filariasis

The Filariae
These are long, thread-like nematodes that inhabit portions of the lymphatic system,
subcutaneous and deep connective tissue. They comprise some of the most important diseases
of man. Some filariae worms of medical importance are grouped as follows, according to
habitat of adult worms:
1) Lymphatic filariae (Lf)
Wuchereria bancrofti (man only)
Brugia malayi (mainly man but also other mammals)
Brugia timori
2) Subcuteneous (and connective tissue) Filariae
Onchocerca volvulus
Loa loa
Dracunculus medinensis
3) Serous cavity (or connective tissue) filariaae
Mansonella perstans
Mansonella ozzardi

Lymphatic filariasis (Lf)

Wuchereria bancrofti
W. bancfrofti (or Bancroftian filariasis) is widely distributed in the tropical and
subtropical countries. In Africa it tends to occur approximately between 20N and 20
S and in Madagascar and along the African coast of the Mediterranean. Scattered
cases have been reported in Turkey. In Asia, the disease maybe found along the
Arabian seacoast, India, Pakistan, Burma, Thailand, in the Philippines, Bangladesh,
Korea, Sri Lanka etc. It occurs extensively in the Pacific Islands (e.g. Fiji, Tahiti,
Samoa and New Guinea). It used to be seen on the northern and eastern coasts of
Australia, but it is very rare now if at all. It is also common in some Caribbean
Islands Haiti, Puerto Rico, and Trinidad; In South America it is found in Panama,
Guyana, Surinam, Brazil etc. It occurs in periodic and sub-periodic forms. The
periodic form, with marked nocturnal periodicity, is characteristic of humid tropics of
the world and is transmitted by night biting mosquitoes. The other form is diurnally
periodic, restricted to Polynesia, and transmitted by mainly day biting Aedes.

Location in the host

The adults live in the lymphatics, either of

Morphology
The adults are long, thread-like worms, (hence the word filaria),
measuring about one to two inches in males and 2 to 4 inches for
females. The head end is slightly swollen and has 2 rows of ten papillae.
The cuticle is smooth with very fine transverse striations and the
posterior end of the females is finely tuberculated. The female has two
posterior ovaries and is viviparous. The eggs in the uterus are enclosed in
a chorionic membrane which becomes a sheath to the living embryos
(microfilariae). The sheathed microfilaria are emitted by the female and
travel via the lymphatics into the blood stream whence they are ingested
by mosquitoes. They can live in the blood circulation for 3 to 6 months.
The sheath is actually the egg shell, which is very thin and delicate and
surrounds the mf embryo as it circulates in the blood; it is not lost until it
is digested away in the stomach of the mosquito. The microfilariae
contain a large number of nuclei as well as the rudiments of some organs
of the adult worm.

The World Geographical Distribution of Filariasis

Developmental Cycle
Male and female adult worms live in the lymphatics where they can
survive for 10 to 18 years
The disease is caused by infestation of filarial worms (nematodes).
Lymphatic filariasis is transmitted to man by various mosquito species
Anopheles, Culex and Aedes species. Transmission by the Anopheles
mosquitoes mainly occurs in rural areas which are favourable for this
mosquito to breed, whereas Culex transmit mainly in urban areas.
Adults live in lymph glands and block flow of lymph fluids. They mate
and release sheathed microfilariae (mf) which travel via the lymphatics
into the peripheral blood six months to one year after infection. In most
parts of the world the microfilariae show a marked nocturnal periodicity;
they are found in the peripheral circulation from 22.00 to 02.00 hours,
whilst during the day they hide in arterioles of the lungs.
When microfilariae are ingested with a blood meal by a suitable species of
mosquito they undergo 3 stages of development in the insect host. They
lose their sheath within about 15 to 30 minutes in the stomach of the
insect. Some penetrate the stomach wall and migrate to the thoracic
muscles in 1 to 24 hours.

Here they metamorphose into sausage shaped larvae and after further
development in about 10 days they migrate to the head where they enter
the proboscis and migrate to the tip (the labilla) of the proboscis. The
larvae emerge from the labilla when the mosquito takes a blood meal, and
penetrate man through the puncture caused by the proboscis. The
penetration is likely to be more successful in areas of high humidity where
the skin will be moist. However, the mosquito secretes a drop of fluid
before feeding, which supports the survival of the larvae on the skin for a
short period of time. On entering they migrate to the lymph glands where
they molt twice before maturing into male and female adult worms. The
female produces microfilariae about six months to one year after infection.
The adults may also be found in dilated lymphatic vessels distal to
lymphatic obstruction anywhere in the body. They can live up to 17 years.
The development in the mosquito is necessary therefore man to man
transmission does not occur

Clinical manifestation
Many cases are symptomless for years or throughout life and the only evidence of infection is
the presence of micfrofilariae in the blood. In the cases showing symptoms there may be
recurring attacks of acute lymphagitis (inflammation of the lymph ducts), with inflamed tender
lymph nodes, headache, nausea and sometimes urticaria, from about the third month after entry
of the larvae. The most serious clinical manifestations are due to disturbances of the lymphatic
system, which may result in lymphadenitis (inflammation of the lymph nodes), lymphoedoema,
lymphocoeles, chyluria (lymph containing fat in the urine) and, in males, genital lesions
including hydrocoele and lymph scrotum leading in time to the disfiguring elephantiasis. The
nature of lesions varies in different parts of the world, reflecting different sites of obstruction. In
Africa, elephantiasis is less common than in the Pacific Islands (with gross elephantiasis of the
arm, breast, legs, scrotum or vulva, and hydrocoele in males with a probable reduction in
fertility) and it is usually confined to the legs. Hydrocoele is common in East Africa.
The adults of the nocturnal periodic strains of W. bancrofti usually develop in the lymphatics of
the lower limbs and groin while those of the subperiodic Pacific strain are also found in the
lymphatics of the upper limbs. It is estimated that there are at least 250 million cases in the
world, with the resulting debilitation continuously affecting the economies of the developing
countries.

Pathogenesis
The earliest signs occur 4 weeks after infection and involve the lymph glands as a result of an
immunological response by the host. There is a marked cell-mediated response in the lymph
gland followed by an antibody-mediated response in the afferent lymphatics caused by
antimicrofilarial antibody. This response is the cause of the local gland enlargement in early
filariasis. The early symptoms are reversible following chemotherapy, but later as a result of
collagen deposit and probable streptococcal infection the lymphatics are permanently
destroyed by fibrous obliteration which causes elephantiasis, a process which is not
reversible. The presence of numerous living worms leads to dilatation of the afferent
lymphatic vessels and leakage of lymph into the tissues (causing lymphodoema), with
increase in tissue fluid content. The later stage of elephantiasis presents with hyperplasia
(abnormal cell increase in an organ) and fibrosis (excessive fibrous tissue) of affected tissues,
in which the oedema becomes hard and the skin thickens and folds, often with verrucous
(warty lesion) growths. Dead worms calcify and become surrounded by fibrosis and may
form lymphatic abscesses, obliterating the lymphatics and adding to the pathogenesis. In
addition there could be secondary infection with streptococcus and this combined with
collagen deposit, the lymphatics are permanently destroyed.

Scrotum extending beyond the knees. Upper limbs, scrotum and lower limbs

Other conditions:
Chyluria results from rupture of obstructed and
dilated small intestinal lymphaticsinto the urinary
tract so the chyle (milky lymph from emulsified
fats) no longer returns to the blood. This results in
the loss of fat with loss of weight, electrolyte,
protein and other deficiencies.
Occular filariasis adult worms may invade the
orbit giving rise to proptosis (forward projection or
displacement especially of the eyeball), keratitis or
glaucoma

Differential Diagnosis
Observation of various telltale clinical manifestations listed above; e.g. varicose groin
glands, filarial glandular enlargement, Chyluria and elephantiasis.
Laboratory examination
This can be done by finding the microfilaria in the blood;
Blood thick smear slide, stained with a Romanowsky stain, e.g. Giemsa stain for
microfilaria
Membrane filters blood filtered through either a Millipore or Nucleopore membrane.
The filter may be examined fresh or stained as above. This method is very sensitive.
ICT card test - Examination for the circulating filarial antigen (CFA) due to infection
with microfilariae can be done using Immunochromatographic (ICT) card test. In this
test 100l of finger-prick blood is obtained using heparinized capillary and the blood
specimen transferred to an ICT card, the card closed and results read after 10 minutes
to determine if individual is infected or not.
DEC given at a small dose during the day can provoke the nocturnal mf from the lungs
and into the peripheral circulation during the daytime.

Treatment
Diethylcarbamazine (DEC) (Banocide, Hetrazan, Notezone) destroys
microfilaria and also capable of killing the adult worms when given at a
dose of 2-6 mg/kg body weight per day for 2 to 3 weeks. When given at
6mg/kg body weight it should be divided into 3 daily doses of 2mg/kg.
Other drugs used include:
Furapyramidone in China. Said to be active against mf and adults.
Metrifonate - given at a dose of 10-15mg/kg every 14 days for 5 to 16
doses specifically good for mf but also kills adults in a proportion of
cases. Where Schistosoma haematobium occurs this drug will also kill
the Schistosome worms.
Control
-Mass chemotherapy with DEC
-Vector control including insecticide treated bednets
-Combined methods
-Personal prophylaxis

Brugia malayi
Most aspects similar to W. bancrofti, Mf with 2 isolated nuclei at the tip of
the tail. No nuclei at the end of tail for the W. bancrofti.
It is distributed in South and South-East Asia from India in the West to
Korea in the East. The worms resemble those of W. bancrofti and the life
cycle is similar. However B. malayi exhibits both diurnal and nocturnal
periodicities and the worms inhabit the lymphatic glands and lymph
vessels usually of the lower limbs and groin. This filariasis also affects
other animals including monkeys, cats, civets and pangolins.
Brugia timori
The only difference from the other two is that the sheath does not stain in
Giemsa. It has a small distribution in the South-east Indonesia in Timor
and Flores Islands. It is nocturnally periodic and transmitted by Anopheles
mosquitoes.