RARE DISEASE
Lymphatic filariasis
Lymphatic filariasis
Lymphatic filariasis
Drug discovery
2
drugs
With orphan designations
Overview
Lymphatic filariasis (LF) is a mosquito-borne parasitic disease caused by Wuchereria bancrofti, Brugia malayi, or B. timori. Infection damages the lymphatic system, leading to lymphedema, elephantiasis, hydrocele, and recurrent bacterial infections. Most cases are asymptomatic initially, but chronic manifestations cause severe disability and stigma. Transmission is halted via mass drug administration (MDA), while morbidity management focuses on hygiene, infection control, and surgery for hydrocele [1][2][11].
Burden
Pre-MDA economic burden: $5.8 billion/year (productivity loss, healthcare costs) [4].
Causes 5.25 million DALYs annually, with chronic complications (lymphedema, hydrocele) affecting >36 million [1][4][12].
WHO reports a 74% reduction in infections since 2000 due to MDA, but focal transmission persists [1][9].
Therapies
MDA: Annual community-wide regimens (DEC + albendazole or ivermectin in co-endemic areas; triple therapy [IDA] in select regions) [1][3][13].
Morbidity management: Limb hygiene, antifungal/antibacterial care, surgery for hydrocele, and complex decongestive therapy for lymphedema [1][3][6].
Antiparasitics: DEC (6 mg/kg) for active infections; doxycycline (4–6 weeks) targets adult worms [3][11].
Categories: rare infectious diseases
Research Papers
2,007 drug discovery papers about Lymphatic filariasis, with 3 next-in-class emerging drug candidates forecasted to outperform the average preclinical success rate. Recent publications:
2,007 drug discovery papers about Lymphatic filariasis, with 3 next-in-class emerging drug candidates forecasted to outperform the average preclinical success rate. Recent publications:
categories:
Small molecules
vaccines
2025-09-01 | Targeting Mitogen‐Activated Protein Kinase‐Activating Death Domain Protein of Brugia malayi for Construction of a Multi‐Epitope Subunit Vaccine Against Lymphatic Filariasis
ABSTRACT Background Lymphatic filariasis (LF) is a disease caused by parasitic worms that can lead to a debilitating condition known as elephantiasis. According to the World Health Organization, 657 million people across 39 countries are at risk of contracting LF. Eliminating LF remains a challenge despite ongoing efforts, primarily due to the ineffectiveness of existing treatments and the rise of drug resistance. Currently, no vaccines are available for LF. The main objective of this study was to design a vaccine that targets the MAP kinase‐activating death domain (MADD) protein of Brugia malayi . Methods Employing an in silico approach, we screened proteins to identify B‐ and T‐cell epitopes and assess their safety. These epitopes were combined with adjuvants and linkers to design a multi‐epitope vaccine. The six resulting vaccine models were refined using the GalaxyRefine tool to determine the most stable vaccine candidate, which was further validated through molecular dynamic simulations. Immune simulations were carried out using the final selected vaccine candidate. Results Here, we show significant stimulation of humoral and cell‐mediated immune responses resulting in the production of numerous memory B cells and T cells and a substantial increase in the production of the IgG1 antibody. These antibodies are crucial in clearing microfilariae from the peripheral circulation of infected individuals. Conclusion Our findings highlight MADD protein as a promising vaccine candidate to target LF.
2024-09-19 | Designing of a chimeric multiepitope vaccine against bancroftian lymphatic filariasis through immunoinformatics approaches.
The filarial worms of Wuchereria bancrofti are the primary cause of lymphatic filariasis (LF), a mosquito-borne disease among the neglected tropical parasitic diseases. Considering the global endemic consequences of the disease, there is a need to develop a successful vaccine candidate against LF. Using advanced immunoinformatics approaches, we designed two multiepitope vaccines targeting W. bancrofti's glutathione S-transferase and thioredoxin. Therefore, we predicted several MHC-1, MHC-2, and B-cell epitopes from these proteins and mapped two vaccine candidates (V1 and V2). The vaccines were subsequently employed for physicochemical analysis, structural prediction and validation, docking and normal mode analysis, codon optimization, and immune simulation. The selected MHC-1, MHC-2, and B-cell epitopes were antigenic without allergenicity or toxicity. The designed vaccines were expected to be soluble, stable proteins under physiological conditions. Compared to V2, V1's secondary and tertiary structures were simultaneously favorable, with Ramachandran plot analysis revealing 95.6% residues in favored areas. Subsequently, the molecular docking analysis indicated that the V1 had a high binding affinity for the TLR-2, TLR-4 and TLR-5, as suggested by the docking scores of -1248.7, -1038.5 and -1562.8, respectively. The NMA of these complexes further indicated their structural flexibility. Molecular dynamics simulations of V1-TLR complexes revealed V1-TLR-4 as the most stable, with the lowest free energy and minimal fluctuations, indicating the strongest binding affinity. The results of the codon optimization showed high levels of expression, with a favorable CAI score (<1.0). A three-dose vaccination analysis showed significant and persistent immunological responses, including adaptive and innate immune responses. The findings emphasize the potential of the V1 against W. bancrofti, but further validation is required through in vitro, in vivo, and clinical trials.
2024-05-11 | Immune targeting of filarial glutaredoxin through a multi-epitope peptide-based vaccine: A reverse vaccinology approach.
Despite the efforts of global programme to eliminate lymphatic filariasis (GPELF), the threat of lymphatic filariasis (LF) still looms over humanity in terms of long-term disabilities, and morbidities across the globe. In light of this situation, investigators have chosen to focus on the development of immunotherapeutics targeting the physiologically important filarial-specific proteins. Glutaredoxin (16.43 kDa) plays a pivotal role in filarial redox biology, serving as a vital contributor. In the context of the intra-host survival of filarial parasites, this antioxidant helps in mitigating the oxidative stress imposed by the host immune system. Given its significant contribution, the development of a vaccine targeting glutaredoxin holds promise as a new avenue for achieving a filaria-free world. Herein, multi-epitope-based vaccine was designed using advanced immunoinformatics approach. Initially, 4B-cell epitopes and 6 T-cell epitopes (4 MHC I and 2 MHC II) were identified from the 146 amino acid long sequence of glutaredoxin of the human filarid, Wuchereria bancrofti. Subsequent clustering of these epitopes with linker peptides finalized the vaccine structure. To boost TLR-mediated innate immunity, TLR-specific adjuvants were incorporated into the designed vaccine. After that, experimental analyses confirm the designed vaccine, Vac4 as anefficient ligand of human TLR5 to elicit protective innate immunity against filarial glutaredoxin. Immune simulation further demonstrated abundant levels of IgG and IgM as crucial contributors in triggering vaccine-induced adaptive responses in the recipients. Hence, to facilitate the validation of immunogenicity of the designed vaccine, Vac4 was cloned in silico in pET28a(+) expression vector for recombinant production. Taken together, our findings suggest that vaccine-mediated targeting of filarial glutaredoxin could be a future option for intervening LF on a global scale.
2024-05-09 | Enhancing encapsulation of filarial antigen Brugia malayi thioredoxin in nano-liposomes: The role of lecithin composition.
Lymphatic filariasis is a debilitating infectious disease prevalent in endemic areas, necessitating the development of an effective vaccine for eradication. Although recombinant vaccine candidates have been deemed safe, they often fail to provide sufficient protection, which can be overcome by encapsulating them in nano-liposomes. In this study, we have optimised the liposomal composition for enhanced stability and encapsulation of filarial antigen Brugia malayi thioredoxin (Bm-TRX). Nano-liposomes were prepared using egg phosphatidylcholine (EPC) and cholesterol via thin-film hydration, followed by sonication and characterizing. Encapsulation efficiency was optimised using different weight ratios of EPC to cholesterol (8:2, 7:3, and 6:4) and total lipid (EPC+Cholesterol) concentration to antigen Bm-TRX (10:1, 10:2, and 10:3) followed by release kinetics study. Optimised parameters yielded spherical liposomes measuring 209 nm in diameter with narrow polydispersity. Our findings demonstrated the highest encapsulation efficiency of 70.685 % and stability of 10 hours for an EPC to cholesterol weight ratio of 7:3. The in silico study proved the antigenic nature of TRX. The liposomal formulations loaded with TRX, as optimized in this study, hold promise for improving antigen efficiency by enhancing stability, bioavailability, and prophylactic effects by acting as immune potentiators.
2024-01-23 | Identification and prioritisation of potential vaccine candidates using subtractive proteomics and designing of a multi-epitope vaccine against Wuchereria bancrofti
Abstract This study employed subtractive proteomics and immunoinformatics to analyze the Wuchereria bancrofti proteome and identify potential therapeutic targets, with a focus on designing a vaccine against the parasite species. A comprehensive bioinformatics analysis of the parasite's proteome identified 51 probable therapeutic targets, among which "Kunitz/bovine pancreatic trypsin inhibitor domain-containing protein" was identified as the most promising vaccine candidate. The candidate protein was used to design a multi-epitope vaccine, incorporating B-cell and T-cell epitopes identified through various tools. The vaccine construct underwent extensive analysis of its antigenic, physical, and chemical features, including the determination of secondary and tertiary structures. Docking and molecular dynamics simulations were performed with HLA alleles, Toll-like receptor 4 (TLR4), and TLR3 to assess its potential to elicit the human immune response. Immune simulation analysis confirmed the predicted vaccine’s strong binding affinity with immunoglobulins, indicating its potential efficacy in generating an immune response. However, experimental validation and testing of this multi-epitope vaccine construct would be needed to assess its potential against W. bancrofti and even for a broader range of lymphatic filarial infections given the similarities between W. bancrofti and Brugia .
small molecules
2026-09-30 | Secreted filarial acetylcholine analogs modulate parasite reproduction and host physiology.
Lymphatic filariasis, caused by Brugia malayi, leads to chronic lymphatic dysfunction and lymphedema. The molecular mechanisms underlying interactions between filarial worms and their hosts remain poorly understood. Using untargeted metabolomics, we identify previously unknown acetylcholine analogs synthesized from leucine and isoleucine that are secreted by Brugia adult males. In the mammalian host, these metabolites selectively activate host M2 muscarinic acetylcholine receptors, alter lymphatic endothelial cell integrity, and trigger constriction of lymphatic vessels. These metabolites added to cultures also reduce microfilarial production in B. malayi and egg-laying in Caenorhabditis elegans, implying a role in regulating nematode reproduction. Their production is potently inhibited by ethacrynic acid, an existing FDA-approved drug. Our findings reveal a previously unexplored role for filarial-derived cholinergic signaling in parasite reproduction that impacts host lymphatic homeostasis. This work offers insights into the biochemical adaptations that function in the worm life cycle and reveals potential metabolic vulnerabilities in filarial worms.
2026-09-26 | Computational Validation of Tecomella undulata Bark as a Source of Anti-Filarial Leads Targeting UDP-Galactopyranose Mutase.
Lymphatic filariasis remains a major neglected tropical disease and there is an urgent need for parasite-specific therapeutic targets. The enzyme UDP-galactopyranose mutase (UGM) is essential for galactofuranose biosynthesis in Brugia malayi and is absent in humans, which makes it a promising drug target. In this study, we investigated phytochemicals from the bark of Tecomella undulata to find potential drug candidates against B. malayi UGM using an in silico approach. The structure of the target protein was predicted using the Alphafold model, and the active site was predicted using the combination of PrankWeb, DoGSiteScorer, and FTMap servers and further supported by superposition with a homologous experimentally determined UGM structure. Forty phytochemicals of T. undulata bark were screened by molecular docking using AutoDock Tools. Docking analysis showed Dehydrotectol (- 11.73 kcal/mol), Daucosterol (- 11.35 kcal/mol), urs-12-ene (- 10.87 kcal/mol), β-sitosterol (- 10.72 kcal/mol), and betulinic acid (- 10.47 kcal/mol) are the top-scoring ligands. Based on predicted binding free energy and interaction with key catalytic residues of UGM, Daucosterol was selected for molecular dynamics simulation using the GROMACS package. MD analysis and MM/PBSA calculations supported the thermodynamic stability of the docked complex. ADMET predictions indicated acceptable drug-likeness and low toxicity of several phytoconstituents of T. undulata bark. This study provides computational evidence supporting T. undulata bark phytochemicals can be a new drug formulation against B. malayi.
2026-09-17 | Diethylcarbamazine: A review of its modes of action.
Filariases are neglected tropical diseases caused by Clade III parasitic nematodes transmitted by biting insects as microfilaria which mature into female and male adults in the host. One example of filariasis is lymphatic filariasis or elephantiasis, caused by three species of filaria: Brugia malayi, Wuchereria bancrofti, and/or Brugia timori. Elephantiasis results from the occlusion of lymphatic vessels by adult parasites and subsequent swelling of the limbs. It is a disfiguring disease that occurs in 120 million people worldwide. Another filarial disease is onchocerciasis caused by Onchocerca volvulus. Microfilaria of this parasite invade the eye producing corneal scarring and blindness. The infected female blackflies that transmit these microfilaria belong to the Simulium genus, and breed in fast flowing rivers. Onchocerciasis occurs near these rivers and gives rise to the common name of the disease, i.e., "river blindness." Diethylcarbamazine (HetrazanR) was described as effective for treating filariases over 75 years ago by Yellapragada Subbarow and collaborators and is currently still in use. Diethylcarbamazine is characterized by a simple but flexible structure that provides it with the ability to combine with several target proteins, and a complex mode of action with effects on both filarial parasites and hosts. This Chapter reviews new observations on the activation of Transient Receptor Potential (TRP) ion-channels of B. malayi and older observations on the mechanisms of action of diethylcarbamazine. Diethylcarbamazine has three major effects: 1) A direct activating effect on filaria TRP channels producing transient inhibition of motility; 2) Reduction of host and parasite PGI2 and PGE2 production, thereby reducing host immune suppression; and 3) Activation and adhesion of host granulocytes which attack the filaria. We emphasize recent observations that include activation of TRP channels by diethylcarbamazine, an underappreciated mode of action of this classic anthelmintic.
2026-09-16 | Integrating Community Practices, Vector Resistance, and Molecular Xenomonitoring of Wuchereria Bancrofti: A One Health Implementation Study in Lymphatic Filariasis-Endemic Communities.
Lymphatic filariasis (LF), caused primarily by Wuchereria bancrofti and transmitted by mosquitoes, remains a public health challenge in Nigeria. Insecticides and insecticide-treated nets (ITNs) are used as control measures. However, limited public awareness and widespread insecticide resistance impede elimination. Molecular xenomonitoring is essential for detecting active transmission and determining when it is halted. This study assessed community knowledge, attitudes, and practices (KAPs) on LF, insecticide resistance, and xenomonitoring of W. bancrofti in Bodinga Local Government Area (LGA). A semi-structured questionnaire was administered to 258 participants from three wards to assess KAPs. Anopheles and Culex larvae were collected, reared, and tested for susceptibility to deltamethrin, permethrin, and alphacypermethrin using the Centre for Disease Control (CDC) bioassay. Comparative expression of cytochrome P450 genes (CYP6M2, CYP9M10) was also evaluated. Blood-fed mosquitoes were collected with a Prokopack aspirator for microfilaria screening and molecular xenomonitoring using polymerase chain reactions (PCRs). Only 41.9% of respondents had heard of LF, indicating significant knowledge gaps. Anopheles and Culex were resistant to all pyrethroids (6-44% mortality). Piperonyl butoxide (PBO) restored susceptibility to alphacypermethrin (98-99%). Of 1,510 mosquitoes, 5 (0.33%) were detected as infected by microscopy; 3 (0.20%) were PCR-confirmed W. bancrofti, and the L3 larvae was detected using quantitative reverse transcription PCR (qRT-PCR). Real-time PCR of microscopy-negative pools showed no infections. CYP6M2 and CYP9M10 were downregulated (0.26-fold and 0.77-fold, respectively) in infected mosquitoes. The study highlights low LF knowledge, pyrethroid resistance, and possible active transmission in Bodinga LGA. Awareness campaigns, PBO-based interventions, and further resistance mechanism studies are recommended.
2026-08-30 | A CASE STUDY ON THE EFFECTIVE TREATMENT OF LYMPHATIC FILARIASIS WITH PANCHAKARMA THERAPY
Background: This study evaluates the efficacy and outcomes of effective Panchakarma treatment in Lymphatic Filariasis. While antiparasitic drugs help prevent disease transmission and treat early-stage infections, they have limited ability to reverse chronic disease-related damage. Method: The successful management of a 67-year-old female patient with lymphatic filariasis was considered significant enough to be documented. Lymphatic filariasis affects an estimated 14 million people worldwide, and evidence on Ayurvedic management remains limited. The patient presented with bilateral lower limb swelling causing difficulty in walking, low back pain radiating to the left leg, and left knee pain for two years. The patient’s condition was assessed through Anthropometric Assessment, Visual Analogue Scale for Pain Score-7, Oswestry Disability Index Score – 52%, Knee Injury and Osteoarthritis Outcome Score (KOOS) -22%. According to Ayurveda, the clinical manifestation was diagnosed under Shleepada and managed according to Ayurvedic principles, taking into account the stage of the disease. Panchakarma therapies including Avagahana, Utsadana, Sarvanga Abhyanga, Sarvanga Bashpa Swedana followed by Mridu Virechana were administered along with Shamana Aushadhis, Pre and Post Indian Manual Lymph Drainage (IMLD), Yoga Exercises and Pranayam for 21 days with Comprehensive Bandaging of both lower limbs with cotton cloth for 8-10 hrs and follow-up of 3 months. Results: Evident improvement in bilateral lower limb anthropometric measurements was noted. Visual Analogue Scale Score decreased to 2, Oswestry Disability Index Score decreased to 32%, KOOS Score improved to -47%. Conclusion: This case study underscores Ayurveda’s potential as a promising alternative approach for managing Lymphatic Filariasis.
antibodies
2026-09-16 | Applied Research Module 10 — Disease-Associated Human Physiological Buffering Capacity: A Population-Level Systems Study of Lymphatic Filariasis, Nutrition, and Human Adaptive Resilience in Sri Lanka
Disease-Associated Human Physiological Buffering Capacity: A Population-Level Systems Study of Lymphatic Filariasis, Nutrition, and Human Adaptive Resilience in Sri Lanka Version 2.0.0DOI: 10.5281/zenodo.22791699 Author: Mohammad PiranIndependent Interdisciplinary Researcher (Former PhD Candidate 2015) Parent Repository:Human Adaptive Capacity, Cognitive Readiness, and Experimental Human DevelopmentDOI: 10.5281/zenodo.21904652 This repository presents Applied Research Module 10, a hypothesis-generating applied research component within the broader Human Adaptive Capacity research programme. The module investigates whether chronic or residual disease-associated burden — exemplified by lymphatic filariasis morbidity in Sri Lanka after WHO validation of elimination as a public-health problem in 2016 — can be examined as a population-level contributor to Human Physiological Buffering Capacity. Core research proposition:Population-level physiological buffering capacity may be shaped by the interaction of chronic disease burden, nutritional adequacy, socioeconomic resources, functional limitation, recovery opportunities, and access to morbidity management services. These interactions are treated as testable systems hypotheses, not as established causal pathways. Key features of this release:• Positions residual LF morbidity after transmission-level elimination as a natural research setting for adaptive-capacity questions• Integrates disease burden, nutrition, socioeconomic inequality and physiological recovery within a multilevel framework• Maintains strict scientific boundaries: no clinical claims, no treatment recommendations, no assertion that LF directly causes cognitive decline• Explicitly falsifiable: the buffering construct must demonstrate added explanatory value beyond conventional measures or be revised Research status: Hypothesis-generating / Pre-empirical / Population-level systems framework This module does not claim clinical validation, WHO endorsement, or established causality. All higher-order links to cognitive readiness and human development remain provisional and require empirical testing within the parent Adaptive Capacity programme. Keywords: Human Physiological Buffering Capacity; Lymphatic Filariasis; Sri Lanka; Residual Morbidity; Nutritional Adequacy; Socioeconomic Inequality; Adaptive Capacity; Cognitive Readiness; Population-Level Systems; Disease-Associated Burden; Human Adaptive Capacity; Experimental Human Development; Morbidity Management; Quality of Life; Resilience Recommended citation:Piran, M. (2026). Applied Research Module 10 — Disease-Associated Human Physiological Buffering Capacity: A Population-Level Systems Study of Lymphatic Filariasis, Nutrition, and Human Adaptive Resilience in Sri Lanka (Version 2.0.0). Zenodo. https://doi.org/10.5281/zenodo.22791699 Parent repository citation:Piran, M. (2026). Human Adaptive Capacity, Cognitive Readiness, and Experimental Human Development (Version 0.0.0). Zenodo. https://doi.org/10.5281/zenodo.21904652 License: Creative Commons Attribution–NonCommercial–NoDerivatives 4.0 International (CC BY-NC-ND 4.0)Copyright © 2026 Mohammad Piran. All Rights Reserved.
2026-08-04 | Persistent morbidity and knowledge gaps in a near‑elimination setting: A cross‑sectional study of lymphatic filariasis in northern Ghana
De-identified participant-level data underlying the results reported in the associated manuscript. Personal identifiers have been removed in accordance with ethical and data protection requirements.
2026-07-01 | AB118. The sudden surge of lymphatic filariasis cases in Tuaran: a cross-sectional study
Background: Lymphatic filariasis (LF) is a vector-borne neglected tropical disease that remains endemic in several regions of Malaysia, particularly in Sabah. The predominant causative parasite is Brugia malayi. Tuaran District had no previously recorded cases of LF until 2023. However, a sudden emergence of 40 confirmed LF cases in 2024 raised concerns regarding undetected transmission and limitations in local surveillance as well as early response efforts. This study aims to describe the sociodemographic characteristics and spatial analysis of LF cases in Tuaran District, Sabah, from 2020 to 2024. It aims to outline the public health response and preventive measures implemented during the surge in the number of confirmed cases.Methods: This cross-sectional study was conducted using secondary data from the Vector Control Unit, Tuaran District Health Office, covering a 5-year period from 2020 to 2024. Data sources included case notifications, field investigation records, community screening outcomes, and entomological investigation findings.Results: The first LF case was detected in 2023. Active case detection involved 394 residents across four localities, resulting in 38 individuals testing positive. In Tuaran, LF cases were more common among adults aged ≥40 years and those with outdoor jobs. Up till 2024, only 43.9% of positive cases received treatment. Spatial analysis shows LF cases clustering around villages within the Tamparuli sub-district, particularly where the landscape is dominated by plantations and forest margins. Entomological investigation at three sites showed no active vector presence. Public health interventions focused on morbidity management, continuous case surveillance, and targeted community health education.Conclusions: LF remains a significant public-health burden. Sabah still has endemic implementation units and sporadic cases, underscoring the need for more resources, consistent access to diagnostics and treatment, stronger community entomological surveillance, and better integration of local actions with national strategies.
2026-01-31 | Cross-sectional epidemiological assessment of lymphatic filariasis situation in areas under post-mass drug administration surveillance and the associated risk of transmission in the context of migrants in India: a study protocol.
India targets to eliminate lymphatic filariasis (LF) in alignment with the global goals. By 2024, 106 out of a total of 345 endemic districts have passed all three serial transmission assessment surveys (TAS) and are under post-mass drug administration (MDA) surveillance for a variable period. However, the current epidemiological situation of LF is not known in these districts. With increased mobility of population from the endemic districts currently under MDA to these post-MDA areas, resurgence of LF in these areas cannot be ruled out. Therefore, a study is planned to understand the current LF status in areas under post-MDA surveillance with the following objectives: (1) To assess the epidemiological situation of LF in terms of human and vector infection prevalence in selected evaluation units (EUs) under different durations of post-MDA phase and (2) to estimate the filarial infection (in terms of filarial antigen and microfilaria) among migrants (from endemic districts) in these EUs. This cross-sectional study will measure the filarial infection in (1) adult population aged ≥20 years (following the WHO 2025 protocol for monitoring and evaluation of MDA) among general population (n=3150 per EU), (2) migrant population (aged 2 years and above) in the post-MDA area originating from endemic areas (n=1000 per EU) and (3) vectors (n=7500 per EU) using molecular xenomonitoring (MX) to confirm sustenance of transmission interruption or identify any potential risk of resurgence in three EUs under post-MDA phase. In one MDA-naive EU that shares borders with endemic districts, filarial infection status will be assessed in (1) school children aged 9-14 years (as per WHO mini-TAS protocol, n=480), (2) migrants (aged 2 years and above) from endemic areas (n=1000) and (3) vectors (n=7500). EU-wide prevalence of microfilaria, circulating filarial antigen and vector infection rates with 95% CIs will be estimated. Multivariate logistic regression analysis will be carried out to find factors associated with LF positivity. In addition, knowledge, attitude and practice surveys will also be conducted among the adult migrants (n=1000 per EU). Thirty in-depth interviews will be conducted among the migrants, local community and health workers (in each EU) and the results will be suitably analysed and triangulated. The study results will enable the national programme to confirm sustenance of transmission interruption or assist in taking a decision to reinitiate MDA in these areas under post-MDA surveillance. It will also enable devising specific strategies to treat migrants. This study has been approved by the institutional ethics committee (IHEC 03-0824/N/F). A workshop will be held with all stakeholders to disseminate the study findings.
2026-01-27 | Finding the Gaps: Integrated Serosurveillance and Spatial Clustering of Vaccine Preventable Diseases in Samoa, 2018-2019.
Seroprevalence of antibodies for vaccine-preventable diseases (VPDs), due to vaccination or previous infection, can provide a more accurate estimate of immunity compared to vaccination coverage data alone. This study aimed to examine the seroepidemiology and spatial distribution of VPD seroprevalence in Samoa in 2018 and 2019. Dried blood spot (DBS) samples were collected from two nationally representative community-based surveys of participants aged ≥5 years from the Surveillance and Monitoring to Eliminate Lymphatic Filariasis and Scabies from Samoa (SaMELFS) project. DBSs were tested using multiplex bead assays (MBAs) to detect antibodies against measles, rubella, diphtheria, and tetanus. Seroprevalence was estimated at the national and primary sampling unit (PSU) levels, and cluster analysis was completed using SaTScan. Overall, 8394 valid MBA results were analysed across 35 PSUs. The highest overall seroprevalence was observed for tetanus (91.0%; 95% CI: 90.2-91.7), followed by diphtheria (83.7%; 95% CI: 82.7-84.7), rubella (79.3%; 95% CI: 78.2-80.3), and measles (45.8%; 95% CI: 44.8-46.9) with substantial heterogeneity across PSUs. Clusters of seronegativity to measles (relative risk [RR]: 1.16, p < 0.001) and diphtheria (RR: 1.16, p < 0.001) were also identified. These findings demonstrate significant variation in seroprevalence and pockets of low population immunity to multiple VPDs, highlighting the key advantage of an integrated rather than siloed approach. The relatively high seroprevalence to rubella suggests potential community transmission, emphasising the need to strengthen congenital rubella surveillance and improve vaccination coverage. Identifying low immunity to VPDs can provide an early warning to potential outbreak risk and support the Ministry of Health to target public health interventions in higher-risk areas.
proteins
2026-07-28 | Development of a Human Lymphatic Filariasis Vaccine, LFGuard for Clinical Testing 2306046
Abstract Introduction Lymphatic filariasis (LF) is a neglected tropical disease that causes disability and impairment of the lymphatic system. Millions of people in the endemic area still suffer from LF, even after decades of mass drug administration (MDA). The target of MDA is to block the transmission. A preventive vaccine is needed to eliminate the infection in the endemic countries. Our laboratory developed a tetravalent fusion protein vaccine, rBmHAXT, which demonstrated significant protection and immunogenicity in rodent and non-human primate models. The vaccine has now completed the Good Manufacturing Practice (cGMP) guidelines for use in clinical trials. Methods This study aims to confirm whether the final cGMP product (LFGuard) retains the safety, immunogenicity, and efficacy as observed with the parent vaccine in a mouse model. Three doses of the vaccine were given s/c or I/m along with Al-T4 adjuvant, an alum adsorbed TLR-4 agonist to promote a balanced Th1/Th2 response against the filarial infection. To evaluate safety, we measured the body weight, haematological parameters, liver function, and kidney function. Immunogenicity was determined by evaluating the levels of antigen-specific IgG antibody titer. The vaccine efficacy was determined by a challenge study. Results Our results show that vaccine is safe and has no adverse effects on the body weight, haematological parameters, liver or kidney functions in all vaccinated animals compared to controls irrespective of the route of immunization. All immunized mice showed a high titer of antigen-specific IgG antibodies (1:80,000) in their serum as expected. These mice also had a significantly (p > 0.001) higher number of CD4+ TCM in their spleen. The vaccinated mice also showed significantly higher levels of protection (90.7%) compared to the controls. Conclusion This is the most crucial step in bridging the vaccine to phase I clinical testing. These pre-IND-enabling studies will help bring the LF vaccine close to the clinics. Funding Source N/A Topic Categories Vaccines and Immunotherapy (VAC)
2025-07-23 | Sequence Localization of SeGPx in S. digitata Genome Contigs and Determination of its Presence in the Whole Worm Extract.
Lymphatic filariasis, caused by three major filarial species, is marked by immune evasion strategies involving antioxidant enzymes. The role of selenium-dependent glutathione peroxidase (SeGPx) in this process remains underexplored. This study aimed to identify and characterise SeGPx in Setaria digitata, a genomic analogue of Wuchereria bancrofti, and evaluate its potential as a diagnostic antigen. segpx sequences were identified through bioinformatics tools, including BLAST and UniProt databases. Due to limited nematode entries, a validated SeGPx sequence from Lymnaea stagnalis was used as a proxy in PSI-BLAST to identify homologues. Enzymatic activity was confirmed through spectrophotometric assay and activity staining on SDS-PAGE to confirm its enzymatic activity and molecular mass confirmation. The segpx gene was localised within the S. digitata genome data (Contig 127, nucleotides 56,000-58,000). The enzyme assay showed a time-dependent decline in absorbance at 340 nm due to NADPH oxidation, plateauing after 13 min. Enzyme activity was calculated as 0.139 U, with a specific activity of 0.198 U/mg protein. A clear band at ~ 20 kDa was visualised via activity staining, confirming SeGPx presence. Combined sequence-based identification and enzymatic validation confirm the functional presence of SeGPx in S. digitata. These findings support its role in oxidative stress mitigation and potential as a diagnostic antigen. The precise gene localisation offers a foundation for recombinant cloning, providing a streamlined alternative to conventional purification approaches for diagnostic development in filariasis.
2024-07-20 | Nature-derived Peptides as Promising Antiparasitic Agents against Neglected Tropical Diseases
Abstract Neglected tropical diseases (NTDs) are a group of at least 20 infectious diseases that primarily affect tropical regions. Despite impacting 1.6 billion people worldwide, these diseases have not received adequate global priority and attention. Currently, NTDs caused by protozoa have limited therapeutic options, and the emergence of drug-resistant strains further exacerbates the situation. In recent years, several antimicrobial peptides (AMPs) have emerged as potential therapeutic candidates against NTDs. This review analyzes the contemporary trends of AMPs, explores their antiparasitic properties, and mechanisms of action against three parasitic protozoan NTDs: Chagas disease, human African trypanosomiasis, and leishmaniasis and one parasitic helminth NTD: lymphatic filariasis. Furthermore, notable drawbacks associated with AMPs are highlighted, and future research directions are proposed. Overall, this review points out the potential of AMPs as therapeutic agents for these three protozoan neglected tropical diseases and one parasitic helminth NTDs as well as emphasizes the imperative need for continued research in this field.
2024-07-03 | Revelation of potent ES-62 activity of a hypothetical protein from Wuchereria bancrofti proteome by in-silico based characterization and functional annotation
Lymphatic filariasis (LF) is a well-known disease caused primarily by the parasitic worm Wuchereria bancrofti, although other Filarioidea parasites, including Brugia malayi and Brugia timori, can also be responsible. These parasites can frequently affect the lymphatic system during their microfilariae stage. These parasites often produce numerous excretory-secretory (ES) products that can modulate or impede the activities of diverse immune system cells. Thus, this study utilized computational characterization and functional annotation to assess the impact of a hypothetical protein from Wuchereria brancrofti, specifically its role as an ES-62 product. The analysis of functional domain annotation indicates that the hypothetical protein shares functional domains comparable to those found in ES-62 (Zinc-binding metallopeptidase family protein). Additionally, the hypothetical protein has significant sequence similarities (73.83 %) with the ES-62 of Acanthocheilonema viteae, as shown by the multiple sequence alignment and phylogeny analyses. Furthermore, the hypothetical protein's secondary and tertiary structure and its tertiary model structure's quality possess an acceptable standard quality (Z-score of −9.45). Moreover, the molecular docking study demonstrates that the hypothetical protein shows a significant affinity for the TLR-4 receptor (center energy score of −1145.9 and the lowest energy score of −1096.5), a finding that is subsequently confirmed by normal mode analysis. These in silico findings suggest that the observed hypothetical protein could aid in studying filarial infection and developing pharmaceuticals to treat lymphatic filariasis.
2024-03-27 | Unpacking Immune Modulation as a Site of Therapeutics Innovation for Nematode Parasite Wuchereria bancrofti: A Temporal Quantitative Phosphoproteomics Profiling of Macrophage Migration Inhibitory Factor 2.
Nematode infections are common in both humans and livestock, with major adverse planetary health and economic impacts. Wuchereria bancrofti is a parasitic nematode that causes lymphatic filariasis, a neglected tropical disease that can lead to severe disability and deformity worldwide. For the long-term survival of the bancroftian parasites in the host, a complex immune invasion strategy is involved through immunomodulation. Therefore, immunomodulation can serve as a site of research and innovation for molecular targets. Macrophage migration inhibitory factor (MIF) is a pleiotropic cytokine crucial to the host antimicrobial alarm system and stress response. Interestingly, the nematode parasite W. bancrofti also produces two homologs of MIF (Wba-MIF1 and 2). Using a mass spectrometry-based phosphoproteomics approach, we report new findings on the immunomodulatory effect and signaling mechanism of Wba-MIF2 in macrophage cells. Accordingly, we observed 1201 phosphorylated sites on 467 proteins. Out of the 1201 phosphorylated sites, 1075, 117, and 9 were found on serine (S), threonine (T), and tyrosine (Y) residues, respectively. Our bioinformatics analysis led to identification of major pathways, including spliceosomes, T cell receptor signaling pathway, Th17 differentiation pathway, interleukin-17 signaling pathway, and insulin signaling pathway upon Wba-MIF2 treatment. Wba-MIF2 treatment also enriched CDK4, CDK1, and DNAPK kinases. The comparison of the signaling pathway of Wba-MIF2 with that of human-MIF suggests both share similar signaling pathways. These findings collectively offer new insights into the role and mechanism of Wba-MIF2 as an immunomodulator and inform future diagnostics and drug discovery research for W. bancrofti.
other
2026-04-25 | Strengthening lymphatic filariasis elimination programmes with molecular xenomonitoring: critical utility and unmet operational needs.
Molecular xenomonitoring (MX)-the detection of filarial DNA in mosquito vectors-has become an important component of post- mass drug administration surveillance within the Global Programme to Eliminate Lymphatic Filariasis (GPELF). MX offers non-invasive, high-sensitivity detection of residual or recrudescent Wuchereria bancrofti transmission, particularly where human microfilaraemia and antigenemia surveys have limited power. However, the current operational model relies heavily on gravid-trap-based sampling, which captures a physiologically narrow, behaviourally biased subset of mosquitoes, often dominated by zoophagic Culex quinquefasciatus. This restricts interpretation and programme decision-making. We propose a restructured MX approach focused on representative multi-physiological sampling, routine blood-meal profiling, stage-specific molecular assays and harmonized analytical frameworks. With these refinements, MX can evolve into an actionable transmission-intelligence platform vital for sustaining lymphatic filariasis elimination in the endgame phase.
2025-04-03 | Germline transformation of the West Nile virus and avian malaria vector Culex quinquefasciatus Say using the piggyBac transposon system.
Culex quinquefasciatus Say is a mosquito which acts as a vector for numerous diseases including West Nile virus, lymphatic filariasis and avian malaria, over a broad geographical range. As the effectiveness of insecticidal mosquito control methods declines, the need has grown to develop genetic control methods to curb the spread of disease. The piggyBac transposon system - the most widely used genetic transformation tool in insects, including mosquitoes - generates quasi-random insertions of donor DNA into the host genome. However, despite the broad reported species range of piggyBac, previous attempts to use this tool to transform Culex quinquefasciatus mosquitoes have failed. Here we report the first successful transformation of Culex quinquefasciatus with the piggyBac transposon system. Using commercially synthesised piggyBac mRNA as a transposase source, we were able to generate three independent insertions of a ZsGreen fluorescent marker gene, with transformation efficiencies of up to 5 %. Through this work, we have expanded the genetic toolkit available for the genetic manipulation of Culex mosquitoes and thus removed a barrier to developing novel genetic control methods in this important disease vector.
2023-11-20 | CRISPR-based gene drives generate super-Mendelian inheritance in the disease vector Culex quinquefasciatus
Abstract Culex mosquitoes pose a significant public health threat as vectors for a variety of diseases including West Nile virus and lymphatic filariasis, and transmit pathogens threatening livestock, companion animals, and endangered birds. Rampant insecticide resistance makes controlling these mosquitoes challenging and necessitates the development of new control strategies. Gene drive technologies have made significant progress in other mosquito species, although similar advances have been lagging in Culex . Here we test a CRISPR-based homing gene drive for Culex quinquefasciatus , and show that the inheritance of two split-gene-drive transgenes, targeting different loci, are biased in the presence of a Cas9-expressing transgene although with modest efficiencies. Our findings extend the list of disease vectors where engineered homing gene drives have been demonstrated to include Culex alongside Anopheles and Aedes , and pave the way for future development of these technologies to control Culex mosquitoes.
2023-10-13 | Symbiotic Wolbachia in mosquitoes and its role in reducing the transmission of mosquito-borne diseases: updates and prospects
Mosquito-borne diseases such as malaria, dengue fever, West Nile virus, chikungunya, Zika fever, and filariasis have the greatest health and economic impact. These mosquito-borne diseases are a major cause of morbidity and mortality in tropical and sub-tropical areas. Due to the lack of effective vector containment strategies, the prevalence and severity of these diseases are increasing in endemic regions. Nowadays, mosquito infection by the endosymbiotic Wolbachia represents a promising new bio-control strategy. Wild-infected mosquitoes had been developing cytoplasmic incompatibility (CI), phenotypic alterations, and nutrition competition with pathogens. These reduce adult vector lifespan, interfere with reproduction, inhibit other pathogen growth in the vector, and increase insecticide susceptibility of the vector. Wild, uninfected mosquitoes can also establish stable infections through trans-infection and have the advantage of adaptability through pathogen defense, thereby selectively infecting uninfected mosquitoes and spreading to the entire population. This review aimed to evaluate the role of the Wolbachia symbiont with the mosquitoes ( Aedes, Anopheles, and Culex ) in reducing mosquito-borne diseases. Global databases such as PubMed, Web of Sciences, Scopus, and pro-Quest were accessed to search for potentially relevant articles. We used keywords: Wolbachia , Anopheles , Aedes , Culex , and mosquito were used alone or in combination during the literature search. Data were extracted from 56 articles’ texts, figures, and tables of the included article.
2023-08-28 | Xenorhabdus and Photorhabdus Bacteria as Potential Candidates for the Control of Culex pipiens L. (Diptera: Culicidae), the Principal Vector of West Nile Virus and Lymphatic Filariasis
Vector-borne diseases pose a severe threat to human and animal health. Culex pipiens L. (Diptera: Culicidae) is a widespread mosquito species and serves as a vector for the transmission of infectious diseases such as West Nile disease and Lymphatic Filariasis. Synthetic insecticides have been the prime control method for many years to suppress Cx. pipiens populations. However, recently, the use of insecticides has begun to be questioned due to the detrimental impact on human health and the natural environment. Therefore, many authorities urge the development of eco-friendly control methods that are nontoxic to humans. The bacterial associates [Xenorhabdus and Photorhabdus spp. (Enterobacterales: Morganellaceae)] of entomopathogenic nematodes (EPNs) (Sterinernema spp. and Heterorhabditis spp.) (Rhabditida: Heterorhabditidae and Steinernematidae) are one of the green approaches to combat a variety of insect pests. In the present study, the mosquitocidal activity of the cell-free supernatants and cell suspension (4 × 107 cells mL−1) of four different symbiotic bacteria (Xenorhabdus nematophila, X. bovienii, X. budapestensis, and P. luminescens subsp. kayaii) was assessed against different development stages of Cx. pipiens (The 1st/2nd and 3rd/4th instar larvae and pupa) under laboratory conditions. The bacterial symbionts were able to kill all the development stages with varying levels of mortality. The 1st/2nd instar larvae exhibited the highest susceptibility to the cell-free supernatants and cell suspensions of symbiotic bacteria and the efficacy of the cell-free supernatants and cell suspensions gradually declined with increasing phases of growth. The highest effectiveness was achieved by the X. bovienii KCS-4S strain inducing 95% mortality to the 1st/2nd instar larvae. The results indicate that tested bacterial symbionts have great potential as an eco-friendly alternative to insecticides.
vaccines
2025-09-01 | Targeting Mitogen‐Activated Protein Kinase‐Activating Death Domain Protein of Brugia malayi for Construction of a Multi‐Epitope Subunit Vaccine Against Lymphatic Filariasis
ABSTRACT Background Lymphatic filariasis (LF) is a disease caused by parasitic worms that can lead to a debilitating condition known as elephantiasis. According to the World Health Organization, 657 million people across 39 countries are at risk of contracting LF. Eliminating LF remains a challenge despite ongoing efforts, primarily due to the ineffectiveness of existing treatments and the rise of drug resistance. Currently, no vaccines are available for LF. The main objective of this study was to design a vaccine that targets the MAP kinase‐activating death domain (MADD) protein of Brugia malayi . Methods Employing an in silico approach, we screened proteins to identify B‐ and T‐cell epitopes and assess their safety. These epitopes were combined with adjuvants and linkers to design a multi‐epitope vaccine. The six resulting vaccine models were refined using the GalaxyRefine tool to determine the most stable vaccine candidate, which was further validated through molecular dynamic simulations. Immune simulations were carried out using the final selected vaccine candidate. Results Here, we show significant stimulation of humoral and cell‐mediated immune responses resulting in the production of numerous memory B cells and T cells and a substantial increase in the production of the IgG1 antibody. These antibodies are crucial in clearing microfilariae from the peripheral circulation of infected individuals. Conclusion Our findings highlight MADD protein as a promising vaccine candidate to target LF.
2024-09-19 | Designing of a chimeric multiepitope vaccine against bancroftian lymphatic filariasis through immunoinformatics approaches.
The filarial worms of Wuchereria bancrofti are the primary cause of lymphatic filariasis (LF), a mosquito-borne disease among the neglected tropical parasitic diseases. Considering the global endemic consequences of the disease, there is a need to develop a successful vaccine candidate against LF. Using advanced immunoinformatics approaches, we designed two multiepitope vaccines targeting W. bancrofti's glutathione S-transferase and thioredoxin. Therefore, we predicted several MHC-1, MHC-2, and B-cell epitopes from these proteins and mapped two vaccine candidates (V1 and V2). The vaccines were subsequently employed for physicochemical analysis, structural prediction and validation, docking and normal mode analysis, codon optimization, and immune simulation. The selected MHC-1, MHC-2, and B-cell epitopes were antigenic without allergenicity or toxicity. The designed vaccines were expected to be soluble, stable proteins under physiological conditions. Compared to V2, V1's secondary and tertiary structures were simultaneously favorable, with Ramachandran plot analysis revealing 95.6% residues in favored areas. Subsequently, the molecular docking analysis indicated that the V1 had a high binding affinity for the TLR-2, TLR-4 and TLR-5, as suggested by the docking scores of -1248.7, -1038.5 and -1562.8, respectively. The NMA of these complexes further indicated their structural flexibility. Molecular dynamics simulations of V1-TLR complexes revealed V1-TLR-4 as the most stable, with the lowest free energy and minimal fluctuations, indicating the strongest binding affinity. The results of the codon optimization showed high levels of expression, with a favorable CAI score (<1.0). A three-dose vaccination analysis showed significant and persistent immunological responses, including adaptive and innate immune responses. The findings emphasize the potential of the V1 against W. bancrofti, but further validation is required through in vitro, in vivo, and clinical trials.
2024-05-11 | Immune targeting of filarial glutaredoxin through a multi-epitope peptide-based vaccine: A reverse vaccinology approach.
Despite the efforts of global programme to eliminate lymphatic filariasis (GPELF), the threat of lymphatic filariasis (LF) still looms over humanity in terms of long-term disabilities, and morbidities across the globe. In light of this situation, investigators have chosen to focus on the development of immunotherapeutics targeting the physiologically important filarial-specific proteins. Glutaredoxin (16.43 kDa) plays a pivotal role in filarial redox biology, serving as a vital contributor. In the context of the intra-host survival of filarial parasites, this antioxidant helps in mitigating the oxidative stress imposed by the host immune system. Given its significant contribution, the development of a vaccine targeting glutaredoxin holds promise as a new avenue for achieving a filaria-free world. Herein, multi-epitope-based vaccine was designed using advanced immunoinformatics approach. Initially, 4B-cell epitopes and 6 T-cell epitopes (4 MHC I and 2 MHC II) were identified from the 146 amino acid long sequence of glutaredoxin of the human filarid, Wuchereria bancrofti. Subsequent clustering of these epitopes with linker peptides finalized the vaccine structure. To boost TLR-mediated innate immunity, TLR-specific adjuvants were incorporated into the designed vaccine. After that, experimental analyses confirm the designed vaccine, Vac4 as anefficient ligand of human TLR5 to elicit protective innate immunity against filarial glutaredoxin. Immune simulation further demonstrated abundant levels of IgG and IgM as crucial contributors in triggering vaccine-induced adaptive responses in the recipients. Hence, to facilitate the validation of immunogenicity of the designed vaccine, Vac4 was cloned in silico in pET28a(+) expression vector for recombinant production. Taken together, our findings suggest that vaccine-mediated targeting of filarial glutaredoxin could be a future option for intervening LF on a global scale.
2024-05-09 | Enhancing encapsulation of filarial antigen Brugia malayi thioredoxin in nano-liposomes: The role of lecithin composition.
Lymphatic filariasis is a debilitating infectious disease prevalent in endemic areas, necessitating the development of an effective vaccine for eradication. Although recombinant vaccine candidates have been deemed safe, they often fail to provide sufficient protection, which can be overcome by encapsulating them in nano-liposomes. In this study, we have optimised the liposomal composition for enhanced stability and encapsulation of filarial antigen Brugia malayi thioredoxin (Bm-TRX). Nano-liposomes were prepared using egg phosphatidylcholine (EPC) and cholesterol via thin-film hydration, followed by sonication and characterizing. Encapsulation efficiency was optimised using different weight ratios of EPC to cholesterol (8:2, 7:3, and 6:4) and total lipid (EPC+Cholesterol) concentration to antigen Bm-TRX (10:1, 10:2, and 10:3) followed by release kinetics study. Optimised parameters yielded spherical liposomes measuring 209 nm in diameter with narrow polydispersity. Our findings demonstrated the highest encapsulation efficiency of 70.685 % and stability of 10 hours for an EPC to cholesterol weight ratio of 7:3. The in silico study proved the antigenic nature of TRX. The liposomal formulations loaded with TRX, as optimized in this study, hold promise for improving antigen efficiency by enhancing stability, bioavailability, and prophylactic effects by acting as immune potentiators.
2024-01-23 | Identification and prioritisation of potential vaccine candidates using subtractive proteomics and designing of a multi-epitope vaccine against Wuchereria bancrofti
Abstract This study employed subtractive proteomics and immunoinformatics to analyze the Wuchereria bancrofti proteome and identify potential therapeutic targets, with a focus on designing a vaccine against the parasite species. A comprehensive bioinformatics analysis of the parasite's proteome identified 51 probable therapeutic targets, among which "Kunitz/bovine pancreatic trypsin inhibitor domain-containing protein" was identified as the most promising vaccine candidate. The candidate protein was used to design a multi-epitope vaccine, incorporating B-cell and T-cell epitopes identified through various tools. The vaccine construct underwent extensive analysis of its antigenic, physical, and chemical features, including the determination of secondary and tertiary structures. Docking and molecular dynamics simulations were performed with HLA alleles, Toll-like receptor 4 (TLR4), and TLR3 to assess its potential to elicit the human immune response. Immune simulation analysis confirmed the predicted vaccine’s strong binding affinity with immunoglobulins, indicating its potential efficacy in generating an immune response. However, experimental validation and testing of this multi-epitope vaccine construct would be needed to assess its potential against W. bancrofti and even for a broader range of lymphatic filarial infections given the similarities between W. bancrofti and Brugia .
small molecules
2026-09-30 | Secreted filarial acetylcholine analogs modulate parasite reproduction and host physiology.
Lymphatic filariasis, caused by Brugia malayi, leads to chronic lymphatic dysfunction and lymphedema. The molecular mechanisms underlying interactions between filarial worms and their hosts remain poorly understood. Using untargeted metabolomics, we identify previously unknown acetylcholine analogs synthesized from leucine and isoleucine that are secreted by Brugia adult males. In the mammalian host, these metabolites selectively activate host M2 muscarinic acetylcholine receptors, alter lymphatic endothelial cell integrity, and trigger constriction of lymphatic vessels. These metabolites added to cultures also reduce microfilarial production in B. malayi and egg-laying in Caenorhabditis elegans, implying a role in regulating nematode reproduction. Their production is potently inhibited by ethacrynic acid, an existing FDA-approved drug. Our findings reveal a previously unexplored role for filarial-derived cholinergic signaling in parasite reproduction that impacts host lymphatic homeostasis. This work offers insights into the biochemical adaptations that function in the worm life cycle and reveals potential metabolic vulnerabilities in filarial worms.
2026-09-26 | Computational Validation of Tecomella undulata Bark as a Source of Anti-Filarial Leads Targeting UDP-Galactopyranose Mutase.
Lymphatic filariasis remains a major neglected tropical disease and there is an urgent need for parasite-specific therapeutic targets. The enzyme UDP-galactopyranose mutase (UGM) is essential for galactofuranose biosynthesis in Brugia malayi and is absent in humans, which makes it a promising drug target. In this study, we investigated phytochemicals from the bark of Tecomella undulata to find potential drug candidates against B. malayi UGM using an in silico approach. The structure of the target protein was predicted using the Alphafold model, and the active site was predicted using the combination of PrankWeb, DoGSiteScorer, and FTMap servers and further supported by superposition with a homologous experimentally determined UGM structure. Forty phytochemicals of T. undulata bark were screened by molecular docking using AutoDock Tools. Docking analysis showed Dehydrotectol (- 11.73 kcal/mol), Daucosterol (- 11.35 kcal/mol), urs-12-ene (- 10.87 kcal/mol), β-sitosterol (- 10.72 kcal/mol), and betulinic acid (- 10.47 kcal/mol) are the top-scoring ligands. Based on predicted binding free energy and interaction with key catalytic residues of UGM, Daucosterol was selected for molecular dynamics simulation using the GROMACS package. MD analysis and MM/PBSA calculations supported the thermodynamic stability of the docked complex. ADMET predictions indicated acceptable drug-likeness and low toxicity of several phytoconstituents of T. undulata bark. This study provides computational evidence supporting T. undulata bark phytochemicals can be a new drug formulation against B. malayi.
2026-09-17 | Diethylcarbamazine: A review of its modes of action.
Filariases are neglected tropical diseases caused by Clade III parasitic nematodes transmitted by biting insects as microfilaria which mature into female and male adults in the host. One example of filariasis is lymphatic filariasis or elephantiasis, caused by three species of filaria: Brugia malayi, Wuchereria bancrofti, and/or Brugia timori. Elephantiasis results from the occlusion of lymphatic vessels by adult parasites and subsequent swelling of the limbs. It is a disfiguring disease that occurs in 120 million people worldwide. Another filarial disease is onchocerciasis caused by Onchocerca volvulus. Microfilaria of this parasite invade the eye producing corneal scarring and blindness. The infected female blackflies that transmit these microfilaria belong to the Simulium genus, and breed in fast flowing rivers. Onchocerciasis occurs near these rivers and gives rise to the common name of the disease, i.e., "river blindness." Diethylcarbamazine (HetrazanR) was described as effective for treating filariases over 75 years ago by Yellapragada Subbarow and collaborators and is currently still in use. Diethylcarbamazine is characterized by a simple but flexible structure that provides it with the ability to combine with several target proteins, and a complex mode of action with effects on both filarial parasites and hosts. This Chapter reviews new observations on the activation of Transient Receptor Potential (TRP) ion-channels of B. malayi and older observations on the mechanisms of action of diethylcarbamazine. Diethylcarbamazine has three major effects: 1) A direct activating effect on filaria TRP channels producing transient inhibition of motility; 2) Reduction of host and parasite PGI2 and PGE2 production, thereby reducing host immune suppression; and 3) Activation and adhesion of host granulocytes which attack the filaria. We emphasize recent observations that include activation of TRP channels by diethylcarbamazine, an underappreciated mode of action of this classic anthelmintic.
2026-09-16 | Integrating Community Practices, Vector Resistance, and Molecular Xenomonitoring of Wuchereria Bancrofti: A One Health Implementation Study in Lymphatic Filariasis-Endemic Communities.
Lymphatic filariasis (LF), caused primarily by Wuchereria bancrofti and transmitted by mosquitoes, remains a public health challenge in Nigeria. Insecticides and insecticide-treated nets (ITNs) are used as control measures. However, limited public awareness and widespread insecticide resistance impede elimination. Molecular xenomonitoring is essential for detecting active transmission and determining when it is halted. This study assessed community knowledge, attitudes, and practices (KAPs) on LF, insecticide resistance, and xenomonitoring of W. bancrofti in Bodinga Local Government Area (LGA). A semi-structured questionnaire was administered to 258 participants from three wards to assess KAPs. Anopheles and Culex larvae were collected, reared, and tested for susceptibility to deltamethrin, permethrin, and alphacypermethrin using the Centre for Disease Control (CDC) bioassay. Comparative expression of cytochrome P450 genes (CYP6M2, CYP9M10) was also evaluated. Blood-fed mosquitoes were collected with a Prokopack aspirator for microfilaria screening and molecular xenomonitoring using polymerase chain reactions (PCRs). Only 41.9% of respondents had heard of LF, indicating significant knowledge gaps. Anopheles and Culex were resistant to all pyrethroids (6-44% mortality). Piperonyl butoxide (PBO) restored susceptibility to alphacypermethrin (98-99%). Of 1,510 mosquitoes, 5 (0.33%) were detected as infected by microscopy; 3 (0.20%) were PCR-confirmed W. bancrofti, and the L3 larvae was detected using quantitative reverse transcription PCR (qRT-PCR). Real-time PCR of microscopy-negative pools showed no infections. CYP6M2 and CYP9M10 were downregulated (0.26-fold and 0.77-fold, respectively) in infected mosquitoes. The study highlights low LF knowledge, pyrethroid resistance, and possible active transmission in Bodinga LGA. Awareness campaigns, PBO-based interventions, and further resistance mechanism studies are recommended.
2026-08-30 | A CASE STUDY ON THE EFFECTIVE TREATMENT OF LYMPHATIC FILARIASIS WITH PANCHAKARMA THERAPY
Background: This study evaluates the efficacy and outcomes of effective Panchakarma treatment in Lymphatic Filariasis. While antiparasitic drugs help prevent disease transmission and treat early-stage infections, they have limited ability to reverse chronic disease-related damage. Method: The successful management of a 67-year-old female patient with lymphatic filariasis was considered significant enough to be documented. Lymphatic filariasis affects an estimated 14 million people worldwide, and evidence on Ayurvedic management remains limited. The patient presented with bilateral lower limb swelling causing difficulty in walking, low back pain radiating to the left leg, and left knee pain for two years. The patient’s condition was assessed through Anthropometric Assessment, Visual Analogue Scale for Pain Score-7, Oswestry Disability Index Score – 52%, Knee Injury and Osteoarthritis Outcome Score (KOOS) -22%. According to Ayurveda, the clinical manifestation was diagnosed under Shleepada and managed according to Ayurvedic principles, taking into account the stage of the disease. Panchakarma therapies including Avagahana, Utsadana, Sarvanga Abhyanga, Sarvanga Bashpa Swedana followed by Mridu Virechana were administered along with Shamana Aushadhis, Pre and Post Indian Manual Lymph Drainage (IMLD), Yoga Exercises and Pranayam for 21 days with Comprehensive Bandaging of both lower limbs with cotton cloth for 8-10 hrs and follow-up of 3 months. Results: Evident improvement in bilateral lower limb anthropometric measurements was noted. Visual Analogue Scale Score decreased to 2, Oswestry Disability Index Score decreased to 32%, KOOS Score improved to -47%. Conclusion: This case study underscores Ayurveda’s potential as a promising alternative approach for managing Lymphatic Filariasis.
antibodies
2026-09-16 | Applied Research Module 10 — Disease-Associated Human Physiological Buffering Capacity: A Population-Level Systems Study of Lymphatic Filariasis, Nutrition, and Human Adaptive Resilience in Sri Lanka
Disease-Associated Human Physiological Buffering Capacity: A Population-Level Systems Study of Lymphatic Filariasis, Nutrition, and Human Adaptive Resilience in Sri Lanka Version 2.0.0DOI: 10.5281/zenodo.22791699 Author: Mohammad PiranIndependent Interdisciplinary Researcher (Former PhD Candidate 2015) Parent Repository:Human Adaptive Capacity, Cognitive Readiness, and Experimental Human DevelopmentDOI: 10.5281/zenodo.21904652 This repository presents Applied Research Module 10, a hypothesis-generating applied research component within the broader Human Adaptive Capacity research programme. The module investigates whether chronic or residual disease-associated burden — exemplified by lymphatic filariasis morbidity in Sri Lanka after WHO validation of elimination as a public-health problem in 2016 — can be examined as a population-level contributor to Human Physiological Buffering Capacity. Core research proposition:Population-level physiological buffering capacity may be shaped by the interaction of chronic disease burden, nutritional adequacy, socioeconomic resources, functional limitation, recovery opportunities, and access to morbidity management services. These interactions are treated as testable systems hypotheses, not as established causal pathways. Key features of this release:• Positions residual LF morbidity after transmission-level elimination as a natural research setting for adaptive-capacity questions• Integrates disease burden, nutrition, socioeconomic inequality and physiological recovery within a multilevel framework• Maintains strict scientific boundaries: no clinical claims, no treatment recommendations, no assertion that LF directly causes cognitive decline• Explicitly falsifiable: the buffering construct must demonstrate added explanatory value beyond conventional measures or be revised Research status: Hypothesis-generating / Pre-empirical / Population-level systems framework This module does not claim clinical validation, WHO endorsement, or established causality. All higher-order links to cognitive readiness and human development remain provisional and require empirical testing within the parent Adaptive Capacity programme. Keywords: Human Physiological Buffering Capacity; Lymphatic Filariasis; Sri Lanka; Residual Morbidity; Nutritional Adequacy; Socioeconomic Inequality; Adaptive Capacity; Cognitive Readiness; Population-Level Systems; Disease-Associated Burden; Human Adaptive Capacity; Experimental Human Development; Morbidity Management; Quality of Life; Resilience Recommended citation:Piran, M. (2026). Applied Research Module 10 — Disease-Associated Human Physiological Buffering Capacity: A Population-Level Systems Study of Lymphatic Filariasis, Nutrition, and Human Adaptive Resilience in Sri Lanka (Version 2.0.0). Zenodo. https://doi.org/10.5281/zenodo.22791699 Parent repository citation:Piran, M. (2026). Human Adaptive Capacity, Cognitive Readiness, and Experimental Human Development (Version 0.0.0). Zenodo. https://doi.org/10.5281/zenodo.21904652 License: Creative Commons Attribution–NonCommercial–NoDerivatives 4.0 International (CC BY-NC-ND 4.0)Copyright © 2026 Mohammad Piran. All Rights Reserved.
2026-08-04 | Persistent morbidity and knowledge gaps in a near‑elimination setting: A cross‑sectional study of lymphatic filariasis in northern Ghana
De-identified participant-level data underlying the results reported in the associated manuscript. Personal identifiers have been removed in accordance with ethical and data protection requirements.
2026-07-01 | AB118. The sudden surge of lymphatic filariasis cases in Tuaran: a cross-sectional study
Background: Lymphatic filariasis (LF) is a vector-borne neglected tropical disease that remains endemic in several regions of Malaysia, particularly in Sabah. The predominant causative parasite is Brugia malayi. Tuaran District had no previously recorded cases of LF until 2023. However, a sudden emergence of 40 confirmed LF cases in 2024 raised concerns regarding undetected transmission and limitations in local surveillance as well as early response efforts. This study aims to describe the sociodemographic characteristics and spatial analysis of LF cases in Tuaran District, Sabah, from 2020 to 2024. It aims to outline the public health response and preventive measures implemented during the surge in the number of confirmed cases.Methods: This cross-sectional study was conducted using secondary data from the Vector Control Unit, Tuaran District Health Office, covering a 5-year period from 2020 to 2024. Data sources included case notifications, field investigation records, community screening outcomes, and entomological investigation findings.Results: The first LF case was detected in 2023. Active case detection involved 394 residents across four localities, resulting in 38 individuals testing positive. In Tuaran, LF cases were more common among adults aged ≥40 years and those with outdoor jobs. Up till 2024, only 43.9% of positive cases received treatment. Spatial analysis shows LF cases clustering around villages within the Tamparuli sub-district, particularly where the landscape is dominated by plantations and forest margins. Entomological investigation at three sites showed no active vector presence. Public health interventions focused on morbidity management, continuous case surveillance, and targeted community health education.Conclusions: LF remains a significant public-health burden. Sabah still has endemic implementation units and sporadic cases, underscoring the need for more resources, consistent access to diagnostics and treatment, stronger community entomological surveillance, and better integration of local actions with national strategies.
2026-01-31 | Cross-sectional epidemiological assessment of lymphatic filariasis situation in areas under post-mass drug administration surveillance and the associated risk of transmission in the context of migrants in India: a study protocol.
India targets to eliminate lymphatic filariasis (LF) in alignment with the global goals. By 2024, 106 out of a total of 345 endemic districts have passed all three serial transmission assessment surveys (TAS) and are under post-mass drug administration (MDA) surveillance for a variable period. However, the current epidemiological situation of LF is not known in these districts. With increased mobility of population from the endemic districts currently under MDA to these post-MDA areas, resurgence of LF in these areas cannot be ruled out. Therefore, a study is planned to understand the current LF status in areas under post-MDA surveillance with the following objectives: (1) To assess the epidemiological situation of LF in terms of human and vector infection prevalence in selected evaluation units (EUs) under different durations of post-MDA phase and (2) to estimate the filarial infection (in terms of filarial antigen and microfilaria) among migrants (from endemic districts) in these EUs. This cross-sectional study will measure the filarial infection in (1) adult population aged ≥20 years (following the WHO 2025 protocol for monitoring and evaluation of MDA) among general population (n=3150 per EU), (2) migrant population (aged 2 years and above) in the post-MDA area originating from endemic areas (n=1000 per EU) and (3) vectors (n=7500 per EU) using molecular xenomonitoring (MX) to confirm sustenance of transmission interruption or identify any potential risk of resurgence in three EUs under post-MDA phase. In one MDA-naive EU that shares borders with endemic districts, filarial infection status will be assessed in (1) school children aged 9-14 years (as per WHO mini-TAS protocol, n=480), (2) migrants (aged 2 years and above) from endemic areas (n=1000) and (3) vectors (n=7500). EU-wide prevalence of microfilaria, circulating filarial antigen and vector infection rates with 95% CIs will be estimated. Multivariate logistic regression analysis will be carried out to find factors associated with LF positivity. In addition, knowledge, attitude and practice surveys will also be conducted among the adult migrants (n=1000 per EU). Thirty in-depth interviews will be conducted among the migrants, local community and health workers (in each EU) and the results will be suitably analysed and triangulated. The study results will enable the national programme to confirm sustenance of transmission interruption or assist in taking a decision to reinitiate MDA in these areas under post-MDA surveillance. It will also enable devising specific strategies to treat migrants. This study has been approved by the institutional ethics committee (IHEC 03-0824/N/F). A workshop will be held with all stakeholders to disseminate the study findings.
2026-01-27 | Finding the Gaps: Integrated Serosurveillance and Spatial Clustering of Vaccine Preventable Diseases in Samoa, 2018-2019.
Seroprevalence of antibodies for vaccine-preventable diseases (VPDs), due to vaccination or previous infection, can provide a more accurate estimate of immunity compared to vaccination coverage data alone. This study aimed to examine the seroepidemiology and spatial distribution of VPD seroprevalence in Samoa in 2018 and 2019. Dried blood spot (DBS) samples were collected from two nationally representative community-based surveys of participants aged ≥5 years from the Surveillance and Monitoring to Eliminate Lymphatic Filariasis and Scabies from Samoa (SaMELFS) project. DBSs were tested using multiplex bead assays (MBAs) to detect antibodies against measles, rubella, diphtheria, and tetanus. Seroprevalence was estimated at the national and primary sampling unit (PSU) levels, and cluster analysis was completed using SaTScan. Overall, 8394 valid MBA results were analysed across 35 PSUs. The highest overall seroprevalence was observed for tetanus (91.0%; 95% CI: 90.2-91.7), followed by diphtheria (83.7%; 95% CI: 82.7-84.7), rubella (79.3%; 95% CI: 78.2-80.3), and measles (45.8%; 95% CI: 44.8-46.9) with substantial heterogeneity across PSUs. Clusters of seronegativity to measles (relative risk [RR]: 1.16, p < 0.001) and diphtheria (RR: 1.16, p < 0.001) were also identified. These findings demonstrate significant variation in seroprevalence and pockets of low population immunity to multiple VPDs, highlighting the key advantage of an integrated rather than siloed approach. The relatively high seroprevalence to rubella suggests potential community transmission, emphasising the need to strengthen congenital rubella surveillance and improve vaccination coverage. Identifying low immunity to VPDs can provide an early warning to potential outbreak risk and support the Ministry of Health to target public health interventions in higher-risk areas.
proteins
2026-07-28 | Development of a Human Lymphatic Filariasis Vaccine, LFGuard for Clinical Testing 2306046
Abstract Introduction Lymphatic filariasis (LF) is a neglected tropical disease that causes disability and impairment of the lymphatic system. Millions of people in the endemic area still suffer from LF, even after decades of mass drug administration (MDA). The target of MDA is to block the transmission. A preventive vaccine is needed to eliminate the infection in the endemic countries. Our laboratory developed a tetravalent fusion protein vaccine, rBmHAXT, which demonstrated significant protection and immunogenicity in rodent and non-human primate models. The vaccine has now completed the Good Manufacturing Practice (cGMP) guidelines for use in clinical trials. Methods This study aims to confirm whether the final cGMP product (LFGuard) retains the safety, immunogenicity, and efficacy as observed with the parent vaccine in a mouse model. Three doses of the vaccine were given s/c or I/m along with Al-T4 adjuvant, an alum adsorbed TLR-4 agonist to promote a balanced Th1/Th2 response against the filarial infection. To evaluate safety, we measured the body weight, haematological parameters, liver function, and kidney function. Immunogenicity was determined by evaluating the levels of antigen-specific IgG antibody titer. The vaccine efficacy was determined by a challenge study. Results Our results show that vaccine is safe and has no adverse effects on the body weight, haematological parameters, liver or kidney functions in all vaccinated animals compared to controls irrespective of the route of immunization. All immunized mice showed a high titer of antigen-specific IgG antibodies (1:80,000) in their serum as expected. These mice also had a significantly (p > 0.001) higher number of CD4+ TCM in their spleen. The vaccinated mice also showed significantly higher levels of protection (90.7%) compared to the controls. Conclusion This is the most crucial step in bridging the vaccine to phase I clinical testing. These pre-IND-enabling studies will help bring the LF vaccine close to the clinics. Funding Source N/A Topic Categories Vaccines and Immunotherapy (VAC)
2025-07-23 | Sequence Localization of SeGPx in S. digitata Genome Contigs and Determination of its Presence in the Whole Worm Extract.
Lymphatic filariasis, caused by three major filarial species, is marked by immune evasion strategies involving antioxidant enzymes. The role of selenium-dependent glutathione peroxidase (SeGPx) in this process remains underexplored. This study aimed to identify and characterise SeGPx in Setaria digitata, a genomic analogue of Wuchereria bancrofti, and evaluate its potential as a diagnostic antigen. segpx sequences were identified through bioinformatics tools, including BLAST and UniProt databases. Due to limited nematode entries, a validated SeGPx sequence from Lymnaea stagnalis was used as a proxy in PSI-BLAST to identify homologues. Enzymatic activity was confirmed through spectrophotometric assay and activity staining on SDS-PAGE to confirm its enzymatic activity and molecular mass confirmation. The segpx gene was localised within the S. digitata genome data (Contig 127, nucleotides 56,000-58,000). The enzyme assay showed a time-dependent decline in absorbance at 340 nm due to NADPH oxidation, plateauing after 13 min. Enzyme activity was calculated as 0.139 U, with a specific activity of 0.198 U/mg protein. A clear band at ~ 20 kDa was visualised via activity staining, confirming SeGPx presence. Combined sequence-based identification and enzymatic validation confirm the functional presence of SeGPx in S. digitata. These findings support its role in oxidative stress mitigation and potential as a diagnostic antigen. The precise gene localisation offers a foundation for recombinant cloning, providing a streamlined alternative to conventional purification approaches for diagnostic development in filariasis.
2024-07-20 | Nature-derived Peptides as Promising Antiparasitic Agents against Neglected Tropical Diseases
Abstract Neglected tropical diseases (NTDs) are a group of at least 20 infectious diseases that primarily affect tropical regions. Despite impacting 1.6 billion people worldwide, these diseases have not received adequate global priority and attention. Currently, NTDs caused by protozoa have limited therapeutic options, and the emergence of drug-resistant strains further exacerbates the situation. In recent years, several antimicrobial peptides (AMPs) have emerged as potential therapeutic candidates against NTDs. This review analyzes the contemporary trends of AMPs, explores their antiparasitic properties, and mechanisms of action against three parasitic protozoan NTDs: Chagas disease, human African trypanosomiasis, and leishmaniasis and one parasitic helminth NTD: lymphatic filariasis. Furthermore, notable drawbacks associated with AMPs are highlighted, and future research directions are proposed. Overall, this review points out the potential of AMPs as therapeutic agents for these three protozoan neglected tropical diseases and one parasitic helminth NTDs as well as emphasizes the imperative need for continued research in this field.
2024-07-03 | Revelation of potent ES-62 activity of a hypothetical protein from Wuchereria bancrofti proteome by in-silico based characterization and functional annotation
Lymphatic filariasis (LF) is a well-known disease caused primarily by the parasitic worm Wuchereria bancrofti, although other Filarioidea parasites, including Brugia malayi and Brugia timori, can also be responsible. These parasites can frequently affect the lymphatic system during their microfilariae stage. These parasites often produce numerous excretory-secretory (ES) products that can modulate or impede the activities of diverse immune system cells. Thus, this study utilized computational characterization and functional annotation to assess the impact of a hypothetical protein from Wuchereria brancrofti, specifically its role as an ES-62 product. The analysis of functional domain annotation indicates that the hypothetical protein shares functional domains comparable to those found in ES-62 (Zinc-binding metallopeptidase family protein). Additionally, the hypothetical protein has significant sequence similarities (73.83 %) with the ES-62 of Acanthocheilonema viteae, as shown by the multiple sequence alignment and phylogeny analyses. Furthermore, the hypothetical protein's secondary and tertiary structure and its tertiary model structure's quality possess an acceptable standard quality (Z-score of −9.45). Moreover, the molecular docking study demonstrates that the hypothetical protein shows a significant affinity for the TLR-4 receptor (center energy score of −1145.9 and the lowest energy score of −1096.5), a finding that is subsequently confirmed by normal mode analysis. These in silico findings suggest that the observed hypothetical protein could aid in studying filarial infection and developing pharmaceuticals to treat lymphatic filariasis.
2024-03-27 | Unpacking Immune Modulation as a Site of Therapeutics Innovation for Nematode Parasite Wuchereria bancrofti: A Temporal Quantitative Phosphoproteomics Profiling of Macrophage Migration Inhibitory Factor 2.
Nematode infections are common in both humans and livestock, with major adverse planetary health and economic impacts. Wuchereria bancrofti is a parasitic nematode that causes lymphatic filariasis, a neglected tropical disease that can lead to severe disability and deformity worldwide. For the long-term survival of the bancroftian parasites in the host, a complex immune invasion strategy is involved through immunomodulation. Therefore, immunomodulation can serve as a site of research and innovation for molecular targets. Macrophage migration inhibitory factor (MIF) is a pleiotropic cytokine crucial to the host antimicrobial alarm system and stress response. Interestingly, the nematode parasite W. bancrofti also produces two homologs of MIF (Wba-MIF1 and 2). Using a mass spectrometry-based phosphoproteomics approach, we report new findings on the immunomodulatory effect and signaling mechanism of Wba-MIF2 in macrophage cells. Accordingly, we observed 1201 phosphorylated sites on 467 proteins. Out of the 1201 phosphorylated sites, 1075, 117, and 9 were found on serine (S), threonine (T), and tyrosine (Y) residues, respectively. Our bioinformatics analysis led to identification of major pathways, including spliceosomes, T cell receptor signaling pathway, Th17 differentiation pathway, interleukin-17 signaling pathway, and insulin signaling pathway upon Wba-MIF2 treatment. Wba-MIF2 treatment also enriched CDK4, CDK1, and DNAPK kinases. The comparison of the signaling pathway of Wba-MIF2 with that of human-MIF suggests both share similar signaling pathways. These findings collectively offer new insights into the role and mechanism of Wba-MIF2 as an immunomodulator and inform future diagnostics and drug discovery research for W. bancrofti.
other
2026-04-25 | Strengthening lymphatic filariasis elimination programmes with molecular xenomonitoring: critical utility and unmet operational needs.
Molecular xenomonitoring (MX)-the detection of filarial DNA in mosquito vectors-has become an important component of post- mass drug administration surveillance within the Global Programme to Eliminate Lymphatic Filariasis (GPELF). MX offers non-invasive, high-sensitivity detection of residual or recrudescent Wuchereria bancrofti transmission, particularly where human microfilaraemia and antigenemia surveys have limited power. However, the current operational model relies heavily on gravid-trap-based sampling, which captures a physiologically narrow, behaviourally biased subset of mosquitoes, often dominated by zoophagic Culex quinquefasciatus. This restricts interpretation and programme decision-making. We propose a restructured MX approach focused on representative multi-physiological sampling, routine blood-meal profiling, stage-specific molecular assays and harmonized analytical frameworks. With these refinements, MX can evolve into an actionable transmission-intelligence platform vital for sustaining lymphatic filariasis elimination in the endgame phase.
2025-04-03 | Germline transformation of the West Nile virus and avian malaria vector Culex quinquefasciatus Say using the piggyBac transposon system.
Culex quinquefasciatus Say is a mosquito which acts as a vector for numerous diseases including West Nile virus, lymphatic filariasis and avian malaria, over a broad geographical range. As the effectiveness of insecticidal mosquito control methods declines, the need has grown to develop genetic control methods to curb the spread of disease. The piggyBac transposon system - the most widely used genetic transformation tool in insects, including mosquitoes - generates quasi-random insertions of donor DNA into the host genome. However, despite the broad reported species range of piggyBac, previous attempts to use this tool to transform Culex quinquefasciatus mosquitoes have failed. Here we report the first successful transformation of Culex quinquefasciatus with the piggyBac transposon system. Using commercially synthesised piggyBac mRNA as a transposase source, we were able to generate three independent insertions of a ZsGreen fluorescent marker gene, with transformation efficiencies of up to 5 %. Through this work, we have expanded the genetic toolkit available for the genetic manipulation of Culex mosquitoes and thus removed a barrier to developing novel genetic control methods in this important disease vector.
2023-11-20 | CRISPR-based gene drives generate super-Mendelian inheritance in the disease vector Culex quinquefasciatus
Abstract Culex mosquitoes pose a significant public health threat as vectors for a variety of diseases including West Nile virus and lymphatic filariasis, and transmit pathogens threatening livestock, companion animals, and endangered birds. Rampant insecticide resistance makes controlling these mosquitoes challenging and necessitates the development of new control strategies. Gene drive technologies have made significant progress in other mosquito species, although similar advances have been lagging in Culex . Here we test a CRISPR-based homing gene drive for Culex quinquefasciatus , and show that the inheritance of two split-gene-drive transgenes, targeting different loci, are biased in the presence of a Cas9-expressing transgene although with modest efficiencies. Our findings extend the list of disease vectors where engineered homing gene drives have been demonstrated to include Culex alongside Anopheles and Aedes , and pave the way for future development of these technologies to control Culex mosquitoes.
2023-10-13 | Symbiotic Wolbachia in mosquitoes and its role in reducing the transmission of mosquito-borne diseases: updates and prospects
Mosquito-borne diseases such as malaria, dengue fever, West Nile virus, chikungunya, Zika fever, and filariasis have the greatest health and economic impact. These mosquito-borne diseases are a major cause of morbidity and mortality in tropical and sub-tropical areas. Due to the lack of effective vector containment strategies, the prevalence and severity of these diseases are increasing in endemic regions. Nowadays, mosquito infection by the endosymbiotic Wolbachia represents a promising new bio-control strategy. Wild-infected mosquitoes had been developing cytoplasmic incompatibility (CI), phenotypic alterations, and nutrition competition with pathogens. These reduce adult vector lifespan, interfere with reproduction, inhibit other pathogen growth in the vector, and increase insecticide susceptibility of the vector. Wild, uninfected mosquitoes can also establish stable infections through trans-infection and have the advantage of adaptability through pathogen defense, thereby selectively infecting uninfected mosquitoes and spreading to the entire population. This review aimed to evaluate the role of the Wolbachia symbiont with the mosquitoes ( Aedes, Anopheles, and Culex ) in reducing mosquito-borne diseases. Global databases such as PubMed, Web of Sciences, Scopus, and pro-Quest were accessed to search for potentially relevant articles. We used keywords: Wolbachia , Anopheles , Aedes , Culex , and mosquito were used alone or in combination during the literature search. Data were extracted from 56 articles’ texts, figures, and tables of the included article.
2023-08-28 | Xenorhabdus and Photorhabdus Bacteria as Potential Candidates for the Control of Culex pipiens L. (Diptera: Culicidae), the Principal Vector of West Nile Virus and Lymphatic Filariasis
Vector-borne diseases pose a severe threat to human and animal health. Culex pipiens L. (Diptera: Culicidae) is a widespread mosquito species and serves as a vector for the transmission of infectious diseases such as West Nile disease and Lymphatic Filariasis. Synthetic insecticides have been the prime control method for many years to suppress Cx. pipiens populations. However, recently, the use of insecticides has begun to be questioned due to the detrimental impact on human health and the natural environment. Therefore, many authorities urge the development of eco-friendly control methods that are nontoxic to humans. The bacterial associates [Xenorhabdus and Photorhabdus spp. (Enterobacterales: Morganellaceae)] of entomopathogenic nematodes (EPNs) (Sterinernema spp. and Heterorhabditis spp.) (Rhabditida: Heterorhabditidae and Steinernematidae) are one of the green approaches to combat a variety of insect pests. In the present study, the mosquitocidal activity of the cell-free supernatants and cell suspension (4 × 107 cells mL−1) of four different symbiotic bacteria (Xenorhabdus nematophila, X. bovienii, X. budapestensis, and P. luminescens subsp. kayaii) was assessed against different development stages of Cx. pipiens (The 1st/2nd and 3rd/4th instar larvae and pupa) under laboratory conditions. The bacterial symbionts were able to kill all the development stages with varying levels of mortality. The 1st/2nd instar larvae exhibited the highest susceptibility to the cell-free supernatants and cell suspensions of symbiotic bacteria and the efficacy of the cell-free supernatants and cell suspensions gradually declined with increasing phases of growth. The highest effectiveness was achieved by the X. bovienii KCS-4S strain inducing 95% mortality to the 1st/2nd instar larvae. The results indicate that tested bacterial symbionts have great potential as an eco-friendly alternative to insecticides.
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Drug Discovery Landscape
2 orphan drug designations for Lymphatic filariasis.
2 orphan drug designations for Lymphatic filariasis.
Drug | Therapy type | Orphan designation | Clinical trial status | Sponsor |
|---|---|---|---|---|
4¿-(p-fluorobenzyl)tylosin A | small molecules | FDA | — | AbbVie Inc. |
flubendazole | small molecules | FDA | — | Janssen Research & Development, LLC |
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