Since viral haemorrhagic fever (VHF) was designated a notifiable infectious disease in 1978, only two cases have been reported in the Netherlands (1-3). Both patients acquired Lassa fever while working in endemic areas. In 1980, an expatriate from Burkina Faso (formerly Upper Volta), who was not seriously ill, was admitted to a Dutch hospital. The patient’s symptoms were evaluated after discharge from hospital, and laboratory tests for Lassa fever were carried out, which confirmed the diagnosis. The second case was notified in 2000 and served as a test case for the existing policies and procedures. In this article we report on the procedures and lessons learnt.

Previously, VHF was classified as a group A infectious disease, requiring notification to the local municipal health department (Gemeentelijke Gezondheids Dienst, GGD) as soon as the disease is suspected. In 1999, the Infectious Diseases Act was adjusted to comply with European legislation and prevailing privacy regulations. VHF was one of many diseases relocated to group B (notification within 24 hours after laboratory confirmation of the diagnosis). Since its inception in 1995, the National Infectious Disease Control Coordination Structure (Landelijke Coördinatiestructuur Infec-tieziektebestrijding, LCI) (4) has developed guidelines for the management of patients with VHF and their contacts. Awaiting specific hospital guidelines for VHF, these LCI procedures are applied for patient nursing and laboratory safety.

In July 2000, a 48 year old male patient with Lassa fever was admitted to Leiden University Medical Centre (Leids Universitair Medisch Centrum, LUMC). He had been working as a surgeon in Kenema (Sierra Leone), where viral haemorrhagic fever is endemic, and was referred by his general practitioner for persistent fever on the day of his arrival in the Netherlands. As typhoid fever was considered to be the most likely diagnosis, the patient was admitted to hospital under barrier isolation (gloves and protective clothes were used while nursing or handling excreta). The patient’s travel history was not considered until the third day of admission, when methicillin resistant Staphylococcus aureus (MRSA) isolation guidelines were initiated (nursing in a single room with negative air pressure and provision of an anteroom, only to be entered when wearing gloves, a mask, and protective clothing). On day six of admission, the diagnoses of malaria and typhoid fever were ruled out, and Lassa fever was considered the most likely diagnosis. Ribavirin treatment was started. On day eight, the diagnosis was confirmed by polymerase chain reaction (PCR) through the European Network for Diagnostics of Imported Viral Diseases (ENIVD, Bernhard-Nocht-Institut, Hamburg, Germany). For laboratory procedures and waste management, biosafety level 4 was initiated. The case was notified to the local GGD (GGD Zuid-Holland Noord) on the same day. Three days later, the patient died during endotracheal intubation.

Contact tracing

In accordance with the guidelines of the LCI (4) and the Centers for Disease Control and Prevention (5), the GGD started a contact investigation in collaboration with LUMC. One hundred and twenty eight people were identified as close unprotected contacts (121 hospital workers and seven family members). These contacts were asked to record body temperature twice daily until three weeks after the date of the last unprotected contact. They also were asked to report immediately to the first aid department of LUMC if their body temperature exceeded 38°C. Guidelines indicate the daily collection of temperature lists for early detection of secondary cases (4). This was considered to be too laborious as many contacts worked irregularly or were on holiday. After lengthy discussion, we decided to collect temperature lists twice a week. Since many of the contacts had a medical background, we expected that they would not delay seeking medical care if they developed fever and therefore the time delay in detecting secondary cases would be minimal. At the time of notification, nine days had already passed since the first high risk contact had taken place, and so it was concluded that the effectiveness of ribavirin prophylaxis would be very low and it was therefore not indicated. Furthermore, the patient had not initially been very contagious (no vomiting or diarrhoea). Three contacts developed fever, but medical investigation made Lassa fever very unlikely. Afterwards, blood samples of 123 of a total of 189 both protected and unprotected close contacts proved to be negative for Lassa virus serology. No secondary clinical cases of Lassa fever were shown.

This second patient led to a number of further recommendations. A diagnostic test for Lassa fever was requested immediately after other diagnoses were ruled out, although Lassa fever had been considered as a possibility from the outset. The obstacles to obtaining Lassa fever tests were unnecessarily high due to the rarity of the disease and insufficient information on laboratory procedures for VHF in the Netherlands. As a consequence, LUMC has now developed a protocol for early management of patients with fever from areas where VHF is endemic. This protocol ‰ ‰ gives criteria for assessing the risk of VHF and early initiation of protective measures and diagnostic tests. It was used in a recent case of a patient with fever coming from Sierra Leone. PCR testing on VHF was negative within 24 hours (performed at the Laboratory for Exotic Virus Infections, Institute of Virology, University Hospital Rotterdam, which is headed by Dr J. Groen, and participates in ENIVD). The case showed that facilities for correct laboratory safety procedures were present only in the microbiological department. Intense efforts were needed for the coordination of laboratory tests and waste management. The need for national guidelines on the care of patients with haemorrhagic fevers is evident. The Working group on infection prevention (Werkgroep Infectie Preventie) will develop these guidelines for Dutch hospitals, which should at least cover clinical care, laboratory safety, transport of patients, and measures for funeral services.

It has been demonstrated that early reporting of a suspected case of VHF to the local GGD is essential for a more timely inventory of close unprotected contacts and for taking safety measures in the hospital wards and laboratories. Notification of VHF in the Netherlands is currently required after laboratory confirmation. Notification at the time of clinical suspicion would help to initiate the contact investigation and take appropriate precautions at a more adequate time point. Although post-exposure prophylaxis with ribavirin generally is recommended for all close contacts (5,6), its effectiveness is not proven. Since contagiousness can vary widely between patients, the contact investigation and the feedback frequency of body temperatures are hard to standardise. In the management of VHF, guidelines are never expected to serve as blueprints, but appropriate handling of contacts is still a matter of timely and thoughtful consideration.