How Does the Proportion of Never Treatment Influence the Success of Mass Drug Administration Programs for the Elimination of Lymphatic Filariasis?

BACKGROUND: Mass drug administration (MDA) is the cornerstone for the elimination of lymphatic filariasis (LF). The proportion of the population that is never treated (NT) is a crucial determinant of whether this goal is achieved within reasonable time frames. METHODS: Using 2 individual-based stochastic LF transmission models, we assess the maximum permissible level of NT for which the 1% microfilaremia (mf) prevalence threshold can be achieved (with 90% probability) within 10 years under different scenarios of annual MDA coverage, drug combination and transmission setting. RESULTS: For Anopheles-transmission settings, we find that treating 80% of the eligible population annually with ivermectin + albendazole (IA) can achieve the 1% mf prevalence threshold within 10 years of annual treatment when baseline mf prevalence is 10%, as long as NT <10%. Higher proportions of NT are acceptable when more efficacious treatment regimens are used. For Culex-transmission settings with a low (5%) baseline mf prevalence and diethylcarbamazine + albendazole (DA) or ivermectin + diethylcarbamazine + albendazole (IDA) treatment, elimination can be reached if treatment coverage among eligibles is 80% or higher. For 10% baseline mf prevalence, the target can be achieved when the annual coverage is 80% and NT ≤15%. Higher infection prevalence or levels of NT would make achieving the target more difficult. CONCLUSIONS: The proportion of people never treated in MDA programmes for LF can strongly influence the achievement of elimination and the impact of NT is greater in high transmission areas. This study provides a starting point for further development of criteria for the evaluation of NT.

Diethylcarbamazine elicits Ca2+ signals through TRP-2 channels that are potentiated by emodepside in Brugia malayi muscles.

Filarial nematode infections are a major health concern in several countries. Lymphatic filariasis is caused by Wuchereria bancrofti and Brugia spp. affecting over 120 million people. Heavy infections can lead to elephantiasis, which has serious effects on individuals' lives. Although current anthelmintics are effective at killing microfilariae in the bloodstream, they have little to no effect against adult parasites found in the lymphatic system. The anthelmintic diethylcarbamazine is one of the central pillars of lymphatic filariasis control. Recent studies have reported that diethylcarbamazine can open transient receptor potential (TRP) channels in the muscles of adult female Brugia malayi, leading to contraction and paralysis. Diethylcarbamazine has synergistic effects in combination with emodepside on Brugia, inhibiting motility: emodepside is an anthelmintic that has effects on filarial nematodes and is under trial for the treatment of river blindness. Here, we have studied the effects of diethylcarbamazine on single Brugia muscle cells by measuring the change in Ca2+ fluorescence in the muscle using Ca2+-imaging techniques. Diethylcarbamazine interacts with the transient receptor potential channel, C classification (TRPC) ortholog receptor TRP-2 to promote Ca2+ entry into the Brugia muscle cells, which can activate Slopoke (SLO-1) Ca2+-activated K+ channels, the putative target of emodepside. A combination of diethylcarbamazine and emodepside leads to a bigger Ca2+ signal than when either compound is applied alone. Our study shows that diethylcarbamazine targets TRP channels to promote Ca2+ entry that is increased by emodepside activation of SLO-1 K+ channels.

Efficacy and safety of triple therapy versus dual therapy for lymphatic filariasis: A systematic review and meta-analysis.

OBJECTIVE: Lymphatic filariasis is a serious public health issue. Recent studies showed that a single dosage of triple therapy (Ivermectin, Diethylcarbamazepine, and Albendazole) is more effective than dual therapy (Ivermectin plus Albendazole or Diethylcarbamazepine plus Albendazole) for clearing microfilaria from the blood. We aimed to evaluate the efficacy and safety of triple therapy versus dual therapy in patients infected with microfilaria and communities endemic to lymphatic filariasis. METHODS: For this systematic review and meta-analysis, we searched MEDLINE, EMBASE, SCOPUS, Cochrane Central Register of Controlled Trials, and Web of Science until 24th June 2021. We included randomized control trials that compared triple with dual therapy given to patients with lymphatic filariasis or endemic communities. This study was registered with PROSPERO (CRD42021266724). RESULTS: We included eight articles after the screening process. Triple therapy caused more clearance of microfilaria in the blood (RR: 1.52; 95% CI: 1.15, 2.02; p = 0.003), while dual therapy caused more clearance of the circulating filariae antigen in the blood (RR: 0.76; 95% CI: 0.65, 0.88; p = 0.0003), both 12 months after drug administration. The triple therapy had a similar adverse effect compared with the dual therapy group. CONCLUSION: Based on the greater efficacy in the clearance of microfilaria and the safety of triple therapy, it constitutes a better strategy for the eradication programs of lymphatic filariasis in endemic regions. However, further studies are needed to confirm our results.

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 <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 < .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.

Population Pharmacokinetics of Diethylcarbamazine in Patients with Lymphatic Filariasis and Healthy Individuals.

Diethylcarbamazine (DEC) is a drug of choice to treat lymphatic filariasis (LF) either used alone or in combination as mass drug administration (MDA) preventive strategies. The objective of this study was to develop a population pharmacokinetics (PK) model for DEC in subjects infected with lymphatic filariasis (LF) compared to healthy individuals, and to evaluate the effect of covariates on the volume of distribution (V/F) and oral clearance (CL/F) of DEC. This was an open-label cohort study of treatment-naive Wuchereria bancrofti-infected (n = 32) and uninfected (n = 24) adults residing in the Agboville District of Côte d'Ivoire. The population pharmacokinetics model for DEC was built using Phoenix NLME 8.0 software. The covariates included in the model-building process were age, gender, body weight, infection status, creatinine clearance (CLCR), and aspartate aminotransferase (AST) and alanine aminotransferase (ALT) levels. A total of 56 adults were enrolled in the study, and a total of 728 samples were obtained over 168 h. A one-compartment linear pharmacokinetics model with first-order absorption with an absorption lag time (Tlag) best described the data. After determining the pharmacokinetics (PK) parameters of DEC, body weight and gender were found to be the significant covariates for DEC V/F. The final population pharmacokinetics model adequately described the pharmacokinetics of DEC in the studied population. Model-based simulation indicated that the body weight significantly impacted the exposure in both the male and female populations. This analysis may further support the drug-drug interaction model development of DEC with different coadministered drugs or agents in disease control programs. (This study is registered at clinicaltrials.gov under identifier NCT02845713.).

Heterogeneous response of Wuchereria bancrofti-infected persons to diethylcarbamazine (DEC) and its implications for the Global Programme to Eliminate Lymphatic Filariasis (GPELF).

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.

Efficacy and Safety of a Single Dose of Ivermectin, Diethylcarbamazine, and Albendazole for Treatment of Lymphatic Filariasis in Côte d'Ivoire: An Open-label Randomized Controlled Trial.

BACKGROUND: Improved drug regimens are needed to accelerate elimination of lymphatic filariasis in Africa. This study determined whether a single co-administered dose of ivermectin plus diethylcarbamazine plus albendazole [IDA] is noninferior to standard 3 annual doses of ivermectin plus albendazole (IA) used in many LF-endemic areas of Africa. METHODS: Treatment-naive adults with Wuchereria bancrofti microfilaremia in Côte d'Ivoire were randomized to receive a single dose of IDA (n = 43) or 3 annual doses of IA (n = 52) in an open-label, single-blinded trial. The primary endpoint was the proportion of participants who were microfilaria (Mf) negative at 36 months. Secondary endpoints were Mf clearance at 6, 12, and 24 months; inactivation of adult worm nests; and safety. RESULTS: At 36 months posttreatment with IDA, 18/33 (55%; 95% CI, 38-72%) cleared Mf versus 33/42 (79%; 67-91%) with IA (P = .045). At 6 and 12 months IDA was superior to IA in clearing Mf (89% [77-99%] and 71% [56-85%]), respectively, versus 34% (20-48%) and 26% (14-42%) (P < .001). IDA was equivalent to IA at 24 months (61% [45-77%] vs 54% [38-72%]; P = .53). IDA was superior to IA for inactivating adult worms at all time points. Both treatments were well tolerated, and there were no serious adverse events. CONCLUSIONS: A single dose of IDA was superior to 2 doses of IA in reducing the overall Mf burden by 24 months. Reinfection may have contributed to the lack of sustained clearance of Mf with IDA. CLINICAL TRIALS REGISTRATION: NCT02974049.

Radioprotective effect of diethylcarbamazine on radiation-induced acute lung injury and oxidative stress in mice.

The present study was designed to evaluate the radioprotective effect of diethylcarbamazine (DEC) against oxidative stress and acute lung injury induced by total body radiation (TBI) in mice. For study the optimum dose for radiation protection of DEC, mice were administrated with three dose of DEC (10, 50 and 100 mg/kg), once daily for eight consecutive days. Animals were exposed whole body to 5 Gy X-radiation on the 9 day. The radioprotective potential of DEC in lung tissues was assessed using oxidative stress examinations at 24 h after TBI and histopathological assay also was analyzed one week after TBI. Results from biochemical analyses demonstrated increased malonyldialdehyde (MDA), nitric oxide (NO) and protein carbonyl (PC) levels of lung tissues in only irradiated group. Histopathologic findings also showed an increase in the number of inflammatory cells and the acute lung injury in this group. DEC pretreatment significantly mitigated the oxidative stress biomarkers as well as histological damages in irradiated mice. The favorable radioprotective effect against lungs injury was observed at a dose of 10 mg/kg of DEC in mice as compared with two other doses (50 and 100 mg/kg). The data of this study showed that DEC at a dose of 10 mg/kg with having antioxidant and anti-inflammatory properties can be used as a therapeutic candidate for protecting the lung from radiation-induced damage.

Imported loiasis in France: a retrospective analysis of 167 cases with comparison between sub-Saharan and non sub-Saharan African patients.

BACKGROUND: Imported loiasis is a rare cause of consultation at the return of stay in central Africa, which often poses difficult diagnostic and therapeutic questions to practitioners especially those who are unaccustomed to tropical medicine. These difficulties can lead to risks for the patients especially if inappropriate treatment is given. Large series of imported loiasis are scarce. METHODS: We retrospectively studied the data including outcome in patients diagnosed with imported loiasis between 1993 and 2013 in the Paris area on the basis of a parasitological diagnosis (microfilaremia > 1/ml and/or serologic tests). We compared sub-Saharan and non sub-Saharan African patients. RESULTS: Of the 177 identified cases, 167 could be analysed. Sex ratio was 1, mean age 41 years and 83% were sub-Saharan Africans. Cameroon was the main country of exposure (62%). Incubation time may be long (up to 18 months). Of the 167 cases, 57% presented with characteristic symptoms (Calabar swellings, creeping dermatitis, eyeworm) whereas 43% were diagnosed fortuitously. Microfilaremia was evidenced in 105 patients (63%), and specific antibodies in 53%. Compared to sub-Saharan Africans, other patients were presenting less frequently with eyeworm migration and microfilaremia whereas they had higher eosinophilia and positive serology. Prevalence of Calabar swellings was not significantly different between the two groups. Cure rates were 52% with ivermectin alone, and 77% with ivermectin followed by diethylcarbamazine. No severe adverse event was reported. CONCLUSIONS: Presentation of imported loiasis varies according to ethnicity. A systematic screening should be recommended in patients with potential exposure in endemic country. Treatment with ivermectin followed by diethylcarbamazine could be a valuable option.

Efficacy of High-Dose Albendazole with Ivermectin for Treating Imported Loiasis, Italy.

We describe the outcomes of 16 cases of imported loiasis in Italy. Patients had microfilaremia <20,000/mL and were treated with high-dose albendazole for 28 days and a single dose of ivermectin. This combination might be an effective treatment option in nonendemic areas, when diethylcarbamazine, the drug of choice, is not available.

The use of variable temperature 13 C solid-state MAS NMR and GIPAW DFT calculations to explore the dynamics of diethylcarbamazine citrate.

Experimental 13 C solid-state magic-angle spinning (MAS) Nuclear Magnetic Resonance (NMR) as well as Density-Functional Theory (DFT) gauge-including projector augmented wave (GIPAW) calculations were used to probe disorder and local mobility in diethylcarbamazine citrate, (DEC)+ (citrate)- . This compound has been used as the first option drug for the treatment of filariasis, a disease endemic in tropical countries and caused by adult worms of Wuchereria bancrofti, which is transmitted by mosquitoes. We firstly present 2D 13 C─1 H dipolar-coupling-mediated heteronuclear correlation spectra recorded at moderate spinning frequency, to explore the intermolecular interaction between DEC and citrate molecules. Secondly, we investigate the dynamic behavior of (DEC)+ (citrate)- by varying the temperature and correlating the experimental MAS NMR results with DFT GIPAW calculations that consider two (DEC)+ conformers (in a 70:30 ratio) for crystal structures determined at 293 and 235 K. Solid-state NMR provides insights on slow exchange dynamics revealing conformational changes involving particularly the DEC ethyl groups.

Diethylcarbamazine attenuates the expression of pro-fibrogenic markers and hepatic stellate cells activation in carbon tetrachloride-induced liver fibrosis.

BACKGROUND AND AIM: While diethylcarbamazine citrate (DEC) displays important anti-inflammatory effects in experimental models of liver injury, the mechanisms of its action remain poorly understood. The aim of the present study was to investigate the fibrolytic potential of DEC. METHODS: Mice receive two injections of carbon tetrachloride (CCl4) per week for 8 weeks. DEC 50 mg/kg body weight was administered through drinking water during the last 12 days of liver injury. RESULTS: The expression of hepatic stellate cells (HSCs) activation markers, including smooth muscle α-actin (α-SMA), collagen I, transforming growth factor-ß 1 (TGF-ß1), matrix metalloproteinase-2 (MMP-2) and tissue inhibitor of metalloproteinase-1 (TIMP-1) was assessed. The influence of DEC on the intracellular MAPK pathways of the HSCs (JNK and p38 MAPK) was also estimated. DEC inhibited HSCs activation measured as the production of α-SMA and collagen I. In addition, it down regulated the production of TGF-ß1 and TIMP-1, and concomitantly increased MMP-2 activity. Furthermore, DEC significantly inhibited the activation of the JNK and p38 MAPK signaling pathways. CONCLUSIONS: In conclusion, DEC significantly attenuated the severity of CCl4-induced liver injury and the progression of liver fibrosis, exerting a potential fibrolytic effect in the CCl4-induced fibrosis model.

Posttreatment Reactions After Single-Dose Diethylcarbamazine or Ivermectin in Subjects With Loa loa Infection.

Background: Severe adverse reactions have been observed in individuals with Loa loa infection treated with either diethylcarbamazine (DEC), the drug of choice for loiasis, or ivermectin (IVM), which is used in mass drug administration programs for control of onchocerciasis and lymphatic filariasis in Africa. In this study, posttreatment clinical and immunologic reactions were compared following single-dose therapy with DEC or IVM to assess whether these reactions have the same underlying pathophysiology. Methods: Twelve patients with loiasis and microfilarial counts <2000 mf/mL were randomized to receive single-dose DEC (8 mg/kg) or IVM (200 µg/kg). Clinical and laboratory assessments were performed at 4, 8, 24, 48, and 72 hours and 5, 7, 9, and 14 days posttreatment. Results: Posttreatment adverse events were similar following DEC or IVM, but peaked earlier in subjects who received DEC, consistent with a trend toward more rapid and complete microfilarial clearance in the DEC group. After a transient rise (post-IVM) or fall (post-DEC) in the first 24 hours posttreatment, the eosinophil count rose significantly in both groups, peaking at day 5 in the DEC group and day 9 in the IVM group. Serum interleukin 5 levels and eosinophil activation, as assessed by surface expression of CD69 and serum levels of eosinophil granule proteins, were increased posttreatment in both groups. Conclusions: Despite differences in eosinophil and lymphocyte counts during the first 24 hours posttreatment, the overall pattern of hematologic and immunologic changes suggest that posttreatment reactions following DEC and IVM share a common pathophysiology. Clinical Trials Registration: NCT01593722.

Loiasis in US Traveler Returning from Bioko Island, Equatorial Guinea, 2016.

The filarial parasite Loa loa overlaps geographically with Onchocera volvulus and Wuchereria bancrofti filariae in central Africa. Accurate information regarding this overlap is critical to elimination programs targeting O. volvulus and W. bancrofti. We describe a case of loiasis in a traveler returning from Bioko Island, Equatorial Guinea, a location heretofore unknown for L. loa transmission.

Diethylcarbamazine: A potential treatment drug for pulmonary hypertension?

The present study demonstrated the potential effects of diethylcarbamazine (DEC) on monocrotaline (MCT)-induced pulmonary hypertension. MCT solution (600mg/kg) was administered once per week, and 50mg/kg body weight of DEC for 28days. Three C57Bl/6 male mice groups (n=10) were studied: Control; MCT28, and MCT28/DEC. Echocardiography analysis was performed and lung tissues were collected for light microscopy (hematoxylin-eosin and Masson's trichrome staining), immunohistochemistry (αSMA, FADD, caspase 8, caspase 3, BAX, BCL2, cytochrome C and caspase 9) western blot (FADD, caspase 8, caspase 3, BAX, BCL2, cytochrome C and caspase 9) and qRt-PCR (COL-1α and αSMA). Echocardiography analysis demonstrated an increase in the pulmonary arterial blood flow gradient and velocity in the systole and RV area in the MCT28 group, while treatment with DEC resulted in a significant reduction in these parameters. Deposition of collagen fibers and αSMA staining around the pulmonary arteries was evident in the MCT28 group, while treatment with DEC reduced both. Western blot analysis revealed a decrease in BMPR2 in the MCT28 group, in contrast DEC treatment resulted in a significant increase in the level of BMPR2. DEC also significantly reduced the level of VEGF compared to the MCT28 group. Apoptosis extrinsic and intrinsic pathway markers were reduced in the MCT28 group. After treatment with DEC these levels returned to baseline. The results of this study indicate that DEC attenuates PH in an experimental monocrotaline-induced model by inhibiting a series of markers involved in cell proliferation/death.

Probing intermolecular interactions in a diethylcarbamazine citrate salt by fast MAS 1H solid-state NMR spectroscopy and GIPAW calculations.

Fast magic-angle spinning (MAS) NMR is used to probe intermolecular interactions in a diethylcarbamazine salt, that is widely used as a treatment against adult worms of Wuchereria bancrofti which cause a common disease in tropical countries named filariasis. Specifically, a dihydrogen citrate salt that has improved thermal stability and solubility as compared to the free form is studied. One-dimensional 1H, 13C and 15N and two-dimensional 1H-13C and 14N-1H heteronuclear correlation NMR experiments under moderate and fast MAS together with GIPAW (CASTEP) calculations enable the assignment of the 1H, 13C and 14N/15N resonances. A two-dimensional 1H-1H double-quantum (DQ) -single-quantum (SQ) MAS spectrum recorded with BaBa recoupling at 60kHz MAS identifies specific proton-proton proximities associated with citrate-citrate and citrate-diethylcarbamazine intermolecular interactions.

Efficacy and tolerability of treatment with single doses of diethylcarbamazine (DEC) and DEC plus albendazole (ABZ) for three consecutive years in lymphatic filariasis: a field study in India.

Lymphatic filariasis (LF) affects 73 countries, causes morbidity and impedes socioeconomic development. We had found no difference in safety and micro (Mf) and macro filarial action of single-dose diethylcarbamazine (DEC) and DEC + albendazole (ABZ) in an F01 study done in India (year 2000). There was a programmatic need to evaluate safety and efficacy of multiple annual treatments (F02). Subjects (155) from the F01 study, meeting inclusion-exclusion criteria, were enrolled in F02 and treated with further two annual doses of DEC or DEC + ABZ. Efficacy was evaluated for Mf positivity by peripheral smear (PS) and nucleopore (NP) filter, circulating filarial antigen (CFA) and filarial dance sign (FDS) positivity and Mf count at yearly follow-up. Safety was assessed for 5 days after drug administration. Total of 139 subjects evaluated for efficacy (69 DEC and 70 DEC + ABZ group). Mf positivity prevalence declined progressively by 95% (PS), 66% (NP), and 95% (PS) and 86% (NP); CFA positivity prevalence declined by 15% and 9%; FDS by 100% each; Mf count declined by 75.5 and 76.9% with three annual treatment of DEC and DEC + ABZ, respectively. Addition of ABZ did not show any advantage over DEC given as three annual rounds for LF. DEC and DEC + ABZ were well tolerated. There was no correlation between result of CFA and FDS, (both claimed to be indicative of adult worm). Analysis of published studies and our data indicate that macrofilaricidal effect of DEC/DEC + ABZ may be seen in children and not adults, with three or more annual dosing.

Efficacy, Safety, and Pharmacokinetics of Coadministered Diethylcarbamazine, Albendazole, and Ivermectin for Treatment of Bancroftian Filariasis.

BACKGROUND: Available treatments for lymphatic filariasis (LF) are limited in their longterm clearance of microfilaria from the blood. The safety and efficacy of a single-dose triple-drug therapy of the antifilarial drugs diethylcarbamazine (DEC), ivermectin (IVM), and albendazole (ALB) for LF are unknown. METHODS: We performed a pilot study to test the efficacy, safety, and pharmacokinetics of single-dose DEC, IVM, and ALB in Wuchereria bancrofti-infected Papua New Guineans. Adults were randomized into 2 treatment arms, DEC 6 mg/kg + ALB 400 mg (N = 12) or DEC 6 mg/kg + ALB 400 mg + IVM 200 µg/kg (N = 12), and monitored for microfilaria, parasite antigenemia, adverse events (AEs), and serum drug levels. RESULTS: Triple-drug therapy induced >2-log reductions in microfilaria levels at 36 and 168 hours after treatment compared with approximately 1-log reduction with 2 drugs. All 12 individuals who received 3 drugs were microfilaria negative 1 year after treatment, whereas 11 of 12 individuals in the 2-drug regimen were microfilaria positive. In 6 participants followed 2 years after treatment, those who received 3 drugs remained microfilaria negative. AEs, particularly fever, myalgias, pruritus, and proteinuria/hematuria, occurred in 83% vs 50% of those receiving triple-drug compared to 2-drug treatment respectively (P = .021); all resolved within 7 days after treatment. No serious AEs were observed in either group. There was no significant effect of IVM on DEC or ALB drug levels. CONCLUSIONS: Triple-drug therapy is safe and more effective than DEC + ALB for Bancroftian filariasis and has the potential to accelerate elimination of lymphatic filariasis. CLINICAL TRIALS REGISTRATION: NCT01975441.

Detection for cross-reactive proteins in filarial worm Setaria equina, MCF-7 human breast cancer, and Huh-7 hepatoma cells.

This study aimed to detect the cross-reactive proteins in filarial parasite adult worm Setaria equina and two different tumor cell lines (MCF-7 human breast cancer and Huh-7 hepatoma cells). This was performed using rabbit anti-S. equina extract (SeqE) or DEC (Diethylcarbamazine citrate) polyclonal IgG antibodies by indirect ELISA and western blotting. The results indicated cross-reactive bands at 70 and 75 kDa in all extracts by anti-DEC and SeqE antibodies, respectively. In addition, the expression of 70 kDa protein was only reduced in filarial worms and Huh-7 after in vitro DEC treatment compared to the control.