Efektivitas Pengobatan Massal Filariasis Setelah Empat Tahun Pengobatan Massal di Desa Ploso, Demak, Jawa Tengah

TThe filariasis elimination program is carried out through mass treatment with Diethylcarbamazine Citrate (DEC) and albendazole once a year for five years. Filariasis mass treatment, which was carried out for five years, aims to reduce the prevalence rate of microfilaria < 1%. Evaluation of community treatment needs to be done, one of which is the Finger Blood Preparation (SDJ) and Polymerase Chain Reaction (PCR) methods. The purpose of this research was to know the effectiveness of mass treatment of filariasis after four years in Karang Ploso Village, Demak, Indonesia. This study is a descriptive study with a cross-sectional approach with a sample of 350 people. The study variables were an examination of SDJ microfilariae, PCR molecular examination, and interviews about filariasis knowledge. The examination methods used were SDJ and PCR. The data analysis used was univariate, microfilaria rate. The results of SDJ and PCR examinations were not found microfilariae, so that the Mf rate was 0%. As many as 97.4% of people adhered to taking medication, 91.1% of people had moderate knowledge of filariasis, 98.3% had an average experience of the Mass Drug Administration (MDA). The Mf rate results by SDJ and PCR in Demak after the fourth filariasis treatment program in 2019 was 0%. There was a decrease in SDJ results from 2016-2019, namely 1% to 0% in 2019.

Safety and Tolerability of Mass Diethylcarbamazine and Albendazole Administration for the Elimination of Lymphatic Filariasis in Kenya: An Active Surveillance Study

Preventive chemotherapy with diethylcarbamazine citrate (DEC) and albendazole (ALB) is the core intervention strategy to eliminate lymphatic filariasis (LF). We conducted a large-scale prospective active safety surveillance study to identify the incidence, type, severity, and risk factors for adverse events (AEs) following mass drug administration (MDA) of single-dose DEC and ALB in 10,010 participants from Kilifi County, Kenya. AEs were actively monitored and graded at 24 h, 48 h, and on day 7 Post-MDA. Out of 10,010 enrolled study participants, 1621 participants reported a total of 3102 AEs during a seven-day follow-up. The cumulative incidence of AEs was 16.2% (95% CI, 15.5–16.9%). The proportion of participants who experienced one, two, or ≥ three types of AEs was 9.2%, 4.6%, 2.4%, respectively. AEs were mild (87.3%), moderate (12.4%), and severe (0.3%) and resolved within 72 h. The five most common AEs were dizziness (5.9%), headache (5.6%), loss of appetite (3.3%), fever (2.9%), and drowsiness (2.6%). Older age, taking concurrent medications, ≥ three tablets of DEC, and type of meal taken before MDA were significant predictors of AEs. One in six participants experienced systemic mild-to-moderate severity grading and transient AEs. DEC and ALB co-administration for the elimination of LF is generally safe and well-tolerated.

A multicenter, community-based, mixed methods assessment of the acceptability of a triple drug regimen for elimination of lymphatic filariasis

Background Many countries will not reach elimination targets for lymphatic filariasis in 2020 using the two-drug treatment regimen (diethylcarbamazine citrate [DEC] and albendazole [DA]). A cluster-randomized, community-based safety study performed in Fiji, Haiti, India, Indonesia and Papua New Guinea tested the safety and efficacy of a new regimen of ivermectin, DEC and albendazole (IDA). Methodology/Principal findings To assess acceptability of IDA and DA, a mixed methods study was embedded within this community-based safety study. The study objective was to assess the acceptability of IDA versus DA. Community surveys were performed in each country with randomly selected participants (>14 years) from the safety study participant list in both DA and IDA arms. In depth interviews (IDI) and focus group discussions (FGD) assessed acceptability-related themes. In 1919 individuals, distribution of sex, microfilariae (Mf) presence and circulating filarial antigenemia (CFA), adverse events (AE) and age were similar across arms. A composite acceptability score summed the values from nine indicators (range 9–36). The median (22.5) score indicated threshold of acceptability. There was no difference in scores for IDA and DA regimens. Mean acceptability scores across both treatment arms were: Fiji 33.7 (95% CI: 33.1–34.3); Papua New Guinea 32.9 (95% CI: 31.9–33.8); Indonesia 30.6 (95% CI: 29.8–31.3); Haiti 28.6 (95% CI: 27.8–29.4); India 26.8 (95% CI: 25.6–28) (P<0.001). AE, Mf or CFA were not associated with acceptability. Qualitative research (27 FGD; 42 IDI) highlighted professionalism and appreciation for AE support. No major concerns were detected about number of tablets. Increased uptake of LF treatment by individuals who had never complied with MDA was observed. Conclusions/Significance IDA and DA regimens for LF elimination were highly and equally acceptable in individuals participating in the community-based safety study in Fiji, Haiti, India, Indonesia, and Papua New Guinea. Country variation in acceptability was significant. Acceptability of the professionalism of the treatment delivery was highlighted.

Tri-Model Therapy: Combining Macrocyclic Lactone, Piperazine Derivative and Herbal Preparation in Treating Humpsore in Cattle

Stephanofilariasis or humpsore is a chronic parasitic dermatitis of cattle. Various treatment regimens were attempted in the past but were found to be partially effective. Here, we claim a successful treatment regime using an FDA-approved macrocyclic lactone, a piperazine derivative, and an herbal preparation. Twenty-four cattle (18 affected and 6 unaffected) were selected and divided into Gr 1: positive control (infected without treatment; n = 6), Gr 2: treatment group (infected with treatment with ivermectin; n = 6), Gr 3: treatment group (infected with treatment with tri-model therapy including ivermectin, diethylcarbamazine citrate, and an herbal ointment, n = 6), and Gr 4: negative control (non-infected animals; n = 6). In Gr 2 and Gr 3, treatment to the ailing animals were given for 30 days. Lesion was significantly reduced in day 15 of post-treatment and completely healed on day 30 of post-treatment in Gr 3. Tri-model therapy recorded significant improvement in the surface area of the sore as compared to ivermectin administration alone. Antioxidants were increased and malondialdehyde (MDA) and cortisol concentrations were decreased significantly (p < 0.05) in Gr 3 than in untreated control group at day 14, 21 and 28. Histopathological changes in infected animals were characterized by parakeratotic hyperkeratosis along with presence of nucleated keratinocytes. There were infiltrations of polymorphonuclear cells specially eosinophils along with a few monomorphonuclear cells. Microfilarial organism was observed beneath the epidermis, which was surrounded by fibrocytes and infiltrated cells. In the tri-model-treated animal after recovery, the skin revived a normal architecture. Therefore, tri-model therapy has the potential to cure humpsore.

A Randomized, Placebo-controlled, Double-blind Pilot Study of Single-dose Humanized Anti-IL5 Antibody (Reslizumab) for the Reduction of Eosinophilia Following Diethylcarbamazine Treatment of Loa loa Infection

Background Diethylcarbamazine citrate (DEC) treatment of loiasis is complicated by adverse reactions that are correlated with the number of circulating microfilariae (mf). The cause of these reactions is unknown, but they are accompanied by a dramatic interleukin-5 (IL-5)-dependent increase in eosinophilia and evidence of eosinophil activation. Methods To explore the role of IL-5 driven eosinophilia in post-DEC reactions, 8 adults with confirmed loiasis and &lt;5000 mf/mL blood were enrolled in a randomized, double-blind, placebo-controlled trial of the humanized anti-IL-5 antibody, reslizumab, (1.0 mg/kg IV) administered 3 to 7 days prior to initiation of DEC treatment (9 mg/kg/day for 21 days). The primary endpoint was the reduction in absolute eosinophil count (AEC) during the first week of DEC treatment. Results Baseline characteristics were comparable between the two groups. Single dose reslizumab lowered the AEC by 77% prior to initiation of DEC therapy (vs. 12% in the placebo group, P &lt; .05). More importantly, AEC remained below baseline in the first week of DEC treatment in all subjects who received reslizumab and in none of the placebo subjects. Mf clearance occurred within 2 days of initiation of DEC in all 7 mf-positive subjects. Mild to moderate adverse events were seen in all 8 subjects and were not significantly different between the groups. Conclusions In summary, although reslizumab was able to blunt peripheral eosinophilia post-DEC treatment in subjects with loiasis and had no effect on microfilarial clearance, the reduction in AEC appeared to have been insufficient to prevent post-treatment AEs.

Enhancement of Anti-allergic Effect of Diethylcarbamazine Citrate in Asthmatic Mouse Model: Testing of Anti-drug Antibodies and Querceti

Diethylcarbamazine citrate (DEC) is known as an effective treatment for bronchial asthma because of its ability to reduce eosinophil trafficking to the lung tissue. The current study aimed to potentiate the anti-allergic effect of the drug by passive immunization of the asthmatic model with anti-DEC antibody or prior treatment with quercetin (Qur). Eight mice groups were categorized into control, the model of lung asthma, treated with DEC, passively immunized with anti(α)-bovine serum albumin Ab, anti-DEC Ab, prior exposure to 10, 20, or 40 mg Qur/Kg. b.wt. Both eosinophil peroxidase (EPO) and eotaxin2 in the lung tissues were performed. Serum levels of cytokines, bronchoalveolar lavage fluid (BALF) IgE, rabbit anti-bovine serum albumin (anti-BSA), and DEC IgG in lung tissue homogenates were assayed by ELISA. Regarding the effect of anti-DEC Ab and Qur on DEC-induced recovery of histopathological alterations showed that the Ova group had peri-bronchial hyperplasia, mononuclear leukocyte infiltration, thickening in the wall of alveoli, and congested blood vessels. However, the reduction of inflammatory cells and thickened alveolar walls was dependent on the Qur dose. Qur40 enhanced the anti-allergic effect of DEC. Moreover, the present data revealed high levels of Th2 cytokines (IL-4 and IL-5) and IgE in the Ova group. An increased leukocyte infiltration/thickening of the alveolar wall and lung tissue EPO/eotaxin2 were also observed. Qur-40 could show an enhancement effect on DEC for the reduction of IL-4, IL-5, IgE, EPO, and eotaxin 2. Consequently, the IFN-γ/IL-4 ratio was increased. Qur at 40 mg/Kg could be recommended to enhance the DEC effect suggesting a novel approach for treatment.

Diethylcarbamazine (DEC) in Relapse Cases of Nephrotic Syndrome in Filarial Endemic Region: A Case Series

Introduction: Incidence of nephrotic syndrome (NS) and filariasis both is high in China, Japan & India. Studies have shown the association of filariasis in NS. In the coastal belt of Gujarat, Filariasis occurs as the mosquito responsible is still prevalent. Therefore, filariasis association may be causing persistence of oedema in NS relapse cases. After a 7th relapse patient was treated successfully with diethylcarbamazine citrate (DEC), we decided to observe the effect of DEC on weight loss and urine protein, in relapse patients of NS. Case Details: In relapse patients of NS, DEC was given by oral route in the dose of 72 mg/kg/cycle for 7 days. Weight record and urine protein were measured daily. Steroid as Tab prednisolone was administered at 2 mg/k/d. Outcome: The 1st case was a steroid-dependent nephrotic syndrome with the 7th relapse; she had been on prednisolone and Levamisol for 3 years. DEC was started on day 3 of admission and response was seen on the 5th day. Urinary protein became nil on day 10, and the patient has been relapse free for 1 year. In each of the other 4 cases with 1st, 2nd, 2nd and 4th relapse respectively, the response of DEC was seen within 2 days. Thus, after starting DEC weight and urine protein reduced within 2 days in 5 relapse cases. Filaria was not detected in blood film of any patient and Elisa tests done in 2 were negative. Conclusion: Randomized studies with controls and better filarial detection methods are required for DEC to be considered as an add-on drug in relapse cases of NS in, Filarial endemic regions, as it is faster acting, effective, similar to Levamisol and safe.

Development of HPLC Method for Stress Testing of Combination of Two Drugs Using Design of Experiment Concept

This study was conducted to develop, an High Performance Liquid Chromatography using photodiode array detector (HPLC-PDA) method to analyse the samples generated by the stress testing of antifilarial combination (albendazole and diethylcarbamazine citrate) in the solution state. The concept of Quality by Design (Design of Experiment, DoE) approach was used for the development. For the separation of the drugs and its degradation products (DPs), DoE was applied in two stages, i.e., primary parameter stage where factors having major effect were selected. This stage gives us CQA (Critical Quality Attribute) which along with minor factors affecting were varied to get the secondary design. For each of the stage a different design was selected; for primary stage IV optimal design (Response Surface Method) was selected whereas for secondary stage, Taguchi orthogonal array design was selected. The major primary parameters affecting the HPLC method as screened by preliminary studies were the buffer pH, organic modifier (methanol or acetonitrile), initial hold time (start of gradient) and gradient time. The primary stage was completed successfully. The results were compiled in form of resolution of peak from next peak and analysed by DoE. The process fixed the values for buffer pH (4.38), organic modifier (acetonitrile) and gradient time (30 min). The CQA from primary run was initial hold time. This parameter along with other parameters: initial and final concentration of organic modifier, buffer type (phosphate or acetate), buffer strength (mM) and oven temperature were further varied and samples withdrawn were analysed. The data of secondary design was compiled in the form of resolution (R), analysed by Design Expert and final value for secondary parameter for HPLC method were fixed. The resolution of the peaks for some secondary runs was sufficient reflecting some type of interaction between the drugs and/or degradation products.