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Dr.Nan Nitra Than M.B.,B.S DTM&H M.C.T.M(Tropical medicine)

The outcome  Able to illustrate the basic concepts and terminologies used in zoonosis  Able to illustrate the epidemiological concepts relating to Rabies  Able to state the epidemiological concepts relating to Plague

Contents  Classification of zoonosis  The epidemiology of Rabies  The epidemiology of Plague

Definition 4

 Zoonoses are diseases of vertebrate animals (WHO 1959)  Transmitted to man: either directly or indirectly through an insect vector( Arbovirus infection)  Not all arboviral diseases are zoonosis e.g. dengue and urban yellow fever  Examples of viral zoonoses that can be transmitted to man directly include rabies, hantaviruses, lassa and ebola fevers

Zoonoses: Classification 5

DIRECT ZOONOSES:[one host for completion of its life cycle] Rabies, Trichinosis, Brucellosis CYCLOZOONOSES:[at least two species of vertebrates as definitive and intermediate hosts] Human Taeniasis, Echinococcosis

METAZOONOSES: [Requires both a vertebrate and an invertebrate host for completion of the life cycle] Arboviral diseases, Plague, schistosomiasis


: [A zoonosis whose causative agent requires both a

vertebrate host and a non animal reservoir or developmental site for completion of its life cycle]Various Larva migrans and mycoses


Zoonoses: Animal Species Dogs & Cats 


Round worm


Lyme Disease (dogs only)

Cat Scratch Disease (cats only)

Food Animals 


E. coli



Zoonoses: Animal Species 

Birds: 


West Nile


Reptiles, Fish, & Amphibians 



Wild Animals 





Zoonoses: Viral Examples

Zoonoses: Bacterial Examples

Zoonoses: Parasitic Examples

Zoonoses: Mycotic Examples 12

Aspergillosis Blastomycosis Cryptococcosis Dermatophytosis Histoplasmosis

Structure  ‘bullet’ shaped , RNA structure  Caused by neurotropic viruses in the family Rhabdoviridae, genus Lyssavirus.


M protein

G protein

RNP core

 Regardless of the viral variant found throughout the world, all lyssa viruses cause rabies Picture from Centers for Disease Control and Prevention

Distribution of important rabies vector species 15


Domestic dog, jackals, mongoose

AMERICAS: Fox, skunk, racoon, bats, dog ASIA: EUROPE:

Domestic dog, wolf Fox, wolf, dog, bats

High Risk Animals

 Raccoon  Skunk  Groundhog  Fox  Bat  “free-roaming” cats

Intermediate Risk Animals  Dogs  Cats – vaccinated or non-roaming  Livestock – horses, cattle, pigs  Other non-rodent wild animal species i.e, bear, deer, coyote, etc

Low Risk Animal

 Squirrels, chipmunks  Rats  Mice  Indoor small caged pet rodents  Logomorphs

Public Health importance 19

 > 2.5 billion at risk in over 100 countries  50,000-70,000 human deaths annually  10 million people treated for exposure to rabies every year  90% in developing countries in Tropics i.e. Africa, Asia, South America, Oceania

Global distribution of mammalian reservoirs and vectors 21

Mode of Transmission 22

1) ANIMAL CONTACT: inoculation of virus laden saliva into a wound or on a mucous membrane (BITES & LICKS)

2) Human-to-Human: very rare! (corneal grafts,transplacental infection?)

3) INHALATION: very rare! (bat-infested caves, laboratories)

Pathogeneis  Virus binds to a nerve cell & migrates to spinal cord to brain (centripetal spread)- viral replication occurs & produces encephalitis

 Viral particles travel out from brain (centrifugal spread) via nerve cells to salivary glands, where further replication occurs & secretion in saliva, rendering the person or animal to be infectious  At the time it gets to the salivary glands, this is the end stage of the disease, and death usually occurs shortly thereafter – within several days

Transmission Cycle of Rabies 24

Rabies attacks the Central Nervous System ď‚— rabies virus from an exposure on the leg spreads up the spinal cord to the brain and throughout the rest of the body

Rabies virus entering the body.


Was There An Exposure?  A bite (penetration of the skin by teeth) from a known or suspect rabid animal  Scratches, abrasions, open wounds (bleeding within 24 hrs), or mucous membranes (eyes) contaminated with saliva or other potentially infectious material from a known or suspect rabid animal  Other contact - such as petting an animal or contact with urine, feces or skunk spray - does NOT constitute an exposure

WHO Definition of Exposure Category

Type of contact

Type of exposure

Recommended treatment


Touching or feeding of animals; Licks on intact skin;


None if reliable history is taken


Nibbling of uncovered skin Minor scratches or abrasions without bleeding


Administer vaccine immediately; Stop treatment if animal remains healthy for of 10 days or if animal is proven to be negative for rabies by a reliable laboratory using appropriate diagnostic techniques


Single or multiple transdermal bites or scratches, licks on broken skin; Contamination of mucous membrane with saliva (i.e. licks); Exposures to bats


Administer RIG and vaccine immediately. Stop if animal remains healthy for 10 days or if animal is negative for rabies

Symptoms  Headache, fever, sore throat  Nervousness, confusion  Pain or tingling at the site of the bite  Hallucinations  Seeing things that are not really there ( Cowering in the corner like a caged animal)  Hydrophobia  “Fear of water" due to spasms in the throat(I throw up every time I try to eat or drink something. I can’t swallow my spit)  Paralysis

Laboratory Diagnosis 30

 Histopathology - Negri bodies are pathognomonic of rabies. Negri bodies are only present in 71% of cases  Rapid virus antigen detection -Direct Fluorescent Antibody test (DFA)  Virus cultivation - definitive means of diagnosis  Serology - circulating antibodies appear slowly in the course of infection but they are usually present by the time of onset of clinical symptoms

Diagnosis of Rabies


Management and Prevention Inactivated whole virus vaccines •Nervous Tissue Preparation e.g. Sample Vaccine associated with the rare complication of demyelinating allergic encephalitis. • Duck Embryo Vaccine - this vaccine strain is grown in embryonated duck eggs, (a lower risk of allergic encephalitis but is considerably less immunogenic) •Human Diploid Cell Vaccine (HDCV) - currently the best vaccine •Other Cell culture Vaccines - (developing countries)

Prevention Pre- exposure prophylaxis • Provides protection from unapparent exposures and when treatment is delayed • persons at increased risk of being exposed to rabies e.g. vets, animal handlers, laboratory workers etc. • spending 1 month or more in countries with endemic dog rabies and in which PEP would likely be significantly delayed to geographic distances/ lack of medical infrastructure 11/3/13

Pre-exposure Vaccination Protocol  Three doses of vaccine administered on days 0, 7 and 21 or 28  Dosage: 1.0 ml administered IM in the upper deltoid

 Test serum every 2 years to determine if an adequate antibody level persists

 If absent, administer booster

WHO Recommended Pre-exposure(PreEP)

3-dose series intramuscular or intradermal regimen




21 or 28

day 0

Exposure: No Rabies immunoglobulin needed


WHO Recommended Post-exposure prophylaxis 1.

Immediate flushing and washing of the wound with soap and water, or other detergent ď‚Ą

If soap or detergent are not available, flush extensively with water


Passive immunization: Administration of Rabies immune globulin for Category III contacts/exposures


Active immunization: Administration of tissue culture vaccine according to one of WHO regimens

WHO Recommended PEP Schedule

Essen intramuscular Regimen Standard intramuscular regimen. One dose into deltoid on each of days:

5 vials 5 visits day 0




Rabies immunoglobulin


Control of Rabies 38

 Urban - canine rabies accounts for more than 99% of all human rabies. Control measures against canine rabies include; stray dog control Vaccination of dogs quarantine of imported animals  Wildlife - this is much more difficult to control than canine rabies { trials in Europe -where bait containing rabies vaccine is given to foxes}


Introduction Plague has a long history as a biological weapon A bacterial disease, caused by Yersinia pestis  Primarily affects wild rodents- spread from one rodent to another by fleas-Humans bitten by an infected flea  Develop a bubonic form of plague(a bubo- a swelling of the lymph node) draining the flea bite site IP, Bubonic plague appear 7–10 days after infection If the bacteria reach the lungs, the patient develops pneumonia (pneumonic plague) - transmissible from person to person (coughing)

The History of Plague 41

ď śHistorians think that the plague arrived in England during the summer of 1348. By 1350, nearly the whole of Britain was infected with the plague ď śAt the end of 1350 nearly two and a half million people were dead!

Epidemiology First Pandemic: Early Middle Ages (Plague of Justinian) Second Pandemic: 14th (Black Death) to 19th century Third Pandemic: 19th and 20th centuries

 10 August 2010 -Plague in Peru  11 August 2009 -Plague in China  7 November 2006 - Suspected plague in the Democratic Republic of the Congo  13 October 2006/June 2006 /15 March 2005 -Plague in the Democratic Republic of the Congo


Causative Agent - Yersinia pestis (Gram-ve coccobacilli, non-motile) Virulence- cytotoxin & endotoxin RESERVOIR: Wild rodents, gerbils, Skunks etc In India: Tatera indica (Immune to plague) Source of infection: Infected RODENTS FLEAS & Case of Pneumonic Plague


REGURTITATES Plague Bacilli Inoculation

Frantic Efforts to suck blood

Blood meal (0.5 cu m)contain Up to 5000 bacilli

Multiply enormously in the GUT

blocked proventriculus Food cannot pass through


Blocked is an efficient transmitter of plague Blocked flea eventually dies A partially blocked flea may live longer and more efficient transmitter


 All ages & both sexes

Man may contact with natural ‘foci’ while Hunting, grazing, cultivation & harvesting Movement of people and Cargo by sea or land No natural immunity


Season: from September to May Temperature: 20-25 C Humidity 60%, POOR HOUSING conditions & abundance of Rats and rat fleas VECTORS: Xenopsilla cheopis - Rat Flea, Others X. astia, X. braziliensis ,Pulex Irritans—Human Flea


Disease Progression in Human 51

Incubation period: Bubonic and septicemia 2-7 days Pneumonic- 2-3 days BUBONIC PLAGUE: sudden fever, chills, headache, prostration, painful buboes PNEUMONIC PLAGUE: complication of bubonic-septicemic plague SEPTICEMIC PLAGUE: Rare, lab infection


Bubonic plague 53


Laboratory Criteria for Diagnosis 1. Presumptive • Elevated serum antibody titer(s) to Yersinia pestis fraction 1 (F1) antigen or • Detection of F1 antigen in a clinical specimen by immunofluorescent assay

2. Confirmatory • Isolation of Y. pestis from a clinical specimen {Yersinia pestis… Non spore forming , G (-) ,non motile coccus bacillus ( exhibit bipolar stainingcharacteristic safety pin appearance)} or • Fourfold or greater change in serum antibody titer to Y. pestis F1 antigen



If diagnosed early, bubonic plague can be successfully treated with antibiotics

Pneumonic plague ( most deadly infectious diseases)-patients can die 24 hours after infection

The mortality rate depends on how soon treatment is started, but is always very high.

Prevention & Control 57

 Isolate infected animals  Limit number of people in contact  Personal protection Surgical mask, gloves, eye protection

 Flea control  Dogs and cats (Use flea control products for the pets)  Spring to fall

 Commercial Premise for rat control

 Prevent roaming or hunting of pets 58  ( Cats & dogs should not be allow to roam freely or hunt- outdoor cats are at risk)

 Rodent control  Eliminate rodent habitat around home [Brush, food sources, firewood, junk]

 Undertaken only after insecticide use

 Insect repellents for skin & clothes for flea bites [DEET to skin and permethrin on clothes]

 Insecticide use in epizootic areas


Public health education 60

 Prophylactic antibiotics [ tetra or sulfonamides 23wks]  Plague outbreak/flea bites  Handled infected animal  Close contact with plague case

 Vaccine

Live and killed developed/No longer available in the U.S.

Prevention and Awareness 61

Report suspected animal cases  State health department  State veterinarian

Education of clients and public  Risks, transmission, prevention

Take precautions in enzootic and epizootic areas


Bioterrorist Event • Yersinia pestis has been classified as a "category A" agent for bioterrorism • easily disseminated by aerosol, can be transmitted from person to person (pneumonic plague) • capacity to cause severe illness and death • An intentional release (bioterrorist event) should be suspected if unusual clusters of pneumonia are seen in otherwise healthy individuals or in people in buildings with common ventilation systems • In the setting of a biological attack, antibiotic prophylaxis may be recommended for those with a suspected or known exposure to Y. pestis, as determined by public health officials


• Rabies • Plague





Dr.Nan Nitra Than


Dr.Nan Nitra Than