Two decades of antifilarial drug discovery: a review

Sangshetti, Jaiprakash N.; Shinde, Devanand B.; Kulkarni, Abhishek

doi:10.1039/c7ra01857f

Cited by 21 publications

(12 citation statements)

References 229 publications

(177 reference statements)

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“…Several recent reports suggest that despite significant progress made towards elimination of LF from endemic regions using the MDA approach, active transmission of LF continues at low levels (Drexler et al, 2012; Cano et al, 2014; Sunish et al, 2014; Ramaswamy, 2016; Sangshetti et al, 2017). Human subject non-compliance appears to be one of the major factors hindering the success of the elimination strategy based on MDA only (Nujum et al, 2012; Krentel et al, 2013).…”

Section: Discussionmentioning

confidence: 99%

Prospects of developing a prophylactic vaccine against human lymphatic filariasis – evaluation of protection in non-human primates

Khatri

Chauhan

Vishnoi

et al. 2018

International Journal for Parasitology

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Lymphatic filariasis (LF) affects 120 million people around the world and another 856 million people are at risk of acquiring the infection. Mass Drug Administration (MDA) spearheaded by the World Health Organization is the only current strategy to control this infection. Recent reports suggest that despite several rounds of MDA, elimination has not been achieved and there is a need for more stringent control strategies for control of LF. An effective prophylactic vaccine combined with MDA has significant potential. Initial trials using a prophylactic trivalent recombinant Brugia malayi heat shock protein 12.6, abundant larval transcript -2 and tetraspanin large extra-cellular loop (rBmHAT) vaccine developed in our laboratory conferred only 35% protection in macaques. Therefore, the focus of the present study was to improve the current vaccine formulation to obtain better protection in non-human primates. We made two modifications to the current formulation: (i) the addition of another antigen, thioredoxin peroxidase-2 (TPX-2) to make it a tetravalent vaccine (rBmHAXT) and (ii) the inclusion of an adjuvant; AL019 (alum plus glucopyranosyl lipid adjuvant-stable emulsion) that is known to promote a balanced Th1/Th2 response. A double-blinded vaccination trial was performed with 40 macaques that were divided into three treatment groups and one control group (n = 10/group). Vaccinated animals received 4 immunisations at 1 month intervals with 150 µg/ml of rBmHAT plus alum, rBmHAT plus AL019 or rBmHAXT plus AL019. Control animals received AL019 only. All vaccinated macaques developed significant (P ≤ 0.003) titers of antigen-specific IgG antibodies (1:20,000) compared with the controls. One month after the last dose, all macaques were challenged s.c. with 130-180 B. malayi L3s. Our results showed that seven out of 10 (70%) of macaques given the improved rBmHAXT vaccine did not develop the infection compared with AL019 controls, of which seven out of 10 macaques developed the infection. Titers of antigen-specific IgG1 and IgG2 antibodies were significantly (P ≤ 0.01) higher in vaccinated animals and there was an increase in the percentage of IL-4 and IFN-γ secreting antigen-responding memory T cells. These studies demonstrated that the improved formulation (rBmHAXT plus AL019) is a promising vaccine candidate against human lymphatic filariasis.

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Section: Discussionmentioning

confidence: 99%

Prospects of developing a prophylactic vaccine against human lymphatic filariasis – evaluation of protection in non-human primates

Khatri

Chauhan

Vishnoi

et al. 2018

International Journal for Parasitology

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“…In Tokyo, Yushitaro Matsuura found a female adult worm in an inguinal lymph node (1896). Later, a lot of work was done in defining various manifestations of filariasis and the aim of current researches is concentrated on prevalence, treatment, transmission cycles, and newly discovered species [6][7][8][9][10].…”

Section: Some Early Scientific Discoveries In Filariasis History Inclmentioning

confidence: 99%

Lymphatic Filariasis: An Overview

Al-Tameemi

Kabakli

2019

Asian J Pharm Clin Res

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Lymphatic filariasis (LF) is a tropical disease caused by infection with the parasitic filarial worms: Wuchereria bancrofti, Brugia malayi, and Brugia timori. The symptoms of this chronic disease appear in adults (in men more than in women) and include damage to the lymphatic system, arms, legs, and genitals, which cause significant pain, reducing productivity, and social problems. LF is a cause of continued disability, pain, disfigurement, and sexual disability in the world, so the knowledge of the disease and the infection control is very important. In addition to the importance of prevention, that includes giving medicine and using controlling ways of mosquitoes. Moreover, the prevention of disease is important, that includes giving medicine and using controlling ways of mosquitoes. However, although the efforts of health organizations to reduce the LF infections, there are still many challenges including the early diagnosis and control of infection among people.

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“…Wuchereria bancrofti (accounts for 90% of the cases) and Brugia malayi cause LF that affects more than 120 million people worldwide, primarily in poor and developing countries. While onchocerciasis, caused by Onchocerca volvulus , affects more than 37 million people mostly in sub‐Saharan Africa, Yemen and isolated areas of Central and South America ,. Despite several efforts for control, these diseases still continue to be a worsening problem due to the lack of drugs that can eliminate all the stages of parasite.…”

Section: Introductionmentioning

confidence: 99%

“…While onchocerciasis, caused by Onchocerca volvulus, affects more than 37 million people mostly in sub-Saharan Africa, Yemen and isolated areas of Central and South America. [1,2] Despite several efforts for control, these diseases still continue to be a worsening problem due to the lack of drugs that can eliminate all the stages of parasite. The current drugs are mainly microfilaricidal in nature (kill only circulating microfilariae) and show little effect on macrofilariae as a result adult parasite remain unaffected and continue producing millions of microfilariae.…”

Section: Introductionmentioning

confidence: 99%

Synthesis, Structure Elucidation, Homology Modeling and Antifilarial Activity of 7‐Benzamidocoumarin Derivatives

et al. 2019

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A series of 7‐benzamidocoumarin derivatives 10–25 starting from 7‐amino coumarins 7 and 8 has been synthesized, characterized and evaluated in vitro for antifilarial activity against the human lymphatic filarial parasite, Brugia malayi. Compounds 13 and 20–23 showed permanent paralysis of the worm with 90–95% inhibition of motility of adult worms at 10 μM. All the synthesized compounds were docked on the modeled receptor of Onchocerca volvulus chitinase OvCHT1. Compound 13 with binding energy of −7.95 Kcal/mol showing three hydrogen bonds with the active site of the enzyme emerged as the best inhibitor.

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Two decades of antifilarial drug discovery: a review

Abstract: Filariasis is one of the oldest, most debilitating, disabling, and disfiguring neglected tropical diseases with various clinical manifestations and a low rate of mortality, but has a high morbidity rate, which results in social stigma.

Cited by 21 publications

References 229 publications

Prospects of developing a prophylactic vaccine against human lymphatic filariasis – evaluation of protection in non-human primates

Prospects of developing a prophylactic vaccine against human lymphatic filariasis – evaluation of protection in non-human primates

Lymphatic Filariasis: An Overview

Synthesis, Structure Elucidation, Homology Modeling and Antifilarial Activity of 7‐Benzamidocoumarin Derivatives

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