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BMC Infectious Diseases Jul 2023Haemophagocytic lymphohistiocytosis is a rare and life-threatening condition caused by uncontrolled immune activation leading to excessive inflammation and tissue...
INTRODUCTION
Haemophagocytic lymphohistiocytosis is a rare and life-threatening condition caused by uncontrolled immune activation leading to excessive inflammation and tissue destruction. It could either be due to a primary genetic defect or be triggered by secondary causes such as infections, autoimmune diseases, rheumatological diseases or post-transplant immunosuppression. We here report the case of a 4-year-old child with a recent AIDS diagnosis who developed a severe systemic inflammation.
CASE REPORT
We here report the case of a 4-year-old child with a recent AIDS diagnosis who was admitted to the ER with acute respiratory failure due to Pneumocystis jiroveci infection and Aspergillosis; the following microbiological assessment also showed a CMV, HSV, EBV and HHV-7 coinfection. On the 51st day after she'd started antiretroviral therapy, 39th after she'd followed a course of Bactrim and Caspofungin for PJI and Ambisome for pulmonary Aspergillosis, she started presenting fever, unresponsive to broad-spectrum antibiotic therapy. She also presented worsening of her clinical conditions, with evidence at the laboratory assessments of progressive raise in inflammatory indexes, coagulopathy, trilinear cytopenia and hyperferritinemia. To perform the differential diagnosis between IRIS and HLH, HLA-DR on T cells was studied, turning out negative for IRIS. Therefore, in the suspicion of HLH, a bone marrow aspirate and biopsy were performed with evidence of trilinear cytopenia, prevalence of T-cells and macrophages with signs of phagocytosis. She was started on high-dose steroids and Anakinra for a total of 29 days, resulting in prompt apyrexia and progressive improvement of her clinical conditions and laboratory results.
CONCLUSION
To the best of our knowledge there is poor literature available about the differential diagnosis of HLH and IRIS, therefore medical management in the concurrence of these two conditions needs to be further investigated, especially in a setting where immunological testing is not quickly available. The clinical differences between these pathologies are blurred and the bone marrow biopsy within marker for IRIS helped us to distinguish these two entities.
Topics: Humans; Female; Child, Preschool; Lymphohistiocytosis, Hemophagocytic; Acquired Immunodeficiency Syndrome; Immune Reconstitution Inflammatory Syndrome; HIV Infections; Inflammation
PubMed: 37464267
DOI: 10.1186/s12879-023-08457-9 -
Arthritis Care & Research Feb 2024This manuscript assesses the incidence of Pneumocystis jiroveci pneumonia (PJP) among patients receiving contemporary treatment regimens for antineutrophil cytoplasmic...
OBJECTIVE
This manuscript assesses the incidence of Pneumocystis jiroveci pneumonia (PJP) among patients receiving contemporary treatment regimens for antineutrophil cytoplasmic antibody-associated vasculitis (AAV) and adverse events associated with PJP prophylaxis.
METHODS
Incident users of rituximab or cyclophosphamide for AAV were identified in the TriNetX electronic health records database from 2011 to 2022. The incidence rates (IRs) of PJP in the first 6 months of induction therapy with rituximab and/or cyclophosphamide and during postinduction maintenance therapy with rituximab were calculated. Cox proportional hazard models were used to estimate hazard ratios (HRs) and confidence intervals (CIs) for the risk of adverse events commonly associated with PJP prophylaxis.
RESULTS
We identified 1,461 AAV cases who received induction therapy with rituximab (69.7%), cyclophosphamide (18.9%), or both (11.4%). Prophylaxis prescribed within 30 days of induction included trimethoprim-sulfamethoxazole (30.7%), atovaquone (5.4%), dapsone (3.8%), and pentamidine (0.8%). During induction therapy, 10 cases of PJP were identified (IR 15.0 cases per 1,000 patient-years); no deaths occurred. In adjusted analyses, those who received prophylaxis had a higher risk of leukopenia (HR 3.1; 95% CI 1.1-8.6), rash (HR 1.9; 95% CI 1.0-3.6), and nephropathy (HR 2.6; 95% CI 1.3-5.1) than those who did not. During rituximab maintenance therapy (n = 709), five cases of PJP were identified (IR 2.1 cases per 1,000 person-years), one of whom died during the hospitalization associated with a PJP diagnosis.
CONCLUSION
Rates of PJP in patients with AAV were lower than previously observed, and few cases occurred during rituximab maintenance therapy. PJP prophylaxis was associated with adverse events.
Topics: Humans; Rituximab; Pneumocystis carinii; Incidence; Pneumonia, Pneumocystis; Cyclophosphamide; Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis
PubMed: 37643919
DOI: 10.1002/acr.25222 -
BMC Infectious Diseases Nov 2023Droplet digital PCR (ddPCR) is a novel assay to detect pneumocystis jjrovecii (Pj) which has been defined to be more sensitive than qPCR in recent studies. We aimed to...
OBJECTIVE
Droplet digital PCR (ddPCR) is a novel assay to detect pneumocystis jjrovecii (Pj) which has been defined to be more sensitive than qPCR in recent studies. We aimed to explore whether clinical features of pneumocystis pneumonia (PCP) were associated with ddPCR copy numbers of Pj.
METHODS
A total of 48 PCP patients were retrospectively included. Pj detection was implemented by ddPCR assay within 4 h. Bronchoalveolar fluid (BALF) samples were collected from 48 patients with molecular diagnosis as PCP via metagenomic next generation sequencing (mNGS) or quantitative PCR detection. Univariate and multivariate logistic regression were performed to screen out possible indicators for the severity of PCP. The patients were divided into two groups according to ddPCR copy numbers, and their clinical features were further analyzed.
RESULTS
Pj loading was a pro rata increase with serum (1,3)-beta-D glucan, D-dimmer, neutrophil percentage, procalcitonin and BALF polymorphonuclear leucocyte percentage, while negative correlation with albumin, PaO2/FiO2, BALF cell count, and BALF lymphocyte percentage. D-dimmer and ddPCR copy number of Pj were independent indicators for moderate/severe PCP patients with PaO2/FiO2 lower than 300. We made a ROC analysis of ddPCR copy number of Pj for PaO2/FiO2 index and grouped the patients according to the cut-off value (2.75). The high copy numbers group was characterized by higher level of inflammatory markers. Compared to low copy number group, there was lower level of the total cell count while higher level of polymorphonuclear leucocyte percentage in BALF in the high copy numbers group. Different from patients with high copy numbers, those with high copy numbers had a tendency to develop more severe complications and required advanced respiratory support.
CONCLUSION
The scenarios of patients infected with high ddPCR copy numbers of Pj showed more adverse clinical conditions. Pj loading could reflect the severity of PCP to some extent.
Topics: Humans; Pneumonia, Pneumocystis; Retrospective Studies; DNA Copy Number Variations; Bronchoalveolar Lavage Fluid; Polymerase Chain Reaction; Pneumocystis; Respiratory Distress Syndrome; Pneumocystis carinii
PubMed: 38012564
DOI: 10.1186/s12879-023-08580-7 -
Frontiers in Immunology 2024Clinical and prognostic features of Anti-MDA5-Positive Dermatomyositis (MDA5+ DM) are diverse. This study aimed to examine the peripheral immune cell profiles of...
OBJECTIVE
Clinical and prognostic features of Anti-MDA5-Positive Dermatomyositis (MDA5+ DM) are diverse. This study aimed to examine the peripheral immune cell profiles of patients with MDA5+ DM, identify disease endotypes related to the heterogeneous manifestations and prognosis, and guide individualized therapy regimen.
METHODS
This inpatient cohort included 123 patients with MDA5+ DM. Unsupervised hierarchical clustering analysis was used to derive disease endotypes from the circulating immune cell profiles on admission. Clinical symptoms, laboratory test results, inpatient treatments, and disease outcomes were then analyzed among the identified endotypes.
RESULTS
Three disease endotypes in MDA5+ DM were identified from peripheral immune cell profiles. Endotype1 had the highest percentages of CD4 T cells and monocytes, and the lowest percentage of neutrophils; Endotype2 had the highest percentage of B cells; Endotype3 had the highest percentage of CD8 T cells and NK cells. Clinical and prognostic heterogeneity of the endotypes were revealed. Endotype1 had the lowest 3-month mortality with the high incidence of periungual capillary changes. Endotype2 and Endotype3 had higher prevalence of rapidly progressive interstitial lung disease (RPILD) and mortality at 3 months than Endotype1. Meanwhile, Endotype3 had higher pneumocystis jiroveci and CMV viremia cases with significantly elevated of activated CD8 T cells and multiple cytokines than Endotype1.
CONCLUSION
Clustering analysis of peripheral immune cell profiles identified three different endotypes in MDA5+ dermatomyositis. Endotpye2 and 3 showed higher RPILD, 3-month mortality, pneumocystis jiroveci and CMV viremia.
Topics: Humans; Interferon-Induced Helicase, IFIH1; Dermatomyositis; CD8-Positive T-Lymphocytes; Viremia; Lung Diseases, Interstitial; Cytomegalovirus Infections
PubMed: 38533498
DOI: 10.3389/fimmu.2024.1349611 -
Annals of Clinical Microbiology and... Jan 2024Pneumocystis jirovecii (P. jirovecii) is an opportunistic fungus responsible for Pneumocystis pneumonia (PCP) in deeply immunocompromised patients and for pulmonary...
BACKGROUND
Pneumocystis jirovecii (P. jirovecii) is an opportunistic fungus responsible for Pneumocystis pneumonia (PCP) in deeply immunocompromised patients and for pulmonary colonization in individuals with mild immunosuppression or impaired respiratory function. PCP and Cytomegalovirus (CMV) co-infections have been widely described whereas those involving other Herpesviruses (HVs) such as Epstein-Barr virus (EBV), Herpes simplex virus type 1 and type 2 (HSV-1 and -2), and Varicella zoster virus (VZV) remain scarce. To date, no data are available concerning HVs co-infections in P. jirovecii colonization.
METHODS
Our main objective was to evaluate the frequency of HVs in bronchoalveolar lavage fluid (BALF) samples from patients with PCP or with pulmonary colonization. The secondary objective was to assess the relationship between HVs and the mortality rate in PCP patients. A retrospective single-center study over a seven-year period was conducted. All patients with P. jirovecii detected using PCR in a BALF sample and for whom a PCR assay for HVs detection was performed were included in the study.
RESULTS
One hundred and twenty-five patients were included, corresponding to 77 patients with PCP and 48 colonized patients. At least one HV was detected in 54/77 (70.1%) PCP patients and in 28/48 (58.3%) colonized patients. EBV was the most frequent in both groups. Furthermore, the 30-day survival rate in PCP patients was significantly lower with [EBV + CMV] co-infection than that with EBV co-infection, [EBV + HSV-1] co-infection and without HV co-infection.
CONCLUSION
Our results show that the frequency of HV, alone or in combination is similar in PCP and colonization. They also suggest that [EBV + CMV] detection in BALF samples from PCP patients is associated with an increased mortality rate, underlying the significance to detect HVs in the course of PCP.
Topics: Humans; Pneumocystis carinii; Retrospective Studies; Pneumonia, Pneumocystis; Coinfection; Epstein-Barr Virus Infections; Herpesvirus 4, Human; Herpesviridae; Cytomegalovirus Infections
PubMed: 38245721
DOI: 10.1186/s12941-023-00663-2 -
Mycopathologia May 2024To describe the epidemiology of Pneumocystis jirovecii pneumonia and colonization diagnosed by next-generation sequencing (NGS) and explore the usefulness of the number...
OBJECTIVES
To describe the epidemiology of Pneumocystis jirovecii pneumonia and colonization diagnosed by next-generation sequencing (NGS) and explore the usefulness of the number of P. jirovecii sequence reads for the diagnosis of P. jirovecii pneumonia.
METHODS
We examined the NGS results for P. jirovecii in respiratory samples collected from patients and analysed their clinical, radiological and microbiological characteristics.
RESULTS
Among 285 respiratory samples collected over a 12-month period (January to December 2022), P. jirovecii sequences were detected in 56 samples from 53 patients. Fifty (94.3%) of the 53 patients were HIV-negative. Following our case definitions, 37 (69.8%) and 16 (30.2%) of the 53 patients had P. jirovecii infection and colonization respectively. P. jirovecii infection was associated with presence of underlying disease with immunosuppression (94.6% vs 18.8%, P < 0.05), positive serum 1,3-β-D-glucan (41.2% vs 0%, P < 0.01) and higher number of P. jirovecii sequence reads (P < 0.005). In contrast, P. jirovecii colonization was associated with the male sex (93.8% vs 54.1%, P < 0.01), another definitive infectious disease diagnosis of the respiratory tract (43.8% vs 2.7%, P < 0.001) and higher survival (100% vs 67.6%, P < 0.01). Although P. jirovecii pneumonia was associated with higher number of P. jirovecii reads in respiratory samples, only a sensitivity of 82.14% and a specificity of 68.75% could be achieved.
CONCLUSION
Detection of P. jirovecii sequences in respiratory samples has to be interpreted discreetly. A combination of clinical, radiological and laboratory findings is still the most crucial in determining whether a particular case is genuine P. jirovecii pneumonia.
Topics: Humans; Pneumonia, Pneumocystis; Male; High-Throughput Nucleotide Sequencing; Pneumocystis carinii; Female; Middle Aged; Aged; Adult; Aged, 80 and over; Respiratory System; Young Adult; Molecular Diagnostic Techniques
PubMed: 38704795
DOI: 10.1007/s11046-024-00849-y -
Clinical Transplantation May 2024Pneumocystis jirovecii pneumonia (PJP), an opportunistic infection, often leads to an increase in hospitalization time and mortality rates in kidney transplant (KT)... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND AND OBJECTIVE
Pneumocystis jirovecii pneumonia (PJP), an opportunistic infection, often leads to an increase in hospitalization time and mortality rates in kidney transplant (KT) recipients. However, the risk factors associated with PJP in KT recipients remain debatable. Therefore, we conducted this meta-analysis to identify risk factors for PJP, which could potentially help to reduce PJP incidence and improve outcome of KT recipients.
METHODS
We systematically retrieved relevant studies in PubMed, EMBASE, and the Cochrane Library up to November 2023. Pooled odds ratios (ORs) or mean differences (MDs) and the corresponding 95% confidence intervals (CIs) were calculated to assess the impact of potential risk factors on the occurrence of PJP.
RESULTS
27 studies including 42383 KT recipients were included. In this meta-analysis, age at transplantation (MD = 3.48; 95% CI = .56-6.41; p = .02), cytomegalovirus (CMV) infection (OR = 4.00; 95% CI = 2.53-6.32; p = .001), BK viremia (OR = 3.38; 95% CI = 1.70-6.71; p = .001), acute rejection (OR = 3.66; 95% CI = 2.44-5.49; p = .001), ABO-incompatibility (OR = 2.51; 95% CI = 1.57-4.01; p = .001), estimated glomerular filtration rate (eGFR) (MD = -14.52; 95% CI = -25.37- (-3.67); p = .009), lymphocyte count (MD = -.54; 95% CI = -.92- (-.16); p = .006) and anti-PJP prophylaxis (OR = .53; 95% CI = .28-.98; p = .04) were significantly associated with PJP occurrence.
CONCLUSION
Our findings suggest that transplantation age greater than 50 years old, CMV infection, BK viremia, acute rejection, ABO-incompatibility, decreased eGFR and lymphopenia were risk factors for PJP.
Topics: Humans; Kidney Transplantation; Pneumonia, Pneumocystis; Risk Factors; Prognosis; Pneumocystis carinii; Postoperative Complications; Graft Rejection
PubMed: 38690617
DOI: 10.1111/ctr.15320 -
BMC Pulmonary Medicine Nov 2023Pneumocystis pneumonia (PCP) is a life-threatening pulmonary fungal infection that predominantly affects immunocompromised individuals, including kidney transplant...
BACKGROUND
Pneumocystis pneumonia (PCP) is a life-threatening pulmonary fungal infection that predominantly affects immunocompromised individuals, including kidney transplant recipients. Recent years have witnessed a rising incidence of PCP in this vulnerable population, leading to graft loss and increased mortality. Immunosuppression, which is essential in transplant recipients, heightens susceptibility to viral and opportunistic infections, magnifying the clinical challenge. Concurrently, the global impact of coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has been profound. Kidney transplant recipients have faced severe outcomes when infected with SARS-CoV-2, often requiring intensive care. Co-infection with COVID-19 and PCP in this context represents a complex clinical scenario that requires precise management strategies, involving a delicate balance between immunosuppression and immune activation. Although there have been case reports on management of COVID-19 and PCP in kidney transplant recipients, guidance on how to tackle these infections when they occur concurrently remains limited.
CASE PRESENTATIONS
We have encountered four kidney transplant recipients with concurrent COVID-19 and PCP infection. These patients received comprehensive treatment that included adjustment of their maintenance immunosuppressive regimen, anti-pneumocystis therapy, treatment for COVID-19 and other infections, and symptomatic and supportive care. After this multifaceted treatment strategy, all of these patients improved significantly and had favorable outcomes.
CONCLUSIONS
We have successfully managed four kidney transplant recipients co-infected with COVID-19 and PCP. While PCP is a known complication of immunosuppressive therapy, its incidence in patients with COVID-19 highlights the complexity of dual infections. Our findings suggest that tailored immunosuppressive regimens, coupled with antiviral and antimicrobial therapies, can lead to clinical improvement in such cases. Further research is needed to refine risk assessment and therapeutic strategies, which will ultimately enhance the care of this vulnerable population.
Topics: Humans; Pneumonia, Pneumocystis; COVID-19; Kidney Transplantation; Retrospective Studies; Transplant Recipients; SARS-CoV-2; Immunosuppressive Agents; Pneumocystis carinii
PubMed: 37990199
DOI: 10.1186/s12890-023-02764-2 -
Indian Journal of Pediatrics Aug 2023
Topics: Humans; Pneumocystis carinii; SARS-CoV-2; Coinfection; X-Linked Combined Immunodeficiency Diseases; COVID-19; Pneumonia, Pneumocystis
PubMed: 37249831
DOI: 10.1007/s12098-023-04661-2 -
Clinical Infectious Diseases : An... Apr 2024Glucocorticoids are widespread anti-inflammatory medications used in medical practice. The immunosuppressive effects of systemic glucocorticoids and increased... (Review)
Review
Glucocorticoids are widespread anti-inflammatory medications used in medical practice. The immunosuppressive effects of systemic glucocorticoids and increased susceptibility to infections are widely appreciated. However, the dose-dependent model frequently used may not accurately predict the risk of infection in all patients treated with long-term glucocorticoids. In this review, we examine the risks of opportunistic infections (OIs) in patients requiring glucocorticoid therapy by evaluating the influence of the glucocorticoid dose, duration, and potency, combined with biological and host clinical factors and concomitant immunosuppressive therapy. We propose strategies to prevent OIs, which involve screening, antimicrobial prophylaxis, and immunizations. While this review focuses on patients with autoimmune, inflammatory, or neoplastic diseases, the potential risks and preventative strategies are likely applicable to other populations. Clinicians should actively assess the benefit-harm ratios of systemic glucocorticoids and implement preventive efforts to decrease their associated infections complications.
Topics: Adult; Humans; Glucocorticoids; Opportunistic Infections; Immunosuppressive Agents; Anti-Inflammatory Agents
PubMed: 37669916
DOI: 10.1093/cid/ciad474