Department of Parasitology

Lymphatic filariasis

Organ affected: lymphatic system

Function of lymphatic system:

Keeping in balance the bodys fluid
Fighting bacteria that cause infections
 Lymphatic

filariasis
Caused by a thread-like nematode: the filaria

The worm is ovoviviparous.

After mating, female worm releases larvae called
microfilariae (mf)

The development of the worm takes place in:

Mosquitoes as intermediate host (Vector)
Human as definitive host
 Lymphatic filariasis
Filarial parasites infecting human are:
Wuchereria bancrofti
Brugia malayi
Most widely distributed in Indonesia
Brugia timori
Only eastern parts of Indonesia
 Lymphatic filariasis
Distributed in tropical and subtropical countries
 PENYEBARAN
Spesies Daerah Periodisitas Vektor Perindukan Hewan
endemis (mikrofilaria
)
Wuchereria Kota Nokturna Culex Air kotor -
bancrofti quenquefasciatus
Wuchereria Endemis Nokturna banyak Bionomi -
bancrofti rendah berbeda
kecuali Papua

Brugia Sawah Nokturna Anopheles Sawah -

malayi barbirostris
Brugia Rawa Subperiodik Mansonia sp Rawa +
malayi Nokturna
Brugia Hutan Non periodik Mansonia sp Rawa hutan +
malayi

Brugia Sawah Periodik Anopheles Sawah _

timori nokturna barbirostris
 Lymphatic filariasis

Endemic in 80 countries.
Estimated 1.1 billion people at risk.

Approximately 120 million people

infected.

90% W. bancrofti

10% Brugia malayi + Brugia timori
 Filariasis Prevalence in
Indonesia
Ranging from 0.5 % - 19.64% with
average of 3.1% (P2M & PLP, 1999).

About 6500 chronic cases found in rapid

mapping (P2M & PLP 2000).

Distributed from DI ACEH - PAPUA

Lymphatic filariasis in
Indonesia
Vektor W. bancrofti
 Lymphatic filariasis
Prevalences increase with age, with a slight
to moderate decrease in older indviduals.

More prevalent in men than women.

 Life cycle
VECTOR-STAGE DEVELOPMENT
L2 to L3 molt in flight muscles

Microfilariae migrate from mosquito midgut L3 migrate to mouth parts

to thorasic flight muscles and undergo
L1 to L2 molt

release of sheathed L3 penetrates into host and

microfilariae into peripheral undergoes molt to L4
blood

Adult male and female reside in

lumen of lymphatics

VERTEBRATE-STAGE DEVELOPMENT
 Life cycle
Adult : Live in the lumen of lymphatic
worms in vessels. The longevity of adults is
human about 8 10 years.

: Live for about 1 year.

Microfilariae Migrate from lymphatic circulation
in human into the bloodstream.
Present in the peripheral blood at
certain time, called periodicity.
Stage 1 3 : . Live in the mosquitoes.
larvae in . Infective larvae (stage 3 larvae) enter
mosquito the host via mosquitos biting.
 Host
Human host:
Wuchereria bancrofti
Brugia timori
Brugia malayi anthropophilic

Human and animal hosts

Brugia malayi zoophilic
Animal host called reservoir hosts such as
monkey, cat.
 Morphology of adult worm
The size of female worm is bigger and larger than male
worm Wuchereria bancrofti
Female
Female : 65 100 mm x 0.25 mm.
Male : 40 mm x 0.1 mm

Brugia malayi
Female : 55 mm x 0.16 mm.
Male : 22 23 mm x 0.09 mm

Male Brugia timori

Female : 21 39 mm x 0.1 mm.
Male : 13 23 mm x 0.08 mm.

Tail: curly end

 Morphology of microfilaria
Microfilariae stained with
giemsa

W. B. B. timori
bancrofti malayi
Species differentiation is based on as follow
Cephalic space: W. bancrofti B. malayi B. timori
(Length : width) 1:1 2:1 3:1

Terminal nuclei None 2 2

Sheath in Giemsa staining: Pale Red Pale

(extend from head to tail)
 Periodicity
Periodicity: the period when microfilariae appear in the
peripheral blood

Nocturnal : Mf disappear in the blood circulation during the

periodic day and reach the peak at night (10 p. m 2
a.m)
Nocturnal : Mf appear in blood the whole day but reach the
subperiodi peak at night
c

Aperiodic : Mf appear in blood the whole day.

 Periodicity
Periodicity: the period when microfilariae appear in the
peripheral blood
 Lymphatic filariasis
Species Type Periodicit Host Vector
y
Wuchereria Rural Nocturnal Human Anopheles sp.
bancrofti periodic
Urban Culex
quinquefasciatus
Brugia Anthropophil Nocturnal Human Anopheles
malayi ic periodic barbirostris
Zoophilic Nocturnal Human Mansonia sp.
subperiodic &
animal
Aperiodic Human
&
animal
Brugia Nocturnal Human Anopheles
timori periodic barbirostris
 Breeding places
W. bancrofti

Culex Anopheles subpictus

quinquefascia (brackish water)
 Breeding places
Brugia sp

Mansonia uniformis Anopheles

(water plants at ponds/swamps)barbirostris
 Pathogenesis
Four factors may be responsible to
the pathology of lymphatic filariasis:
Live adult worms
Dead adult worms
Secondary bacterial infections
Immune reactions of host against
microfilariae.
 Pathogenesis
Live adult worms block the lymph vessels &
cause dilatation of the lymph vessels
lymphangiectasia

If the number of adult worms in the lymphatic

system is high or the lymphangiectasia is
extensive, the lymphatic dysfunction will
occur in the location of adult worms.
In men: hydrocele, lymph scrotum, chyluria
In women: enlargement of breast / vulva, chyluria
 Pathogenesis
Cuts or scratches in the skin and between toes
will allow bacteria / fungus to infect the skin.

The secondary bacteria infections will

predispose to acute attacks, enhancing the
progression of lymphatic dysfunction into
lymphedema.

Elephantiasis in extremities or elephantiasis

scroti (scrotal skin is affected) final stage
 Pathogenesis
Dead adult worms (spontaneously or by drug
treatment)

Enlargement of lymphatic nodes with

minimal symptoms or subclinical or
represented as an acute attack (AFL) which
can be followed by lymphedema that
resolved spontaneously.
 Pathogenesis

Immune reaction:
Hyperresponsive to microfilariae causing
tropical eosinophilia.
 Clinical manifestations

Microfilaraemic
Asymptomatic
Symptomatic (Adenolymphangitis)

Chronic pathology

Tropical Pulmonary Eosinophilia

 Clinical Signs and

Symptoms :
Acute manifestations
Recurrent fever associated with

Lymphadenitis (inflammation of the lymph nodes)

Lymphangitis (inflammation of the lymph vessels)
termed Adenolymphangitis (ADL)
attacks in bancroftian filariasis < brugian filariasis
affected sites: inguinal, axillary, epitrochlear regions.
in bancroftian filariasis, male & female genital organ can
affected: (male genitalia: funiculitis, epididymitis,
orchitis or combination)
last for several days or up to 4 6 weeks with a
fulminating episode which may prolong inability to work.
 Clinical Signs and
Symptoms
Two distinct types of acute ADL episodes in
endemic areas:
Acute Filarial Lymphangitis (AFL):
caused by the death of adult worms (spontaneous/by
therapy)

the main feature is lymphadenitis and/ retrogade

lymphangitis with local pain and tenderness.

In bancroftian filariasis: male patients can have

painful & red scrotum with testicular tenderness,
with or without acute hydrocele.

etrograde means the inflammation spreads from proximal to distal lymphatic ves
 Clinical Signs and Symptoms

Acute Filarial Lymphangitis (AFL):

Lymphadenitis can progress into abcess

burst into clean ulcer with serosanguinous fluid

and the formation of scar

Patients can have minor constitutional

symptoms (fever, headache, malaise) and
rarely accompanied by distal lymphoedema
(reversible)

frequently precipitated by hard physical work

 Clinical Signs and
Symptoms
Acute Dermatolymphangioadenitis
(ADLA):

caused by bacterial or fungal infection +

lymphatic dysfunction
entry lesions: interdigital/nail area,

trauma, burns, insect bites, radiation,

chemical injury.

The acute skin inflammation starts in the

skin & spreads out along the lymphatic
vessel to the lymph node ascending
lymphangitis and/ adenitis.
This condition can lead to abcess formation
 Clinical Signs and Symptoms

Acute Dermatolymphangioadenitis (ADLA):

The patients suffer more severe constitutional
symptoms than AFL.

Distal oedema is more severe and frequent.

Without proper care the patients with lymphedema

can have repeated ADLA which could worsen the
existing lymphedema into persistent lymphedema/
elephantiasis
 Clinical Signs and
Symptoms
Chronic manifestations :
Lymphedema
Hydrocele
Lymph scrotum only in W. bancrofti.
Chyluria
Elephantiasis
whole part of upper/ lower extremities + sexual organs W.
bancrofti.

Part of upper/ lower extremities below elbow/ knee without
sexual organs involvement Brugia malayi / Brugia timori.

Patients with lymphedema/elephantiasis often suffer

acute attacks
 Clinical Signs and Symptoms
Hydrocele:
The most frequent chronic manifestation in
bancroftian filariasis
Resulted by the accumulation of fluid (usually
clear) in the tunica vaginalis.
Transillumination with a flashlight in dark
room:used to identify hydrocele.
 Clinical Signs and
Symptoms
Chyluria occurs when dilated lymphatic
vessels of the urinary excretory system
rupture, causing leaking of lymphatic
fluid and chyle into the urine

The urine is milky white in color and

rich in fat.
 Clinical Signs and
Symptoms
Lymph scrotum is a rupture of
superficial dilated lymph vessels of the
scrotal skin intermittent discharge
of lymph fluid
Clinical Signs and Symptoms
Filarial-associated abcesses
on extremities
 Clinical signs and
symptoms W. bancrofti
Young woman with
enlargement of external
genitalia

Woman with enlargement of breast

 Clinical Signs and Symptoms

Lymphedema in arm
 Clinical signs and
symptoms
Lymphedema
(Brugia sp).

Lymphedema
(W. bancrofti)
 Symptoms in
Expatriats/Transmigrants
Expatriats or transmigrants who are
infected filariasis manifest prominent signs
& symptoms of inflammatory (including
allergic) reactions to the mature or
maturing parasites (not seen in endemic
populations).

The manifestations include lymphangitis,

genital pain along with rash & eosinophilia.
 Tropical Pulmonary
Eosinophilia
Commonly in men than in women, nonexistent in
young children

Immunological hyperresponsiveness to
microfilariae (mf).

Mf is not found in blood but remnants of mf

surrounded by aggregates of eosinophils are
sometimes found in spleen, liver, lymph nodes or
lungs
 Tropical Pulmonary
Eosinophilia
Symptoms: similar to bronchial asthma (Paroxysmal
nocturnal cough, breathlessness, wheezing)

sometimes associated with lymphadenopathy or

hepatosplenomegaly.

Chest x-ray: diffuse patchy infiltration of lungs (not

pathognomonic).

Laboratory findings:
Massive hyper-eosinophilia (>3000 per ul)

High level of anti filarial IgG4 and IgE antibodies

 Tropical Pulmonary
Eosinophilia
Dosage: DEC 6 mg/kg BW for 21 or
28 days.

Rapid progression of the clinical

symptoms & a decrease in the
number of eosinophils
 Diagnosis
Conventional method:
Microscopic: thick blood smear or filtration of
night blood (taken at 08.00 12.00 p.m.)
Serology: night or day blood
Antigen detection for Wuchereria bancrofti ,
using ICT (Immuno Chromatographic Test).
Antibody detection (IgG4) for Brugia malayi and
Brugia timori, using Brugia Rapid test (not
specific)
Molecular biology: DNA
Polymerase Chain Reaction (PCR) for Brugia
malayi and Brugia timori, Wuchereria bancrofti
 Treatment
The goals of treatment for lymphatic
filariasis are:
To prevent progression of disease,

To interrupt transmission of the parasite.

The drug of choice is DEC

(Diethycarbamazine citrate).
Effective to kill microfilariae and adult

worms.
 Treatment
Individual treatment
Standard dose:

DEC 6mg/kg body weight for 10-15 days

Mass treatment
Single dose (recommended by WHO):

DEC 6 mg/kg body weight plus albendazole 400

mg yearly for at least 5 years above 2 years old

(elimination filariasis programme in Indonesia started in 2002

first year)
 Treatment (individual)
Clinical manifestation Probability of DEC treatment
active infection (standard dose)
Asymptomatic, subclinical
-Microfilaria-positive 100% Yes
- Adult worm carriers* 100% Yes

Microfilaria positive 100% Yes

Acute attacks
-Acute filarial adenolymphangitis 100% Yes (after acute
-Dermatolymphangioadenitis Variable attack)
If infected (after
acute attack) +
Chronic manifestation antibiotics
-Lymphedema of the legs* Low
-Hydrocele* Variable
If infected
If infected
* Chronic patients who are positive antigen or DNA detection have to be treated

with DEC

 Adverse reactions of
treatment
Due to immunological reactions to the
death of :
adult worm (localised): adenolymphangitis,
sometimes accompanied by acute
lymphoedema or hydrocele begin 2 4
days post treatment
microfilariae (systemic): fever, headache,
malaise, myalgia, arthralgia begin a
few to 48 hours post treatment
 Side effects of treatment

Symptoms associated with DEC,

regardless of filarial infection status:
nausea, gastrointestinal upset,
drowsiness

More frequently as the dosage

increases
 Case Management
Lymphedema cases
Aims: to decrease the frequency of reccurrent
infections
to stop the progression of lymphedema
Personal hygiene such as:
washing the extremities with soap twice daily.
keeping the nails clean.
wearing slippers / shoes
Treatment of skin lesions with antibiotics or antifungal
Exercise, elevation of the affected limb, gentle
massage. During acute attack: only elevation of the
limb.
Surgery: less effective
 Case Management
Surgical procedures must be subjected
to hydrocele patients in order to drain
the fluid and render the tunica
vaginalis incapable of trapping and
retaining it again.
 Exceptional rule of Th2-cell
skewing
Commonly helminth infection induce Th2
responses within 24 hours of entry into the
host eosinophilia, mastocytosis etc.

However, there is an exceptional rule of Th2

cell skewing by helminths observed in
Schistosoma & filariasis infections.
 Exceptional rule of Th2-cell
skewing
Filarial parasite:
The presence of wolbachia (endosymbiotic bacteria)
in filarial worms induce a unique immune system.
 Wolbachia surface protein (WSP) induce pro-
inflammatory cytokines, IL-6, TNF by
macrophages & chemotactic activity by
neutrophils.

Excessive pro-inflammatory mediator

the alteration of lymphatic vessels

dilation & obstruction

lymphatic pathology (oedema, hydrocele)

Three broad outcomes associated with specific
immune responses to filarial infection
- Susceptible individuals with Th2-cell responses,
low levels of Th1 cells, high level of IL-10
indicated by a strong Treg activity, and Th2
type antibody dominated by IgG4 isotype with
relatively little IgE.
-

- Resistant individuals who are clinically silent

infections and the main reservoir for onward
transmission having balance of Th1/Th2.

- Chronic individuals (elephantiasis) develop

uncontrolled inflammatory (Th1) with high level
of IgE compared to IgG4. The balanced Th1 and
Th2 cell responses are needed to kill the
parasite.