The objective of this study was to understand the epidemiology of the WNV outbreak in Texas. We examined surveillance data for all reported cases for which symptom onset occurred during the calendar year, and we used descriptive statistics to describe the clinical features and demographic characteristics of reported case-patients.
Epi Info 7. Figure 1. Dates of onset ranged from May 1, , through December 6, Figure 1. The outbreak peaked during week 33 mid-August with reported cases, which is historically the same peak for all reported WNV cases in Texas during — 2.
The median time from date of symptom onset to date of official report to TxDSHS was 27 days range 6— days. Median age of all case-patients was 54 years range 1 month— years. As each age category increased, the attack rates also increased Table.
The median age of the 89 case-patients who died was 79 years range 25— years. Figure 2. Numbers in parentheses indicate the number of counties that fell within each range.
The overall incidence rate for the state was 7. These 4 counties had a combined incidence rate of 16 cases per , population. The WNV outbreak in Texas was unexpected in terms of the magnitude of virus transmission and number of human cases.
We recently observed a 3-year pattern of increases in reported human cases in Texas, as seen in , , and 2. In , the dramatic epidemic was consistent with this prior observation, with the 1, reported cases being more than double the historic high, which occurred in cases. In addition to the dramatic increase in human cases in , the state also reported an increase in equine cases cases in compared with 6 cases in The exact factors that contributed to this epidemic are unknown and most likely complex, considering that successful transmission depends on supportive environmental conditions, vector abundance, avian reservoir and susceptible host abundance, pathogenicity of the virus, and sizeable populations of immunologically naive reservoir species.
During , there was some media speculation that more cases of severe disease occurred in younger persons and that the circulating strain of virus possibly was more pathogenic than in prior years.
Compared with Texas data for —, we did not find any statistically significant differences in median ages of reported WNND or fatal cases in using the Kruskal-Wallis 1-way analysis of variance on ranks.
Our findings from remain consistent with our experience from prior years; however, it remains critical to emphasize the importance of recognizing disease and testing persons of any age who have clinical signs and symptoms consistent with WNV infection.
The WNV outbreak in Texas greatly affected the state economically. On the basis of the acute medical care and productivity loss cost estimates provided by Barber et al. In addition to these acute costs, the outbreak also required an increase in resources for mosquito control and public health efforts to respond to the epidemic.
The long-term economic impact of this outbreak also is expected to be substantial as a consequence of long-term rehabilitation and disability costs 8 , possible risk for chronic kidney disease 9 , and risk for premature death in severe cases The unprecedented outbreak confirms the need for continued vigilance for surveillance to enable timely implementation of control measures to prevent virus transmission. We expect Texas will continue to experience endemic levels of virus transmission with periodic epizootics.
PubMed Google Scholar. Recurrent St. Am J Epidemiol. Petersen LR, Fischer M. Unpredictable and difficult to control—the adolescence of West Nile virus. N Engl J Med. State electronic disease surveillance systems—United States, and Division of Notifiable Diseases and Healthcare Information.
Centers for Disease Control and Prevention website. Use of the vector index and geographic information system to prospectively inform West Nile virus interventions. J Am Mosq Control Assoc. Emerg Infect Dis. Biggerstaff BJ. PooledInfRate, version 4. United States Census Bureau website. Getis A, Ord JK.
The analysis of spatial association by use of distance statistics. Geogr Anal. Google Scholar Crossref. Spatial risk assessments based on vector-borne disease epidemiologic data: importance of scale for West Nile virus disease in Colorado.
Am J Trop Med Hyg. Local Climatological Data Publication. National Climatic Data Center website. Code-based syndromic surveillance for influenzalike illness by International Classification of Diseases, Ninth Revision. Pesticide spraying for West Nile virus control and emergency department asthma visits in New York City, Environ Health Perspect.
MacKinlay AC. Event studies in economics and finance. J Econ Lit. Google Scholar. The emergence of West Nile virus during a large outbreak in Illinois in Behavioral risks for West Nile virus disease, northern Colorado, CDC website. June 14, Accessed June 21, Seasonal patterns for entomological measures of risk for exposure to Culex vectors and West Nile virus in relation to human disease cases in northeastern Colorado. J Med Entomol.
Parasit Vectors. Cross-correlation map analyses show weather variation influences on mosquito abundance patterns in Saginaw County, Michigan, Walsh MG. The role of hydrogeography and climate in the landscape epidemiology of West Nile virus in New York State from to PLoS One.
Permissive summer temperatures of the European West Nile fever upsurge. Inter-annual associations between precipitation and human incidence of West Nile virus in the United States. Vector Borne Zoonotic Dis. Ecological factors associated with West Nile virus transmission, northeastern United States. Land use and West Nile virus seroprevalence in wild mammals. Predictive mapping of human risk for West Nile virus WNV based on environmental and socioeconomic factors.
Delinquent mortgages, neglected swimming pools, and West Nile virus, California. Ecological correlates of risk and incidence of West Nile virus in the United States.
Fine-scale variation in vector host use and force of infection drive localized patterns of West Nile virus transmission. Efficacy of aerial spraying of mosquito adulticide in reducing incidence of West Nile virus, California, Evaluation of efficacy and human health risk of aerial ultra-low volume applications of pyrethrins and piperonyl butoxide for adult mosquito management in response to West Nile virus activity in Sacramento County, California.
A review of ultralow-volume aerial sprays of insecticide for mosquito control. Aerial application for control of public health pests. Asp Appl Biol. A human-health risk assessment for West Nile virus and insecticides used in mosquito management. Risk assessments for exposure of deployed military personnel to insecticides and personal protective measures used for disease-vector management.
J Toxicol Environ Health A. Bystander exposure to ultra-low-volume insecticide applications used for adult mosquito management. West Nile virus economic impact, Louisiana, Recurrence of West Nile Virus. Petersen and coauthors reviewed the ecology, virology, epidemiology, clinical characteristics, diagnosis, prevention, and control of West Nile virus after searching the PubMed electronic database through February 5, In an Editorial, Ostroff urges maintenance of vector surveillance and control programs.
Lyle R. Brault, PhD; Roger S. Nasci, PhD. Save Preferences. The homogenates were centrifuged and SARS-CoV titers in the clarified fluids were determined by serial dilution in quadruplicate wells of Vero E6 cells in well plates. Neutralizing antibody titers, lung virus titers, histopathologic lesion score and eosinophilic infiltration scores were averaged for each group of mice. Comparisons were conducted using parametric and nonparametric statistics as indicated. The three experiments performed, vaccines and dosages used and controls for each experiment are shown in Table 1.
The vaccines were evaluated for immunogenicity and efficacy; however, because of the previous report of immunopathology on challenge of ferrets and nonhuman primates that had been vaccinated with a whole virus adjuvanted vaccine and mice that had been vaccinated with a VLP vaccine, the primary orientation was to assess for immunopathology among animals in relation to type of vaccine, dosage, serum antibody responses, and virus infection.
The vaccine preparations were made for human trials so identifying a preparation that was likely to be both safe and protective in humans was desired.
The rationale for each experiment is described. To differentiate between vaccines, three vaccine preparations were simultaneously evaluated, the double-inactivated formalin and UV whole virus vaccine DIV , the rDNA-expressed S protein vaccine SV , and the previously evaluated chimeric viral-like particle vaccine VLP that had led to immunopathology with virus challenge [16] , [17] , [20]. Geometric mean serum neutralizing antibody titers for each group on day 56 are shown in figure 1A.
Serum neutralizing neut antibody and lung virus titers for each vaccine dosage group. Geometric mean serum antibody titer as log 2 and standard error of the mean S.
Seven to eight mice per group. Five mice per group were given 0. Analyses: A. Two days after challenge, lungs were obtained from all animals for virus quantitation and histology. CoV titers are shown in figure 1B. Geometric mean lung titers in the alum and PBS control groups were 10 7. All vaccine groups exhibited lower titers or no detectable virus on day two after challenge. In the vaccine comparison experiment, lung lesion scores for histopathology were graded for individual animals on a scale of 0 to 4 where 0—2 represented degree of cellular infiltration and 3—4 represented the degree of bronchiolar epithelial cell necrosis and airway cellular debris figure 2A.
As shown, all animals exhibited pathologic changes after challenge including those animals with no measurable virus on day two suggesting virus infection had occurred but was not detectable on day two because of a short duration of infection or neutralization of virus by antibody in the lung during processing.
Mean lesion score and standard error of the mean S. All mice exhibited lung histopathology. Scores are mean of scores for seven to eight mice per group. Mean percent eosinophils on histologic evaluation for seven to eight mice in each vaccine dosage group. Mean for each mouse is the mean percent eosinophils on five separate microscopy fields of lung sections. SV lower than controls p. When the characteristics of the infiltrates were compared, animals given alum or PBS exhibited epithelial cell necrosis and peribronchiolar and perivascular mononuclear cell infiltrates consistent with epithelial cell infection and an inflammatory response seen in viral infections.
In addition to mononuclear cells, however, infiltrates among vaccinated animals contained neutrophils and eosinophils that were not seen in the lesions of the animals that had been previously given PBS or alum only figure 2B suggesting a T helper cell type 2 hypersensitivity reaction; increased eosinophils are a marker for a Th2-type hypersensitivity reaction.
Percent eosinophils was lower in these vaccinated animals mean 1—3. This pattern of excess eosinophils in cellular infiltrates seen in lung sections from animals given vaccine and not in control animals was as seen in the earlier study with VLP vaccine and those later with other vaccines although the percent eosinophils was lower in this study. Serum neutralizing antibody responses are shown in figure 3A.
Geometric mean serum antibody titer and standard error of the mean S. Five mice per group given 0. Shown in figure 4A are the mean lesion scores on histologic evaluations. The scoring system for experiments two and three were developed by a replacement pathologist who preferred a scale of 0 to 3 which corresponded to a judgment of mild, moderate or severe figure 4A.
Of interest is that those given live virus and then challenged with live virus two months later exhibited an infiltrative disease severity comparable to the PBS and vaccinated groups despite no detectable virus on day two, again suggesting some degree of infection may have occurred earlier. Scoring - 0 - no definite pathology, 1 - mild peribronchiole and perivascular cellular infiltration, 2 - moderate peribronchiole and perivascular cellular infiltration, 3 - severe peribronchiolar and perivascular cellular infiltration with thickening of alveolar walls, alveolar infiltration and bronchiole epithelial cell necrosis and debris in the lumen.
Ten to 20 microscopy fields were scored for each mouse lung. Mean score and standard error of the mean S. The mean eosinophil scores for the lung infiltrations were lower for the S protein vaccine groups [SV vs.
Representative photo micrographs of lung sections from mice in this experiment two days after challenge with SARS-CoV are shown in figure 5. Perivascular and peribronchial inflammatory infiltrates were observed in most fields along with desquamation of the bronchial epithelium, collections of edema fluid, sloughed epithelial cells, inflammatory cells and cellular debris in the bronchial lumen.
Large macrophages and swollen epithelial cells were seen near lobar and segmental bronchi, small bronchioles and alveolar ducts. Necrotizing vasculitis was prominent in medium and large blood vessels, involving vascular endothelial cells as well as the tunica media, and included lymphocytes, neutrophils, and eosinophils in cellular collections.
Occasional multinucleated giant cells were also seen. The eosinophil component of infiltrates was very prominent in animals vaccinated with the experimental vaccine preparations when compared to animals mock-vaccinated using PBS, or those exposed earlier to live virus figure 6 ; few to no eosinophils were seen in those lung sections.
Thus, while pathology was seen in sections from the control mice, the hypersensitivity-type pathologic reaction with eosinophils was not seen.
DAB chromogen provided the brown eosinophil identity stain. As shown in the images, eosinophils are prominent brown DAB staining in all sections examined.
Exposure to SARS-CoV is associated with prominent inflammatory infiltrates characterized by a predominant eosinophilic component. As shown in the middle and bottom row images, although exposure to SARS-CoV elicits inflammatory infiltrates and accumulation of debris in the bronchial lumen, eosinophils in all groups remain within normal limits.
The different groups of vaccinated animals showed similar trends in severity of pathology and of eosinophils in inflammatory infiltrates; however, the DIV and BPV preparations at high dosage tended to produce a greater infiltration with eosinophils.
Experiment 3 was performed to evaluate vaccine and mouse strain specificity. Neutralizing antibody titers are shown in figure 7A.
The serum antibody responses after BPV and live virus administration were similar for the two mouse strains. After challenge, mean lung virus titers were similar for the PBS control challenged mice of both mouse strains 10 6. Photomicrographs of the different vaccine and mouse strain groups are shown in figure 9. Both vaccines in both mouse strains exhibited significant cellular infiltrations that included numerous eosinophils as shown in the MBP stained sections, a finding consistent with a hypersensitivity component of the pathology.
Prior influenza vaccine did not lead to an eosinophil infiltration in the lung lesions after challenge. Scoring 0 - no definite pathology, 1 - mild peribronchiole and perivascular cellular infiltration, 2 - moderate peribronchiole and perivascular cellular infiltration, 3 - severe peribronchiole and perivascular cellular infiltration with thickening of alveolar walls, alveolar infiltration and bronchiole epithelial cell necrosis and debris in the lumen. The emergence of the disease SARS and the rapid identification of its severity and high risk for death prompted a rapid mobilization for control at the major sites of occurrence and at the international level.
Part of this response was for development of vaccines for potential use in control, a potential facilitated by the rapid identification of the causative agent, a new coronavirus [8] — [9]. Applying the principles of infection control brought the epidemic under control but a concern for reemergence naturally or a deliberate release supported continuation of a vaccine development effort so as to have the knowledge and capability necessary for preparing and using an effective vaccine should a need arise.
For this purpose, the National Institute of Allergy and Infectious Diseases supported preparation of vaccines for evaluation for potential use in humans. This effort was hampered by the occurrence in the initial preclinical trial of an immunopathogenic-type lung disease among ferrets and Cynomolgus monkeys given a whole virus vaccine adjuvanted with alum and challenged with infectious SARS-CoV [14].
That lung disease exhibited the characteristics of a Th2-type immunopathology with eosinophils in the lung sections suggesting hypersensitivity that was reminiscent of the descriptions of the Th2-type immunopathologic reaction in young children given an inactivated RSV vaccine and subsequently infected with naturally-occurring RSV [32] — [33].
Most of these children experienced severe disease with infection that led to a high frequency of hospitalizations; two children died from the infection [33] , [40] , [41]. The conclusion from that experience was clear; RSV lung disease was enhanced by the prior vaccination.
This type of tissue response is associated with an increase in type 2 cytokines including IL4, IL5, and IL13 and an influx of eosinophils into the infected lung; [32] , [33] , [42] , [44]. Histologic sections of tissues exhibiting this type of response have a notable eosinophilic component in the cellular infiltrates. Recent studies indicate that the Th2-type immune response has both innate and adaptive immune response components [33] , [43].
In addition to the RSV experience, concern for an inappropriate response among persons vaccinated with a SARS-CoV vaccine emanated from experiences with coronavirus infections and disease in animals that included enhanced disease among infected animals vaccinated earlier with a coronavirus vaccine [31].
0コメント