The impact of influenza vaccination on infection, hospitalisation and mortality in the Netherlands between 2003 and 2015.

Influenza epidemics annually cause substantial morbidity and mortality. For this reason, vaccination is offered yearly to persons with an elevated risk for complications. Assessments of the impact of vaccination are, however, hampered by year-to-year variation in epidemic size and vaccine effectiveness. We estimate the impact of the current vaccination programme comparing simulations with vaccination to counterfactual simulations without vaccination. The simulations rely on an age- and risk-structured transmission model that tracks the build-up and loss of immunity over successive seasons, and that allows the vaccine match to vary between seasons. The model parameters are estimated with a particle Monte Carlo method and approximate Bayesian computation, using epidemiological data on vaccine effectiveness and epidemic size in the Netherlands over a period of 11 years. The number of infections, hospitalisations and deaths vary greatly between years because waning of immunity and vaccine match may differ every season, which is in line with observed variation in influenza epidemic sizes. At an overall coverage of 21%, vaccination has averted on average 13% (7.2-19%, 95% range) of infections, 24% (16-36%) of hospitalisations, and 35% (16-50%) of deaths. This suggests that vaccination is mainly effective in protecting vaccinees from infection rather than reducing transmission. As the Dutch population continues to grow and age, the vaccination programme is projected (up to 2025) to gain in impact, despite a decreasing infection attack rate

Empathy Gaps Between Helpers and Help-Seekers: Implications for Cooperation

Help-seekers and potential helpers often experience an “empathy gap” – an inability to understand each other’s unique perspectives. Both parties are concerned about their reputation, self-esteem, and relationships, but these concerns differ in ways that lead to misinterpretation of the other party’s actions, and, in turn, missed opportunities for cooperation. In this article, we review research that describes the role-specific concerns of helpers and help-seekers. We then review studies of emotional perspective-taking, which can help explain why help-seekers and helpers often experience empathy gaps. We go on to discuss recent work that illustrates the consequences of empathy gaps between helpers and help-seekers—social prediction errors that prevent helping and misguided intentions that can lead to unhelpful help. Finally, we discuss some promising directions for future research

Variation in loss of immunity shapes influenza epidemics and the impact of vaccination.

Protective antibody immunity against the influenza A virus wanes in 2-7 years due to antigenic drift of the virus' surface proteins. The duration of immune protection is highly variable because antigenic evolution of the virus is irregular. Currently, the variable nature of the duration of immunity has had little attention in analyses of the impact of vaccination, including cost-effectiveness studies

Comparison of the transmission characteristics of low and high pathogenicity avian influenza virus (H5N2)

Low pathogenicity avian influenza A strains (LPAI) of the H5 and H7 type are noted for their ability to transform into highly pathogenic counterparts (HPAI). Here we compare the transmission characteristics in poultry of LPAI H5N2 (A/Chicken/Pennsylvania/83) and corresponding HPAI virus by means of transmission experiments. In the experiments, five inoculated animals are placed in a cage with five contact animals, and the infection chain is monitored by taking blood samples, and samples from the trachea and cloaca. The data are analysed by final size methods and a generalized linear model. The results show that HPAI virus is more infectious and induces a longer infectious period than LPAI. In fact, fully susceptible animals are invariably infected when confronted with HPAI virus and die within six days after infection. Animals previously infected with LPAI virus, on the other hand, survive an infection with HPAI virus or escape infection all together. This implies that a previous infection with LPAI virus effectively reduces susceptibility of the host to infection and decreases transmission of HPAI virus. We discuss the implications of these conclusions for the control and evolution of avian influenza viruses

A novel doxorubicin-glucuronide prodrug DOX-GA3 for tumour-selective chemotherapy: distribution and efficacy in experimental human ovarian cancer

The doxorubicin (DOX) prodrug N -[4-doxorubicin- N -carbonyl (oxymethyl) phenyl] O -β-glucuronyl carbamate (DOX-GA3) was synthesised for specific activation by human β-glucuronidase, which is released in necrotic areas of tumour lesions. This novel prodrug was completely activated to the parent drug by human β-glucuronidase with V max= 25.0 μmol min–1mg–1and K m= 1100 μM. The pharmacokinetics and distribution of DOX-GA3 in nude mice bearing human ovarian cancer xenografts (OVCAR-3) were determined and compared with DOX. Administration of DOX at 8 mg kg–1i.v. (maximum tolerated dose, MTD) to OVCAR-3-bearing mice resulted in a peak plasma concentration of the drug of 16.4 μM (t = 1 min). A 7.6-times lower peak plasma concentration of DOX was measured after injection of DOX-GA3 at 250 mg kg–1i.v. (50% of MTD). In normal tissues the prodrug showed peak DOX concentrations that were up to 5-fold (heart) lower than those found after DOX administration. DOX-GA3 activation by β-glucuronidase in the tumour yielded an almost 5-fold higher DOX peak concentration of 9.57 nmol g–1(P< 0.05) than the peak concentration of only 2.14 nmol g–1observed after DOX. As a consequence, the area under the curve of DOX calculated in tumour tissue after DOX-GA3 (13.1 μmol min–1g–1) was 10-fold higher than after DOX (1.31 μmol min–1g–1). The anti-tumour effects of DOX-GA3 and DOX were compared at equitoxic doses in OVCAR-3 xenografts at a mean tumour size of 125 mm3. The prodrug given i.v. at 500 mg kg–1weekly × 2 resulted in a maximum tumour growth inhibition of 87%, while the standard treatment with DOX at a dose of 8 mg kg–1i.v. weekly × 2 resulted in a maximum tumour growth inhibition of only 56%. Treatment with DOX-GA3 was also given to mice with larger tumours containing more necrosis. For tumours with a mean size of 400 mm3the specific growth delay by DOX-GA3 increased from 2.7 to 3.9. Our data indicate that DOX-GA3 is more effective than DOX and suggest that the prodrug will be specifically advantageous for treatment of advanced disease. © 2001 Cancer Research Campaign http://www.bjcancer.co