A Neglected Tropical Disease: Filariasis Caused by Brugia

Malayi Infections
1
Erdiansyah Adhami, 1Devisda Shafiy A, 1Bagas W.U., 1Febri Z F, 1Totalenesya R S,
1
Wilsa Patricia, 1Nita Alfianti, 1Yunita Dewi Anggraeni, 1Winaspita Aulia Putri, 1Rafi
Bintang P, 1Madha Qoyuledy T, 1Prisma Diandari dan 2Yudha Nurdian

1
Mahasiswa, Fakultas Kedokteran, Universitas Jember, Indonesia
2
Fakultas Kedokteran, Universitas Jember, Indonesia
Email: erdiansyahadham@gmail.com; 162010101024@students.unej.ac.id

Lymphatic filariasis, known as elephantiasis, is a neglected tropical disease.

Infection occurs when filarial parasites are transmitted to humans through
mosquitoes. Infection is usually acquired in childhood causing hidden damage to
the lymphatic system.

The painful visible manifestations of the disease, lymphoedema,

elephantiasis and scrotal swelling occur later in life. These people do not know they
have lymphatic filariasis unless tested. The standard method for diagnosing active
infection is the identification of microfilariae in a blood smear by microscopic
examination. The microfilariae that cause lymphatic filariasis circulate in the blood
at night (nocturnal periodicity). Blood collection should be done at night to coincide
with the appearance of the microfilariae. The person will develop lymphedema.
This is caused by fluid collection because of improper functioning of the lymph
system resulting in swelling. This mostly affects the legs, but can also occur in the
arms, breasts, and genitalia. Most people develop these symptoms years after being
infected.

The global baseline estimate of people affected by lymphatic filariasis was

25 million men with hydrocele and over 15 million people with lymphoedema. At
least 36 million people remain with these chronic disease manifestations.
Eliminating lymphatic filariasis can prevent unnecessary suffering and contribute
to the reduction of poverty.
 Lymphatic filariasis is caused by infection with parasites classified as
nematodes of the family Filariodidea (wuchereria bancrofti, brugia malayi). Adult
worms lodge in the lymphatic vessels and disrupt the normal function of the
lymphatic system. The worms can live for 6–8 years and, during their life time,
produce millions of microfilariae (immature larvae) that circulate in the blood.

The filarial parasite Brugia malayi is a causative agent of human lymphatic

filariasis in South and South-East Asia. B. malayi is transmitted by mosquitoes,
which take up the blood-borne microfilarial stage (Mf) of the parasite. For the
majority of the day, Mf sequester predominantly in the lungs of the host and they
only appear in the peripheral blood circulation for a few hours, which coincides
with maximal mosquito feeding . While sequestered in the lungs, B. malayi Mf are
likely to interact with vascular endothelial cells (EC) and we have observed them
binding to the surface of vascular EC (manuscript in preparation). Helminths are
potent modulators of the immune response and filarial nematodes, in particular,
have been shown to influence the secretion of inflammatory mediators from a
number of different cell types . Vascular EC themselves can modulate the immune
response by producing pro-inflammatory cytokines and chemokines, in addition to
several angiogenic mediators. Vascular EC also play a critical role in extravasation
of leukocytes to the site of inflammation .

Mosquitoes are infected with microfilariae by ingesting blood when biting

an infected host. Microfilariae mature into infective larvae within the mosquito.
When infected mosquitoes bite people, mature parasite larvae are deposited on the
skin from where they can enter the body. The larvae then migrate to the lymphatic
vessels where they develop into adult worms, thus continuing a cycle of
transmission.

The typical vector for Brugia malayi filariasis are mosquito species from
the genera Mansonia and Aedes. During a blood meal, an infected mosquito
introduces third-stage filarial larvae onto the skin of the human host, where they
penetrate into the bite wound. They develop into adults that commonly reside in the
lymphatics. The adult worms resemble those of Wuchereria bancrofti but are
smaller. Female worms measure 43 to 55 mm in length by 130 to 170 μm in width,
and males measure 13 to 23 mm in length by 70 to 80 μm in width. Adults produce
microfilariae, which are sheathed and have nocturnal periodicity. The microfilariae
migrate into lymph and enter the blood stream reaching the peripheral blood. A
mosquito ingests the microfilariae during a blood meal. After ingestion, the
microfilariae lose their sheaths and work their way through the wall of the
proventriculus and cardiac portion of the midgut to reach the thoracic muscles .
There the microfilariae develop into first-stage larvae and subsequently into third-
stage larvae.

Lymphatic filariasis infection involves asymptomatic, acute, and chronic

conditions. The majority of infections are asymptomatic, showing no external signs
of infection while contributing to transmission of the parasite. These asymptomatic
infections still cause damage to the lymphatic system and the kidneys, and alter the
body's immune system. When lymphatic filariasis develops into chronic conditions
it leads to lymphoedema (tissue swelling) or elephantiasis (skin/tissue thickening)
of limbs and hydrocele (scrotal swelling).

Acute episodes of local inflammation involving skin, lymph nodes and

lymphatic vessels often accompany chronic lymphoedema or elephantiasis. Some
of these episodes are caused by the body's immune response to the parasite. Most
are the result of secondary bacterial skin infection where normal defences have been
partially lost due to underlying lymphatic damage.

Elimination of lymphatic filariasis is possible by stopping the spread of the

infection through Mass Drug Administration (MDA). MDA involves administering
an annual dose of medicines to the entire at-risk population. The medicines used
have a limited effect on adult parasites but effectively reduce the density of
microfilariae in the bloodstream and prevent the spread of parasites to mosquitoes.
The MDA regimen recommended depends on the co-endemicity of lymphatic
filariasis with other filarial diseases. WHO recommends the following MDA
regimens albendazole (400 mg) alone twice per year for areas co-endemic with
loiasis, ivermectin (200 mcg/kg) with albendazole (400 mg) in countries with
onchocerciasis, diethylcarbamazine citrate (DEC) (6 mg/kg) and albendazole (400
mg) in countries without onchocerciasis

Recent evidence indicates that the combination of all three medicines can
safely clear almost all microfilariae from the blood of infected people within a few
weeks, as opposed to years using the routine two-medicine combination.

Mosquito control is a supplemental strategy supported by WHO. It is used

to reduce transmission of lymphatic filariasis and other mosquito-borne infections.
Depending on the parasite-vector species, measures such as insecticide-treated nets,
indoor residual spraying or personal protection measures may help protect people
from infection. The use of insecticide-treated nets in areas where Anopheles is the
primary vector for filariasis enhances the impact on transmission during and after
MDA. Historically, vector control has in select settings contributed to the
elimination of lymphatic filariasis in the absence of large-scale preventive
chemotherapy.

CONCLUSIONS

Lymphatic filariasis, is a neglected tropical disease. Infection occurs

when filarial parasites are transmitted to humans through mosquitoes. The visible
manifestations of the disease, lymphoedema, elephantiasis and scrotal swelling
occur later in life. The standard method for diagnosing active infection is the
identification of microfilariae in a blood smear by microscopic examination. The
filarial parasite Brugia malayi is a causative agent of human lymphatic filariasis in
South and South-East Asia. B. malayi is transmitted by mosquitoes, which take up
the blood-borne microfilarial stage (Mf) of the parasite. The typical vector
for Brugia malayi filariasis are mosquito species from the
genera Mansonia and Aedes. Acute episodes of local inflammation involving skin,
lymph nodes and lymphatic vessels often accompany chronic lymphoedema or
elephantiasis. When lymphatic filariasis develops into chronic conditions it leads to
lymphoedema (tissue swelling) or elephantiasis (skin/tissue thickening) of limbs
and hydrocele (scrotal swelling). Elimination of lymphatic filariasis is possible by
stopping the spread of the infection through Mass Drug Administration (MDA) and
mosquito control.

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