Mansonella perstans

In 1890, the microfilariae of M. perstans were first discovered by Manson in the blood of a patient from West Africa who was hospitalized with sleeping sickness in London. Because the microfilariae were first noted in a patient with African trypanosomiasis, M. perstans was initially suspected to be the cause of this disease. M. perstans as the cause of African trypanosomyasis was later ruled out by the Royal Society Sleeping Sickness Commission, who showed the geographical distribution of sleeping sickness did not coincide with that of M. perstans infection.

Upon their discovery, the microfilariae were named Filaria sanguinis hominis minor, due to their relatively small size when compared to another type of microfilarae found in the same patient (Filaria sanguinis hominis major, which is now known as Loa loa). The name was later changed to Filaria sanguinis hominis perstans, and later again shortened to Filaria perstans to comply with the binary system of nomenclature. Over time, the name continued to change as changes in the generic status of the parasite took place. In 1984, Eberhard and Orihel redefined the genus Mansonella and included the M. perstans species in it, so it is currently known as M. perstans.

The adult worms of M. perstans were first recovered during post mortem examination of two aboriginal Indians in British Guiana from their mesentery and subpericardial fat. While an insect vector was hypothesized, it took many years of investigation before the true vector of M. perstans was discovered.[4]

While Mansonella infections are often asymptomatic, they can be associated with angioedema (similar to Calabar swellings of loaisis), recurrent pruritic subcutaneous lesions, fever, headaches, arthralgia, and neurologic manifestations.[5] Eosinophilia, headache, fever, or abdominal pain may also be present. M. perstans may also present with a condition known as kampala, or Ugandan eye worm.[6] This occurs when adult worms of M. perstans invade the conjunctiva or periorbital connective tissues in the eye. This condition was first attributed to M. perstans in Uganda, when six patients presented with nodules in the conjunctiva.[6] The adult worms were identified as adult female M. perstans in five of these six cases. The symptoms of M. perstans may be confounded with those of other filarial infections, such as onchocerciasis, lymphatic filariasis and loiasis, because coinfection often occurs.[7]

A 36-year-old man was admitted to the outpatient clinic at the Goundi Missionary Hospital in the south of Chad in May 2001. He complained of visual impairment in the left eye, ocular and abdominal pruritus, and abdominal pain. He had previously been treated with DEC for M. perstans infection five months prior to his visit. A blood sample was taken at 11:00 am, and examined microscopically as a thick blood film stained with Giemsa's solution. The thick blood film revealed the presence of M. perstans, and no other parasites were found. He had 3% eosinophilia. A visual acuity test showed a reduction of visual acuity to 4/10 for the left eye, while the right eye was 9/10. However, no abnormalities were observed during examination of the anterior left eye chamber. Upon examination of the fundus of his left eye, a narrow, white, motionless, and linear lesion of 6–7 mm was found. He was then treated with a second course of DEC (400 mg daily in two doses for eight days, after a three-day dosage increase), and by the end of treatment, he did not have pruritus, but his visual impairment was unchanged. The M. perstans burden was significantly reduced, and the peripheral eosinohpil count decreased to 1%. He was then treated with mebendazole (100 mg twice a day, for 14 days), and at the end of his treatment, his visual impairment was the only symptom remaining. After a week, with no further treatment, his vision improved and acuity was increased to 8/10 in the left eye. While ocular symptoms occur quite frequently in symptomatic M. perstans infection, intraocular localization had not been described prior to this study. This case also is an example of the difficulty of treating mansonelliasis, and shows that combined drug regimens can be more effective than treatment using a single drug.[8]

M. perstans might potentially interfere with the host's regulatory mechanisms and influence the outcome of other infections, such as malaria, tuberculosis and HIV, which often thrive in similar environments.

Recent research has also focused on coinfection of M. perstans and other filarial parasites. A study examining the epidemiology of Loa loa, Onchocerca volvulus, and M. perstans in the rain forest villages of Cameroon found a high prevalence of coinfection with O. voluvulus and M. perstans.[7] It also found a low prevalence of L. loa and O. voluvulus coinfection, as well as low prevalence of L. loa and M. perstans coinfection.[7] Coinfection also has significant implications for treatment, because efficacious drugs for M. perstans are different from those for most filarial infections.

Another study evaluated the effectiveness of ivermectin and albendazole in M. perstans and Wuchereria bancrofti coinfection in a filarial endemic region of Mali, finding that M. perstans infection did not have a significant effect on the treatment of W. bancrofti.[9] Other studies have evaluated the efficacy of other treatments on co-infection with other filarial parasites and M. perstans.[9]

M. perstans is transmitted by the bite of species of Culicoides midges. Only the female midges take blood meals, because the blood is needed for the maturation of eggs within the female.

Humans are the only known reservoir for M. perstans. No animal reservoirs for M. perstans occur as there are for Mansonella streptocerca.

Various species of Culicoides can be found worldwide, and in some areas, their high numbers make them a biting nuisance to humans and domestic animals. Culicoides species are stout flies with short vertical probosces and wings folded scissor-like over their abdomens at rest. They generally measure 1–4 mm in length. The wings of most species have a pattern of light and dark marks. While certain species of Culicoides, such as C. austeni and C. grahamii have been hypothesized to play a larger role than other species in the transmission of M. perstans, very few studies have attempted to identify the species of vectors of M. perstans in endemic areas. This issue is further complicated because the taxonomy of tropical Culicoides species is still uncertain.

Biting midges progress from egg, to larva, pupa, and finally the adult stage. The complete cycle takes 2–6 wk, and is dependent on environmental conditions. The females usually bite around dawn and dusk, although often at other times. Eggs are laid 3–4 d after the blood meal, and about 70-180 eggs are laid each time. Moisture is essential for the vector, and the development of its eggs and larvae. Adults survive for a few weeks, and their flight range is limited to a few hundred meters from their larval habitats.[1]

Adults are white and thread-like, and have been found to be cylindrical in shape. Males are 35–56 mm long and 45–60 μm wide.[2][5] Females are bigger, 70–80 mm long and 80–120 μm wide.[5] The tail is half a coil in females and a full coil in males. Adult worms are rarely seen, but sometimes can be recovered from a laparotomy or autopsy.[10]

Microfilariae of M. perstans are unsheathed, have blunt tails, and their nuclei extend to the end of the tail. The microfilariae have a length of 200 μm, and a width of 4.5 μm. They have the ability to elongate and contract, so they can vary in measurement and form. They are smaller than those of Loa loa, which have tapered tails and are frequently coiled. The microfilariae of M. perstans are smaller than those of W. bancrofti and the caudal end is blunt with a terminal nucleus.

https://web.archive.org/web/20090115010310/http://www.dpd.cdc.gov/dpdx/html/frames/a-f/filariasis/body_Filariasis_m_perstans.htm

During a blood meal, an infected midge (Culicoides grahami and C. austeni) introduces third-stage (L3) filarial larvae onto the skin of the human host, where they penetrate into the bite wound. Body heat likely activates the larvas and prompts them to leave the vector and actively penetrate the skin.

The third-stage larvae develop into adults that live in body cavities, most commonly the pleural and peritoneal cavities. They also can live in mesentery, perirenal spaces, retroperitoneal spaces, or the pericardium, and mature into adults.

Adults in the body cavities mate and produce unsheathed and subperiodic microfilariae that reach the bloodstream. The microfilariae can also be found in the cerebrospinal fluid. While the periodicity of these midges has been unclear, the most recent study suggests microfilariae indicate a weak but significant diurnal periodicity with a peak around 8 am.[11]

A midge ingests microfilariae during a blood meal. After ingestion, the microfilariae migrate from the midge's midgut through the hemocoel to the thoracic muscles of the midge. In the thoracic muscles, the microfilariae develop into second-stage larvae. They subsequently develop into third-stage larvae, which are infective.

The third-stage larvae migrate to the midge's proboscis, where they can infect another human when the midge takes a blood meal.[5]

Similar to other filarial parasites, M. perstans is diagnosed by the identification of microfilariae in the peripheral blood. Because the microfilariae are present in the peripheral blood in almost equal concentrations during day and night, blood samples can be obtained at any time (unlike other filarial microfilariae). The microfilariae are short and thin, unsheathed, and have rounded tails with nuclei at the extremity. The head spot sometimes has a V-shaped appearance. The blood sample can be a thick smear, stained with Giemsa or hematoxylin and eosin.[5] For increased sensitivity, concentration techniques can be used. These include centrifugation of the blood sample lysed in 2% formalin (Knott's technique), or filtration through a Nucleopore® membrane.[5] Serology is not very useful for diagnosis. Because the adult worms live mainly in pleural and peritoneal cavities, they are only rarely observed. At times, they can be observed during a laparotomy. M. perstans often occurs with other filarial infections, such as onchocerciasis and lymphatic filariasis. It should be distinguished from Microfilaria semiclarum (a parasite of animals which sometimes causes accidental infections in humans[10]). Sometimes, confusion is possible if the blood smear is randomly infected during or after preparation with a mould such as Helicospora. This organism, however, is considerably smaller and thinner than a microfilaria. The DEC, or Mazzotti test, has been shown to have minor effects on microfilariae intensity, but it is not of practical use for diagnosis of mansonelliasis.

M. perstans is one of the most difficult human filarial infections to treat. Effective treatment for mansonelliasis is lacking, with no consensus among the scientific community on the optimal approach.[12] Numerous trials evaluating traditional antifilarial drugs such as ivermectin and DEC, as well as other benzimidazoles such as mebendazole, albendazole, levamisole, and thiabendazole, have been conducted. Recently, clinical trials assessing the effectiveness of doxycycline to treat M. perstans infection have also been documented.

Generally, DEC is ineffective in the treatment of M. perstans infection.[12] Other drugs such as ivermectin and praziquantel have been tried, but are neither reliable nor rapidly effective. Mebendazole and thiabendazole have a greater effect than previously described drugs, but are not sufficient for treatment alone. Combination treatments with DEC and mebendazole have had the most success.[12] In the most recent clinical trials, doxycycline has had success comparable to, if not better than, that of combination treatments. However, because it is a relatively recent discovery, the use of doxycycline is relatively limited to clinical trials. If the patient is asymptomatic, no treatment is necessary. An analysis of the results of various clinical trials for each drug is illustrated below:

M. perstans is found in tropical Africa, central and eastern South America, Central America, and the Caribbean. The parasite is widespread in many parts of sub-Saharan Africa. Infections have been reported from 33 countries in this region.[1] In certain locations, extremely high proportions of the inhabitants show signs of infection. It often occurs among poor populations living in rural villages. M. perstans is also found in the Americas in Venezuela, Trinidad, Guyana, Suriname, northern Argentina and the Amazon basin. This parasite does not occur in Asia.[10] It also does not occur in the most northern and southern regions of Africa. A recent review of M. perstans in Africa states that about 114 million people are infected with this parasite in Africa today.[20]

The ongoing large-scale programs for control of onchocerciasis and lymphatic filariasis have paid little attention to mansonelliasis. Despite the high prevalence of M. perstans in areas of tropical Africa, such as Uganda, the Congo, the Republic of Cameroon, and Gabon, no vector programs have been instituted for any of the mansonelliasis-causing parasites. Major reasons for this lack of attention are that M. perstans infections prevail in poor, rural populations and that infection with the parasite has not been linked with a clear and distinct medical picture. Much of the information regarding M. perstans has been obtained as a byproduct from studies of other filarial parasites.[1] Mansonelliasis can thus be classified as one of the most neglected among the neglected tropical diseases.[1] Culicoides midges are small enough to pass through screening or mosquito nets, so these would not be helpful. Protection of visitors to endemic areas can be achieved through the use of insect repellents.

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