This presentation contains a compression data on the Zoonosis, its types and classification. Along with it aslo contains data on bacterial and viral diseases that are zoonotic. There are terminologies related to epidemiology.

1. Zoonosis and its
classification
Dr. Sidra Saher
Dept: Epidemiology and Public Health

2. Zoonosis
 Zoonosis (singular) / Zoonoses (plural)
Zoon = animals
Noses = diseases
 Infections or agents that are naturally transmitted
Animals Humans
 Diseases and infections which are naturally transmitted between vertebrate
animals and humans

3. Classification of zoonosis
 Etiological agents
 Transmission cycle
 Reservoir hosts

4. Classification based on Etiological
agents.
 Bacterial
Ex. Brucellosis, leptospirosis, listeriosis, TB
 Viral
Ex. Rabies, Dengue
 Rickettsial
Ex. Rocky mountain spotted fever
 Mycotic / Fungal
Ex. Dermatophytosis

5.  Parasitic
Protozoan
Ex. Toxoplasmosis, Babesiosis, African Trypanosomiasis
Trematode / Fluke
Ex. Fascioliasis
Cestodes / Tapeworms
Ex. Cysticercosis, Hydatidosis
Nematodes / Roundworms
Ex. Trichinellosis

6. Classification based on Transmission
Cycle
 Direct zoonoses (Orthozoonoses).
Zoonotic diseases are perpetuated in nature by a single
vertebrate species
Transmission is either by direct or indirect contact
Ex. Anthrax, Rabies, Tuberculosis, Brucellosis

7.  Cyclozoonoses.
Zoonotic diseases require two or more vertebrate hosts to complete
transmission cycle of an infectious agent
Subdivided into 2 subtypes
Obligatory cyclozoonoses (Euzoonoses) - human is must for completion
of Life Cycle Ex. .Taenia solium, Taenia saginata
Non-Obligatory cyclozoonoses - human is accidentally invovled in
completion of Life cycle Ex. Hydatid disease, Toxoplasmosis

8.  Metazoonoses (Pherozoonoses).
Both vertebrate and invertebrate species are involved in the transmission
of an infectious agent.
In invertebrate hosts, infectious agent may multiply, develop or remain
dormant.
Ex. Yellow fever, plague.

9.  Saprozoonoses.
Zoonotic diseases require a non-animate substance for completion of life
cycle in addition to vertebrate or invertebrate host.
An infectious agent may multiply, develop or propogate in an inanimate
site.
Ex. Fungal infections

10. Classification based on Reservoir hosts
 Anthrapozoonoses
These are diseases of domestic and wild animals which occur in nature
independent of man. Human beings get infected from animals in
unusual circumstances, through occupational contact or food .
Ex. Leptospirosis, Rift valley fever, rabies.

11.  Zooanthroponoses
These are diseases which normally pass from human to other vertebrate
animals. Ex. Tuberculosis (Human type).
 Amphixenoses
The agent can pass from man to animal and animal to man. Ex.
Streptococcosis, non-host specific Salmonellosis, Staphylococcosis

12. Thanks

13. Zoonoses terminologies

14.  Infection
Entry and development or multiplication of an infectious agent in the
body of the host. Ex. bacterial, viral, parasitic, fungal infections.
 Infestation
Lodgement and development of arthropodes or endoparasites on or in
the body. Ex. Ticks, mites, lice.

15.  Carrier
Infected person or animal which harbours a specific infectious agent in
absence of clinical symptoms and serves as potential source of infection for
others.
 Asymptomatic carrier are those who become infected but show no signs
and symptoms. Ex. TB, HIV
 Incubatory carrier are those who can transmit the agent during the
incubation period before the clinical illness begins. Ex. Common cold virus,
Measles
 Convalescent carrier are those who have recovered from illness but
remain capable of transmitting to others. Ex. Typhoid, diarrhoea patients

16.  Disease
A condition of a body, organ or part in which its functions are impaired or
affected.
 Iatrogenic (physician induced ) disease
Any untoward consequence of a preventive, diagnostic or therapeutic
procedures that cause impairment or disability resulting from professional
activity of a physician or health related personnel.

17.  Communicable disease
A disease resulting from infection or infestation capable of being directly
or indirectly transmitted to a new host or from the environment through any
vehicle.
 Contagious disease
A disease that is transmitted by direct contact between an infected host
and a susceptible host. Ex. Fungal infections
 Nosocomial infection
An infection acquired or contracted in a hospital or other health care
facility.

18.  Notifiable disease
Occurrence of a disease that requires immediate reporting to the higher
health authority to take necessary action for preventing further spread.
 Host
Animal or man which affords lodgment or penetration of an infectious
agent under natural conditions.
 Definite/Definitive host
Animal or man in which infectious agent attains its maturity.

19.  Intermediate host
Host which provides a medium for larval or asexual or sexual phase of life
cycle of an infectious agent.
 Non-obligatory host
Animal or man which may accidentally or occasionally provide
nourishment to an infectious agent.
 Obligate host
Host which is essentially required for growth and multiplication of
infectious agent, in absence of which it may die.

20.  Epidemiology
Study of distribution and determinants of disease occurrence in the
population.
 Epizootic
Epidemic in animal population.
 Epornithic
Epidemic in bird population.
 Eradication
Total removal or elimination of a disease or a etiological agent from a
region.

21.  Exzootic
A disease that has been eliminated or stamped out from a country.
 Antigenic shift
 A sudden, major change in the antigenic structure of a virus, usually the result of genetic
mutation.
 Phenotypic expression is altered
 Results in pandemic
 Ex. Influenza A virus
 Antigenic drift
 A gradual relatively minor change in the antigenicity of a strain periodically
 Phenotypic expression is unaltered
 Results in epidemics
 Ex. Influenza B, C virus

22.  Endemic
The constant presence of a disease or an infectious agent within a
geographical area without importation from outside.
 Sporadic
Incidence at intervals of single or scattered cases of a disease.
 Epidemic
Occurrence of a disease in a community clearly in excess of normal
expectation for that population based on past experience.

23.  Pandemic
Diseases spread over wide geographical areas involving several species,
countries, and continents.
 Prevalence
Total number of cases both old and new at a given time in a population.
 Incidence
Frequency of occurrence of new cases of a particular disease in a
population.

24.  Source
Any living or non-living object from which an infectious agent passes to a
susceptible host.
 Reservoir
An animate or inanimate object on or in which an infectious agent usually
lives, multiplies and survives in such a manner that it can be transmitted to a
susceptible host.
 Vector
An invertebrate host or arthropod transmits the infection by biting or by
depositing infective material on the skin or on food or other objects.

25.  Vehicle
A non-living substance through which an infectious agent passes from the
source to the susceptible host.
 Prevention
Measures to protect man or animal from disease.
 Control
Measures to reduce incidence or prevalence of disease or infection in
man or animal.

26.  Quarantine
Restraint placed upon the movement of man, animals, plants or goods
which are suspected of being carrier or vehicles of infection or of having been
exposed to infection.
 Surveillance
Exercise of continuous scrutiny or watchfulness over the distribution and
spread of infections and related factors for effective control.

27. Transmission of zoonoses
 Transmission cycles
 Sylvatic cycle
 propagates among wild animals, hunters and forest rangers or domestic
animals e.g. Monkey pox
 Synanthropic cycle.
 The pathogens occur and propagate in domestic animals via synanthropic
animals like rodents, birds and lizards
 Man is often exposed to zoonotic diseases propagating in the synanthropic
cycle. e.g. Plague
 Human cycle.
 man to man cycle and can also pass from man to animals e.g. Human
tuberculosis

28. Modes of transmission
 Direct
 Direct contact. - direct contact between the source of infection and the
susceptible host. e.g. Leptospirosis, Pox, Dermatophytosis. Droplet infection:
sneezing, coughing or talking. e.g. Tuberculosis, common cold.
 Contact with soil. e.g. Hookworm infection, tetanus.
 Bite of an animal. e.g. Rabies.
 Transplacental / vertical transmission from mother to offspring. e.g.
Toxoplasmosis, Salmonella

29.  Indirect
 Vector-borne transmission.
 Mechanical transmission. - infectious agent is mechanically transmitted -
no development or multiplication of an infectious agent on or within the
vector. e.g. Amoebiasis, Cholera.
 Biological transmission. - infectious agent undergoes growth and
multiplication in vector

30.  Biological transmission
 Propagative type
The agent merely multiplies in the vector, but does grow. e.g. Plague
bacilli in rat fleas.
 Cyclo-propagative type. The agent undergoes both growth and
multiplication in the vector. e.g. Malaria parasites in mosquitoes.
 Cyclo-developmental type. The agent undergoes only development but
no multiplication. e.g. Microfilaria in mosquitoes.
 Transovarian type. The agent is transmitted from one generation to other.
e.g. Tick borne encephalitis

31.  Vehicle-borne transmission.
Transmission of an infectious agent through either water, food, blood,
serum and other biological products such as tissues and organs. -
Transmitted mechanically or biologically e.g.
Water - Hepatitis A virus,
Meat - Salmonellosis , Trichinella spiralis,
Milk - Tuberculosis, brucellosis,
Fish - Vibrio parahaemolyticus,
Blood - Hepatitis B virus,
Organ - Cytomegalo virus in kidney transplants

32.  Air borne transmission
 Droplet nuclei. - minute particles formed either by evaporation of cough or
in laboratory, slaughterhouse or autopsy room. - remain air borne for long
period of time and may be disseminated by air currents to different places.
e.g. Tuberculosis, Q-fever.
 Dust. - larger droplets which are expelled during talking, coughing or
sneezing - settle down along with dust and cause air-borne transmission.
e.g. Streptococcal infection, fungal spores.

33.  Fomite-borne infections.
Fomites include soil, clothes, towels, cups, glasses, spoons, door handles,
etc. e.g. typhoid fever, skin infections.
 Unclean hands and fingers.
Most common mode of transmission e.g. Staphylococcosis and
streptococcosis, Salmonellosis, Colibacillosis.

34. Bacterial Zoonoses
D r
.Muhammad Rizwan
Assistant Professor
Department of Clinical Sciences

35. Campylobacterioses
 Etiology:
 Campylobacter spp.C.jejuni,C. coli,C. lari,C. upsaliensis,
and C.hyointestinalis
 Occurrence:
 Worldwide and are in many European countries.
 The natural habitat of the zoonotic species is the
gastrointestinal tract of various animals.
 minimal infective dose is approximately 500 bacteria
 Transmission:
 Ingestion of contaminated food
 contaminated drinking or surface water
 contact with animal excreta
 directly from human to human

36.  Clinical Manifestation: In human
 acute enteritis, diarrhea, fever up to 40 °C,chills,
headache,muscle aches,nausea
 In animals cause diarrhea,Mastitis,hepatitis ,infertility
and abortion.
 Diagnosis:
 by culture from stool,milk,blood or material from
abortion.
 PCR methods
 Results of serological tests have not been satisfactory as
there are over 50 different serovars of C. jejuni.
 Differential Diagnosis:
 Salmonella,Shigella,Y
ersinia and Clostridium

37.  Therapy:
 Replacement of fluid and electrolytes is of prime
importance
 Antibiotics e.g ciprofloxacin,gentamicin
 Prophylaxis:
 Food hygiene,cook the food
 Avoidance of unpasteurized milk
 proper hygiene of drinking water
 immediate handwashing with soap and disinfection after
contact with humans or animals

38. Glanders
 Etiology:
 Malleus (glanders,farcy) is caused by Burkholderia mallei,
characterized by pustular skin lesion,multiple abscesses,necroses in
respiratory tract,pneumonia,and sepsis.
 Gram negative rod
 Occurrence:
 Horses,donkeys,and mules are the animals most susceptible to B.
mallei
 the disease is still seen in Mongolia,China, India,Pakistan,Indonesia,
the Philippine Iraq,Iran etc.
 Risk groups are veterinarian,horse dealers,riders,farmers,knackers
 Potential pathogen for biological warfare-special BSL level
 Public health programs have eliminated glanders in many countries

39.  Transmission:
 contact with infected animals,nasal secretion,pus,
 Can penetrate mucus membrane or minute skin lesions
 Indirectly through fomites,such as food,litter etc.
 Airborne transmission
 human-to-human transmission is rare
 Clinical Manifestations
 Incubation period 1-5 days but may become chronic
 high fever
,chills, regional lymphadenitis pustules and
nodules on skin,nose,lung,and other organs
 Diagnosis:
 Culture by pustules,pus,sputum and nasal discharge
 PCR
 CF test and ELISA

41.  Differential Diagnosis:
 Melioidosis,Tuberculosis, Anthrax,Erysipelas,Smallpox,and
Syphilis
 Therapy:
 Replacement of fluid and electrolytes is of prime importance
 Antibiotics e.g doxycycline or trimethoprim sulfamethoxazole
 Treatment of diseased or possibly infected animals is prohibited
in many countries
 Prophylaxis:
 No vaccines or antisera
 Fomites have to be destroyed or thoroughly cleaned and
disinfected.
 ban on import animals from endemic areas
 No contact with infected animals .

42. Leptospiroses
 Leptospiroses are actute systemic infections of human and animals
caused by various serovars of Leptospira interrogans.
 Etiology:
 Leptospirae bacteria e.g L.canicola ,L.hardjo,L.ictero- haemorrhagiae ,L..Pomona
 Leptospiraes are motile,gram-negative spiral-shaped bacteria with terminal hooks.
 Occurrence:
 wide spectrum of hosts of including humans and >180 animals specises
 Worldwide occurrence
 peak cases in summer and fall
 At risk are agricultural workers,vets,breeders,abbatoir workers,butchers,cooks,
dogs owners,sewage workers.
 Transmission:
 Portal of entry in humans is usually skin lesions from professional exposure,
mucus membranes
 Infected animals excrete e.g urine,amniotic fluid,and materials from abortion
 contaminated (e.g.,canal) water
 Infection via contaminated foodstuffs is rare

43. ⚫ C linical Manifestations:in human
 fever ,chill anemia,bloody urine, hemorrhages, vomiting,
convulsions,nephritis,and hepatitis with jaundice
nonproductive cough
 In animals causes agalactia,stillbirths,abortion,neonatal
weakness ,infertility,equine uveitis and same clinical signs as in
human
 Incubation period 5-14 days (range 2-26 days)
 Diagnosis:
 History
 Culture by sample
 Microagglutination test
 ELISA,PCR
⚫ Differential Diagnosis:
 influenza,rheumatic fever
,streptococcal tonsillitis,and,
,malaria,dengue

44.  Therapy:
 Antibiotics e.g ceftriaxone,doxycycline
 renal failure,dialysis is done
 Diseased animals are treated with tetracycline or
streptomycin.
 Prophylaxis:
 rat and mouse control
 Vaccination in animals
 Barefoot walking and swimming in stagnant waters
should be avoided in endemic areas
 personal protection measurements

45. Listeriosis
 Listeriosis is a disease of animals and humans ,usually
food borne in humans
 Etiology:
 Listeria monocytogenes
 Occurrence:
 Listeriosis occurs worldwide in humans and animals.
 Peak incidence in human shown in summer and fall than in winter
 in animals,there is a peak between February andApril.
 Transmission:
 consumption of contaminated foodstuffs
 Inhalation
 Contact with infected animals and silage
 conjunctivae ofcontacts

46.  Clinical Manifestations:
 Incubation period may ranges from 1-4 weeks
 In human abortion,fever
,encephalitis,Papulous and
pustulous skin lesion Liver abscesses,arthritis and
swelling of the regional lymph nodes
 In animals causes Cerebral listeriosis,premature delivery,
abortion,mastitis,gastroenteritis,and ocular infection
 Diagnosis:
 History
 Culture by blood,CSF
, feces or placenta etc.
 PCR
 Differential Diagnosis:
 Enteroviruses,staphylococci,Candida,and
cercariae,Haemophilus influenzae

47.  Therapy:
 antibioticsAmpicillin plus gentamicin
 Replacement of fluid and electrolytes is of prime
importance
 Prophylaxis:
 General hygienic measures
 washing of raw vegetables
 Avoidance from infected silage
 Pregnant women and immunocompromised individuals
should avoid contact with infected material,raw food
and vegetables,undercooked meat,cheeses

48. plague
 One of the oldest and most dangerous zoonoses, most
virulent, potentially lethal.Three clinical forms,: bubonic,
septicemic,and pneumonic plague
 Etiology:
 Y
ersinia pestis belong to Enterobacteriaceae.
 Occurrence:
 main reservoirs are rats,ground and rock squirrels
 Present inAsia,Africa and U.S
 Europe andAustralia are free ofplague at present.
 Transmission:
 the bite of the rat flea
 Human-to-human transmission
 Through skin wound or inhalation

49.  Clinical Manifestations:
 lymphadenopathy (bubo), hepatosplenomegaly,renal
failure,disseminated intravascular coagulation,cough,and
bloody or purulent pustules,carbuncles on skin
 Diagnosis:
 History
 Culture
 IF
,CF
 PCR
⚫ Differential Diagnosis:
 malaria,typhus,toxoplasmosis,brucellosis,cat scratch
disease,typhoid, lymph node tuberculosis

50.  Therapy:
 The antibiotics of choice are streptomycin (2×1
g/day i.m.) or gentamicin 5 mg/
kg/
day in 3 doses
i.m.or i.v
.
 Prophylaxis:
 Rat and insect control is important in urban areas
 dog and cats population control
 Official surveillance should be done
 no vaccation

51. Mycobacterium
 Etiology:
 MycobacteriumT
uberculosis,Mycobacterium Bovis
 Occurrence:
 Worldwide in people and in wild and domesticated mammals
 Transmission:
 Aerogenic route
 Oral route
 Direct injury to the skin and mucous membranes.
 Clinical Manifestations
 High and sustained fever
,Night sweats,Dry cough,Malaise,
Spleenomagally,

52.  Bone and J
ointT
uberculosis,CutaneousTB,andTB of
another organs of body in human and animal.
 Diagnosis:
 Culture by sample
 T
uberculin test
 Serological Methods
 History
 PCR
 Radio graph,

53.  Therapy:
 The combination of 4 drugs
 Rifampin,Ethambutol.Pyrazinamide,Isoniazid
 Prophylaxis:
 M.Bovis BCG Vaccination
 No contact with infected person or animal
 Use mask

54. Enterohemorrhagic
Escherichia coli (EHEC) Infections
 Etiology:
 Escherichia coli strains
 Occurrence:
 present inAmericas,Europe,Asia,andAfrica,with a
peak incidence between J
une and September.
 cattle,sheep,and goats are carriers and excrete these
strains
 Transmission:
 fecal-oral route.
 direct contact with infected animals

55.  Clinical Manifestations:
⚫ severe abdominal pain accompanied by initially non
bloody watery diarrhea,nausea and vomiting.
⚫ Fever is rare.
 Diagnosis:
 History
 Culture
 enzyme immunoassay(EIA)
 PCR
 Differential Diagnosis:
 Entamoeba histolytica,intussusception,ulcerative colitis,
and ileus,

56.  Therapy.
 Fluid and electrolyte replacement
 Antimicrobial treatment
 Prophylaxis:
 general hygienic measures
 handwashing with water and soap before meals and after
contact with animals
 Raw vegetables must be peeled or thoroughly washed.
 Use cooked food and clean water

57. thanks

58. Viral Zoonoses
Dr. Muhammad Rizwan
Assistant Professor
Department of Clinical Sciences,
BZU Multan

59. VIRAL ZOONOSES
PART I
ARTHROPOD BORNE
2

60. VIRAL ZOONOSES
 ZOONOTIC VIRUSES
 TRANSMISSIBLE FROM ANIMALS
 ARTHROPODS
 often via a blood sucking arthropod
 VERTEBRATES
 bites, body fluids, inhalation etc

61. transmission
 arthropod vectors (blood sucking)
 Many arboviral diseases world wide
(hundreds)
4

62. ARBOVIRUSES
5
FAMILY ENVELOPE
yes
yes
no
SYMMETRY
icosahedral
helical
icosahedral
GENOME
ssRNA (+ve)
ssRNA (-ve)
segmented
dsRNA,
segmented

63. 6
PREVENTION
 SURVEILLANCE
 VECTOR CONTROL
 REPELLENTS
 CLOTHING
 TIMING OF ACTIVITY (OR
CANCELLATION)
 VACCINE

64. 7
ARBOVIRAL DISEASE
 MANY DIFFERENT ARBOVIRUSES
CAUSE DISEASE
 OFTEN SUB-CLINICAL

65. 8
ARBOVIRAL DISEASE
 INITIAL VIRAL REPLICATION
 endothelial cells
 macrophages/monocyte lineage
 INTERFERON (RNA VIRUSES)
 headache, fever, myalgia
 VIREMIA
 spread to target tissues, depending on
tropism of virus

66. 9
RECOVERY
 INTERFERON
 CELL-MEDIATED IMMUNITY
 ANTIBODY MAY PLAY A ROLE IN
PREVENTING SPREAD DURING
VIREMIC PHASE

67. 10
DIAGNOSIS
 Immunological techniques
 RT-PCR for viral RNA

68. 11
ARBOVIRUSES – ENCEPHALITIS
FAMILY DISTRIBUTION
FLAVIVIRIDAE
West Nile virus encephalitis North America, parts of Europe, parts of Africa
St Louis encephalitis North America
TOGAVIRIDAE
Eastern equine encephalitis East US, Canada
Western equine encephalitis West US, Canada, Mexico, Brazil
BUNYAVIRIDAE
California serogroup (La Crosse etc) North America
JAPANESE ENCEPHALITIS

69. West Nile and
Eastern Equine Encephalitis
 Carriers – horses, birds and other animals
 Transmission – mosquito bite
 Vector- mosquito
 Reservoir: birds
 human, horse
 dead end hosts
 Symptoms (horses) – neurologic problems
 Symptoms (people)
 90% do not become ill
 Illness in the geriatric and immunocompromised
 Fever, signs of meningitis (neck pain, headache, neurologic
problems)
 Treatment - supportive
 Prognosis – fatal in a small number of people
 Prevention – mosquito control, vaccinate horses

70. 13
WEST NILE VIRUS
http://www.cdc.gov/ncidod/dvbid/westnile/cycle.htm
flavivirus
More rarely:
Acute flaccid paralysis
West Nile polio-like
paralysis
poliomyelitis -
inflammation spinal
cord

71. 14
50
1999
52
20
2003
1999 200
2003
50
1999
52
20
2003
1999 200
2003
50
1999
2000
54
2003
1999
2000
20
20
2003
50
1999
2000
54
2003
1999
2000
20
20
2003
51
2000
2000
51
2000
2000
52
2001
2003
2001
3
52
2001
2003
2001
3
50
51
2000
52
53
2002
54
2003
2000 2002
2003
50
51
2000
52
53
2002
54
2003
2000 2002
2003
flavivirus
West Nile virus

72. 15
West Nile Virus
For every ~150 people infected
 ~30 mild symptoms
 mild fever, headache, body ache, maybe rash
 may never see physician, even if do, may not be diagnosed
 ~1 severe illness
 e.g. encephalitis, meningitis, high fever, stiff neck,
stupor, disorientation, coma, tremors, convulsions,
muscle weakness
 frequency of flaccid paralysis unknown, but much less than
frequency of encephalitis
flavivirus

73. 16
Case fatality ratio:
 Seen in all age groups but higher in
the elderly
 the majority of cases of neuroinvasive
diseases and fatalities are over 50 yrs age
 Transplant recipients may be at higher
risk
 increased incidence of clinical disease
 increased risk of severe disease
WEST NILE VIRUS
flavivirus

74. 17
WEST NILE VIRUS
flavivirus
transmission:
 Mosquito (vast majority of cases)
 Blood transfusion (blood supply is now screened)
 Organ donation

75. 18
WEST NILE VIRUS
flavivirus

76. 19
EASTERN EQUINE ENCEPHALITIS
 Reservoir: birds
 Vector: mosquito
 Sentinels
 horse,quail, turkey
 Under 15yrs, over 50yrs
at higher risk
 CFR ~35%
 ~5 cases/year av.
 horses and humans
dead end hosts
CDC
togavirus

77. 20
ARBOVIRUSES – FEVER AND
HEMORRHAGIC FEVER
FAMILY
FLAVIVIRIDAE
Dengue
Yellow fever
REOVIRIDAE
Colorado tick fever
DISTRIBUTION
World wide,
especially tropics
Africa, S. and C. America
North America
MAIN DISEASES
fever, hemorrhagic fever
hemorrhagic fever
fever

78. 21
DENGUE FEVER
 jungle cycle (monkeys-mosquitoes)
 urban cycle (man-mosquitoes)
 rapidly increasing disease in tropics
 approx. 100-200 cases/yr in US due to import
 occasional indigenous transmission
 50-100 million cases per year worldwide
 ~900,000 cases in Central and S. America in 2007
flavivirus

80. 23
Patients being treated for Dengue fever in a hospital
flavivirus

82. 25
DENGUE FEVER
 Fever (overlaps with viremic phase)
 headache
 retro-orbital pain
 myalgia, arthralgia
 severe joint and muscle pain
‘breakbone fever’
 sometimes rash
 may look like flu, measles, rubella
 more rarely encephalitis
flavivirus

83. 26
DENGUE HEMORRHAGIC FEVER/DENGUE SHOCK
SYNDROME
 hemorrhages
 plasma leakage
 hemoconcentration
 hypotension
 circulatory failure
 shock
flavivirus

84. 27
DHF - petechiae
CDC
flavivirus

85. 28
Dengue hemorrhagic fever - pleural effusion
CDC
Vaughn DW et al. J Infect Dis 1997; 176:322-30.

86. 29
DENGUE HEMORRHAGIC
FEVER
 immunopathological
 4 serotypes (1, 2, 3, 4)
 increase in areas in which all 4 circulate has led to more
cases DHF fever
 maternal antibody
flavivirus

87. 30
DENGUE HEMORRHAGIC
FEVER
 do not give aspirin, ibuprofen
 because of anticoagulant affects
 (acetaminophen OK)
 children more severe disease
 CFR depends on rapid response
 can be as low as 1%
flavivirus

88. 31
(Time Dec 2007)

89. 32

90. 33

91. 34
CDC
YELLOW FEVER
 jungle and urban cycles
 hemorrhages
 degeneration liver, kidney,
heart
 CFR 50%
 Vaccine (live attenuated)
 important to consider in travel
to areas with yellow fever
 egg grown
 contraindicated in immune
suppression
flavivirus
last yellow fever epidemic in US - 1905

92. 35
VIRAL ZOONOSES
PART I I
VERTEBRATE VECTORS

93. Definition
 Zooneses are diseases of vertebrate animals that can be
transmitted to man: either directly or indirectly through an insect
vector.
 When an insect vector is involved, the disease is also known as
an arboviral disease.
 However, not all arboviral diseases are zoonosis: where the
transmission cycle takes place exclusively between insect vector
and human 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.

94. Viral Zoonoses
 Rabies
 Monkeypox
 Avian flu
 Hantavirus
 Lymphochoriomeningitis

95. 38
RODENT BORNE
FAMILY ENVELOPE
yes
yes
SYMMETRY
helical
helical
GENOME
ssRNA
ambi-sense
segmented
ssRNA (-ve)
segmented
Hantavirus genus
of Bunyaviridae

96. 39
CDC
 rodent urine
 contaminated materials (aerosols)
 respiratory tract
ROUTE OF INFECTION

97. 40
ARENAVIRUS-ASSOCIATED
HEMORRHAGIC FEVERS
 Lassa fever, Bolivian, Argentine, Venezuelan,
Brazilian hemorrhagic fever
 A few recent cases in California of deaths
thought to be associated with an arenavirus
(Whitewater Arroyo Virus)
 dehydration, hemoconcentration,
hemorrhage, shock, cardiovascular collapse
 CFR 5-35%
CDC

98. Arenaviruses
 Enveloped ssRNA viruses
 virions 80-150nm in diameter
 genome consists of 2 pieces of
ambisense ssRNA.
 7-8 nm spikes protrude from the
envelope.
 host cell ribosomes are usually seen
inside the outer membrane but play
no part in replication.
 Members of arenaviruses include
Lassa fever, Junin and Macupo
viruses.
Lassa fever virus particles budding
from the surface of an infected cell.
(Source: CDC)

99. Lassa Fever
 Found predominantly in West Africa, in
particular Nigeria, Sierra Leone and
Liberia.
 The natural reservoir is multimammate rat
(Mastomys)
 Man may get infected through contact with
infected urine and faeces.
 Man to man transmission can occur
through infected bodily fluids and Lassa
fever had caused well-documented
nosocomial outbreaks.
Mastomys

100. Clinical Manifestations
 Incubation period of 3-5 days.
 Insidious onset of non-specific symptoms such as fever, malaise,
myalgia and a sore throat.
 Typical patchy or ulcerative pharyngeal lesions may be seen.
 Severe cases may develop the following:
 Myocarditis
 Pneumonia
 Encephalopathy
 Haemorrhagic manifestations
 Shock
 The reported mortality rate for hospitalized cases of Lassa fever is 25%.
It carries a higher mortality in pregnant women.

101. Laboratory Diagnosis
Lassa fever virus is a Group 4 Pathogen. Laboratory diagnosis should only
be carried out in specialized centers.
 Detection of Virus Antigen - the presence of viral antigen in sera can be
detected by EIA. The presence of viral antigen precedes that of IgM.
 Serology - IgM is detected by EIA. Using a combination of antigen and
IgM antibody tests, it was shown that virtually all Lassa virus
infections can be diagnosed early.
 Virus Isolation - virus may be cultured from blood, urine and throat
washings. Rarely carried out because of safety concerns.
 RT-PCR - being used experimentally.

102. Management and Prevention
 Good supportive care is essential.
 Ribavirin - had been shown to be effective against Lassa fever with a 2
to 3 fold decrease in mortality in high risk Lassa fever patients. Must
be given early in the illness.
 Hyperimmune serum - the effects of hyperimmune serum is still
uncertain although dramatic results have been reported in anecdotal
case reports.
 Postexposure Prophylaxis - There is no established safe prophylaxis.
Various combinations of hyperimmune immunoglobulin and/or oral
ribavirin may be used.
 There is no vaccine available, prevention of the disease depends on
rodent control.

103. 46
LYMPHOCYTIC CHORIOMENINGITIS
VIRUS
 Arenavirus
 5% wild mice infected, without obvious disease
 can also get from pet rodents such as hamsters
 often sub-clinical
 clinical cases:
 flu like symptoms, plus nausea, vomiting
 may get meningitis, and/or encepalitis and/or myelitis
 usually recover, may be sequelae
 problems for fetus (1st- 2nd trimester)
 has been associated with deaths in transplant recipients

104. LYMPHOCYTIC CHORIOMENINGITIS
VIRUS

105. Lymphochoriomeningitis (LCMV)
 Carriers
 Rodents - including pocket pets such as hamsters.
 Symptoms in people
 Mostly a problem in geriatric and immunocompromised
people.
 The early phase - flu-like symptoms
 The late phase – neurologic problems like rabies and rarely
death

106. 49
HANTAVIRUSES - all have rodent vector
NAME
Korean HFRS
HFRS
Hantavirus
pulmonary
syndrome (HPS)
TYPE OF DISEASE
hemorrhagic fever with
renal syndrome (HFRS)
hemorrhagic fever with
renal syndrome
hantavirus pulmonary
syndrome
OCCURRENCE
S.E.Asia
Europe, Asia
North and South
America
Rodent vector - limited number species per virus
BUNYAVIRIDAE

107. Hantaviruses
 Forms a separate genus in the
Bunyavirus family.
 Unlike under bunyaviridae, its
transmission does not involve an
arthropod vector.
 Enveloped ssRNA virus.
 Virions 98nm in diameter with a
characteristic square grid-like
structure.
 Genome consists of three RNA
segments: L, M, and S.

108. History
 Haemorrhagic Fever with Renal Syndrome (HFRS: later
renamed hantavirus disease) first came to the attention of the
West during the Korean war when over 3000 UN troops were
afflicted.
 It transpired that the disease was not new and had been
described by the Chinese 1000 years earlier.
 In 1974, the causative agent was isolated from the Korean
Stripped field mice and was called Hantaan virus.
 In 1995, a new disease entity called hantavirus pulmonary
syndrome was described in the “four corners” region of the
U.S.

109. Some Subtypes of hantaviruses
associated with human disease
 Hantaan, Porrogia and related viruses - This group is found in China,
Eastern Russia, and some parts of S. Europe. It is responsible for the
severe classical type of hantavirus disease. It is carried by stripped field
mice. (Apodemus agrarius)
 Seoul type - associated with moderate hantavirus disease. It is carried by
rats and have a worldwide distribution. It has been identified in China,
Japan, Western Russia, USA and S.America.
 Puumala type - mainly found in Scandinavian countries, France, UK and
the Western Russia. It is carried by bank voles (Clethrionomys glareolus)
and causes mild hantavirus disease (nephropathia epidemica).
 Sin Nombre - found in many parts of the US, Canada and Mexico. Carried
by the Deer Mouse (Peromyscus maniculatus) and causes hantavirus
pulmonary syndrome.

110. Rodent Carriers of Hantaviruses
Stripped field mouse (Apodemus agrarius)
Bank vole (Clethrionomys glareolus)
Deer Mouse (Peromyscus maniculatus) Rat (Rattus)

111. Clinical Features of Hantavirus Disease
 The multisystem pathology of HVD is characterized by damage to
capillaries and small vessel walls, resulting in vasodilation and
congestion with hemorrhages.
 Classically, hantavirus disease consists of 5 distinct phases. These
phases may be blurred in moderate or mild cases.
 Febrile phase - abrupt onset of a severe flu-like illness with a
erythematous rash after an incubation period of 2-3 days.
 Hypotensive phase - begins at day 5 of illness
 Oliguric phase - begins at day 9 of illness. The patient may develop acute
renal failure and shock. Haemorrhages are usually confined to petechiae.
The majority of deaths occur during the hypotensive and oliguric phases
 Diuretic phase - this occurs between days 12-14 .
 Convalescent phase - this may require up to 4 months.

112. Hantavirus Pulmonary Syndrome (HPS)
 More than 250 cases of HPS have been reported throughout North
and South America with a mortality rate of 50%
 In common with classical HVD, HPS has a similar febrile phase.
 However, the damage to the capillaries occur predominantly in the
lungs rather than the kidney.
 Shock and cardiac complications may lead to death.
 The majority of HPS cases are caused by the Sin Nombre virus.
The other cases are associated with a variety of other hantaviruses
e.g. New York and Black Creek Canal viruses.

113. Diagnosis
 Serological diagnosis - a variety of tests including IF, HAI, SRH, ELISAs
have been developed for the diagnosis of HVD and HPS.
 Direct detection of antigen - this appears to be more sensitive than
serology tests in the early diagnosis of the disease. The virus antigen can
be demonstrated in the blood or urine.
 RT-PCR - found to of great use in diagnosing hantavirus pulmonary
syndrome.
 Virus isolation - isolation of the virus from urine is successful early in
hantavirus disease. Isolation of the virus from the blood is less consistent.
Sin Nombre virus has never been isolated from patients with HPS.
 Immunohistochemistry - useful in diagnosing HPS.

114. Treatment and Prevention
 Treatment of HVD and HPS depends mainly on supportive
measures.
 Ribavirin - reported to be useful if given early in the course of
hantavirus disease. Its efficacy is uncertain in hantavirus
pulmonary syndrome.
 Vaccination - an inactivated vaccine is being tried out in China.
Other candidate vaccines are being prepared.
 Rodent Control - control measures should be aimed at reducing
contact between humans and rodents.

115. 58
HANTAVIRUS-ASSOCIATED
HEMORRHAGIC FEVERS
 Korean hemorrhagic fever with renal
syndrome (CFR ~7%)
 other HFRS viral diseases around the
world
 HPS (CFR ~36%)
CDC
Hantavirus genus

116. 59
VECTOR UNKNOWN
HEMORRHAGIC FEVERS DUE TO EBOLA,
MARBURG VIRUSES

117. 60
VECTOR UNKNOWN
FAMILY ENVELOPE
yes
SYMMETRY
helical
GENOME
ssRNA (-ve)
Filoviruses may be up to ~14,000 nm long (rhabdoviruses
have similar diameter but are only ~180 nm long)

118. 61
EBOLA AND MARBURG VIRUSES
 hemorrhagic fevers
 case fatality rate can be as high as 60-90%
for certain strains
 occur in Africa, natural reservoir and vector
unknown
 infections seen in laboratory monkeys, but these
do not seem to be natural host
 bats may be a natural host
 high viremia - strict barrier nursing

119. Rabies Virus
 member of the Lyassavirus of the Rhabdoviridae.
 ssRNA enveloped virus, characteristic bullet-shaped appearance
with 6-7 nm spike projections.
 virion 130-240nm * 80nm
 -ve stranded RNA codes for 5 proteins; G, M, N, L, S
 Exceedingly wide range of hosts.
 There are 5 other members of Lyassavirus : Mokola, Lagosbat,
Duvenhage, EBL-1, and EBL-2.
 Duvenhage and EBL-2 have been associated with human rabies.

120. Rabies Virus
Structure of rabies virus (Source: CDC)
Rabies virus particles

121. Epidemiology
Rabies is a zoonosis which is prevalent in wildlife. The main
animals involved differs from continent to continent.
Europe fox, bats
Middle East wolf, dog
Asia dog
Africa dog, mongoose, antelope
N America foxes, skunks, raccoons,
insectivorous bats
S America dog, vampire bats

122. Pathogenesis
 The commonest mode of transmission in man is by the bite of a
rabid animal, usually a dog. Rabies is an acute infection of the CNS
which is almost invariably fatal.
 Following inoculation, the virus replicates in the striated or
connective tissue at the site of inoculation and enters the peripheral
nerves through the neuromuscular junction.
 It then spreads to the CNS in the endoneurium of the Schwann cells.
 Terminally, there is widespread CNS involvement but few neurons
infected with the virus show structural abnormalities. The nature of
the profound disorder is still not understood.

123. Laboratory Diagnosis
 Histopathology - Negri bodies are pathognomonic of rabies. However,
Negri bodies are only present in 71% of cases.
 Rapid virus antigen detection - in recent years, virus antigen detection
by IF had become widely used. Corneal impressions or neck skin
biopsy are taken. The Direct Fluorescent Antibody test (DFA) is
commonly used.
 Virus cultivation - The most definitive means of diagnosis is by virus
cultivation from saliva and infected tissue. Cell cultures may be used
or more commonly, the specimen is inoculated intracerebrally into
infant mice. Because of the difficulties involved, this is rarely offered
by diagnostic laboratories.
 Serology - circulating antibodies appear slowly in the course of
infection but they are usually present by the time of onset of clinical
symptoms.

124. Negri Body in neuron cell
(source: CDC)
Positive DFA test (Source: CDC
Diagnosis of Rabies

125. Management and Prevention
 Pre-exposure prophylaxis - Inactivated rabies vaccine may be
administered to persons at increased risk of being exposed to rabies e.g.
vets, animal handlers, laboratory workers etc.
 Post-exposure prophylaxis - In cases of animal bites, dogs and cats in a
rabies endemic area should be held for 10 days for observation. If signs
develop, they should be killed and their tissue.
 Wild animals are not observed but if captured, the animal should be
killed and examined. The essential components of postexposure
prophylaxis are the local treatment of wounds and active and passive
immunization.
 Once rabies is established, there is nothing much that could be done
except intensive supportive care. To date, only 2 persons with proven
rabies have survived.

126. Postexposure Prophylaxis
 Wound treatment - surgical debridement should be carried out.
Experimentally, the incidence of rabies in animals can be reduced by
local treatment alone.
 Passive immunization - human rabies immunoglobulin around the area
of the wound; to be supplemented with an i.m. dose to confer short
term protection.
 Active immunization - the human diploid cell vaccine is the best
preparation available. The vaccine is usually administered into the
deltoid region, and 5 doses are usually given.
 There is convincing evidence that combined treatment with rabies
immunoglobulin and active immunization is much more effective than
active immunization alone. Equine rabies immunoglobulin (ERIG) is
available in many countries and is considerably cheaper than HRIG.

127. Rabies Vaccines
The vaccines which are available for humans are present are inactivated whole
virus vaccines.
 Nervous Tissue Preparation e.g. Semple Vaccine - associated with the rare
complication of demyelinating allergic encephalitis.
 Duck Embryo Vaccine - this vaccine strain is grown in embryonated duck
eggs This vaccine has a lower risk of allergic encephalitis but is considerably
less immunogenic.
 Human Diploid Cell Vaccine (HDCV) - this is currently the best vaccine
available with an efficacy rate of nearly 100% and rarely any severe reactions.
However it is very expensive.
 Other Cell culture Vaccines - because of the expense of HDCV, other cell
culture vaccines are being developed for developing countries. However
recent data suggests that a much reduced dose of HDCV given intradermally
may be just be effective.

128. Control of Rabies
 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. However, there are on-going trials in Europe where bait
containing rabies vaccine is given to foxes. Success had been
reported in Switzerland.