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Expert Review of Anti-infective Therapy Sep 2017Pneumocystis pneumonia is a potentially life-threatening pulmonary infection that occurs in immunocompromised individuals and HIV-infected patients with a low CD4 cell... (Review)
Review
Pneumocystis pneumonia is a potentially life-threatening pulmonary infection that occurs in immunocompromised individuals and HIV-infected patients with a low CD4 cell count. Trimethoprim-sulfamethoxazole has been used as the first-line agent for treatment, but mutations within dihydropteroate synthase gene render potential resistance to sulfamide. Despite advances of combination antiretroviral therapy (cART), Pneumocystis pneumonia continues to occur in HIV-infected patients with late presentation for cART or virological and immunological failure after receiving cART. Areas covered: This review summarizes the diagnosis and first-line and alternative treatment and prophylaxis for Pneumocystis pneumonia in HIV-infected patients. Articles for this review were identified through searching PubMed. Search terms included: 'Pneumocystis pneumonia', 'Pneumocystis jirovecii pneumonia', 'Pneumocystis carinii pneumonia', 'trimethoprim-sulfamethoxazole', 'primaquine', 'trimetrexate', 'dapsone', 'pentamidine', 'atovaquone', 'echinocandins', 'human immunodeficiency virus infection', 'acquired immunodeficiency syndrome', 'resistance to sulfamide' and combinations of these terms. We limited the search to English language papers that were published between 1981 and March 2017. We screened all identified articles and cross-referenced studies from retrieved articles. Expert commentary: Trimethoprim-sulfamethoxazole will continue to be the first-line agent for Pneumocystis pneumonia given its cost, availability of both oral and parenteral formulations, and effectiveness or efficacy in both treatment and prophylaxis. Whether resistance due to mutations within dihydropteroate synthase gene compromises treatment effectiveness remains controversial. Continued search for effective alternatives with better safety profiles for Pneumocystis pneumonia is warranted.
Topics: AIDS-Related Opportunistic Infections; Anti-Bacterial Agents; Anti-HIV Agents; Antiretroviral Therapy, Highly Active; Bacterial Proteins; CD4 Lymphocyte Count; Dihydropteroate Synthase; Drug Resistance, Bacterial; HIV-1; Humans; Immunocompromised Host; Mutation; Pneumocystis carinii; Pneumonia, Pneumocystis; Treatment Outcome; Trimethoprim, Sulfamethoxazole Drug Combination
PubMed: 28782390
DOI: 10.1080/14787210.2017.1364991 -
BMC Immunology Jun 2021Pneumocystis pneumonia (PcP), which is caused by Pneumocystis carinii, is a life-threatening infection that affects immunocompromised individuals. Unfortunately,...
BACKGROUND
Pneumocystis pneumonia (PcP), which is caused by Pneumocystis carinii, is a life-threatening infection that affects immunocompromised individuals. Unfortunately, chemoprophylaxis and dapsone are only effective for half of the patients with PcP, indicating that additional preventive methods are needed. We predicated the pneumocystis surface protein A12 sequence 1-85 by DNAStar software and BepiPred, and identified it as a potential vaccine candidate by bioresearch.
METHODS
We used recombinant A12 as antigen to immunized mice and detected serum titer of IgG, expression of inflammatory factors by EILSA, qRT-PCR and flow cytometry.
RESULTS
Our results showed that immunization with recombinant A12 increased the serum titer of IgG, promoted the secretion of T lymphocytes, increased the expression of inflammatory factors, and elevated lung inflammatory injury in mice.
CONCLUSIONS
Our findings suggest that A12 is a potential vaccine target for preventing Pneumocystis carinii. The evaluation of A12-elicited antibodies in the prevention of PcP in humans deserves further investigation.
Topics: Animals; Antibodies, Fungal; Antigens, Fungal; Cells, Cultured; Disease Models, Animal; Female; Fungal Vaccines; Humans; Immunization; Immunocompromised Host; Immunoglobulin G; Lung; Lymphocyte Activation; Mice; Mice, Inbred BALB C; Peptides; Pneumocystis carinii; Pneumonia, Pneumocystis; Recombinant Proteins; T-Lymphocytes
PubMed: 34174820
DOI: 10.1186/s12865-021-00436-6 -
Terapevticheskii Arkhiv 2016Pneumocystosis is well known as an opportunistic infection that is presently most frequently registered in patients with HIV infection and in those with other...
Pneumocystosis is well known as an opportunistic infection that is presently most frequently registered in patients with HIV infection and in those with other immunodeficiency states. Earlier, after the Second World War, Pneumocystis pneumonia was most commonly detected in debilitated and premature children; nosocomial outbreaks of pneumocystosis were studied in detail in the 1960s and 1970s. The pathogen is transmitted through the air, but a number of references indicate that it can be transmitted through the placenta. Despite the increasing number of publications on pneumocystosis in pediatrics, physicians remain unfamiliar with this disease. The paper provides evidence that Pneumocystis jiroveci can infect the fetus in utero. If unrecognized, the disease can lead to a child's death due to severe respiratory failure. The authors describe their case of generalized pneumocystosis that has developed in a child with evidence of intrauterine infection (detection of the pathogen in the autopsy material and placenta and identification of serological markers in his/her parents). The issues that are associated with intrafamilial infection and a risk for in utero transmission of P. jiroveci are discussed.
Topics: Child; Female; HIV Infections; Humans; Infectious Disease Transmission, Vertical; Male; Opportunistic Infections; Pneumocystis; Pneumocystis Infections; Pneumocystis carinii; Pneumonia, Pneumocystis; Pregnancy; Pregnancy Complications, Infectious
PubMed: 28005039
DOI: 10.17116/terarkh2016881199-102 -
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 -
Medical Mycology Journal 2016Pneumocystis jirovecii is a prototypical opportunistic pathogen, causing an asymptomatic or mild infection in normal hosts and fulminating pneumonia (Pneumocystis... (Review)
Review
Pneumocystis jirovecii is a prototypical opportunistic pathogen, causing an asymptomatic or mild infection in normal hosts and fulminating pneumonia (Pneumocystis pneumonia, PCP) in immunocompromised hosts. PCP is a leading cause of morbidity and mortality in immunocompromised patients such as AIDS patients. Microscopic detection of cysts and trophic forms of P. jirovecii in respiratory secretions is simple and useful but may underestimate the P. jirovecii infection. Conventional polymerase chain reaction (PCR) and nested PCR increase the sensitivity and specificity to identify PCP and provide an approach to discriminate PCP from pulmonary P. jirovecii colonization, but the targeted genes and cut-off value from quantitative real-time PCR remain to be determined. Serum (1-3)-β-D-glucan level and the specific serum antibody titer are ancillary indicators for PCP diagnosis. The successful cultivation of P. jirovecii in vitro is an important progress for PCP research. The diagnosis of PCP relies on the combination of these laboratory examinations as well as the clinical presentations.
Topics: Antibodies, Fungal; Biomarkers; DNA, Fungal; Humans; Immunocompromised Host; Pneumocystis carinii; Pneumonia, Pneumocystis; Polymerase Chain Reaction; Proteoglycans; Sensitivity and Specificity; beta-Glucans
PubMed: 27904052
DOI: 10.3314/mmj.16-00019 -
Journal of Hospital Medicine Aug 2019
Topics: Anti-Bacterial Agents; Anti-Inflammatory Agents; Antigens, Viral; Capsid Proteins; Ceftriaxone; Chills; Diagnosis, Differential; Dyspnea; Fatal Outcome; Fever; Humans; Male; Middle Aged; Pneumocystis carinii; Pneumonia, Bacterial; Prednisolone; Shock, Hemorrhagic
PubMed: 31251159
DOI: 10.12788/jhm.3224 -
Pharmacological Research Aug 2018Pneumocystis jirovecii pneumonia (PJP) is an opportunistic infection diagnosed in immunocompromized patients. After solid organ transplantation, early infection has... (Review)
Review
Pneumocystis jirovecii pneumonia (PJP) is an opportunistic infection diagnosed in immunocompromized patients. After solid organ transplantation, early infection has decreased as a result of effective prophylaxis, but late infections and even outbreaks caused by interpatient transmission of pneumocystis by air are present in the SOT community. Different risk factors for PJP have been described and several indications for PJP prophylaxis have to be considered by clinicians in patients even years after transplantation. Diagnosis of PJP is confirmed by microscopy and immunofluorescence staining of bronchial fluid but PCR as well as serum ß-D-Glucan analysis have become increasingly valuable diagnostic tools. Treatment of choice is Trimethoprim/sulfamethoxazole and early treatment improves prognosis. However, mortality of PJP in solid organ transplant patients is still high and many aspects including the optimal management of immunosuppression during PJP treatment require further investigations.
Topics: Antifungal Agents; Humans; Immunocompromised Host; Immunosuppressive Agents; Opportunistic Infections; Organ Transplantation; Pneumocystis carinii; Pneumonia, Pneumocystis; Practice Guidelines as Topic; Risk Factors; Treatment Outcome
PubMed: 29890253
DOI: 10.1016/j.phrs.2018.06.010 -
Parasitology Research Oct 2015Pneumocystis pneumonia is an opportunistic disease caused by invasion of unicellular fungus Pneumocystis jirovecii. Initially, it was responsible for majority of... (Review)
Review
Pneumocystis pneumonia is an opportunistic disease caused by invasion of unicellular fungus Pneumocystis jirovecii. Initially, it was responsible for majority of morbidity and mortality cases among HIV-infected patients, which later have been reduced due to the introduction of anti-retroviral therapy, as well as anti-Pneumocystis prophylaxis among these patients. Pneumocystis pneumonia, however, is still a significant cause of mortality among HIV-negative patients being under immunosuppression caused by different factors, such as transplant recipients as well as oncologically treated ones. The issue of pneumocystosis among these people is particularly emphasized in the article, since rapid onset and fast progression of severe symptoms result in high mortality rate among these patients, who thereby represent the group of highest risk of developing Pneumocystis pneumonia. In contrast, fungal invasion in immunocompetent people usually leads to asymptomatic colonization, which frequent incidence among healthy infants has even suggested the possibility of its association with sudden unexpected infant death syndrome. In the face of emerging strains with different epidemiological profiles resulting from genetic diversity, including drug-resistant genotypes, the colonization phenomenon desires particular attention, discussed in this article. We also summarize specific and sensitive methods, required for detection of Pneumocystis invasion and for distinguish colonization from the disease.
Topics: AIDS-Related Opportunistic Infections; Genotype; Humans; Immunocompromised Host; Pneumocystis carinii; Pneumonia, Pneumocystis
PubMed: 26281787
DOI: 10.1007/s00436-015-4678-6 -
Current Rheumatology Reports Feb 2020The management of patients with idiopathic inflammatory myositis (IIM) can be complex and challenging due to the myriad of complications they can experience. The... (Review)
Review
PURPOSE OF REVIEW
The management of patients with idiopathic inflammatory myositis (IIM) can be complex and challenging due to the myriad of complications they can experience. The continued use of corticosteroids, in addition to the rise of combination immunosuppressive therapy, has contributed to the ongoing concern for infection. Perhaps the most feared infection in IIM patients is Pneumocystis jirovecii pneumonia (PJP) given its infrequent occurrence yet high mortality. The field has been, and continues to be, without evidence-based guidelines to help clinicians determine which patients with IIM to prescribe prophylaxis. Herein, we review this literature to provide the clinician with an up-to-date view of infections in IIM.
RECENT FINDINGS
In the past 5 years, a number of studies have been reported highlighting various infectious complications, which help us better understand their frequency and associated risk factors. In addition, data has been published on the potential harms of PJP prophylaxis, to better inform the risk/benefit of our decision-making. Infection remains a major contributor to morbidity and mortality in IIM. A better understanding of which patient subgroups are at risk for particular infections will inform optimal management strategies.
Topics: Antibiotic Prophylaxis; Glucocorticoids; Humans; Immunosuppressive Agents; Incidence; Infection Control; Infections; Myositis; Pneumocystis carinii; Pneumonia, Pneumocystis; Vaccines
PubMed: 32020305
DOI: 10.1007/s11926-020-0883-0 -
Medical Mycology Sep 2023Pneumocystis jirovecii is a transmissible fungus responsible for severe pneumonia (Pneumocystis pneumonia [PCP]) in immunocompromised patients. Missense mutations due to... (Review)
Review
Pneumocystis jirovecii is a transmissible fungus responsible for severe pneumonia (Pneumocystis pneumonia [PCP]) in immunocompromised patients. Missense mutations due to atovaquone selective pressure have been identified on cytochrome b (CYB) gene of P. jirovecii. It was recently shown that atovaquone prophylaxis can lead to the selection of specific P. jirovecii CYB mutants potentially resistant to atovaquone among organ transplant recipients. In this context, our objectives were to provide data on P. jirovecii CYB mutants and the putative selective pressure exerted by atovaquone on P. jirovecii organisms in France. A total of 123 patients (124 P. jirovecii specimens) from four metropolitan hospitals and two overseas hospitals were retrospectively enrolled. Fourteen patients had prior exposure to atovaquone, whereas 109 patients did not at the time of P. jirovecii detection. A 638 base-pair fragment of the CYB gene of P. jirovecii was amplified and sequenced. A total of 10 single nucleotide polymorphisms (SNPs) were identified. Both missense mutations C431T (Ala144Val) and C823T (Leu275Phe), located at the Qo active site of the enzyme, were significantly associated with prior atovaquone exposure, these mutations being conversely incidental in the absence of prior atovaquone exposure (P < 0.001). Considering that the aforementioned hospitals may be representative of the national territory, these findings suggest that the overall presence of P. jirovecii CYB mutants remains low in France.
Topics: Animals; Pneumocystis carinii; Atovaquone; Cytochromes b; Retrospective Studies; Mutation
PubMed: 37656874
DOI: 10.1093/mmy/myad095