Filariasis
From Free net encyclopedia
Template:DiseaseDisorder infobox-Template:ICD9 | }} Lymphatic Filariasis is a parasitic and infectious tropical disease, caused by the thread-like parasitic filarial worms, Wuchereria bancrofti, Brugia malayi, and Brugia timori, all transmitted by mosquitoes. It is extremely rare in Western countries. Loa loa is another filarial parasite of humans, transmitted by the deer fly. Image:Filariasis 01.png In 1866, Otto Wucherer demonstrated the presence of microfilariae, or filarial larvae, in urine. In 1871, Timoth Lewis discovered the presence of microfilariae in peripheral blood; later, in 1876, Joseph Bancroft discovered the adult form. Finally in 1878, Patrick Manson observed the development of W. bancrofti in mosquitoes.
Filariasis is endemic in tropical regions of Asia, Africa, Central and South America.
The most spectacular symptom of lymphatic filariasis is elephantiasis (thickening of the skin and underlying tissues), which was the first disease discovered to be transmitted by insects. Elephantiasis is caused when the parasites lodge in the lymphatic system.
Elephantiasis affects above all the lower extremities, whereas ears, mucus membranes, and amputation stumps are rarely affected; however, it depends on the species of filaria. W. bancrofti can affect the legs, arms, vulva, breasts, while Brugia timori rarely affects the genitals. Infection by Onchocerca volvulus and the migration of its microfilariae through the cornea is a major cause of blindness (Onchocerciasis).
=Screening for antifilarial activity
[A] In vitro methods:
Adult worms: - Litomosoides carinii,
Acanthocheilonema viteae.
Onchocerca gibsoni
Setaria cervi
Microfilareae: -L. carinii, Dirofilaria, Conspiculum guidense, S. cervi
(1) Setaria cervi
SINGHAL, K. C., SAXENA. P. N. and JOHRI. M. B. L. (1973): Studies on the use of Setaria cervi for in vitro antifilarial screening, Jap. J. Pharmacology, 23, 793-797.
Whole worm preparation Adult S. cervi (Nematoda: Filarioidea) obtained from peritoneal cavity of the freshly slaughtered cattle Transported to the laboratory in a vacuum flask containing modified Ringer’s solution, (NaCl-9g, CaCl2- 0.24g, KCl- 0.42g, NaHCO3- 0.5g,Glucose- 0.25g/Litre) 20 ml capacity isolated organ bath containing modified Ringer’s solution at 37% used for suspending the worm. Posterior end tied to hook at the bottom of the bath. The anterior end was attached to a frontal writing lever. At least 15 min allowed for a worm to stabilize Drug added in increasing conc., movements recorded on slow moving drum. Drug -- inactive if it does not modify movements in 10 minutes. Fresh worm used to test each dose of a drug.
Nerve – muscle preparation:
Worm placed in petri dish containing modified ringer (370 C).
2 dissecting needles inserted at one end, cuticle split longitudinally.
Intestine, uterus removed.
Ant. 1 cm of worm removed to eliminate influence of nerve ring, cephalic ganglia
Remaining part tied, suspended, tested as above.
(2) Onchocerca gibsoni Trop Med Parasitol. 1987 Jun; 38(2): 128-30 In vitro drug screening in isolated male Onchocerca gibsoni using motility suppression. Nowak M, Hutchinson GW, Copeman DB.
A primary in vitro screen was developed to screen for drug activity against Onchocerca volvulus. Assay estimates variation in motility through motility meter. Results compared favorably with reported in vivo tertiary screens for activity against Onchocerca species. Effects of these drugs were not reversible. Thus reduction in motility regarded as indicating significant metabolic damage.
(3) Acanthocheilonema viteae.
Jpn J Exp Med. 1990 Dec; 60(6): 303-9. A new technique of in vitro assay of antifilarials using different life forms of Acanthocheilonema viteae. Singh DP, Misra S, Chatterjee RK.
In vitro experiments conducted using three life-forms (adult, microfilariae and infective larva) of Acanthocheilonema viteae using different antifilarial agents.
Study indicated that this in vitro screening system can be used for primary screening of potential antifilarial agents provided three life forms of A. viteae are used simultaneously to avoid false negative results.
[B] In vivo models:
(1) Litomosoides carinu – cotton rat system
Mites (Ornithonyssus bacoti) allowed to feed on Litomosoides infected cotton rats (1 week) Then on clean cotton rats 2 weeks (development in mites takes 2 wks.) De-mited – microfilareae in blood after 50 days Rats with at least 250 microfilareae/mm3 blood used Drug in 1/5 MTD given i.p. for 6 days Blood examined for microfilareae weekly Rats showing disappearance of microfilareae after 7 wks autopsied Absence of adult worm in pleural & peritoneal cavities observed.
(2) Setaria cervi – rat system:
Adult Setaria cervi collected from freshly slaughtered cattle. Rats (100- 150 gms), anaesthetized with ether, incision ½” long in abdominal wall 2 male & 2 female worms put in peritoneal cavity Peritoneum, body wall stitched, Antiseptic applied daily Microfilareae in blood after 10±3 days, last for 54± 6 days Rats showing Microfilareae for 3 consecutive days used Treated with test drug orally/ i.p. Complete disappearance of Microfilareae from blood for 3 consecutive days – evidence of antifilarial action.
(3) B. pahangi in Mongolian jirds (Meriones unguiculatus)
G W Jeffers et al Infect Immun. 1984
Mongolian Jirds < 1 yr. used.
s.c. inoculation of 100 infective larvae of B. pahangi obtained from infected mosquitoes. Animals sacrificed at 90,140,200 days post infection Total adult worm recovery Location of worms—heart, lymphatics Microfilareae in peripheral blood (4) Brugia malayi in Jirds (Maeda R et al Jpn J Exp Med. 1988)
Jirds infected subcutaneously with infective stage larvae (L3) of Brugia malayi evaluated as animal model for assessing macrofilaricides
Animals treated with a test compound
Change in microfilaria density observed
DEC at 50 mg/kg for 5 consecutive days for clearing the existing mf from the blood stream.
(5) Molinema dessetae in Proechimys oris
Brienne MJ et al (J Med Chem. 1987)
Evaluated drugs for antifilarial activity against Molinema dessetae in vivo in its natural host, the rodent Proechimys oris
(6) Wuchereria kalimantani in leaf monkeys
Trials in leaf monkeys (Presbytis cristatus) infected with Wuchereria kalimantani. Kurniawan A et al (Southeast Asian J Trop Med Public Health. 1992)
Filaricidal drugs in given for 5 consecutive days to leaf monkeys (Presbytis cristatus) infected with Wuchereria kalimantani.
Optimal microfilaricidal effect occurred at 200-mg/kg body weight of Ivermectin.
(7) Setaria digitata microfilaraemia in Mastomys coucha: an animal model for chemotherapeutic and immunobiological studies.
Mukhopadhyay S et al (Parasitology. 1996)
Intraperitoneal implantation of adult gravid females of the bovine filarial parasite, Setaria digitata in Mastomys coucha (multimammate mice) was found to induce microfilaraemia lasting for about 125 days.
Microfilariae could be detected 4 days post-implantation
Peak levels (about 30 mf /20 μl blood observed by 21 days
The mf in circulation eliminated by oral adm. of DEC indicating usefulness of the model for screening potential anti-microfilarial drugs.
Induction of antibodies to various fractionated antigenic components of adult parasites demonstrated by enzyme immunoassay in M. coucha implanted with live or cold-stunned adult worms.
S. digitata-M. coucha model thus found amenable to perform chemotherapeutic and immunobiological investigations in experimental filariasis.
(8) O. volvulus in chimpanzees
Primate model for onchocerciasis research.
Greene BM. (Ciba Found Symp. 1987)
Infected 18 chimpanzees by s.c. inj. of 250 third-stage larvae of O. volvulus. Six received test drug on day 1, another six received test drug on day 28 after infection, and six received no drug. Four control animals received no infective larvae and no drug. Developed a pattern of infection that closely resembles that seen in humans- formation of nodules by adult worms, the subcutaneous distribution of microfilariae Antibody responses have also been increasing with time.
External links
de:Filariose fr:Filariose it:Filariosi ja:フィラリア ms:Penyakit Untut pt:Filaríase