BACKGROUND: Human rabies infection continues to be a significant public health 
burden globally, and is occasionally imported to high income settings where the 
Milwaukee Protocol for intensive care management has recently been employed, 
with limited success in improving survival. Access to molecular diagnostics, 
pre- and post-mortem, and documentation of pathophysiological responses while 
using the Milwaukee protocol, can add useful insights for the future of rabies 
management.
CASE PRESENTATION: A 58-year-old British Asian woman was referred to a regional 
general hospital in the UK with hydrophobia, anxiety and confusion nine weeks 
after receiving a dog bite in North West India. Nuchal skin biopsy, saliva, and 
a skin biopsy from the site of the dog bite wound, taken on the day of 
admission, all demonstrated the presence of rabies virus RNA. Within 48 hours 
sequence analysis of viral RNA confirmed the diagnosis and demonstrated that the 
virus was a strain closely related to canine rabies viruses circulating in South 
Asia. Her condition deteriorated rapidly with increased agitation and autonomic 
dysfunction. She was heavily sedated and intubated on the day after admission, 
treated according to a modified Milwaukee protocol, and remained stable until 
she developed heart block and profound acidosis and died on the eighth day. 
Analysis of autopsy samples showed a complete absence of rabies neutralizing 
antibody in cerebrospinal fluid and serum, and corresponding high levels of 
virus antigen and nucleic acid in brain and cerebrospinal fluid. Quantitative 
PCR showed virus was also distributed widely in peripheral tissues despite mild 
or undetectable histopathological changes. Vagus nerve branches in the heart 
showed neuritis, a probable Negri body but no demonstrable rabies antigen.
CONCLUSION: Rapid molecular diagnosis and strain typing is helpful in the 
management of human rabies infection. Post-mortem findings such as vagal 
neuritis highlight clinically important effects on the cardiovascular system 
which are typical for the clinical course of rabies in humans. Management guided 
by the Milwaukee protocol is feasible within well-resourced intensive care 
units, but its role in improving outcome for canine-derived rabies remains 
theoretical.