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Culex Mosquitoes and West Nile Virus CLOSE ENCOUNTERS WITH THE ENVIRONMENT What’s Eating You? Culex Mosquitoes and West Nile Virus Marissa Lobl, BS; Taylor Kay Thieman, BS; Dillon Clarey, MD; Shauna Higgins, MD; Ryan M. Trowbridge, MD, MS, MA; Angela Hewlett, MD; Ashley Wysong, MD, MS What is West Nile virus? How is it contracted, PRACTICE POINTS and who can becomecopy infected? • Dermatologists should be aware of the most com- West Nile virus (WNV) is a single-stranded RNA virus mon rash associated with West Nile virus (WNV), of the Flaviviridae family and Flavivirus genus, a lineage which is a nonspecific maculopapular rash appear- that also includes the yellow fever, dengue, Zika, Japanese ing on the trunk and extremities around 5 days encephalitis, and Saint Louis encephalitis viruses.1 Birds after the onset of fever, fatigue, and other nonspe- serve as the reservoir hosts of WNV, and mosquitoes not 2 cific symptoms. acquire the virus during feeding. West Nile virus then • Rash may serve as a prognostic indicator for is transmitted to humans primarily by bites from Culex improved outcomes in WNV due to its association mosquitoes, which are especially prevalent in wooded with decreased risk of encephalitis and death. areas during peak mosquito season (summer through • An IgM enzyme-linked immunosorbent assay forDo early fall in North America).1 Mosquitoes also can infect WNV initially may yield false-negative results, as the horses; however, humans and horses are dead-end hosts, development of detectable antibodies against the meaning they do not pass the virus on to other biting virus may take up to 8 days after symptom onset. mosquitoes.3 There also have been rare reports of trans- mission of WNV through blood and donation as well as mother-to-baby transmission.2 West Nile virus (WNV) commonly presents cutaneously as a macu- What is the epidemiology of WNV in lopapular rash on the trunk and extremities that most often appears the United States? around the time of defervescence and may serve as a positive Since the introduction of WNV to the United States prognostic indicator. Several laboratory tests can aid in diagnosis of in 1999, it has become an important public health WNV, including an IgM enzyme-linkedCUTIS immunosorbent assay (ELISA), concern, with 48,183 cases and 2163 deaths reported but an antibody response may not be detectable for up to 8 days 2,3 after symptom onset. Taking a comprehensive history in any patient since 1999. In 2018, Nebraska had the highest presenting with a generalized maculopapular rash, fever, nonspecific number of cases of WNV (n=251), followed by California symptoms, or neurologic changes can aid the astute dermatologist (n=217), North Dakota (n=204), Illinois (n=176), and in promptly recognizing the possibility of WNV. South Dakota (n=169).3 West Nile virus is endemic Cutis. 2021;107:244-247. to all 48 contiguous states and Canada, though the Great Plains region is especially affected by WNV due Ms. Lobl, Ms. Thieman, and Drs. Clarey, Hewlett, and Wysong are from the University of Nebraska Medical Center, Omaha. Ms. Lobl, Ms. Thieman, and Drs. Clarey and Wysong are from the Department of Dermatology, and Dr. Hewlett is from the Division of Infectious Diseases. Dr. Higgins is from the Department of Dermatology, University of Southern California, Los Angeles. Dr. Trowbridge is from CHI Health, Omaha. Ms. Lobl, Ms. Thieman, and Drs. Clarey, Higgins, Trowbridge, and Hewlett report no conflict of interest. Dr. Wysong serves as a Research Principal Investigator for Castle Biosciences. Correspondence: Ashley Wysong, MD, MS, 985645 Nebraska Medical Center, Omaha, NE 68198 ([email protected]). doi:10.12788/cutis.0251 244 I CUTIS® WWW.MDEDGE.COM/DERMATOLOGY Copyright Cutis 2021. No part of this publication may be reproduced, stored, or transmitted without the prior written permission of the Publisher. CLOSE ENCOUNTERS WITH THE ENVIRONMENT to several factors, such as a greater percentage of rural reported include an ill-defined pseudovesicular rash with land, forests, and irrigated areas.4 The Great Plains erythematous papules on the palms and pink, scaly, pso- region also has been thought to be an ecological niche riasiform papules on the feet and thighs, as well as neuro- for a more virulent species (Culex tarsalis) compared to invasive WNV leading to purpura fulminans.14,15 A diffuse, other regions in the United States.5 erythematous, petechial rash on the face, neck, trunk, and The annual incidence of WNV in the United States extremities was reported in a pediatric patient, but there peaked in 2003 at 9862 cases (up from 62 cases in 1999), have been no reports of a petechial rash associated with then declined gradually until 2008 to 2011, during which WNV in adult patients.16 These findings suggest some the incidence was stable at 700 to 1100 new cases per potential variability in the presentation of the WNV rash. year. However, there was a resurgence of cases (n=5674) in 2012 that steadied at around 2200 cases annually in What role does the presence of rash subsequent years.6 Although there likely are several fac- play diagnostically and prognostically? tors affecting WNV incidence trends in the United States, The rash of WNV has been implicated as a potential prog- interannual changes in temperature and precipitation nostic factor in predicting more favorable outcomes.17 have been described. An increased mean annual tem- Using 2002 data from the Illinois Department of Public perature (from September through October, the end of Health and 2003 data from the Colorado Department peak mosquito season) and an increased temperature of Public Health, Huhn and Dworkin17 found the age- in winter months (from January through March, prior adjusted risk of encephalitis and death to be decreased to peak mosquito season) have both been associated in WNV patients with a rash (relative risk, 0.44; 95% with an increased incidence of WNV.7 An increased CI, 0.21-0.92). The reasons for this are not definitively temperature is thought to increase population numbers known, but we hypothesize that the rash may prompt of mosquitoes both by increasing reproductive rates and patients to seek earliercopy medical attention or indicate creating ideal breeding environments via pooled water a more robust immune response. Additionally, a rash areas.8 Depending on the region, both above average and in WNV more commonly is seen in younger patients, below average precipitation levels in the United States whereas WNV neuroinvasive disease is more common in can increase WNV incidence the following year.7,9 older patients, who also tend to have worse outcomes.10 One notstudy found rash to be the only symptom that dem- What are the signs and symptoms onstrated a significant association with seropositivity of WNV infection? (overall risk=6.35; P<.05; 95% CI, 3.75-10.80) by multi- Up to 80% of those infected with WNV are asymptom- variate analysis.18 atic.3 After an incubation period of roughly 2 to 14 days, the remaining 20% may develop symptoms of WestDo Nile How is WNV diagnosed? What are the fever (WNF), typically a self-limited illness that consists downsides to WNV testing? of 3 to 10 days of nonspecific symptoms such as fever, Given that the presenting symptoms of WNV and WNF headache, fatigue, muscle pain and/or weakness, eye are nonspecific, it becomes challenging to arrive at the pain, gastrointestinal tract upset, and a macular rash that diagnosis based solely on physical examination. As usually presents on the trunk or extremities.1,3 Less than 1% of patients affected by WNV develop neuroinvasive disease, including meningitis, encephalitis, and/or acute flaccid paralysis.10 West Nile virus neuroinvasive disease can cause permanent neurologic sequelae such as muscle weakness, confusion, CUTISmemory loss, and fatigue; it carries a mortality rate of 10% to 30%, which is mainly depen- dent on older age and immunosuppression status.1,10 What is the reported spectrum of cutaneous findings in WNV? Of the roughly 20% of patients infected with WNV that develop WNF, approximately 25% to 50% will develop an associated rash.1 It most commonly is described as a morbilliform or maculopapular rash located on the chest, back, and arms, usually sparing the palms and soles, though 1 case report noted involvement with these areas (Figure).11,12 It typically appears 5 days after symptom onset, can be associated with defervescence, and lasts Maculopapular rash in a patient with West Nile virus distributed over less than a week.1,13 Pruritus and dysesthesia are some- the upper back and posterior arm. Reproduced with permission from Sejvar,12 Viruses; published by MDPI, 2014. times present.13 Other rare presentations that have been WWW.MDEDGE.COM/DERMATOLOGY VOL. 107 NO. 5 I MAY 2021 245 Copyright Cutis 2021. No part of this publication may be reproduced, stored, or transmitted without the prior written permission of the Publisher. CLOSE ENCOUNTERS WITH THE ENVIRONMENT such, the patient’s clinical and epidemiologic history, $500 to $1000 and is only performed in reference laborato- such as timing, pattern, and appearance of the rash or ries. Although these tests remain in the repertoire for WNV recent history of mosquito bites, is key to arriving at diagnosis, financial stewardship is important. the correct diagnosis. With clinical suspicion, possible If there are symptoms of photophobia, phonophobia, diagnostic tests include an IgM enzyme-linked immu- nuchal rigidity, loss of consciousness, or marked person- nosorbent assay (ELISA) for WNV, a plaque reduction ality changes, a lumbar puncture for WNV IgM in the neutralization test (PNRT), and blood polymerase chain cerebrospinal fluid can be performed. As with most viral reaction (PCR). infections, cerebrospinal fluid findings normally include An ELISA is a confirmatory test to detect IgM anti- an elevated protein and lymphocyte count, but neutro- bodies to WNV in the serum.
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