View source for Onchocerca volvulus

{{Short description|Nematode}}
{{Use dmy dates|date=May 2014}}
{{Speciesbox
| image = Onchocerca volvulus mf1 DPDx.JPG
| image_caption = ''Onchocerca volvulus'', the causative agent of river blindness
| genus = Onchocerca
| species = volvulus
| authority = [[Rudolf Leuckart|Leuckart]], 1893<ref>{{GBIF|taxon=''Onchocerca volvulus'' Leuckart, 1893|id=7031770|access-date=7 June 2023}}</ref>
}}

'''''Onchocerca volvulus''''' is a [[wikt:filarial|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 disease]]s listed by the [[World Health Organization]], with elimination from certain countries expected by 2025.<ref name="NTDs">{{cite web|title=Neglected tropical diseases|url=https://www.who.int/neglected_diseases/diseases/en/|work=World Health Organization|access-date=17 March 2017|date=March 2017}}</ref>

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]].<ref name="renamed_from_1874_on_20170331133907">{{cite journal|last1=O’Neill|first1=J.|title=On the presence of a filaria in "craw-craw."|journal=The Lancet|date=1875|pages=265–266|url=https://web.stanford.edu/class/humbio103/ParaSites2006/Onchocerciasis/filaria_original_description.pdf|doi=10.1016/s0140-6736(02)30941-3|volume=105|issue=2686}}</ref> A Guatemalan doctor, [[Rodolfo Robles]], first linked it to [[visual impairment]] in 1917.<ref name="renamed_from_1917_on_20170331133907">{{cite journal|last1=Robles|first1=R.|title=Enfermedad nueva en Guatemala|journal=La Juventud Médica|date=1917}}</ref>

''Onchocerca 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 [[host (biology)|definitive host]].<ref name="Human lifecycle">{{Cite journal|last=Duke|first=B.O.|date=1993|title=The population dynamics of ''Onchocerca volvulus'' in the human host|journal=Tropical Medicine and Parasitology|volume=44|issue=2|pages=61–68|issn=0177-2392|pmid=8367667}}</ref>

==Morphology==
[[File:Onchocerca volvulus 01.tif|thumb|210px|Photomicrograph (glycine mount) of several ''O. volvulus'' individuals]]
''Onchocerca volvulus'' parasites obtain nutrients from the human host by ingesting blood or by diffusion through their [[cuticle]]. They may be able to trigger [[angiogenesis|blood-vessel formation]] because dense [[circulatory system|vascular networks]] are often found surrounding the worms.<ref name="feeding">{{Cite journal|last=Burnham|first=G.|date=1998|title=Onchocerciasis|journal=Lancet|volume=351|issue=9112|pages=1341–1346|doi=10.1016/S0140-6736(97)12450-3|issn=0140-6736|pmid=9643811|s2cid=208794023|doi-access=free}}</ref> 
They are distinguished from other human-infecting [[filariasis|filarial nematodes]] by the presence of deep [[wikt:transverse|transverse]] [[wikt:striations|striations]].<ref name="morphology">{{Cite journal|last=Neafie|first=R.C.|date=1972|title=Morphology of ''Onchocerca volvulus''|journal=American Journal of Clinical Pathology|volume=57|issue=5|pages=574–586|doi=10.1093/ajcp/57.5.574|pmid=5025601|issn=0002-9173}}</ref>

It is a [[dioecy|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&nbsp;mm in length compared to 230–700&nbsp;mm in females.<ref name="morphology"/>

The release of [[oocyte]]s (eggs) in female worms does not depend upon the presence of a male worm, although they may attract male worms using unidentified pheromones.<ref name="worm mating">{{Cite journal|last1=Schulz-Key|first1=H.|last2=Soboslay|first2=P.T.|date=1994|title=Reproductive biology and population dynamics of ''Onchocerca volvulus'' in the vertebrate host|journal=Parasite|language=en|volume=1|issue=1S|pages=S53–S55|doi=10.1051/parasite/199401s1053|issn=1252-607X|doi-access=free}}</ref> The first larval stage, [[microfilaria]]e, are 300 μm in length and unsheathed, meaning that when they mature into microfilariae, they exit from the envelope of the egg.<ref name="Onchocerca nodules">{{Cite journal|last=Udall|first=D.N.|date=2007|title=Recent updates on onchocerciasis: diagnosis and treatment|journal=Clinical Infectious Diseases|volume=44|issue=1|pages=53–60|doi=10.1086/509325|issn=1537-6591|pmid=17143815|doi-access=free}}</ref>

==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 [[circulatory system|bloodstream]] causes little to no immune response until death or degradation of the microfilariae or adult worms.<ref name ="Lifespan">{{Cite journal|last=Schulz-Key|first=H.|date=1990|title=Observations on the Reproductive Biology of ''Onchocerca volvulus''|journal=Acta Leidensia|language=nl|volume=59|issue=1–2|pages=27–44|pmid=2378210}}</ref>

===Blackfly stages===
[[File:Life Cycle of Onchocerca volvulus PLoS Medicine.jpg|thumb|right|250px|The lifecycle of ''O. volvulus'']]
# The microfilariae of ''O. volvulus'' are found in the [[dermis]] layer of skin in the host. 
# When a female ''Simulium'' blackfly takes a [[anautogeny|blood meal]] from an infected host, the microfilariae are also ingested. 
# From here, the microfilariae penetrate the gut and migrate to the [[Insect flight|thoracic flight muscles]], where they enter the first juvenile phase, J<sub>1</sub>. 
# After maturing into J<sub>2</sub>, the second juvenile phase, they migrate to the [[proboscis]], where they are found in the [[saliva]]. 
# J<sub>2</sub> stage juveniles then mature into infectious stage three juveniles, J<sub>3</sub>, in the saliva. The lifecycle in the blackfly takes between one and three weeks.<ref name = "Blackfly lifecycle">{{Cite journal|last1=Eichner|first1=M.|last2=Renz|first2=A.|last3=Wahl|first3=G.|last4=Enyong|first4=P.|date=1991|title=Development of ''Onchocerca volvulus'' microfilariae injected into ''Simulium'' species from Cameroon|journal=Medical and Veterinary Entomology|language=en|volume=5|issue=3|pages=293–298|doi=10.1111/j.1365-2915.1991.tb00555.x|pmid=1768922|s2cid=2794018|issn=1365-2915}}</ref>

===Human stages===
# When the female blackfly takes a blood meal, J<sub>3</sub> juveniles pass into the human bloodstream. 
# 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. 
# After maturation, the smaller adult males migrate from nodules to subcutaneous tissue, where they mate with the larger adult females.
# 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.
# The microfilariae are taken up by a female blackfly when it takes a blood meal, thus completing the lifecycle of ''O. volvulus''.<ref name="Human lifecycle"/>

==Disease==
''Onchocerca 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 [[visual impairment|blindness]].<ref name="Onchocerca nodules"/> 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 [[drug resistance|resistance]] to this drug has been reported as developing.<ref>{{Cite journal|last1=Lustigman|first1=S.|last2=McCarter|first2=J.P.|date=2007|title=Ivermectin Resistance in ''Onchocerca volvulus'': Toward a Genetic Basis|journal=PLOS Neglected Tropical Diseases|volume=1|issue=1|pages=e76|doi=10.1371/journal.pntd.0000076|issn=1935-2735|pmid=17989789|pmc=2041823 |doi-access=free }}</ref> 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.<ref>{{Cite journal|last1=Ejere|first1=Henry O. D.|last2=Schwartz|first2=Ellen|last3=Wormald|first3=Richard|last4=Evans|first4=Jennifer R.|date=2012-08-15|title=Ivermectin for onchocercal eye disease (river blindness)|journal=The Cochrane Database of Systematic Reviews|volume=2012 |issue=8|pages=CD002219|doi=10.1002/14651858.CD002219.pub2|issn=1469-493X|pmc=4425412|pmid=22895928}}</ref>

''Onchocerca volvulus'' has been proposed as one of the causative agents of [[Nodding disease|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.<ref name="nodding syndrome">{{Cite journal|last1=Idro|first1=R.|last2=Opar|first2=B.|last3=Wamala|first3=J.|last4=Abbo|first4=C.|last5=Onzivua|first5=S.|last6=Mwaka|first6=D.A.|last7=Kakooza-Mwesige|first7=A.|last8=Mbonye|first8=A.|last9=Aceng|first9=J.R.|date=2016|title=Is nodding syndrome an ''Onchocerca volvulus''-induced neuroinflammatory disorder? Uganda's story of research in understanding the disease|journal=International Journal of Infectious Diseases |volume=45|pages=112–117|doi=10.1016/j.ijid.2016.03.002|issn=1878-3511|pmid=26987477|doi-access=free}}</ref>

==Epidemiology==
[[File:Geographical distribution of Onchocerciasis, including previously endemic countries.svg|thumb|275px|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.<ref name="WHO2017">{{cite web|title=Onchocerciasis Fact sheet N°374|url=https://www.who.int/mediacentre/factsheets/fs374/en/|work=World Health Organization|access-date=16 March 2017|date=March 2017}}</ref>]]
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 year|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.<ref name="Risk">{{cite web|title=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|url=https://www.who.int/onchocerciasis/resources/who_wer9143|archive-url=https://web.archive.org/web/20170323144206/http://www.who.int/onchocerciasis/resources/who_wer9143/|url-status=dead|archive-date=23 March 2017|work=World Health Organization|access-date=17 March 2017|date=March 2017}}</ref>

''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. [[Water resources|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.<ref name="’water systems and blackfly’">{{Cite journal|last1=Myburgh|first1=E.|last2=Nevill|first2=E.M.|date=2003|title=Review of blackfly (Diptera: Simuliidae) control in South Africa|journal=The Onderstepoort Journal of Veterinary Research|volume=70|issue=4|pages=307–316|issn=0030-2465|pmid=14971733|doi=10.4102/ojvr.v70i4.295|doi-access=free|hdl=2263/17828|hdl-access=free}}</ref>

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]].<ref name="WHO2017"/> The disease is thought to have been imported into [[Latin America]] through the slave trade.<ref name="America">{{Cite journal|last1=Gustavsen|first1=K.|last2=Hopkins|first2=A.|last3=Sauerbrey|first3=M.|date=2011|title=Onchocerciasis in the Americas: from arrival to (near) elimination|journal=Parasites & Vectors|volume=4|pages=205|doi=10.1186/1756-3305-4-205|issn=1756-3305|pmid=22024050|pmc=3214172 |doi-access=free }}</ref> Onchocerciasis was eliminated from Colombia in 2013, Ecuador in 2014, Mexico in 2015, and Guatemala in 2016<ref name="Risk"/> due to [[Onchoceriasis|control programs]] that used [[mass drug administration]] with ivermectin.<ref name="WHO2017"/>

==Genome==
[[File:Chromosome2 merge.png|thumb|right|180px|Representation of the possible chromosome fusion seen in ''O. volvulus'']]
The total [[genome]] size of ''O. volvulus'' is 1.5{{X10^|8}} [[base pairs]] and contains around 4,000 [[gene]]s, with genes for [[collagen]] and [[cuticle|cuticular proteins]] being highly expressed in mature adults.<ref name="genome">{{Cite journal|last1=Unnasch|first1=Thomas R|last2=Williams|first2=S.A.|date=2000|title=The genomes of ''Onchocerca volvulus''|journal=International Journal for Parasitology|volume=30|issue=4|pages=543–552|doi=10.1016/S0020-7519(99)00184-8|pmid=10731575}}</ref> ''O. volvulus'' has four [[chromosome|chromosome pairs]], which include a single pair of [[allosome|sex chromosomes]]. A large [[X chromosome|X sex chromosome]] and a smaller [[Y chromosome|Y sex chromosome]] determine male worms, while two X chromosomes determine female worms.<ref name="chromosomes">{{Cite journal|last=Post|first=R.|date=2005|title=The chromosomes of the Filariae|journal=Filaria Journal|volume=4|pages=10|doi=10.1186/1475-2883-4-10|issn=1475-2883|pmid=16266430|pmc=1282586 |doi-access=free }}</ref>

One of the three [[autosome|nonsex chromosomes]] is thought to have formed by a fusion event between two smaller chromosomes.<ref name="genome"/>

==Evolution==
(Simplified [[phylogenetic tree]] of the genus ''Onchocerca''.<ref name="phylogeny"/>)
{{clade
  |{{clade
         |1=''[[Dirofilaria]]''
         |2={{clade
               |1=''[[Onchocerca flexuosa]]''
               |2={{clade
                     |1=''[[Onchocerca lupi]]''
                     |2={{clade
                         |1={{clade
                               |1=''[[Onchocerca ochengi]]''
                               |2='''''Onchocerca volvulus'''''|thickness=3
                               }}
                         |2={{clade
                                |1=''[[Onchocerca gibsoni]]''
                                |2={{clade
                                      |1=''[[Onchocerca gutturosa]]''
                                      |2=''[[Onchocerca jakutensis]]''
                                      }}
                                }}
                          }}
                    }}
              }}
       }}
}}

''Onchocerca 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.<ref name="genome"/> 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 switch|host shift]] event from [[cattle]] allowed ''O. volvulus'' to infect humans.<ref name="cattle">{{Cite journal|last1=Morales-Hojas|first1=R.|last2=Cheke|first2=R.A.|last3=Post|first3=R.J.|date=2007|title=A preliminary analysis of the population genetics and molecular phylogenetics of ''Onchocerca volvulus'' (Nematoda: Filarioidea) using nuclear ribosomal second internal transcribed spacer sequences|journal=Memórias do Instituto Oswaldo Cruz|volume=102|issue=7|pages=879–882|doi=10.1590/S0074-02762007005000114|pmid=17992364|issn=0074-0276|doi-access=free|hdl=1807/57422|hdl-access=free}}</ref> This is also supported by genetic data that place ''O. ochengi'' (a cattle-infecting strain) as the [[sister group]] to ''O. volvulus''.<ref name="phylogeny">{{Cite journal|title=Human case of ''Onchocerca lupi'' infection, Germany, August 2014|journal=Eurosurveillance|volume=20|issue=16|last=team|first=European Centre for Disease Prevention and Control (ECDC)—Health Communication Unit—Eurosurveillance editorial|date=23 April 2015|language=en|doi=10.2807/1560-7917.es2015.20.16.21099|pmid=25953271|doi-access=free}}</ref>

==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 [[antigen]]s and antigens found on the surface of microfilariae and infective J<sub>3</sub> 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.<ref name="’immune response’">{{Cite journal|last1=Greene|first1=B.M.|last2=Gbakima|first2=A.A.|last3=Albiez|first3=E.J.|last4=Taylor|first4=H.R.|date=1985|title=Humoral and cellular immune responses to ''Onchocerca volvulus'' infection in humans|journal=Reviews of Infectious Diseases|volume=7|issue=6|pages=789–795|issn=0162-0886|pmid=4070916|doi=10.1093/clinids/7.6.789}}</ref>

The immune response involves raising [[antibody|antibodies]] ([[Immunoglobulin G|IgG]], [[IgM]] and [[IgE]] type) that can react with soluble antigens released by ''Onchocerca volvulus''.<ref name="immunology">{{Cite journal|last1=Ngu|first1=J.L.|last2=Blackett|first2=K.|date=1976|title=Immunological studies in onchocerciasis in Cameroon|journal=Tropical and Geographical Medicine|volume=28|issue=2|pages=111–120|issn=0041-3232|pmid=788262}}</ref> [[Antibody opsonization|Opsonising antibodies]] that tag cells for destruction are also found against the infective J<sub>3</sub> stage and microfilariae, but there is not enough evidence at the moment to say whether this is protective.<ref name="opsonisation">{{Cite journal|last1=Greene|first1=B.M.|last2=Taylor|first2=H.R.|last3=Aikawa|first3=M.|date=1981|title=Cellular killing of microfilariae of ''Onchocerca volvulus'': eosinophil and neutrophil-mediated immune serum-dependent destruction|journal=Journal of Immunology|volume=127|issue=4|pages=1611–1618|doi=10.4049/jimmunol.127.4.1611 |issn=0022-1767|pmid=7276574}}</ref>

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.<ref name="’immune response’"/>

===Modulation by ''Onchocerca volvulus''===
Microfilariae can also modulate the immune system to avoid destruction. The [[complement system]] is used to enhance the effect of antibodies and [[phagocyte|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.<ref name="Complement">{{Cite journal|last1=Meri|first1=T.|last2=Jokiranta|first2=T.S.|last3=Hellwage|first3=J.|last4=Bialonski|first4=A.|last5=Zipfel|first5=P.F.|last6=Meri|first6=S.|date=2002|title=''Onchocerca volvulus'' microfilariae avoid complement attack by direct binding of factor H|journal=The Journal of Infectious Diseases|volume=185|issue=12|pages=1786–1793|doi=10.1086/340649|pmid=12085326|issn=0022-1899|doi-access=free}}</ref>

==Endosymbiotic relationship with ''Wolbachia''==
''Onchocerca volvulus'', along with most [[filariasis|filarial nematodes]], share an [[endosymbiont|endosymbiotic]] relationship with strains of the bacterium ''[[Wolbachia]]''. In the absence of ''Wolbachia'', larval development of ''O. volvulus'' is disrupted or ceased.<ref name = "Wolbachia">{{Cite journal|last1= Saint André|first1=A.V.|last2=Blackwell|first2=N.M. |last3=Hall|first3=L.R.|last4=Hoerauf|first4=A.|last5=Brattig|first5=N.W.|last6=Volkmann|first6=L.|last7=Taylor|first7=M.J.|last8=Ford|first8=L.|last9=Hise|first9=A.G.|date=2002|title=The Role of Endosymbiotic ''Wolbachia'' Bacteria in the Pathogenesis of River Blindness|journal=Science|language=en|volume=295|issue=5561|pages=1892–1895|doi=10.1126/science.1068732|issn=0036-8075|pmid=11884755|url=https://opus.bibliothek.uni-wuerzburg.de/files/2648/v_Arnim.pdf|bibcode=2002Sci...295.1892S|s2cid=22130066}}</ref> These bacteria have been proposed to enhance the symptoms and severity of onchocerciasis by triggering [[inflammatory response]]s in the host.<ref name="’Wolbachia pathogenicity’">{{Cite journal|last1=Tamarozzi|first1=F.|last2=Halliday|first2=A.|last3=Gentil|first3=K.|last4=Hoerauf|first4=A.|last5=Pearlman|first5=E.|last6=Taylor|first6=M.J.|date=2011|title=Onchocerciasis: the Role of ''Wolbachia'' Bacterial Endosymbionts in Parasite Biology, Disease Pathogenesis, and Treatment|journal=Clinical Microbiology Reviews|language=en|volume=24|issue=3|pages=459–468|doi=10.1128/CMR.00057-10|issn=0893-8512 |pmid=21734243|pmc=3131055}}</ref>

==References==
{{Reflist}}

==External links==
*{{cite web |title=''Onchocerca volvulus'' |work=NCBI Taxonomy Browser |url=https://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&id=6282 |id=6282}}

{{Helminthiases}}
{{Taxonbar|from=Q137224}}
{{Authority control}}

[[Category:Spirurida]]
[[Category:Parasitic nematodes of humans]]
[[Category:Taxa named by Rudolf Leuckart]]
[[Category:Nematodes described in 1894]]