A comparative evaluation of sequence classification programs

Background

Here we present two new computer tools, PREMIM and EMIM, for the estimation of parental and child genetic effects, based on genotype data from a variety of different child-parent configurations. PREMIM allows the extraction of child-parent genotype data from standard-format pedigree data files, while EMIM uses the extracted genotype data to perform subsequent statistical analysis. The use of genotype data from the parents as well as from the child in question allows the estimation of complex genetic effects such as maternal genotype effects, maternal-foetal interactions and parent-of-origin (imprinting) effects. These effects are estimated by EMIM, incorporating chosen assumptions such as Hardy-Weinberg equilibrium or exchangeability of parental matings as required.

Results

In application to simulated data, we show that the inference provided by EMIM is essentially equivalent to that provided by alternative (competing) software packages such as MENDEL and LEM. However, PREMIM and EMIM (used in combination) considerably outperform MENDEL and LEM in terms of speed and ease of execution.

Conclusions

Together, EMIM and PREMIM provide easy-to-use command-line tools for the analysis of pedigree data, giving unbiased estimates of parental and child genotype relative risks.     

A model for influenza with vaccination and antiviral treatment

Compartmental models for influenza that include control by vaccination and antiviral treatment are formulated. Analytic expressions for the basic reproduction number, control reproduction number and the final size of the epidemic are derived for this general class of disease transmission models. Sensitivity and uncertainty analyses of the dependence of the control reproduction number on the parameters of the model give a comparison of the various intervention strategies. Numerical computations of the deterministic models are compared with those of recent stochastic simulation influenza models. Predictions of the deterministic compartmental models are in general agreement with those of the stochastic simulation models.     

Origin of the 1918 Spanish influenza virus: a comparative genomic analysis

To test the avian-origin hypothesis of the 1918 Spanish influenza virus we surveyed influenza sequences from a broad taxonomic distribution and collected 65 full-length genomes representing avian, human and "classic" swine H1N1 lineages in addition to numerous other swine (H1N2, H3N1, and H3N2), human (H2N2, H3N2, and H5N1), and avian (H1N1, H4N6, H5N1, H6N1, H6N6, H6N8, H7N3, H8N4, H9N2, and H13N2) subtypes. Amino acids from all eight segments were concatenated, aligned, and used for phylogenetic analyses. In addition, the genes of the polymerase complex (PB1, PB2, and PA) were analyzed individually. All of our results showed the Brevig-Mission/1918 strain in a position basal to the rest of the clade containing human H1N1s and were consistent with a reassortment hypothesis for the origin of the 1918 virus. Our genome phylogeny further indicates a sister relationship with the "classic" swine H1N1 lineage. The individual PB1, PB2, and PA phylogenies were consistent with reassortment/recombination hypotheses for these genes. These results demonstrate the importance of using a complete-genome approach for addressing the avian-origin hypothesis and predicting the emergence of new pandemic influenza strains.     

Removing barriers to global pandemic influenza vaccination

This article clarifies the regulatory issues surrounding influenza pandemic vaccine for the larger policy community and describes the need for regulatory harmonization. Vaccination would save lives in an influenza pandemic, but a lack of global manufacturing capacity will leave most of the world without access to vaccine. Capacity can be expanded if governments harmonize their regulatory policies. This article details the regulatory approaches taken by the United States, the European Union, and Japan for pandemic vaccine development, three regions that produce the majority of the world's seasonal influenza vaccine. They should quickly converge on regulatory requirements, intellectual property considerations, the use of recombinant DNA techniques for vaccine production, and technical issues about the composition of pandemic vaccine.     

Decreased elimination of theophylline after influenza vaccination.

The elimination of theophylline is decreased after vaccination against influenza. In three patients receiving 200 mg of oxtriphylline (equivalent to 128 mg of theophylline) every 6 hours by mouth the serum theophylline levels rose after vaccination, and in four healthy volunteers given the same dose of oxtriphylline 24 hours after vaccination the half-life of theophylline increased by an average of 122%. Two of the three patients showed signs of a toxic reaction to the drug. These results suggest that the elimination of theophylline is impaired to a clinically important degree after influenza vaccination and that the resulting levels of the drug can be toxic even when conventional therapeutic doses of theophylline are given.     

Effect of influenza vaccination in patients with asthma

BACKGROUND:Although annual influenza vaccination is recommended for persons with asthma, its effectiveness in this patient population is not well described. We evaluated the effect of influenza vaccination in the current and previous seasons in preventing influenza among people with asthma.METHODS:Using population health data from the Navarre region of Spain for the 2015/16 to 2019/20 influenza seasons, we conducted a test-negative case–control study to assess the effect of influenza vaccination in the current and 5 previous seasons. From patients presenting to hospitals and primary health care centres with influenza-like illness who underwent testing for influenza, we estimated the effects of influenza vaccination among patients with asthma overall and between those presenting as inpatients or outpatients, as well as between patients with and without asthma.RESULTS:Of 1032 patients who had asthma and were tested, we confirmed that 421 had influenza and the remaining 611 were test-negative controls. We found that the average effect of influenza vaccination was 43% (adjusted odds ratio [OR] 0.57, 95% confidence interval [CI] 0.40 to 0.80) for current-season vaccination regardless of previous doses, and 38% (adjusted OR 0.62, 95% CI 0.39 to 0.96) for vaccination in previous seasons only. Effects were similar for outpatients and inpatients. Among patients with asthma and confirmed influenza, current-season vaccination did not reduce the odds of hospital admission (adjusted OR 1.05, 95% CI 0.51 to 2.18). Influenza vaccination effects were similar for patients with and without asthma.INTERPRETATION:We estimated that, on average, current or previous influenza vaccination of people with asthma prevented almost half of influenza cases. These results support recommendations that people with asthma receive influenza vaccination.

Influenza can lead to serious complications in people with risk factors, and the main preventive measure is vaccination. ¹ Influenza infection can exacerbate symptoms of asthma. Because people with asthma have an increased risk of severe complications and hospital admission when infected with influenza virus,^2–5 annual influenza vaccination is recommended worldwide for people with asthma.^1,5–8People who are targeted for influenza vaccination frequently accumulate several doses over successive years,⁹ and adherence to influenza vaccination has been found to be higher in those with asthma.¹⁰ Patients with asthma frequently receive long-term corticosteroid treatment (inhaled or oral), therefore, their systemic immunity may have a reduced response to vaccines.^5,11,12Effectiveness of influenza vaccines in preventing primary health care consultations or hospital admissions in people with asthma has been evaluated in observational studies,^13–15 but we are unaware of any studies that compared the effect in preventing outpatient and inpatient cases or assessed the effect of vaccination in previous seasons.^13,16 The test-negative design is the suggested method to evaluate effectiveness of influenza vaccines in preventing laboratory-confirmed influenza, because it achieves good comparability and control of bias.^17–19 Only 1 study used this method for people with asthma over several seasons.¹³ The pooled analysis of several seasons, the inclusion of inpatients and outpatients, and consideration of vaccination history would provide a complete view of the effect of influenza vaccination in people with asthma.Our objective was to assess the average effect of influenza vaccination status in the current and previous seasons on preventing laboratory-confirmed influenza among people with asthma. We also aimed to compare these estimates with those of the target population for influenza vaccination.     

Measuring the performance of vaccination programs using cross-sectional surveys: a likelihood framework and retrospective analysis

Background

The performance of routine and supplemental immunization activities is usually measured by the administrative method: dividing the number of doses distributed by the size of the target population. This method leads to coverage estimates that are sometimes impossible (e.g., vaccination of 102% of the target population), and are generally inconsistent with the proportion found to be vaccinated in Demographic and Health Surveys (DHS). We describe a method that estimates the fraction of the population accessible to vaccination activities, as well as within-campaign inefficiencies, thus providing a consistent estimate of vaccination coverage.

Methods and Findings

We developed a likelihood framework for estimating the effective coverage of vaccination programs using cross-sectional surveys of vaccine coverage combined with administrative data. We applied our method to measles vaccination in three African countries: Ghana, Madagascar, and Sierra Leone, using data from each country''s most recent DHS survey and administrative coverage data reported to the World Health Organization. We estimate that 93% (95% CI: 91, 94) of the population in Ghana was ever covered by any measles vaccination activity, 77% (95% CI: 78, 81) in Madagascar, and 69% (95% CI: 67, 70) in Sierra Leone. “Within-activity” inefficiencies were estimated to be low in Ghana, and higher in Sierra Leone and Madagascar. Our model successfully fits age-specific vaccination coverage levels seen in DHS data, which differ markedly from those predicted by naïve extrapolation from country-reported and World Health Organization–adjusted vaccination coverage.

Conclusions

Combining administrative data with survey data substantially improves estimates of vaccination coverage. Estimates of the inefficiency of past vaccination activities and the proportion not covered by any activity allow us to more accurately predict the results of future activities and provide insight into the ways in which vaccination programs are failing to meet their goals. Please see later in the article for the Editors'' Summary     

A comparison of methods for estimating raccoon abundance: Implications for disease vaccination programs

Accurate estimates of demographic parameters are critical to the management of wildlife populations, including management programs focused on controlling the spread of zoonotic diseases. Rabies managers in the United States Department of Agriculture (USDA) have applied a simple raccoon (Procyon lotor) abundance index (RAI) based on cumulative catch of unique raccoons per unit area to determine vaccine-bait distribution densities. This approach was designed to allow for both the collection of biological samples and to index raccoon abundance to determine bait densities for oral rabies programs. However, post-baiting surveillance data indicate that, on average, only 30% of raccoons sampled have vaccine induced rabies antibody titers, suggesting that bait densities may not be well calibrated to raccoon densities. We trapped raccoons using both capture-mark-recapture (CMR) and the standard RAI to evaluate the accuracy of the current index-based methodology for estimating raccoon density. We then developed a resource selection function from spatial data collected from radio-collared raccoons to standardize trap placement within the existing RAI protocol, and evaluated the performance of this modified RAI approach relative to CMR for estimating raccoon population size. Both abundance and density estimates derived using the RAI consistently underestimated raccoon population sizes compared with CMR methods. Similarly, although the use of resource selection models to inform trap placement appeared to improve the accuracy of the RAI, the effectiveness of this method was inconsistent because of an inability to account for variance in detection probabilities. Despite the logistical advantages of using indices to estimate population parameters to determine vaccine bait distribution densities, our results suggest that adjustments may be necessary to more accurately quantify raccoon abundance, which should improve the effectiveness of rabies management in the United States. In particular, estimates of detection probabilities are needed to more precisely quantify abundance estimates and ensure appropriate vaccine coverage rates. © 2012 The Wildlife Society.