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PubMed1982

Litomosoides carinii: effect of diethylcarbamazine on microfilaremias of Mastomys natalensis harboring old infections, new infections, and transfused microfilariae.

Mastomys natalensis, matched according to age and microfilaremia, were divided into Experimental and Control groups. The former were given diethylcarbamazine (Caricide, 500 mg/kg) per os. Microfilariae counts were made at 15, 30, 60, and 120 min and at 1, 5, and 12 days. This protocol was performed on rats with: old infections (patent for 7 mo), new infections (patent for 10 days), and no infection but made microfilaremic by injection of blood or culture-derived microfilariae. In all treated groups, the microfilaremia dropped precipitously within the first 15 min. Microfilaremias of animals with old infections remained low until day 12 after treatment when they began to rise, whereas those of animals with new infections began to rise immediately, i.e., within minutes after the initial decline. Microfilaremias of animals with no adult worms present remained depressed for the duration of the experiment. Thus, the resurgence of microfilariae after treatment with diethylcarbamazine is the result of release of new microfilariae by the female worms rather than release of trapped microfilariae by the host. This investigation also demonstrates that elimination of microfilariae by a nonsensitized host is possible upon treatment with diethylcarbamazine.

Animals↗

PubMed1986

Effects of diethylcarbamazine on the motility of Angiostrongylus cantonensis and Dirofilaria immitis.

Effects of piperazine derivatives, especially of diethylcarbamazine (DEC) on adult Angiostrongylus cantonensis and Dirofilaria immitis were examined. Piperazine (3 X 10(-5)-10(-4) M) paralyzed A. cantonensis and the action was antagonized by picrotoxin. 1,1-dimethyl-4-phenylpiperazinium iodide (DMPP) (10(-5)-10(-4) M) caused contraction but little effect was produced by strychnine. An inhibitory effect on untreated preparations was caused by lower concentrations (3 X 10(-6)-10(-5) M) of diethylcarbamazine citrate (DEC) and also on the preparations contracted by eserine. A stimulatory effect was also seen when higher concentrations (10(-4)-3 X 10(-4) M) of this drug were applied to both preparations. The inhibitory action of DEC was antagonized by gabergic antagonists such as picrotoxin and bicuculline, but not by alpha-adrenergic antagonists like dibenamine and phentolamine. When the worm preparation was paralyzed by strychnine or hexylresorcinol (inhibitors of the release of acetylcholine in this worm), the stimulatory effect of DEC was blocked, but pyrantel (a nicotinic cholinergic agonist) contracted the paralyzed preparation. However, the effect of DEC on D. immitis (10(-7)-3 X 10(-4) M) was inhibitory, and this action was also antagonized by picrotoxin. These results suggest that the DEC inhibitory and stimulatory action is through the gabergic and cholinergic mechanisms in adult A. cantonensis and D. immitis.

Angiostrongylus↗

PubMed1978

Failure of diethylcarbamazine as a provocative test in subperiodic Wuchereria bancrofti filariasis.

The effect of diethylcarbamazine (DEC) on levels of microfilaraemia in 70 patients with subperiodic, Pacific-variant Wuchereria bancrofti infection was studied one hour after oral administration of 5 mg/kg of drug. In contrast to the immediate DEC-induced increase in microfilaraemia which had been previously described in patients with nocturnally periodic filariasis, diethylcarbamazine failed to elicit such a response in patients with subperiodic bancrofti infection. Indeed, one hour after oral DEC the number of circulating microfilariae was reduced to about 8% of pre-treatment values.

Adolescent↗

PubMedDate not supplied

Microfilaraemia, serum antibody and development of clinical disease in microfilaraemic subjects infected with Wuchereria bancrofti and treated with diethylcarbamazine citrate.

A seroepidemiological survey of bancroftian filariasis was carried out in 2 townships in Sri Lanka with the objectives of determining the microfilaraemia rates, dependence on age and sex, susceptibility to re-infection, effect of diethylcarbamazine therapy on serum antibodies to microfilarial surface antigens, and the predictive value of the indirect fluorescent antibody test. The mean microfilaraemia rate was 5.4%. Microfilaraemia was not sex-dependent but a marginally elevated incidence was seen in the 6-35 year age groups. In up to 58% of the microfilaraemic patients who had been treated for microfilaraemia previously, a second phase of microfilaraemia was seen 2-7 years after treatment. This was unlikely to have been due to incomplete parasite elimination. Antibodies to microfilarial surface were found in 24-35% of microfilaraemic patients and in 14-63% of amicrofilaraemic symptomatic subjects. Serum anti-microfilarial surface antibody levels did not alter with chemotherapy with diethylcarbamazine citrate. The findings of follow-up investigations of microfilaraemic subjects were compatible with the notion that microfilaraemia does not necessarily lead to clinical disease.

Adolescent↗

PubMed1981

In vivo suppression of delayed hypersensitivity by thiabendazole and diethylcarbamazine.

Several anthelminthic agents, such as niridazole and metronidazole, have been demonstrated to have striking effects on the immune system, apparently independent of their antiparasitic activities. In the present study, we have examined the effect of thiabendazole and diethylcarbamazine on two parameters of delayed hypersensitivity, lung granuloma formation around Schistosoma mansoni eggs and delayed footpad edema in response to schistosome egg antigens. Both drugs caused significant reduction of lung granuloma size in unsensitized animals when given as daily doses for 8 days. Thiabendazole was the more potent suppressant, affecting granuloma size in unsensitized animals when given as single dose and in sensitized animals using a multiple dose regimen. Diethylcarbamazine was without effect on granuloma size in sensitized animals, but inhibited delayed footpad swelling when given daily for 6 days. Neither drug affected granulomas induced by non-antigenic plastic beads. These data support the hypothesis that some of the clinical activities of these drugs may be mediated by interference with host response to antigenic stimuli.

Animals↗

PubMed1995

Therapeutic effects of diethylcarbamazine and 3'-azido-3'-deoxythymidine on feline leukemia virus lymphoma formation.

Twenty-four specific pathogen-free kittens were infected with the Rickard strain of feline leukemia virus (FeLVR). The kittens were divided into four equal groups and were orally administered either a high dose of diethylcarbamazine (DECH, 12 mg kg-1), a low dose of diethylcarbamazine (DECL, 3 mg kg-1), 3'-azido-3'-deoxythymidine (AZT, 15 mg kg-1, b.i.d.), or a placebo (250 mg granular dextrose) daily for 10 weeks. Blood was collected at 2-week intervals for complete blood counts (CBC) and flow cytometric analysis (FACS) of peripheral blood lymphocytes (PBL). Plasma was assayed for antibodies to FeLV gp70 and for FeLV p27 antigen using ELISA assays. For FACS analysis, lymphocytes were incubated with monoclonal antibodies to feline Pan T, CD8+, CD4+, and B cell (Anti-Ig) antigens. In the placebo treated cats, FeLVR infection caused an early (2 weeks p.i.) and persistent decrease in leukocyte numbers attributable primarily to a decrease in neutrophil numbers and a secondary lesser decrease in B and CD4+ lymphocyte numbers. The DEC-treated groups showed a delayed but similar leukopenia by 4 weeks p.i. The lymphopenia in the DEC groups (primarily B cells and CD4+ cells) was reversed by 10 weeks p.i., but the neutropenia persisted. AZT treatment inhibited FeLVR-induced lymphopenia but did not prevent a reduction in neutrophil numbers. A marked p27 antigenemia that peaked at 4 weeks p.i. was noted in the placebo treated cats and in most cats (11/12) treated with either dose of DEC. However, AZT significantly inhibited the p27 antigenemia and all cats were negative for p27 antigen between 6 and 10 weeks of treatment. In general, placebo treated cats as well as DECH and DECL cats had low levels of antibody to gp70 throughout the study, suggesting FeLVR-induced immunosuppression. In contrast, significantly higher titers of anti-gp70 antibodies were seen in AZT-treated cats at 6 weeks p.i., and were maintained throughout treatment. Eighteen month survival rates provide efficacy data for AZT as well as both DEC treatment groups. While all placebo treated cats were euthanized by 52 weeks p.i. due to FeLV associated lymphomas with a mean survival time of 35.5 weeks p.i., median survival time of the AZT treated group was > or = 102 weeks p.i., while that of the DECH and DECL groups was 69.7 and 72 weeks p.i., respectively. Thus, DEC as well as AZT therapy delays the development of lymphomas associated with FeLV infection and significantly improves survival.

Animals↗

PubMed1987

Effect of diethylcarbamazine on cats given feline leukaemia virus vaccine.

Leukocell (Norden Laboratories, Lincoln, NE, USA), a commercially available retroviral vaccine, is given to protect susceptible cats against feline leukaemia virus. Oral diethylcarbamazine, an immunomodulator used in the treatment of filariasis, when given with 1 ml i.m. Leukocell, increased titres and duration of serum antibodies to feline oncornavirus-associated cell membrane antigen and transient average monocyte counts in treated/vaccinated cats as compared to cats that received vaccine without diethylcarbamazine. These results may have implications for the development of more effective retroviral vaccination techniques for humans as well as for cats.

Animals↗

PubMed2005

The effects of diethylcarbamazine on the ultrastructure of lung cells in vivo.

The pulmonary surfactant synthesis is disturbed in experimentally induced asthma, as are the intracellular storage capacity and its physical activity. These alterations may also be present in chronic asthmatic patients, and therefore the dysfunction of the pulmonary surfactant system may play an important role in the pathophysiology of asthma. Some clinical reports have described favorable results with the use of diethylcarbamazine (DEC) in patients with bronchial asthma showing that DEC is effective in terminating acute attacks of bronchial asthma. The present study aimed to analyze the ultrastructural alterations of lung cells after treatment in vivo with diethylcarbamazine. After 12 days of treatment with DEC, when compared with control samples, type II pneumocytes showed active nuclei with abundant euchromatin and evident nucleoli, and a substantially greater number of mature secretion vesicle. On the other hand, type I pneumocytes showed no morphological alterations. After DEC treatment, lung macrophages also presented several characteristics of cellular activation such as nuclei with a prominence of euchromatin and central nucleoli as well as an abundance of early and late endossomes distributed throughout the cytoplasm. These results confirm that DEC exerts a role in the activation of important pulmonary cellular pathways, which are probably related to the clinical improvement of asthma symptoms after DEC treatment.

Animals↗

PubMed2004

Impact of two annual single-dose mass drug administrations with diethylcarbamazine alone or in combination with albendazole on Wuchereria bancrofti microfilaraemia and antigenaemia in south India.

A two-arm community-based lymphatic filariasis elimination trial is being carried out in Tamil Nadu state, India to assess the effect of 2 annual single-dose mass drug administrations of diethylcarbamazine + albendazole (DEC + ALB) on microfilaraemia and antigenaemia in one arm, and diethylcarbamazine(DEC) alone in the other arm. In a cross-sectional survey at each time-point, 450-650 subjects in childhood (2-9 years old) and young adulthood (10-25 years old) were screened from each treatment arm. After 2 annual mass drug administrations, microfilaraemia prevalence in the 2-drug arm was reduced by 54% and 62% in the 2-9 year old and 10-25 year old groups respectively; and corresponding figures for the single-drug arm were 26% and 37%. Though higher reductions were recorded for geometric mean intensity of microfilaraemia in the 2-9 year old groups for both treatment arms, reduction was more pronounced in the 2-drug arm than the single drug arm (74% vs. 24%) in the 10-25 year old group. The reduction in the antigenaemia prevalence in the 2-9 year old group was evident in both treatment arms, but in the 10-25 year old group the reduction was only 16.8% in the 2-drug arm. Our results suggest that the annual, single-dose combination (DEC + ALB) mass treatment regimen has an enhanced effect against bancroftian filariasis compared to single-drug therapy.

Adolescent↗

PubMed2006

Effect of yearly mass drug administration with diethylcarbamazine and albendazole on bancroftian filariasis in Egypt: a comprehensive assessment.

BACKGROUND: Egypt was one of the first countries to implement a national programme to eliminate lymphatic filariasis based on WHO's strategy of repeated rounds of mass drug administration (MDA) with diethylcarbamazine and albendazole (target population, 2.5 million in 181 localities). We assessed the effect of five yearly rounds of MDA on filariasis in four sentinel villages in Egypt. METHODS: We studied two areas with different infection rates before MDA: the Qalubyia study area had a low infection rate because of previous treatment with diethylcarbamazine; this was typical of most filariasis-endemic villages in Egypt before MDA. The Giza study area had a high baseline infection rate. We undertook repeated surveys in villages for treatment compliance and tests for microfilaraemia and circulating filarial antigenaemia, antibodies to filarial antigen Bm14 in schoolchildren, and infections in indoor-resting mosquitoes (assessed by PCR). FINDINGS: MDA compliance rates were excellent (>80%). In Giza after MDA, prevalence rates of microfilaraemia and circulating filarial antigenaemia fell from 11.5% to 1.2%, and from 19.0% to 4.8%, respectively (p<0.0001). Corresponding rates in Qalubyia fell from 3.1% to 0% and 13.6% to 3.1%, respectively (p<0.0001). Rates of antifilarial antibody and circulating filarial antigenaemia in schoolchildren (aged about 7-8 years), fell from 18.3% to 0.2% (p<0.0001) and from 10.0% to 0.4% (p<0.0001) in Giza, respectively, and from 1.7% to 0% and 1.7% to 0% (both p=0.13) in Qalubyia, respectively. Mosquito infection rates fell from 3.07% (95% CI 2.38-3.88) to 0.19% (0.08-0.38) in Giza and from 4.37% (3.07-5.99) to 0% (0-0.05) in Qalubyia. INTERPRETATION: MDA greatly affects variables related to infection (microfilaraemia and circulating filarial antigenaemia prevalence rates) and transmission (antifilarial antibodies in young children and mosquito infection rates). Our results suggest that after five rounds of MDA filariasis is likely to have been eliminated in most endemic localities in Egypt.

Albendazole↗

PubMed1991

Tropical eosinophilia: clinical and physiological response to diethylcarbamazine.

Fifty patients with tropical eosinophilia were studied clinically and physiologically, before and after a standard 3-week course of diethylcarbamazine. Before treatment the main physiological abnormality was a reduction in the carbon monoxide transfer factor. One month after the start of treatment most patients had shown a marked symptomatic improvement, but peripheral blood eosinophilia persisted in 52%, radiographic abnormalities in 44%, cough in 22% and chest signs in 8%. Significant improvement was noted in almost all aspects of lung function including blood gases, but the mean values for forced expiratory volume in one second, forced vital capacity, transfer factor and transfer coefficient continued to be significantly lower than predicted values. This study demonstrates the incomplete reversal of clinical, haematological, radiological and physiological changes in tropical eosinophilia one month after starting a 3-week course of diethylcarbamazine.

Adolescent↗

PubMed1990

Antifilarial activity of intravenous suramin and oral diethylcarbamazine citrate on subperiodic Brugia malayi in the leaf-monkey, Presbytis cristata.

The known filaricides, suramin and diethylcarbamazine citrate, were tested against subperiodic Brugia malayi infection in the leaf-monkey, Presbytis cristata. As expected, intravenous suramin at 10 mg/kg daily x 5 days or 17 mg/kg weekly x 5 weeks, did not show any microfilaricidal activity, but substantially reduced the recovery of live adult worms to 50.6% and 13.6% of controls respectively. Oral diethylcarbamazine citrate at 6 mg/kg daily x 6 or 10 days reduced final microfilarial counts to 30% of initial counts four weeks post-treatment and adult worm recovery was reduced to 4.5% and 0% of controls respectively. Although the antifilarial activity of these drugs against the infection in this non-human primate model appears to be similar to that seen in man, these results have to be confirmed using larger groups of animals.

Administration, Oral↗

PubMed1977

Antifilarial agents. 3-Aminopyrrolidine and 1,4-diazabicyclo[3.2.1]octane derivatives as analogues of diethylcarbamazine.

3-Aminopyrrolidines bearing acyl substituents on either nitrogen and N-acylated 1,4-diazabicyclo[3.2.1]octanes are potent microfilaricides in the Litomosoides carinii gerbil test system but have no effect on adult worms. The high activity of the pyrrolidine derivatives establishes that diethylcarbamazine (DEC) like antifilarial activity does not require that both pharmacophores be incorporated into one ring. Results with the 1,4-diazabicyclo[3.2.1]octanes establish that an axial conformation of the alkyl substituent corresponding to the equatorial N-methyl group of diethylcarbamazine is fully consistent with high activity. Other conformational consideration pertinent to DEC analogues are discussed.

Animals↗

PubMed1997

Diethylcarbamazine: effect on lysosomal enzymes and acetylcholine in Wuchereria bancrofti infection.

We measured the levels of lysosomal enzymes and acetylcholine in Wuchereria bancrofti-infected asymptomatic microfilaraemic human serum, and found a significant decrease in the activity of beta-glucuronidase and acid phosphatase compared to normal serum. Acetylcholine levels were also decreased during infection. However, after giving diethylcarbamazine (6 mg/kg body wt/day) the level of lysosomal enzymes and acetylcholine increased and reached a normal value after two weeks of therapy. It is proposed that parasites secrete acetylcholinesterase in the circulation which degrades acetylcholine. Since acetylcholine stimulates the release of lysosomal enzymes and phagocytosis, the immune response of the host is suppressed during infection. During diethylcarbamazine (DEC) therapy the parasitic enzyme is inhibited by the drug and the normal level of acetylcholine is resumed, which again stimulates the release of lysosomal enzyme and the process of phagocytosis.

Acetylcholine↗

PubMed1999

Treatment of the microfilaraemia of asymptomatic brugian filariasis with single doses of ivermectin, diethylcarbamazine or albendazole, in various combinations.

Several new chemotherapeutic tools are now available for the control of lymphatic filariasis. Combinations of single doses of antifilarial drugs are generally superior to single drugs. The efficacy and safety of albendazole in combination with diethylcarbamazine (DEC) or ivermectin, for the treatment of Brugia malayi infection, were investigated, for the first time, in an open, hospital-based study. Fifty-one asymptomatic microfilaraemics (with 108-4034 microfilariae/ml; median = 531) of both sexes and aged 14-70 years were randomly allocated to receive single-dose treatments of ivermectin (200 micrograms/kg) with diethylcarbamazine (DEC; 6 mg/kg), ivermectin (200 micrograms/kg) with albendazole (400 mg), DEC (6 mg/kg) with albendazole (400 mg), or albendazole (400 mg) alone. Albendazole alone had no effect on the microfilarial levels at the 1-year follow-up but both groups given DEC had significantly lower microfilaraemias (P < 0.015 and P < 0.02) than that given ivermectin with albendazole. Overall, 47%-64% of those given DEC but only 14% of those given ivermectin with albendazole appeared to be amicrofilaraemic 1 year post-treatment. The adverse reactions seen in the study were mild, transient and qualitatively similar to those seen earlier with ivermectin and DEC. The combination of DEC and albendazole, both well tested drugs, offers a new option for countries such as India where there is no onchocerciasis or loiasis and where ivermectin may not be immediately available. The direct and indirect effects of albendazole on intestinal helminths would be additional benefits.

Adolescent↗

PubMed1958

Action of diethylcarbamazine in vitro on infective larvae of Wuchereria bancrofti.

Infective larvae of Wuchereia bancrofti were obtained from laboratory infected Culex fatigans and maintained in serum containing diethylcarbamazine. There was no difference in the survival time of these larvae and larvae maintained in control serum without diethylcarbamazine. In one of the three experiments reported the survival time of the larvae was much longer than in the other two experiments. It is suggested that this may have been due to the presence of filarial antibodies which killed the larvae in two of the sera used. In the serum which did not contain antibodies, the larvae survived very much longer.

Animals↗

PubMed1977

Dangerous reactions to treatment of onchocerciasis with diethylcarbamazine.

Nine Nigerians with severe onchocerciasis who were treated with diethylcarbamazine developed clinical changes, ranging in severity from mild itching to distress, cough, and syncope. Physiological changes (fever, tachypnoea, tachycardia, or hypotension) were seen in eight. In five patients the systolic blood pressure fell by more than 25 mm Hg, and one patient collapsed on attempting to sit up. Circulating eosinophils decreased profoundly in all cases, reaching their lowest levels just before or during the clinical and physiological changes. A fall in serum complement (c3) accompanied the reaction but there was no fall in antibody titre. Diethylcarbamazine probably acts on the parasite's cuticle, thus exposing it to the body's defence mechansims. The reaction coincides with the death of microfilariae, and the accompanying physiological changes may be so severe, even in generally healthy patients, the treatment should perferably be started in hospital.

Adolescent↗

PubMed1996

Effect of sodium nitroprusside and diethylcarbamazine on hypoxic pulmonary vasoconstriction and regional distribution of pulmonary blood flow in experimental pneumonia.

The interaction between the effects of indomethacin and sodium nitroprusside or diethylcarbamazine infusion on the efficacy of hypoxic pulmonary vasoconstriction (HPV) and regional distribution of lung blood flow was studied in 15 pentobarbital-anesthetized dogs with acute pneumonia caused by Pseudomonas aeruginosa. After induction of pneumonia central hemodynamics, gas exchange, and regional distribution of lung blood flow (radionuclide-labeled microsphere method) were measured during ventilation of both lungs with oxygen and again with one lung ventilated with nitrogen. The dogs were then randomly assigned to one of three treatment groups: Group I (n = 5) received indomethacin alone (2 mg/kg); Group I-D received indomethacin and diethylcarbamazine (50 mg/kg over 20 min followed by 1 mg/kg/min for the rest of the experiment); Group I-N (n = 5) received indomethacin with sodium nitroprusside to achieve a 20- to 30-mm Hg reduction in mean blood pressure. All measurements were then repeated during both oxygen ventilation and one-lung nitrogen ventilation. In all three groups there was no effect of nitrogen inhalation on distribution of lung blood flow prior to drug treatment, indicating absence of HPV. After treatment, in Group I, perfusion of the pneumonic lung fell from 0.27 +/- 0.08 to 0.10 +/- 0.03 (p < 0.05) of total lung blood flow, and nitrogen ventilation of the left lung reduced perfusion to that region from 0.23 +/- 0.02 to 0.13 +/- 0.02 (p < 0.05), indicating restoration of HPV. In Groups I-D and I-N, HPV was persistently absent or markedly attenuated after treatment, but the percentage of the cardiac output perfusing the pneumonia region fell by an amount similar to that in Group I (0.26 +/- 0.07 to 0.11 +/- 0.04 in Group I-D and 0.35 +/- 0.03 to 0.21 +/- 0.06 in Group I-N, both p < 0.05). Because these two chemically unrelated pulmonary vasodilators effectively blocked HPV restoration but had no effect on vasoconstriction in the pneumonia region after indomethacin, it is concluded that regional lung blood flow redistribution in pneumonia is mediated by a mechanism other than HPV.

Animals↗