INTRODUCTION:

Lymphatic filariasis is the mosquito-borne parasitic disease that is caused by three species of tissue dwelling filaroids; Wuchereria bancrofti, Brugia malayi, and Brugia timori. These worms occupy the lymphatic system, including the lymph nodes, and in chronic cases these worms lead to the disease elephantiasis. W. bancrofti accounts for more than 90 % infection widely distributed throughout tropical Africa, Asia, America and India. B. Malayi is restricted to areas of Southeast Asia, China, and a very small focus in south-western India, while B. timori is restricted to the islands of Timor and a few other small islands of Indonesia. [1, 2]

Human filarial nematode worms have complicated life cycles. Infection is initiated when the host-seeking mosquito deposits an infective third- stage larva (L3) on the skin of the host during the process of obtaining a blood meal. The infective larva penetrates the skin at the site of bite and migrates to the lymphatic system of the host where they mature into fecund adult worms after 6 - 10 months. The reproductive lifespan of the adult worms is estimated at 4- 6 years, during which millions of microfilaria (MF) are produced, each with a lifespan of approx. 12 months. MF circulates in the host bloodstream and the lifecycle is completed when they are ingested with the blood meal taken by female mosquitoes. Within susceptible vectors, MF penetrates the gut wall and migrates to the flight muscles where they developed from L2 larvae into the infective stage larva (L3). [3]

Prevalence of the public health problems:

Lymphatic filariasis constitutes a serious public health issue in tropical and sub-tropical regions. According to World Health Organization (WHO) estimates more than 1.3 billion people in 7 countries worldwide are threatened by lymphatic filariasis, commonly known as elephantiasis. Over 120 million people are currently infected, with about 40 million disfigured and incapacitated by the disease. Lymphatic filariasis does not directly cause death, but its chronic manifestation is an important cause of disability and reduced quality of life. Hydrocele and lymphodema are associated with impaired mobility and social activity, reduced work capacity, sexual dysfunction; serve psycho-social problems, stigma and bad marital prospects. [4] The burden of disease in 2012 was estimated at 5.5 million disability adjusted life years (DANYs). It is world’s second leading cause of long-term disability. [5]

Control and Treatment of Lymphatic Filariasis:

Lymphatic filariasis is a disease targeted of elimination. The availability of safe, single-dose, two-drug treatment regimens capable of reducing microfilaria to near -zero levels for one year or more, along with remarkable improvements in techniques for diagnosis the infection, resulted in advocacy for a global strategy to eliminate the disease through mass drug administration (MDA). [6] In 1997, the World Health Assembly adopted a resolution, calling for the worldwide elimination of lymphatic filariasis as a public health problem (World Health Organization 1997) and in 1998 the global programme to eliminate lymphatic filariasis (GPELF) was initiated. In 2000, the global alliance to eliminate lymphatic filariasis launched the global programme to eliminate lymphatic filariasis (GPELF) by 2020. The GPELF has two major objectives: to interrupt transmission of parasite (transmission control) and to provide care for those who suffer the devastating clinical manifestation of the disease (morbidity control). [7, 8] WHO recommended strategy for interrupting transmission is preventive chemo-therapy and transmission (PCT), mainly through MDA of albendazole in combination with either ivermectin or dimethylcarbamazine citrate (DEC). Repeated once yearly, MDA dramatically reduces the reservoir of the transmissible MF stage available for uptake by vectors of LF. There is a threshold for MF density in the human host and vector contact rates below which transmission will be interrupted. Where LF is co-endemic with onchocerciasis, the regimen is ivermectin 200-400 micro gram/ Kg plus albendazole 400 micro grams; elsewhere, the regimen should be DEC 6 mg/Kg plus albendazole 400 mg. [9, 10]

Diethylcarbamazine:

Diethylcarbamazine (DEC) has been the mainstay drug for the treatment of filariasis since its discovery in 1948. Its mode of action of different from any other class of anthelmintic and it appear to require host components from the arachidonic acid pathway, innate immune system and nitric oxide for its activity, according for its lack of activity in-vitro. It is indicated for the treatment of individual patients of LF. Given as a single dose of 6 mg/Kg, DEC is effective for reduction of acute and chronic cases of MF for at least 1 year, and is the basis of mast drug distribution by the global programme to eliminate lymphatic filariasis (GPELF) in areas without coo-endemic onchocerciasis the optimum single dose of DEC does not clear all MF in a person with infection and not all adult worms are killed but these is unlikely to be attributed to the drug resistance. [11]

Ivermectin:

Ivermectin (22, 23-dihydroiermectin B1a plus 22, 23-dihydroivermectin B1b) is a broad-spectrum anti-parasitic agent. Ivermectin is an anthelmintic drug fur treatment of onchocerciasis and for strongyloidiosis, ascariasis, trichuriasis, and enterobiasis. It is highly effective, well tolerated drug at doses of 100-200 micro gram/Kg for reduction of MF in lymphatic filariasis. Ivermectin has limited effects on the survival of adult filarial in humans or other animals, at least acutely, despite the fact that this drug is extremely potent and highly efficacious against almost all species of non-filarial adult nematodes except human hook worms. [12]

Albendazole:

Albendazole is a broad-spectrum anthelmintic given orally that is effective against nematodes, cestodes, and flatworms. The drug inhibits polymerization of beta-tubulin and microtubule formation. A 400 mg dose of albendazole is routinely included with annual treatments of DEC or ivermectin in lymphatic filariasis control programmes. The activity of the albendazole component in this regimen is uncertain, and whether combination therapy confers benefits over DEC or ivermectin alone remains controversial. [11]

Doxycycline:

Treatment of bancroftian filariasis with a 4-,6-, or 8- week course of a 200mg/day dose of doxycycline result in long term sterility and eventual death of adult worms. In addition to the anti parasitic effects of treatment, individuals treated anti-wolbachial therapy show significant improvements in lymphatic pathology and the severity of lymphoedema and hydrocele. Attempts to resolve these issues had led to the establishment of an anti-wolbachial drug discovery and development program (A-WOL), which aims to develop anti-wolbachial therapy that is compatible with MDA approaches. This program includes objectives to test combination of antibiotics active against wolbachia given for reduced period of time to optimize antiwolbachial treatment with existing tools. [13]

Major problems and challenges for disease control:

There is now greater international momentum for lymphatic filariasis eliminations, several important issues remain to be resolved, before the disease can be eliminated. There is urgent need for appropriate tools, procedures and criteria for monitoring and evaluating the impact of elimination programmes. It is also becoming increasingly important to be able to predict and demonstrate the public health and socioeconomic impacts of the elimination efforts. The available interventions have significant limitations. The current drugs require repeated annual treatment and there is a need for the development of MH/ curative drugs. Drug resistance may become a critical issue after prolonged mass treatment with the current drugs. Therefore there is a need for early detection of resistance to drugs and replacement drugs. The major challenge with the currently available drugs is that the interruption of transmission requires very high treatment coverage to achieve elimination, but current approaches to drug delivery do not achieve this. Hence, there is an urgent need for more effective drug delivery strategies for lymphatic filariasis elimination that are adapted to regional differences and variations in health sector development. [14]

Herbal approaches for control of lymphatic filariasis:

Novel drug designing research recommended by WHO boosts up traditional therapeutics under herbal medicinal principles which is already time tested and widely accepted across various cultural and socio-economic strata. However the pharmacological effect of these medicines is unexplored. Medicinal plants have been used as therapeutic aid for deviating human ailments from Vedic ages and still provide ingredients for formulations of new medicines in pharmaceutical industries. WHO has listed over 21000 plants species to be of medicinal use around the world, more than 60% of the world’s human populations relies on plant medicine for primary health care needs. There are very few success stories related to antifilarial activity, with the possible exception of ivermectin which is a macrocyclic lactone derived of straptomyces avrmitilis. There are many plants against filarial parasites on in-vitro and in-vivo study. Some plants which effective lymphatic filariasis are Adenia gummifera, Aegle marmelos corr., Alstonia scholaris, Andrographis paniculata, Argyria, boehavia repens, Butea monosperma, Caesalpinia bonducella, Calotropis giganteal, Calotropis procera, Crapa procera, Cayaponia mertiana, Cinnamomum culilawal, Cleistopholis glauca, Clerodendrum capitum, Cyrotomium fortunnei, Delonix elata, Dichrostachys Cinerea, D. glomerata, Dombeya amaniensis, Eclipta alba, Elaeophorbie drupifera, Elephantopus scaber, Emicostema littorale, Eucalyptus robusta, Hilleria latifolia, Kigelia africana, Lantana camara, Limeum ptercartum, Lycopodium rubrum, Melia azidirachta, Microglossa afzelli, Mussaenda elegans, Myrianthus arboreus, Newbouldia laevis, Odyendea gabunensis, pachyelasma, pessmanii, Pachypodanthium staudtii, Physendra longipas, Phychotria tanganyikensis, Piper betle L., Raphia ferinifer, Ricinus communis, Richiea caparoydes, Rymchosia hirita. [15]

CONCLUSION:

Lymphatic filariasis is a mosquito-bourne parasitic disease that is caused by three species of tissue dwelling filaroids: wuchereria bancrofti, brugia malayi, and brugia timori.For both the acute and chronic manifestation of lymphatic filariasis, supportive or specific clinical care is obtain of more critical importance than that of anti-parasitic medication. Diagnostic tools are not available to reliably distinguish filarial lymphoedema or hydrocele from cases that are not of filarial etiology. Fortunately, this discrimination is usually not necessary to initiate appropriate treatment. Already available anti-filarial drugs offer their own limitation as they are incapable of killing adult worms and associated with problem of resistance in filarial parasite. Therefore a newer approach utilizing herbal medicine was proven to be effective against filariasis. Further new researches can be made in search of potential herbs and their constituents for safe and effective treatment against filariasis.

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Received on 10.10.2015 Modified on 12.11.2015

Res. J. Pharmacology & P’dynamics. 7(4): Oct.-Dec., 2015; Page 196-198

DOI: 10.5958/2321-5836.2015.00040.3