non-HIV Immunosuppressed Patients Research Articles

The impact of immunosuppression on the mortality and hospitalization of Monkeypox: a systematic review and meta-analysis of the 2022 outbreak

BackgroundLimited data is available regarding the severity and mortality of Mpox in individuals with immunocompromised conditions. Therefore, we performed this meta-analysis to understand the impact of HIV- or non-HIV-associated immunosuppression on the severity of Mpox requiring hospitalization and mortality.MethodsA thorough literature search was performed from 2022 up to January 2024. The results were presented as odds ratios (ORs). We only included patients who required hospitalization for severity rather than isolation.ResultsA total of 34 studies were included in this analysis. Our analysis did not find a significant difference in the hospitalization risk between HIV-positive individuals and those who were HIV-negative (OR = 1.03; P = 0.85; 7 studies; CD4 count of fewer than 200 cells/µL was less than 0.5% across all studies). Patients with a CD4 count lower than 200 cells/µL or an unsuppressed RNA viral load (> 200 copies/ml) had a significantly higher hospitalization risk (OR = 5.3, P < 0.001) and (OR = 3, P < 0.001), respectively. Most of the reported deaths were reported in patients with HIV with CD4 counts below 200 cells/µL, with some fatal cases occurring in non-HIV immunosuppressed patients, particularly organ transplant recipients. Based on the autopsy findings, Mpox was confirmed in multiple organs, particularly the digestive tract, lung, and testes. Furthermore, some studies documented cases of death that were suspected to be related to hemophagocytic lymphohistiocytosis (HLH) and immune reconstitution inflammatory syndrome (IRIS). Most of the death reports showed concomitant non-Mpox infections at the time of hospitalization and deathConclusionsOur finding shows that Mpox acts as an opportunistic pathogen in immunocompromised individuals. These individuals should be prioritized for early care and closely monitored for signs of deteriorating clinical conditions. Clinical manifestations and autopsy findings strongly suggest Mpox dissemination to multiple organs, particularly the digestive tract, and lungs. However, the presence of concomitant non-Mpox infections complicates the assessment of the attribution of Mpox to death. Caution should be exercised when interpreting data suggesting poorer outcomes in individuals with non-HIV immunosuppression, as current evidence is scarce and further research is needed.

P171 Pneumocystis Jirovecii Pneumonia in non-HIV immunosuppressed patients: Acase series

Poster session 2, September 22, 2022, 12:30 PM - 1:30 PMObjectiveIncreased usage of immunosuppressive medications and lack of guidance about when to initiate primary Pneumocystis Jirovecii Pneumonia (PCP) prophylaxis has led to a rising incidence of PCP in non-HIV immunosuppressed patients. The objective of this case series is to review clinical challenges in diagnosis and management of these patients.Patients, methods, and resultsThis is a retrospective case series of all 6 cases which were seen at Jupiter Hospital from January 2020 to October 2021 (Table 1).ConclusionThe presence of the above-mentioned predisposing factors should raise the suspicion of PCP. Non-invasive investigations like serum LDH, BDG, PET CT scan/HRCT scan of chest can help in the diagnosis. This can be confirmed by BAL PCR, which is both, more sensitive and specific than immunofluorescence microscopy. Trimethoprim- sulfamethoxazole (TMP- SMX), the standard treatment, cannot be used in some circumstances and alternate treatment may have to be used.Guidance about prophylaxis, antimicrobial therapy for PCP, and adjuvant steroid therapy in non-HIV patients is unavailable, which is an unmet clinical need.

Diagnostic Value of Bronchoalveolar Lavage Fluid Metagenomic Next-Generation Sequencing in Pneumocystis jirovecii Pneumonia in Non-HIV Immunosuppressed Patients.

IntroductionThis study aims to assess the value of metagenomic next-generation sequencing (mNGS) of bronchoalveolar lavage fluid (BALF) in the diagnosis of Pneumocystis jirovecii pneumonia (PJP) and its mixed infection in non-human immunodeficiency virus (HIV) immunosuppressed patients.MethodsA total of 198 non-HIV immunosuppressed patients with severe pneumonia were enrolled, including 77 PJP patients and 121 patients infected by other pathogens. BALF-mNGS and traditional detection methods were used.ResultsThe positive detection rate of various pathogens of BALF-mNGS was higher than that of the conventional methods, especially for mixed pathogens. The sensitivity and specificity of BALF-mNGS for the diagnosis of PJP were 97.40% and 85.12%, respectively. Compared with traditional methods, the sensitivity of BALF-mNGS was significantly higher than that of blood fungal G (BG)/lactate dehydrogenase (LDH) and BALF-microscopy (p<0.05), and its specificity was significantly higher than that of BG/LDH (p<0.05). In addition, the average detection time of BALF-mNGS (32.76 ± 10.32 h) was also significantly shorter than conventional methods (p<0.01), especially for mixed infections that were common in non-HIV immunosuppressed patients. In patients only detected as positive by BALF-mNGS, the underlying diseases mainly manifested as hematological malignancies with agranulocytosis and within 8 months after hematopoietic stem cell or solid organ transplantation.ConclusionsBALF-mNGS technology is faster, more sensitive, and more comprehensive in detecting P. jirovecii and its mixed infection in immunosuppressed patients.

A rare but increasing aetiology of febrile dyspnea in the elderly

Pneumocystis jirovecii pneumonia (PJP) is an opportunistic infectious disease well described in patients living with HIV (PLHIV) but that can occur in other immunosuppressed patients. Currently, its incidence decreases in PLHIV but increases in non-HIV immunosuppressed patients, particularly in case of hematological diseases. Thus, in elderly, the diagnosis of PJP should be evoked in case of subacute pneumonia rapidly evolving to an acute respiratory distress, with or without interstitial pneumonia at chest radiography, and a context of immunosuppression.

Forty years of Tuberculous meningitis: The new face of an old enemy

BackgroundTuberculous meningitis (TBM) occurs in 1–5% of cases of tuberculosis. Without early treatment, mortality and permanent disability rates are high. MethodsA retrospective study performed at a tertiary hospital in Madrid (Spain) to describe clinical, diagnostic, and therapeutic aspects of TBM and analyze epidemiological trends over forty years, divided into two intervals (1979−1998 and 1999−2018). ResultsOverall, TBM was diagnosed in 65 patients (1.8% of new tuberculosis diagnoses), 48 in the first period and 17 in the second one. Median age at diagnosis increased from 38.5 to 77 years (p = 0.003). The proportion of non-HIV immunosuppressed patients increased (from 2.1% to 29.4%, p < 0.001), while the percentage of patients with a history of drug-abuse decreased (from 33.3% to 5.9%, p = 0.027). The median time between the onset of neurological symptoms and lumbar puncture increased from seven to 15 days (p = 0.040). The time between the onset of symptoms and the initiation of tuberculostatic treatment also increased from eleven to 18 days (p = 0.555). Results from image, biochemical, and microbiological tests showed no differences between both periods. A decreasing trend was observed in survival rates at 1-week (from 97.9% to 64.7%, p < 0.001), 1-month (from 91.7% to 58.8%, p = 0.002) and 1-year (from 85.4% to 47.1%, p = 0.002) after TBM diagnosis. ConclusionsThe profile of patients diagnosed with TBM has changed from a young HIV-infected patient with a history of drug addiction to an elderly patient with non-HIV immunosuppression. Diagnosis and start of treatment both experienced a noticeable delay in the second period, which could help explain the increase in mortality observed across the two periods.

Management of Cytomegalovirus Retinitis in HIV and Non-HIV Patients.

As CMVR continues to affect HIV-positive and non-HIV immunosuppressed patients, ophthalmologists must continue to tailor diagnostics and therapeutics to individual cases. In HIV-related disease, ocular fluid sampling and intravitreal drug delivery are considerations, but systemic antiviral therapy is paramount in the initial management from both ophthalmic and systemic morbidity standpoints. Non-HIV-related disease should be approached with a multidisciplinary team, including an ophthalmologist/vitreoretinal/uveitis specialist for consideration of intravitreal antiviral therapy with qualitative and quantitative aqueous PCR monitoring, and consideration of PCR genome sequencing for CMV strains that may become resistant to antiviral therapies from long-term antiviral prophylactic exposure. Hematologists or oncologists may help with patients who remain bone marrow-suppressed following transplantation or systemic chemotherapy. Because of related toxicities of the anti-CMV medications and immunosuppressive medications (eg, bone marrow suppression and cytopenias), infectious disease consultation can help in the treatment and monitoring of side effects.

Elucidating a role for eosinophils and discovering novel vaccine targets in Pneumocystis pneumonia using transcriptomics (MPF6P.651)

Abstract Pneumocystis (PC) pneumonia remains the most common serious opportunistic infection in patients with HIV/AIDS and is re-emerging in non-HIV infected immunosuppressed patients. Clearance of PC occurs through CD4+ T-cells with antibodies acting as one documented mechanism of clearance, although protective antibody epitopes have yet to be elucidated. To address the role of CD4+ T-cells, we used transcriptomics in mice over the course of PC infection and we observed a strong eosinophil signature in CD4-replete animals by RNA sequencing and by BAL analysis. Hypereosinophilic CD4-depleted mice receiving pIL5 via hydrodynamic injection had increased eosinophils in the lung and decreased PC burden. Finally, mice deficient in eosinophilopoiesis, had no change in burden with pIL5 treatment following CD4-depletion, further implicating eosinophils as novel mediators of immunity against PC. To identify protective antibody epitopes as potential vaccine candidates, we used a life-cycle based approach and sequenced RNA from the ascus and troph life forms of PC and found GSC-1 (ascus) and Meu10 (troph) were differentially regulated. Both GSC-1 and Meu10 generate strong humoral immune responses. Meu10 peptide vaccination decreases PC burden in CD4+ T-cell depleted animals, while immunization with recombinant GSC-1 failed to provide complete protection in a challenge model. Future studies will evaluate a multivalent life-cycle based vaccine in both a PC challenge model and a co-housing model.

Mycobacterium genavense Infections in a Tertiary Hospital and Reviewed Cases in Non-HIV Patients

Mycobacterium genavense is a relatively new species of nontuberculous mycobacterium reported to cause disseminated infections in patients with AIDS and later on in non-HIV immunosuppressed patients. We describe clinical and laboratory features and response to therapy in 7 patients, three of them with HIV infection and four non-HIV—three organ transplant recipients and one with hyper-IgE syndrome—in Valencia, Spain, in a ten years period. We then summarize the published cases of M. avium complex infection, with invasion of peripheral blood, liver, spleen, bone marrow, lymph nodes, and lungs. In clinical samples a large number of acid-fast bacilli were observed. M. genavense grew only from liquid media and after a prolonged incubation period. Its identification was accomplished through molecular methods. Patients were treated with prolonged combinations of antimicrobial agents. There was clinical favourable outcome in 4 patients.

Cerebral microsporidiosis manifesting as progressive multifocal leukoencephalopathy in an HIV-infected individual - a case report.

Microsporidia have become increasingly recognized as opportunistic pathogens since the genesis of the AIDS epidemic. The incidence of microsporidiosis has decreased with the advent of combination antiretroviral therapy but it is frequently reported in non-HIV immunosuppressed patients and as a latent infection in immunocompetent individuals. Herein, we describe an HIV-infected male (46 years) with suspected progressive multifocal leukoencephalopathy that has not responded to optimal antiretroviral therapy, steroids, or cidofovir. Post-mortem examination revealed cerebral microsporidiosis. No diagnostic clue however, was found when the patient was alive. This report underscores the need for physicians to consider microsporidiosis (potentially affecting the brain) when no other etiology is established both in HIV, non-HIV immunosuppressed patients and in immunocompetent individuals.

Cryptococcal infection in non-HIV immunosuppressed patients – Three case reports in a nephrology setting

Cryptococcal infection has been increasing among immunosuppressed population. We report three cases of Cryptococcus neoformans infection in immunosuppressed patients – two renal transplanted and one with lupus nephritis. Early infection (<3months) was diagnosed in two – an allograft Cryptococcus infection and a central nervous system involvement. The third, a 10-year transplant vintage patient, presented with cryptococcal meningitis. Amphotericin B provided good clinical outcomes. We outline the importance of suspicion for cryptococcal infection in immunosuppressed patients.

Successful Treatment of Severe Pneumocystis Pneumonia with Clindamycin-Primaquine in an HIV-Negative Patient

Pneumocystis pneumonia is an increasingly recognized threat in non-HIV immunosuppressed patients and is associated with worse outcomes compared to HIV-infected patients. The preferred first line treatment is trimethoprim-sulfamethoxazole; however, second line treatments for those intolerant of this regimen have been primarily studied in patients with acquired immunodeficiency syndrome (AIDS). We report a case of Pneumocystis pneumonia in a 75-year-old man with chronic lymphocytic leukemia (CLL) and a history of sulfa allergy successfully treated with clindamycin-primaquine.

Initial CT manifestations of invasive pulmonary aspergillosis in 45 non-HIV immunocompromised patients: association with patient outcome?

Purpose: To assess early high-resolution computer tomographic (CT) signs of invasive pulmonary aspergillosis (IPA) in non-HIV immunosuppressed patients and their potential association with patient's outcome, including frequency and severity of pulmonary hemorrhage, taking also in consideration the impact of other known risk factors contributory to IPA. Material and methods: A retrospective review of serial CT scans was performed in 45 immunocompromised patients with a total of 46 episodes of invasive pulmonary aspergillosis. All patients underwent CT beginning with the day they showed clinical or laboratory signs of infection. Serial follow-up CT included more than two, up to 12 CT examinations. Patient's outcome was judged by clinical and radiological follow-up and classified as survival, death by IPA, or death unrelated to IPA. The influence of patient's age, underlying disease, hematopoietic stem cell transplantation, neutropenia, graft versus host disease, and antifungal therapy onset was also statistically considered. Results: Three main CT findings were identified: small nodules (<1 cm) 43% (20/46), large nodules 21% (10/46) and consolidations, either in patchy ± segmental 26% (12/46), or peribronchial distribution ± tree in bud 9% (4/46). In 11 patients (24%) we found a combination of two or more of these signs: 9 (19%) patients presented concurrent small nodules accompanied by reticulation, tree in bud or peribronchial infiltrates, while 2 (4%) patients showed large pulmonary nodules accompanied by large consolidations. An accompanying “halo” sign was observed in 38 patients (82%). Crescent sign followed by cavitation was encountered in 29 patients (63%). Two patients succumbed to massive pulmonary bleeding caused by IPA. Twenty-one patients (15/46) deceased in this series, 12 of them succumbed to IPA, 1 died from cerebral invasive aspergillosis, while in 9 patients the cause of death was not primarily IPA. Manifest pulmonary hemorrhage occurred in 19% (9/46) of IPA episodes. Conclusion: Initial CT findings of invasive pulmonary aspergillosis consist mainly of small nodules or patchy consolidations, showing in 82% of cases an early halo sign. Serious pulmonary hemorrhage was an infrequent clinical complication in our series, with an attributable mortality of 4.3%. IPA-related lethality was 26%, in our cohort. None of the early HRCT signs seemed to predict outcome.

The unmasking of Pneumocystis jiroveci pneumonia during reversal of immunosuppression: case reports and literature review

BackgroundPneumocystis jiroveci pneumonia (PCP) is an important opportunistic infection among immunosuppressed patients, especially in those infected with human immunodeficiency virus (HIV). The clinical presentation of PCP in immunosuppressed patients have been well-reported in the literature. However, the clinical importance of PCP manifesting in the setting of an immunorestitution disease (IRD), defined as an acute symptomatic or paradoxical deterioration of a (presumably) preexisting infection, which is temporally related to the recovery of the immune system and is due to immunopathological damage associated with the reversal of immunosuppressive processes, has received relatively little attention until recently.Case presentationWe aim to better define this unique clinical syndrome by reporting two cases of PCP manifesting acutely with respiratory failure during reversal of immunosuppression in non-HIV infected patients, and reviewed the relevant literature. We searched our databases for PCP cases manifesting in the context of IRD according to our predefined case definition, and reviewed the case notes retrospectively. A comprehensive search was performed using the Medline database of the National Library of Medicine for similar cases reported previously in the English literature in October 2003. A total of 28 non-HIV (excluding our present case) and 13 HIV-positive patients with PCP manifesting as immunorestitution disease (IRD) have been reported previously in the literature. During immunorestitution, a consistent rise in the median CD4 lymphocyte count (28/μL to 125/μL), with a concomitant fall in the median HIV viral load (5.5 log10 copies/ml to 3.1 log10 copies/ml) was observed in HIV-positive patients who developed PCP. A similar upsurge in peripheral lymphocyte count was observed in our patients preceding the development of PCP, as well as in other non-HIV immunosuppressed patients reported in the literature.ConclusionsPCP manifesting as IRD may be more common than is generally appreciated. Serial monitoring of total lymphocyte or CD4 count could serve as a useful adjunct to facilitate the early diagnosis and pre-emptive treatment of this condition in a wide range of immunosuppressed hosts, especially in the presence of new pulmonary symptoms and/or radiographic abnormalities compatible with the diagnosis.

Utility of testing bronchoalveolar lavage fluid for cryptococcal ribosomal DNA.

Bronchoalveolar lavage (BAL) specimens from 88 patients (33 infected with human immunodeficiency virus [HIV], 45 non-HIV immunosuppressed patients and 10 immunocompetent patients with primary pulmonary disease) were analysed for the presence of Cryptococcus neoformans. Staining, culture and an antigen testing were performed, and C. neoformans ribosomal DNA (rDNA) detected using the polymerase chain reaction (PCR). C. neoformans was detected, by staining and culture, in BAL specimens from two HIV-infected patients with pulmonary cryptococcosis, and the antigen test and rDNA assay were also positive in these samples. C. neoformans rDNA was detected by PCR in a non-HIV immunocompromised patient with Pneumocystis pneumonia, whose staining, culture and antigen tests were negative. The antigen test was positive for an immunocompetent patient with sarcoidosis, while staining, culture and the PCR assay were negative. These results do not support routine testing of BAL specimens for C. neoformans rDNA.