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PubMed1999

Albendazole therapy for loiasis refractory to diethylcarbamazine treatment.

Although diethylcarbamazine is curative in approximately 60% of patients who acquire loiasis as long-term visitors to an endemic area, some individuals continue to have signs and symptoms of infection despite multiple courses of diethylcarbamazine. On the basis of a study of albendazole treatment of loiasis in microfilaremic patients that suggested a macrofilaricidal effect of the drug, we treated three patients who had symptomatic loiasis refractory to more than four courses of diethylcarbamazine with albendazole. At the time of treatment, all patients had persistent symptoms despite decreasing titers of antifilarial antibodies and normal eosinophil counts. Symptoms resolved in all three patients following albendazole therapy. In one patient, nonspecific symptoms recurred 2 years later, but unlike her symptoms before albendazole therapy, they were not accompanied by the appearance of subcutaneous nodules containing adult worms. The other two patients have been symptom-free in the 8 years after albendazole treatment. In summary, albendazole may be useful for the treatment of loiasis when diethylcarbamazine is ineffective or cannot be used.

Adult↗

PubMed1983

Diethylcarbamazine citrate, an antifilarial drug, stimulates human granulocyte adherence.

Incubation with diethylcarbamazine citrate caused significant augmentation of human neutrophil and eosinophil adherence to tissue culture plastic. This effect was dose dependent and cell dependent, with eosinophils showing greater sensitivity and a greater adhesive response to the drug than did neutrophils. Eosinophils preincubated with diethylcarbamazine citrate demonstrated decreased adhesive responses to other adherence-augmenting stimuli. Use of Fc-treated plastic augmented diethylcarbamazine citrate-stimulated neutrophil (but not eosinophil) adherence. Direct stimulation of host effector cell adherence may explain, in part, the therapeutic action of diethylcarbamazine citrate in vivo.

Cell Adhesion↗

PubMed2000

Pharmacokinetics of diethylcarbamazine: prediction by concentration in saliva.

The concentration of diethylcarbamazine in saliva was used to determine pharmacokinetic parameters, in comparison to plasma and urine concentrations. Six healthy adult male volunteers were administered 150 mg diethylcarbamazine with 400 ml of water. At seven different time intervals, blood, urine and saliva samples were taken, and different pharmacokinetic parameters measured. The plasma-saliva concentration ratio was calculated as 1.53 whereas the observed ratio was 3.82. The half lives, times to reach peak plasma concentration, and elimination rate constants did not show any significant difference in the different samples. The plasma peak concentration and areas under the curve were significantly (p<0.05) increased from those of the saliva. At 24 h, when diethylcarbamazine was absent in urine, the plasma and saliva concentrations were almost zero. Diethylcarbamazine is secreted in saliva, and its concentration in saliva can be used to monitor drug therapy.

Adult↗

PubMed1988

Persistence of parasite antigenemia following diethylcarbamazine therapy of bancroftian filariasis.

This study was designed to reexamine the efficacy of diethylcarbamazine for bancroftian filariasis with special reference to changes in serum parasite antigen levels and antifilarial antibody titers after treatment. Patients with asymptomatic microfilaremia were treated with 6 mg/kg diethylcarbamazine daily for 12 days. Microfilaria counts fell dramatically after treatment, as expected. IgG antibody titers to adult and microfilarial antigens of B. malayi were increased 1 month after treatment in most patients. Titers fell slowly to or below pretreatment levels, but remained positive during subsequent months. Parasite antigen levels, measured by monoclonal antibody-based enzyme immunoassay, decreased to 72%, 58%, 53%, and 48% of pretreatment values 1, 3, 6, and 12 months after diethylcarbamazine treatment, respectively. Parasite antigen levels decreased similarly in subjects with and without residual microfilaremia after treatment. These results suggest that diethylcarbamazine has only partial macrofilaricidal activity against W. bancrofti with this dosage schedule. The sustained, impressive reductions in microfilaria counts after treatment despite significant persistence of parasite antigenemia may be explained by sublethal effects of the drug on adult worms. We believe that parasite antigen detection represents a valuable new approach for monitoring the efficacy of antifilarial drug therapy which we hope will lead to improved use of existing drugs and aid in the evaluation of new drugs for filariasis.

Animals↗

PubMedDate not supplied

Experimental filariasis of Dipetalonema dessetae in Proechimys oris: 3. Effects of parasitism on the pharmacokinetics of diethylcarbamazine.

The pharmacokinetic parameters of diethylcarbamazine were compared in the plasma and peritoneal fluid of 5 non-infected rodents. In the filarial animals, the absorption rate constant and the elimination rate constant were significantly increased. The peak plasma concentration was twofold higher in the infested rodents than the control animals, and this may account for the rapid action of diethylcarbamazine on blood-circulating microfilariae. The area under the curve was unchanged. Total clearance is slightly increased in filarial rodents. These data are explained by an important reduction of renal clearance combined with a moderate increase of extra renal clearance. High levels of diethylcarbamazine in peritoneal fluid, resulting from the excellent diffusion of the drug in filarial animals explains the activity on adult worms. But the parasitism does not affect the mechanism of distribution of the drug between plasma and peritoneal liquid.

Animals↗

PubMed1986

Dirofilaria immitis: diethylcarbamazine-induced anaphylactoid reactions in infected dogs.

The immunopathogenesis of the anaphylactoid Mazzotti reactions has been studied by comparing physiologic and immunologic aspects of diethylcarbamazine-induced shock in Dirofilaria immitis infected dogs with antigen induced anaphylaxis in infected and uninfected controls. Filarial antigen, specific host IgG antibody, and C1 and C3 complement levels were quantitatively measured over time in relation to the levels of histamine and prostaglandin D2 in the blood and changes in mean blood pressure. D. immitis antigen injected into uninfected dogs having no detectable IgG antibody to D. immitis or Toxocara canis produced a rapid drop in blood pressure that paralleled a drop in C1 and C3 levels and an increase in prostaglandin D2. Antigen injected into infected dogs with IgG antibody produced a similar drop in blood pressure and complement and increase in prostaglandin D2 which differed from the uninfected group only in the slower clearance of antigen from the blood. Diethylcarbamazine alone produced no measurable changes in blood pressure or complement in uninfected hosts. Diethylcarbamazine, however, administered into skin test positive infected dogs, produced a temporally slower but quantitatively similar loss in blood pressure, drop in complement, and increase in prostaglandin D2 and histamine to that induced by antigen injection. Complement activation and immune complex formation are initiated by antigen release, and subsequent vasoactive mediator release leads to shock with prostaglandin D2 being quantitatively higher in blood than is histamine.

Airway Resistance↗

PubMedDate not supplied

Serum-dependent interaction of granulocytes with Onchocerca volvulus microfilariae in generalized and chronic hyper-reactive onchocerciasis and its modulation by diethylcarbamazine.

The adherence and cytotoxicity of granulocytes to microfilariae of Onchocerca volvulus were examined in vitro. Reactivity and modulation by diethylcarbamazine of isolated eosinophilic and neutrophilic granulocytes from patients with generalized and chronic hyper-reactive onchocerciasis (sowda or localized form) from endemic foci in Liberia were evaluated under varying serum conditions. In the presence of pooled sera from patients with generalized onchocerciasis granulocytes from both polar groups of patients exhibited similar adherence rates, whereas immobilization rates were higher for eosinophils than for neutrophils. In localized onchocerciasis, the use of autologous serum resulted in a significant decrease in adherence and immobilization rates for both eosinophils and neutrophils. After preincubation of eosinophils, but not of microfilariae, with diethylcarbamazine autologous serum-mediated adherence and cytotoxicity were enhanced to rates similar to those found with pooled serum from individuals with generalized onchocerciasis. These results suggest that granulocytes from both forms of onchocerciasis did not differ with respect to their anti-parasitic reactivity and that antibodies as well as additional serum factors appear to contribute to the functional activity of these effector cells. The findings indicate that predominantly eosinophils, compared to neutrophils, damage the larvae of O. volvulus and support earlier observations which suggest that diethylcarbamazine influences the effector cells rather than the parasite itself.

Adolescent↗

PubMed1988

Effect of diethylcarbamazine on serum antibodies to feline infectious peritonitis in cats.

In preceding studies by the author, use of the immunomodulator drug diethylcarbamazine resulted in the detection of antibodies to feline oncornavirus-associated cell membrane antigen in nine feline leukaemia virus infected cats that had previously given negative results to this antibody. In the present report, seven diethylcarbamazine-treated cats developed higher serum antibody titres to feline infectious peritonitis more frequently than did seven untreated controls. Since feline infectious peritonitis is caused by a coronavirus, these results suggest that diethylcarbamazine treatment could be exploited for vaccination and treatment strategies for non-retroviral in addition to retroviral infections.

Animals↗

PubMed1992

Kinetics of circulating human IgG4 after diethylcarbamazine and ivermectin treatment of bancroftian filariasis.

Patent filarial infections are associated with elevated levels of parasite-specific IgG4. This study investigated the shifts of filarial-specific human IgG and IgG4 antibodies after diethylcarbamazine and ivermectin treatment of bancroftian filariasis. Thirty adult Haitians were treated first with a 1-mg clearing dose of ivermectin and then with either one or two 200-micrograms/kg doses of ivermectin or with 12 daily 6-mg/kg doses of diethylcarbamazine. Posttreatment levels of antifilarial IgG4 were dependent on both treatment group and time of follow-up. IgG4 increased markedly to a maximum by day 30 in all treatment groups and then began to decrease; the greatest decrease was among diethylcarbamazine-treated patients. Posttreatment microfilaremia was inversely correlated with the decrease in IgG4; thus, shifts in IgG4 were associated with treatment response for all groups. Antifilarial IgG levels were not correlated with drug treatment and did not change to the same degree as did IgG4 responses.

Animals↗

PubMed2006

Model-based analysis of trial data: microfilaria and worm-productivity loss after diethylcarbamazine-albendazole or ivermectin-albendazole combination therapy against Wuchereria bancrofti.

OBJECTIVES: To determine the efficacies of combinations of ivermectin or diethylcarbamazine and albendazole, which are recommended for use in mass treatment programmes against lymphatic filariasis. METHOD: Review of published trends in microfilarial (mf) intensities after treatment with these combination therapies. By fitting a mathematical model of treatment effects to the trial data, we quantified the efficacy of treatment, distinguishing between the killing of mf (mf loss) and a reduction in mf production by adult worms (worm-productivity loss). After diethylcarbamazine-albendazole treatment mf density dropped immediately, then slowly but steadily decreased further (four trials). After ivermectin-albendazole treatment, mf densities immediately dropped to near-zero levels, followed by a small increase (five trials). For diethylcarbamazine-albendazole treatment the average mf loss was approximately 83% (ranging from 54% to 100% in the different studies) and worm-productivity loss was 100% (in all studies). For ivermectin-albendazole treatment, average mf loss was 100% (ranging from 98% to 100%) and worm productivity loss was 96% (ranging from 83% to 100%). The effects were dose-dependent. Sensitivity analysis showed that the estimates did not depend on assumptions on worm lifespan or premature period and little on assumptions on mf lifespan. CONCLUSION: The two therapies differ with respect to their direct effect on mf, but both are highly effective against adult worms. If mass treatment with these combination therapies achieves high coverage, they can have a large impact on lymphatic filariasis transmission.

Adolescent↗

PubMedDate not supplied

[Diethylcarbamazine in the treatment of Bancroft's filariasis].

The authors presented a detailed review about the treatment of bancroftian filariasis with diethylcarbamazine. The interesting aspects about the drug discovery and the basic concepts about its pharmacology were reported in a summarised form. On the other hand, emphasis was made about the speculation done by several authors about the intriguing findings regarding its efficacy reported in the literature. Latter, it was brought the new advances about the disease, as for example, the visualization by ultrasound of living Wuchereria bancrofti adult worm on its natural host--the human being. This made possible the comprehension of several paradoxical issues reported, focusing the treatment of infection using diethylcarbamazine. So far, because of the lack of ideal drug with micro and macrofilaricidal properties, together with the new understand about the disease and the new parameters for monitoring the efficacy of the drug, diethylcarbamazine has back its importance conquered at the begin of its discovery, almost fifth years ago.

Animals↗

PubMedDate not supplied

Efficacy of mass single-dose diethylcarbamazine and DEC-fortified salt against bancroftian filariasis in Papua New Guinea six months after treatment.

The efficacy of two diethylcarbamazine (DEC) treatment strategies to control bancroftian filariasis, diethylcarbamazine-fortified salt (DEC-FS) and a single DEC dose on mass administration, was evaluated in two communities in Papua New Guinea with pretreatment antigen prevalence of 55% and 71%. In the first community 0.2% w/w diethylcarbamazine-fortified salt was distributed monthly to accepting households at no cost for 12 months. In the second community a single DEC dose based on body size but designed to give about 6 mg/kg was administered to eligible acceptors. Despite wide variation in antigen prevalence among study villages there were marked reductions in prevalences under both treatment strategies. Among individuals antigenaemic on day 0, DEC-FS and a single DEC dose gave filaria antigen clearance rates of 43% and 13%, respectively. In the salt-treated community the incidence of antigenaemia after 6 months in acceptors from households that received 5 kg or more of DEC-FS was 14% whereas in those receiving less than 5 kg salt was 4%. The incidence rates in the second community in those that received < 2.5 and > or = 2.5 tablets were 16% and 8%, respectively. The two treatment strategies were simple to manage and appropriate for developing countries and were widely accepted. DEC-FS was more efficacious than single-dose DEC tablets but a single administration of DEC tablets is easier to administer.

Adolescent↗

PubMedDate not supplied

Daily diethylcarbamazine for the treatment of Brugia malayi microfilaria carriers.

BACKGROUND: Diethylcarbamazine is effective for the treatment of brugian filaria carriers. However, the 12-day course with a daily dose of 6 mg per kg body weight is rarely completed. The World Health Organization has indicated the need for better regimes to control filariasis. METHODS: We evaluated the long term effects of three different dosage regimes of diethylcarbamazine--6, 9 and 12 mg per kg body weight--to a total of 72 mg on 93 microfilaria carriers of Brugia malayi. RESULTS: All cases treated with the 6 mg daily dose showed complete clearance of microfilaria immediately after the treatment. However, at the 9 and 12 mg daily doses only 91% and 85% of cases respectively showed complete clearance. There was a close association between the daily dose and the proportion of cases developing side-effects. The mean initial microfilaria counts were significantly higher in those who had side-effects than in those who did not. An 11-month follow up showed that with the 6 mg daily dose the recurrence rate of microfilaraemia was 29% while with the 12 mg daily dose it was 67%. Four per cent of patients on a daily dose of 6 and 9 mg discontinued treatment while 21% of those on the 12 mg daily dose did so. CONCLUSION: The 6 mg daily dose of diethylcarbamazine was the most effective and best accepted regime.

Adolescent↗

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↗

PubMed1967

Control of Bancroftian filariasis by cooking salt medicated with diethylcarbamazine.

In small-scale pilot trials, filarial infection can usually be reduced to low levels by oral administration of diethylcarbamazine to all the persons concerned; but in mass campaigns it is often difficult to persuade large numbers of people to swallow the tablets. In order to overcome this difficulty the authors propose that the compound be incorporated into cooking salt, as has been done with chloroquine to control malaria. There are many reasons why this method of medication should be more effective against filariasis than it has often been against malaria.Laboratory trials showed that cooking the compound in food did not make it toxic for rats or diminish its antifilarial activity. A pilot trial was carried out at Recife, Brazil, in which 1000 adults received salt containing 0.4% diethylcarbamazine (corresponding to a daily intake of 100 mg/day) for 40 days, and then salt containing 0.1% compound for a year. This medication was simple to administer; it was quite acceptable to the subjects; it caused no untoward effects; and it removed almost all the microfilariae from the blood. Administration of medicated salt (0.3%) for 18 days to another group of 1300 adults was well tolerated and produced a considerable reduction of the microfilarial load; but this short period was insufficient to remove all the microfilariae.The authors recommend that this method of administering diethylcarbamazine to large numbers of people should be investigated further to see if it could be used for mass campaigns to control filariasis.

Adult↗

PubMed1969

The effect of salt medicated with diethylcarbamazine in bancroftian filariasis.

The paper describes a trial conducted in Tanzania of the effect on bancroftian microfilaraemia of common salt medicated with diethylcarbamazine at a 0.1% (w/w) concentration, when given to a closed population of 600-700 with a known salt intake.After good observer agreement in microfilarial counting had been demonstrated, quantitative blood surveys were performed monthly on known carriers. Paired pretreatment microfilarial counts from the same patients at an interval of 4 months suggested a natural fluctuation in microfilarial densities and emphasized the need for parallel concurrent controls during treatment.During the trial the mean microfilarial densities fell steadily, being reduced by 73% at 3 months and 90% after 6 months. Tolerance to the drug-salt mixture was extremely good.Problems of planning, salt preparation and assessment of results are discussed and the importance of correct experimental design in future trials is stressed. The authors suggest that a trial of salt containing 0.2% (w/w) diethylcarbamazine may achieve optimum results. They point out that, while the use of diethylcarbamazine-medicated salt may prove useful in reducing transmission in closed communities or in endemic areas with no alternative source of salt, its extension to national populations as a sole means of bancroftian filariasis control would be of problematical value.

Diethylcarbamazine↗

PubMed1981

Serum microfilarial antibody titres before and after treatment of bancroftian microfilaraemia with diethylcarbamazine.

Eight Filipino patients with Wuchereria bancrofti microfilaraemia were treated with diethylcarbamazine. The intensity of microfilaraemia and titre of microfilarial agglutinating antibodies were measured over the ensuing six weeks. Nuclepore filtration of blood indicated clearing of microfilaraemia in five patients and a reduction in numbers in the other three. Several patterns of antibody response were observed. Five patients had high initial antibody titres; they did not change significantly after diethylcarbamazine therapy. Antibody was not detectable before treatment in three patients; elimination of microfilaraemia was associated with the appearance of antibody in two of the subjects, while microfilariae were not totally cleared and antibodies never appeared in the third patient. This study confirms that diethylcarbamazine is not always successful in the treatment of bancroftian microfilaraemia. It is consistent with, but does not prove, the hypothesis that the presence or absence of microfilariae and microfilarial antibodies depends upon the relative release of microfilariae into the bloodstream and the rate of synthesis of microfilarial antibodies.

Antibodies↗

PubMed1982

Diethylcarbamazine-enhanced activation of complement by intact microfilariae of Dirofilaria immitis and their in vitro products.

Microfilariae of Dirofilaria immitis and their products inhibited hemolytic complement in sera from various animal species. Inhibition of hemolytic complement activity, fluorescent antibody detection of specific complement proteins binding to microfilarial surfaces, and immunoelectrophoretic evaluation of complement protein C3 conversion demonstrated that (1) intact microfilariae depleted hemolytic complement activity maximally in the presence of diethylcarbamazine whereas the complement-fixing activity of microfilarial products was little affected by diethylcarbamazine; (2) complement proteins C3, properdin, and C5 bound to the cuticular surface of microfilariae; and (3) C3 was converted to a faster-migrating species during incubation with microfilariae or their products. The complement-depleting activity of in vitro products from viable microfilariae was soluble in 10% trichloroacetic acid, resistant to beta-elimination with 0.5 M NaOH, susceptible to treatment with 0.2 M periodate, and composed of 56% neutral sugar, 18% protein, 12% hexosamine, and 10% sulfate. The polysulfated, acidic mucopolysaccharide nature of the surfaces of microfilariae and the results presented here indicate that polyanionic components on worm surfaces or shed by microfilariae react with host complement proteins. This interaction may be enhanced by diethylcarbamazine and contribute to the pathology associated with microfilaremias.

Animals↗