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.
A control programme against subperiodic brugian filariasis was implemented in three villages, (Kg. Ampungan, Kg. Sebangkoi and Kg. Sebamban) in Sarawak, Malaysia. In Kampong Ampungan, the mass administration of diethylcarbamazine (DEC-citrate) combined with residual house spraying of pirimiphos-methyl reduced microfilarial rate to 8% of the pre-treatment level and microfilarial density (MfD50) to 44% of the pre-treatment level over a period of four years. In Kampong Sebangkoi and Kampong Sebamban, where only mass DEC therapy was applied, the microfilarial rate and MfD50 declined distinctly in the second blood survey but increased gradually in two subsequent follow-up blood surveys. In Kg, Ampungan, we observed a significant reduction of infective biting rate (88.3%), infection rate (62.5%) and transmission potential (88.1%) of Mansonia bonneae at the fourth spray round. The corresponding reduction rates in Kg. Sebangkoi and Kg. Sebamban were 35.3%, 26.7%, 42.2% and 24%, 30.8% and 15.4% respectively. The biting density of the vector was reduced by 79.8% indoors and 31.8% outdoors at the sprayed village, while only a slight decrease in densities (17.9% indoors and 12.4% outdoors) was observed at the unsprayed village. Bioassay tests revealed that pirimiphos-methyl had a substantial fumigant effect on the vector. The integrated control measure in controlling subperiodic brugian filariasis is discussed.
Till today, there is no effective treatment protocol for the complete clearance of Wuchereria bancrofti (W.b) infection that causes secondary lymphoedema. In a double blind randomized control trial (RCT), 146 asymptomatic W. b infected individuals were randomly assigned to one of the four regimens for 12 days, DEC 300 mg + Doxycycline 100 mg coadministration or DEC 300 mg + Albendazole 400 mg co-administration or DEC 300 mg + Albendazole 400 mg sequential administration or control regimen DEC 300 mg and were followed up at 13, 26 and 52 weeks post-treatment for the clearance of infection. At intake, there was no significant variation in mf counts (F(3,137)=0.044; P=0.988) and antigen levels (F(3,137)=1.433; P=0.236) between the regimens. Primary outcome analysis showed that DEC + Albendazole sequential administration has an enhanced efficacy over DEC + Albendazole co-administration (80.6 Vs 64.7%), and this regimen is significantly different when compared to DEC + doxycycline co-administration and control (P<0.05), in clearing microfilaria in 13 weeks. Secondary outcome analysis showed that, all the trial regimens were comparable to control regimen in clearing antigen (F(3, 109)=0.405; P=0.750). Therefore, DEC + Albendazole sequential administration appears to be a better option for rapid clearance of W. b microfilariae in 13 weeks time. (Clinical trials.gov identifier - NCT02005653).
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.
The study compared the effectiveness of a single dose of diethylcarbamazine (DEC) (6mg/kg) with the standard regimen of 6 doses (total 36 mg/kg) in mass chemotherapy for the control of brugian filariasis. Mass chemotherapy with single-dose DEC was instituted in one area and standard dose in the other and treatment was repeated after one year. Parasitological surveys were conducted before, and 3, 7 and 12 months after treatment. Pretreatment characteristics were not significantly different between the 2 treatment areas. There was a significant reduction in microfilaraemia prevalence rate from 24.7% to 14.7% at 12 months and to 6.8% at 19 months in the single dose area and from 22.8% to 9.6% at 12 months and to 2.7% at 19 months with the standard dose. Maximum reduction was at 7 months after treatment with both regimens. There was also significant progressive reduction in mean microfilarial density from 4.39 +/- 20.37 to 0.89 +/- 4.16 per 60 microL in the single-dose area and from 4.43 +/- 17.31 to 0.75 +/- per 60 microL in the standard dose area. There was a greater reduction of both microfilarial prevalence and density using the standard regimen but it was not statistically significant. Thus, a single dose of DEC is as effective as the standard dose in controlling periodic brugian filariasis.
We are reporting a case of an eye lesion caused by an adult Brugia malayi. The patient was a 3-year-old Chinese boy from Kemaman District, Terengganu, Peninsular Malaysia. He presented with a one week history of redness and palpebral swelling of his right eye. He claimed that he could see a worm in his right eye beneath the conjunctiva. He had no history of traveling overseas and the family kept dogs at home. He was referred from Kemaman Hospital to the eye clinic of Hospital Tengku Ampuan Afzan, Kuantan, Pahang, Malaysia. On examination by the ophthalmologist, he was found to have a subconjunctival worm in his right eye. Full blood count revealed eosinophilia (10%). Four worm fragments, each about 1 cm long were removed from his right eye under general anesthesia. A thick blood smear stained with Giemsa was positive for microfilariae of Brugia malayi. A Brugia Rapid test done was positive. He was treated with diethylcarbamazine.
Study site: Opthamolagy clinic, Hospital Tengku Ampuan Afzan
Matched MeSH terms: Diethylcarbamazine/therapeutic use
Two field trials in the control of subperiodic brugian filariasis vectors, mainly Mansonia bonneae and Mansonia dives were carried out in Sarawak, East Malaysia. In the first trial, malathion ultra-low volume (ULV) spray was used to control the Mansonia mosquitos in two filariasis endemic villages. Six spray rounds were applied at biweekly intervals at Kampung Rasau and two spray rounds were applied at monthly intervals in Kampung Triboh. ULV malathion spray reduced biting Ma. bonneae population for 3 days after spraying. The biting density decreased to 50% of the pre-treatment level by the 12th - 13th day and reached the pre-treatment level by the 24th - 25th day. Contact bioassay tests on caged Mansonia mosquitos revealed considerable penetration of the malathion aerosol indoors and relatively adequate coverage outdoors. The estimated number of bites per case per day was 1.09 to 4 times less in the sprayed kampung than in an unsprayed control kampung. The parous and daily survival rates of Mansonia mosquitos were not significantly affected by the spraying. In a second trial, chemotherapy with diethylcarbamazine citrate (DEC) was combined with vector control through indoor residual spraying in Kampung Ampungan. The results were compared with the use of only DEC mass treatment in Kampung Sebangkoi and Kampung Sebamban. The combined control measures in Kampung Ampungan reduced the MfD-50 to 44% of the pre-treatment level over a period of 4 years. In the other two kampungs where only mass DEC therapy was applied, the microfilarial rate and MfD-50 declined significantly in the second blood survey but increased gradually in two subsequent follow-up blood surveys. The total insecticidal impact for Ma. bonneae was 3.9 to 1 indoors and 2.7 to 1 outdoors. These results indicated that quarterly pirimiphos-methyl indoor spraying used in integrated control could reduce indoor transmission by 3.9 times. The infective rate from the Ma. bonneae dissected in all three kampungs after the interventions, irrespective of DEC treatment alone or in combination with pirimiphos-methyl residual spraying were reduced by two fold. However the infection rate of brugian filarial larvae in Kampung Ampungan was significantly reduced after the use of DEC and insecticide. Annual Transmission Potential (ATP) showed a high significant reduction in Kampung Ampungan (p > 0.001) compared with Kampungs Sebangkoi and Schambam. In Ampungan, the ATP was reduced by 8.5 times indoors after the MDA and insecticidal application and 3 times outdoors. The reduction rate for Sebangkoi and Sebamban both indoors and outdoors were less than 2 fold.(ABSTRACT TRUNCATED AT 400 WORDS)
Matched MeSH terms: Diethylcarbamazine/therapeutic use
Lymphatic filariasis is the most widespread of human filarial infections, a group of vector-borne infestations. After the discovery of diethylcarbamazine (DEC), little advance was made in the development of new chemotherapeutic agents for the treatment of lymphatic filariasis until 1985. Since then, several new initiatives have occurred as the result of a global effort by the World Bank/UNDP/WHO Special Programme on Tropical Diseases and the Onchocerciasis Control Programme. Some of these global research initiatives are reviewed in this paper. Recent observations throw a new light on the rational use of DEC including its deployment as a medicated salt. Ivermectin, an established drug for the treatment of river-blindness is examined for its potential use in the treatment of lymphatic filariasis. Experimental results from two novel compounds out of several being developed by the WHO/OCP Macrofil project are considered in respect to their potential macrofilaricidal activity, particularly in relation to lymphatic filarial infections.
Matched MeSH terms: Diethylcarbamazine/therapeutic use
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
The diverse clinical syndromes characterized by asthmatic symptoms, transient pulmonary infiltrates, and eosinophilia have tended to obscure the specific association of one such entity with filarial infections. Serum IgE levels were determined before and after therapy in a group of well-characterized patients with tropical eosinophilia (TE), studied earlier in Singapore. The mean serum IgE level in 14 cases before treatment with diethylcarbamazine was 2,355 ng. per milliliter, with a trend but statistically nonsignificant decrease in levels to 600-1,000 ng. occurring 8 to 12 weeks after therapy. Leukocyte and eosinophil counts showed a rapid reduction after treatment, and although mean complement-fixing (cf) titers to Dirofilarial antigen tended to decrease, they were not significantly reduced until 5 to 6 weeks. The historical development of evidence supporting the filarial etiology of TE was reviewed. Many basic questions engendered by the clinical syndrome of tropical eosinophilia make it an excellent model for study of the immunopathology of parasitic infections.
Matched MeSH terms: Diethylcarbamazine/therapeutic use
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.
An active worm was seen in the right eye of a 62-year-old man in Malaysia. The worm was behind the lens and attached at one end to some vitreous fibers. It was tentatively identified as an immature Dirofilaria immitis. There appear to be only five previous authentic reports of filariae in the vitreous.
Matched MeSH terms: Diethylcarbamazine/therapeutic use
DEC or ivermectin (IVM) in combination with albendazole (ALB) has been the recommended strategy of the Global Programme to Eliminate Lymphatic Filariasis (GPELF) since 2000. Despite effective population coverage (> 65%) with several rounds of MDA with DEC or combination of DEC plus ALB, microfilariae persist in few individuals and they continue to be the source of infection for transmitting LF. We report an individual's variability in response to DEC by defining the response as complete absence of microfilaria (mf) (post-treatment mf count = 0) and non-response as presence of mf (post-treatment mf count ≥ 1). We analyzed follow-up data on individual's response to treatment from two randomized clinical trials in which 46 microfilaremic individuals were treated with single-dose DEC (6 mg/kg body weight). They were classified into low, medium, and high mf density categories based on their pre-treatment mf counts. Of the 46 individuals, 65.2% have not responded throughout the 12-month post-treatment period. Application of a logistic regression model with fixed (age, gender, mf density, post-treatment time, and their interactions) and random (individual's response over time) effects indicated that treatment response is independent of age, gender, and time. The overall treatment response increases in low and decreases in high mf density categories. Furthermore, the estimates for the random coefficients model showed that there is a greater variability in response between individuals over post-treatment time. The results substantiate that individual variation in response to DEC exists which indicate the importance of studying the parasite as well as host genetic factors associated with DEC action.