The autoinducer-3 (AI-3)/epinephrine (Epi)/norepinephrine (NE) interkingdom signaling system mediates chemical communication between bacteria and their mammalian hosts. The three signals are sensed by the QseC histidine kinase (HK) sensor. Salmonella enterica serovar Typhimurium is a pathogen that uses HKs to sense its environment and regulate virulence. Salmonella serovar Typhimurium invades epithelial cells and survives within macrophages. Invasion of epithelial cells is mediated by the type III secretion system (T3SS) encoded in Salmonella pathogenicity island 1 (SPI-1), while macrophage survival and systemic disease are mediated by the T3SS encoded in SPI-2. Here we show that QseC plays an important role in Salmonella serovar Typhimurium pathogenicity. A qseC mutant was impaired in flagellar motility, in invasion of epithelial cells, and in survival within macrophages and was attenuated for systemic infection in 129x1/SvJ mice. QseC acts globally, regulating expression of genes within SPI-1 and SPI-2 in vitro and in vivo (during infection of mice). Additionally, dopamine β-hydroxylase knockout (Dbh -/- ) mice that do not produce Epi or NE showed different susceptibility to Salmonella serovar Typhimurium infection than wild-type mice. These data suggest that the AI-3/Epi/NE signaling system is a key factor during Salmonella serovar Typhimurium pathogenesis in vitro and in vivo. Elucidation of the role of this interkingdom signaling system in Salmonella serovar Typhimurium should contribute to a better understanding of the complex interplay between the pathogen and the host during infection.
by
Samantha I Pitts;
Nisa M Maruthur;
Gayle E Langley;
Tracy Pondo;
Kathleen A Shutt;
Rosemary Hollick;
Stephanie J Schrag;
Ann Thomas;
Megin Nichols;
Monica Farley;
James P Watt;
Lisa Miller;
William Schaffner;
Corinne Holtzman;
Lee H Harrison
Background. Rates of invasive group B Streptococcus (GBS) disease, obesity, and diabetes have increased in US adults. We hypothesized that obesity would be independently associated with an increased risk of invasive GBS disease. Methods. We identified adults with invasive GBS disease within Active Bacterial Core surveillance during 2010-2012 and used population estimates from the Behavioral Risk Factor Surveillance System to calculate invasive GBS incidence rates. We estimated relative risks (RRs) of invasive GBS using Poisson analysis with offset denominators, with obesity categorized as class I/II (body mass index [BMI] = 30-39.9 kg/m2) and class III (BMI ≥ 40.0 kg/m2). Results. In multivariable analysis of 4281 cases, the adjusted RRs of invasive GBS disease were increased for obesity (class I/ II: RR, 1.52; 95% confidence interval [CI], 1.14-2.02; and class III: RR, 4.87; 95% CI, 3.50-6.77; reference overweight) and diabetes (RR, 6.04; 95% CI, 4.77-7.65). The adjusted RR associated with class III obesity was 3-fold among persons with diabetes (95% CI, 1.38-6.61) and nearly 9-fold among persons without diabetes (95% CI, 6.41-12.46), compared with overweight. The adjusted RRs associated with diabetes varied by age and BMI, with the highest RR in young populations without obesity. Population attributable risks of invasive GBS disease were 27.2% for obesity and 40.1% for diabetes. Conclusions. Obesity and diabetes were associated with substantially increased risk of infection from invasive GBS. Given the population attributable risks of obesity and diabetes, interventions that reduce the prevalence of these conditions would likely reduce the burden of invasive GBS infection.
SETTING: Although diabetes mellitus (DM) is an established risk factor for active tuberculosis (TB) disease, little is known about the association between pre-DM, DM, and latent tuberculous infection (LTBI).
OBJECTIVE: To estimate the association between DM and LTBI. DESIGN: We conducted a cross-sectional study among recently arrived refugees seen at a health clinic in Atlanta, GA, USA, between 2013 and 2014. Patients were screened for DM using glycosylated-hemoglobin (HbA1c), and for LTBI using the QuantiFERONw-TB (QFT) test. HbA1c and QFT results, demographic information, and medical history were abstracted from patient charts.
RESULTS: Among 702 included patients, 681 (97.0%) had HbA1c and QFT results. Overall, 54 (7.8%) patients had DM and 235 (33.8%) had pre-DM. LTBI was prevalent in 31.3% of the refugees. LTBI prevalence was significantly higher (P < 0.01) among patients with DM (43.4%) and pre-DM (39.1%) than in those without DM (25.9%). Refugees with DM (adjusted OR [aOR] 2.3, 95%CI 1.2-4.5) and pre-DM (aOR 1.7, 95%CI 1.1-2.4) were more likely to have LTBI than those without DM.
CONCLUSION: Refugees with DM or pre-DM from high TB burden countries were more likely to have LTBI than those without DM. Dysglycemia may impair the immune defenses involved in preventing Mycobacterium tuberculosis infection.
SETTING: The country of Georgia has a high burden of multi- (MDR-TB) and extensively drug-resistant tuberculosis (XDR-TB). OBJECTIVE: To assess the performance of the Geno- Type® MTBDRsl assay in the detection of resistance to kanamycin (KM), capreomycin (CPM) and ofloxacin (OFX), and of XDR-TB.
DESIGN: Consecutive acid-fast bacilli smear-positive sputum specimens identified as MDR-TB using the MTBDRplus test were evaluated with the MTBDRsl assay and conventional second-line drug susceptibility testing (DST).
RESULTS: Among 159 specimens, amplification was adequate in 154 (97%), including 9 of 9 culture-negative and 2 of 3 contaminated specimens. Second-line DST revealed that 17 (12%) Mycobacterium tuberculosis isolates were XDR-TB. Compared to DST, the MTBDRsl had 41% sensitivity and 98% specificity in detecting XDR-TB and 81% sensitivity and 99% specificity in detecting OFX resistance. Sensitivity was low in detecting resistance to KM (29%) and CPM (57%), while specificity was respectively 99% and 94%. Median times from sputum collection to second-line DST and MTBDRsl results were 70-104 vs. 10 days.
CONCLUSION: Although the MTBDRsl assay had a rapid turnaround time, detection of second-line drug resistance was poor compared to DST. Further genetic mutations associated with resistance to second-line drugs should be included in the assay to improve test performance and clinical utility.
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.
by
C Hendricks Brown;
David C. Mohr;
Carlos G. Gallo;
Christopher Mader;
Lawrence Palinkas;
Gina Wingood;
Guillermo Prado;
Sheppard G. Kellam;
Hilda Pantin;
Jeanne Poduska;
Robert Gibbons;
John McManus;
Mitsunori Ogihara;
Thomas Valente;
Fred Wulczyn;
Sara Czaja;
Geoff Sutcliffe;
Juan Villamar;
Christopher Jacobs
African Americans and Hispanics in the United States have much higher rates of HIV than non-minorities. There is now strong evidence that a range of behavioral interventions are efficacious in reducing sexual risk behavior in these populations. Although a handful of these programs are just beginning to be disseminated widely, we still have not implemented effective programs to a level that would reduce the population incidence of HIV for minorities. We proposed that innovative approaches involving computational technologies be explored for their use in both developing new interventions and in supporting wide-scale implementation of effective behavioral interventions. Mobile technologies have a place in both of these activities. First, mobile technologies can be used in sensing contexts and interacting to the unique preferences and needs of individuals at times where intervention to reduce risk would be most impactful. Second, mobile technologies can be used to improve the delivery of interventions by facilitators and their agencies. Systems science methods including social network analysis, agent-based models, computational linguistics, intelligent data analysis, and systems and software engineering all have strategic roles that can bring about advances in HIV prevention in minority communities. Using an existing mobile technology for depression and 3 effective HIV prevention programs, we illustrated how 8 areas in the intervention/implementation process can use innovative computational approaches to advance intervention adoption, fidelity, and sustainability.
SETTINGS: Three universities located in eastern Ethiopia: Haramaya University, Haramaya; Dire-Dawa University, Dire-Dawa; and Jigjiga University, Jigjiga. OBJECTIVES: To determine the burden of pulmonary tuberculosis (PTB) among university students and to identify risk factors for the development of TB disease. DESIGN: All full-time university students were screened for symptoms of PTB and sputum was collected for acid-fast bacilli (AFB) examination and culture for Mycobacterium tuberculosis. RESULTS: Of 35 344 students screened, we identified 153 PTB cases that occurred over the 1-year study period, or 433/100 000 students. Of these, 117 (76%) PTB cases were found through passive case finding at student health centres, while 36 (24%) previously undiagnosed patients were identified through active case finding. Sixteen cases detected using active case finding (44%) were smear-positive. Living in a dormitory with 75 students and attending university for 72 years were both significantly associated with PTB (adjusted OR 2.49 and 3.79, respectively, P, 0.001). In persons who underwent drug susceptibility testing, 11 (30.5%) had resistance to at least one first-line anti-tuberculosis drug. CONCLUSIONS: We found a high burden of TB among university students in eastern Ethiopia. Screening for PTB upon university admission and at regular intervals should be considered to minimise TB transmission on university campuses.
SETTING: Georgia has a high burden of tuberculosis (TB), including multidrug-resistant TB. Enhancing early diagnosis of TB is a priority to reduce transmission. OBJECTIVE: To quantify delays in TB diagnosis and identify risk factors for delay in the country of Georgia. DESIGN: In a cross-sectional study, persons with newly diagnosed, culture-confirmed pulmonary TB were interviewed within 2 months of diagnosis and medical and laboratory records were abstracted. RESULTS: Among 247 persons enrolled, the mean and median total TB diagnostic delay was respectively 89.9 and 59.5 days. The mean and median patient delay was 56.2 and 23.5 days, while health care system delay was 33.7 and 14.0 days. In multivariable analysis, receipt of a medication prior to TB diagnosis was associated with increased overall diagnostic delay (adjusted odds ratio [aOR] 2.28, 95%CI 1.09-4.79); antibiotic use prior to diagnosis increased the risk of prolonged health care delay (aOR 4.16, 95%CI 1.97-8.79). TB cases who had increased patient-related diagnostic delay were less likely to have prolonged health care diagnostic delay (aOR 0.38, 95%CI 0.19-0.74). CONCLUSION: Prolonged delays in detecting TB are common in Georgia. Interventions addressing the misuse of antibiotics and targeting groups at risk for prolonged delay are warranted to reduce diagnostic delays and enhance TB control.
by
Allison Eckard;
Mary Ann O'Riordan;
Julia C. Rosebush;
Joshua H. Ruff;
Ann Chahroudi;
Danielle Labbato;
Julie E. Daniels;
Monika Uribe-Leitz;
Vin Tangpricha;
Grace A. McComsey
Background
Low bone mineral density (BMD) is a significant co-morbidity in HIV. However, studies evaluating vitamin D supplementation on bone health in this population are limited. This study investigates changes in bone health parameters after 12 months of supplementation in HIV-infected youth with vitamin D insufficiency.
Methods
This is a randomized, active-control, double-blind trial investigating changes in bone parameters with 3 different vitamin D3 doses [18,000 (standard/control dose), 60,000 (moderate dose) and 120,000 IU/monthly (high dose)] in HIV-infected youth 8–25 years old with baseline serum 25-hydroxyvitamin D (25(OH)D) concentrations <30 ng/mL. Bone mineral density and bone turnover markers were measured at baseline and 12 months.
Results
One hundred and two subjects enrolled. Over 12 months, serum 25(OH)D concentrations increased with all doses, but the high dose (i.e. 120,000 IU/monthly) maintained serum 25(OH)D concentrations in an optimal range (≥30 ng/mL or ≥20 ng/mL) throughout the study period for more subjects (85% and 93%, respectively) compared to either the moderate (54% and 88%, respectively) or standard dose (63% and 80%, respectively). All dosing groups showed some improvement in BMD; however, only the high-dose arm showed significant decreases in bone turnover markers for both procollagen type 1 amino-terminal propeptide (−3.7 ng/mL; P=0.001) and B-CrossLaps (−0.13 ng/mL; P=0.0005).
Conclusions
High dose vitamin D supplementation (120,000 IU/month) given over 12 months decreases bone turnover markers in HIV-infected youth with vitamin D insufficiency, which may represent an early, beneficial effect on bone health. High vitamin D doses are needed to maintain optimal serum 25(OH)D concentrations.
Tuberculosis (TB) cellular immune responses were examined in the breast milk of human immunodeficiency virus infected mothers using the T-SPOT®.TB interferon-gamma release assay (IGRA). Positive TB interferon-gamma (IFN-γ) responses were detected in 6 of 8 (75%) valid breast milk assays. Among 7 mothers with paired breast milk and blood assays, TB IFN-γ responses were higher in breast milk than in blood (P = 0.02). The magnitude of TB IFN-γ responses in maternal breast milk and blood were correlated. Elucidating the influence of TB immune responses in breast milk on infant TB susceptibility and immunity may inform future maternal TB vaccine strategies.