LeptospirosisLeptospirosis

Dr.T.V.Rao MDDr.T.V.Rao MD

Leptospirosis - ZoonosisLeptospirosis - Zoonosis

Leptospirosis is an acute anthropo-zoonotic Leptospirosis is an acute anthropo-zoonotic infection of worldwide significance caused by infection of worldwide significance caused by spirochaete Leptospira interrogans which has 23 spirochaete Leptospira interrogans which has 23 serogroups and >200 serovars. Various factors serogroups and >200 serovars. Various factors influencing the animal activity, suitability of the influencing the animal activity, suitability of the environment for the survival of the organism and environment for the survival of the organism and behavioral and occupational habits of human behavioral and occupational habits of human beings can be the determinants of incidence and beings can be the determinants of incidence and prevalence of the disease. prevalence of the disease.

What is leptospirosis?What is leptospirosis?

Leptospirosis, also known as canicola fever, Leptospirosis, also known as canicola fever, hemorrhagic jaundice, infectious jaundice, mud hemorrhagic jaundice, infectious jaundice, mud fever, spirochetal jaundice, swamp fever, fever, spirochetal jaundice, swamp fever, swineherd's disease, caver's flu or sewerman's swineherd's disease, caver's flu or sewerman's flu, is a bacterial infection resulting from flu, is a bacterial infection resulting from exposure to the exposure to the Leptospira interrogansLeptospira interrogans bacterium. There is an acute form of human bacterium. There is an acute form of human infection known as Weil's disease, where the infection known as Weil's disease, where the patient suffers from jaundice, though this term is patient suffers from jaundice, though this term is often (incorrectly) used to describe any case of often (incorrectly) used to describe any case of infection.. infection..

Leptospirosis – A Major Zoonotic Leptospirosis – A Major Zoonotic InfectionInfection

Weil's disease is comparatively rare, Weil's disease is comparatively rare, though 'mild' cases of leptospirosis though 'mild' cases of leptospirosis happen everywhere there are carriers, and happen everywhere there are carriers, and it is believed that leptospirosis is one of it is believed that leptospirosis is one of the most common zoonotic infections in the most common zoonotic infections in the world. Millions of people are infected the world. Millions of people are infected each year, but information and treatment each year, but information and treatment can be limited, especially in the developed can be limited, especially in the developed world where cases are considered 'rare' by world where cases are considered 'rare' by the medical community. the medical community.

Animals spread LeptospirosisAnimals spread Leptospirosis

Rats, Mice, Wild Rodents, Rats, Mice, Wild Rodents, Dogs, Swine, Cattle are Dogs, Swine, Cattle are principle source of principle source of infectioninfection

The above animals excrete The above animals excrete Leptospira both in active Leptospira both in active infection and infection and Asymptomatic stageAsymptomatic stage

The Leptospira survive The Leptospira survive and remain viable for and remain viable for several weeks in stagnant several weeks in stagnant water.water.

What causes LeptospirosisWhat causes Leptospirosis

Leptospirosis is a bacterial disease that Leptospirosis is a bacterial disease that affects humans and animals. Leptospira affects humans and animals. Leptospira bacteria are found worldwide and there bacteria are found worldwide and there are many different types or serovars are many different types or serovars capable of causing disease. Disease capable of causing disease. Disease caused by Leptospira bacteria is most caused by Leptospira bacteria is most common in temperate or tropical climates common in temperate or tropical climates and appears to be rare in North America.and appears to be rare in North America.

Scientific BeginningScientific Beginning

It was first described by It was first described by Adolf WeilAdolf Weil in in 18861886 when he reported an "acute infectious when he reported an "acute infectious disease with disease with enlargement of spleenenlargement of spleen, , jaundicejaundice and and nephritisnephritis". ". LeptospiraLeptospira was was first observed in first observed in 19071907 from a from a post mortempost mortem renal tissuerenal tissue slice. slice.[2][2]

Pathogenic strains x Non pathogenic Pathogenic strains x Non pathogenic LeptospirosisLeptospirosis

There are several species of Leptospira only few There are several species of Leptospira only few are pathogenic to Humans, rest to some Animals are pathogenic to Humans, rest to some Animals and Many in Nature as saprophytesand Many in Nature as saprophytes

Leptospira Interrogans is Pathogenic there are Leptospira Interrogans is Pathogenic there are 200 serovars.200 serovars.

Leptospira biflexa Non Pathogenic there are 60 Leptospira biflexa Non Pathogenic there are 60 serovarsserovars

Further classifications are made on shared Further classifications are made on shared antigensantigens

Genomic based classificationGenomic based classification

DNA – DNA hybridization studies proved DNA – DNA hybridization studies proved more specificmore specific

The traditional serologic classification has The traditional serologic classification has limitations at Molecular level, but useful at limitations at Molecular level, but useful at Epidemiological studies.Epidemiological studies.

MorphologyMorphology

The Leptospira appear The Leptospira appear tighly coiled thin flexible tighly coiled thin flexible Spritochetes 5 – 15 Spritochetes 5 – 15 microns long.microns long.

Fine spiral of 0.1 – 0.2 Fine spiral of 0.1 – 0.2 micronsmicrons

One end appears bent One end appears bent forms a hook.forms a hook.

Actively motileActively motile

Seen best with dark field Seen best with dark field Microscopy.Microscopy.

Greater Understanding with Greater Understanding with Electron MicroscopyElectron Microscopy

Electron Microscopy Electron Microscopy show thin axial show thin axial filament and a filament and a delicate membranedelicate membrane

In dark field it may In dark field it may appear as chain of appear as chain of miniature cocci.miniature cocci.

Comparative Morphology of Comparative Morphology of SpritochetesSpritochetes

Culturing of LeptospiraCulturing of Leptospira

Leptospira grwos best Leptospira grwos best under aerobic conditions under aerobic conditions at 28at 280 0 to 30to 3000c best c best demonostrated in demonostrated in Semisolid agar mediaSemisolid agar media

Optimal MediaOptimal Media

Fletchers MediaFletchers Media

Stuarts MediaStuarts Media

Optimal growth after 1 – 2 Optimal growth after 1 – 2 weeksweeks

Growth requirementsGrowth requirements

Leptospira derive Leptospira derive energy from oxidation energy from oxidation of long chain fatty of long chain fatty acids, and cannot use acids, and cannot use or carbohydrates or or carbohydrates or amino acids as major amino acids as major energy source.energy source.

Antigenic structureAntigenic structure

All isolates of L.inttterogans from different parts All isolates of L.inttterogans from different parts of the world are serologically related and exhibit of the world are serologically related and exhibit cross reactions in serologic tests.cross reactions in serologic tests.Overlapping of Antigens do occur in different Overlapping of Antigens do occur in different species.species.Outer envelop contains large amount of Outer envelop contains large amount of Lipopolysaccharides ( LPS )Lipopolysaccharides ( LPS )Antigenic structure varies from one strain to Antigenic structure varies from one strain to otherotherThis variation forms the basis of serologic This variation forms the basis of serologic classificationclassification

Genome of LeptospiraGenome of Leptospira

L. interrogans serogroup IcterhaemorrhagiaeL. interrogans serogroup Icterhaemorrhagiae consists of a 4.33 megabase large chromosome consists of a 4.33 megabase large chromosome and a 359 kilobase small chromosome, totaling and a 359 kilobase small chromosome, totaling 4,768 predicted genes. A series of genes have 4,768 predicted genes. A series of genes have been discovered that could potentially be related been discovered that could potentially be related to adhesion. This genome differs from the two to adhesion. This genome differs from the two other pathogenic spirochaete (other pathogenic spirochaete (Treponema Treponema palladium and Borrelia burgdorferipalladium and Borrelia burgdorferi), though ), though some similar genes are visible (CHGC, 2004). some similar genes are visible (CHGC, 2004).

PathogenesisPathogenesis

Leptospira are present in the water bodiesLeptospira are present in the water bodiesEnter through breaks in the skin ( cuts and Enter through breaks in the skin ( cuts and abrasions ) and mucous membranesabrasions ) and mucous membranesEnters through Mouth – Nose – Conjunctive Enters through Mouth – Nose – Conjunctive Rarely enters though ingestion.Rarely enters though ingestion.Incubation period 1 – 2 weeksIncubation period 1 – 2 weeksWhen multiples blood stream produces fever.When multiples blood stream produces fever.May establish organ involvement in Kidney and May establish organ involvement in Kidney and Liver,Liver,May produce hemorrhage and necrosis in the May produce hemorrhage and necrosis in the tissues and initiates dysfunction of these organstissues and initiates dysfunction of these organs

Sequence of Leptospira InfectionSequence of Leptospira Infection

May present withMay present with

JaundiceJaundice

HemorrhageHemorrhage

Nitrogen retentionNitrogen retention

The Illness is Biphasic with initial temperature The Illness is Biphasic with initial temperature when the second phase comes with raise of IgM when the second phase comes with raise of IgM titers raisetiters raise

Aseptic meingitis – initial headache, stiffness of Aseptic meingitis – initial headache, stiffness of neck, pleocytosis of Cerebro spinal fluidneck, pleocytosis of Cerebro spinal fluid

Presenting with Jaundice is Presenting with Jaundice is significant and Important, significant and Important,

Serious ManifestationSerious Manifestation

May present with Major May present with Major ComplicationsComplications

NephritisNephritis

Hepatitis.Hepatitis.

Manifestations in eyeManifestations in eye

Muscular lesionsMuscular lesions

Many infections are Many infections are mild and subclinicalmild and subclinical

Weil’s SyndromeWeil’s Syndrome

Weil's syndromeWeil's syndrome is a severe form of is a severe form of leptospirosis that causes a continuous fever, leptospirosis that causes a continuous fever, stupor, and a reduction in the blood's ability to stupor, and a reduction in the blood's ability to clot, which leads to bleeding within tissues. clot, which leads to bleeding within tissues. Blood tests reveal anemia. By the third to sixth Blood tests reveal anemia. By the third to sixth day, signs of kidney damage and liver injury day, signs of kidney damage and liver injury appear. Kidney abnormalities may cause blood appear. Kidney abnormalities may cause blood in the urine and painful urination. Liver injury in the urine and painful urination. Liver injury tends to be mild and usually heals completely. tends to be mild and usually heals completely.

Hepatitis - LeptospirosisHepatitis - Leptospirosis

Hepatitis is the Hepatitis is the frequent complicationfrequent complication

Elevation of serum Elevation of serum creatine phosphilipae creatine phosphilipae enzyme raise enzyme raise differentiates from differentiates from Viral hepatitis where Viral hepatitis where the enxyme is not the enxyme is not raisedraised

Nephritis - LeptospirosisNephritis - Leptospirosis

Kidney involvement in Kidney involvement in animals produce chronic animals produce chronic disease of the kidney and disease of the kidney and the infected animal starts the infected animal starts shedding large number of shedding large number of leptospira and main leptospira and main source of environmental source of environmental contamination of bacteria contamination of bacteria and results I human and results I human infectionsinfectionsHuman urine also contain Human urine also contain Spirochetes in the second Spirochetes in the second and third week of and third week of infectioninfection

Early and Prompt Diagnosis is Early and Prompt Diagnosis is Highly EssentialHighly Essential

The development of simpler, rapid assays The development of simpler, rapid assays for diagnosis has been based largely on for diagnosis has been based largely on the recognition that early initiation of the recognition that early initiation of antibiotic therapy is important in acute antibiotic therapy is important in acute disease but also on the need for assays disease but also on the need for assays which can be used more widely. which can be used more widely.

Laboratory DiagnosisLaboratory Diagnosis

Specimens Specimens

1 1 Blood to be collected in a Blood to be collected in a heparin tubeheparin tube

2 CSF, Tissues2 CSF, Tissues Microscopic examinationMicroscopic examination 3 Urine to be collected with 3 Urine to be collected with

great care to avoid great care to avoid contaminationcontamination

4 Serum for agglutination 4 Serum for agglutination teststests

Culturing LeptospiraCulturing LeptospiraBlood and Urine be cultured Blood and Urine be cultured

in Fletcher’s semisolid in Fletcher’s semisolid agar or other mediaagar or other media chemically defined chemically defined protein-free media for the protein-free media for the growth of leptospires have growth of leptospires have been proposed. In order to been proposed. In order to obtain the desired rapid obtain the desired rapid and abundant growth of and abundant growth of organisms necessary for organisms necessary for the efficient production of the efficient production of vaccines, it has been vaccines, it has been necessary to supplement necessary to supplement such media with a source such media with a source of fatty acids, of fatty acids,

SerologySerology

Agglutinating Agglutinating antibodies raise to antibodies raise to very high titersvery high titers

1 : 10,000 or higher1 : 10,000 or higher

occurs 5 – 10 weeks occurs 5 – 10 weeks after onset of infectionafter onset of infection

Serology - ELISASerology - ELISA

Several Several Immunoassays are Immunoassays are available as available as commercial kitscommercial kits

Detection of IgM and Detection of IgM and razing titers of IgG will razing titers of IgG will guide in association guide in association with clinical history with clinical history will help in Diagnosiswill help in Diagnosis

TreatmentTreatment

Antibiotic of choice is Antibiotic of choice is Benzyl Pencillin Benzyl Pencillin given by injection in doses of 5 mega units given by injection in doses of 5 mega units in a day, for 5 days.in a day, for 5 days.

If the patients are genuinely hypertensive If the patients are genuinely hypertensive to Pencillin opted with Erythromycin to Pencillin opted with Erythromycin 250mgs four times a day for a period of 5 250mgs four times a day for a period of 5 days.days.

Treatment - Other alternativesTreatment - Other alternatives

The leptospirosis can be effectively treated The leptospirosis can be effectively treated withwith

DoxycyclineDoxycycline

AmpicillinAmpicillin

AmoxicillinAmoxicillin

Severe patients need administration Severe patients need administration Intravenous Pencillin or AmoxcillinIntravenous Pencillin or Amoxcillin

EpidemiologyEpidemiology

Leptospirosis causes several animal infectionsLeptospirosis causes several animal infections

Most wide spread zoonotic infection in NatureMost wide spread zoonotic infection in Nature

Human infections are accidental associated with Human infections are accidental associated with contamination of water, other materials contamination of water, other materials contaminated with excreta and animal flesh.contaminated with excreta and animal flesh.

Animal carriers often excrete upto 100million Animal carriers often excrete upto 100million leptospirosis per ml of urineleptospirosis per ml of urine

Epidemiology - Epidemiology - OccupationOccupation

Certain Certain occupational occupational

groups such as groups such as agriculture workers agriculture workers

in rice and cane in rice and cane fields, miners and fields, miners and sever cleaners are sever cleaners are potential victims potential victims

How Man gets InfectedHow Man gets Infected

Water the great sourceWater the great source

DrinkingDrinking

SwimmingSwimming

Bathing, as the urine of Bathing, as the urine of Rodents chronically Rodents chronically infected contaminate infected contaminate water sourceswater sources

Children get infected Children get infected when in contact with when in contact with infected Dogsinfected Dogs

Control of LeptospirosisControl of Leptospirosis

Rodent control is Rodent control is most important.most important.

Human’s should avoid Human’s should avoid contact with water contact with water contaminated with contaminated with animal contact.animal contact.

ChemoprophylaxisChemoprophylaxis

Doxycycline 200 Doxycycline 200 mg orally once a mg orally once a week is simple week is simple

effective measure. effective measure. When heavy When heavy exposure is exposure is anticipatedanticipated

Vaccination in humansVaccination in humans

Vaccination for humans is justified where they Vaccination for humans is justified where they cannot be separated from animal sources or cannot be separated from animal sources or where the animals cannot be immunized where the animals cannot be immunized successfullysuccessfullyNecessity of human vaccinated will arise where Necessity of human vaccinated will arise where people live and work in proximity to rodents in people live and work in proximity to rodents in wet, tropical conditions, in wet rice planting and wet, tropical conditions, in wet rice planting and harvesting, in military operations, or working in harvesting, in military operations, or working in sewers.sewers.Yet no universally accepted vaccine is Yet no universally accepted vaccine is available for humansavailable for humans

Vaccination of AnimalsVaccination of Animals

Vaccinating animals have a dual purpose Vaccinating animals have a dual purpose 1 Protecting animals1 Protecting animals

2 Protecting humans who may contract 2 Protecting humans who may contract leptospirosis from themleptospirosis from them

It is probably true as that immunization of animals It is probably true as that immunization of animals will prevent leptospirosis in people in contact with will prevent leptospirosis in people in contact with

them.them. It proved true in 1980 when extensive vaccination It proved true in 1980 when extensive vaccination

of dairy cows in New Zealand lead to marked of dairy cows in New Zealand lead to marked decreased incidence in Humans.decreased incidence in Humans.

Animals immunized experimentally with Animals immunized experimentally with polysaccharide derived from Leptospira LPS linked polysaccharide derived from Leptospira LPS linked

to diphtheria Toxoid were protected against to diphtheria Toxoid were protected against challengeschallenges

Several other vaccines in use to suit local needs.Several other vaccines in use to suit local needs.

New Vaccine trails - LeptospiraNew Vaccine trails - Leptospira

Created for Health Created for Health awareness on awareness on LeptospirosisLeptospirosis

Dr.T.V.Rao MDDr.T.V.Rao MD

EmailEmail

doctortvrao@gmail.comdoctortvrao@gmail.com