Guidance on Performing Routine Diagnostic Testing for Patients with Suspected VHFs or Other High-Consequence Disease

Scope of guidance

This guidance applies to viral hemorrhagic fevers (VHFs) caused by infections with:

• Filoviruses (ebolaviruses and marburgviruses),
• Arenaviruses [Lassa, Lujo, and South American hemorrhagic fever viruses (Guanarito virus, Sabia virus, Junin virus, Chapare virus, Machupo virus)],
• Rift Valley fever virus, and
• Crimean Congo hemorrhagic fever virus.

This guidance also applies to other high-consequence diseases that require a specialized laboratory, are highly pathogenic, and have no vaccine or treatment currently available, like Nipah virus disease.

Background

Following CDC's Standard Precautions for All Patient Care, which includes OSHA's Bloodborne Pathogens Standard, has shown to effectively prevent laboratory acquired illnesses from bloodborne pathogens, such as VHFs and other high-consequence diseases.

VHFs and other high-consequence diseases can be confused with more common causes of febrile illness like malaria, influenza, COVID-19, typhoid fever, meningococcemia, and other bacterial or viral infections. Additionally, patients may present with concurrent infections.

Healthcare providers and laboratory professionals can safely and effectively perform other diagnostic testing on clinical specimens from these patients by following Standard Precautions for All Patient Care and the Bloodborne Pathogen Standard (29 CFR 1910.1030).

If a patient is determined to meet criteria for testing for a VHF or other high-consequence disease, the patient should be managed under isolation precautions in a healthcare facility until receiving a negative test result on a specimen collected > 72 hours after symptom onset.

If a hospital facility is unable to provide appropriate clinical care and laboratory/diagnostic testing, the patient should be transferred to a facility that is able to provide appropriate management until VHF or other high-consequence testing is completed.

Clinical laboratory testing

The following routine clinical laboratory tests are critical in evaluating an ill traveler.

• Complete blood count (CBC), including differential and platelet count
• Sodium, potassium, bicarbonate, blood urea nitrogen, creatinine, and glucose concentrations
• Liver function tests
• Coagulation testing, specifically prothrombin time (PT), expressed as an international normalized ratio (INR)
• Chemical urinalysis (dipstick)
• Blood culture for bacterial pathogens. The early initiation of blood cultures may be important, even if the patient will be transported prior to culture results, as blood cultures may be an essential component of the ultimate diagnosis.

Based on clinical evaluation, diagnostic testing for other common causes of acute febrile illness in returning travelers may be indicated. This includes malaria and common causes of respiratory and gastrointestinal illnesses. If warranted based on the patient’s presenting symptoms, consider use of multiplex PCR panels that detect common respiratory or gastrointestinal pathogens. Also evaluate for the following:

Malaria

CDC recommends immediate blood smears with same-day results for malaria testing. If timely blood smears are not available, a rapid diagnostic test (RDT) can be done while processing a blood smear with pre-treatment blood (blood gathered prior to treatment with antimalarials). This can confirm the results of the RDT and determine the percent of infected red blood cells and malaria species. Facilities that do not have the expertise or CLIA certificate to perform definitive malaria testing on site should contact their state health department to facilitate the definitive diagnosis. CDC and state health departments can assist with providing a timely diagnosis of malaria. See the Malaria Risk Assessment for Travelers and Malaria Diagnosis & Treatment in the United States for more information.

Respiratory diseases such as COVID-19, Influenza, and RSV

If COVID-19 is suspected, refer to COVID-19 testing guidance to find information on testing for SARS-CoV-2 with nucleic acid amplification tests and antigen tests, as well as specific guidance for point-of-care testing and self-testing.

Consider testing for influenza during periods of high prevalence. Refer to Information for Clinicians on Influenza Virus Testing | CDC and Rapid Diagnostic Testing for Influenza: Information for Clinical Laboratory Directors | CDC.

Consider testing for respiratory syncytial virus (RSV) during RSV season, particularly in infants, young children, older adults, and adults with chronic medical conditions. Refer to For Healthcare Professionals: RSV (Respiratory Syncytial Virus) | CDC.

Risk Assessment and Mitigation

All laboratory personnel who collect, handle, or test human specimens must comply with the OSHA Bloodborne Pathogens Standard (29 CFR § 1910.1030). In addition, laboratory staff should perform site and activity specific risk assessments before beginning testing. Performing a laboratory risk assessment helps to identify:

1. The hazards of working with an infectious or potentially infectious agent
2. The likelihood of a person's exposure to that agent
3. The consequences of such an exposure to lab personnel

These risk assessments should evaluate the specimen's path throughout the laboratory as well as all work processes to identify potential exposure risks. The results of the risk assessment should be documented in an exposure control plan, as required by the Bloodborne Pathogens Standard (29 CFR § 1910.1030), that includes engineering controls, administrative controls (including work practices), and appropriate personal protective equipment to mitigate the identified risks. The following areas should be considered priority items to focus on during a risk assessment.

• Specimen management and transport, including the path of the specimen through the laboratory, particularly avoiding transport through high-traffic areas. Pneumatic tube systems should not be used.
• Use of any needles or other sharps, including glass, and their disposal
• Potential for splashing, spraying, spattering, or generation of droplets
• Equipment hazards (e.g., the potential for creating aerosols, sprays, splashes of the specimen while testing and using equipment)
• Biosafety cabinet (BSC) certification, operation, and safe work practices
• Decontamination procedures, including spill response, and methods for surface decontamination and, if necessary, decontamination of equipment
• Infectious waste management
• Engineering controls and safety equipment
• Administrative controls (e.g., communication protocols, entry and exit procedures, personnel training and competency, medical surveillance, exposure response)
• PPE selection and use, including donning and doffing procedures

For additional information on conducting a risk assessment, see Biological Risk Assessment: General Considerations for Laboratories.

Personal protective equipment (PPE)

Refer to the following guidance for more information on the proper PPE for specimen collection.

PPE during specimen collection

PPE during laboratory testing

When manipulating clinical specimens from patients with a suspected VHF or other high-consequence disease, staff should use a combination of engineering controls, work practices, and PPE to protect their mouth, nose, eyes, and bare skin from coming into contact with patient specimens. For example:

• Proper PPE:
  • Disposable gloves
  • Solid-front wrap-around gowns that are fluid-resistant or fluid-impermeable
  • Surgical mask to cover all of nose and mouth
  • Eye protection such as a full-face shield or goggles/safety glasses with side shields

• Manufacturer-installed safety features for instruments that reduce the likelihood of exposure
• A Class II BSC should be used for specimen manipulation (e.g., opening a tube, preparing an aliquot)
• Staff should use a secondary container when transporting specimens within and outside of the laboratory

If clinical laboratories decide to require supplementary PPE beyond what is recommended above, this may necessitate additional steps (e.g., respiratory protection). These facilities must provide additional training and have staff practice procedures using the PPE before using them in the laboratory. Using unfamiliar equipment or PPE without sufficient training and practice may lead to unsafe practices and increases the risk of exposure, especially when removing PPE. Consistently following specific PPE procedures is essential to protect personnel. Periodic review of donning and doffing processes with staff at regular intervals is strongly recommended.

Laboratory Equipment

When determining what laboratory equipment is appropriate for use with specimens from patients with a suspected VHF or other hihg-consequence diseases, laboratories should consider several factors.

• In general, the risk of transmission of VHFs or other high-consequence diseases in a clinical laboratory is similar to the risk or transmission of other bloodborne pathogens, including HIV, Hepatitis B, and Hepatitis C.
• Laboratories should consider using equipment with closed tube systems in which the specimen container (e.g., vacutainer tube) stays capped during testing.
• Centrifugation poses a risk of aerosolization. If centrifugation is necessary for testing, centrifuges should have sealed buckets or sealed rotors. The rotors and buckets should be loaded and unloaded in a BSC.
• Blood culture instruments (automated and benchtop) have been used successfully after careful evaluation through a risk assessment. Subculture of any positive blood culture bottles (whether from automated, benchtop, or manual procedures) should be performed within a BSC. (Cornish NE, Anderson NL, Arambula DG, et al. Clinical Laboratory Biosafety Gaps: Lessons Learned from Past Outbreaks Reveal a Path to a Safer Future. Clin Microbiol Rev. 2021;34(3):e0012618. doi:10.1128/CMR.00126-18)

Decontamination

VHFs and many other high-consequence diseases result from infection by an enveloped virus — the easiest type of virus to inactivate — and are readily inactivated by standard chemical decontamination procedures used in laboratories and hospitals. When disinfectants damage their lipid envelope and/or denature proteins, the virus is no longer infectious. EPA's Disinfectants for Emerging Viral Pathogens List Q contains products with disinfection claims against specific pathogens. EPA's List L contains additional disinfectants qualified for use against Ebola virus, which are also effective for marburgviruses. Check product registration against the pathogen.

Cleaning and Disinfecting Testing Surfaces

Decontamination can be performed on laboratory surfaces and the outside of instrument surfaces using EPA List L: Disinfectants for Use Against Ebola Virus products that are compatible with instrumentation. However, not every instrument surface will be compatible since some of the products on List L are sodium hypochlorite-based (i.e., bleach) and can be corrosive if used in high concentrations. In addition, enveloped viruses can be inactivated with solutions on EPA List Q: Disinfectants for Emerging Viral Pathogens, which includes isopropyl alcohol. Check product registration against the pathogen.

Instrument Use and Decontamination for Non-VHF or other high-consequence diseases

Testing In general, laboratory instruments can be maintained as they normally would with any other bloodborne pathogen, and as recommended in the Bloodborne Pathogen Standard. The Bloodborne Pathogen Standard should ensure safe use of instruments for all testing, including for high-risk patients and specimens. Most blood testing instruments are closed systems that do not require any decontamination between patient specimens. However, laboratories should consult the manufacturers' instructions, or the manufacturer directly, on whether there is a need and how to decontaminate the interior surfaces or areas of their specific laboratory instruments. CDC can help laboratories speak directly to instrument manufacturers about decontamination or warranty coverage by contacting DLSInquiries@cdc.gov.

Handlings spills

The basic principles for blood or other potentially infectious material spill management are outlined in the OSHA Bloodborne Pathogens Standard and the CDC Biosafety in Microbiological and Biomedical Laboratories. Points to consider are:

• If the spill creates aerosols, evacuate staff until the aerosols have had time to settle.
• Limit the number of personnel involved in the clean-up.
• Develop protocols for safely remediating spills containing broken glass. Do not handle broken glass or other sharps directly.
• Before any spill clean-up is initiated, ensure staff are trained and wear PPE as identified in the site-specific risk assessment to protect against direct skin and mucous membrane exposure of cleaning chemicals, contamination, and splashes. PPE use must be in accordance with the OSHA PPE (29 CFR 1910.132) and Respiratory Protection (29 CFR 1910.134) standards.
• PPE should include, at a minimum:
  • Disposable gloves
  • Solid-front wrap-around gowns that are fluid-resistant or fluid-impermeable
  • NIOSH Approved® particulate respirator equipped with an N95 filter or greater or surgical mask
  • Eye protection such as a full-face shield or goggles/safety glasses with side shields
  • Shoe covers if the spill is large and there is a splash area to avoid tracking potentially infectious material away from the spill area.
• When cleaning up a spill, look for areas of splashes away from the main spill and clean the spill working from the outside of the spill radius inwards.
• For small spills, absorbent material wetted with disinfectant can be used to clean the area. Be sure to allow for the appropriate amount of contact time.
• For larger spills, cover the spill with absorbent material and douse the area with disinfectant. It may be necessary to increase the concentration of the disinfectant used to offset the dilution factor caused by the volume of the spilled material and/or increase contact time.
• All materials used for cleanup must be treated as infectious and disposed of in a biohazard waste container. Any sharps should be placed into a sharps container.

Waste management

Managing waste from a patient infected with a VHF or other high-consequence disease virus should be handled and disposed of as a Category A agent. For information about procedures and regulations regarding waste associated with the care of patients with a VHF or other high-consequence disease, refer to CDC's Waste Management Guidance, DOT's Planning Guidance for Handling Category A Solid Waste, DOT's Managing Solid Waste Contaminated with a Category A Infectious Substance, and your local or state jurisdictional regulations.

Considerations of Select Agent Concerns

Specimens collected from a suspected case of a VHF or other HCID are not select agents. Clinical specimens from patients confirmed to be infected with a VHF or other HCID virus by viral isolation are classified as select agents. CDC will work with the facility to determine proper reporting and handling of specimens from these patients.

Waste generated during the handling and testing of specimens from patients with suspect or confirmed VHF or other HCID virus infections are not subject to Federal Select Agent regulations (42 CFR § 73.3(d)(1)) unless viable viruses from VHFs or other HCID are intentionally isolated from that waste.