Chronic particulate matter less than 2.5 μm in diameter (PM2.5) exposure can leave infants more susceptible to illness. Our objective is to estimate associations of the chronic PM2.5exposure with infant bronchiolitis and otitis media (OM) clinical encounters. We obtained all first time bronchiolitis (n = 18,029) and OM (n = 40,042) clinical encounters among children less than 12 and 36 months of age, respectively, diagnosed from 2001 to 2009 and two controls per case matched on birthdate and gestational age from the Pregnancy to Early Life Longitudinal data linkage system in Massachusetts. We applied conditional logistic regression to estimate odds ratios (OR) and confidence intervals (CI) per 2-μg/m3increase in lifetime average satellite based PM2.5exposure.Effect modification was assessed by age, gestational age, frequency of clinical encounter, and income. We examined associations between residential distance to roadways, traffic density, and infant bronchiolitis and OM risk. PM2.5was not associated with infant bronchiolitis (OR = 1.02, 95% CI = 1.00, 1.04) and inversely associated with OM (OR = 0.97, 95% CI = 0.95, 0.99). There was no evidence of effect modification. Compared to infants living near low traffic density, infants residing in high traffic density had elevated risk of bronchiolitis (OR = 1.23, 95% CI = 1.14, 1.31) but not OM (OR = 0.98, 95% CI = 0.93, 1.02) clinical encounter. We did not find strong evidence to support an association between early-life long-term PM2.5exposure and infant bronchiolitis or OM. Bronchiolitis risk was increased among infants living near high traffic density.
National guidelines recommend annual human immunodeficiency virus (HIV)/sexually transmitted disease testing for sexually active men who have sex with men (MSM) and vaccination against human papillomavirus for MSM through age 26. A 2012 online survey of 2,794 MSM found that 51%, 36%, and 14% reported receiving human immunodeficiency virus testing, sexually transmitted disease testing, and human papillomavirus vaccination, respectively.
Although pyrazinamide is commonly used for tuberculosis treatment, drug-susceptibility testing is not routinely available. We found polymorphisms in the pncA gene for 70% of multidrug-resistant and 96% of extensively drugresistant Mycobacterium tuberculosis isolates from South Africa and Georgia. Assessment of pyrazinamide susceptibility may be prudent before using it in regimens for drugresistant tuberculosis.
Translation is a critical process in protein synthesis, but translational regulation in antigen-specific T cells in vivo has not been well defined. Here we have characterized the translatome of virus-specific CD8 + effector T cells (T eff cells) during acute infection of mice with lymphocytic choriomeningitis virus (LCMV). Antigen-specific T cells exerted dynamic translational control of gene expression that correlated with cell proliferation and stimulation via the T cell antigen receptor (TCR). The translation of mRNAs that encode translation machinery, including ribosomal proteins, was upregulated during the T cell clonal-expansion phase, followed by inhibition of the translation of those transcripts when the CD8 + T eff cells stopped dividing just before the contraction phase. That translational suppression was more pronounced in terminal effector cells than in memory precursor cells and was regulated by antigenic stimulation and signals from the kinase mTOR. Our studies show that translation of transcripts encoding ribosomal proteins is regulated during the differentiation of CD8 + T eff cells and might have a role in fate 'decisions' involved in the formation of memory cells.
by
Kohei Hasegawa;
Rachel Linnemann;
Jonathan M. Mansbach;
Nadim J. Ajami;
Janice A. Espinola;
Joseph F. Petrosino;
Pedro A. Piedra;
Michelle D. Stevenson;
Ashley F. Sullivan;
Amy D. Thompson;
Carlos A. Camargo
Background: Little is known about the relationship of airway microbiota with bronchiolitis in infants. We aimed to identify nasal airway microbiota profiles and to determine their association with the likelihood of bronchiolitis in infants. Methods: A case-control study was conducted. As a part of a multicenter prospective study, we collected nasal airway samples from 40 infants hospitalized with bronchiolitis. We concurrently enrolled 110 age-matched healthy controls. By applying 16S ribosomal RNA gene sequencing and an unbiased clustering approach to these 150 nasal samples, we identified microbiota profiles and determined the association of microbiota profiles with likelihood of bronchiolitis. Results: Overall, the median age was 3 months and 56% were male. Unbiased clustering of airway microbiota identified 4 distinct profiles: Moraxella-dominant profile (37%), Corynebacterium/Dolosigranulum-dominant profile (27%), Staphylococcus-dominant profile (15%) and mixed profile (20%). Proportion of bronchiolitis was lowest in infants with Moraxella-dominant profile (14%) and highest in those with Staphylococcus-dominant profile (57%), corresponding to an odds ratio of 7.80 (95% confidence interval, 2.64-24.9; P < 0.001). In the multivariable model, the association between Staphylococcus-dominant profile and greater likelihood of bronchiolitis persisted (odds ratio for comparison with Moraxella-dominant profile, 5.16; 95% confidence interval, 1.26-22.9; P = 0.03). By contrast, Corynebacterium/Dolosigranulum-dominant profile group had low proportion of infants with bronchiolitis (17%); the likelihood of bronchiolitis in this group did not significantly differ from those with Moraxella-dominant profile in both unadjusted and adjusted analyses. Conclusions: In this case-control study, we identified 4 distinct nasal airway microbiota profiles in infants. Moraxella-dominant and Corynebacterium/Dolosigranulum-dominant profiles were associated with low likelihood of bronchiolitis, while Staphylococcus-dominant profile was associated with high likelihood of bronchiolitis.
Background: Men who have sex with men (MSM) in the United States experience an approximately 100-fold greater rate of primary and secondary (P&S) syphilis diagnoses compared with men who have sex with women only. As in the general population, racial/ethnic disparities in P&S syphilis diagnosis rates may exist among MSM, but MSM-specific P&S syphilis rates by race/ethnicity are unavailable. We enhanced a published modeling approach to estimate area-level MSM populations by race/ethnicity and provide the first estimates of P&S syphilis among black and white non-Hispanic MSM. Methods: We used data from the American Community Survey (ACS), published findings from the National Health and Nutrition Examination Survey (NHANES), and national syphilis surveillance data to estimate state-level rates of P&S syphilis diagnoses among MSM, overall and for black and white non-Hispanic MSM. We also used variability around ACS and NHANES estimates to calculate 95% confidence intervals for each rate. Results: Among 11,359 cases of P&S syphilis among MSM with known race/ethnicity in 2014, 72.5% were among white (40.3%) or black (32.2%) MSM. The national rate of P&S syphilis diagnosis was 168.4/100,000 for white MSM and 583.9/100,000 for black MSM. Regional rates for black MSM ranged from 602.0/100,000 (South) to 521.5/100,000 (Midwest) and were consistently higher than those for white MSM. Conclusions: Although white MSM accounted for more P&S syphilis diagnoses than black MSM in 2014, when evaluating diagnoses based on rate per 100,000, black MSM had consistently and markedly higher rates than white MSM, with the highest impacted states located in the US South.
by
Alice Y. Guh;
Susan Hocevar Adkins;
Qunna Li;
Sandra N. Bulens;
Monica Farley;
Zirka Smith;
Stacy M. Holzbauer;
Tory Whitten;
Erin C. Phipps;
Emily B. Hancock;
Ghinwa Dumyati;
Cathleen Concannon;
Marion A. Kainer;
Brenda Rue;
Carol Lyons;
Danyel M. Olson;
Lucy Wilson;
Rebecca Perlmutter;
Lisa G. Winston;
Erin Parker;
Wendy Bamberg;
Zintars G. Beldavs;
Valerie Ocampo;
Maria Karlsson;
Dale N. Gerding;
L. Clifford McDonald
Background: An increasing proportion of Clostridium difficile infections (CDI) in the United States are community-associated (CA). We conducted a case-control study to identify CA-CDI risk factors. Methods: We enrolled participants from 10 US sites during October 2014-March 2015. Case patients were defined as persons age ≥18 years with a positive C. difficile specimen collected as an outpatient or within 3 days of hospitalization who had no admission to a health care facility in the prior 12 weeks and no prior CDI diagnosis. Each case patient was matched to one control (persons without CDI). Participants were interviewed about relevant exposures; multivariate conditional logistic regression was performed. Results: Of 226 pairs, 70.4% were female and 52.2% were ≥60 years old. More case patients than controls had prior outpatient health care (82.1% vs 57.9%; P < .0001) and antibiotic (62.2% vs 10.3%; P < .0001) exposures. In multivariate analysis, antibiotic exposure-that is, cephalosporin (adjusted matched odds ratio [AmOR], 19.02; 95% CI, 1.13-321.39), clindamycin (AmOR, 35.31; 95% CI, 4.01-311.14), fluoroquinolone (AmOR, 30.71; 95% CI, 2.77-340.05) and beta-lactam and/or beta-lactamase inhibitor combination (AmOR, 9.87; 95% CI, 2.76-340.05),-emergency department visit (AmOR, 17.37; 95% CI, 1.99-151.22), white race (AmOR 7.67; 95% CI, 2.34-25.20), cardiac disease (AmOR, 4.87; 95% CI, 1.20-19.80), chronic kidney disease (AmOR, 12.12; 95% CI, 1.24-118.89), and inflammatory bowel disease (AmOR, 5.13; 95% CI, 1.27-20.79) were associated with CA-CDI. Conclusions: Antibiotics remain an important risk factor for CA-CDI, underscoring the importance of appropriate outpatient prescribing. Emergency departments might be an environmental source of CDI; further investigation of their contribution to CDI transmission is needed.
Background: HIV incidence among US young, black men who have sex with men (YBMSM) is high, and structural barriers (eg lack of health insurance) may limit access to Pre-exposure prophylaxis (PrEP). Research studies conducted with YBMSM must ensure access to the best available HIV prevention methods, including PrEP. Methods: We implemented an optional, nonincentivized PrEP program in addition to the standard HIV prevention services in a prospective, observational cohort of HIV-negative YBMSM in Atlanta, GA. Provider visits and laboratory costs were covered; participant insurance plans and/or the manufacturer assistance program were used to obtain drugs. Factors associated with PrEP initiation were assessed with prevalence ratios and time to PrEP initiation with Kaplan-Meier methods. Results: Of 192 enrolled YBMSM, 4% were taking PrEP at study entry. Of 184 eligible men, 63% indicated interest in initiating PrEP, 10% reported no PrEP interest, and 27% wanted to discuss PrEP again at a future study visit. Of 116 interested men, 46% have not attended a PrEP initiation appointment. Sixty-three men (63/184; 34%) initiated PrEP; 11/63 (17%) subsequently discontinued PrEP. The only factor associated with PrEP initiation was reported sexually transmitted infection in the previous year (prevalence ratio 1.50, 95% confidence interval: 1.002 to 2.25). Among interested men, median time to PrEP initiation was 16 weeks (95% confidence interval: 7 to 36). Conclusions: Despite high levels of interest, PrEP uptake may be suboptimal among YBMSM in our cohort even with amelioration of structural barriers that can limit use. PrEP implementation as the standard of HIV prevention care in observational studies is feasible; however, further research is needed to optimize uptake for YBMSM.
HIV-infected individuals are at increased risk of neurocognitive impairment compared to the general population. Studies suggest that, despite combination antiretroviral therapy (cART), HIV infection causes immune activation which results in neural damage; however, few data exist in HIV-infected youth. Methods: HIV-infected youth 8–26-years-old on cART with virological suppression were prospectively enrolled along with healthy controls. Neurocognitive performance was assessed by age-appropriate Wechsler Intelligence Scales. Soluble and cellular markers of T-lymphocyte and monocyte activation were measured by ELISA and flow cytometry, respectively. Results: 45 HIV-infected subjects and 21 controls were enrolled. Markers of T-cell and monocyte activation were higher in the HIV-infected subjects compared to controls, but proportions of inflammatory and patrolling monocytes were similar. Although there were no significant differences in neurocognitive scores between the HIV-infected and control groups, scores were low-average for four of five testing domains for the HIV-infected subjects and average for all five in the controls, and % of HIV-infected subjects with scores classified as ‘low average’ or below was higher than in the controls. Variables most associated with neurocognitive performance among HIV-infected subjects included activated CD4 + T-cells (% CD4+CD38+HLA-DR), monocyte activation (soluble CD14), HIV duration, age and sex. Conclusions: HIV-infected youth on cART with virological suppression show subtle evidence of neurocognitive impairment compared to healthy controls, and increased immune activation appears to play a role. Additional studies are needed to develop strategic interventions beyond cART to potentially improve neurocognitive performance and/or minimize further impairment in this vulnerable population. ClinicalTrials.gov Identifier: NCT01523496.
The transmission of tuberculosis is complex. Necessary factors include a source case with respiratory disease that has developed sufficiently for Mycobacterium tuberculosis to be present in the airways. Viable bacilli must then be released as an aerosol via the respiratory tract of the source case. This is presumed to occur predominantly by coughing but may also happen by other means. Airborne bacilli must be capable of surviving in the external environment before inhalation into a new potential host-steps influenced by ambient conditions and crowding and by M. tuberculosis itself. Innate and adaptive host defenses will then influence whether new infection results; a process that is difficult to study owing to a paucity of animal models and an inability to measure infection directly. This review offers an overview of these steps and highlights the many gaps in knowledge that remain.