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Leptospirosis is commonly caused by Leptospira interrogans, a corkscrew-shaped bacterium (spirochete). 11/28/2010 Dr.T.V.Rao MD 2 What is Leptospirosis? : What is Leptospirosis? Leptospirosis, also known as canicola fever, hemorrhagic jaundice, infectious jaundice, mud fever, spirochetal jaundice, swamp fever, swineherd's disease, caver's flu or sewerman's flu, is a bacterial infection resulting from exposure to the Leptospira interrogans bacterium. There is an acute form of human infection known as Weil's disease, where the patient suffers from jaundice, though this term is often (incorrectly) used to describe any case of infection.. 11/28/2010 Dr.T.V.Rao MD 3 CDC Definition of LeptospirosisClinical description : CDC Definition of LeptospirosisClinical description An illness characterized by fever, headache, chills, myalgia, conjunctival suffusion, and less frequently by meningitis, rash, jaundice, or renal insufficiency. Symptoms may be biphasic. 11/28/2010 Dr.T.V.Rao MD 4 Leptospirosis is still less understood Disease : Leptospirosis is still less understood Disease Leptospirosis is a zoonotic disease that has emerged as an important cause of morbidity and mortality among impoverished populations. One hundred years after the discovery of the causative spirochaetal agent, little is understood about Leptospira spp. pathogenesis, which in turn has hampered the development of new intervention strategies to address this neglected disease 11/28/2010 Dr.T.V.Rao MD 5 Epidemiology : Epidemiology In 1886, Weil, a German doctor observed 4 cases of Leptospirosis with jaundice, than this disease is called as Weil disease In China: in 1937, Professor Tang zeguang discovered Leptospirosis in Guangzhou Early History : Early History The disease was first described by Adolf Weil in 1886 when he reported an "acute infectious disease with enlargement of spleen, jaundice and nephritis". Leptospira was first observed in 1907 from a post mortem renal tissue slice. In 1908, Inada and Ito first identified it as the causative organism and in 1916 noted its presence in rats. 11/28/2010 Dr.T.V.Rao MD 7 Leptospirosis - Zoonosis : Leptospirosis - Zoonosis Leptospirosis is an acute anthropo-zoonotic infection of worldwide significance caused by spirochete Leptospira interrogans which has 23 serogroups and >200 serovars. Various factors influencing the animal activity, suitability of the environment for the survival of the organism and behavioural and occupational habits of human beings can be the determinants of incidence and prevalence of the disease. 11/28/2010 Dr.T.V.Rao MD 8 Leptospirosis – A Major Zoonotic Infection : Leptospirosis – A Major Zoonotic Infection Weil's disease is comparatively rare, though 'mild' cases of Leptospirosis happen everywhere there are carriers, and it is believed that Leptospirosis is one of the most common zoonotic infections in the world. Millions of people are infected each year, but information and treatment can be limited, especially in the developed world where cases are considered 'rare' by the medical community. 11/28/2010 Dr.T.V.Rao MD 9 Leptospirosis can be a Serious Health Problem : Leptospirosis can be a Serious Health Problem Leptospirosis, an infectious disease with a wide global distribution, has been by and large neglected as a serious health problem till recently. The increasing reports of outbreaks and clusters of cases, particularly from Southeast Asia and North and Central American countries, has brought attention to the public health problem posed by this spirocheatal infection 11/28/2010 Dr.T.V.Rao MD 10 Slide 11: INDIA The first of its kind in India was reported in the 1920s from Andaman and Nicobar Islands. In 1993, a serosurvey of conservancy workers in Madras (using MAT) revealed a prevalence rate of 32.9%. In 1994, an increase in the number of individuals with uveitis was noted at Aravind Eye hospital, Madurai, India after an epidemic of leptospirosis in South India; the epidemic followed severe flooding of the Tamil Nadu District in the autumn of 1993 In 1995, a seroprevalence rate of 12% leptospirosis was found among febrile and jaundice patients in Pondicherry Major reports on LeptospirosisIndia : Major reports on LeptospirosisIndia The first of its kind in India was reported in the 1920s from Andaman and Nicobar Islands. In 1993, a serosurvey of conservancy workers in Madras (using MAT) revealed a prevalence rate of 32.9%. In 1994, an increase in the number of individuals with uveitis was noted at Aravind Eye hospital, Madurai, India after an epidemic of leptospirosis in South India; the epidemic followed severe flooding of the Tamil Nadu District in the autumn of 1993 In 1995, a seroprevalence rate of 12% leptospirosis was found among febrile and jaundice patients in Pondicherry 11/28/2010 Dr.T.V.Rao MD 12 Animals spread Leptospirosis : Animals spread Leptospirosis Rats, Mice, Wild Rodents, Dogs, Swine, Cattle are principle source of infection The above animals excrete Leptospira both in active infection and Asymptomatic stage The Leptospira survive and remain viable for several weeks in stagnant water. 11/28/2010 Dr.T.V.Rao MD 13 LeptospirosisReservoir (Maintenance Host) : LeptospirosisReservoir (Maintenance Host) Cattle Cats (rare) Dogs Horses Pigs Rodents Wildlife (opossum, raccoons, skunks and many other species) 11/28/2010 Dr.T.V.Rao MD 14 What causes Leptospirosis : What causes Leptospirosis Leptospirosis is a bacterial disease that affects humans and animals. Leptospira bacteria are found worldwide and there are many different types or serovars capable of causing disease. Disease caused by Leptospira bacteria is most common in temperate or tropical climates and appears to be rare in North America. 11/28/2010 Dr.T.V.Rao MD 15 Pathogenic strains x Non pathogenic Leptospirosis : Pathogenic strains x Non pathogenic Leptospirosis There are several species of Leptospira only few are pathogenic to Humans, rest to some Animals and Many in Nature as saprophytes Leptospira Interrogans is Pathogenic there are 200 serovars. Leptospira biflexa Non Pathogenic there are 60 serovars Further classifications are made on shared antigens 11/28/2010 Dr.T.V.Rao MD 16 Morphology : Morphology The Leptospira appear tightly coiled thin flexible Spirochetes 5 – 15 microns long. Fine spiral of 0.1 – 0.2 microns One end appears bent forms a hook. Actively motile Can be Seen with dark field Microscopy. 11/28/2010 Dr.T.V.Rao MD 17 Important species in Leptospirosis : Important species in Leptospirosis The genera Leptospira contains three species, namely L interrogans, L biflexa and L parva. The first includes 23 serogroups and more than 250 serovars and is the principal cause of leptospirosis in humans and animals. most common being L. canicola, L. hardjo and L. hebdomadis. Two types of leptospirosis: 1. Anicteric leptospirosis or self-limited illness (85% to 90% of the cases) 2. Icteric leptospirosisor weil’s syndrome (5% to 10) Antigenic structure : Antigenic structure All isolates of L.inttterogans from different parts of the world are serologically related and exhibit cross reactions in serologic tests. Overlapping of Antigens do occur in different species. Outer envelop contains large amount of Lipopolysaccharides ( LPS ) Antigenic structure varies from one strain to other This variation forms the basis of serologic classification 11/28/2010 Dr.T.V.Rao MD 19 Genome of Leptospira : Genome of Leptospira L. interrogans serogroup Icterhaemorrhagiae consists of a 4.33 megabase large chromosome and a 359 kilo base small chromosome, totalling 4,768 predicted genes. A series of genes have been discovered that could potentially be related to adhesion. This genome differs from the two other pathogenic spirochete (Treponema palladium and Borrelia burgdorferi), though some similar genes are visible (CHGC, 2004). 11/28/2010 Dr.T.V.Rao MD 20 Epidemiology - Occupation : Epidemiology - Occupation Certain occupational groups such as agriculture workers in rice and cane fields, miners and sever cleaners are potential victims Pathogenesis : leptospira Skin,mucous membranes Blood stream Type of Influenza-typhoid fever Organs leptospiramia Pathogenesis LeptospirosisPathogenesis : LeptospirosisPathogenesis Leptospires penetrate mucous membranes or abraded skin and multiply rapidly upon entering the blood stream. They spread to the kidney, liver, spleen, central nervous system, eyes and genital tract. Initial antibody response clears most organs except the kidneys where the infection can remain and be shed for weeks to months. Leptospirosis causes a severe vasculitis with endothelial damage. Kidney damage, shock, heart damage with arrhythmias. Liver damage with icterus and low vit k levels Eye disease-Uveitis* 11/28/2010 Dr.T.V.Rao MD 23 Pathogenesis : Pathogenesis Leptospira are present in the water bodies Enter through breaks in the skin ( cuts and abrasions) and mucous membranes Enters through Mouth – Nose – Conjunctive Rarely enters though ingestion. Incubation period 1 – 2 weeks When multiples blood stream produces fever. May establish organ involvement in Kidney and Liver, May produce hemorrhage and necrosis in the tissues and initiates dysfunction of these organs 11/28/2010 Dr.T.V.Rao MD 24 Pathology : Pathology The basic pathological finding is infectious-toxic lesion of the systemic capillary In some cases severe damage can be seen in the organs and tissues Liver: cellular infiltration around the portal area Kidney: Interstitial nephritis Lung: pulmonary congestion and hemorrhage Brain: perivascular cuffing Slide 26: 11/28/2010 Dr.T.V.Rao MD 26 Slide 27: 11/28/2010 Dr.T.V.Rao MD 27 LEPTOSPIROSIS : LEPTOSPIROSIS Clinical features incubation period: 7-14 days biphasic commonly involves CNS, kidneys, and liver often misdiagnosed as hepatitis or meningitis petechial rash, morbilliform or urticarial in appearance - in 10-30%of cases within first 2 days, sometimes pruritic LEPTOSPIROSIS : LEPTOSPIROSIS Clinical features acute leptospiremia phase abrupt onset of fever severe headache muscle pain nausea jaundice in more severe cases symptoms persist for up to 7 days Incubation period: Biphasic illness. 2 to 20 days (~ 10). : Incubation period: Biphasic illness. 2 to 20 days (~ 10). Fever, chills and rigors. Myalgia (calf & lumbar0 Conjunctival suffusion. GI symptoms. Lymphadenitis, hepatosplenomegaly. Leptospires isolated in blood/CSF. Aseptic meningitis – retro-orbital headache and photophobia. CSF – neutrophilic pleocytosis Lepto PCR positive. Coincides with appearance of antibodies. Aseptic meningitis. Rash and uveitis.. Haemorrhagic pneumonitis. Hepato renal damage. Death due to MOF / pulm hge. Leptospires isolated in urine/aqueous humor/kidney. Aseptic meningitis – headache/vomiting. CSF – lymphocytic pleocytosis Lepto PCR negative. 11/28/2010 Dr.T.V.Rao MD 30 Slide 31: Clinical ManifestationsType of Influenza-typhoid fever 3 Symptoms: Chills and Fever Myalgia Fatigue 3 signs: Conjunctival suffusion Calf muscle tenderness Enlargement of lymph nodes 。 May present with : May present with Jaundice Hemorrhage Nitrogen retention The Illness is Biphasic with initial temperature when the second phase comes with raise of IgM titers raise Aseptic meningitis – initial headache, stiffness of neck, pleocytosis of Cerebro spinal fluid 11/28/2010 Dr.T.V.Rao MD 32 Clinical Manifestations : Complicated clinical manifestations One serotype can result in many kinds of clinical manifestations One clinical type can be caused by many serotypes Clinical manifestations vary greatly in different patients Incubation period: 7-13 days(2-28d) Clinical Manifestations Weil’s syndrome is said to be present when the following clinical feature are present: : Weil’s syndrome is said to be present when the following clinical feature are present: Altered sensorium Acute renal failure Myocarditis and hypotension Pulmonary hemorrhage Features of acute hepatic failure Weil’s Syndrome : Weil’s Syndrome Weil's syndrome is a severe form of Leptospirosis that causes a continuous fever, stupor, and a reduction in the blood's ability to clot, which leads to bleeding within tissues. Blood tests reveal anaemia. By the third to sixth day, signs of kidney damage and liver injury appear. Kidney abnormalities may cause blood in the urine and painful urination. Liver injury tends to be mild and usually heals completely. 11/28/2010 Dr.T.V.Rao MD 35 Hepatitis - Leptospirosis : Hepatitis - Leptospirosis Hepatitis is the frequent complication Elevation of serum creatine phosphilipae enzyme raise differentiates from Viral hepatitis where the enzyme is not raised 11/28/2010 Dr.T.V.Rao MD 36 Renal manifestations : Renal manifestations Some form of renal involvement is invariable in Leptospirosis. It usually occurs as asymptomatic urinary abnormality in the form of mild proteinuria with few casts & cells in the urine. Severe renal involvement in the form of acute renal failure, (which occurs in icteric Leptospirosis) is rare. 11/28/2010 Dr.T.V.Rao MD 37 Nephritis - Leptospirosis : Nephritis - Leptospirosis Kidney involvement in animals produce chronic disease of the kidney and the infected animal starts shedding large number of Leptospira and main source of environmental contamination of bacteria and results I human infections Human urine also contain Spirochetes in the second and third week of infection 11/28/2010 Dr.T.V.Rao MD 38 Presenting with Jaundice is significant and Important, Serious Manifestation : Presenting with Jaundice is significant and Important, Serious Manifestation 11/28/2010 Dr.T.V.Rao MD 39 May present with Major Complications : May present with Major Complications Nephritis Hepatitis. Manifestations in eye Muscular lesions Many infections are mild and subclinical 11/28/2010 Dr.T.V.Rao MD 40 Ocular manifestations : Ocular manifestations Conjunctival suffusion / hemorrhage Late complication Anterior uveal tract inflammation Iritis / Iridocyclitis / chorioretinitis occurs 2 weeks – 1 yr (6 months) 11/28/2010 Dr.T.V.Rao MD 41 Pulmonary manifestations : Pulmonary manifestations Manifested in most cases through cough & chest pain and in few cases by hemoptysis. Severe involvement leading to respiratory failure does not occur in anicteric leptospirosis 11/28/2010 Dr.T.V.Rao MD 42 Slide 43: Clinical Manifestations Type of pulmonary hemorrhage 1 Type of mild hemorrhage Cough and hemoptysis A little bit of moist rale can be heard Dot-like or small nodular densities in chest X-ray Prognosis is fine if treatment is given in time COMPLICATIONS can be Life Threat : COMPLICATIONS can be Life Threat Azotemia Oliguria Hemorrhage Purpura Hemolysis Gastrointestinal bleeding Hypoprothrombinemia and Thrombocytopenia Differential Diagnosis : Differential Diagnosis Influenza Meningitis (encephalitis) Viral hepatitis Rickettsiosis Typhoid fever Septicemia Toxoplasmosis Legionnaire’s disease If with jaundice during or after an acute febrile illness, Malaria,septicemia, alcoholic hepatitis and typhoid fever Leptospirosis High Risk Situations. : Leptospirosis High Risk Situations. High Risk Situations. Swimming and scuba diving. Kayaking and canoeing. Sailing, windsurfing, fishing and skiing. Caving and underground exploration. Cleaning and jetting operations. Animal handling, control and management. 11/28/2010 Dr.T.V.Rao MD 46 Medical professional’s GuidanceLeptospirosis : Medical professional’s GuidanceLeptospirosis The infection is extremely easy to miss in initial stages; often the symptoms are misdiagnosed as influenza, viral illness or Pyrexia of unknown origin. Patients often ignore the significance of their symptoms unless prior education. To allow for correct diagnosis the patient must inform of having any potential or prior contact with affected areas. Other Facts onLeptospirosis : Other Facts onLeptospirosis An infection from one strain will provide immunity but only to that strain. Exposure to other strains will still cause infection. It is usual for more than one strain to exist within a specific population of infected animals. Immunity to one type is no great advantage to reducing your risk Laboratory Diagnosis : Laboratory Diagnosis Specimens 1 Blood to be collected in a heparin tube 2 CSF, Tissues Microscopic examination 3 Urine to be collected with great care to avoid contamination 4 Serum for agglutination tests 11/28/2010 Dr.T.V.Rao MD 49 Laboratory Diagnosis : Laboratory Diagnosis Laboratory diagnostic tests are broadly divided into two categories via, direct evidences (isolation of organism or demonstration of leptospires or amplification of specific fragment of leptospiral DNA) and indirect evidences (detection of antibodies to leptospires). 11/28/2010 Dr.T.V.Rao MD 50 Laboratory Diagnosis : Laboratory Diagnosis Alternatively, the different methods used in the laboratory can be categorized into bacteriological, microscopic, immunological/serological and molecular techniques. 11/28/2010 Dr.T.V.Rao MD 51 Diagnosis : Diagnosis Direct visualization of leptospires in blood (early phase) or urine (late phase) by dark field microscopic examination Low sensitivity (40.2%) and specificity (61.5%) Need special media (Fletcher's, Ellinghausen's, polysorbate 80) Takes 2-3 weeks to be positive IgM antibodies appear in late phase (5-7 days) Microscopic agglutination test (MAT), ELISA Titer >1:100 helps, but fourfold rise in titer is diagnostic (need convalescent sample) Microscopic Agglutination test : Microscopic Agglutination test Serial dilutions of patients sera are reacted with live suspensions of leptospiral serovars The MAT is ready by dark- field microscopy Tightly agglutinated clumps of leptospires are seen in cases of positive sera The end point is the highest dilution of serum at which 50% agglutination occurs The end point is determined by presence of approximately 50% free, unagglutinated leptospires compared to the control suspension Considerable effort is required to reduce the subjective effect of observer variation, even within laboratories. 11/28/2010 Dr.T.V.Rao MD 53 Microscopic Agglutination TestMAT : Microscopic Agglutination TestMAT The MAT is a complex test to control, perform and interpret. Live cultures of all serovars required to be tested have to be maintained The range of antigens used should include all locally common serovars Cut-off depends on prevalence of antibodies in the population Paired sera (at 2 weeks interval) are required to confirm a diagnosis with certainty 11/28/2010 Dr.T.V.Rao MD 54 Serological testsMAT : Serological testsMAT Microscopic agglutination test (MAT) is the benchmark test for serodiagnosis of leptospirosis. It is complex and time consuming. But it is an invaluable tool not only for diagnosis, but for epidemiology and serological characterization of leptospiral isolates. 11/28/2010 Dr.T.V.Rao MD 55 Culturing of Leptospira : Culturing of Leptospira Leptospira grows best under aerobic conditions at 280 to 300c best demonstrated in Semisolid agar media Optimal Media Fletchers Media Stuarts Media Optimal growth after 1 – 2 weeks 11/28/2010 Dr.T.V.Rao MD 56 IgM ELISA : IgM ELISA Use broadly reacting antigen Serogroup cannot be identified Positive earlier than MAT Ready made reagents with long shelf-life Need ELISA reader and washer. Many commercial kits are now available to detect IgM antibodies by plate ELISA e,g. Serion classic, Panbio 11/28/2010 Dr.T.V.Rao MD 57 Early and Prompt Diagnosis is Highly Essential : Early and Prompt Diagnosis is Highly Essential The development of simpler, rapid assays for diagnosis has been based largely on the recognition that early initiation of antibiotic therapy is important in acute disease but also on the need for assays which can be used more widely. 11/28/2010 Dr.T.V.Rao MD 58 Monitoring of the following laboratory parameters is essential: : Monitoring of the following laboratory parameters is essential: WBC and platelet counts Blood urea and serum creatinine Serum electrolytes Electrocardiogram for Myocarditis Serum Amylase for pancreatitis Emerging Trends in Molecular Diagnostic Methods : Emerging Trends in Molecular Diagnostic Methods Several PCR-based DNA fingerprinting methods have become popular and are being used routinely for characterization of leptospires. Random amplified polymorphic DNA (RAPD) fingerprinting, arbitrarily primed PCR (APPCR), single nucleotide polymorphism of specific PCR products are some of the examples. REP-PCR (repetitive extragenic PCR) and FAFLP (fluorescent amplified fragment length polymorphism) are recent methods in the characterization of leptospires. 11/28/2010 Dr.T.V.Rao MD 60 Epidemiology : Epidemiology Leptospirosis causes several animal infections Most wide spread zoonotic infection in Nature Human infections are accidental associated with contamination of water, other materials contaminated with excreta and animal flesh. Animal carriers often excrete up to 100million Leptospirosis per ml of urine LeptospirosisEpidemiology : LeptospirosisEpidemiology Leptospires are transmitted to incidental hosts by direct and indirect contact. Direct contact (host to host) is via urine, body secretions, Tran placental and thru the milk. Indirect contact (via urine) in water, on bedding or environmental contaminated products 11/28/2010 Dr.T.V.Rao MD 62 How Man gets Infected : How Man gets Infected Water the great source Drinking Swimming Bathing, as the urine of Rodents chronically infected contaminate water sources Children get infected when in contact with infected Dogs 11/28/2010 Dr.T.V.Rao MD 63 Control of Leptospirosis : Control of Leptospirosis Rodent control is most important. Human’s should avoid contact with water contaminated with animal contact. 11/28/2010 Dr.T.V.Rao MD 64 Injection Crystalline penicillin is the drug of choice in treating weil’s disease because : Injection Crystalline penicillin is the drug of choice in treating weil’s disease because It is a leptospiral disease Organism is uniformly sensitive to penicillin No resistance against penicillin is reported so far It is mostly without any undesirable side effects Earlier the treatment started, better is the outcome Medications that may be routinely prescribed in uncomplicated weils : : Medications that may be routinely prescribed in uncomplicated weils : Acetaminophen 650 mg orally SOS Doxycycline 100mg twice daily orally for seven days OR Tetracycline 500mg 6 hourly OR Ciprofloxacin 500mg BID Frusemide 40mg IV q 12hrly in case of impending renal failure 11/28/2010 Dr.T.V.Rao MD 66 Chemoprophylaxis : Chemoprophylaxis Doxycycline 200 mg orally once a week is simple effective measure. When heavy exposure is anticipated 11/28/2010 Dr.T.V.Rao MD 67 LeptospirosisPrevention : LeptospirosisPrevention Elimination of carrier Vaccination for dogs Protection is serovar-specific Current vaccination is for 3 sero types and is considered very effective Past vaccination was for 2 sero types which are no longer as important. The past vaccine was not as pure as current vaccines and was commonly associated with vaccine allergic reactions…. Prevention : Prevention Rodent control measures Immunization of animals with killed vaccines short-lived, requires boosters Protective clothing, footwear Burning canefield prior to harvest (young shoots can cut hands) Doxycycline prophylaxis for high-risk workers (Takafugi ET, NEJM 1984) The following statements regarding prognosis of Weil’s disease are true: : The following statements regarding prognosis of Weil’s disease are true: Temperature falls by lysis within 3-4 days of treatment Temperature may rise again in the anicteric form Admission to MICU and close observation are mandatory If untreated mortality in weil’s syndrome is 15-20% Those who recover do so with residual complications Medical professional’s should be cautious Leptospirosis : Medical professional’s should be cautious Leptospirosis “The infection may progress rapidly to fatal septicemic multisystemic failure or remain as a barely detectable subclinical illness. There is no reliable method to identify the final route of the infection from the initial stage of the disease, and all cases must be treated as potentially life-threatening.” New Vaccine trails - Leptospira : New Vaccine trails - Leptospira 11/28/2010 Dr.T.V.Rao MD 72 ICMR contributes to Knowledge on Leptospirosis : ICMR contributes to Knowledge on Leptospirosis The Regional Medical Research Centre (ICMR), Port Blair is the National Leptospirosis Reference Centre of India and WHO Collaborating Centre for Diagnosis, Research, Reference and Training in Leptospirosis. It maintains one of the largest Leptospira repositories in the world and is the only facility in India for serological and genetic typing of Leptospira. 11/28/2010 Dr.T.V.Rao MD 73 Slide 74: Programme created by Dr.T.V.Rao MD for benefit of Medical and Paramedical Professionals , and Students Email firstname.lastname@example.org 11/28/2010 Dr.T.V.Rao MD 74 You do not have the permission to view this presentation. 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