Viral Zoonoses - Rabies and Viral haemorrhagic fevers

Dr F Noordeen Department of Microbiology Faculty of Medicine University of Peradeniya May 2013

Learning outcomes
Modes of transmission and the pathogenesis of viral zoonoses including rabies in humans Clinical features of viral zoonoses including rabies Principles of diagnosis, management and prevention viral zoonoses including rabies in Sri Lanka

Aim:
Make ake students aware pathogenesis & clinical significance of rabies virus Objectives:
1. to diagnose a clinical presentation of rabies (History + Symptoms + Lab) 2. to prevent disease progression after an exposure (post exposure immunization) 3. to prevent/control rabies in Sri Lanka

Rabies and rabies virus

Rabies - Acute viral infection resulting in encephalomyelitis Family - RHABDOviridae - (Bullet shaped) Genus - LYSSAvirus - (Madness) Genome - ssRNA Envelope - Lipoprotein envelope Hosts - All warm blooded animals + man

EM appearance Rabies virus

Pathogenesis
Animal bite
1. Virus acquisition Sensory nerves Centripetal spread

CNS
Neuronal axons Centrifugal spread

Conjunctival/ olfactory nerve

Aerosol
2. Virus acquisition

Salivary glands + hair bearing tissues

ClinicoClinico -pathological aspects

Incubation period - 10 days to year or > 1. Quantity of virus deposited 2. Distance of bite site from head Onset - Insidious with 1-10 days of prodrome malaise, fever, headache, psychological disturbances, pain and tingling around the bite - neurological phase

Clinical presentation
Paralysis

Furious rabies
80% patients Hyperactive to various stimuli

Dumb rabies
20% patients Hyperactivity is absent

Furious form of rabies

1. After 3/4 days symptoms become worse 2. Restless and hypersensitive to stimuli

Furious form of rabies cont...

3. Hydrophobia 4. On attempting/site of water produces violent spasms in respiratory & swallowing actions 5. Respiratory & cardiac arrest Death

Dumb rabies
1. 20% patients may present with this form 2. Hyperactivity is absent 3. Expressionless 4. Paralysis and death

Infection of brain - coma and death Antibody response is apparent only in latter stage of the disease when virus has entered the CNS and other tissues Rx with antibodies X progression to C N S Rabies is fatal unless the vaccine is given

Diagnosis

Clinical - History of animal bite and neurological signs Lab tests - to confirm diagnosis
Viral antigen in skin by FAT (AM) Viral specific inclusion bodies (70-90%) hippocampus of brain (PM) (Sellers stain or Mann stain) Antibodies in serum + CSF in terminal disease

Rabies virus antigen -IFA

Negri bodies in the brain section

Epidemiology

Spread - Zoonosis Urban rabies - Unvaccinated dogs & cats Wild rabies - Wild animals Transmission - Animal bite or aerosols Risk group - Veterinarians, veterinary students, animal handlers, wild life officers, students/scientists involve in ecological/zoological camping

Occurrence - Worldwide, common in Sri Lanka, India and Latin America Free in Australia and some islands Prevention 1. Vaccination of reservoirs (pet dogs/cats) 2. Vaccination of high risk personals 3. Stray dog elimination 4. Proper post exposure immunization 5. Public education programs on rabies

Treatment

Human vaccine - human diploid cell culture vaccine - HDCV (killed by formaldehyde or propiolactone) Post exposure treatment - prevent disease
Immediate cleaning of wound Vaccination with killed vaccine Administration of human rabies Igs (ARS) Symptoms - Death is inevitable

Rabies immunisation (HDVC)

Pre-exposure Rx 3 dose regime Day 0, 7, 21 or 28 Route - deep subcutaneous/IM

Post-exposure Rx 5 dose regime Day 0, 3, 7, 14, 28 Route - deep subcutaneous/IM

Human rabies
a. May be transmitted by the bite of cats b. May be prevented by adequate immunization and control of dogs c. The best available vaccine is the human diploid cell culture vaccine d. Specific immunoglobulin should be injected around the bite wound as soon as possible after the bite e. The development of hypersensitivity reactions are major complication of the human diploid cell culture vaccine

RNA viruses include

a. Chicken pox virus b. Rabies virus c. Hepatitis A virus d. Hepatitis C virus e. Hepatitis B virus

Viral haemorrhagic fevers (VHFs)

Aetiology: A number of arboviruses (Toga and Bunyaviruses) and some similar viruses (Arena and Filoviruses) Disease: Similar to the rather non-specific flu-like illness but which rapidly progresses to a severe disseminated illness with a marked bleeding tendency and multi-organ failure

There is usually a considerable mortality in VHFs The following may produce a similar clinical picture & requires to be excluded
Meningococcal disease Rickettsial disease Leptospirosis Hepatitis Malaria Snake bites Tryponosomiasis

Crimean Congo Haemorrhagic Fever (CCHF) Eastern Europe, Central and Southern Africa Yellow fever Lassa fever Ebola Marburg Hanta Could be urban West Africa Africa Central Africa Africa and Asia

Hantavirus infection/disease

FAMILY Bunyaviridae GENUS Hantavirus More than 30 different hantavirus species have been found (20 of which are known to be pathogenic to humans)

Hantavirus disease

1. Hemorrhagic fever with renal syndrome (HFRS) 2. Hantavirus pulmonary disease (HPS)

Deer mouse

Hantavirus vectors

Cotton rat

Rice rat

White footed mouse

Prevention

Avoid contact with rodents and their habitats Do not keep rodents as pets Keep all food in sealed containers Virions may be stable for 2 days on a dry surface so disinfect areas contaminated by rodents Disinfect using a 10% solution of household bleach Eradication unlikely due to the large percentage of rodents which carry these viruses

Three young men presented to Pollunnaruwa hospital with a 2 day history of high fever with chills, intense myalgia and deteoriating renal function. Two required ventilation due to respiratory complications. They all gave a history of exposure to rats during different activities they perform in the paddy stores and warehouses they work. 1. What 2 infective diseases may produce these clinical features and what is the route of transmission in each of the diseases? (30 Marks) 2.How can you make an aetiological diagnosis of ONE disease that you have identified in 2.2. (50 Marks) 3.How can you advise those who work in similar settings to prevent exposure to infective agent responsible for the above clinical scenario. (20 marks)