Introduction

Acanthocheilonemiasis, now known as Mansonelliasis or Mansonellosis, is defined as a rare infectious disease transmitted through a bite of tropical flies called A. coliroides or biting midges. A parasite, Acanthocheilonema or dipletalonema perstans, has currently been renamed and redefined as Mansonella perstans, part of the group of nematodes, which are roundworms responsible for causing the filarial disease. Furthermore, 3 other species sharing the same genus with M. perstans can cause acanthocheilonemasis, which are M. streptocerca and M. ozardi. The parasites are normally found in the ground where independent species like animals would be found, and they feed on bacteria, fungi, and other nematodes, additionally consuming open food items.¹

History of M. perstans

M. perstans was first discovered in 1890, extracting the microfilariae from a hospitalised patient in London. The microfilariae was initially named a similar species to the parasite that causes Loa Loa infection. The name was later changed to Filaria perstans. The following years it was known as either Acantheilonema or Dipetalonema perstans before, in 1984, Eberhard and Orihel renamed it to Mansonella perstans.²

Epidemiology

The nematode can be found distributed in Africa, except for the most northern and southern points, also found in central and South America. Stoll (1947) estimated that 19 million Africans are affected by M. perstans infection, which, when inflated, to todays number would correspond to 114 million infections. Especially in endemic regions, the prevalence and intensity of M. perstans microfilaraemia increased gradually with age. M. ozzardi, on the other hand, is only found in central, south-american, and Caribbean regions. Finally, M. streptocerca is normally found in the western and central parts of africa. Debra et al. (2017) did an epidemiological study on M. perstans in Ghana. The results showed that males and the age group between 20 and 45 years had a higher chance of being infected by M. perstans. Additionally, they observed that communities in plantain vegetation that was more dense and swampy with faeces from livestock had a higher prevalence of M. perstans infections.²

Signs and symptoms

Acanthocheilonemiasis doesn’t have many specific clinical symptoms, but the main feature of Acanthocheilonemiasis is eosinophilia, which is when the body produces too many eosinophils, a specific white blood cell that targets parasitic worms. Furthermore, other non-specific symptoms include:³

• Itchy skin
• Abdominal pain
• Chest pain
• Headache
• Localised swelling 
• Muscle and joint pain
• Subcutaneous swelling similar to Calabar swelling of the Loa Loa infection

Further complications also include

• Abnormal immune reactions
• Inflammation of the lining of the lungs
• Enlarged liver and spleen
• Neurological and psychological symptoms
• Fatigue

Acanthocheilonemiasis caused by M. ozzardi can also cause the symptoms of ocular (eye) lesions and chills in the lower limb, while M. streptocerca can cause papular rashes, which are red swelling and changes in pigmentation of the skin along with the swelling of the lymph node (inguinal lymphadenopathy). It’s important to note that the microfilariae of M. ozzardi and M. perstans can be found in the bloodstream, while the M. streptocerca microfilariae is commonly found in the skin and subcutaneous tissues.⁴

Pathophysiology of Acanthocheilonemiasis

Life cycle of Mansonella perstans

Biting midges belonging to the genus Culiroides causes acanthocheilonemiasis. They are stout in shape with a short vertical proboscis and scissor-like wings. The developmental cycle of the vector takes roughly 2–6 weeks to complete, dependent on environmental conditions. The female M. perstans worm is usually the more common worm to infect humans. Transmission to humans occurs when the biting midge takes a blood meal and the female worm releases a sharp-tailed microfilariae. It’s theorised that environmental factors like body temperature activate the microfilariae and cause them to leave the vector and penetrate the skin and reach the bloodstream. Once within the bloodstream, further development takes place where the microfilariae becomes a mature adult. A female worm can then reproduce by releasing more living microfilariae.

When another biting midge takes a blood meal from the infected individual, they’ll ingest the newly released microfilariae. The ingested microfilariae migrate through the stomach wall to the thoracic muscles, where development takes place. The microfilariae develop into the first larvae and develop into third larvae. The third-stage larvae shorten and thicken; on the 5th day, they increase in length and migrate to the biting midge’s proboscis, ready to infect another individual.⁵

Progression of Acanthocheilonemiasis

Once the Manosella parasitic worm enters an individual, the pathogenic mechanism of Acanthocheilonemiasis is similar to other filarial diseases like Wuchereria bancrofti infections. The parasitic worm travels to the lymph nodes, particularly the femoral lymph node. In turn causing lymphoedema and elephantiasis. Lymphoedema is the swelling of lymph node due to blockage of the lymphatic vessel and elephantiasis is a complex term for lymphatic filariasis infection. Furthermore, this enlargement of the lymph node can cause a reduction of the lymphatic drainage, and the larvae basically clog the vessel. This activates the innate immune response and causes inflammation in the parasitic worm. This causes a cycle of immune dysregulation, turning an acute filarial infection into a chronic one, where poor drainage causes an increase in susceptibility to infection, which leads to inflammation and causes damage to the lymphatic vessels.

The activation of an innate immune response is an important feature of a filariasis infection. The activation of cytokine IL-5, which activates and mature eosinophils, which play an important role in eliminating parasitic infections, but this can aggravate larvae growth and shedding. Interestingly, this seems to be a response to increase immune surveillance to maximise reproduction to increase the number of offspring. A study (2010) has shown IL-4 and IL-5 are important in the regulation of a parasitic worm’s fertility, they found mice without IL-4 and IL-5 to have more microfilariae compared to the control. Additionally, Babu et al. (2011) examined how different Toll ligands, receptors for the first line of innate defence against pathogens, would affect the cytokine response. They found that TLR2 and TLR9 would mediate the production of pro-inflammatory cytokines IFN-y, TNF-a, IL-12, and IL-1β. A study did find that individuals with lymphoedema have significantly higher concentrations of IL-8, macrophage inflammatory protein-1a (MIP-1β), and monocyte chemotactic protein 1 compared to unaffected individuals.

Moreover, the innate immune response can cause the release of vascular endothelial growth factor (VEGF), which causes hyperplasia and hypoxia, alongside other conditions like lymphangiectasia and granulomatous responses. VEGF increases the disease progression of filariasis and aggravates lymphoedema. For example, VEGF-A can cause the leakage and accumulation of fluids. Additionally, the activation of immmune signalling pathways like MAPK and NF-kB was associated with the development of human lymphatic filariasis. Finally, it’s likely hypothesised that the production and release of Th1 cytokines can assist the growth of filarial larvae, as a study found that third-stage larvae can elicit a Th1-like inflammatory response in host cells.

That active lymphatic remodelling of endothelial cells like growth and proliferation is an early clinical pathology of filarial diseases. A recent study (2009) suggests that live filarial parasites induce lymphatic endothelial cell activation, proliferation, and tube formation. Moreover, the persistent immune activation is associated with elevations of circulating microbial products, acute-phase proteins, and microbial translocation molecules; these microbial products can translocate into the periphery of the intestine, which can cause inflammation via immune effector cells. Another study (2012) found elevated levels of circulating LPS and decreased LPS-binding protein to be a pathologic feature of lymphatic filariasis.⁶

Considerations

Many researchers struggle to determine whether or not the acanthocheilonemiasis can be considered a disease due to the high prevalence of asymptomatic cases. So, in turn, research looking into acanthocheilonemiasis is relatively little and lacking sufficient data, so that’s why the pathophysiology is based off the pathogenesis of filarial diseases in general. Currently, it’s hard to determine the true mortality of acanthocheilonemasis as research funds looking into tropical diseases have omitted acanthocheilonemiasis. That it can be troubling as the M. perstan infection can produce false-positive tests, which can mimic other similar filarial infections like Loa Loa when researchers or doctors attempt to diagnose the disease.⁷

Summary

Acanthocheilonemiasis is a tropical parasitic disease that infects humans via a biting midge vector taking blood meals. The nematodes responsible for this disease are three species: Mansonella perstans, Mansonella ozzardi, and Mansonella strepocerca. The pathophysiology of acanthocheilonemiasis can be summarised as the pathogenesis of lymphatic filariasis diseases. The parasitic worm enters the bloodstream and travels to the lymph node, where it can elicit an immune response, block lymphatic vessels, which causes the buildup of lymphatic fluid in the subcutaneous areas. This cascade can create a chronic condition where it releases cytokines and chemokines like VEGF and IL-5 to cause damage and structural changes to the lymphatic vessels or assist the development of the larvae. Additionally, releasing pathogenic products like LPS  can further exacerbate the already dysfunctional immune response.