Rash Observations About West Nile Virus Colorado, 2003

1. Rash Observations About West Nile Virus — Colorado, 2003 Dayna Ferguson, MD Colorado Dept of Public Health and Environment Office of Workforce and Career Development, CDC Good morning (I’m Dayna Ferguson – EIS Officer with the Colorado Department of Public Health and Environment) It’s my pleasure today to present observations of the rash associated with West Nile Virus based on the 2003 outbreak in Colorado. Good morning (I’m Dayna Ferguson – EIS Officer with the Colorado Department of Public Health and Environment) It’s my pleasure today to present observations of the rash associated with West Nile Virus based on the 2003 outbreak in Colorado.

2. 2 Rash Investigations Clinical description of rash associated with WNV fever Analysis of Colorado 2003 surveillance data I’ll be presenting data from two studies. First, a small investigation to describe rash associated with WN fever. Second, an analysis of Colorado’s 2003 surveillance data to describe how rash is associated with WNV disease and death. I’ll be presenting data from two studies. First, a small investigation to describe rash associated with WN fever. Second, an analysis of Colorado’s 2003 surveillance data to describe how rash is associated with WNV disease and death.

3. WNV-Associated Rash Description Erythematous maculopapules Neck, trunk, arms and legs 19%–57% of patients withWNV disease WNV-associated rash has been briefly described in the literature Most commonly as an erythematous maculopapular rash – or a combination small red flat and raised spots. The distribution includes the neck, trunk, arms, and legs The reported percentage of WNV patients who develop rash has varied widely from 19% in New York City in 1999 to 57% in a study of WN fever patients in Illinois in 2002WNV-associated rash has been briefly described in the literature Most commonly as an erythematous maculopapular rash – or a combination small red flat and raised spots. The distribution includes the neck, trunk, arms, and legs The reported percentage of WNV patients who develop rash has varied widely from 19% in New York City in 1999 to 57% in a study of WN fever patients in Illinois in 2002

4. Rash Investigation Goal – describe WNV-associated rash Case definition =18 years New rash Fever, headache or myalgias Positive anti-WNV IgM WNV fever Clinicians described rash Questionnaire In Sept 2003, we set out to better describe WNV-associated rash We investigated patients at CDC and clinics in the Fort Collins area who met the case definition >18 years, With new rash, either fever, headache, or myalgias a positive anti-WNV IgM And a diagnosis of WN fever Clinicians described the rash and administered a questionnaire to patients In Sept 2003, we set out to better describe WNV-associated rash We investigated patients at CDC and clinics in the Fort Collins area who met the case definition >18 years, With new rash, either fever, headache, or myalgias a positive anti-WNV IgM And a diagnosis of WN fever Clinicians described the rash and administered a questionnaire to patients

5. Demographics(n=17) Median age, y (range) 43 (24–65) Female, n (%) 10 (59) We had a convenience sample of 17 patients with WN fever and rash The median age was 43 years 59% of patients were female No hospitalizations or death occurred We had a convenience sample of 17 patients with WN fever and rash The median age was 43 years 59% of patients were female No hospitalizations or death occurred

6. Rash Timeline Median Range Illness duration, d 14 (7–123) Rash duration, d 7 (3–28) Illness–Rash, d 5 (0–7) The illness lasted a median of 14 days The rash lasted a median of 7 days Rash occurred a median of 5 days after illness onsetThe illness lasted a median of 14 days The rash lasted a median of 7 days Rash occurred a median of 5 days after illness onset

7. Rash Description (n=17) Description No. (%) Maculopapular 13 (76) Macular 3 (18) Vesicular 1 (6) Most patients 76% had a maculopapular rash 18% had a macular rash (made up of only small flat lesions) And 1 patient was described as having a vesicular rashMost patients 76% had a maculopapular rash 18% had a macular rash (made up of only small flat lesions) And 1 patient was described as having a vesicular rash

8. Rash Distribution (n=17) Site of rash No. (%) Trunk 16 (94) Upper extremities 15 (88) Lower extremities 13 (76) Head/neck 9 (53) Rash was located on the trunk in 94% of patients upper extremities in 88% lower extremities in 76% And the head or neck in 53% We also looked at sites of onset and spread to determine if there was a pattern that was characteristic for WNV disease. But we did not identify such a patternRash was located on the trunk in 94% of patients upper extremities in 88% lower extremities in 76% And the head or neck in 53% We also looked at sites of onset and spread to determine if there was a pattern that was characteristic for WNV disease. But we did not identify such a pattern

9. Additional Findings (n=17) Characteristic No. (%) Dysesthesia 6 (35) Hyperesthesia 3 (18) Pruritis 5 (29) Some interesting findings were that 35% of patients reported dysesthesias where rash was associated with numbness or tingling of the skin Of these patients, 3 also described hyperesthesia where it hurt to touch the skin. One described it as feeling like a sunburn 29% of patients reported pruritis or itching Some interesting findings were that 35% of patients reported dysesthesias where rash was associated with numbness or tingling of the skin Of these patients, 3 also described hyperesthesia where it hurt to touch the skin. One described it as feeling like a sunburn 29% of patients reported pruritis or itching

10. Maculopapular Rash – Thigh The next three slides show pictures of the rash in patients with WN fever. This picture shows a patient’s posterior thigh with a maculopapular rash – a combination of small, flat and raised red lesions. The next three slides show pictures of the rash in patients with WN fever. This picture shows a patient’s posterior thigh with a maculopapular rash – a combination of small, flat and raised red lesions.

11. Maculopapular Rash - Back This picture shows maculopapular rash on a patient’s backThis picture shows maculopapular rash on a patient’s back

12. Maculopapular Rash - Flank This picture again shows a maculopapular rash on a patient’s flankThis picture again shows a maculopapular rash on a patient’s flank

13. IgM Test Results Median, d Range Acute test pos (n=6) Onset–test 1 17 (7–25) Acute test neg (n=11) Onset–test 1 5 (0–8) Onset–test 2 23 (11–42) We found that only 6 or 35% of patients were positive on their initial test for anti WNV IgM antibodies Among the 6 that were positive, the median duration between illness onset and initial sera collection was 17 days In contrast, in 11 patients with a negative initial test, sera were collected earlier in the disease with a median of 5 days between illness onset and sera collection Among these patients the median duration between onset and a positive convalescent sera was 23 days. So, in more than ½ of our patients rash was present before anti-WNV IgM antibodies were detectable. We found that only 6 or 35% of patients were positive on their initial test for anti WNV IgM antibodies Among the 6 that were positive, the median duration between illness onset and initial sera collection was 17 days In contrast, in 11 patients with a negative initial test, sera were collected earlier in the disease with a median of 5 days between illness onset and sera collection Among these patients the median duration between onset and a positive convalescent sera was 23 days. So, in more than ½ of our patients rash was present before anti-WNV IgM antibodies were detectable.

14. Summary of Rash Characteristics New Findings Nonspecific pattern of onset and spread Dysesthesia & hyperesthesia were somewhat common Pruritis was somewhat common Rash does not appear to be antibody mediated New findings of this investigation are that WNV rash had a nonspecific pattern of onset and spread Dysesthesia and hyperesthesia have not previously been associated WN fever. Pruritis was also somewhat commonly associated with rash in this study. To my knowledge, pruritis has only been described with WNV rash once in the literature. As rash occurred a median of 5 days after illness onset and the majority of patients in the study were IgM negative WNV-associated rash does not appear to antibody-mediated New findings of this investigation are that WNV rash had a nonspecific pattern of onset and spread Dysesthesia and hyperesthesia have not previously been associated WN fever. Pruritis was also somewhat commonly associated with rash in this study. To my knowledge, pruritis has only been described with WNV rash once in the literature. As rash occurred a median of 5 days after illness onset and the majority of patients in the study were IgM negative WNV-associated rash does not appear to antibody-mediated

15. Analysis ofColorado 2003 Surveillance Data How common is rash inWNV disease? Is rash associated with outcome? Now I am going to transition to an analysis of Colorado’s 2003 surveillance data. I sought to answer the following questions: How common is rash among patients with WNV disease? Is rash is associated with outcome? Now I am going to transition to an analysis of Colorado’s 2003 surveillance data. I sought to answer the following questions: How common is rash among patients with WNV disease? Is rash is associated with outcome?

16. Surveillance Case Definition Colorado resident 2003 Compatible illness Positive serum or CSF anti-WNV IgM A WNV patient was defined as a Colorado resident in 2003 with a compatible illness And a Positive serum or cerebrospinal fluid anti WNV IgM A person with a compatible illness (a non-specific, self-limited, febrile illness caused by infection with WNV, clinical disease generally occurs 2-6 days following the bite of an infected mosquito. Typical cases are characterized by the acute onset of fever, headache, arthralgias, myalgias, and fatigue. Maculopapular rash and lymphadenopathy generally are observed in less than 20% of cases. Illness typically lasts 2-7 days.) A WNV patient was defined as a Colorado resident in 2003 with a compatible illness And a Positive serum or cerebrospinal fluid anti WNV IgM A person with a compatible illness (a non-specific, self-limited, febrile illness caused by infection with WNV, clinical disease generally occurs 2-6 days following the bite of an infected mosquito. Typical cases are characterized by the acute onset of fever, headache, arthralgias, myalgias, and fatigue. Maculopapular rash and lymphadenopathy generally are observed in less than 20% of cases. Illness typically lasts 2-7 days.)

17. WNV Disease Category Fever Compatible illness No evidence CNS disease Meningitis Evidence of CNS disease Normal mental status WNV Patients were categorized as having WN fever, meningitis or encephalitis. A WN fever patient was defined as a patient with a compatible illness, And no clinical or laboratory evidence of central nervous system disease. A meningitis patient was defined as a patient with clinical or laboratory evidence of central nervous system disease but normal mental status WNV Patients were categorized as having WN fever, meningitis or encephalitis. A WN fever patient was defined as a patient with a compatible illness, And no clinical or laboratory evidence of central nervous system disease. A meningitis patient was defined as a patient with clinical or laboratory evidence of central nervous system disease but normal mental status

18. WNV Disease Category Encephalitis Evidence of CNS disease Altered mental status Acute flaccid paralysis Not counted An encephalitis patient was defined as a patient with clinical or laboratory evidence of central nervous system disease, and specifically with altered mental status Of note, we did not count acute flaccid paralysis cases An encephalitis patient was defined as a patient with clinical or laboratory evidence of central nervous system disease, and specifically with altered mental status Of note, we did not count acute flaccid paralysis cases

19. Surveillance Data Collection Lab reportable condition Standard interview Chart review Death certificates WNV is a lab reportable condition in Colorado. local health dept staff interviewed patients or family members using a standard interview to collect information about demographics, and symptoms In additions I performed chart review on two groups: Encephalitis patients who weren’t interviewed and Patients listed as dying from WN fever or meningitis Deaths were recorded during interviews and supplemented with death certificate review, counting cases where WNV disease was listed as the underlying condition or a significant contributing conditionWNV is a lab reportable condition in Colorado. local health dept staff interviewed patients or family members using a standard interview to collect information about demographics, and symptoms In additions I performed chart review on two groups: Encephalitis patients who weren’t interviewed and Patients listed as dying from WN fever or meningitis Deaths were recorded during interviews and supplemented with death certificate review, counting cases where WNV disease was listed as the underlying condition or a significant contributing condition

20. 2003 Surveillance Results(n=2626) Characteristic No. (%) Rash 1564 (60) Female 1344 (51) =65 years 455 (17) Died 63 (2) We interviewed 89% of 2947 patients identified as having WNV disease in 2003 Of these 2626 patients, 60% reported rash 51% were female 17% were aged =65 And 2% diedWe interviewed 89% of 2947 patients identified as having WNV disease in 2003 Of these 2626 patients, 60% reported rash 51% were female 17% were aged =65 And 2% died

21. Rash by Disease Category This slide shows that the percentage of patients reporting rash differed by disease category 64% of WN fever patients reported rash Vs 55% of meningitis patients And only 33% of encephalitis patients This slide shows that the percentage of patients reporting rash differed by disease category 64% of WN fever patients reported rash Vs 55% of meningitis patients And only 33% of encephalitis patients

22. Rash by Age Group Similarly, the percentage of patients reporting rash differed by age group. 67% of patients <65 reported rash as compared with 25% of patients >65 Similarly, the percentage of patients reporting rash differed by age group. 67% of patients <65 reported rash as compared with 25% of patients >65

23. Rash by Sex Although not as great, there was also a difference in reported rash by sex. 65% of female patients reported rash vs 54% of male patients Although not as great, there was also a difference in reported rash by sex. 65% of female patients reported rash vs 54% of male patients

24. Association betweenDisease Category and Rash Disease category AOR* (95% CI) Fever 1 Ref Meningitis 0.7 (0.6–0.9) Encephalitis 0.5 (0.3–0.6) *Adjusted for age group, sex, and age group by sex This table shows results of our multivariable logistic regression model and the adjusted odds ratios for patients comparing meningitis and encephalitis with WN fever, adjusted for age group, sex, and an interaction term between age group and sex. Meningitis patients were 0.7 times as likely to report rash as fever patients. Encephalitis patients were 0.5 times as likely to report rash as fever patients This table shows results of our multivariable logistic regression model and the adjusted odds ratios for patients comparing meningitis and encephalitis with WN fever, adjusted for age group, sex, and an interaction term between age group and sex. Meningitis patients were 0.7 times as likely to report rash as fever patients. Encephalitis patients were 0.5 times as likely to report rash as fever patients

25. Risk Factors for Death 63 total deaths 61 (97%) WNV encephalitis I’m going to transition now and look at death as the outcome with rash, age group, and sex as potential risk factors for death There were 63 total death associated with WNV in 2003 61 or 97% were associated with encephalitis So, therefore the following analysis was limited to patients with WN encephalitis I’m going to transition now and look at death as the outcome with rash, age group, and sex as potential risk factors for death There were 63 total death associated with WNV in 2003 61 or 97% were associated with encephalitis So, therefore the following analysis was limited to patients with WN encephalitis

26. Encephalitis Deathsby Age Group and Rash This graph demonstrates the % of patients with encephalitis who died stratified by age-group and rash The two bars on the left represent patients <65. The two bars on the right patients >65 The yellow bars represent patients with rash. The blue bars patients without rash Younger Patients with rash had the lowest risk of death with 4% dying Younger Patients without rash had a greater risk of death with 10% dying Older Patients with rash had an even greater risk of death with 25% dying Finally, older patients without rash had the highest risk of death with 48% dying So although age had the largest association with death. Within each age group, the presence of rash was associated with a lower risk of death. (2/55 7/67 6/24 46/96)This graph demonstrates the % of patients with encephalitis who died stratified by age-group and rash The two bars on the left represent patients <65. The two bars on the right patients >65 The yellow bars represent patients with rash. The blue bars patients without rash Younger Patients with rash had the lowest risk of death with 4% dying Younger Patients without rash had a greater risk of death with 10% dying Older Patients with rash had an even greater risk of death with 25% dying Finally, older patients without rash had the highest risk of death with 48% dying So although age had the largest association with death. Within each age group, the presence of rash was associated with a lower risk of death. (2/55 7/67 6/24 46/96)

27. Association between Age Group, Rash, Sex, and Death Variable AOR 95% CI <65 years 0.1 (0.05–0.3) Rash 0.3 (0.1–0.8) Female 0.8 (0.4–1.6) This table shows results of exact logistic regression modeling for the association between age group, rash, sex and death. encephalitis patients <65 had 0.1 times the likelihood of death as older patients Encephalitis patients who reported rash had 0.3 times the likelihood of death as patients without rash This table shows results of exact logistic regression modeling for the association between age group, rash, sex and death. encephalitis patients <65 had 0.1 times the likelihood of death as older patients Encephalitis patients who reported rash had 0.3 times the likelihood of death as patients without rash

28. Rash is Protective New Finding Rash associated with 70% reduction in likelihood of death among encephalitis patients I think that the most important new findings of this analysis was that the presence of rash was associated with a 70% reduction in the likelihood of death in patients with encephalitis I think that the most important new findings of this analysis was that the presence of rash was associated with a 70% reduction in the likelihood of death in patients with encephalitis

29. Rash Associated with Disease Category, Age Group and Sex New Finding Rash reported more frequently by specific patients with WNV disease Fever > Meningitis > Encephalitis Younger age > Older age Females > Males The other new finding of this analysis was that rash was reported more frequently by specific patient groups Patients with WN fever reported rash more frequently than meningitis and encephalitis patients Younger patients more than older patients And females more than males The other new finding of this analysis was that rash was reported more frequently by specific patient groups Patients with WN fever reported rash more frequently than meningitis and encephalitis patients Younger patients more than older patients And females more than males

30. Possible Interpretation Host immune factors associated with rash Protective against severe disease Protective against death So what do we make of this? A possible hypothesis is that host immune factors associated with rash Are more likely to be present in younger patients and seem to be protective against developing severe disease such as encephalitis Additionally, these factors appear to be protective against death in patients who do develop encephalitis . So what do we make of this? A possible hypothesis is that host immune factors associated with rash Are more likely to be present in younger patients and seem to be protective against developing severe disease such as encephalitis Additionally, these factors appear to be protective against death in patients who do develop encephalitis .

31. Limitations Interviews of sickest patients through family members Rash might influencehealthcare-seeking behavior Potential misclassification of disease categories There were at least 3 limitations to this investigation First, we conducted interviews with family members for the sickest patients. They might have been unaware of rash resulting in underreporting of rash in the encephalitis group. Second, rash might have influenced healthcare-seeking behavior making patients with rash more likely to seek medical care. This might inflate rash reporting in the WN fever group. Third, there was potential for misclassification of patient’s disease category. Some disease categories were changed after chart review. Since not all charts were reviewed, there are still potentially mislabeled patientsThere were at least 3 limitations to this investigation First, we conducted interviews with family members for the sickest patients. They might have been unaware of rash resulting in underreporting of rash in the encephalitis group. Second, rash might have influenced healthcare-seeking behavior making patients with rash more likely to seek medical care. This might inflate rash reporting in the WN fever group. Third, there was potential for misclassification of patient’s disease category. Some disease categories were changed after chart review. Since not all charts were reviewed, there are still potentially mislabeled patients

32. Summary – 1st Study WNV can cause generalized erythematous, maculopapular rash Might be associated with dysesthesia and pruritis Nonspecific pattern of onset and spread Febrile rash illness during WNV season can facilitate diagnosis To summarize findings of the 1st study: WNV can cause a generalized, erythematous, maculopapular rash Rash may be associated with dysesthesia and pruritis Although onset and spread are nonspecific, Febrile rash illness during WNV season can direct testing and aid in making the diagnosisTo summarize findings of the 1st study: WNV can cause a generalized, erythematous, maculopapular rash Rash may be associated with dysesthesia and pruritis Although onset and spread are nonspecific, Febrile rash illness during WNV season can direct testing and aid in making the diagnosis

33. Summary – 2nd Study Rash is common symptom of WNV disease – 60% of patients Rash occurs more frequently in specific subgroups WNV fever Younger patients Females Rash associated with decreased risk of death To summarize findings of the second study Rash occurs commonly in WNV disease occurring in up to 60% of patients in our study Rash appears to occur more commonly in specific subgroups WV fever patients younger patients And female patients Additionally, The presence of rash is associated with decreased risk of death in patients with encephalitisTo summarize findings of the second study Rash occurs commonly in WNV disease occurring in up to 60% of patients in our study Rash appears to occur more commonly in specific subgroups WV fever patients younger patients And female patients Additionally, The presence of rash is associated with decreased risk of death in patients with encephalitis

34. Recommendations Confirm findings with other surveillance data Study pathogenesis of rash Some recommendations for additional study include: To confirm these finding with other surveillance data And begin to study the pathogenesis of rash in WNV. Skin biopsies on patients with rash would be a potential place to start. Some recommendations for additional study include: To confirm these finding with other surveillance data And begin to study the pathogenesis of rash in WNV. Skin biopsies on patients with rash would be a potential place to start.

35. Acknowledgments Local Health Dept Staff CDPHE Steve Burnite Ken Gershman Nicole Haubert John Pape LCDHE Adrienne Lebailly DVBID – CDC Ned Hayes Lyle Petersen OWCD – CDC Anindya De Tom Török Family Practice Assoc James Sprowell There were many people I would like to acknowledge without whose help I could not have done this analysis THANK YOU.There were many people I would like to acknowledge without whose help I could not have done this analysis THANK YOU.

36. Surveillance Results – Colorado, 2003 Disease Category Interviewed/Total (%) Fever 2002 / 2280 (88) Meningitis 379 / 420 (90) Encephalitis 244 / 246 (99) Unknown 1 / 1 (100) Total 2626 / 2947 (89) Based on these surveillance data, we interviewed or reviewed records of 2002 of 2280 patients or 88% of patients with WNV fever, 379 of 420 patients or 90% of patients with WNV meningitis and 244 of 246 or 99% patients with WNV encephalitis. There was an additional patient whose disease category was unknown So a total of 2626 of 2947 or 89% of case patients with WNV disease were interviewed or had their chart reviewed.Based on these surveillance data, we interviewed or reviewed records of 2002 of 2280 patients or 88% of patients with WNV fever, 379 of 420 patients or 90% of patients with WNV meningitis and 244 of 246 or 99% patients with WNV encephalitis. There was an additional patient whose disease category was unknown So a total of 2626 of 2947 or 89% of case patients with WNV disease were interviewed or had their chart reviewed.

37. Rash by Age Group and Sex In analyzing these data, we noted that the percentage of rash reported by men and women varied by age group This shows the percentage of patients reporting rash stratified for Age Group and Sex. Patients <65 years are shown on the left two bars. And, patients >65 years are shown in the right two bars Females are shown in yellow and males in blue There was a difference in the percentage of women and men <65 years who reported rash. 73% of younger women reported rash as compared with 60% of younger men In comparison, there was minimal difference in the % of females and males reporting rash in the older age-group 26% vs. 25% In analyzing these data, we noted that the percentage of rash reported by men and women varied by age group This shows the percentage of patients reporting rash stratified for Age Group and Sex. Patients <65 years are shown on the left two bars. And, patients >65 years are shown in the right two bars Females are shown in yellow and males in blue There was a difference in the percentage of women and men <65 years who reported rash. 73% of younger women reported rash as compared with 60% of younger men In comparison, there was minimal difference in the % of females and males reporting rash in the older age-group 26% vs. 25%

38. Association betweenAge Group, Sex and Rash Male Female Age Group AOR* (CI) AOR* (CI) <65 years 4 (3–6) 7 (5–10) =65 years 1 Ref 1 (0.6–2) *Adjusted for disease category This table shows the adjusted odds ratio for patients reporting rash based on age group and sex, adjusted for disease category These odd’s ratio are reported separately for males and females because of the interaction term between age group and sex Males >65 were made the reference group shown in yellow Females >65 were equally likely to report rash. Males <65 were 4 times as likely to report rash as older males Females <65 were 7 times as likely to report rash as older malesThis table shows the adjusted odds ratio for patients reporting rash based on age group and sex, adjusted for disease category These odd’s ratio are reported separately for males and females because of the interaction term between age group and sex Males >65 were made the reference group shown in yellow Females >65 were equally likely to report rash. Males <65 were 4 times as likely to report rash as older males Females <65 were 7 times as likely to report rash as older males

39. Encephalitis Deaths by Age Group Not surprisingly, as this has been reported in the literature, increased age was associated with an increased risk of death among patients with WNV disease Only 7% of patients <65 years with encephalitis died as compared with 43% of patients >65 years with encephalitisNot surprisingly, as this has been reported in the literature, increased age was associated with an increased risk of death among patients with WNV disease Only 7% of patients <65 years with encephalitis died as compared with 43% of patients >65 years with encephalitis

40. Encephalitis Deaths by Rash It was surprising that rash also appeared to be associated with outcome. Among WNV encephalitis patients with rash, 10% died as compared with 32% of patients who had encephalitis without reported rashIt was surprising that rash also appeared to be associated with outcome. Among WNV encephalitis patients with rash, 10% died as compared with 32% of patients who had encephalitis without reported rash

41. Encephalitis Deaths by Sex On the other hand,the risk of death was not significantly different between female and male patients with WNV encephalitisOn the other hand,the risk of death was not significantly different between female and male patients with WNV encephalitis

42. Discussion – Rash Frequency Median age Outbreak % Rash % Fever (years) NYC (1999) 19 8 71 Israel (2000) 22 24 65 Israel (1950) 50 98 18–20 Illinois (2002) 57 100 <65 Colorado (2003) 60 77 47 If you recall from earlier in this talk, the frequency of rash associated with WNV disease has varied substantially in the literature. This is the same list of studies I showed earlier to which I have added our data shown in yellow Looking at WNV disease category and age group might help explain different frequencies of rash reported in the literature In NYC in 1999 and Israel in 2000 only 19-22% of patients had rash. In those outbreak, however, only 8-24% of patients had WNV fever and patients were older with median ages of 65 – 71 In comparison, in Israel in 1950, 50% of patients had rash, a much higher %, 98% had WNV fever and patients were much younger, most between 18 and 20 years In Illinois in 2002, 57% of patients reported rash. In this study, which was specifically focused on WNV fever, 100% had WNV fever and the median age was <65 years In our data 60% of patients reported rash and again a higher % of patients 77% had WNV fever and patients were relatively younger with a median age of 47 These combined studies are consistent with our conclusion that rash is more common in WNV fever and younger patients If you recall from earlier in this talk, the frequency of rash associated with WNV disease has varied substantially in the literature. This is the same list of studies I showed earlier to which I have added our data shown in yellow Looking at WNV disease category and age group might help explain different frequencies of rash reported in the literature In NYC in 1999 and Israel in 2000 only 19-22% of patients had rash. In those outbreak, however, only 8-24% of patients had WNV fever and patients were older with median ages of 65 – 71 In comparison, in Israel in 1950, 50% of patients had rash, a much higher %, 98% had WNV fever and patients were much younger, most between 18 and 20 years In Illinois in 2002, 57% of patients reported rash. In this study, which was specifically focused on WNV fever, 100% had WNV fever and the median age was <65 years In our data 60% of patients reported rash and again a higher % of patients 77% had WNV fever and patients were relatively younger with a median age of 47 These combined studies are consistent with our conclusion that rash is more common in WNV fever and younger patients

43. Percentage with Rash byAge Group

44. Patients who Died by Age Group This slide shows the percentage of patients who died by age group Unlike the other slides in this part of the analysis, it shows the percentage of patients who died with WNV disease not just WNV encephalitis We looked at the frequency of death by 5 year intervals. You could make the argument that we should use =60 years as the older age group based on the slope of the curve. To be consistent with the rash analysis we elected to use =65 yearsThis slide shows the percentage of patients who died by age group Unlike the other slides in this part of the analysis, it shows the percentage of patients who died with WNV disease not just WNV encephalitis We looked at the frequency of death by 5 year intervals. You could make the argument that we should use =60 years as the older age group based on the slope of the curve. To be consistent with the rash analysis we elected to use =65 years

45. Duration Between Illness Onset and Death Median Duration, d Range No rash (N=54) 29 (1–248) Rash (N=8) 29 (4–210)