Introduction

Definition of acanthocheilonemiasis

Acanthocheilonemiasis is a rare infectious disease caused by Acanthocheilonema perstans, a type of parasite (previously referred to as Mansonella perstans).¹ This parasite is part of a group of parasitic diseases called filarial diseases (nematode).³ When tropical flies and mosquitoes feed on food contaminated with this parasite, they can transfer it to humans when biting them.²

Epidemiology

Acanthocheilonema perstans is generally found in central Africa and some regions in South America. People are more likely to develop acanthocheilonemiasis when visiting areas in which this parasite is found more frequently. Therefore, the disease usually affects people who live in these regions, so its prevalence is highly endemic.

Pathophysiology and symptoms

Life cycle of acanthocheilonema

This parasite usually develops in the human host.⁴ Its transmission cycle begins when an infected midge, such as a fly or mosquisto, bites a human, taking a blood meal from the person affected. This allows the parasite (stage 3 (L3) larvae) to enter the human system through the skin wound. When inside the body, the parasite develops into an adult in the abdominal cavities (peritoneal cavity) and/or lungs (pleural cavity), sometimes even in the heart (pericardium). Female worms range from sizes of 70 to 80 mm in length and 120 µm in diameter, and the males measure approximately 45 mm by 60 µm⁴. Adults then produce stage 1 (L1) larvae (200 µm long, 4.5 µm wide) that reach the bloodstream. The disease can be diagnosed during this period.

These larvae are then transmitted through insect vectors. When a midge bites an individual that has these larvae in their bloodstream, the midge ingests these larvae. The larvae migrate from the gut to the chest of the midge and grow. When they have grown sufficiently, they migrate to the head and proboscis, which midges use to feed. The next time this midge takes a blood meal from a human, the larvae can enter the wound, entering the human body. This then restarts the cycle, which can be seen more clearly in the figure below.

Link: https://www.cdc.gov/dpdx/mansonellosis/modules/M_perstans_LifeCycle_lg.jpg 

Clinical manifestations

Many infections are asymptomatic, especially among individuals living in endemic regions. However, those with acanthocheilonemiasis can show the following symptoms:

• Headache
• Skin lesions, including red, itchy skin (pruritis)
• Abdominal pain
• Chest pain
• Muscular pain (myalgia)
• Swelled-up areas (edema)

It is important to understand the importance of treating this disease, as it can also lead to other complications if it’s not treated promptly:

• Exaggerated growth of the liver and spleen (hepatosplenomegaly)
• Abnormal immune reactions
• High white blood cell levels (eosinophilia)
• Inflammation of:
  • The lining of the lungs (pleuritis)
  • The muscles surrounding the heart (pericarditis)
  • The abdomen and chest

This review aims to provide a comprehensive overview of the different treatment options for acanthocheilonemiasis.

Diagnosis

Clinical diagnosis

A physical examination is carried out to diagnose this disease. During this examination, the healthcare provider would search for subcutaneous swellings, which can vary in size. They also look for skin lesions or itchy rashes that can be localized or spread throughout the skin, depending on the severity of the infection. Additionally, there might be swelling in different areas where the larvae have migrated to. Other symptoms that are checked for are discomfort in these specific areas, fever, headaches, and fatigue.

The history of exposure is an important factor that determines whether this disease is acanthoceilonemiasis or caused by a different parasite. If the individual has lived or travelled to areas where Acanthocheilonema perstans is endemic, it is likely that the disease is acanthocheilonemiasis. Furthermore, the duration and onset of the disease can help clarify whether the infection is recent (acute) or if it has developed (chronic), providing information about the severity of the disease.

Laboratory diagnosis

Microscopy

Larvae of Acanthocheilonema perstans and other parasites such as Mansonella ozzardi can be identified by looking at blood samples under the microscope. Others are identified in skin snips. These patients may show higher levels of these parasites in their blood in the morning hours. 

Concentration techniques (e.g. Knott’s concentration) may increase sensitivity.⁴ 

Molecular detection

Polymerase chain reaction (PCR) tests can be used to amplify and detect specific DNA sequences of the Acanthocheilonema perstans larvae. It is done through the extraction of DNA from a patient’s tissue sample (skin snip), and then by identifying the specific genetic material of the parasite. This confirms that the specific parasite causing the disease is Acanthocheilonema perstans, and the patient is not suffering from an alternative disease.

Serological testing (antibody detection)

Serological tests detect antibodies produced in response to an infection. However, the serological assays developed for the detection of this specific parasite are not completely reliable because of cross-reactions with other parasites and potentially nematodes.⁴

Treatment options

Pharmacological treatment options

There is no specific drug that is effective against all types of parasite infections, and some infections have no treatment at the moment. In the case of acanthocheilonemiasis, there are several effective options. Antifilarial medication is the most commonly used option; however, there are also non-pharmacological interventions. If there are only eggs and larvae, antiparasitic drugs like ivermectin, albendazole, and diethylcarbamazine (DEC) can be used to reduce the number of larvae and relieve the symptoms that they cause. In more severe cases where the number and size of worms can be life-threatening and antiparasitic drugs are not effective, the patient might need to undergo surgery to remove the parasite.²

Antifilarial medications

Ivermectin

Ivermectin is a drug which is typically used against parasitic diseases. This drug binds to specific brain receptors (glutamate-gated chloride channels) within the parasite, causing them to be paralyzed and die. It also affects their feeding and reproduction. These receptors are not present in vertebrates, offering a safety margin to those who take this drug.⁶ The most effective dose is 200 μg/kg for all nematode and parasitic infections. Its usage may have adverse symptoms such as oedema, rash, headache, and ocular (eye) issues.⁵ These effects are generally mild and do not last long. 

Albendazole

The mechanism of action of albendazole is unknown. However, research has shown that it affects the parasite’s metabolism through different pathways, affecting its energy production.⁸ It also kills eggs and larvae.^9,10 The recommended dose is one 400 mg tablet that is taken orally twice a day with food. It is usually taken for 8 to 30 days.⁷ The side effects reported in literature are very low, with a frequency of just >1%, and generally being gastrointestinal side effects.⁶ However, it can also cause headaches, dizziness, and reversible hair loss. 

Diethylcarbamazine (DEC)

DEC stimulates the immune system, making the larvae stick to the immune cells that degrade them,¹¹ acting as an anti-inflammatory drug. It has been found that DEC reduces larvae levels by 95.8%.¹² The recommended oral dose is based on body weight and should be determined by a doctor. It is usually 2-3 mg per kg of body weight, three times a day for adults. In the case of children, the dose is calculated alternatively by the prescribing healthcare professional.¹³

Combination therapy

An alternative option is using several medications to treat acanthocheilonemiasis. This increases the effectiveness as the drugs explained above target the parasite differently. Additionally, this can be useful in the case that the patient has been infected by multiple parasites. There are several drug combinations, usually, 2 or 3 drugs are taken at the same time. Common double-drug therapies include DEC and Albendazole or Ivermectin and Albendazole, which attack the parasite’s metabolism and structure at the same time. A common triple-drug combination is formed by ivermectin, DEC, and Albendazole, which is used in endemic areas.

It has been found that using triple-drug therapy is significantly more effective than double-drug therapy or just taking an individual drug.¹⁴ However, there is a higher risk of suffering from adverse effects, such as fever, muscle pain, and itchy skin, although these side effects are rarely serious.

Alternative treatment options

An alternative option is taking treatments that do not directly target the parasite. Treatment can be taken to manage the symptoms, like analgesics (e.g., aspirin) to manage the pain or anti-inflammatory drugs (e.g., ibuprofen) to manage the swelling and inflammation. In more severe cases, surgery might be needed to remove the parasite and prevent the spread of the infection.

Preventive measures

Several measures can be taken to reduce the likelihood of developing acanthocheilonemiasis. Firstly, it is important to avoid insect bites. The use of insecticides such as sprays is very useful, in addition to wearing protective clothing and bed nets. Avoiding areas with many insects is also a measure. In the case that you were bitten by an insect, it is essential that you take care of the wound, keeping it dry and covered, as well as cleaning it to ensure it does not get infected.

Summary

There are several options of treatments for acathocheilonemiasis, including antiparasitic medications like ivermectin, albendazole, and diethylcarbamazepine (DEC). These can also be used in combination to increase the efficacy. Surgical interventions may be necessary in severe cases, while symptomatic treatments can help manage pain and inflammation. Understanding and using these treatments can help patients relieve their pain and reduce the symptoms so the infection does not spread. Preventive measures, such as avoiding insect bites, are also essential to reduce the risk of infection. Acanthocheilonemiasis is a rare infectious disease caused by Acanthocheilonema perstans, a type of parasite transmitted by bites from infected midges (flies or mosquitoes). The infection can cause symptoms like headaches, skin lesions, abdominal and chest pain, and muscular pain, but many cases remain asymptomatic.