Rash Illness Testing Protocol

Acute, Generalized Vesicular or Pustular Rash Illness Testing Protocol in the United States

Introduction

This protocol has been developed to guide the sequence and type of laboratory testing to be undertaken in situations involving specimens from patients with acute, generalized vesicular or pustular rash illness, or suspected smallpox vaccine (vaccinia virus) adverse event. This protocol may also be followed to test environmental specimens which may contain an Orthopoxvirus. The testing protocol includes four flowchart diagrams, each illustrating a different testing circumstance. The protocol has been designed for use alongside the Centers for Disease Control and Prevention’s clinical assessment tool, Evaluating Patients for Smallpox: Acute, Generalized Vesicular or Pustular Rash Illness Protocol. The laboratory testing protocol is designed to address testing needs in a pre-event setting, when no poxvirus emergency has been detected or declared. In the event of a smallpox (variola virus) outbreak, critical updates will be announced by the Laboratory Response Network (LRN).

Chart 1 lists the major and minor criteria of smallpox used to categorize a patient’s risk of smallpox – high, moderate, or low.

Chart 2 depicts the sequence of laboratory testing for specimens from patients with acute, generalized vesicular or pustular rash illness. The sequence and type of laboratory tests performed will depend on the outcome of the risk assessment using the clinical assessment tool, Evaluating Patients for Smallpox: Acute, Generalized Vesicular or Pustular Rash Illness Protocol (see Chart 1 for abstraction of the protocol). A two-armed testing algorithm is presented to ensure that testing of high-risk specimens is confined to laboratories with appropriate biosafety levels and expertise. This approach also reduces the time to receive test results.

Major points:

• High-risk specimens/cases require consultation with CDC prior to testing.
• Low-or moderate-risk specimens/cases should be worked-up for common causes of febrile exanthema.
• Due to differences in the thermocycling conditions used for the Non-variola Orthopoxvirus and Orthopoxvirus PCR assays, they cannot be performed simultaneously on the same instrument.

Chart 3 presents a testing algorithm that should be used when a smallpox vaccine adverse event is suspected.

Chart 4 presents an Orthopoxvirus testing algorithm for environmental specimens. This testing algorithm should be used in conjunction with the LRN Multiple-Agent Screen.

When examining specimens from low- or moderate-risk cases it may be possible, though unlikely, that a positive result may be obtained using the Orthopoxvirus PCR assay and a negative result with Non-variola Orthopoxvirus PCR assay. This could signal a laboratory error, the presence of a previously uncharacterized Orthopoxvirus in the specimen, or that the patient has modified smallpox. Consultation with CDC should occur before running Variola virus specific PCR assays on specimens not initially determined to be high-risk.

The testing protocols are supported at the LRN reference laboratories. Details on the performance and interpretation of each assay are specified in each LRN procedure. Communication between laboratories and local or state epidemiologists is encouraged prior to laboratory testing, especially if high-risk specimens are involved. Refer to LRN policy regarding notification of test results.