Efficacy of five annual single doses of diethylcarbamazine for treatment of lymphatic filariasis in Fiji

Annual single-dose treatments with diethylcarbamazine citrate (DEC) at a dose of 6 mg/kg have been reported effective in reducing microfilariae (mf) rate and density and applicable to large-scale filariasis control campaigns. However, the efficacy of such treatments has not been studied quantitatively in relation to different pretreatment levels of endemicity. This study of 32 villages in Fiji revealed that five treatments repeated annually steadily reduced village mf rate, and that the degree of reduction was not influenced by pretreatment levels of mf density or rate. This indicates that an annual dosage scheme is applicable to high-endemicity areas. The results also suggest that such treatment affected juvenile forms of Wuchereria bancrofti and may prevent them from reproducing.     

Adverse reactions following diethylcarbamazine (DEC) intake in 'endemic normals', microfilaraemics and elephantiasis patients.

This paper reports on adverse reactions following a 12-day course of 6 mg/kg diethylcarbamazine (DEC) therapy in brugian filariasis patients in Indonesia. Microfilaria-positive individuals (n = 26), 'endemic normals' (n = 12) and elephantiasis patients (n = 17) were included in the study. Fever, headache and body aches started between 2 and 24 h after DEC intake. Adverse reactions were categorized into 'no or mild', 'moderate' or 'severe' depending on the total reaction score. Four microfilaraemic individuals (15.4%) suffered from severe adverse reactions and their pre-treatment microfilarial levels (geometric mean, GM = 3060 mf/10 mL) were significantly higher than in the 5 microfilaraemic individuals (19.2%) suffering from moderate reactions (GM = 1268 mf/10 mL) and in the 17 microfilaraemic patients (65.4%) who experienced no or mild reactions (GM = 6 mf/10 mL)(P < 0.001 and P < 0.001, respectively). Endemic normals showed no or mild adverse reactions. No or mild adverse reactions were also recorded in all but 2 elephantiasis patients after DEC intake. Two elephantiasis patients with moderate reactions had high levels of circulating microfilariae at pre-treatment (2097 and 7375 mf/10 mL). Concentrations of DEC were measured in plasma, but could not explain the differences in the severity of adverse reactions.     

Impact of 10 years of diethylcarbamazine and ivermectin mass administration on infection and transmission of lymphatic filariasis

The potential of repeated mass administration of diethylcarbamazine (DEC) and ivermectin to eliminate lymphatic filariasis has been examined in a study implemented in 10 villages with a population of 18415 in south India. During ten rounds of mass drug administration, 49-84% of the eligible population received treatment in different villages. Ten rounds of mass administration of DEC alone reduced the microfilaria (mf) prevalence and intensity by 93% and 97%, respectively, and the vector infection and infectivity rates by 91% and 89%, respectively. The corresponding figures with nine rounds of administration of ivermectin alone were 83%, 90%, 89% and 79%. Out of five villages in each treatment arm, the mf rate declined to 相似文献   

Periodic mass treatment with diethylcarbamazine for the control of filariasis in American Samoa

Filariasis surveys made during 1962-63 in 5 villages in American Samoa among persons over 5 years of age gave an elephantiasis rate of 3.4%, a microfilarial rate of 26% and a median microfilarial rate (MfD₅₀) of 29. These rates were somewhat higher than those found in surveys made in the same villages among villagers of the same ages some 20 years previously. A mass treatment programme with diethylcarbamazine was then decided on.     

Comparative efficacy of annual and semi-annual doses of ivermectin or diethylcarbamazine for the prevention of lymphatic filariasis]

A double blind randomized trial was performed on 58 healthy Polynesian Wuchereria bancrofti carriers, they were randomly allocated to treatments with repeated annual or semi-annual doses of ivermectin 100 mcg/kg or diethylcarbamazine (DEC) 3 mg/kg, or with repeated annual doses of DEC 6 mg/kg. After the 12-month treatment, the clearance of microfilaremia was complete in 7 of the 23 carriers treated with ivermectin and in 3 of the 35 treated with DEC. Nine months after that treatment, the lowest mean microfilaremia was observed in the carriers treated with 3 successive semi-annual doses of DEC 3 mg/kg. Adverse reactions were comparable in carriers treated with ivermectin and in those treated with DEC, and did not interfere with daily activities of treated subjects.     

A randomized, double-blind, placebo-controlled study with diethylcarbamazine for the treatment of hydrocoele in an area of Tanzania endemic for lymphatic filariasis.

Hydrocoele is common in men in Wuchereria bancrofti-endemic areas, the treatment for which is currently surgical intervention. Two community studies have recently suggested that the antifilarial drug diethylcarbamazine (DEC) may have a beneficial effect of reducing the size of hydrocoeles of filarial origin. To test this hypothesis, a double-blind, placebo-controlled study was carried out in 1998 and 1999 in an area of north-eastern Tanzania where microfilaria (mf) carrier rates and hydrocoele prevalence rates were known to be high. Ninety-eight adult male volunteers (aged > or = 15 years) with chronic hydrocoele received DEC 300 mg per day for 12 days (49 patients), or placebo (49 patients). Circumferential and ultrasonographic measurements of the scrotum, and a serum sample for measuring W. bancrofti antigen, were obtained at the onset and after 3, 6 and 12 months. Scrotal size and hydrocoele fluid volume indices were calculated. No statistically significant differences in volumetric measurements between the DEC and placebo groups were found at any of the follow-ups. Separate analyses dividing patients by antigen status, hydrocoele size or presence of thickening of the scrotal skins gave similar results. Geometric mean intensity of W. bancrofti antigen was significantly lower in the DEC group than in the placebo group (P = 0.008), indicating that lack of compliance was not a significant factor. Two months into the treatment trial, mass treatment with monthly low-dose DEC was given to the rest of the community. We conclude that DEC is not effective in reducing the size of hydrocoele of filarial origin. Interventions to replace or supplement hydrocoelectomy should be investigated.     

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.     

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.     

The effect of diethylcarbamazine treatment of Bancroftian filariasis on the immunological reactivity of microfilaraemic individuals

Patent filarial infection has been correlated with a profound suppression of humoral and cellular responses to filarial antigens. In the present study, the filarial antigen-specific humoral and cellular reactivity of 30 Haitian subjects with patent Wuchereria bancrofti infection was monitored before and after treatment with diethylcarbamazine. Microfilarial density was reduced from a pre-treatment mean of 1778/ml to 9/ml, with residual microfilaraemias detectable in 10 subjects. Peripheral blood mononuclear cells from 18 of the 30 patients responded to an extract of Brugia pahangi before treatment, and this number increased to 25 after treatment. There was no significant change in the mean level of response to B. pahangi in patients who were responsive to filarial antigen before treatment; however, the mean responsiveness to B. pahangi of individuals who were classified as nonresponders before treatment was significantly increased following treatment. Cellular reactivity to purified protein derivative and geometric mean titres to soluble B. pahangi, measured by enzyme-linked immunosorbent assay, were unaffected by treatment. Similarly, most post-treatment sera did not recognize new B. pahangi bands on Western blots, compared to pre-treatment controls. These observations imply that the relationship between microfilariae and immunosuppression is complex.     

Epidemiology of subperiodic bancroftian filariasis in Samoa 8 years after control by mass treatment with diethylcarbamazine

In 1979, a microfilarial prevalence study was conducted in a population of 8385 persons inhabiting 28 villages in Samoa using both the nuclepore filtration (NP) method (with 1 ml blood) and the fingerprick (FP) method (with 60 mm³ blood). The overall prevalence rate was 4.5% by the NP method and 3.8% by the FP method. The average microfilarial prevalence in males was 2.3 times higher than in females, and the rate among males aged 30 years and over was as high as 20%. The positive cases were found to be concentrated in certain households.     

The efficacy of annual single-dose treatment with diethylcarbamazine citrate against diurnally subperiodic bancroftian filariasis in Samoa

Treatment of subperiodic bancroftian filariasis, which is endemic in Samoa, with diethylcarbamazine citrate (DEC-C) in single doses of 4 mg/kg, 6 mg/kg, and 8 mg/kg body weight was evaluated using the nuclepore filtration method (with 1 ml blood) and compared in terms of efficacy against the microfilariae (mf) and side-reactions produced. The 6 mg/kg single-dose treatment assessed at six months showed that the effect of DEC-C to eliminate microfilariae was closely associated with the pre-treatment microfilarial level. The treatment cured nearly 60% of the low-density carriers with ≤20 mf/ml but only about 10% of the carriers with ≥501 mf/ml. However, the percentage decrease in the microfilarial count, which averaged 89.3%, did not seem to differ greatly according to the level of the pre-treatment count. The age group 20-29 years showed a poorer response to the treatment compared with the other age groups. When the different dosage regimens (4 mg/kg, 6 mg/kg and 8 mg/kg) were compared at 6 and 12 months after treatment, the 6 mg/kg regimen was found to be more effective than the 4 mg/kg regimen in reducing the microfilarial count, and it produced fewer adverse reactions than the 8 mg/kg regimen. The comparison between the annual single-dose treatment at 6 mg/kg and the six-monthly two doses/year treatment at the same dosage (total 12 mg/kg/year) showed that the latter had little advantage over the former, thus indicating the effectiveness of the single-dose treatment for longer than six months.     

A placebo-controlled double-blind trial for the treatment of bancroftian filariasis with ivermectin or diethylcarbamazine.

Therapeutic efficacy and clinical side-effects of ivermectin (single dose of 100 micrograms/kg) and diethylcarbamazine (DEC) (3 mg/kg for one day, then 6 mg/kg daily for 12 d) were evaluated for microfilaricidal effect in Bancroftian filariasis. Seventy-one microfilaraemic consenting adult male patients (greater than or equal to 100 microfilariae (mf)/ml) were randomly assigned to receive ivermectin, DEC or placebo and kept in hospital for 15 d. Those receiving placebo were treated with ivermectin on day 9. Ivermectin (19 'double-blinded' and 22 'unblinded' patients) caused an abrupt reduction in mf count to 1.5% of the pre-treatment level 12 h after drug administration and to 0.06% on day 14, with recrudescence to 1.8% after one month and to 9.2% after 3 months. DEC (30 patients) caused a gradual drop in mf count to 1.1% of the pre-treatment level on day 14, which increased to 2.4% after one and 3 months. The total scores of side-effects were 77 (1%), 305 (2.1%) and 311.5 (3.0%) for placebo, ivermectin and DEC respectively; the differences between DEC or ivermectin and placebo were statistically significant. Ivermectin produced lower side-reaction scores than DEC and the differences were highly significant at the 95% confidence level. Side-effects were mainly headache and body aches in the ivermectin patients, which appeared as early as 4 h after drug administration, resolved within 36 to 48 hours, and were significantly related to mf densities. Side-effects in DEC patients were mainly testicular and epididymal pain and swelling, unrelated to mf densities, which began at day 2 and continued to day 7.(ABSTRACT TRUNCATED AT 250 WORDS)     

Chemotherapy with spaced doses of diethylcarbamazine preceded by levamisole in Bancroftian filariasis

The administration of levamisole (2 · 5 mg/kg) in a single oral dose, the day before beginning weekly spaced doses of diethylcarbamazine (DEC), resulted in low blood levels of microfilariae of Wuchereria bancrofti six weeks after commencing treatment. This rapid decrease in microfilaraemia associated with the addition of levamisole overcomes a major disadvantage of using DEC alone—namely the necessity to commence spaced dose treatment several months before the transmission season.A further advantage of combined levamisole-DEC therapy is that levamisole is effective in ascariasis and hookworm—conditions which often co-exist in areas endemic for Bancroftian filariasis.     

Long-term efficacy of single-dose combinations of albendazole, ivermectin and diethylcarbamazine for the treatment of bancroftian filariasis

In a 'blinded' trial (in Sri Lanka, 1996-98) of 47 male asymptomatic microfilaraemic subjects with Wuchereria bancrofti infection, the safety, tolerability and filaricidal efficacy of 3 single-dose combination regimens were compared: albendazole 400 mg with ivermectin 200 micrograms/kg, albendazole 400 mg with diethylcarbamazine citrate (DEC) 6 mg/kg or albendazole 600 mg with ivermectin 400 micrograms/kg. Treated subjects were followed-up for 24 months. This represents the first long-term study using combinations of albendazole with DEC or ivermectin in the above doses against bancroftian filariasis. All subjects had pre-treatment microfilaria (mf) counts over 100/mL. All 3 treatments significantly reduced mf counts, with the albendazole-DEC-treated group showing the lowest mf levels at 18 and 24 months post-treatment. Filarial antigen tests suggested that all 3 treatments had significant activity against adult W. bancrofti; albendazole-DEC combination had the greatest activity according to this test, with antigen levels decreasing to 30.5% of pre-treatment antigen levels, 24 months after therapy. All 3 treatments were clinically safe and well tolerated. These results suggest that a single dose of albendazole 400 mg together with DEC 6 mg/kg is a safe and effective combination for suppression of microfilaraemia of bancroftian filariasis that could be considered for use in filariasis control programmes based on mass treatment of endemic populations.     

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

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

Some observations on filariasis in Western Samoa after mass administration of diethylcarbamazine.

An extremely efficient diethylcarbamazine administration campaign to eradicate Wuchereria bancrofti has been carried out in Western Samoa. The use of the membrane-filtration technique has shown that a large number of people exhibit extremely low microfilarial densities, often with less than 10 in 1 ml of venous blood. It was found that one of these low level microfilaria carriers readily infected the local vector Aedes polynesiensis and that development took place to the infective stage. It was estimated that 497 infective larvae of W. bancrofti will enter the human population of Western Samoa daily from these vectors. Resumption of filariasis transmission is possible and surveillance of the human and mosquito populations should be continued for a number of years and control measures taken quickly if further transmission occurs.