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Air pollution is defined as the presence of noxious substances in the air at levels that impose a health hazard. Thus, there has been long-standing interest in the possible role of indoor and outdoor air pollutants on the development of respiratory disease. In this regard, asthma has been of particular interest but many studies have also been conducted to explore the relationship between air pollution, allergic rhinitis, and atopic dermatitis. Traffic-related air pollutants or TRAP refers to a broad group of pollutants including elemental carbon, black soot, nitrogen dioxide (NO2), nitric oxide (NO), sulfur dioxide (SO2), particulate matter (PM2.5 and PM10), carbon monoxide (CO), and carbon dioxide (CO2). In this review, we aim to examine the current literature regarding the impact of early childhood exposure to TRAP on the development of asthma, allergic rhinitis, and atopic dermatitis. Although there is growing evidence suggesting significant associations, definitive conclusions cannot be made with regard to the effect of TRAP on these diseases. This conundrum may be due to a variety of factors, including different definitions used to define TRAP, case definitions under consideration, a limited number of studies, variation in study designs, and disparities between studies in consideration of confounding factors. Regardless, this review highlights the need for future studies to be conducted, particularly with birth cohorts that explore this relationship further. Such studies may assist in understanding more clearly the pathogenesis of these diseases, as well as other methods by which these diseases could be treated.

•CMV seronegative girls between 12 and 17 years of age received CMV glycoprotein B (gB) vaccine with MF59 or saline placebo at 0, 1 and 6 months.•The vaccine was generally well tolerated, although local and systemic adverse events were significantly more common in the vaccine group.•In the per protocol population vaccine efficacy was 43% after 3 doses, p=0.20 and 45%, p=0.08 after 2 doses.•We conclude the vaccine was safe and immunogenic and although the efficacy did not reach significance, the results are consistent with a previous study in adult women (Pass et al NEJM 360:1191, 2009) using the same formulation. Cytomegalovirus (CMV) is a leading cause of congenital infection and an important target for vaccine development. CMV seronegative girls between 12 and 17 years of age received CMV glycoprotein B (gB) vaccine with MF59 or saline placebo at 0, 1 and 6 months. Blood and urine were collected throughout the study for evidence of CMV infection based on PCR and/or seroconversion to non-vaccine CMV antigens. 402 CMV seronegative subjects were vaccinated (195 vaccine, 207 placebo). The vaccine was generally well tolerated, although local and systemic adverse events were significantly more common in the vaccine group. The vaccine induced gB antibody in all vaccine recipients with a gB geometric mean titer of 13,400EU; 95%CI 11,436, 15,700, after 3 doses. Overall, 48 CMV infections were detected (21 vaccine, 27 placebo). In the per protocol population (124 vaccine, 125 placebo) vaccine efficacy was 43%; 95%CI: −36; 76, p=0.20. The most significant difference was after 2 doses, administered as per protocol; vaccine efficacy 45%, 95%CI: −9; 72, p=0.08. The vaccine was safe and immunogenic. Although the efficacy did not reach conventional levels of significance, the results are consistent with a previous study in adult women (Pass et al. N Engl J Med 2009;360:1191) using the same formulation.

With the advent of the rotavirus vaccine, the causes of acute gastroenteritis in children are evolving. In this report from three sentinel U.S. sites, norovirus is identified as a leading causal organism in acute gastroenteritis in children. Norovirus-associated acute gastroenteritis is characterized by the sudden onset of intense vomiting and dehydrating diarrhea, typically lasting 1 to 3 days, with high rates of transmission to persons of all ages. 1 Norovirus is a leading etiologic pathogen implicated in severe gastroenteritis outbreaks in the United States. 2 , 3 However, the endemic burden of norovirus-associated acute gastroenteritis identified through active, laboratory-confirmed surveillance of U.S. pediatric populations has not been fully characterized. Given the substantial decline in pediatric rotavirus-associated acute gastroenteritis in the United States since the introduction of rotavirus vaccines, 4 – 8 and given recent advances in the development of candidate norovirus vaccines, . . .

Herpes simplex virus type 1 (HSV-1) and herpes simplex virus type 2 (HSV-2) are two of the most prevalent human viruses worldwide. They are known to cause a variety of diseases including genital herpes, meningitis, encephalitis, cold sores and herpes stromal keratitis. The seropositive rate for HSV-1 is around 90%, whereas for HSV-2 it remains around 20–25% for the general adult population. The infections caused by these viruses remain difficult to study because a large proportion of infected individuals are asymptomatic. Furthermore, given the neurotropic characteristics of the virus, studies aimed at understanding the complex pathogenesis in humans is difficult. As a result, animal models have been developed to understand several characteristics of HSV biology, pathogenesis, disease and host responses to infection. These models are also commonly used as the first evaluation of new drugs and vaccines. There are several well-established animal models to study infection with HSV, including mice, guinea pigs and rabbits. Variables within the animal models depend on the species of animal, route of infection, viral strain, dosage, etc. This review aims at summarizing the most commonly used animal models to study HSV pathogenesis and therapies.

In this study of 34,989 births, a PCR-based detection method was found to have reasonable sensitivity and specificity for identifying congenital CMV from either liquid or dried saliva. This advance has implications for a variety of potential detection strategies. Cytomegalovirus (CMV) is a frequent cause of congenital infection and a leading nongenetic cause of sensorineural hearing loss. 1 – 5 In most infants with congenital CMV infection, clinical abnormalities do not manifest at birth; rather, the infection is asymptomatic. However, sensorineural hearing loss eventually develops in approximately 10 to 15% of CMV-positive children, 3 , 4 , 6 – 8 in a substantial proportion who are not diagnosed by means of newborn hearing screening. 7 – 9 Screening of newborns for CMV infection will permit early identification of at-risk congenitally infected infants for purposes of targeted monitoring and intervention during critical stages of speech and language development. . . .

There is no vaccine to prevent herpes simplex virus (HSV) infection. In this trial in 8323 women, a candidate HSV vaccine containing glycoprotein D was found to be ineffective in preventing HSV-2 infection. Both herpes simplex virus type 1 (HSV-1) and type 2 (HSV-2) can cause primary infection of the genital tract, and HSV-1 infection has become an increasingly frequent cause of genital disease. 1 The majority of HSV infections are asymptomatic, and only 10 to 25% of persons with HSV-2 antibodies have recurrent genital disease. 2 , 3 Transmission of HSV from infected women to neonates may lead to severe neurologic disease or death in the newborn. Strategies to control genital herpes infection and disease have mainly focused on antiviral chemotherapy, education, and the use of condoms. The availability of an effective prophylactic vaccine would . . .

Background. Genital herpes simplex virus type 2 (HSV-2) infection causes recurrent lesions and frequent viral shedding. GEN-003 is a candidate therapeutic vaccine containing HSV-2 gD2△ TMR and ICP4.2, and Matrix-M2 adjuvant. Methods. Persons with genital herpes were randomized into 3 dose cohorts to receive 3 intramuscular doses 21 days apart of 10 μg, 30 μg, or 100 μg of GEN-003, antigens without adjuvant, or placebo. Participants obtained genital swab specimens twice daily for HSV-2 detection and monitored genital lesions for 28-day periods at baseline and at intervals after the last dose. Results. One hundred and thirty-four persons received all 3 doses. Reactogenicity was associated with adjuvant but not with antigen dose or dose number. No serious adverse events were attributed to GEN-003. Compared with baseline, genital HSV-2 shedding rates immediately after dosing were reduced with GEN-003 (from 13.4% to 6.4% for 30 μg [P < .001] and from 15.0% to 10.3% for 100 μg [P < .001]). Lesion rates were also significantly (P < .01) reduced immediately following immunization with 30 μg or 100 μg of GEN-003. GEN-003 elicited increases in antigen binding, virus neutralizing antibody, and T-cell responses. Conclusions. GEN-003 had an acceptable safety profile and stimulated humoral and cellular immune responses. GEN-003 at doses of 30 μg and 100 μg reduced genital HSV shedding and lesion rates. Clinical Trials Registration. NCT01667341 (funded by Genocea).

Saliva cytomegalovirus (CMV) polymerase chain reaction for newborn screening is highly sensitive. This study uses nationally published CMV seroprevalence and breastfeeding rates to demonstrate false-positive rates are unlikely to be significantly influenced by breastfeeding or other perinatal exposures. Abstract Real-time polymerase chain reaction (PCR) of saliva is highly sensitive for newborn congenital cytomegalovirus (CMV) screening. This study uses nationally published CMV seroprevalence and breastfeeding rates to estimate the contribution of CMV DNA in breast milk to false-positive saliva PCR results. The false-positive rates adjusted for breastfeeding ranged from 0.03% in white Hispanic persons to 0.14% in white non-Hispanic persons. Saliva CMV PCR for newborn screening is highly sensitive, and the low false-positive rates in this study suggest that saliva PCR results are unlikely to be significantly influenced by breastfeeding or other perinatal exposures.

Inhaler technique errors are common in chronic obstructive pulmonary disease (COPD) treatment, potentially leading to poor disease management. Our pooled analysis approach assessed correct use and ease-of-use of a placebo ELLIPTA dry-powder inhaler (DPI) in patients with COPD. Adults with COPD from open-label/non-blinded studies evaluating a placebo ELLIPTA DPI and reporting outcomes of correct use (based on the ELLIPTA DPI patient information leaflet [PIL]) and/or ease-of-use were included. Correct use and ease-of use at study end were primary and secondary endpoints, respectively. Data from patients in the placebo ELLIPTA DPI arm of each study were pooled, and the intent-to-treat (ITT) population was used for all analyses. Four placebo ELLIPTA DPI studies, reporting correct use (n = 4) and ease-of-use (n = 2), were included in the analysis. The ITT population comprised 1232 patients (mean age 66.2 years). For the primary endpoint, 80.1% (n = 975/1217) of patients demonstrated correct use at study end (95% confidence interval [CI]: 77.8%-82.3%). For the secondary endpoint, 95.7% (n = 797/833) of patients rated placebo ELLIPTA DPI use \"easy\"/\"very easy\" at study end (95% CI: 94.1%-97.0%). Correct use and \"easy\"/\"very easy\" user ratings remained high across younger (40-64 years) and older (≥65 years) age groups. Across age groups, most patients used the placebo ELLIPTA DPI correctly and rated it \"easy\"/\"very easy\" to use. Consistent with the Global Initiative for Chronic Obstructive Lung Disease 2021 report, our findings emphasize that proper training and clear instructions on PILs are important for optimal inhaler use.

Background. Noroviruses cause significant morbidity and mortality from acute gastroenteritis in all age groups worldwide. Methods.We conducted 2 phase 1 double-blind, controlled studies of a virus-like particle (VLP) vaccine derived from norovirus GI.1 genotype adjuvanted with monophosphoryl lipid A (MPL) and the mucoadherent chitosan. Healthy subjects 18–49 years of age were randomized to 2 doses of intranasal Norwalk VLP vaccine or controls 21 days apart. Study 1 evaluated 5-, 15-, and 50-μg dosages of Norwalk antigen, and study 2 evaluated 50-and 100-μg dosages. Volunteers recorded symptoms for 7 days after dosing, and safety was followed up for 180 days. Blood samples were collected for serological profile, antibody secreting cells (ASCs), and analysis of ASC homing receptors. Results. The most common symptoms were nasal stuffiness, discharge, and sneezing. No vaccine-related serious adverse events occurred. Norwalk VLP-specific immunoglobulin G and immunoglobulin A antibodies increased 4.8-and 9.1-fold, respectively, for the 100-μg dosage level. All subjects tested who received the 50-or 100-μg vaccine dose developed immunoglobulin A ASCs. These cells expressed molecules associated with homing to mucosal and peripheral lymphoid tissues. Conclusions. The intranasal monovalent adjuvanted Norwalk VLP vaccine was well tolerated and highly immunogenic and is a candidate for additional study. Trial Registration. ClinicalTrials.gov identifier: NCT00806962.