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Onchocerciasis

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Onchocerciasis Powered By Docstoc
					                                                                 Nnenna Aguocha
                                                              Human Biology 103
                                                       Parasites and Pestilence
                                                                Dr. Scott Smith
                                                                   May 22, 2001


                                 Onchocerciasis
Introduction
     Onchocerciasis, also known as river blindness because of its most extreme
manifestation, is caused by the parasitic nematode Onchocerca volvulus. Onchocerca
volvulus, like various other blood and tissue-dwelling nematodes is a filarial parasite that
thrives in the blood vascular system and tissues of humans as well as other vertebrate
species. Filariae are long thread-like nematodes, or roundworms, that mature and mate in
specific host tissues. Female adult worms produce eggs that after fertilization undergo
several developmental stages to become elongated and worm-like in appearance. These
modified eggs also known as microfilariae aggregate in the human lymphatic system, as
well as in subcutaneous and deep connective tissues. These adaptations are critical for
migration and survival in tissues where they can persist, without further development for
extended periods of time. To become infective larvae, these microfilariae must first be
ingested by an arthropod vector and inoculated into a suitable host when the vector takes
a blood meal. For Ochocerciasis, the vector of transmission is the bite of a Simulium
black fly, which thrives in rich, oxygenated water in rapidly flowing rivers and streams,
hence the term- “river blindness.”

Epidemiology
     Onchocerciasis, is the second leading cause of infectious blindness in the world.
This disease, which also causes disfiguring skin disorders is endemic along fertile
riverside areas in 36 countries in Africa, the Arabian peninsula, as well as countries in
South and Central America including Mexico, Guatemala, Brazil, Venezuela, Ecuador
and Colombia. The African and American forms of onchocerciasis exhibit different
symptoms and characteristics, possibly due to the biting patterns of the vectors. In
Colombia, the simuliid vectors for onchocerciasis are zoophilic with the result that in
areas where large numbers of livestock are found, onchocerciasis affects domestic



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livestocks. In areas where there are no large pockets of domestic livestock onchocercal
infections in humans persist, thus suggesting a possible link between the abundance of
domestic livestock and the prevalence of onchocerciasis in human populations.
       The World Health Organization (WHO) estimates that of the 120 million people
worldwide who are at risk of contracting Onchocerciasis, 96% are in Africa. In addition,
WHO also hypothesizes that of the estimated 18 million people worldwide who are
infected with the disease, 99% reside in Africa. Among this infected population,
Onchocerciasis has led to an estimated 270,000 cases of blindness and 500,000 cases of
severe visual impairment. Although Onchocerciasis is most commonly associated with
blindness, in reality, it is a chronic systemic illness that leads to extensive damage in the
musculoskeletal tissue of infected individuals. In addition this disease leads to adverse
changes in the immune systems of infected individuals, and in some areas of Africa, is
closely associated with increased rates of epilepsy, weight loss and growth arrest.
       Although Onchocerciasis is endemic in several countries throughout the world, as
a public health concern, it is most closely associated with Africa where it has debilitated
populations, leaving over 25 million hectares of fertile land, capable of feeding 17
million people a year, inhospitable and uncultivable. Thus, Onchocerciasis transcends the
category of a “public health concern” to emerge as a disease that constitutes not only a
threat to health and well-being, but also a serious obstacle to socio-economic
development in some of the world’s poorest areas.

Classification And Taxonomy- attach image of worm with tree
Scientific Name: Onchocerca volvulus
     Class: Secernenta
     Subclass: Spiruria
     Order: Spirurida
     Super family: Filarioidea
     Family: Onchocercidae

Synonyms
 River Blindness
 River Eye Blindness

History of Discovery




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       John O’Neill, a scientist in the Gold Coast studying a filarial parasitic infection
known as “craw-craw,” or dermatitis, first observed the microfilariae of Onchocerca
volvulus in 1875. Nearly twenty years later in 1893, Leuckart using samples collected
and sent by missionaries from the Gold Coast first described the morphology of the adult
worm. Although these discoveries were critical in identifying the morphology of the
filarial parasite, scientists remained puzzled about the life cycle of the parasite as well as
its transmission from person to person. This missing link was finally provided in 1915 by
Robles who discovered the presence of onchocerciasis among coffee plantation workers
in Guatemala, possibly introduced to endemic areas of Latin Americas as a result of the
slave trade. He noted that laborers who resided outside the disease zone, and entered
endemic areas only during the day to work, became infected with onchocerciasis. Using
these case studies, he hypothesized that the vector of the disease was a day-biting insect,
and more specifically, two anthropohilic species of Simulium flies found in the endemic
areas. Although Robles conveyed his assumptions to his colleagues, he failed to carry out
investigations to verify his hypothesis.
       Eleven years later in 1926, Blacklock, working in Africa, picked up where Robles
had left off and demonstrated that Simulium black flies were indeed the vectors of
transmission for onchocerciasis, by conducting a series of experiments using infected
patients and Simulium damnosum flies. Females Simulium black flies seek blood meals
after mating, and thus ingest microfilariae if the meal is taken from an individual infected
with onchocerciasis. Thus, Blacklock collected several wild Simulium damnosum flies
and proceeded to infect them by placing the within close proximity of infected
individuals. He then proceeded to trace the development of the parasite in the gut, thorax,
head and proboscis of the flies thus providing the final piece of the puzzle for the life
cycle of the disease.
       These early discoveries laid the foundation for later discoveries, and in 1946,
Hissette working in the Congo finally linked onchocerciasis with blindness even though
Ghanaians living along the Red Volta River had long associated the biting flies with skin
lesions and blindness. These ground breaking discoveries led to more investigations into
the distribution of vector species as well as the transmission patterns and possible
characteristic symptoms of various strains of the disease. Today, many lines of evidence



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suggest that there at least two trains of Onchocerca volvulus- a savanna strain and a forest
train. The savanna strain is more common in the woodlands and savannas of West Africa
and is presumed to be the strain that induces the most serious cases of ocular pathology
and blindness. The latter strain, or forest strain is endemic in the West African rain forest,
and scientists have noted that endemic areas within these regions have more cases of
hyperpigmentation and other skin diseases related to onchocerciasis. These observations
have been confirmed in recent years with the advent of new technological systems that
have allowed scientists to utilize DNA probes to prove the existence of two virulent
strains of the disease.

Vector
     There are six sibling species of the black fly species complex Simulium
damnosum sensu lato that are capable of transmitting onchocerciasis. These vectors can
be found in 30 sub-Saharan African countries, Yemen and six countries in Central and
South America including Mexico, Guatemala, Brazil, Venezuela, Ecuador and Colombia.
Two of these sibling species, S sirbanum and S damnosum sensu stricto, are the primary
vectors in the African savanna, and two, S yahense and S squamosum, are the primary
vectors in rain forests. All fur of these species conglomerate in certain endemic areas to
from transition zones where intermediate disease patterns exist, and where the rate of
blindness falls halfway between the rates of prevalence for the two strains. The final two
vectors, S leonense and S anctipauli have restricted distributions. S leonense is found
primarily in the lowlands of Sierra Leone while the latter species is restricted to the large
coastal rivers of West Africa.




Transmission and Incubation
        Onchocerciasis is transmitted from person to person through the bite of an
infected black fly. This fly specie lays its eggs in rich oxygenated water, typically fast-
flowing streams and rivers. These eggs then undergo various developmental processes
with adult forms emerging after a period of 8-12 days. These adult flies can live for up to




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four weeks, during which time they can travel hundreds of kilometers in flight to reach
areas that are suitable for mating and reproduction.
        Once mating has occurred, the female black fly must ingest a blood meal to
acquire nutrients necessary for egg development. If the blood meal is taken from a person
infected with onchocerciasis, microfilariae are also ingested along with blood.
Microfilariae that survive this uptake and escape the peritropic membrane that forms
around the blood meal penetrate the midgut and move into the flight muscles of the fly.
After 28 hours, the microfilariae begin to differentiate into L1 larvae, and by 96 hours
they molt and enter the L2 larva stage. The second molting process occurs by day 7, and
after this, the L3 or infective larva travels to the head of the insect as well as other areas
of the black fly. The infective larvae that succeed in finding their way to the proboscis of
the fly enter the skin of an individual when the insect takes its next blood meal. The
infective larvae that survive this stage of inoculation into the host begin to molt into the
L4 stage within seven days, and by 1-3 months the worms complete differentiation into
male or female adult species. Once maturity is complete, adult worms mate and female
species begin to produce as many as 1300-1900 microfilariae a day. This daily production
can continue for up to fourteen years depending on how long the worm persists in the
human host, and microfilariae may live in the host for up to two years.
        Adult worms of Onchocerca volvulus have a propensity to congregate over bony
prominences and thus become encapsulated in a fibrous, tumor-like mass or nodules that
usually appear around the pelvic area and the skull within a year after infection,
depending on the biting habits of the vector. For instance, in Venezuela and Africa mot
nodules are located on the patient’s trunk or limbs, with a few nodules forming on the
head. In Mexico and Guatemala however, nodules are frequently seen on a patient’s scalp
and appear less often in other parts of the body. These nodules range from a few
millimeters to several centimeters in diameter and serve as the site of release for
microfilariae. From these release points microfilariae travel mainly to the skin and they
eyes of the infected host. In the skin, they are found predominantly in the lymphatics of
the sub epidermis. In the eye, most microfilariae aggregate in the anterior chamber, the
retina and the optic nerve. When a Simulium fly bites an infected individual to take a




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blood meal, microfilariae in the skin are ingested along with the blood meal and thus
perpetuate the life cycle of the parasite.

Morphology
     Adult worms are white, long and thread-like. They are typically knotted together
in pairs in the subcutaneous tissue and are characteristically slender and blunt at both
ends. Female adult worms may be as long as 50cm in length and as thick as 0.5mm in
diameter. The male adult worms are shorter and typically measure no more than 5cm in
length and 2.2mm in diameter. These worms typically lack lips and buccal capsules but
display two circles of four papillae around the mouth; the esophagus lacks conspicuous
divisions. In females, the vulva lies behind the posterior end of the esophagus, and in
males the tail is a curled ventrad that lacks alae. Microfilariae of this parasite are
unsheathed and typically measure 250-300 microns in length.

Reservoir
     Although there are zoophilic forms of onchocerciasis, there are no known
reservoirs of the strains that affect humans.


Clinical Manifestations
     The predominant symptoms associated with onchocerciasis are rashes, lesions,
and nodules over bony areas, blindness and severe visual impairment, intense itching and
hyper-pigmentation, and lymphadenitis, which lead to hanging groins and elephantiasis
of the genitals. Other symptoms in certain endemic areas of Africa include epilepsy,
growth arrest and general malaise and debilitation. These clinical manifestations of the
disease begin to appear within one to three years after the injection of the infected larvae
and are almost entirely de to localized host inflammatory responses to dead or dying
microfilariae. These immune responses are typically antibody and cell mediated
responses. The strength of the immune response varies from person to person depending
on the length of exposure to antigens as well as the regulating activities of the host.
        Eosinophils are typically found around the nodules that encapsulate adult worms
and are critical in the inflammatory response of the host. Microfilariae migrating in the
skin typically destroy elastic tissue over a period of years, thus causing the formation of
redundant folds in the host. Skin lesions are the most pervasive consequences of


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onchocerciasis. In surveys conducted in seven endemic areas in five African countries,
40% to 50% of all adults surveyed reported severe itching. Thus, in its mildest form
onchocerciasis manifests as a localized musculopapular rash. These reactive lesions and
itching sometimes clear up within months without treatment. In more severe cases of
itching edemas occurs as well as chronic papular dermatitis, and lichenified,
hyperkeratoic lesions which often heal with hyper pigmentation.
         Lesions of the eye typically take several years to develop and occur mostly in
individuals over the age of 40. In the eye, microfilariae migrate along sheaths of the
ciliary vessels and nerves from under the bulbar conjunctiva directly into the cornea,
through nutrient vessels present in the optic nerve. Invasion of the cornea by microfilariae
leads to the inflammation of the sclera, or white of the eye, followed by an invasion of
fibrous tissue. This leads to extensive vascularization of the cornea, and thus, severely
impairs the vision of the host. Subsequent invasions and immune responses frequently
lead to complete blindness.
         Microfilariae can also wreak havoc in the lymphatic system of the host. The
lymphatic system is responsible for removing foreign substances from distal skin regions;
however, with the invasion of microfilariae into this system, this function is severely
compromised leading general inflammation in regions distal to the lymph nodes as well
as a loss of elasticity and the creation of protruding lymph glands enfolded in hanging
pockets of skin. This condition, prominent around in the pelvic region of the host, is
called the “hanging groin effect,” and may be classified as minor elephantiasis in severe
cases.




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Diagnostic Tests
     Onchocerciasis can be diagnosed by observing skin snips taken from the shoulder
and other areas of infected individuals. These snips are then immersed in saline solution
and observed under a microscope for the presence of emerging microfilariae. Another
method that is utilized when microfilariae cannot be observed is the administration of
6mg of diethylcarbamazine (DEC). This test is known as the Mazotti test, and results in
itching as well as severe inflammation where microfilariae are present. Because of the
severe side effects associated with the Mazotti test, health care workers have opted to use
less invasive alternative methods such as searching for signs of nodules in areas where
onchocerciasis is prevalent, and using slit lamps to detect microfilariae in the cornea and
anterior chamber of the eye. Other alternative methods include polymerase chain
amplification of parasite DNA and recombinant antigen-based immunoassays, which are
utilized for individual diagnosis and confirmation in some cases.

Management And Therapy




Public Health and Prevention Strategies
Useful Links
References




Before the 1980s, the only available method for control of onchocerciasis was
elimination of black fly vector populations. This strategy was used with considerable
success in
                   The Onchocerciasis Control Program in West Africa (OCP). The
discovery of ivermectin, the first effective drug suitable for mass treatment of
onchocerciasis, has revived
                   International interest not only in fundamental research but also in
development of new strategies to control onchocerciasis in the countries outside the OCP
area. This report




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                   gives an overview of current parasitological, clinical, epidemiological
and diagnostic data about onchocerciasis. Although little is known about the early
development of
                   Onchocerca volvulus in the human host, significant insight has been
gained into the population dynamics of the parasite. The pathogenesis of cutaneous and
ocular
                   manifestations in onchocerciasis is now better understood.
Epidemiological studies are under way to evaluate the extent of systemic manifestations.
Recently developed
                   diagnostic methods are more sensitive than conventional
parasitological techniques. A new method for rapid assessment of endemic level has
provided a detailed picture of
                   the distribution of onchocerciasis. Species- and strain-specific DNA
probes have been developed for identification of parasites in West Africa. New methods
for quantifying
                   disability allow evaluation of the socio-economic impact of the
cutaneous and ocular complications of onchocerciasis.




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