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BMJ Open Respiratory Research Mar 2021Although asthma is the most commonly diagnosed respiratory disease, its pathogenesis is complex, involving both genetic and environmental factors. A role for the...
BACKGROUND
Although asthma is the most commonly diagnosed respiratory disease, its pathogenesis is complex, involving both genetic and environmental factors. A role for the respiratory microbiome in modifying asthma severity has been recently recognised. Airway colonisation by has previously been associated with multiple chronic lung diseases, including chronic obstructive pulmonary disease (COPD) and severe asthma (SA). Decreased incidence of pneumonia in HIV-infected individuals and reduced severity of COPD is associated with naturally occurring antibody responses to the antigen, Kexin (KEX1).
METHODS
104 paediatric patients were screened for KEX1 IgG reciprocal end point titre (RET), including 51 with SA, 20 with mild/moderate asthma, 20 non-asthma and 13 with cystic fibrosis (CF) in a cross-sectional study.
RESULTS
Patients with SA had significantly reduced KEX1 titres compared with patients with mild/moderate asthma (p=0.018) and CF (p=0.003). A binary KEX1 RET indicator was determined at a threshold of KEX1 RET=1000. Patients with SA had 4.40 (95% CI 1.28 to 13.25, p=0.014) and 17.92 (95% CI 4.15 to 66.62, p<0.001) times the odds of falling below that threshold compared with mild/moderate asthma and patients with CF, respectively. Moreover, KEX1 IgG RET did not correlate with tetanus toxoid IgG (r=0.21, p=0.82) or total IgE (r=0.03, p=0.76), indicating findings are specific to antibody responses to KEX1.
CONCLUSIONS
Paediatric patients with SA may be at higher risk for chronic infections and asthma symptom exacerbation due to reduced levels of protective antibodies. Plasma KEX1 IgG titre may be a useful parameter in determining the clinical course of treatment for paediatric patients with asthma.
Topics: Antibody Formation; Asthma; Child; Cross-Sectional Studies; Humans; Pneumocystis; Pneumonia, Pneumocystis
PubMed: 33762359
DOI: 10.1136/bmjresp-2020-000842 -
Annals of Medicine Dec 2023To evaluate diagnostic performance of metagenomic next-generation sequencing (mNGS) for pneumonia (PCP), in comparison with polymerase chain reaction (PCR), Gomori...
AIM
To evaluate diagnostic performance of metagenomic next-generation sequencing (mNGS) for pneumonia (PCP), in comparison with polymerase chain reaction (PCR), Gomori methenamine silver (GMS) staining and serum 1,3-β-d-Glucan (BG) assay.
METHODS
52 PCP patients and 103 patients with non-pneumocystic jirovecii pneumonia (non-PCP) were enrolled, and comparative analysis was conducted of different diagnostic tests. Clinical features and co-pathogen characteristics were reviewed.
RESULTS
The diagnostic sensitivity (92.3%) and specificity (87.4%) of mNGS did not show significant differences compared with that of PCR while mNGS had the advantage over PCR in the detection of co-pathogens. Despite its excellent specificity, the sensitivity of GMS staining (9.3%) was inferior to that of mNGS ( < .001). The combination of mNGS with serum BG statistically outperformed mNGS or serum BG alone in the areas under the receiver operating characteristic curves (AUCs, = .0013 and = .0015, respectively). Notably, all the blood samples showing positive mNGS for came from PCP patients. The leading co-pathogens among patients with PCP were cytomegalovirus, Epstein-Barr virus and Torque teno virus.
CONCLUSIONS
mNGS shows superiority over several common clinical methods in the diagnosis of suspected PCP. Serum BG in conjunction with mNGS further improved the diagnostic efficacy of mNGS.
Topics: Humans; Pneumonia, Pneumocystis; Epstein-Barr Virus Infections; Sensitivity and Specificity; Herpesvirus 4, Human; High-Throughput Nucleotide Sequencing; Respiratory System
PubMed: 37403381
DOI: 10.1080/07853890.2023.2232358 -
The Korean Journal of Parasitology Oct 2022This study determined the recent status and trend of Pneumocystis jirovecii pneumonia (PcP) in the non-human immunodeficiency virus (HIV) (non-HIV-PcP) and HIV (HIV-PcP)...
This study determined the recent status and trend of Pneumocystis jirovecii pneumonia (PcP) in the non-human immunodeficiency virus (HIV) (non-HIV-PcP) and HIV (HIV-PcP) infected populations using data from the Health Insurance Review & Assessment Service (HIRA) and the Korea Disease Control and Prevention Agency (KDCA). SaTScan and Joinpoint were used for statistical analyses. Non-HIV-PcP cases showed an upward trend during the study period from 2010 to 2021, with the largest number in 2021 (551 cases). The upward trend was similar until 2020 after adjusting for the population. Seoul had the highest number of cases (1,597) in the non-HIV-PcP group, which was the same after adjusting for the population (162 cases/1,000,000). It was followed by Jeju-do (89 cases/1,000,000). The most likely cluster (MLC) for the non-HIV-PCP group was Seoul (Relative Risk (RR)=4.59, Log Likelihood Ratio (LLR)=825.531), followed by Jeju-do (RR=1.59, LLR=5.431). An upward trend was observed among the non-HIV-PcP group in the Jeju-do/Jeollanam-do/Jeollabuk-do/Gyeongsangnam-do/Busan/Daejeon/Daegu/Ulsan joint cluster (29.02%, LLR=11.638, P<0.001) located in the southern part of Korea. Both women and men in the non-HIV groups showed an overall upward trend of PcP during the study period. Men in the 60-69 age group had the highest annual percentage change (APC 41.8) during 2014-2019. In contrast, the HIV groups showed a falling trend of PcP recently. Men in the 60-69 age group had the most decrease (APC -17.6) during 2018-2021. This study provides an analytic basis for health measures and a nationwide epidemiological surveillance system for the management of PcP.
Topics: Female; Humans; Pneumocystis carinii; Pneumonia, Pneumocystis; HIV Infections; Risk; Republic of Korea
PubMed: 36320109
DOI: 10.3347/kjp.2022.60.5.327 -
Journal of Medical Case Reports Feb 2024Pneumocystis jirovecii (PJP) pneumonia is a serious life-threatening condition in immunocompromised individuals and is often associated with human immunodeficiency virus...
INTRODUCTION AND IMPORTANCE
Pneumocystis jirovecii (PJP) pneumonia is a serious life-threatening condition in immunocompromised individuals and is often associated with human immunodeficiency virus (HIV) + patients. We describe a case of PJP pneumonia which provided a diagnostic challenge in a patient who presented with no known risk factors leading to a delay in initiation of appropriate antibiotic therapy.
CASE PRESENTATION
A 71-year-old previously healthy white/Caucasian male presented with subacute hypoxic respiratory failure due to multifocal pneumonia with diffuse bilateral ground glass opacities with consolidations despite prior treatment with antibiotics and steroids. He was admitted and started on intravenous broad-spectrum antibiotics but continued to deteriorate, eventually requiring intubation and transfer to the ICU. Bronchoscopy revealed PJP and treatment was initiated, but the patient developed refractory shock and multiorgan failure, and ultimately died. It was later discovered that he was HIV-1 positive.
CLINICAL DISCUSSION
PJP, as a potential cause of his presentation, was not considered given that our patient lacked any overt risk factors for PJP pneumonia. He continued to worsen despite broad spectrum antibiotic therapy and hence bronchoscopy was pursued. His clinical profile, in hindsight, was suspicious for PJP pneumonia and early PJP-directed antibiotic therapy may have prevented a fatal outcome, as in this case. There was an element of cognitive bias across multiple providers which may have contributed to the delay in treatment despite his rapid clinical decline while on conventional pneumonia treatment protocol. His diagnosis was later evident when his BAL-DFA grew PJP in addition to his low levels of CD4 and CD8 cells. He was found to be HIV-1 positive five days after his death; there was a delay in this diagnosis since all positive HIV tests from the hospital are reported as 'pending' until the presumptive positive sample goes to the Connecticut Department of Public Health State laboratory for the confirmatory test. PJP-targeted therapies were initiated later in our patient's hospital course when the infection had progressed to refractory septic shock with multiorgan failure and eventual death.
CONCLUSION
PJP pneumonia is a fatal disease if not recognized early in the course of illness, and the patient usually undergoes multiple antibiotic regimens before they are diagnosed and receive appropriate clinical care. The gold standard of diagnostic testing for PJP is by obtaining bronchial washings through a flexible bronchoscopy and the turnaround time for such results may take a few days to result. A significant proportion of patients may not have any overt risk factors of immunosuppression and early empiric treatment for PJP may be clinically appropriate as the delay in diagnosis may be associated with significant morbidity and mortality risk.
Topics: Humans; Male; Aged; Pneumonia, Pneumocystis; Pneumocystis carinii; Risk Factors; Anti-Bacterial Agents; HIV Infections
PubMed: 38342895
DOI: 10.1186/s13256-024-04350-4 -
The Malaysian Journal of Pathology Dec 2020Report of a 3-month old girl child who died due to multi-systemic infection of cytomegalovirus (CMV) involving the lungs, liver and kidneys along with pneumocystis...
Report of a 3-month old girl child who died due to multi-systemic infection of cytomegalovirus (CMV) involving the lungs, liver and kidneys along with pneumocystis jiroveci pneumonia (PJP). The mother of the child tested positive for CMV IgG and HIV with a very low CD4 count (160/ μl). Co-infection of cytomegalovirus and pneumocystis jiroveci always occurs in the setting of immunocompromise. Congenital CMV infection is transmitted through the placenta, especially during the first trimester and causes severe multi-systemic disease whereas perinatal infection is acquired during childbirth/ breastfeeding where the babies have maternal protective antibodies leading to much milder or asymptomatic infection. PJP is more common in infancy and presents as hypoxic pneumonia. CMV causes cyto-nucleomegaly and classic "owl's eye" inclusions on histology while PJP presents with characteristic fluffy "cotton ball" alveolar exudates.
Topics: Coinfection; Cytomegalovirus Infections; Female; Humans; Immunocompromised Host; Infant; Infectious Disease Transmission, Vertical; Pneumocystis carinii; Pneumonia, Pneumocystis
PubMed: 33361734
DOI: No ID Found -
Antimicrobial Agents and Chemotherapy Aug 2022A3IS (Mycosinate) is a synthetic product which only contains ingredients found naturally within honey. A3IS is a broad-spectrum antimicrobial product which produces a...
A3IS (Mycosinate) is a synthetic product which only contains ingredients found naturally within honey. A3IS is a broad-spectrum antimicrobial product which produces a sustained release of hydrogen peroxide at low but therapeutic levels. The product elicits this release through an enzymatic reaction between glucose oxidase and the substrate glucose once the product is hydrated. As medical uses for different honeys are being re-evaluated, the purpose of this study was to evaluate the effects of A3IS against a comprehensive panel of human pathogens, including Pneumocystis species, providing a unique assessment against a panel of eukaryotic pathogens. Without exception, A3IS exhibited significant efficacy at 50% and 100% inhibitory concentrations against a broad spectrum of human pathogens including yeasts, molds (both hyaline and dematiaceous), and dimorphic fungi. Notably, A3IS was effective against fungal strains with a high level of resistance to fluconazole or voriconazole. The 50% inhibitory concentrations for Pneumocystis carinii and P. murina (surrogates for ) were considered "Marked" and "Moderate" on an established rank scale, and would be considered for studies, based on an established pipeline. These results indicate that A3IS is a novel anti-fungal agent against an extensive range of human fungal pathogens.
Topics: Antifungal Agents; Fluconazole; Fungi; Humans; Microbial Sensitivity Tests; Pneumocystis; Pneumonia, Pneumocystis; Voriconazole
PubMed: 35852368
DOI: 10.1128/aac.00521-22 -
Frontiers in Immunology 2022is a ubiquitous fungal pathogen that causes pneumonia (PCP) and pulmonary sequelae in HIV-infected individuals and other immunocompromised populations. With the success...
INTRODUCTION
is a ubiquitous fungal pathogen that causes pneumonia (PCP) and pulmonary sequelae in HIV-infected individuals and other immunocompromised populations. With the success of anti-retroviral therapy for HIV-infected individuals the frequency of PCP in that population has decreased, however, PCP remains a significant cause of morbidity and mortality in individuals with hematologic and solid malignancies, and in individuals treated with immunosuppressive therapies for autoimmune diseases, and following bone marrow and solid organ transplantation. Despite the clinical need, there is no approved vaccine to prevent PCP in vulnerable populations. The ultimate goal of the field is to develop an effective vaccine that can overcome immune deficits in at risk populations and induce long-lasting protective immunity to . Toward this goal, our laboratory has established a model of PCP co-infection in simian immunodeficiency virus (SIV)-infected non-human primates (NHP) and identified a recombinant protein sub-unit vaccine, KEX1, that induces robust anti- immunity in immune-competent macaques that is durable and prevents PCP following simian immunodeficiency virus (SIV)-induced immunosuppression. Type I, or invariant natural killer T (iNKT) cells have the potential to provide B cell help under conditions of reduced CD4+ T cell help.
METHODS
In the present study, we used the SIV model of HIV infection to address whether therapeutic vaccination with the iNKT cell-activating adjuvant α-galactosylceramide (α-GC) and KEX1 (α-GC+KEX1) can effectively boost anti- humoral immunity following virus-induced immunosuppression.
RESULTS
Immunization of antigen-experienced NHPs with α-GC+KEX1 during the early chronic phase of SIV-infection significantly boosted anti- humoral immunity by increasing memory B cells and antibody titers, and enhanced titer durability during SIV-induced immunosuppression. This therapeutic vaccination strategy boosted anti- immune responses during SIV-infection and contributed to protection against co-infection in KEX1-vaccinated macaques.
CONCLUSION
These studies present a novel strategy for stimulating durable anti- humoral immunity in the context of complex, chronic SIV-induced immunosuppression and may be further applied to immunization of other immunosuppressed populations, and toward other common recall antigens.
Topics: Animals; HIV Infections; Pneumocystis; Pneumonia, Pneumocystis; Simian Acquired Immunodeficiency Syndrome; Coinfection; Simian Immunodeficiency Virus; Immunocompromised Host; Vaccines, Synthetic; Primates; Adjuvants, Immunologic; Macaca
PubMed: 36561749
DOI: 10.3389/fimmu.2022.1036658 -
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 -
The Journal of Infectious Diseases Feb 2022Pneumocystis species interaction with myeloid cells is well known, especially in macrophages; however, how the organism binds to lung epithelial cells is incompletely...
Pneumocystis species interaction with myeloid cells is well known, especially in macrophages; however, how the organism binds to lung epithelial cells is incompletely understood. Ephrin type-A receptor 2 (EphA2) has been previously identified as a lung epithelial pattern recognition receptor that binds to fungal β-glucans. Herein, we also report that EphA2 can also bind Pneumocystis β-glucans, both in isolated forms and also on exposed surfaces of the organism. Furthermore, binding of Pneumocystis β-glucans resulted in phosphorylation of the EphA2 receptor, which has been shown to be important for downstream proinflammatory response. Indeed, we also show that interleukin 6 cytokine is significantly increased when lung epithelial cells are exposed to Pneumocystis β-glucans, and that this response could be blocked by preincubation with a specific antibody to EphA2. Our study presents another Pneumocystis lung epithelial cell receptor with implications for initial colonization and possible therapeutic intervention.
Topics: Carrier Proteins; Epithelial Cells; Humans; Lung; Pneumocystis; Pneumonia, Pneumocystis; Receptor, EphA2; beta-Glucans
PubMed: 34289046
DOI: 10.1093/infdis/jiab384 -
Frontiers in Microbiology 2021pneumonia (PCP) is an opportunistic infection that commonly occurs in immunocompromised individuals. A definite diagnosis of PCP can be made only when the organism is...
pneumonia (PCP) is an opportunistic infection that commonly occurs in immunocompromised individuals. A definite diagnosis of PCP can be made only when the organism is identified in a respiratory specimen. It remains unclear whether qPCR can differentiate patients with PCP from those with colonization. In this study, we retrospectively collected data from HIV and non-HIV patients during 2013-2019. A diagnosis of definite, probable PCP, or PCP excluded was made based on clinical criteria, radiological reports, and three standard laboratory staining methods with blinding to qPCR data. Data from qPCR that was performed to determine the fungal burden (DNA copies/μl) in the BAL specimens of 69 HIV and 286 non-HIV patients were then obtained and reviewed. Receiver Operating Characteristic (ROC) curve analysis was performed to determine the upper and lower cut-off values for PCP diagnosis in HIV and non-HIV groups. In the non-HIV group, the lower cut-off value of 1,480 DNA copies/μl yielded a sensitivity of 100% (95% confidence interval [CI], 91.0-100), specificity of 72.9% (95% CI, 64.0-80.7), a positive predictive value (PPV) of 54.9% (95% CI, 47.6-62.1), and a negative predictive value (NPV) of 100% with Youden index of 0.73 for PCP diagnosis. In this group, the upper cut-off value of 9,655 DNA copies/μl showed the sensitivity of 100% (95% CI, 91.0-100) and specificity of 95.8% (95% CI, 90.4-98.6) with PPV of 88.6% (95% CI, 76.8-94.8) and a NPV of 100% with Youden index of 0.96 for PCP diagnosis. Regarding the HIV group, the lower cut-off value of 1,480 DNA copies/μl showed the sensitivity of 100% (95% CI, 92.5-100%) and specificity of 91.7% (95% CI, 61.5-99.8) with PPV of 97.9% (95% CI, 87.8-99.7) and a NPV of 100% with Youden index of 0.92 for PCP diagnosis. The sensitivity and specificity of the upper cut-off value of 12,718 DNA copies/μl in this group were 97.9% (95%CI, 88.7-100) and 100% (95%CI, 73.5-100), respectively. The values above the upper cut-off point had a PPV of 100% (95% CI, N/A) and a NPV of 92.3% (95% CI, 63.3-98.8) with Youden index of 0.98 for PCP diagnosis in the HIV group.
PubMed: 34745031
DOI: 10.3389/fmicb.2021.729193