Diagnosis, management and post-mortem findings of a human case of rabies imported into the United Kingdom from India: a case report
Open accessAbstract
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.
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Death commonly follows within an average survival time between 6 and 11 days after first symptomatic onset for furious or paralytic forms, leaving little time and extremely limited therapeutic options.
“While incubation phases vary, death commonly follows within an average survival time between 6 and 11 days after first symptomatic onset for furious or paralytic forms, respectively, thus leaving little time and extremely limited therapeutic options [1,2].”
From An mRNA Vaccine Encoding Rabies Virus Glycoprotein Induces Protection against Lethal Infection in Mice and Correlates of Protection in Adult and Newborn Pigs (2016) · cites this paper as [2]
The Background says clinical rabies is invariably fatal, and the Conclusion describes limited evidence for the Milwaukee Protocol’s efficacy. The Case presentation records one patient’s deterioration through day 10, but the paper does not give average survival times of 6 and 11 days after symptom onset for furious and paralytic rabies, respectively. (LLM, conf=0.88)
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“While incubation phases vary, death commonly follows within an average survival time between 6 and 11 days after first symptomatic onset for furious or paralytic forms, respectively, thus leaving little time and extremely limited therapeutic options [1,2].”
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- Authors
- Pathak, S., Horton, D. L., Lucas, S., Brown, D., Quaderi, S., Polhill, S., Walker, D., Nastouli, E., Núñez, A., Wise, E. L., Fooks, A. R., & Brown, M.
- Affiliations
- University College London Hospitals NHS Foundation Trust (GB)
- Animal and Plant Health Agency (GB)
- St Thomas' Hospital (GB)
- Public Health England (GB)
- University of Liverpool (GB)
- University College Hospital (GB)
- Corresponding author
- Brown, Michael
- ORCID
- Venue
- Virology Journal
- Published
- 2014-04-07
- Volume
- 11
- Issue
- 1
- Pages
- 63-63
- ISSN
- 1743-422X (ISSN-L)
- PMC
- PMC3977668
- OpenAlex
- W2105851482
- Cited by
- 19
- References
- 52
- Citations by year
- 2026: 2 · 2025: 1 · 2024: 1 · 2022: 1 · 2021: 2 · 2020: 4 · 2017: 4 · 2016: 2 · 2015: 1 · 2014: 1
- FWCI
- 1.19
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- Virology Journal (publishedVersion, cc-by)
- Europe PMC (PubMed Central) (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- LSHTM Research Online (London School of Hygiene and Tropical Medicine) (acceptedVersion)
- Open Research (University of Surrey) (submittedVersion)
- Surrey Research Insight Open Access (The University of Surrey) (submittedVersion)
- Funders
- Department for Environment, Food and Rural Affairs, UK Government (SV3500)
- Public Health England
- Animal Health and Veterinary Laboratories Agency
- Topics
- Life Sciences › Immunology and Microbiology › Virology › Rabies epidemiology and control
- Health Sciences › Medicine › Infectious Diseases › Infectious Encephalopathies and Encephalitis
- Health Sciences › Medicine › Epidemiology › Virology and Viral Diseases
- Keywords
- human rabies, imported rabies, dog bites, viral strain typing, autopsy findings, atrioventricular block, acidosis, Negri bodies, intensive care management, rabies neutralizing antibodies
- MeSH terms
- Animals, Bites and Stings, Dogs, Female, United Kingdom, Humans, India, Middle Aged, Rabies, Rabies virus, RNA, Viral, Travel, Fatal Outcome
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