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Am. J. Trop. Med. Hyg., 76(2), 2007, pp. 285-292
Copyright © 2007 by The American Society of Tropical Medicine and Hygiene

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HUMAN EASTERN EQUINE ENCEPHALITIS IN MASSACHUSETTS: PREDICTIVE INDICATORS FROM MOSQUITOES COLLECTED AT 10 LONG-TERM TRAP SITES, 1979–2004

MASAHIKO HACHIYA, MATTHEW OSBORNE, CYNTHIA STINSON, AND BARBARA G. WERNER*
State Laboratory Institute, Massachusetts Department of Public Health, Boston, Massachusetts


ABSTRACT
TOP
 ABSTRACT
INTRODUCTION
 MATERIALS AND METHODS
 RESULTS
 DISCUSSION
 REFERENCES
 
Human eastern equine encephalitis (EEE) is a life-threatening mosquito-borne disease. To determine whether mosquito abundance and EEE virus infection rates are associated with human EEE disease, we evaluated retrospectively a total of 592,637 mosquitoes and onset dates for 20 confirmed human cases over 26 years in Massachusetts. Annual Culiseta melanura populations at 10 defined sites decreased over the study period (P = 0.002). Weekly infection rates and number of infected Culiseta melanura captured per trap night were positively associated EEE cases (P < 0.023 and P < 0.001, respectively), whereas abundance was not (P = 0.077). The infection rate for Culiseta melanura of 0.39 per 1,000 tested mosquitoes identified human cases with a sensitivity of 0.87, a specificity of 0.82, a positive predictive value of 0.14, and a negative predictive value of 0.995. Timely mosquito testing and infection rate calculation are critical for disease risk estimation and outbreak control efforts.


INTRODUCTION
TOP
 ABSTRACT
 INTRODUCTION
MATERIALS AND METHODS
 RESULTS
 DISCUSSION
 REFERENCES
 
Human eastern equine encephalitis (EEE) is relatively rare (4.92 cases per year in the United States from 1964 to 2000), but the disease produces significant morbidity and mortality (31–74%) and profound neurologic sequelae in 55–96% of survivors.1–5 Additionally, human EEE outbreaks have caused significant public concern, probably because of their intensity and infrequency.5 Considering its serious consequences and social and economic impact, EEE is of public health importance.5,6 Thus, accurate human risk estimation and outbreak prevention measures are needed.

EEE is a mosquito-borne disease caused by an alphavirus.5 The primary hosts are wild birds and ornithophilic mosquitoes, Culiseta melanura, the enzootic vectors in the United States.7,8 Infection among humans and horses is most likely incidental and occurs when the virus circulates widely and expands from the enzootic cycle.9,10 Bridging vectors are believed to be in the genera Aedes, Coquillettidia, and Culex.11–13 Monitoring mosquito abundance and EEE virus infection rates may offer useful estimation of human disease risk.14

The first human EEE outbreak was recognized in Massachusetts in 1938, and 34 cases with 25 fatalities were recorded.15,16

One case occurred the following year, but subsequent human disease occurred irregularly, and outbreaks often lasted > 1 year: for example, in 1955 and 1956 (16 cases); from 1970 to 1974 (7 cases); and from 1982 to 1984 (10 cases).17–21 In the 1990s, three cases occurred in 1990 and one case each in 1992, 1995, and 1997. After single cases in 2000 and 2001, in 2004, the state experienced an EEE outbreak with four human cases (two fatalities) and seven equine cases. The overall mortality rate through 2004 was 50.6%. Based on historical trends, 2004 may be considered as the beginning of another outbreak. For this reason, timely human risk estimation is desirable during the next several years. The Massachusetts State Laboratory Institute has monitored entomologic and ecologic conditions and human EEE cases, but quantitative analysis, which evaluates the association of mosquito indicators with human disease, has been limited.

We carried out these analyses to test the hypothesis that the abundance and EEE virus infection rates among mosquitoes can quantitatively estimate the likelihood of human EEE disease. In particular, we described the annual populations of given mosquito species and provided the weekly mosquito density and EEE virus infection rates. Using these findings, we tested the association between these mosquito indicator values and human cases.


MATERIALS AND METHODS
TOP
 ABSTRACT
 INTRODUCTION
 MATERIALS AND METHODS
RESULTS
 DISCUSSION
 REFERENCES
 
Study sites. General descriptions of the study sites, their locations, and the climate have been reported previously.20 In brief, the area chosen for this study was southeastern Massachusetts, specifically Bristol (five sites), Plymouth (four sites), and Norfolk (one site) counties, where the majority of human and horse cases have occurred. All sites are located in large areas of forested wetlands, densely covered by white cedar/ red maple swamps, and were chosen primarily to collect Cs. melanura.

Sampling procedure. Battery-operated standard CDC miniature light traps without CO2 were used to sample adult mosquito populations from late May or early June to late September or early October. Collection usually ended after the first hard, extensive frost occurred. A pair of traps hung ~1.5 m above the ground was placed far enough apart to avoid competition.20,21 Traps were set once or twice weekly and were picked up the following morning. Collections were stored on dry ice and transported to the State Laboratory Institute (SLI). Female mosquitoes were sorted on the basis of date, site, trap number, and species and processed for virus isolation. Weekly mosquito abundance was described as mean number captured per trap per night during a week. A week was defined from Saturday to Friday, with the first week ending on the first Friday of the year. In this study, we analyzed data from 1979 to 2004, collected using CDC light traps set by the SLI staff at 10 long-term sites only. Mosquitoes collected in other types of traps, at other sites, and by regional Mosquito Control Districts were excluded from the analysis.

Virus identification. Mosquitoes were sorted by species and sex, pooled into groups of 50 or less, and ground in diluent. Plaque assay, on primary chick embryo tissue culture through 1996, and subsequently on Vero cells or BHK-2 cells, was performed on all supernatants of pools of female mosquitoes and followed by immunofluorescence assay for identification.22,23 Virus isolations were expressed as minimum infection rates (MIRs, number of virus positive pools per 1,000 mosquitoes tested).14 This standard computation for MIR ignores the possibility that multiple mosquitoes may be infected in a pool.

Case definitions. Case surveillance and definitions were consistent with CDC recommendations. SLI identified 22 human cases of EEE during the study period. Laboratory confirmation was made by detection of EEE specific IgM antibody in the cerebrospinal fluid (CSF), virus isolation from patients’ brains or CSF, or serum antibody titers increasing 4-fold or more from acute to convalescent phase or converting from IgM to IgG using IgM- and IgG-specific enzyme immunoassays and plaque reduction assays.22,24,25 Two cases were excluded from the analysis, because epidemiologic evidence supports that they were exposed in New Jersey or in Hampden County, Massachusetts, > 100 km from the study sites. Illness onset dates for the remaining 20 cases were included.

Data analysis. A simple linear regression was used to examine whether the mosquito population and MIR have changed over time. Poisson regression was used to study whether the risk of human EEE disease was associated with mosquito indicators. We compared mosquito indicator values in years with cases and those without using Wilcoxon rank sum test. Categorical data were compared by Fisher exact test. A receiver operator characteristic curve and the area under the curve were used to estimate whether mosquito indicators classify human disease and to compare different indicators. All statistical analyses were performed using Inter-cooled Stata 8.0 (Stata Corp., College Station, TX). Statistical significance between groups was determined with two-tailed tests, and values of P < 0.05 were considered significant.


RESULTS
TOP
 ABSTRACT
 INTRODUCTION
 MATERIALS AND METHODS
 RESULTS
DISCUSSION
 REFERENCES
 
Data for a total of 612,265 mosquitoes representing seven genera and 23 species were stored in a database from June 1979 through October 2004, and 4 species were systematically differentiated (Table 1Go). Although Cs. melanura was the largest group throughout the study period (84.6%), Coquillettidia perturbans, Ochlerotatus canadensis, and Aedes vexans have been recorded as epizootic vector candidates in Massachusetts.20,26,27


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TABLE 1
Annual recorded mosquitoes by species captured in unbaited CDC light traps at 10 sites in Massachusetts, 1979–2004
 
Annual mosquito abundance and human cases. To determine the chronologic mosquito density trends, we compared annual mean abundance in each species. Cs. melanura significantly decreased during the study period (P = 0.002; Figure 1Go, top). Abundance of Cs. melanura dropped at all sites, and the results were statistically significant in 7of 10 sites. On the other hand, the density of Cq. perturbans, Oc. canadensis, and Ae. vexans did not decrease (P = 0.30, P = 0.74, and P = 0.68, respectively) but fluctuated (Figure 1Go, middle). Human cases clustered from 1982 to 1984, in 1990, and in 2004 and did not decrease over time (P = 0.89; Figure 1Go, bottom). Cs. melanura was abundant before and during the first two epidemics (from 1982 to 1984 and in 1990) but was less plentiful in 2004. Annual Cs. melanura collections are decreasing; however, the abundance does not correlate with the number of human cases.


Figure 1
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  		    FIGURE 1. Mosquito abundance in unbaited CDC light traps at 10 long-term sites (top and middle) and human cases (bottom) in Massachusetts, 1979–2004. Numbers of mosquitoes were calculated as mean number of captured mosquitoes per trap per night during the entire season. Two cases presumably exposed to the virus outside of eastern Massachusetts are indicated as shaded bar (bottom). Cs, Culiseta; Cq, Coquillettidia; Oc, Ochlerotatus; Ae, Aedes.

 
Annual minimal infection rate among mosquitoes. To determine the chronologic EEE virus MIR trends among mosquitoes, we compared annual MIRs (Table 2Go). In total, 19,362 mosquito pools were examined for virus, with 376 EEE recorded as positive and Cs. melanura accounting for the majority of positive pools (98.7%). Overall MIR for Cs. melanura was 0.71, and yearly MIR oscillated and has not decreased over time (P = 0.21). Overall MIR for Cq. perturbans (0.096) and Oc. canadensis (0.068) were significantly lower than that of Cs. melanura (P < 0.001 and P = 0.001, respectively). Annual EEE virus MIR for Cs. melanura varied. No significant associations were observed between annual MIR values and the number of human cases.


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TABLE 2
Tested and EEE virus-positive pools and EEE virus MIR for Cs. melanura captured in unbaited CDC light traps at 10 sites in Massachusetts, 1979–2004
 
Weekly mosquito indicators and human cases. To estimate the relative association of EEE virus MIR and abundance of Cs. melanura on human disease, we plotted the seasonal distribution of mosquito indicators for 9 years with and 17 years without human cases. EEE virus–positive pools were found earlier in years with than in years without human cases (Figure 2Go, top). The former had greater MIRs than the latter throughout the season. The MIR differences were significant in weeks 29, 33, 34, 36, and 38 (P = 0.048, P = 0.0046, P = 0.0066, P = 0.018, and P = 0.0013, respectively). The MIRs were higher late in the season. Indeed, 7 of 9 human case years and 6 of 17 non-case years had their highest weekly MIRs during or after week 37. The difference in mean abundance between the two groups seems the greatest from July to August, but for each week, the values were not significantly different (Figure 2Go, middle). Human cases occur as Cs. melanura MIR and abundance increase (Figure 2Go, bottom).


Figure 2
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  		    FIGURE 2. Mean weekly EEE virus MIR (top), mean weekly abundance (middle) of Cs. melanura, and human EEE disease onset dates (bottom) in Massachusetts, 1979–2004. MIR, minimum infection rate.

 
Minimal infection rates in years with multiple cases. To elucidate the chronologic association between MIRs and human disease, we described weekly data in three different years with multiple cases (Figure 3Go). Human EEE cases tended to cluster in 1983 (first five patients occurred within 15 days) and 1990 (three patients within 8 days), but were scattered in 2004 when the onsets were at least 12 days apart. MIR levels at, or 1 or 2 weeks before, the onset dates were > 1.0 for all cases shown in the figure. The highest MIRs for the 10 long-term sites were 13.51, 7.49, and 12.05 in 1983, 1990, and 2004, respectively. Human case onset dates follow high MIR values during EEE outbreaks.


Figure 3
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  		    FIGURE 3. EEE virus MIR for Cs. melanura for each outbreak year (thick solid line), 1983 (top), 1990 (middle), and 2004 (bottom), in Massachusetts, 1979–2004. Thin solid and dotted lines indicate the mean and the upper 95% confidence interval of MIRs in 17 years without human cases. Arrows indicate human case onset dates and an open arrow represents aerial malathion application. A fourth case in the 44th week in 2004 is not shown. MIR, minimum infection rate.

 
Mosquito indicators association with human cases. To quantify the association between mosquito indicators and human EEE disease, we compared weekly mosquito indicator values and the number of human cases in the same week. EEE virus MIRs were significantly associated with human disease (P = 0.023), whereas abundance alone was not (P = 0.077). The third index, number of infected Cs. melanura per trap per night, which is the product of the former two indicators, showed the most significant association with human cases (P < 0.001). Abundance of Cq. perturbans, Oc. canadensis, and Ae. vexans were not associated with human EEE disease (P = 0.26, P = 0.91, and P = 0.86, respectively). Years with virus positive zoophilic mosquitoes were not associated with those with human diseases (P = 0.45). For practical use, we reported sensitivity and specificity for a variety of indicator values using the receiver operator characteristic curve and calculated the area under the curve (Figure 4Go). Area under the curve for MIR was 0.83 (95% confidence interval [CI]: 0.74, 0.93) and was significantly greater than that for abundance (0.63; 95% CI: 0.48, 0.78; P = 0.019). The greatest accuracy was obtained at an MIR of 0.39, which classifies human cases with a sensitivity of 0.87, a specificity of 0.82, a positive predictive value of 0.14, and a negative predictive value of 0.995. The area under the curve for the number of infected Cs. melanura was 0.83 (95% CI: 0.73, 0.92) and was not significantly different from that of the MIR (P = 0.78). The greatest accuracy was obtained with a value of 19.29 infected Cs. melanura, which detects human cases with a sensitivity of 0.87, a specificity of 0.81, a positive predictive value of 0.13, and a negative predictive value of 0.995.


Figure 4
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  		    FIGURE 4. Receiver operating characteristic curve based on EEE virus MIR and abundance of Cs. melanura for human EEE cases.

 

DISCUSSION
TOP
 ABSTRACT
 INTRODUCTION
 MATERIALS AND METHODS
 RESULTS
 DISCUSSION
REFERENCES
 
Our study has three major findings. First, annual collections of Cs. melanura have decreased significantly at 10 trap sites since 1979. Second, weekly EEE virus MIR and the number of infected Cs. melanura per trap per night were associated with human disease, whereas abundance of this vector alone and that of other vectors were not. Finally, weekly EEE virus MIR and the abundance of infected Cs. melanura considered together were also able to estimate the likelihood of human EEE disease in the same week.

We found that the captured Cs. melanura in southeast Massachusetts have decreased. Possible explanations of our findings are as follows. First, the important wetland habitat for Cs. melanura might have decreased near collection sites. Although forest cover declined as a result of industrial, transportation, and housing development from 1971 to 1999,28 the overall acreage of white cedar swamp has probably not decreased substantially in the past few decades (G. Motzkin, Harvard Forest, personal communication, 2005). Total white cedar wetland may be relatively stable, but individual swamp patches have been altered.29 Second, in recently developed areas, illumination from street lights or houses may compete with light traps and cause reduced mosquito collections. SLI staff recently conducted field assessments that revealed extensive woodcut in a single site and construction of new houses, buildings, and a pump station not far from trap locations in at least 4 of 10 sites in the past few years (unpublished data). Although these assessments were limited, reduced collections of Cs. melanura were most likely caused by diminished habitat around the trap sites. Trap site conditions should be evaluated periodically to obtain sufficient mosquito vectors for analysis.

Weekly MIR differences between years with and without human cases combined with a significant association between mosquito indicators and human illness clearly showed that Cs. melanura plays an essential role in EEE virus transmission. Of the three mosquito indicators, the strongest association with human disease was observed with the number of infected Cs. melanura. Although previous reports identified that the abundance of this vector correlated with mammalian disease, we could not find a significant association as was observed with horses in New York.30–32 We confirmed that vector abundance alone is not associated at a statistically significant level with human EEE disease.5

Unlike most reports, associations between zoophilic mosquito indicators and human disease were not found. Because these vectors have been thought to be responsible for mammalian infection in the state from a variety of evidence,33,34 these results may well be caused in part by small numbers of captured mosquitoes and low infection rates. There are two possible approaches to clarify the roles of human biting vectors. First, trapping strategy could be changed to obtain more mosquitoes. As we previously reported, CO2-unbaited CDC light traps do not collect large numbers of human biting species.35 Other types of traps set in other habitats may collect enough vectors for meaningful calculation; however, how many zoophilic vectors need to be collected in terms of human disease prediction remains unresolved.36 Another possibility is implementing more sensitive testing for virus detection. Findings in this report are based on the results from culture-based tests, but these conventional methods may miss mosquitoes with low viral titers or non-replicating virus.37 Real-time detection polymerase chain reaction (RTD-PCR) may detect larger proportion of infected vectors. SLI now performs RTD-PCR for all mosquito samples. Attention should be paid to interpretation and comparison to older data.

MIRs for Cs. melanura increased as its population decreased toward the end of the season. The same phenomenon was observed in Alabama and could be caused by blood meal preferences, host availability, and host–vector interaction change in late summer.33,37–39 High MIRs do not seem to indicate a significant public health threat late in the season, because human-biting vectors become inactive in Massachusetts in late September,27 and only one patient was reported with disease onset after the 39th week (Figure 1Go). Whether an increased MIR among Cs. melanura late in the season plays a role in over-wintering of EEE virus is not known.

The Massachusetts Department of Public Health has developed guidelines for a phased response to EEE virus surveillance data.40 The guidelines include five risk categories that take into account prior and current year EEE virus activity in mosquitoes, equines, and humans. The risk of human outbreak probability ranges from level 1(remote) through level 5(critical). For example, level 1 requires no previous year or current year virus activity before July and recommends routine surveillance and measures to reduce mosquito breeding. On the other hand, level 5 requires multiple EEE virus isolations from mosquitoes, horses, or human cases and recommends stronger action such as active surveillance and increased adulticiding. This study offers quantitative basis for mosquito control policy in Massachusetts. This report presents sensitivity, specificity, positive predictive value, and negative predictive value to estimate human arthropod-borne disease risk on a weekly basis.

This work has some limitations. To eliminate bias and to have consistency in data collected and evaluated throughout the long study period, we excluded potentially useful data that was collected from supplemental trapping efforts. For instance, CO2-baited light traps are set in response to increased virus activity in Cs. melanura, and additional surveillance sites are set in response to human or equine EEE cases. Extensive surveillance using gravid traps and CO2-baited traps to collect Culex mosquitoes began in response to the arrival of West Nile virus (WNV) in New York City in 1999; these mosquitoes are tested for EEEV as well as WNV. In addition, for many years, regional Mosquito Control Districts have played a major role in mosquito surveillance for EEE and WNV in Massachusetts, with selected collections also tested at the SLI. Further analyses should include the supplemental data. Second, southeast Massachusetts is a large area, and we only estimate overall risk in this area. Site-specific data, however, is used to target areas for additional surveillance and possible responses. Third, during the time of this study, the lack of timeliness for confirming positive mosquito pools was a factor. Turnaround time was previously reported as 4 days for mosquito results from cell culture, but RTD-PCR has currently shortened this to as little as 24 hours from mosquito collection to report.20 Considering that an EEE incubation period may be 5–7 days, public awareness should ideally be increased 1–2 weeks before the time of the highest risk.41 Early awareness of the possibility of human EEE cases may also improve the timeliness of having appropriate clinical specimens tested at the SLI. Geographic Information System–based analyses for both mosquito and human data will allow us to improve the estimates of time-spatial risk assessment. For instance, data loggers to record site-specific weather conditions are now in place. Fourth, the positive predictive value of EEE virus MIR for Cs. melanura was low (0.14). This may be attributed to the low incidence of human EEE. A threshold value of an MIR of 0.39 for the long-term sites does have use, however, if one considers that values < 0.39 indicate a low risk of human disease; MIR values > 0.39 indicate the need for increased surveillance efforts, such as supplemental trapping and early notifications of the presence of virus to health care providers and the public. For practical purposes, an increasing or a sustained elevation in MIR in a focal area, taking into consideration all trapping, increases the level of response in those communities. Finally, mosquito indicators combined with other environmental and ecologic information, such as temperature and precipitation, wind trajectory, wild bird population and immunity, and EEE virus strains may offer more precise evaluation of human EEE disease risks.19,20,42–46

We provided a quantitative analysis of the association between mosquito indicators and human EEE disease risk. Our study is unique in reporting weekly population and EEE virus MIR for Cs. melanura captured by a single trap type at 10 fixed sites for 26 years with three human EEE disease out-breaks. EEEV MIR and the abundance of infected Cs. melanura are significantly associated with human EEE disease occurrence. Timeliness in the evaluation of suspect human cases for EEE plays a critical role in the assessment of public health risk. Indications of early season MIR values increasing above mean values must trigger increased active surveillance and fast-tracking of suspect human specimens for EEE virus and antibody testing. To prevent future outbreaks, it is crucial to conduct timely testing and MIR calculations and to use the data to inform and, if need be, alert Mosquito Control Districts, health care providers, and the public.

Received December 30, 2005. Accepted for publication November 13, 2006.

Acknowledgments: We are grateful to the field, laboratory, and epidemiology staff of the Arbovirus Surveillance Program at the Massachusetts State Laboratory over the course of the study period, especially former laboratory directors, G. F. Grady and R. J. Timperi. The authors thank A. DeMaria and J. Yasuoka for critical review of the manuscript; H. Uno for suggestions about the statistical analyses; and A. Spielman, R. Pollack, A. Kiszewski, S. Telford, and colleagues for discussions about arboviral surveillance. Our special thanks to the Mosquito Control District personnel, local health departments, and health care providers who make arbovirus surveillance possible in Massachusetts. M.H. was supported in part by Drs K. and H. Mukaiyama Fund, Yokohama Medical Association.

* Address correspondence to Barbara G. Werner, State Laboratory Institute, 305 South Street, Boston, MA 02130. E-mail: barbara. werner{at}state.ma.us Back

Authors’ addresses: Masahiko Hachiya, Matthew Osborne, Cynthia Stinson, and Barbara G. Werner, State Laboratory Institute, 305 South Street, Boston, MA 02130, Telephone: 617-983-6365, Fax: 617-983-6363, E-mails: barbara.werner{at}state.ma.us, hachiya.masahiko{at}post.harvard.edu, matthew.a.osborne{at}dph.state.ma.us, and cynthia.stinson{at}state.ma.us.


REFERENCES
TOP
 ABSTRACT
 INTRODUCTION
 MATERIALS AND METHODS
 RESULTS
 DISCUSSION
 REFERENCES
 

  1. Centers for Disease Control and Prevention, 2000. Chart: Confirmed and probable eastern equine encephalitis cases, human, United States, 1964–2000, by state. Available at http://www.cdc.gov/ncidod/dvbid/arbor/cases-eee-1964-2000.htm. Accessed July 27, 2005.
  2. Ayres JC, Feemster RF, 1949. The sequelae of eastern equine encephalomyelitis. N Engl J Med 240: 960–962.[Medline]
  3. Przelomski MM, O’Rourke E, Grady GF, Berardi VP, Markley HG, 1988. Eastern equine encephalitis in Massachusetts: A report of 16 cases, 1970–1984. Neurology 38: 736–739.[Abstract/Free Full Text]
  4. Deresiewicz RL, Thaler SJ, Hsu L, Zamani AA, 1997. Clinical and neuroradiographic manifestations of eastern equine encephalitis. N Engl J Med 336: 1867–1874.[Abstract/Free Full Text]
  5. Morris CD, 1988. Eastern equine encephalomyelitis. Monath TP, ed. The Arboviruses: Epidemiology and Ecology. Boca Raton, FL: CRC Press, 1–20.
  6. Villari P, Spielman A, Komar N, McDowell M, Timperi R, 1995. The economic burden imposed by a residual case of eastern encephalitis. Am J Trop Med Hyg 52: 8–13.[Abstract/Free Full Text]
  7. Hayes RO, Daniels JB, Anderson KS, Parsons MA, Maxfield HK, Lamotte LC, 1962. Detection of eastern encephalitis virus and antibody in wild and domestic birds in Massachusetts. Am J Hyg 75: 183–189.[ISI][Medline]
  8. Howard JJ, Wallis RC, 1974. Infection and transmission of eastern equine encephalomyelitis virus with colonized Culiseta melanura (Coqillett). Am J Trop Med Hyg 23: 522–525.[Abstract/Free Full Text]
  9. Hayes RO, Beadle LD, Hess AD, Sussman O, Bonese MJ, 1962. Entomological aspects of the 1959 outbreak of eastern encephalitis in New Jersey. Am J Trop Med Hyg 11: 115–121.[Abstract/Free Full Text]
  10. Morris CD, Caines AR, Woodall JP, Bast TF, 1975. Eastern equine encephalomyelitis in upstate New York, 1972–1974. Am J Trop Med Hyg 24: 986–991.[ISI][Medline]
  11. Merrill MH, Lacaillade CW Jr, Ten Broeck C, 1934. Mosquito transmission of equine encephalomyelitis. Science 80: 251–252.[Free Full Text]
  12. Davis WA, 1940. A study of birds and mosquitoes as hosts for the virus of eastern equine encephalomyelitis. Am J Hyg 32: 45–59.
  13. Chamberlain RW, Sikes RK, Nelson DB, Sudia WD, 1954. Studies on the North American arthropod-borne encephalitidis. Quantitative determinations of virus-vector relationship. Am J Hyg 60: 278–285.
  14. Moore CG, McLean RG, Mitchell CJ, Nasci RS, Tsai TF, Calisher CH, Marfin AA, Moore PS, Gubler DJ, 1993. Division of Vector-Borne Infectious Diseases. Guidelines for Arbovirus Surveillance Programs in the United States. Atlanta: Centers for Disease Control and Prevention.
  15. Fothergill LD, Dingle JH, Farber S, Connerley ML, 1938. Human encephalitis caused by the virus of the eastern variety of equine encephalomyelitis. N Engl J Med 219: 411.[ISI]
  16. Getting VA, 1941. Equine encephalomyelitis in Massachusetts. An analysis of the 1938 outbreak, a follow-up of cases and a report of a mosquito survey. N Engl J Med 224: 999–1006.[ISI]
  17. Winter WD, 1956. Eastern equine encephalomyelitis in Massachusetts in1955. Report of two cases in infants. N Engl J Med 255: 262–267.[ISI][Medline]
  18. Webster HF, 1956. Eastern equine encephalomyelitis in Massa-chusetts. Report of two cases, diagnosed serologically, with complete clinical recovery. N Engl J Med 255: 267–270.[ISI][Medline]
  19. Feemster RF, Wheeler RE, Daniels JB, Rose HD, Schaeffer M, Kissling RE, Hayes RO, Alexander ER, Murray WA, 1958. Field and laboratory studies on equine encephalitis. N Engl J Med 259: 107–113.[ISI][Medline]
  20. Grady GF, Maxfield HK, Hildreth SW, Timperi RJ Jr, Gilfillan RF, Rosenau BJ, Francy DB, Calisher CH, Marcus LC, Mad-off MA, 1978. Eastern equine encephalitis in Massachusetts, 1957–1976: A prospective study centered upon analyses of mosquitoes. Am J Epidemiol 107: 170–178.[Abstract/Free Full Text]
  21. Edman JD, Timperi R, Werner B, 1993. Epidemiology of eastern equine encephalitis in Massachusetts. J Fla Mosq Control Assoc 64: 84–96.
  22. Beatty BJ, Calisher CH, Shope RE, 1989. Arboviruses. Schmidt NJ, Emmons RW, eds. Diagnostic Procedures for Viral, Rickettsial and Chlamydial Infections. 6th ed. Washington, DC: American Public Health Association, 797–855.
  23. Lanciotti RS, Kerst AJ, Nasci RS, Godsey MS, Mitchell CJ, Savage HM, Komar N, Panella NA, Allen BC, Volpe KE, Davis BS, Roehrig JT, 2000. Rapid detection of West Nile virus from human clinical, field-collected mosquitoes, and avian samples by a TaqMan reverse transcriptase-PCR assay. J Clin Microbiol 38: 4066–4071.[Abstract/Free Full Text]
  24. Martin DA, Muth DA, Brown T, Johnson AJ, Karabatsos N, Roehrig JT, 2000. Standardization of immunoglobulin M capture enzyme-linked immunosorbent assays for routine diagnosis of arboviral infections. J Clin Microbiol 38: 1823–1826.[Abstract/Free Full Text]
  25. Johnson AJ, Martin DA, Karabatsos N, Roehrig JT, 2000. Detection of anti-arboviral immunoglobulin G by using a monoclonal antibody-based capture enzyme-linked immunosorbent assay. J Clin Microbiol 38: 1827–1831.[Abstract/Free Full Text]
  26. Main AJ, Tonn RJ, Randall EJ, Anderson KS, 1966. Mosquito densities at heights of five and twenty-five feet in southeastern Massachusetts. Mosquito News 26: 243–248.
  27. Main AJ, Hayes RO, Tonn RJ, 1968. Seasonal abundance of mosquitoes in southeastern Massachusetts. Mosquito News 28: 619–626.
  28. Hall B, Motzkin G, Foster DR, Syfert M, Burk J, 2002. Three hundred years of forest and land-use change in Massachusetts, USA. J Biogeography 29: 1319–1335.
  29. Zampella RA, Lathrop RG, 1997. Landscape changes in Atlantic white cedar (Chamaecyparis thyoides) wetlands of the New Jersey Pinelands. Landscape Ecol 12: 397–408.
  30. Wallis RC, Howard JJ, Main Jr. Frazier C, Hayes C, 1974. An increase of Culiseta melanura coinciding with an epizootic of eastern equine encephalitis in Connecticut. Mosq News 34: 63–65.
  31. Ross WA, Kaneene JB, 1996. Evaluation of outbreaks of disease attributable to eastern equine encephalitis virus in horses. J Am Vet Med Assoc 208: 1988–1997.[ISI][Medline]
  32. Howard JJ, Morris CD, Emord DE, Grayson MA, 1988. Epizootiology of eastern equine encephalitis virus in upstate New York, USA. VII. Virus surveillance 1978–85, description of 1983 outbreak, and series conclusions. J Med Entomol 25: 501–514.[ISI][Medline]
  33. Nasci RS, Edman JD, 1981. Blood-feeding patterns of Culiseta melanura (Diptera: Culicidae) and associated sylvan mosquitoes in southeastern Massachusetts eastern equine encephalitis enzootic foci. J Med Entomol 18: 493–500.
  34. Moncayo AC, Edman JD, 1999. 1999. Toward the incrimination of epidemic vectors of eastern equine encephalomyelitis virus in Massachusetts: Abundance of mosquito populations at epidemic foci. J Am Mosq Control Assoc 15: 479–492.[ISI][Medline]
  35. Buckley D, Timperi R, Tobin M, Werner B, 1994. Comparison of three methods used to collect mosquitoes in Massachusetts. J Fla Mosq Control Assoc 65: 8–11.
  36. Gu W, Novak RJ, 2004. Short report: detection probability of arbovirus infection in mosquito populations. Am J Trop Med Hyg 71: 636–638.[Abstract/Free Full Text]
  37. Cupp EW, Klingler K, Hassan HK, Viguers LM, Unnasch TR, 2003. Transmission of eastern equine encephalomyelitis virus in central Alabama. Am J Trop Med Hyg 68: 495–500.[Abstract/Free Full Text]
  38. Stamm DD, Chamberlain RW, Sudia WD, 1962. Arbovirus studies in south Alabama 1957–58. Am J Hyg 76: 61–81.[ISI][Medline]
  39. Le Duc JE, Suyemoto W, Eldridge BF, Saugstad ES, 1972. Ecology of arboviruses in a Maryland freshwater swamp, II. Blood feeding patterns of potential mosquito vectors. Am J Epidemiol 96: 123–128.[Abstract/Free Full Text]
  40. Massachusetts Department of Public Health. 2006 Massachusetts Arbovirus Surveillance and Response Plan. Available at http://www.mass.gov/dph/wnv/arbovirus_surveillance_plan_2006.doc.
  41. Calisher CH, 1994. Medically important arbovirus of the United States and Canada. Clin Microbiol Rev 7: 89–116.[Abstract/Free Full Text]
  42. Hayes RO, Hess AD, 1964. Climatological conditions associated with outbreaks of eastern encephalitis. Am J Trop Med Hyg 13: 851–858.[Abstract/Free Full Text]
  43. Sellers RF, Maarouf AR, 1990. Trajectory analysis of winds and eastern equine encephalitis in USA, 1980–5. Epidemiol Infect 104: 329–343.[Medline]
  44. Main AJ, Anderson KS, Maxfield HK, Rosenau B, Oliver C, 1988. Duration of Alphavirus neutralizing antibody in naturally infected birds. Am J Trop Med Hyg 38: 208–217.[Abstract/Free Full Text]
  45. Komar N, Dohm DJ, Turell MJ, Spielman A, 1999. Eastern equine encephalitis virus in birds: Relative competence of European starlings (Sturnus vulgaris). Am J Trop Med Hyg 60: 387–391.[Abstract]
  46. Weaver SC, Hagenbaugh A, Bellew LA, Gousset L, Mallampalli V, Holland JJ, Scott TW, 1994. Evolution of alphaviruses in the eastern equine encephalomyelitis complex. J Virol 68: 158–169.[Abstract/Free Full Text]




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