Introduction

Filariasis is the general term for infectious tropical diseases caused by filarial parasites.¹ These are roundworms (nematodes) which have a thread-like appearance. The terms ‘filarial nematodes’ and ‘filarial parasites’ will be used interchangeably in this article. Some sources may also refer to worms as helminths. Parasitic organisms take advantage of their host, without giving back to them. 

Neglected tropical diseases (NTDs) such as filariasis occur throughout impoverished areas, where access to healthcare and proper housing is poor. Treatment and control of parasitic diseases is difficult due to their complex life cycle. 

Additionally, many are associated with vectors (other organisms that carry the disease without contracting it themselves). For example, the Anopheles species of mosquitoes are vectors which transmit malaria to humans. Malaria is caused by a pathogen known as Plasmodium.

Bites from infected host mosquitoes allow Plasmodium to enter the blood, where they reproduce. This results in the onset of symptoms of illness, like fever.²

Neglected tropical diseases caused by filarial parasites are generally named after the organism that causes them. Known filarial parasites which infect humans include:

• Wuchereria bancrofti, Brugia malayi (and in rare occurrences, Brugia timori) cause  lymphatic filariasis – repeated infections can lead to elephantiasis, profuse swelling of the legs and genitals
• Loa contributes to loiasis, which is usually asymptomatic
• Mansonella perstans and Mansonella streptocerca cause mansonellosis³
• Acanthocheilonema perstans, and acanthocheilonemiasis
• Onchocerca volvulus, leading to onchocerciasis (river blindness)⁴

A zoonosis is a disease that can be transferred from other animals to humans. As of now, new species of zoonotic filarial nematodes are still to be discovered and confirmed. 

Examples of known species of filarial parasites that have been extracted from humans and other animals include:

• Dirofilaria repens, Dirofilaria tenuis, Dirofilaria ursi, Dirofilaria immitis and Dirofilaria subdermata
• Dipetalonema arbuta, and Dipetalonema sprenti⁵
• Brugia pahangi
• Setaria digitata and Setaria labiatopapillosa⁶

This article will describe the common stages that filarial parasites must go through to mature, reproduce and spread. A wider understanding of the life cycle of these organisms can provide ideas for disease control and prevention, especially in tropical regions.

Life cycle stages of filarial parasites

Filarial nematode evolution is driven by how well they can take advantage of the host, amidst other factors. As a result, some developmental stages are shared between species, as it has been so successful for the survival of these parasites.

Stage 1: Microfilariae in the host's bloodstream

The life cycle of filarial parasites begins in humans, following a bite from an infected mosquito. Adult worms that get inside the bloodstream release microfilariae. This is the prelarval stage of filarial nematodes.

In some species like Wuchereria bancrofti, these microfilariae circulate in the host’s bloodstream at night – a mechanism called nocturnal periodicity. This allows the parasite to spread further when it encounters the mosquito vector, which will usually bite when humans are sleeping.⁷

Stage 2: Transmission to the mosquito vector

Blood meals are vital to the survival of mosquitoes, specifically female mosquitoes, which require nutrients from blood in order to grow their eggs.⁸

Filarial nematodes use mosquitoes as an intermediate host. This means that mosquitoes support the non-reproductive stage of the parasite before they reach sexual maturity.⁹

When a mosquito bites an infected human, it ingests the microfilariae that are in the bloodstream. 

Genera of mosquito vectors include:

• Aedes
• Anopheles
• Culex
• Mansonoid

Multiple species of these mosquito vectors are able to ingest and host the larvae once they are transferred from the bloodstream to the mosquito.

Stage 3: development within the mosquito

In the gut of the mosquito, the microfilariae continue to mature in a series of moulting stages until they become larvae. This encompasses first and second-stage larvae transformations (L1 and L2 respectively).

Once the larvae reach a certain moult (L3) they enter the head and proboscis of the mosquito, to become an infective parasite. 

Stage 4: transmission to new host

The proboscis is a long mouthpart that a mosquito uses to suck blood.¹⁰ L3 infective parasites are deposited onto the skin of humans and enter through the newly made bite wound. 

From here, they make their way towards the tissue under the skin as well as the lymphatic system.

Stage 5: maturation in the human host

After biting a human, these larvae enter the wound. They make their way to the vessels and lymph nodes, where they eventually mature. Wuchereria bancrofti and Brugia malayi finish this process in the lymphatic system, involved in the immune response.

Alternatively, they may also enter the subcutaneous tissue – this is the case with Onchocerca volvulus and Loa loa.¹¹

Sexual maturity occurs after four to nine months. These worms can live for five to seven years. Damage to the lymphatic system results in blockages, fever and swelling. 

Stage 6: reproduction and release of microfilariae

10,000 microfilariae can be released into the host bloodstream from adult female filarial parasites. 

This continues the cycle, and microfilariae circulate once again in the host bloodstream.¹²

Host and vector interactions

Humans and mosquitoes play important roles in the survival of filarial parasites, providing an environment where they can reproduce and spread.

Filarial infections can have varying effects on us, as well as mosquitoes. 

Human host response

Our bodies have a unique way to fight off infections. In the case of parasites, specialised white blood cells known as eosinophils help out by releasing enzymes that kill the nematodes while promoting inflammation for healing.¹³

Other parts of the immune system are involved following filarial infection, such as macrophages – these are white blood cells that engulf and digest worms to destroy them. Antibodies also help to induce inflammation to provide support.¹⁴

Vector biology and behaviour

Mosquito vectors allow the vulnerable larvae of filarial parasites to mature before they become infectious. Similar to our immune system, some mosquitoes have their own resistance mechanisms that damage the microfilariae.¹⁵

Diagnosis and detection

Clinical signs and symptoms

Infection by filarial parasites may go undetected for years. It is common for these diseases to be asymptomatic, however, in late-stage infections, they can occur.

Lymphatic filariasis, the most prolific filariasis disease, has symptoms such as:

• Hardened skin
• Scrotum swelling in assigned male at birth (AMAB) individuals
• Lymphoedema, swelling of the breasts, genitals and limbs
• A persistent cough
• Wheezing
• Breathlessness

Onchocerciasis (river blindness) causes these symptoms:

• Itchy skin
• Loss of vision
• Lumps under the skin

Loiasis (eye worm) can cause these symptoms:

• Itchy but not painful swelling on limbs
• Movement of worms across the eye, or beneath the skin surface
• Itching all over the whole body
• Tiredness or weakness
• Pain in the muscles or joints

Mansonellosis symptoms include:

• Fever
• Tiredness
• Pain in the joint and abdominal region
• Occasional swelling
• Vision impairment, if the worm enters the eye
• Rashes
• Inflammation of the heart lining (pericarditis)

These symptoms can be used to distinguish between different filarial diseases.¹⁶

Laboratory diagnosis

To confirm the presence of microfilariae, blood smears may also be used. This is the standard diagnostic test for loiasis. The amount of microfilariae present on the smear can suggest directions for treatment.

A characteristic sign of filarial infection is eosinophilia, which is an abnormally high amount of eosinophils in the blood. It is a sign that there may be a parasitic infection taking place.

Further validation includes serological tests, which check the blood for any markers of filarial parasite infection.¹⁷

Polymerase chain reaction (PCR) allows a small DNA sample to be studied and has been used to identify types of worms present in a filarial parasite infection.¹⁸

Imaging and ultrasound

Imaging techniques such as ultrasonography may also be used to detect adult worms within the body. 

Swelling of the lymph nodes (lymphadenopathy) and nodules forming after worm death can be visualised.

Prevention and control

Vector control strategies

Several measures can be taken to control mosquitoes. Nets treated with insecticide can be placed around windows or doors. Spraying insecticide in living spaces can help to eliminate insects indoors.

Removing sources of standing water, such as pools and containers can stop mosquitoes from finding somewhere to breed.

Mass drug administration (MDA)

Mass drug administration has been used to control infections in endemic areas. Antiparasitic medications used in these regions include:

• Albendazole
• Diethylcarbamazine
• Ivermectin

Though MDA has been implemented as part of the Global Programme to Eliminate Lymphatic Filariasis (GPELF), its efficacy has been hindered by other factors such as weaker health systems or inaccurate data reporting. 

Personal protection measures

Using protective clothing that covers the skin and wearing insect repellent can prevent mosquito bites. Community education can help to provide knowledge to a wide amount of people and reduce filarial parasite infections. 

Treatment

Pharmacological interventions

Medication for lymphatic filariasis usually targets the adult worm. The first line of treatment is diethylcarbamazine citrate (DEC), which is effective against microfilariae and adult worms. 

Ivermectin has been used as an antibiotic against Wuchereria bancrofti microfilariae, but cannot kill the adult parasite.¹⁹
Other medications have been used in treatment programmes, however, some pose harmful side effects or have long administration regimens. This makes it difficult to scale up treatment to a larger group of people.²⁰

Management of complications

Following filarial parasite infection, a number of chronic complications can occur. With proper healthcare systems, these can be managed to improve the quality of life for the patient.

Hydrocele can be alleviated with surgery. 

Controlling lymphoedema can be done through decongestive lymphatic therapy, using four components:

• Manual lymphatic drainage (MLD) massage
• Use of compression bandages
• Proper skin care
• Exercise which promotes lymph drainage.

It is important to have ongoing supportive care for individuals affected by filariasis. The GPELF endeavours to distribute care packages that treat infections and other chronic manifestations of filarial parasite infection. 

Summary

The beginning of filarial parasite life cycle begins with pre-larval microfilariae in the host bloodstream, which are picked up by mosquitoes when they suck blood from humans.

These microfilariae undergo two moulting stages and then migrate to the head and proboscis of the mosquito at L3.

Now an infective parasite, the filarial nematode is deposited onto the skin of the human. After the mosquito bites, the worm enters through the bite wound. It will mature in the subcutaneous tissue or lymphatic system, causing disturbances such as fever and swelling.

Adult worms release new microfilariae into the human bloodstream to repeat the cycle.

Interrupting the life cycle of filarial parasites is key to controlling and eliminating filariasis, as well as other neglected tropical diseases that involve mosquito vectors. 

More research is needed to develop better control strategies, as well as global cooperation in order to bring awareness to these diseases and provide better funding for protective measures in tropical countries.