# Presentation: 078919

## West Nile neuroinvasive disease in hospitalized patients

- Amy V. Bode
- 2006 National Conference on West Nile Virus in the United States
- February 23-24, 2006
- San Francisco, California

## Background:

- Significant morbidity with all West Nile viral (WNV) illnesses
- Small portion of infected people develop encephalitis
- Risk factors for WNV encephalitis & prognosis of hospitalized patients still undefined
- Associated complications of encephalitis undefined but may add significant cost

## Goals:

- Identify risk factors (RFs) for encephalitis among hospitalized persons with WNV illness
- Describe outcome of index hospitalization
- Describe clinical complications among persons hospitalized with confirmed WNV illness
- Determine true cost of illness to discuss potential utility of a WNV vaccine

## Previous studies of hospitalized persons:

***Romania, 1996, Hahn et al.:***
- Meningoencephalitis (ME) :
- Associated with more time outdoors
- Not significantly associated with hypertension, smoking, diabetes mellitus (DM), age nor gender
***New York City, 1999, Nash et al.:***
- Case fatality ratio (CFR) 12%
- Death among persons with ME & muscle weakness associated with:
- Age ≥75 years (adjusted RR: 8.5 [1.2,59.1])
- DM (age-adjusted RR: 5.1 [1.5,17.3])

**Notes:**
Factor% of ME patients with factor (no./total)% of asymptomatically infected persons (no./total)POdds ratio95% confidence interval
Hypertension22 (11/50)29 (11/38).461.440.49 4.28
Chronic lung disease14 (7/50)11 (4/38).750.720.16 3.11
Diabetes mellitus6 (3/50)16 (6/38).172.940.58 16.40
History of cerebrovascular disease4 (2/50)3 (1/38)1.00.650.02 9.82
History of myocardial infarction0 (0/50)5 (2/38).18 Cancer0 (0/50)5 (2/38).18 None of the above conditions58 (29/50)61 (23/38).810.900.35 2.32
Smokes >1 package cigarettes/day38 (19/50)31 (11/35).541.340.48 3.73
Smoked for  1 year44 (22/50)44 (16/36).970.980.38 2.57
Spent >6 h/day in garden29 (14/49)8 (3/38).024.671.10 22.84
Spent >6 h/day outdoors60 (30/50)21 (8/38)<.015.631.96 16.65

## Previous studies of hospitalized persons:

***Louisiana, 2002, Sejvar et al.:***
- Of 16 hospitalized persons with serologically-confirmed
- WNV neuro disease (5 meningitis; 8 encephalitis; 3 AFP)
- 15 (94%) had tremor
-   5 (31%) had myoclonus
- 11 (69%) had parkinsonism
-   1 died
***Ontario, 2002, Pepperell et al.:***
- Of 57 WNV patients with encephalitis, 10 (18%) died
- Of 47 survivors, only 13 (28%) discharged without support

**Notes:**
Factor% of ME patients with factor (no./total)% of asymptomatically infected persons (no./total)POdds ratio95% confidence interval
Hypertension22 (11/50)29 (11/38).461.440.49 4.28
Chronic lung disease14 (7/50)11 (4/38).750.720.16 3.11
Diabetes mellitus6 (3/50)16 (6/38).172.940.58 16.40
History of cerebrovascular disease4 (2/50)3 (1/38)1.00.650.02 9.82
History of myocardial infarction0 (0/50)5 (2/38).18 Cancer0 (0/50)5 (2/38).18 None of the above conditions58 (29/50)61 (23/38).810.900.35 2.32
Smokes >1 package cigarettes/day38 (19/50)31 (11/35).541.340.48 3.73
Smoked for  1 year44 (22/50)44 (16/36).970.980.38 2.57
Spent >6 h/day in garden29 (14/49)8 (3/38).024.671.10 22.84
Spent >6 h/day outdoors60 (30/50)21 (8/38)<.015.631.96 16.65

## Colorado, 2003: WNV Epicenter

**Colorado, 2003: WNV Epicenter**

- 4.6M residents; 64 counties
- 2,947 WNV illnesses
- 621 neuroinvasive illnesses
- 63 fatalities among
- neuroinvasive disease
- cases (CFR 10%)

## Colorado, 2003: WNV Epicenter

**Colorado, 2003: WNV Epicenter**

- Boulder, Denver, Larimer,
- & Weld Cos.
- 1.3M residents (~30% CO’s population)
- 1,531 WNV illnesses (~52% CO’s reported cases)
- 333 hospitalized with WNV illness

## 4-County Review, Colorado, 2003

- Large, population-based study; 333 hospitalized cases
- 4-County resident, confirmed WNV, hospitalized in 2003
- Retrospective multi-hospital medical record review
- Assigned clinical syndrome
- Demographic information
- Past medical history & behaviors
- Hospital course
- Disposition
- Short-term outcome
- RFs for encephalitis, limb weakness & death

## Results: Colorado, 2003

- 228 (69% of hospitalized persons) medical records reviewed
- 221 patients included
-  103 with West Nile meningitis (WNM)
-    65 with West Nile encephalitis (WNE)
-    53 with West Nile fever (WNF)
- 7 excluded
- 1 ADEM following SLE viral infection
- 6 without fever

**Notes:**
In addition to the different signs and symptoms specified by the case definitions, the clinical presentation of WNE and WNM differed (Table 2). WNM patients were significantly more likely than WNE patients to have nausea, vomiting, myalgia, rash, back pain, and arthralgia. WNE patients were significantly more likely than WNM patients to have memory problems, bulbar dysfunction (dysarthria and dysphagia) and focal motor abnormalities including cranial nerve palsies. No differences in frequency of tremor, limb weakness, myoclonus and seizures were noted between the two. Although 20 (20%) patients with WNM had confusion and/or other mental status changes, these signs or symptoms lasted less than 24 hours and, as a result, these persons were not classified as WNE cases. 
Based on the total of 333 cases reported among residents of this four-county area, the incidence of hospitalized WNV disease was 26.0 cases per 100,000. Assuming that these 228 patients were similar to the other 105 patients, the incidence of WNE, WNM, and WNF requiring hospitalization was 7.4, 11.7, and 6.0, respectively, per 100,000. 

## Proportion of persons with specific West Nile viral syndromes

## Impact on hospitalization rates,4-Counties, Colorado, 2003

- Projecting from 221 cases
- All WNV illnesses: 25 hospitalized / 105 population
-   WNE:    7 hospitalized / 105
-   WNM:  12 hospitalized / 105
-   WNF:     6 hospitalized / 105

## Results: Colorado, 2003

***Risk factors for WNE ***compared to persons with WNF*
- Age – Adjusted OR (AOR): 1.04/year [1.01,1.07]
- Alcohol abuse – AOR: 7.5 [1.5, 37.8]
- Diabetes mellitus – AOR: 4.1 [1.2,13.6]
***Risk factors for limb weakness**** *compared to those without weakness*
- Age – AOR: 1.02 per year [1.01,1.04]
- WNE - AOR: 3.2 [1.5, 6.5]

- *Backward & forward, stepwise logistic regression

**Notes:**
Encephalitis Alcohol abuse, diabetes, hypertension, and tobacco use, were more commonly noted in the medical records of WNE patients than others (Table 1). In univariate analysis, age ≥50 years, alcohol abuse, diabetes, and immunosuppression were significantly more commonly associated with WNE than WNF (Table 3). In multivariate analysis, patients with alcohol abuse recorded in their past medical history were 7.5 times more likely to develop WNE and those with diabetes were 4.1 times more likely. For each year of age, WNE patients were 1.04 times more likely to develop WNE (Table 3). Because no WNF patients had organ transplantation, this factor could not be included in multivariate analysis

## Results: Colorado, 2003

***Risk factors for death among persons with encephalitis ***compared to survivors*
- Age – AOR: 1.14 per year [1.02,1.29]
- Immunosuppression – AOR: 26.5 [3.0,234]
- Mechanical ventilation – AOR: 12.7 [1.2,139]
- History of stroke – AOR: 42.7 [2.4,756]

- *Backward & forward, stepwise logistic regression

**Notes:**
In univariate analysis limited to WNE patients, age ≥ 50 years, vasopressor treatment, and a history of solid-organ cancer, hypertension, stroke, or immunosuppression were associated with death. All 12 deaths occurred among WNE patients ≥ 50 years old; no deaths occurred among 11 younger WNE patients. In multivariate analysis, endotracheal intubation, a previous stroke, immunosuppression, and age ≥ 50 years were retained in the final logistic model (Table 5).

## Despite syndrome, patients with limb weakness more likely to be intubated
Bulbar dysfunction (brainstem encephalitis?) associated with respiratory failure
WNE patients 4 times more likely to have bulbar dysfunction than WNM patients

*Bulbar dysfunction* (brainstem encephalitis?) associated with respiratory failure
- WNE patients 4 times more likely to have bulbar dysfunction than WNM patients

- Who will need intubation & ventilation?

*Take-home: Persons with limb weakness and bulbar dysfunction (dysarthria,*
*dysphagia) at high risk for respiratory failure despite attributed clinical syndrome*

**Notes:**
In univariate analysis limited to WNE patients, age ≥ 50 years, vasopressor treatment, and a history of solid-organ cancer, hypertension, stroke, or immunosuppression were associated with death. All 12 deaths occurred among WNE patients ≥ 50 years old; no deaths occurred among 11 younger WNE patients. In multivariate analysis, endotracheal intubation, a previous stroke, immunosuppression, and age ≥ 50 years were retained in the final logistic model (Table 5).

## Complications by clinical syndrome

- * Excludes sinus bradycardia & tachycardia

## Disposition following index hospitalization

| Disposition | WNM | WNE | WNF |
| --- | --- | --- | --- |
| Rehabilitation facility
Chronic care facility
Home with assistance
Home without assistance
Died | 6%
3%
11%
80%
0% | 29%
17%
15%
20%
18% | 15%
2%
17%
68%
0% |

- by clinical syndrome

## Conclusions :

- Age is risk factor for encephalitis, limb weakness & death
- In addition:
- DM & history of alcohol abuse increase risk of WNE
- History of stroke, respiratory failure, or  immunosuppression increase mortality among those with WNE
- WNE increases risk of limb weakness
- Respiratory failure, limb weakness, & arrhythmias occurred in WNE, WNM, & WNF but more so in WNE
- Limb weakness & bulbar dysfunction – Watch for respiratory failure

## Acknowledgments:

- Roy Campbell
- Jim Sejvar
- John Pape
- Anthony Marfin
- Jen Lehman
- Krista Kniss
- Peggy Collins
- Stephanie Kuhn

- Laura Polakowski
- David Berndt
- Many Infection Control practitioners, Infectious Disease subspecialists, Neurology subspecialists of Weld, Larimer, Boulder and Denver counties, Colorado