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Cureus Apr 2024Hypercalcemia in human immunodeficiency virus (HIV) patients can be challenging due to various underlying mechanisms. 1,25- dihydroxycholecalciferol (1,25 (OH)2 vitamin...
Hypercalcemia in human immunodeficiency virus (HIV) patients can be challenging due to various underlying mechanisms. 1,25- dihydroxycholecalciferol (1,25 (OH)2 vitamin D)-mediated hypercalcemia due to increased activity of extrarenal 1-alpha hydroxylase is one of the well-known mechanisms of hypercalcemia described in HIV patients. (MAI) is a granulomatous disease that can cause hypercalcemia due to ectopic production of alpha -1 hydroxylase and result in increased levels of 1,25 (OH)2 vitamin D. Herein, we present a case of "late-onset" hypercalcemia in a patient with HIV/AIDS and MAI infection in the setting of suspected immune reconstitution inflammatory syndrome (IRIS). The hypercalcemia workup showed an inappropriately average level of 1,25 (OH)2 vitamin D while the rest of the workup was unrevealing. Unusually normal levels of vitamin D metabolites were the driving mechanism of hypercalcemia in this case. The late presentation of hypercalcemia was likely due to IRIS unmasking an underlying granulomatous infection, and this consideration led to the successful treatment of the patient with steroid administration. This case emphasizes the importance of considering IRIS in evaluating hypercalcemia that presents late in the course of granulomatous infections in HIV patients.
PubMed: 38715997
DOI: 10.7759/cureus.57773 -
The Pediatric Infectious Disease Journal May 2024Hematopoietic stem cell transplant recipients are prone to infectious complications. Infections caused by nontuberculous mycobacteria have increased in adults but...
Severe Impairment of T-cell Immunity and Pulmonary GvHD Are Major Risk Factors for Nontuberculous Mycobacterial Infection After Pediatric Allogeneic Hematopoietic Stem Cell Transplantation.
Hematopoietic stem cell transplant recipients are prone to infectious complications. Infections caused by nontuberculous mycobacteria have increased in adults but literature in children is scarce. We report 6 episodes of disseminated or pulmonary nontuberculous mycobacteria infection among 5 pediatric hematopoietic stem cell transplant recipients. All but one were caused by Mycobacterium avium complex. Four patients died, 2 related to nontuberculous mycobacteria infection.
PubMed: 38713829
DOI: 10.1097/INF.0000000000004380 -
Frontiers in Immunology 2024complex (MAC) is a non-tuberculous mycobacterium widely distributed in the environment. Even though MAC infection is increasing in older women and immunocompromised...
complex (MAC) is a non-tuberculous mycobacterium widely distributed in the environment. Even though MAC infection is increasing in older women and immunocompromised patients, to our knowledge there has been no comprehensive analysis of the MAC-infected host-cell transcriptome-and particularly of long non-coding RNAs (lncRNAs). By using cultured primary mouse bone-marrow-derived macrophages (BMDMs) and Cap analysis of gene expression, we analyzed the transcriptional and kinetic landscape of macrophage genes, with a focus on lncRNAs, during MAC infection. MAC infection of macrophages induced the expression of immune/inflammatory response genes and other genes similar to those involved in M1 macrophage activation, consistent with previous reports, although (M1 activation) and (M2 activation) had distinct expression profiles. We identified 31 upregulated and 30 downregulated lncRNA promoters corresponding respectively to 18 and 26 lncRNAs. Upregulated lncRNAs were clustered into two groups-early and late upregulated-predicted to be associated with immune activation and the immune response to infection, respectively. Furthermore, an Ingenuity Pathway Analysis revealed canonical pathways and upstream transcription regulators associated with differentially expressed lncRNAs. Several differentially expressed lncRNAs reported elsewhere underwent expressional changes upon M1 or M2 preactivation and subsequent MAC infection. Finally, we showed that expressional change of lncRNAs in MAC-infected BMDMs was mediated by toll-like receptor 2, although there may be other mechanisms that sense MAC infection. We identified differentially expressed lncRNAs in MAC-infected BMDMs, revealing diverse features that imply the distinct roles of these lncRNAs in MAC infection and macrophage polarization.
Topics: RNA, Long Noncoding; Animals; Macrophages; Mycobacterium avium Complex; Mice; Gene Expression Profiling; Mycobacterium avium-intracellulare Infection; Transcriptome; Macrophage Activation; Mice, Inbred C57BL; Cells, Cultured; Gene Expression Regulation
PubMed: 38711507
DOI: 10.3389/fimmu.2024.1374437 -
Scientific Reports May 2024Mammals are generally resistant to Mycobacterium avium complex (MAC) infections. We report here on a primary immunodeficiency disorder causing increased susceptibility...
Mammals are generally resistant to Mycobacterium avium complex (MAC) infections. We report here on a primary immunodeficiency disorder causing increased susceptibility to MAC infections in a canine breed. Adult Miniature Schnauzers developing progressive systemic MAC infections were related to a common founder, and pedigree analysis was consistent with an autosomal recessive trait. A genome-wide association study and homozygosity mapping using 8 infected, 9 non-infected relatives, and 160 control Miniature Schnauzers detected an associated region on chromosome 9. Whole genome sequencing of 2 MAC-infected dogs identified a codon deletion in the CARD9 gene (c.493_495del; p.Lys165del). Genotyping of Miniature Schnauzers revealed the presence of this mutant CARD9 allele worldwide, and all tested MAC-infected dogs were homozygous mutants. Peripheral blood mononuclear cells from a dog homozygous for the CARD9 variant exhibited a dysfunctional CARD9 protein with impaired TNF-α production upon stimulation with the fungal polysaccharide β-glucan that activates the CARD9-coupled C-type lectin receptor, Dectin-1. While CARD9-deficient knockout mice are susceptible to experimental challenges by fungi and mycobacteria, Miniature Schnauzer dogs with systemic MAC susceptibility represent the first spontaneous animal model of CARD9 deficiency, which will help to further elucidate host defense mechanisms against mycobacteria and fungi and assess potential therapies for animals and humans.
Topics: Animals; CARD Signaling Adaptor Proteins; Dogs; Genetic Predisposition to Disease; Mycobacterium avium-intracellulare Infection; Mycobacterium avium Complex; Genome-Wide Association Study; Dog Diseases; Sequence Deletion; Pedigree; Female; Male; Whole Genome Sequencing; Homozygote; Lectins, C-Type
PubMed: 38710903
DOI: 10.1038/s41598-024-61054-x -
Heliyon May 2024The healthcare burden of nontuberculous mycobacterial pulmonary disease (NTM-PD) is increasing, but the diagnosis remains challenging and sometimes requires considerable...
BACKGROUND
The healthcare burden of nontuberculous mycobacterial pulmonary disease (NTM-PD) is increasing, but the diagnosis remains challenging and sometimes requires considerable time. This nested case-control study aims to clarify the time to diagnosis of NTM-PD, the factors that affect diagnosis and diagnostic delay, and changes in CT findings before diagnosis.
PATIENTS AND METHODS
We retrospectively analyzed 187 patients suspected of having NTM-PD based on computed tomography (CT) findings at our institution between January 2019 and September 2020. We investigated the time to diagnosis of NTM-PD for all suspected and diagnosed patients. Multivariate analyses identified the factors affecting diagnosis and diagnostic delay over 6 months. We also evaluated longitudinal changes in CT findings during the observation period using CT scoring system.
RESULTS
The median times to diagnosis of NTM-PD were 71.8 months in all suspected patients and 3.2 months in only the diagnosed patients. Multivariable analysis showed that severity of the cavity domain of the CT score and -glycopeptidolipid (GPL)-core immunoglobulin A (IgA) antibody positivity were significantly associated with establishing the diagnosis. A low CT score in the cavity domain was a risk factor for delayed diagnosis. In patients with delayed diagnosis, the total CT score was less severe than that in the early diagnosis patients at their first visits; however, it had deteriorated prior to the diagnosis.
CONCLUSION
The diagnosis of NTM-PD sometimes required several years, and the absence or mild cavitation predicted a diagnostic delay. Of concern, a delay in diagnosis can result in a delay in treatment.
PubMed: 38707468
DOI: 10.1016/j.heliyon.2024.e30060 -
The European Respiratory Journal May 2024https://bit.ly/3PUGvbV
https://bit.ly/3PUGvbV
Topics: Humans; Mycobacterium avium-intracellulare Infection; Rifampin; Mycobacterium avium Complex; Anti-Bacterial Agents; Lung Diseases; Treatment Outcome
PubMed: 38697635
DOI: 10.1183/13993003.02210-2023 -
QJM : Monthly Journal of the... May 2024
PubMed: 38696764
DOI: 10.1093/qjmed/hcae091 -
Rhode Island Medical Journal (2013) May 2024We report a rare case of mycobacterial periprosthetic joint infection (PJI) after primary total knee arthroplasty 14 years earlier. Progressive knee pain over three...
CASE
We report a rare case of mycobacterial periprosthetic joint infection (PJI) after primary total knee arthroplasty 14 years earlier. Progressive knee pain over three years with a negative PJI infectious workup led to revision total knee arthroplasty. A surprising result was isolation of Mycobacterium avium from tissue cultures taken at time of revision surgery. After six months of antibiotic treatment, the patient is alive with well- functioning pain-free TKA at over one-year follow-up.
CONCLUSION
Periprosthetic joint infection can present acutely or chronically years following total knee arthroplasty. Depending on the infecting organism, patients can present with sepsis, or a more indolent slower course that mimics aseptic loosening. In the absence of positive pre-operative labs and cultures, and based on the Musculoskeletal Infection Society (MSIS) criteria, aseptic loosening is a diagnosis of exclusion. An atypical infectious organism should be considered a possible cause and may require specialized cultures of operative specimens.
Topics: Aged; Female; Humans; Male; Anti-Bacterial Agents; Arthroplasty, Replacement, Knee; Mycobacterium avium; Mycobacterium avium-intracellulare Infection; Prosthesis-Related Infections; Reoperation
PubMed: 38687260
DOI: No ID Found -
Microbiology Spectrum Jun 2024The latest guidelines include azithromycin as a preferred regimen for treating complex (MAC) pulmonary disease. However, serially collected susceptibility data on...
The latest guidelines include azithromycin as a preferred regimen for treating complex (MAC) pulmonary disease. However, serially collected susceptibility data on clinical MAC isolates are limited, and no breakpoints have been determined. We investigated the minimum inhibitory concentrations (MICs) of azithromycin and clarithromycin for all MAC strains isolated in 2021 from a single center in Japan, excluding duplicates. The MICs were determined using a panel based on the microbroth dilution method, according to the latest Clinical and Laboratory Standards Institute recommendations. The MICs were determined for 318 MAC strains. Although there was a significant positive correlation between the MICs of azithromycin and clarithromycin, the MICs of azithromycin tended to be higher than those of clarithromycin. Among the cases in which the strains were isolated, 18 patients initiated treatment, including azithromycin treatment, after sample collection. Some patients infected with stains with relatively high azithromycin MICs achieved a microbiological cure with azithromycin-containing regimens. This study revealed a higher MIC distribution for azithromycin than clarithromycin, raising questions about the current practice of estimating azithromycin susceptibility based on the clarithromycin susceptibility test result. However, this was a single-center study that included only a limited number of cases treated with azithromycin. Therefore, further multicenter studies that include a greater number of cases treated with azithromycin are warranted to verify the distribution of azithromycin MICs and examine the correlation between azithromycin MICs and treatment effectiveness.IMPORTANCEThe macrolides serve as key drugs in the treatment of pulmonary complex infection, and the administration of macrolide should be guided by susceptibility test results. Azithromycin is recommended as a preferred choice among macrolides, surpassing clarithromycin; however, drug susceptibility testing is often not conducted, and clarithromycin susceptibility is used as a surrogate. This study represents the first investigation into the minimum inhibitory concentration of azithromycin on a scale of several hundred clinical isolates, revealing an overall tendency for higher minimum inhibitory concentrations compared with clarithromycin. The results raise questions about the appropriateness of using clarithromycin susceptibility test outcomes for determining the administration of azithromycin. This study highlights the need for future discussions on the clinical breakpoints of azithromycin, based on large-scale clinical research correlating azithromycin susceptibility with treatment outcomes.
Topics: Azithromycin; Humans; Microbial Sensitivity Tests; Japan; Mycobacterium avium Complex; Clarithromycin; Anti-Bacterial Agents; Mycobacterium avium-intracellulare Infection; Female; Male; Aged; Middle Aged; Aged, 80 and over; Adult
PubMed: 38687080
DOI: 10.1128/spectrum.00218-24 -
Journal of Applied Microbiology May 2024This study aimed to identify specific genomic targets for the detection and strain typing of Map and analyse their sensitivity and specificity, and detect Map directly...
AIMS
This study aimed to identify specific genomic targets for the detection and strain typing of Map and analyse their sensitivity and specificity, and detect Map directly from faeces.
METHODS AND RESULTS
A comparative genomics approach was used to identify specific genomic targets for the detection and strain typing of Map. A Map specific qPCR using the primer pair 7132 that targets a DNA segregation ATPase protein was able to detect all strains of Map and is more sensitive than the current Johne's disease PCR assays with a sensitivity of 0.0002 fg µl-1. A strain specific qPCR using the Atsa primer pair that targets the arylsulfase gene was able to differentiate between Type S and Type C strains of Map and was more sensitive than the IS1311 PCR and REA with a sensitivity of 40 fg µl-1 and was specific for Type S Map. Both assays successfully detected Map directly from faeces.
CONCLUSION
This study developed and validated two genomics informed qPCR assays, 7132B Map and Atsa Type S and found both assays to be highly specific and sensitive for the detection of Map from culture and directly from faeces. This is the first time that a probe-based qPCR has been designed and developed for Map strain typing, which will greatly improve the response time during outbreak investigations.
Topics: Real-Time Polymerase Chain Reaction; Mycobacterium avium subsp. paratuberculosis; Feces; Animals; Genomics; Paratuberculosis; Sensitivity and Specificity; Cattle; DNA, Bacterial; Cattle Diseases; DNA Primers
PubMed: 38684472
DOI: 10.1093/jambio/lxae107