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British Medical Journal (Clinical... Feb 1983
Topics: Animals; Drug Combinations; Female; Humans; Infant; Male; Pentamidine; Pneumonia, Pneumocystis; Rats; Sulfamethoxazole; Trimethoprim; Trimethoprim, Sulfamethoxazole Drug Combination
PubMed: 6402123
DOI: 10.1136/bmj.286.6364.499 -
Trends in Parasitology Oct 2021The clinical picture of the fungal disease, Pneumocystis pneumonia, resembles the course of coronavirus disease 2019 (COVID-19), presenting a diagnostic challenge in the...
The clinical picture of the fungal disease, Pneumocystis pneumonia, resembles the course of coronavirus disease 2019 (COVID-19), presenting a diagnostic challenge in the pandemic era. We discuss the concern of Pneumocystis jirovecii and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) coinfection, their similarities, and the impact of immunosuppression, with a suggested diagnostic pathway for their suspected coinfection.
Topics: COVID-19; Coinfection; Humans; Immunosuppression Therapy; Pandemics; Pneumocystis carinii; Pneumonia, Pneumocystis
PubMed: 34364804
DOI: 10.1016/j.pt.2021.07.010 -
Frontiers in Cellular and Infection... 2022can result in a serious pulmonary infection, pneumonia, in immunocompetent hosts. The diagnosis of pneumonia has long been a major clinical concern, and there are...
BACKGROUND
can result in a serious pulmonary infection, pneumonia, in immunocompetent hosts. The diagnosis of pneumonia has long been a major clinical concern, and there are limitations with the currently utilized immunostaining and polymerase chain reaction diagnosis/detection technologies (, insufficient sensitivity and accuracy). Hence, we sought to establish a rapid and RNA-specific transcription mediated amplification and CRISPR/Cas13a-based diagnostics targeted -mitochondrial large subunit ribosomal RNA.
METHODS
The procedure of the diagnostics included amplification of the extracted RNA samples by transcription mediated amplification, followed by CRISPR/Cas13 detection, and ultimately, the judgment of the results after 30 minutes of fluorescence signal. Later, the diagnostic performance of the CRISPR/Cas13-based diagnostics were tested on the 62 surplus clinical samples.
RESULTS
This CRISPR/Cas13-based diagnostics achieved limits of detection of approximately 2 copies/µL transcribed RNA templates, with no cross reaction to other respiratory pathogens, including bacteria and fungi. Similar to in-house quantitative real-time polymerase chain reaction, CRISPR/Cas13-based diagnostics was still positive in 243-fold diluted bronchial alveolar lavage fluid. A preliminary evaluation of 62 surplus bronchial alveolar lavage fluid samples from patients suspected of pneumonia showed that CRISPR/Cas13-based diagnostics achieved a 78.9% sensitivity and a 97.7% specificity in the diagnosis of pneumonia.
CONCLUSION
Our study demonstrates that the CRISPR/Cas13-based diagnostics technique has good performance for the accurate and specific diagnosis of pneumonia.
Topics: CRISPR-Cas Systems; Humans; Pneumocystis carinii; Pneumonia, Pneumocystis; RNA; Real-Time Polymerase Chain Reaction
PubMed: 35782118
DOI: 10.3389/fcimb.2022.904485 -
Journal of Infection in Developing... Oct 2018Pneumocystis jirovecii (PJ) pneumonia (PJP) is an important opportunistic infection affecting various types of immunocompromised patients and is associated with an...
INTRODUCTION
Pneumocystis jirovecii (PJ) pneumonia (PJP) is an important opportunistic infection affecting various types of immunocompromised patients and is associated with an increased risk of mortality. PJ is a unique fungal pathogen which is increasingly common and maybe associated with a higher mortality rate in patients without AIDS. We present the characteristics of PJP, diagnosis, and treatment outcomes between AIDS and non-AIDS patients.
METHODOLOGY
We conducted a review of studies of AIDS and non-AIDS patients with PJP using PubMed to search for studies until December 2017.
RESULTS
The annual incidence of AIDS-PJP decreased from 13.4 to 3.3 per 1000 person-years in industrialized countries, while the incidence of non-AIDS-PJP varied widely. Both groups had similar clinical manifestations and radiological features, but the non-AIDS-PJP group potentially had a more fulminant course, more diffuse ground glass opacities, and fewer cystic lesions. The mortality rate decreased in the AIDS-PJP group after the advent of antiretroviral therapy; however, the mortality rate remained high in both groups. A laboratory diagnosis was usually nonspecific; CD4+ T-cell < 200 cells/mL or < 14% favored AIDS-PJP. Serum 1,3-β-D-glucan (BDG) had a high diagnostic odds ratio. Combining BDG and lactic dehydrogenase improved the diagnosis of AIDS-PJP. Histopathological staining and polymerase chain reactions could not discriminate infection from colonization when the result was positive. The use of antibiotics, prophylaxis, and adjunctive corticosteroids was controversial.
CONCLUSIONS
Early diagnosis and treatment can be achieved through vigilance, thereby improving the survival rate for PJP in immunocompromised patients.
Topics: AIDS-Related Opportunistic Infections; Case-Control Studies; Early Diagnosis; Humans; Immunocompromised Host; Pneumocystis carinii; Pneumonia, Pneumocystis; Survival Rate
PubMed: 32004150
DOI: 10.3855/jidc.10357 -
Journal of Mother and Child Jan 2021Pneumocystis carinii pneumonia is a common opportunistic respiratory infection among children with human immunodeficiency virus and a weakened immune system. The primary... (Review)
Review
Pneumocystis carinii pneumonia is a common opportunistic respiratory infection among children with human immunodeficiency virus and a weakened immune system. The primary infection in immunocompetent patients may be asymptomatic, whereas fever, shortness of breath, night sweats, nonproductive (dry) cough, pneumonia, progressive respiratory distress and apnea are cardinal symptoms of full-blown pneumocystis pneumonia. The diagnosis can be confirmed by histochemical staining of biological specimens or, recently, by polymerase chain reaction. International recommendations indicate that the drug of choice is the intravenously administered trimethoprim-sulfamethoxazole combination. Early diagnosis and appropriate treatment reduce the mortality of the disease. This article briefly highlights the epidemiology of Pneumocystis pneumonia, its diagnosis and therapeutic options in the pediatric population.
Topics: AIDS-Related Opportunistic Infections; Child; Humans; Pneumonia, Pneumocystis; Risk Factors; Trimethoprim, Sulfamethoxazole Drug Combination
PubMed: 33759428
DOI: 10.34763/devperiodmed.20192303.159162 -
Parasite (Paris, France) Feb 2011Pneumocystis pneumonia (PcP) remains a significant cause of morbidity and mortality in immunocompromised persons, especially those with human immunodeficiency virus... (Review)
Review
Pneumocystis pneumonia (PcP) remains a significant cause of morbidity and mortality in immunocompromised persons, especially those with human immunodeficiency virus (HIV) infection. Pneumocystis colonization is described increasingly in a wide range of immunocompromised and immunocompetent populations and associations between Pneumocystis colonization and significant pulmonary diseases such as chronic obstructive pulmonary disease (COPD) have emerged. This mini-review summarizes recent advances in our clinical understanding of Pneumocystis and PcP, describes ongoing areas of clinical and translational research, and offers recommendations for future clinical research from researchers participating in the "First centenary of the Pneumocystis discovery".
Topics: AIDS-Related Opportunistic Infections; Biomedical Research; Drug Resistance, Fungal; Humans; Pneumocystis; Pneumonia, Pneumocystis; Translational Research, Biomedical
PubMed: 21395200
DOI: 10.1051/parasite/2011181003 -
PloS One 2013Pneumocystis jirovecii pneumonia (PCP), the commonest opportunistic infection in HIV-infected patients in the developed world, is less commonly described in tropical and... (Review)
Review
OBJECTIVE
Pneumocystis jirovecii pneumonia (PCP), the commonest opportunistic infection in HIV-infected patients in the developed world, is less commonly described in tropical and low and middle income countries (LMIC). We sought to investigate predictors of PCP in these settings.
DESIGN
Systematic review and meta-regression.
METHODS
Meta-regression of predictors of PCP diagnosis (33 studies). Qualitative and quantitative assessment of recorded CD4 counts, receipt of prophylaxis and antiretrovirals, sensitivity and specificity of clinical signs and symptoms for PCP, co-infection with other pathogens, and case fatality (117 studies).
RESULTS
The most significant predictor of PCP was per capita Gross Domestic Product, which showed strong linear association with odds of PCP diagnosis (p<0.0001). This was not explained by study design or diagnostic quality. Geographical area, population age, study setting and year of study also contributed to risk of PCP. Co-infection was common (444 episodes/1425 PCP cases), frequently with virulent organisms. The predictive value of symptoms, signs or simple tests in LMIC settings for diagnosis of PCP was poor. Case fatality was >30%; treatment was largely appropriate. Prophylaxis appeared to reduce the risk for development of PCP, however 24% of children with PCP were receiving prophylaxis. CD4 counts at presentation with PCP were usually <200×10(3/)ml.
CONCLUSIONS
There is a positive relationship between GDP and risk of PCP diagnosis. Although failure to diagnose infection in poorer countries may contribute to this, we also hypothesise that poverty exposes at-risk patients to a wide range of infections and that the relatively non-pathogenic P. jirovecii is therefore under-represented. As LMIC develop economically they eliminate the conditions underlying transmission of virulent infection: P. jirovecii, ubiquitous in all settings, then becomes a greater relative threat.
Topics: Developing Countries; Humans; Meta-Analysis as Topic; Pneumocystis carinii; Pneumonia, Pneumocystis
PubMed: 23936365
DOI: 10.1371/journal.pone.0069969 -
Journal of the Formosan Medical... Nov 2008Pneumocystis pneumonia (PcP) in humans is caused by Pneumocystis jirovecii, which has recently been reclassified as a fungus because its cell wall composition and... (Review)
Review
Pneumocystis pneumonia (PcP) in humans is caused by Pneumocystis jirovecii, which has recently been reclassified as a fungus because its cell wall composition and nucleotide sequences are more similar to those of fungi. PcP occurs only in immunocompromised individuals such as those with AIDS. Despite the use of highly active antiretroviral therapy, PcP remains the leading opportunistic infection in AIDS patients. Based on nucleotide sequence variations in the internal transcribed spacer region of rRNA genes, more than 60 different types of P. jirovecii have been identified. Although type differences do not appear to correlate with the clinical characteristics of PcP, nucleotide sequence variations of the organism have been useful in epidemiologic studies. As a result, some recurrent infections are found to be due to re-infection with new types, and outbreaks due to the same types of P. jirovecii have been identified. Initial diagnosis of PcP is usually based on symptoms and chest radiography. A characteristic histopathologic feature is the presence of acellular eosinophilic exudates and organisms in the alveoli. Ultimate diagnosis of PcP is achieved by demonstration of the organism in induced sputum or bronchoalveolar lavage fluid by tinctorial staining or polymerase chain reaction (PCR). Among the many different PCR methods, the nested PCR that targets the large subunit mitochondrial rRNA gene is the most sensitive and specific. Combination of trimethoprim and sulfamethoxazole is the first choice of drugs for both treatment and prophylaxis of PcP. Other drugs that can be used include a combination of primaquine and clindamycin, pentamidine, atovaquone, and a combination of dapsone and trimethoprim. Pneumocystis organisms have the ability to inactivate the phagocytic activity of alveolar macrophages and to induce them to undergo apoptosis. This apoptosis is due to activation of caspase 9 by polyamines that are present in high levels in the lung and alveolar macrophages during PcP.
Topics: Humans; Pneumonia, Pneumocystis
PubMed: 18971152
DOI: 10.1016/S0929-6646(08)60199-0 -
Swiss Medical Weekly 2016Every year, Candida, Aspergillus, Cryptococcus and Pneumocystis infect an estimated two million individuals worldwide. Most are immunocompromised or critically ill.... (Review)
Review
Every year, Candida, Aspergillus, Cryptococcus and Pneumocystis infect an estimated two million individuals worldwide. Most are immunocompromised or critically ill. Candida is the most common fungal pathogen of the critically ill and of recipients of transplanted abdominal organs. In high-risk haemato-oncological patients, in contrast, the introduction of antifungal prophylaxis with fluconazole and later with mould-active posaconazole has led to a remarkable reduction of invasive candidiasis and is likely to have a similar effect on invasive aspergillosis. Invasive aspergillosis remains the dominant invasive fungal disease (IFD) of haemato-oncological patients and solid-organ transplant recipients and is increasingly found in individuals with exacerbated chronic obstructive pulmonary disease on corticosteroids. In the developed world, owing to antiretroviral therapy Pneumocystis pneumonia and cryptococcosis have become rare in patients with human immunodeficiency virus (HIV) and are mainly found in solid-organ transplant recipients or immunocompromised patients. In the developing world, cryptococcosis remains a common and highly lethal disease of HIV positive individuals. With invasive candidiasis and invasive aspergillosis, timely diagnosis is the principal challenge. The clinical presentation is nonspecific and current diagnostic tests lack sensitivity and specificity. The combination of several tests improves sensitivity, but not specificity. Standardised polymerase chain-reaction-based assays may be promising tools for more rapid and specific diagnosis of candidiasis and invasive aspergillosis. Nevertheless, initiation of treatment is often based solely on clinical suspicion. Empirical therapy, however, may lead to over-treatment of patients without IFD or it may miss its target in the case of resistance. Despite the success of antifungal prophylaxis in reducing the incidence of IFDs in haemato-oncological patients, there are a considerable number of breakthrough infections demonstrating not only fungal resistance but also the emergence of rare and often lethal fungal pathogens. Knowledge of the local epidemiology and antifungal resistance is therefore pivotal. Current trial-based guidelines leave major gaps in identifying those most at risk, who may benefit from prophylaxis. Ongoing searches for disease-associated genetic polymorphisms may contribute to the establishment of individual risk profiles and targeted prophylaxis.
Topics: Antifungal Agents; Aspergillosis; Candidiasis, Invasive; Cryptococcosis; HIV Infections; Humans; Immunocompromised Host; Pneumonia, Pneumocystis; Switzerland
PubMed: 26901377
DOI: 10.4414/smw.2016.14281 -
International Journal of Infectious... Sep 2022To investigate the clinical outcomes and risk factors of mortality in patients with rheumatic diseases complicated by Pneumocystis pneumonia (PCP).
OBJECTIVES
To investigate the clinical outcomes and risk factors of mortality in patients with rheumatic diseases complicated by Pneumocystis pneumonia (PCP).
METHODS
Between November 2015 and April 2021, patients with rheumatic diseases with PCP in a tertiary referral hospital were retrospectively enrolled. The diagnosis of PCP requires the fulfillment of clinical, radiographic, and microbiological criteria. Factors associated with in-hospital, 30-day, and 90-day mortality were evaluated.
RESULTS
A total of 128 patients with rheumatic diseases who had a positive quantitative polymerase chain reaction assay for Pneumocystis jirovecii were screened, and 72 patients were included in the final analysis. The median (interquartile range [IQR]) pneumonia severity index (PSI) was 101.5 (77.0-132.0). The median (IQR) adjunctive corticosteroid dosage was 0.6 (0.4-0.9) mg/kg/day prednisolone equivalent. The receiver operating characteristic curve analysis showed that the optimal cutoff point of median adjunctive corticosteroid dosage was 0.6 mg/kg/day to predict in-hospital, 30-day, and 90-day mortality. In the multivariable logistic regression analysis, median adjunctive corticosteroid dosage ≥0.6 mg/kg/day and PSI >90 were independent factors of in-hospital, 30-day, and 90-day mortality.
CONCLUSION
A median adjunctive corticosteroid dosage of ≥0.6 mg/kg/day might be associated with mortality in patients with rheumatic diseases complicated by PCP.
Topics: Adrenal Cortex Hormones; Humans; Pneumocystis carinii; Pneumonia, Pneumocystis; Prognosis; Retrospective Studies; Rheumatic Diseases
PubMed: 35918031
DOI: 10.1016/j.ijid.2022.07.070