RESUMEN
As influenza vaccination is now widely recommended, randomized clinical trials are no longer ethical in many populations. Therefore, observational studies on patients seeking medical care for acute respiratory illnesses (ARIs) are a popular option for estimating influenza vaccine effectiveness (VE). We developed a probability model for evaluating and comparing bias and precision of estimates of VE against symptomatic influenza from two commonly used case-control study designs: the test-negative design and the traditional case-control design. We show that when vaccination does not affect the probability of developing non-influenza ARI then VE estimates from test-negative design studies are unbiased even if vaccinees and non-vaccinees have different probabilities of seeking medical care against ARI, as long as the ratio of these probabilities is the same for illnesses resulting from influenza and non-influenza infections. Our numerical results suggest that in general, estimates from the test-negative design have smaller bias compared to estimates from the traditional case-control design as long as the probability of non-influenza ARI is similar among vaccinated and unvaccinated individuals. We did not find consistent differences between the standard errors of the estimates from the two study designs.
Asunto(s)
Virus de la Influenza A/inmunología , Vacunas contra la Influenza/normas , Gripe Humana/prevención & control , Modelos Teóricos , Probabilidad , Vacunación/normas , Sesgo , Estudios de Casos y Controles , Humanos , Vacunas contra la Influenza/inmunología , Gripe Humana/virología , Proyectos de InvestigaciónRESUMEN
Microsatellite markers were isolated and developed from Culex pipiens quinquefasciatus Say (Diptera: Culicidae) sampled in Johannesburg, South Africa, to identify those that are broadly useful for analyzing Cx. pipiens complex populations between continents. Suitable loci should be 1) inherited in a codominant Mendelian manner, 2) polymorphic, 3) selectively neutral, 4) randomly associated, 5) without null alleles, and 6) applicable across broad regions and between diverse biotypes. Loci in Cx. p. quinquefasciatus from Johannesburg ranged from two to 17 alleles per locus and expected heterozygosities (H(e)) were 0.02-0.87. Loci in Cx. p. pipiens L. from Johannesburg had five to 19 alleles per locus and H(e) values ranging from 0.57 to 0.93, whereas those from George, South Africa, had five to 17 alleles per locus and H(e) values ranging from 0.54 to 0.88. Loci in North American mosquitoes were more variable. Cx. p. quinquefasciatus from South Carolina had five to 19 alleles per locus and H(e) values ranging from 0.64 to 0.90, whereas Cx. p. pipiens from Massachusetts had six to 28 alleles per locus and with H(e) values ranging from 0.65 to 0.94. All loci were associated randomly. Overall, four of nine of these new loci satisfied all six criteria for broad utility for analyzing the genetic structure of Cx. pipiens populations.