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Medical Mycology Jun 2024This systematic review evaluates the current global impact of invasive infections caused by Pneumocystis jirovecii (principally pneumonia: PJP), and was carried out to...
Features and global impact of invasive fungal infections caused by Pneumocystis jirovecii: A systematic review to inform the World Health Organization fungal priority pathogens list.
This systematic review evaluates the current global impact of invasive infections caused by Pneumocystis jirovecii (principally pneumonia: PJP), and was carried out to inform the World Health Organization Fungal Priority Pathogens List. PubMed and Web of Science were used to find studies reporting mortality, inpatient care, complications/sequelae, antifungal susceptibility/resistance, preventability, annual incidence, global distribution, and emergence in the past 10 years, published from January 2011 to February 2021. Reported mortality is highly variable, depending on the patient population: In studies of persons with HIV, mortality was reported at 5%-30%, while in studies of persons without HIV, mortality ranged from 4% to 76%. Risk factors for disease principally include immunosuppression from HIV, but other types of immunosuppression are increasingly recognised, including solid organ and haematopoietic stem cell transplantation, autoimmune and inflammatory disease, and chemotherapy for cancer. Although prophylaxis is available and generally effective, burdensome side effects may lead to discontinuation. After a period of decline associated with improvement in access to HIV treatment, new risk groups of immunosuppressed patients with PJP are increasingly identified, including solid organ transplant patients.
Topics: Humans; Pneumocystis carinii; Invasive Fungal Infections; World Health Organization; Immunocompromised Host; Risk Factors; Global Health; Pneumonia, Pneumocystis; Antifungal Agents; Incidence
PubMed: 38935910
DOI: 10.1093/mmy/myae038 -
Transplant Infectious Disease : An... Jun 2024Previous studies showed HIV-negative immunocompromised patients are susceptible to Pneumocystis pneumonia (PCP). However, the PCP outcome has not been compared among...
BACKGROUND
Previous studies showed HIV-negative immunocompromised patients are susceptible to Pneumocystis pneumonia (PCP). However, the PCP outcome has not been compared among HIV-negative immunocompromised patients.
METHODS
In this retrospective cohort study at the University Health Network, we included all HIV-negative immunocompromised patients who fulfilled the European Organization for Research and Treatment of Cancer (EORTC) PCP diagnosis criteria from December 2018 to December 2019. We compared the demographics, comorbidities, course of illness, and PCP outcome (28-day mortality and composite outcome [i.e., death or intensive care unit (ICU) admission]) between solid organ transplant (SOT) and non-SOT patients.
RESULTS
Of 160 non-HIV patients with PCP diagnoses, 118 patients fulfilled EORTC criteria (76 males [64.4%], median [range] age: 65.5 [21-87] years). PCP presentation in SOT recipients (n = 14) was more severe than non-SOT patients (n = 104): acute presentation (onset <7 days before admission: 11/14 [78.6%] vs. 51/104 [56%], p = .037), shortness of breath (100% vs. 75/104 [74.3%], p = .037), median [range] O saturation (88% [75%, 99%] vs. 92%[70%, 99%], p = .040), and supplemental O requirement (12/14 [85.7%] vs. 59/104 [56.7%], p = .044). The mortality [4/14, (28.6%) vs. 15/104 (14.4%), p = .176], ICU admission (10/14 [71.4%] vs. 18/104 [17.3%], p < .0001), and mechanical ventilation (8/14 [57.1%] vs. 18/104 [17.3%], p = .0007) in SOT patients was different from non-SOT patients. In multivariable analysis, SOT recipients were at greater risk of composite outcome than non-SOT patients (aOR [CI95%]: 12.25 [3.08-48.62], p < .001).
CONCLUSION
PCP presentation and outcomes in SOT recipients are more severe than in non-SOT patients. Further studies are required to explore the biological reasons for this difference.
PubMed: 38932716
DOI: 10.1111/tid.14321 -
Cureus May 2024Diagnosing pneumonia (PJP) can be complex, particularly in cases of significant respiratory failure. The 1,3-β-D-glucan (BDG) serum assay has emerged as a promising...
Diagnosing pneumonia (PJP) can be complex, particularly in cases of significant respiratory failure. The 1,3-β-D-glucan (BDG) serum assay has emerged as a promising non-invasive diagnostic tool for detecting fungal infections, including PJP. However, factors that can confound the interpretation of BDG levels by causing elevation in serum levels have been documented. Here, we present the case of 51-year-old woman with underlying autoimmune disorder, hematologic malignancy, and chronic steroid use, who was admitted for acute hypoxemic respiratory failure. Obtaining the BDG assay after the administration of intravenous immunoglobulin (IVIG) posed a diagnostic challenge, as the patient was unable to undergo bronchoscopy. This circumstance led to a debate regarding the possibility of a false-positive BDG due to IVIG use or the presence of PJP. Ultimately, the patient was empirically treated for PJP. This case underscores the importance of comprehending factors that may contaminate BDG results, particularly in immunocompromised individuals.
PubMed: 38919241
DOI: 10.7759/cureus.61121 -
Cureus Jun 2024X-linked inhibitor of apoptosis (XIAP) deficiency is a rare primary immunodeficiency with a broad spectrum of clinical manifestations, including susceptibility to...
X-linked Inhibitor of Apoptosis (XIAP) Deficiency Complicated by Hemophagocytic Lymphohistiocytosis on Immunotherapy Leading to Acute Respiratory Distress Syndrome and Multiorgan Failure Secondary to Opportunistic Infections.
X-linked inhibitor of apoptosis (XIAP) deficiency is a rare primary immunodeficiency with a broad spectrum of clinical manifestations, including susceptibility to hemophagocytic lymphohistiocytosis (HLH), inflammatory bowel disease (IBD), hypogammaglobulinemia, and severe infections. We present a case of a 39-year-old male with a past medical history of XIAP deficiency complicated by HLH, Crohn's disease, and hypogammaglobulinemia, who developed acute respiratory distress syndrome (ARDS) due to Pneumocystis jiroveci pneumonia (PJP) and concurrent multiorgan failure due to disseminated Mycobacterium avium intracellulare (MAI) infection. This case highlights the challenges in managing XIAP deficiency, emphasizing the importance of early recognition, and the need for further research to improve outcomes in this population.
PubMed: 38912075
DOI: 10.7759/cureus.62703 -
Cureus May 2024pneumonia (PCP) is a life-threatening condition found in immunocompromised individuals, especially in human immunodeficiency virus (HIV) positive patients. Here, we...
pneumonia (PCP) is a life-threatening condition found in immunocompromised individuals, especially in human immunodeficiency virus (HIV) positive patients. Here, we report a case of PCP in a presumably immunocompetent 25-year-old male patient who presented with a one-month history of chest pain, dyspnea, and a nonproductive cough with recent development of night sweats. The patient recently immigrated to the United States without any known medical or family history. A chest radiograph revealed moderate pneumothorax for which a chest tube was placed. A chest computed tomography (CT) scan revealed diffuse lung disease with multiple thin- and thick-walled cystic lesions on a background of diffuse ground-glass opacities. Based on these radiologic findings and subsequent positive HIV serology, there was a high suspicion of PCP. Bronchoalveolar lavage was performed, and PCR for was positive. Appropriate treatment was initiated, and the patient recovered well. Through this report, we aim to highlight the importance of recognizing the various clinical and radiologic findings of PCP even in patients with no overt risk factors. Prompt and targeted treatment could mitigate morbidity and mortality associated with this opportunistic pathogen.
PubMed: 38899257
DOI: 10.7759/cureus.60697 -
Journal of Clinical Immunology Jun 2024Patients with chromosome 18q deletion syndrome generally experience hypogammaglobulinemia. Herein, we describe two patients with chromosome 18q deletion syndrome who...
Patients with chromosome 18q deletion syndrome generally experience hypogammaglobulinemia. Herein, we describe two patients with chromosome 18q deletion syndrome who presented with late-onset combined immune deficiency (LOCID), which has not been previously reported. Patient 1 was a 29-year-old male with 18q deletion syndrome, who was being managed for severe motor and intellectual disabilities at the Yamabiko Medical Welfare Center for 26 years. Although the patient had few infections, he developed Pneumocystis pneumonia at the age of 28. Patient 2, a 48-year-old female with intellectual disability and congenital malformations, was referred to Tokyo Medical and Dental University Hospital with abnormal bilateral lung shadows detected on her chest radiography. Computed tomography showed multiple lymphadenopathies and pneumonia. A lymph node biopsy of the inguinal region revealed granulomatous lymphadenitis, and a chromosomal examination revealed 18q deletion. Array-based genomic hybridization analysis revealed deletion at 18q21.32-q22.3 for patient 1 and at 18q21.33-qter for patient 2. Immune status work-up of the two patients revealed panhypogammaglobulinemia, decreased number of memory B cells and naïve CD4 and/or CD8 cells, reduced response on the carboxyfluorescein diacetate succinimidyl ester T-cell division test, and low levels of T-cell receptor recombination excision circles and Ig κ-deleting recombination excision circles. Consequently, both patients were diagnosed with LOCID. Although patients with 18q deletion syndrome generally experience humoral immunodeficiency, the disease can be further complicated by cell-mediated immunodeficiency, causing combined immunodeficiency. Therefore, patients with 18q deletion syndrome should be regularly tested for cellular/humoral immunocompetence.
Topics: Humans; Chromosome Deletion; Male; Female; Chromosomes, Human, Pair 18; Chromosome Disorders; Adult; Middle Aged; Age of Onset; Severe Combined Immunodeficiency; Intellectual Disability; Immunologic Deficiency Syndromes
PubMed: 38896123
DOI: 10.1007/s10875-024-01751-4 -
BMC Pulmonary Medicine Jun 2024Persistent inflammatory damage and suppressed immune function play a crucial role in the pathogenesis and progression of the pneumocystis jirovecii pneumonia (PjP).... (Observational Study)
Observational Study
Persistent inflammatory damage and suppressed immune function play a crucial role in the pathogenesis and progression of the pneumocystis jirovecii pneumonia (PjP). Therefore, we aimed to investigate the correlation between the combined immune and inflammatory indicator: the neutrophil-to-lymphocyte ratio (NLR) and prognosis of non-human immunodeficiency virus (non-HIV) PjP.In the retrospective analysis conducted in ICUs at Beijing Chao-Yang Hospital, we examined data from 157 patients diagnosed with non-HIV PjP. Our findings reveal a concerning hospital mortality rate of 43.3%, with the 28-day mortality rate reaching 47.8%.Through multivariable logistic and Cox regression analyses, we established a significant association between elevated NLR levels and hospital mortality (adjusted odd ratio, 1.025; 95% CI, 1.008-1.043; p = 0.004) or 28-day mortality (adjusted hazard ratio, 1.026; 95% CI, 1.008-1.045; p = 0.005). Specifically, patients with an NLR exceeding 20.3 demonstrated markedly lower overall survival rates, underscoring the biomarker's predictive value for both hospital and 28-day mortality.In conclusion, non-HIV PjP patients in the ICU still have a high rate of mortality and a poor short-term prognosis after discharge. A high level of NLR was associated with an increased risk of hospital mortality and 28-day mortality.
Topics: Humans; Pneumonia, Pneumocystis; Retrospective Studies; Male; Female; Middle Aged; Neutrophils; Prognosis; Aged; Hospital Mortality; Pneumocystis carinii; Lymphocytes; China; Logistic Models; Intensive Care Units; Biomarkers; Proportional Hazards Models; Adult
PubMed: 38890590
DOI: 10.1186/s12890-024-03093-8 -
Open Forum Infectious Diseases Jun 2024Prior reports have suggested a possible increase in the frequency of invasive fungal infections (IFIs) with use of a Bruton tyrosine kinase inhibitor (BTKi) for...
Risk of Invasive Fungal Infections in Patients With Chronic Lymphocytic Leukemia Treated With Bruton Tyrosine Kinase Inhibitors: A Case-Control Propensity Score-Matched Analysis.
BACKGROUND
Prior reports have suggested a possible increase in the frequency of invasive fungal infections (IFIs) with use of a Bruton tyrosine kinase inhibitor (BTKi) for treatment of chronic lymphoid malignancies such as chronic lymphocytic leukemia (CLL), but precise estimates are lacking. We aim to characterize the prevalence of IFIs among patients with CLL, for whom a BTKi is now the first-line recommended therapy.
METHODS
We queried TriNetX, a global research network database, to identify adult patients with CLL using the code (C91.1) and laboratory results. We performed a case-control propensity score-matched analysis to determine IFIs events by BTKi use. We adjusted for age, sex, ethnicity, and clinical risk factors associated with an increased risk of IFIs.
RESULTS
Among 5358 matched patients with CLL, we found an incidence of 4.6% of IFIs in patients on a BTKi versus 3.5% among patients not on a BTKi at 5 years. Approximately 1% of patients with CLL developed an IFI while on a BTKi within this period. Our adjusted IFI event analysis found an elevated rate of pneumonia (PJP) (0.5% vs 0.3%, = .02) and invasive candidiasis (3.5% vs 2.7%, = .012) with the use of a BTKi. The number needed to harm for patients taking a BTKi was 120 and 358 for invasive candidiasis and PJP, respectively.
CONCLUSIONS
We found an adjusted elevated rate of PJP and invasive candidiasis with BTKi use. The rates are, however, low with a high number needed to harm. Additional studies stratifying other IFIs with specific BTKis are required to identify at-risk patients and preventive, cost-effective interventions.
PubMed: 38887474
DOI: 10.1093/ofid/ofae115 -
Current HIV Research Jun 2024Vitamin D deficiency and/or insufficiency (hypovitaminosis D) has been associated with several disorders including autoimmune diseases, like type 1 diabetes mellitus;...
BACKGROUND
Vitamin D deficiency and/or insufficiency (hypovitaminosis D) has been associated with several disorders including autoimmune diseases, like type 1 diabetes mellitus; cardiovascular diseases; neoplasms; obesity; insulin resistance, and type 2 diabetes mellitus. This problem is common in southern European countries, especially in elderly and institutionalized persons. In HIV-infected individuals, hypovitaminosis D has been correlated with various complications like tuberculosis, hyperparathyroidism, bone mass loss, premature atherosclerosis, and systemic arterial hypertension, deterioration of immune function, progression of the disease and overall mortality.
OBJECTIVE
The objective of this study was to examine the prevalence and causes of hypovitaminosis D in a cohort of Greek HIV-infected patients, the factors, and possible complications associated with it.
METHODS
All patients attending our HIV unit for a period of 5 months were included in this study. Vitamin D status, medical anamnes, and laboratory tests were obtained at baseline; patients were followed for 3 years and HIV-related complications were noted. No patient received vitamin D supplementation during the follow-up period.
RESULTS
Hypovitaminosis D was common, with 83.7% of the patients showing levels below 30ng/dl and 55.4% below 20ng/dl. After multivariable analysis, age and duration of treatment were the only significant factors for low vitamin D levels. During follow-up, 26 patients exhibited a total of 34 HIV-related complications, the most common being pneumonocystis jiroveci pneumonia (PCP). Hypovitaminosis D showed a positive correlation with overall complications, PCP as well as wasting syndrome.
CONCLUSION
Overall, our study shows that hypovitaminosis D is common in HIV-infected individuals and should probably be treated as soon as possible to protect these patients from serious HIVrelated complications like PCP or wasting syndrome.
PubMed: 38874038
DOI: 10.2174/011570162X302844240605104855 -
Infection and Drug Resistance 2024The administration of trimethoprim-sulfamethoxazole (TMP-SMX) for the prophylaxis of Pneumocystis jirovecii pneumonia (PJP) has proven to be highly efficacious in...
Clinical Characteristics and Epidemiological Analysis of Pneumocystis Jirovecii Pneumonia Infection in Kidney Transplant Patients with Trimethoprim-Sulfamethoxazole Dose Reduction Prophylaxis Strategy.
BACKGROUND
The administration of trimethoprim-sulfamethoxazole (TMP-SMX) for the prophylaxis of Pneumocystis jirovecii pneumonia (PJP) has proven to be highly efficacious in individuals who have undergone kidney transplantation. Nevertheless, the potential for severe adverse reactions associated with this treatment cannot be overlooked, and the determination of an optimal dosage regimen continues to be a matter of investigation. The current study evaluated the effectiveness of low-dose TMP-SMX for PJP prophylaxis in kidney transplant patients and conducted an analysis of the clinical characteristics and epidemiological trends in patients with PJP infection.
METHODS
This retrospective analysis studied electronic medical records of 1763 kidney transplant recipients from 2017 to 2020. These patients were initially prescribed a daily half-strength TMP-SMX (40 mg/200 mg), and the efficacy of this regimen was assessed during a follow-up period of 3-51 months.
RESULTS
Under our PJP prevention and adjustment strategy, 24 patients were infected with PJP. The overall morbidity of PJP infection in our study was 1.36%, corroborates with findings from previously published studies. Among these 24 patients, up to 87.5% had their dosage adjusted due to increased creatinine or other adverse reactions, the most frequent dose was daily quarter-strength TMP-SMX (20 mg/100 mg). TMP-SMX prophylaxis successfully postponed and distributed the onset of PJP, with the mean duration from transplantation to the occurrence of PJP being 13.50±7.11 months.
CONCLUSION
Daily administration of half-strength TMP-SMX can effectively prevent PJP, and prolonging prophylaxis with this medication may potentially reduce the incidence of infection.
PubMed: 38868399
DOI: 10.2147/IDR.S461206