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PubMed1999

Efficacy of albendazole and its combinations with ivermectin or diethylcarbamazine (DEC) in the treatment of Trichuris trichiura infections in Sri Lanka.

The efficacy of the drugs currently available for treatment of infection with Trichuris trichiura is low compared with that of the drugs used against roundworm and hookworm. Single-dose combinations of albendazole with ivermectin or of albendazole with diethylcarbamazine (DEC) have recently been seen to produce raid and sustained reductions in Wuchereria bancrofti microfilaraemia. This observation prompted the present study, on the efficacy of these combinations against trichuriasis. The drug regimens tested were albendazole (400 mg) alone, albendazole (400 mg) with ivermectin (200 micrograms/kg), and albendazole (400 mg) with DEC (6 mg/kg). Most (155) of the 176 children (4-14 years of age) who each provided a single, pre-treatment, stool sample were found positive for Trichuris ova. These 155 were each randomly allocated to one of the three treatment groups and checked for infection 3 weeks post-treatment, again by a single stool examination. Single-dose therapy with albendazole plus ivermectin produced a 'cure rate' (79.3%) and an egg-reduction rate (93.8%) which were significantly higher than the corresponding rates produced by albendazole alone or albendazole plus DEC (P < 0.01 for each). The efficacies of albendazole with DEC and of albendazole alone were statistically equivalent. Single-dose treatment with the albendazole-ivermectin combination appears to be highly effective against trichuriasis and could prove valuable for routine use.

Adolescent↗

PubMed1999

A double-blind, placebo-controlled study of the efficacy of oral penicillin, diethylcarbamazine or local treatment of the affected limb in preventing acute adenolymphangitis in lymphoedema caused by brugian filariasis.

Acute attacks of adenolymphangitis (ADL) contribute significantly to the morbidity seen in cases of filarial lymphoedema. Such cases are now being treated with multiple courses of the antifilarial drug diethylcarbamazine (DEC), either alone or in combination with antibiotics or anti-inflammatory drugs, based on anecdotal experience. In this, the first double-blind, placebo-controlled study, 150 patients with lymphoedema caused by brugian filariasis, each of whom recalled two or more ADL attacks in the previous year, were enrolled on a comprehensive foot-care programme. Each was also randomly allocated to one of the following five daily regimens (30 patients/regimen) for 1 year: 800 mg oral penicillin; 1 mg DEC/kg; 800 mg oral penicillin plus 1 mg DEC/kg; local antibiotics; or placebo. Each patient was followed up for another year. For each regimen group (including the placebo group), the number of ADL attacks in the treatment year was significantly less than that in the year prior to treatment (P < 0.001). Although, in all but the placebo group, there was a slight increase in the number of episodes in the follow-up year compared with the treatment year, the increase was only significant in the two groups given penicillin. Of all the treatments tested therefore, foot care seems to play the most important role in the prevention of ADL attacks. Additional benefit may accrue from local or systemic antibiotic use in those with high grades of oedema, but antifilarials have no place in the prevention of ADL attacks in an individual patient. These observations should help in the rational management and prevention of ADL attacks in filarial lymphoedema, so that the progression of the disease may be halted and morbidity reduced.

Acute Disease↗

PubMed2003

Immunomodulator tuftsin augments antifilarial activity of diethylcarbamazine against experimental brugian filariasis.

In the present study, we evaluated the potential of an immunomodulator tuftsin in increasing the efficacy of liposomised diethylcarbamazine (DEC) against experimental filarial infection of Brugia malayi. The liposomised form of DEC, when used at sub-optimal dose of 25 mg/kg body weight, successfully eliminated filarial parasite from systemic circulation in animals inflicted with B. malayi infection. However, the formulation was effective upto 60 days post infection only, followed by recurrence of the infection. In contrast, the co-administration of liposomal formulation of DEC along with an immunomodulator tuftsin was found to be competent enough to suppress microfilarial stage of parasite till 90 days post treatment. Interestingly, tuftsin bearing DEC liposomes were found to be effective against adult parasite as well.

Adjuvants, Immunologic↗

PubMed1999

Eotaxin expression in Onchocerca volvulus-induced dermatitis after topical application of diethylcarbamazine.

In persons with onchocerciasis, topical application of the anthelminthic diethylcarbamazine (DEC) induces clinical and histologic responses similar to acute papular onchodermatitis, including recruitment of eosinophils to the skin. To determine whether the eosinophil chemokine eotaxin is likely to be associated with eosinophil recruitment in onchodermatitis, DEC was applied to a 5-cm2 area on the skin of infected persons, and biopsies were taken from lesions 24 h later. Histologic analysis showed elevated dermal and epidermal eosinophils compared with tissue from an adjacent (untreated) site. Reverse transcription-polymerase chain reaction showed that eotaxin gene expression in DEC-treated skin was elevated 2- to 17-fold compared with control tissue. Eotaxin immunoreactivity was noted in mononuclear cells and eosinophils in the perivascular region of the dermis and in lymphatic and vascular endothelial cells. Together, these observations are consistent with a role for eotaxin in recruitment of eosinophils to the dermis in early stage onchocercal skin disease.

Administration, Topical↗

PubMed2000

Strong association of interleukin-6 and lipopolysaccharide-binding protein with severity of adverse reactions after diethylcarbamazine treatment of microfilaremic patients.

To assess the involvement of inflammatory mediators in the development of adverse reactions in filarial patients undergoing treatment, 29 microfilaremic subjects were treated with diethylcarbamazine (DEC). Before and at serial time points after initiation of treatment, plasma levels of inflammatory mediators and DEC were measured, and adverse reactions were recorded. Patients experienced no or mild, moderate, or severe adverse reactions. Increasing pretreatment microfilarial counts were associated with escalating severity of adverse reactions. Plasma concentrations of DEC were not different among patients suffering from varying degrees of illness. Interleukin (IL)-6, IL-10, lipopolysaccharide-binding protein (LBP), and soluble tumor necrosis factor receptors (sTNF-Rs) increased after treatment. IL-6 and LBP, however, showed the strongest association with adverse reactions. Increasing levels of these molecules were closely correlated with the mounting severity of adverse reactions, which raises the possibility that they play an important role in systemic inflammation that arises after DEC treatment of filarial patients.

Acute-Phase Proteins↗

PubMed1996

Diethylcarbamazine-induced reversal of early lymphatic dysfunction in a patient with bancroftian filariasis: assessment with use of lymphoscintigraphy.

Exposure of expatriates to the infective larvae of Wuchereria bancrofti can result in the early development of signs of lymphatic obstruction. The findings on the clinical presentation of expatriates are distinct from the chronic pathological findings seen among the native population and are similar to the findings in experimentally infected persons. We report the case of a Peace Corps volunteer who developed acute lymphatic dysfunction within 3 months of arriving in an area that was endemic for filariasis. The diagnosis was established clinically and by demonstrating the presence of antibodies to recombinant proteins specific for patients with lymphatic filariasis. Lymphatic flow was markedly abnormal when assessed with use of 99mTc-lymphoscintigraphy. Treatment with diethylcarbamazine reversed both the physical and lymphoscintigraphic abnormalities.

Adult↗

PubMedDate not supplied

Efficacy of diethylcarbamazine in eradicating infection with lymphatic-dwelling filariae in humans.

Diethylcarbamazine (DEC) is an effective microfilaricidal drug against Wuchereria bancrofti, Brugia malayi, and Brugia timori--the three lymphatic-dwelling filariae infecting humans. However, effectiveness in killing the adult stage of these parasites has been more difficult to establish. The present review of available evidence from the literature suggests that: (1) in addition to being a microfilaricidal agent, DEC in conventional dosages effectively kills adult worms of these three parasites in many patients; (2) relatively high total dosages of DEC (including dosages considerably in excess of those currently recommended) generally give better long-term therapeutic results than lower dosages; (3) spaced doses of DEC (weekly or monthly) are more effective than the same total dosage given in consecutive daily doses; (4) chronic administration of low-dose DEC, as in medicated salt, can effectively control filariasis caused by W. bancrofti or B. malayi; and (5) rational determination of the DEC regimen ideal for the killing of adult filarial parasites awaits the development of assays capable of sensitively detecting the presence of living adult parasites.

Animals↗

PubMed1983

Ocular and systemic complications of diethylcarbamazine therapy for onchocerciasis: association with circulating immune complexes.

Diethylcarbamazine (DEC) therapy for Onchocerca volvulus infection results in frequent ocular and systemic complications, but the pathogenesis of these complications is unclear. Twenty men with O. volvulus infection were treated over a period of six months with DEC given daily for one week and weekly thereafter. Major systemic and ocular complications included proteinuria, severe pruritus, visual field constriction, optic nerve pallor, chorioretinitis, anterior uveitis, and punctate keratitis. Levels of circulating immune complexes (CICs) were increased (greater than 11% [125I]C1q binding) in 14 of the 20 men prior to treatment. Persons with pretreatment C1q binding activity of greater than 30% were at increased risk to develop constriction of visual fields (P less than 0.05) and proteinuria (P less than 0.015). Linear regression analysis revealed a striking correlation between pretreatment levels of CICs and the total number of both systemic and ocular complications (P less than 0.001) and ocular complications alone (P less than 0.005). These results suggest that CICs may be important in the pathogenesis of the delayed systemic and ocular complications following DEC therapy for O. volvulus infection.

Antigen-Antibody Complex↗

PubMed1991

Evidence of nonsusceptibility to diethylcarbamazine in Wuchereria bancrofti.

This study assessed Wuchereria bancrofti-infected patients who received diethylcarbamazine (DEC) to determined if drug levels were comparable between individuals who continued to harbor circulating microfilariae and those whose blood became clear of parasites, between those with high and low microfilaria counts, and between infected and noninfected persons. Haitian volunteers undergoing treatment for W. bancrofti and two nonendemic controls were enrolled. DEC levels in serum and urine samples were determined using a gas chromatographic method. No correlation was found between pre- and posttreatment microfilarial levels and drug levels. Drug levels were comparable in persons with or without residual microfilaria and in infected and uninfected persons. These results indicate that incomplete drug regimens, differences in serum drug levels, and inadequate drug dosage are not the primary causes of treatment failure and suggest there is a degree of parasite tolerance for DEC.

Animals↗

PubMed1991

Changes in circulating parasite antigen levels after treatment of bancroftian filariasis with diethylcarbamazine and ivermectin.

This study assessed changes in circulating parasite antigen levels after diethylcarbamazine (DEC) and ivermectin treatment of bancroftian filariasis to determine effects of these drugs on adult Wuchereria bancrofti in vivo. Thirty adult Haitians with microfilaremia were treated with 1 mg of ivermectin to reduce counts of microfilariae. Later, subjects were treated with either one or two 200 micrograms/kg doses of ivermectin or with 12 daily 6 mg/kg doses of DEC. Macrofilaricidal activity of these drugs was indirectly monitored by measuring circulating W. bancrofti antigen by EIA. Antigen levels fell by 75% after DEC and by 34% after ivermectin. These results suggest that low-dose ivermectin treatment followed by a standard course of DEC is a more effective macrofilaricidal regimen for W. bancrofti than either of the multidose ivermectin regimens used in this study.

Animals↗

PubMed1994

Effectiveness of diethylcarbamazine in treating loiasis acquired by expatriate visitors to endemic regions: long-term follow-up.

Although successful treatment of loiasis with diethylcarbamazine (DEC) has been reported, little is known about the long-term success rate of therapy or the predisposing factors for treatment failure. To address these questions, 32 patients were followed 2-15 years (median, 4.5) after DEC treatment; all had acquired infection while expatriate visitors to endemic areas of Africa. Using a strict definition of successful treatment, 12 (38%) appeared to be cured after one course of therapy and 5(16%) after two courses. Of the remaining 15 patients, 3 continued to be symptomatic despite more than four courses of treatment. Although 12 of the 17 patients who relapsed did so within 1 year of treatment, several had relatively long asymptomatic periods (2-8 years). There was no predictive difference in clinical or laboratory parameters (including eosinophilia and specific filarial serology) between patients requiring one or more courses of therapy.

Diethylcarbamazine↗

PubMed1995

Elevated cellular immune responses and interferon-gamma release after long-term diethylcarbamazine treatment of patients with human lymphatic filariasis.

Cellular immune responses to filarial antigens were examined in persons before and 1 year after beginning treatment with diethylcarbamazine (DEC). The subjects (17 microfilaremics, 13 asymptomatic amicrofilaremics, and 13 with elephantiasis) had not responded to Brgia malayi adult worm antigen (BmA) before chemotherapy. T cell proliferative responses to BmA improved significantly after therapy in the 3 clinical groups (P < .05) but was highest in the elephantiasis patients and asymptomatic amicrofilareimics. Cytokine release profiles after stimulation with parasite antigen were analyzed. Production of interferon (IFN)-gamma by BmA-stimulated mononuclear cells increased significantly after DEC treatment (geometric mean, 39.6-55.7 U/mL; P < .05), largely due to improved responses in elephantiasis patients and asymptomatic amicrofilaremics. In contrast, BmA-induced interleukin (IL)-4 release did not change significantly in these same patients after treatment. Thus, both microfilaremic and amicrofilaremic infections with B. malayi are associated with similar down-regulation of proliferative T cell function and IFN-gamma release.

Adolescent↗

PubMed1995

Clearance of circulating filarial antigen as a measure of the macrofilaricidal activity of diethylcarbamazine in Wuchereria bancrofti infection.

Small doses of diethylcarbamazine (DEC) clear microfilariae (MF) from the blood of Wuchereria bancrofti-infected persons, but the dose and regimen required to kill adult worms is not clearly defined. A prospective study was undertaken to examine the macrofilaricidal effect of DEC and the ability of an assay for circulating filarial antigen (CFA) to define the effect. Twenty-five MF-positive subjects and 7 MF-negative but CFA-positive subjects were treated with DEC and followed for 18 months. Of the 25 MF-positive patients, 24 cleared MF, and 22 of 26 CFA-positive subjects cleared CFA. A significantly greater decrease in antifilarial IgG4 was seen in patients who cleared CFA than in those who did not. The complete clearance of CFA observed after therapy with DEC indicates that assessment of CFA clearance is a useful means for detecting macrofilaricidal effects of antifilarial chemotherapy.

Adolescent↗

PubMed1995

Differential decline in filaria-specific IgG1, IgG4, and IgE antibodies in Brugia malayi-infected patients after diethylcarbamazine chemotherapy.

In human filariasis, the predominant serum antibody is IgG4, accompanied by significant IgE production. The ratio of IgG4 to IgE is highest in asymptomatic microfilaremic carriers, while chronic disease is associated with elevated IgG1-3. The changes in isotypes following chemotherapy with diethylcarbamazine (DEC) were studied in 2 groups of Brugia malayi-infected patients from Sumatra and South Kalimantan, Indonesia. Similar results were obtained from each group. IgG4 levels decreased sharply (65%-78%) within 12 months. IgG1 levels declined in a less consistent and extreme manner, and levels of IgG2 and IgG3 declined only in patients with elephantiasis, who also had the highest initial levels of these antibodies. IgE responses were relatively stable to therapy in microfilaremic patients (7%-28% reduction) and showed only moderate decline (56% over 2 years) in elephantiasis patients. Active filarial infection is thus associated with specific IgG4 antibodies, but there is independent expression of the IgE and IgG4 isotypes in filariasis.

Adult↗

PubMed1997

Reduction of Wuchereria bancrofti adult worm circulating antigen after annual treatments of diethylcarbamazine combined with ivermectin in French Polynesia.

Circulating filarial antigen (CFA), determined with Og4C3 ELISA, is a marker of Wuchereria bancrofti adult worm infection. The reduction of CFA over 2 years was determined in 185 microfilaremic and 111 amicrofilaremic but CFA+ adults given an annual dose of either diethylcarbamazine (DEC) or ivermectin or the two combined. Reduction of CFA level was good with DEC but weak with ivermectin and followed the same pattern in amicrofilaremic and microfilaremic groups. Combinations and DEC alone had a similar impact on CFA level. CFA clearance was observed in amicrofilaremic but not in microfilaremic persons in all DEC-containing treatments. However, the highest clearance rate was observed in persons treated with DEC at 6 mg/kg combined with ivermectin. Continuous reduction of CFA level after repeated treatments shows that elimination of W. bancrofti infection, monitored by CFA clearance, might be achieved within a few years with annual treatments of DEC combined with ivermectin.

Adult↗

PubMed2000

The effects of diethylcarbamazine on the morphology and ultrastructure of foetal mouse cerebellar neurons in culture.

This paper examines morphological and ultrastructural changes in foetal mouse cerebellar neurons treated with a culture medium containing diethylcarbamazine (DEC), a widely used anti-parasitic drug known to interfere with vesicle transfer to and from the Golgi apparatus. The effects of DEC were drastic, with the complete disorganization of the Golgi apparatus and the appearance of large vacuoles within the cytoplasm. Quantitative data comparing normal and DEC-treated neurons in culture demonstrated significant differences between the length of Golgi cisternae and numbers of clear vesicles and secretory vesicles. The evidence therefore suggests that the various synthetic and secretory activities involving these organelles are severely impaired.

Animals↗

PubMed1981

The effect of variations in urinary pH on the pharmacokinetics of diethylcarbamazine.

1 The partitioning of diethylcarbamazine (DEC) between octan-1-ol and aqueous buffer was shown to be dependent upon the pH of the buffer. 2 Buccal absorption of DEC in five subjects was shown to increase with increasing pH. 3 In view of these findings, the disposition of DEC was investigated in the same five subjects following the oral administration of 50 mg DEC citrate on two occasions. 4 The elimination half-life (T1/2) of DEC and the area under the plasma concentration v time curve (AUC) were significantly increased when an alkaline urinary pH was maintained compared with the values of these parameters obtained on a second occasion when an acidic urinary pH was maintained. Renal clearance and total urinary excretion of DEC were significantly less at alkaline urinary pH than under acidic conditions. 5 The clinical significance of these observations is discussed both with respect to dose modification under conditions of changing urinary pH and the possibility of the manipulation of urinary pH in order to produce more effective dosage regimens.

Absorption↗

PubMed1982

The effect of renal disease on the pharmacokinetics of diethylcarbamazine in man.

1 The pharmacokinetics of diethylcarbamazine (DEC) were studied in twelve patients with chronic renal function impairment. 2 Selected pharmacokinetic parameters, plasma half-life (T1/2), area under the plasma concentration-time curve (AUC), elimination rate constant (Kel) and 24 h urinary excretion were regressed versus parameters indicative of renal function. 3 Significant negative correlations were observed between creatinine clearance and both plasma T1/2 and log10 T1/2. 4 Significant positive correlations were obtained between (a) creatinine clearance and elimination rate constant of DEC and (b) reciprocal serum creatinine and l/T1/2. Creatinine clearance was significantly and positively correlated with 24 h urinary excretion of DEC. 5 No significant correlations were observed between age, sex or weight and renal function but DEC excretion did appear to decrease with increasing urinary pH. 6 Plasma half-life, and area under the plasma concentration-time curve were increased and 24 h urinary excretion of DEC was significantly reduced in patients with chronic renal function impairment, compared with normal volunteer subjects receiving an identical dosage of DEC at acidic urinary pH.

Adult↗