Filarial disease

Our perspective is thus one of general significance to chronic infection, as well as one that will provide specific pathways to novel treatments of human schistosomiasis, and lymphatic filariasis. These two diseases represent a massive public health problem with 300 million people infected in the world today. Intervention by ablating parasite-specific Tregs in these patients will solve the specific problems of schistosomiasis and filarial diseases, while at the same time proving a principle which will be applicable to chronic infections in general. 

THERAPEUTIC USES Recommended regimens for filarial infections differ according to whether the drug is used for population-based chemotherapy, control of filarial disease, or prophylaxis against infection. 

The activity of ivermectin against the filarial parasite Dirofilaria immitis in dogs suggested a possible role for the control of filarial parasites of humans (20). It has been extensively tested in human onchocerciasis and is now considered to be the dmg of choice. In a single yearly oral dose, it suppresses microfilariae in the skin and eyes and, in most cases, prevents the progression of the disease to blindness. Table 4 shows the results of a 30-patient double-blind study recorded over one year. 

The timing of the collection of blood specimens depends on the parasite disease suspected. For example, for certain filarial infections, specimens are best obtained between 10 00 p.m. and midnight, whereas for other infections, specimens are best obtained during the day. In malaria, the numbers and stages of parasites in the peripheral blood vary with different parts of the cycle. 

The filarial worms differ from other nematodes in that they are threadlike and are found in blood and tissue. The infective larvae enter following the bite of an infected arthropod (fly or mosquito). They then enter the lymphatics and lymph nodes. Fever, lymphangitis, and lymphadenitis are associated with the early stage of the disease. Chronic infections may be characterized by elephantiasis as a result of lymphatic obstruction. Some species of filarial worms migrate in the subcutaneous tissues and produce nodules and blindness (onchocerciasis). 

Phyllanthus virgatus, is rubbed around the ear for ear infections. Extract of different dried parts of the palm are taken orally for filari-asis. A water solution of the cmshed dried bark or husk and grated bark of Hibiscus tiliaceus is used externally to soak fractures and sprains. Crushed aerial root tips of Ficus prolixa are fried with coconut cream made of fresh endosperm, and the resulting oil is taken orally as a laxative in treating serious diseases " . 

For obvious reasons of structural analogy to heparinoids the focus of this review is on sulfated carbohydrate derivatives. While it is not in all cases clear that these compounds really mimic the physiological activity of heparinoids, it is even less so for non-carbohydrate sulfates or sulfonates. Examples of the latter class include suramin and the simple 1,3-propanediol disulfate. Suramin is a sulfonat-ed bis-naphthalene derivative used as a drug to treat African trypanosomiasis and onchocerciasis (a filarial infection) it was also tested in a number of other indications including adrenocortical carcinomas and AIDS. A wider use is, however, restricted by various toxic effects [66]. 1,3-Propanediol disulfate reduced inflammation-associated amyloid progression in vivo after oral administration which may be relevant to the treatment of Alzheimer s disease [67]. 

A fortunate fallout of the avermectin work was the finding that Ivermectin has activity against the black fly vector of human onchocerciasis ( river blindness ). It interferes with transmission of the filarial nematode. Onchocerca volvulus, to the human population. Since 40 million people are affected by this disease, the decision by Merck to supply ivermectin free of charge to the World Health Organization, for use in humans in the tropics, was met with great enthusiasm and hope for conquering this parasitic disease. 

The guinea worm infection is a very old parasitic disease caused by Dracuncu-lus medinensis which are enlongated thread-like filarial worms living in the deep connective and subcutaneous tissues of man. The infection has been reported from different parts of Africa, South America and Asia however, it is endemic in Cameroon, Lake Chad, Sudan, Uganda and India. 

Filariasis We already discussed about the effects of ES-62 on experimental models of human diseases. The canine filarial nematode Dirofilaria immitis-AtmtA antigen (DiAg) is a purified 15kDa protein able to induce antigen non-specific IgE in rats and mice, as well as polyclonal proliferation of B cells. A timely treatment of NOD mice at 6 weeks of life with DiAg completely prevented the insulin-dependent... 

Parasitic helminth (worm) infections are widespread and may be the most common disease in the world. Estimates by the WHO and others are that one type of schistosomiasis, the blood flukes, has 200 million people infected. Ascaris, a large roundworm, accounts for at least 650 million, hookworm 450 million, and the several filarial worm species add another 250 million victims to the total. The situation has improved little in the past decade. 

Wuchereria bancrofti, a mosquito-transmitted parasite, is the major cause of human lymphatic filariasis in tropic areas. Current estimates suggest that about 120 million people are infected. Infection often leads to microfilaremia without clinical manifestations. The most common clinical presentation of this disease are asymptomatic microfilaremia, filarial fever, and lymphatic obstruction. Ivermectin rapidly reduces microfilaremia concentration in peripheral blood and may inhibit larval development in mosquitoes. Because the drug does not kill adult worms, microfilaremia concentration begins to increase gradually 3-12 months after treatment. 

Filarial infections. Both the adult and larval (microtiluriiie) forms of the tilariac occur in humans. Transmission is by the bite of bloodsucking insects. The adult worms arc very long-lived, and the shedding of microfi loriae la-sts for many years. The severil y of the disease depends on the adult worm burden of the host. 

Onchocerciasis is a blinding disease caused by infection with the filarial nematode parasite. Onchocerca volvulus. This disease is endemic in many parts of the tropics, particularly... 

The effect of helminth infections on allergic-type diseases has prompted a search for helminth-derived fectors with therapeutic potential. Cystatin is a filarial-derived molecule with antiallergic and anti-inflammatory properties. Treatment with cystatin protects mice from DSS colitis and lung hypersensitivity responses to OVA allergen challenge. Cystatin induces macrophages to make ILIO, which could mediate this protection. 

Loaiasis Tropical eye disease caused by the filarial worm Loa loa. 

Onchocerciasis Ana eye disease caused by the filarial larvae of the nematode Onchocerca volvulus, transmitted by blackflies, common in Africa and Central America. Known also as river blindness. 

The Drugs for Neglected Diseases initiative (DNDi) is a collaborative, nonprofit R D organization aiming to deliver new treatments for neglected diseases. In particular, these include sleeping sickness (human African trypanosomiasis), Chagas disease, leishmaniasis, filarial parasitic-worm infections, and pediatric HIV. The primary aim is to deliver a total of 11-13 new treatments by 2018. 

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