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Filariasis Paul R. Earl Facultad de Ciencias Biológicas Universidad Autónoma de Nuevo León San Nicolas, NL 664551, Mexico pearl@dsi.uanl.mx.

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Presentation on theme: "Filariasis Paul R. Earl Facultad de Ciencias Biológicas Universidad Autónoma de Nuevo León San Nicolas, NL 664551, Mexico pearl@dsi.uanl.mx."— Presentation transcript:

1 Filariasis Paul R. Earl Facultad de Ciencias Biológicas Universidad Autónoma de Nuevo León San Nicolas, NL , Mexico

2 Six pathogenic species of nematodes (roundworms) belonging to the superfamily Filarioidea develop to the adult stage in humans. These and the vectors are 1/Wuchereria bancrofti Mosquito, 2/Brugia malayi Mosquito, 3/Brugia timori Mosquito, 4/Loa loa Deerfly (Chrysops), 5/Onchocerca volvulus Blackfly (Simulium) and 6/Mansonella streptocerca Midge (Culicoides).

3 The life cycles of the filarias are similar
The life cycles of the filarias are similar. Many filarias parasitize wildlife. Dirofilaria immitis of dogs and even cats, foxes and raccoons, known as dog heartworm, is an example in domestic and wild animals. Larvas (microfilarias) in the blood of human hosts are ingested when the insect vectors feed. Within the vector, the microfilarias migrate to specific sites and develop from first-stage larvas into infective third-stage larvas. The vector transmits the infective larvas into a human host when feeding. The worm molts twice more to become an adult worm that may be found in the lymphatic vessels, lymph nodes, subcutaneous tissue or the body cavity.

4 One hundred and twenty million people in at least 80 nations of the world have lymphatic filariasis. One billion people are at risk of getting infected. Ninety percent of these infections are caused by Wuchereria bancrofti, and most of the remainder by Brugia malayi. For W. bancrofti, humans are the exclusive host, and even though certain strains of B. malayi can also infect some felines and monkeys. The life-cycles in humans and in these other animals generally remain epidemiologically distinct so that little overlap exists. The major vectors for W. bancrofti are culicine mosquitoes in most urban and semiurban areas, anophelines in the more rural areas of Africa and elsewhere, and Aedes species in many of the endemic Pacific islands. For the brugian parasites, Mansonia species serve as the major vector, but in some areas anopheline mosquitoes are responsible for transmitting the infection. Brugian parasites are confined to areas of eastern and southern Asia especially India, Malaysia, Indonesia, the Philippines and China. One-third of the people infected with the disease live in India, one third are in Africa and most of the remainder are in South Asia, the Pacific and the Americas.

5 New World countries with filariasis, likely onchocerciasis, include Mexico, Guatemala, El Salvador, Nicaragua, Honduras, Costa Rica, Colombia, Ecuador, Brazil, Venezuela, Dominican Republic, Haiti, Guyana, Suriname and Trinidad & Tobago. A typical case of lymphatic filariasis in India is seen posteriorly.

6 Onchocerciasis (river blindness) occurs in over 34 countries in Africa, Latin America and the Arabian Peninsula. The vast majority of the estimated 18 million persons infected with the causative agent, the parasite Onchocerca volvulus, live in Africa. Pockets of O. volvulus in Mexico, Guatemala into Costa Rica are ignored very effectively. A typical case in Brazil is shown posteriorly.

7 Filariasis may be difficult to eradicate just because it occupies vast terrains
Central America and Mexico are underestimated for Onchocerca volvulu

8 Microfilaria of Wuchereria bancrofti. Giemsa stain.

9 Microfilaria of Mansonella ozzardi
Microfilaria of Mansonella ozzardi Apparently, it died out of Campeche, Mexico. Stain: methylene blue.

10 Life cycles. Mosquitoes and flies are the usual vectors with mammals but even frogs are filarial hosts.

11 Simulium spp. The vector of onchocerciasis in the old and New Worlds.

12 Life cycle of Brugia that also applies to Wuchereria by CDC

13 Opening the dog’s heart discloses adult filarias.

14 Lymphatic filariasis in India.

15 Clinical features. There are chronic, acute and asymptomatic presentations of lymphatic filarial disease, as well as some syndromes associated with these infections. Among chronic manifestations, hydrele, even though found only with W. bancrofti infections not in Brugia infections is the most common clinical manifestation of lymphatic filariasis. Uncommon in childhood, it is seen more frequently postpuberty and with a progressive increase in prevalence with age. In many endemic communities 40-60% of all adult males have hydrocele. It often develops in the absence of overt inflammatory reactions. Many patients with hydrocele also have microfilarias in the circulation. In bancroftian filariasis, the scrotal lymphatics are the preferred site for localization of the adult worms, and their presence stimulates the proliferation of lymphatic endothelium. The localization of adult worms in the lymphatics of the spermatic cord leads to a thickening of the cord. The hydroceles can become massive, but still occur without lymphedema or elephantiasis developing in the penis and scrotum, since the lymphatic drainage of these tissues is separate and more superficial.

16 Importation of black slaves from Africa to colonies in the New World dictated the importaion of Onchocerca volvulus, the cause of river blindness. It occurs in southern Mexico, Guatemala, El Salvador, Nicaragua, Honduras and Costa Rica or in much of Central America and is neglected by these countries that do not have the political will to manage and in fact eradicate tropical disease vectors. In the Mexican states of Oaxaca and Chiapas, onchocerciasis was imported with French Senegalese troops. The microfilarias of Onchocerca volvulus migrate through the eye and cause subretinal granulomas therefore blindness.

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18 While lymphedema can develop in the absence of overt inflammatory reactions and in the early stages be associated with microfilaremia, the development of elephantiasis (either of the limbs or the genitals) is most often associated with a history of recurrent inflammation. The early pitting edema gives rise to a stronger edema with the hardening of the tissues. Still later, hyperpigmentation and hyperkeratosis develop, often with wartlike protuberances which, on histological section, reveal dilated loops of lymphatic vessels within the nodular lesions. Patients with chronic lymphedema or elephantiasis rarely are microfilaremic. Redundant skin folds, of the skin provide havens for bacteria and fungi to thrive and intermittently penetrate the epidermis to lead to either local or systemic infections. Sometimes the skin over the breaks down, causing the dilated lymphatic within to rupture and discharge its lymph fluid directly into the environment, at the same time serving as a causeway for penetration of bacterial or fungal organisms directly into the lymphatic system. Chyluria, another of the chronic filarial syndromes, is caused by the intermittent discharge of intestinal lymph (chyle) into the renal pelvis and subsequently into the . The clinical course is intermittent, sometimes remitting.

19 Diagnosis. Until very recently, diagnosing lymphatic filariasis had been extremely difficult, since parasites had to be detected microscopically in the blood, and in most parts of the world, the parasites have a nocturnal periodicity that restricts their appearance in the blood to only the hours around midnight. The new development of a very sensitive, very specific simple card test to detect circulating parasite antigens without the need for laboratory facilities and using only finger-prick blood droplets taken anytime of the day has completely transformed the approach to diagnosis. With this and other new diagnostic tools, it will now be possible both to improve our understanding of where the infection actually occurs and to monitor more easily the effectiveness of treatment and control programs.

20 Treatment. Communities where filariasis is endemic
Treatment. Communities where filariasis is endemic. The primary goal of treating the affected community is to eliminate microfilariae from the blood of infected individuals so that transmission of the infection by the mosquito can be interrupted. Recent studies have shown that single doses of diethylcarbamazine (DEC) have the same long-term (1-year) effect in decreasing microfilaremia as the formerly-recommended 12-day regimens of DEC and, even more importantly, that the use of single doses of 2 drugs administered concurrently (optimally albendazole or ivermectin with DEC) is 99% effective in removing microfilarias from the blood.

21 It is patently obvious that lymphatic filariasis and also onchocerciasis should be eliminated in a decade provided the determination is expressed. The international and particularly the national detractors do not want to spend the money. Note also than subSahara Africa is deeply in debt, and also India is seriously in debt just as it is a true health problem. Regardless, external money for disease eradication (example polio) is flowing into endemic areas by astounding billions. Then those countries that will not function for various eradications are badly misinformed and also have governments with malicious elements. Is the World Bank continuously putting targeted money into the hands of honest governments that assign all of it to their honest PH officials?

22 Treating the individual
Treating the individual. Both albendazole and DEC have been shown to be effective in killing the adult-stage filarial parasites. It is clear that this antiparasite treatment can result in improvement of patients' elephantiasis and hydrocele (especially in the early stages of disease) ), but the most significant treatment advance to alleviate the suffering of those with elephantiasis has come from recognizing that much of the progression in pathology results from bacterial like Wolbachia associated with the parasite and also the fungal superinfections of tissues with compromised lymphatic function caused by earlier filarial infection. Thus, rigorous hygiene to the affected limbs, with accompanying adjunctive measures to minimize infection and promote lymph flow, results both in a dramatic reduction in frequency of acute episodes of inflammation ("filarial fevers") and in an astonishing degree of improvement of the elephantiasis itself.

23 WHO's Strategy to Eliminate Lymphatic Filariasis The strategy of the World Health Organization (WHO) of the Global Programme to Eliminate Lymphatic Filariasis has 2 aims: a) to stop the spread of infection (interrupt transmission), and secondly b) to alleviate the suffering of affected individuals.

24 To interrupt transmission, districts in which lymphatic filariasis is endemic must be identified, and then community-wide ("mass treatment") programs implemented to treat the entire at risk population. In most countries, the program will be based on once-yearly administration of single doses of 2 drugs given together: albendazole plus either diethylcarbamazine (DEC) or ivermectin, the latter in areas where either onchocerciasis, loiasis or another may also be endemic. Single-dose treatment must be carried out for 4-6 years. An alternative community-wide regimen with equal effectiveness is the use of common table/ cooking salt fortified with DEC in the endemic region for a period of one year.

25 To alleviate the suffering caused by the disease, it will be necessary to implement community education programmes to raise awareness in affected patients. This would promote the benefits of intensive local hygiene and the possible improvement, both in the damage that has already occurred, and in preventing the debilitating and painful, acute episodes of inflammation.

26 The pledge in 1998 by GlaxcoSmithKline to collaborate with the WHO in its elimination efforts included the donation of numerous resources, but especially albendazole free of charge, for as long as necessary. This donation, coupled with the recent decision by Merck to expand its wellknown Mectizan® (ivermectin). The Merck Donation Programme includes treatment of lymphatic filariasis where appropriate, and the creation of additional partnerships with other private, public and international organizations have all further strengthened the prospects for success of these elimination efforts. However, very many PH officers in many nations are not aware of these moves.

27 Immunologic notes. Schistosomiasis and filariasis can of course be discussed together, mainly because they are being simultaneously eliminated in the same territories by praziquantel, albendazole and invermectin. The disease symptoms are mainly reactions to parasite and related antigens. Then tests for surveillance are needed for eradicated territories and others. A simple dot blot assay (DBA) using an antigen fraction of female O. volvulus parasites is replacing microscope searches of skin snips for microfilarias. Progress in current immunology is considerable. Disease resistance following cure seems to be the most important theme.

28 Histologically, proliferation of lymphatic endothelium can be identified, and the abnormal lymphatic function associated with these changes can be readily documented by lymphoscintigraphy. Interestingly, all of these changes can occur in the absence of overt inflammatory responses and, even by themselves can lead to both lymphedema and hydrocele formation. The immune system is then in this early pathology down-regulated through the production of antiinflammatory immune molecules; specifically, the characteristic mediators of Th2-type T-cell responses (interferon IL-4, IL-5, IL-10) and antibodies of the Immunoglobin G4 (non-complement-fixing) subclass that serve as blocking antibodies.

29 Economic and Social Impact
Economic and Social Impact. In recent years, lymphatic filariasis has steadily increased because of the expansion of slum areas and poverty, especially in Africa and the Indian subcontinent. More breeding sites are provided for vectors, some at urban-civic interfaces. As many filariasis patients are physically incapacitated, it is also a disease that prevents patients from having a normal working life. The fight to eliminate lymphatic filariasis is also a fight against poverty. Nonetheless, it is admitted there are countries that do nothing about onchocerciasis, other filariases or any tropical disease, e. g., malaria.

30 Lymphatic filariasis exerts a heavy social burden that is especially severe because of the specific attributes of the disease, particularly since chronic complications are often hidden and are considered shameful. For men, genital damage is a severe handicap leading to physical limitations and social stigmatization. For women, shame and taboos are also associated with the disease. When affected by lymphedema, they are considered undesirable and when their lower limbs and genital parts are enlarged they are severely stigmatized. Marriage in many situations is an essential source of security and is often impossible.

31 Histologically, proliferation of lymphatic endothelium can be identified, and the abnormal lymphatic function associated with these changes can be readily documented by lymphoscintigraphy. Interestingly, all of these changes can occur in the absence of overt inflammatory responses and, even by themselves can lead to both lymphedema and hydrocele formation. The immune system is then in this early pathology down-regulated through the production of antiinflammatory immune molecules; specifically, the characteristic mediators of Th2-type T-cell responses (interferon IL-4, IL-5, IL-10) and antibodies of the Immunoglobin G4 (non-complement-fixing) subclass that serve as blocking antibodies.

32 However, filariasis, schistosomiasis, malaria and other tropical diseases can be eradicated by honest efforts, allowing a better life for many. More information can be obtained from WHO at and from The Global Alliance to Eliminate Lymphatic Filariasis at and from The Global Alliance to Eliminate Lymphatic Filariasis at


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