Since the introduction of WNV into the United States in 1999, WNF and WNND have caused at least 31,365 illnesses and 1,250 deaths (27
). Once considered to be a mild influenza-like illness, WNF is now understood to be an acute viral infection, often followed by months of illness associated with depression, altered moods, headaches, and fatigue (28–30
). The illness associated with WNND, including meningitis, encephalitis, and acute flaccid paralysis, has been associated with persistent motor and cognitive deficits and incomplete recovery (28,31
). Reported cases of WNF and WNND underrepresent the actual number of WNV cases in the U.S. population (32,33
), and symptomatic persons represent only a fraction of those infected. In addition to individual suffering, the medical and public health costs associated with WNV average >$40,000 per case (34
) at a time when many health agencies are facing serious budgetary shortfalls.
The individual health toll and associated medical costs present a strong case for active intervention. Current means to prevent WNV infection include integrated vector management by larval mosquito control to arrest viral amplification and, in an outbreak, ground or aerial adulticide applications to eliminate infectious female mosquitoes and personal protection to avoid mosquito bites. Emergency application of adulticides became particularly controversial in California (35
), even though it is the only method that targets mosquitoes capable of transmitting virus and is cost-effective for preventing human cases (36
). In light of this controversy, mosquito control agencies in California are often hesitant to apply adulticides until epidemics appear imminent on the basis of available risk estimates or the occurrence of human cases. Our study comparatively evaluated 3 risk measures currently used as decision support tools for intervention and for predicting human cases.
By using only indicators of enzootic transmission, the CMVRA consistently produced estimates in the emergency planning range before human case occurrence; however, epidemic thresholds were not reached until after human cases had been detected. Risk assessment by this method required a robust arboviral surveillance program, with regular sampling for multiple surveillance indicators. The specificity and PPV when the epidemic threshold of 4.1 was used were excellent; however, this was at the expense of adequate lead time for initiating intervention efforts before some human cases. Additionally, the sensitivity of the risk estimate was less than desirable at 0.317, meaning that fewer than one third of the high-risk periods were correctly identified. The CMVRA using the 4.1 threshold was poor at predicting high-risk intervals but good at predicting low-risk intervals.
The 2.6 emergency planning threshold for the CMVRA increased sensitivity and provided a predictive indication of human cases before their onset. The likelihood ratio positive was better than the DYCAST risk estimates, and the likelihood ratio negative was the best of all methods. In addition, the associated risk for human cases, measured by the Mantel-Haenszel relative risk, was the greatest. At the 2.6 emergency planning threshold, the CMVRA was excellent at predicting high-risk periods and good at predicting low-risk periods.
The vector index was simple to calculate and required only a mosquito surveillance and testing program, thereby saving costs associated with sentinel chicken maintenance and sampling and dead bird reporting and testing programs. Unfortunately, this measure did not have preestablished risk thresholds. In our study, it appeared that setting the threshold to >0 (i.e., whenever mosquito infection was detected) would be adequate for predicting human cases in urban settings, such as Los Angeles, where Cx. p. quinquefaciatus mosquitoes are the primary vectors and temperatures generally permit viral amplification. The estimates of the vector index increased before case occurrence in 5 of the 7 years. The sensitivity and specificity were comparable with those of the CMVRA, but the likelihood ratio positive was the greatest of all risk estimates. The likelihood ratio negative was better than that of the DYCAST but not as good as that of the CMVRA. Therefore, the vector index was moderate at predicting high-risk periods and very good at predicting low-risk periods. The measure of risk associated with a high-risk value, assessed by the Mantel-Haenszel relative risk, was also better than the DYCAST risk estimate but not as good as either CMVRA threshold.
The DYCAST risk estimate was useful in years with amplified enzootic transmission, when dead birds were considered the primary WNV surveillance indicator (4,37–39
). However, after the initial epidemic, WNV activity has been progressively more difficult to predict by using DYCAST because of reduced reporting to the California Dead Bird Hotline. Whether this decrease resulted from truly decreased numbers of dead birds as bird populations became progressively more resistant to infection or to public apathy/decreased awareness was not possible to ascertain. Losing time precision by aggregating estimates clearly increased measures of validity, which considering the uncertainty regarding time between WNV exposure and disease onset seemed appropriate to improve predictive power. The sensitivity of the weekly DYCAST risk estimate was similar to that of the CMVRA, but the specificity, PPV, likelihood ratio positive, and likelihood ratio negative were all uniformly worse than the other 2 methods, even when aggregated spatially. Additionally, the measure of relative risk associated with risk estimates was less than that of the CMVRA and the vector index.
In conclusion, critical decisions on intervention by using risk estimates require knowledge of the strengths and weaknesses of the selected method to respond in an adequate and timely manner to prevent human cases while reducing unnecessary response and costs associated with falsely identified high-risk periods. The goals we set for a good WNV risk estimate were a balance of these attributes and were achieved best in urban and suburban Los Angeles by the CMVRA by using the 2.6 epidemic planning threshold. In light of this finding, an evaluation of the CMVRA should be done in other ecologic settings with transmission driven by other vector species to determine whether the threshold should be adjusted to provide better antecedent estimates of human risk.