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PubMed1997

Antibodies to diethylcarbamazine potentiate the antifilarial activity of the drug.

The antifilarial drug diethylcarbamazine citrate (DEC) is known to mediate in vivo microfilaricidal activity in conjunction with the host immune system. In this study passive transfer of antibodies to DEC elicited by immunization with methyl piperazine carboxylic acid (MPCA) coupled to bovine serum albumin (BSA), was found to potentiate microfilaricidal activity of subcurative doses of DEC in Setaria digitata infected Mastomys coucha. Active immunization of microfilaraemic animals with MPCA-BSA followed by administration of subcurative doses of DEC also resulted in rapid clearance of microfilaraemia in both S. digitata and Brugia malayi infected M. coucha indicating the synergistic activity of DEC and the antibodies to the drug. Since some of the filarial antibodies are known to react with DEC, it is proposed that such antibodies may potentiate the microfilaricidal activity of the drug in vivo.

Aedes↗

PubMed1996

Development of a competitive enzyme-linked immunosorbent assay for diethylcarbamazine.

A sensitive and reproducible competitive enzyme-linked immunosorbent assay (ELISA) for the determination of the concentration of diethylcarbamazine (DEC) in biological fluids was developed. Since DEC has no functional group to conjugate with bovine serum albumin (BSA), N-(2-aminoethyl)-N-ethyl-4-methyl-1-piperazinecarboxamide (DEC-NH2) was first synthesized. This compound was then converted to carboxyl DEC (DEC-COOH) and conjugated to BSA and to poly-L-lysine for use as immunogen and solid-phase marker, respectively. The competitive ELISA was conducted by simultaneously incubating DEC with mouse anti-DEC antiserum over DEC-poly-L-lysine solid phase. Subsequently, the binding of anti-DEC antibody was detected by using sheep anti-mouse IgG peroxidase conjugate as a tracer. The reliability, determined by the coefficient of variation for inter and intra-assay, was satisfactory. The cross-reactivities of anti-DEC antibodies with DEC metabolites, related compounds and ivermectin were negligible. Using this assay, DEC levels were easily determined in serum of Mongolian jirds (Meriones unguiculatus) up to 4 hours following a single dose of DEC citrate base (100 mg/kg of body weight) via intraperitoneal route.

Animals↗

PubMed1996

Cost and cost effectiveness of mass diethylcarbamazine chemotherapy for the control of bancroftian filariasis: comparison of four strategies in Tanzania.

This study examines the costs and cost effectiveness of four different mass diethylcarbamazine (DEC) chemotherapy regimens-standard dose, semi-annual single dose, low monthly dose and DEC-medicated salt-in reducing microfilarial (mf) prevalence at the community level. Costs were estimated for each intervention in relation to both ingredient and activity, by the derivation and use of detailed itemized cost menus. The most expensive and most effective strategy in reducing community mf prevalence over 2 years was DEC salt intervention, followed in order of costs by the standard, low monthly and semi-annual DEC strategies. The most cost effective strategy was the low monthly DEC treatment. Cost and sensitivity analyses, however, suggest that the optimal choice of mass DEC strategy for reducing mf is very sensitive to programme design parameters. In particular, the results demonstrate that if the salt delivery structure is simplified, DEC salt has the potential to be the dominant intervention for filariasis control. The results suggest that economies of scale considerations might militate against the adoption of this intervention for large-scale applications, unless perhaps offset by its potential for cost recovery by direct patient purchase. Further analyses require a more realistic evaluation of filariasis intervention effectiveness by addressing changes in infection intensity and by accounting for the population dynamics of parasite transmission and control.

Adolescent↗

PubMed2001

Effect of aggressive prolonged diethylcarbamazine therapy on circulating antigen levels in bancroftian filariasis.

BACKGROUND: Single dose diethylcarbamazine (DEC) as used in control programmes is effectively microfilaricidal for periods of up to a year or more but has incomplete ability to kill Wuchereria bancrofti adult parasites. These regimens can be effective in breaking transmission by suppression of circulating microfilariae available to mosquito vectors. Whether prolonged or aggressive therapy with DEC has a significant effect on adult worms, which may live up to 12 years or more, and is important in the context of the treatment of individual patients, is still incompletely understood. METHODS: In order to investigate the adulticidal effect of aggressive therapy, DEC was given at 6 mg/kg/day for 12-day courses at 0, 6, 12, and 18 months and Og4C3 antigenaemia followed over two years in 38 CAg + Brazilians in a W. bancrofti endemic area. RESULTS: At two year follow-up, the median level of antigenaemia was 21% of the pre-treatment value. 92% of individuals had antigen levels < 50% of pretreatment values, but only 26% had completely cleared antigenaemia. The clearance rate at 24 months was only 12% (3/26) in the asymptomatic CAg + patients but 58% (7/12) in those with clinical manifestations of filariasis. The latter individuals cleared significantly more antigen (median of 0% pretreatment antigenaemia vs. 26%; P=0.02) than asymptomatic but infected individuals. CONCLUSION: Aggressive repeated therapy with DEC alone is ineffective in consistently eradicating adult W. bancrofti, especially in infected but asymptomatic individuals. Prolonged courses of combination therapy with other antifilarial drugs should be investigated for treatment of individual patients with the means to pursue aggressive personal medical care.

Adolescent↗

PubMed2002

Efficacy of co-administration of albendazole and diethylcarbamazine against geohelminthiases: a study from South India.

The efficacy of single-dose combination drug therapy with diethylcarbamazine (DEC) plus albendazole (ALB), and single-drug therapy with DEC alone against geohelminths was compared as part of a mass drug administration (MDA) for elimination of filariasis. This study was conducted in two blocks of Villupuram District of Tamil Nadu State, India, covering a population of 321 000 including about 100 000 children 1-15 years of age. Prevalence and intensity of geohelminth infection were determined by the Kato-Katz technique immediately before and 3 weeks after the MDA. A pre-treatment cross-sectional survey was undertaken in 18 statistically selected villages out of 204 villages, including 646 school children. About 60% were infected with one or more geohelminths. The overall prevalence rates were 53.9%, 12.4% and 5.7% for Ascaris lumbricoides, hookworms and Trichuris trichiura, respectively. Combination therapy (DEC + ALB) produced a cure rate of 74.3% and an egg reduction rate of 97.3% for geohelminths, which were higher than the corresponding rates (30.4% and 79.0%) observed in the single drug therapy arm with DEC alone. The odds of cure with combination therapy were significantly higher for roundworm (5.3 times) and hookworms (3.5 times), then odds of cure with DEC alone. Both therapies were equally effective against trichuriasis, recording cure rates >77% and egg reduction rates >83%. In combination therapy, 53.5% of the children noticed expulsion of worms after MDA, while in single drug therapy only 20.9% did. Our study indicated that MDA of combination therapy was operationally feasible at the community level, and it may secure higher community compliance because of its perceived benefits and enhanced efficacy against geohelminths than single-drug therapy.

Adolescent↗

PubMed2002

The effect of six rounds of single dose mass treatment with diethylcarbamazine or ivermectin on Wuchereria bancrofti infection and its implications for lymphatic filariasis elimination.

Annual mass treatment with single-dose diethylcarbamazine (DEC) or ivermectin (IVM) in combination with albendazole (ALB) for 4-6 years is the principal tool of lymphatic filariasis (LF) elimination strategy. This placebo-controlled study examined the potential of six rounds of mass treatment with DEC or IVM to eliminate Wuchereria bancrofti infection in humans in rural areas in south India. A percentage of 54-75 of the eligible population (> or =15 kg body weight) received treatment during different rounds of treatment - 27.4% in the DEC arm and 30.7% in the IVM arm received all six treatments, 4.8% and 5.6% received none, and the remainder received one to five treatments. After six cycles of treatment, the microfilaria (Mf) prevalence in treated communities dropped by 86% in the DEC arm (P < 0.01) (n = 5 villages) and by 72% in the IVM arm (P < 0.01) (n = 5 villages), compared with 37% in the placebo arm (P < 0.05) (n = 5 villages). The geometric mean intensity of Mf fell by 91% (t = 8.11, P < 0.05), 84% (t = 6.91, P < 0.05) and 46% (t = 2.98, P < 0.05) in the DEC, IVM and placebo arms, respectively. The proportion of high-count Mf (>50 Mf per 60 mm(3) of blood) carriers was reduced by 94% (P < 0.01) in the DEC arm and by 90% (P < 0.01) in the IVM arm. Among those who received all six treatments, 1.4% in the DEC arm and 2.4% in the IVM arm remained positive for Mf. Two of five villages in the DEC arm and one of five in the IVM arm showed zero Mf prevalence, but continued to have low levels of transmission of infection. The results also indicate that DEC is as effective as or slightly better than IVM against microfilaraemia. Results from this and other recent operational studies proved that single-dose treatment with antifilarials is very effective at community level, feasible, logistically easier and cheap and hence a highly appropriate strategy to control or eliminate LF. Higher treatment coverage than that observed in this study and a few more than six cycles of treatment and more effective treatment tools/strategies may be necessary to reduce microfilaraemia to zero level in all communities, which may lead to elimination of LF.

Animals↗

PubMed1996

[Combinations of ivermectin and diethylcarbamazine for improved control of lymphatic filariasis].

Since 1993, a three arm double-blind controlled trial was implemented in French Polynesia to compare the efficacy of single doses of diethylcarbamazine (DEC) 6 mg/kg vs. ivermectin (IVR) 400 micrograms/kg vs. the combination IVR 400 + DEC 6 for treatment of Wuchereria bancrofti mf carriers. Of the 57 treated male patients, three groups of 19 were randomly selected and allocated to one of the three treatments. Twelve months after the first then the second treatment (M12 then M24) respectively, 3 (16%) then 10 (53%), 3 (16%) then 5 (26%), 7 (27%) then 10 (53%) of patients were mf negative in groups DEC 6, IVR 400 and IVR+DEC. Mf percent return was significantly lower in the group IVR+DEC (2% at M12 then M24) than for the groups DEC 6 (15% at M12 then 4% at M24) and IVR 400 (12% at M12 then 10% at M24). The combination IVR+DEC showed promising results for an annual strategy; to achieve the best results from a control program it is necessary to associate IVR+DEC.

Adult↗

PubMed2004

Delayed macrofilaricidal activity of diethylcarbamazine against Brugia pahangi in Mongolian jirds.

The macrofilaricidal activity of diethylcarbamazine (DEC) was confirmed in jirds infected with Brugia pahangi. Seventy jirds were inoculated subcutaneously with 100 infective larvae. At 20 weeks post-infection, the microfilaraemic jirds were divided into two groups, untreated and treated. For the treated group, 200 mg kg(-1) of DEC was injected intraperitoneally for 5 consecutive days. One, 4, 8, 12, 16 and 27 weeks after the final treatment, 4-7 jirds in each group were sacrificed to measure adult worm burdens. The number of adult worms recovered from treated jirds was comparable to controls at earlier necropsy (1 and 4 weeks post-treatment). However, at late necropsy (8 weeks and later) the recovery rate of adult worms in treated jirds was significantly lower than that in untreated controls, indicating an adultcidal effect of DEC. The present study demonstrates that DEC requires 8 weeks to kill B. pahangi adult worms in jirds and that the Mongolian jird is a useful model for screening antifilarial activity.

Animals↗

PubMed2001

Annual single-dose diethylcarbamazine plus ivermectin for control of bancroftian filariasis: comparative efficacy with and without vector control.

Two intervention strategies for the control of bancroftian filariasis were compared in rural villages of southern India: annual mass treatment with single-dose diethylcarbamazine plus ivermectin, either on its own or combined with vector control. Vector control, based on the use of polystyrene beads and larvivorous fishes in the major breeding sites of Culex quinquefasciatus, brought about a drastic and sustained reduction in vector density and man-biting rates. After the first round of treatment, chemotherapy alone brought about a 60% drop in the annual transmission potential (ATP) whereas the integrated strategy reduced ATP by 96% (P < 0.05). After two annual rounds of treatment, the reduction in ATP was similar for both strategies (91%-96%), with the prevalences of microfilaraemia reduced by 88%-92%. However, when drug pressure was removed in the third and final year of the study, transmission was resumed in the absence of vector control whereas no infective female mosquitoes were detected in the villages with vector control. Vector control, though obviously not cost-effective in the short term, could play an important role in an integrated programme, by preventing re-establishment of transmission after chemotherapy is completed.

Adolescent↗

PubMed1978

Long-term treatment of onchocerciasis in children with low doses of diethylcarbamazine.

Two groups of children were treated daily with 12.5 or 25 mg diethylcarbamazine for five months and a further group with 12.5 mg daily for seven weeks; 88 children completed the course. The trial was under constant supervision and ophthalmic and parasitological examinations were carried out at approximately one-month intervals. The acceptability of the drug was poor owing to adverse reactions, but the clinical response to treatment good.

Child↗

PubMed1990

Eradication of bancroftian filariasis by diethylcarbamazine-medicated common salt on Little Kinmen (Liehyu district), Kinmen (Quemoy) Islands, Republic of China.

Since bancroftian filariasis constituted a major public health problem on Little Kinmen (Liehyu District), Kinmen (Quemoy) Islands, a control programme was conducted on this island from 1970 to 1982. A pre-control survey recorded a microfilarial rate (mfr) of 9.6%, a night blood microfilarial density (mfd) of 14.4/20 microliters blood, and a clinical rate of 26.2%. Culex quinquefasciatus was found to be the only vector of the parasitosis on the island, with an infection rate (Ir) with all filarial larval stages of 9.1% and a larval density (Ld) of 6.2. Diethylcarbamazine (DEC)-medicated salt (0.33% w/w) was administered to the whole population on Little Kinmen. Each person was estimated to take 12.7 g salt with 42 mg DEC daily for six months (July-December 1974). All accepted the programme, and no adverse side-effect was noted. During the control, the mfr and mfd were reduced to 0.3% and 1.9/20 microliters blood. The Ir and Ld were reduced to 0.8% and 1.3. Eight post-control surveys (1975-1982) revealed only two of 459 pre-control carriers positive and the remaining population of 7125 inhabitants negative. The two carriers were cured with a course of 5 g DEC. All family members of these carriers and their neighbours' families were given DEC-medicated salt for four months to clear the only remaining source of filarial transmission. In addition to a reduction in the prevalence of filariasis in humans and in mosquitoes to zero, the clinical manifestations disappeared in 52.4% of the pre-control carriers and improved in 19.0%. There was no change in 19.8 and 8.7% had new manifestations.

Adolescent↗

PubMed1990

Effect of diethylcarbamazine on adult Loa in monkeys.

The effect of diethylcarbamazine citrate (DEC) treatment (43-150 mg kg-1 daily for 12-21 days) on adult Loa worms in five drills (Mandrillus leucophaeus) is described. In individual monkeys, between one-third and all of the adult worms survived the treatment, and most of the surviving females were still producing live microfilariae. These experiments provide direct evidence which may explain the common clinical experience that single courses of DEC do not always succeed in eliminating the signs and symptoms of loiasis in humans. Further work on the chemotherapy of loiasis in monkeys, using DEC and other filaricides, might improve the treatment of this disease.

Animals↗

PubMed1993

Reduction of filaritic lymphoedema and elephantiasis by 5,6 benzo-alpha-pyrone (coumarin), and the effects of diethylcarbamazine (DEC).

Chronic filaritic lymphoedema and elephantiasis, in India, were treated orally with 5,6 benzo-alpha-pyrone (56 BaP; 1,2 benzo-alpha-pyrone; coumarin) in a double-blind, randomized, matched-group trial. Each group finally contained 40-55 patients. Patients were observed for about 2 years (ranging from 6 to 45 months, with 75% completing the 2 years). The 56 BaP slowly, but very significantly (P < 0.0001), reduced all grades of lymphoedema and elephantiasis. Two thirds of the oedema was lost by grade 2 over 2 years. Grades 3 to 5 were reduced by a fifty over that time. The greater the initial oedema, the greater was its rate of resolution. A slowly worsening condition thus became a slowly improving one. Slowness has its advantages: compression stockings, that are impractical in hot, wet or dirty conditions, are not necessary. The slowly remodelling fibrous tissue, while lessening in amount, is still able to hold the tissues together. The 56 BaP considerably improved many symptoms and complications, particularly bursting-pains, inflammation and ulcers. It is cheap and of very low toxicity. Diethylcarbamazine (DEC) was studied with and without 56 BaP. DEC alone gave some reduction of the oedema, but this was much smaller than that with 56 BaP. It considerably worsened the reductions by 56 BaP, while 56 Bap slightly improved those by DEC and reduced the fever caused by DEC. Together, they reduced feelings of swelling and bursting-pain, fungal infections, lymphangitis and lymphadenitis more than when used alone.

Adult↗

PubMed1993

A comparative study of the efficacy and tolerability of single and split doses of ivermectin and diethylcarbamazine in periodic brugian filariasis.

The use of ivermectin in lymphatic filariasis (both bancroftian and brugian) has been recently explored in several studies. We report in this paper, for the first time, a direct comparison of the efficacy and tolerability of single doses of ivermectin and diethylcarbamazine (DEC) in brugian filariasis. We also present our findings on the use of split doses of ivermectin and DEC on microfilaraemia levels and the occurrence of adverse reactions. Fifty male, asymptomatic microfilaremics drawn from the Alleppey District, Kerala, India, were allocated one of the following five treatment regimens in a double blind randomized study: (1) single oral 6 mg/kg dose of DEC; (2) single oral 6 mg/kg dose of DEC preceded by 1 mg/kg DEC primer; (3) single oral 220 micrograms/kg dose of ivermectin; (4) single oral 200 micrograms/kg dose of ivermectin preceded by a 20 micrograms/kg ivermectin primer; or (5) a single oral 400 micrograms/kg dose of ivermectin preceded by a 20 micrograms/kg ivermectin primer. The kinetics of microfilaria clearance differed in the two (DEC/ivermectin) groups in the first month post-treatment. At the end of 1 year there were no differences in the microfilaria levels in the two DEC-tested groups and the 420 micrograms/kg ivermectin group. The safety of the 400 micrograms/kg dose of ivermectin was established in this study which has also shown that, currently, this dose would be the best choice for brugian filariasis. Patients in the ivermectin groups had significantly lower adverse reaction scores than patients who had received DEC. There was no advantage in splitting the dose of either DEC or ivermectin, either in terms of efficacy or tolerability.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗

PubMed2000

Two-year follow-up of the microfilaraemia of asymptomatic brugian filariasis, after treatment with two, annual, single doses of ivermectin, diethylcarbamazine and albendazole, in various combinations.

Repeated, single, oral doses of combinations of ivermectin, diethylcarbamazine (DEC) or albendazole are recognized as important tools for parasite control in lymphatic filariasis. In order to assess the effects of re-treatment using these combinations in Brugia malayi infections, 40 asymptomatic microfilaraemics were re-treated at the end of the first year, with an additional, single, dose of the combination they had previously received. They were then followed-up for another year. The subjects, of both sexes and aged 14-70 years, each received a two-drug combination: ivermectin (200 micrograms/kg) with DEC (6 mg/kg); ivermectin (200 micrograms/kg) with albendazole (400 mg); or DEC (6 mg/kg) with albendazole (400 mg). The kinetics of microfilarial clearance were similar to that seen during the first treatment, the members of the two groups given DEC having less intense microfilaraemias, 1 year after the re-treatment, than those given ivermectin with albendazole (P < 0.001 for each comparison). At this time, the two DEC groups also had a higher proportion of amicrofilaraemic individuals (22 of 26) than the ivermectin + albendazole group (three of nine). There were fewer adverse reactions in all the groups after re-treatment than seen after the first treatment. In countries such as India, where there is no co-endemicity of onchocerciasis or loiasis, the options for control programmes in areas where brugian filariasis is endemic are DEC alone or DEC in combination with ivermectin or albendazole. Where there is no access to ivermectin, transmission control must be based on DEC alone or in combination with albendazole.

Adolescent↗

PubMed1998

Treatment of microfilaraemia in asymptomatic brugian filariasis: the efficacy and safety of the combination of single doses of ivermectin and diethylcarbamazine.

Although combinations of ivermectin and diethylcarbamazine (DEC) have been shown to be superior to either drug alone in the suppression of bancroftian microfilariae, their efficacy against infections with Brugia malayi has never been investigated. The present, open trial is the first on the efficacy and safety of a combination of single doses of ivermectin and DEC when used against microfilaraemias of brugian filariasis. Twenty-one, asymptomatic but microfilaraemic (109-6934 microfilariae/ml blood, with a median of 841/ml) men, aged 18-48 years, each received oral doses of ivermectin (400 micrograms/kg) and DEC (6 mg/kg) as a single treatment. Twelve hours post-treatment, 96.5%-100% of the microfilariae in each subject had been cleared and 12 of the subjects were amicrofilaraemic. A further reduction in microfilarial counts was evident 1 month post-treatment (mean clearance = 99.0%) and the counts continued to fall at least until the last follow-up, at 1 year post-treatment, when the mean clearance was 99.9% and 13 (68.4%) of the 19 subjects then investigated were amicrofilaraemic. All subjects experienced adverse reactions of one form or another, lasting for up to 48 h post-treatment; these included fever, myalgia, headache, and lethargy. Postural hypotension was recorded in two subjects and dilated, inflamed lymphatic channels were seen in another two. The combination of ivermectin and DEC demonstrated a microfilaricidal effect superior to that of either drug used alone, both in the initial rapid clearance of microfilariae and in sustaining the effect for 1 year. This finding has important implications for the control of lymphatic filariasis.

Adolescent↗

PubMed1998

Prevention of acute adenolymphangitis in brugian filariasis: comparison of the efficacy of ivermectin and diethylcarbamazine, each combined with local treatment of the affected limb.

Acute attacks of adenolymphangitis (ADL) not only force patients with lymphatic filariasis to seek medical attention but also hasten the progression of filarial oedema. Patients with filariasis-associated ADL are currently treated with repeated courses of the antifilarial drug diethylcarbamazine (DEC), with or without antibiotics and anti-inflammatory agents. In this double-blind, placebo-controlled study, the efficacy of local treatment of the affected limb combined with repeated doses of ivermectin or DEC, in preventing the occurrence of ADL in Brugia malayi lymphatic filariasis, was examined. Overall, 120 patients who had each had at least two ADL attacks in the previous year were each admitted to the study at the time of an ongoing episode of ADL. The patients were randomly allocated to receive 12, monthly treatments of ivermectin (400 micrograms/kg), DEC (10 mg/kg) or placebo, in addition to local care of the affected limbs. There was a significant reduction in the frequency of ADL attacks in each of the three groups during the 2-year study period (P < 0.001 for each comparison). Most importantly, there were no significant differences in frequency of attacks between the three groups, either at the end of the treatment phase or at the end of the post-treatment phase (P > 0.15 for each comparison), suggesting that foot care combined with appropriate use of local antibiotics or antifungals is adequate to reduce the number of ADL attacks. The implications of these observations for planning morbidity control in lymphatic filariasis are discussed.

Acute Disease↗

PubMed1998

The efficacy, tolerability and safety of diethylcarbamazine-fortified salt in the treatment of the microfilaraemias of brugian filariasis: an open, hospital-based study.

Cooking salt fortified with diethylcarbamazine (DEC) has been successfully used to control lymphatic filariasis in several parts of the world. The kinetics and efficacy of DEC-fortified salt in clearing microfilaraemias of Brugia malayi and the salt's tolerability and safety are examined in this study. Twenty individuals with B. malayi microfilaraemias (pre-treatment levels of 108-6358 microfilariae/ml; median = 309/ml) consumed DEC-fortified salt (0.2%, w/w) with their food for 1 year, initially in hospital (for 1 week) and later at home. The mean daily intake of DEC was 21.4 mg (range = 9.0-39.4 mg). Even on the first day of consuming the salt, there was a decrease in the microfilarial levels of 14 patients and a sharp increase in six patients. Microfilarial levels tended to fluctuate thereafter but there was a progressive, general decline. At the end of the study year, eight patients were amicrofilaraemic and microfilarial clearance was > 95% in 58% of the patients. Eight patients did not develop any adverse reactions. Lymph-node tenderness and enlargement were seen in eight patients (40%), and dilated, inflamed lymphatic channels standing out as cords ('string sign') were seen in another five patients. These reactions were transient and did not require any specific treatment. The DEC-fortified salt was well accepted by the study population. The DEC content of fortified salt and the duration of its use for the control of brugian filariasis need to be re-examined. Health education should include messages that mild, self-limiting, adverse reactions are likely to occur even with the use of such salt.

Adolescent↗