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  1. 1. Filarial Nematodes Filariasis Dr Kamran Afzal Asst Prof Microbiology
  2. 2. Nematodes <ul><li>Nematodes </li></ul><ul><li>Round worms; appear round in cross section, they have body cavities, a straight alimentary canal and an anus </li></ul><ul><li>Tissue </li></ul><ul><ul><li>Trichinella spiralis </li></ul></ul><ul><ul><li>Dracunculus medinensis </li></ul></ul><ul><ul><li>Toxocara canis </li></ul></ul><ul><ul><li>Toxocara cati </li></ul></ul><ul><li>Intestinal </li></ul><ul><li>Ascaris (roundworm) </li></ul><ul><li>Trichuris (whipworm) </li></ul><ul><li>Ancylostoma (hookworm) </li></ul><ul><li>Necator (hookworm) </li></ul><ul><li>Enterobius (pinworm or threadworm) </li></ul><ul><li>Strongyloides </li></ul><ul><li>Blood and tissue </li></ul>
  3. 3. Filarial nematodes (Blood and tissue) <ul><li>Genus Wuchereria Species W. bancrofti </li></ul><ul><li>Genus Brugia Species B. malayi </li></ul><ul><li>Species B. timori </li></ul><ul><li>Genus Loa Species L. loa </li></ul><ul><li>Genus Mansonella Species M. ozzardi </li></ul><ul><li>Genus Dipetelonema Species D. perstans Species D. streptocerca </li></ul><ul><li>Genus Onchocerca Species O. volvulus </li></ul>
  4. 4. Insect Vectors
  5. 5. Terms to Know… <ul><li>Filariasis: is a parasitic disease caused by roundworms </li></ul><ul><li>Elephantiasis: is a disease that is characterized by the thickening of the skin and underlying tissues, especially in the legs and genitals </li></ul><ul><li>Lymph Edema: Is a condition of localized fluid retention caused by a compromised lymphatic system </li></ul>
  6. 6. Elephantiasis <ul><li>A debilitating disease </li></ul><ul><li>Abnormal accumulation of watery fluid in the tissues causing severe swelling </li></ul><ul><li>Skin usually develops a thickened, pebbly appearance and may become ulcerated and darkened </li></ul>
  7. 7. Epidemiology <ul><li>Source of infection: Humans harbor microfilariae in the blood stream </li></ul><ul><li>Distribution: Filariasis of W. bancrofti is world-wide distribution, while filariasis of B. malayi is in Asia </li></ul>
  8. 8. Geographic Range <ul><li>Lymphatic filariasis occurs in the tropics of India, Africa, Southern Asia, the Pacific, and Central and South America. </li></ul>
  9. 9. Morphology - Adult <ul><li>Adults 2-10 cm long </li></ul><ul><li>100 – 300 um in breadth </li></ul><ul><li>Thread Like </li></ul><ul><li>Small mouth </li></ul><ul><li>No buccal cavity </li></ul><ul><li>Cylindrical oesophagus </li></ul><ul><li>Separate sexes </li></ul><ul><li>Viviparous </li></ul><ul><li>Need a second host for the development of larvae </li></ul>
  10. 10. Morphology - Larvae <ul><li>Immature Larvae (Microfilariae) </li></ul><ul><ul><li>50-300 um </li></ul></ul><ul><ul><li>Sheath </li></ul></ul><ul><ul><li>Arrangement of column of nuclei </li></ul></ul>
  11. 11. Morphology - W. bancrofti <ul><li>W. bancrofti is sexually dimorphic </li></ul><ul><li>The adult male worm is long and slender, between 4 to 5 cm in length, a tenth of a centimeter in diameter, and has a curved tail </li></ul><ul><li>The female is 6 to 10 cm long, and three times larger in diameter than the male </li></ul>
  12. 12. Morphology - B. malayi <ul><li>Microfilariae are sheathed, and about 200 to 275 µm </li></ul><ul><li>Not much is known about the adult worms, as they are not often recovered </li></ul><ul><li>B. malayi microfilariae are slightly smaller than those of W. bancrofti </li></ul><ul><li>One distinctive feature of B. malayi is that the microfilarial nuclei extend to the tip of the tail </li></ul>
  13. 16. Life Cycle <ul><li>Biohelminth: Intermediate hosts (vector) are mosquitoes, bancroftian filaria is transmitted by Culex in which the larval development takes 10-14 days, the development of malayan filaria in Anopheles sinensis, requires 6-6.5 days </li></ul><ul><li>Infective stage: Filariform larva (L3) </li></ul><ul><li>Infective route: By skin (the wound bitten by mosquito) </li></ul>
  14. 17. <ul><li>Site of inhabitation: lymphatic tissue </li></ul><ul><li>Life span: 4-10 years </li></ul><ul><li>Microfilariae may survive 1-3 months </li></ul><ul><li>Nocturnal periodicity : The microfilariae present in the peripheral blood during daytime is very low in density. The number of microfilariae gradually increases from evening to midnight </li></ul>
  15. 18. Periodicity <ul><li>Nocturnal </li></ul><ul><ul><li>W. bancrofti </li></ul></ul><ul><ul><li>B. malayi </li></ul></ul><ul><ul><li>B. timori </li></ul></ul><ul><li>Diurnal </li></ul><ul><ul><li>L. loa </li></ul></ul><ul><li>Subperiodic </li></ul><ul><ul><li>Some strains of </li></ul></ul><ul><ul><li>W. bancrofti and B. malayi </li></ul></ul><ul><li>Aperiodic </li></ul><ul><ul><li>Mansonella </li></ul></ul>
  16. 19. Intermediate Host <ul><li>W. bancrofti is transmitted by Culex, Aedes, and Anopheles species </li></ul><ul><li>B. malayi is transmitted by Anopheles and Mansonia species </li></ul>Anopheles Aedes Culex Mansonia
  17. 20. Definitive Host <ul><li>Humans are the definitive host </li></ul><ul><li>There are no known reservoirs for W. bancrofti </li></ul><ul><li>B. malayi has been found in macaques, monkeys, cats and civet cats </li></ul>
  18. 21. Organ Distribution <ul><li>Adults </li></ul><ul><ul><li>Lymphatics </li></ul></ul><ul><ul><ul><li>W. bancrofti </li></ul></ul></ul><ul><ul><ul><li>B. malayi </li></ul></ul></ul><ul><ul><ul><li>B. timori </li></ul></ul></ul><ul><ul><ul><li>L. loa </li></ul></ul></ul><ul><ul><li>Skin </li></ul></ul><ul><ul><ul><li>Onchocerca volvulus </li></ul></ul></ul><ul><ul><li>Deep tissues/serous cavities </li></ul></ul><ul><ul><ul><li>Mansonella ozardii </li></ul></ul></ul><ul><ul><ul><li>Dipetalonema perstans </li></ul></ul></ul>
  19. 22. Pathogenesis: Acute stage <ul><li>Maturing larvae and adults provoke strong inflammatory reaction </li></ul><ul><li>Acute symptoms are painful lymph node and lymph channel inflammation and swelling which is often accompanied by fever </li></ul><ul><li>Acute reactions are more pronounced (e.g. formation of abscesses) </li></ul>
  20. 23. Pathogenesis: Chronic stage <ul><li>Progressive chronic disease can lead to wide spread fibrosis and damage of lymphatic vessels, which can result in rupture and discharge of lymph into the urinary system (chyluria) or the scrotum </li></ul>
  21. 24. Pathogenesis: Chronic stage <ul><li>In men chronic infection often results in hydrocele, the swelling of the scrotum </li></ul><ul><li>No effects on fertility, but wide spread sexual disability </li></ul><ul><li>Profound effects on patients self esteem and family life </li></ul>
  22. 25. Pathogenesis: Chronic stage <ul><li>Dead filaria are especially potent in triggering inflammation, and episodes of fever, pain and acute inflammation </li></ul><ul><li>Secondary bacterial and fungal infections play an important role in acute episodes and chronic progression of the disease </li></ul>
  23. 27. Clinical Presentation <ul><li>Acute phase </li></ul><ul><li>Filarial fever </li></ul><ul><li>Acute lymphangitis </li></ul><ul><li>Acute lymphadenitis </li></ul><ul><li>Chronic disease </li></ul><ul><li>Hydrocoele </li></ul><ul><li>Chyluria </li></ul><ul><li>Lymphoedema </li></ul><ul><li>Elephantiasis </li></ul>
  24. 28. Elephantiasis
  25. 30. Clinical Features specific to Filarial type <ul><li>W. bancrofti </li></ul><ul><ul><li>1. Asymptomatic </li></ul></ul><ul><ul><li>2. Inflammatory - lymphangitis - arms 25%, legs 11% </li></ul></ul><ul><ul><ul><li>Epididimitis, 42% </li></ul></ul></ul><ul><ul><ul><li>‘ Filarial fevers’, orchitis, filarial abscess </li></ul></ul></ul><ul><ul><li>3. Obstructive - elephantiasis </li></ul></ul><ul><ul><ul><li>Chyluria </li></ul></ul></ul><ul><ul><ul><li>Hydrocoele </li></ul></ul></ul><ul><ul><li>4. Tropical pulmonary eosinophilia </li></ul></ul><ul><li>B. malayi </li></ul><ul><ul><li>Elephantiasis </li></ul></ul><ul><ul><li>Scrotal involvement not present </li></ul></ul>
  26. 31. Loasis (African eye worm) <ul><li>Localized pain/ itching </li></ul><ul><li>Calabar swellings </li></ul><ul><li>Complications </li></ul><ul><li>Emboli </li></ul><ul><li>Endomyocardial fibrosis </li></ul><ul><li>Renal disease </li></ul>
  27. 32. Identification Scheme
  28. 33. Sheathed Microfilariae Tail nuclei Absent Present W. bancrofti B. Malayi L. loa
  29. 34. Unsheathed Microfilariae Tail nuclei Absent Present M. ozzardi O. volvulus M. perstans M. streptocera
  30. 35. <ul><li>Presumptive diagnosis: depends on the symptoms, signs and history of living in endemic areas </li></ul><ul><li>Adults rarely found – on autopsy or a surgical operation </li></ul><ul><li>Confirmative diagnosis: depends on the demonstration of microfilariae </li></ul><ul><ul><li>First choice method is thick and thin blood smears, taking blood at night from 9pm-2am </li></ul></ul><ul><ul><li>Millipore membrane filtration is used for screening the patients or checking curative effect in the endemic areas with the low infective rate </li></ul></ul>Diagnosis
  31. 36. Diagnosis <ul><li>Demonstration of microfilariae in blood, or lymph (has to be done at midnight!) </li></ul><ul><li>Antibody and antigen capture assays (dip stick format) </li></ul><ul><li>Adult filariae can be detected in the scrotal lymph vessels of men with hydrocele by ultra sound </li></ul>
  32. 37. Diagnosis (other tests) <ul><li>PCR </li></ul><ul><li>Histopathology </li></ul><ul><li>Fine needle aspiration cytology </li></ul><ul><li>Lymphoscintigraphy </li></ul><ul><li>Ultrasonography </li></ul>
  33. 38. Prevention and Treatment <ul><li>Control of Vector </li></ul><ul><ul><li>Abolishing breeding sites </li></ul></ul><ul><ul><li>Larval and adult mosquito insecticides </li></ul></ul><ul><li>Avoiding mosquito bites </li></ul><ul><li>Treating Microfilariae, not adult worms </li></ul><ul><ul><li>Chemotherapy </li></ul></ul><ul><ul><ul><li>Diethylcarbamazine DEC (6mg/KgBW) </li></ul></ul></ul><ul><ul><ul><li>Ivermectin (400micrograms/KgBW) </li></ul></ul></ul><ul><ul><li>Other modalities </li></ul></ul><ul><ul><ul><li>Elastic stockings </li></ul></ul></ul><ul><ul><ul><li>Surgery </li></ul></ul></ul>
  34. 39. Proboscis of a mosquito containing filariform larvae
  35. 40. <ul><li>Eight Species of Filariae Parasitizing Humans </li></ul><ul><li>_______________________________________________________________________ </li></ul><ul><li>Species Site of inhabitation Vector Pathogenesis Distribution </li></ul><ul><li>_______________________________________________________________________ </li></ul><ul><li>W. bancrofti lymphatic tissues mosquito lymphatic damage worldwide </li></ul><ul><li>_______________________________________________________________________ </li></ul><ul><li>Brugia malayi lymphatic tissues mosquito lymphatic damage Asian </li></ul><ul><li>_______________________________________________________________________ </li></ul><ul><li>Brugia timor i lymphatic tissues mosquito lymphatic damage Island of timor ____________________________________________________________________ </li></ul><ul><li>Onchocerca subcutaneous; eye black fly river blindness Africa </li></ul><ul><li>volvulus </li></ul><ul><li>_______________________________________________________________________ </li></ul><ul><li>Loa loa subcutaneous deer fly skin swellings Africa </li></ul><ul><li>_______________________________________________________________________ </li></ul><ul><li>Dipetalonema subcutaneous midge indefinite Africa </li></ul><ul><li>streptocerca </li></ul><ul><li>_______________________________________________________________________ </li></ul><ul><li>Dipetalonema thoracic and midge indefinite Middle and </li></ul><ul><li>perstans abdominal cavities South America </li></ul><ul><li>_______________________________________________________________________ </li></ul><ul><li>Mansonella peritoneal cavity midge indefinite South America </li></ul><ul><li>ozzardi </li></ul>