West Nile virus (WNV) and St. Louis encephalitis virus (SLEV) are closely related mosquito-borne flaviviruses (Petersen et al. 2013, Curren et al. 2018). The majority of WNV and SLEV infections are asymptomatic, but can also result in nonspecific febrile illness or neurologic disease. When neuroinvasive disease occurs, it typically presents as encephalitis, meningitis, or acute flaccid paralysis. Older persons and those with certain underlying medical conditions are at higher risk for developing neuroinvasive disease (Jean et al. 2007, Lindsey et al. 2012).

Both viruses are endemic throughout much of the United States and share the same transmission cycle, including Culex species mosquito vectors and avian hosts. SLEV was first identified in St. Louis, Missouri, in 1933, and >50 outbreaks were reported in the United States during the next 70 years (Lumsden 1958, Kopp et al. 2013). SLEV disease incidence has been substantially lower than WNV disease incidence since WNV was first identified in the United States in 1999 (Reimann et al. 2008). However, isolated cases and limited outbreaks of SLEV disease still occur sporadically in the United States.

WNV disease and SLEV disease are both nationally notifiable conditions in the United States (CDC 2018). During 2010–2014, a total of 537 patients with WNV disease and only one patient with SLEV disease were reported to Arizona Department of Health Services (ADHS). However during 2015, by the end of July, seven patients with SLEV disease had been identified among Maricopa County residents; 22 patients with WNV disease also had been reported (Venkat et al. 2015). No outbreaks involving the two viruses circulating in the same location at the same time had previously been identified. An investigation was initiated to ascertain the magnitude and describe the epidemiology of the outbreak in Maricopa County, and compare the demographic and clinical features of patients with SLEV or WNV neuroinvasive disease.

The first known concurrent outbreaks of WNV and SLEV, two closely related flaviviruses, occurred in Maricopa County, Arizona in 2015. We found no apparent differences in clinical characteristics among 21 neuroinvasive WNV cases compared with 14 neuroinvasive SLEV cases.

The reason for the concurrent disease outbreaks in 2015 is unknown. Both WNV and SLEV are maintained in nature in mosquito/bird/mosquito transmission cycles, and changes in both Culex mosquito vector and avian host populations, linked to environmental factors, likely produced conditions favorable for transmission (Diaz et al. 2018). A factor contributing to reemergence of SLEV in Arizona is thought to be introduction of a new strain of SLEV closely related to an epidemic strain from Argentina (Diaz et al. 2018).

Although there were no significant differences in clinical characteristics of WNV and SLEV neuroinvasive cases, we found a higher proportion of SLEV neuroinvasive cases among persons ≥ 60 years of age compared with WNV neuroinvasive cases. Similar to our results that showed 57% of all SLEV neuroinvasive cases among persons ≥ 60 years of age, some previous studies have also suggested ~60% of SLEV neuroinvasive cases occur in persons in this age group (Powell and Blakey 1977). However, in contrast, reports from the U.S. National Notifiable Disease Surveillance System and most SLEV studies have shown 30–45% of SLEV neuroinvasive disease is in persons ≥ 60 years of age (Hopkins et al. 1975, Reimann et al. 2008, Curren et al. 2018). We found only 19% of all WNV neuroinvasive cases occurred in persons ≥ 60 years of age, but previous surveillance data have indicated that 45%–50% of neuroinvasive cases caused by WNV occur in this age group (Reimann et al. 2008, Lindsey et al. 2014). Therefore, the importance of our finding of the different comparative age distributions is uncertain. One possible explanation could be a focal area of SLEV transmission in an area of Maricopa County with a higher percentage of people ≥ 60 years of age, although this was not supported by the widespread geographical distribution and lack of clustering of WNV and SLEV cases. Our results might also have been affected by the inability to determine the specific infecting virus in 15 (27%) of the 56 neuroinvasive cases, resulting in these unspecified flavivirus cases being excluded from the analysis.

One interesting clinical finding was the higher frequency of rash in WNV cases compared with SLEV cases, with this symptom reported among 33% of 21 WNV cases and only 7% of 14 SLEV cases. No studies have directly compared patients during concurrent outbreaks, but disease-specific descriptions of the clinical presentations of these diseases support a higher frequency of rash in patients with WNV compared with SLEV neuroinvasive disease (Southern et al. 1969, Jones et al. 2002, Sejvar et al. 2003, Bode et al. 2006).

Several limitations should be considered. First, even though this was the largest outbreak of SLEV disease in >10 years, and the first outbreak of WNV and SLEV diseases occurring concurrently, relatively few neuroinvasive cases were available for the comparative analysis (Curren et al. 2018). Asymptomatic to symptomatic infection ratios are high for both WNV and SLEV infections, so patients with clinical disease represent only a small proportion of all infections (Reisen et al. 2008, Petersen et al. 2013). Inability to define the infecting virus because of flavivirus crossreactivity resulted in unspecified flavivirus diagnoses and contributed to the few WNV and SLEV cases for the comparative analysis. Limited case numbers also prevented us from performing multivariate analysis. Second, data were gathered from medical record reviews conducted for surveillance purposes and relevant information might not have been documented in the medical record. Third, clinical information was typically collected soon after hospital admission and the interval between symptom onset and admission could have influenced the likelihood of presence of symptoms and reported clinical findings.

Given that both WNV and SLEV diseases are caused by closely related flaviviruses, it is not surprising that the comparison of patient demographic and clinical characteristics did not clearly indicate specific features that could reliably differentiate the two infections. Nonetheless, it was useful to confirm these clinical findings during the first recognized outbreak that involved these two viruses circulating in the same location at the same time.

Health care providers should consider both WNV and SLEV infections in the differential diagnosis in patients with aseptic meningitis and encephalitis and obtain appropriate CSF samples, serum samples, or both for laboratory testing. Confirmatory testing at state health departments or CDC will be required to distinguish these flavivirus infections. Although clinical management for both diseases involves the same approach of supportive care, differentiating both infections is helpful for better understanding of their epidemiology, including any change in disease transmission patterns. Because human vaccines against domestic arboviruses are not available, prevention of arboviral infection depends on local vector control, community and household efforts to reduce vector populations (e.g., removal of standing water), and individual efforts to decrease exposure to mosquitoes (e.g., applying mosquito repellant, wearing protective clothing, and eliminating mosquito breeding sites).