The Pivotal Role of Histopathology in the Diagnosis of a Novel Old World Arenavirus Viral Haemorrhagic Fever Outbreak in Southern Africa
MJ Hale, SR Zaki, CD Paddock, W-J Shieh, JT Paweska, R Swanepoel. University of the Witwatersrand & National Health Laboratory Service, Johannesburg, South Africa; Centers for Disease Control and Prevention, Atlanta, GA; National Institute for Communicable Disease, Johannesburg, South Africa
Background: Viral haemorrhagic fevers are caused by a spectrum of viruses including arenaviruses and are endemic to Southern Africa with a high index of suspicion in the minds of medical staff attending to patients presenting with fever, a bleeding diathesis, petechial rash and altered consciousness. Such patients are investigated for a trio of infections including meningococcal meningitis, tick bite fever and viral haemorrhagic fever. Serology and culture are pivotal to confirmation of the diagnosis and initiation of containment measures.
Design: The index patient, an adult female, was evacuated by air from Zambia to South Africa with severe myalgia, facial swelling, sore throat, a petechial rash and liver failure. Three days after admission she died. Nine days after exposure, a paramedic who attended the index patient on the flight became ill with similar symptoms and died 12 days later. A further 3 patients with either secondary or tertiary contact became ill, 2 of whom died with the third surviving after protracted care. A haemorrhagic fever outbreak was considered, but as repeated serology and RT-PCR for known viruses was negative it was decided that post-mortem liver and skin biopsy were essential in the two patients in whom this was possible. These biopsies, performed under P4 conditions were retained for histology, electron microscopy and viral culture.
Results: Histology of the liver and skin biopsies showed features of a haemorrhagic fever. Extensive pan lobular hepatocellular necrosis was identified in both patients, with numerous acidophil bodies, severe intracellular cholestasis, macrovesicular steatosis and lymphocytic infiltration. Immunohistochemistry for Old World arenavirus antigen showed cytoplasmic staining confirming the H&E diagnosis of a viral haemorrhagic fever, providing the first evidence of a potential aetiology. The skin biopsies showed a lymphocytic vasculitis of dermal blood vessels with infarction of the overlying epidermis. Later, molecular methodology and viral culture identified the virus as a novel highly pathogenic arenavirus now named the Lujo virus.
Conclusions: This report demonstrates the vital role of histology in the diagnosis of hitherto undescribed disease.
Wednesday, March 24, 2010 1:00 PM
Poster Session VI # 212, Wednesday Afternoon