Mycobacterial Infection Research Articles

Non-Mycobacteria Tuberculosis in Africa: A Literature Review.

Non-tuberculous mycobacteria (NTM) have been reported to cause pulmonary and extrapulmonary infections. These NTMs are often misdiagnosed as MTB due to their similar clinical presentations to tuberculosis, leading to inappropriate treatment and increased morbidity and mortality rates. This literature review aims to provide an overview of the prevalence, clinical manifestations, diagnosis, and management of NTM infections in Africa. A systematic search was performed using various electronic databases including PubMed, Scopus, and Web of Science. The search was limited to studies published in the English language from 2000 to 2021. The following keywords were used: "non-tuberculous mycobacteria", "NTM", "Africa", and "prevalence". Studies that focused solely on the Mycobacterium tuberculosis complex or those that did not report prevalence rates were excluded. Data extraction was performed on eligible studies. Overall, a total of 32 studies met the inclusion criteria and were included in this review. In our literature review, we identified a total of 32 studies that reported non-tuberculosis mycobacteria (NTM) in Africa. The majority of these studies were conducted in South Africa, followed by Ethiopia and Nigeria. The most commonly isolated NTM species were Mycobacterium avium complex (MAC), Mycobacterium fortuitum, and Mycobacterium abscessus. Many of the studies reported a high prevalence of NTM infections among HIV-positive individuals. Other risk factors for NTM infection included advanced age, chronic lung disease, and previous tuberculosis infection. In conclusion, this literature review highlights the significant burden of non-tuberculosis mycobacteria infections in Africa. The prevalence of these infections is high, and they are often misdiagnosed due to their similarity to tuberculosis. The lack of awareness and diagnostic tools for non-tuberculosis mycobacteria infections in Africa is a major concern that needs to be addressed urgently. It is crucial to improve laboratory capacity and develop appropriate diagnostic algorithms for these infections.

Divergent proinflammatory immune responses associated with the differential susceptibility of cattle breeds to tuberculosis.

Tuberculosis (TB) in the bovine is one of the most predominant chronic debilitating infectious diseases primarily caused by Mycobacterium bovis. Besides, the incidence of TB in humans due to M. bovis, and that in bovines (bovine TB, bTB) due to M. tuberculosis- indicates cattle as a major reservoir of zoonotic TB. While India accounts for the highest global burden of both TB and multidrug-resistant TB in humans, systematic evaluation of bTB prevalence in India is largely lacking. Recent reports emphasized markedly greater bTB prevalence in exotic and crossbred cattle compared to indigenous cattle breeds that represent more than one-third of the total cattle population in India, which is the largest globally. This study aimed at elucidating the immune responses underlying the differential bTB incidence in prominent indigenous (Sahiwal), and crossbred (Sahiwal x Holstein Friesian) cattle reared in India. Employing the standard Single Intradermal Tuberculin Test (SITT), and mycobacterial gene-targeting single as well as multiplex-PCR-based screening revealed higher incidences of bovine tuberculin reactors as well as Mycobacterium tuberculosis Complex specific PCR positivity amongst the crossbred cattle. Further, ex vivo mycobacterial infection in cultures of bovine peripheral blood mononuclear cells (PBMC) from SITT, and myco-PCR negative healthy cattle exhibited significantly higher intracellular growth of M. bovis BCG, and M. tuberculosis H37Ra in the crossbred cattle PBMCs compared to native cattle. In addition, native cattle PBMCs induced higher pro-inflammatory cytokines and signaling pathways, such as interferon-gamma (IFN-γ), interleukin-17 (IL-17), tank binding kinase-1 (TBK-1), and nitric oxide (NO) upon exposure to live mycobacterial infection in comparison to PBMCs from crossbred cattle that exhibited higher expression of IL-1β transcripts. Together, these findings highlight that differences in the innate immune responses of these cattle breeds might be contributing to the differential susceptibility to bTB infection, and the resultant disparity in bTB incidence amongst indigenous, and crossbred cattle.

Comparative Proteomic Analysis of Exosomes Derived from Patients Infected with Non-Tuberculous Mycobacterium and Mycobacterium tuberculosis.

The non-tuberculous mycobacterium (NTM) is a very troublesome opportunistic pathogen, placing a heavy burden on public health. The pathogenesis of NTM pulmonary infection is not well-revealed yet, and its diagnosis is always challenging. This study aimed to use a comprehensive proteomics analysis of plasma exosomes to distinguish patients with rapidly growing NTM M. abscessus (MAB), slowly growing NTM M. intracellulare (MAC), and Mycobacterium tuberculosis (MTB). The identified protein components were quantified with label-free proteomics and determined with a bioinformatics analysis. The complement and coagulation were significantly enriched in patients with Mycobacterium infection, and a total of 24 proteins were observed with up-regulation, which included C1R, C1S, C2, MASP2, C4B, C8B, C9, etc. Of them, 18 proteins were significantly up-regulated in patients with MAB, while 6 and 10 were up-regulated in patients with MAC or MTB, respectively. Moreover, MAB infection was also related to the HIF-1 signaling pathway and phagosome processes, and MTB infection was associated with the p53 signaling pathway. This study provided a comprehensive description of the exosome proteome in the plasma of patients infected with MAB, MAC, and MTB and revealed potential diagnostic and differential diagnostic markers.

Lung infection with nontuberculous mycobacteria

ObjectiveTo describe the epidemiology and CT findings for nontuberculous mycobacterial lung infections and outcomes depending on the treatment. Material and methodsWe retrospectively studied 131 consecutive patients with positive cultures for nontuberculous mycobacteria between 2005 and 2016. We selected those who met the criteria for nontuberculous mycobacterial lung infection. We analysed the epidemiologic data; clinical, microbiological, and radiological findings; treatment; and outcome according to treatment. ResultsWe included 34 patients (mean age, 55 y; 67.6% men); 50% were immunodepressed (58.8% of these were HIV+), 20.6% had COPD, 5.9% had known tumors, 5.9% had cystic fibrosis, and 29.4% had no comorbidities. We found that 20.6% had a history of tuberculosis and 20.6% were also infected with other microorganisms. Mycobacterium avium complex was the most frequently isolated germ (52.9%); 7 (20.6%) were also infected with other organisms. The most common CT findings were nodules (64.7%), tree-in-bud pattern (61.8%), centrilobular nodules (44.1 %), consolidations (41.2%), bronchiectasis (35.3%), and cavities (32.4%). We compared findings between men and women and between immunodepressed and immunocompetent patients. Treatment was antituberculosis drugs in 67.6% of patients (72% of whom showed improvement) and conventional antibiotics in 20.6% (all of whom showed radiologic improvement). ConclusionThe diagnosis of nontuberculous mycobacterial lung infections is complex. The clinical and radiologic findings are nonspecific and a significant percentage of pateints can have other, concomitant infections.

The performance of interferon gamma release assays in patients with nontuberculous mycobacterial infection: a systematic review and meta-analysis.

The actual positive rate of interferon gamma release assays (IGRAs) in patients with nontuberculous mycobacteria (NTM) infections remains unclear. This review and meta-analysis present the prevalence of positive IGRAs (T-SPOT.TB and QuantiFERON [QFT] tests) among patients infected with NTM isolates (with or without ESAT-6/CFP-10). Several databases, including PubMed, Scopus, Embase, and Web of Science were searched (until June 18th, 2022). Studies that had the following data were included: (1) results of T-SPOT.TB, QuantiFERON (QFT) test, or both, (2) NTM species, and (3) NTM diseases, or NTM colonization. The metaprop command that incorporates a Freeman-Tukey double arcsine transformation is used for pooling proportions. A total of 11 articles (n = 929) were deemed eligible for inclusion. Meta-analysis identified that the overall pooled positive and indeterminate rates of IGRA results in patients with NTM infections was 16% and 5%, respectively. Subgroup analysis showed that the positive rate of IGRAs in patients infected with NTM (without ESAT-6/CFP-10) was 7% (95% CI, 1%-18%), and 44% (95%CI, 22%-68%) in patients infected with NTM (with ESAT-6/CFP-10). In addition, the indeterminate rate of QFT (7%, 95% CI: 4%-12%) was higher than that of T-SPOT.TB (0%; 95% CI, 0%-2%) among the overall population with NTM infections. The IGRAs have a moderate positive rate for the diagnosis of NTM (expressing ESAT-6/CFP-10) infections, and a significant indeterminate rate is observed among the overall population infected with NTM. However, these findings should be interpreted with caution because of the high heterogeneity among studies.

Current management of cervicofacial nontuberculous mycobacterial infections in the pediatric population.

The purpose of this review is to analyze and consolidate recently published literature to provide updated guidelines on the diagnosis and management of nontuberculous mycobacterial lymphadenitis (NTM LAD) in the pediatric population and to suggest areas of further research. Diagnosis of NTM LAD relies on a detailed clinical history, physical examination, laboratory tests, and imaging techniques. Treatment strategies vary widely, with a shift towards complete surgical excision being observed due to its higher cure rate, improved aesthetic outcomes, and lower recurrence rates. However, patient-specific factors must be considered. The role of genetic factors, such as Mendelian susceptibility to mycobacterial disease (MSMD), is being increasingly recognized and could lead to targeted therapies. Despite strides in the understanding and management of NTM LAD, substantial gaps remain in key areas such as the role of diagnostic imaging, optimal treatment parameters, postoperative care, and surveillance strategies. In this article, we explain our approach to NTM using the most relevant evidence-based medicine while offering directions for future work.

Zinc excess impairs Mycobacterium bovis growth through triggering a Zur-IdeR-iron homeostasis signal pathway.

Zinc excess is toxic to bacteria and, thus, represents an important innate defense mechanism of host cells, especially against mycobacterial infections. However, the signaling pathway triggered by zinc excess and its relationship with iron homeostasis remain poorly understood in mycobacteria. Here, we characterize a novel Zur-IdeR-iron homeostasis signaling pathway that modulates the growth of Mycobacterium bovis under zinc toxicity. We found that the regulator Zur interacts with the iron-homeostasis regulator IdeR, enhancing the DNA-binding ability of IdeR. Excess zinc disrupts this interaction and represses ideR transcription through Zur, which promotes the expression of iron uptake genes and leads to the accumulation of intracellular iron in M. bovis. The elevated iron levels lower the bacterial survival ability under excess zinc stress. Consistently, deleting zur hinders intracellular iron accumulation of M. bovis and enhances bacterial growth under stress, while silencing ideR impairs the growth of the wild-type and zur-deleted strains under the same conditions. Interestingly, both Zur and IdeR are conserved in bacteria facing zinc toxicity. Overall, our work uncovers a novel antimicrobial signal pathway whereby zinc excess disrupts iron homeostasis, which may deepen our understanding of the crosstalk mechanism between iron and zinc homeostasis in bacteria.IMPORTANCEAs a catalytic and structural cofactor of proteins, zinc is essential for almost all living organisms. However, zinc excess is toxic and represents a vital innate immunity strategy of macrophages to combat intracellular pathogens, especially against mycobacterial pathogens such as Mycobacterium tuberculosis, the causative agent of tuberculosis. Here, we first characterize an antibacterial signaling pathway of zinc excess and its relationship with iron homeostasis in M. bovis. We found that excess zinc inhibits the transcription of ideR and its DNA-binding activity through Zur, which, in turn, promotes the expression of iron uptake genes, causes intracellular iron accumulation, and finally impairs the bacterial growth. This study reveals the existence of the Zur-IdeR-iron homeostasis pathway triggered by zinc excess in M. bovis, which will shed light on the crosstalk mechanisms between zinc and iron homeostasis in bacteria and the antimicrobial mechanisms of host-mediated zinc toxicity.

Acute carpal tunnel syndrome secondary to MAC infection with rice bodies: a case report

The authors describe a case of mycobacterial hand infection presenting as acute carpal median nerve compression requiring surgical intervention with rice bodies found intraoperatively.

What do the clinical features of positive nontuberculous mycobacteria isolates from patients with HIV/AIDS in China reveal? A systematic review and meta-analysis.

China has a high burden of nontuberculous mycobacterial (NTM) infections. Immunocompromised populations, such as those with human immunodeficiency virus/acquired immunodeficiency syndrome (HIV/AIDS), are at a higher risk of being infected with NTM than immunocompetent individuals. Yet, there is a paucity of information on the clinical features of positive NTM isolates from patients with HIV/AIDS in China. To address this gap, we conducted a systematic review and meta-analysis of existing studies, comparing them against current expert consensus to provide guidance for clinical practice. Two researchers independently searched eight databases (SinoMed, China National Knowledge Infrastructure, Wanfang, VIP, Cochrane Library, PubMed, Embase, and Web of Science) from inception to 26 December 2022 to retrieve published Chinese- and English-language studies reporting clinical features of NTM-positive isolates among patients with HIV/AIDS in China. We included 28 studies with 1861 patients. The rate of positive NTM isolates detected from men among all patients was 87.3%. NTM species distribution was mainly Mycobacterium avium complex (64.3%), which was predominant in different regions. The five most common clinical symptoms were fever (68.5%), cough or expectoration (67.0%), appetite loss (49.4%), weight loss (45.5%), and superficial lymphadenectasis (41.1%). The prevalence of laboratory tests were as follows: albumin <35 g/L (55.6%), erythrocyte sedimentation rate >20 mm/h (91.4%), anaemia (59.0%), predominantly mild, CD4+ T cell count ≤50 pieces/μL (70.3%), and CD4+ T cell count 51-200 pieces/μL (22.1%). Lesion manifestations in thoracic imaging mainly included bilateral lung involvement (83.8%), showed stripe shadows (60.3%), patchy shadows (42.9%), nodules (40.6%), and bronchiectasis (38.6%). Accompanied signs included thoracic lymph node enlargement (49.5%). Seventy per cent of symptoms improved after treatment. Focusing on clinical symptoms, laboratory tests, and thoracic imaging helps with initial screening for NTM infections. Physicians should raise awareness of the diagnosis and treatment of Mycobacterium avium complex, providing guidance for experimental treatment, screening of priority populations for NTM infections, and prophylactic treatment of NTM disease. PROSPERO CRD42023388185.

Impact of Allergic Disease on the Risk of Mycobacterial Disease.

The association between allergic diseases andthe risk of mycobacterial disease is unclear. To evaluate the association between allergic diseases and mycobacterial diseases. This was a population-based cohort study of 3,838,680 individuals, without prior mycobacterial disease, who participated in the 2009 National Health Screening Exam. We evaluated the incidence of mycobacterial disease (tuberculosis or nontuberculous mycobacterial infection) in participants with allergic disease (asthma, allergic rhinitis, or atopic dermatitis) and those without allergic disease. We followed the cohort up until the date of mycobacterial disease diagnosis, follow-up loss, death, or December2018. During a median follow-up of 8.3 (interquartile range, 8.1-8.6) years, 0.6% of participants developed mycobacterial disease. The incidence of mycobacterial disease was significantly higher in those with allergic diseases than in those without allergic diseases (1.0 vs 0.7/1000 person-years; P<.001), with an adjusted hazard ratio of 1.13 (95% CI, 1.10-1.17). Asthma (adjusted hazard ratio, 1.37; 95% CI, 1.29-1.45) and allergic rhinitis (adjusted hazard ratio, 1.07; 95% CI, 1.04-1.11) increased the hazard of mycobacterial disease, whereas atopic dermatitis did not. The association between allergic diseases and hazard of mycobacterial disease was more prominent in older (age ≥ 65 years, P for interaction= .012) and obese (body mass index ≥ 25 kg/m2, P for interaction <.001) participants. Allergic diseases including asthma and allergic rhinitis were associated with an increased risk of mycobacterial disease, whereas atopic dermatitis was not.

Bronchiectasis

Bronchiectasis is a final common pathway of a wide variety of underlying conditions including infectious, autoimmune, allergic, genetic and inflammatory conditions. Patients experience a chronic disease with variable clinical symptoms and course, but most experience cough, sputum production and recurrent exacerbations. Symptoms of bronchiectasis lead to poor quality of life and exacerbations are the major driver of morbidity and mortality. Patients are often chronically infected with bacteria with the most common being Pseudomonas aeruginosa and Haemophilus influenzae. Treatment of bronchiectasis includes standardised testing to identify the underlying cause with targeted treatment if immune deficiency, allergic bronchopulmonary aspergillosis or non-tuberculous mycobacterial infection, for example, are identified. Airway clearance is the mainstay of therapy for patients with symptoms of cough and sputum production. Frequently exacerbating patients may benefit from long term antibiotic or mucoactive therapies. Bronchiectasis is a heterogeneous disease and increasingly precision medicine approaches are advocated to target treatments most appropriately and to limit the emergence of antimicrobial resistance.

Metagenomic next-generation sequencing assistance in identifying non-tuberculous mycobacterial infections.

The advent of metagenomics next-generation sequencing (mNGS) has garnered attention as a novel method for detecting pathogenic infections, including Non-Tuberculous Mycobacterial (NTM) and tuberculosis (TB).However, the robustness and specificity of mNGS in NTM diagnostics have not been fully explored. In this retrospective study, we enrolled 27 patients with NTM genomic sequences via mNGS and conducted a comprehensive clinical evaluation. Pulmonary NTM disease was the most commonly observed presentation, with a subset of patients also presenting with extrapulmonary NTM infections.mNGS analysis identified six distinct NTM species, primarily Mycobacteriumavium complex (MAC), followed by Mycobacterium intracellulare andMycobacterium abscessus. Conventional routine culture methods encountered challenges, resulting in negative results for all available 22 samples. Among the 10 patients who underwent quantitative polymerase chain reaction (qPCR) testing, five tested positive for NTM. It is important to note that further species typing is necessary to determine the specific NTM type, as traditional pathogen detection methods serve as an initial step. In contrast, when supplemented with pathogen data, enables the identification of specific species, facilitating precise treatment decisions. In conclusion, mNGS demonstrates significant potential in aidingthe diagnosis of NTMdisease by rapidly detecting NTM pathogens and guiding treatment strategies. Its enhanced performance, faster turnaround time (TAT), and species identification capabilities make mNGS a promising tool for managing NTM infections.

Dipeptidyl peptidase IV inhibitors and the risk of mycobacterial pulmonary infections in type 2 diabetes mellitus

BackgroundType 2 diabetes mellitus (DM) is a risk factor for mycobacterial pulmonary infections (MPI), including tuberculosis (TB) and nontuberculous mycobacterial lung disease (NTM-LD). Dipeptidyl peptidase IV inhibitor (DPP4i), a common DM medication, has an immune-modulation effect that raises concerns about developing MPI. However, there is scarce research on the topic. MethodsThis retrospective study was conducted in a tertiary-referral center in Taiwan from 2009 to 2016. Patients with type 2 DM who were receiving any DM medication were enrolled. TB and NTM-LD were defined by microbiological criteria. We analyzed the risk of MPI in DPP4i users using Cox proportional hazard regression with adjusted inverse probability of treatment weighting. ResultsA total of 9963 patients were included. Among them, 3931 were classified as DPP4i users, and 6032 patients were DPP4i nonusers. DPP4i users had no increase in incidences of MPI (604 vs. 768 per 100,000 person-years, p = 0.776), NTM-LD (174 vs. 255 per 100,000 person-years, p = 0.228), and TB (542 vs. 449 per 100,000 person-years, p = 0.663) relative to those of DPP4i nonusers. After adjustment, the adjusted hazard ratios for MPI (aHR: 1.07, 95% CI: 0.79–1.45), TB (aHR: 1.15, 95% CI: 0.81–1.64) and NTM-LD (aHR: 0.85, 95% CI: 0.49–1.47) were not significantly increased relative to those of nonusers. The subgroup analysis also showed that DPP4i use did not increase the risk of MPI in different DM severities and comorbidities. ConclusionsAccording to our large cohort study, DPP4i use is safe for patients with type 2 DM and might not increase the risk of MPI.

Expression, Purification, and Crystallization of the Vγ9Vδ2 T-cell Receptor Recognizing Protein/Peptide Antigens.

γδ T cells, especially Vγ9Vδ2 T cells, play an important role in mycobacterial infection. We have identified some Vγ9Vδ2 T cells that recognize protein/peptide antigens derived from mycobacteria, which may induce protective immune responses to mycobacterial infection. To clarify the structural basis of the molecular recognition mechanism, we tried many methods to express the Vγ9Vδ2 T-cell receptor (TCR). The Vγ9Vδ2 TCR was not expressed well in a prokaryotic expression system or a baculovirus expression system, even after extensive optimization. In a mammalian cell expression system, the Vγ9Vδ2 TCR was expressed in the form of a soluble heterodimer, which was suitable for crystal screening. Reduced-temperature cultivation (cold shock) increased the yield of the recombinant TCR. The recombinant purified TCR was used for crystal trials, and crystals that could be used for X-ray diffraction were obtained. Although we have not yet determined the crystal structure of the Vγ9Vδ2 TCR, we have established a procedure for Vγ9Vδ2 TCR expression and purification, which is useful for basic research and potentially for clinical application.

P24 Recurrent skin ulcerations as an isolated manifestation of ISG15 deficiency

Abstract Type I interferonopathies are characterized by a very broad phenotypic spectrum; however, some overlapping clinical features are seen across the type I interferonopathies, most particularly brain and skin involvement. We report a female patient presenting at 7 months of age with ulcerations in her groin and axilla. The lesions in her axilla healed; however, she continued having recurrent ulcerations in both sides of her groin and she developed lipoatrophy of the lower abdomen. Skin biopsy revealed deep-seated inflammation with abnormal adipose tissue; no bacteria were isolated. Extensive immunology blood work-up did not reveal any abnormalities, and the inflammatory markers were normal. Because of the extent of the clinical findings and pending results of genetic screening with targeted next-generation sequencing, we commenced methotrexate at 1 year of age (15 mg m–2). Following the initiation of methotrexate, there was marked improvement in the clinical features, with resolution of active skin ulceration. Genetic screening revealed a homozygous stop mutation in ISG15 p.Q16X. A CT scan of her head did not show any calcifications. Methotrexate was stopped at age 3 years. She remains well with no further skin ulcerations, and her development continues to be age appropriate. ISG15 deficiency is a type I interferonopathy, previously described in association with intracranial calcifications and increased susceptibility to mycobacteria infections. However, more recent reports have described skin ulcerations as a main finding in addition to neurological and immunological manifestations. Our patient is not showing any signs of neurological or other immunological manifestations but remains under careful monitoring.

Therapeutically useful mycobacteriophages BPs and Muddy require trehalose polyphleates

Mycobacteriophages show promise as therapeutic agents for non-tuberculous mycobacterium infections. However, little is known about phage recognition of Mycobacterium cell surfaces or mechanisms of phage resistance. We show here that trehalose polyphleates (TPPs)—high-molecular-weight, surface-exposed glycolipids found in some mycobacterial species—are required for infection of Mycobacterium abscessus and Mycobacterium smegmatis by clinically useful phages BPs and Muddy. TPP loss leads to defects in adsorption and infection and confers resistance. Transposon mutagenesis shows that TPP disruption is the primary mechanism for phage resistance. Spontaneous phage resistance occurs through TPP loss by mutation, and some M. abscessus clinical isolates are naturally phage-insensitive due to TPP synthesis gene mutations. Both BPs and Muddy become TPP-independent through single amino acid substitutions in their tail spike proteins, and M. abscessus mutants resistant to TPP-independent phages reveal additional resistance mechanisms. Clinical use of BPs and Muddy TPP-independent mutants should preempt phage resistance caused by TPP loss.

A novel GATA2 distal enhancer mutation results in MonoMAC syndrome in 2 second cousins

AbstractMutations in the transcription factor GATA2 can cause MonoMAC syndrome, a GATA2 deficiency disease characterized by several findings, including disseminated nontuberculous mycobacterial infections, severe deficiencies of monocytes, natural killer cells, and B lymphocytes, and myelodysplastic syndrome. GATA2 mutations are found in ∼90% of patients with a GATA2 deficiency phenotype and are largely missense mutations in the conserved second zinc-finger domain. Mutations in an intron 5 regulatory enhancer element are also well described in GATA2 deficiency. Here, we present a multigeneration kindred with the clinical features of GATA2 deficiency but lacking an apparent GATA2 mutation. Whole genome sequencing revealed a unique adenine-to-thymine variant in the GATA2 –110 enhancer 116,855 bp upstream of the GATA2 ATG start site. The mutation creates a new E-box consensus in position with an existing GATA-box to generate a new hematopoietic regulatory composite element. The mutation segregates with the disease in several generations of the family. Cell type–specific allelic imbalance of GATA2 expression was observed in the bone marrow of a patient with higher expression from the mutant-linked allele. Allele-specific overexpression of GATA2 was observed in CRISPR/Cas9-modified HL-60 cells and in luciferase assays with the enhancer mutation. This study demonstrates overexpression of GATA2 resulting from a single nucleotide change in an upstream enhancer element in patients with MonoMAC syndrome. Patients in this study were enrolled in the National Institute of Allergy and Infectious Diseases clinical trial and the National Cancer Institute clinical trial (both trials were registered at www.clinicaltrials.gov as #NCT01905826 and #NCT01861106, respectively).

Nontuberculous mycobacterial infections in patients with hematologic malignancies and recipients of hematopoietic stem cell transplantation.

The incidence of mycobacterial infections in patients with hematologic malignancies and hematopoietic stem cell transplant (HSCT) recipients is increasing, contributing to significant mortality and morbidity. This review explores the epidemiology, risk factors, clinical presentation, diagnosis, and treatment of nontuberculous mycobacteria (NTM) in this population. A literature search was performed using PubMed with keywords and MeSH terms pertaining to the topics of nontuberculous mycobacteria, hematologic malignancies, hematopoietic stem cell transplant, cellular therapies, chimeric antigen therapies, epidemiology, diagnosis, and treatment. Additionally, we examined the reference lists of the included articles to identify other pertinent studies. Diagnosing mycobacterial disease among patients with hematologic disease and treatment-associated immunosuppressive conditions is challenging due to the lack of distinctive clinical, radiographic, and laboratory markers, as well as the atypical manifestations compared to immunocompetent patients. Treatment involves using a combination of antibiotics for extended durations, coupled with strategies to achieve source control and reduce immunosuppression when feasible. This is complicated by the absence of clear data correlating in-vitro drug susceptibility and clinical outcome for many antimicrobials use to treat NTM, adverse drug-drug interactions, and the frequent challenges related to poor medication tolerability and toxicities. The rising incidence and corresponding clinical challenges of mycobacterial infections in this unique patient population necessitate a heightened awareness and familiarity of NTM disease by clinicians to achieve timely diagnosis and favorable treatment outcomes.

Modeling the importance of fish condition, overall health, and disease on the fecundity of White Perch in the Choptank River.

Modeling of fecundity with allometric, nutritional, and environmental covariates has increased sensitivity of reproductive metrics in many fish species. In estuaries with heavy anthropogenic influence, resident species often experience sublethal health impacts because of increased stress, which can include increases in gonadal pathology, intersex, or potential reproductive failure. This study models the fecundity of the estuarine species White Perch Morone americana in response to health parameters identified as signals of habitat stress, including gross pathology presentation, nutritional condition, and disease presence. Subpopulation fecundity in the Choptank River (Maryland) of the Chesapeake Bay was estimated using stereological fecundity sampling methods and modeled using information-theoretic approaches of model selection. Nutritional and health parameters identified through health assessment techniques, specific somatic indices, and disease presence were selected as covariates. Nutrition demonstrated limited influence on model fit as compared to models with only conventional allometric variables such as weight and length. Of the health variables, gross pathology and somatic indices showed minimal influence on selection, but mycobacterial infection, a chronic condition in the Chesapeake Bay among temperate basses, showed measurable influence. Models with mycobacteriosis included were 40 times more likely the best fit when compared to models with only allometric parameters. Whether this has a region-wide influence on all subpopulations will require further research and sampling of the magnitude of mycobacteriosis infection.

Additive Effects of Cyclic Peptide [R4W4] When Added Alongside Azithromycin and Rifampicin against Mycobacterium avium Infection.

Mycobacterium avium (M. avium), a type of nontuberculous mycobacteria (NTM), poses a risk for pulmonary infections and disseminated infections in immunocompromised individuals. Conventional treatment consists of a 12-month regimen of the first-line antibiotics rifampicin and azithromycin. However, the treatment duration and low antibiotic tolerability present challenges in the treatment of M. avium infection. Furthermore, the emergence of multidrug-resistant mycobacterium strains prompts a need for novel treatments against M. avium infection. This study aims to test the efficacy of a novel antimicrobial peptide, cyclic [R4W4], alongside the first-line antibiotics azithromycin and rifampicin in reducing M. avium survival. Colony-forming unit (CFU) counts were assessed after treating M. avium cultures with varying concentrations of cyclic [R4W4] alone or in conjunction with azithromycin or rifampicin 3 h and 4 days post-treatment. M. avium growth was significantly reduced 4 days after cyclic [R4W4] single treatment. Additionally, cyclic [R4W4]-azithromycin and cyclic [R4W4]-rifampicin combination treatments at specific concentrations significantly reduced M. avium survival 3 h and 4 days post-treatment compared with single antibiotic treatment alone. These findings demonstrate cyclic [R4W4] as a potent treatment method against M. avium and provide insight into novel therapeutic approaches against mycobacterium infections.