1. Filariasis

2. Outline of presentation  History of Filariasis  Introduction  Classification  Epidemiology  Morphology  Life Cycle  Clinical Manifestations  Occult Filariasis  Tropical Pulmonary Eosinophilia

3. History  Existence recorded since Indian, Chinese and Egyptian times  Recorded origin of Lymphatic Filariasis seems to be unknown.  However, there are beliefs that the infection dates back to 2000BC.  The reasoning behind this belief is that there is a statue of Pharaoh Mentuhotep II with what appears to be swollen limbs, a characteristic of the disease (ASM).  Then in 600BC elephantiasis was described by doctors in the India region (NCBI).

4. Timeline  1863: Demarquay in Paris found microfilariae in hydrocele liquid of a Cuban.  1866: Wucherer found microfilariae in chyluria.  1872: Lewis found microfilariae in blood.  1877: Bancroft found a female adult filarial worm in the ulcer of lymph node of the arm.  1877: Manson found microfilariae in the stomach of blood sucked mosquito, = “birth” of medical entomology.  1879: Manson found microfilarial nocturnal periodicity.  1888: Sibthorpe found male adult worms.

5. Introduction  Widely spread disease caused by different species of filariae  The adults of filariae inhabit the lymphatics, subcutaneous tissue, deep connective tissue, peritoneal or thoracic cavity

6. Classification-habitat of adult worm. Lymphatic filariasis:  Wuchereria bancrofti.  Brugia malayi  Brugia timori Subcutaneous filariasis:  Loa Loa  Onchocerca volvulus  Mansonella streptocerca Serous cavity filariasis:  Mansonella ozzardi  Mansonella perstans.

7. Wuchereria bancrofti Sheath, no nuclei in the tip of the tail Brugia malayi Sheath, 2 distinct nuclei in the tip of the tail Loa loa Sheath, nuclei extending to the tip of the tail Onchocerca volvulus (skin) No sheath, no nuclei in the tip of the tail Mansonella perstans No sheath, nuclei extending to the tip of the tail Mansonella ozzardi No sheath, no nuclei in the tip of the tail Mansonella streptocerca (skin) No sheath, nuclei extending to the tip of the hooked tail

9.  Larvae known as microfilariae appear in the circulating blood or tissue fluids  W. bancrofti and B. malayi - most commonly responsible for lymphatic filariasis  Microfilariae circulate in peripheral blood once each day.  Mosquito is essential vector and intermediate host

10. Geographical distribution Epidemiology W. bancrofti - widely distributed throughout the tropics and subtropics. It is prevalent in Africa, Asia, and certain islands in the Pacific Ocean B. malayi -Malaysia, it occurs in India, Indonesia, New Guinea, Thailand, Vietnam, Korea, Japan and China In India along coastal areas; B.malayi in Orissa, Kerala, MP, Assam

12. Global scenario Epidemiology Population at risk: 1.2 Billion No. of countries: > 80 Mf carriers: 76 Million Diseased: 44 Million Hydrocele: 27 Million Lymphoedema: 16 Million

13. Filariasis problem in India India contributes about 40% of the total global burden and accounts for about 50% of the people at the risk of infection.] ]  A total of 553 million people are at risk of infection and there are approximately 21 million people with symptomatic filariasis and 27 million microfilaria carriers.  W. bancrofti is the predominant species accounting for about 98% of the national burden, widely distributed in 17 states and six union territories.  B. malayi is restricted in distribution, with decreasing trend. An overview of the traditional endemic foci shows a concentration of infection mainly around river basins and eastern and western coastal parts of India [Figure - 1].[19][Figure - 1][19]

15. Wuchereria bancrofti and Brugia malayi

17. Adult Worms Slender, thread-like Transparent,creamy white in color Male:- 2.5-4 cm x 0.1mm ; has a curved tail, Female:- 5-10 cm x 0.2mm; straight end Remain coiled together Viviparous and liberates sheathed embryos(Microfilaria)

18.  Microfilaria;- 177-296 µm in length, encased in a sheath with free endings.  Bluntly rounded anteriorly and tapers to a point posteriorly.  A large number of nuclei seen in the body are arranged in a column from head to the posterior Wuchereria bancrofti Brugia malayi Morphology -- Larva

19. Morphological differences W. bancroftiBrugia malayi SizeLarger, 244-296 by 5.3-7 µm Smaller, 177-230 by 5-6 µm ShapeCurves of body are natural, smooth Curves of body are rigid, 2ºkinks Cephalic spaceShorter (length is equal to or less than width) Longer (length is two times as long as width) Body nucleiEqual sized, clearly defined, countable Unequal sized, coalescing, uncountable Terminal nucleiNoTwo

21. Life cycle

22. Microfilariae Blood meal Microfilariae Take off sheath, migrate to thoracic muscles Sausage larvae Molt Infective larvae Adults Molt 2 times Lymphatics Molt Migrate to prosbocis Blood meal Infective larvae Peripheral blood Ovoviviparity Human stageMosquito stage

23.  Host: mosquitoes - intermediate host, human - final host  Location: lymphatic vessels and lymph nodes (inginal, scrotal and abdominal)  Infective stage: infective larvae  Transmission stage: microfilariae  Diagnostic stage: microfilariae Characteristics of life cycle

24. Different parasitic sites between the two species  W. bancrofti parasitizes in the superficial and deep lymphatic systems, including in the genitourinary lymphatic system;  B. malayi parasitizes in the shallow lymphatic system only, especially in the lymphatics of limbs Characteristics of life cycle

25. Nocturnal periodicity: No of microfilariae present greatest density at 10 p.m. to 2 a.m. Mechanism  For this phenomenon - still not clear.  It may be related to the change of oxygen tension in cerebral and the pulmonary vessels Characteristics of life cycle

26. Pathogenesis  Due to presence of adult worms in the L.node and vessels  Results from a complex interplay of the pathogenic potential of parasite, the immune response of the host, and external bacterial and fungal infections.

27. Pathogenesis Acute stage  Dilatation of the lymphatics /  Hyperplastic changes in the vessel endothelium /  Infiltration by lymphocytes, plasma cells and eosinophils / thrombus formation  Enlarged lymph nodes

28. Pathogenesis  Chronic lesion--the changes include granuloma formation, fibrosis, and permanent lymphatic obstruction  Repeated infections eventually result in massive lymphatic blockade  The skin and subcutaneous tissues become edematous, thickened, and fibrotic  Dilated vessels may rupture, spilling lymph into the tissue to cause lymphedema and elephantiasis

29. Causes of lymphatic obstruction  Mechanical blocking of the lumen by dead worms  Obliterative endolymphangitis  Obliterative excessive fibrosis of the lymphatic vessels  Fibrosis of afferent lymph nodes draining particular area.

30.  Asymptomatic amicrofilariaemic  Asymptomatic microfilariaemic  Acute manifestation  Obstructive (Chronic) lesions Clinical manifestations

31.  Asymptomatic amicrofilariaemic--in endemic areas, a proportion of population does not show microfilariae or clinical manifestation even though they have some degree of exposure to infective larva.  Laboratory diagnostic techniques are not able to determine whether they are infected or free Clinical manifestations

32.  Asymptomatic microfilariaemic- asymptomatic for months and years, though they have circulating microfilariae.  They are an important source of infection.  They can be detected by night blood survey and other suitable procedures Clinical manifestations

33.  Acute manifestation--during initial months and years, there are recurrent episodes of acute inflammation in the lymph vessel/node of the limb & scrotum that are consisting of filarial fever, lymphangitis, lymphadinitis, epididymitis, orchitis Clinical manifestations

34. Lymphangitis Lymphoedema

35.  Obstructive (Chronic) lesions--takes 10-15 years, main pathological change is lymph obstruction. The lymph circulation is disturbed and lymphedema occurs.  The affected limb feels soft at first and becomes fibrotic after extensive growth of connective tissue as elephantiasis develops. e.g. hydrocoele (40~60%), elephantiasis of scrotum, penis, leg, arm, vulva, breast, and chyluria Clinical manifestations

36. Penis Scrotum Hydrocoele

37. Leg

38. Arm

39. Chyluria and haematuria

40. Occult Filariasis  Microfilaria are absent.  Occult filariasis is due to hyper responsiveness to filarial antigens derived from mf.  Seen more in males.  Massive eosinophilia (30-80%)  Eosinophilic granulomas in affected organs (eosinophils surrounding microfilaria or its remnants)  Responds to DEC

41. Tropical Pulmonary Eosinophilia(TPE)  Manifestation of Occult filariasis  Marked increase in Serum IgE  Antibodies to filarial are present in high titre  Is a hypersensitivity reaction to Microfilariae  Microfilariae are usually not found in blood

42. Tropical Pulmonary Eosinophilia(TPE)  Patients present with  paroxysmal cough and wheezing,  low grade fever,  scanty sputum with occasional haemoptysis, adenopathy and increased eosinophilia.  X-ray shows diffused nodular mottling and interstitial thickening.

43. Lymphatic Filariasis Diagnostic Methods

44. Laboratory Diagnosis. Demonstration of microfilarae in the peripheral blood a. Thick blood smear: 2-3 drops of free flowing blood by finger prick method, stained with haematoxylin or Giemsa b. Membrane filtration method: 1-2 ml intravenous blood filtered through 3µm pore size membrane filter c. DEC provocative test (2mg/Kg): After consuming DEC, mf enters into the peripheral blood in day time within 30 - 45 minutes.

46. Characteristics of mf of W. bancrofti mf usually in blood 210-320um in length Loose sheath which when stained with Giemsa is pale pinky blue and does not stain well Nuclei are discrete and tail ends taper evenly No nuclei on the tip of the tail

47. Lab diagnosis cont...  Acridine orange microhaematocrit tube technique  A microhaematocrit tube containing acridine orange, heparin and EDTA is centrifuged  Parasites concentrated in the buffy coat and can be seen thru clear glass of the tube.  Acridine stains the DNA of the parasites and morphology including nuclear characteristics of the tail tip are seen by fluorescent microscopy.

48. Lab diagnosis  Immuno Chromatographic Test (ICT):Antigen detection assay can be done by Card test and through ELISA.  Specificity is near complete, sensitivity is greater than all other parasite detection assays,  will detect antigen in amicrofilaraemic as well as with clinical manifestations like lymphoedema, elephantiasis.

49. Haematology :Increase eosinophil count Ultrasonography: Ultrasonography can locate and visualize the movements of living adult worms of W.b. in the scrotal lymphatics of asymptomatic males with microfilaraemia. The constant thrashing movements described as “Filaria dance sign” can be visualized.

50. Lymphoscintigraphy: The structure and function of the lymphatics of the involved limbs can be assessed by lymphoscintigraphy after injecting radio-labelled albumin or dextran in the web space of the toes. The structural changes can be imaged using a Gamma camera. Lymphatic dilation & obstruction can be directly demonstrated even in early clinically asymptomatic stage of the disease. X-ray Diagnosis: X-ray are helpful in the diagnosis of Tropical pulmonary eosinophilia. Picture will show interstial thickening, diffused nodular mottling..

51. Treatment and prevention  The source of infection should be eradicated by mass survey and treatment  All person with microfilariae should be treated with diethylcarbamazine (DEC) which is the low toxicity but most effective drug. 200mg tid for seven days as one course. DEC added to table salt (3:1000) and distributed in endemic areas over a period of six months, results in great reduction of microfilaria in the blood stream  Elimination of vectors and protection of the people from mosquito bites are important to control filariasis

52. Chemotherapy of Filariasis Drugs effective against filarial parasites 1. Diethyl Carbamazine (DEC) 2. Ivermectin 3. Albendazole 4. Couramin compound Treatment of microfilaraemic patients may prevent chronic obstructive disease and may be repeated every 6 months till mf and/or symptoms disappears.

53. Diethyl Carbamazine (Hetrazan, Banocide, Notezine)  Mode of action: DEC do not have direct action of parasite but mediate through host immune system.  Very effective against mf (Microfilariacidal)  Effective against adult worms in 50% of patients in sensitive cases.  Dose: 6mg/Kg/12 days  Drug of choice in the treatment of TPE.

54. Ivermectin  Mode of action: Directly acts on mf and no action on adults.  Lowers mf level even in single dose of 200µg – 400µg/Kg body weight  No action on TPE  Drug of choice in Co-endemic areas of Onchocerciasis with LF.  Adverse reactions are lesser but similar to that of DEC  Microfilariae reappears faster than DEC

55. Albendazole  This antihelmenthic kills adult worms  No action on microfilariae  Dose: 400mg/twice day /2 weeks  With combination of DEC & Ivermectin, it enhances the action of the drugs.  It induces severe adverse reactions in hydrocele cases due to the death of adult worms.

56. Lymphatic Filariasis Control

57. Lymphatic Filariasis Control Programme The current strategy of filariasis control (Elimination) is based on: 1. Interruption of transmission 2. Control of Morbidity Interruption of the transmission can be achieved through: a. Chemotherapy b. Vector control An integrated programme is in place for the control of lymphatic filariasis. Earlier, vector control was the main method of control. There are three main reasons why filariasis never causes explosive epidemics 1. The microfilariae does not multiply in the vector 2. Infective larvae do not multiply in man 3. Life cycle of the parasite is relatively long (>15 )

58.  Case detection and treatment in low endemic areas are suitable for preventing transmission and controlling the disease.  In high endemic areas, Mass chemotherapy is the approach.  DEC medicated salt is also a form of Mass treatment using low dose of drug over a long period of time (1-2 gm /Kg of Salt).

59. Vector Control Vector control involves anti larval measures, anti adult measures, personal prophylaxis. An integrated method using all the vector control measures alone will bring about sustained vector control. I. Anti larval measures: 1. Chemical control a. Mosquito larvicidal oil b. Pyrosene oil c. Organo phosphorous compounds such as Temephos, Fenthion, 2. Removal of pistia plants 3. Minor environmental measures

60. Vector Control II. Anti adult measures: Anti adult measures as indoor residual spay using DDT, HCH and Dieldrin. Pyrethrum as a space spray is also followed. III. Personal Prophylaxis: Reduction of man mosquito contact by using mosquito nets, screening of houses, etc.

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