Leptospirosis

&
Rabies
Leptospirosis
Synonyms
 Over View
• Most common, underdiagnosed zoonosis
• India - cases are reported from Kerala, Tamil Nadu,
AP, Karnataka, Maharashtra, Gujarat & Andamans.
• Source - Animals (rodents and domestic animals)
Epidemiological factors
• Contaminated environment, Rainfall
• High risk groups, endemic in all states of India
• First description by Weil in 1886
 Over View continued
• Rural > Urban
• Male > Female (10 : 1)
• Clinical Features –mild to severe life threatening
• Mimics many common febrile illnesses
• Diagnosis - difficult to confirm
• Treatment – effective, if started early (<5 days)
• Not to be confused with rat bite fever (SM)
The Causative Bacterium
Leptospira under the Microscope

Dark Field Microscopy FL

Long, Thin, Highly Coiled

 Epidemiology
• Rainfall; Contaminated environment
• Poor Sanitation; Inadequate drainage facilities
• Presence of rodents, cattle & stray dogs
• Walking/ working bare foot poses high risk
• Difficult to pinpoint the source of infection
• Any person can get infected, if exposed to
contaminated and environment
 Risk Groups
Occupational exposure
•Farmers – Rice, Sugarcane, Vegetables, Cattle, Pigs
•Sewerage workers; Abattoirs, Butchers
•Vetenarians, Lab staff, Miners, Soldiers
•Fishermen – Inland (not on the sea)
Recreational activities
•Swimming, Sailing, Marathon runners, Gardening
 Reservoirs of Infection
• Rodents
– (Rattus rattus, Rattus norvegicus, Mus
musculus)
• Dogs
• Wild animals
• Domesticated animals
• Caged game animals
• Leptospira are excreted in the urine
 Modes of Transmission
1. Direct contact with urine or tissue of infected animal
Through skin abrasions, intact mucus membrane
2. Indirect contact
Broken skin with infected soil, water or vegetation
Ingestion of contaminated food & water
3. Droplet infection
Inhalation of droplets of infected urine
Transmission
Natural History
 Pathogenesis of Severe Disease

Damage to small
Vasculitis
blood vessels
Leptospira

Massive migration of fluid from Direct cytotoxic injury

Intravascular to interstitial compartment Immunological injury

Renal dysfunction, vascular

Injury to internal organs
Clinical Illnesses
Clinical Presentation
Anicteric Presentation
Icteric Leptospirosis
 Icteric Leptospirosis
KIDNEYS – Mild to Severe
Urinalysis : Hematuria / Pyuria / Proteinuria
Renal Failure: Pre renal azotemia, ATN / AIN
Oliguric / Non Oliguric
Mechanism
Nephrotoxicity – Endotoxin, (Direct )
Bacterial migration, Toxic Metabolites
Hypoperfusion – Hypotension, Fluid loss/ Fluid shift
G.I. Bleed, Myocarditis
 Hemorrhagic Manifestations
Hemorrhagic Fever - Vascular injury
•Respiratory, Alimentary, Renal & Genital tracts
•More common in Icteric & with Renal Failure
•Reported in Korea, Andaman’s & Brazil
Hemorrhagic Pneumonitis
•Hemoptysis / Respiratory failure
•CXR : Single/ Multiple ill defined opacities
•Occurs in 2nd week (as early as 24-48 hours)
•Reported in Korea, Andaman’s & Nicaragua
Atypical Pneumonia
 Cardiac Form
Cardiac manifestations
•Hemorrhagic Myocarditis
•Cardiomyopathy / Cardiac failure
•Arrhythmias, Hypotension / Death
•Atrial fibrillation / Conduction defects
ECG changes
•Non Specific ST-T changes
•Low voltage complexes
Reported in Srilanka, Barbados & Portugal
 Other Manifestations
Aseptic Meningo-encephalitis
•It is rare; It occurs in the Immune phase
•CSF –­proteins , ­lymphocytes 
•Convulsions, Encephalitis, Myelitis & Polyneuropathy
Ocular manifestations
•Late complication; Conjunctival suffusion/hemorrhage
•Anterior uveitis, Iritis, Iridocyclitis, chorioretinitis
•Occurs in 2 weeks to 1 yr. (average 6 months)
Differential Diagnosis
 Laboratory Tests
• TC / DC / ESR / Hb / Platelet count
• Serum Bilirubin / SGOT/ SGPT
• Blood Urea, Creatinine & Electrolytes
• Chest X-Ray; ECG
• Tests for diagnosis of Leptospirosis
– Culture for Leptospira: Positive
– MAT; Sero conversion or 4 fold rise/ high titer
– ELISA / MSAT : positive
• MAT: Microscopic agglutination test
• (M)SAT: Microscopic slide agglutination Test
 Problems in Diagnosis

Dip-S-Ticks (PanBio, Inc; Baltimore, Maryland)

Interpretation of Tests
Interpretation of Tests
Time Relationship of Tests

MAT

ELISA or SAT
WHO Guide - Faine’s Criteria
Approach to Diagnosis
 Treatment

Oral Treatment 7 to 10 day IV Treatment 5 to 7 days

Special Measures
Prognosis and Mortality
Prevention
Rabies
 By definition
• Rabies is an acute viral disease of the central nervous
system
• affects humans and other mammals but is most
common in carnivores (flesh-eaters).
• It is sometimes referred to as a zoonosis, or disease of
animals that can be communicated to humans. Rabies
is almost exclusively transmitted through saliva from
the bite of an infected animal.
• If rabies is not prevented by immunization, it is almost
always fatal.
 The Rabies Virus
• Lyssavirus of the Rhabdoviridae family
• Bullet-shaped, RNA virus
• Infects only mammals
• Various strains of rabies virus exist
 Rabies virus structure

Matrix protein
Envelope
Glycoprotein

Nucleocapsid protein

Source: http://www.cdc.gov
 Rabies Epidemiology — World
• >55,000 deaths worldwide
– Mainly Africa and Asia
• 60–70% of human cases are children 5–
15 years of age
• ~98% of human cases caused by dog
bites
 Rabies Transmission
• Saliva from bite of infected animal
• Scratch
– Theoretical risk
• Saliva or neural tissue contact with
mucous membrane (mouth, nose)
• Saliva or neural tissue introduced into
fresh, open wound*

* Fresh, open wound is defined as wound that has bled in past 24 hours
 Rabies Pathogenesis
• Virus introduced through bite wound, open
skin wound, or mucous membrane
• Travels along nerves from site of bite to
brain
• Virus multiplies in brain leading to
inflammation
• Virus moves from brain to salivary glands
and saliva where virus is shed
 Rabies Pathogenesis
• Virus introduced through bite wound, open
skin wound, or mucous membrane
• Travels along nerves from site of bite to
brain
• Virus multiplies in brain leading to
inflammation
• Virus moves from brain to salivary glands
and saliva where virus is shed
 PATOGENESA
• Setelah memperbanyak diri dalam neuron-
neuron sentral, virus kemudian kearah
perifer dalam serabut saraf eferen dan
pada saraf volunter maupun saraf otonom.
Dengan demikian virus menyerang hampir
tiap organ dan jaringan didalam tubuh,
dan berkembang biak dalam jaringan-
jaringannya, seperti kelenjar ludah, ginjal,
dan sebagainya.
 Rabies Incubation Period
• Time between bite and appearance of
symptoms
• Weeks to months
• No risk of rabies transmission from
infected animal during incubation period
• Used to establish confinement periods for
animals exposed to potentially rabid
animals
 Clinical manifestations
Non-classical / Atypical Classic
• Very rare • Consisted of 5 clinical
• Mostly by bat-bite phases:
• Neuropathic pain, sensory • Incubation
& motoric disturbance, • Prodromal
koreiform movement (in
the bitten limb), cranial • Acute neurological
nerve disturbance, • Koma
myoclonus and seizure
• death
 Clinical manifestations
Incubation 2 weeks – 6 months (average 2 – 3 months)
Depend on viral load and bite location – the closer to the nerve
system, the shorter incubation period
Prodromal 2 – 10 days
Neuropathy, itchy on bite-site.
Fatigue, naussea, vomits, cephalgia, loss of appetite, fever
Acute 2 – 7 days.
neurological Two forms: furious (80%) and paralytic (20%)
In furious form there is hyperexitability episode: confusion,
hyperesthesia, halusination, agitated, agresif (infection in the
neuron of limbic area)
Hydrophobia – characteristic of Rabies.
In oaralytic form: paresis in four extremities and disturbance of anal
sphingter. Hydrophobia, larynx spasm
Koma After the acute neurological phase
Death After 2 weeks of koma
Clinical forms of rabies
• encephalitic = furious
– ~ 80%

• paralytic = dumb
– ~ 20%
 Rabies Diagnosis
• Animal diagnosis
– Post-mortem testing
– Direct Fluorescent Antibody (DFA) test
• Antigen of virus in brain tissue
• Human diagnosis
– Several tests required for ante-mortem
diagnosis
– Saliva, serum, cerebrospinal fluid, hair follicle
from nape of neck
 Clinical case definition:
a person presenting with an acute neurological
syndrome (encephalitis) dominated by forms of
hyperactivity (furious rabies) or paralytic syndromes
(dumb rabies) progressing towards coma and death,
usually by respiratory failure, within 7-10 days after
the first symptom if no intensive care is instituted.
 Laboratory criteria
one or more of the following:
• Detection of rabies viral antigens by direct fluorescent antibody
test (FAT) or by ELISA in clinical specimens, preferably brain tissue
(collected post mortem).
• Detection by FAT on skin biopsy (ante mortem).
• FAT positive after inoculation of brain tissue, saliva or CSF in cell
culture, or after intracerebral inoculation in mice or in suckling
mice.
• Detectable rabies-neutralizing antibody titre in the serum or the
CSF of an unvaccinated person.
• Detection of viral nucleic acids by PCR on tissue collected post
mortem or intra vitam in a clinical specimen (brain tissue or skin,
cornea, urine or saliva).
 CASE CLASSIFICATION (HUMANS)
Human rabies
•Suspected: A case that is compatible with the clinical
case definition.
Excerpt from “WHO recommended standards and
strategies for surveillance, prevention and control of
communicable diseases"
•Probable: A suspected case plus history of contact with a
suspected rabid animal.
•Confirmed: A suspected case that is laboratory-
confirmed.
Human exposure to rabies
•Possible exposure: A person who had close contact (usually a
bite or scratch) with a rabies-susceptible animal in (or originating
from) a rabies-infected area.
•Probable exposure: A person who had close contact (usually a
bite or scratch) with an animal displaying clinical signs consistent
with rabies at time of the exposure, or within 10 days following
exposure in a rabies-infected area.
•Exposed: A person who has had close contact (usually a bite or
scratch) with a laboratory-confirmed rabid animal.
 Rabies Treatment and Prevention in
Humans
• No effective treatment once clinical signs appear
• Rabies post-exposure prophylaxis (PEP) given
before onset of symptoms is nearly 100%
effective
• Rabies PEP
– Wound cleansing
– Rabies Immunoglobulin (RIG)
– Rabies Vaccination
– No time limit to give PEP
 Clinical Management
• Perform in isolation room
• All health care personnel should wear
Personnel Protection Equipment (PPE)
• No specific Management, only supportive
Suggestion form The working group for the
management of human rabies
1. Rabies vaccine
2. Immunoglobulin against rabies
3. Monoclonal antibodies
4. Ribavirin and amantadine
5. Interferon – halting virus replication (not yet
shown clinical benefit)
6. Ketamin – halting genome transcription
 Rabies PEP — Wound Cleansing
• Should occur as quickly as possible after
wound received
• Soap and water or povidone-iodine
 Rabies PEP — Rabies
ImmunoGlubulin
• Given only once with first vaccine dose
• If not given with first vaccine dose, can be
given up to 7 days after first vaccine dose
received
• If person has previously received PEP or
pre-exposure prophylaxis, RIG should not
be given
 Rabies PEP — Vaccination
• Previously unvaccinated persons get 4 doses
– Days 0, 3, 7, and 14
– 5th dose dropped from vaccine schedule last year
– Intramuscular injections
• Previously vaccinated persons get 2 doses
– Days 0 and 3
– No RIG given
 Rabies Pre-exposure Prophylaxis
• Recommended for certain high-risk groups
– Veterinarians, wildlife biologists, animal
control personnel
• 3 vaccine doses
– Days 0, 7, and 21 or 28
• Does not eliminate need for medical care
after an exposure
 Rabies Treatment and Prevention in
Animals
• No treatment for animal rabies
• No post-exposure prophylaxis for animals
• Routine vaccination is the only way to
prevent animal rabies
• Vaccination schedule for dogs and cats
– First vaccine at 3 months of age
– Booster vaccine 1 year later
– Vaccinate every 3 years after this
 Populations at increased risk of
exposure to rabies
• Rabies research laboratory workers
• Veterinarians, staff, veterinary students
• Animal control and wildlife workers
• Bat handlers
• Travellers to certain rabies-endemic areas

MMWR 48: (RR-1), 1999

 Assessing the Rabies Risk for Travellers

• Destination
• Duration of travel
• Anticipated activities

 Access to medical care and

appropriate PEP biologics
 Rabies prevention - Summary
• Rabies is a preventable disease.
• Failure to recognize a risk of infection results in
human deaths.
• Increased awareness of sources and routes of
virus transmission could save lives.
• Pre-exposure vaccination should be used widely.
• Post-exposure treatment is urgent.
• For previously vaccinated people post -exposure
treatment is simpler, cheaper and more effective.

Modified from MJ Warrell, University of Oxford