Non-human Immunodeficiency Virus-infected Patients Research Articles

Clinical features of pneumocystis pneumonia in non-human immunodeficiency virus-infected patients: A systemic review and meta-analysis

Objectives: Pneumocystis pneumonia (PCP) is an opportunistic disease that causes potentially fatal pneumonia in immunocompromised individuals. The clinical features of PCP without HIV remain incompletely understood. Methods: This study aimed to identify the clinical features of PCP without HIV in a systematic review following a meta-analysis. Results: 65 articles that included 10,133 PCP patients without HIV infection were enrolled. PCP occurred most commonly at age 59.2 years (95%CI: 57.7, 60.7) in a gender ratio of approximately 3 to 2 (males to females). Dyspnea, fever, cough, and sputum were nonspecific clinical findings in 73% (95%CI: 69, 79), 73% (95%CI: 65, 81), 56% (95%CI: 48%, 64%), and 32% (96%CI: 16, 48) of patients, respectively. Viral, bacterial, and fungal co-infection were observed in 28% (95%CI: 13, 44), 19% (95%CI: 13, 25), and 11% (95%CI: 6, 16) of patients, respectively. Laboratory data showed a trend of elevated WBC, LDH, CRP, β-D glucan, and KL-6. Ground glass opacity (GGO) was found in 87% (95%CI: 83, 91) of patients. In-hospital mortality was 41% (95%CI: 35, 46). Conclusions: PCP is a life-threatening disease in immune-compromised patients. Despite being a nonspecific clinical finding, GGO might offer a clue to diagnosing PCP in high-risk patients.

Antifungal susceptibility profiles of Cryptococcus neoformans strains clinically isolated from non-HIV-infected patients in Nagasaki, Japan.

Data on antifungal susceptibility of Cryptococcus neoformans are limited in Japan. A total of 89 C. neoformans strains isolated from 83 non-human immunodeficiency virus-infected patients with cryptococcosis between 1997 and 2021 in Nagasaki, Japan, were investigated. Using the reference method M27-Ed4 by the Clinical and Laboratory Standards Institute, the minimum inhibitory concentration for 90% of isolates of fluconazole, itraconazole, voriconazole, amphotericin B, and flucytosine were 4, 0.125, 0.06, 0.5, and 4µg/ml, respectively, which were below the reported epidemiological cutoff values, without any detectable non-wild-type strains. Our findings imply no increasing trend of antifungal-resistant C. neoformans in Nagasaki, Japan.

Treatment of Pneumocystis jirovecii pneumonia in non-human immunodeficiency virus-infected patients using a combination of trimethoprim-sulfamethoxazole and caspofungin.

BACKGROUND Pneumocystis jirovecii pneumonia (PJP) is an infectious disease common in immunocompromised hosts. However, the currently, the clinical characteristics of non-HIV patients with PJP infection have not been fully elucidated.AIMTo explore efficacy of trimethoprim–sulfamethoxazole (TMP-SMX) and caspofungin for treatment of non-human immunodeficiency virus (HIV)-infected PJP patients.METHODSA retrospective study enrolled 22 patients with non-HIV-infected PJP treated with TMP-SMX and caspofungin from 2019 to 2021. Clinical manifestations, treatment and prognosis of the patients were analyzed. RESULTSFive patients presented with comorbidity of autoimmune diseases, seven with lung cancer, four with lymphoma, two with organ transplantation and four with membranous nephropathy associated with use of immunosuppressive agents. The main clinical manifestations of patients were fever, dry cough, and progressive dyspnea. All patients presented with acute onset and respiratory failure. The most common imaging manifestation was ground glass opacity around the hilar, mainly in the upper lobe. All patients were diagnosed using next-generation sequencing, and were treated with a combination of TMP-SMX and caspofungin. Among them, 17 patients received short-term adjuvant glucocorticoid therapy. All patients recovered well and were discharged from hospital.CONCLUSIONNon-HIV-infected PJP have rapid disease progression, high risk of respiratory failure, and high mortality. Combination of TMP-SMX and caspofungin can effectively treat severe non-HIV-infected PJP patients with respiratory failure.

Metagenomic Next-Generation Sequencing for the Diagnosis of Pneumocystis jirovecii Pneumonia in Non-HIV-Infected Patients: A Retrospective Study.

IntroductionThis study aimed to evaluate the utility of metagenomic next-generation sequencing (mNGS) for the diagnosis of Pneumocystis jirovecii pneumonia (PJP) in non-human immunodeficiency virus-infected patients.MethodsWe conducted a retrospective study. A total of 60 non-human immunodeficiency virus-infected PJP patients and 134 patients diagnosed with non-PJP pneumonia were included. P. jirovecii and other co-pathogens identified by mNGS in bronchoalveolar lavage fluid and/or blood samples were analyzed. Using clinical composite diagnosis as the reference standard, we compared the diagnostic performance of mNGS in PJP with conventional methods, including Gomori methenamine silver staining and serum (1,3)-β-d-glucan. Modifications of antimicrobial treatment for PJP patients after the report of mNGS results were also reviewed.ResultsmNGS reached a sensitivity of 100% in diagnosing PJP, which was remarkably higher than Gomori methenamine silver staining (25.0%) and serum (1,3)-β-d-glucan (67.4%). The specificity of mNGS (96.3%) significantly surpassed serum (1,3)-β-d-glucan (81.4%). Simultaneous mNGS of bronchoalveolar lavage fluid and blood samples was performed in 21 out of 60 PJP patients, and it showed a concordance rate of 100% in detecting P. jirovecii. Besides, mNGS showed good performance in identifying co-pathogens of PJP patients, among which cytomegalovirus and Epstein-Barr virus were most commonly seen. Initial antimicrobial treatment was modified in 71.7% of PJP patients after the report of mNGS results.ConclusionmNGS is a useful diagnostic tool with good performance for the diagnosis of PJP and the detection of co-pathogens. mNGS of bronchoalveolar lavage fluid and/or blood samples is suggested in patients with presumptive diagnosis of PJP. Blood samples may be a good alternative to bronchoalveolar lavage fluid for mNGS when bronchoscopic examination is not feasible.

Comparison of pleural effusion features and biomarkers between talaromycosis and tuberculosis in non-human immunodeficiency virus-infected patients

BackgroundDue to the similar clinical, lung imaging, and pathological characteristics, talaromycosis is most commonly misdiagnosed as tuberculosis. This study aimed to identify the characteristics of talaromycosis pleural effusion (TMPE) and to distinguish TMPE from tuberculosis pleural effusion (TPE).MethodsWe enrolled 19 cases each of TMPE and TPE from Guangxi, China. Patients’ clinical records, pleural effusion tests, biomarker test results, and receiver operating characteristic curves were analyzed.ResultsIn total, 39.8% (65/163) of patients exhibited serous effusion, of whom 61 were non-human immunodeficiency virus (HIV)-infected patients; 68.85% of the non-HIV-infected patients (42/61) had TMPE. Thoracentesis was performed only in 19 patients, all of whom were misdiagnosed with tuberculosis and received long-term anti-tuberculosis treatment. In four of these patients, interleukin (IL)-23, IL-27, and interferon-gamma (IFN-γ) measurements were not performed since pleural effusion samples could not be collected because the effusion had been drained prior to the study. In the remaining 15 patients, pleural effusion samples were collected. Talaromyces marneffei was isolated from the pleural effusion and pleural nodules. Most TMPEs were characterized by yellowish fluid, with marked elevation of protein content and nucleated cell counts. However, neutrophils were predominantly found in TMPEs, and lymphocytes were predominantly found in TPEs (both p < 0.05). Adenosine deaminase (ADA) and IFN-γ levels in TMPEs were significantly lower than those in TPEs (all p < 0.05) and provided similar accuracies for distinguishing TMPEs from TPEs. IL-23 concentration in TMPEs was significantly higher than that in TPEs (p < 0.05), and it provided similar accuracy for diagnosing TMPEs. IL-27 concentrations in TMPEs were significantly lower than those in TPEs (all p < 0.05) but was not useful for distinguishing TMPE from TPE.ConclusionsTalaromycosis can infringe on the pleural cavity via the translocation of T. marneffei into the pleural space. Nonetheless, this phenomenon is still commonly neglected by clinicians. TMPE is a yellowish fluid with exudative PEs and predominant neutrophils. Higher neutrophil counts and IL-23 may suggest talaromycosis. Higher lymphocyte counts, ADA activity, and IFN-γ concentration may suggest tuberculosis.

Low-dose trimethoprim-sulfamethoxazole treatment for pneumocystis pneumonia in non-human immunodeficiency virus-infected immunocompromised patients: A single-center retrospective observational cohort study

The efficacy of low-dose trimethoprim-sulfamethoxazole (TMP-SMX) may be acceptable for the treatment of pneumocystis pneumonia (PCP) in non-human immunodeficiency virus (HIV)-infected patients, with a low incidence of adverse reactions. This study is aimed to evaluate the efficacy and safety of such a regimen for the treatment of non-HIV PCP. We retrospectively enrolled 24 consecutive patients diagnosed with non-HIV PCP who were treated with low-dose TMP-SMX (TMP, 4-10mg/kg/day; SMX, 20-50mg/kg/day). Data of the conventional-dose treatment were used as reference. The primary endpoints were the 30- and 180-day survival rates from the day of treatment, and secondary endpoints were the incidence of each adverse reaction and dropout rate from the initial TMP-SMX regimen. The survival rate was estimated using the Kaplan-Meier method with 95% confidence interval (CI). The median age of patients was 72 years (54.2% men), and connective tissue disease was the most frequent underlying disease (66.7%) in the low-dose group. The 30- and 180-day survival rates were 95.8% (95% CI: 88.2-100.0%) and 91.0% (95% CI: 79.9%-100.0%), respectively, in the low-dose group and 69.0% (95% CI: 54.0%-88.0%) and 51.5% (95% CI: 36.1%-73.4%), respectively, in the conventional-dose group. The total adverse reaction rate was 58.3% in the low-dose group and 72.4% in the conventional-dose group. A total of 75.0% of patients in the low-dose group and 31.0% in the conventional-dose group completed treatment with the initial regimen. Low-dose TMP-SMX may be a treatment option for patients with non-HIV PCP.

Late paradoxical lymph node enlargement during and after anti-tuberculosis treatment in non-HIV-infected patients.

A tertiary referral centre in South Korea. To investigate the incidence, clinical characteristics and outcomes of late paradoxical response (>4 months after the initiation of anti-tuberculosis treatment) during and after anti-tuberculosis treatment in non-human immunodeficiency virus (HIV) infected patients with lymph node tuberculosis (TB). We retrospectively reviewed the medical records of non-HIV-infected patients with lymph node TB between 1997 and 2007, and prospectively enrolled patients with newly diagnosed lymph node TB between 2008 and 2013. Of 467 patients with confirmed and probable lymph node TB, 83 (18%) displayed a paradoxical response: 57 of these (69%) were classified as early and 26 (31%) as late paradoxical response. Patients with late paradoxical response (median 12 months) received more prolonged anti-tuberculosis treatment than those with early (median 9 months, P < 0.001) or no paradoxical response (median 9 months, P < 0.001). The frequency of post-treatment lymph node enlargement increased progressively from those without any paradoxical response (6%), through those with an early response (12%) to those with a late response (23%). Paradoxical response presents late in about one third of non-HIV-infected patients with lymph node TB who experience a response. Although anti-tuberculosis treatment is commonly prolonged in patients with late paradoxical response, post-treatment lymph node enlargement is more frequent in these patients.

Acquired immunodeficiency syndrome‐related lymphoma

Highly active antiretroviral therapy (HAART) has improved the survival of patients with acquired immunodeficiency syndrome-related lymphoma (ARL). The German ARL Study Group investigated whether HAART administered concomitantly with cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) chemotherapy compromised the course of immune parameters during and after chemotherapy and exerted a positive effect on remission and survival. From 1997 to 2001, 72 patients with ARL were stratified prospectively into a standard-risk group (n = 48 patients) and a high-risk group (n = 24 patients) with either 0-1 or 2-3 of the following risk factors: CD4 < 50/microL, prior opportunistic infection, and/or a World Health Organization performance status > or = 3. Patients in the high-risk group received > or =75% of the CHOP regimen. In the standard-risk group (CD4 = 223/muL; age-adjusted International Prognostic Index [aaIPI], 38% > or = 2), the complete remission (CR) rate was 79%, and median survival was not reached after a median 47 months of follow-up. CD4 counts did not change from baseline to 4 weeks after the end of chemotherapy (206/microL). In the high-risk group (CD4 = 34/muL; aaIPI, 88% > or = 2), the CR rate was 29%, and the median survival was 7.2 months (3 patients survived for > 3 yrs). Toxicity was moderate: Leukopenia Grade 3 or 4 occurred in 100 of 249 chemotherapy cycles (40%) in the standard-risk group and in 70 of 102 cycles (69%) in the high-risk group. Based on the aaIPI, the survival of patients in the standard-risk group was very similar to that achieved by nonhuman immunodeficiency virus-infected patients who had aggressive lymphomas. Concurrent CHOP plus HAART can be administered in an outpatient setting. Thus, the authors recommend using this modality as first-line therapy for patients with ARL.

Isolation and molecular identification of Candida dubliniensis from non-human immunodeficiency virus-infected patients in Kuwait.

Candida dubliniensis is an emerging pathogen capable of causing oropharyngeal, vaginal and bloodstream infections. Although C. dubliniensis is similar to Candida albicans in several phenotypic characteristics, it differs from it with respect to epidemiology, certain virulence factors and the ability to develop resistance to fluconazole rapidly. In this study, the first seven isolations of C. dubliniensis from Kuwait are described, all originating from non-human immunodeficiency virus (HIV)-infected patients. The isolates were initially identified by the Vitek 2 yeast identification system, positive germ tube test, production of rough colonies and chlamydospores on Staib agar and by their inability to assimilate xylose, trehalose or methyl alpha-D-glucoside. The species identity of the isolates was subsequently confirmed by specific amplification of rDNA targeting the internally transcribed spacer 2 (ITS2), restriction endonuclease digestion of the amplified DNA and direct DNA sequencing of the ITS2. Using the E-test method, the MICs of C. dubliniensis test isolates were in the range 0.125-0.75 microg ml(-1) for fluconazole, 0.002-0.75 microg ml(-1) for itraconazole, 0.006-0.125 microg ml(-1) for ketoconazole, 0.002-0.5 microg ml(-1) for amphotericin B and 0.002-0.016 microg ml(-1) for voriconazole. Two of the isolates were resistant to 5-flucytosine (>32 microg ml(-1)), but none against fluconazole. The study reinforces the current view that C. dubliniensis has a much wider geographical and epidemiological distribution.

Kaposi sarcoma-associated herpes-like virus (human herpesvirus type 8) DNA sequences in multicentric Castleman's disease: is there any relevant association in non-human immunodeficiency virus-infected patients? [letter; comment

Kaposi sarcoma-associated herpes-like virus (human herpesvirus type 8) DNA sequences in multicentric Castleman's disease: is there any relevant association in non-human immunodeficiency virus-infected patients? [letter; comment

Kaposi Sarcoma-Associated Herpes-Like Virus (Human Herpesvirus Type 8) DNA Sequences in Multicentric Castieman's Disease: Is There Any Relevant Association In Non-Human Immunodeficiency Virus-Infected Patients?

Kaposi Sarcoma-Associated Herpes-Like Virus (Human Herpesvirus Type 8) DNA Sequences in Multicentric Castieman's Disease: Is There Any Relevant Association In Non-Human Immunodeficiency Virus-Infected Patients?

Torulopsis glabrata: azole susceptibilities by microdilution colorimetric and macrodilution broth assays

Fluconazole and itraconazole MICs were determined by both the standard macrodilution method of the National Committee for Clinical Laboratory Standards and a colorimetric broth microdilution method for 140 isolates of Torulopsis (Candida) glabrata obtained over a 15-year period. Using the method of the National Committee for Clinical Laboratory Standards the MICs at which 90% of isolates are inhibited (MIC50) for all isolates were 32 and 1.6 micrograms/ml for fluconazole and itraconazole, respectively. For fluconazole, the MIC90 rose from 16 to > 64 micrograms/ml when the MIC90s for isolates collected from July 1980 to June 1991 were compared with those for isolates collected from July 1991 to March 1995. For itraconazole, the MIC90s for isolates from the same time periods were 0.8 and 3.2 micrograms/ml, respectively. Although for isolates from some non-human immunodeficiency virus-infected patients the MICs rose, most of the high MICs were found for isolates from human immunodeficiency virus-infected patients who had been extensively treated with azole drugs for thrush. The colorimetric method yielded endpoints that were more definitive; concordances within 2 dilutions for the two methods were 87% for fluconazole and 86% for itraconazole.