Clinical Management of Cases

Differential Diagnosis

There are many diseases that have similar presentations to VHF and in case of a deliberate release a high degree of suspicion is needed by the clinicians to consider VHF. The most frequent causes of similar illnesses and their distinguishing features are:

Malaria - presents with acute fever, headache and sometimes diarrhoea (children). Blood smears must be examined for malaria parasites. Presence of parasites does NOT exclude concurrent viral infection. Antimalarial drugs must be prescribed in an attempt at therapy.
Shigellosis and other bacterial enteric infections are a common initial diagnoses of VHF - presents with diarrhoea, possibly bloody, accompanied by fever, nausea, and sometimes toxaemia, vomiting, cramps, and tenesmus. Stools contain blood and mucous in a typical case. A search for possible sites of bacterial infection, together with cultures and blood smears, should be made. Presence of leucocytosis distinguishes bacterial infections.
Typhoid fever presents with fever, headache, rash, gastrointestinal symptoms, with lymphadenopathy, relative bradycardia, cough and leucopenia and sometimes a sore throat. A therapeutic trial with chloramphenicol or tetracyclines may be indicated. Blood and stool culture can demonstrate causative bacteria.
Yellow fever and other Flaviviridae present with haemorrhagic complications. Epidemiological investigation may reveal a pattern of disease transmission by an insect vector. Molecular biological techniques together with virus isolation and serological investigation serves to distinguish these viruses. Confirmed history of previous yellow fever vaccination will rule out yellow fever.
Others - systemic plague, systemic tularemia, viral hepatitis, leptospirosis, rheumatic fever, typhus, and mononucleosis produce signs and symptoms that may be confused with VHF in the early stages of infection.

Note that most of the above diseases are not endemic in UK but may occur if there is an appropriate travel history. In the absence of travel history suspicion should be raised.

Precautions for sampling

Blood specimens should be taken by a doctor or nurse experienced in phlebotomy. Urine samples should only be taken by experienced staff (a 20 ml syringe should be used to transfer urine from a bedpan to the specified container).

Protective measures include:

a protective gown
a waterproof protective apron
latex gloves
particulate filter face mask
eye protection
washing hands and exposed skin thoroughly

The following techniques are recommended when obtaining specimens of blood:

dry cotton wool balls or gauze swabs (not disposable alcohol swabs) should be used to apply pressure to venepuncture wounds
use of a vacuum blood sampling system
specimen tubes should be labelled with patient details before being filled
use of the most familiar equipment and procedure (unfamiliar procedures are more likely to lead to accidents and spillages)

Samples to be taken from acutely ill humans

The emphasis here is to minimise investigations until a diagnosis is confirmed or excluded. The specific diagnostic samples are needed from acutely ill patients:

acute phase whole blood obtained from a patient within 7 days of onset of illness
convalescent sera collected from patients at least 14 days after onset of illness - paired serum samples are ideal, usually collected 7-20 days apart

This does not include other routine blood samples. Chain of evidence documentation should also accompany all specimens; however in larger incidents this would only be required for several of the initial cases. All samples should be identified as High Risk according to local protocols. There is no need to separate acute phase sera from blood clots (a procedure that may significantly increase the risk of accidental infection). The use of sealed sterile dry tubes (Vacutainer® type) is recommended.

Ideally, blood samples should be kept in their original tube and stored at 4ºC to allow virus isolation/ PCR. If separate blood samples are collected purely for serological or biochemical purposes, they can be frozen. Each collected blood sample must be coded and dated for easy connection with the corresponding record of the case database. The use of labels prepared in advance for both the collection of clinical samples and case report forms is recommended.

Transport of samples

Strict procedures should be followed for the transport of samples to the laboratory. These are outlined in transporting samples to the laboratory. VHFs fall into category A for the purposes of transport. All samples should be transported as per UN602 as described in Appendix 1.2 Transport of infectious substances in Biological agents: Managing the risks in laboratories and healthcare premises (external link) ACDP, HSE May 2005.

Treatment

Supportive care is essential for patients. Many deaths attributed to VHF are due to severe dehydration; management of patients should be supportive, with careful maintenance of hydration, and minimal trauma - in particular, injections and parenteral interventions must be kept to a minimum. Replacement of coagulation factors and of platelets may be of value.

Specific treatment with ribavirin may be effective for Lassa fever and CCHF. No specific treatments (antiviral drugs, cytokines or vasoactive agents) have been shown to date to influence the course of the other two VHF agents (Ebola and Marburg).

Infection Control Practice

Decontamination of exposed person

The risk of acquiring infection from the contaminated clothing of exposed persons is low. Heavily exposed persons should be instructed to remove outer clothing, which should be double bagged in sealed plastic bags prior to washing according to local infection control policies. They should then be instructed to shower thoroughly with soap and water. An incident specific risk assessment will be required.

Isolation of Patients

Person-to-person spread may occur through exposure to blood or body fluids. Although airborne transmission of these agents appears to be rare the precautionary principle applies. Patients known or strongly suspected to be suffering from a VHF agent should be admitted to a designated High Security Infectious Disease Unit, or to an intermediate isolation facility after consultation with the physician in charge of the patient. In the event of a large-scale event, patients may be cohort isolated in a designated ward.

Cleaning and waste disposal

Normal procedures for standard isolation are appropriate. Contaminated environmental surfaces should be cleaned with hypochlorite solution (5000ppm available chlorine).

Post-mortem

Autopsy
The risk of acquiring a VHF agent following contact with the body of a person who has died from the disease is moderate to high, because person-to-person transmission occurs via blood and body fluids and there is evidence of autopsy transmission.

Autopsy examinations should not be performed if VHF is suspected, as all the body fluids in a patient who has died of VHF will have large numbers of virus present and there is documented evidence of transmission during autopsy. If an autopsy is necessary expert advice must be sought from the HPA. The Pathologist must be informed of the known or suspected diagnosis. Precautions for post-mortem examinations on patients infected with Containment Level 4 organisms are appropriate. Instruments should be autoclaved.

Body preparation procedures should not be undertaken and the coffin should not be opened. Cremation is the preferred method for disposal of the deceased. Embalming of bodies must not take place because the body fluids will have large numbers of haemorrhagic fever viruses present and therefore the process of embalming exposes the embalmer to unacceptably high risk.

Pacemaker removal
Pacemaker removal is permitted provided personnel take appropriate precautions. PPE should include a full length fluid-impermeable gown, apron, hair cover, overshoes, correctly fitting FFP3 mask, suitable eye protection, and disposable gloves. Pacemaker should be treated with hypochlorite solution (10,000ppm available chlorine), bagged and disposed of appropriately (not by incineration).

Last reviewed: 11 May 2011