Onchocerca volvulus

Last updated

Onchocerca volvulus
Onchocerca volvulus mf1 DPDx.JPG
Onchocerca volvulus, the causative agent of river blindness
Scientific classification OOjs UI icon edit-ltr.svg
Domain: Eukaryota
Kingdom: Animalia
Phylum: Nematoda
Class: Chromadorea
Order: Rhabditida
Family: Onchocercidae
Genus: Onchocerca
Species:
O. volvulus
Binomial name
Onchocerca volvulus
Leuckart, 1893 [1]

Onchocerca volvulus is a filarial (arthropod-borne) nematode (roundworm) that causes onchocerciasis (river blindness), and is the second-leading cause of blindness due to infection worldwide after trachoma. It is one of the 20 neglected tropical diseases listed by the World Health Organization, with elimination from certain countries expected by 2025. [2]

Contents

John O'Neill, an Irish surgeon, first described Onchocerca volvulus in 1874, when he found it to be the causative agent of 'craw-craw', a skin disease found in West Africa. [3] A Guatemalan doctor, Rodolfo Robles, first linked it to visual impairment in 1917. [4]

O. volvulus is primarily found in sub-Saharan Africa, and there is also disease transmission in some South American nations, as well as Yemen (see global map bottom right). It is spread from person to person via female biting blackflies of the genus Simulium , and humans are the only known definitive host. [5]

Morphology

Photomicrograph (glycine mount) of several O. volvulus individuals Onchocerca volvulus 01.tif
Photomicrograph (glycine mount) of several O. volvulus individuals

O. volvulus parasites obtain nutrients from the human host by ingesting blood or by diffusion through their cuticle. They may be able to trigger blood-vessel formation because dense vascular networks are often found surrounding the worms. [6] They are distinguished from other human-infecting filarial nematodes by the presence of deep transverse striations. [7]

It is a dioecious species, containing distinct males and females, which form nodules under the skin in humans. Mature female worms permanently reside in these fibrous nodules, while male worms are free to move around the subcutaneous tissue. The males are smaller than females, with male worms measuring 23 mm in length compared to 230–700 mm in females. [7]

The release of oocytes (eggs) in female worms does not depend upon the presence of a male worm, although they may attract male worms using unidentified pheromones. [8] The first larval stage, microfilariae, are 300 μm in length and unsheathed, meaning that when they mature into microfilariae, they exit from the envelope of the egg. [9]

Lifecycle

The average adult worm lifespan is 15 years, and mature females can produce between 500 and 1,500 microfilariae per day. The normal microfilarial lifespan is 1.0 to 1.5 years; however, their presence in the bloodstream causes little to no immune response until death or degradation of the microfilariae or adult worms. [10]

Blackfly stages

The lifecycle of O. volvulus Life Cycle of Onchocerca volvulus PLoS Medicine.jpg
The lifecycle of O. volvulus
  1. The microfilariae of O. volvulus are found in the dermis layer of skin in the host.
  2. When a female Simulium blackfly takes a blood meal from an infected host, the microfilariae are also ingested.
  3. From here, the microfilariae penetrate the gut and migrate to the thoracic flight muscles, where they enter the first juvenile phase, J1.
  4. After maturing into J2, the second juvenile phase, they migrate to the proboscis, where they are found in the saliva.
  5. J2 stage juveniles then mature into infectious stage three juveniles, J3, in the saliva. The lifecycle in the blackfly takes between one and three weeks. [11]

Human stages

  1. When the female blackfly takes a blood meal, J3 juveniles pass into the human bloodstream.
  2. From here, the juveniles migrate to the subcutaneous tissue, where they form nodules and mature into adult worms over a period of 6–12 months.
  3. After maturation, the smaller adult males migrate from nodules to subcutaneous tissue, where they mate with the larger adult females.
  4. The eggs mature internally to form stage-one microfilariae, which are released from the female's body one at a time and remain in the subcutaneous tissue.
  5. The microfilariae are taken up by a female blackfly when it takes a blood meal, thus completing the lifecycle of O. volvulus. [5]

Disease

O. volvulus causes onchocerciasis, which causes severe itching. Long-term infection can cause keratitis, an inflammation of the cornea in the eye, and ultimately leads to blindness. [9] Symptoms are caused by the microfilariae and the immune response to infection, rather than the adults themselves. The most effective treatment involves using ivermectin, although resistance to this drug has been reported as developing. [12] Ivermectin prevents female worms from releasing microfilariae for several months, thus relieving symptoms and temporarily preventing transmission. However, this does not kill adult worms, so it must be taken once annually as long as adult worms are present. [13]

O. volvulus has been proposed as one of the causative agents of nodding syndrome, a condition that affects children aged 5 to 15 and is currently only observed in South Sudan, Tanzania, and northern Uganda. Although the cause of the disease is unknown, O. volvulus is being increasingly studied as a possible cause due to its ubiquity in areas where the disease is found. [14]

Epidemiology

Geographical distribution of O. volvulus as of March 2017: Endemic countries are shown in red, previous endemic countries in blue, and countries with no local cases in orange. Geographical distribution of Onchocerciasis, including previously endemic countries.svg
Geographical distribution of O. volvulus as of March 2017: Endemic countries are shown in red, previous endemic countries in blue, and countries with no local cases in orange.

An estimated 187 million people are at risk of O. volvulus infection, with 17–25 million people infected and 0.8 million showing some impairment of vision. O. volvulus has not directly caused a single death, but has cost 1.1 million disability adjusted life years, which measure the number of years of healthy life lost due to a specific disease and show the burden of a disease. [16]

Simulium blackfly adults require moving water to breed and eggs remain in water until they exit from the pupa and enter the adult stage of their lifecycle. Due to this restriction, O. volvulus is only found around streams or rivers. Artificial water systems, such as hydroelectric power plants, built in Africa, provide ideal conditions all year for blackfly development and make controlling its spread difficult. [17]

About 99% of cases of onchocerciasis are found in 31 countries in sub-Saharan Africa, although areas of limited transmission occur in Brazil, Venezuela, and Yemen. [15] The disease is thought to have been imported into Latin America through the slave trade. [18] Onchocerciasis was eliminated from Colombia in 2013, Ecuador in 2014, Mexico in 2015, and Guatemala in 2016 [16] due to control programs that used mass drug administration with ivermectin. [15]

Genome

Representation of the possible chromosome fusion seen in O. volvulus Chromosome2 merge.png
Representation of the possible chromosome fusion seen in O. volvulus

The total genome size of O. volvulus is 1.5x108 base pairs and contains around 4,000 genes, with genes for collagen and cuticular proteins being highly expressed in mature adults. [19] O. volvulus has four chromosome pairs, which include a single pair of sex chromosomes. A large X sex chromosome and a smaller Y sex chromosome determine male worms, while two X chromosomes determine female worms. [20]

One of the three nonsex chromosomes is thought to have formed by a fusion event between two smaller chromosomes. [19]

Evolution

(Simplified phylogenetic tree of the genus Onchocerca. [21] )

Dirofilaria

Onchocerca flexuosa

Onchocerca lupi

Onchocerca ochengi

Onchocerca volvulus

Onchocerca gibsoni

Onchocerca gutturosa

Onchocerca jakutensis

O. volvulus has low genetic variation between individuals. This suggests a population bottleneck occurred in the past that caused a rapid decrease in the population size. [19] It also shows high haplotype diversity, which is a measure of how unique a group of linked genes is. This pattern of low genetic variation and high haplotype diversity suggests fast population expansion after a bottleneck and has led to the theory that a host shift event from cattle allowed O. volvulus to infect humans. [22] This is also supported by genetic data that place O. ochengi (a cattle-infecting strain) as the sister group to O. volvulus. [21]

Immune response

Adult worms are found in nodules and are hidden from most components of the human immune system. Microfilariae are more vulnerable to attack by immune cells because they exit nodules to complete their lifecycle. O. volvulus can be detected by the immune system through the release of soluble antigens and antigens found on the surface of microfilariae and infective J3 juveniles. These antigens allow the immune system to detect the presence of a foreign organism in the body and trigger an immune response to clear infection. [23]

The immune response involves raising antibodies (IgG, IgM and IgE type) that can react with soluble antigens released by Onchocerca volvulus. [24] Opsonising antibodies that tag cells for destruction are also found against the infective J3 stage and microfilariae, but there is not enough evidence at the moment to say whether this is protective. [25]

The antigens of O. volvulus are highly complex and show cross-reactivity with several other filarial worms. Little evidence indicates that antibodies made are specific to O. volvulus. However, after the age of 40, the number of parasites carried (the intensity of infection) decreases, suggesting that over time, some sort of protective immune response develops. [23]

Modulation by O. volvulus

Microfilariae can also modulate the immune system to avoid destruction. The complement system is used to enhance the effect of antibodies and phagocytic cells, which engulf and destroy other cells. Microfilariae block this pathway by cleaving C3b—an important protein in this process—to form iC3b. iC3b cannot go on to activate the next step in the pathway and allows microfilariae to remain in the body with little to no attack by the immune system. [26]

Endosymbiotic relationship with Wolbachia

O. volvulus, along with most filarial nematodes, share an endosymbiotic relationship with strains of the bacterium Wolbachia . In the absence of Wolbachia, larval development of O. volvulus is disrupted or ceased. [27] These bacteria have been proposed to enhance the symptoms and severity of onchocerciasis by triggering inflammatory responses in the host. [28]

Related Research Articles

<i>Loa loa</i> filariasis Medical condition

Loa loa filariasis is a skin and eye disease caused by the nematode worm Loa loa. Humans contract this disease through the bite of a deer fly or mango fly, the vectors for Loa loa. The adult Loa loa filarial worm migrates throughout the subcutaneous tissues of humans, occasionally crossing into subconjunctival tissues of the eye where it can be easily observed. Loa loa does not normally affect one's vision but can be painful when moving about the eyeball or across the bridge of the nose. The disease can cause red itchy swellings below the skin called "Calabar swellings". The disease is treated with the drug diethylcarbamazine (DEC), and when appropriate, surgical methods may be employed to remove adult worms from the conjunctiva. Loiasis belongs to the so-called neglected diseases.

<i>Loa loa</i> Species of roundworm

Loa loa is a filarial (arthropod-borne) nematode (roundworm) that causes Loa loa filariasis. Loa loa actually means "worm worm", but is commonly known as the "eye worm", as it localizes to the conjunctiva of the eye. Loa loa is commonly found in Africa. It mainly inhabits rain forests in West Africa and has native origins in Ethiopia. The disease caused by Loa loa is called loiasis and is one of the neglected tropical diseases.

<span class="mw-page-title-main">Diethylcarbamazine</span> Chemical compound

Diethylcarbamazine is a medication used in the treatment of filariasis including lymphatic filariasis, tropical pulmonary eosinophilia, and loiasis. It may also be used for prevention of loiasis in those at high risk. While it has been used for onchocerciasis, ivermectin is preferred. It is taken by mouth.

<span class="mw-page-title-main">Onchocerciasis</span> Human helminthiasis (infection by parasite)

Onchocerciasis, also known as river blindness, is a disease caused by infection with the parasitic worm Onchocerca volvulus. Symptoms include severe itching, bumps under the skin, and blindness. It is the second-most common cause of blindness due to infection, after trachoma.

<span class="mw-page-title-main">Filariasis</span> Parasitic disease caused by a family of nematode worms

Filariasis is a parasitic disease caused by an infection with roundworms of the Filarioidea type. These are spread by blood-feeding insects such as black flies and mosquitoes. They belong to the group of diseases called helminthiases.

<i>Wuchereria bancrofti</i> Species of parasitic worm

Wuchereria bancrofti is a filarial (arthropod-borne) nematode (roundworm) that is the major cause of lymphatic filariasis. It is one of the three parasitic worms, together with Brugia malayi and B. timori, that infect the lymphatic system to cause lymphatic filariasis. These filarial worms are spread by a variety of mosquito vector species. W. bancrofti is the most prevalent of the three and affects over 120 million people, primarily in Central Africa and the Nile delta, South and Central America, the tropical regions of Asia including southern China, and the Pacific islands. If left untreated, the infection can develop into lymphatic filariasis. In rare conditions, it also causes tropical pulmonary eosinophilia. No vaccine is commercially available, but high rates of cure have been achieved with various antifilarial regimens, and lymphatic filariasis is the target of the World Health Organization Global Program to Eliminate Lymphatic Filariasis with the aim to eradicate the disease as a public-health problem by 2020. However, this goal was not met by 2020.

<i>Brugia malayi</i> Medical condition

Brugia malayi is a filarial (arthropod-borne) nematode (roundworm), one of the three causative agents of lymphatic filariasis in humans. Lymphatic filariasis, also known as elephantiasis, is a condition characterized by swelling of the lower limbs. The two other filarial causes of lymphatic filariasis are Wuchereria bancrofti and Brugia timori, which both differ from B. malayi morphologically, symptomatically, and in geographical extent.

<i>Dirofilaria immitis</i> Species of worm that causes parasitic disease in animals

Dirofilaria immitis, also known as heartworm or dog heartworm, is a parasitic roundworm that is a type of filarial worm, a small thread-like worm, and which causes dirofilariasis. It is spread from host to host through the bites of mosquitoes. Four genera of mosquitoes transmit dirofilariasis, Aedes, Culex, Anopheles, and Mansonia. The definitive host is the dog, but it can also infect cats, wolves, coyotes, jackals, foxes, ferrets, bears, seals, sea lions and, under rare circumstances, humans.

Brugia pahangi is a parasitic roundworm belonging to the genus Brugia. It is a filarial nematode known to infect the lymph vessels of domestic cats and wild animals, causing a disease filariasis.

Acanthocheilonema is a genus within the family Onchocercidae which comprises mainly tropical parasitic worms. Cobbold created the genus Acanthocheilonema with only one species, Acanthocheilonema dracunculoides, which was collected from aardwolf in the region of South Africa in the nineteenth century. These parasites have a wide range of mammalian species as hosts, including members of Carnivora, Macroscelidea, Rodentia, Pholidota, Edentata, and Marsupialia. Many species among several genera of filarioids exhibit a high degree of endemicity in studies done on mammalian species in Japan. However, no concrete evidence has confirmed any endemic species in the genus Acanthocheilonema.

<span class="mw-page-title-main">Lymphatic filariasis</span> Medical condition

Lymphatic filariasis is a human disease caused by parasitic worms known as filarial worms. Usually acquired in childhood, it is a leading cause of permanent disability worldwide, impacting over a hundred million people and manifesting itself in a variety of severe clinical pathologies While most cases have no symptoms, some people develop a syndrome called elephantiasis, which is marked by severe swelling in the arms, legs, breasts, or genitals. The skin may become thicker as well, and the condition may become painful. Affected people are often unable to work and are often shunned or rejected by others because of their disfigurement and disability.

In population ecology, density-dependent processes occur when population growth rates are regulated by the density of a population. This article will focus on density dependence in the context of macroparasite life cycles.

<i>Mansonella perstans</i> Species of roundworm

Mansonella perstans is a filarial (arthropod-borne) nematode (roundworm), transmitted by tiny blood-sucking flies called midges. Mansonella perstans is one of two filarial nematodes that causes serous cavity filariasis in humans. The other filarial nematode is Mansonella ozzardi. M. perstans is widespread in many parts of sub-Saharan Africa, parts of Central and South America, and the Caribbean.

Mansonelliasis is the condition of infection by the nematode Mansonella. The disease exists in Africa and tropical Americas, spread by biting midges or blackflies. It is usually asymptomatic.

Mansonella ozzardi is a filarial (arthropod-borne) nematode (roundworm). This filarial nematode is one of two that causes serous cavity filariasis in humans. The other filarial nematode that causes it in humans is Mansonella perstans. M. ozzardi is an endoparasite that inhabits the serous cavity of the abdomen in the human host. It lives within the mesenteries, peritoneum, and in the subcutaneous tissue.

<i>Dirofilaria repens</i> Species of roundworm

Dirofilaria repens is a filarial nematode that affects dogs and other carnivores such as cats, wolves, coyotes, foxes, and sea lions, as well as muskrats. It is transmitted by mosquitoes. Although humans may become infected as aberrant hosts, the worms fail to reach adulthood while infecting a human body.

<span class="mw-page-title-main">Filarioidea</span> Superfamily of roundworms

The Filarioidea are a superfamily of highly specialised parasitic nematodes. Species within this superfamily are known as filarial worms or filariae. Infections with parasitic filarial worms cause disease conditions generically known as filariasis. Drugs against these worms are known as filaricides.

Mansonella streptocerca,, is a filarial (arthropod-borne) nematode (roundworm) causing the disease streptocerciasis. It is a common parasite in the skin of humans in the rain forests of Africa, where it is thought to be a parasite of chimpanzees, as well.

<span class="mw-page-title-main">Jean Hissette</span>

Jean Hissette was a Belgian ophthalmologist.

Onchocerca lupi is a nematode that causes ocular onchocerciasis, an eye disease, in canines and felines. The parasite was first described in 1967 in a wolf from Georgia. The other Onchocerca spp., O. volvulus, is a human parasite that causes ocular onchocerciasis in human and affects 37 million people globally.

References

  1. ↑ "Onchocerca volvulus Leuckart, 1893". Global Biodiversity Information Facility . Retrieved 7 June 2023.
  2. ↑ "Neglected tropical diseases". World Health Organization. March 2017. Retrieved 17 March 2017.
  3. ↑ O’Neill, J. (1875). "On the presence of a filaria in "craw-craw."" (PDF). The Lancet. 105 (2686): 265–266. doi:10.1016/s0140-6736(02)30941-3.
  4. ↑ Robles, R. (1917). "Enfermedad nueva en Guatemala". La Juventud Médica.
  5. 1 2 Duke, B.O. (1993). "The population dynamics of Onchocerca volvulus in the human host". Tropical Medicine and Parasitology. 44 (2): 61–68. ISSN   0177-2392. PMID   8367667.
  6. ↑ Burnham, G. (1998). "Onchocerciasis". Lancet. 351 (9112): 1341–1346. doi: 10.1016/S0140-6736(97)12450-3 . ISSN   0140-6736. PMID   9643811. S2CID   208794023.
  7. 1 2 Neafie, R.C. (1972). "Morphology of Onchocerca volvulus". American Journal of Clinical Pathology. 57 (5): 574–586. doi:10.1093/ajcp/57.5.574. ISSN   0002-9173. PMID   5025601.
  8. ↑ Schulz-Key, H.; Soboslay, P.T. (1994). "Reproductive biology and population dynamics of Onchocerca volvulus in the vertebrate host". Parasite. 1 (1S): S53–S55. doi: 10.1051/parasite/199401s1053 . ISSN   1252-607X.
  9. 1 2 Udall, D.N. (2007). "Recent updates on onchocerciasis: diagnosis and treatment". Clinical Infectious Diseases. 44 (1): 53–60. doi: 10.1086/509325 . ISSN   1537-6591. PMID   17143815.
  10. ↑ Schulz-Key, H. (1990). "Observations on the Reproductive Biology of Onchocerca volvulus". Acta Leidensia (in Dutch). 59 (1–2): 27–44. doi:10.1126/science.1068732. PMID   2378210.
  11. ↑ Eichner, M.; Renz, A.; Wahl, G.; Enyong, P. (1991). "Development of Onchocerca volvulus microfilariae injected into Simulium species from Cameroon". Medical and Veterinary Entomology. 5 (3): 293–298. doi:10.1111/j.1365-2915.1991.tb00555.x. ISSN   1365-2915. PMID   1768922. S2CID   2794018.
  12. ↑ Lustigman, S.; McCarter, J.P. (2007). "Ivermectin Resistance in Onchocerca volvulus: Toward a Genetic Basis". PLOS Neglected Tropical Diseases. 1 (1): e76. doi: 10.1371/journal.pntd.0000076 . ISSN   1935-2735. PMC   2041823 . PMID   17989789.
  13. ↑ Ejere, Henry O. D.; Schwartz, Ellen; Wormald, Richard; Evans, Jennifer R. (15 August 2012). "Ivermectin for onchocercal eye disease (river blindness)". The Cochrane Database of Systematic Reviews. 2012 (8): CD002219. doi:10.1002/14651858.CD002219.pub2. ISSN   1469-493X. PMC   4425412 . PMID   22895928.
  14. ↑ Idro, R.; Opar, B.; Wamala, J.; Abbo, C.; Onzivua, S.; Mwaka, D.A.; Kakooza-Mwesige, A.; Mbonye, A.; Aceng, J.R. (2016). "Is nodding syndrome an Onchocerca volvulus-induced neuroinflammatory disorder? Uganda's story of research in understanding the disease". International Journal of Infectious Diseases. 45: 112–117. doi: 10.1016/j.ijid.2016.03.002 . ISSN   1878-3511. PMID   26987477.
  15. 1 2 3 "Onchocerciasis Fact sheet N°374". World Health Organization. March 2017. Retrieved 16 March 2017.
  16. 1 2 "Progress towards eliminiating onchocerciasis in the WHO region of the Americas: Verification of elimination of transmission in Guatemala and progress report on the elimination of human onchocerciasis, 2015-2016". World Health Organization. March 2017. Archived from the original on 23 March 2017. Retrieved 17 March 2017.
  17. ↑ Myburgh, E.; Nevill, E.M. (2003). "Review of blackfly (Diptera: Simuliidae) control in South Africa". The Onderstepoort Journal of Veterinary Research. 70 (4): 307–316. doi: 10.4102/ojvr.v70i4.295 . hdl: 2263/17828 . ISSN   0030-2465. PMID   14971733.
  18. ↑ Gustavsen, K.; Hopkins, A.; Sauerbrey, M. (2011). "Onchocerciasis in the Americas: from arrival to (near) elimination". Parasites & Vectors. 4: 205. doi: 10.1186/1756-3305-4-205 . ISSN   1756-3305. PMC   3214172 . PMID   22024050.
  19. 1 2 3 Unnasch, Thomas R; Williams, S.A. (2000). "The genomes of Onchocerca volvulus". International Journal for Parasitology. 30 (4): 543–552. doi:10.1016/S0020-7519(99)00184-8. PMID   10731575.
  20. ↑ Post, R. (2005). "The chromosomes of the Filariae". Filaria Journal. 4: 10. doi: 10.1186/1475-2883-4-10 . ISSN   1475-2883. PMC   1282586 . PMID   16266430.
  21. 1 2 team, European Centre for Disease Prevention and Control (ECDC)—Health Communication Unit—Eurosurveillance editorial (23 April 2015). "Human case of Onchocerca lupi infection, Germany, August 2014". Eurosurveillance. 20 (16). doi: 10.2807/1560-7917.es2015.20.16.21099 . PMID   25953271.
  22. ↑ Morales-Hojas, R.; Cheke, R.A.; Post, R.J. (2007). "A preliminary analysis of the population genetics and molecular phylogenetics of Onchocerca volvulus (Nematoda: Filarioidea) using nuclear ribosomal second internal transcribed spacer sequences". Memórias do Instituto Oswaldo Cruz. 102 (7): 879–882. doi: 10.1590/S0074-02762007005000114 . hdl: 1807/57422 . ISSN   0074-0276. PMID   17992364.
  23. 1 2 Greene, B.M.; Gbakima, A.A.; Albiez, E.J.; Taylor, H.R. (1985). "Humoral and cellular immune responses to Onchocerca volvulus infection in humans". Reviews of Infectious Diseases. 7 (6): 789–795. doi:10.1093/clinids/7.6.789. ISSN   0162-0886. PMID   4070916.
  24. ↑ Ngu, J.L.; Blackett, K. (1976). "Immunological studies in onchocerciasis in Cameroon". Tropical and Geographical Medicine. 28 (2): 111–120. ISSN   0041-3232. PMID   788262.
  25. ↑ Greene, B.M.; Taylor, H.R.; Aikawa, M. (1981). "Cellular killing of microfilariae of Onchocerca volvulus: eosinophil and neutrophil-mediated immune serum-dependent destruction". Journal of Immunology. 127 (4): 1611–1618. ISSN   0022-1767. PMID   7276574.
  26. ↑ Meri, T.; Jokiranta, T.S.; Hellwage, J.; Bialonski, A.; Zipfel, P.F.; Meri, S. (2002). "Onchocerca volvulus microfilariae avoid complement attack by direct binding of factor H". The Journal of Infectious Diseases. 185 (12): 1786–1793. doi: 10.1086/340649 . ISSN   0022-1899. PMID   12085326.
  27. ↑ Saint André, A.V.; Blackwell, N.M.; Hall, L.R.; Hoerauf, A.; Brattig, N.W.; Volkmann, L.; Taylor, M.J.; Ford, L.; Hise, A.G. (2002). "The Role of Endosymbiotic Wolbachia Bacteria in the Pathogenesis of River Blindness" (PDF). Science. 295 (5561): 1892–1895. Bibcode:2002Sci...295.1892S. doi:10.1126/science.1068732. ISSN   0036-8075. PMID   11884755. S2CID   22130066.
  28. ↑ Tamarozzi, F.; Halliday, A.; Gentil, K.; Hoerauf, A.; Pearlman, E.; Taylor, M.J. (2011). "Onchocerciasis: the Role of Wolbachia Bacterial Endosymbionts in Parasite Biology, Disease Pathogenesis, and Treatment". Clinical Microbiology Reviews. 24 (3): 459–468. doi:10.1128/CMR.00057-10. ISSN   0893-8512. PMC   3131055 . PMID   21734243.
This page is based on this Wikipedia article
Text is available under the CC BY-SA 4.0 license; additional terms may apply.
Images, videos and audio are available under their respective licenses.