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  1. 1. Leptospirosis Dr.T.V.Rao MD
  2. 2. Leptospirosis - Zoonosis <ul><li>Leptospirosis is an acute anthropo-zoonotic infection of worldwide significance caused by spirochaete 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 behavioral and occupational habits of human beings can be the determinants of incidence and prevalence of the disease. </li></ul>
  3. 3. What is leptospirosis? <ul><li>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.. </li></ul>
  4. 4. Leptospirosis – A Major Zoonotic Infection <ul><li>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. </li></ul>
  5. 5. Animals spread Leptospirosis <ul><li>Rats, Mice, Wild Rodents, Dogs, Swine, Cattle are principle source of infection </li></ul><ul><li>The above animals excrete Leptospira both in active infection and Asymptomatic stage </li></ul><ul><li>The Leptospira survive and remain viable for several weeks in stagnant water. </li></ul>
  6. 6. What causes Leptospirosis <ul><li>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. </li></ul>
  7. 7. Scientific Beginning <ul><li>It was first described by Adolf Weil in 1886 when he reported an &quot;acute infectious disease with enlargement of spleen , jaundice and nephritis &quot;. Leptospira was first observed in 1907 from a post mortem renal tissue slice. [2] </li></ul>
  8. 8. Pathogenic strains x Non pathogenic Leptospirosis <ul><li>There are several species of Leptospira only few are pathogenic to Humans, rest to some Animals and Many in Nature as saprophytes </li></ul><ul><li>Leptospira Interrogans is Pathogenic there are 200 serovars. </li></ul><ul><li>Leptospira biflexa Non Pathogenic there are 60 serovars </li></ul><ul><li>Further classifications are made on shared antigens </li></ul>
  9. 9. Genomic based classification <ul><li>DNA – DNA hybridization studies proved more specific </li></ul><ul><li>The traditional serologic classification has limitations at Molecular level, but useful at Epidemiological studies. </li></ul>
  10. 10. Morphology <ul><li>The Leptospira appear tighly coiled thin flexible Spritochetes 5 – 15 microns long. </li></ul><ul><li>Fine spiral of 0.1 – 0.2 microns </li></ul><ul><li>One end appears bent forms a hook. </li></ul><ul><li>Actively motile </li></ul><ul><li>Seen best with dark field Microscopy. </li></ul>
  11. 11. Greater Understanding with Electron Microscopy <ul><li>Electron Microscopy show thin axial filament and a delicate membrane </li></ul><ul><li>In dark field it may appear as chain of miniature cocci. </li></ul>
  12. 12. Comparative Morphology of Spritochetes
  13. 13. Culturing of Leptospira <ul><li>Leptospira grwos best under aerobic conditions at 28 0 to 30 0 c best demonostrated in Semisolid agar media </li></ul><ul><li>Optimal Media </li></ul><ul><li>Fletchers Media </li></ul><ul><li>Stuarts Media </li></ul><ul><li>Optimal growth after 1 – 2 weeks </li></ul>
  14. 14. Growth requirements <ul><li>Leptospira derive energy from oxidation of long chain fatty acids, and cannot use or carbohydrates or amino acids as major energy source. </li></ul>
  15. 15. Antigenic structure <ul><li>All isolates of L.inttterogans from different parts of the world are serologically related and exhibit cross reactions in serologic tests. </li></ul><ul><li>Overlapping of Antigens do occur in different species. </li></ul><ul><li>Outer envelop contains large amount of Lipopolysaccharides ( LPS ) </li></ul><ul><li>Antigenic structure varies from one strain to other </li></ul><ul><li>This variation forms the basis of serologic classification </li></ul>
  16. 16. Genome of Leptospira <ul><li>L. interrogans serogroup Icterhaemorrhagiae consists of a 4.33 megabase large chromosome and a 359 kilobase small chromosome, totaling 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 spirochaete ( Treponema palladium and Borrelia burgdorferi ), though some similar genes are visible (CHGC, 2004). </li></ul>
  17. 17. Pathogenesis <ul><li>Leptospira are present in the water bodies </li></ul><ul><li>Enter through breaks in the skin ( cuts and abrasions ) and mucous membranes </li></ul><ul><li>Enters through Mouth – Nose – Conjunctive </li></ul><ul><li>Rarely enters though ingestion. </li></ul><ul><li>Incubation period 1 – 2 weeks </li></ul><ul><li>When multiples blood stream produces fever. </li></ul><ul><li>May establish organ involvement in Kidney and Liver, </li></ul><ul><li>May produce hemorrhage and necrosis in the tissues and initiates dysfunction of these organs </li></ul>
  18. 18. Sequence of Leptospira Infection
  19. 19. May present with <ul><li>Jaundice </li></ul><ul><li>Hemorrhage </li></ul><ul><li>Nitrogen retention </li></ul><ul><li>The Illness is Biphasic with initial temperature when the second phase comes with raise of IgM titers raise </li></ul><ul><li>Aseptic meingitis – initial headache, stiffness of neck, pleocytosis of Cerebro spinal fluid </li></ul>
  20. 20. Presenting with Jaundice is significant and Important, Serious Manifestation
  21. 21. May present with Major Complications <ul><li>Nephritis </li></ul><ul><li>Hepatitis. </li></ul><ul><li>Manifestations in eye </li></ul><ul><li>Muscular lesions </li></ul><ul><li>Many infections are mild and subclinical </li></ul>
  22. 22. Weil’s Syndrome <ul><li>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 anemia. 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. </li></ul>
  23. 23. Hepatitis - Leptospirosis <ul><li>Hepatitis is the frequent complication </li></ul><ul><li>Elevation of serum creatine phosphilipae enzyme raise differentiates from Viral hepatitis where the enxyme is not raised </li></ul>
  24. 24. Nephritis - Leptospirosis <ul><li>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 </li></ul><ul><li>Human urine also contain Spirochetes in the second and third week of infection </li></ul>
  25. 25. Early and Prompt Diagnosis is Highly Essential <ul><li>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. </li></ul>
  26. 26. Laboratory Diagnosis <ul><li>Specimens </li></ul><ul><li>1 Blood to be collected in a heparin tube </li></ul><ul><li>2 CSF, Tissues </li></ul><ul><li>Microscopic examination </li></ul><ul><li>3 Urine to be collected with great care to avoid contamination </li></ul><ul><li>4 Serum for agglutination tests </li></ul>
  27. 27. Culturing Leptospira <ul><li>Blood and Urine be cultured in Fletcher’s semisolid agar or other media chemically defined protein-free media for the growth of leptospires have been proposed. In order to obtain the desired rapid and abundant growth of organisms necessary for the efficient production of vaccines, it has been necessary to supplement such media with a source of fatty acids, </li></ul>
  28. 28. Serology <ul><li>Agglutinating antibodies raise to very high titers </li></ul><ul><li>1 : 10,000 or higher </li></ul><ul><li>occurs 5 – 10 weeks after onset of infection </li></ul>
  29. 29. Serology - ELISA <ul><li>Several Immunoassays are available as commercial kits </li></ul><ul><li>Detection of IgM and razing titers of IgG will guide in association with clinical history will help in Diagnosis </li></ul>
  30. 30. Treatment <ul><li>Antibiotic of choice is Benzyl Pencillin given by injection in doses of 5 mega units in a day, for 5 days. </li></ul><ul><li>If the patients are genuinely hypertensive to Pencillin opted with Erythromycin 250mgs four times a day for a period of 5 days. </li></ul>
  31. 31. Treatment - Other alternatives <ul><li>The leptospirosis can be effectively treated with </li></ul><ul><li>Doxycycline </li></ul><ul><li>Ampicillin </li></ul><ul><li>Amoxicillin </li></ul><ul><li>Severe patients need administration Intravenous Pencillin or Amoxcillin </li></ul>
  32. 32. Epidemiology <ul><li>Leptospirosis causes several animal infections </li></ul><ul><li>Most wide spread zoonotic infection in Nature </li></ul><ul><li>Human infections are accidental associated with contamination of water, other materials contaminated with excreta and animal flesh. </li></ul><ul><li>Animal carriers often excrete upto 100million leptospirosis per ml of urine </li></ul>
  33. 33. Epidemiology - Occupation <ul><li>Certain occupational groups such as agriculture workers in rice and cane fields, miners and sever cleaners are potential victims </li></ul>
  34. 34. How Man gets Infected <ul><li>Water the great source </li></ul><ul><li>Drinking </li></ul><ul><li>Swimming </li></ul><ul><li>Bathing, as the urine of Rodents chronically infected contaminate water sources </li></ul><ul><li>Children get infected when in contact with infected Dogs </li></ul>
  35. 35. Control of Leptospirosis <ul><li>Rodent control is most important. </li></ul><ul><li>Human’s should avoid contact with water contaminated with animal contact. </li></ul>
  36. 36. Chemoprophylaxis <ul><li>Doxycycline 200 mg orally once a week is simple effective measure. When heavy exposure is anticipated </li></ul>
  37. 37. Vaccination in humans <ul><li>Vaccination for humans is justified where they cannot be separated from animal sources or where the animals cannot be immunized successfully </li></ul><ul><li>Necessity of human vaccinated will arise where people live and work in proximity to rodents in wet, tropical conditions, in wet rice planting and harvesting, in military operations, or working in sewers. </li></ul><ul><li>Yet no universally accepted vaccine is available for humans </li></ul>
  38. 38. Vaccination of Animals <ul><li>Vaccinating animals have a dual purpose </li></ul><ul><li>1 Protecting animals </li></ul><ul><li>2 Protecting humans who may contract leptospirosis from them </li></ul><ul><li>It is probably true as that immunization of animals will prevent leptospirosis in people in contact with them. </li></ul><ul><li>It proved true in 1980 when extensive vaccination of dairy cows in New Zealand lead to marked decreased incidence in Humans. </li></ul><ul><li>Animals immunized experimentally with polysaccharide derived from Leptospira LPS linked to diphtheria Toxoid were protected against challenges </li></ul><ul><li>Several other vaccines in use to suit local needs. </li></ul>
  39. 39. New Vaccine trails - Leptospira
  40. 40. Created for Health awareness on Leptospirosis Dr.T.V.Rao MD Email [email_address]