conclusions. The clinical data and genotyping results are compatible with either interhuman transmission or an environmental source of infection. More complex models may account for PCP clusters. [ABSTRACT FROM AUTHOR]

The article presents information on a study that was conducted to examine reasons behind substantial morbidity among HIV-infected persons despite availability of effective prophylaxis, Pneumocystis jiroveci pneumonia (PCP) in the U.S. A total of 483 episodes of PCP were diagnosed during 7315 person-years. Incidence was lowest among persons prescribed both antiretroviral therapy (ART) and PCP prophylaxis, while persons not prescribed prophylaxis had higher PCP incidence.

Background. Trimethoprim-sulfamethoxazole (TMP-SMZ) has been used extensively for the prevention of Pneumocystis carinii (also referred to as "Pneumocystis jiroveci") pneumonia (PCP) and other opportunistic infections in human immunodeficiency virus (HIV)-infected children. Because the efficacy of TMP-SMZ for treatment of bacterial infections is limited, it is sometimes poorly tolerated, and there is risk of emergence of drug-resistant strains associated with widespread use, we evaluated a regimen that included atovaquone and azithromycin. Methods. A randomized, double-blind, placebo-controlled trial was designed to determine whether atova- quone-azithromycin had equivalent efficacy to TMP-SMZ for the prevention of serious bacterial infections and to compare the long-term tolerance, PCP breakthrough rates, and nonserious bacterial infection rates among HIV- infected children aged 3 months to 19 years. Children qualified for PCP prophylaxis (on the basis of Centers for Disease Control and Prevention recommendations) were randomized to receive atovaquone-azithromycin or TMP- SMZ daily for ≥2 years. Results. Data from 366 of the 369 eligible patients (median duration of follow-up, 3 years) showed that the estimated rates of serious bacterial infection-related events were lower among atovaquone-azithromycin recipients than among TMP-SMZ recipients (17.3 vs. 24.2 events per 100 patient-years; difference, 6.9 events per 100 patient- years; 95% confidence interval [CI], -0.22 to 14.12). Rates for all end points (serious bacterial infection, PCP, Mycobacterium avium complex infection, and serious and nonserious bacterial infection-related deaths) were 19.7 and 27.7 events per 100 patient-years, respectively (difference, 7.9 events per 100 patient-years; 95% CI, -0.28 to 15.54 events per 100 patient-years). The results marginally favored atovaquone-azithromycin therapy statistically. Atovaquone-azithromycin and TMP-SMZ therapies had similar adverse event profiles. Conclusions. We conclude that, in HIV-infected children, atovaquone-azithromycin is as effective as TMP- SMZ for the prevention of serious bacterial infections and is similarly tolerated. [ABSTRACT FROM AUTHOR]

Background. Pneumocystis jiroveci (formerly Pneumocystis carinii) pneumonia (PCP) is a major cause of mortality in human immunodeficiency virus (HIV)-infected infants in Africa, but the prevalence of mutations in the gene encoding dihydropteroate synthase (DHPS) in isolates from Africa has not been reported. Methods. This study investigated the prevalence of DHPS mutations in P. jiroveci isolates from South African HIV-infected children with PCP by amplifying DNA using 2 different polymerase chain reactions. Results. P. jiroveci DNA from 30 respiratory specimens was amplified; 26 specimens (86.7%) contained wild-type DHPS alleles. Of the 4 samples (13.3%) with DHPS mutations, 2 contained a homogenous population with single DHPS mutations, 1 contained a homogenous population with 2 DHPS mutations, and the fourth contained a heterogenous population of organisms with both wild-type and single-mutant DHPS genotypes. Only 1 child was receiving trimethoprim-sulphamethoxazole (TMP-SMZ) prophylaxis; this patient was infected with wild-type P. jiroveci. The mortality rate (overall, 20 [66.7%] of 30 children) was not significantly different between children infected with wild-type P. jiroveci (17 [65.4%] of 26) and those infected with mutant strains (3 [75%] of 4; P = .8). Conclusions. DHPS mutations are uncommon in P. jiroveci isolates from South Africa. However, increasing use of TMP-SMZ prophylaxis may result in widespread development of mutations. [ABSTRACT FROM AUTHOR]

This study describes the genotype distribution of Pneumocystis jiroveci in 79 respiratory samples obtained from 15 patients with acquired immunodeficiency syndrome (AIDS) with P. jiroveci pneumonia and 64 human immunodeficiency virus-negative subjects with different chronic pulmonary diseases. The genotyping was based in analysis of 2 independent genetic loci: the mitochondrial large subunit ribosomal RNA (mt LSU rRNA) fragment (assessed by direct sequencing) and the gene for dihydropteroate synthase (DHPS; assessed by restriction fragment-length polymorphism). The mt LSU rRNA analysis revealed the presence of 3 different polymorphisms for both populations. The major genotype, 85C/248C, was found to be significantly higher in patients with AIDS and P. jiroveci pneumonia than in patients with pulmonary disease. The rate of genotypes 85A/248C and 85T/248C was similar in both groups. The analysis of DHPS genotypes assesses the prevalence of its 4 possible genotypes, with 35.5% of genotypes related to sulfa resistance. The data suggest a common source of infection between both groups. [ABSTRACT FROM AUTHOR]

Focuses on sputum induction (SI) vis-a-vis Pneumocystis pneumonia in immunocompromised patients without HIV in the U.S. Application of SI among immunocompromised patients; Importance of the application of SI for diagnosis of Pneumocystis pneumonia; Comparison of the clinical study on the outcome of SI between immunocompromised patients with HIV and those without HIV.

We compared the incidence of bacterial pneumonia among 336 patients who discontinued trimethoprim-sulfamethoxazole (TMP-SMX) as prophylaxis against Pneumocystis carinii pneumonia (PCP) with that among 75 patients who fulfilled the criteria for discontinuation but continued receiving prophylaxis. The difference in the overall incidence rates for the 2 groups (1.2 events per 100 person-years) was not statistically significant. Discontinuation of TMP-SMX prophylaxis against PCP is not associated with a significant increase in the incidence of bacterial pneumonia among patients with a sustained CD4 cell count increase to >200 cells/μL. [ABSTRACT FROM AUTHOR]

We review Pneumocystis carinii pneumonia (PCP) in patients in the developing world (i.e., Africa, Asia, the Philippines, and Central and South America) who have acquired immunodeficiency disease (AIDS). During the first decade of the AIDS pandemic, PCP rarely occurred in African adults. More recent reports have noted that PCP comprises a significantly greater percentage of cases of pneumonia than it did in the past. This trend dramatically contrasts with that observed in industrialized nations, where a reduction in the number of cases of PCP has occurred as a result of the widespread use of primary P. carinii prophylaxis and highly active antiretroviral therapy. Throughout the developing world, the rate of coinfection with Myco-bacterium tuberculosis and PCP is high, ranging from 25% to 80%. Initiation of treatment when PCP is in an advanced stage may account for the high mortality rates (20%-80%) associated with pediatric PCP in the developing world. [ABSTRACT FROM AUTHOR]

African human immunodeficiency virus type 1 (HIV-1)-infected children were evaluated to define the burden of Pneumocystis carinii pneumonia (PCP) and its interaction with bacterial and viral pathogens. P. carinii was identified in 101 (43.7%) of 231 episodes of pneumonia among 185 HIV-1-infected children (median age, 4.5 months; range, 1.7-27.3 months). Receipt of trimethoprim-sulfamethoxazole (TMP-SMX) prophylaxis was not associated with a significant reduction (36%; 95% confidence interval [CI], - 15.4% to 64.5%) in isolation of P. carinii among children considered to have received adequate prophylaxis (37.7% of children) compared with children who had never received any prophylaxis (48.5% of children). However, deaths among children with PCP who had been taking TMP-SMX prophylaxis were markedly reduced (98.6%; 95% CI, 89.1%-99.8%) compared with children who were not taking prophylaxis. Concurrent P. carinii infection was observed in 6 of 18, 11 of 26, and 4 of 6 HIV-1-infected children who had bacteremia, a respiratory virus isolated, or Mycobacterium species isolated, respectively. [ABSTRACT FROM AUTHOR]

There are few data on Pneumocystis carinii pneumonia (PCP) in critically ill human immunodeficiency virus (HIV)-negative patients. Improved knowledge of the presenting symptoms of and prognostic factors for PCP may help to reduce the high mortality rate associated with PCP in such patients. We retrospectively studied 39 consecutive patients with acute PCP-related respiratory failure and malignancy who were treated at 2 intensive care units (ICUs) during a 10-year period. Univariate logistic regression identified the following 8 predictors of mortality at 30 days after patient admission to the ICU (30-day mortality rate, 33%): complete remission of the malignancy (odds ratio [OR], 0.18), receipt of >1 course of antimalignancy chemotherapy (OR, 17.2), involvement of 4 lobes noted on a chest radiograph (OR, 5), >15% neutrophils in bronchoalveolar lavage [BAL] fluid specimens (OR, 6), Organ System Failure score (OR, 7.33), Simplified Acute Physiology Score II (OR, 1.12), and the need for either mechanical ventilation (OR, 63) or vasopressors (OR, 25.9). Studies are needed to determine whether aggressive monitoring and treatment of patients with >15% neutrophils in BAL fluid specimens can improve the outcome of critically ill patients with malignancy and PCP. [ABSTRACT FROM AUTHOR]

We performed a meta-analysis and a decision analysis on the discontinuation of prophylaxis for Pneumocystis carinii pneumonia (PCP) in patients infected with human immunodeficiency virus who had adequate immune recovery while receiving highly active antiretroviral therapy. In the meta-analysis (14 studies with 3584 subjects who had discontinued prophylaxis), 8 cases of PCP occurred during 3449 person-years (0.23 cases per 100 person-years [95% confidence interval, 0.10--0.46]). In the decision analysis, mortality and time spent alive without immunodeficiency in the modeled discontinuation strategy were similar to those in the continuation strategy. For patients who received primary prophylaxis, the discontinuation strategy led to slightly fewer episodes of PCP and fewer toxicity-related prophylaxis withdrawals (e.g., 8.6 vs. 34.5 cases per 100 patients during a 10-year period). Patients on the discontinuation strategy were more likely to be receiving trimeth-oprim- sulfamethoxazole when they became immunodeficient. Comparative results were similar for patients with prior PCP. Discontinuation of PCP prophylaxis in patients with adequate immune recovery is a useful strategy that should be widely considered. [ABSTRACT FROM AUTHOR]

Focuses on the prevention of infection caused by Pneumocystis carinii in patients who undergo organ and hematopoietic transplantation. Features of the life cycle of Pneumocystis species that are relevant to consideration of the antimicrobial agents used in prophylaxis and therapy; Rate of risk in immunocompromised patients who do not have AIDS; Implication of the occurrence of infection while receiving prophylaxis.

Discusses strategies in preventing infections after organ transplantation. Avoidance of epidemiologic exposure after transplantation; Effectiveness of perioperative antibacterial prophylaxis in preventing wound infections in kidney transplant recipiensts; Prevention of Pneumocystis carinii and Toxoplasma gondii infections.

Discusses a medical case where pleura-based masses and hilar adenopathy were seen on a chest radiograph of an AIDS patient who had a history of pneumocystis carinii infection. Explanation for the differential diagnosis of the case; Atypical and extrapulmonary manifestations of P. carinii infection in a patient receiving prophylaxis with dapsone; High-risk group; Extrapulmonary site of the infection.