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BMJ (Clinical Research Ed.) Oct 2019People with immunoreactivity to tuberculosis are thought to have lifelong asymptomatic infection and remain at risk for active tuberculosis. argue that most of these...
People with immunoreactivity to tuberculosis are thought to have lifelong asymptomatic infection and remain at risk for active tuberculosis. argue that most of these people are no longer infected
Topics: AIDS-Related Opportunistic Infections; Antigens, Bacterial; Humans; Immunocompromised Host; Immunosuppression Therapy; Latent Tuberculosis; Mycobacterium tuberculosis; Tissue Transplantation; Tuberculosis; Virus Activation
PubMed: 31649096
DOI: 10.1136/bmj.l5770 -
Seminars in Arthritis and Rheumatism Feb 2023The availability of Janus kinase (JAK) inhibitors has transformed the management of rheumatoid arthritis (RA), helping patients achieve clinical remission. However, the... (Review)
Review
BACKGROUND
The availability of Janus kinase (JAK) inhibitors has transformed the management of rheumatoid arthritis (RA), helping patients achieve clinical remission. However, the emergence of opportunistic infections (OIs) associated with the use of JAK inhibitors has been reported. This structured literature review was conducted to summarize reports of OIs associated with JAK inhibitor treatment for RA in clinical trials.
METHODS
Structured searches were performed in MEDLINE® and Embase® to identify relevant clinical trial data through March 2021. Bibliographic searches of recent reviews were also conducted, and gray literature searches were used to supplement key gap areas. Publications were screened, extracted, and quality assessed. Data were narratively synthesized.
RESULTS
Following screening, 105 publications describing 62 unique clinical trials reporting the rates of OIs in RA patients treated with JAK inhibitors were included. Overall, the highest exposure-adjusted incidence rate was reported for herpes zoster (HZ) infection (any form), followed by OI (any) and tuberculosis based on limited data from clinical trials with approved doses of JAK inhibitors. Lack of head-to-head trials and differences in trial design preclude direct comparison across JAK inhibitors. Higher rates of OIs were noted in the Asian and Australian populations compared with the global population. Higher rates of OIs were also noted with increasing dose of JAK inhibitors in most clinical trial data.
CONCLUSIONS
HZ was the most common OI reported among RA patients using all currently approved JAK inhibitors in clinical trials, although tuberculosis and other OIs were also reported. More long-term safety studies in the real-world setting are needed to compare the risk of OIs between various JAK inhibitors.
Topics: Humans; Arthritis, Rheumatoid; Australia; Herpes Zoster; Janus Kinase Inhibitors; Opportunistic Infections; Tuberculosis; Clinical Trials as Topic
PubMed: 36347212
DOI: 10.1016/j.semarthrit.2022.152120 -
Journal of Molecular Biology Jul 2019Environmental fungi are globally ubiquitous and human exposure is near universal. However, relatively few fungal species are capable of infecting humans, and among... (Review)
Review
Environmental fungi are globally ubiquitous and human exposure is near universal. However, relatively few fungal species are capable of infecting humans, and among fungi, few exposure events lead to severe systemic infections. Systemic infections have mortality rates of up to 90%, cost the US healthcare system $7.2 billion annually, and are typically associated with immunocompromised patients. Despite this reputation, exposure to environmental fungi results in a range of outcomes, from asymptomatic latent infections to severe systemic infection. Here we discuss different exposure outcomes for five major fungal pathogens: Aspergillus, Blastomyces, Coccidioides, Cryptococcus, and Histoplasma species. These fungi include a mold, a budding yeast, and thermal dimorphic fungi. All of these species must adapt to dramatically changing environments over the course of disease. These dynamic environments include the human lung, which is the first exposure site for these organisms. Fungi must defend themselves against host immune cells while germinating and growing, which risks further exposing microbe-associated molecular patterns to the host. We discuss immune evasion strategies during early infection, from disruption of host immune cells to major changes in fungal cell morphology.
Topics: Fungi; Host Microbial Interactions; Humans; Immune Evasion; Mycoses; Opportunistic Infections
PubMed: 31078554
DOI: 10.1016/j.jmb.2019.05.003 -
Microbiology Spectrum Oct 2022Increasing evidence shows that the gut fungal mycobiota is implicated in human disease. However, its relationship with chronic helminth infections, which cause...
Increasing evidence shows that the gut fungal mycobiota is implicated in human disease. However, its relationship with chronic helminth infections, which cause immunosuppression and affect over 1 billion people worldwide, remains unexplored. In this study, we investigated the gut mycobiome and its associations with gut homeostasis in a severe helminth disease worldwide: liver echinococcosis. Fecal samples from 63 patients and 42 healthy controls were collected to characterize the fungal signatures using ITS1 sequencing, QIIME pipeline, and machine learning analysis. The levels of fecal calprotectin and serological anti-Saccharomyces cerevisiae antibodies (ASCA) in these subjects were experimentally measured. We found that fungal microbiota was significantly skewed in disease, with an overrepresentation of Aspergillus, Candida, Geotrichum, Kazachstania, and Penicillium and a decrease of Fusarium. Machine learning analysis revealed that the altered fungal features could efficiently predict infection with high sensitivity and specificity (area under the curve [AUC] = 0.93). The dysbiosis was characterized by expansions of multiple opportunistic pathogens (Aspergillus spp. and Candida spp.). Clinical association analysis revealed that host immunity might link to the expansions of the invasive fungi. Accompanying the opportunistic pathogen expansion, the levels of fungi-associated fecal calprotectin and serological ASCA in the patients were elevated, suggesting that gut inflammation and microbiota translocation occurred in this generally assumed extraintestinal disease. This study highlights enteric fungal pathogen expansions and increased levels of markers for fungi-associated mucosal inflammation and intestinal permeability as hallmarks of liver echinococcosis. Helminth infection affects over 1 billion people worldwide. However, its relationship with the gut mycobiome remains unknown. Among the most prevalent helminth diseases, human hydatid disease (echinococcosis) is highlighted as one of the most important (second/third for alveolar/cystic echinococcosis) foodborne parasitic diseases at the global level. Herein, we investigated the mycobiome and gut homeostasis (i.e., inflammation and permeability) in human echinococcosis. Our results revealed that fungal dysbiosis with an expansion of opportunistic pathogens and increased levels of fecal calprotectin and serum ASCA are hallmarks of human liver echinococcosis. Host immunity is associated with enteric fungal expansions. These findings suggest that an extraintestinal helminth infection is able to alter gut fungal microbiota and impair gut homeostasis, which resembles concomitant gut symptoms in inflammatory gut-related diseases (e.g., AIDS). In clinical practice, physicians need to take cautious medical consideration of gut health for nonintestinal helminth diseases.
Topics: Humans; Candida; Dysbiosis; Echinococcosis; Feces; Fungi; Inflammation; Leukocyte L1 Antigen Complex; Liver; Aspergillus; Opportunistic Infections
PubMed: 36098525
DOI: 10.1128/spectrum.01453-22 -
Current Opinion in Infectious Diseases Aug 2019The current review gives a concise and updated overview of the relative new field of anticytokine autoantibodies (ACAA) and associated infections with a focus on recent... (Review)
Review
PURPOSE OF REVIEW
The current review gives a concise and updated overview of the relative new field of anticytokine autoantibodies (ACAA) and associated infections with a focus on recent findings regarding clinical manifestions, diagnostic and treatments.
RECENT FINDINGS
Several recent case reports of unusual presentations of patients with neutralizing autoantibodies to IFN-γ and granulocyt macrophage colony-stimulating factor and expand the spectrum of clinical manifestations and suggest that anticytokine-mediated acquired immunodeficiency causing susceptibility to infection may be underdiagnosed. There is an expanding geographical distribution of antigranulocyt macrophage colony-stimulating factor associated Cryptococcus gattii infection. The spectrum of identified infections in patients with neutralizing antibodies to IFN-γ has a strong endemic component. Rituximab or cyclophophamide in addition to antimycobacterials could be a treatment options in refractory cases. NF-κB2 deficiency may be associated with a complex pattern of high titre neutralizing ACAA similar to autoimmune polyglandular syndrome type I and Thymoma. New technique for the detection of anticytokine antibodies are presented. Quantiferon testing, which is widely available for TB-diagnostic, may be repurposed to detect anti-IFN-γ autoantibodies. We propose that this test could be as well used to show if they are neutralizing.
SUMMARY
ACAA are an emerging cause of acquired immunodeficiency which is likely underdiagnosed. Recent case reports document expanding spectra of clinical manifestations. NF-κB2 deficiency may be associated with a complex anti cytokine autoantibody pattern.
Topics: Antibodies, Neutralizing; Autoantibodies; Cytokines; Disease Susceptibility; Genetic Predisposition to Disease; Granulocyte Colony-Stimulating Factor; Humans; Infections; Interferon-gamma; Mycobacterium Infections; NF-kappa B; Opportunistic Infections; Severity of Illness Index
PubMed: 31116133
DOI: 10.1097/QCO.0000000000000561 -
BMC Infectious Diseases Dec 2022There is a high prevalence of anemia among people living with HIV in Guangxi, China. Therefore, we investigated anemia and opportunistic infections in hospitalized...
BACKGROUND
There is a high prevalence of anemia among people living with HIV in Guangxi, China. Therefore, we investigated anemia and opportunistic infections in hospitalized people living with HIV and explored the risk factors related to anemia in people living with HIV to actively prevent anemia in people living with HIV.
METHODS
We retrospectively studied people living with HIV admitted to Guangxi Chest Hospital from June 2016 to October 2021. Detailed information on the sociodemographic and clinical features of the participants was collected. The X test was used to compare the prevalence between the anemic and non-anemic groups. The logistic regression analysis was applied to exclude confounding factors and identify factors related to anemia.
RESULTS
Among 5645 patients with HIV, 1525 (27.02%) had anemia. The overall prevalence of mild, moderate, and severe anemia was 4.66%, 14.08%, and 8.27%, respectively. The factors significantly related to increased risk of anemia were CD4 count < 50 cells/µl (aOR = 2.221, 95% CI = [1.775, 2.779]), CD4 count 50-199 cells/µl (aOR = 1.659, 95% CI = [1.327, 2. 073]), female (aOR = 1.644, 95% CI = [1.436, 1.881]) co-infected with HCV (aOR = 1.465, 95% CI = [1.071, 2.002]), PM (aOR = 2.356, 95% CI = [1.950, 2.849]), or TB (aOR = 1.198, 95% CI = [1.053, 1.365]).
CONCLUSIONS
Within Guangxi of China, 27.02% of hospitalized people living with HIV presented with anemia. Most patients with anemia were in the mild to moderate stage. The low CD4 count, female gender, and concomitant infection with Penicillium marneffei, Hepatitis C virus, or Tuberculosis were independent correlates of anemia. Thus, these findings would be helpful to clinicians in preventing and intervening in anemia in people living with HIV.
Topics: Humans; Female; Retrospective Studies; China; Opportunistic Infections; Anemia; HIV Infections
PubMed: 36474196
DOI: 10.1186/s12879-022-07910-5 -
Emerging Infectious Diseases Aug 2022To further clarify differences in the risk for nontuberculous mycobacterial pulmonary infection (NTM-PI) among ethnic populations in Hawaii, USA, we conducted a... (Review)
Review
To further clarify differences in the risk for nontuberculous mycobacterial pulmonary infection (NTM-PI) among ethnic populations in Hawaii, USA, we conducted a retrospective cohort study among beneficiaries of Kaiser Permanente Hawaii (KPH). We abstracted demographic, socioeconomic, clinical, and microbiological data from KPH electronic health records for 2005-2019. An NTM-PI case-patient was defined as a person from whom >1 NTM pulmonary isolate was obtained. We performed Cox proportional hazards regression to estimate incidence of NTM-PI while controlling for confounders. Across ethnic groups, risk for NTM-PI was higher among persons who were underweight (body mass index [BMI] <18.5 kg/m). Among beneficiaries who self-identified as any Asian ethnicity, risk for incident NTM-PI was increased by 30%. Low BMI may increase susceptibility to NTM-PI, and risk may be higher for persons who self-identify as Asian, independent of BMI.
Topics: Ethnicity; Hawaii; Humans; Incidence; Mycobacterium Infections, Nontuberculous; Nontuberculous Mycobacteria; Opportunistic Infections; Retrospective Studies
PubMed: 35876462
DOI: 10.3201/eid2808.212375 -
Gut and Liver Sep 2022Opportunistic infection in inflammatory bowel disease (IBD) has become a serious problem. However, its status of doctors' opinions and test equipment in hospitals are...
BACKGROUND/AIMS
Opportunistic infection in inflammatory bowel disease (IBD) has become a serious problem. However, its status of doctors' opinions and test equipment in hospitals are unclear. The aim of the study was to investigate these issues to improve the prognosis of IBD patients.
METHODS
This retrospective, multicenter study was conducted by 83 investigators who were members of the Asian Organization for Crohn's and Colitis. Data on opportunistic infection were collected from hospital databases between January 2017 and December 2017. The survey consisted of 11 items.
RESULTS
Most physicians appreciated the diagnostic value of tissue cytomegalovirus (CMV) DNA, accounting for 86.1% of members in China, 37.5% in Japan, 52.9% in South Korea, and 66.7% in Southeast Asia. Only 83.1% of hospitals had the ability to test for CMV immunohistochemistry in Asia. Hepatitis B surface antigen (HBsAg) screening was recommended by all members. However, only 66.7% in China, 70.6% in South Korea, and 66.7% in Southeast Asia agreed to routinely vaccinate IBD patients when HBsAg tested negative. Most members preferred metronidazole (74.7%) as the first choice for patients with infection. However, the proportion of stool toxin test was lower in China than in other areas (75.0% in China vs 95.8% in Japan and 100% in South Korea and Southeast Asia, p<0.05).
CONCLUSIONS
Opportunistic infection from CMV, hepatitis B virus, and should be of high concern for IBD patients. More efforts are needed, such as understanding consensus in clinical practice and improving testing facilities in hospitals.
Topics: Asia; Clostridioides difficile; Cytomegalovirus Infections; Hepatitis B Surface Antigens; Humans; Inflammatory Bowel Diseases; Opportunistic Infections; Retrospective Studies; Surveys and Questionnaires
PubMed: 35611664
DOI: 10.5009/gnl210217 -
Sarcoidosis, Vasculitis, and Diffuse... 2020Sarcoidosis is a systemic inflammatory disease characterized by granuloma formation in affected organs and caused by dysregulated immune response to an unknown antigen.... (Review)
Review
Sarcoidosis is a systemic inflammatory disease characterized by granuloma formation in affected organs and caused by dysregulated immune response to an unknown antigen. Sarcoidosis patients receiving immunosuppressive medications are at increased risk of infection. Lymphopenia is also commonly seen among patient with sarcoidosis. In this review, risk of infections, including opportunistic infections, will be outlined. Recommendations for vaccinations and prophylactic therapy based on literature review will also be summarized. .
Topics: Host-Pathogen Interactions; Humans; Immunization Schedule; Immunocompromised Host; Immunosuppressive Agents; Opportunistic Infections; Risk Factors; Sarcoidosis; Treatment Outcome; Vaccination
PubMed: 33093774
DOI: 10.36141/svdld.v37i2.9599 -
Der Internist May 2022Infections are an important warning sign for a weakened immune system. In the internal medical practice acquired (secondary), particularly drug-induced... (Review)
Review
Infections are an important warning sign for a weakened immune system. In the internal medical practice acquired (secondary), particularly drug-induced immunodeficiencies, are much more frequent than congenital (primary) immunodeficiencies. The management starts as early as the planning phase before initiation of immunosuppression. The risk of infection should be individually stratified and protective vaccinations should be completed. Depending on the immunosuppressive treatment, there can be a necessity for preventive treatment, e.g. for latent tuberculosis infection or hepatitis B. The serological results on varicella zoster virus and JC polyomavirus must also be considered. The basic immunological diagnostics include differential blood count and the determination of immunoglobulins (IgG, IgA, IgM) prior to and during immunosuppressive treatment. Relevant conspicuous laboratory results before initiation of treatment should prompt advanced immunological work-up for the identification of primary immunodeficiencies, which are often accompanied by clinical signs of immune dysregulation. Depending on the type of pathogen, localization, frequency and duration as well as the severity of the infection, prophylactic antibiotic treatment may be required. Patients with chronic severe lymphocytopenia, in particular with CD4 positive T (helper) cells < 200/µl, are at increased risk for opportunistic infections so that an antibiotic prophylaxis is recommended. In patients with significantly increased proneness to infections and detection of a relevant quantitative (IgG < 4 g/l) and/or qualitative antibody deficiency (impaired vaccine response), additional immunoglobulin replacement therapy may be necessary and can be administered intravenously (IVIG) or subcutaneously (SCIG) as home treatment. In accordance with the localization of the infection, multidisciplinary clarification and management is warranted.
Topics: Humans; Immunization, Passive; Immunoglobulin G; Immunologic Deficiency Syndromes; Opportunistic Infections; Vaccination
PubMed: 35412057
DOI: 10.1007/s00108-022-01326-8