Incidence of West Nile virus infection in the Dallas-Fort Worth metropolitan area during the 2012 epidemic.

The 2012 West Nile virus (WNV) epidemic was the largest since 2003 and the North Texas region was the most heavily impacted. We conducted a serosurvey of blood donors from four counties in the Dallas-Fort Worth area to characterize the epidemic. Blood donor specimens collected in November 2012 were tested for WNV-specific antibodies. Donors positive for WNV-specific IgG, IgM, and neutralizing antibodies were considered to have been infected in 2012. This number was adjusted using a multi-step process that accounted for timing of IgM seroreversion determined from previous longitudinal studies of WNV-infected donors. Of 4971 donations screened, 139 (2·8%) were confirmed WNV IgG positive, and 69 (1·4%) had IgM indicating infection in 2012. After adjusting for timing of sampling and potential seroreversion, we estimated that 1·8% [95% confidence interval (CI) 1·5-2·2] of the adult population in the Dallas-Fort Worth area were infected during 2012. The resulting overall estimate for the ratio of infections to reported WNV neuroinvasive disease (WNND) cases was 238:1 (95% CI 192-290), with significantly increased risk of WNND in older age groups. These findings were very similar to previous estimates of infections per WNND case, indicating no change in virulence as WNV evolved into an endemic infection in the United States.

Use of laboratory reports as predictors of West Nile virus disease cases, Texas, 2008-2012.

We evaluated laboratory reports as early indicators of West Nile virus (WNV) disease cases in Texas. We compared WNV laboratory results in the National Electronic Disease Surveillance System Base System (NBS) to WNV disease cases reported to the state health department from 2008 to 2012. We calculated sensitivity and positive predictive value (PPV) of NBS reports, estimated the number of disease cases expected per laboratory report, and determined lead and lag times. The sensitivity and PPV of NBS laboratory reports were 86% and 77%, respectively. For every 10 positive laboratory reports, we expect 9·0 (95% confidence interval 8·9-9·2) reported disease cases. Laboratory reports preceded case reports with a lead time of 7 days. Electronic laboratory reports provided longer lead times than manually entered reports (P < 0·01). NBS laboratory reports are useful estimates of future reported WNV disease cases and may provide timely information for planning public health interventions.

Estimated cumulative incidence of West Nile virus infection in US adults, 1999-2010.

West Nile virus (WNV) was first recognized in the USA in 1999. We estimated the cumulative incidence of WNV infection in the USA from 1999 to 2010 using recently derived age- and sex-stratified ratios of infections to WNV neuroinvasive disease (WNND) and the number of WNND cases reported to national surveillance. We estimate that over 3 million persons have been infected with WNV in the USA, with the highest incidence rates in the central plains states. These 3 million infections would have resulted in about 780 000 illnesses. A substantial number of WNV infections and illnesses have occurred during the virus' first decade in the USA.

Vector competence of Culex restuans (Diptera: Culicidae) from two regions of Chicago with low and high prevalence of West Nile virus human infections.

Vector competence studies for West Nile virus (WNV) were conducted for two Culex (Culex) restuans Theobald populations Edison Park (EP) and Illinois Medical District (IMD), in Chicago, IL. The aim was to determine if there were differences between mosquito populations that contributed to the observed differences in the prevalence of WNV. Percentages of orally infected, disseminated, and transmitting mosquitoes were estimated using a generalized linear mixed effects model including a random effect for family to account for anticipated within-family correlation. Analysis indicated that percentages of infected, disseminated, and transmitting mosquitoes were not significantly different between EP and IMD. The within-family correlation was 0.46 (95% CI 0.28, 0.67), indicating reasonably strong tendency for WNV titers of bodies, saliva, and legs within families to be similar. Overall, our results show that vector competence of Cx. restuans for WNV is not a contributing factor to the observed differences in WNV human cases between the EP and IMD areas of Chicago.

Transmission dynamics of primary pneumonic plague in the USA.

Plague is thought to have killed millions during three catastrophic pandemics. Primary pneumonic plague, the most severe form of the disease, is transmissible from person-to-person and has the potential for propagating epidemics. Efforts to quantify its transmission potential have relied on published data from large outbreaks, an approach that artificially inflates the basic reproductive number (R(0)) and skews the distribution of individual infectiousness. Using data for all primary pneumonic plague cases reported in the USA from 1900 to 2009, we determined that the majority of cases will fail to transmit, even in the absence of antimicrobial treatment or prophylaxis. Nevertheless, potential for sustained outbreaks still exists due to superspreading events. These findings challenge current concepts regarding primary pneumonic plague transmission.

Borreliacidal activity of saliva of the tick Amblyomma americanum.

Amblyomma americanum (Linneaus) (Acari: Ixodidae), an important tick vector of human and animal disease, is not a competent vector of the bacterial agent of Lyme disease, Borrelia burgdorferi, although its range overlaps the geographical distribution of Lyme disease within the United States. A possible mechanism that could prevent acquisition of B. burgdorferi spirochetes from infected hosts is the toxic effect of A. americanum saliva on B. burgdorferi. The data presented here indicate that after 24 and 48 h of exposure to A. americanum saliva, significantly fewer B. burgdorferi were alive compared to treatment controls as assessed by spirochete motility under dark-field microscopy and resistance to the dead stain, propidium iodide. After 48 h, fewer than 13% of saliva-exposed B. burgdorferi were alive. In contrast, significantly more B. burgdorferi exposed to Ixodes scapularis (Acari: Ixodidae) saliva survived after 24 or 48 h compared to A. americanum saliva or treatment controls.

Epidemic West Nile encephalitis, New York, 1999: results of a household-based seroepidemiological survey.

BACKGROUND: In the summer of 1999, West Nile virus was recognised in the western hemisphere for the first time when it caused an epidemic of encephalitis and meningitis in the metropolitan area of New York City, NY, USA. Intensive hospital-based surveillance identified 59 cases, including seven deaths in the region. We did a household-based seroepidemiological survey to assess more clearly the public-health impact of the epidemic, its range of illness, and risk factors associated with infection. METHODS: We used cluster sampling to select a representative sample of households in an area of about 7.3 km(2) at the outbreak epicentre. All individuals aged 5 years or older were eligible for interviews and phlebotomy. Serum samples were tested for IgM and IgG antibodies specific for West Nile virus. FINDINGS: 677 individuals from 459 households participated. 19 were seropositive (weighted seroprevalence 2.6% [95% CI 1.2-4.1). Six (32%) of the seropositive individuals reported a recent febrile illness compared with 70 of 648 (11%) seronegative participants (difference 21% [0-47]). A febrile syndrome with fatigue, headache, myalgia, and arthralgia was highly associated with seropositivity (prevalence ratio 7.4 [1.5-36.6]). By extrapolation from the 59 diagnosed meningoencephalitis cases, we conservatively estimated that the New York outbreak consisted of 8200 (range 3500-13000) West Nile viral infections, including about 1700 febrile infections. INTERPRETATION: During the 1999 West Nile virus outbreak, thousands of symptomless and symptomatic West Nile viral infections probably occurred, with fewer than 1% resulting in severe neurological disease.

West Nile virus serosurvey and assessment of personal prevention efforts in an area with intense epizootic activity: Connecticut, 2000.

West Nile virus (WNV) can cause large outbreaks of febrile illness and severe neurologic disease. This study estimates the seroprevalence of WNV infection and assesses risk perception and practices regarding potential exposures to mosquitoes of persons in an area with intense epizootics in 1999 and 2000. A serosurvey of persons aged > or = 12 years was conducted in southwestern Connecticut during October 10-15, 2000, using household-based stratified cluster sampling. Participants completed a questionnaire regarding concern for and personal measures taken with respect to WNV and provided a blood sample for WNV testing. Seven hundred thirty persons from 645 households participated. No person tested positive for WNV (95% CI: 0-0.5%). Overall, 44% of persons used mosquito repellent, 56% practiced > or = two personal precautions to avoid mosquitoes, and 61% of households did > or = two mosquito-source reduction activities. In multivariate analyses, using mosquito repellent was associated with age < 50 years, using English as the primary language in the home, being worried about WNV, being a little worried about pesticides, and finding mosquitoes frequently in the home (P<0.05). Females (OR = 2.0; CI = 1.2-2.9) and persons very worried about WNV (OR = 3.8; CI = 2.2-6.5) were more likely to practice > or = two personal precautions. Taking > or = two mosquito source reductions was associated with persons with English as the primary language (OR = 2.0; CI = 1.1-3.5) and finding a dead bird on the property (OR = 1.8; CI = 1.1-2.8). An intense epizootic can occur in an area without having a high risk for infection to humans. A better understanding of why certain people do not take personal protective measures, especially among those aged > or = 50 years and those whose primary language is not English, might be needed if educational campaigns are to prevent future WNV outbreaks.

La Crosse encephalitis virus habitat associations in Nicholas County, West Virginia.

Aedes triseriatus (Say) population density patterns and La Crosse encephalitis virus infection rates were evaluated in relation to a variety of habitat parameters over a 14-wk period. Ovitraps and landing collections were used in a La Crosse virus-enzootic area in Nicholas County, WV. Study sites were divided into categories by habitat type and by proximity to the residences of known La Crosse encephalitis cases. Results demonstrated that Ae. triseriatus population densities were higher in sugar maple/red maple habitats than in hemlock/mixed hardwood habitats or in a site characterized by a large number of small red maple trees. Sites containing artificial containers had higher population densities than those without. La Crosse virus minimum infection rates in mosquitoes collected as eggs ranged from 0.4/1,000 to 7.5/1,000 in the 12 study sites, but did not differ significantly among sites regardless of habitat type or proximity to human case residences. La Crosse virus infection rates in landing Ae. triseriatus mosquitoes ranged from 0.0/1,000 to 27.0/1,000. La Crosse virus was also isolated from host-seeking Ae. canadensis (Theobald) in two study sites, at rates similar to those found in the Ae. triseriatus populations. The Ae. triseriatus oviposition patterns and La Crosse virus infection rates suggest that this mosquito species disperses readily in the large woodlands of central West Virginia. The La Crosse enzootic habitats in Nicholas County, WV, are contrasted with those studied in other geographic regions where La Crosse virus is found.

Transmission of the agent of human granulocytic ehrlichiosis by Ixodes spinipalpis ticks: evidence of an enzootic cycle of dual infection with Borrelia burgdorferi in Northern Colorado.

Previous work described an enzootic cycle of Borrelia burgdorferi sensu lato (hereafter referred to as B. burgdorferi) maintained by the rodent Neotoma mexicana and the tick Ixodes spinipalpis in northern Colorado. We investigated the incidence of coinfection among rodents with the agent of human granulocytic ehrlichiosis (aoHGE). aoHGE was detected in 23.5% of 119 rodent spleens examined. Biopsy results indicated that 78 (65.5%) of the 119 rodents were positive for B. burgdorferi, whereas 22 (78.5%) of the 28 animals that harbored aoHGE were also infected with B. burgdorferi. In 14 of 25 I. spinipalpis tick pools, aoHGE was detected by amplifying both the 16s rRNA and p44 gene of aoHGE. The ability of I. spinipalpis to transmit aoHGE was examined in C3H/HeJ mice. aoHGE was detected in their blood 5 days after I. spinipalpis infestation. This study confirms that both B. burgdorferi and aoHGE can be transmitted by I. spinipalpis ticks and that there is a high incidence of coinfection in rodents, predominantly Peromyscus maniculatus and N. mexicana, that inhabit the foothills of northern Colorado.

Comparing diagnostic tests: a simple graphic using likelihood ratios.

The diagnostic abilities of two or more diagnostic tests are traditionally compared by their respective sensitivities and specificities, either separately or using a summary of them such as Youden's index. Several authors have argued that the likelihood ratios provide a more appropriate, if in practice a less intuitive, comparison. We present a simple graphic which incorporates all these measures and admits easily interpreted comparison of two or more diagnostic tests. We show, using likelihood ratios and this graphic, that a test can be superior to a competitor in terms of predictive values while having either sensitivity or specificity smaller. A decision theoretic basis for the interpretation of the graph is given by relating it to the tent graph of Hilden and Glasziou (Statistics in Medicine, 1996). Finally, a brief example comparing two serodiagnostic tests for Lyme disease is presented. Published in 2000 by John Wiley & Sons, Ltd.

Genetic differentiation in the yellow fever virus vector, Aedes simpsoni complex, in Africa: sequence variation in the ribosomal DNA internal transcribed spacers of anthropophilic and non-anthropophilic populations.

Mosquitoes of the Aedes simpsoni complex are important vectors of yellow fever virus in Africa. We examined the ribosomal DNA sequence divergence in the internal transcribed spacer regions (ITS-1 and ITS-2) for populations of mosquitoes that were determined to be anthropophilic or non-anthropophilic in their bloodmeal host preference. A neighbour-joining tree produced two clades: one contained all of the individual mosquitoes from anthropophilic populations and the other contained all of the individual mosquitoes from non-anthropophilic populations. There was no segregation of the taxa within each of the two clades based on geographical origin. The data suggest the exisf'tence of two distinct species of Ae. simpsoni s.l. in Uganda that correlates with their host blood-feeding preference. The current taxonomic status of the complex is discussed in relation to these findings.

Incorporating variability in estimates of heterogeneity in the random effects model in meta-analysis.

When combining results from separate investigations in a meta-analysis, random effects methods enable the modelling of differences between studies by incorporating a heterogeneity parameter tau 2 that accounts explicitly for across-study variation. We develop a simple form for the variance of Cochran's homogeneity statistic Q, leading to interval estimation of tau 2 utilizing an approximating distribution for Q; this enables us to extend the point estimation of DerSimonian and Laird. We also develop asymptotic likelihood methods and compared them with this method. We then use these approximating distributions to give a new method of calculating the weight given to the individual studies' results when estimating the overall mean which takes into account variation in these point estimates of tau 2. Two examples illustrate the methods presented, where we show that the new weighting scheme is between the standard fixed and random effects models in down-weighting the results of large studies and up-weighting those of small studies.

Bayesian meta-analysis, with application to studies of ETS and lung cancer.

Meta-analysis enables researchers to combine the results of several studies to assess the information they provide as a whole. It has been used to give a systematic overview of many areas in which data on a possible association between an exposure and an outcome have been collected in a number of studies but where the overall picture remains obscure, both as to the existence or size of the effect. This paper outlines some innovations in meta-analysis, based on using Markov chain Monte Carlo (MCMC) techniques for implementing Bayesian hierarchical models, and compares these with a more well-known random effects (RE) model. The new techniques allow different aspects of variation to be incorporated into descriptions of the association, and in particular enable researchers to better quantify differences between studies. Both the classical and Bayesian methods are applied, in this paper, to the current collection of studies of the association between incidence of lung cancer in female never-smokers and exposure to environmental tobacco smoke (ETS), both in the home through spousal smoking and in the workplace. In this paper it is demonstrated that compared with the RE model, the Bayesian methods: (a) allow more detailed modeling of study heterogeneity to be incorporated; (b) are relatively robust against a wide choice of specifications of such information on heterogeneity; (c) allow for more detailed and satisfactory statements to be made, not only about the overall risk but about the individual studies, on the basis of the combined information. For the workplace exposure data set, the Bayesian methods give a somewhat lower overall estimate of relative risk of lung cancer associated with ETS, indicating the care that needs to be taken in using point estimates based on any one method of analysis. On the larger spousal data set the methods give similar answers. Some of the other concerns with meta-analysis are also considered. These include: consistency between different geographic areas (Asia and the United States), and our studies show that Bayesian methods permit an account of the overall picture to be taken, thus improving the ability to estimate accurately in the subgroups; and publication bias which, as shown with the spousal exposure data, may lead to an inflated excess risk.

Passive smoking in the workplace: classical and Bayesian meta-analyses.

There are currently several classical and Bayesian methods of meta-analysis available for combining epidemiological results. We describe and compare these in a consistent framework, and apply them to published studies of the relative risk of lung cancer associated with exposure to environmental tobacco smoke in the workplace. We find that although all methods give reasonably similar combined estimates of relative risk of lung cancer associated with this exposure (none of which is significantly raised above unity, in either a frequentist or a Bayesian sense), the approximations arising from classical methods appear to be nonconservative and should be used with caution. The Bayesian methods, which account more explicitly for possible inhomogeneity in studies, give slightly lower estimates again of relative risk and wider posterior credible intervals, indicating that inference from the non-Bayesian approaches might be optimistic.