5.22 VIRAL HAEMORRHAGIC FEVERS (VHF)

Basic facts

Viruses causing haemorrhagic fevers (HF) belong to different taxonomic groups and are characterized by different modes of transmission, geographical distribution, disease severity and propensity to display haemorrhagic signs in their presentation (Table 5.17). HF viruses include some of the most frequently lethal infectious agents, and some of them can be highly transmissible by direct contact from person to person, resulting in community outbreaks or nosocomial transmission.

The incubation period is usually 5-10 days (range 2-21 days), with the exception of haemorrhagic fever with renal syndrome (HFRS, caused by Hantaan virus) in which symptoms appear on average 2-3 weeks after infection.

Depending on the area at risk and the infectious agent involved, disasters and war conditions may increase the risk of HF occurrence through different circumstances: contact with rodents (HFRS, Lassa fever, New World VHF), contact with carcasses of wild infected animals (Ebola HF, Crimean-Congo HF) or breakdown of mosquito control programmes (yellow fever, dengue, Rift Valley fever). Moreover, the poor condition of many health care facilities frequently seen in emergency-affected countries increases the risk of nosocomial outbreaks of VHF agents transmitted by blood or fomites, particularly with the lack of minimal barrier nursing procedures, the lack of safe disposal of sharps and the re-use of infected needles and syringes.

Clinical features

Initial symptoms of VHF are not specific and overlap with the clinical presentation of more common infectious diseases seen in endemic areas: fever, headache, back pain, myalgias, nausea, vomiting, diarrhoea, prostration and conjunctival injection.

More specific signs (maculopapular rash with filoviruses, severe pharyngitis with Lassa fever, jaundice with Rift Valley fever) are inconsistent or difficult to assess under field conditions.

Haemorrhages (petechiae, nosebleeds, bleeding gums, ecchymosis, melaena, haemetemesis, bloody diarrhoea) are by definition the distinguishing feature of VHF, but they are not always present, even in the late stages of the disease. The combination of compatible clinical symptoms, endemic area and clustered cases is essential to suspect an outbreak of VHF (see WHO case definition, Annex 5).

When isolated patients present with fever and haemorrhagic signs outside of an outbreak situation, standard barrier nursing procedures must be reinforced. Nevertheless, more common diseases are likely to be the cause (e.g. malaria or typhoid fever complicated with disseminated intravascular coagulation).

Diagnosis

Depending on the circumstances of sampling and on the causal agent, laboratory confirmation of VHF can be based on (a) antigen or antibody detection in serum, (b) polymerase chain reaction from any infected sample, (c) virus isolation or (d) immunohistochemical staining of autopsy material. The latter method has been shown to allow the retrospective diagnosis of filovirus infection from dead bodies, and a relatively safe procedure has been developed for sampling and shipment of diagnostic skin snips in fixative solution. Any other method involving the manipulation, shipment and analysis of material potentially infected with VHF agents should follow strict biosafety procedures. As soon as one case of VHF is suspected, contact should be made with public health officers, and ultimately with WHO representatives, in order to organize an appropriate outbreak response, including collection/shipment of diagnostic material under safe conditions to a reference laboratory.

Table 5.17. Some features of the main agents of viral haemorrhagic fevers

Family	Disease	Vector in nature	Geographical distribution	Mortality	Risk of person-to-person transmission and nosocomial outbreaks
Filoviridae	Ebola HF, Marburg HF	Unknown a	Equatorial Africa	50-90% (Ebola HF), 23-70% (Marburg HF)	Yes
Arenaviridae	Lassa fever	Rodent	West Africa	15-20%	Yes
	New World VHF b	Rodent	Americas	15-30%	Yes
Bunyaviridae	Crimean-Congo HF	Tick	Africa, central Asia, eastern Europe, Middle East	20-50%	Yes
	Rift Valley fever	Mosquito	Africa, Arabic peninsula	< 1%	No
	Haemorrhagic fever with renal syndrome	Rodent	Asia, Balkans, Europe, Eurasia	1-15%	No
Flaviviridae	Dengue fever, dengue HF, dengue shock syndrome (see Section 5.5)	Mosquito	Asia, Africa, Pacific, Americas	< 1%	No
	Yellow fever (see Section 5.23)	Mosquito	Africa, tropical Americas	20%	No

^a Contact with infected apes through hunting activities or consumption of ape meat have been the origin of several outbreaks.

^b Argentine, Bolivian, Brazilian and Venezuelan haemorrhagic fevers.

Case management

In most cases of VHF there is no specific treatment, but some general principles of case management are essential to follow.

· As long as diagnosis of VHF is not confirmed, consider and treat for more common and potentially confounding diseases, in particular malaria, typhoid fever, louse-borne typhus, relapsing fever or leptospirosis.

· Avoid nosocomial transmission by strict implementation of barrier nursing. If barrier nursing material is not available and a highly transmissible form of VHF is likely, avoid any invasive procedure (e.g. blood sampling, injections, placement of infusion lines or nasogastric tube) and put on at least one layer of gloves for any direct contact with the patient.

· Supportive treatment - analgesic drugs (excluding aspirin and non-steroidal anti-inflammatories), fluid replacement or antimicrobial therapy if secondary infection is suspected - can make a difference, at least in the comfort of the patient. In the case of HFRS, dengue HF and dengue shock syndrome, proper management of fluid and electrolyte balance can be life-saving.

· Ribavirin (ideally given intravenously) improves dramatically the prognosis if given early in Lassa fever episodes, and probably also in cases of Crimean-Congo HF, HFRS and some New World HF.

Prevention and control measures

Where outbreaks of VHF are known to occur, routine prevention measures should include reinforced sanitation, hospital infection control, case detection and health education. In addition, there are specific interventions that can be implemented either to prevent outbreaks, or to limit the extension of an established outbreak (Table 5.18). Commercial vaccines against VHF are not available except for yellow fever, where mass immunization is the mainstay of epidemic control (see Section 5.5).

In the case of an outbreak, population movements can contribute to the spread of infection to non-affected areas. Contacts under daily follow-up should be encouraged to limit their movements.

Table 5.18. Specific interventions to prevent or limit disease outbreaks

Disease	Specific preventive measures	Reactive measures/outbreak
Ebola HF, Marburg HF		Strict barrier nursing in suspected/confirmed cases
Lassa fever	Rodent control
New World VHF	Rodent control
Crimean-Congo HF	Avoidance of contact with tick-infested animals
Rift Valley fever	Mosquito control	Mosquito control
Haemorrhagic fever with renal syndrome	Avoidance of contact with rodents	Rodent control
Dengue fever, dengue HF, and dengue shock syndrome (see Section 5.5)	Mosquito control (see Section 2.4.1)	Mosquito control
Yellow fever (see Section 5.23)	Mosquito control (see Section 2.4.1)	Mass immunization plus mosquito control

Barrier nursing

To prevent secondary infections, contact with the patient's lesions and body fluids should be minimized using standard isolation precautions:

· isolation of patients
· restriction of access to patients' wards
· use of protective clothing
· safe disposal of waste
· disinfection of reusable supplies and equipment
· safe burial practices.

Simple guidelines have been developed (see selected reading below) on how to implement these principles, even where resources are limited.

Further reading

Infection control for viral haemorrhagic fevers in the African health care setting. Geneva, World Health Organization, 1998 (document WHO/EMC/ESR/98.2).