Overview 

Acanthocheilonemiasis, currently referred to as mansonelliasis or mansonellosis is an infectious filarial disease caused by nematodes from the Acanthocheilonema (presently known as Mansonella) genus. It is a rare parasitic infection mainly caused by Acanthocheilonema perstans (Mansonella perstans). Other species also infect humans, such as Mansonella ozzardi and Mansonella streptocerca. 

The disease is typically asymptomatic, often presenting with mild non-specific symptoms such as fever, fatigue, and abdominal or joint pain. Acanthocheilonemiasis is a vector-borne disease transmitted by biting midges (Culicoides spp.). Acanthocheilonema perstans infections are endemic in tropical regions of Africa and neotropical regions of Central and South America, affecting millions of people living in those areas. 

Several regimens of anthelmintic drugs were proposed for the treatment of acanthocheilonemiasis depending on the parasite causing the infection. However, there is still ongoing research in the development of the best treatment for the asymptomatic Mansonella perstans (henceforth referred to as M. perstans) infection. The lack of proper vector control programmes targeting biting midges is also a rising concern, especially in endemic areas.  

Aetiology and pathogenesis 

Acanthocheilonemiasis (currently known as mansonellosis) is a rare type of filariasis, or in other words, a type of parasitic infectious disease caused by a genus of nematodes (roundworm) called Acanthocheilonema (Mansonella).¹ Filariasis diseases mainly affect mammals, including humans and domestic animals, and are caused by parasitic nematodes (filarial parasites) of different species.² Two of the most common filarial parasite species are Wuchereria bancrofti and Brugia malayi. Different species within the Acanthocheilonema genus affect different mammalian species. For instance, A. perstans (M. perstans) is seen to specifically infect humans, while Acanthocheilonema reconditum primarily affects canines.² 

As acanthocheilonemiasis is a vector-borne disease,  it is transmitted by blood-sucking biting midges of the Culicoides spp.³ Female adult parasites produce microfilaria within a human host. The microfilaria are transferred into the midges’ circulation during a blood meal. Microfilaria migrates from the midgut to the thoracic muscles to undergo three maturation stages (L1 to L3). After developing into an infective larvae (L3), it migrates to the midge’s proboscis to be introduced into another human host during a blood meal.⁴ This marks a successful human-to-human transmission. Adult worms primarily reside in body cavities such as pericardium, peritoneum and pleura and in connective tissues such as fascia, while microfilaria generally remains in the bloodstream.⁴ 

Clinical presentation 

To date, clinical presentations of the disease remain elusive. Most Mansonella infections are asymptomatic, and they often present with non-specific symptoms that are generally mild. Despite its asymptomatic nature, it is reported that acanthocheilonemiasis infection can drastically impact our immune system, thus resulting in immunosuppression, subsequently increasing the risks of co-infections or secondary infections such as HIV, malaria and tuberculosis(TB).⁵  

Most of the symptoms associated with the disease are believed to be a result of the migration of the parasites in the host. For example, subcutaneous oedema, pericarditis, pleuritis and ocular impairment. Ocular manifestation,  more precisely known as “bulge” eye disease, is considered a rare phenomenon in M. perstans infections, which is caused by the migration of the adult worm into the eye region. Dermatological symptoms are also observed, such as rashes and itching (pruritus). Studies also reported the occurrence of Calabar swellings of loiasis in M. perstans infections.⁶ 

Other non-specific systemic manifestations of the disease include: 

• Fatigue
• Fever
• Abdominal pain 
• Arthralgias (joint pain)
• Eosinophilia
• Lymphadenopathy

These symptoms might not be representative of the disease, as most of the symptoms documented are not taken from patients who originate or have lived their whole lives in the endemic regions. The pathogenicity of the infection might be greatly influenced by the presentation of other infectious diseases that are also prevalent in tropical regions where there is widespread acanthocheilonemiasis.⁶ 

Diagnostic methods 

Clinical diagnosis

Since the disease only presents non-specific symptoms, the diagnosis of the disease is a lot harder for clinicians. The aforementioned symptoms that are reported to be highly associated with the disease, such as fever, skin rashes, and abdominal pain, are not specific enough to provide sufficient evidence for a solid clinical diagnosis of the disease. These symptoms might be manifestations of a co-infection caused by other pathogens in the same endemic region. This statement is further proven by the manifestations of cornea lesions seen in both M. ozzardi (another Mansonella sp. that infects humans) infected patients and non-infected patients from the same endemic area. Therefore, a physical examination is not feasible for a reliable diagnosis of acanthocheilonemiasis.⁶ 

Laboratory diagnosis

As the symptoms presented are generally non-specific, laboratory processing is often needed for an accurate diagnosis of the infection.  Parasitological diagnosis is the most widely implemented diagnosis method for acanthocheilonemiasis. The presence of Mansonella microfilariae in the blood is identified under the microscope (blood smear test). Blood samples are usually collected via finger pricks. As some other Mansonella spp. such as M. ozzardi and M. streptocerca, which also cause human infections, often reside in the skin rather than circulating in the bloodstream, skin-snips of about 1.5mg (~2mm diameter) obtained using Holth corneoscleral punch are utilised for the detection of microfilariae.^4,6 

Differential diagnosis

Although filarial worm species possess different morphological and behavioural traits, false diagnoses and failure to distinguish between the microfilariae of different species (M. ozzardi, M. streptocerca and O.volvulus; M. perstans, L. loa and W. bancrofti) were still inevitable.⁶ Therefore, DNA-based molecular diagnosis techniques (real-time PCR assays, RT-PCR) are introduced to aid the differentiation between different filarial worms. This technique is proven to provide the most accurate and sensitive result in the diagnosis of acanthocheilonemiasis. Recently, a new molecular diagnosis technique that does not require any infrastructural support has been introduced for the diagnosis of Mansonella infections, which is the DNA-detecting loop-mediated isothermal amplification (LAMP) assay. Nonetheless, further research is required to test its feasibility and potential as a novel research tool for acanthocheilonemiasis infections.^6,7 

Treatment and management 

Anthelmintic drugs are usually prescribed to acanthocheilonemiasis patients to reduce microfilaria loads in the human host. Anthelmintics that are frequently prescribed are: 

• Ivermectin
• Diethyl-carbamazine (DEC)
• Mebendazole
• Albendazole

These drugs are given individually or in combination depending on the Mansonella sp. causing the infection. The standard combination of drugs that is effective for the eradication of microfilaria for each Mansonella sp. are as follows:⁸ 

Nonetheless, various case studies propose different regimens, each claiming to be the ‘best’ intervention for treating the infection. Further research is needed to compare and validate the efficacy of each regimen.⁸ 

Out of the three Mansonella spp., M. perstans is claimed to be the most difficult to treat. Currently, there is no international guideline suggested for the best treatment for M. perstans infections. Recently, a new therapeutic intervention using doxycycline (an anti-Wolbachia treatment) to target M. perstans infections seems to demonstrate promising results. However, its lengthy regimen of 6 weeks makes it impractical for disease control programmes. Nevertheless, due to its high efficacy profile, it is still regarded as a highly recommended treatment on occasions when the length of the regimen is feasible.⁶  

Prevention and control 

Vector control

Vector-borne diseases are often tightly controlled by vector control programmes and interventions in areas where vector-borne diseases are prevalent.  Some filarial diseases are successfully controlled by interventions implemented for other diseases that are transmitted by the same vector. For example, mosquito eradication programmes that are enforced for the management of malaria disease indirectly contribute to the control of lymphatic filariasis disease due to the similarity in their transmission route.⁹ 

In contrast, no eradication programmes specifically targeting the vector of acanthocheilonemiasis are being implemented despite its high prevalence across various tropical regions. One of the main reasons is the lack of other disease control programmes that target the same vector as acanthocheilonemiasis in regions with widespread infection, such as Africa and the Caribbean.  Also, the use of bed nets, which is an effective method for the management of mosquito-borne diseases, doesn’t seem to be of much help in preventing the transmission of acanthocheilonemiasis. This is due to the size of Culicoides, which are much smaller than mosquitoes.⁹

Personal preventive measures

People living in endemic areas of the disease are encouraged to practise Insecticide Residual Spraying (IRS) in places where the insects are likely to reside and in their homes. IRS control is widely used for malaria control, and studies have proven its efficacy in reducing the abundance of adult Culicoides in homes and animal shelters, though further research is still required to validate its impact on the control of acanthocheilonemiasis.⁹ 

Summary 

Acanthocheilonemiasis is tagged as the most neglected human filarial infection, most probably due to its asymptomatic trait. However, there is a scarce source of clinical literature and studies providing insights into the disease, not to mention the insufficient database on the research of therapeutic interventions for the infection.  Likely due to its high prevalence in rural and low-income areas and its lack of specific clinical manifestations, acanthocheilonemiasis is not explicitly targeted  by the World Health Organisation (WHO), World Bank (WB), or any other NGOs.⁹ The massive disease burden of acanthocheilonemiasis in the aforementioned endemic regions points out the necessity for more attention and research to be conducted by the respective authorities in hopes of enhancing global health.