Intracellular cytokine production by dengue virus-specific T cells correlates with subclinical secondary infection.

The pathophysiology of dengue virus infection remains poorly understood, although secondary infection is strongly associated with more severe disease. In the present study, we performed a nested, case-control study comparing the responses of pre-illness peripheral blood mononuclear cells between children who would subsequently develop either subclinical or symptomatic secondary infection 6-11 months after the baseline blood samples were obtained and frozen. We analyzed intracellular cytokine production by CD4(+) and CD8(+) cells in response to stimulation with dengue antigen. We found higher frequencies of dengue virus-specific TNFα, IFNγ-, and IL-2-producing T cells among schoolchildren who subsequently developed subclinical infection, compared with those who developed symptomatic secondary dengue virus infection. Although other studies have correlated immune responses during secondary infection with severity of disease, to our knowledge this is the first study to demonstrate a pre-infection dengue-specific immune response that correlates specifically with a subclinical secondary infection.

Clinical development and regulatory points for consideration for second-generation live attenuated dengue vaccines.

Licensing and decisions on public health use of a vaccine rely on a robust clinical development program that permits a risk-benefit assessment of the product in the target population. Studies undertaken early in clinical development, as well as well-designed pivotal trials, allow for this robust characterization. In 2012, WHO published guidelines on the quality, safety and efficacy of live attenuated dengue tetravalent vaccines. Subsequently, efficacy and longer-term follow-up data have become available from two Phase 3 trials of a dengue vaccine, conducted in parallel, and the vaccine was licensed in December 2015. The findings and interpretation of the results from these trials released both before and after licensure have highlighted key complexities for tetravalent dengue vaccines, including concerns vaccination could increase the incidence of dengue disease in certain subpopulations. This report summarizes clinical and regulatory points for consideration that may guide vaccine developers on some aspects of trial design and facilitate regulatory review to enable broader public health recommendations for second-generation dengue vaccines.

Streptococcus anginosus Group Bacterial Infections.

BACKGROUND: The Streptococcus anginosus group (SAG) causes a variety of infections in adults. To better understand the burden of SAG infections and their associated morbidity and mortality, we conducted a retrospective analysis of these infections in adults at a tertiary care center. METHODS: A retrospective review of all cultures positive for SAG in adults and a corresponding review of the patients' medical records were conducted at a tertiary care facility in central New York. Patients with these cultures during the period of January 2007-December 2011 were included. Demographic data, area of residence, clinical features and underlying illnesses, site of infection, length of hospital stay, antibiotic susceptibility and antibiotic therapy were recorded and analyzed. RESULTS: There were 332 SAG cases; most patients were males (59%), mean age of 47 years and 84% lived in urban areas. Overall mortality was 3% with underlying conditions common such as diabetes (25%), hypertension (31%) and immunodeficiency (22%). Most of the infections were related to skin and soft tissue (72%) and polymicrobial (70%) with gram-negative anaerobes and Enterobacteriaceae commonly isolated with SAG. CONCLUSIONS: We present the largest study, thus far, reviewing the clinical presentation, management and outcome of infections due to the SAG of organisms. Notable findings from our study are the low mortality associated with SAG infection, and the propensity to present as a skin and tissue and polymicrobial infection. Our findings will assist clinicians in managing patients with SAG infections and recognizing that S anginosus may be one of several organisms responsible for infection.

Interferon alfacon1 is an inhibitor of SARS-corona virus in cell-based models.

Preliminary data examining interferon alfacon1 treatment of SARS-CoV (severe acute respiratory syndrome-corona virus)-infected patients suggests this therapy is well tolerated and of therapeutic benefit. We report herein that interferon alfacon1, has potent in vitro antiviral activity against SARS-CoV. In a cytopathic effect protection (CPE) assay, interferon alfacon1 inhibited the generation of CPE in a dose-dependent manner with an IC50 of 0.001 microg/ml, a clinically achievable level. Furthermore, interferon alfacon1 also demonstrated significant antiviral activity in yield reduction and plaque reduction assays. The in vitro antiviral activity of interferon alfacon1 against SARS-CoV suggests continued evaluation of interferon alfacon1 as a therapeutic treatment for patients infected with SARS-CoV.

Sustained transmission of dengue virus type 1 in the Pacific due to repeated introductions of different Asian strains.

Outbreaks of dengue due to dengue virus type 1 (DENV-1) occurred almost simultaneously in 2001 in Myanmar and at multiple sites almost 10,000 km away in the Pacific. Phylogenetic analyses of the E protein genes of DENV-1 strains recovered from Asia and the Pacific revealed three major viral genotypes (I, II, and III) with distinct clades within each. The majority of strains from the Pacific and Myanmar, and a number of other Asian strains fell into genotype I. Genotype II comprised a smaller set of Asian and Pacific strains, while genotype III contained viruses from diverse geographical localities. These analyses suggested that the continuing outbreak of dengue in the Pacific has been due to multiple, direct, introductions of dengue viruses from a variety of locations in Asia followed by local transmission. There was no evidence that the introduction of these viruses into the Pacific was associated with any adaptive changes in the E protein of the viruses.