WUCHERERIA BANCROFTI AND ONCHOCERCA VOLVULUS

WUCHERERIA BANCROFTI & ONCOCERCA VOLVULUS. INTRODUCTION. SUPERFAMILY-FILARIOIDEA. This group include spirurate filiform nematodes adapted to inhabiting the deeper tissues eg circulatory, lymphatics and connective tissue layers. They are transmitted by blood sucking insects. 8 spp of filarial worms infecting man who is definitive host, of them 6 are pathogens. Wuchereria bancrofti, Brugia malay, and B timori, causes lymphatic filariasis, Loa loa causes calabar swelling, and allergic reactions, Onchocerca volvulus causes eye lesion and dermatitis, Mansonella streptocerca leads to skin disease

WUCHERERIA BANCROFTI WUCHERERIA- is a parasitic filarian nematode (roundworm) spread by a mosquito bite. It is one of the three parasites that cause lymphatic filariasis, an infection of the lymphatic system by filarial worms. It affects over 120 million people, primarily in Africa, South America, and other tropical and sub-tropical countries. If the infection is left untreated it can develop into a chronic disease called elephantiasis. Limited treatment modalities exist and no vaccine have been developed.

THE GENUS: WUCHERERIA. Kingdom: Animalia Phylum: Nematoda Class: secernentea Order: spirurida Suborder: spirurina Family: onchocercidae Genus: Wuchereria Species: bancrofti

Aetiology. W. bancrofti exhibits considerable sexual dimorphism. The adult worm is long, slender, and smooth with rounded ends. It has a short cephalic region, dispersed nuclei throughout its body cavity, with no nuclei at the tail tip.

The male is worm 40mm long and 100micrometer wide and features a curved tail. In contrast, the female is 6 cm to 10 cm long and 300 μm wide, nearly three times larger in diameter than the male. Females are ovoviviparous and can produce thousands of juveniles known as microfilariae. Microfilariae of W. bancrofti retain the egg membrane as a sheath and are often considered advanced embryos.

EPIDEMIOLOGY. W. bancrofti is responsible for 90% of lymphatic filariasis. Recently, it was estimated that there were 120 million worldwide cases of lymphatic filariasis. W. bancrofti largely affects areas across the broad equatorial belt (Africa, the Nile Delta, Turkey, India, the East Indies, Southeast Asia, Philippines, Oceanic Islands, Australia, and parts of South America.) The mosquito vectors of W. bancrofti have a preference for human blood and it appears that humans are the only animals naturally infected with W. bancrofti. There is no reservoir host.

LIFE CYCLE. -W. bancrofti carry out their life cycle in two hosts. Human being serve as the definitive host while mosquito as intermediate host -The adult parasites reside in the lymphatics of the human host. They are ovoviviparous. The first stage larvae are known as microfilariae The microfilariae are present in the circulation. -The microfilariae migrate between the deep and the peripheral circulation.

LIFE CYCLE cont.. W. bancrofti is a periodic strain that exhibits nocturnal periodicity. During the day they are present in the deep veins and during the night they migrate to the peripheral circulation. Next, the microfilariae are transferred into a vector; the most common vectors are the mosquito species: Culex, Anopheles , Mansonia, and Aedes. Inside the mosquito vector, also known as the intermediate host, the microfilariae mature into motile larvae called juveniles.

LIFE CYCLE cont.. When the mosquito vector has its next blood meal, W. bancrofti is injected via the mosquito’s proboscis into the blood stream of the new human host. The larvae move through the lymphatic system to regional lymph nodes, predominantly in the legs and genital area. The larvae develop into adult worms over the course of a year and reach sexual maturity in the afferent lymphatic vessels. After mating, the adult female worm can produce thousands of microfilariae that migrate into the bloodstream. A mosquito vector can bite the infected human host, ingest the microfilariae, and thus repeat the life cycle of W. bancrofti. There is no multiplication of microfilaria in the mosquito and one microfilaria develops into one infective larva only.

BIOLOGY In humans, the adult W. bancrofti reside in the lymphatic ducts and are found mostly in the lymph glands of the afferent lymphatic channels in the lower part of the body. The microfilariae produced by the female worms have a membrane "sheath". This "sheath", along with the area in which the worms reside, makes identification of the type of species of microfilariae in humans easier to determine. The microfilariae are found mainly in the peripheral blood and can be found at peak amounts from 10 p.m. to 2 a.m. The cause of this periodicity remains unknown but the advantages of the microfilariae being in the peripheral blood during these hours may ensure that the vector, the nighttime mosquito, will have a higher chance of transmitting them elsewhere.

BIOLOGY cont.. There are physiological changes associated with sleeping, such as lowered body temperature, oxygen tension and adrenal activity, and an increased carbon dioxide tension, among other physical alterations, any of which could be the signals for the rhythmic behavior of microfilarial parasites. If the host sleeps by day and is awake at night, their periodicity is reversed. In the South Pacific, where W. bancrofti shows diurnal periodicity it is known as periodic

PATHOGENESIS AND CLINICAL MANIFESTATIONS. The pathogenesis of W. bancrofti infection is dependent on the immune system and inflammatory responses of the host. After infection, the worms will mature within 6–8 months, male and female worms will mate and then release the microfilariae. These microfilariae worms can be released for up to ten years.

PATHO…. Filariasis range from carrier to chronic state. Does not kill but may cause great suffering, disfiguration and disability. The earliest manifestation are seeing during stage of invasion, when the infective larvae enter the body and undergo development. In some person hypersensitivity to the antigen causes symptoms such as nausea, malaise, headache, vomiting, and low grade fever. Recurrent attacks of pruritus, and urticarial may occur. Some develop fugitive swelling, raised painless, tender, diffuse, red areas on the skin, this may disappear and reappear at the same site or different site.

The characteristic manifestations of filariasis is due to : Obstruction of lymph vessels and nodes The essential feature are lymphadenopathy, lymphangitis, lymphangiovarix, lymphorrhagia or chylorrhagia, hydrocele, lymphedema and elephantiasis. These features depends on the site affected.

Lymphadenitis Repeated episodes of acute lymphadenitis with fever, occur very frequently. The inguinal nodes are most affected, and axillary nodes less common. The swollen nodes may be painful

Lymphangitis Acute inflammation of lymph vessels seen red under the skin. Lymphatics of the tests and spermatic cord are frequently involved with epiddidymo-orchits and funiculitis. Acute lymphangitis is due to allergic or inflammatory reaction to filarial infection

Filarial fever High fever of sudden onset , often with rigor lasting for two to three days is the typical feature. This occurs repeatedly at interval of weeks or months. Its accompanied by lymphangitis and lymphadenitis with resulted lymphoedema.

Lymphangiovarix Dilatation of lymph vessels commonly occur in the inguinal, scrotal, testicular and abdominal sites.

Lymphorrhagia Rapture of lymph varices leads to the release of lymph or chyle. The clinical picture depends on the sites involved and included lymph scrotum, Lymphocoel, chyluria, chylous,diarrhoea, chylous ascites and chylothorax.

Hydrocoele Is common manifestation of filariasis. Accumulation of fluid occurs due to obstruction of lymph vessels of the spermatic cord and also by exudation from the inflamed tests and epididymis. The fluid is clear and straw coloured, but sometimes be cloudy, milky, or hemorrhage. The hydrocele may be unilateral or bilateral and is generally small in size in the early stage. The largest reported hydrocele weight over 100 kilogram

Lymphoedema Swelling around the ankle, spreading to the back of the foot and leg. It may affect the arms, breast, scrotum, vulva, or any other part of the body. Initially the oedema is pitting in nature, but in course of time becomes hard and nonpitting.

Elephantiasis This is delayed sequel to repeat lymphangitis, obstruction, and lymphoedema. The skin surface become coarse, with warty excrescences. Cracks and fissures develop with secondary bacteria infection. Seen most in leg but may also involve other parts of the body including the arm, breast, scrotum, penis and vulva.

Occult filariasis Find on it.

Diagnosis Depends on clinical features, history of exposure in endemic areas,and laboratory findings. Lab test Demonstration of microfilaria in peripheral blood Demonstration of adult worm in biopsy specimen Skin test with filarial antigen Demonstration of filarial antigen by serological test Demonstration of filarial antigen in blood by serological test Indirect evidence such as eosinophilia.

DIAGNOSIS. A blood smear is a simple and fairly accurate diagnostic tool, provided that the blood sample is taken during the period in the night when the juveniles are in the peripheral circulation. Technicians analyzing the blood smear must be able to distinguish between W. bancrofti and other parasites potentially present. A polymerase chain reaction (PCR)test can also be performed to detect a minute fraction, as little as 1 pg, of filarial DNA.

DIAGNOSIS cont.. Sometimes infected people do not have microfilariae in their blood. As a result, tests aimed to detect antigens from adult worms can be used. Ultrasonography can also be used to detect the movements and noises caused by the movement of adult worms. Dead, calcified worms can be detected by X-ray examinations.

TREATMENT. The severe symptoms caused by the parasite can be avoided by cleansing the skin, surgery, or the use of therapeutic drugs, such as Diethylcarbamazine (DEC), ivermectin, or albendazole. The drug of choice however, is DEC, which can eliminate the microfilariae from the blood and also kill the adult worms with a dosage of 6 mg/kg semiannually or annually . A polytherapy treatment that includes ivermectin with DEC or albendazole is more effective than each drug alone. Surgical excision.

PREVENTION AND CONTROL. Protection is similar to that of other mosquito spread illnesses; one can use barriers both physical (a mosquito net), chemical (insect repellent), or mass chemotherapy as a method to control the spread of the disease. Mass chemotherapy should cover the entire endemic area at the same time. This will decrease the overall micro-filarial titer in blood significantly in mass, hence decreasing the transmission through mosquitoes during their subsequent bites.

PREVENTION AND CONTROL Prevention focuses on protecting against mosquito bites in endemic regions. Insect repellents and mosquito nets are useful manners in which to protect against mosquito bites. Public education efforts must also be made within the endemic areas of the world in order to successfully lower the prevalence of W. bancrofti infections.

ONCOCERCA VOLVULUS. Onchocerciasis, also known as river blindness and Robles' Disease, is a parasitic disease caused by infection by Onchocerca volvulus, a nematode (roundworm). Onchocerciasis is the world's second-leading infectious cause of blindness. It is not the nematode but its endosymbiont, Wolbachia pipientis, that causes the severe inflammatory response that leaves many blind. The vector for transmitting the infection is Simulin spp. The larval nematodes spread throughout the body. When the worms die their Wolbachia symbionts are released, triggering a host immune system system response that causes intense itching and can destroy nearby tissue, such as the eye.

HISTORY and DISTRIBUTION Onchocerca volvulus or blinding filaria causing onchorcerciasis was first described by leuckart in 1993. Human onchocerciasis is found in both the Old and New World but about 95% of all cases are in Africa. Important foci exist in Mexico, Guatemala, Venezuela, and most of Western Africa.

Epidemiology cont.. 99% of onchocerciasis cases occur in Africa. As of 2008 about 18 million people were infected with this parasite; approximately 300,000 had been permanently blinded. Onchocerciasis is currently endemic in 30 African countries, Yemen, and isolated regions of South America. Travelers who do not stay long in those areas have little risk of developing the disease as it requires prolonged exposure to the fly bites and parasite introduction.

Epidemiology cont.. Onchocerciasis is endemic in 36 countries across Africa, Latin America and Yemen. Over 85 million people live in endemic areas and half of these reside in Nigeria. Another 120 million people are at risk for contracting the disease. Due to the vector’s breeding habitat, the disease is more severe along the major rivers in the northern and central areas of the continent, and severity declines in villages farther from rivers.

LIFE CYCLE A Simulium female black fly takes a blood meal on an infected human host ingesting microfilaria. The microfilaria enter the gut and thoracic flight muscles of the black fly progressing into the first larval stage . The larvae mature into the second larval stage and moves to the proboscis and into the saliva in its third larval stage (J3.). Mature in about 7 days. The black fly takes another blood meal passing the larvae into the next human host’s blood

Life cycle cont.. The larvae migrate to the subcutaneous tissue and form nodules as they mature into adult worms over six to twelve months. After maturing, adult male worms mate with female worms in the subcutaneous tissue to produce between 700 and 1,500 microfilaria per day. The microfilaria migrate to the skin during the day and the black flies only feed in the day, so the parasite is in a prime position for the female fly to ingest it. Black flies take blood meals to ingest these microfilaria to restart the cycle.

LIFE CYCLE.

PATHOGENESIS Pathogenesis depends on the hosts allergic and inflammatory reactions to the adult and microfilariae. Adult worms remain in subcutaneous nodules which are circumscribed, firm, non tender, tumor result of fibroblastic reaction. Limiting access to the host's immune system. Microfilariae in contrast, are able to induce intense inflammatory responses, especially upon their death. Skin involvement typically consists of intense itching, swelling, and inflammation is observed.

CLINICAL SIGNS One of the earliest signs of infection with Onchocerca is the raised nodules that can be seen under the skin around areas over bony prominence

CLINICAL SIGNS cont.. Reactions to dead microfilaria around these nodules can lead to several unpleasant conditions. In the skin there is destruction of the elastic tissues and the formation of redundant folds. There is also often a loss of pigmentation and the histological appearance of advances cases often resemble the skin of very old normal subjects

CLINICAL SIGNS cont… The microfilaria can also cause inflammation of regional lymph glands which remove foreign material from the distal skin. This inflammation along with the loss of tissue elasticity can lead to protruding lymph glands enfolded in pockets of skin. This condition is especially prominent in the areas around the scrotum (often called the 'hanging groin' effect) and in severe cases is classified as minor elephantiasis

CLINICAL SIGNS cont.. The microfilaria can also enter the eye by passing along the sheaths of the ciliary vessels and nerves from under the bulbar conjunctiva directly into the cornea, via the nutrient vessels into the optic nerve, and via the posterior perforating ciliary vessels into the choroids. Dead microfilariae in the eye lead to an inflammatory immune response and the eventual formation of secondary cataracts and ocular lesions

CLINICAL SIGNS Cont.. Acute papular onchodermatitis - scattered pruritic papules Chronic papular onchodermatitis - larger papule, resulting in hyperpigmentation; Lichenified onchodermatitis - hyper pigmented papules and plaques with edema, lymphadenopathy, pruritus and common secondary bacterial infections; Skin atrophy - loss of elasticity, skin resembles tissue paper, 'lizard skin' appearance; Depigmentation - 'leopard skin' appearance, usually on anterior lower leg.

DIAGNOSIS History and clinical signs and symtoms. Demonstration of microfilariae in sliced off sliver skin which is placed in a water or saline. Best time to collect specimen at midday.

Diagnosis cont.. The Mazzotti reaction, first described in 1948, is a symptom complex seen in patients after undergoing treatment of onchocerciasis with the medication diethylcarbamazine (DEC). Mazzotti reactions can be life-threatening and are characterized by fever, urticaria, swollen and tender lymph nodes, tachycardia, hypotension, arthralgias, oedema, and abdominal pain that occur within seven days of treatment of microfilariasis. The phenomenon is so common when DEC is used for the treatment of onchocerciasis that this drug is the basis of a skin patch test used to confirm that diagnosis. The drug patch is placed on the skin, and if the patient is infected with the microfilaria of Onchocerca volvulus, localized pruritus and urticaria are seen at the application site.

TREATMENT The treatment for onchocerciasis is ivermectin (Mectizan); infected people can be treated with two doses of Ivermectin, six months apart, repeated every three years. The drug paralyses and kills the microfilariae, causing fever, itching, and possibly oedema, arthritis and lymphadenopathy. Intense skin itching is eventually relieved and progression towards blindness halted. In addition, while the drug does not kill the adult worm, it does prevent them from producing additional offspring. The drug therefore prevents both morbidity and transmission.

Antibiotics. For the treatment of individuals, doxycline is used to kill the Wolbachia bacteria that live in adult worms. This adjunct therapy has been shown to significantly lower microfilarial loads in the host, and may have activity against the adult worms, due to the symbiotic relationship between Wolbachia and the worm. In four separate trials over ten years with various dosing regimes of doxycycline for individualized treatment, doxycycline was found to be effective in sterilizing the female worms and reducing their numbers over a period of four to six weeks. Research on other antibiotics such as rifampicin has shown it to been effective in animal models at reducing Wolbachia both as an alternative and as an adjunct to doxycycline. However, doxycycline treatment requires daily dosing for at least four to six weeks, making it more difficult to administer in the affected areas.

Treatment cont.. A study of 2501 people in Ghana showed that the prevalence rate doubled between 2000 and 2005 despite treatment, suggesting that the parasite is developing resistance to the drug. A clinical trial of another antiparasitic agent, mexidectin (manufactured by Wyeth), began on July 1, 2009 .

prevention There are various control programs that aim to stop onchocerciasis from being a public health problem. The first was the Onchocerciasisi Control Programme (OCP), which was launched in 1974 and at its peak covered 30 million people in eleven countries. Through the use of larvicide spraying of fast flowing rivers to control black fly populations and, from 1988 onwards, the use of ivermectin to treat infected people, the OCP eliminated onchocerciasis as a public health problem. The OCP, a joint effort of the World Health Organization, the World Bank, the United Nations Development Programme and the UN Food and Agriculture Organization was considered to be a success and came to an end in 2002. Continued monitoring ensures that onchocerciasis cannot reinvade the area of the OCP.

Prevention cont.. In 1992 the Onchocerciasis Elimination for the America (OEPA) was launched. The OEPA also relies on ivermectin. In 1995 the African Programme for Onchorcerciasis Control (APOC) began covering another nineteen countries and mainly relying upon the use of ivermectin. Its goal is to set up a community-directed supply of ivermectin for those who are infected. In these ways, transmission has declined.

Prevention cont.. Since 1988, ivermectin has been provided free of charge for use in humans by Merck through the Mectizan donation program (MDP). The MDP works together with ministries of health and non-governmental development organizations such as the World Health Organization to provide free ivermectin to those who need it in endemic areas.

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