Onchocerca volvulus
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''Onchocerca volvulus'' is a
filaria ''Filaria'' is a genus of nematodes belonging to the family Filariidae. The genus has cosmopolitan distribution. Species: *'' Filaria acutiuscula'' *'' Filaria bufonis'' *'' Filaria loliginis'' *'' Filaria martis'' *'' Filaria piscium'' ...
l (
arthropod Arthropods (, (gen. ποδός)) are invertebrate animals with an exoskeleton, a Segmentation (biology), segmented body, and paired jointed appendages. Arthropods form the phylum Arthropoda. They are distinguished by their jointed limbs and Arth ...
-borne)
nematode The nematodes ( or grc-gre, Νηματώδη; la, Nematoda) or roundworms constitute the phylum Nematoda (also called Nemathelminthes), with plant-Parasitism, parasitic nematodes also known as eelworms. They are a diverse animal phylum inhab ...
(roundworm) that causes
onchocerciasis 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 blindne ...
(river blindness), and is the second-leading cause of
blindness Visual impairment, also known as vision impairment, is a medical definition primarily measured based on an individual's better eye visual acuity; in the absence of treatment such as correctable eyewear, assistive devices, and medical treatment ...
due to infection worldwide after
trachoma Trachoma is an infectious disease caused by bacterium ''Chlamydia trachomatis''. The infection causes a roughening of the inner surface of the eyelids. This roughening can lead to pain in the eyes, breakdown of the outer surface or cornea of ...
. It is one of the 20
neglected tropical disease Neglected tropical diseases (NTDs) are a diverse group of tropical disease, tropical infections that are common in low-income populations in Developing country, developing regions of Africa, Asia, and the Americas. They are caused by a variety ...
s listed by the
World Health Organization The World Health Organization (WHO) is a specialized agency of the United Nations responsible for international public health. The WHO Constitution states its main objective as "the attainment by all peoples of the highest possible level of h ...
, with elimination from certain countries expected by 2020. 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 West Africa or Western Africa is the westernmost region of Africa. The United Nations defines Western Africa as the 16 countries of Benin, Burkina Faso, Cape Verde, The Gambia, Ghana, Guinea, Guinea-Bissau, Ivory Coast, Liberia, Mali, Maurit ...
. A Guatemalan doctor,
Rodolfo Robles Rodolfo Robles (1878–1939) was a Guatemalan physician and philanthropist. In 1915, he was the first to describe onchocerciasis in Latin America, which was known and widespread on the African continent and first described in 1890 by Sir Patr ...
, first linked it to
visual impairment Visual impairment, also known as vision impairment, is a medical definition primarily measured based on an individual's better eye visual acuity; in the absence of treatment such as correctable eyewear, assistive devices, and medical treatment ...
in 1917. ''O. volvulus'' is primarily found in
sub-Saharan Africa Sub-Saharan Africa is, geographically, the area and regions of the continent of Africa that lies south of the Sahara. These include West Africa, East Africa, Central Africa, and Southern Africa. Geopolitically, in addition to the List of sov ...
, and humans are the only known
definitive host In biology and medicine, a host is a larger organism that harbours a smaller organism; whether a parasitic, a mutualistic, or a commensalist ''guest'' ( symbiont). The guest is typically provided with nourishment and shelter. Examples include ...
; 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 ''Simulium'' is a genus of black flies, which may transmit diseases such as onchocerciasis (river blindness). It is a large genus with several hundred species, and 41 subgenera. The flies are pool feeders. Their saliva, which contains antico ...
''.


Morphology

''O. volvulus'' parasites obtain nutrients from the human host by ingesting blood or by diffusion through their
cuticle A cuticle (), or cuticula, is any of a variety of tough but flexible, non-mineral outer coverings of an organism, or parts of an organism, that provide protection. Various types of "cuticle" are non- homologous, differing in their origin, structu ...
. They may be able to trigger blood-vessel formation because dense vascular networks are often found surrounding the worms. They are distinguished from other human-infecting
filarial nematodes 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. These pa ...
by the presence of deep
transverse Transverse may refer to: *Transverse engine, an engine in which the crankshaft is oriented side-to-side relative to the wheels of the vehicle *Transverse flute, a flute that is held horizontally * Transverse force (or ''Euler force''), the tangen ...
striations Striations means a series of ridges, furrows or linear marks, and is used in several ways: * Glacial striation * Striation (fatigue), in material * Striation (geology), a ''striation'' as a result of a geological fault * Striation Valley, in ...
. It is a
dioecious Dioecy (; ; adj. dioecious , ) is a characteristic of a species, meaning that it has distinct individual organisms (unisexual) that produce male or female gametes, either directly (in animals) or indirectly (in seed plants). Dioecious reproductio ...
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 subcutaneous tissue (), also called the hypodermis, hypoderm (), subcutis, superficial fascia, is the lowermost layer of the integumentary system in vertebrates. The types of cells found in the layer are fibroblasts, adipose cells, and macr ...
. The males are smaller than females, with male worms measuring 23 mm in length compared to 230–700 mm in females. The release of
oocyte An oocyte (, ), oöcyte, or ovocyte is a female gametocyte or germ cell involved in reproduction. In other words, it is an immature ovum, or egg cell. An oocyte is produced in a female fetus in the ovary during female gametogenesis. The female ...
s (eggs) in female worms does not depend upon the presence of a male worm, although they may attract male worms using unidentified pheromones. The first larval stage,
microfilaria ::''Microfilaria may also refer to an informal "collective group" genus name, proposed by Cobbold in 1882. While a convenient category for newly discovered microfilariae which can not be assigned to a known species because the adults are unknown, ...
e, are 300 μm in length and unsheathed, meaning that when they mature into microfilariae, they exit from the envelope of the egg.


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 The blood circulatory system is a system of organs that includes the heart, blood vessels, and blood which is circulated throughout the entire body of a human or other vertebrate. It includes the cardiovascular system, or vascular system, tha ...
causes little to no immune response until death or degradation of the microfilariae or adult worms.


Blackfly stages

# The microfilariae of ''O. volvulus'' are found in the
dermis The dermis or corium is a layer of skin between the epidermis (with which it makes up the cutis) and subcutaneous tissues, that primarily consists of dense irregular connective tissue and cushions the body from stress and strain. It is divided i ...
layer of skin in the host. # When a female ''Simulium'' blackfly takes a
blood meal Blood meal is a dry, inert powder made from blood, used as a high-nitrogen organic fertilizer and a high protein animal feed. N = 13.25%, P = 1.0%, K = 0.6%. It is one of the highest non-synthetic sources of nitrogen. It usually comes from cattle ...
from an infected host, the microfilariae are also ingested. # From here, the microfilariae penetrate the gut and migrate to the thoracic flight muscles, where they enter the first juvenile phase, J1. # After maturing into J2, the second juvenile phase, they migrate to the
proboscis A proboscis () is an elongated appendage from the head of an animal, either a vertebrate or an invertebrate. In invertebrates, the term usually refers to tubular mouthparts used for feeding and sucking. In vertebrates, a proboscis is an elong ...
, where they are found in the
saliva Saliva (commonly referred to as spit) is an extracellular fluid produced and secreted by salivary glands in the mouth. In humans, saliva is around 99% water, plus electrolytes, mucus, white blood cells, epithelial cells (from which DNA can be ...
. # 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.


Human stages

# When the female blackfly takes a blood meal, J3 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 she takes a blood meal, thus completing the lifecycle of ''O. volvulus''.


Disease

''O. volvulus'' causes
onchocerciasis 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 blindne ...
, which causes severe itching. Long-term infection can cause
keratitis Keratitis is a condition in which the eye's cornea, the clear dome on the front surface of the eye, becomes inflamed. The condition is often marked by moderate to intense pain and usually involves any of the following symptoms: pain, impaired e ...
, an inflammation of the
cornea The cornea is the transparent front part of the eye that covers the iris, pupil, and anterior chamber. Along with the anterior chamber and lens, the cornea refracts light, accounting for approximately two-thirds of the eye's total optical power ...
in the eye, and ultimately leads to
blindness Visual impairment, also known as vision impairment, is a medical definition primarily measured based on an individual's better eye visual acuity; in the absence of treatment such as correctable eyewear, assistive devices, and medical treatment ...
. Symptoms are caused by the microfilariae and the
immune response An immune response is a reaction which occurs within an organism for the purpose of defending against foreign invaders. These invaders include a wide variety of different microorganisms including viruses, bacteria, parasites, and fungi which could ...
to infection, rather than the adults themselves. The most effective treatment involves using
ivermectin Ivermectin (, '' EYE-vər-MEK-tin'') is an antiparasitic drug. After its discovery in 1975, its first uses were in veterinary medicine to prevent and treat heartworm and acariasis. Approved for human use in 1987, today it is used to treat i ...
, although resistance to this drug has been reported as developing. 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. ''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 South Sudan (; din, Paguot Thudän), officially the Republic of South Sudan ( din, Paankɔc Cuëny Thudän), is a landlocked country in East Africa. It is bordered by Ethiopia, Sudan, Central African Republic, Democratic Republic of the C ...
,
Tanzania Tanzania (; ), officially the United Republic of Tanzania ( sw, Jamhuri ya Muungano wa Tanzania), is a country in East Africa within the African Great Lakes region. It borders Uganda to the north; Kenya to the northeast; Comoro Islands and ...
, and northern
Uganda }), is a landlocked country in East Africa East Africa, Eastern Africa, or East of Africa, is the eastern subregion of the African continent. In the United Nations Statistics Division scheme of geographic regions, 10-11-(16*) territor ...
. 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.


Epidemiology

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. ''Simulium'' blackfly adults require moving water to breed and eggs remain in water until they exit from the
pupa A pupa ( la, pupa, "doll"; plural: ''pupae'') is the life stage of some insects undergoing transformation between immature and mature stages. Insects that go through a pupal stage are holometabolous: they go through four distinct stages in their ...
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 Hydroelectricity, or hydroelectric power, is electricity generated from hydropower (water power). Hydropower supplies one sixth of the world's electricity, almost 4500 TWh in 2020, which is more than all other renewable sources combined and ...
, built in Africa, provide ideal conditions all year for blackfly development and make controlling its spread difficult. About 99% of cases of onchocerciasis are found in 31 countries in sub-Saharan Africa, although areas of limited transmission occur in
Brazil Brazil ( pt, Brasil; ), officially the Federative Republic of Brazil (Portuguese: ), is the largest country in both South America and Latin America. At and with over 217 million people, Brazil is the world's fifth-largest country by area ...
,
Venezuela Venezuela (; ), officially the Bolivarian Republic of Venezuela ( es, link=no, República Bolivariana de Venezuela), is a country on the northern coast of South America, consisting of a continental landmass and many islands and islets in th ...
, and
Yemen Yemen (; ar, ٱلْيَمَن, al-Yaman), officially the Republic of Yemen,, ) is a country in Western Asia. It is situated on the southern end of the Arabian Peninsula, and borders Saudi Arabia to the Saudi Arabia–Yemen border, north and ...
. The disease is thought to have been imported into
Latin America Latin America or * french: Amérique Latine, link=no * ht, Amerik Latin, link=no * pt, América Latina, link=no, name=a, sometimes referred to as LatAm is a large cultural region in the Americas where Romance languages — languages derived f ...
through the slave trade. Onchocerciasis was eliminated from Colombia in 2013, Ecuador in 2014, Mexico in 2015, and Guatemala in 2016 due to control programs that used
mass drug administration The administration of drugs to whole populations irrespective of disease status is referred to as mass drug administration (MDA). This article describes the administration of antimalarial drugs to whole populations an intervention which has been u ...
with ivermectin.


Genome

The total
genome In the fields of molecular biology and genetics, a genome is all the genetic information of an organism. It consists of nucleotide sequences of DNA (or RNA in RNA viruses). The nuclear genome includes protein-coding genes and non-coding ge ...
size of ''O. volvulus'' is 1.5x108
base pairs A base pair (bp) is a fundamental unit of double-stranded nucleic acids consisting of two nucleobases bound to each other by hydrogen bonds. They form the building blocks of the DNA double helix and contribute to the folded structure of both DNA ...
and contains around 4,000
gene In biology, the word gene (from , ; "...Wilhelm Johannsen coined the word gene to describe the Mendelian units of heredity..." meaning ''generation'' or ''birth'' or ''gender'') can have several different meanings. The Mendelian gene is a ba ...
s, with genes for
collagen Collagen () is the main structural protein in the extracellular matrix found in the body's various connective tissues. As the main component of connective tissue, it is the most abundant protein in mammals, making up from 25% to 35% of the whole ...
and cuticular proteins being highly expressed in mature adults. ''O. volvulus'' has four chromosome pairs, which include a single pair of
sex chromosomes A sex chromosome (also referred to as an allosome, heterotypical chromosome, gonosome, heterochromosome, or idiochromosome) is a chromosome that differs from an ordinary autosome in form, size, and behavior. The human sex chromosomes, a typical ...
. A large X sex chromosome and a smaller Y sex chromosome determine male worms, while two X chromosomes determine female worms. One of the three nonsex chromosomes is thought to have formed by a fusion event between two smaller chromosomes.


Evolution

(Simplified
phylogenetic tree A phylogenetic tree (also phylogeny or evolutionary tree Felsenstein J. (2004). ''Inferring Phylogenies'' Sinauer Associates: Sunderland, MA.) is a branching diagram or a tree showing the evolutionary relationships among various biological spec ...
of the genus ''Onchocerca''.) ''O. volvulus'' has low genetic variation between individuals. This suggests a
population bottleneck A population bottleneck or genetic bottleneck is a sharp reduction in the size of a population due to environmental events such as famines, earthquakes, floods, fires, disease, and droughts; or human activities such as specicide, widespread violen ...
occurred in the past that caused a rapid decrease in the population size. It also shows high
haplotype A haplotype ( haploid genotype) is a group of alleles in an organism that are inherited together from a single parent. Many organisms contain genetic material ( DNA) which is inherited from two parents. Normally these organisms have their DNA or ...
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 Cattle (''Bos taurus'') are large, domesticated, cloven-hooved, herbivores. They are a prominent modern member of the subfamily Bovinae and the most widespread species of the genus ''Bos''. Adult females are referred to as cows and adult mal ...
allowed ''O. volvulus'' to infect humans. This is also supported by genetic data that place ''O. ochengi'' (a cattle-infecting strain) as the
sister group In phylogenetics, a sister group or sister taxon, also called an adelphotaxon, comprises the closest relative(s) of another given unit in an evolutionary tree. Definition The expression is most easily illustrated by a cladogram: Taxon A and t ...
to ''O. volvulus''.


Immune response

Adult worms are found in nodules and are hidden from most components of the human
immune system The immune system is a network of biological processes that protects an organism from diseases. It detects and responds to a wide variety of pathogens, from viruses to parasitic worms, as well as cancer cells and objects such as wood splinte ...
. 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 In immunology, an antigen (Ag) is a molecule or molecular structure or any foreign particulate matter or a pollen grain that can bind to a specific antibody or T-cell receptor. The presence of antigens in the body may trigger an immune response. ...
s 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. The immune response involves raising
antibodies An antibody (Ab), also known as an immunoglobulin (Ig), is a large, Y-shaped protein used by the immune system to identify and neutralize foreign objects such as pathogenic bacteria and viruses. The antibody recognizes a unique molecule of the ...
(
IgG Immunoglobulin G (Ig G) is a type of antibody. Representing approximately 75% of serum antibodies in humans, IgG is the most common type of antibody found in blood circulation. IgG molecules are created and released by plasma B cells. Each IgG ...
,
IgM Immunoglobulin M (IgM) is one of several isotypes of antibody (also known as immunoglobulin) that are produced by vertebrates. IgM is the largest antibody, and it is the first antibody to appear in the response to initial exposure to an antig ...
and
IgE Immunoglobulin E (IgE) is a type of antibody (or immunoglobulin (Ig) " isotype") that has been found only in mammals. IgE is synthesised by plasma cells. Monomers of IgE consist of two heavy chains (ε chain) and two light chains, with the ε c ...
type) that can react with soluble antigens released by ''Onchocerca volvulus''. 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. The antigens of ''O. volvulus'' are highly complex and show
cross-reactivity Cross-reactivity, in a general sense, is the reactivity of an observed agent which initiates reactions outside the main reaction expected. This has implications for any kind of test or assay, including diagnostic tests in medicine, and can be a ...
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.


Modulation by ''O. volvulus''

Microfilariae can also modulate the immune system to avoid destruction. The
complement system The complement system, also known as complement cascade, is a part of the immune system that enhances (complements) the ability of antibodies and phagocytic cells to clear microbes and damaged cells from an organism, promote inflammation, and at ...
is used to enhance the effect of antibodies and
phagocytic cells Phagocytes are cells that protect the body by ingesting harmful foreign particles, bacteria, and dead or dying cells. Their name comes from the Greek ', "to eat" or "devour", and "-cyte", the suffix in biology denoting "cell", from the Greek ' ...
, which engulf and destroy other cells. Microfilariae block this pathway by cleaving
C3b C3b is the larger of two elements formed by the cleavage of complement component 3, and is considered an important part of the innate immune system. C3b is potent in opsonization: tagging pathogens, immune complexes (antigen-antibody), and apopto ...
—an important protein in this process—to form
iC3b iC3b is a protein fragment that is part of the complement system, a component of the vertebrate immune system. iC3b is produced when complement factor I cleaves C3b.Robbins Basic Pathology 8th ed 2007. R Cotran, S Robbins, V Kumar, J Perkins. W.B ...
. 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.


Endosymbiotic relationship with ''Wolbachia''

''O. volvulus'', along with most
filarial nematodes 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. These pa ...
, share an
endosymbiotic An ''endosymbiont'' or ''endobiont'' is any organism that lives within the body or cells of another organism most often, though not always, in a mutualistic relationship. (The term endosymbiosis is from the Greek: ἔνδον ''endon'' "within ...
relationship with the bacterium ''
Wolbachia ''Wolbachia'' is a genus of intracellular bacteria that infects mainly arthropod species, including a high proportion of insects, and also some nematodes. It is one of the most common parasitic microbes, and is possibly the most common reproduct ...
''. In the absence of ''Wolbachia'', larval development of ''O. volvulus'' is disrupted or ceased. These bacteria have been proposed to enhance the symptoms and severity of onchocerciasis by triggering
inflammatory response Inflammation (from la, inflammatio) is part of the complex biological response of body tissues to harmful stimuli, such as pathogens, damaged cells, or irritants, and is a protective response involving immune cells, blood vessels, and molecu ...
s in the host.


References


External links

* {{DEFAULTSORT:Onchocerca Volvulus Spirurida Parasitic nematodes of humans Taxa named by Rudolf Leuckart Nematodes described in 1894