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
CGP 20376, a 5-methoxyl-6-dithiocarbamic-S- (2-carboxy-ethyl) ester derivative of benzothiazole was evaluated for its antifilarial properties and shown to be extremely effective against subperiodic Brugia malayi in the leaf-monkey, Presbytis cristata at oral doses of 20-100 mg/kg. The compound and/or its metabolites had complete micro- and microfilaricidal activities even when given at a single dose of 20 mg/kg. Lower doses had incomplete filaricidal action.
A rapid and selective high-performance liquid chromatographic assay for simultaneous quantitative determination of a new antifilarial drug (UMF-058, I) and mebendazole (MBZ) is described. After a simple extraction from whole blood, both compounds were analysed using a C18 Nova Pak reversed-phase column and a mobile phase of methanol-0.05 M ammonium dihydrogenphosphate (50:50, v/v) adjusted to pH 4.0, with ultraviolet detection at 291 nm. The average recoveries of I and MBZ over a concentration range of 25-250 ng/ml were 92.0 +/- 7.7 and 84.4 +/- 4.4%, respectively. The minimum detectable concentrations in whole blood for I and MBZ were 7 and 6 ng/ml, respectively. This method was found to be suitable for pharmacokinetic studies.
CGI 18041, an adduct of benzothiazol isothiocyanate N-methyl piperazine, was evaluated for its antifilarial properties in subperiodic Brugia malayi infected Presbytis cristata. Animals experimentally infected with 200-400 subperiodic Brugia malayi infective larvae, were matched according to microfilaria density, infective dose, and duration of infection. They were then randomly assigned to various treatment and control groups. The compound was suspended in 1% Tween 20 in distilled water, sonicated, and then fed to monkeys using a stomach tube. Control animals received an equivalent volume of drug diluent. CGI 18041 at a single oral dose of 50 mg/kg had complete adulticidal and microfilaricidal activities against subperiodic B. malayi in P. cristata. It was also extremely effective at a single dose of 25 mg/kg, the final geometric mean microfilaria count being 1.6% of initial level, and only 1.0% of the infective dose was recovered as live adult worms at autopsy 6 weeks post-treatment. In control animals, these were 226.9% and 5.56% respectively.
Serum IgG levels and complement C3 levels were assayed on Day 0, 1, 3-4, 7 and 56-70 post-treatment with diethylcarbamizine citrate (DEC) in a series to 26 patients with Brugia malayi infection and 6 volunteers without infection. On treatment, the microfilariae were cleared from the blood within 24 hours. The eosinophils decreased dramatically on Day 1 post-treatment but increased rapidly by Day 4 to 7 and then dropped to normal levels in 45 days. The serum IgG mean levels decreased briefly following treatment with DEC but then returned to original levels. However, the complement C3 levels gradually increased over the 2 months period of study reaching statistical significance levels (p less than 0.01) in patients with initial high blood microfilariae. The observation suggests that Brugia malayi infection probably induces a high rate of synthesis of complement C3 and this process continued in the post-treatment phase. Since, DEC treatment did not cause a decrease in complement C3 with the elimination of blood microfilariae, it would appear that the complement C3 is consumed following antibody attachment to the microfilariae as they enter the blood circulation.
Ivermectin at single doses of 0.2-1.0 mg/kg body weight reduced the microfilarial counts of subperiodic Brugia malayi in Presbytis cristata by 59.9%-89.6% of initial counts, 4 weeks after treatment. Adult filaricidal activity was poor, live adult worms being recovered from all animals at autopsy. There was no serious side effect at these doses.
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.
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).
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.
A clinical trial on the efficacy of a single oral dose of ivermectin at 20, 50, 100, and 200 micrograms/kg was carried out in 40 subjects with subperiodic Brugia malayi microfilaremia. There was no significant difference in the clearance of microfilaremia in the four treatment groups, and the lowest geometric mean microfilarial count (GMC) achieved in the 40 subjects was 8.8/ml or 8.3% of the initial count (106.1/ml), at two weeks post-treatment. The GMC started to increase at one month post-treatment and by six months was 22.2% of the initial GMC. Only 27.5%, 23.1%, 15.0%, and 18.9% of subjects were amicrofilaremic at two, four, 12, and 24 weeks post-treatment, respectively. Mild fever in 35% of the subjects was the primary side reaction and was more common in those with microfilarial counts > or = 500/ml (85.7%) than in those with counts < 500/ml (32%). The clearance of B. malayi microfilaremia by ivermectin was less rapid than that reported for Wuchereria bancrofti. The smaller number of side reactions encountered in the present study compared with those reported for bancroftian filariasis is probably related to the lower microfilarial density in the present subjects. Since ivermectin at a single oral dose of 20-200 micrograms/kg can reduce the GMC to less than 10% at two weeks and maintain it below 25% of the initial level even at six months post-treatment, it is recommended that the drug be seriously evaluated for use in the control of brugian filariasis.
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.
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.
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.
Lymphatic filariasis (LF) is a vector borne disease caused by parasitic worms such as Wuchereria bancrofti, Brugia malayi and B. timori, which are transmitted by mosquitoes. Current therapeutics to treat LF are mainly microfilarcidal, and lack activity against adult worms. This set back, poses a challenge for the control and elimination of filariasis. Thus, in this study the activities of caffeic acid phenethyl ester (CAPE) against the filarial worm B. pahangi and its bacterial endosymbiont, Wolbachia were evaluated. Different concentrations (2, 5, 10, 15, 20 μg/ml) of CAPE were used to assess its effects on motility, viability and microfilarial (mf) production of B. pahangi in vitro. Anti-Wolbachial activity of CAPE was measured in worms by quantification of Wolbachial wsp gene copy number using real-time polymerase chain reaction. Our findings show that CAPE was found to significantly reduce adult worm motility, viability, and mf release both in vitro and in vivo. 20 μg/ml of CAPE halts the release of mf in vitro by day 6 of post treatment. Also, the number of adult worms recovered in vivo were reduced significantly during and after treatment with 50 mg/kg of CAPE relative to control drugs, diethylcarbamazine and doxycycline. Real time PCR based on the Wolbachia ftsZ gene revealed a significant reduction in Wolbachia copy number upon treatment. Anti-Wolbachia and antifilarial properties of CAPE require further investigation as an alternative strategy to treat LF.
The lymphatic filarial parasite Brugia timori occurs only in eastern Indonesia where it causes high morbidity. The absence of an animal reservoir, the inefficient transmission by Anopheles mosquitoes and the high sensitivity to DEC/albendazole treatment make this species a prime candidate for elimination by mass drug administration (MDA).