Status of oral rabies vaccination in wild carnivores in the United States

Persistence of multiple variants of rabies virus in wild Chiroptera and Carnivora presents a continuing challenge to medical, veterinary and wildlife management professionals. Oral rabies vaccination (ORV) targeting specific Carnivora species has emerged as an integral adjunct to conventional rabies control strategies to protect humans and domestic animals. ORV has been applied with progress toward eliminating rabies in red foxes (Vulpes vulpes) in western Europe and southern Ontario, Canada. More recently since 1995, coordinated ORV was implemented among eastern states in the U.S.A. to prevent spread of raccoon (Procyon lotor) rabies and to contain and eliminate variants of rabies virus in the gray fox (Urocyon cinereoargenteus) and coyote (Canis latrans) in Texas. In this paper, we describe the current cooperative ORV program in the U.S.A. and discuss the importance of coordination of surveillance and rabies control programs in Canada, Mexico and the U.S.A. Specifically, several priorities have been identified for these programs to succeed, which include additional oral vaccines, improved baits to reach target species, optimized ORV strategies, effective communication and legal strategies to limit translocation across ORV barriers, and access to sufficient long-term funding. These key priorities must be addressed to ensure that ORV has the optimal chance of achieving long range programmatic goals of eliminating specific variants of rabies virus in North American terrestrial carnivores.     

HIV-1 RNA levels and development of clinical disease in two different adolescent populations

HIV infection rates in American youth continue to increase unabated. As adolescent-specific therapeutic interventions are planned, information on HIV infection's course and its predictors becomes critically important for valid and precise study design. We report on age-specific disease rates stratified by estimated time since infected and predictors of HIV disease progression through four clinical categories in two distinct adolescent populations. Adolescents with hemophilia infected through contaminated blood products showed disease progression rates of 18 to 23 events per 100 person-years (PYs) by age and years infected. Predictors of first progression included HIV-1 RNA >30,000 copies/ml (rate ratio [RR], 2.4; 95% confidence interval [CI], 1.5-3.9), antiretroviral monotherapy (RR, 2.4; 95% CI, 1.7-3.3); Latino/a ethnicity (RR, 2.2; 95% CI, 1.2-4.2) and initial intermediate clinical status (RR, 1.9; 95% CI, 1.3-2.9). Sexually-infected adolescents >18 years who had been infected >3 to 6 years had a disease progression rate of 16 events per 100 PY. For these youths, the sole predictor of first progression was viral load (VL) (RR for VL >30,000 copies per ml, 8.4; 95% CI, 2.8-25.1). This article examines the predictive capacity of viral load and evaluates other cofactors for disease progression in different adolescent populations. These data will be of value in clinical trial design.     

Essential role for caspase 8 in T-cell homeostasis and T-cell-mediated immunity

Defects in death receptor-mediated apoptosis have been linked to cancer and autoimmune disease in humans. The in vivo role of caspase 8, a component of this pathway, has eluded analysis in postnatal tissues because of the lack of an appropriate animal model. Targeted disruption of caspase 8 is lethal in utero. We generated mice with a targeted caspase 8 mutation that is restricted to the T-cell lineage. Despite normal thymocyte development in the absence of caspase 8, we observed a marked decrease in the number of peripheral T-cells and impaired T-cell response ex vivo to activation stimuli. caspase 8 ablation protected thymocytes and activated T-cells from CD95 ligand but not anti-CD3-induced apoptosis, or apoptosis activated by agents that are known to act through the mitochondria. caspase 8 mutant mice were unable to mount an immune response to viral infection, indicating that caspase 8 deletion in T-cells leads to immunodeficiency. These findings identify an essential, cell-stage-specific role for caspase 8 in T-cell homeostasis and T-cell-mediated immunity. This is consistent with the recent identification of caspase 8 mutations in human immunodeficiency.     

Development of Coombs positive haemolytic anaemia in NZB mice injected with Freund's complete adjuvant

Intraperitoneal injection of young adult NZB mice with Freund's complete adjuvant emulsion, alone or incorporating BALB/c mouse erythrocytes, resulted in accelerated direct Coombs conversion and development of splenomegaly. Incorporation of adjuvant with NZB erythrocytes caused an accelerated reactivity in some animals, but in others resulted in a delayed Coombs conversion. In contrast, positive Coombs tests failed to develop at all in NZB mice injected with a Freund's complete adjuvant preparation containing ten times the usual amount of Mycobacterium. These observations might be explained in part by the relative influences of adjuvancy and of antigenic competition on the availability of precursor cells capable of responding to autoantigenic stimulation.     

Do adults in contact with Australia's public sector mental health services get better?

This paper describes the outcomes of episodes of care for adults in public sector mental health services across Australia, with a view to informing the debate on service quality. Health of the Nation Outcome Scales (HoNOS) change scores and effect sizes were calculated for 14,659 acute inpatient episodes and 23,692 community episodes. The results showed that people in contact with public sector mental health services generally do get better, although the magnitude of improvement depends on the setting and episode type. This confirmatory finding is particularly positive, given current community concerns about the quality and effectiveness of mental health services.     

Use of class II tetramers for identification of CD4+ T cells

Multivalent MHC class II molecules containing peptide antigens are useful tools for the detection of antigen specific human CD4+ T cells. Tetramers produced by exogenous peptide loading onto empty class II molecules are comparable to tetramers with peptide tethered to the class II chain covalently, but have many practical advantages. Conditions for optimal peptide loading to generate tetramers are discussed and optimal conditions of using tetramers for staining T cells are examined. As the frequency of antigen specific CD4+ T cells in peripheral blood is low, we demonstrate that an in vitro expansion step is effective in detecting low frequency T cells. Two new applications with tetramers, their uses for mapping T cell epitopes and for the detection of low affinity T cells are described. In a clinical setting, potential applications include using these reagents for monitoring disease progression during clinical intervention.