LYMPHATIC FILARIASIS - A COMMON TROPICAL DISEASE

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INTRODUCTION:

            Filarial worms are nematodes that remain in subcutaneous tissues and lymphatics. Eight species infect human of which 4 are responsible for serious filarial infection. They are W. bancrofti, B. malayi, O.volvulus, L. loa. About 170 millions are infected world wide, transmitted by specific mosquitoes or arthropodes, a complex life cycle of larva in insects and adult worm in humans. The adult worms produce microfilaria which vary in size (200 – 250 mm long and
5-7 mm wide), may have loose sheath, when ingested by insect develop in 1-2 weeks. Adult worm survives for many years but microfilaria survives for 3-36 months. A rickettsia like bacteria Wolbachia has been seen intracellularly in cases of Brugia, Wuchereria, Mansonella and Onchocerca.

            Infection is established by repeated exposure to infective larvae. In natives of endemic areas the presentation is chronic debilitating whereas in travelers and  recent exposure it presents as acute manifestation.

CHARACTERISTIC OF FILARIASIS (LYMPHATICS):

            The three responsible parasites remain viable in lymphatic tissues for more than 2 decades.

EPIDEMIOLOGY:

1.      W. bancrofti: Widely distributed affecting 115 millions , found in Tropics and subtropics. Human is only definitive host.

?         In Tropic – the microfilariae are found more at night (nocturnal ) than day.

?         In subtropic specially Pacific islands – microfilarae are found throughout the day reaching maximum in afternoon.

?         Natural Vector Culex fatigen is urban areas and Anopheline or Aedian  in rural areas.

2.      B. malayi: Distributed in India, Indonesia, China, Korea, Japan, Philipines. Common nocturnal form is found in coastal rice fields but Subtropical form is found in forest areas.

3.      B. timori:  Found only in Indonesian archipelago.

PATHOGENESIS & PATHOLOGY:

The adult worms cause inflammatory damage to lymphatics. The worm remain in afferent lymphatic or lymphnode sinuses causing lymphatic dilatation and thickening. Plasma cell, eosinophils, macrophages infiltrate in and around the infected vessels associated with endothelial and connective tissue proliferation leading to lymphatic tortuosity and lymphatic valve damage or incompetence. The overlying skin develops lymphedema and chronics stasis with hard or brawny oedema. The direct effect of worm and inflammatory response of host produce filariasis. The granulomatous and proliferative inflammatory response precede total lymphatic obstruction. Lymphatic vessels remain patent till worm is alive. After death of the worm enhanced granulomatous reaction and fibrosis occur. 

CLINICAL FEATURES

The common presentations are Asymptomatic (Subclinical) micro filaremia, Hydrocele, Acute Adenolymphangitis (ADL), TPE and Chronic manifestations.

1.      Asymptomatic microfilaremia – In endemic areas of W. bancrofti and B. malayi though large number of microfilaria circulate in peripheral blood many may be asymptomatic. Some present with microscopic haematuria and/or protinuria, dilated or tortous lymphatic and scrotal lymphangiectasia (in men). Few progress to acute or chronic stage.

2.      ADL – High fever, lymphatic inflammation (lymphangitis, lymphadenitis) transient local oedema are presentation. Lymphangitis is retrograde from draining L.node becoming indurated and tender. Lymphnode is enlarged. Local thrombophlebitis may be associated. In both bancroftian and brugian variety upper and lower limbs are involved. In brugian filariasis local abscess usually form along lymphatics which bursts to skin. Genitals are usually affected by bancroftian manifested by funiculitis, epididymitis, orchitis.

In endemic areas another acute inflammatory syndrome occurs called dermatolymphangioadenitis (DLA) characterized by high fever, chill, myalgia, headache, edematous inflammatory plaques, vesicles, ulcers, hyperpigmentation, diagnosed as cellulites. History of trauma, burn, radiation, insect bite and chemical injury may be there.

3.      Chronic – Progressive lymphatic damage leads from transient pitting lymphedema to lymphatic obstruction and elephantiasis and brawny edema. Thickening of S.C. tissues, hyperkeratosis, fissuring of skin and hyperplastic changes occur, with superadded infection to these poor vascularized tissues.

In bancroftian filariasis involving genitalia leads to hydrocele, scrotal lymphoedema and elephantiasis. In retroperitoneal lymphatic obstruction increased renal lymphatic pressure leads to rupture of renal lymphatics producing chyluria, most marked in early morning urine.

Lymphedema may be classified:

Grade I           : Pitting, reversible in elevation

Grade II           : Nonpitting, not spontaneously reversible on elevation & loss of

   elasticity of skin

Grade III          : Elephantiasis with skin folds and pappules

4.      Manifestation of travelers and transmigrants to endemic area – After a number of bites by infected vector they develop acute lymphangitis, scrotal swelling, urticarie, localized angioedema. Epitrochlear , axillary , femoral , inguinal lymphadenitis with retrograde lymphangitis occur. Classically they are afebrile and symptoms short lived.

5.      Tropical pulmonary eosinophilia (T.P.E)

Distinct syndrome in some cases of lymphatic filariasis . Male are more effected. Seen in India, Pakistan, China, Brazil

Pathology: Symptoms are due to allergy and inflammation by lungs which clear the antigen and parasite. In some trapping of microfilaria in RE system cause hepatosplenomegaly and lymphadenopathy. The eosinophil enriched intraalveolar infiltration releases cytotoxic proinflammatory granular protein which mediate some pathology. Without successful treatment interstitial fibrosis leads to progressive pulmonary damage.

Clinical Features: With history of residing in endemic area, there is paroxysmal cough , wheeze  (nocturnal), weight loss, low grade fever, lymphadenopathy, high eosinophil count (> 3000/ml). Chest X-ray may be normal, increased bronchovascular marks, diffuse miliary or mottled opacities in middle and lower lungs. PFT shows restrictive abnormalities in most and obstructive defect in 50%. Serum IgE raised (10,000 to 100,000 ng/mL) and elevated antifilarial antibodies.

D/D : Asthma, LÖfflers syndrome, Allergic bronchopulmonary aspergillosis, Allergic granulomatosis with angitis (Churg-Strauss Syndrome), Systemic vasculitis (Pariarteritis nodosa, Wegner’s granulomatosis), Chronic eosinophilic pneumonia, Idiopathic eosinophilic syndrome.

H/O exposure, nocturnal wheeze, high antibody titre and response to DEC are distinguished points.

Treatment: DEC in a dose of 6 mg/kg daily for 14 days. Relapse may occur in 25% cases requiring retreatment.

6.      Others rare presentations may be Monoarthnitis (knee > Ankle), Endomyocardial fibrosis, Tenosinovitis, Thrombophlebitis and Nerve Paralysis

DIAGNOSIS:        

            Demonstration of parasites (Adult or microfilaria) though difficult is diagnostic.

1.      Detection of microfilaria in  Blood, hydrocele fluid and other body fluids under  Direct microscopy. For greater sensitivity: 

                                                              i.      Filtration through a polycarbonate cylinder (pore size 3 mm).

                                                            ii.      Centrifuge in 2% formalin (Knott’s Technique)

?         Timing of blood collection depends on periodicity

?         DEC provocation day test – 50-100 mg of DEC provoking microfilaria to circulation after 30-60 min.

2.      Antigen assay – In cases of cryptic (amicrofilaremic infections) and cases where microfilaria not demonstrated it is helpful.

For W. bancrofti – Antigen can be detected by ELISA or Rapid format immunochromatographic card test. Both are 96-100% sensitive and 100% specific.

For B. malayi – No test to detect antigen

3.      PCR (Polymerase chain reaction) based assay for DNA of W. bancrofti and B. malayi have developed which has greater specificity.

4.      Detection of adult worm in suspected cases examination of scrotum and breast using high frequency ultrasound with Doppler study may reveal, motile worm in dilated lymphatics (the typical movement is called filaria dance sign).

5.      Radionuclide lymphoscintigram of limbs- demonstrate widespread lymphatic abnormalities both in asymptomatic and clinical cases.

6.      Supportive diagnosis: Eosionophilia, elevated serum IgE and antifilatrial antibodies. (There is cross reactivity between filarial and other helminthtic antigen making interpretation a problem. Besides non-infected persons in endemic areas become sensitized to filarial antigen by exposure to infected mosquito bites).

DIFFERENTIAL DIAGNOSIS:

1.      Acute episode – Differentiate from : Thrombophlebitis, Infection, Trauma

2.      Chronic filarial lymphedema: Differentiate from Malignancy, Postoperative scaring, Trauma, Chronic oedematous states and Congenital lymphatic system abnormalities

TREATMENT

1.      DEC (Diethyl carbamazine) 6mg/kg daily for 12 days is treatment of choice for active lymphatic filariasis (micofilaremia, antigen positive, adult worm on USG). DEC is both macro and microfilaricidal.

?         Albendazole 400mg twice daily for 21 days is also macrofilaricidal.

2.      All Cases  of asymptomatic microfilaremia (W. bancrifti , B. malayi) should be treated to prevent lymphatic complications.

3.      ADL cases are to be treated symptomatically along with antibiotic.

4.      Asymptomatic adult worm carriers are to be treated with DEC.

5.      Chronic lymphatic manifestations – maintaining hygiene, secondary bacterial infection prevention, physiotherapy like other non filarial lymphedema (complex decongestive physiotherapy and complex lymphedema therapy) are accepted. Hydrocele needs repeated drainage or surgery. Drug treatment during active infection may show clinical improvement and reversal of lymphedema.

Some data  indicate that single dose of DEC of 6mg/kg or Ivermectin (150 mgm /kg)or combination of single dose of albendazole with DEC/Ivermectin have sustained microfilaricidal effect.

Side effect of DEC:

·               Fever, chill , arthralgia, headache, nausea, vomiting.

·               Severity of symptoms are related to number of circulating microfilaria, hypersensitivity reaction of antigens relased by dead or dying parasite or inflammatory reaction by lipopolysaccharides from intracellular Wolbachia.

Side effects of Ivermectin  - Similar to DEC

Dose 150mgm/kg

PREVENTION & CONTROL:

Avoidance of mosquito bite: but using  Insect repellent, Mosquito net, Impregnated bed nets. Prophylactic use of DEC

Community based intervention like Mass annual distribution of albendazole with DEC or Ivermectin to suppress microfilaria,  DEC forfified use  and Community education and clinical care are helpful.
 

CLINICAL FOCUS:

?               Filariasis (lymphatic) remains one of the most common debilitating disease in trophic & subtropic.

?               Long life span of the adult worm and presence of mosquito are responsible for non-eradication from human.

?               Microfilaria of all species are circulated in blood and sheathed. Most of them are nocturnal.

?               Lymphatic system is primarily involved leading to various presentations.

?               Genitalia are involved by W. bancrofti.

?               TPE is a common form of inflammatory allergic response in pulmonary lymphatics.

?               Demonstration of microfilaria and adult worm is diagnostic.

?               Newer diagnostic method like antigen assay, PCR based DNA assay are also specific.

?               Acute and chronic filariasis are to be differentiated from other common conditions

?               DEC is the only drug of choice for acute and chronic cases. Other drugs like Albendazole and Ivermectin alone or in combination are also micro and macro filaricidal.

M.C.Q

1.      Filarial worms are

a. Cestodes         b. Trematodes           c. Nematodes            d. Protozoa

2.      Microfilaria are usually

a. Diurnal             b. Nocturnal                c. Both                        d. None of these

3.      B.timori is found in

a. India                 b. China                      c. Korea                     d. Indonesia

4.      Local abscess along lymphatic seen in

a. Bancroftian filariasis                          b. Brugian filariasis

c. Both                                                      d. None of these

5.      Lymphedema in filariasis is

a. Pitting               b. Nonpitting              c. Both                        d. None of these

6.      In TPE the Eosinophil count is

a. >1000/ml          b. >2000/ml                 c. >3000/ml                 d. <3000/ml

7.      In TPE chest x-ray may show

a. Normal                                                 b. Milliary opacities  

c. Increased bronchovascular marks d. All of the above

8.      Newer diagnostic method for W. bancrofti are

a. Antigen detection by ELISA              b. PCR based DNA assay

c. Elevated Serum IgE                           d. All of the above 

9.      Drugs used for lymphatic filariasis

a. DEC                 b. Albendazole          c. Ivermectin               d. Any of the above

10.  Side effects during treatment are due to

a. Hypersensitivity reaction to released antigen         b. Inflammatory reaction by Wolbachia

c. Gastric irritation                                                          d. All of the above

ANSWER