Open access peer-reviewed chapter


Written By

Sharba Kausar

Submitted: February 22nd, 2019 Reviewed: August 31st, 2019 Published: December 14th, 2019

DOI: 10.5772/intechopen.89454

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Filariasis is one of the most debilitating tropical neglected diseases with high morbidity rate and less rate of mortality with various clinical symptoms. According to the World Health Organization (WHO) reports, about 120 million people from 81 countries are infected at present, and an estimated 1.34 billion people live in areas endemic to filariasis and are at risk of infection. Currently available drugs are only effective against the larval stage of the worms with side effects, and their repetitive use gives rise to drug resistance. Till date, no effective vaccine is available for the treatment of filariasis; to fulfill this need, new drug development becomes the priority for the researchers. This chapter reviews different synthetic and natural origin drugs, drug targets, and use of bioinformatics to discover new antifilarial agents which can control this debilitating disease, including the types of filariasis, their prevalence, and eradication programs which are discussed.


  • filariasis
  • drug targets
  • antifilarials
  • bioinformatics

1. Introduction

A variety of parasitic diseases which are associated with morbidity and mortality have received less attention worldwide. Among these, filariasis is one of the most debilitating neglected tropical diseases. Filariasis is a vector-borne disease transmitted by arthropod vector which is endemic in the tropics and subtropics that results in social stigma. It is a group of human and animal infectious diseases caused by nematode parasites generally called “filariae” that include several hundred species of worms that are slender and elongated and are parasitic in tissues of various vertebrate hosts. This parasite known to cause human infections belongs mainly to the genera Wuchereria, Brugia, Onchocerca, Dipetalonema, Mansonella, and Loa. They reside either in lymphatics or muscles, connective tissues, body cavities, etc. of vertebrate hosts. They may be classified into three main groups based on the habitat of the adult worm, i.e., the cutaneous group, the lymphatic group, and the body cavity group. Based on the habitat of the adult worm, a few of the filarial species infecting man and the disease caused by them with their intermediate hosts are listed in Table 1. The infection is transmitted by intermediate hosts which are always blood-sucking arthropods of the order Diptera. Only two genera, Wuchereriaand Brugia, are mainly responsible for human lymphatic filariasis. The common animal parasites are Setaria digitataand S. cervi(bovine), Dirofilaria immitis(dog), D. uniformis(rabbit), Litomosoides cariniiand Dipetalonema vitae(gerbils), Brugia pahangi(cat), and Acanthocheilonema viteae(jird).

Filarial wormHabitatIntermediate hostDisease
Wuchereria bancroftiLymphaticsMosquito sp.Elephantiasis
Brugia malayiLymphaticsMosquito sp.Malayan filariasis
B. timoriLymphaticsMosquito sp.Timor fever
Loa loaConnective tissueChrysopsissp. (C. dimidiata)—Horse fliesLoaiasis
Mansonella ozzardiSerous membranesCulicoidessp. (C. furens)—biting midgesOzzard’s filaria
Onchocerca volvulusSkinSimuliumsp. (S. damnosum)—black fliesOnchocerciasis

Table 1.

List of filarial worms with their habitats and intermediate host infecting humans.

According to recent surveys, about 120 million people in 81 countries of the world are infected from this disease, and 1.34 billion people who live in endemic areas are at high risk of this life-threatening infection [1]. To eradicate filariasis globally, research plans are needed to design effective drugs and drug targets, new vector control strategies, and diagnostic techniques. At the same time, the treatment of filariasis also requires disease-specific clinical care and patient education with counseling to eradicate this disease. Moreover, statistical analysis along with bioinformatics tools of the mass drug administration (MDA) surveillance reports should be carried out which could provide new opportunities to get an insight into the proteins or genome which may contribute to its inhibition process.

In current surveillance report, five World Health Organization (WHO) regions are endemic with lymphatic filariasis (LF). Worldwide, 1.39 billion people require preventive chemotherapy. In Southeast Asia region, 877 million people of 9 countries and 432 million people of 39 countries in the Africa region are brutally affected from this disease and require proper treatment. From the Western Pacific Region which includes the Mekong Plus region and the Pacific region, nearly 40 million people are at a risk of lymphatic filariasis. Cambodia, China, Cook Islands, Niue, the Marshall Islands, Palau, the Republic of Korea, Tonga, Vanuatu, Viet Nam, and Wallis and Futuna are the countries of this region that successfully eradicated this disease, whereas American Samoa, Brunei Darussalam, Fiji, French Polynesia, Kiribati, Lao People’s Democratic Republic, Malaysia, Federated States of Micronesia, New Caledonia, Papua New Guinea, Philippines, Samoa and Tuvalu are the 13 countries where lymphatic filariasis remains endemic [1, 2].


2. History of filariasis

In India first, ancient documented evidence of filariasis was reported in Sushruta Samhita(approximately 600 BC) by the famous physician Sushruta. According to some records, the first reliable documentation of filariasis was reported in the late fifteenth and early sixteenth centuries. In 1849 William Prout explained the pathological condition of chyluria in which the passage of lymph occurs in urine, a condition associated with lymphatic filariasis. The French surgeon Jean Nicolas in 1863 was the first person who observed the microfilariae in the hydrocele fluid. For the first time, in 1872 Timothy Lewis observed the microfilariae in the human blood in India. In 1876, Joseph Bancroft recovered female filarial worms and named them Filaria bancrofti, which later merged in the genus Wuchereria. In 1877, Sir Patrick Manson discovered the main cause of transmission of filariasis, by studying the parasitic development of microfilariae in the mosquito stomach that was fed on the blood of an infected gardener and thus reported that filariasis is transmitted by the mosquito. In 1960 and 1977, two other filarial worm species were identified and named as Brugia malayiand B. timori, respectively.


3. Filariasis: an overview

Among all the filariasis, lymphatic filariasis is the most debilitating which causes disability in humans. Wuchereria bancroftiand Brugia malayior B. timoriare the main cause of lymphatic filariasis, each of which is transmitted by the bite of a specific insect vector. The various vectors that cause LF belong to the genera Anopheles, Culex, Aedes, and Mansonia. According to the WHO, increase in the microfilarial density in the infected individuals and the feeding rate of vector population are the causes of high transmission rates of filariasis in a particular area. Onchocerca volvulusand Loa loaare the two other filarial worms that reside in the cutaneous and subcutaneous tissues of the host and cause onchocerciasis and loaiasis, respectively. Wuchereria bancroftiand O. volvulusare the two filarial worms which do not require an animal host as reservoir.

Data collected from the survey depicted the picture of depressive illness of an individual caused by LF and estimated 5.09 million disability-adjusted life years (DALYs) [3, 4, 5]. In infants microfilaremia starts at the age of 5 after acquiring infection, but the actual signs of filariasis (including hydroceles) appear during puberty. Previous survey reports indicated that once the individual acquired infection chances of cure becomes very low [6].

Filarial worms inhabiting the lymphatic system live up to 8 years and release millions of microfilariae into the bloodstream. The WHO started the Global Alliance to Eliminate Lymphatic Filariasis (GPELF) in 2000 with the goal of eradicating this disease by 2020 through the use of MDA [7]. In the history of public health, GPELF is the most successfully expanding global health program. Fifty-three out of the 81 endemic countries have started mass drug administration to halt the transmission of filariasis. Two strategies have been developed to achieve the target of eliminating filariasis. According to the first strategy, single annual doses of diethylcarbamazine or ivermectin plus albendazole will be provided to the entire endemic area to prevent the disease. The second strategy is to reduce disability rate by providing knowledge about how to maintain hygiene and skin care, to those with lymphedema and performing surgery in patients with hydrocele. The investment for chemotherapy to control this disease is approximately US$ 105–208 million per year during 2015–2020. The WHO determined two objectives, which include “70% of endemic countries demanding MDA will have to enter post-intervention surveillance by 2016” and “all other endemic countries have to complete the post-intervention surveillance by 2020” [8, 9]. The abovementioned antifilarial drugs are only effective against the microfilariae and have no effect on the adult worms which therefore provide a partial treatment to the infected individuals. Repetitive use of these drugs resulted in drug resistance. Till date no vaccines are developed, and treatment depends only on the antifilarial. Researchers are developing various new antifilarials and combination therapies to overcome this disease [10].


4. General life cycle of filarial worm

Man is the definitive host of filarial worm, in whose lymphatic system, the adult worms reside. Adult females discharge the live embryo called microfilariae (290 μ). Microfilariae flow in the peripheral blood and can survive for a considerable time without undergoing metamorphosis until they are taken up by the intermediate host, i.e., the culicine mosquitoes during their blood meal. After reaching in the mosquitoes, microfilariae undergo development and become infective-stage larvae as described in Figure 1.

Figure 1.

Life cycle of filarial wormSetaria cervigiven by Prof. Wajihullah and Dr. Sharba Kausar.


5. Diagnosis of lymphatic filariasis

LF is primarily diagnosed using the immunochromatographic card test kit via antigen detection methods (which also detects latent infections). The traditional diagnosis of LF is performed by microscopy to detect circulating microfilariae. Molecular xenomonitoring of parasites in mosquitoes, serological testing, ultrasonography, PCR tests, lymphoscintigraphy, detection of exposure to transmission in children via antibody detection, and the recently introduced filariasis test strip (FTS) are some of the other diagnostic approaches that are currently used.


6. Biological point for designing new drug

A clear knowledge of parasite physiology is very important to identify drug targets for understanding the mode of action of antifilarial drug. Sometimes compounds are also tested, without prior knowledge of the target. Compounds which are effective against the whole parasite are defined as hits, while compounds that are found to be active in vivo are considered as leads. Lead compounds require standardization for increasing their efficacy. Once a compound is optimized, it can be tested clinically in patients and defined as a “drug candidate.” Based on the physiological processes and symptoms, a drug should be formulated and designed to combat the disease. To overcome filariasis a number of drug targets should be covered for developing new antifilarial, viz., macrofilaricidal and microfilaricidal drugs, drugs preventing exsheathment in microfilariae and drugs that can cause hindrance in the movement of microfilariae. Different biochemical pathways are summarized in Table 2 which are used in designing new drugs. On the other hand, vaccine development and mosquito repellent practices such as the use of insecticide nets, body lotions, insecticides spray, coils, etc. along with good knowledge of sanitization can prevent vector development which together helps in combating filarial worm infection in a community. The pathology associated with lymphatic filariasis like elephantiasis, hydrocoele, and lymphedema is due to the hyporesponsiveness of D4+ T cells of the host immune system [11, 12, 13]. Therefore, immunological studies are also playing an important role in the field of drug development. Drugs are also designed to combat symptoms associated with filariasis, viz., drugs used for the treatment of lymphatic filariasis (drugs effective against adenolymphadenitis, funiculitis, epididymo-orchitis, lymphedema, hydrocele, chyluria, chylocele, lymph scrotum) and drugs used in the treatment of other manifestations like asymptomatic microfilaremia, occult filariasis, onchocerciasis, and loaiasis.

Wolbachiaare proteobacteria 61 potential drug targets (outer membrane proteins, ribosomal proteins, DNA polymerases, mutases, ligases, isomerases, cell division proteins, transferases, synthetases, reductases, etc.) and four potential vaccine extracellular targets such as putative peptidoglycan lipid II flippase, deoxycytidine triphosphate deaminase, GTP cyclohydrolase II, and RNA pyrophosphohydrolaseContribute to the nucleotide pool of nematodesTetracycline was resulted in the depletion of these Wolbachiaresulting in the upregulation of phosphate permease gene, required for nucleotide synthesis Another study with doxycycline showed that Wolbachiadepletion was associated with a reduction in the levels of vascular endothelial growth factors (VEGFs) that are essential for lymphangiogenesis (18)
Wolbachiacell division protein FtsZ a GTPaseBacteria-specific filamenting temperature-sensitive protein (important in bacterial cytokinesis) that was
expressed in all developmental stages of B. malayi
E. coliFtsZ inhibitor berberine, a natural alkaloid, was examined by researchers against GTPase activity of FtsZ in B. malayi, and it was observed that at 10–40 mM concentration, berberine had adversely affected production of microfilariae as well as motility of adult females of B. malayi
Myristoyltransferase (NMT)The addition of myristic acid, a 14-carbon unsaturated fatty acid, to the N-terminus of glycine in a subset of proteins via myristoyl-CoA:protein N-myristoyltransferase (NMT) promotes their binding to cell membraneA known NMT enzyme inhibitor in tripanosomatids, DDD85646, and its analog DDD100870, were tested against B. malayiNMT proteins and provided IC50 values of 10 nM and 2.5 nM, respectively

Proteins and amino acids
Free amino acids are required for intracellular osmoregulation and protein synthesis
S-adenosylmethionine methyltransferase, methionine adenosyltransferase, and S-adenosylhomocysteine hydrolaseAre required for the conversion of methionine to homocysteine in the methionine
Enzyme prolyl-4-hydroxylase has been reported toPlay a vital role in the biosynthesis of this collagen
TransaminoglutamasePlay a significant role in the growth, development, and maturation of the nematodeA pseudosubstrate, monodansylcadaverine (MDC), and active site inhibitors cystamine or iodoacetamide were found to inhibit L3-stage parasite mobility in a dose-dependent manner that was associated with irreversible biochemical lesions, resulting in the death of the parasite
Retinoic acid-binding proteins (RABPs)Parasitic nematodes require lipophilic retinol for various biological processes, such as embryogenesis, differentiation, and growth
For inter- as well as intracellular movement
Ivermectin(II) was found to compete efficiently with retinol for the retinol-binding sites on RBP of the parasite but not for the host RBP sites
Biogenic amines and polyamines
Norepinephrine (NE), histamine, 5-hydroxytryptamine (5-HT), and dopamineBiogenic amines play a role in neuromuscular activity and behavioral coordination in nematodes
Monoamine oxidase (i.e., MAO), acetylcholinesterase, and dopamine-b-hydroxylaseDEC, levamisole, and centperazine were found to inactivate these enzymes
Putrescine, spermine, and spermidineAre required for growth, differentiation, and macromolecular synthesis in all living organisms as constituents of the polyamine salvage pathway
S-adenosylmethionine decarboxylase (SAMDC)Which is required for polyamine biosynthesisBerenil and aromatic methylglyoxal bis(guanylhydrazone) analogs are inhibitors of an important regulatory enzyme
Carbohydrate metabolism
Fructose 1,6-diphosphate aldolaseIts immunogenic component in filarial worms is distinguishable from that of mammals, thus identifying it as possible vaccine target238
Phosphoenolpyruvate carboxykinaseInhibited by DEC
Fumarate reductaseInhibited by DEC and benzimidazoles
Succinate dehydrogenaseInhibited by DEC
PhosphofructokinaseBlocked by antimonial stibophen in B. pahangiand L. cariniiwhen compared to isofunctional mammalian enzyme
Glucose uptakeAltered by DEC, amoscanate, and arsenicals
Utilization of glucoseDecreased by levamisole

Lipid metabolism
QuinonesPlay a role in filarial electron transport
Geranyl geraniolUnknown roleThe biosynthesis of genanyl geraniol and dolichols was inhibited by mevinolin
Juvenile hormonesRegulators of larval development
DolicholsRequired for glycoprotein synthesis
Isopentyl pyrophosphateIPP constituent of filarial tRNA
HMG-CoA reductase is a rate limiting enzymeInvolved in the isoprenoid pathway of filariaInhibited by mevinolin
Folate metabolism
Enzymes, such as reductases, transferases, synthases, dehydrogenases, hydrolases, mutases, ligases, and deaminasesAre involved in the interconversation of folate analogs observed in the synthesis of different tetrahydrofolate cofactors by macrofilariae. Specifically, dihydrofolate reductase activity, which is commonly observed in macrofilariae, was found to be absent in the microfilariae of B. pahangiDEC and suramin were found to inhibit some enzymes involved in folate metabolism
10-Formyl FH4 dehydrogenase enzymeWhich was found to play a vital role in the regulation of the endogenous FH4 cofactor concentrations, was more active in B. pahangithan in mammals
Glutamate-cysteine ligase (rate-g-glutamyl transpeptidase)Glutathione has been proposed to constitute the antioxidant system (g-glutamyl cycle) that extends the survival of filarial parasites in mammalian hosts, thereby protecting them from host-mediated membrane lipid peroxidationArsenicals depletes filarial glutathione (262–264)
Phytocompounds such as plumbagin, curcumin, and a phenoxyacetic acid derivative were found to inhibit filarial GST
In a report of a homology modeling approach via in silico analysis of the filarial GST of B. malayi, albendazole, and a methyl-substituted chalcone showed non-competitive type of inhibition of GST activity
Glutathione-transferases (GSTs)The major detoxifying systems in filarial parasites and can detoxify cytotoxic products of lipid peroxidation via the conjugation of glutathione (GSH) to various endogenous xenobiotic electrophiles

Table 2.

Antifilarial targets for designing drugs.


7. Currently used antifilarial drugs

7.1 Diethylcarbamazine (DEC)

Diethylcarbamazine (DEC), a piperazine derivative, is the most common and widely used drug over many decades. The antifilarial activity of DEC was first tested against Litomosoides carinii- and Dirofilaria immitis-infected cotton rats and dogs, respectively [8]. The observations revealed DEC as a potential microfilaricidal agent. Clinical trial of DEC was started in 1947 against human filariasis. Later, strong antimicrofilarial activity of DEC was also observed against W. bancrofti, B. malayi, O. volvulus, and Loa loainfection in humans [14, 15, 16, 17]. DEC acts rapidly by stimulating the host immune system. In some reports macrofilaricidal effect of DEC was also recorded along with its antimicrofilarial activity [18, 19, 20, 21]. Peixoto et al. [22] described the direct mechanism of action of this drug during their in vitro and in vivo studies; they observed apoptosis and organelle damage of W. bancroftimicrofilariae by DEC [22]. To enhance the effect of DEC against microfilariae, nitric oxide was induced by some researchers and was found to be a good synergist [23]. However, DEC combined with albendazole [24] revealed an effective killing of W. bancroftimicrofilariae, but the combination therapy increased the development of hydroceles in the treated patient [25].

7.2 Ivermectin (IVM)

It is a broad-spectrum anthelmintic and an effective macrofilaricidal drug introduced in 1981 also known as Mectizan [2], which was the first commercially available macrocyclic lactone. Chemically, it is a 22,23-dihydro semisynthetic derivative of avermectin B1, which is a fermentation product of actinomycetes S. avermitilisdiscovered by Merck in the mid-1970s [11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32]. IVM alone or in combination with DEC [8] resulted in long-term suppression of microfilariae in both bancroftian and brugian filariasis [20, 33, 34].

7.3 Suramin

Suramin [35] initially was a drug used to cure trypanosomiasis and onchocerciasis. Chemically it is an 8,80-(carbonylbis[imino-3,1-phenylenecarbonylimino(4-methyl-3,1-phenylene)carbonylimino])bis-1,3,5-naphthalenetrisulfonic acid hexasodium salt. Presently it is the only macrofilaricidal drug that is effective against W. bancroftiand O. volvulus.

7.4 Albendazole

This anthelmintic drug is [24] a benzimidazole derivative. Recently this has been used in a clinical trial to check out its efficacy as antifilarial drug [36]. Its efficacy was increased when administered in combination with either DEC [8] or IVM [2].

7.5 Levamisole

This is an ascaricidal drug with no side effects at the recommended doses. It has also been found as a microfilaricidal drug against the microfilariae of Wuchereria bancroftiand Brugia malayi[37].

Unfortunately, most of the chemical antifilarials are characterized by adverse side effects. The list of currently used antifilarials with their side effects is summarized in Table 3. Hence, researches on exploring new therapeutic drugs, especially less hazardous drugs of natural origin, are highly recommended. The application of biomedicines to treat disease is among the oldest forms of therapy. These biomedicines including plant extracts and their secondary metabolites were believed to exert their bioefficacy through immunomodulatory elicitation of Th1/Th2 response, either by single (Th1, Th2) or mixed adjuvant activity. Therefore, in the context of filariasis, synthetic and naturally originated antifilarials are summarized in Tables 4 and 5.

Antifilarial agentRecommended doseRoute of administrationMechanism of actionFilarial wormSide effects
Diethyl carbamazine (piperazine derivative)6 mg/kg for 12 days (individual treatment)
6 mg/kg in 24 hours (weekly/monthly/single annual dose in mass treatment) for treating W. bancroftiinfection
OralAlterations in arachidonic acid metabolism of host endothelial cells and microfilariae, resulting in blood vessel constriction and host granulocyte and platelet aggregation; apoptosis and org nelle damageW. bancroftiinfectionEncephalitis and retinal hemorrhage. Increasing dose include systemic reaction: nausea, GIT upset, malaise, body aches, and anorexia. Localized reactions: abscess formation, lymphadenitis, and transient lymphedema
3–6 mg/kg for 6–12 days (individual treatment)
3–6 mg/kg in 24 hours (6 times at weekly or monthly in mass treatment) for treating B. malayiand B. timoriinfections
B. malayiand B. timoriinfections
8 mg/kg for 14 days
For the treatment of occult filariasis
Occult filariasis
Table salt + Diethylcarbamazine0.1% for 6 months treatment of LFW. bancrofti(lymphatic filariasis)
0.3% for 3–4 months B. malayiis endemicB. malayi
Ivermectin (macrocyclic lactone)400 mg/kg single dose treatment
4800 mg/kg for 6 months treatment of B. malayiand single dose remove microfilariae W. bancrofti
OralTargets glutamate gated Cl- and K+ ion channels in nematodes, results in hyperpolarization that causes paralysis of the body wall muscle and pharynx. The drug also affects ligand-gated chloride ion channels gated by GABA. It competes with retinol for the retinol-binding site on retinol-binding proteins (RBPs) in the parasite onlyBancroftian and brugian filariasisSame as DEC, and special care must be considered, such as avoiding its use in cases of pregnancy and in children younger than 5 years old
Suramin66.7 mg/kg in 6 incremental weekly doses (3.3, 6.7, 10.0, 13.3, 16.7, 16.7 mg/kg for the first and sixth weeks, respectively)Intravenous (10% solution in water)It adversely affects enzymes associated with glucose catabolism and destabilizes DNA and protein kinase enzymes in filarial wormsW. bancrofti, O. volvulusFatal collapse, albuminuria, ulceration, and persistent high fever; polyuria, tiredness, tenderness, anorexia, and increased thirst; among others are some of the milder side effects
LevimazolAn initial dose of 100 mg followed by the same dose twice daily for 10 days was found to be as effective as the total oral dosage of DEC at 126 mg per kg body weightOralActs as nicotinic receptor agonist that causes prolonged activation of the excitatory nicotinic acetylcholine (nACh) receptors on the body wall muscle of parasites, leading to spastic muscle paralysis in the wormW. bancrofti, B. malayiNo side effects at recommended doses
Albendazole (benzimidazole)
Albendazole+ DEC
Albendazole (400 mg) + diethylcarbamazine (DEC) (6 mg/kg)OralBlock tubulin polymerization, thereby inhibiting microtubule formation. It also inhibits parasite intestinal cells, preventing glucose uptake leading to the death of the parasiteMacrofilaricidalEmbryotoxicity and teratogenicity
Albendazole+ ivermectinAlbendazole (400 mg) + ivermectin (150–200 mg/kg)

Table 3.

Summary of the recommended doses of currently used antifilarials.

Antifilarial agentActionParasiteDoseReference
Trisubstituted pyrimidine derivatives (the amino group and 4-aminophenyl group at the second position plays an important role in exerting antifilarial activity)ATP-dependent DNA topoisomerase II inhibitory activityS. cervi10–40 mg/ml[38, 39]
2-Sulfanyl-6-methyl-1,4-dihydropyrimidinesB. malayi(in vitro)
B. malayi–Mastomys coucha
25 and 50 μM
100 mg/kg
Indole derivatives B-carbolineL. carinii–S. hispidus(cotton rats)
A. viteae–M. natalensis
30 mg/kg for 5 days
50 mg/kg for 5 days
[40, 41, 42, 43]
b-Carbolines (substituted 9Hpyrido[3,4-b]indoles)L. carinii, A. viteaeand B. malayiin a M. couchamodel50 mg/kg for 5 days
Quinoline and related compounds 7-chloro-4-(substituted amino)quinolinesA. viteae[44, 45, 46, 47]
3-Nitro-4-quinolones via ipso-nitrationThymidylate kinase inhibitory activityBrugia malayiIC50 2.9 mM
Quinolones compound 7-chloro-4-(substituted amino)quinolinesEvaluation against DNA topoisomerase II enzyme, compoundScreened in vivo against A. viteae200 mg/kg for 5 days
3-Nitro-4-quinolonesBrugia malayithymidylate kinase inhibitory activityB. malayiIC50 2.9 mM
Glycoside cinnamoyl glycosidesS. cerviMIC (3.40 nM), IC50 (6.90 nM) and LC50 (25 nM) values, CC50 value of approximately 103 nM[48]
Cinnamoyl glycosidesChromatin condensation and DNA fragmentation; this compound also damaged the cuticular sheath of the microfilariaeW. bancroftiMIC and IC50 values were 4.4 nM/ml and 8.96 nM/ml, respectively
Dioxocine 3,6-epoxy dioxocinesB. malayi–M. couchaIC50 values (0.4 mg/ml and 1.8 mg/ml, with selectivity indices (SI) of 100 and 22.2 with respect to macrofilariae and microfilariae, respectively[49]
CompoundB. malayiin jiridFound to be potent in terms of both in vitro (IC50 1.6 mg/ml and 3.5 mg/ml for macrofilariae and microfilariae, respectively) and in vivo antifilarial activity, 200 mg/kg
Alcohols cyclohexanol, 2- substituted propanol
Cyclooctanol derivatives
A. viteaeand L. cariniiin rodents
A. viteaein rodent
100% macrofilaricidal activity (at a dose of 200 mg/kg for 5 days)
81% sterilization of female worms (at a dose of 100 mg/kg for 5 days) against
TriazineDHFR (dihydrofolate reductase) inhibitors, good inhibitory activity (approximately 74%) against PARP (polyadenosine diphosphate ribose polymerase)enzymeB. malayiAlmost 100% loss of motility of filarial worms at 20 mg/ml showed better activity (IC50 10.90 mM) when compared with standard antifolate (positive control) compounds, i.e., trimethoprim (IC50 12.92 mM) and pyrimethamine (IC50 20.10 mM[51, 52]
Benzopyran (coumarin)B. malayi–M. coucha
B. malayi–jirid model
When administered orally at a dose of 300 mg/kg for 5 days showed 53.6% macrofilaricidal and 46% microfilaricidal activity
At a dose of 100 mg/ kg for 5 days, showed 75% adulticidal and 50% microfilaricidal activity
[53, 54, 55]
Naphthalene derivative 1,4-naphthoquinones1,3-Dimethyl substitution on the butylamino side chain favors an increased lipophilicity with potentially improved binding to the active site, which results in elevated macrofilaricidal activity (133)Setaria digitataED50 value of 2.6 mM after a 24 h incubation and 0.91 mM after a 48 h incubation[56]
Thiazolidine heterocyclic thiazolidine compounds compound (31) and compound (32)B. malayiIC50 values of 5.2 mM and 1.78 mM
LD50 values of 349 mM and 17.59 mM, respectively
Butylated hydroxy anisole (BHA)Oxidative stress-induced apoptosis was found to be its major killing mechanism (135)S. cerviAt 100 mM was found to be a potent adulticide[15]
Piperazine benzoyl piperazine derivatives (two compounds, viz., compound (34) and compound (35) containing a 4-chloro (para) substituent and 3-methyl (meta) substituent on the aromatic ring)S. cerviWorms were immotile following treatment with these two compounds at a concentration of 8 mg ml 1[16, 17, 57]
Pyrrolidine chalcone derivative (36) containing the pyrrolidine-methoxy groupShowed a significant suppression of glutathione-S-transferase (GST) activity in the macrofilariae of female S. cerviat a concentration of 3 mM in vitroS. cervi100% inhibition
Diaminoalkane N1,Nn-xylofuranosylated diaminoalkanesB. malayi–M. coucha
B. malayi–jirid
At 50 mg kg 1 provided approximately 38.7% recovery of macrofilariae and 63.80% sterilization of female parasites
The same compound also showed 33.5% adulticidal action along with 50% sterilization of female worms
Secondary aminesA. viteaeAt a dose of 200 mg/kg for 5 days exhibited 100% macrofilaricidal activity, whereas compound elicited a microfilaricidal response of approximately 93%[59]
Glycyrrhetinic acid derivatives and the benzylamide analogB. malayiKilling microfilariae and macrofilariae at 50 and 25 mM, respectively
The IC50 values were found to be 2.2 mM against microfilariae and 8.8 mM against macrofilariae of the worm
B. malayi–jiridAt a dose of 100 mg/kg for 5 days exhibited 40% adulticidal activity
Nitazoxanide and tizoxanideThe researchers further reported that both compounds reduced microfilarial production and impaired embryogenesis in female worms. They also suggested that mitochondria in the worms may be a possible target of NTZ (41) and TZ (42) because in addition to damaged worm tissues, they found alterations in the mitochondriaB. malayiMacrofilariae were found completely immotile after 6 days when cultured with these two compounds at concentrations of 20 mg/ml
On day 8 of culture at concentrations of 2.5 mg/ml, both drugs also caused a 50% decrease in worm viability
Microfilarial motility was also hampered by these compounds at concentrations exceeding 5 mg/ml, and the worms were completely immotile following treatment with 20 mg/ml (after 48 h)
Nitazoxanide + silver nanoparticles
Inhibit TCA cycle enzymesS. cervi100% mortality of microfilariae at 100 μg/ml
100% mortality of microfilariae at 30 μg/ml
[62, 63]
Anthraquinone 3-methylcatechol with a substitution of acylium ionsMarked effects on intrauterine embryos of parasiteB. malayiinfection in humansAt 5 ppm (18–19 mM) showed 100% mortality within 1, 5, and 3 days against microfilariae and adult male and female worms[64]
Sulfonamide sulfonamide chalconesB. malayiIC50 value was found to be 4.4 mM, LD50 value of 188 mMt 500 mM concentration after 48 h of incubation[65]
Benzothiazole novel chalcone–benzothiazole hybridsIt showed higher binding interactions at the active site of BmTMK (B. malayithymidylate kinase, an essential enzyme for nucleotide metabolism in B. malayi).B. malayiIC50 values of 2.12 mM and 1.63 mM, respectively, for adult worms as well as microfilariae
MIC value of 5 mM for both the forms
IC50 value was 95.3 mM
Thiazole chalcone–thiazole derivativesB. malayi–jirid
B. malayi–M. coucha
At a dose of 100 mg/kg for 5 days showed 100% embryostatic activity
Exerted approximately 49% macrofilaricidal activity and
Benzimidazole derivatives HOE 33258 mebendazole,
2,2′-Dicarbomethoxyamino-5,5′-dibenzimidazolyl ketone
At 5 × 2.5 mg/kg and 1 × 25 mg/kg in jirds and 1 × 100 mg/kg in cats when administered by subcutaneous injection
A dose of 3 mg/kg (i.p.) and 50 mg/kg (oral) × 5 days of Comp. 82/437
At a dose of 150 and 200 mg/kg for 5 days
L. cariniiand D. immitis
Evaluated in jirds (Meriones unguiculatus) and cats (Felis catus) infected with Brugia pahangi
L. cariniiin cotton rats
Dipetalonema viteaeand Brugia malayiin Mastomys natalensis
Macrofilaricidal. It also killed developing larvae in jirds. It was not microfilaricidal
Eliminated almost 100% of adult worms and microfilariae
It killed 100% of the macrofilariae and 97% of the microfilariae
[68, 69, 70, 71, 72, 73, 74, 75, 76, 77, 78, 79]
SilverNanosilverB. malayiLD50 concentration (by trypan blue exclusion) of 101.2 mM and an IC50 value of 50.6 mM (complete microfilariae population found immotile). At 4.6 mM only, nanosilver caused a 50% decrease in the motility of the parasite[80]

Table 4.

List of synthetic and naturally originated antifilarials.

PlantExtractTargetAntifilarial efficiencyAuthor
Streptomycessp. 17,944Three new tirandamycinsB. malayiInhibit the asparaginyl-tRNA-synthetase (BmAsnRS) enzyme at an IC50 value of 30 mM[81]
Streptomycessp. 9078DepsipeptideB. malayiIC50 value of 50 mM[82]
Streptomycessp. 4875Four adipostatins (alkyl resorcinols) potent among the compoundsB. malayiKill the worms at 1 mM concentrations[83]
Lantana camaraCrude extractA. viteaeLC100 62.5 μg/ml[84]
B. malayiLC100 500 mg/ml
Chloroform, n-butanol and aqueousB. malayiLC100 250 μg/ml
Fractions of n-hexane oleanonic acidB. malayiLC100 31.25 μg/ml
Oleanonic acidLC100 62.5 μg/ml
Crude extract 1 g/kg × 5 daysA. viteae/M. couchamodel95.05% reduction in Mf 23.65% effective against adult
B. malayi transplanted/M. unguiculatus80% effective against adult
Taxodium distichumA001 (crude ethanolic extract of aerial part)
F001 (hexane fraction)
K003(labda-8(20),13-diene-15-oic acid) and K004 (metasequoic acid A)
SF1 (fraction)
SF4 (fraction)
B. malayimf (LC100 3.91 μg/ml) than adult worms
(LC100 15.63 μg/ml)
IC50 values for the respective parasite stages were found to be 1.95 and 10.00 μg/ml
mf (LC100 7.83 μg/ml)
adult worms (LC100 31.25 μg/ml)
mf (LC100 31.25 μg/ml) and adult worms
(LC100 125 μg/ml)
mf (LC100 7.83 μg/ml) than adult (LC100 31.25 μg/ml)
mf (LC100 62.5 μg/ml) adult (LC100 125 μg/ml)
A001 (500 mg/kg × 5 days; orally)
K003 (100 mg/kg × 5 days) exerted
At 100 mg/kg dose, both K003 and K004
K003 (100 mg/kg × 5 days)
B. malayi/M. unguiculatus
B. malayi/M. coucha model
100% effective against Adult
>95%; remarkable embryostatic
Produced >25% macrofilaricidal
Exerted 53.94% macrofilaricidal
Azadirachta indicaAlcoholic extract of flowers
Aqueous extract of flowers
S. cerviMf(LC50 of 15 ng/ml)
(LC90 ¼ 23 ng/ ml),
mf(LC50 of 18 ng/ml)
(LC90 ¼ 25 ng/ ml)
[86, 87, 88]
Methanolic extract of leaves
Ethanolic extract of leaves
S. cerviMf 100% mortality at 200 μg/ml in 135 min
Mf 90% mortality at 200 μg/ml in 135 min
Ethanolic extract of A. indicaleavesS. cerviShowed significant worm reduction at 25 lg/ml and highest mortality at 100 lg/ml after 24 h of incubation when applied against the microfilariae
Eucalyptus tereticornisUrsolic acid obtained from the leavesB. malayiLC100 50 mM and IC50 8.84 mM against microfilariae, and LC100 100 mM and IC50 35.36 mM against adult worms[89]
Senecio nudicaulisAqueous leaf extract
Alcoholic leaf extract
Setaria cerviBoth the extracts exhibited macrofilaricidal activity LC50 10 ng/ml and LC90 15 ng/ml
LC50 5 ng/ml and LC90 12 ng/ml
Hibiscus sabdariffan-Butanol insoluble fraction of leaf extractB. malayiAt 250 mg/ml concentration demonstrated a high microfilarial motility[91]
At a dose of 500 mg/kg × 5 days
1 g/kg × 5 days
B. malayi–jirid model
B. malayi–M. couchamodel
Showed 30% macrofilaricidal activity
Showed 57% macrofilaricidal activity
Trachyspermum ammiMethanolic extract of fruit
The 2-isopropyl-5-methyl phenol (thymol) was the active component
Its positional isomer (i.e., 5-isopropyl-2-methyl phenol, carvacrol,) also
showed promising result
S. digitataIC50 0.067 and 0.019 mg/ml after 24 h and 48 h, respectively
IC50 were 0.024 mg/ml and 0.002 mg/ml after 24 h and 48 h incubation, respectively
Macrofilaricidal IC50 values were 0.025 mg/ml and 0.004 mg/ml after 24 h and 48 h incubation, respectively.
2-Isopropyl-5-methyl phenol at a dose of 50 mg/ kg for 5 daysB. malayi–M. couchaMacrofilarial mortality of 58.93%
Bauhinia racemosa (B. racemosa)Galactolipid (n-butanol fraction) obtained from ethanolic extraction of the leavesB. malayiThe MIC values against adult worms 3.9 mg/ml and 15.6 mg/ml against microfilariae
The IC50 values were 1.25 mg/ml and 1.607 mg/ml, respectively, against adult worms and microfilariae
50 mg/kg × 5 daysB. malayi infection58.3% adult worm mortality
Piper betelCrude methanolic at a dose of 100 mg/kgB. malayi–M. couchaSuppress mf most effectively and showed 26% efficacy against adult worm[94]
Hibiscus mutabilisActive ferulic acid, from the leavesS. cerviApproximately 97 and 90%, of reductions in viability of microfilariae and adult worms, respectively[95]
Caesalpinia bonducellaCrude extract from the seed kernelB. malayi96% macrofilaricidal activity[96]
Melaleuca cajuputiThe flower extractB. pahangiHalted the release of mf and worm mobility after 6 days at 1000 mg/ml[97]
Xylocarpus granatumAqueous–ethanolic extract
fruit extract
B. malayiIC50 value of 15.46 and 13.17 mg/ml against macrofilariae and microfilariae, respectively[98]
The ethyl acetate soluble fraction demonstratedAn IC50 value of 8.5 and 6.9 mg ml−1 against macrofilariae and microfilariae, respectively
At a dose of 50 mg/kg for 5 daysB. malayi–M. coucha53% macrofilaricidal and 63% embryostatic effects
Gedunin (64)
Mf (IC50 2.03 mg/ml)
Adult (IC50 0.239 mg/ml)
Mf (IC50 2.23 mg/ml)
Adult (IC50 0.213 mg/ml)
Gedunin at a dose of 100 mg/kg for 5 days
Photogedunin at a dose of 100 mg/kg for 5 days
B. malayi–M. couchaKilled 80.0% of the transplanted adult worms
70.0% adult worm mortality
Vitex negundo(V. negundo) and Aegle marmelos(A. marmelos)The root extract from V. negundoand the leaf extract from A. marmelosB. malayiAt a concentration of 100 ng/ml caused a complete loss of microfilarial motility after 48 h of incubation[99]
Aegle marmelosMethanolic extracts of Aegle marmelosCorr. (Rutaceae) leavesS. cervi(IC50) was 0.168 mg/ml[100]
Diospyros peregrinan-Butanol extract (NBE) of D. peregrinastem bark on Setaria cerviS. cerviMf (IC50 56.1 μg/ml, (IC50), adult (IC50 57.6 μg/ml)
Mf (LD100 187.17 μg/ml) after 24 h of treatment
Cajanus scarabaeoides(L)The polyphenol-rich ethanolic extract obtained from the stem partS. cerviLD50 values were 2.5, 10 and 35 μg/ml, against the oocytes, microfilariae (Mf) and adults, respectively[102]
Ficus racemosaAlcoholic and aqueous extract of fruits of F. racemosaSetaria cerviLC50 and LC90 were 21 and 35 ng/ml, respectively, for alcoholic, while for aqueous extracts were 27 and 42 ng/ml, respectively[103]
Botryocladia leptopodaThe crude ethanolic extract from the marine red alga B. leptopodaA. viteae
L. sigmodontis
Brugia malayi
LC100 of 62.5 mg ml−1
LC100 of 31.25 mg ml−1
LC100 of 125 mg ml−1
At a dose of 200 mg/kg for 5 daysL. sigmodontis–cotton rats
A. viteae–M. coucha and
B. malayi–M. coucha
Exhibited 71.6% 63.2% (ethanolic extract) and 45% (hexane fraction) macrofilaricidal activity, respectively
Haliclona oculataThe methanolic extract
Chloroform fraction and its one chromatographic fraction
B. malayiMf (IC50 5 mg/ml)
Adult (1.88 mg/ml)
Showed antimacrofilarial activity IC50 1.80 mg/ml and 1.62 mg/ml, respectively, whereas concentrations of 1.72 mg/ml and 1.19 mg/ml were effective against microfilariae
At a dose of 100 mg/kg for 5 days the methanol extract, chloroform fraction, and chromatographic fraction (contain four major alkaloids: xestospongin-C, araguspongin-C, mimosamycin, and xestospongin-D), respectivelyB. malayi–jiridRevealed 51.3%, 64% and 70.7% macrofilaricidal activities in the methanol extract, chloroform fraction, and chromatographic fraction, respectively.
Haliclona exiguaMethanol extract, the n-butanol-soluble fraction
Chloroform fraction
Araguspongin C
B. malayi(LC100 31.25 mg/ml)
(LC100 15.6 mg/ml)
Macrofilaricidal activity at 15.6 mg/ml
Eucalyptus globulusThe leaf extract from E. globuluswas active in vitroB. malayiIC50 values 62.5 and 31.2 mg/ml, respectively, against adult worms and microfilariae[107]
At a dose of 100 mg/kg for 5 daysB. malayi–M. coucha model and transplanted B. malayi jiridExhibited 66.7% adulticidal activity and an embryostatic effect
Terminalia bellerica, Terminalia chebula, Terminalia catappaLeaf extracts in different solventsSetaria cerviThe methanol extract exhibited more than 80% activity at the highest dose level of 10 mg/ml. The IC50 obtained in methanol extracts are 2.7, 1.96 and 2.58 mg/ml[108]
Moringa oleiferaThe gum extract obtained from M. oleiferashowed at a dose of 500 mg/kg for 5 days
In contrast, at a dose of 1000 mg/kg for 5 days
B. malayi
B. malayi–jirid
B. malayi–M. coucha
Mf (LC100 1000 mg/ml)
Adult (LC100 125 mg/ml)
Mf (IC50 > 1000 mg/ml)
Adult (IC50 74.33 mg/ml)
Extract showed 69% adulticidal activity and sterilized 83% of the female worms
Extract showed 44% adulticidal activity
Butea monospermaThe leaf and root extract
Methanol and hexane–ethanol fraction of the leaf extract
B. malayi
S. cervi
Microfilarial motility in a dose-dependent manner
Showed IC50 values of 1.25 and 3.6 mg/ml, respectively, against macrofilariae
[110, 111]
Ricinus communisMethanolic extract of the seedB. malayi90% death in the developmental stages of the parasite[112, 113, 114]
Rutin and hesperetinS. digitataShowed macrofilaricidal activity a 500 mg/ml
NaringeninB. malayiShowed macrofilaricidal activity at 125 mg/ml IC50 value at2.5 mg/ml
At 50 mg/kgB malayi–Meriones and B. malayi-M. couchaEliminate adult worms 73 and 31%, respectively
Exhibit macrofilaricidal activity at 62.5 mg/ml and inhibit the adult motility at 31.2 mg/ml
Showed macrofilaricidal activity at 2.50 mg/ml

Table 5.

List of naturally originated antifilarials are summarized below.


8. Role of bioinformatics in filarial research

Bioinformatics is a science of computer-based analysis for the biological datasets in which biology and computer science are mutually helping and influencing each other in the field. Bioinformatics has increased the understanding of molecular mechanism of various cellular processes. Nowadays bioinformatics covers several fields of biological sciences and drug discovery to overcome biological problems.

8.1 Genomic approach in filarial research

Genomic research in bioinformatics is a useful technique used to understand the structure and function of all the genes within an organism. Genomics help to find the particular gene and other biological aspects in the entire genome sequence of the organism. Screening of drug targets can also be done using the genomics approach. Casiraghi et al. [115] had carried out phylogenetic analysis using bioinformatics of 11 filarial and Spirurida nematodes and identified the sequence of mitochondrial cytochrome oxidase-I (COI).

Hoerauf et al. [116] detected the mutual interaction between the intracellular bacteria (endobacteria) and filarial nematodes, which is further used as antifilarial drug targets. Nuchprayoon et al. [117] identified the genetic diversity using phylogenetic analysis parsimony tool (PAUP) between the DNA sequences of two strains of Wbfound in Myanmar and Thailand. Ghedin et al. [118] reported the nuclear genome draft of Bm(95-Mb), which contains 88,363,057 bp sequences with 17.84% protein coding sequence [118]. The full genome sequences are available at NEMBASE4 database. Investigators identified a variety of filarial parasite genes and their novel functions that are involved in miRNA regulation and processing.

8.2 Proteomic approach in filarial research

Proteomics approach involved highly efficient methods of protein separation like two-dimensional-poly acrylamide gel electrophoresis (2DPAGE) and detection, using modern tools of bioinformatics. Proteomic analysis of the several stages of Bmhas identified 557 Bmproteins and 11,508 protein coding genes which helps to define various proteins by using reverse-phase liquid chromatography-tandem mass spectroscopy.

Afterwards Bennuru et al. [119] have also done the same in identifying the excretory/secretory (ES) and somatic proteins of adult, mf, and infective stages of larvae of Brugia malayi. Some workers gathered the molecular information of the particular protein of interest through 3D structure which plays a significant role in drug designing and vaccine development for lymphatic filariasis. In 2005 Bhargavi et al. [120] analyzed the 3D model of GST of Wuchereria bancroftiand Brugia malayifor better drug development. For the development of potential drugs, novel drug targets are modeled using bioinformatics approach including either ligand-based drug designing (LBDD) or structure-based drug designing (SBDD). LBDD provides crucial understanding of the interaction between the drug target and ligand molecule and provides information about the biologically active molecules [121]. Currently 3D quantitative structural activity relationship (QSAR) and pharmacophore modeling of small molecules are carried out to define their minimum necessary structural characteristics through which it inhibits the target. These 3D structure analyses of a protein were designed from the experimental-based method such as X-ray crystallography, NMR, electron microscopy, etc. If an experimental data are not available for the target proteins, homology modeling is carried out to build the 3D structure using target protein sequence [122].

Potential inhibitor can be designed on the basis of their binding sites or can be identified from the small-sized molecule databases such as Cambridge Structural Database [123], ChemBank [124], DrugBank [125], PubChem [126], and ZINC database [127] and databases that are available at Lignad.Info: molecule database [128] to inspect the biological activity of the particular protein.

8.3 Web-based available resources for LF

Web-based biological data plays a significant role in bioinformatics which plays a significant role in analyzing biological data for large amount of nucleotide sequences, amino acid sequences, and 2D or 3D structures for the broad range of organisms and their drug targets. Currently, there are only few databases available for LF (Table 6), but the specified database for LF is not available, which is an urgent need in the field of drug development and to overcome the emerging drug resistance. Some of the important databases which are available for LF research have been discussed below.

DBEMFDD diseases databaseIt is an annotated bibliography for filariasis, malaria, dengue, and diarrhea. It also contains the findings of the literature survey
FilaDBDatabase on filaria detection, clinico-immuno monitoring, and management has been developed for Kasturba Hospital and private practitioners to screen the filarial infection
NEMBASE2Contains the EST sequence for Brugia malayiand other nematodes
Filaria JournalFull and freely access journal of filariasis
WormbaseIt is an online database for the biology and genome of the Ceand related nematodes
WHOIt contains the related publication of filariasis, reports of elimination program, control of neglected tropical diseases and some important links
PHISIt contains the news and updated from filariasis elimination program
Disease databaseIt contains the general information regarding diseases
TDR-lymphatic filariasisIt contains knowledge about the parasite genomes for African lymphatic filariasis and other diseases TDR is now focusing on providing capacity to use the parasite genome data and on supporting developments in applied genomics and bioinformatics
Filarial worms databaseThis database provides the genome sequence of organisms rapidly and broadly available to the scientific community.

Table 6.

List of online databases for lymphatic filariasis are as follows.

NEMBASE:It contains databases containing information of filarial nematodes such as filarial biology and pathology, nomenclature of filarial genome, mapping of filarial gene, and Bmgenome survey sequencing (GSS). Recently, genome sequencing of wBmand Onchocerca volvulus(Ov) was also included with the Sanger Institute, NEB, and TIGR.

WormBase:It’s an open access database repository for nematode biology which contains the genome browser for Bm, C. elegans, H. contortus, etc., and the gene predictions and orthology assignments from a range of related nematodes.

FilaDB:It is a database for screening filarial patients with the objective of providing information on the incidence of mf and types of acute, chronic, and occult manifestations and age, sex, and distribution area of filariasis cases for clinico-immuno monitoring and management of filariasis.

Filarial worm database at broad institute:This database used to study the minute phenotypic difference between the closely related filarial species of Loa loa, Wb, and Ov( Filarial worm database also has the sequence data on Wolbachiaendosymbionts of Wb, Ov, and Bm. Filarial diseases are still remaining as a major public health concern in India. There is a need of comprehensive database, which should contain:

  1. Curated links between genes relevant to filariasis and their sequences in GenBank and Swiss-Prot.

  2. Sequence homology between different filariasis causing genes.

  3. Primary and secondary information of pathogens.

  4. Availability of various drugs and their targets.

  5. Expressed sequence tagged (EST) sequences from different filarial species.

  6. Supporting references from published literatures.

  7. Bioinformatics tools to analyze those data. Database should also contain the epidemiological data on age and gender-wise incidences of disease, remission, and transition rates of disease sequelae.


9. Conclusions

Filariasis is one of the most disabling and disfiguring neglected tropical diseases with various clinical manifestations and a high morbidity rate. Repetitive use of antifilarials has given rise to drug resistance. Most of them are effective against microfilariae and have no effect on the adult worms. Till date numbers of antifilarial targets have been explored, but their evaluation with reference to assay feasibility, target validation, drugability, toxicity, resistance potential, and structural information needs to be discovered in the future. There is a need to explore the mechanism through which drug resistance occurs so that new effective combination therapy could be discovered at an early stage.


  1. 1. World Health Organization. Global programme to eliminate lymphatic filariasis. In: Lymphatic Filariasis, Progress Report 2000–2009 and Strategic Plan 2010–2020; Geneva. 2010. pp. 1-78
  2. 2. World Health Organization. Three more countries eliminate lymphatic filariasis. 2018. Available from:
  3. 3. World Health Organization. Global Programme to eliminate lymphatic filariasis: Progress report, 2013. Weekly Epidemiological Record. 2014;89:409-418
  4. 4. Ramaiah KD, Das PK, Michael E, Guyatt H. The economic burden of lymphatic filariasis in India. Parasitology Today. 2000;16(6):251-253
  5. 5. Ton TG, Mackenzie C, Molyneux DH. The burden of mental health in lymphatic filariasis. Infectious Diseases of Poverty. 2015;4:1-8
  6. 6. Meyrowitsch DW, Simonsen PE, Magesa SM. A 26-year follow-up of bancroftian filariasis in two communities in north-eastern Tanzania. Annals of Tropical Medicine and Parasitology. 2004;98:155-169
  7. 7. Molyneux DH, Zagaria N. Lymphatic filariasis elimination: Progress in global programme development. Annals of Tropical Medicine and Parasitology. 2002;96:S15-S40
  8. 8. World Health Organization. Sustaining the drive to overcome the global impact of neglected tropical diseases. In: Second WHO Report on Neglected Tropical Diseases, Geneva. 2013. pp. 1-137
  9. 9. Third WHO Report on Neglected Tropical Diseases, Investing to Overcome the Global Impact of Neglected Tropical Diseases. Geneva: WHO; 2015
  10. 10. Liu LX, Weller PF. Antiparasitic drugs. The New England Journal of Medicine. 1996;334:1178-1184
  11. 11. Pink R, Hudson A, Mouriès MA, Bendig M. Opportunities and challenges in antiparasitic drug discovery. Nature Reviews Drug Discovery. 2005;4(9):727-740
  12. 12. Hewitt RI, Kushner S, Stewart H, White E, Wallace W, Subbarow Y. Experimental chemotherapy of filariasis. III. Effect of 1-diethyl-carbamyl-4-methylpiperazine hydrochloride against naturally acquired filarial infections in cotton rats and dogs. Journal of Laboratory and Clinical Medicine. 1947;32:1314-1329
  13. 13. Babu S, Nutman TB. Immunology of lymphatic filariasis. Parasite Immunology. 2014;36(8):338-346
  14. 14. Mandvikar A, Hande SV, Yeole P, Goswami K, Reddy MVR. Therapeutic potential of novel heterocyclic thiazolidine compounds against human lymphatic filarial parasite: Anin vitrostudy. International Journal of Pharmaceutical Sciences and Research. 2016;7(4):1480-1492
  15. 15. Rathaur S, Yadav M, Singh N, Singh A. Effect of diethylcarbamazine, butylated hydroxy anisole and methyl substituted chalcone on filarial parasiteSetaria cervi: proteomic and biochemical approaches. Journal of Proteomics. 2011;74(9):1595-1606
  16. 16. Saxena R, Sharma S, Iyer RN, Anand N. Potential filaricides. 5.3-Ethyl-8-methyl-1,3,8-triazabicyclo[4.4.0]decan-2-one, a new antifilarial agent. Journal of Medicinal Chemistry. 1971;14(10):929-931
  17. 17. Kalyanasundaram M, Mathew N, Paily KP, Prabhakaran G. Synthesis and screening of 1-methyl-4-substituted benzoyl piperazides against adultSetaria digitatafor antifilarial activity. Acta Tropica. 2009;111(2):168-171
  18. 18. Melrose W. Lymphatic Filariasis: A Review 1862–2002. Australia: Warwick Educational Publishing Inc.; 2004. pp. 1-80
  19. 19. Weil GJ, Lammie PJ, Richards FO, Eberhard ML. Changes in circulating parasite antigen levels after treatment of bancroftian filariasis with diethylcarbamazine and ivermectin. Journal of Infectious Diseases. 1991;164(4):814-816
  20. 20. Ismail MM, Weil GJ, Jayasinghe KSA, Premaratne UN, Abeyewickreme W, Rajaratnam HN, et al. Prolonged clearance of microfilaraemia in patients with Bancroftian filariasis after multiple high doses of ivermectin of diethylcarbamazine. Transactions of the Royal Society of Tropical Medicine and Hygiene. 1996;90:684-688
  21. 21. McCarthy JS, Guinea A, Weil GJ, Ottesen EA. Clearance of circulating filarial antigen as a measure of the macrofilaricidal activity of diethylcarbamazine inWuchereria bancroftiinfection. The Journal of Infectious Diseases. 1995;172(2):521-526
  22. 22. Peixoto CA, Rocha A, Aguiar-Santos A, Florencio MS. The effects of diethylcarbamazine on the ultrastructure of microfilariae ofWuchereria bancrofti in vivoandin vitro. Parasitolology Research. 2004;92(6):513-517
  23. 23. Subramanian S, Vanamail P, Das PK, Pani SP, Ravi R. Randomized controlled clinical trials of antifilarial drugs for lymphatic filariasis: Endpoints of outcome measures influence drug efficacy. In: Presented at: Proceedings of the 23rd Conference of the Indian Society for Medical Statistics, Jawaharlal Nehru Medical College, Belgaum, India, January. 2005. pp. 19-21
  24. 24. Singh PK, Ajay A, Kushwaha S, Tripathi RP, Misra-Bhattacharya S. Towards novel antifilarial drugs: Challenges and recent developments. Future Medical Chemistry. 2010;2(2):251-283
  25. 25. Hussein O, Setouhy ME, Ahmed ES, Kandil AM, Ramzy RM, Helmy H, et al. Duplex Doppler sonographic assessment of the effects of diethylcarbamazine and albendazole therapy on adult filarial worms and adjacent host tissues in Bancroftian filariasis. American Journal of Tropical Medicine and Hygiene. 2004;71:471-477
  26. 26. Mak JW. Antifilarial compounds in the treatment and control of lymphatic filariasis. Tropical Biomedicine. 2004;21(2):27-38
  27. 27. Woodruff HB, Burg RW. The Antibiotics Explosion. Discoveries in Pharmacology. In: Parnhamand MJ, Bruinvels J, editors. Pharmacological Methods, Receptors and Chemotherapy. Vol. 3. Amsterdam, The Netherlands: Elsevier; 1986. pp. 338-341
  28. 28. Thylefors B. Eliminating onchocerciasis as a public health problem. Tropical Medicine and International Health. 2004;9(4):A1-A3
  29. 29. Schares G, Hofmann B, Zahner H. Antifilarial activity of macrocyclic lactones: Comparative studies with ivermectin, doramectin, milbemycin A4 oxime, and moxidectin inLitomosoides carinii,Acanthocheilonema viteae,Brugia malayi, andB. pahangiinfection ofMastomys coucha. Tropical Medicine and Parasitology. 1994;45(2):97-106
  30. 30. Campbell WC. Ivermectin as an antiparasitic agent for use in humans. Annual Review of Microbiology. 1991;45:445-474
  31. 31. Ottesen EA, Campbell WCJ. Ivermectin in human medicine. Journal of Antimicrobial Chemotherapy. 1994;34:195-203
  32. 32. Townson S, Tagboto SK, Castro J, Lujan A, Awadzi K, Titanji VPK. Comparison of the sensitivity of different geographical races ofOnchocerca volvulusmicrofilariae to ivermectin: Studiesin vitro. Transactions of the Royal Society of Tropical Medicine and Hygiene. 1994;88:101-106
  33. 33. Dreyer G, Noroes J, Amaral F, Nen A, Medeiros Z, Coutinho A, et al. Comparison of the sensitivity of different geographical races ofOnchocerca volvulusmicrofilariae to ivermectin: Studiesin-vitro. Transactions of the Royal Society of Tropical Medicine and Hygiene. 1995;89:441-443
  34. 34. Shenoy RK, Kumaraswami V, Rajan K, Thankom S, Jalajakumari A. A comparative study of the efficacy and tolerability of single and split doses of ivermectin and diethylcarbamazine in periodic Brugian filariasis. Annals of Tropical Medicine and Parasites. 1993;87:459-467
  35. 35. Simonsen PE, Malecela MN, Michael E, Mackenzie CD, editors. Lymphatic Filariasis, Research and Control in Eastern and Southern Africa. Denmark: DBL-Center for Health and Research Development; 2008. pp. 1-155
  36. 36. McCarthy J. Is anthelmintic resistance a threat to the program to eliminate lymphatic filariasis? American Journal of Tropical Medicine and Hygiene. 2005;73(2):232-233
  37. 37. Miller MJ. Use of levamisole in parasitic infections. Drugs. 1980;20(2):122-130
  38. 38. Katiyar SB, Bansal I, Saxena JK, Chauhan PMS. Syntheses of 2,4,6-trisubstituted pyrimidine derivatives as a new class of antifilarial topoisomerase II inhibitors. Bioorganic & Medicinal Chemistry Letters. 2005;15(1):47-50
  39. 39. Singh BK, Mishra M, Saxena N, Yadav GP, Maulik PR, Sahoo MK, et al. Synthesis of 2-sulfanyl-6-methyl-1,4-dihydropyrimidines as a new class of antifilarial agents. European Journal of Medicinal Chemistry. 2008;43(12):2717-2723
  40. 40. Agarwal A, Agarwal SK, Singh SN, Fatma N, Chatterjee RK.In vivopotent antifilarial β-carbolines. Bioorganic & Medicinal Chemistry Letters. 1996;6(3):225-228
  41. 41. Srivastava SK, Agarwal A, Chauhan PMS, Agarwal SK, Bhaduri AP, Singh SN, et al. Potent 1,3-disubstituted-9H-pyrido[3,4-b] indoles as new lead compounds in antifilarial chemotherapy. Journal of Medicinal Chemistry. 1999;42(9):1667-1672
  42. 42. Hewitt RI, Kushner S, Stewart H, White E, Wallace WS, Subbarow Y. Experimental chemotherapy of filariasis. III. Effect of 1-diethylcarbamyl-4-methylpiperazine hydrochloride against naturally acquired filarial infections in cotton rats and dogs. Journal of Laboratory and Clinical Medicine. 1947;32(11):1314-1329
  43. 43. World Health Organization. Report of the Seventh Meeting of the Scientific Working Group on Filariasis: Filaricide Screeners TDR/Fil/SWG(7)82,3. Geneva: World Health Organization; 1982
  44. 44. Tewari S, Chauhan PMS, Bhaduri AP, Fatima N, Chatterjee RK. Syntheses and antifilarial profile of 7-chloro-4-(substituted amino) quinolines: A new class of antifilarial agents. Bioorganic & Medicinal Chemistry Letters. 2000;10(13):1409-1412
  45. 45. Azad SC, Balaramnavar VM, Khan IA, Doharey PK, Saxena JK, Saxena AK. Operative conversions of 3-carboxy-4-quinolones into 3-nitro-4-quinolonesvia ipso-nitration: Potential antifilarial agents as inhibitors ofBrugia malayithymidylate kinase. RSC Advances. 2015;5(100):82208-82214
  46. 46. Srivastava SK, Chauhan PMS, Agarwal SK, Bhaduri AP, Singh SN, Fatima N, et al. Syntheses and antifilarial profile of 5-amino and 5,8-diamino-isoquinoline derivatives: A new class of antifilarial agents. Bioorganic & Medicinal Chemistry Letters. 1996;6(22):2623-2628
  47. 47. Srivastava SK, Chauhan PMS, Bhaduri AP, Fatima N, Chatterjee AK. Quinolones: Novel probes in antifilarial chemotheraphy. Journal of Medicinal Chemistry. 2000;43(11):2275-2279
  48. 48. Roy P, Dhara D, Parida PK, Kar RJ, Bhunia A, Jana K, et al.C-cinnamoyl glycosides as a new class of anti-filarial agents. European Journal of Medicinal Chemistry. 2016;114:308-317
  49. 49. Sashidhara KV, Kumar A, Rao KB, Kushwaha V, Saxena K, Murthy PK.In vitroandin vivoantifilarial activity evaluation of 3,6-epoxy [1,5] dioxocines: A new class of antifilarial agents. Bioorganic & Medicinal Chemistry Letters. 2012;22(4):1527-1532
  50. 50. Agarwal A, Awasthi SK, Murthy PK.In vivoantifilarial activity of some cyclic and acylic alcohols. Medicinal Chemistry Research. 2011;20(4):430-434
  51. 51. Sharma RD, Bag S, Tawari NR, Degani MS, Goswami K, Reddy MVR. Exploration of 2,4-diaminopyrimidine and 2,4-diamino-s-triazine derivatives as potential antifilarial agents. Parasitology. 2013;140(8):959-965
  52. 52. Bag S, Tawari NR, Sharma R, Goswami K, Reddy MV, Degani MS.In vitrobiological evaluation of biguanides and dihydrotriazines againstBrugia malayiand folate reversal studies. Acta Tropica. 2010;113(1):48-51
  53. 53. Tripathi RP, Tripathi R, Bhaduri AP, Singh SN, Chatterjee RK, Murthy PK. Antifilarial activity of some 2H-1-benzopyran-2-ones (coumarins). Acta Tropica. 2000;76(2):101-106
  54. 54. Tripathi RP, Tiwari VK, Misra-Bhattacharya S, Tyagi K, Srivastava VML, Murthy PK. 7-O-[4-methyl piperazine-1-(2-acetyl)]-2H-1-benzopyran-2-one: A novel antifilarial lead compound. Acta Tropica. 2003;87(2):215-224
  55. 55. Misra S, Singh LK, Gupta PJ, Misra-Bhattacharya S, Katiyar D. Synthesis and biological evaluation of 4-oxycoumarin derivatives as a new class of antifilarial agents. European Journal of Medicinal Chemistry. 2015;94:211-217
  56. 56. Mathew N, Karunan T, Srinivasan L, Muthuswamy K. Synthesis and screening of substituted 1,4-naphthoquinones (NPQs) as antifilarial agents. Drug Development Research. 2010;71:188-196
  57. 57. Awasthi SK, Mishra N, Dixit SK, Singh A, Yadav M, Yadav SS, et al. Antifilarial activity of 1,3-diarylpropen-1-one: Effect on glutathione-S-transferase, a phase II detoxification enzyme. American Journal of Tropical Medicine and Hygiene. 2009;80(5):764-768
  58. 58. Tiwari VK, Tewari N, Katiyar D, Tripathi RP, Arora K, Gupta S, et al. Synthesis and antifilarial evaluation of N1,Nn-xylofuranosylated diaminoalkanes. Bioorganic & Medicinal Chemistry. 2003;11(8):1789-1800
  59. 59. Srivastava SK, Chauhan PMS, Bhaduri AP, Murthy PK, Chatterjee RK. Secondary amines as new pharmacophores for macrofilaricidal drug design. Bioorganic & Medicinal Chemistry Letters. 2000;10(4):313-314
  60. 60. Kalani K, Kushwaha V, Verma R, Murthy KP, Srivastava SK. Glycyrrhetinic acid and its analogs: A new class of antifilarial agents. Bioorganic & Medicinal Chemistry Letters. 2013;23(9):2566-2570
  61. 61. Rao RU, Huang Y, Fischer K, Fischer PU, Weil GJ.Brugia malayi: Effects of nitazoxanide and tizoxanide on adult worms and microfilariae of filarial nematodes. Experimental Parasitology. 2008;121(1):38-45
  62. 62. Kausar S, Khan W, Azam A. The effect of DEC, NTZ and NTZ + AgNPs on the TCA cycle enzymes of the microfilariae ofSetaria cervi in vitro. Asian Journal of Pharmacy and Pharmacology. 2016;2(6):154-161
  63. 63. Kausar S, Khan W. Comparative efficacy of diethylcarbamazine, nitazoxanide and nanocomposite of nitazoxanide and silver nanoparticles on the dehydrogenases of TCA cycle inSetaria cervi, in vitro. Iranian Journal of Parasitology. 2018;13(3):399-405
  64. 64. Dhananjeyan MR, Milev YP, Kron MA, Nair MG. Synthesis and activity of substituted anthraquinones against a human filarial parasite,Brugia malayi. Journal of Medicinal Chemistry. 2005;48(8):2822-2830
  65. 65. Bahekar SP, Hande SV, Agarwal NR, Chandak HS, Bhoj PS, Goswami K, et al. Sulfonamide chalcones: Synthesis andin vitroexploration for therapeutic potential againstBrugia malayi. European Journal Medicinal Chemistry. 2016;124:262-269
  66. 66. Sashidhara KV, Avula SR, Doharey PK, Singh LR, Balaramnavar VM, Gupta J, et al. Designing, synthesis of selective and high-affinity chalcone-benzothiazole hybrids asBrugia malayithymidylate kinase inhibitors:In vitrovalidation and docking studies. European Journal Medicinal Chemistry. 2015;103:418-428
  67. 67. Sashidhara KV, Rao KB, Kushwaha V, Modukuri RK, Verma R, Murthy PK. Synthesis and antifilarial activity of chalcone–thiazole derivatives against a human lymphatic filarial parasite,Brugia malayi. European Journal of Medicinal Chemistry. 2014;81:473-480
  68. 68. Raether W, Lammler G. The filaricidal effect of basically substituted 2,6-bis-benzimidazoles inLitomosoides cariniiinfection of the cotton rat (Sigmodon hispidus). Annals of Tropical Medicine and Parasitology. 1971;65(1):107-115
  69. 69. Denham DA, Suswillo RR, Rogers R. The anthelmintic effects of flubendazole onBrugia pahangi. Transactions of the Royal Society of Tropical Medicine and Hygiene. 1978;72:546-547
  70. 70. Denham DA, Samad R, Cho SY, Suswillo RR, Skippins SC. The anthelmintic effects of flubendazole onBrugia pahangi. Transactions of the Royal Society of Tropical Medicine and Hygiene. 1979;73:673-676
  71. 71. Dominguez-Vazquez A, Taylor HR, Ruvalcaba-Macias AM, Murphy RP, Greene BM, Rivas-Alcala AR, et al. Comparison of flubendazole and diethylcarbamazine in treatment of onchocerciasis. Lancet. 1983;1:139-143
  72. 72. Denham DA. Anthelmintic properties of flubendazole againstDipetalonema viteaein jirds. Transactions of the Royal Society of Tropical Medicine and Hygiene. 1980;74(6):829
  73. 73. Reddy AB, Rao UR, Chandrashekar R, Shrivastava R, Subrahmanyam D. Comparative efficacy of some benzimidazoles and amoscanate (Go.9333) against experimental filarial infections. Tropenmedizin und Parasitologie. 1983;34(4):259-262
  74. 74. Maertens K, Wery M. Effect of mebendazole and levamisole onOnchocerca volvulusandDipetalonema perstans. Transactions of the Royal Society of Tropical Medicine and Hygiene. 1975;69:359-360
  75. 75. World Health Organization. Technical Report Series 702. In: Lymphatic Filariasis. 1984
  76. 76. Fatima N, Sharma S, Chatterjee RK. 2,2′-Dicarbomethoxyamino-5,5′-dibenzimidazolyl ketone—A new antifilarial agent. Acta Tropica. 1989;46:311-321
  77. 77. Ram S, Wise DS, Wotring LL, McCall JW, Townsend LB. Synthesis and biological activity of certain alkyl 5-(alkoxycarbonyl)-1H-benzimidazole-2-carbamates and related derivatives: A new class of potential antineoplastic and antifilarial agents. Journal of Medicinal Chemistry. 1992;35(3):539-547
  78. 78. O’Neill M, Mansour A, DiCosty U, Geary J, Dzimianski M, McCall SD, et al. Anin vitro/in vivomodel to analyze the effects of flubendazole exposure on adult femaleBrugia malayi. PLoS Neglected Tropical Diseases. 2016;10(5):e0004698
  79. 79. O'Neill M, Ballesteros C, Tritten L, Burkman E, Zaky WI, Xia J, et al. Profiling the macrofilaricidal effects of flubendazole on adult femaleBrugia malayiusing RNAseq. International Journal of Parasitology: Drugs and Drug Resistance. 2016;6(3):288-296
  80. 80. Singh SK, Goswami K, Sharma RD, Reddy MVR, Dash D. Novel microfilaricidal activity of nanosilver. International Journal of Nanomedicine. 2012;7:1023-1030
  81. 81. Yu Z, Vodanovic-Jankovic S, Ledeboer N, Huang SX, Rajski SR, Kron M, et al. Tirandamycins fromStreptomycessp. 17944 inhibiting the parasiteBrugia malayiasparagine tRNA synthetase. Organic Letters. 2011;13(8):2034-2037
  82. 82. Yu Z, Vodanovic-Jankovic S, Kron M, Shen B. New WS9326A congeners fromStreptomycessp. 9078 inhibitingBrugia malayiasparaginyl-tRNA synthetase. Organic Letters. 2012;14(18):4946-4949
  83. 83. Rateb ME, Yang D, Vodanovic-Jankovic S, Yu Z, Kron MA, Shen B. Adipostatins A–D fromStreptomycessp. 4875 inhibitingBrugia malayiasparaginyl-tRNA synthetase and killing adultBrugia malayiparasites. The Journal of Antibiotics. 2015;68:540-542
  84. 84. Misra N, Sharma M, Raj K, Dangi A, Srivastava S, Misra-Bhattacharya S. Chemical constituents and antifilarial activity ofLantana camaraagainst human lymphatic filariidBrugia malayiand rodent filariidAcanthocheilonema viteaemaintained in rodent hosts. Parasitology Research. 2007;100(3):439-448
  85. 85. Kushwaha V, Saxena K, Verma R, Katoch D, Kumar N, Lal B, et al. Antifilarial activity of diterpenoids fromTaxodium distichum. Parasites Vectors. 2016;9(1):132
  86. 86. Mishra V, Parveen N, Singhal KC, Khan NU. Antifilarial activity ofAzadirachta indicaon cattle filarial parasiteSetaria cervi. Fitoterapia. 2005;76(1):54-61
  87. 87. Mukherjee N, Saini P, Mukherjee S, Roy P, Babu SPS.In vitroantifilarial activity ofAzadirachta indicaaqueous extract through reactive oxygen species enhancement. Asian Pacific Journal of Tropical Medicine. 2014;7(11):841-848
  88. 88. Kausar S.In vitroevaluation of antifilarial effect ofAzadirachta indicaleaves extract in different solvents on the microfilariae ofSetaria cervi. Journal of Parasitic Diseases. 2016;41(1):9-15
  89. 89. Kalani K, Kushwaha V, Sharma P, Verma R, Srivastava M, Khan F, et al.In vitro, in silicoandin vivostudies of ursolic acid as an anti-filarial agent. PLoS One. 2014;9:1-13
  90. 90. Singh R, Khan NU, Singhal KC.In vitroantifilarial activity ofSencio nudicaulisBuch. Ham.—Effect onSetaria cervi(Nematoda Filarioidea). Indian Journal of Physiology and Pharmacology. 1996;40(3):231-236
  91. 91. Saxena K, Dube V, Kushwaha V, Gupta V, Lakshmi M, Mishra S, et al. Antifilarial efficacy ofHibiscus sabdariffaon lymphatic filarial parasiteBrugia malayi. Medicinal Chemistry Research. 2011;20(9):1594-1602
  92. 92. Mathew N, Misra-Bhattacharya S, Perumal V, Muthuswamy K. Antifilarial lead molecules isolated fromTrachyspermum ammi. Molecules. 2008;13(9):2156-2168
  93. 93. Sashidhara KV, Singh SP, Misra S, Gupta J, Misra-Bhattacharya S. Galactolipids fromBauhinia racemosaas a new class of antifilarial agents against human lymphatic filarial parasite,Brugia malayi. European Journal of Medicinal Chemistry. 2012;50:230-235
  94. 94. Singha M, Shakya S, Soni VK, Dangi A, Kumar N, Misra-Bhattacharya S. The n-hexane and chloroform fractions ofPiper betleL. trigger different arms of immune responses in BALB/c mice and exhibit antifilarial activity against human lymphatic filaridBrugia malayi. International Immunopharmacology. 2009;9(6):716-728
  95. 95. Saini P, Gayen P, Nayak A, Kumar D, Mukherjee N, Pal BC, et al. Effect of ferulic acid fromHibiscus mutabilison filarial parasiteSetaria cervi: Molecular and biochemical approaches. Parasitology International. 2012;61(4):520-531
  96. 96. Gaur RL, Sahoo MK, Dixit S, Fatima N, Rastogi S, Kulshreshtha DK, et al. Antifilarial activity ofCaesalpinia bonducellaagainst experimental filarial infections. Indian Journal of Medical Research. 2008;128(1):65-70
  97. 97. Al-Abd NM, Nor ZM, Mansor M, Hasan MS, Kassim M. Antifilarial and antibiotic activities of methanolic extracts ofMelaleuca cajuputiflowers. Korean Journal of Parasitology. 2016;54(3):273-280
  98. 98. Misra S, Verma M, Mishra SK, Srivastava S, Lakshmi V, Misra-Bhattacharya S. Gedunin and photogedunin ofXylocarpus granatumpossess antifilarial activity against human lymphatic filarial parasiteBrugia malayiin experimental rodent host. Parasitology Research. 2011;109:1351-1360
  99. 99. Sahare KN, Anandhraman V, Meshram VG, Meshram SU, Reddy MV, Tumane PM, et al. Anti-microfilarial activity of methanolic extract ofVitex negundoandAegle marmelosand their phytochemical analysis. Indian Journal of Experimental Biology. 2008;46(2):128-131
  100. 100. Sahare KN, Singh V.In-vitroantifilarial activity of methanol extract ofAegle marmelos. Indo American Journal of Pharmaceutical Research. 2013;3(6):1-7
  101. 101. Saini P, Mukherjee N, Mukherjee S, Roy P, Gayen P, Kumar D, et al.Diospyros perigrenabark extract induced apoptosis in filarial parasiteSetaria cervithrough generation of reactive oxygen species. Pharmaceutical Biology. 2015;53(6):813-823
  102. 102. Ray AS, Joardar N, Mukherjee S, Rahaman CH, Babu SPS. Polyphenol enriched ethanolic extract ofCajanus scarabaeoides(L.) Thouars exerts potential antifilarial activity by inducing oxidative stress and programmed cell death. PLoS One. 2018;13(12):e0208201
  103. 103. Mishra V, Khan NU, Singhal KC. Potential antifilarial activity of fruit extracts ofFicus racemosaLinn. againstSetaria cervi in vitro. Indian Journal of Experimental Biology. 2005;43:346-350
  104. 104. Lakshmi V, Kumar R, Gupta P, Varshney V, Srivastava MN, Dikshit M, et al. The antifilarial activity of a marine red alga,Botryocladia leptopoda,against experimental infections with animal and human filariae. Parasitology Research. 2004;93:468-474
  105. 105. Gupta J, Misra S, Mishra SK, Srivastava S, Srivastava MN, Lakshmi V, et al. Antifilarial activity of marine spongeHaliclona oculataagainst experimentalBrugia malayiinfection. Experimental Parasitology. 2012;130(4):449-455
  106. 106. Lakshmi V, Srivastava S, Mishra SK, Misra S, Verma M, Misra-Bhattacharya S. In-vitro and in-vivo antifilarial potential of marine sponge,Haliclona exigua(Kirkpatrick) against human lymphatic filarial parasiteBrugia malayi. Parasitology Research. 2009;105(5):1295-1301
  107. 107. Lakshmi V, Misra-Bhattacharya S. Antifilarial activity ofEucalyptus globulus Labill.leaves againstBrugia malayi. Bangladesh Pharmaceutical Journal. 2016;19:44-47
  108. 108. Behera DR, Bhatnagar S. Assessment of macrofilaricidal activity of leaf extracts ofTerminaliasp. against bovine filarial parasiteSetaria cervi. Journal of Infection and Public Health. 2018;11(5):5643-5647
  109. 109. Kushwaha V, Saxena K, Verma SK, Lakshmi V, Sharma RK, Murthy PK. Antifilarial activity of gum fromMoringa oleiferaLam. on human lymphatic filariaBrugia malayi. Chronicles of Young Scientists. 2016;2:201-206
  110. 110. Sahare KN, Anandharaman V, Meshram VG, Meshram SU, Gajalakshmi D, Goswami K, et al.In vitroeffect of four herbal plants on the motility ofBrugia malayimicrofilariae. Indian Journal of Medical Research. 2008;127(5):467-471
  111. 111. Deshmukh M, Sahare KN, Patidar RK, Mahajan B, Singh V. Antifilarial activity ofButea monospermaL. leaves extracts againstSetaria cervi. Trends in Vector Research and Parasitology. 2014;1:1-5
  112. 112. Shanmugapriya R, Ramnathan T. Antifilarial activity of seed extracts ofRicinus communisagainstBrugia malayi. Journal of Pharmacy Research. 2012;5(3):1448-1450
  113. 113. Lakshmi V, Joseph SK, Srivastava S, Verma SK, Sahoo MK, Dube V, et al. Antifilarial activityin vitroandin vivoof some flavonoids tested againstBrugia malayi. Acta Tropica. 2010;116(2):127-133
  114. 114. Srinivasan L, Mathew N, Muthuswamy K.In vitroantifilarial activity of Glutathione S transferase inhibitors. Parasitology Research. 2009;105(4):1179-1182
  115. 115. Casiraghi M, Anderson TJ, Bandi C, Bazzocchi C, Genchi CA. Phylogenetic analysis of filarial nematodes: Comparison with the phylogeny ofWolbachiaendosymbionts. Parasitology. 2001;122:93-103
  116. 116. Hoerauf A, Nissen-Pahle K, Schmetz C, Henkle-Duhrsen K, Blaxter ML, Buttner DW, et al. Tetracycline therapy targets intracellular bacteria in the filarial nematodeLitomosoides sigmodontisand results in filarial infertility. Journal of Clinical Investigation. 1999;103:11-17
  117. 117. Nuchprayoon S, Junpee A, Poovorawan Y. Random amplified polymorphic DNA (RAPD) for differentiation between Thai and Myanmar strains ofWuchereria bancrofti. Filaria Journal. 2007;6:6
  118. 118. Ghedin E, Wang S, Spiro D, Caler E, Zhao Q, Crabtree J, et al. Draft genome of the filarial nematode parasiteBrugia malayi. Science. 2007;317:1756-1760
  119. 119. Bennuru S, Meng Z, Ribeiro JM, Semnani RT, Ghedin E, Chan K, et al. Stage-specific proteomic expression patterns of the human filarial parasiteBrugia malayiand its endosymbiontWolbachia. Proceedings of the National Academy of Sciences of the United States of America. 2011;108:9649-9654
  120. 120. Bhargavi R, Vishwakarma S, Murty US. Modeling analysis of GST (glutathione-s-transferases) fromWuchereria bancroftiandBrugia malayi. Bioinformation. 2005;1:25-27
  121. 121. Acharya C, Coop A, Polli JE, Mackerell AD Jr. Recent advances in ligand-based drug design: Relevance and utility of the conformationally sampled pharmacophore approach. Current Computer-Aided Drug Design. 2011;7:10-22
  122. 122. Anderson AC. The process of structure-based drug design. Chemical Biology. 2003;10:787-797
  123. 123. Allen FH, Taylor R. Research applications of the Cambridge structural database (CSD). Chemical Society Reviews. 2004;33:463-475
  124. 124. Seiler KP, George GA, Happ MP, Bodycombe NE, Carrinski HA, Norton S. ChemBank: A small-molecule screening and cheminformatics resource database. Nucleic Acids Research. 2008;36:D351-D359
  125. 125. Knox C, Law V, Jewison T, Liu P, Ly S, Frolkis A, et al. DrugBank 3.0: A comprehensive resource for ‘omics’ research on drugs. Nucleic Acids Research. 2011;39:D1035-D1041
  126. 126. Li Q, Cheng T, Wang Y, Bryant SH. PubChem as a public resource for drug discovery. Drug Discovery Today. 2010;15:1052-1057
  127. 127. Irwin JJ, Shoichet BK. ZINC: A free database of commercially available compounds for virtual screening. Journal of Chemical Information and Modeling. 2005;45:177-182
  128. 128. Von Grotthuss M, Koczyk G, Pas J, Wyrwicz LS, Rychlewski L. Ligand: Info small-molecule meta-database. Combinatorial Chemistry & High Throughput Screening. 2004;7:757-761

Written By

Sharba Kausar

Submitted: February 22nd, 2019 Reviewed: August 31st, 2019 Published: December 14th, 2019