Mansonellosis refers to diseases caused by the filarial nematodes (worms) Mansonella perstans, M. ozzardi, and M. streptocerca. Transmission is by biting midges or blackflies. Infections are often asymptomatic, but symptoms can occur. The diagnosis of M. perstans and M. ozzardi infection is confirmed by identifying microfilariae in blood smears; neither species displays significant periodicity, so blood can be drawn at any time. The diagnosis of M. streptocerca is based on identifying microfilariae in skin snips or biopsies. Treatment depends on the infecting Mansonella species.
Three species of Mansonella cause most human disease. As with other filarial diseases, their life cycle is complex (see DPDx - Laboratory Identification of Parasites of Public Health Concern: Mansonellosis).
(See also Approach to Parasitic Infections and Overview of Filarial Nematode Infections.)
Mansonella perstans
M. perstans is transmitted by the bites of midges (Culicoides) in sub-Saharan Africa and in the Americas from Panama to Argentina. It is estimated that more than 114 million people are infected worldwide (1). The likelihood of infection increases with age, and prevalence can approach 100% in highly endemic areas.
Adult worms reside in pleural, pericardial, and peritoneal cavities and in the retroperitoneum and mesentery. Unsheathed microfilariae are found in the bloodstream. Midges acquire worms when they take a blood meal from an infected human.
Most infections are asymptomatic or mild. Migrating adult worms can cause transient subcutaneous swellings similar to those of Loa loa (Calabar swellings), inflammation of the pericardium or pleura, conjunctival nodules, retinal damage, and periocular inflammation. Nonspecific symptoms include pruritus, urticaria, arthralgias, and malaise. Neuropsychiatric manifestations, meningoencephalitis, and hepatitis have been attributed to M. perstans on rare occasions.
The diagnosis of M. perstans is made by identifying non-sheathed microfilariae in a blood smear. Microfilariae can be identified in blood both day and night. Eosinophilia is often present. Molecular diagnostics have also been developed (2).
M. perstans is relatively resistant to medications used to treat other filarial diseases, including diethylcarbamazine. Targeting the endosymbiotic Wolbachia bacteria in adult M. perstansworms with doxycycline 200 mg once a day for 4 to 6 weeks is presumed to interrupt the reproduction of adult worms and can be curative.Wolbachia has been seen in M. perstans worms from Mali, Cameroon, Ghana, and Gabon. There are divergent reports of the presence of Wolbachia in Uganda, possibly due to methodological constraints or the presence of multiple strains of M. perstans. Doxycycline has been shown to be effective against M. perstans in Mali (3) and Ghana (4), but the utility of doxycycline for treatment of infections in regions where Wolbachia are absent has not been systematically studied. In cases where doxycyclineis ineffective, combination therapy with diethylcarbamazine and mebendazole for 3 weeks has improved activity relative to monotherapy (5).
Mansonella ozzardi
M. ozzardi is endemic in Central and South America and in a number of Caribbean islands. Humans are the major reservoir of infection.
M. ozzardi is transmitted by biting midges (Culicoides) and blackflies (Simulium amazonicum). The life cycle is similar to that of M. perstans except adult worms reside in lymphatics as well as in the thoracic and peritoneal cavities. Microfilariae are present in both the blood and skin.
Most people with M. ozzardi infection are asymptomatic, but some have rash, lymphadenopathy, arthralgias, fever, headache, or pulmonary symptoms. M. ozzardi microfilaremia-induced keratitis has been reported from the Amazon region of Brazil.
The diagnosis of M. ozzardi is confirmed by identifying microfilariae in blood or skin. Blood can be drawn at any time. Eosinophilia is common. Serologic tests may also be useful in identifying infection, but they are not specific.
Treatment is with a single dose of ivermectin 200 mcg/kg orally (6). Before treatment with ivermectin, patients should be assessed for coinfection with the filarial parasite Loa loa if they have been in areas of central Africa where both parasites are transmitted because ivermectin can cause severe reactions in patients with heavy Loa loa coinfection. Endosymbiotic Wolbachia are present in M. ozzardi, but the efficacy of doxycycline for therapy has not been assessed.
Mansonella streptocerca
M. streptocerca is transmitted in tropical rainforests in west and central Africa and Uganda. The prevalence of M. streptocerca is not known. Nonhuman primates are occasionally infected but are not major reservoirs of infection.
The life cycle of M. streptocerca is similar to that of M. perstans except that adult worms reside in the dermis of the upper trunk and shoulder areas. Microfilariae are found in the skin. Most people with M. streptocerca are asymptomatic. Thickening of the dermis, hypopigmented macules, and bilateral axillary or inguinal lymphadenopathy may be present. Unlike Onchocerca volvulus, adult M. streptocerca do not form subcutaneous nodules.
The diagnosis of M. streptocerca is made by identifying microfilariae in skin snips or biopsies. Eosinophilia is common. Serology may also be useful in identifying filarial infection, but it is not specific.
Diethylcarbamazine (DEC) 2 mg/kg orally 3 times a day for 12 days is used to treat M. streptocerca. DEC kills both microfilariae and adult worms. However, it can exacerbate skin and systemic symptoms due to the release of antigens from dying microfilariae. DEC should not be administered to patients with concurrent O. volvulus or heavy Loa loa infection because of the potential for severe adverse effects.
Ivermectin (150 mcg/kg orally single dose) can reduce the microfilarial loads ofM. streptocerca, but its impact on the course of infection is uncertain. Before treatment with ivermectin, patients should be assessed for coinfection with Loa loa, another filarial parasite, if they have been in areas of central Africa where both parasites are transmitted because ivermectin can cause severe reactions in patients with heavy Loa loa coinfection. It is not known whether M. streptocerca harbors Wolbachia or whether doxycycline has a role in treatment.
References
1. Simonsen PE, Onapa AW, Asio SM. Mansonella perstans filariasis in Africa. Acta Trop. 2011;120 Suppl 1:S109-S120. doi:10.1016/j.actatropica.2010.01.014
2. Keiser PB, Coulibaly Y, Kubofcik J, et al. Molecular identification of Wolbachia from the filarial nematode Mansonella perstans. Mol Biochem Parasitol. 2008;160(2):123-128. doi:10.1016/j.molbiopara.2008.04.012
3. Coulibaly YI, Dembele B, Diallo AA, et al. A randomized trial of doxycycline for Mansonella perstans infection. N Engl J Med. 2009;361(15):1448-1458. doi:10.1056/NEJMoa0900863
4. Batsa Debrah L, Phillips RO, Pfarr K, et al. The Efficacy of Doxycycline Treatment on Mansonella perstans Infection: An Open-Label, Randomized Trial in Ghana. Am J Trop Med Hyg. 2019;101(1):84-92. doi:10.4269/ajtmh.18-0491
5. Bregani ER, Rovellini A, Mbaïdoum N, Magnini MG. Comparison of different anthelminthic drug regimens against Mansonella perstans filariasis. Trans R Soc Trop Med Hyg. 2006;100(5):458-463. doi:10.1016/j.trstmh.2005.07.009
6. de Almeida Basano S, de Souza Almeida Aranha Camargo J, Fontes G, et al. Phase III Clinical Trial to Evaluate Ivermectin in the Reduction of Mansonella ozzardi infection in the Brazilian Amazon. Am J Trop Med Hyg. 2018;98(3):786-790. doi:10.4269/ajtmh.17-0698
Key Points
The epidemiology, clinical manifestations, and recommended treatment vary between Mansonella species, and infections are frequently asymptomatic.
If treatment with ivermectin is planned, assess patients for coinfection withLoa loa if they have been in areas of central Africa where it is transmitted.
Assistance with serologic and other diagnostic tests for all Mansonella species is available from the Centers for Disease Control and Prevention's (CDC) DPDx Diagnostic Procedures and the National Institutes of Health's Laboratory of Parasitic Diseases (1-301-496-5398).
