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PubMed1980

Studies on Bancroftian filariasis in Liberia, West Africa. IV. Notes on side effects observed during a diethylcarbamazine treatment campaign in a rural area endemic for Wuchereria bancrofti and Onchocerca volvulus.

464 persons of whom 189 proved to be infected with microfilariae of Wuchereria bancrofti and/or Onchocerca volvulus were examined for adverse reactions due to diethylcarbamazine, which was administered during a filariasis control campaign. Persons older than 20 years of age were significantly more affected than younger persons and men showed distinctly more side effects than women. The most frequent complaints were skin reactions followed by gastrointestinal complications. The significantly highest rate of adverse reactions was observed in persons being infected with microfilariae of O. volvulus, whereas no significant difference was registered between side effect rates of bancroftian microfilaria carriers and non-infected persons. It is concluded that in areas where both filarial species are endemic, infections with O. volvulus are a limiting factor for the control of bancroftian filariasis by means of mass treatment with diethylcarbamazine.

Adolescent↗

PubMed1982

Effect of diethylcarbamazine on Strongylus vulgaris infection in ponies.

Shetland ponies (n = 4) were given diethylcarbamazine orally at a dose level of 22 mg/kg/day for 1 week before they were inoculated with 800 third-stage larvae of Strongylus vulgaris. Treatment was continued for 86 (1 pony) or 200 days (3 ponies) after the inoculation. As compared with the changes seen in a similarly inoculated group of ponies (group 2) which were not treated, diethylcarbamazine did not prevent the clinical or pathologic changes due to the migrating larvae. Fewer adult parasites were recovered at necropsy from treated ponies than from nontreated (group 2) ponies, even when treatment was discontinued 86 days after inoculation. Treatment appeared to have a detrimental effect on 4th-stage larvae either in the arteries or their intestinal wall, but not until after arterial lesions resulted.

Animals↗

PubMed1998

Long-term effect of diethylcarbamazine citrate on microfilaraemia status in treated individuals.

Follow up of microfilaraemic individuals infected with Wuchereria bancrofti at five years after treatment was carried out in a tea workers population. Diethylcarbamazine citrate in the dose schedule of 72 mg/kg body weight given in equal daily doses over a period of 21 days cleared 51.6 per cent microfilaraemic individuals five year post-treatment. Eighty five subjects were successfully followed and among these, 10 (11.8%) showed increase in mf counts, 31 (36.4%) showed reduction but remained microfilaraemic and 44 (51.8%) became amicrofilaraemic. The age and sex of the host had no significant effect on the clearance of mf. Persistence of a relatively stable low number of mf in treated individuals is more likely due to survival of one or more female worms after the therapy or due to reinfection which could not be ruled out in the present study. Overall, findings indicated that diethylcarbamazine citrate appeared to give a long-term benefit to treated individuals.

Adolescent↗

PubMed1998

Diethylcarbamazine (DEC) does not induce nitric oxide (NO) synthesis.

Diethylcarbamazine (DEC) was discovered in 1947 as a potent therapeutic agent in lymphatic filariasis and has been a mainstay of antifilarial therapy over the past five decades (R. I. Hewitt, et al., 1947, Journal of Laboratory and Clinical Medicine 32, 1304-1313). Several hundred million doses of this drug have been administered to people. Despite its widespread and successful use over this prolonged time scale, its mechanism of action remains obscure (R. M. Maizels and D. A. Denham, 1992, Parasitology 105 Suppl. 549-560). Numerous studies suggest that DEC has no direct effect on the parasite (F. Hawking and W. Laurie, 1949, Lancet 2, 146-147) and that it exerts its action by stimulating host immune defense mechanisms (F. Hawking et al., 1948, Lancet 2, 730-731), or by activating host platelets to become microfilaricidal (J. Y. Cesbron et al., 1987, Nature 325(6104) 533-536). Recent data from two different laboratories suggest that NO may be involved in host defense against filarial parasites (T. V. Rajan et al., 1996, Infection and Immunity 64(8), 3351-3353; M. J. Taylor et al., 1996, Parasitology 112, 315-322). We investigated whether DEC stimulates the production of NO from murine macrophages or rat endothelial cells. DEC did not stimulate the synthesis or secretion of NO from either, nor did it synergize with interferon-gamma or tumor necrosis factor-alpha in the induction of inducible NO synthase (iNOS). In addition, there was no consistent increase in the output of inorganic nitrate, the end product of NO metabolism, in the urines of rats treated with DEC. These data suggest that DEC does not achieve its therapeutic efficacy through the induction of host iNOS.

Animals↗

PubMed2000

Acceleration of body clearance of diethylCarbamazine by oral activated charcoal.

The effect of activated charcoal (AC) on body clearance of diethylcarbamazine (DEC) was investigated in six healthy volunteers. On three occasions at weekly intervals, each subject received 150 mg of DEC with 350 ml of water. One and two weeks later, 150 mg of DEC plus 7.5 g and 15 g of AC, respectively, in 350 ml of water as a charcoal slurry. The non-renal clearance of DEC expressed as the total body clearance of DEC was increased after treatment with AC. The 45.2, 79.6 percent and 58.6, 81.6 percent reductions in maximum concentration and area under the concentration-time curve, respectively, suggest an appreciable adsorption of DEC by AC (7.5 and 15 g) in the gut. Serum eliminating half-life was decreased upon treatment with AC (7.5 and 15 g). These results indicate that AC accelerates the body clearance of DEC by increasing non-renal elimination of the drug.

Administration, Oral↗

PubMed1986

The effect of diethylcarbamazine on microfilariae of Litomosoides carinii in vitro and in vivo.

Culture-derived Litomosoides carinii microfilariae (MFF) were used in in vitro and in vivo systems to investigate the effect of diethylcarbamazine (DEC) on these MFF. In vivo: Male rats, Mastomys natalensis, all of the same age, were injected intrathoracically (12) or intraperitoneally (36) with 10(3) or 10(4) MFF. After 30 min one half of each group of rats was given DEC per os. At 30, 60, and 120 min after DEC administration, two rats from the treated and two from the untreated group were bled and killed. The pleural or peritoneal cavities were rinsed with warm saline (0.15 M NaCl) to recover MFF. In both the intrathoracic and intraperitoneal experiments, equal numbers of MFF were recovered from treated and control rats at 30 and 120 min. However, at 60 min 85.5% fewer were recovered from the treated than from the nontreated animals. MFF were not found in the blood. In vitro: MFF were added to tissue culture dish wells (Linbro Div., Flow Labs, Hamden, Conn) prepared as follows: DEC-Serum (serum from normal rats given DEC at 500 mg/kg), DEC + Serum (serum with added DEC), serum only, RPMI 1640 only, and RPMI 1640 + DEC. Furthermore, the five treatments were prepared either with or without unstimulated peritoneal exudate (PE) cells. At 30 min in the DEC-Serum wells 45% of the MFF had adherent PE cells; in the remaining wells these cells adhered to 11% or fewer MFF. We interpret the aforementioned phenomena as representing the first step in the trapping and elimination of MFF after DEC treatment of L. carinii-infected M. natalensis.

Animals↗

PubMed1983

Studies on the chemoprophylaxis of subperiodic Brugia malayi infection in the leaf monkey (Presbytis melalophos) with diethylcarbamazine citrate.

The chemoprophylactic use of diethylcarbamazine citrate at total oral doses of 15--180 mg/kg body weight was tested against subperiodic Brugia malayi infection in the leaf monkey (Presbytis melalophos). A total dose of 45 mg/kg body weight given over 9 days killed all developing infective larvae. Similarly, a total dose of 35 mg/kg body weight given over 7 days killed all fourth stage larvae. The minimum effective dose that prevents infection would be 5 mg/kg body weight daily for 7 days every month.

Administration, Oral↗

PubMed1983

Occurrence of microfilariae in various hollow organs and in the peritoneal cavity after treatment of Litomosoides carinii infected Mastomys natalensis with diethylcarbamazine and haloxon.

Treatment of Litomosoides carinii infected Mastomys natalensis with diethylcarbamazine (DEC: 500 mg/kg p.o.) was followed by increased occurrence of microfilariae in the bronchi of the host after 40 min and lasting at least until 6 h after treatment. After 4 h, increased levels of larvae were observed in the gut. Only a few microfilariae occurred in the bladder and sputum. Accumulations of microfilariae were found furthermore in the Lnn. hepaticae whereas no changes were observed in the inguinal or jejunal and lung and pleura associated lymph nodes. Increased numbers of microfilariae were found in the peritoneal cavity only after 8 and continuing until at least 48 h after treatment. In contrast, after haloxon treatment (100 mg/kg p.o.) an accumulation of microfilariae was found in the peritoneal cavity only, following a time course similar to that after DEC.

Animals↗

PubMed1985

Action of diethylcarbamazine citrate on protective immunity in rats infected with Nippostrongylus brasiliensis.

Rats made immune to Nippostrongylus brasiliensis and treated with diethylcarbamazine citrate (DEC) orally (250 mg/kg X 6) exhibited significant suppression of functional immunity. Similarly, administration of compound 48/80 (100 micrograms/rat i.p.) made the immune rats susceptible to challenge infection. Treatment of rats, with 22-day infection with compound 48/80, histamine (20 mg/rat, per os), or L-histidine (20 mg/rat, orally s.c.) did not accelerate worm expulsion. A massive complement-dependent adherence of peritoneal cells (1 X 10(8], isolated from immune DEC-treated and untreated rats, to infective larvae (L3) was observed. Likewise, heavy congregation of normal peritoneal cells to larvae was noticed when the cells were incubated with sera obtained from immune, DEC-treated or untreated rats. The rats receiving mesenteric lymph node cells (125 X 10(6) i.v.) or sera (0.5 ml or 1 ml X 3 i.p.), obtained from immune DEC-treated rats and challenged with infective larvae developed 50% more worms than those which received cells or serum from untreated immune donors. DEC appears to cause suppression of functional immunity and worm expulsion is not histamine mediated.

Animals↗

PubMedDate not supplied

[Experimental filariasis in Proechimys oris by Dipetalonema dessetae: 4. Effect of parasitism on protein and tissue binding of diethylcarbamazine].

Several groups of control and filaria-infected Rodents were treated by radio-labelled diethylcarbamazine in order to study the effect of parasitism on the protein binding and tissue distribution of the drug. These studies were performed using equilibrium dialysis, chromatography and autoradiography. The plasmatic protein concentrations were lower in the group of infected Rodents, due to a decrease of albumin. The binding rate depended on the electrophoretic fractions, but remained low and unaffected by parasitism. The radioactivity of DEC and its metabolites appeared very quickly in the tissues, particularly in infected Rodents. This was due to the fact that the already rapid intestinal absorption and diffusion were enhanced by filariasis.

Animals↗

PubMedDate not supplied

[Experimental filariasis in Proechimys oris by Dipetalonema dessetae. 5. Effect of parasitism on metabolism of diethylcarbamazine].

The metabolism of diethylcarbamazine (DEC) in healthy and filaria-infected Proechimys oris Rodents was investigated. DEC and 14C labelled DEC were orally administrated (100 mg/kg). The drug was quickly and intensively metabolised. About 90% of the dose administered was eliminated in the urine within 24 hours. Monodeethylation was the major pathway. The major urinary metabolites were ethylcarbamazine and its N-oxide. Traces of N methylpiperazine 2,5 dione and their N-oxide were also found. Elimination was faster in filarial than in healthy animals, but metabolites were the same.

Animals↗

PubMed2004

The effects of diethylcarbamazine on the ultrastructure of microfilariae of Wuchereria bancrofti in vivo and in vitro.

An ultrastructural study of microfilariae of Wuchereria bancrofti was performed after treatment in vitro and in vivo with diethylcarbamazine citrate (DEC). The morphological alterations produced by treatment in vitro with 5 micro g/ml of DEC were the loss of microfilarial sheaths and lysis of the cytoplasm, with the destruction of all organelles and the formation of several vacuoles, the contents of which presented various degrees of electron-density, or showed an empty appearance. Some of these vacuoles seemed to be extruding from the cytoplasm as apoptotic bodies and others presented organelles inside. Similar alterations were observed after in vivo treatment. At 40 min after treatment of a microfilaremic individual with DEC, almost all microfilariae observed had lost their sheaths; and, in some of them, remains of the microfilarial sheath on the larval surface could be detected. Numerous vacuoles were observed, mainly in the hypodermis and somatic cells, showing organelles inside or an empty appearance. Condensed chromatin was also observed in some somatic cells. At 1 h after treatment of a microfilemic individual with DEC, microfilariae presented drastic morphological alterations, with large vacuoles within somatic cell cytoplasm and complete lysis of all cellular organelles. Therefore, both treatments with DEC in vitro and in vivo had a direct mechanism of action on the microfilariae of W. bancrofti, including organelle damage and apoptosis.

Animals↗

PubMed1990

Diethylcarbamazine, antifilarial drug, inhibits microtubule polymerization and disrupts preformed microtubules.

The effect of diethylcarbamazine (DEC) on microtubules was studied by using microtubule protein prepared from porcine brain. DEC inhibited assembly of microtubules and disassembled preformed microtubules in vitro. When the reassembled or disassembled products were examined in the presence of DEC by electron microscopy, ribbon-microtubules were frequently observed. Subsequently, the effect of DEC on the cytoplasmic microtubules complex was studied. The cells used in our study were LLC-MK2. DEC inhibited proliferation of these cells, and cells grown in the presence of DEC were likely to separate from each other and became round in shape. Immunofluorescence microscopy revealed that the cells exposed to DEC were devoid of the delicate pattern of the cytoplasmic microtubule complex.

Animals↗

PubMed1983

Myocardial depressant effects of diethylcarbamazine citrate in vitro.

The effects of diethylcarbamazine citrate (DECC) have been examined in isolated, electrically driven left atria of guinea-pigs. This anthelmintic drug (DECC, 10(-9) -10(-4) M) produced a sustained, concentration-dependent depression of atrial contractile tension that was reversible by replacing the incubation fluid with DECC-free physiological solution. The negative inotropic response induced by DECC was antagonized in a competitive manner by increasing the calcium ion (Ca2+) concentration of the bathing fluid. On the contrary, the myocardial depressant effects of DECC were antagonized in a non-competitive manner by noradrenaline (NA). The present findings suggest a direct negative inotropic effect of DECC and indicate that this anthelmintic drug interferes with the empirical function of Ca2+ in the events leading to mechanical activity of the isolated atrial myocardium.

Animals↗

PubMed1976

Some observations on filariasis in Western Samoa after mass administration of diethylcarbamazine.

An extremely efficient diethylcarbamazine administration campaign to eradicate Wuchereria bancrofti has been carried out in Western Samoa. The use of the membrane-filtration technique has shown that a large number of people exhibit extremely low microfilarial densities, often with less than 10 in 1 ml of venous blood. It was found that one of these low level microfilaria carriers readily infected the local vector Aedes polynesiensis and that development took place to the infective stage. It was estimated that 497 infective larvae of W. bancrofti will enter the human population of Western Samoa daily from these vectors. Resumption of filariasis transmission is possible and surveillance of the human and mosquito populations should be continued for a number of years and control measures taken quickly if further transmission occurs.

Adult↗

PubMed1979

A simple method to control Brugia timori by diethylcarbamazine administration.

The results of mass treatment using 50 mg diethylcarbamazine per kg body-weight followed one year later by short term selective re-treatment in a highly endemic area of Brugia timori are described. The criteria for selection of re-treatment are simple and practical for use in rural areas. The microfilaria rate by finger prick decreased from 24% to 0 and by Nuclepore filtration from 30% to 2.5%. The disease rates were also affected favourably. 88% of persons receiving the drug reacted to treatment, this percentage slightly exceeding the total filarial infection rate (71%). The prevalence, onset, duration and nature of side reactions are briefly discussed and related to the presence of microfilaraemia and disease manifestations among the study population.

Brugia↗

PubMed1980

Drug trials with levamisole hydrochloride and diethylcarbamazine citrate in Bancroftian and Malayan filariasis.

Seventy-eight microfilaraemic patients with Wuchereria bancrofti and Brugia malayi infections were treated with various oral levamisole hydrochloride total dosage regimes of 150 to 3,150 mg and total diethylcarbamazine citrate (DEC) of 36 and 126 mg per kg body-weight. Significant microfilaricidal and probable macrofilaricidal effects were seen at total levamisole hydrochloride dosages of 300 to 3,150 mg and the DEC dosages. The optimum dosage regime with levamisole hydrochloride recommended for treatment of microfilaraemic patients is 100 mg initially followed by 100 mg twice daily for 10 days. This dosage regime was as effective as a total oral dosage of DEC at 126 mg per kg body-weight. Side reactions were dose-dependent, mild and transient, with fever being the most common. One patient developed fits after 150 mg levamisole hydrochloride. The pathophysiology of these side reactions is discussed and it is recommended that levamisole hydrochloride, as a probable alternative for the treatment of patent and occult filariasis, should be used only under close medical supervision.

Adolescent↗

PubMed1981

Litomosoides carinii infection in cotton-rats: evolution of microfilaraemia before and after treatment with diethylcarbamazine and suramin.

The activity of diethylcarbamazine (DEC) and suramin (S) on Litomosoides carinii filariasis was assessed by the study of microfilaraemia in 30 cotton-rats (Sigmodon hispidus). DEC (per os) and S (injected subcutaneously) were administered alone or in combination, at doses of 50 mg/kg/day for five consecutive days. 15 rats were treated at day 91 after infection and 15 others at day 184. The immediate but temporary efficacy observed with DEC was in contrast to the delayed and long-lasting effect of S. With combined therapy there was neither antagonism nor synergism. The demonstration of an apparently smaller reduction of parasitaemia in the rats treated with DEC before the plateau phase of the microfilaraemia was consistent with the lack of action of this drug on microfilariae outside the blood system.

Animals↗