Cuticular profiling of insecticide resistant Aedes aegypti.

Insecticides have made great strides in reducing the global burden of vector-borne disease. Nonetheless, serious public health concerns remain because insecticide-resistant vector populations continue to spread globally. To circumvent insecticide resistance, it is essential to understand all contributing mechanisms. Contact-based insecticides are absorbed through the insect cuticle, which is comprised mainly of chitin polysaccharides, cuticular proteins, hydrocarbons, and phenolic biopolymers sclerotin and melanin. Cuticle interface alterations can slow or prevent insecticide penetration in a phenomenon referred to as cuticular resistance. Cuticular resistance characterization of the yellow fever mosquito, Aedes aegypti , is lacking. In the current study, we utilized solid-state Nuclear Magnetic Resonance (ssNMR) spectroscopy, gas chromatography/mass spectrometry (GC-MS), and transmission electron microscopy (TEM) to gain insights into the cuticle composition of congenic cytochrome P450 monooxygenase insecticide resistant and susceptible Ae. aegypti . No differences in cuticular hydrocarbon content or phenolic biopolymer deposition were found. In contrast, we observed cuticle thickness of insecticide resistant Ae. aegypti increased over time and exhibited higher polysaccharide abundance. Moreover, we found these local cuticular changes correlated with global metabolic differences in the whole mosquito, suggesting the existence of novel cuticular resistance mechanisms in this major disease vector.

An incremental economic evaluation of targeted and universal influenza vaccination in pregnant women.

OBJECTIVE: Pregnancy is associated with increased influenza hospitalizations and physician visits (events) in healthy women and those with co-morbidities. Annual influenza immunization is recommended for all pregnant women. Although vaccination is expected to reduce influenza-related events, the economic implications are unclear. We developed an economic model to estimate the cost-effectiveness (CE) of different vaccination strategies in Nova Scotia. METHODS: A decision tree characterized the one-year costs and consequences of targeted (pregnant women with co-morbidities only) and universal (all pregnant women) vaccination strategies relative to a no-vaccination strategy. Baseline event probabilities, vaccine effectiveness, costs and quality-of-life weights were derived from individual-level Nova Scotia administrative databases, health system sources and published reports. Sensitivity analyses tested the impact of varying key parameters, including vaccine effectiveness and mode of delivery. RESULTS: Targeted vaccination was cost-saving relative to no vaccination when delivered by public health clinics (PHC) or routine family practitioner (FP) visit. Cost per quality-adjusted life year gained by universal vaccination relative to targeted strategy was < $40,000 when delivered by PHC or routine FP visit. Net cost of universal vaccination by PHC or a routine FP visit was < $10 per pregnant woman. CONCLUSION: Universal vaccination of pregnant women appears cost-effective when delivered by PHC or as part of a routine FP prenatal visit. Targeted vaccination of pregnant women with co-morbidities can be cost-saving, but the possibility of higher vaccine uptake with a universal compared to a targeted strategy must be considered in addition to costs in program planning.

Meningococcal serogroup C conjugate vaccination in Canada: how far have we progressed? How far do we have to go?

Since routine meningococcal C conjugate vaccination was introduced into Canada in 2002, there have been a large regional variation in the routine programs, changes to the timing of the infant series in some provinces, and wide differences in catch-up programs. As immunization is viewed as a provincial responsibility, less attention has been paid to determining national coverage rates and the direct and indirect effects of the widely varying provincial/territorial vaccination programs on the nation as a whole. Canada's disjointed regional immunization campaigns leave the population at risk of disease for an extended length of time. The United Kingdom has proven that with a pro-active approach to planning, coordination, and implementation of a national immunization program, excellent long-term control of invasive meningococcal disease in a large population could be achieved in as little as one year. A summation of the current meningococcal immunization strategies used in Canada and an estimate of overall vaccine coverage of children and youth is provided.

Optimizing the delivery and use of a new monoclonal antibody in children with congenital heart disease: a successful provincial respiratory syncytial virus prophylaxis program.

OBJECTIVES: To describe a program for passive immunization against respiratory syncytial virus infection in infants with hemodynamically significant congenital heart disease (CHD) in accordance with the Canadian Paediatric Society recommendations. METHODS: A provincial coordinating committee composed of specialists in pediatrics, cardiology, infectious diseases, neonatology and public health collaborated to develop and implement a program to identify children with hemodynamically significant heart disease and offer respiratory syncytial virus prophylaxis. Database records for all children younger than two years of age who were seen by the provincial pediatric cardiology referral service were reviewed. Children with hemodynamically significant heart disease, as determined by a clinical assessment and echocardiography, were considered to be eligible for monthly palivizumab prophylaxis for five winter months. All physicians in the province were notified that approval of the provincial cardiology service was required for prophylaxis to be administered. Immunization rates were compared with projected rates based on the expected population-based immunization rates in infants with CHD in other provinces. RESULTS: 401 children with any cardiac diagnoses were identified, representing 545 potential patient-seasons of prophylaxis over two years in a birth cohort of 20,173 and 19,227 children, in each respective season (13.8 patient-seasons per 1000 births). Of these, 21 children were eligible for palivizumab prophylaxis according to the Canadian Paediatric Society criteria. All eligible children were immunized, and no ineligible children received the immunization. A review of palivizumab use in other provinces revealed highly variable rates of prophylaxis. CONCLUSIONS: The use of palivizumab for children with CHD can be optimized through a provincial model, in which children requiring prophylaxis are prospectively identified and reviewed by pediatric cardiologists -- and to whom evidence-based guidelines developed by a multidisciplinary team -- are applied. Such a model ensures that all patients requiring prophylaxis receive the appropriate immunization and avoids the immunization of low-risk children with CHD, in whom the benefits of palivizumab have not been proven.

The influence of genetic and environmental factors on plasma homocysteine concentrations in a population at high risk for coronary artery disease.

BACKGROUND: Elevated plasma total homocysteine (tHcy) predisposes to vascular disease and results from interactions between genetic and nutritional factors. MTHFR C(677)T increases tHcy in association with low folate. CBS 844ins68 lowers tHcy and negates the raising effect of MTHFR C(677)T in healthy subjects, but it is unclear if this is the case in subjects at high risk of vascular disease. This study examines the effect on plasma tHcy of interactions between these polymorphisms in an at-risk group. METHODS: Blood samples were collected from 376 subjects at increased risk of coronary artery disease. Plasma tHcy and vitamin B(6) were measured by HPLC and red cell folate and serum vitamin B(12) were measured by immuno-luminometric assay. MTHFR C(677)T and CBS 844ins68 status was established by standard PCR techniques. RESULTS: MTHFR TT predisposed to hyperhomocysteinaemia; this was increased in the presence of low folate (P<0.05) and vitamin B(12) (P<0.01). An inverse relationship was found between tHcy and folate (r=-0.42, P<0.0001), vitamin B(12) (r=-0.26, P<0.0005) and vitamin B(6) (r=-0.25, P<0.01). There was no interaction between plasma tHcy, vitamins or MTHFR C(677)T and CBS 844ins68. DISCUSSION: In this population at high risk of coronary artery disease, plasma tHcy was determined by vitamin status. This was exacerbated by the MTHFR C(677)T mutation. CBS 844ins68 did not influence tHcy and did not negate the tHcy-raising effect of MTHFR C(677)T.

Influenza vaccine programs and pregnancy: a need for more evidence.

Influenza viruses are the most common cause of seasonal respiratory morbidity in the world. Annual influenza vaccination is recommended for persons at high risk for serious disease. In the United States, in 2004, the Advisory Committee on Immunization Practices added all pregnant women to its high-risk list. In Canada, the National Advisory Committee on Immunization only includes pregnant women who have other underlying risk factors in the high-priority category for influenza immunization. This commentary provides an overview of maternal morbidity in pandemic and nonpandemic influenza seasons as well as a list of research questions whose answers are needed for evidence-based public health policy in this area.

Effects of enhanced patient education on compliance with silicone gel sheeting and burn scar outcome: a randomized prospective study.

The purpose of this study was to determine whether enhanced patient education increases compliance with silicone gel sheeting (SGS) on hypertrophic (HT) scars and to determine whether this results in any improvement in scar outcome. Outpatients with a HT burn scar were randomized to either a conventional education group (CEG), which received routine instruction on the use of SGS or to an enhanced education Group (EEG), which also received routine instruction, along with a detailed 5-page handout and a 26-minute videotape. The CEG (n = 12, 67% male, age 38 +/- 10 years) and the EEG (n = 13, 77% male, age 47 +/- 10 years) were followed monthly for 6 months. Subjects in the EEG wore SGS for 21.8 +/- 3.0 hr/day compared with only 10.1 +/- 7.5 hr/day of use in the CEG (P <.001). Scars in the EEG had significantly better Vancouver Scar Scale ratings for pigmentation (P =.02), height (P =.03), and pliability (P =.02) by 6 months. Patients in the EEG had significantly better subjective ratings for the parameters of scar itch (P =.01), color (P =.02), hardness (P =.01), and elevation (P =.01). Finally, scars in the EEG had significantly better ratings for border height (P =.002) and thickness (P =.01) at 6 months based on evaluation of digital photographs. Detailed multimedia patient education improves compliance with SGS and results in a better scar outcome.