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1J.N. Medical College, Belgaum
06/08/14
J.N. Medical College, Belgaum 2
Mr A is a 38 year old sheep farmer who presented with a 3 day history of generalised muscle aches, anorexia, mild diarrhoea and vomiting. Mr A had a fever of 38 degrees and a normal physical examination.
J.N. Medical College, Belgaum 3
The initial diagnosis was a viral illness with gastroenteritis and he was advised to take paracetamol, rest and return if the symptoms changed or worsened
J.N. Medical College, Belgaum 4
The patient returned within 2 days with a backache and worsening of his generalised muscle pain. He also had hyperaemic conjunctiva and headaches that were the worst he had ever experienced. Further examination did not demonstrate any further clinical signs and he did not have any neck stiffness.
J.N. Medical College, Belgaum 5
Due to rapid ecological changes, many zoonosis have emerged as epidemics
Leptospirosis is a zoonosis spread throughout the world
Surveillance data suggests - most common zoonosis in the world
6J.N. Medical College, Belgaum
The disease is often overlooked and under reported
It is an emerging zoonotic disease of major public health problem
It often peaks seasonally sometimes in outbreaks
7J.N. Medical College, Belgaum
Leptospira -from the Greek leptos, meaning fine or thin, and the Latin spira, meaning coil
1886- Adolf Weil described the disease1907- Stimson named the organism Spirochaeta
interrogans1915- etiologic agent by Inada and Ido1930- it was identified as a separate disease
entity
8J.N. Medical College, Belgaum
It is most widespread disease in the world
Incidence of the disease is significantly higher in tropical countries as compared to temperate regions
Outbreaks mostly occur – heavy rainfalls and consequent flooding
9J.N. Medical College, Belgaum
The number of human cases worldwide is not known precisely know
The WHO estimates- incidence ranges from approx 0.1 - 1 per 1,00,000 per year in temperate climates
10 - 100 per 1,00,000 in the humid tropics.
10J.N. Medical College, Belgaum
11J.N. Medical College, Belgaum
Epidemics of Leptospirosis - Andaman and Nicobar islands, southern and western parts of India
For the past 10 years Mumbai - seasonal increase
A post – cyclone outbreak was reported in Orissa, India in 1999.
12J.N. Medical College, Belgaum
Outbreaks of leptospirosis have increasingly been reported from Kerala, Gujarat, Tamil Nadu and Karnataka
Sporadic cases have been reported from Goa, Andhra Pradesh and Assam
13J.N. Medical College, Belgaum
Kerala, Gujarat, Andaman & Nicobar, KarnatakaKerala, Gujarat, Andaman & Nicobar, Karnataka200420041111
Tamil NaduTamil Nadu1984198411
Andaman & NicobarAndaman & Nicobar1988198822
Kerala, Gujarat, Tamil Nadu, A & NKerala, Gujarat, Tamil Nadu, A & N200320031010
Kerala, Maharashtra, Gujarat, Tamil NaduKerala, Maharashtra, Gujarat, Tamil Nadu2002200299
Maharashtra, Gujarat, Tamil Nadu, Kerala & GoaMaharashtra, Gujarat, Tamil Nadu, Kerala & Goa2001200188
Maharashtra, Gujarat, Tamil Nadu, KeralaMaharashtra, Gujarat, Tamil Nadu, Kerala2000200077
Gujarat, Tamil NaduGujarat, Tamil Nadu1999199966
Gujarat, A & NGujarat, A & N1997199755
GujaratGujarat1995199544
GujaratGujarat1994199433
StateStateYearYearS. No.S. No.
14J.N. Medical College, Belgaum
J.N. Medical College, Belgaum 15
7th Day disease Weil’s disease Ictero-hemorrhagic fever Swineherd's disease Rice-field fever Pea picker’s disease Cane-cutter fever
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Swamp fever Mud fever Hemorrhagic jaundice Stuttgart disease Infectious jaundice Canicola fever
17J.N. Medical College, Belgaum
1) Agent Order: Spirochetales Family: Leptospirideae Genus: Leptospira Species: L. interrogans (pathogenic) and L.
biflexa (saprophytic) Serovars: > 250 Serogroups: 23; L. icterohemorrhagica,
gryppotyphosa, caniciola, pomona, andmanii, etc
18J.N. Medical College, Belgaum
MORPHOLOGY:Delicate, flexibleHelical rodsActively motile. aerobicHooked ends- umbrella handlesSeen best with dark field Microscopy6-20micrmeter long0.1micrometer thick
19J.N. Medical College, Belgaum
o Electron Microscopy
show thin axial filament
a delicate membraneo In dark field it
chain of miniature cocci.
20J.N. Medical College, Belgaum
Culture:o Leptospira grows best under aerobic conditions
at 280 to 300c best demonstrated in Semisolid agar media
o Optimal Media
Stuart’s and Fletcher’s Media
EMJH (semisynthetic media)
Optimal growth after 1 – 2 weeks
21J.N. Medical College, Belgaum
Resistance :
o Susceptible to heato Sensitive to acido Destroyed by chlorine, antisepticso Hence their survival depends on-
Temperature, acidity, salinity
Die rapidly in non aerated sewage, acid urine, saltish and brackish water
22J.N. Medical College, Belgaum
o Source of infection: Urine of infected animals Rodents excrete in urine for lifelong. o Animal reservoirs:
Wild and domestic animals Rodents – Rats, mice and voles Domestic animals – cows, buffalo, sheep, goats, pigs, horses.
Pet animals – dogs
23J.N. Medical College, Belgaum
24J.N. Medical College, Belgaum
Host : Animals- Rodents, insectivores, dogs, cattle,
pigs, horses, etc Humans – accidental infection contact with infected urine Even some birds
• Micro-abrasions, intact skin and mucosa• Infected animal tissues and blood
25J.N. Medical College, Belgaum
Age: children > adults
Sex: males > females
Immunity : serovar specific immunity
Occupation:
26J.N. Medical College, Belgaum
1 Farmers
2 Sewage workers
3 Veterinarians
4 Fishermen and water bailiffs
5 Abattoir workers
Recreational hazard- water sports, tourists
27J.N. Medical College, Belgaum
28J.N. Medical College, Belgaum
Leptospira – survive for weeks in soil and water
Poor housing, limited water supply, inadequate waste disposal are risk factor both rural and urban population.
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30J.N. Medical College, Belgaum
Mode of transmission:1) Direct contact
2) Indirect contact
3) Droplet infection
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32J.N. Medical College, Belgaum
Incubation period : usually 10days
2-20days
Entry: through cuts and abrasions in skin & mucous membranes of the eyes, nose and mouth
Inhalation- rare
Ingestion- rare
Human-to-human transmission –rare33J.N. Medical College, Belgaum
Leptospiremic/ Septicaemic phase› Systemic vasculitis› Migration of organisms into tissues-
inflammation and multi-organ dysfunction from direct cyto-toxicity
Immune phase/ Leptospiruric Phase› Second fever and organ involvement
through immunological mechanisms- Persistence of organisms› Renal tubules, aqueous humor
34J.N. Medical College, Belgaum
Wide range of severity and clinical featuresA. Subclinical infectionB. Self limited systemic illness 90 %C. Severe potentially fatal illness consisting of
Renal failure 15 % Liver failure 15% Pneumonitis >30 to 40% mortality Hemorrhagic diathesis
35J.N. Medical College, Belgaum
Leptospiremic/ Septicaemic phase
Immune phase/ Leptospiruric Phase
36J.N. Medical College, Belgaum
High fever and chills Severe headache, eyeball pain, photophobia Mental confusion Muscle pain & tenderness (calves and back) Redness in the eyes & conjunctival injection Sore throat Rash- maculopapular
37J.N. Medical College, Belgaum
Abdominal pain Vomiting and diarrhea Jaundice, hepatosplenomegaly Lymphadenopathy -rare Hemorrhages in skin and mucous
membranes Cough, chest pain & hemoptysis
38J.N. Medical College, Belgaum
Early myalgia. Hepatitis with fever. Renal impairment. Lymphocytic meningitis. Conjunctivitis. Rash, sometimes haemorrhagic. Thrombocytopenia. Blood, protein and/or bilirubin in the urine. Rare, nodular pneumonitis.
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40J.N. Medical College, Belgaum
41J.N. Medical College, Belgaum
42J.N. Medical College, Belgaum
Severe Leptospirosis (Weil's Syndrome)
Weil's syndrome-,characterized by jaundice, renal dysfunction, and hemorrhagic diathesis
By pulmonary involvement in many cases
mortality rates of 5–15
This syndrome is frequently but not exclusively associated with infection due to serovar L. icterohaemorrhagiae/copenhageni.
43J.N. Medical College, Belgaum
Renal Failure: › Migrate to interstitium, renal tubules and tubular
lumen – interstitial nephritis and tubular necrosis
› Hypovolemia
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Liver: › Centrilobular necrosis and Kupffer cell
hyperplasia
› No hepatocellular necrosis
45J.N. Medical College, Belgaum
Pulmonary: Hemorrhage and not much inflammation- hemoptysis, patchy lung - infiltrates and ARDS
Muscles: Direct cytotoxicity
CNS: Organisms in the CSF X 2 weeks with mild CSF changesMeningitis in immune phase
46J.N. Medical College, Belgaum
Rhabdomyolysis Hemolysis Myocarditis Pericarditis CHF Necrotising Pancreatitis MOF
47J.N. Medical College, Belgaum
Faine had evolved a criteria (WHO Guidelines) for diagnosis of Leptospirosis
On basis of clinical (A), epidemiological (B) laboratory data (C) (A+B+C)
48J.N. Medical College, Belgaum
49J.N. Medical College, Belgaum
50J.N. Medical College, Belgaum
51J.N. Medical College, Belgaum
Diagnosis of Leptospirosis
(Part A) or (Part A& Part B Score) : 26 or more
Part A, B & C (Total) : 25 or more
52J.N. Medical College, Belgaum
Isolation of organism1. Before tenth day of illness:Blood -i. Dark field examination of the patient’s bloodii. Culture on a semisolid medium (eg. Fletcher’s
EMJH)
53J.N. Medical College, Belgaum
2. After tenth day of illness:
Urine -
i. Dark field examination of the patient’s urine
ii. Culture of urine (for several months in untreated patient)
54J.N. Medical College, Belgaum
SerologyAggutination tests : Paired sera (fourfold or
greater rise in titer)
i. Microscopic, using live organisms (MAT)
ii. Macroscopic, using killed antigen
55J.N. Medical College, Belgaum
o ELISA IgM and Slide agglutination tests (SAT) :
- Measure IgM antibodies
- Single sample adequate
- The ELISA IgM test helpful for early diagnosis (positive 2 days into illness)
o Dot-ELISA and dip-stick methods:
- Newer screening methods (for detecting IgM antibodies)
56J.N. Medical College, Belgaum
Detection of specific DNA PCR test Leptospiral DNA: - Detected in blood, urine, CSF,
and aqueous humor
57J.N. Medical College, Belgaum
In September 2002, my mother was admitted in a Hyderabad nursing home with what was thought to be viral hepatitis. The doctor said she was doing fine. But she died after 12 days. She was only 47 years old. I was 17.
Ten days later, I developed the same symptoms that my mother had.
58J.N. Medical College, Belgaum
The doctor in Tirupati we consulted insisted that it was viral hepatitis. When I didn’t get better, a trainee nurse suggested a blood test for Leptospirosis, which was confirmed at Tirupati and Chennai labs
Alekhya Mandadi, Tirupati, Andhra Pradesh
59J.N. Medical College, Belgaum
Influenza Meningitis (encephalitis) Viral hepatitis Rickettsiosis Malaria Typhoid fever Septicemia Toxoplasmosis Legionnaire’s disease
60J.N. Medical College, Belgaum
General and Supportive Care› Antipyretics
› Antimicrobial
› Rest
› Hydration
› Ventilator support
› Liver support
› Renal support
› Transfusion support
61J.N. Medical College, Belgaum
Antimicrobials
Penicillin- 6 million units daily intravenously is the drug of choice in severe leptospirosis
Effective if started within first four days of illness.
Jarisch-Herxheimer reactions may occur
Total duration of therapy should be 10-14 days
62J.N. Medical College, Belgaum
Amoxycillin and erythromycin
Doxycycline in a dosage of 100 mg twice daily for 7 days
Effective in treatment of mild and moderate leptospirosis
63J.N. Medical College, Belgaum
Anicteric leptospirosis usually has a good prognosis.
Without jaundice the disease is almost never fatal
Fatal pulmonary haemorrhage and myocarditis have been reported occasionally in anicteric cases
case fatality rate for Weil’s disease is 15-40% higher for patients over 60 years of age
64J.N. Medical College, Belgaum
Prevention and control should be targeted at:
a) Source of infection
b) Route of transmission
c) Infection/ Disease in humans
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a) Source of infection Prevent contamination of living, working and
recreational areas by urine of infected animals.
Control rodent populations in areas of human habitation.
Contact with wildlife ( e.g., do not feed pets outside or allow animals to roam unsupervised)
66J.N. Medical College, Belgaum
Do not allow animals to urinate in or near ponds or pools.
Keep animals away from gardens, playgrounds, sandboxes, and other places children may play.
Among domesticated animals, vaccination of swine, cattle, and dogs.
67J.N. Medical College, Belgaum
b) Interruption of transmission Avoid swimming- contaminated water Protective clothing, footwear Adopt a reasonable standard of hygiene Public health engineering Waste management
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c) Human protection
Chemoprophylaxis
Effective prophylaxis consists of doxycycline,200 mg orally once weekly, during the risk of exposure
Vaccination IEC activities
69J.N. Medical College, Belgaum
Government of India – pilot project For control of Leptospirosis(Gujarat, TN- 2008 trial ; Karnataka , Maharashtra
2011) NCDC is the nodal agency Main Objective- Reduce morbidity and mortality related to
leptospirosis
J.N. Medical College, Belgaum 70
Leptospirosis Burden Epidemiology Reference Group (LERG)
Goals: To provide estimates on the global burden of
Leptospirosis according to age, sex and region. To increase awareness of and commitment to
the disease in developing countries. To encourage developing countries to
undertake active disease surveillance and strengthen control measures.
71J.N. Medical College, Belgaum
In the ICD10 disease classification system, leptospirosis is code A27
The International Leptospirosis Society (ILS) was formed in 1994 to promote knowledge on leptospirosis through the organisation of regional and global leptospirosis meetings
72J.N. Medical College, Belgaum
Leptospirosis should be a notifiable disease
Need to increase awareness
Better diagnosis and surveillance programmes
J.N. Medical College, Belgaum 73
74J.N. Medical College, Belgaum
A 40 y/o police officer presents with fever and muscle aches. He is pale, has a temperature of 102°F. His physical exam and labs are unremarkable so he is discharged and given flu instructions. He says his partner is also ill.
75J.N. Medical College, Belgaum
Later, a 35 y/o female clerk also presents complaining of myalgias, shaking chills, and vomiting. She is pale, and has a temperature of 102.4°F. Her physical exam is non-focal, she improves with antipyretics and the patient is sent home with viral syndrome instructions.
76J.N. Medical College, Belgaum
The next day several more patients present with fever, chills and myalgias
77J.N. Medical College, Belgaum
The 40 yr policeman returns 3 days later because he is feeling much worse and is short of breath.
This is the chest x-ray that was obtained
78J.N. Medical College, Belgaum
A mother brings in her adolescent son for a strange black scab/rash that started out as a small papule but formed a black painless eschar over the past 5 days
79J.N. Medical College, Belgaum
80J.N. Medical College, Belgaum
The word “Anthrax” originates from Greek for black or coal
The black eschar which is characteristic of the cutaneous form of Anthrax infection.
It is principally a disease of herbivores
But has the potential to infect all mammals
and even some birds81J.N. Medical College, Belgaum
Bacillus anthracis , zoonotic disease
Anthrax may be the prototypic disease of bioterrorism
Humans almost invariably contract anthrax directly or indirectly from animals
“Malignant pustule” and “Wool sorter’s disease”.82J.N. Medical College, Belgaum
83J.N. Medical College, Belgaum
84J.N. Medical College, Belgaum
Bacillus anthracis› Aerobic, Gram positive rod
› Long (1-10μm), thin (0.5-2.5μm)
› Forms inert spores when exposed to O2
Infectious form, hardy Approx 1μm in size
› Vegetative bacillus Non-infectious, fragile
85J.N. Medical College, Belgaum
Environmental Survival Spores
Resistant to drying, boiling <10 minutesSurvive for years in soil
Favorable soil factors for spore viabilityHigh moistureOrganic content Alkaline pHHigh calcium concentration
86J.N. Medical College, Belgaum
Anthrax is a seasonal disease
The occurrence of anthrax among animals in any one place is related to temperature and
rains.
However, the conditions which predispose to outbreaks differ widely
87J.N. Medical College, Belgaum
› Primarily disease of herbivorous animals
Sheep, goats, cattle Many large documented epizootics Carnivores are not immune
› Human disease Epidemics have occurred but uncommon Rare in developed world
88J.N. Medical College, Belgaum
Many countries have weaponized anthrax› Former bioweapon programs
U.S.S.R.,U.S.,U.K., and Japan
› Recent bioweapon programs Iraq
› Attempted uses as bioterrorism agent WW I: Germans inoculated Allied livestock WW II: Alleged Japanese use on prisoners
89J.N. Medical College, Belgaum
In September 2001, the American public was exposed to anthrax spores as a bio-weapon delivered through the U.S. Postal System
CDC identified 22 confirmed cases
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J.N. Medical College, Belgaum 91
J.N. Medical College, Belgaum 92
Features of anthrax suitable as BT agent
› Fairly easy to obtain, produce and store
› Spores easily dispersed as aerosol
› Moderately infectious
› High mortality for inhalational (86-100%)
93J.N. Medical College, Belgaum
Three forms of natural disease› Inhalational
Rare (<5%) Most likely encountered in bioterrorism
event› Cutaneous
Most common (95%) Direct contact of spores on skin
› Gastrointestinal Rare (<5%), never reported in U.S. Ingestion
94J.N. Medical College, Belgaum
Mortality
› Inhalational 86-100% (despite treatment) Era of crude intensive supportive care
› Cutaneous <5% (treated) – 20% (untreated)
› GI approaches 100%
95J.N. Medical College, Belgaum
Incubation Period
› Time from exposure to symptoms
› Very variable for inhalational 2-43 days reported Theoretically may be up to 100 days Delayed germination of spores
96J.N. Medical College, Belgaum
Transmission› No human-to-human (very rare)› Naturally occurring cases
Skin exposure Ingestion Airborne
› Bioterrorism Aerosol (likely) Small volume powder (possible) Foodborne (unlikely)
97J.N. Medical College, Belgaum
Anthrax has at least three proteins which play a role in virulence
A-B model of toxicity
Edema factor (EF), Lethal factor (LF) and Protective antigen (PA)
EF and LF need PA to get into the cell to cause damage
98J.N. Medical College, Belgaum
99J.N. Medical College, Belgaum
Progression of painless lesionsPapule/macule – pruritic
Vesicle/bulla – clear or serosanguinous
Ulcer – non-pitting, gelatinous edema
Eschar – black, depressed, scars
100J.N. Medical College, Belgaum
101J.N. Medical College, Belgaum
Initially starts with a non-specific flu-like illness and then progresses to:› Respiratory Distress› Shock
› May see a widened mediastinum on x-ray
102J.N. Medical College, Belgaum
103J.N. Medical College, Belgaum
Nausea, anorexia, vomiting, fever Progresses to severe abdominal pain and
bloody emesis and diarrhea Ascites may develop on day 2 - 4 Death 2 to 5 days after onset of symptoms Very difficult to diagnose
104J.N. Medical College, Belgaum
Microscopy Blood culture Serology- Specific Enzyme - Linked
Immunosorbent Assays (ELISAs)
105J.N. Medical College, Belgaum
J.N. Medical College, Belgaum 106
Stained with polychrome methylene blue (M’Fadyeanstain).
On blood agar, the colony is non-haemolytic
J.N. Medical College, Belgaum 107
PLET agar. These are typically ‘”bee’s-eye”
Anthrax Meningitis : Haematogenous spread of the pathogen
Meningitis - to 100% mortality.
J.N. Medical College, Belgaum 108
Inhalational, GI, Sepsis Ciprofloxacin, 400 mg IV q12h or
Doxycycline, 100 mg IV q12 plus
Clindamycin, 900 mg IV q8h and/or rifampin, 300 mg IV q12h; switch to PO when stable x60 d total
109J.N. Medical College, Belgaum
Cutaneous Anthrax without systemic signs, extensive edema or
lesions located on head and neck. Initial recommended treatment:
Doxycycline 100mg BD or Ciprofloxacin 500mg BD PO for 60 days
(Amox 500 mg PO q8h, likely to be effective if strain penicillin sensitive)
110J.N. Medical College, Belgaum
Cutaneous Anthrax with systemic signs,
extensive edema or lesions on the head and neck.
Initial recommended treatment:
› Doxycycline or Ciprofloxacin IV
› May switch to PO when clinically appropriate
111J.N. Medical College, Belgaum
Control of the disease in animals
Correct disposal of carcasses of anthrax cases
Proper disinfection, decontamination and disposal of contaminated materials
J.N. Medical College, Belgaum 112
Vaccine› Anthrax Vaccine Adsorpbed (AVA)
› Supply- controlled by CDC
Newer vaccines including a plasmid DNA vaccine and vaccines for intranasal use are under development
113J.N. Medical College, Belgaum
Chemoprophylaxis: Ciprofloxacin or Doxycycline for four weeks for
unimmunized individuals.
longer duration - for complete clearance of spores from the lungs
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Suspicious letters/packages – “Do not X-ray”, “Fragile”, “Confidential”Do not open or shakePlace in plastic bag or leakproof containerIf visibly contaminated or container
unavailableGently cover – paper, clothing, box, trash canLeave room/area, isolate room from othersThoroughly wash hands with soap and waterReport to local security / law enforcement
J.N. Medical College, Belgaum 115
NCDC under the Ministry Of Health – Proposed to set up Surveillance system for micro-organisms with bio-terrorism potential
J.N. Medical College, Belgaum 116
Single inhalational case is an emergency› Contact Local Health Departments
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1. Harrison’s Principles of Internal Medicine- 18th edition2. Goldman Cecil Medicine- 23rd ed.3. Park’s textbook of Preventive &Social Medicine 22nd
edition4. Text Book of Public Health and Community Medicine-
AFMC Pune5. Leptospirosis – An Overview TK Dutta, M Christopher.6. Ananthanarayan and Paniker’s Textbook Of
Microbiology- 18th edn7. National Health Programs Of India -J. Kishore’s 11th
edn
J.N. Medical College, Belgaum 118
8) Infection Microbiology and Management Barbara Bannister
9) Guidelines for the Surveillance and Control of Anthrax in Human and Animals. 3rd edition
10) Leptospirosis in India and the Rest of the World
Rao R. Sambasiva, Gupta Naveen.
11) www.who.org.in
12) www.google.in
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