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Lymphatic filariasis: Wuchereria bancrofti

Lymphatic filariasis Overview

120 million people in 72  countries are affected by Lymphatic filariasis. This disease can be found throughout the tropics and sub-tropics of Asia, Africa, the Western Pacific, and parts of the Caribbean and South America.

Lymphatic filariasis is a leading cause of permanent disability worldwide. Communities frequently shun and reject women and men disfigured by the disease. Affected people frequently are unable to work because of their disability, and this harms their families and their communities.

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What is Lymphatic filariasis? 

Lymphatic filariasis is a parasitic disease caused by three microscopic, thread-like worms, called Wuchereria bancrofti, Brugia malayi and Brugia timori. These worms infect the lymphatic system and cause Lymphatic filariasis. The adult worm can be found in the human lymph system, this system helps to maintain the body’s fluid balance and fights against infections. 

  • The infected people can experience lymphedema and elephantiasis and in men, swelling of the scrotum,  known as hydrocele. 
  • These nematodes are transferred through the bite of a number of mosquito species such as Anopheles, Culex and Mansonia and Ochlerotatus.
  • If a person gets repeated bites of mosquitoes over several months to years are needed to get lymphatic filariasis.
  • When a mosquito stings an infibidua who has lymphatic filariasis, microscopic worms circling in the person’s blood enter and infect the mosquito. 
  • When biting infective third-stage larvae break out of the mosquito proboscis and enter the skin through the puncture wound and travel to the lymph vessels. 
  • In the lymph vessels, the parasite grows into adults which takes over 6-12 months. An adult worm exists for about 5–7 years.
  • The adult worms mate and release millions of microscopic worms, termed microfilariae, into the blood. People with the worms in their blood can give the infection to others through mosquitoes.
  • The diagnosis of this disease can be done by examining the blood sample under the microscope to distinguish the microscopic worms, known as microfilariae. 
  • Those peoples are lived in tropical or sub-tropical areas for a long time are at the greatest risk for infection, because this disease is common in tropical or sub-tropical areas.

Causative Agent of Lymphatic filariasis

Lymphatic filariasis is caused by three microscopic, thread-like worms, called Wuchereria bancrofti, Brugia malayi and Brugia timori. 

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Wuchereria bancrofti under microscope
Wuchereria bancrofti under microscope | Image modified from https://www.pathologyoutlines.com/topic/cervixcytologywuchereria.html

Characters of Wuchereria bancrofti Adult worms

  • It is a filarial (arthropod-borne) nematode (roundworm).
  • Wuchereria bancrofti is the causative agent of lymphatic filariasis.
  • This organism shows sexual dimorphism (Sexual dimorphism is the condition where the two sexes of the same species exhibit different characteristics beyond the differences in their sexual organs).
  • As adult worm is long, cylindrical, slender, and smooth with rounded ends.
  • The Wuchereria bancrofti worm is white in color or almost transparent.
  • The body of Wuchereria b. is very fragile, creating removing it from tissues difficult.
  • It contains a short cephalic or head region which is connected to the main body by a short neck.
  • Dark pinches are disbanded nuclei throughout the body cavity, with no nuclei at the tail tip. 
  • The male worm is smaller in size, about 40 mm (1.6 in) long and 100 μm (0.0039 in) wide, and contains a ventrally bowed tail. The tail tip contains 15 pairs of minute caudal papillae, the sensory organs. The anal area is consisting of 12 sets of papillae, of which 8 are in front and four are after the anus. 
  • The female worm is three times larger in diameter than the male. It is about 60 millimetres (2.4 in) to 100 millimetres (3.9 in) long and 300 micrometers (0.012 in) wide. The tail of the female worm is gradually tapered and curved at the tip. Additional sensory structures are absent. Its vulva extends towards the anterior region, about 0.25 mm from the head. 
  • Sometimes the adult males and females are coiled together and are difficult to separate them
  • The average lifespan is about  5 years.
  • Wuchereria bancrofti lacks visual senses and rather relies on chemosensation to identity the chemicals in its environment and pheromones discharged by other members of its species. 
  • Additionally, papillae, both oral and outside of the body, helps in tactile communication with the environment and food.
  • It uses its chemosensory capabilities to identify the variation in oxygen levels between arterial and venous blood vessels.
  • They use the mouth to feed on the body and tissue fluids of its human host.

Microfilariae (Embryos)

  • The female’s worms are ovoviviparous and can generate thousands of juveniles termed as microfilariae.
  • The microfilaria is a minute adult, which contains the egg membrane as a sheath, and is often called the advanced embryo.
  • The microfilaria is about 290 mm in length by 6-7 mm in breadth.
  • It looks very structureless in vivo, but histological staining makes its primitive gut, nerve ring, and muscles apparent.
  • Microfilariae are very aggressive and can migrate with and against the bloodstream.
  • Their life span in the human body is presumably 70 days.

Morphological characters of Microfilariae (Embryos)

When Microfilariae is stained with Romanowsky’s dye, these following characters appear;

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  • Hyaline sheath: It is a sac-like envelope that is much longer (359 mm) as compared to the larval body serves as the chorionic envelope of the eggs. It persists as investing membrane throughout the larva.
  • Cuticle: It is bordered by subcuticular cells and is observed only with essential stains.
  • Somatic cells or nuclei: The characteristics feature of this parasite is the nucleus, which appears as granules in the middle axis of the body and stretch from the head to the tail end, except the terminal 5% of the tip of the tail. A space has been observed at  the anterior end devoid of granules known as cephalic space. The granules are broken at certain areas helping as the markers for identification of the species.
 Wuchereria bancrofti and Microfilariae (Embryos)
Wuchereria bancrofti and Microfilariae (Embryos) | Image modified from https://www.studyandscore.com/studymaterial-detail/wuchereria-general-characters-life-cycle-and-filariasis

Geographic Range of Wuchereria bancrofti

  • It is a common human parasite which can be found in tropical regions worldwide. There are about 106 million infected people in 76 countries.
  • Wuchereria bancrofti can be found in Central Africa and the Nile delta, South and Central America, and the tropical regions of Asia including southern China and the Pacific.
  • There are two main factors that limiting the geographical distribution of this nematode such as the climate requirement of its intermediate host, the mosquito.

Habitat of Wuchereria bancrofti

Habitat Regionstropical, freshwater
Terrestrial Biomesrainforest
Aquatic Biomeslakes and ponds, rivers and streams, temporary pools
Wetlandsmarsh, swamp
Other Habitat Featuresurban, suburban, agricultural

Host of Wuchereria bancrofti

Mode of Infection/Life cycle

The causative agents of Lymphatic filariasis follow this life cycle or mode of infection;

The life cycle of Wuchereria bancrofti 

An infected mosquito (e.g. Mansonia spp. and Aedes spp.) injects third-stage filarial larvae within the skin of the human host during a blood meal. The filarial larvae penetrate through the bite wound.

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Life cycle in Human

  1. After penetration, they moved to lymphatics and started to develop to form adult worms.
  2. The female worms measure 80 to 100 mm in length and 0.24 to 0.30 mm in diameter, while the males measure about 40 mm by 1 mm. Adults produce microfilariae measuring 244 to 296 μm by 7.5 to 10 μm, which are sheathed and have nocturnal periodicity, except the South Pacific microfilariae which have the absence of marked periodicity. 
  3. The microfilariae migrate into lymph and blood channels moving actively through lymph and blood.
  4. These microfilariae stay in the deep blood vessels of man during the daytime and during the night they come to the surface in peripheral or superficial blood vessels. 
  5. They circulate in the blood for 6 months to 2 years and then die if not taken by a mosquito.

Life cycle in Mosquito

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  1. During the blood meal of a mosquito, they ingest the microfilariae.
  2. After ingestion, they lose their sheaths within 2 to 6 hours and while some of them are run their way through the surface of the proventriculus and cardiac part of the mosquito’s midgut and enter the thoracic muscles.
  3. They enter into the stomach wall and within 4 to 17 hours leave to thoracic muscles or wing musculature where they undergo metamorphosis and grow.
  4. In the next 2 days, they become short and thick like sausages having short spiky tails and measures 124 to 250µm in length and 10 to 17µm in diameter, also possess rudimentary digestive tract. These are first-stage larvae (L1).
  5. Within the following 3 to 7 days they develop quickly and molt once or double to become the second stage larvae (L2) which range from 225 to 33oµm in length and 15 to 3o µm in diameter.
  6. Metamorphosis finally ends by 10-11 days into third-stage filariform larvae (L3) which measure about 1500 to 2000 µm in length and 18-23 µm in diameter.
  7. The 3rd stage larvae are actively motile and infective.
  8. These larvae move through the hemocoel to the mosquito’s labium(proboscis).

Infection of the new human host

  1. When this infected mosquito penetrates its proboscis in the warm and moist skin of man, the larvae creep out of labium to human skin,
  2. Then, it penetrates the skin and finally comes to settle down into lymphatics.
  3. In the lymph vessels, they grow and become fully adult and sexually mature within a period of 5 to 18 months.
  4. The sexually mature worms start reproduction to repeat life history.
 life cycle of Wuchereria bancrofti
life cycle of Wuchereria bancrofti | Image Source https://www.cdc.gov/dpdx/lymphaticfilariasis/index.html

The life cycle of Brugia Malayi

An infected mosquito (e.g. Mansonia spp. and Aedes spp.) injects third-stage filarial larvae within the skin of the human host during a blood meal. The filarial larvae penetrate through the bite wound.

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The life cycle of Brugia Malayi
The life cycle of Brugia Malayi | Image Source https://www.cdc.gov/dpdx/lymphaticfilariasis/index.html
  1. After penetration, they moved to lymphatics and started to develop to form adult worms.
  2. The newly formed adult worms morphologically look like of those Wuchereria bancrofti but are smaller in size. Female worms mainly range from 43 to 55 mm in length by 130 to 170 μm in width, and males are range from 13 to 23 mm in length by 70 to 80 μm in width. Whereas, Adults produce microfilariae, which ranges from 177 to 230 μm in length and 5 to 7 μm in width, which are covered and have late periodicity (in some regions B. malayi may be sub-periodic, and note that microfilariae are usually not produced in B. pahangi infections). The microfilariae move into lymph and enter the bloodstream arriving the peripheral blood.
  3. During the blood meal of a mosquito, they ingest the microfilariae.
  4. After ingestion, they lose their sheaths and while some of them are run their way through the surface of the proventriculus and cardiac part of the mosquito’s midgut and enter the thoracic muscles.
  5. There now the microfilariae develop into first-stage.
  6. Worms and subsequently into third-stage infective worms
  7. The third-stage infective worms move into the hemocoel to the mosquito’s prosbocis.
  8. Again it can affect another human when the mosquito takes a blood meal.

Vectors of Lymphatic Filariasis

The main vector of Lymphatic Filariasis is mosquitoes. A variety of mosquitoes helps in the transmission of Lymphatic Filariasis, depending on the geographic area. For example in Africa, Anopheles is most common vector of Lymphatic Filariasis, while in the Americas, it is Culex quinquefasciatus. In Pacific and Asia,  Aedes and Mansonia help in the transmission of infection.

Some examples of mosquito which act as a Vectors of Lymphatic Filariasis;

  • Anopheles gambiae
  • Culex quinquefasciatus
  • Aedes polynesiensis

Lymphatic filariasis symptoms

Most of the people who infected by lymphatic filariasis are asymptomatic and they will never show clinical symptoms, despite the evidence that the parasite harms the lymph system. Few of them will show lymphedema or, in men, an inflammation of the scrotum termed hydrocele.

Lymphedema mainly occurs due to improper functioning of the lymph system which leads to fluid accumulation and swelling. Lymphedema mainly hits the legs, but can additionally occur in the arms, breasts, and genitalia. These clinical manifestations mainly appear years after being infected.

The body cannot fight back against germs and infections anymore due to the swelling and the decrease in function of the lymph system. As a result different bacterial infections started to occurs in the skin and lymph system. This may lead to the hardening and thickening of the skin, which is termed elephantiasis. 

Men can develop hydrocele or inflammation of the scrotum due to infection with one of the species of parasites that causes LF, especially W. bancrofti.

LF also responsible for tropical pulmonary eosinophilia syndrome. Eosinophilia is a higher than average level of disease-fighting white blood cells, termed eosinophils. This sign is typically seen in infected persons in Asia. 

Clinical symptoms of tropical pulmonary eosinophilia syndrome can be cough, shortness of breath, and wheezing. The eosinophilia is usually co-occurred by immense levels of Immunoglobulin E ( IgE) and antifilarial antibodies.

Lymphatic filariasis symptoms
Lymphatic filariasis symptoms Image modified from https://i0.wp.com/rxharun.com/wp-content/uploads/2019/07/960x540_Blog-Image-12-1.jpg?ssl=1 and https://www.who.int/lymphatic_filariasis/disease/lymphatic_filariasis_disease_490_HR.jpg

Stages in Lymphatic Filariasis Symptoms

There are four stages in Lymphatic Filariasis such as;

  1. Asymptomatic amicrofilariaemic stage
  2. Asymptomatic microfilariaemic stage
  3. Stage of Acute manifestation
  4. Stage of Obstructive (Chronic) lesions 

Asymptomatic amicrofilariaemic stage

  • In endemic regions, a proportion of the society does not exhibit microfilaria or clinical manifestation even though they have some degree of exposure to infective larva related to those who become infected. 
  • Laboratory diagnostic methods are not capable to determine whether they are infected or not.

Asymptomatic microfilariaemic stage

  • Considerable proportions are asymptomatic for months and years, though they have circulating microfilariae. They are an important source of infection. 
  • They can be detected by Night Blood Survey and other suitable procedures.
  • Patients may have hidden damage to the lymphatic system and kidneys.

Stage of Acute manifestation

  • During initial months and years, there are recurrent episodes of Acute inflammation in the lymph vessel/node of the limb & scrotum that are related to bacterial & fungal super infections of the tissue that are already compromised lymphatic function. 
  • Clinical manifestations are consisting of:
    • Filarial fever (Another clinical syndrome is known as filarial fever. This is characterized by acute, self-limiting episodes of fever, often in the absence of any obvious lymphangitis or lymphadenopathy.)
    • Lymphangitis
    • Lymphadinitis
    • Epididimo orchitis

Diagnosis of lymphatic filariasis

  • The diagnosis of lymphatic filariasis can be done by detecting the presence of microfilariae in a blood smear by using a microscope.
  • Serologic techniques can be used to diagnose lymphatic filariasis, as the infected person contains elevated levels of antifilarial IgG4 in the blood and these can be detected using routine assays.
  • PCR-based assays for DNA
  • Imaging studies (high frequency ultrasound, lymphoscintigraphy)
  • Detection of circulating filarial antigen – rapid format card test/ immunochromatographic card test (ICT)

The microfilariae circulate in the blood at night (termed nocturnal periodicity). Blood sample collection should be done at night to match with the appearance of the microfilariae, and prepare a thick smear and stained with Giemsa or hematoxylin and eosin. For increased sensitivity, concentration techniques can be used.

Prevention of lymphatic filariasis

We can prevent lymphatic filariasis by avoiding mosquito bites. Because it mainly transmitted through the mosquito. If you are living in an area with lymphatic filariasis then follow these following steps;

  • During night
    • Sleep in an air-conditioned room or
    • Sleep under a mosquito net
  • Between dusk and dawn
    • Wear long sleeves and trousers and
    • Use mosquito repellent on exposed skin.
  • Use medication or pesticides to kill the microscopic worms to control mosquitoes.

Lymphatic filariasis treatment

For treatment of lymphatic filariasis the following drugs can be used;

  • Diethylcarbamazine citrate (DEC): DEC exerts its nematicidal activity by targeting the arachidonic acid metabolic pathway.    
  • Ivermectin (IVM): IVM disrupts glutamate-gated chloride channels in the nematode that control release of excretory/secretory vesicles that would normally suppress the immune response.
  • Albendazole (ALB): ALB is a benzimidazole used to disrupt the nematode microtubule of cytoskeleton.
Note:
  • These drugs are mainly microfilaricidal for short period.
  • All three drugs do show a limited macrofilaricidal effect.
  • These drugs can show adverse side reactions.

References and Further Reading

  • https://www.cdc.gov/parasites/lymphaticfilariasis/gen_info/index.html
  • https://animaldiversity.org/accounts/Wuchereria_bancrofti/
  • https://www.cdc.gov/dpdx/lymphaticfilariasis/index.html
  • https://en.wikipedia.org/wiki/Wuchereria_bancrofti
  • http://www.antimicrobe.org/new/b141.asp
  • https://www.msdsonline.com/resources/sds-resources/free-safety-data-sheet-index/wuchereria-bancrofti/
  • https://thebiologynotes.com/wuchereria-bancrofti-habitat-morphology-and-life-cycle/
  • https://www.onlinebiologynotes.com/wuchereria-bancrofti-morphology-life-cycle-and-epidemiology/

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