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Cite this article: Dhra G, Nusrat, Bhandari P, Kumar J, Patanjali PK (2017) Advanced Pesticide Formulations for Dengue Preventions. J Fever 1(2): 1007.

*Corresponding authorPK Patanjali, Institute of Pesticide Formulation Technology (IPFT), Sec-20, Udyog Vihar, Opposite to Ambience Mall, Gurugram-122016 (Haryana), India, Tel: +91-9811221652; Email:

Submitted: 02 August 2017

Accepted: 27 December 2017

Published: 29 December 2017

Copyright© 2017 Patanjali et al.

OPEN ACCESS

Keywords•DF/DHF•Aedesaegypti•Etiology•Haematocrit•Pesticide•Formulations

Research Article

Advanced Pesticide Formulations for Dengue PreventionsGulshan Dhra, Nusrat, Pinki Bhandari, Jitendra Kumar, and PK Patanjali*Institute of Pesticide Formulation Technology (IPFT), India

Abstract

Dengue fever (DF) is a serious disease, transmitted by Aedes mosquitoes. Dengue fever virus has four serotypes and is associated with high grade fever, rashes, haemorrhage and shock. This article reviews the spreading distribution around the world, pathophysiology, symptoms and vector control studies by synthetic and herbal agents. We are also highlighting the herbal/natural vector control/repellent formulations, developed particularly at IPFT with no or minimal harmful effects on environment and human kind.

INTRODUCTIONDengue, Malaria, Chikungunya, Yellow fever and Lymphatic

filariasis etc., are some of the most common vectors borne diseases. Dengue fever (DF) is an ancient disease, and was found in the Chinese encyclopaedia of disease; symptoms and remedies record in A.D 610.The virus of dengue was first isolated in Japan in 1943, by the inoculation of serum of patients in suckling mice (Kimura and Hotia 1944). The severe form of dengue, called DHF (dengue hemorragic fever) epidemic occurred first time in Manila, Philippines in 1953 to 1954 (Rigau-Perez et al., 1998). The mosquito vector, Aedes aegypti and the dengue viruses spread to new geographic areas causing major epidemics. The dengue virus and its vector (Aedes aegypti) had a large distribution worldwide, Figure 1.

By various data analysis, it was estimated that approximately 40 % world population is at risk. World Health Organization reported that, there are 50-100 million infections occur annually across the globe. The rapidly increasing footprint of the disease is a health challenge with lot of economic burden for vaccines, medicinal agents and vector control strategies.

DENGUE AND INDIA Since 1956, dengue virus keeps on persisting year after year.

The major affected areas include southern part of the country. The first outbreak was reported in Vellore in 1961 and viral etiology was conducted by isolating the virus (Carey et al., 1966). After that the infectious disease spread towards north and reached Delhi in 1967 (Balaya et al., 1969). Eventually, the whole country was in the grim with the four types of the serotype of dengue virus. The viral studies conducted at that time, confirmed the presence of dengue 2 in 1964 (De, Ranitz et al., 1965), dengue

3 in 1966 (Myer et al., 1969) and all four types in 1968 outbreak (Myer et al., 1970).DHF was reported in 1963 from Calcutta city for the first time and later in Delhi in 1996 in India. The case fatality was above 1% for last decade. Year 1996 onwards, again DF outbreak was discovered in the years 2003,2005 and 2006 but less severe than earlier cases.

SPREADING THE DISEASEThere are various types of the dengue viruses (Figure 2), and

transmitted to human by infected Aedes mosquitoes (A. aegypti). This species distributed tropically and sub-tropically worldwide. The first stage of the Aedes larvae have found in fresh water containers near the human habitat. It is observed that, female Aedes mosquitoes spend most of the time near or in the houses where they emerges as an adult. It means that people rapidly transmitted the virus among them and animals (Figure 3).

Dengue infections attributed particularly to Aedes albopictus, Aedes polynesensis and Aedes sutellaris complex. Aedes albopictus spread from Asia to Africa subcontinents via various types of trades’ especially by the used tyres of the vehicles. The eggs can adhere to the tyres and remain viable for many months without water. The mosquitoes get infected by dengue virus by biting an infected human. They infect and replicates inside the mosquito midgut epithelium and eventually spread to hemolymph to replicate in different parts of the body (organs) and finally infect the salivary gland at an average of 10-14 days after the blood meal. From the salivary gland the virus inoculated into human host, when a mosquito acquires a blood meal, hence spreading of the disease. The transmission coverage of the disease keep on expanding due to many direct and indirect causes associated to urban trails, increased travel and global warming etc.

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DENGUE PATHOPHYSIOLOGYDengue has systematic characteristics with a broad clinical

spectrum, which have both types of non-severe to severe signs. So inoculation onwards the infection/disease starts rapidly with three distinct phases namely, febrile, critical and recovery. The key management is the early recognition of the symptoms and considerations of the problems during the disease period, which leads to good clinical results [1-6].

SYMPTOMS OF DENGUECommon symptoms of the disease are as follows:

First stage shows high grade fever, facial flushing, skin erythema, body ache, myalgia, headache, anorexia, nausea, nose and gum bleeding etc., for 2-7 days.

Second stage includes plasma leakage, decreased platelets count, chest X-ray and abdominal ultrasound is the best diagnosis. Some patients feel shocks and that is due to large volume of the plasma loss. After this recovery starts and all the body functions returns to normal conditions. Severe dengue conditions may be considered from patients if he/she is from an area of dengue risk with the following symptoms.

• Severe plasma leakage

• Significant bleeding

• Altered consciousness

• Severe gastrointestinal involvement (vomiting, abdominal pain and jaundice)

• Organs impairments.

DIAGNOSISThe complete diagnosis of the disease is conducted by the

following laboratory tests:

• Platelet count

• Haematocrit test

• Detecting specific antibodies

• Isolation of the virus etc.

Figure 1 Dengue affected areas worldwide.

Figure 2 General structure of dengue virus.

Figure 3 Transmission of the dengue virus in human.

Figure 4 Controlled Release Granular Formulation.

Figure 5 Neem Based Floating Tablets.

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TREATMENTS OF DENGUETreatment of dengue includes the simple strategy to eliminate

the virus/pathogen and making the treatment easy. Symptomatic treatment is widely accepted to reduce the complications of the infection. Fluid therapy is the most important and used based on the conditions of the patient. In the normal condition of the dengue fever only oral fluid is sufficient but with more serious condition hospitalization is preferred. The fluid replacement therapy helps in the fluid loss during the fever. Intravenous fluid replacement includes 0.9 % saline solution at a rate of 20 ml/kg/h for the first 2 hours. The rate can be tuned according the condition of the patient. Electrolyte and water level should be maintained in the treatment. It is observed that loss of platelet count and rise with haematocrit leads to shock, so these should be monitored after the discontinuation of the intravenous fluid administration.

Other type of treatment is, to use antiviral drugs, but unfortunately yet to be developed. As far as antiviral drugs are concerned some sulphated polysaccharides have been studied and found effective against the dengue virus. In modern medicine ribavirin, glycyrrizin and 6-azuridine are most effective while ‘NITD008’ is an adenosine equivalent is another promising preparation currently being studied [7-11].

AYURVEDIC TREATMENTThere are some herbs which found effective against the

dengue fever these includes, Amaltas, Belladonna, Coriander leaves, Gentiana chirayata, Fenugreek, Boerhavia diffusa, Roj marinus officinalis, Basil leaves etc., for reducing fever, treating convulsions, intermittent and recurrent fever.

VECTOR PREVENTIONS AND CONTROLThere are numerous methods to cure and control the vectors

of malaria, chikungunya and dengue in particular and eventually the disease. But some methods are more convenient and easy than others. These methods depend on a number of factors given below.

• Ecology of the vectors

• Epidemiology of the disease

• Activities of the human beings

• Economic and social conditions of the person affected

• Environmental changes

Currently used methods

• Insecticidal treated bed nets

• Indoor pesticide spray

• Outdoor pesticide spray

• Chemicals addition to water

• Repellents coils

• Vaporizer mats and liquids

• Aerosols

Figure 6 Neem Oil Based Spreading Formulation.

Figure 7 Neem Powder Based Mosquito Coils.

Figure 8 Neem Oil Gel Impregnated formulation for Mosquito Net.

Figure 9 Nano-spray For Impregnating Military Uniform.

• Insecticide impregnated curtains

• Environmental management

• Biological control

• Water management

• Housing management

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• Medication

• Vaccines

• Personal protection

Indoor spray is approximately effective for 2-3 months. The insecticides should be chosen with utmost care e.g., DDT is come under persistent organic pollutants (POPs). Outdoor spray can be an effective method to keep the mosquitoes and other vectors away for some short duration. Repellents coils, liquid vaporizers and aerosols contain vaporizable insecticides e.g., coils have Pyrethroids as active ingredient (AI). Aerosols are used for immediate effect. In biological control some parasitic plants or animals are used e.g., larvivorous fish for Aedes larvae and Azolla an aquatic plant that grows on the water surface, making it difficult for the respiration (breathing) of the mosquitos’ larvae on the water surface.Medication includes Prophylaxis for malaria, Albendazole plus diethylcarbamazine for Lymphatic filariasis. As far as vaccines are concerned there are no any successful vaccines for dengue and malaria.

Botanical formulations against mosquitoes developed at IPFT

Mosquitoes are most disease transmitting vector worldwide and estimated to infect more than 700 million people annually. These cause more human suffering than any other vector and over one million people die from mosquito-borne diseases annually. In Africa, South America, Central America, Mexico and much of Asia with millions of resulting deaths. In Europe, Russia, Greenland, Canada, the United States, Australia, New Zealand, Japan and other temperate and developed countries, mosquito bites are now mostly an irritating nuisance. They can transmit disease without being affected themselves. Mosquito is a perfect example of one of the many organisms that can host diseases. Of the known 14,000 infectious microorganisms, 600 are shared between animals and human. So, it is imperative to first control these types of vectors, which eventually reduces the chance of being infected. Therefore, keeping this in mind we have developed a number of formulations to control mosquitoes borne disease without using harmful synthetic chemicals.

Mosquitoes can breed in any standing water, but they are particularly drawn to standing water with lots of organic debris. Nasty water is a common place to find mosquito larvae. In India, Institute of Pesticide Formulation Technology (IPFT) has

Figure 10 Mosquito Repellent Cream Based on Neem Oil.

developed many insecticides granules to eliminate mosquito breeding sites where removal of water is not possible like ground pools (Figure 4).

Larvae control

Larviciding is a general term for killing immature mosquitoes by applying some chemical agents, collectively called larvicides, to control mosquito larvae. Larval source management (LSM) involves both the modification of water habitats, often referred to as source reduction and the direct application of larvicides to control mosquito breeding.

Insect growth regulators (IGR): Methoprene an insect growth regulator agent that interrupts the growth cycle of insect larvae, preventing them from development beyond the pupa stage. Methopreneis moderately toxic to some fishes, shrimps, lobsters, and crayfish, but highly toxic to other fishes, freshwater invertebrates etc. It bio- accumulates in fish tissues.

We have formulated various larvicides based on plant origin e.g., tablets, pellets and granules. These can applied to control the breeding of mosquito. Here at IPFT, we have developed a novel formulation in the form of controlled release floating tablets with 10 % active ingredient. The tablet has a specific gravity of less than 1.0, so that it floats on the water surface. The floating tablet assures slow release of the pesticide. This can be utilized wherever desirable in stagnant waters, such as in lakes, ponds, swamp, storm sewer, catch basins, swimming pools and portable water containers such as rain barrels. This reduces the frequency of dosing and isnon-toxic to untargeted organisms, hence improving the selectivity (Figure 5).

Spreading oil

We have also developed neem oil based spreading formulation having the characteristics of maintaining the network cover over the surface of standing water to suffocate mosquito larvae. This formulation is safe for non-target, give enhanced biological activity, and cost effective (Figure 6).

Coils

A mosquito coil usually made into a spiral, and typically made from a dried paste of pyrethrum powder. IPFT has developed mosquito coil containing 28.8% neem kernel powder+28.8% botanical synergist. Coils were found more effective than commercially available synthetic pyrithroid based coils (Figure 7).

Mosquito net

A mosquito net offers protection against mosquitoes. It is possible to increase the effectiveness of a mosquito net greatly by treating it with an appropriate insecticide or mosquito repellant. These nets are dip-treated using a synthetic pyrethroid insecticide such as deltamethrin or permethrin which will double the protection over a non-treated net by killing and repelling mosquitoes. Therefore we have also developed natural pesticide based mosquito net (Figure 8).

Formulations developed at IPFT using chitosan encapsulation for impregnation in military uniforms Aedes Mosquitoe. In this Chitosan encapsulated permethrin was cross linked with TPP

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Cite this article

and sodium citrate in 1:1 ratio (Figure 9).

Cream as repellent

We have also developed repellent cream based on neem oil, and its bio-efficacy increased by adding a synergist agent (Figure 10).

CONCLUSIONSo it is concluded that, we have successfully developed and

tested at IPFT, various botanical based pesticide formulations. These formulations are safe for human, animals and environment.

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