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Ethiopian Journal of Health Sciences Sep 2023Non-tuberculous mycobacteria (NTMs) are ubiquitous, free-living, environmental saprophytic microorganisms. NTMs belong to the genus Mycobacterium which includes...
BACKGROUND
Non-tuberculous mycobacteria (NTMs) are ubiquitous, free-living, environmental saprophytic microorganisms. NTMs belong to the genus Mycobacterium which includes Mycobacterium tuberculosis (MTB). NTMs have lately been a major cause of pulmonary disease (PD) in immuno-compromised individuals including HIV-1 patients. NTMs and MTB appear similar based on microscopy, radiology, and clinical symptoms; consequently, this may lead to misdiagnosis. This study sought to establish the prevalence of NTM pulmonary disease in HIV-1 patients presumed to have pulmonary tuberculosis.
METHODS
A cross-sectional analytical laboratory study design was used targeting 617 adult HIV-1 infected patients presenting with presumptive pulmonary TB at Bungoma County Hospital Comprehensive Care Clinic in Western Kenya between July 2021 to June 2022.
RESULTS
A total of 75 (12.2%, 4.6 -9.8 CI) of the participants presented with presumptive MTB and had TB-like symptoms while 542 (87.8%, 12.5 -30.7 CI) were negative. Additionally, 56 (9.1%) were infected with NTMs. HIV-positive participants had a significantly higher prevalence of NTMs 62 (11.8%, 5.6 -9.2 CI) compared to 2 (2.1%, 0.4 -1.8 CI). In HIV + study participants P<0.0001. M. avium was the most prevalent NTM, 25(33.3%), followed by M. fortuitum 20 (26.7%). A significant number of the isolates were M. tuberculosis 10 (13.3%) as well as M. kansasii 8 (10.7%).
CONCLUSION
There seems to be a high prevalence of NTMPD in HIV-1 patients which is assumed to be pulmonary TB. Differential diagnosis of the mycobacterium species is necessary to help improve disease management and outcomes in this group of patients.
Topics: Humans; Kenya; Male; Adult; Female; Mycobacterium Infections, Nontuberculous; Cross-Sectional Studies; Prevalence; Tuberculosis, Pulmonary; HIV Infections; Middle Aged; Nontuberculous Mycobacteria; HIV-1; Young Adult
PubMed: 38784500
DOI: 10.4314/ejhs.v33i5.3 -
International Journal of... Jan 2024Microorganisms belonging to the Mycobacterium avium complex (MAC) are ubiquitous in the environment, but only a minority of infected persons develop disease. An...
Microorganisms belonging to the Mycobacterium avium complex (MAC) are ubiquitous in the environment, but only a minority of infected persons develop disease. An underlying lung disease or immune deficiency is a prerequisite for clinical manifestation. However, disseminated MAC disease primarily manifests in people living with human immunodeficiency virus (HIV) in the severe immunodeficiency stage with a whole host of clinical symptoms. We present two cases of disseminated M. avium infection in people living with HIV in the stage of severe immunodeficiency. Both patients exhibited distinct disease progression, with the absence of pulmonary symptoms being a common characteristic. The first patient predominantly experienced high fever, accompanied by diarrhea and severe anemia. The normothermia in the second patient was incongruent with the presence of marked cachexia, severe abdominal pain, and magnetic resonance imaging evidence of abdominal lymph node involvement. The causative agent was isolated from both sputum and stools. The patients underwent treatment that comprised aminoglycoside, macrolide, ethambutol, and rifampicin. Although both patients achieved optimal viral suppression of HIV, the immunologic response to antiretroviral therapy was suboptimal. The first patient died in the setting of severe immunodeficiency due to the development of decompensated liver cirrhosis, while the second patient demonstrated a slight reverse course of the disease.
Topics: Adult; Humans; Male; AIDS-Related Opportunistic Infections; Fatal Outcome; HIV Infections; Mycobacterium avium Complex; Mycobacterium avium-intracellulare Infection; Sputum
PubMed: 38771289
DOI: 10.4103/ijmy.ijmy_23_24 -
MBio Jun 2024Nontuberculous mycobacteria (NTM) are environmentally ubiquitous organisms that predominately cause NTM pulmonary disease (NTMPD) in individuals over the age of 65. The...
UNLABELLED
Nontuberculous mycobacteria (NTM) are environmentally ubiquitous organisms that predominately cause NTM pulmonary disease (NTMPD) in individuals over the age of 65. The incidence of NTMPD has increased in the U.S., exceeding that of . However, the mechanisms leading to higher susceptibility and severity of NTMPD with aging are poorly defined in part due to the lack of animal models that accurately recapitulate human disease. Here, we compared bacterial load, microbial communities, and host responses longitudinally between three young (two female and one male) and two aged (two female) rhesus macaques inoculated with subsp. (MAH) in the right caudal lobe. Unilateral infection resulted in a low bacterial load in both young and aged animals confined to the infected side. Although a robust inflammatory response was only observed in the inoculated lung, immune cell infiltration and antigen-specific T cells were detected in both lungs. Computed tomography, gross pathology, and histopathology revealed increased disease severity and persistence of bacterial DNA in aged animals. Additional analyses showed the translocation of gut and oral-pharyngeal bacterial DNA into the lower respiratory microbiome. Finally, single-cell RNA sequencing revealed a heightened inflammatory response to MAH infection by alveolar macrophages in aged animals. These data are consistent with the model that increased disease severity in the aged is mediated by a dysregulated macrophage response that may be sustained through persistent antigen presence.
IMPORTANCE
Nontuberculous mycobacteria (NTM) are emerging as pathogens of high consequence, as cases of NTM pulmonary disease (NTMPD) have exceeded those of . NTMPD can be debilitating, particularly in patients over 65 years of age, as it causes chronic cough and fatigue requiring prolonged treatments with antibiotics. The underlying mechanisms of this increased disease severity with age are poorly understood, hampering the development of therapeutics and vaccines. Here, we use a rhesus macaque model to investigate the impact of age on host-NTM interactions. This work shows that aging is associated with increased disease severity and bacterial persistence in aged rhesus macaques, thus providing a preclinical model to develop and test novel therapeutics and interventions.
Topics: Mycobacterium Infections, Nontuberculous; Lung; Macaca mulatta; Animals; Male; Female; Age Factors; Tomography, X-Ray Computed; Transcriptome; Microbiota
PubMed: 38771046
DOI: 10.1128/mbio.00829-24 -
Radiology Case Reports Aug 2024Disseminated mycobacterium avium complex (MAC) infection is rare and is classically associated with immunodeficient states. Osteomyelitis is a rare manifestation of...
Disseminated mycobacterium avium complex (MAC) infection is rare and is classically associated with immunodeficient states. Osteomyelitis is a rare manifestation of disseminated MAC infection. The overwhelming majority of MAC infections occur in patients with human immunodeficiency virus (HIV). Disseminated MAC infection has been described in interferon gamma receptor deficiency, an immunodeficiency mechanistically linked to mycobacterial infection. We present a case of disseminated MAC vertebral osteomyelitis in a patient with interferon gamma receptor deficiency.
PubMed: 38770391
DOI: 10.1016/j.radcr.2024.04.028 -
Antimicrobial Agents and Chemotherapy May 2024When using amikacin to treat complex pulmonary disease (MAC-PD), a minimum inhibitory concentration resistance breakpoint of ≥64 mcg/mL is recommended. We explored...
When using amikacin to treat complex pulmonary disease (MAC-PD), a minimum inhibitory concentration resistance breakpoint of ≥64 mcg/mL is recommended. We explored whether amikacin resistance characterized by phenotypic drug susceptibility testing was associated with clinical outcomes or mutational resistance in a retrospective cohort of patients with MAC-PD. Despite little aminoglycoside exposure, amikacin resistance was common in our MAC-PD patients but was not associated with worse outcomes or gene mutations.
PubMed: 38758004
DOI: 10.1128/aac.00084-24 -
Frontiers in Veterinary Science 2024Paratuberculosis (PTB), or Johne's disease, is a disease with worldwide distribution caused by subsp (MAP) that leads to chronic enteritis, primarily in ruminants. Even... (Review)
Review
Paratuberculosis (PTB), or Johne's disease, is a disease with worldwide distribution caused by subsp (MAP) that leads to chronic enteritis, primarily in ruminants. Even subclinical infection significantly reduces the animals' performance, and consequences of the disease lead to high economic losses for the cattle industry. To estimate the economic burden of bovine PTB and to evaluate the benefits of a potential control program, accurate estimates of the production effects associated with the disease are required. Therefore, the aim of this scoping review was to provide a comprehensive overview of associations between MAP infection and production parameters in cattle. The studies were collected from three electronic databases. Of the total 1,605 identified studies, 1,432 did not meet the set criteria in the title and abstract screening and a further 106 were excluded during full-text review. Finally, data on 34 different production parameters were extracted from 67 publications. Results show that the magnitude of reported performance losses varies depending on several factors, such as the type of diagnostic test applied, disease status or number of lactations. Studies reported a reduction in milk yield, changes in milk quality (e.g., higher somatic cell count, lower amount of produced milk fat and protein), reduced fertility (e.g., prolonged calving interval and service period, higher abortion rate and calving difficulties), reduced weaning weight, slaughter weight and slaughter value, or a higher risk for mastitis. Results from the studies included in our review show a median decrease of milk yield per infected cow of -452 kg/lactation for raw and -405 kg/lactation for modeled data. Similarly, the amount of produced milk protein fell by a median of -14.41 kg/lactation for modeled data and the amount of produced milk fat by a median of -13.13 kg/lactation. The reviewed studies revealed a prolonged calving interval by around 30 days and a 1.5 to 3 times higher likeliness of culling per lactation in PTB positive animals. Results from this scoping review provide evidence-based inputs for the development of economic models aiming at the estimation of the costs and benefits associated with different disease control scenarios for PTB.
PubMed: 38756521
DOI: 10.3389/fvets.2024.1352623 -
Allergologie Select 2024None.
None.
PubMed: 38756207
DOI: 10.5414/ALX02444E -
Journal of Dairy Science May 2024Mycobacterium avium ssp. paratuberculosis (MAP) is the bacterium responsible for causing Johne's Disease (JD), which is endemic to dairy cattle and also incriminated in...
Systematic assessment of the reliability of quantitative PCR assays targeting IS900 for the detection of Mycobacterium avium ssp. paratuberculosis presence in animal and environmental samples.
Mycobacterium avium ssp. paratuberculosis (MAP) is the bacterium responsible for causing Johne's Disease (JD), which is endemic to dairy cattle and also incriminated in the etiology of Crohn's disease. The difficulty in diagnosing asymptomatic cows for JD makes this disease hard to control. JD is considered a priority under the One Health approach to prevent the spread of the causative agent to humans. Environmental screening is a strategic approach aimed at identifying dairy herds with animals infected with MAP. It serves as the initial step toward implementing more intensive actions to control the disease. Quantitative polymerase chain reaction (qPCR) technology is widely used for diagnosis. Given that genome sequencing is now much more accessible than ever before, it is possible to target regions of the MAP genome that allow for the greatest diagnostic sensitivity and specificity. The aim of this study was to identify among the published qPCR assays targeting IS900 the more cost-effective options to detect MAP and to validate them in the diagnostic context of JD disease. MAP IS900 is a prime target because it is a multicopy genetic element. A total of 136 publications have reported on the use of IS900 qPCR assays over the past 3 decades. Among these records, 29 used the SYBR Green chemistry and TaqMan technology was used in 107 reports. Aside from the 9 reports using commercial assays, 72 TaqMan reports cited previously published work, leaving us with 27 TaqMan qPCR designs. Upon closer examination, 5 TaqMan designs contained mismatches in primer or probe sequences. Additionally, others exhibited high similarity to environmental microorganisms or non-MAP mycobacteria. We assessed the performance of 6 IS900 qPCR designs and their sensitivity when applied to clinical or environmental samples, which varied from 4 to 56 fold overall. Additionally, we provide recommendations for testing clinical and environmental samples, as certain strategies used previously should be avoided due to poor qPCR design (e.g., the presence of mismatches) or a lack of specificity.
PubMed: 38754821
DOI: 10.3168/jds.2023-24566 -
International Journal of Antimicrobial... May 2024Guideline-based therapy for Mycobacterium avium complex (MAC) pulmonary disease achieves sustained sputum conversion rates in only 43-53% of patients. Repurposing of...
INTRODUCTION
Guideline-based therapy for Mycobacterium avium complex (MAC) pulmonary disease achieves sustained sputum conversion rates in only 43-53% of patients. Repurposing of β-lactam antibiotics such as ertapenem could expedite design of more efficacious regimens, compared to developing new drugs.
METHODS
We performed an ertapenem exposure-response study in the hollow fiber system model of intracellular MAC (HFS-MAC). We recapitulated human-like intrapulmonary concentration-time profiles of eight once-daily intravenous doses of ertapenem over 28 days and performed repetitive sampling for drug concentration-time profiles and MAC burden. The % of time concentration persisted above MIC (%T) mediating either 50% or 80% of maximal effect (E, EC) were identified. The EC was used as target exposure in a 10,000 subject Monte Carlo experiments for ertapenem doses of 1G, 2G, or 4G administered once versus twice daily.
RESULTS
The ertapenem MIC ranged from 0.5 to 2 mg/L on three occasions. Ertapenem achieved a half-life of 4.04±0.80h in the HFS-MAC and killed a maximum of 2.17 log CFU/mL below day 0. The EC was %T of 75.9% (95% confidence interval: 68.43% to 86.54%) and the EC was %T of 100%. Target attainment probability was >90% for 1G twice daily up to an MIC of 2 mg/L, while for 2G twice daily the susceptibility MIC breakpoint was 4-8 mg/L.
CONCLUSIONS
Ertapenem microbial kill below day 0 burden was better than guideline-based therapy drugs in the HFS-MAC in the past. Ertapenem is a promising drug for novel combination therapies for MAC lung disease.
PubMed: 38754528
DOI: 10.1016/j.ijantimicag.2024.107204 -
Tuberculosis (Edinburgh, Scotland) Jul 2024Drug susceptibility testing (DST) protocol of omadacycline against non-tuberculous mycobacteria has not yet been established. We developed a method to accurately...
BACKGROUND
Drug susceptibility testing (DST) protocol of omadacycline against non-tuberculous mycobacteria has not yet been established. We developed a method to accurately determine MIC omadacycline MIC against Mycobacterium abscessus (Mab), Mycobacterium avium-complex (MAC), and Mycobacterium kansasii (Mkn).
METHODS
First, we identified the oxyrase concentration not affecting Mab, MAC, and Mkn growth followed by omadacycline MIC experiments with and without oxyrase using reference and clinical strains.
RESULTS
Oxyrase 0.5 % (v/v) stabilized omadacycline in the culture medium. The median omadacycline MIC was 1 mg/L for Mab and 8 mg/L for Mkn. For MAC, the median omadacycline MIC was 2 mg/L for M. avium, 256 mg/L for M. intracellulare, and 4 mg/L for M. chimaera (p < 0.0001). Wilcoxon matched-pairs signed rank test revealed statistically lower MICs with oxyrase for all MAC subspecies (p < 0.0001), all Mab subspecies (p < 0.0001), and Mkn (p = 0.0002). The decrease in MICs with oxyrase was 17/18 of Mab, 14/19 of Mkn, 8/8 of M. avium, 4/5 M. chimera, but only 11/18 of M. intracellulare (p < 0.013).
CONCLUSION
Use of 0.5 % oxyrase could be a potential solution to reliable and reproducible omadacycline MIC of Mab. However, oxyrase demonstrated a variable effect in reducing MICs against MAC and Mkn.
Topics: Microbial Sensitivity Tests; Humans; Antitubercular Agents; Tetracyclines; Mycobacterium abscessus; Mycobacterium kansasii; Mycobacterium avium Complex; Nontuberculous Mycobacteria; Mycobacterium Infections, Nontuberculous
PubMed: 38754247
DOI: 10.1016/j.tube.2024.102519