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Mansonellosis

[Mansonella ozzardi] [Mansonella perstans] [Mansonella streptocerca]

Causal Agents

Filarid nematodes in the genus Mansonella: M. ozzardi, M. perstans, and M. streptocerca.

Life Cycle

During a blood meal, an infected arthropod (midges, genus Culicoides, or blackflies, genus Simulium) introduces third-stage filarial larvae onto the skin of the human host, where they penetrate into the bite wound The number 1. They develop into adults that commonly reside in subcutaneous tissues The number 2. Adult worms are rarely found in humans. The size range for females worms is 65 to 81 mm in length and 0.21 to 0.25 mm in diameter but unknown for males. Adults worms recovered from experimentally infected Patas monkeys measured 24 to 28 mm in length and 70 to 80 µm in diameter (males) and 32 to 62 mm in length and .130 to .160 mm in diameter (females). Adults produce unsheathed and non-periodic microfilariae that reach the blood stream The number 3. The arthropod ingests microfilariae during a blood meal The number 4. After ingestion, the microfilariae migrate from the arthropod's midgut through the hemocoel to the thoracic muscles The number 5. There the microfilariae develop into first-stage larvae The number 6 and subsequently into third-stage infective larvae The number 7. The third-stage infective larvae migrate to arthropod's proboscis The number 8 and can infect another human when the arthropod takes a blood meal The number 1.

During a blood meal, an infected midge (genus Culicoides) introduces third-stage filarial larvae onto the skin of the human host, where they penetrate into the bite wound The number 1. They develop into adults that reside in body cavities, most commonly the peritoneal cavity or pleural cavity, but less frequently in the pericardium The number 2. The size range for female worms is 70 to 80 mm in length and 120 µm in diameter, and the males measure approximately 45 mm by 60 µm. Adults produce unsheathed and subperiodic microfilariae, measuring 200 by 4.5 µm that reach the blood stream The number 3. A midge ingests microfilariae during a blood meal The number 4. After ingestion, the microfilariae migrate from the midge's midgut through the hemocoel to the thoracic muscles of the arthropod The number 5. There the microfilariae develop into first-stage larvae The number 6 and subsequently into third-stage infective larvae The number 7. The third-stage infective larvae migrate to the midge's proboscis The number 8 and can infect another human when the midge takes a blood meal The number 1.

During a blood meal, an infected midge (genus Culicoides) introduces third-stage filarial larvae onto the skin of the human host, where they penetrate into the bite wound The number 1. They develop into adults that reside in the dermis, most commonly less than 1 mm from the skin surface The number 2. The females measure approximately 27 mm in length. Their diameter is 50 µm at the level of the vulva (anteriorly) and ovaries (near the posterior end), and up to 85 µm at the mid-body. Males measure 50 µm in diameter. Adults produce unsheathed and non-periodic microfilariae, measuring 180 to 240 µm by 3 to 5 µm, which reside in the skin but can also reach the peripheral blood The number 3. A midge ingests the microfilariae during a blood meal The number 4. After ingestion, the microfilariae migrate from the midge's midgut through the hemocoel to the thoracic muscles The number 5. There the microfilariae develop into first-stage larvae The number 6 and subsequently into third-stage larvae The number 7. The third-stage larvae migrate to the midge's proboscis The number 8 and can infect another human when the midge takes another blood meal The number 1.

 

 

Geographic Distribution

Mansonella streptocerca is found in Africa; Mansonella perstans occurs in both Africa and South America; and Mansonella ozzardi occurs only ins the Americas, from Mexico south to South America and in the Caribbean.

Clinical Presentation

Infections by Mansonella perstans, while often asymptomatic, can be associated with angioedema, pruritus, fever, headaches, arthralgias, and neurologic manifestations. Mansonella streptocerca can cause skin manifestations including pruritus, papular eruptions and pigmentation changes. Eosinophilia is often prominent in filarial infections. Mansonella ozzardi can cause symptoms that include arthralgias, headaches, fever, pulmonary symptoms, adenopathy, hepatomegaly, and pruritus.

Microfilariae of Mansonella perstans.

 

Microfilariae of Mansonella perstans are unsheathed and measure 190-200 µm in stained blood smears and 180-225 µm in 2% formalin. The tail is blunt and nuclei extend to the tip of the tail. Microfilariae circulate in the blood.
	Figure A

Figure A: Microfilaria of M. perstans in a thick blood smear stained with Giemsa, from a patient from Cameroon.

	Figure B

Figure B: Microfilaria of M. perstans in a thick blood smear stained with Giemsa, from a patient from Cameroon.

	Figure C

Figure C: Microfilaria of M. perstans in a thick blood smear stained with Giemsa, from a patient from Cameroon.

	Figure D

Figure D: Microfilaria of M. perstans in a thin blood smear from the same specimen as Figures A-C.

	Figure E

Figure E: Microfilaria of M. perstans in a thin blood smear from the same specimen as Figures A-D.

	Figure F

Figure F: Microfilaria of M. perstans in a thick blood smear stained with Giemsa. Image courtesy of the Parasitology Department, Public Health Lab, Ontario Agency for Health Protection and Promotion, Canada.

Microfilariae of M. ozzardi.

 

Microfilariae of Mansonella ozzardi are unsheathed and measure 160-205 µm in stained blood smears and 200-255 µm in 2% formalin. The tail tapers to a point and the nuclei end well before the end of the tail. The end of the tail is also bent in a small hook-like shape. Microfilariae circulate in blood.
	Figure A

Figure A: Microfilaria of M. ozzardi in a thick blood smear, stained with Giemsa.

	Figure B

Figure B: Microfilaria of M. ozzardi in a thick blood smear, stained with Giemsa.

	Figure C

Figure C: Microfilaria of M. ozzardi in a thick blood smears, stained with Giemsa.

	Figure D

Figure D: Microfilaria of M. ozzardi in a thick blood smear, stained with Giemsa. Note the hook-like end to the tail in this figure.

Microfilariae of M. streptocerca.

 

Microfilariae of Mansonella streptocerca are unsheathed and measure 180-240 µm. The tail is been into a hook-like shape and the nuclei extend to the end of the tail. Microfilariae are found in skin and do not circulate in the blood.
	Figure A

Figure A: Microfilaria of M. streptocerca, fixed in 2% formalin and stained with hematoxylin.

Laboratory Diagnosis

Mansonella perstans and M. ozzardi are usually diagnosed by the finding of microfilariae circulating in blood. Neither species exhibits periodicity. Mansonella streptocerca is usually diagnosed by finding microfilariae in skin snips.

Skin snips should be think enough to include the outer part of the dermal palpillae but not so thick as to produce bleeding. Skin snips should be placed immediately in normal saline or distilled water, just enough to cover the specimen. Microfilariae tend to emerge more rapidly in saline, however in either medium the microfilariae typically emerge in 30-60 min and can be seen in wet mount preparations. For a definitive diagnosis, allow the wet mount to dry, fix in methanol, and stain with Giemsa or hematoxylin-and-eosin.

Treatment Information

Treatment of Mansonella infections is poorly studied and thus recommendations are based on limited data.

Mansonella perstans

Treatment may vary based on regional strain differences, as Wolbachia were identified in M. perstans in Mali but not in Gabon or Uganda. Strains with Wolbachia should be treated with 6 weeks of doxycycline, which resulted in clearance of microfilaria in 97% of individuals at 12 months and 75% at 36 months. For strains that do not contain Wolbachia, treatment with 21 days of diethylcarbamazine in combination with 21 days of mebendazole resulted in clearance of microfilaria in 37% at one month. A 28-day course of mebendazole resulted in clearance of microfilaria in 21.7% at 1 month. Multiple treatments may be required for cure in individual patients, though there is not published evidence to guide a strategy. Neither ivermectin nor albendazole appear to have notable effects on microfilaremia.

Mansonella streptocerca

A community-based study of ivermectin found that a single dose of ivermectin suppresses microfilaria for a year or more. One year after a single dose, 46% of individuals had no detectable microfilaria on skin biopsy.

Mansonella ozzardi

Case reports suggest that single dose ivermectin might be a useful treatment of M. ozzardi infections. There is also evidence that M. ozzardi contain Wolbachia, so doxycycline might be an effective treatment; however there are no published data to support this treatment option. Diethylcarbamazine has been shown to have no effect on M. ozzardi

Doxycycline

Doxycycline is available for human use in the United States.

Doxycycline is in pregnancy category D. Doxycycline should not be used in pregnant women due to positive evidence of fetal risk. Doxycycline might be indicated in life-threatening situations where no other treatment is available.

Pregnancy Category D: There is positive evidence of human fetal risk, but the benefits from use in pregnant women may be acceptable despite the risk (e.g., if the drug is needed in a life-threatening situation or for a serious disease for which safer drugs cannot be used or are ineffective).

Doxycycline is excreted in breast milk. The American Academy of Pediatrics classifies doxycycline as compatible with breastfeeding, whereas the World Health Organization (WHO) advises to avoid doxycycline in lactating women unless used for malaria. Dental staining and inhibition of bone growth in the infant may occur. Doxycycline should be used during lactation only if the potential benefit of therapy to the mother justifies the known risk to the infant.

Doxycycline is contraindicated in children age 8 years and younger as it may cause permanent discoloration of the teeth. The WHO recommends that doxycycline should be used only for life-threatening infections in children age 8 years and younger. Use of doxycycline in children age 8 and younger should be limited to instances when there are contraindications to the use of other appropriate antibiotics and the potential benefit justifies the known risk.

Mebendazole

Mebendazole is available in the United States only through compounding pharmacies.

Mebendazole is in pregnancy category C. Data on the use of mebendazole in pregnant women are limited. The available evidence suggests no difference in congenital anomalies in the children of women who were treated with mebendazole during mass treatment programs compared with those who were not. In mass treatment programs for which the World Health Organization (WHO) has determined that the benefit of treatment outweighs the risk, WHO allows use of mebendazole in the 2nd and 3rd trimesters of pregnancy. The risk of treatment in pregnant women who are known to have an infection needs to be balanced with the risk of disease progression in the absence of treatment.

Pregnancy Category C: Either studies in animals have revealed adverse effects on the fetus (teratogenic or embryocidal, or other) and there are no controlled studies in women or studies in women and animals are not available. Drugs should be given only if the potential benefit justifies the potential risk to the fetus.

It is not known whether mebendazole is excreted in breast milk. The WHO classifies mebendazole as compatible with breastfeeding and allows the use of mebendazole in lactating women.

The safety of mebendazole in children has not been established. There is limited data in children age 2 years and younger. Mebendazole is listed as an intestinal antihelminthic medicine on the WHO Model List of Essential Medicines for Children, intended for the use of children up to 12 years of age.

Ivermectin

Oral ivermectin is available for human use in the United States.

Ivermectin is pregnancy category C. Data on the use of ivermectin in pregnant women are limited, though the available evidence suggests no difference in congenital abnormalities in the children of women who were accidentally treated during mass prevention campaigns with ivermectin compared with those who were not. The World Health Organization (WHO) excludes pregnant women from mass prevention campaigns that use ivermectin. However, the risk of treatment in pregnant women who are known to have an infection needs to be balanced with the risk of disease progression in the absence of treatment.

Pregnancy Category C: Either studies in animals have revealed adverse effects on the fetus (teratogenic or embryocidal, or other) and there are no controlled studies in women or studies in women and animals are not available. Drugs should be given only if the potential benefit justifies the potential risk to the fetus.

Ivermectin is excreted in low concentrations in human milk. Ivermectin should be used in breast-feeding women only when the risk to the infant is outweighed by the risk of disease progress in the mother in the absence of treatment.

The safety of ivermectin in children who weigh less than 15kg has not been demonstrated. According to the WHO guidelines for mass prevention campaigns, children who are at least 90 cm tall can be treated safely with ivermectin. The WHO growth standard curves show that this height is reached by 50% of boys by the time they are 28 months old and by 50% of girls by the time they are 30 months old, many children less than 3 years old been safely treated with ivermectin in mass prevention campaigns, albeit at a reduced dose.

Albendazole

Oral albendazole is available for human use in the United States.

Albendazole is pregnancy category C. Data on the use of albendazole in pregnant women are limited, though the available evidence suggests no difference in congenital abnormalities in the children of women who were accidentally treated with albendazole during mass prevention campaigns compared with those who were not. In mass prevention campaigns for which the World Health Organization (WHO) has determined that the benefit of treatment outweighs the risk, WHO allows use of albendazole in the 2nd and 3rd trimesters of pregnancy. However, the risk of treatment in pregnant women who are known to have an infection needs to be balanced with the risk of disease progression in the absence of treatment.

Pregnancy Category C: Either studies in animals have revealed adverse effects on the fetus (teratogenic or embryocidal, or other) and there are no controlled studies in women or studies in women and animals are not available. Drugs should be given only if the potential benefit justifies the potential risk to the fetus.

It is not known whether albendazole is excreted in human milk. Albendazole should be used with caution in breastfeeding women.

The safety of albendazole in children less than 6 years old is not certain. Studies of the use of albendazole in children as young as one year old suggest that its use is safe. According to WHO guidelines for mass prevention campaigns, albendazole can be used in children as young as 1 year old. Many children less than 6 years old have been treated in these campaigns with albendazole, albeit at a reduced dose.

 

 

DPDx is an education resource designed for health professionals and laboratory scientists. For an overview including prevention and control visit www.cdc.gov/parasites/.

  • Page last reviewed: May 3, 2016
  • Page last updated: May 3, 2016
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