The chemoprophylactic use of diethylcarbamazine citrate at total oral doses of 15--180 mg/kg body weight was tested against subperiodic Brugia malayi infection in the leaf monkey (Presbytis melalophos). A total dose of 45 mg/kg body weight given over 9 days killed all developing infective larvae. Similarly, a total dose of 35 mg/kg body weight given over 7 days killed all fourth stage larvae. The minimum effective dose that prevents infection would be 5 mg/kg body weight daily for 7 days every month.
The dynamics of the transmission of subperiodic Brugia malayi in a typical endemic area in Malaysia was studied over a period of 4 years. Mass chemotherapeutic control with diethylcarbamazine citrate was found to be inefficient, new cases being detected even after the fifth treatment cycle of 6 mg/kg X 6 days per cycle. This is in marked contrast to the situation in periodic b. malayi areas where mass treatment efficiently controlled the infection. The disparity in results in these two areas is attributed to zoonotic transmission of subperiodic B. malayi from non-human primates where a mean infection rate of 76.3% was found.
Matched MeSH terms: Diethylcarbamazine/therapeutic use
There has been little change since 1955 in the laboratory techniques for seeking new antifilarial compounds, although one valuable addition to laboratory study has been the experimental infection of cats with Brugia malayi.The chief drug for the treatment and control of filariasis-whether caused by Wuchereria bancrofti or by B. malayi-continues to be diethylcarbamazine, and the author reviews the reports recently published on its use. In India and China large-scale campaigns involving the use of this drug have been undertaken; and in Tahiti filariasis has been suppressed and almost eliminated. Campaigns on a smaller scale and pilot projects considered in this survey include those conducted in Pacific islands, Malaya, Ceylon, Brazil, Surinam and East and West Africa.It is generally agreed that the administration of diethylcarbamazine produces a great diminution in the microfilarial counts of those taking it, and in many persons both microfilariae and adult worms are eradicated. The difficulties which arise are due to toxic effects which occur in some recipients and which may adversely affect the acceptability of treatment.
Diethylcarbamazine citrate (DEC) has been used for treatment and control of lymphatic filariasis since the 1950s. Although this remarkable drug is still useful and modified strategies in its usage have been developed, a number of newer antifilarial compounds are now available. Numerous field trials evaluating their efficacy in the control of lymphatic filariasis have been conducted. In particular, ivermectin (IVM), albendazole (ALB), and DEC have been tested singly and in combinations and the results of such field studies should be evaluated. While most of the studies were based on efficacy in the clearance of microfilaraemia, a few clinical trials evaluated the adulticidal activity of these compounds. Some antibiotics are effective in killing Wolbachia bacteria symbionts of filarial worms, but their role in the chemotherapy of lymphatic filariasis is still undefined. This review of randomised controlled field studies and randomised controlled clinical trials with these compounds will summarise the findings and give recommendations on their appropriate use for the control and treatment of lymphatic filariasis.
Annual and biannual mass single dose diethylcarbamazine citrate (DEC) at 6 mg/kg body weight was administered to people in a Brugia malayi endemic area in Shertallai part of Kerala, India, in 1987 and 1988. The coverage of population ranged between 41.33% and 66.01% in different rounds. The highest percentage of treated population developing side reactions was 8.4%. Both annual and biannual regimens were effective in reducing the microfilaria prevalence significantly from 4.90% to 1.23% and from 6.27% to 0.62% respectively and the incidence of infection was minimal in the adult population and zero among children. There was significant reduction in mean microfilaria count in both annual (81.08%) and biannual (98.00%) areas. Marked reduction in the proportion of high density carriers and infectivity index of the population after DEC therapy was also observed. Beneficial effect of mass single dose DEC on clinical cases of filariasis was evident from the reduction in the prevalence of acute manifestations, recent edema cases and the proportion of chronic cases with acute episodes. Results obtained from mass treatment areas were compared with those of the control area.
Matched MeSH terms: Diethylcarbamazine/administration & dosage*; Diethylcarbamazine/adverse effects; Diethylcarbamazine/therapeutic use
Although current programmes to eliminate lymphatic filariasis have made significant progress it may be necessary to use different approaches to achieve the global goal, especially where compliance has been poor and 'hot spots' of continued infection exist. In the absence of alternative drugs, the use of higher or more frequent dosing with the existing drugs needs to be explored. We examined the effect of higher and/or more frequent dosing with albendazole with a fixed 300 mg dose of diethylcarbamazine in a Wuchereria bancrofti endemic area in Odisha, India. Following screening, 104 consenting adults were randomly assigned to treatment with the standard regimen annually for 24 months (S1), or annually with increased dose (800 mg albendazole)(H1) or with increased frequency (6 monthly) with either standard (S2) or increased (H2) dose. Pre-treatment microfilaria counts (GM) ranged from 348 to 459 mf/ml. Subjects were followed using microfilaria counts, OG4C3 antigen levels and ultrasound scanning for adult worm nests. Microfilarial counts tended to decrease more rapidly with higher or more frequent dosing at all time points. At 12 months, Mf clearance was marginally greater with the high dose regimens, while by 24 months, there was a trend to higher Mf clearance in the arm with increased frequency and 800 mg of albendazole (76.9%) compared to other arms, (S1:64%, S2:69.2% & H1:73.1%). Although higher and/or more frequent dosing showed a trend towards a greater decline in antigenemia and clearance of "nests", all regimens demonstrated the potential macrofilaricidal effect of the combination. The higher doses of albendazole did not result in a greater number or more severe side effects. The alternative regimens could be useful in the later stages of existing elimination programmes or achieving elimination more rapidly in areas where programmes have yet to start.
The known filaricides, suramin and diethylcarbamazine citrate, were tested against subperiodic Brugia malayi infection in the leaf-monkey, Presbytis cristata. As expected, intravenous suramin at 10 mg/kg daily x 5 days or 17 mg/kg weekly x 5 weeks, did not show any microfilaricidal activity, but substantially reduced the recovery of live adult worms to 50.6% and 13.6% of controls respectively. Oral diethylcarbamazine citrate at 6 mg/kg daily x 6 or 10 days reduced final microfilarial counts to 30% of initial counts four weeks post-treatment and adult worm recovery was reduced to 4.5% and 0% of controls respectively. Although the antifilarial activity of these drugs against the infection in this non-human primate model appears to be similar to that seen in man, these results have to be confirmed using larger groups of animals.
The author reviews the distribution, epidemiology, and treatment of filarial infection due to Brugia malayi, with special reference to Malaya. B. malayi infection in man is confined to the Far East between longitudes 75 degrees E and 140 degrees E and is essentially rural. The chief vectors are Mansonia spp., Anopheles hyrcanus group, A. barbirostris group, and Aëdes togoi. The epidemiological picture is complicated by the fact that B. malayi and other closely related species have now been found in several species of animals. The existence of an animal reservoir of infection might have important implications for filariasis control. As to the treatment of B. malayi infection, diethylcarbamazine has been found to reduce the microfilaria count and to kill the adult worms; the severe febrile reactions of microfilaria carriers to the initial doses of this drug may be reduced by administration of the steroid prednisolone.
Filariasis continues to be one of the endemic problems worldwide with 40% of the cases in India. We report a case of lymphatic filariasis in a 32-year old female who presented with a non-tender swelling over left upper arm. Blood sample showed no eosinophilia while the FNAC was diagnostic of W. bancrofti. Patient responded well with oral diethylcarbamazine. High index of suspicion of filariasis is indicated when dealing with a swelling of unknown cause especially in filariasis endemic areas.
The intradermal test using as antigen a 1 per cent saline extract of Dirofilaria immitis powder was performed in Singapore on 69 persons with eosinophilic lung, 32 with mild eosinophilia, 49 with filariasis, 75 normal Asians, and 66 normal Britishers. The test was positive in 100 per cent of the cases of eosinophilic lung, 73.5 per cent of the filariasis group, 59.4 per cent of cases of mild eosinophilia, 53.3 per cent of normal Asians, and 4.5 per cent of the Britishers. The filarial complement fixation test using a 1 per cent alcoholic extract of the same antigen gave a positive rate of 100 per cent in the eosinophilic lung group, whereas only 24.5 per cent of the filariasis patients gave a positive reaction. Skin sensitivity to D. immitis antigen persisted in the cases of eosinophilic lung even when the previously positive serologic reactions had become negative following treatment with diethylcarbamazine. Therefore, the intradermal test cannot be useful in the diagnosis of either filariasis or eosinophilic lung in Singapore. In view of the skin sensitivity to a filarial antigen demonstrated in patients suffering from eosinophilic lung, the etiologic possibility of an infection by a species of filarial worm found normally in nonhuman hosts is discussed.
Mass drug administration via 3 modes of delivery reduced the incidence and prevalence rates and intensity of Brugia malayi infection in 3 rural villages in the Bengkoka Peninsula, Sabah, in 1982-1983. A dosage of 6 mg diethylcarbamazine citrate (DEC-C)/kg body weight was administered either daily or weekly (total of 6 doses, 36 mg/kg body weight), and impact on B. malayi cases were comparable in the 3 villages. A total of 384 people participated in the DEC-C regimens, and all pregnant women and children under 2 years were excluded from the study. Bekessy's method of estimation of incidence and recovery rates was applied to data on B. malayi microfilaremia before drug administration. Treatment with DEC-C by any of the 3 modes of delivery drastically reduced the number of episodes of patent microfilaremia, incidence and prevalence, and median microfilarial density. Reduction was sustained for at least 18 to 24 months after treatment.