Brugia Timori Research Articles

An Overview on Antifilarial Efficacy of Heterocyclic Motifs Encompassing Synthetic Strategies, SAR, and Commercialized Medications.

Filariasis is one of the oldest, most dangerous, debilitating, disfiguring diseases and often ignores tropical disorders. It presents with a range of clinical symptoms, a low death rate, and a high morbidity rate, which contributes to social discrimination. This condition has major effects on people's socioeconomic circumstances. This illness is carried by mosquitoes that have spread malaria. Lymphatic filariasis, caused by Wuchereria bancrofti, Brugia malayi, and Brugia timori, is a crippling illness with serious social and economic consequences. The infection persisted despite therapy with conventional antifilarial medications such as diethylcarbamazine (DEC), albendazole, and ivermectin, which are mostly microfilaricides. Current treatments (ivermectin, diethylcarbamazine, and albendazole) have limited effectiveness against adult parasites and produce side effects; therefore, innovative antifilarial medications are urgently required. Hence, macrofilaricides, embryostatic agents, and improved microfilaricides are required. The following article discusses the typical synthetic methodologies established for antifilarial activity as well as their marketed pharmaceuticals, which will help researchers, medicinal chemists, and pharmaceutical scientists to develop new and effective antifilarial therapies. This review can help to identify new lead compounds and optimize existing commercial medications to improve their therapeutic efficacy. The majority of the studies addressed in this review concern the forms of filariasis, parasite life cycle, symptoms, medications used to treat filariasis, synthetic schemes, SAR, and results from the reported research.

Molecular xenomonitoring reveals Anopheles funestus and An. rivulorum as the primary vectors of lymphatic filariasis in coastal Kenya

BackgroundLymphatic filariasis (LF) is an infectious neglected tropical disease caused by mosquito-borne nematodes such as Wuchereria bancrofti, Brugia malayi, and Brugia timori. Globally, LF affects 51 million people, with approximately 863 million at risk in 47 countries. In Kenya, filariasis is endemic along the entire coastal strip, and more recently, at the Kenya–Ugandan border. The World Health Organization (WHO) recommends mass drug administration to reduce disease transmission and morbidity. Monitoring the effectiveness of such interventions relies on robust surveillance, achieved through microscopic examination of microfilariae in nighttime blood, detection of circulating filarial antigens (CFA), and molecular xenomonitoring. We focused on molecular xenomonitoring along the Kenyan coast due to its noninvasive nature and the opportunity to identify new vectors.MethodsIn 2022, mosquitoes were collected from Kilifi, Kwale, and Taita-Taveta counties located within the LF endemic region in Kenya. Subsequently, genomic deoxyribonucleic acid (gDNA) was extracted from these mosquitoes for speciation and analysis of Wuchereria bancrofti infection rates. The impact of sociodemographic and household attributes on infection rates was assessed using generalized estimating equations.ResultsA total of 18,121 mosquitoes belonging to Culicinae (63.0%, n = 11,414) and Anophelinae (37.0%, n = 6707) subfamilies were collected. Morphological identification revealed that Anopheline mosquitoes were dominated by An. funestus (45.4%, n = 3045) and An. gambiae (42.8%, n = 2873). Wuchereria bancrofti infection rates were highest in Kilifi (35.4%; 95% CI 28.0–43.3%, n = 57/161) and lowest in Taita Taveta (5.3%; 95% CI 3.3–8.0%, n = 22/412). The major vectors incriminated are An. rivulorum, An. funestus sensu stricto, and An. arabiensis. Mosquitoes of the An. funestus complex were significantly associated with LF transmission (OR 18.0; 95% CI 1.80–180; p = 0.014). Additionally, a higher risk of transmission was observed outdoors (OR 1.74; 95% CI 1.08–2.82; p = 0.024) and in homesteads that owned livestock (OR 2.00; 95% CI 1.09–3.66; p = 0.025).ConclusionsIn this study, we identified An. funestus s.l. sibling species, An. rivulorum and An. funestus s.s., as the primary vectors of lymphatic filariasis along the Kenyan coast. These findings also highlight that a significant portion of disease transmission potentially occurs outdoors where indoor-based vector control tools, including long-lasting insecticidal nets and indoor residual spray, may not be effective. Therefore, control measures targeting outdoor resting mosquitoes such as zooprophylaxis, larval source management, and attractive sugar baits may have potential for LF transmission reduction.Graphical

Tropical eosinophilia: Case series on varying presentations

ABSTRACT Eosinophilia can be due to both infectious and non-infectious causes, many of which may be clinically indistinguishable. Filariasis, a tropical and subtropical infection, is caused by Wuchereria bancrofti, Brugia timori (B. timori), and Brugia malayi. Filariasis is conventionally diagnosed by demonstration of microfilaria in the peripheral blood smear. The disease may be missed if one is not aware of the possibility. We report two cases in two individuals with eosinophilia due to filaria resulting in tropical pulmonary eosinophilia and deep vein thrombosis (DVT). They had complete symptomatic improvement after a 3-week course of diethylcarbamazine (DEC) +/- ivermectin.

Three decades of research in lymphatic filariasis-lessons learned.

Lymphatic filariasis (LF), one of the 21 Neglected Tropical Diseases (NTD) which is the second leading cause for disability globally. Wuchereria Bancrofti, Brugia malayi and Brugia timori are the parasites causing this infection. World Health Assembly in 1997 declared LF to be eliminated and the Global Program to eliminate LF (GPELF) was launched by WHO in 2000 with the two strategies viz, 1) stop transmission of infection through Mass Drug Administration (MDA) and 2) to alleviate the suffering of the people affected with the disease through Morbidity Management and Disability Prevention (MMDP. The 'Filariasis research unit' recommended by WHO TDR and ICMR was established in Alappuzha, Kerala in 1989 for research studies related to LF. Over the last three decades 23 studies have been completed, which included different trials to find out the dose, effectiveness and safety of the various drugs used in preventive chemotherapy as single drug or combinations, for treatment of microfilaraemia,, various studies related to morbidity management in filarial disease, socio-economic aspects of filarial disability, Pharmacokinetic study of antifilarial drugs, Study on lymphatic filariasis in children, Studies on dignostics of LF, efficacy of drugs in management of lymphedema etc. In this article an attempt is made to explain the lessons learned from these studies and its importance in development of policy decision making for GPELF.

Simultaneous LC-MS/MS Method for the Quantitation of Probenecid, Albendazole, and Its Metabolites in Human Plasma and Dried Blood Spots

Millions of individuals throughout the world suffer from lymphatic filariasis (LF), which is a morbid disease caused by Wuchereria bancrofti, Brugia malayi, and Brugia timori. These infections belong to tissue-invading nematodes and are one of the major neglected tropical diseases that often result in permanent and enduring disability among individuals in endemic regions. Due to combination therapy, LF eradication has drastically decreased infections globally. The development of blood micro-sampling techniques allowing precise quantitation of drugs in blood would facilitate pharmacokinetic (PK) studies in remote populations. Therefore, an LC-MS/MS bioanalytical method was utilized to analyze albendazole (ABZ), albendazole sulfone (ABZ-ON), albendazole sulfoxide (ABZ-OX), and probenecid (PR) in plasma and dried blood spots. Solid-phase extraction was utilized to extract the analyte from both plasma and blood-spiked DBS. Analytes of interest were eluted with a gradient mobile system using 0.05% formic acid in water (A) and 0.05% formic acid in methanol (B) and separated using a reversed-phase Acquity ®BEH C18 UPLC column (100 × 2.1 mm, 1.7 µm). Precision and accuracy at each QC level were within the acceptable limit, i.e., ±15% for all analytes in both the matrices. Tests for stability under laboratory and storage conditions indicated that no notable changes were observed for plasma and DBS. The LC-MS/MS method demonstrated its capability to consistently identify all target analytes (ABZ, ABZ-ON, ABZ-OX, and PR) at low concentrations, even at the small specimen volumes obtained from DBS cards. This confirms the efficacy and durability of DBS cards as a micro-sampling technique. Moreover, it enhances collection efforts for therapeutic drug monitoring in remote locations for patients infected with lymphatic filariasis.

Diagnosis of filariasis: A case report of a reemerging neglected tropical disease

Filariasis is a neglected tropical disease (NTD) of humans caused by the helminthic filarial species Wuchereria (W.) bancrofti, Brugia (B.) timori, and B. malayi. Diverse species of mosquitoes transmit the microfilariae of these worms to cause filaria infection, with the disease presenting classical clinical manifestations such as lymphedema, adenolymphangitis, and hydrocele, which result in permanent disfigurement and psychosocial and economic stigmatization. These sequelae necessitate the need for proper identification and characterization of the etiological agent for therapy and prevention. In this study, we report a case of unilateral lymphedema in a 28-year-old gateman/farmer from the Sabon Gari Local Government Area of Kaduna State, Northern Nigeria. Microscopy of the patient’s blood sample demonstrated the presence of microfilariae, leading to PCR characterization to be W. bancrofti. Upon diagnosis, the patient was treated with tablets of doxycycline 200 mg daily and albendazole 200 mg bid for six weeks, followed by a single dose of ivermectin 150 mg/kg (15 mg) at the 4th week of initiating treatment. This treatment regimen was complemented by a combination of bed rest, use of compression bandage, and limb elevation at night, resulting in remarkable improvement of the patient’s health after six weeks. In conclusion, lymphatic filariasis diagnosis was microscopically confirmed by the demonstration of microfilaria in the blood film obtained at night, leading to molecular characterization by PCR to be W. bancrofti. This is a workup for treating filarial infections in patients with unilateral leg swelling and a history of living in or traveling to endemic areas. This should also be a wake-up call to policymakers and practitioners regarding the possible recrudescence of filariasis in Nigeria.

Wolbachia and Lymphatic Filarial Nematodes and Their Implications in the Pathogenesis of the Disease.

Lymphatic filariasis (LF) is an infection of three closely related filarial worms such as Wuchereria bancrofti, Brugia malayi, and Brugia timori. These worms can cause a devastating disease that involves acute and chronic lymphoedema of the extremities, which can cause elephantiasis in both sexes and hydroceles in males. These important public health nematodes were found to have a mutualistic relationship with intracellular bacteria of the genus Wolbachia, which is essential for the development and survival of the nematode. The host's inflammatory response to parasites and possibly also to the Wolbachia endosymbiont is the cause of lymphatic damage and disease pathogenesis. This review tried to describe and highlight the mutualistic associations between Wolbachia and lymphatic filarial nematodes and the role of bacteria in the pathogenesis of lymphatic filariasis. Articles for this review were searched from PubMed, Google Scholar, and other databases. Article searching was not restricted by publication year; however, only English version full-text articles were included.

Exploring the antifilarial potential of an important medicinal plant Typhonium trilobatum (L. Schoot): Isolation, characterization, and structural elucidation of bioactive compounds against Brugia malayi

Ethnopharmacology relevanceThe plant Typhonium trilobatum has been utilized in traditional medicine for the treatment of many ailments, including parasitic infections. Recent examinations indicate that the bioactive substances from this plant may have antiparasitic activities against Brugia malayi, which have not been determined. PurposeThe parasitic nematodes Brugia malayi, Brugia timori, and Wuchereria bancrofti causing lymphatic filariasis, remain a significant challenge to global public health. Given the ongoing nature of this enduring menace, the current research endeavours to examine the efficacy of an important medicinal plant, Typhonium trilobatum. MethodsDifferent extracts of the T. trilobatum tubers were evaluated for their antiparasitic activity. The most prominent extract was subjected to Gas Chromatography Mass Spectrometry (GC-MS) and High Performance Liquid Chromatography (HPLC) followed by Column Chromatography for isolating bioactive molecules. The major compounds were isolated and characterized based on different spectroscopic techniques (FTIR, NMR and HRMS). Further, the antiparasitic activity of the isolated compounds was evaluated against B. malayi and compared with clinically used antifilarial drugs like Diethylcarbamazine and Ivermectin. ResultsThe methanolic extract of the tuber exhibited significant antiparasitic activity compared to the other extracts. The bioactive molecules isolated from the crude extract were identified as Linoleic acid and Palmitic acid. Antiparasitic activity of both the compounds has been performed against B. malayi and compared with clinically used antifilarial drugs, Ivermectin and DEC. The IC50 value of Linoleic acid was found to be 6.09 ± 0.78 μg/ml after 24 h and 4.27 ± 0.63 μg/ml after 48 h, whereas for Palmitic acid the value was 12.35 ± 1.09 μg/ml after 24 h and 8.79 ± 0.94 μg/ml after 48 h. The IC50 values of both the molecules were found to be similar to the standard drug Ivermectin (IC50 value of 11.88 ± 1.07 μg/ml in 24 h and 2.74 ± 0.43 μg/ml in 48 h), and much better compared to the DEC (IC50 values of 194.2 ± 2.28 μg/ml in 24 h and 101.8 ± 2.06 μg/ml in 48 h). Furthermore, it has been observed that both the crude extracts and the isolated compounds do not exhibit any detrimental effects on the J774.A.1 macrophage cell line. ConclusionThe isolation and characterization of bioactive compounds present in the methanolic tuber extract of Typhonium trilobatum were explored. Moreover, the antimicrofilarial activity of the crude extracts and its two major compounds were determined using Brugia malayi microfilarial parasites without any significant side effects.

Structural studies on azadirachtin targeting the glucuronosyltransferase from lymphatic filariasis and its inhibition

Background and Aims: Brugia malayi, Brugia timori, and Wuchereria bancrofti are parasitic worms that cause lymphatic filariasis, also known as elephantiasis in some parts of the world. Because no effective vaccines and current treatments have adverse pharmacological properties, this condition has sparked much interest in the drug discovery community. This research aims to assess the efficacy of azadirachtin against a possible therapeutic target, intestine glucuronosyltransferase protein, in treating and preventing lymphatic filariasis. Methods: I-Tasser was used to create the protein, Uniprot was used to collect its FASTA sequences, and Galaxy Refine was used to refine the protein model. The protein 3D model was tested using PROCHECK and ERRAT. We used PubChem to get the three-dimensional structure of the azadirachtin ligand molecules. To study the toxicity profiles and pharmacokinetics, researchers employ SwissADME. Molecular docking studies were conducted using the AutoDock tool, and Pymol viewer was used to observe the interactions between the target protein and the ligand molecules. Results: The azadirachtin compound has a satisfactory range of pharmacokinetic parameters in terms of its absorption, distribution, metabolism, and excretion. When compared to the currently existing drug Diethylcarbamazine, molecular docking studies indicate that the azadirachtin molecule binds with the intestinal glucuronosyltransferase proteins of Brugia timori, Wuchereria bancrofti, and Brugia malayi strongly. Conclusions: In sum, our understanding of the mechanism by which azadirachtin, a traditional component derived from plants, inhibits intestinal glucuronosyltransferase protein is enhanced, and this could pave the way for the development of new targeted anti-filarial agents.

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.

Drug- Phospholipid complex: A novel strategy for Lymphatic Filariasis treatment

One of the most terrifying and ugly forms of filariasis to humans is lymphatic filariasis, where adult worms 7-10 cm long are found in the lymphatic system. Mf continues to multiply in the bloodstream of the host and translocates eventually to the LS. Filariasis-causing parasites block the human blood vessels and lymph nodes.The impasse allows fluid to drain into the terminus of the body and accumulate in tissues, causing severe swelling christened “lymphoedema”. LF is caused due Filariodiaceae family roundworms, often these are of three types (Wuchereria bancrofti, Brugia malayi and Brugia timori). All of these are handed down through Anopheles mosquitoes, Aedes mosquitoes and Culex pipiens. In worldwide over 90% of infectious diseases are caused by W. bancrofti. Several synthetic drugs are currently used to treat this disease. However these drugs are not as effective as killing adult worms and at the same time, some side effects are also seen. Conversely, plant actives ingredients complex with phospholipids to form nano-sized vesicles. As parasites live in the small intestine, nanometer-sized phyto vesicles can protect plant actives from deterioration in the stomach and easily reach their target and kill parasites without side effects.

Studi filariasis berbasis pemeriksaan laboratorium di Kota Semarang

Background: Filariasis is a disease caused by parasitic nematodes of Filariae. Filariasis is caused by filarial worm species, namely Wuchereria bancrofti, Brugia malayi, and Brugia timori. This disease is transmitted through the bite of infected mosquitoes (Anopheles, Aedes, and Culex). Symptoms of filariasis in men or women include damage to the lymphatic system swelling of the arms, legs, and genitals, which causes pain, decreased productivity, and social problems. Filarial diagnosis through examination of blood smears to detect filarial parasites in the blood, accompanied by hematological and clinical chemical examinationsObjective: This study aimed to describe filariasis through blood tests (blood smears, hematological examinations, and clinical chemistry examinations) on filariasis respondents using a cross-sectional approach.Method: This type of descriptive research uses a cross-sectional approach. The research subjects were 6 filarial respondents in Pedurungan District, Semarang City. The examination was conducted at the Tologosari Wetan and Kulon Health Centers on September 12-18, 2020. Secondary data collection was obtained from capillary blood examination using thin blood smears, automatic hematological examination using a hematology analyzer, and clinical chemistry examination using the spectrophotometer method with a spectrophotometer. The research data was processed and analyzed using Univariate analysis using maximum, minimum, and average values.Results: Hematological examination for hemoglobin level of 12,5 g%, leukocytes 3200 cells/ml, platelets 137.00 cells, erythrocytes 4,07x106 cells, lymphocytes 35 cells, neutrophils 73 cells, eosinophils 1 cell, monocytes 9 cells, MCH 30,78 pg, MCV 86,48 fl, MCHC 36,24 g/l and clinical chemistry examination results for cholesterol 145,7 g/dl and triglycerides 104,6 g/dl. Meanwhile, on examination of thin blood smears, microfilariae were found.Conclusion: The results of the blood smear evaluation showed an abnormality in the size of the red blood cells in the form of microcytic (smaller red blood cell size), and filarial findings were found. In contrast, hematology and clinical chemistry examination results obtained normal results.

Biophysical and in-silico studies on the structure-function relationship of Brugia malayi protein disulfide isomerase

Human Lymphatic filariasis is caused by parasitic nematodes Wuchereria bancrofti, Brugia malayi, and Brugia timori. Protein disulfide isomerase (PDI), a redox-active enzyme, helps to form and isomerize the disulfide bonds, thereby acting as a chaperone. Such activity is essential for activating many essential enzymes and functional proteins. Brugia malayi protein disulfide isomerase (BmPDI) is crucial for parasite survival and an important drug target. Here, we used a combination of spectroscopic and computational analysis to study the structural and functional changes in the BmPDI during unfolding. Tryptophan fluorescence data revealed two well-separated transitions during the unfolding process, suggesting that the unfolding of the BmPDI is non-cooperative. The binding of the fluorescence probe 8-anilino-1-naphthalene sulfonic acid dye (ANS) validated the results obtained by the pH unfolding. The dynamics of molecular simulation performed at different pH conditions revealed the structural basis of BmPDI unfolding. Detailed analysis suggested that under different pH, both the global structure and the conformational dynamics of the active site residues were differentially altered. Our multiparametric study reveals the differential dynamics and collective motions of BmPDI unfolding, providing insights into its structure-function relationship. Communicated by Ramaswamy H. Sarma

Pharmacoinformatics-based screening of active compounds from Vitex negundo against lymphatic filariasis by targeting asparaginyl-tRNA synthetase.

Lymphatic filariasis, generally called as elephantiasis, is a vector-borne infectious disease caused by the filarial nematodes, mainly Wuchereria bancrofti, Brugia malayi, and Brugia timori, which are transmitted through mosquitoes. The infection affects the normal flow of lymph leading to abnormal enlargement of body parts, severe pain, permanent disability, and social stigma. Due to the development of resistance as well as toxic effects, existing medicines for lymphatic filariasis are becoming ineffective in killing the adult worms. It is essential to search novel filaricidal drugs with new molecular targets. Asparaginyl-tRNA synthetase (PDB ID: 2XGT) belongs to the group of aminoacyl-tRNA synthetases that catalyze specific attachment of amino acids to their tRNA during protein biosynthesis. Plants and their extracts are well-known medicinal practice for the management of several parasitic infectious diseases including filarial infections. In this study, asparaginyl-tRNA synthetase of Brugia malayi was used as a target to perform virtual screening of plant phytoconstituents of Vitex negundo from IMPPAT database, which exhibits anti-filarial and anti-helminthic properties. A total of sixty-eight compounds from Vitex negundo were docked against asparaginyl-tRNA synthetase using Autodock module of PyRx tool. Among the 68 compounds screened, 3 compounds, negundoside, myricetin, and nishindaside, exhibited a higher binding affinity compared to standard drugs. The pharmacokinetic and physicochemical prediction, stability of ligand-receptor complexes via molecular dynamics simulation, and density functionality theory were done further for the top-scored ligands with receptor.

Discovery of potent inhibitors targeting Glutathione S-transferase of Wuchereria bancrofti: a step toward the development of effective anti-filariasis drugs.

Lymphatic filariasis (LF) is one of the major health problems for the human kind in developing countries including India. LF is caused by three major nematodes namely Wuchereria bancrofti, Brugia malayi, and Brugia timori. The recent statistics of World Health Organization (WHO) showed that 51 million people were affected and 863 million people from 47 countries around worldwide remain threatened by LF. Among them, 90% of the filarial infection was caused by the nematode W. bancrofti. Approved drugs were available for the treatment of LF but many of them developed drug resistance and no longer effective in all stages of the infection. In the current research work, we explored the Glutathione S-transferase (GST) of W. bancrofti, the key enzyme responsible for detoxification that catalyzes the conjugation of reduced GSH (glutathione) to xenobiotic compounds. Initially, we analyzed the stability of the WbGST through 200 ns MD simulation and further structure-based virtual screening approach was applied by targeting the substrate binding site to identify the potential leads from small molecule collection. The in silico ADMET profiles for the top-ranked hits were predicted and the predicted non-toxic lead molecules showed the highest docking score in the range of -12.72 kcal/mol to -11.97 kcal/mol. The cross docking of the identified hits with human GST revealed the potential binding specificity of the hits toward WbGST. Through WbGST-lead complex simulation, the lead molecules were observed to be stable and also intactly bound within the binding site of WbGST. Based on the computational results, the five predicted non-toxic molecules were selected for the in vitro assay. The molecules showed significant percentage of inhibition against the filarial worm Setaria digitata which is the commonly used model organism to evaluate the filarial activity. In addition, the molecules also showed better IC50 than the standard drug ivermectin. The identified lead molecules will lay a significant insight for the development of new drugs with higher specificity and lesser toxicity to control and treat filarial infections.

Treatment of Lymphatic Filariasis with Wolbachia Targets

Nematodes are the cause of filariasis. Tissue nematodes as the cause of lymphatic filariasis are 3 species, namely Wuchereria bancrofti, Brugia malayi, Brugia timori.1 Lymphatic filariasis is the second largest cause of long-term disability, namely lymphedema of the extremities (elephantiasis) and hydrocele, especially in the tropics.2 Wolbachia bacteria are found in Onchocercidae, the family of filarial nematodes, including species that cause filarial disease in humans such as lymphatic filariasis and onchocerciasis. The symbiosis of Wolbachia and Onchocercidae shows that Wolbachia bacteria play a role in the treatment of filarial parasitic infections by using antibiotics such as tetracycline, doxycycline or rifampicin causing growth retardation and embryogenesis. 4 The long term use of antibiotics is feared to cause resistance to bacteria. Therefore, it is necessary to use antibiotics with a shorter time.

Treatment of Lymphatic Filariasis with Wolbachia Targets

Nematodes are the cause of filariasis. Tissue nematodes as the cause of lymphatic filariasis are 3 species, namely Wuchereria bancrofti, Brugia malayi, Brugia timori.1 Lymphatic filariasis is the second largest cause of long-term disability, namely lymphedema of the extremities (elephantiasis) and hydrocele, especially in the tropics.2 Wolbachia bacteria are found in Onchocercidae, the family of filarial nematodes, including species that cause filarial disease in humans such as lymphatic filariasis and onchocerciasis. The symbiosis of Wolbachia and Onchocercidae shows that Wolbachia bacteria play a role in the treatment of filarial parasitic infections by using antibiotics such as tetracycline, doxycycline or rifampicin causing growth retardation and embryogenesis. 4 The long term use of antibiotics is feared to cause resistance to bacteria. Therefore, it is necessary to use antibiotics with a shorter time.

Assessment of the progress toward elimination of lymphatic filariasis in the Federal Capital Territory- Abuja, Nigeria

Lymphatic filariasis (LF) is a neglected tropical disease caused by threadlike worms (nematodes) that live in the lymphatic vessels of humans. Although three species of filarial parasites (Wuchereria bancrofti, Brugia malayi and Brugia timori) infect humans; 90% of infection is caused by Wuchereria Bancrofti and humans are its exclusive host. Nigeria is one of over 70 countries endemic for Lymphatic filariasis with an estimated 134 million people at the risk of infection. The Federal Capital Territory (FCT), which is endemic for LF, commenced mass drug administration (MDA) using ivermectin (IVM) and albendazole (ALB) in 2011. While MDA is continuing in two Area Councils, in 2020, we assessed the impact of MDA on LF prevalence in two area councils that had achieved five effective annual rounds of MDA. In 2010, a baseline mapping exercise was conducted in all six area councils of FCT-Abuja. The results revealed that four out of the six area councils were endemic for LF, with prevalence ranging from 1.0%-4.0%. The number of persons treated with ivermectin and albendazole in the four Area Councils was documented during annual MDA and population-based cluster surveys were conducted at least once in each area council during the five years of treatment, to verify the reported geographic and programme MDA coverage. This is the number treated divided by the total population eligible to receive treatment (usually <5years). The survey results confirmed that in two area councils (Abaji and Kuje) the coverage exceeded the target of 65% the while two other Councils did not reach the recommended coverage. A pre-transmission assessment survey (pre-TAS) was conducted in one sentinel site and at least one spot check site in Abaji and Kuje in 2019 and were found to have LF antigenemia (LF Ag) < 2% (range 0.0% to 1.99%). In 2020, transmission assessment surveys (TAS) were conducted in the two area councils that previously passed the Pre-transmission assessment survey. The results showed that the two Evaluation units had achieved the LF Ag threshold required to stop MDA. FCT has made significant progress towards LF elimination with two Area Councils qualifying to stop treatment. However, two other area councils still require a further two years of mass drug administration with effective MDA coverage before these area councils qualify for impact assessment.

Characterization of a novel microfilarial antigen for diagnosis of Wuchereria bancrofti infections.

BackgroundLymphatic filariasis (LF) is a neglected tropical disease caused by the filarial nematodes Wuchereria bancrofti, Brugia malayi and Brugia timori. The Global Program to Eliminate LF uses mass drug administration (MDA) of anti-filarial drugs that clear microfilariae (Mf) from blood to interrupt transmission by mosquitos. New diagnostic tools are needed to assess the impact of MDA on bancroftian filariasis, because available serologic tests can remain positive after successful treatment.Methodology/Principal findingsWe identified Wb-bhp-1, which encodes a W. bancrofti homologue of BmR1, the B. malayi protein used in the Brugia Rapid antibody test for brugian filariasis. Wb-bhp-1 has a single exon that encodes a 16.3 kD protein (Wb-Bhp-1) with 45% amino acid identity to BmR1. Immunohistology shows that anti-Wb-Bhp-1 antibodies primarily bind to Mf. Plasma from 124 of 224 (55%) microfilaremic individuals had IgG4 antibodies to Wb-Bhp-1 by ELISA. Serologic reactivity to Wb-Bhp-1 varied widely with samples from different regions (sensitivity range 32–92%), with 77% sensitivity for 116 samples collected from microfilaremic individuals outside of sub-Saharan Africa. This variable sensitivity highlights the importance of validating new diagnostic tests for parasitic diseases with samples from different geographical regions. Individuals with higher Mf counts were more likely to have anti-Wb-Bhp-1 antibodies. Cross-reactivity was observed with a minority of plasma samples from people with onchocerciasis (17%) or loiasis (10%). We also identified, cloned and characterized BmR1 homologues from O. volvulus and L. loa that have 41% and 38% identity to BmR1, respectively. However, antibody assays with these antigens were not sensitive for onchocerciasis or loiasis.ConclusionsWb-Bhp-1 is a novel antigen that is useful for serologic diagnosis of bancroftian filariasis. Additional studies are needed to assess the value of this antigen for monitoring the success of filariasis elimination programs.

Bma-LAD-2, an Intestinal Cell Adhesion Protein, as a Potential Therapeutic Target for Lymphatic Filariasis.

ABSTRACTLymphatic filariasis is a debilitating disease that afflicts over 70 million people worldwide. It is caused by the parasitic nematodes Wuchereria bancrofti, Brugia malayi, and Brugia timori. Despite substantial success, efforts to eliminate LF will likely require more time and resources than predicted. Identifying new drug and vaccine targets in adult filariae could help elimination efforts. This study’s aim was to evaluate intestinal proteins in adult Brugia malayi worms as possible therapeutic targets. Using short interfering RNA (siRNA), we successfully targeted four candidate gene transcripts: Bma-Serpin, Bma-ShTK, Bma-Reprolysin, and Bma-LAD-2. Of those, Bma-LAD-2, an immunoglobulin superfamily cell adhesion molecule (IgSF CAM), was determined to be essential for adult worm survival. We observed a 70.42% knockdown in Bma-LAD-2 transcript levels 1 day post-siRNA incubation and an 87.02% reduction in protein expression 2 days post-siRNA incubation. This inhibition of Bma-LAD-2 expression resulted in an 80% decrease in worm motility over 6 days, a 93.43% reduction in microfilaria release (Mf) by day 6 post-siRNA incubation, and a dramatic decrease in (4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) reduction. Transmission electron microscopy revealed the loss of microvilli and unraveling of mitochondrial cristae in the intestinal epithelium of Bma-LAD-2 siRNA-treated worms. Strikingly, Bma-LAD-2 siRNA-treated worms exhibited an almost complete loss of pseudocoelomic fluid. A luciferase immunoprecipitation system assay did not detect anti-Bma-LAD-2 IgE in the serum of 30 LF patients, indicating that LF exposure does not result in IgE sensitization to this antigen. These results indicate that Bma-LAD-2 is an essential protein for adult Brugia malayi and may be an effective therapeutic target.