Blood and Tissue Nematodes

General Characters
1- Adult worms live in the lymphatic, subcutaneous
connective tissue or body cavities.
2- Female worms are viviparous.
3- The early first-stage larvae, known as microfilariae
that have no differentiated organs inside, instead
there are columns of cells with prominent nuclei.
4- Filarial worms are transmitted through the bite of an
insect vector.

Filarial worms
They include the following species:
1- Wuchereria bancrofti.

2- Brugia malayi.
3- Onchocerca volvulus.

4- Loa loa.
5- Mansonella perstans.

6- Mansonella ozzardi.

Infective stage:
Filariform larva [3rd stage larva]:
It is about 1.5-2 mm x 20 um, with
cylindrical oesophagus and lies in
the labium of mosquito vector.

Mode of infection:
During

bite

by

mosquito

I.H,

filariform larva pierces human skin

through the puncture wound.

Wuchereria bancrofti
Disease: Bancroftian filariasis, wuchereriasis,
elephantiasis.
D. H.: Man.
I.H. (vector): Female Culex Mosquitoes.
Habitat: Lymphatic tissues of lower limbs &
external genitalia.
Microfilariae appear in the peripheral blood
by night [nocturnal periodicity] & disappear
by day time.

Geographical distribution

Tropical & subtropical countries.

Morphology
Adult worms are whitish & thread like.
Male: 2.5 - 4 cm &
Female: 5-10 cm.

Morphology
Microfilaria: 250-300x8 m in length & surrounded by a loose
sheath.
Body forms smooth (graceful) curves, has rounded anterior end
and tapering tail. Both ends are free of nuclei. It has a nocturnal
periodicity.

Nocturnal [microfilarial]
periodicity theories
1- Biological adaptation between M.F. & night biting activity of
mosquito.
2- Chemical attraction between M.F. & saliva of mosquito.
3- During sleep, decrease oxygen content & increase carbon dioxide
content stimulate M.F. to migrate from blood vessels of lung to
peripheral blood.
4- Khalils theory: Blockage of lymphatics; during day on upright
position of the patient; prevents M.F. to find their way to the
circulation.
By night time & during sleep, relaxation of the patients body will
open the lymphatics allowing M.F. to reach the peripheral blood.

Life cycle of Wuchereria bancrofti

Life cycle
A- Development in man:
1- When an infected mosquito bites man to take a
blood meal, infective larvae are deposited on human
skin usually in pairs, penetrate the skin through the
bite wound or by its own activity.

2- Larvae pass to lymphatic vessels & nodes where

they mature in about one year & mate. The adult
worms are found in lymphatic of lower limbs, groin &
epididymis in males and labial glands in females.
3- Female mosquitoes produce many sheathed
microfilariae which appear in peripheral blood at night
between 10 PM- 2 AM reaching a peak about
midnight [nocturnal periodicity].

Life cycle
B- Development in mosquito:
4- Microfilariae are taken up by a female mosquito
when it sucks a blood meal.
5- In the stomach of mosquito, microfilariae loose their
sheath, penetrate the wall of mid gut & migrate to the
thoracic muscles where they develop into infective
larvae.
6- Development in the mosquito takes 2-3 weeks.
Each ingested microfilaria develops into one filariform
larva [cyclo-developmental transmission].
7- Infective larvae migrate to the head region within
the labium ready to be transmitted when mosquito
takes another blood meal.

Pathogenesis & Clinical picture

1- Many infections are asymptomatic & are
detected only by blood examination.
2- The main pathology of filariasis is caused
mainly by living or dead adult worms.

3- Incubation period: one year or more.

The disease passes in 2 stages:
I- Acute (inflammatory) stage.
II- Chronic (obstructive) stage.

I- Acute (inflammatory) stage

Due to immune response to toxic products of living or dead
adult worms with superimposed 2nd infection.

There is infiltration with plasma cells, eosinophils &

macrophages in & around affected area.
Microfilariae cause less pathology.
Acute stage is characterized by
recurrent attacks of fever, lymphangitis & lymphadenitis.

I- Acute stage (Cont.)

a] Filarial or elephantoid fever: has a sudden onset with rigors
& sweating. It lasts for few hours to several days, then subsides
and often recurs.
b] Lymphangitis: Lymph vessels are distended, red, hot, painful
and tender. The commonly affected lymphatics are those of legs
and genitalia [funiculitis, epididymitis & orchitis].
c] Lymphadenitis: Lymph nodes are enlarged and tender with
temporary oedema of the affected limb.
d] Leucocytosis & eosinophilia.
By time, the attacks get milder & more spaced but the affected
part remains slightly swollen.

II- Chronic (obstructive) stage

Fibrosis following the inflammatory process around worms & presence
of coiled worms inside lymphatics result in:
a- Dilatation of lymphatics leading to varicosity as hydrocele,
scrotal lymphoedema and lymphatic varices.
Hydrocele is the most common chronic manifestation & results from
accumulation of straw lymphatic fluid in sacs around testes.
b- Rupture of distended lymphatics proximal to the obstruction e.g. in
the pleural sac (chylothorax), peritoneal cavity (chylous ascitis), tunica
vaginalis of testis (chylocele), intestine (chylous diarrhea) or in urinary
passages (chyluria) with passage of microfilariae with urine.
c- Elephantiasis: Thickening & hypertrophy of the skin & subcutaneous
connective tissue of legs and genitalia [scrotum, penis& vulva] due to
disturbance of lymph drainage.

Mechanism of Elephantiasis
Increased permeability of obstructed lymphatic walls, leading to
leakage of lymph rich in protein under the skin causing cellular
proliferation of connective tissue & deposition of fibrous tissue.
Clinically: At first, the swelling is pitting but later becomes nonpitting then the skin becomes thickened, rough, fissured and
susceptible to ulceration and 2nd infections with bacteria or
fungi.
Elephantiasis occurs after persistent high infection
for 5-10 years.

Bancroftian filariasis & Elephantiasis

Diagnosis
I- Clinical
History & Clinical picture

II- Laboratory
III- Imaging techniques

II- Laboratory diagnosis

a- Detection of M.F. in peripheral blood at night [between 10 pm
& 2 am]
by
1- Wet drop: for living moving microfilariae.
2- Giemsa stained thin & thick smears: show the
morphological characters of microfilariae .
3- Concentration method: if M.F. are scanty;
* Knott's technique: In a centrifuge tube, mix 5-10 ml of blood with
equal volume of 2% formaline. Allow the mixture to stand for 10
minutes then centrifuge. Decant the supernatant and examine
the sediment for microfilariae.
* Nucleopore filter technique: Filtration of 1-5 ml of heparinized
blood through 5 m Nucleopore filter then stain & examine the
filter on a slide.

Provocative test
To obtain blood at day time, give the patient 50-100 mg DEC orally &
examine the blood within 30- 60 min.

Laboratory diagnosis (Cont.)

b- Detection of M.F. in chylous urine or in fluid aspirated from
hydrocele or peritoneal cavities.
c- Demonstration of the adults worms in lymph node biopsy.

d- Immunodiagnosis
1- Skin test with antigenic extract of the dog filaria Dirofilaria

immitis.
2- IHAT, IFAT and ELISA: for detection of filarial antibodies.
3- Detection of filarial antigens is specific & sensitive and can
detect early infection saving patients from complications of the
disease.
e- Molecular techniques: PCR.
f- High eosinophilia.

==

III- Imaging techniques

a- Ultrasonography: Viable adults may be seen
moving in lymphatics (filarial dance sign).
b- X-ray: shows calcified worms.
c- Lymphangiography: Shows lymphatic changes
e.g. dilatation of vessels.

Treatment
1- Antifilarial drugs:
a- Diethylcarbamazine [DEC]: 6mg/Kg/day for 12
days, repeated every 6 months as long as the patient
remains microfilaraemic or has symptoms.
b- Ivermectin: Single oral dose of 150 ug/Kg body weight.
c- Combination of DEC & ivermectin: gives better results.
2- General measures:
Rest, antibiotics, antifungal, physiotherapy & bandaging.
3- Elephantoid tissues: Corrected surgically.

Prevention & control

1- Mosquito control.
2- Treatment of patients.

Occult Filariasis
* Clinical conditions of hyper-sensitivity reactions to
microfilarial antigens.
* The classical features of lymphatic filariasis are absent.
* Microfilariae are not seen in peripheral blood (due to its
destruction in the lung by the immune response) but
adult worms and microfilariae may be seen in the tissues.
* The condition may be caused by Wuchereria bancrofti,
Brugia malayi or by some animal filarial worms.

Tropical pulmonary eosinophilia (TPE)

TPE is the most important manifestation of occult filariasis.
There are low-grade fever, loss of weight, anorexia & pulmonary
symptoms (as dry nocturnal cough, asthmatic attacks), persistent
hyper-eosinophilia & glandular enlargement.
The condition is associated with a high level of filarial antibodies and
elevated IgE level.
These symptoms are relieved by ant-filarial therapy
[diethylcarbamazine (DEC)].

Brugia malayi
Similar to W. bancrofti in life cycle, diagnosis, treatment
& control and differs as regards:
1- Disease: Malayan filariasis.
2- Distribution: Far East.
3- I.H. (Vector):
Female Mansonia mosquito.
4- Reservoir hosts: Cats & monkeys.
5- Habitat: Lymphatic of upper limbs.

Microfilaria of Brugia malayi

Has loose sheath, with kinky curves & tail end
with 2 deeply stained nuclei; one in front of the other.

Microfilaria shows non periodicity or nocturnal periodicity

Pathogenesis & clinical features are also similar to bancroftian

filariasis, but hydrocele is rare.

Brugian filariasis: Elephantiasis affects legs below the knees

and arms below elbows.