Gut microbiota composition and diversity before, during, and two months after rifamycin-based tuberculosis preventive therapy.

Tuberculosis (TB) preventive therapy (TPT) is an effective strategy to eliminate TB in low-incidence settings. Shorter TPT regimens incorporating the antimicrobial class of rifamycins are designed to improve adherence and completion rates but carry the risk of modifications to the gut microbiota. We enrolled six subjects diagnosed with latent TB infection (LTBI) who accepted to initiate TPT. We also enrolled six healthy volunteers unexposed to the rifamycins. We profiled the gut microbiota using 16S rRNA amplicon sequencing (V1-V2 region) to document the immediate effect of rifamycin-based TPT on the gut microbiota composition and tracked recovery to baseline two months after TPT. Overall, TPT accounted for 17% of the variance in gut microbial community dissimilarity. This rifamycin-based TPT induced dysbiosis was characterized by a depletion of butyrate-producing taxa (Clostridium-XIVa and Roseburia) and expansion of potentially pathogenic taxa within the Firmicutes and Proteobacteria phyla. Recovery of the gut microbial composition was incomplete two months after TPT. Robust clinical studies are necessary to comprehensively catalogue TPT-induced gut microbiota dysbiosis to inform strategies to mitigate potential long-term sequelae of this important TB control intervention.

Therapies for Parkinson's disease and the gut microbiome: evidence for bidirectional connection.

The gut brain axis (GBA), a bidirectional communication pathway has often been linked to health and disease, and gut microbiota (GM), a key component of this pathway shown to be altered in Parkinson's disease (PD), are suggested to contribute to the pathogenesis of PD. There are few studies that report the impact of oral medication therapy on GM, however, there are even fewer studies that discuss the impact of other treatments such as device assisted therapies (DAT) including deep brain stimulation (DBS), levodopa-carbidopa intestinal gel infusion (LCIG) and photobiomodulation (PBM) and how these might impact GM. Here, we review the literature and summarize findings of the potential contributions of GM to the heterogenous clinical response to pharmaceutical therapies among individuals with PD. We also discuss the potential interactions between the GM and DATs such as DBS and LCIG and present evidence for alterations in GM in response to DATs. Given the complexity and highly individual nature of the GM of patients with PD and the potential influence that other external factors such as diet, lifestyle, medications, stage of the disease and other comorbidities, further investigations into the response of GM to therapies are worthy of future study in prospective, controlled trials as well as medication naïve individuals. Such detailed studies will help us further comprehend the relationship between GM in PD patients, and will help investigate the potential of targeting GM associated changes as a treatment avenue for PD.

Evaluation of screen, test, & protect: A public health program to control and prevent COVID-19 at a large academic university.

Background: We evaluate the public health surveillance program, Screen, Test, and Protect (STP) designed to control and prevent COVID-19 at a large academic university in the United States. Methods: STP was established at the University of Florida in May 2020. This report details STP's full-time workforce, centralized database, and testing and vaccination programs. We evaluate the program's success in controlling COVID-19 during the 2020-2021 academic school year. Results: COVID-19 cases rose among the campus community in the first few weeks of campus reopening in Fall 2020. Test positivity levels returned to prefall semester levels within one month, however. A few additional, yet smaller, waves occurred during the 2020-2021 school year and were successfully controlled without any campus-wide closures. Conclusions: This program may serve as a framework for other institutions managing the ongoing COVID-19 crisis, in addition to setting the standard for programmatic management of future emerging infectious diseases at universities.

Multi-Faceted Approach to COVID-19 Surveillance at a Large University Campus in the Southeastern United States.

The coronavirus disease 2019 (COVID-19) pandemic continues to present unique public health challenges both within the United States and across the globe. Institutions of higher learning are tasked with preventing and responding to COVID-19 on campus while also considering implications for the surrounding communities. The process of re-opening campus, whether at full or partial capacity, has tasked these institutions with overcoming complex challenges associated with balancing the resumption of campus operations while simultaneously protecting university affiliates and surrounding community members from COVID-19 through robust surveillance, contact tracing, and testing efforts. Here, we provide a concise outline related to the development and implementation of the comprehensive and sustainable COVID-19 surveillance program at the University of Florida. We also critically discuss the successes and pitfalls of this program while also providing recommendations for the development of similar programs in the future.

Evaluating the Diagnostic Paradigm for Group A and Non-Group A Streptococcal Pharyngitis in the College Student Population.

BACKGROUND: Acute pharyngitis is a frequent illness presenting in outpatient settings. Antibiotics are only recommended for bacterial pharyngitis caused by group A ß-hemolytic streptococci (GAS); however, infections with non-group A ß-hemolytic streptococci (NGAS) have similar clinical presentations and are common in young adult populations. The objective of this study was to analyze the performance of a current (expert) diagnostic algorithm for GAS pharyngitis, the Centor score, and compare it to alternative models developed to predict GAS and NGAS in a college student population. METHODS: Electronic health records were obtained for all patients who received a streptococcal rapid antigen detection test (RADT) and/or a bacterial throat culture (n = 3963) at a southeastern US university in 2014. Bivariate and multivariable regression models (least absolute shrinkage and selection operator [LASSO] and stepwise-selected) were fitted to assess and compare their diagnostic performances for GAS-positive and NGAS-positive infections. RESULTS: Prevalence of GAS was 18.8%. In the subset of RADT-negative patients who received bacterial throat cultures (n = 313), growth of NGAS occurred in 34.8%, with group C streptococci the most frequent isolate. Mean Centor score was higher for NGAS (3.2) vs GAS (2.9) infections (P = .0111). The area under the curve (AUC) for GAS prediction was 0.64 using the Centor score and 0.70 using the LASSO model. For NGAS, the most important features were cough, pharyngeal erythema, tonsillar exudate, and gastrointestinal symptoms (AUC = 0.63). CONCLUSIONS: GAS and NGAS pharyngitis were indistinguishable among college students in this study utilizing a commonly applied decision score. Alternative models using additional clinical criteria may be useful for supporting diagnosis of this common illness.

The Gut-Brain Axis and Its Relation to Parkinson's Disease: A Review.

Parkinson's disease is a chronic neurodegenerative disease characterized by the accumulation of misfolded alpha-synuclein protein (Lewy bodies) in dopaminergic neurons of the substantia nigra and other related circuitry, which contribute to the development of both motor (bradykinesia, tremors, stiffness, abnormal gait) and non-motor symptoms (gastrointestinal issues, urinogenital complications, olfaction dysfunction, cognitive impairment). Despite tremendous progress in the field, the exact pathways and mechanisms responsible for the initiation and progression of this disease remain unclear. However, recent research suggests a potential relationship between the commensal gut bacteria and the brain capable of influencing neurodevelopment, brain function and health. This bidirectional communication is often referred to as the microbiome-gut-brain axis. Accumulating evidence suggests that the onset of non-motor symptoms, such as gastrointestinal manifestations, often precede the onset of motor symptoms and disease diagnosis, lending support to the potential role that the microbiome-gut-brain axis might play in the underlying pathological mechanisms of Parkinson's disease. This review will provide an overview of and critically discuss the current knowledge of the relationship between the gut microbiota and Parkinson's disease. We will discuss the role of α-synuclein in non-motor disease pathology, proposed pathways constituting the connection between the gut microbiome and the brain, existing evidence related to pre- and probiotic interventions. Finally, we will highlight the potential opportunity for the development of novel preventative measures and therapeutic options that could target the microbiome-gut-brain axis in the context of Parkinson's disease.

Gut Microbiota Dynamics in Parkinsonian Mice.

Peripheral immunity is thought to be dysregulated in Parkinson's disease (PD) and may provide an avenue for novel immunotherapeutic interventions. Gut microbiota is a potential factor for modulating immunotherapy response. Considering the possibly complex role of the gut-brain axis in PD, we used a preclinical model to determine the effects of gut microbiota dynamics in mice receiving an immunotherapeutic intervention compared to controls. A total of 17 M83 heterozygous transgenic mice were used in this study. Mice in the treatment arm (N = 10) received adoptive cellular therapy (ACT) by injection, and control mice (N = 7) were injected with saline at 8 weeks of age. All mice received peripheral α-syn fibrils to hasten parkinsonian symptoms via an intramuscular injection 1 week later (9 weeks of age; baseline). Fecal pellets were collected from all mice at three time points postinjection (baseline, 6 weeks, and 12 weeks). DNA from each stool sample was extracted, and 16S rDNA was amplified, sequenced, and analyzed using QIIME2 and RStudio. Differences in the relative abundance of bacterial taxa were observed over time between groups. No significant differences in alpha diversity were found between groups at any time point. UniFrac measures of phylogenetic distance between samples demonstrated distinct clustering between groups postbaseline (p = 0.002). These differences suggest that the gut microbiome may be capable of influencing immunotherapy outcomes. Conclusively, we observed distinctly different microbiota dynamics in treated mice compared to those in the control group. These results suggest a correlation between the gut-brain axis, PD pathology, and immunotherapy.

Microbiota composition in bilateral healthy breast tissue and breast tumors.

PURPOSE: Previous reports suggest that a complex microbiome exists within the female human breast that might contribute to breast cancer etiology. The purpose of this pilot study was to assess the variation in microbiota composition by breast side (left versus right) within individual women and compare the microbiota of normal and breast tumor tissue between women. We aimed to determine whether microbiota composition differs between these groups and whether certain bacterial taxa may be associated with breast tumors. METHODS: Bilateral normal breast tissue samples (n = 36) were collected from ten women who received routine mammoplasty procedures. Archived breast tumor samples (n = 10) were obtained from a biorepository. DNA was extracted, amplified, and sequenced. Microbiota data were analyzed using QIIME and RStudio. RESULTS: The most abundant phyla in both tumor and normal tissues were Bacteroidetes, Firmicutes, Proteobacteria, and Actinobacteria. There were statistically significant differences in the relative abundance of various bacterial taxa between groups. Alpha diversity (Simpson's index) was significantly higher in normal compared to tumor samples (0.968 vs. 0.957, p = 0.022). Based on unweighted UniFrac measures, breast tumor samples clustered distinctly from normal samples (R2 = 0.130; p = 0.01). Microbiota composition in normal samples clustered within women (R2 = 0.394; p = 0.01) and by breast side (left or right) within a woman (R2 = 0.189; p = 0.03). CONCLUSION: Significant differences in diversity between tumor and normal tissue and in composition between women and between breasts of the same woman were identified. These results warrant further research to investigate the relationship between microbiota and breast cancer.

Impact of the 12 January 2010 earthquake on HIV case reporting in Haiti.

OBJECTIVE: To evaluate the impact of the 12 January 2010 earthquake on HIV cases from Haiti's national HIV surveillance system and assess the characteristics of people living with HIV 1-year before and after the earthquake. DESIGN: An interrupted time-series design and cross-sectional analysis. METHODS: We used autoregressive integrated moving average structures to model abrupt changes to the monthly, incident HIV case counts from HIV care clinics as reported to the Haitian Active Longitudinal Tracking of HIV System (French acronym SALVH) by clinical networks (n = 3) and earthquake instrumental intensity zones (n = 4). Preearthquake and postearthquake differences in patient-level characteristics including clinical values were examined using the χ test, t tests, Wilcoxon rank-sum test. RESULTS: In the month immediately following the earthquake, all three clinical networks experienced statistically significant declines in cases reported: iSanté (-31.4%), Groupe Haïtien d'Etude du Sarcome de Kaposi et des Infections Opportunistes (-29.9%) and Zamni Lasante (-32.2%). Zone 8 (the most severe) was the only area with a statistically significant decline (-45.5%). Of the three clinical networks, only iSanté returned to preearthquake reporting levels by the end of our study period. Patient-level characteristics did not change dramatically after the earthquake. CONCLUSION: Despite case reporting declines, especially in clinics near the earthquake epicenter, SALVH remained intact with less impact than expected. This national system is a critical component of Haiti's strategic health information system initiative and plays a central role to HIV monitoring and evaluation efforts.

A review of potential microbiome-gut-brain axis mediated neurocognitive conditions in persons living with HIV.

The microbiome-gut-brain axis, or the various interactions between the gut microbiome and the brain, has been of recent interest in the context of precision medicine research for a variety of disease states. Persons living with human immunodeficiency virus (PLWH) experience higher degrees of neurocognitive decline than the general population, correlating with a disruption of the normal gut microbiome composition (i.e. dysbiosis). While the nature of this correlation remains to be determined, there is the potential that the microbiome-gut-brain axis contributes to the progression of this disease. Previous research has established that the pathology associated with HIV induces alterations in the composition of gut microbiome, including a shift from Bacteroides to Prevotella dominance, and compromises gut barrier integrity, which may promote microbial translocation and consequent systemic inflammation and exacerbation of neuroinflammation. Further, though the use of antiretroviral therapy has been found to partially counteract HIV-related dysbiosis, it may also induce its own dysbiosis patterns, presenting a unique challenge for this research. More recent research has suggested the gut microbiome as a target for therapeutic interventions to improve symptoms associated with a variety of disease states, including HIV. Early findings are promising and warrant further research regarding the gut microbiome as a potential modifiable factor to improve health outcomes for PLWH. This review will discuss the current knowledge concerning the neuropathogenesis of HIV in the brain, role of the gut microbiome in neuroinflammation, and the relationship between HIV-status and the gut microbiome, followed by a conclusion that synthesizes this information within the context of the microbiome-gut-brain axis among PLWH. This review will also highlight the limitations of existing studies and propose future directions of this research.

Evaluating differences in tuberculosis and nontuberculous mycobacterial lung disease in Florida.

BACKGROUND: Currently, very little data exists that compare the features of pulmonary nontuberculous mycobacteria (NTM) and Mycobacterium tuberculosis (TB). Both have similar symptomology and analogous preliminary laboratory results, as both present with positive acid-fast bacilli stains. The objective of this study was to provide data that would help guide clinicians in their decision making regarding isolation precautions for patients, with a preliminary positive result for mycobacteria, prior to species identification. METHODS: We conducted queries for patients who had positive respiratory cultures for mycobacteria via our electronic medical record system, between January 1, 2011, and December 31, 2017. Additionally, we collected demographic and medical history, clinical presentation, and radiographic findings. The 2-sample unpaired Student t test, the Χ2 test, and logistic regression were used to compare each group. RESULTS: Through logistic regression, 8 variables were significantly associated with patients who grew either TB or NTM. History of incarceration, born outside of the United States, cavitation, and lymphadenopathy were associated with TB; tobacco smoke exposure, pre-existing lung disease, immunosuppression, and bronchiectasis were associated with NTM. Incidence of HIV and hemoptysis was not significantly different between the 2 groups. CONCLUSIONS: Through the use of our study findings, improper use of airborne isolation precautions may be reduced or avoided.