Public Health Emergency Preparedness

Chapter 10. Botulinum Neurotoxin

This chapter describes the assumptions in the botulism neurotoxin scenario, including:

• The severity categories.
• The arrival pattern of casualties at the hospital(s).
• The length of stay by hospital unit (i.e., ED, ICU, and the floor).
• The path probability within the hospital(s) and the length of stay.
• The overall outcome probabilities (i.e., probability of discharge and probability of death).
• The assumed level of resource consumption per patient per day per hospital unit.

Footnotes in the text of a particular section refer to references at the end of the section. In the absence of specific references, parameter estimates were obtained from general references listed in the Hospital Module section.

10.1 Severity Categories

For the botulism neurotoxin scenario, patients arrive at the hospital(s) in one of four conditions:

1. Adult Moderate: Adults show symptoms but can be treated outside of the ICU.
2. Child Moderate: Children show symptoms but can be treated outside of the ICU.
3. Adult Severe: Adults present at the hospital with severe symptoms requiring a ventilator.
4. Child Severe: Children present at the hospital with severe symptoms requiring a ventilator.

If the user specifies only the number of casualties, the model assumes the casualties arriving at the hospital(s) are distributed as follows:

Casualty Condition	Percent
Adult Moderate: Adults show symptoms but are able to be treated outside of the ICU	86%
Child Moderate: Children show symptoms but are able to be treated outside of the ICU	14%
Adult Severe: Adults present at the hospital with severe symptoms requiring a ventilator	0%
Child Severe: Children present at the hospital with severe symptoms requiring a ventilator	0%

That is, if a number of moderate and severe casualties is not specified, the model assumes that all casualties arrive in a moderate condition (i.e., individuals do not wait until they have severe symptoms to present at the hospital). The breakdown between the "Adult Moderate" and "Child Moderate" categories is based on the percentage of children (ages 2 to 11) in the population.

Clinical correlation for the pediatric cases is complicated by the fact that the scenario calls for ingestion of a preformed toxin, whereas the vast majority of reported infant and pediatric botulism cases are due to ingestion of spores (e.g., in honey) and the more gradual onset of clinical illness due to bacterial replication in the GI tract.

In the United States, the latest data suggest that the mortality rate for non-terrorism-related foodborne botulism has declined from 15.5 percent between 1950 and 1966 to 6 percent between 1990 and 1996.^2,10 Rapid administration of botulinum antitoxin is a mainstay of medical treatment, but 2-9 percent of antitoxin recipients develop rapid anaphylaxis.^2,10 In the current scenario, the number of affected individuals may hinder the ability to provide antitoxin in a timely fashion, thus worsening expected outcomes.

Mechanical ventilation is required for 20-60 percent of victims of routine foodborne botulism outbreaks; the duration of ventilation ranges from 2 to 8 weeks.¹⁰ The most recent large randomized, controlled trial of human botulism immune globulin for the treatment of infant botulism showed a mechanical ventilation rate of approximately 40 percent, with a mean length of stay of 18.2 days (12.6 days in intensive care).³ This compares with earlier data (from the 1970s) suggesting a 30 percent mechanical ventilation rate and mean length of stay of approximately 70 days.²⁵

Classic foodborne infant botulism has a lower expected mortality rate than adult botulism (approximately 1 percent), with an expected length of stay of approximately 17 days.^1,14 For the purposes of this terrorism-based botulism intoxication scenario, these pediatric figures were applied to the "Pediatric Moderate" patient stream (go to Exhibit 9). Given the large toxin inoculum posited in this scenario, the clinical outcome for the "Pediatric Severe" patient stream was assigned a baseline mortality of approximately 10 times that rate. "Adult Severe" cases, in contrast, were assigned a 30 percent mortality, or roughly double the ratio of mortality for the past half-century, with "Adult Moderate" having similar mortality to the "Pediatric Severe" cases. Given the considerable scientific uncertainty about the actual mortality rates that would occur in the setting of widespread moderate-to-high-dose ingestion of preformed toxin, the model user can choose the highest mortality scenario by selecting the long length of stay and high mortality options, which yield mortality rates of 2, 20, 27, and 62 percent for Moderate (Pediatric and Adult) and Severe (Pediatric and Adult) cases, respectively.

Exhibit 9: Mortality Estimates for Botulism Neurotoxin Scenario

10.2 Casualty Arrival Pattern

Casualties are assumed to present at the hospital(s) as symptoms appear over a 20-day period. The number of casualties increases through the midpoint of this period, and then begins to decline, under the assumption that a product recall campaign has been successful in removing contaminated food product from the area.

10.3 Length of Stay by Hospital Unit

The assumed average lengths of stay (in days) of patients in the ED, in the ICU, and on the floor are:

Average Length of Stay by Hospital Unit	Adult Moderate	Child Moderate	Adult Severe	Child Severe
ED	1	1	1	1
Floor, not via ICU	5.7	5.7	6.3	6.3
Floor, via ICU	5.7	7.3	7.3	7.3
ICU (or ventilator-capable unit)	9.0	9.0	28.0	28.0

10.4 Combined Path Probabilities and Lengths of Stay

The table below shows the assumed probabilities of different "paths" through the hospital(s).

Path	Adult Moderate	Child Moderate	Adult Severe	Child Severe
ED → Discharge	0%	0%	0%	0%
ED → Death	0%	0%	0%	0%
ED → Floor → Discharge	98%	0%	84%	0%
ED → Floor → Death	0%	0%	0%	0%
ED → Floor → ICU → Death	0%	0%	3%	0%
ED → Floor → ICU → Floor → Discharge	0%	0%	10%	0%
ED → Floor → ICU → Floor → Death	0%	0%	1%	0%
ED → ICU → Death	0%	9%	0%	13%
ED → ICU → Floor → Discharge	2%	90%	1%	82%
ED → ICU → Floor → Death	0%	2%	0%	5%

The breakdown of length of stay by patient type summed over all paths is:

Average Length of Stay by Patient Outcome	Adult Moderate	Child Moderate	Adult Severe	Child Severe
Survivors	7.16	17.00	10.75	36.00
Fatalities	5.93	7.38	20.51	17.98
Average Combined	7.16	15.99	11.49	30.66

10.5 Overall Outcome Probabilities

Based on these inputs, the overall discharge and death probabilities are:

Outcome	Adult Moderate	Child Moderate	Adult Severe	Child Severe
Discharge	100%	89%	92%	70%
Death	0%	11%	8%	30%

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