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Cureus Aug 2023Histoplasmosis is a fungal infection that, if left untreated, can result in very serious health outcomes, especially in patient populations that are immunocompromised....
Histoplasmosis is a fungal infection that, if left untreated, can result in very serious health outcomes, especially in patient populations that are immunocompromised. While the manifestations of the disease are very diverse and highly dependent on the individual health conditions of the patient, in severe cases, it can lead to serious pneumonia, acute respiratory distress syndrome, and death if rapid medical intervention is not performed. Here, we present the case of a patient with acquired immunodeficiency syndrome who suffered from histoplasmosis pneumonia with suspected superimposed pneumonia. The patient rapidly decompensated shortly after admission to the hospital; he presented just one week after being discharged of a similar infection. After being transferred to the intensive care unit (ICU), aggressive intervention stabilized the patient's condition enough for him to be discharged several days later. We hope the unique circumstances of this patient's hospital stay can guide clinicians in managing serious infections in immunocompromised patients.
PubMed: 37692718
DOI: 10.7759/cureus.43152 -
Annals of Intensive Care Dec 2023In the last decade, Ibrutinib has become the standard of care in the treatment of several lymphoproliferative diseases such as chronic lymphocytic leukemia (CLL) and...
Severe infections requiring intensive care unit admission in patients receiving ibrutinib for hematological malignancies: a groupe de recherche respiratoire en réanimation onco-hématologique (GRRR-OH) study.
BACKGROUND
In the last decade, Ibrutinib has become the standard of care in the treatment of several lymphoproliferative diseases such as chronic lymphocytic leukemia (CLL) and several non-Hodgkin lymphoma. Beyond Bruton tyrosine kinase inhibition, Ibrutinib shows broad immunomodulatory effects that may promote the occurrence of infectious complications, including opportunistic infections. The infectious burden has been shown to vary by disease status, neutropenia, and prior therapy but data focusing on severe infections requiring intensive care unit (ICU) admission remain scarce. We sought to investigate features and outcomes of severe infections in a multicenter cohort of 69 patients receiving ibrutinib admitted to 10 French intensive care units (ICU) from 1 January 2015 to 31 December 2020.
RESULTS
Median time from ibrutinib initiation was 6.6 [3-18] months. Invasive fungal infections (IFI) accounted for 19% (n = 13/69) of severe infections, including 9 (69%; n = 9/13) invasive aspergillosis, 3 (23%; n = 3/13) Pneumocystis pneumonia, and 1 (8%; n = 1/13) cryptococcosis. Most common organ injury was acute respiratory failure (ARF) (71%; n = 49/69) and 41% (n = 28/69) of patients required mechanical ventilation. Twenty (29%; n = 20/69) patients died in the ICU while day-90 mortality reached 55% (n = 35/64). In comparison with survivors, decedents displayed more severe organ dysfunctions (SOFA 7 [5-11] vs. 4 [3-7], p = 0.004) and were more likely to undergo mechanical ventilation (68% vs. 31%, p = 0.010). Sixty-three ibrutinib-treated patients were matched based on age and underlying malignancy with 63 controls receiving conventional chemotherapy from an historic cohort. Despite a higher median number of prior chemotherapy lines (2 [1-2] vs. 0 [0-2]; p < 0.001) and higher rates of fungal [21% vs. 8%, p = 0.001] and viral [17% vs. 5%, p = 0.027] infections in patients receiving ibrutinib, ICU (27% vs. 38%, p = 0.254) and day-90 mortality (52% vs. 48%, p = 0.785) were similar between the two groups.
CONCLUSION
In ibrutinib-treated patients, severe infections requiring ICU admission were associated with a dismal prognosis, mostly impacted by initial organ failures. Opportunistic agents should be systematically screened by ICU clinicians in this immunocompromised population.
PubMed: 38055081
DOI: 10.1186/s13613-023-01219-5 -
Therapeutic Advances in Infectious... 2024It is of utmost importance to monitor any change in the epidemiology of fungal diseases that may arise from a change in the number of the at-risk population or the...
BACKGROUND
It is of utmost importance to monitor any change in the epidemiology of fungal diseases that may arise from a change in the number of the at-risk population or the availability of local data.
OBJECTIVE
We sought to update the 2015 publication on the incidence and prevalence of serious fungal diseases in Uganda.
METHODS
Using the Leading International Fungal Education methodology, we reviewed published data on fungal diseases and drivers of fungal diseases in Uganda. Regional or global data were used where there were no Ugandan data.
RESULTS
With a population of ~45 million, we estimate the annual burden of serious fungal diseases at 4,099,357 cases (about 9%). We estimated the burden of candidiasis as follows: recurrent vaginitis (656,340 cases), oral candidiasis (29,057 cases), and esophageal candidiasis (74,686 cases) in HIV-infected people. Cryptococcal meningitis annual incidence is estimated at 5553 cases, pneumonia at 4604 cases in adults and 2100 cases in children. For aspergillosis syndromes, invasive aspergillosis annual incidence (3607 cases), chronic pulmonary aspergillosis (26,765 annual cases and 63,574 5-year-period prevalent cases), and prevalence of allergic bronchopulmonary aspergillosis at 75,931 cases, and severe asthma with fungal sensitization at 100,228 cases. Tinea capitis is common with 3,047,989 prevalent cases. For other mycoses, we estimate the annual incidence of histoplasmosis to be 646 cases and mucormycosis at 9 cases.
CONCLUSION
Serious fungal diseases affect nearly 9% of Ugandans every year. Tuberculosis and HIV remain the most important predisposition to acute fungal infection necessitating accelerated preventive, diagnostic, and therapeutic interventions for the management of these diseases.
PubMed: 38328511
DOI: 10.1177/20499361241228345 -
Microbiology Spectrum Aug 2023Two commercial real-time PCR assays for the detection of Pneumocystis jirovecii were compared, the quantitative RealStar P. jirovecii assay and the qualitative DiaSorin...
Two commercial real-time PCR assays for the detection of Pneumocystis jirovecii were compared, the quantitative RealStar P. jirovecii assay and the qualitative DiaSorin P. jirovecii assay, the latter of which can be used without nucleic acid extraction. Archived bronchoalveolar lavage (BAL) specimens ( = 66), previously tested by molecular methods, were tested by both assays, and the results were compared to the respective original result. The RealStar P. jirovecii assay demonstrated good positive percent agreement (PPA) (90% [95% confidence interval (CI), 72 to 97%]; 27/30) and negative percent agreement (NPA) (100% [95% CI, 88 to 100%]; 36/36) with the reference method. The DiaSorin P. jirovecii assay concordantly detected P. jirovecii in 19 of 24 positive BAL samples (PPA = 73% [95% CI, 52 to 88%]). All negative BAL samples gave concordant results (NPA = 100% [95% CI, 87 to 100%]; 34/34). Discordant results occurred mostly in samples with low fungal loads. In conclusion, the RealStar assay demonstrated good concordance with reference results, and the DiaSorin P. jirovecii assay performed well for negative BAL and positive BAL samples with P. jirovecii concentrations of greater than 260 copies/mL. Pneumonia, caused by the opportunistic fungus Pneumocystis jirovecii, poses a significant risk for immunocompromised individuals. Laboratory testing for P. jirovecii is progressively shifting toward the use of molecular tests such as real-time PCR; however, this is often performed at reference laboratories. Many frontline laboratories are looking into improving their service and reducing turnaround times for obtaining P. jirovecii results by bringing molecular P. jirovecii testing in-house. We evaluated and compared two commercial real-time PCR assays with different workflows for the detection of P. jirovecii from bronchoalveolar lavage specimens. The RealStar P. jirovecii assay requires nucleic acid extraction and provides a quantification of fungal load for positive samples. The DiaSorin P. jirovecii assay offers a simple workflow without nucleic extraction from patient samples and qualitative results. Results from this study provide valuable information on performance and workflow considerations for laboratories that wish to implement P. jirovecii molecular testing.
Topics: Humans; Pneumocystis carinii; Bronchoalveolar Lavage Fluid; Real-Time Polymerase Chain Reaction; Pneumonia, Pneumocystis; Sensitivity and Specificity
PubMed: 37260378
DOI: 10.1128/spectrum.01021-23 -
Cureus Aug 2023We report 13 cases of pulmonary pneumocystis (PCP) in human immunodeficiency virus (HIV)-uninfected patients. Of eight males and five females, with a mean age of 55...
We report 13 cases of pulmonary pneumocystis (PCP) in human immunodeficiency virus (HIV)-uninfected patients. Of eight males and five females, with a mean age of 55 years, one had breast neoplasia, two had common variable immunodeficiency (CVID), one had an autoimmune disease "Goodpasture's syndrome", and one had idiopathic fibrosis (nonspecific interstitial pneumonia/fibrosis (NIP)) undergoing prolonged corticosteroid therapy for two years, with no known immunosuppression in the remaining cases. The clinical picture was characterized by constant dyspnea and severe hypoxia in 11 cases. Lymphopenia was present in nine cases with an average rate of 920.76 elements/mm. The diagnosis was confirmed by isolation of (PCJ) from induced sputum, except in two cases where analysis of bronchoalveolar lavage (BAL) fluid was required. With trimethoprim/sulfamethoxazole (TMP/SMX) and corticosteroid therapy, the course was favorable in all cases. Prophylactic treatment was indicated in three cases.
PubMed: 37706120
DOI: 10.7759/cureus.43409 -
BMC Infectious Diseases Oct 2023To validate Japanese claims-based disease-identifying algorithms for herpes zoster (HZ), Mycobacterium tuberculosis (MTB), nontuberculous mycobacteria infections (NTM),...
BACKGROUND
To validate Japanese claims-based disease-identifying algorithms for herpes zoster (HZ), Mycobacterium tuberculosis (MTB), nontuberculous mycobacteria infections (NTM), and Pneumocystis jirovecii pneumonia (PJP).
METHODS
VALIDATE-J, a multicenter, cross-sectional, retrospective study, reviewed the administrative claims data and medical records from two Japanese hospitals. Claims-based algorithms were developed by experts to identify HZ, MTB, NTM, and PJP cases among patients treated 2012-2016. Diagnosis was confirmed with three gold standard definitions; positive predictive values (PPVs) were calculated for prevalent (regardless of baseline disease-free period) and incident (preceded by a 12-month disease-free period for the target conditions) cases.
RESULTS
Of patients identified using claims-based algorithms, a random sample of 377 cases was included: HZ (n = 95 [55 incident cases]); MTB (n = 100 [58]); NTM (n = 82 [50]); and PJP (n = 100 [84]). PPVs ranged from 67.4-70.5% (HZ), 67.0-90.0% (MTB), 18.3-63.4% (NTM), and 20.0-45.0% (PJP) for prevalent cases, and 69.1-70.9% (HZ), 58.6-87.9% (MTB), 10.0-56.0% (NTM), and 22.6-51.2% (PJP) for incident cases, across definitions. Adding treatment to the algorithms increased PPVs for HZ, with a small increase observed for prevalent cases of NTM.
CONCLUSIONS
VALIDATE-J demonstrated moderate to high PPVs for disease-identifying algorithms for HZ and MTB using Japanese claims data.
Topics: Humans; Nontuberculous Mycobacteria; Japan; Retrospective Studies; Cross-Sectional Studies; Mycobacterium Infections, Nontuberculous; Communicable Diseases; Herpes Zoster; Immunocompromised Host
PubMed: 37789253
DOI: 10.1186/s12879-023-08466-8 -
British Medical Bulletin Sep 2023Fungal disease has historically presented a diagnostic challenge due to its often non-specific clinical presentations, relative infrequency and reliance on insensitive...
INTRODUCTION
Fungal disease has historically presented a diagnostic challenge due to its often non-specific clinical presentations, relative infrequency and reliance on insensitive and time-intensive fungal culture.
SOURCES OF DATA
We present the recent developments in fungal diagnostics in the fields of serological and molecular diagnosis for the most clinically relevant pathogens; developments that have the potential to revolutionize fungal diagnosis through improvements in speed, simplicity and sensitivity. We have drawn on a body of evidence including recent studies and reviews demonstrating the effectiveness of antigen and antibody detection and polymerase chain reaction (PCR) in patients with and without concurrent human immunodeficiency virus infection.
AREAS OF AGREEMENT
This includes recently developed fungal lateral flow assays, which have a low cost and operator skill requirement that give them great applicability to low-resource settings. Antigen detection for Cryptococcus, Histoplasma and Aspergillus spp. are much more sensitive than culture. PCR for Candida spp., Aspergillus spp., Mucorales and Pneumocystis jirovecii is more sensitive than culture and usually faster.
AREAS OF CONTROVERSY
Effort must be made to utilize recent developments in fungal diagnostics in clinical settings outside of specialist centres and integrate their use into standard medical practice. Given the clinical similarities of the conditions and frequent co-infection, further study is required into the use of serological and molecular fungal tests, particularly in patients being treated for tuberculosis.
GROWING POINTS
Further study is needed to clarify the utility of these tests in low-resource settings confounded by a high prevalence of tuberculosis.
AREAS TIMELY FOR DEVELOPING RESEARCH
The diagnostic utility of these tests may require revision of laboratory work flows, care pathways and clinical and lab coordination, especially for any facility caring for the immunosuppressed, critically ill or those with chronic chest conditions, in whom fungal disease is common and underappreciated.
Topics: Humans; Mycoses; Candida; Polymerase Chain Reaction
PubMed: 37328942
DOI: 10.1093/bmb/ldad011 -
Journal of Fungi (Basel, Switzerland) Aug 2023Very few cases of pneumonia (PJP) have been reported in COVID-19 so far, and mostly in patients with concomitant HIV infection or in solid-organ transplant recipients....
BACKGROUND
Very few cases of pneumonia (PJP) have been reported in COVID-19 so far, and mostly in patients with concomitant HIV infection or in solid-organ transplant recipients. Despite COVID-19 being associated with lymphopenia and the use of steroids, there are no studies specifically aimed at investigating the risk factors for PJP in COVID-19.
METHODS
A retrospective case-control study was performed. We matched PJP cases with controls with a 1:2 ratio, based on age ± 10 years, solid-organ transplantation (SOT), hematological malignancies, and in the setting of PJP development (ICU vs. non-ICU). A direct immunofluorescence assay on bronchoalveolar lavage fluid was used to diagnose PJP.
RESULTS
We enrolled 54 patients. Among 18 cases of PJP, 16 were diagnosed as "proven". Seven of the eighteen cases were immunocompromised, while the other patients had no previous immunological impairment. Patients with PJP had significantly lower median lymphocyte values ( = 0.033), longer COVID-19 duration ( = 0.014), a higher dose of steroid received ( = 0.026), higher CRP values ( = 0.005), and a lower SARS-CoV-2 vaccination rate than the controls ( = 0.029). Cumulative steroid dose is the independent risk factor for PJP development (OR = 1.004, 95%CI = 1-1.008, = 0.042).
CONCLUSIONS
PJP develops in COVID-19 patients regardless of immunosuppressive conditions and the severity of disease, and it is correlated to the corticosteroid dose received.
PubMed: 37623609
DOI: 10.3390/jof9080838 -
Infection & Chemotherapy Sep 2023Late-onset pneumonia (PCP) can be developed in solid organ transplant (SOT) patients. Granulomatous pneumonia (GPCP) can occur in immunocompromised patients, but has... (Review)
Review
Late-onset pneumonia (PCP) can be developed in solid organ transplant (SOT) patients. Granulomatous pneumonia (GPCP) can occur in immunocompromised patients, but has rarely been reported in SOT recipients. The diagnosis of GPCP is difficult since the sensitivity of sputum and bronchoalveolar lavage is low and atypical patterns are shown. A 60-year-old man, who had undergone renal transplantation 24 years ago presented with nodular and patchy lung lesions. He was asymptomatic and stable. After empirical treatment with a fluoroquinolone, the condition partially resolved but relapsed 4 months later. The pulmonary nodule was resected, and GPCP was confirmed. The pathogenesis of GPCP remains unclear, but in SOT recipients presenting with an atypical lung pattern, GPCP should be considered. This case was discussed at the Grand Clinical Ground of the Korean Society of Infectious Disease conference on November 3, 2022.
PubMed: 37794576
DOI: 10.3947/ic.2023.0084 -
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