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PubMed1978

Studies with Brugia pahangi 17. The anthelmintic effects of diethylcarbamazine.

Diethylcarbamazine (DEC) was active in vitro against infective larvae and microfilariae of Brugia pahangi but only at high concentrations. When fed to mosquitoes which were infected with B. pahangi it had little or no activity. In jirds it was inactive against B. pahangi microfilariae and adults when administered at 300 mg/kg for 5 days either by the intraperitoneal or oral route. In cats given 25 or 50 mg DEC/kg intraperitoneally on 3 or 5 occasions it was not microfilaricidal, but most of the adult worms died within 30 days of the end of treatment. Although most microfilariae disappeared from the blood of cats immediately (i.e., within an hour) after treatment, they reappeared within a few hours in the same numbers. Microfilarial levels were reduced after treatment but there was no precipitate decline as occurs in human B. malayi patients.

Animals↗
PubMed1978

The vectors of Brugia malayi in Southern Thailand.

Mansonia uniformis, with an infective rate of 0.02, was incriminated as the vector of periodic Brugia malayi in Pattani province. Mansonia bonneae and Ma. dives, with infective rates of 0.18 and 0.20 respectively, were the vectors of B. malayi in Narathiwat, where the microfilarial periodicity was the subperiodic form.

Aedes↗
PubMed1979

Incorporation of radioactive precursors into filarial larvae of Brugia developing in susceptible and refractory mosquitoes.

The incorporation of tritiated precursors injected into mosquito hosts parasitized by developing filarial larvae of Brugia patei has been studied by autoradiography in 2 species of mosquito, Aedes togoi in which filarial development was normal and Anopheles labranchiae atroparvus in which filarial development was abnormal. In both mosquito hosts there was significant incorporation into 4--5-day-old developing larvae of uridine and amino acids (isoleucine, leucine, valine, arginine, lysine, cystine, methionine, phenylalanine, tyrosine, tryptophan, histidine, and proline), although lower incorporation of methionine, tyrosine, and tryptophan was found during abnormal development. No incorporation of thymidine, hydroxytryptophan, dopa, or carbohydrate was found at this stage of larval development. Some incorporation of glucose and dopa was found in or around earlier stages of development in An. l. atroparvus. Mosquito flight muscle showed lower incorporation of glucose, but not of amino acids, around the site of filarial parasite development. The flight muscle of An. l. atroparvus showed a higher level of incorporation of lysine compared to that in A. togoi and higher levels of lysine and valine were found in the abnormally developing filarial larvae in the refractory mosquito.

Aedes↗
PubMed1979

De novo synthesis of methionine in normal and Brugia-infected Aedes aegypti.

Crude extracts of normal, adult Aedes aegypti were able to form methionine from homocysteine in the presence of 5-methyltetrahydrofolate (MeFH4) but not betaine. The requirements for the reaction, including a need for vitamin B12, S-adenosylmethionine (SAM), and a reducing system, indicated that it was catalyzed by MeFH4:homocysteine transmethylase (methionine synthetase). The general properties of A. aegypti methionine synthetase were found to be similar to those of the analogous enzyme from bacterial and mammalian sources, except that its apparent affinity for SAM was significantly lower. Extracts of normal, adult A. aegypti females (5 days after emergence, as well as 7 and 12 days after they fed upon uninfected jirds) synthesized methionine at a rate of 0.6 nmole per hr per mg protein. Extracts of female mosquitoes prepared 7 and 12 days after they fed upon Brugia pahangi-infected jirds synthesized methionine at double the normal rate. Because methionine formation by extracts of adult B. pahangi could not be detected, it is probable that methionine synthetase activity increased in the arthropod host in response to filarial infection.

5-Methyltetrahydrofolate-Homocysteine S-Methyltran↗
PubMed1977

Comparative activity and properties of lactate dehydrogenase, xanthine dehydrogenase, and dihydrofolate reductase in normal and Brugia pagangi-infected Aedes aegypti.

The amount of xanthine dehydrogenase (XDH), dihydrofolate reductase (DHFR), and lactate dehydrogenase (LDH) in crude extracts of 4- to 5-day-old adult Aedes aegypti was determined, and the properties of these enzymes were partially characterized. It was then found that the amount and other selected characteristics of XDH and LDH in extracts of female Ae. aegypti processed 5 to 7 days and 12 to 14 days after they had fed upon either normal or Brugia pahangi-infected jirds were indistinguishable from those of these two enzymes in extracts of female mosquitoes that did not have a blood meal. Under the same circumstances, the selected characteristics of DHFR were also unaffected. However, there was a suggestion that the amount of DHFR was slightly increased in extracts of female Ae. aegypti processed 5 to 7 days after they had fed upon B. pahangi-infected jirds; by 12 to 14 days after the blood meal, there was a consistent 30% to 60% increase in the amount of DHFR inextracts of infected mosquitoes. DHFR activity could not be detected in a similarly prepared extract of 4,000 to 5,000 infective (L-3) B. pagangi larvae, the approximate number present in the infected mosquito extracts. It would appear, therefore, that the increased amount of turnover of DHFR in the mosquito host occurs in response to advanced infection with B. pahangi.

Aedes↗
PubMed1979

The effect of diethylcarbamazine in a murine model of Brugia malayi microfilaraemia.

The effect of diethylcarbamazine was tested in a murine model of Brugia malayi microfilaraemia. A course of therapy similar to that used to treat human infection led to more than a 90% decrease in circulating parasites. Experiments in which different amounts of diethylcarbamazine were given as a single dose indicated that its microfilaricidal activity is dose-dependent. The animal model of B. malayi microfilaraemia may be useful for studies of the mechanism of action and pharmacology of diethylcarbamazine and may be applied to the screening of new microfilaricidal drugs.

Administration, Oral↗
PubMed1979

Studies on human filariasis in Malaysia: immunoglobulin and complement levels in persons infected with Brugia malayi and Wuchereria bancrofti.

Levels of immunoglobulins G, A, M and E as well as complement components C3c and C4 have been determined in populations in various endemic areas in Peninsular Malaysia and also in filariasis patients. High immunoglobulin levels were seen. In the microfilarial-negative group IgG was 2009 mg% while IgE was 3967 I.U./ml. In the filariasis group, Wuchereria bancrofti patients had significantly higher levels of IgG, IgM and IgE, namely, 3314 mg%, 804 mg% and 18400 I.U./ml respectively. The significance of these levels is discussed.

Adolescent↗
PubMedDate not supplied

Diethylcarbamazine enhances antibody-mediated cellular adherence to Brugia malayi microfilariae.

Treatment with the antifilarial drug diethylcarbamazine (DEC) results in a rapid decline in the number of microfilariae circulating in the blood of infected hosts. DEC induces morphological changes in the surface layers of microfilariae, but these alterations alone are probably insufficient to cause the death of the parasite, because the drug fails to reduce microfilaraemia in animals lacking filarial antibodies, and also does not shorten the survival of microfilariae in vitro. The effect of DEC in vivo is thought to result from the trapping of microfilariae in the liver, where they undergo lysis.

Animals↗
PubMed1977

Experimental Brugia malayi infections in the rhesus monkey.

Twenty-eight rhesus monkeys in 3 groups were exposed to single (Group I), double (Group II), and multiple (Group III) inoculations with B. malayi infective larvae. Infections were monitored by microfilarial and blood counts, selected biochemical tests, IFA responses, and records of body temperature and lymphadenopathy before and/or after treatment with DEC. As a whole, the highest microfilaraemia levels were observed in Group II and lowest in Group III monkeys. Eosinophilia was a common occurrence but reached the highest mean levels in Group III. Intermittent fevers and lymph node enlargements were observed in all groups of monkeys and the occurrence of these appeared to be correlated. No definite pattern of antibody production was discernable among groups, but an inverse relationship existed between microfilaraemia and detectable microfilarial antibodies. Treatment with DEC produced a microfilaraemia-taxic effect within the initial half hour and responses to treatment varied according to individuals. Although post-treatment reinfection appeared to cause lymphoid responses and tissue eosinophilia, no substantial resistance to reinfection was observed.

Aedes↗