FILARIASIS & RELATED

INFECTIONS

Dr. SARTONO Sp PD
 Filariasis : infection caused by vector-borne tissue dwelling
nematodes called filariae.
D.o. species , adult filaria may dwell in subcutaneous tissues ,
blood vessels, lymphatics, connective tissues & serous
membrane.
Eight species infect humans , 4 responsible for serious
filarial infections i.e. Wuchereria Bancrofti , Brugia Malayi ,
Onchocerca volvulus , & Loa loa.
Filarial parasites :
- about 170 million persons infected worldwide
- transmitted by specific species of mosquitoes or other
arthropods
- have a complex life cycle ( infective larva stages carried by
insects & adult worms , resides in lymphatics or
subcutaneous tissues of human ).
 Microfilariae ( the offspring ) :
- 200 250 m long & 5-7 m wide ( d.o. species )
- may / may not be enveloped in a loose sheeth
- circulate in the blood or migrate through the skin
- to complete the life cycle , microfilariae are ingested by
arthropod vector & over 1-2 weeks new infective larvae
- adult worms live for many years ; microfilariae survive for
3 36 months
- Rickettsia-like endosymbiont Wolbachia found intracellu
larly in all stages of Brugia, Wuchereria, Mansonella &
Onchocerca & is viewed as possible target for antifilarial
chemotherapy.
Infection establised , with repeated, prolonged exposure to
infective larvae.
 Clinical manifestation develops slowy induce chronic disease
with possible long-term debilitating effects.
Based on nature, severity & timing , the clinical manifestation
of Px who are native to endemic areas ( undergo lifelong
exposure ) differs from those who are travellers or recently
moved to these areas.
More acute & intense in newly exposed individuals.
 LYMPHATIC FILARIASIS
- Caused by W. Bancrofti , B. Malayi , B. Timori
- Adult parasites reside in lymphatic channels or lymph nodes
may remain for 2 decades.

EPIDEMIOLOGY
W. Bancrofti affects 115 million people , throughout the
tropics & subtropics, including Asia, the Pacific Islands, Africa,
South America & the Caribbean basin.
Human the only definitive host
The subperiodic form is only in the Pasific Islands ;
elsewhere , W.bancrofti is nocturnally periodic.
( nocturnally periodic forms of microfilariae scarce in
peripheral blood by day & increase at night ;
 subperiodic form present in peripheral blood at all times &
reach maximum level in the afternoon.
Natural vectors for W.bancrofti :
- Culex fatigans in urban settings
- Anopheline or aedean in rural areas
Brugian Filariasis ( B.malayi ),
- occurs primarily in China, India, Indonesia, Korea, Japan,
Malaysia & Philippines.
- two forms : * nocturnal in areas of coastal rice field
* subperiodic in forests
B.malayi naturally infect cats & human
B.timori exist only on islands of the Indonesian archiphelago
 LIFE CYCLE
W. bancrofti, B. malayi, and B. timori are all acquired via the bite of
mosquitoes.
When mosquitoes bite humans, they deposit third-stage infective
larvae into the skin.
These larvae travel through the dermis and enter local lymphatic
vessels. Over a period of approximately nine months, these larvae
undergo a series of molts and develop into mature adult worms, which
range from 20 to 100 mm in length.
These adults reside in the lymphatics, generally several centimeters
from lymph nodes. They survive for approximately five years
(occasionally up to 12 to 15 years), during which time male and
females worms mate and produce microfilariae.
Female parasites can release more than 10,000 microfilariae per day
into the bloodstream. These microfilariae are also known as
embryonic or first-stage larvae, and measure approximately 200 to
300 m by 10 m.
 LIFE CYCLE
Mosquitoes, which bite infected individuals, can take
up these circulating microfilariae. Within the
mosquito, these embryonic larvae develop into
second then third stage larvae over a period of 10 to
14 days. The mosquito is then ready to bite and infect
a new human host, thereby completing the life cycle.
The interval between acquisition of infective larvae
from a mosquito bite and detection of microfilariae in
the blood is known as the prepatent period. This
interval is usually approximately 12 months in
duration.
 PATHOLOGY
Pathologic changes : due to inflamatory damage to lymphatics
, caused by adult worms & not by microfilariae.
Adult worms in afferent lymphatics or sinuses
lymphatic dilatation & thickening of vessel wall.
Infiltration of plasma cells, eosinophils & macrophages in /
around infected vessels , with endothelial & connective tissue
proliferation tortousity of lymphatics & damaged /
incompetent lymp valves lymph edeema & chronic-stasis
changes with hard & brawny edeema in the overlying skin.
These consequences due to :
- direct effect of the worms
- inflamatory response of the host to the parasite
granulamateous & proliferative process lymphatic
obstruction
 Its thought -> lymphatic vessels remains patent as long as the
worm remains viable & the death of worm granulomateous
reaction & fibrosis lymphatic obstruction compromised
lymphatic function ( despite collateralization ).

CLINICAL FEATURES
Most common asymptomatic / subclinical microfilaremia.
( hydrocele, acute adenolymphangitis / ADL, & chronic
lympangitis disease ).
In endemic areas of W.bancrofti & B.malayi , infected
individuals few overt clin. manifestations.
Cinically asymptomatic, microfilaremia subclinical disease
mic. hematuria , and or proteinuria, dilated/tortous lymphatics
and scrotal lymphangiectasia in men.
 ADL , is characterised by :
- high fever
- lymphangitis & lymphadenitis
- transient local edeema
- enlarged regional lymph nodes
- indurated & inflamed lymphatic channels
- thrombophlebitis
- in Brugian filariasis, local abscess may form along lymphatic
tract rupture to the surface
Lympadenitis & lymphangitis can involve upper & lower
extremities in bancroftian & brugian filariasis ; but genital
lymphatics involvement is associated with W.bancrofti infection
( funiculitis, epididymitis, scrotal pain & tenderness ).
 In endemic areas DLA ( Dermato Lymphangio Adenitis )->
syndrome :
- high fever
- chills
- myalgias
- headache
* edeemateous inflammatory plaques
* vesicle, ulcers, hyperpigmentation ( may be noted )
** DLA is often diagnosed as cellulitis.

If lymphatic damage progress transient lymphedema

lymphatic obstruction permanent changes elephantiasis
brawny edeema subcutaneous tissues thickening &
hyperkeratosis.
 Skin fissuring & hyperplastic changes may develop
superinfection of the poorly vascularized tissues.
In bancroftian filariasis genital involvement hydroceles
In advance stages scrotal lymphedema & scrotal
elephantiasis.
If retroperitoneal lymphatics obtruction occur increased
renal lymphatic pressure renal lymphatic rupture
chyluria usually intermittent & prominent in the morning
In travellers or transmigrant , after a number of infected
vectors bite , clinical manifestations develop over 3 6
months period.
Lymphadenitis of epitrochlear, axillary, femoral, inguinal
lymph nodes followed by retrogradely evolving
lymphangitis.
 Chronic Lymphedema
The World Health
Organization (WHO) has
developed a system to grade
the severity of lymphedema.
Grade I Pitting edema that
is reversible by elevating the
leg
Grade II Nonpitting
edema that does not reverse
with elevation of the
extremity
Grade III Severe swelling
with sclerosis and skin
changes
 Chronic Lymphedema
Chronic lymphatic disease can also
involve the genitalia, resulting in the
development of unilateral or bilateral
hydroceles.
Hydroceles can be larger than 30 cm
in diameter but are usually painless
unless complicated by bacterial
infection.
Localization of adult worms in the
lymphatics of the spermatic cord can
also lead to palpable thickening of
the cord.
Lymphatic filariasis of the ovary and
mesosalpinx has also been reported.
 DIAGNOSIS
Dx can be made by detection of the parasites difficult
Adult worm in lymphatic vessels & nodes inacessable
Microfilariae can be found in :
- blood
- hydrocele fluid
- other body fluid ( rare )
Microscopic examination of fluid may be :
- direct , for greater sensitivity
- concentration of parasites by a polycarbonate cylindrical
pore filter ( size 3 m ) or by
- centrifugation of fluid fixed in 2% formalin
Timing of blood collection critical ( d.o. periodicity of micro
filariae
Many infected indduals dont have microfilariae Dx difficult
 Assays for circulating antigen of W.bancrofti Dx
microfilaremic & cryptic ( amicrofilaremic ) infection
Commercially available tests :
- ELISA
- Rapid format immunochromatographic card test
- Both have sensitivities of 96-100 % & specificities approach
ing 100%
PCR based assay for DNA ( W.bancrofti & B.malayi )
In suspected lymphatic filariasis , examination of
- scrotum or
- female breast , by high frequency ultrasound in conjunction
with Doppler techniques identification of motile adult
worms within dilated lymphatics.
Worms may be visualized in lymphatics of the spermatic
cord ( in 80 % of infected men ).
 Filaria dance sign is a distinctive pattern of movement of
adult worms within lymphatic vessels.

Radionuclide lymphoscintigraphic imaging of the limbs

reveals widespread lymphatic abnormalities ( in both
asymptomatic microfilaremic persons or those with clinical
manifestation of lymphatic pathology.

Eosinophilia & elevated serum IgE & antifilarial antibody

support Dx of Lymphatic filariasis
 THERAPY
DEC ( Diethylcarbamazine ), 6 mg/kg daily 12 days
Tx of choice for active lymphatic filariasis ( microfila
remia, antigen positivity, or adult worm on USG ).

Alternative : Albendazol 400 mg bid for 21 days, although its

efficacy is less than DEC.

8-week course of daily doxycyclin ( targeting the intracellular

Wolbachia endosymbiont ) has significant macrofilarial activity
as does a 7-day course of daily DEC / albendazol.

Early Tx of asymptomatic Px is recommended to prevent

further lymphatic damage.
 ADL , supportive Tx ( analgesics & antipyretics ) is
recommended.
Since lymphatic disease is associated with the presence of
adult worm DEC is recommended for microfilaria-negative
adult worm carrier.
Chronic manifestation of lymphatic filariasis , Tx regimen
emphasize hygiene, prevention of sec. bacterial infection, &
physiotherapy.
Hydrocele can be drained repeatedly or managed surgically.
Recommended course of DEC tx ( 12 days ; total dose 72 mg/
kg ) remain standard for many years.
Data indicate that single dose DEC tx with 6 mg/kg may be
equally efficacious.
 Side effects of DEC : - fever
- chills
- arthralgia
- headaches
- nausea & vomiting

PREVENTION & CONTROL

Avoidance of mosquito bites usually is not feasible for resident
of endemic areas
Visitors should use insect repellent & mosquito net.
Community-based intervention filariasis as public health
problem
 Anti microfilarial chemotherapy :
- Albendazol with either DEC or Ivermectin suppress
microfilaremia
- This combinations have secondary effects on GI helminths

Alternative approach the use of salt fortified with DEC

reduces microfilarial density with no adverse effect.
 TROPICAL PULMONARY EOSINOPHILIA
a syndrome , develops in some individuals infected with
lymphatic filariasis.
Males to females ratio : 4 : 1
Reported from India, Pakistan, Srilangka, Brazil, Guyana and
Southeast Asia.

CLINICAL FEATURE
- Paroxismal cough & wheezing ( usually nocturnal )
- weight loss
- low-grade fever
- adenopathy
- blood eosinophilia ( > 3000/L )
 X-ray : may be normal , but generally ......
- increased bronchovascular marking
- diffuse milliary lesions or mottled opacity may be
present in middle & lower field

Pulmonary function test : restrictive or

obstructive defect in half

Elevated total IgE levels ( 10.000 100.000 ng/mL )

Elevated antifilarial antibody titer

 PATHOLOGY
In TPE , microfilariae & parasite antigens rapidly cleared from
the blood stream by the lung.
The clinical symptoms result from allergic & inflammatory
reactions elicited by cleared parasites.
In some Px , trapping of microfilariae in other reticulo
endothelial organs hepatomegaly, splenomegaly,
lymphadenopathy.

DIFFERENTIAL DIAGNOSIS
TPE must be distinguished from :
asthma, Lofflers syndrome, allergic bronchopulmonary
aspergillosis, allergic granulomatosis with angitis, periarteritis
nodosa, chronic eosinophilic pneumonia, ideopathic
hypereosinophilic syndrome.
 THERAPY
4-6 mg /kg/day for 14 days.
Symptom usually resolve within 3-7 days after initiation of
therapy.
Relapse occur in 12-25 % of cases after years
retreatment.
 ONCHOCERCIASIS
Caused by O. volvulus
Majority : equatorial region of Africa ( from Atlantic coast to
the Red Sea )
About 70,000 infected in Guatemala & Mexico

ETIOLOGY & EPIDEMIOLOGY

Infection in human due to deposition of infective larvae on the
skin by the bite of infected blackfly.
Adult O. volvulus females and males 40 60 cm & 3 6 cm
in length
Lifespan can be as long as 18 years with average of 9 years.
 PATHOLOGY
Onchocerciasis affects the skin, eyes, and lymph nodes
The damage is due to microfilariae & not by adult parasites.
In the eye neovascularisation & corneal scarring lead
corneal opacities & blindness.

CLINICAL FEATURES
Skin :
- Pruritus & rash most frequent
- The rash is typically papular eruption, generalised rather
than localised
- Long-term infection premature wrinkling of the skin , loss
of elastic fibre & epidermal atrophy redundant skin &
hypo/hyperpigmentasi.
 DIAGNOSIS
Definitive Dx d.o. detection of adult worm in excised nodule
Eosinophilia & elevated IgE
Assays specific antibodies to Onchocerca & PCR
Mazzotti test > when dx is in doubt , DEC 0.5 1.0 mg /kg
orally > death of dermal microfilariae > pruritus / dermatitis

THERAPI
Goals> prevent development of irreversible lesions & alleviate
symptom
Surgical excision , when nodules are on the head
Ivermectin , a semisynthetic macrocyclic lactone active against
microfilariae.
Given in a single dose of 150 mg/kg , yearly or semiannualy.
PREVENTION
- Vectrol control
- Community based administration of ivermectin every 6-12 months
interrupt transmission in endemic areas
- No drug has proved useful for prophylaxis of O. volvulus