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PubMed1984

Immunoglobulin levels in tears and aqueous humor of horses before and after diethylcarbamazine (DEC) therapy.

A quantitative investigation of equine tear and aqueous humor immunoglobulins was done using normal horses and ponies as well as horses and ponies infected with Onchocerca cervicalis. The equine immunoglobulin isotypes IgGa, IgM, IgA and IgG(T) were quantitated by either single radial immunodiffusion (SRID) or radioimmunoassay (RIA). Tear immunoglobulin levels for IgGa (128 +/- 151 micrograms/ml), IgA (1,664 +/- 1,038 micrograms/ml) and IgM (106 +/- 74 micrograms/ml) were measured, while IgG(T) was not detectable. In horses with ocular inflammation the IgGa was 18-fold higher in the tears, 2,269 +/- 3,077 micrograms/ml. Aqueous humor obtained by paracentesis of the normal equine eye under anaesthesia, resulted in values for IgGa (45.2 +/- 20.0 micrograms/ml), IgG(T) (5.2 +/- 2.0 micrograms/ml), IgM (1.3 +/- 4.8 micrograms/ml) and IgA (0.8 +/- 1.0 micrograms/ml). A pooled sample of normal aqueous fluid obtained from over 100 horses at an equine abbatoir in Indiana gave values of 1,150 micrograms/ml for IgGa, 65 micrograms/ml for IgG(T), 2.5 micrograms/ml for IgA and 3.0 micrograms/ml for IgM. In animals infected with 0. cervicalis and treated with Diethylcarbamazine (DEC), there was a marked elevation of IgGa and IgG(T) in the tears and aqueous humor while IgA and IgG(T) were also elevated slightly in the aqueous. The findings of elevated immunoglobulin isotypes in the aqueous humor may not be related to the DEC treatment and 0. cervicalis infections but rather to repeated paracentesis and the development of acute inflammation of the equine eye as a result of the trauma of paracentesis. The elevations in equine immunoglobulin isotypes in the tears after DEC treatment are not subject to the same caveat. The preferential elevation in IgGa and IgG(T) in the tears precedes the development of corneal opacities observed in the same horses. The concentration of specific antimicrofilarial antibody in these tears remains to be determined but may well account for a major share of the total immunoglobulins detected.

Animals↗

PubMed1988

Antibodies to diethylcarbamazine cross-react with microfilariae of Wuchereria bancrofti.

Antibodies directed against the microfilarial sheath have been instrumental in the immune elimination of circulating microfilariae in human lymphatic filariasis. We report here that antibodies to diethylcarbamazine (DEC, the most commonly used anti-filarial drug) cross-react with the sheath of Wuchereria bancrofti microfilariae. Antibodies with reactivity to DEC were raised in rabbits by immunization with a conjugate of methylpiperazine carboxylic acid (MPCA, an acid hydrolysis product of DEC) coupled to bovine serum albumin. The reactivity of these antibodies with microfilarial sheath of W. bancrofti was demonstrated by indirect immunofluorescent assay and indirect immunoperoxidase assay. This reactivity could be effectively inhibited by pre-incubation of the antisera with different haptens such as DEC, MPCA or piperazine citrate.

Animals↗

PubMed1991

Diethylcarbamazine inhibits endothelial and microfilarial prostanoid metabolism in vitro.

Diethylcarbamazine (DEC) rapidly lowers the number of microfilariae in the peripheral circulation. The mechanism of action is unknown, but may involve alterations of arachidonic acid metabolism in vascular tissues. We studied the effects of DEC on arachidonic acid metabolism by bovine pulmonary arterial endothelium monolayers, human platelets and Brugia malayi microfilariae. DEC at a concentration of 2.5 microM, a level achieved in vivo, rapidly decreased prostacyclin, prostaglandin E2 and thromboxane B2 release from endothelial monolayers by 78% (P less than 0.001), 57% (P = 0.05), and 75% (P less than 0.05), respectively. High-pressure liquid chromatography of extracts of endothelial monolayers incubated with DEC showed similar inhibition of these cyclooxygenase pathway products, but exposure to the drug did not result in formation of new eicosanoids. DEC did not inhibit endothelial phospholipase A2-dependent release of arachidonate from membrane stores, whereas prostaglandin H2 synthase activity (cyclooxygenae, EC 1.14.99.1) was reduced to a degree similar to that effected by acetylsalicylic acid. Microfilarial but not platelet synthesis of cyclooxygenase products was also reduced by DEC. These data suggest that the mechanism by which DEC lowers the level of microfilariae in the circulation may in part involve its effects on host endothelial and parasite eicosanoid production.

Animals↗

PubMed1989

Hematologic effects of short-term oral diethylcarbamazine treatment given to chronically feline leukemia virus-infected cats.

Diethylcarbamazine (N,N-diethyl-4-methyl-1-piperazine carboxamide [DEC]) is widely used, especially in tropical regions, to prevent and treat filariasis. The antifilarial effect of this drug has been attributed to immunomodulation. Evidence is accumulating to indicate that DEC may mitigate the course of feline leukemia virus infection (FeLV) in cats. Previous studies have suggested that continuous oral DEC treatment given shortly after evidence of FeLV infection prevents or delays lymphopenia and prolongs survival. The present study focuses on the hematologic effects of one month oral DEC treatment given to adult chronically FeLV-infected cats and uninfected cats as compared to untreated FeLV-infected cats. Such treatment frequently resulted in abruptly lowered peripheral lymphocyte counts in chronically FeLV-infected cats. Further studies are warranted to evaluate whether administration of DEC could eliminate circulating retroviral-infected cells.

Adjuvants, Immunologic↗

PubMed1991

Influence of diethylcarbamazine and mefloquine on PGI2 synthesis by the rat thoracic aorta and myometrial tissues.

1. The influence of the antifilarial drug diethylcarbamazine citrate (D) and DL-erythro mefloquine hydrochloride (Mf) on PGI2 synthesis by the male rat thoracic aorta and day-20 pregnant rat myometrium was investigated in vitro using a rat platelet antiaggregatory bioassay method. 2. Pretreatment of the tissues with D (25.5-204 microM) or Mf (24-192 microM) for 30 min at 37 degrees C significantly inhibited PGI2 synthesis in a concentration-dependent manner. 3. D exhibited its inhibitory effect even in presence of exogenous arachidonic acid (AA) (16.6 microM) whereas Mf lost its inhibitory effect in presence of AA. 4. Pretreatment of urethane-anaesthetized rats with D (32 mumol kg-1) but not Mf (7.5 mumol kg-1) for 30 min significantly antagonized AA (4 nmol kg-1)-induced hypotension. 5. Furthermore, D (0.25-0.5 microM) antagonized AA-induced aggregation in rabbit platelet-rich plasma without affecting that of ADP. 6. D seemed to interfere with the action of the PG endoperoxide synthase (PG cyclooxygenase) whereas Mf seemed to interfere with the action of phospholipase A2 (PLA2) enzyme. 7. D may have exerted its effect via release of toxic O2 radicals whereas Mf effect may have been due to an interaction with PLA2 substrate phospholipids. 8. The demonstrated inherent property of these two drugs to inhibit the synthesis of the potent vasodilator, platelet antiaggregatory, anticonvulsant and antiinflammatory mediator PGI2 may partly contribute towards better understanding of the biochemical mechanisms that underly some of the previously known but poorly understood actions of these drugs.

Adenosine Diphosphate↗

PubMed1988

Genotoxic potential of diethylcarbamazine, an antifilarial drug.

The mutagenic potential of diethylcarbamazine (DEC) was evaluated by metaphase chromosome analysis and the micronucleus test in bone marrow cells of mice. Both assay systems revealed clastogenicity, although not severe. The time-response study of metaphase chromosomes exhibited an early effect; at 72 h post-treatment the effect came down to the control level. The dose-response analysis showed significantly elevated frequencies of micronuclei (MN) for all the doses tested, but failed to show any influence of the dose on the induction of MN. Data on mitotic index (MI) indicated a lack of cell cycle inhibition. The decrease in aberration frequency with the lapse of time can be probably attributed to the elimination of the drug and its metabolites from the body.

Administration, Oral↗

PubMed1996

Determination of diethylcarbamazine, an antifilarial drug, in human urine by 1H-NMR spectroscopy.

1H-NMR spectroscopy is a convenient method for determination of diethylcarbamazine (DEC) in urine, and can be used to monitor medication with the drug. Urine samples were mixed with 10% of deuterium oxide as a spectrometer field frequency lock, which is the only sample pretreatment required. Tailored excitation with the 1331 pulse was used for water peak suppression. The quantification of DEC was carried out with the triplet of the N-ethyl group, for which the T1 relaxation time was 1 s. In aqueous solutions, amounts below 1 microgram ml-1 of DEC could be easily detected. In urine, the detectability depended on the level of chemical noise but was better than 10 micrograms ml-1. The accuracy and precision of the method were better than 15%. Analysis of urine from volunteers receiving a single therapeutic dose of DEC (6 mg kg-1 body weight orally) showed that the drug was eliminated in unchanged form during 2 days, in agreement with earlier results. The concentration of DEC in urine several hours after the intake exceeded 100 micrograms ml-1 making the 1H-NMR assay rapid and easy. No significant amounts of the N-oxide of DEC could be detected.

Diethylcarbamazine↗

PubMed2005

The ultrastructure of infective larvae (L3) of Wuchereria bancrofti after treatment with diethylcarbamazine.

Although the large use of diethylcarbamazine (DEC), as the major anti-filaricide drug, its mechanism of action remains a matter of controversy. Several authors defend the hypothesis that DEC has no direct effect on nematodes. This study demonstrated that infective larvae (L3) of Wuchereria bancrofti treated in vitro with DEC presented several behaviour and morphological changes. The first alteration produced by treatment for 2 h with 3, 5, 10 microg/ml of DEC was the reduction of motility. Larvae treated with 5, 10 microg/ml DEC showed severely affected organelles, formation of several vacuoles, mainly in neurocytes and in the muscle cells, and dissolution of cytoplasm. Some larvae showed extreme cellular disorganization with abundance of large and dense mitochondria and numerous large vacuoles containing residual organelles. Lamellar bodies, probably related to an assembly of hipodermal membranes, were also observed in some damaged larvae. Thus, undoubtedly in vitro treatment with concentrations of DEC similar to therapeutic conditions, which are 1-5 microg/ml (Hawking, 1979), had a direct effect on infective larvae of W. bancrofti by causing, primarily neuromuscular alterations with subsequent damage to organelles.

Animals↗

PubMed2005

Some morphological aspects of Wuchereria bancrofti uterus after treatment with diethylcarbamazine.

Confocal and EM analyses revealed that some female Wuchereria bancrofti, obtained from volunteers that received recommended diethylcarbamazine dose regimens, showed few or no embryos. Furthermore, inside the gravid uterus of female W. bancrofti treated with DEC we observed a finely granular, electron-dense material organised as strings of pearls, approximately 70 nm in maximal length surrounding intra-uterine microfilariae and apparently secreted by the embryo. Over the eggshells a similar material was also observed, possibly secreted by the uterine wall. The surface of intra-uterine microfilariae presented a material with identical electron-density to the scattered structures observed inside the egg. Similarly, the sheath of blood microfilariae of W. bancrofti also showed electron-dense projections, with shape and size similar to that observed inside the uterus.

Animals↗

PubMed2005

Differential effects of diethylcarbamazine, tetracycline and the combination on Brugia pahangi adult females in vitro.

Anti-filarial effects of diethylcarbamazine (DEC), tetracycline (TC) and the combination on Brugia pahangi adult females were studied in 7-day cell-free culture, in terms of microfilaria release, parasite motility, MTT assay for parasite viability and embryogram. TC 50 microg/ml (TC50) effectively reduced microfilaria release from day 1 of culture. Combined with DEC 100 microg/ml (DEC100) or DEC 500 microg/ml (DEC500), microfilaria release reduced further and synergistically. TC50 also reduced motility, but DEC100 and DEC500 did not. The combination of TC50 and DEC500 reduced motility synergistically. The MTT assay supported the results of motility study in general. The embryogram showed that only DEC500 reduced the total number of intrauterine embryos, especially ova, indicating that DEC500 inhibited early embryogenesis. TC50 did not affect the total number of embryos, but resulted in apparent accumulation of microfilariae in the uterus, suggesting that the drug inhibited release of microfilariae in this in vitro system. These results clarified different anti-female mechanisms between DEC and TC. A PCR-based study showed that endosymbiont bacteria, Wolbachia, in B. pahangi females decreased significantly after TC treatment. However, this study could not determine whether the effects of TC were direct or Wolbachia-mediated.

Animals↗

PubMed2006

Impact of single dose of diethylcarbamazine and other antifilarial drug combinations on bancroftian filarial infection variables: assessment after 2 years.

The impact of single dose mass drug administration of diethylcarbamazine (DEC), DEC with albendazole (ALB), and ivermectin (IVR) with albendazole, was examined on the human bancroftian filarial infections in village scale trials in south India, from a follow-up study after 2 years. The treatment arms administered with DEC alone and DEC+ALB demonstrated long-term benefits in reducing microfilaraemia significantly (P<0.05), while antigenaemia reduction was negligible. The arm with ALB+IVR did not show such reductions. Among the antigenaemic and microfilaraemic individuals, 87% became amicrofilaraemic in DEC+ALB arm, which were higher than that observed in the other 2 treatment arms. Among amicrofilaraemics (but Ag+), nearly 35% cleared of infection in DEC+ALB, while 26% and 6% in DEC alone and IVR+ALB arms, respectively. The drug combination DEC+ALB was observed to demonstrate a significant impact in reducing filarial infection even after 2 years post treatment.

Albendazole↗

PubMed2006

Morphological changes in the testis induced by diethylcarbamazine.

Diethylcarbamazine (DEC) had been proved to be highly effective against lymphatic filariasis, however its effect on vertebrate cells remains uncertain. After 12 days treatment with DEC, most of the Leydig cells were hypertrophied with several lipid droplets, and others had no nucleus and presented characteristic steatosis features. Vacuolization of Sertoli cells was also noted. Ultrastructural analyses of DEC-treated testes revealed spermatogonies with morphological characteristics of apoptosis, as shrinkage of cytoplasm and increased chromosomal density. In addition, Leydig cells showed numerous lipid droplets scattered throughout the cytoplasm, multivesicular bodies and giant whorl-like smooth endoplasmic reticulum. Several spermatids presented vacuolated mitochondriae, which were disorganized in relation to the microtubular axis of the flagellae. These results indicate that DEC probably affects the microtubular function, however the present data does not exclude the possibility that DEC also can act directly on enzymatic hormonal pathways.

Administration, Oral↗

PubMed2004

Long-term effect of three different strategies for mass diethylcarbamazine administration in bancroftian filariasis: follow-up at 10 years after treatment.

The long-term effect of three different strategies for mass diethylcarbamazine (DEC) administration in bancroftian filariasis was assessed 10 years after start of treatment in three endemic communities in Tanzania. The strategies were the standard 12 day treatment (strategy I); a semi-annual single-dose treatment (strategy II); and a monthly low-dose treatment (strategy III). Treatment was given only during the first year. Following reductions immediately after treatment, overall community microfilaraemia levels were approaching pre-treatment levels in all three communities, 10 years later. In individuals who were microfilaria-positive and treated at baseline, the treatment had a long-term effect on microfilarial intensities, with geometric mean intensities being only 11%, 13% and 2% of pre-treatment levels 10 years later for strategies I, II and III, respectively. This suppressive effect was most pronounced for strategy III, which also cleared microfilaraemia and circulating filarial antigenaemia in a larger proportion of treated individuals than the other strategies. Most of the follow-up individuals who developed microfilaraemia between 2 and 10 years after start of treatment had also been microfilaraemic before treatment, suggesting that reappearance of microfilaraemia may be due to surviving female worms and/or that previously microfilaraemic individuals have a higher chance of reinfection than previously amicrofilaraemic individuals.

Adolescent↗

PubMed2006

Efficacy of co-administered diethylcarbamazine and albendazole against adult Wuchereria bancrofti.

Although diethylcarbamazine (DEC) and albendazole are recommended to interrupt transmission of Wuchereria bancrofti, little is known about the macrofilaricidal effect of this drug combination. Forty-seven men with W. bancrofti infection were randomly assigned to receive a single dose of either DEC alone (6 mg/kg) (n=25) or a combination of DEC (6 mg/kg) and albendazole (400 mg) (n=22). Physical examinations for scrotal nodules (resulting from worm death) and ultrasound examinations (to detect living adult worms) were performed before treatment and 7, 14, 30, 45, 60, 90, 180, 270 and 360 days after treatment. Blood was examined for microfilariae before and 30 days and 360 days after treatment. Seven days post treatment, intrascrotal nodules were detected at the site of 21 (46.7%) adult worm nests in men who received DEC alone compared with 2 (6.1%) sites in men who received DEC and albendazole (P=0.002). One year after treatment, 10 (22.2%) original adult worm nests remained detectable by ultrasound among men who received DEC alone compared with 18/32 (56.3%) nests among men who received both drugs (P=0.016). Microfilaraemia prevalence and density decreased to a similar extent in both groups. Addition of albendazole appeared to decrease the macrofilaricidal effect of DEC against W. bancrofti, with no detectable enhancement in microfilarial suppression.

Adolescent↗

PubMed2006

Changes in Wuchereria bancrofti infection in a highly endemic community following 10 rounds of mass administration of diethylcarbamazine.

Mass drug administration (MDA) is the principal strategy of the programme to eliminate lymphatic filariasis (LF). Evaluation of MDA in highly endemic 'sentinel' communities is necessary to understand its impact on LF infection. This study examined the changes in Wuchereria bancrofti infection following 10 rounds of annual mass administration of diethylcarbamazine (DEC) in a highly endemic community. The mean number of DEC treatments received per adult in the community was 7.4+/-2.0. Following 10 rounds of DEC administration, the number of microfilaria (mf) carriers fell from 565 to 55. None of the pre-MDA amicrofilaraemic individuals showed circulating filarial antigen (CFA). However, 54.5% of the pre-MDA microfilaraemic individuals were positive for CFA. All the pre-MDA high intensity mf carriers continued to be positive for CFA, and some of them also showed blood mf. These patients are the most difficult to be cured by MDA and were distributed in 8.2% of the households. All the children born during the last 7 years of the MDA programme were negative for CFA. The study suggests that six to seven DEC treatments per individual suppresses microfilaraemia, except in some people with heavy infection, and repeated MDA has very good potential to prevent infection in children.

Adult↗

PubMed2001

A high performance liquid chromatographic method for the estimation of diethylcarbamazine content in medicated salt samples.

A simple and reproducible method for the estimation of diethylcarbamazine citrate (DEC) by high performance liquid chromatography (HPLC) in DEC-medicated salt was developed. HPLC analysis was conducted with a mobile phase containing acetonitrile/phosphate buffer (20 mM KH(2)PO(4,) adjusted to pH 3.2 with 10% ortho-phosphoric acid) in the ratio of 1:9 and at a flow rate of 1.5 ml/min. A Phenomenex C8 column (15 cmx4.6 mm) of 5 microm particle size was used for the analysis. Analysis was done at UV 210 nm, 0.02 a.u.f. and 40 degrees C. The coefficient of variation was <10% in the range of 1-25 microg/ml and the minimum detectable level was 0.5 microg/ml. The quality of DEC-medicated salt prepared by two methods was analyzed by using the HPLC method. In spray drying method, 29 and 71% of the samples and in rotating drum method, 9 and 12% of samples were found to contain DEC at 0.15-0.25% and >0.25%, respectively. Thus, this quick and simple HPLC method for the estimation of DEC could play a vital role in checking the quality of the DEC medicated salt used for the control of filariasis.

Animals↗

PubMed1978

[Gas chromatographic determination of diethylcarbamazine (Hetrazan) in serum of laboratory rodents (author's transl)].

After chloroform extraction in an alkaline solution, diethylcarbamazine (DEC) is measured in the presence of dipropylacetamid (internal standard), treated in the same manner, by a gas chromatographic procedure using a nitrogen detector in a 10% BDS column. Results can be easily reproduced for analysis of DEC in sera up to levels of 10 mg/1 and sensibility allows determination of approximately 0.5 mg/l levels on 50-microliter samples of serum. This method is suitable for pharmacokinetic studies.

Animals↗

PubMed1997

Respiratory mechanics after chronic diethylcarbamazine.

This study was performed to evaluate the role of diethylcarbamazine (DEC), the drug of choice for treating Lymphatic Filariasis and Tropical Pulmonary Eosinophilia, on respiratory mechanics of higid rats. Thus, during 30 days two groups of six rats each received intraperitoneally either isotonic saline solution, or 12 mg/kg per day of DEC. Thereafter, they were sedated, anesthetized, paralysed and mechanical ventilation followed. After airway occlusion at end inspiration, respiratory system, pulmonary and chest wall resistive pressures (delta P1,rs, delta P1,L, and delta P1,w, respectively) and viscoelastic/inhomogeneous pressures (delta P2,rs, delta P2,L and delta P2,w, respectively) were determined in each group. Total delta pressures (delta Ptot) were calculated as the sum of delta P1 and delta P2, yielding the values of delta Ptot,rs, delta Ptot,L, and delta Ptot,w, respectively. Respiratory system, lung and chest wall static (Est,rs, Est,L, and Est,w, respectively) and dynamic elastances (Edyn,rs, Edyn,L, and Edyn,w, respectively), and the corresponding delta elastances (calculated as Edyn-Est) were also obtained. DEC therapy significantly decreased delta Ptot,rs, delta P tot,L, delta P2,rs, delta P2,L, Est,ts, Est,L, delta Ers and delta EL, in relation to the respective control values. It can be concluded that DEC decreases respiratory system impedance, being potentially useful for allowing airway dilation at the lung periphery.

Airway Resistance↗