Natural Products in Vector-Borne Disease Management

Natural Products in Vector-Borne Disease Management explores the potential application of natural products in vector control and disease management. The chapters discuss the global impact of specific vector-borne diseases, gaps in management, and natural products in specific stages of development - discovery, optimization, validation, and preclinical/clinical development. Toxic effects and mechanisms of action are also discussed. This book also explores how therapeutic plant derivatives can be used to combat the vectors of infection and how natural products can be used to manage and treat vector-borne diseases like malaria, leishmaniasis, dengue, and trypanosomiasis.

With the inclusion of case studies on field and clinical applications and the contributions from experts in the field, Natural Products in Vector-Borne Disease Management is an essential resource to researchers, academics, and clinicians in parasitology, virology, microbiology, biotechnology, pharmacology, and pharmacognosy working in the field of vector-borne diseases.

• Offers an alternative, natural approach to the prevention of vector-borne diseases
• Discusses the current and future perspectives of vector-borne diseases and natural product management
• Covers the properties of plants extracts and their phytoactives in vector-borne disease management
• Explores the advantages and disadvantages of natural products versus western medicine for treatment of vector-borne diseases

• Language: English
• Publisher: Academic Press
• Release date: Mar 2, 2023
• ISBN: 9780323912907

Book preview

Preface

This book, Natural Products in Vector Borne Disease Management, explores a wide range of topics related to the role of natural products from plants or marine sources used in various types of vector-borne diseases, in chapters written by leading industrial and academic experts in the field. Therefore, this book will offer guidance to current, new, and future researchers working in the field of phytopharmaceuticals, ethnopharmacology, ethnomedicine, alternative medicine, clinical medicine, and microbiology.

This book covers the role of natural products in various vector-borne diseases like onchocerciasis, babesiosis, arboviruses, leishmaniosis, schistosomiasis, encephalitis trypanosomiasis, chikungunya, malaria, and dengue. The book has 22 chapters. Chapter 1 discusses natural products in vector-borne disease management. Chapters 2, 3, 4, 6, 10, 11, 12, 13, 15, and 22 explore the role of natural products for the management of onchocerciasis arboviruses, babesiosis, schistosomiasis, leishmanial, dengue, encephalitis, trypanosomiasis, and malaria vectors. Chapters 5, 7, 18, and 20 demonstrate the impact of drug delivery systems like nanobiomaterials and nanoemulsions in various vector-borne diseases like leishmaniasis and malaria. Chapters 8, 9, 14, and 17 extend an expert opinion on marine natural products in vector-borne disease management Chapter 16 discusses the importance of Ayurveda in vector-born disease management, Chapter 19 explores the role of Carica papaya in the effective management of vector-borne disease, and Chapter 21 discusses insect-repellent plants.

This book is valuable for all professionals involved in the prevention, diagnosis, and treatment of vector-borne diseases using natural products. The book provides cutting-edge updated information and future perspectives on natural product bioactives as emerging sources of lead compounds for new drug discovery against vector borne diseases, which offer possible hope for the cure of these fatal diseases.

This work could not have been completed in a timely manner without the cooperation of the contributors, and their expertise and time in the production of this volume. Individually, the authors are the leaders in their field, and collectively, they embody an international collection of knowledge and experience in the phytochemical and pharmacology of natural products, to whom we are very grateful.

We would like to express our sincere gratitude and thanks to helpful Elsevier/Academic Press editorial team members including Howi M. De Ramos, Selvaraj Raviraj, P.K. Sajana Devasi, and Kattie Washington for their continued support, cooperation, and assistance.

We deeply appreciate my long-term mentor Prof. V.K. Dixit, who taught me something new in every conversation. Finally, I would like to thank my daughters Harshita and Ishita, for their love, understanding, support, and encouragement while this book was being written. We hope that you enjoy reading our book.

Nagendra Singh Chauhan

Durgesh Nandini Chauhan

Chapter 1: Potentials of natural products in vector-borne diseases management: Current and future perspectives

Devyani Rajputa; Umesh Kumar Patila; Durgesh Nandini Chauhanb; Kamal Shahc; Nagendra Singh Chauhand    wa Phytomedicine and Natural Product Research Laboratory, Department of Pharmaceutical Sciences, Dr. Harisingh Gour Vishwavidyalaya (A Central University), Sagar, Madhya Pradesh, India

b Columbia Institute of Pharmacy, Raipur, Chhattisgarh, India

c Institute of Pharmaceutical Research, GLA University, Mathura, Uttar Pradesh, India

d Drugs Testing Laboratory Avam Anusandhan Kendra (State Government Lab of AYUSH), Government Ayurvedic College, Raipur, Chhattisgarh, India

Abstract

In the tropical regions, mosquito-borne diseases continue to be a major cause of morbidity and mortality. An increasing burden of disease is being caused by arboviruses, most notably dengue, even in middle-income nations where malaria has been nearly eradicated, despite significant advancements in the control of the disease. This chapter goes over how novel approaches promise to significantly reduce the burden of disease in the future. The chapter highlights the need to increase understanding of disease distributions and critical vectors as well as to build specialized plans and capability for vector-borne illness surveillance, prevention, and outbreak responses. An exhaustive account on identified key knowledge gaps and potential research areas in vector-borne diseases management with botanical products is also given.

Keywords

World Health Organization; Vector-borne; Lymphatic filariasis; Malaria; Japanese encephalitis; Chikungunya; Dengue; West Nile virus; Yellow fever; Zika virus; Leishmaniasis; Sandfly fever

Introduction

An infectious pathogen transmits from an infected human or animal host to an uninfected one by a vector, which is an organism. Arthropods are most frequently used as vectors. Dengue, malaria, Zika virus, yellow fever, chikungunya, onchocerciasis, schistosomiasis, lymphatic filariasis, leishmaniasis, Chagas disease, and Japanese encephalitis are among the most common vector-borne diseases in the world, according to the World Health Organization. Lyme disease, tick-borne encephalitis, African trypanosomiasis, and West Nile fever are additional vector-borne illnesses that are significant in the region. The majority of vector-borne diseases are found in low- and middle-income nations that are tropical or subtropical in climate (Djalante, 2019; Wachsmuth et al., 2018).

The World Health Organization (WHO) estimates that higher than 1 million people die every year as a result of vector-borne illnesses (VBDs), which make up more than 17% of all infectious diseases. A capable vector, such as a mosquito, midge, or fly, transmits vector-borne diseases from one person to another (Lemon & Institute of Medicine U.S. Forum on Microbial Threats, 2008).

Numerous VBDs are categorized as neglected tropical diseases (NTDs), including onchocerciasis, leishmaniasis, human African trypanosomiasis (HAT), and arboviral illnesses including dengue and chikungunya. Prioritization and funding for NTD research have lagged until the last 5 to 10 years, and the burden of these diseases is little recognized. We still do not fully understand key facets of NTD biology, prevention, and epidemiology. While there are fewer deaths from vector-borne NTDs than from malaria globally, these diseases nonetheless generate high rates of morbidity and place a considerable cost on public health; for example, dengue infections grew by about 450% globally from 1990 to 2013 (Undp et al., n.d.-a; Wilson et al., 2020). A few zoonotic NTDs also provide a veterinary health risk. The main way for regulating many VBDs both historically and currently is vector control. Additionally, vector control is now the sole available strategy to safeguard populations against various infections, including West Nile disease, chikungunya, Zika, and dengue (for which a vaccine is licensed but not widely utilized due to safety concerns). By minimizing or preventing human interaction with the vector, vector control seeks to reduce the spread of infections. Targeting young vectors can be accomplished by using larvicides, predator species, chemical or biological larvicides, or by removing suitable aquatic habitats (e.g., habitat modification or manipulation). Adult vectors can be gotten rid of using methods like indoor residual spraying (IRS), space spraying, and others that kill adult vectors and/or minimize adult vector interactions (blood-feeding success) with human and/or animal reservoir hosts (e.g., topical repellents, house screening, insecticide-treated bed nets [ITNs], insecticide-treated dog collars). A number of cutting-edge vector control techniques are also being developed, such as genetically altering mosquitoes, infecting vectors with bacteria (like Wolbachia), and treating eaves tubes with insecticide (Takken and van den Berg, 2019; Undp et al., n.d.-b; Walther et al., 2016).

Ancient

Ayurvedic system of medication looked into causes, indication, and remedial options for a numeral of diseases, such as transmissible diseases. It covers pathogenic with nonpathogenic organisms which are found in the human body. It also includes parasite, worm, and other microbe descriptions. Ayurveda researcher provided details on pathogenic organisms, including their types and nature, with their role in disease progression. Ayurveda describes on epidemics and infectious diseases which connects to the vector-borne diseases management. The Ayurvedic physician also discussed natural treatment options for vector-borne diseases, such as the use of plants and plant-based formulations. Ayurveda is the world’s oldest scientifically codified medical system. According to Ayurveda, there are three types of transmissible diseases: Agantukaroga, Janapadodhwamsa, and Krimi.

Modern

Vector control strategies

Insecticides, predators, pathogens, lure-and-kill trapping, environmental management, and other techniques are used to suppress the vector population, while vector population replacement involves genetically modifying the vector so that it either stops reproducing its nonviable generations, or it loses the capacity to reproduce or spread disease (de Rossiter Corrêa et al., 2004).

Biochemical strategies

●India employs pesticides such as organochlorines (DDT), organophosphates (malathion), and particular classes of synthetic pyrethroids for indoor residual spraying (IRS), fogging, and aerial spraying (deltamethrin, cyfluthrin, alpha-cypermethrin, lambda-cyhalothrin, etc.) (Poopathi and Tyagi, 2006).

●The WHO has approved the treatment of water for larvae with temephos and Bti.

Biological control agents

●Biological agents can be employed to target several mosquito life stages, including parasites, viruses, and predators. To reduce the number of mosquito larvae, viruses, fungi, bacteria, fish, predatory insects like dragonflies and copepods, and notonectids have all been used.

●Materials that have been insecticide-treated, such as long-lasting insecticide nets (LLIN).

●It consists of wall hangings, window curtains, insecticide-treated nets (ITNs), and long-lasting insecticide nets (LLINs), the need for which has risen recently (Sinh Nam et al., 2000).

Repellents

●Repellents are created using chemical substances that have an unpleasant taste or smell to mosquitoes.

●Better repellent plants belong to different families, for example, Poaceae family—particularly Cymbopogon species—being the dominant one. Asteraceae, Fabaceae, and Lamiaceae species all exhibit encouraging outcomes.

●Indalone, N,N-diethyl-m-toluamide, and dimethylphthalate 2-ethyl-1, 3-hexane diol (Rutgers 612) are examples of synthetic compounds that have been utilized as repellents (DEET) (Tisgratog et al., 2016).

Insect traps

●The ovitrap, also known as an oviposition trap, was primarily created for the purpose of monitoring Aedes vectors. Later, it was modified to make it deadly to Aedes aegypti adults or larvae.

●Use of a propane-burning apparatus that produces CO2, heat, and water vapor attracts mosquitoes to the flame. A relatively modern way of eliminating mosquitoes without the use of harmful chemicals involves drawing them into a net or holder where they are gathered (Kline, 2007; Table 1).

Table 1

Vector-borne disease and its management

Malaria

Approximately three billion people live in more than 80 countries where malaria is endemic and spread by anopheline mosquitoes. Sub-Saharan Africa is the area in the globe with the highest prevalence of malaria, accounting for more than 85% of cases and 90% of fatalities, the majority of which are children under the age of 5. Malaria continues to have a very detrimental influence on public health, with 228 million cases reported worldwide, of which 213 million (93%) were reported in Africa alone. Recent big outbreaks have wreaked havoc in many places (Tuteja, 2007).

Filariasis

Wuchereria bancrofti and Brugia spp. are two mosquito-transmitted pathogens that can produce a variety of clinical manifestations (including lymphedema in more than 15 million people and hydrocele in 25 million males), and at least 36 million people still have these symptoms of chronic illness. But it is clear that reducing its vectors is necessary for eradicating lymphatic filariasis (Taylor et al., 2010).

Dengue

The dengue virus, which has four different serotypes, is caused by the flaviviridae family. With 3.6 billion people living in areas at risk of transmission and hundreds of millions of dengue fever cases recorded each year, it is currently the most common arthropod-borne viral disease affecting humans and is responsible for continuing epidemics in many nations (Kularatne, 2015).

Zika virus

Numerous nations in Latin America and the Pacific also have continuing outbreaks brought on by the flaviviridae. While Aedes albopictus is regarded as a secondary vector, Aedes aegypti is thought to be the main vector connected to ZIKV outbreaks. But this virus’s incidence and dissemination are also influenced by a number of additional species. It is currently regarded as one of the diseases that poses the greatest threat to public health (Musso and Gubler, 2016).

Chikungunya

The togaviridae family is the cause of chikungunya fever (CHIKF), which is characterized by an antalgic stance gait and excruciating articular pain. Up to 90% of people with infection who progress to the chronic stage may do so (52% in the American continent). Recently, a number of outbreaks have been reported in a number of nations (Vu et al., 2017).

Yellow fever virus

Flaviviridae is a hemorrhagic, possibly fatal RNA virus that causes outbreaks in a number of nations, particularly in populations that have not received vaccinations. It emerges in cycles, with outbreaks spaced roughly 7–10 years apart. In the summer of 2016, 42 nations detected a danger of transmission, with 29 of them in Africa in 2017. In addition, 47 nations declared YFV endemic. Numerous outbreaks are still being documented, with the highest fatality rate of up to 33.6%. The safest, most affordable, and most efficient means to prevent YF is vaccination; "70 to 90 million doses are generated worldwide annually (Douam and Ploss, 2018)."

Miscellaneous

In each year, the WHO reports 67,000 cases of Japanese encephalitis, of which 20 to 30% result in death and 30% to 50% of survivors develop severe neurological complications. It is still possible to find new strains that are genetically related to bacteria that were present in earlier epidemics. The main arbovirus responsible for epidemic encephalitis in the United States was the St. Louis encephalitis virus (Diaz et al., 2018). Numerous cases are being caused by its resurgence. Horses are the domesticated species that contract the West Nile virus most frequently, much like humans do. Neurological symptoms are the most frequently reported symptom in 80% of instances, and 90% of those 20% who do exhibit clinical signs pass away. However, recent outbreaks involving people have received attention. It is common to find different pathogenic blood-borne bacteria in mosquitoes (Petersen and Roehrig, 2001). It is not yet known if these bacteria can develop and eventually spread during blood meals or if their presence in mosquitoes can be related to their uncommon ingestion of blood meals or environmental acquisition. In adult mosquitoes, various pathogenic alpha-proteobacteria have been discovered (xeno-monitoring studies), including Ehrlichia spp., Anaplasma spp., Bartonella spp., Candidatus Neoehrlichia, and Rickettsia spp. More intriguingly, research has revealed that Anopheles mosquitoes may be capable of transmitting the rickettsiosis-causing agent Rickettsia felis, which causes fever rickettsiosis. The principal vector of the disease in Sweden and Finland is mosquitoes (Aedes), which are first known to carry Francisella tularensis. There are many complex factors that may explain the spread of these diseases; however, climate change and population growth continue to be the main ones. Inadequate vector-control efforts, limited access to high-quality healthcare, rapid and unplanned urbanization of tropical regions combined with unsanitary conditions, and a deterioration of public health infrastructures are just a few of the factors that may be involved (Gofton et al., 2015; Grech-Angelini et al., 2020; Hodžić et al., 2015; Table 2).

Table 2

Natural products

The world of plants contains a vast, untapped reservoir of phytochemicals that could be widely utilized in mosquito control programs in place of industrial insecticides. It has been shown that certain plant-derived secondary components, such as isoflavonoids, steroids, alkaloids, terpenes, pterocarps, and lignans, have the capacity to kill mosquito larvae depending on their chemical make-up. They also reported the isolation of several bioactive toxic components from various plants and described how lethal each of these components was to various mosquito species (Shaalan et al., 2005).

Neem oil

Azadirchata indica is indigenous to India and other Southeast Asian nations; the neem tree is an evergreen tropical tree. Neem is a member of the Meliaceae plant family (Islas et al., 2020). Azadirachtin, Nimbidol, Nimbin, Sodium nimbinate Nimbidin, Gedunin, Salannin, and Quercetin are the active ingredients in the use of neem oil as an insecticide. The ability of neem to naturally repel mosquitoes is a crucial tool in the war against malaria. By altering their behavior and physiology, neem derivatives kill almost 500 pests, including ticks, mites, insects, and nematodes, around the world. Neem typically repels bugs and stunts their growth rather than immediately killing them. Neem treatments are ideal for pest control in rural areas since they are reasonably priced, safe for use on higher animals, and attract the most beneficial insects (Chauhan et al., 2018; Singh, 2019).

Citronella oil

Cymbopogon winterianus Jowitt (Cardiopteridaceae) is a native of tropical Asia and India. It is a common herb in Asian cooking (Afzal et al., 2018). Active ingredients include citronellal, geraniol, and citronellol are all abundant in Cymbopogon winterianus essential oil. Various ingredients in citronella include l-limonene, citronellyl acetate, ellemol, and other sesquiterpene alcohols. The best option is typically citronella oil because it is a safe, natural alternative to pharmaceutical insect repellents like DEET. They come in the form of solid goods like candles and cartridges that repel insects using citronella oil. In addition, citronella oil is applied as tablets or pellets around trees and plants as well as in outdoor living spaces (Dutta et al., 2016; Wany et al., 2013).

Lavender oil

Lavender, True Lavender, Garden Lavender, Lavanda, and Lavandula are other names for Lavandula angustifolia (family Lamiaceae) (De et al., 2012). It is a perennial plant that is evergreen. Active components consist of pinene, linalyl acetate, geraniol, linalool, cineol, limonene, borneol, and tannins are some of the therapeutic substances found in it (Geetha and Roy, 2014).

Peppermint oil

A perennial herb, Mentha piperita L (Labiatae), grows 30–90 cm tall. Square, branching stems that are either upright or rising and always have a quadrangular top (Ilyina et al., 2017). Peppermint oil is watery in viscosity, transparent to pale yellow in color, and has a fresh, menthol-like aroma. Menthone is an active component. p-Menthane-3,8-diol is a significant breakdown product of menthol, the alcohol present in mint oils used as a peppermint flavoring. The EPA has authorized the use of p-menthane-3,8-diol as a mosquito repellant since 2000. The essential oil of Mentha piperita shows outstanding and potential anti-Aedes aegypti adult repellant properties (Regnault-Roger et al., 2012; Werrie et al., 2020).

Allium sativum

Garlic is the common name for Allium sativum L. Oil bulbs have been proven to have larvicidal effect against Culex pipiens mosquito larva, while garlic extracts are used to kill Anopheles stephensi and Culex quinquefasciatus mosquito larva (Cheraghi Niroumand et al., 2016; Muturi et al., 2018).

Citrullus colocynthis L.

Bitter cucumber, bitter apple, and desert ground are common names for Citrullus colocynthis L. Schrad. A medical herb called Citrullus colocynthis is utilized as a mosquito repellent that also kills mosquito eggs and larvae (Afzal et al., 2018). Leaf extracts from Citrullus colocynthis have larvicidal effects on Culex quinquefasciatus larvae in their early fourth instar. Extracts from the entire plant kill the early fourth instar larva of Anopheles stephensi, while extracts from the plant’s seeds also kill the third instar larvae of Culex quinquefasciatus and Anopheles stephensi (Pravin et al., 2013; Rahuman et al., 2008).

Ocimum basilicum L.

Culex quinquefasciatus, Anopheles stephensi, and some female Culex pipiens mosquito species are repulsed by the essential oils of Ocimum basilicum, popularly known as great basil. Ocimum basilicum plant stem extracts have larvicidal effects on Culex quinquefasciatus larvae (Moore, 2006; Paulraj and Ignacimuthu, n.d.).

Dysoxylum malabaricum

This plant, commonly known as white cedar, was investigated for larvicidal, pupicidal, adulticidal, and antiovipositional effects against Anopheles stephensi using methanolic preparations of the leaves (Senthil Nathan et al., 2006). Anopheles stephensi is 90% larvicidal, pupicidal, and adulticidal when the plant is extracted with 4% methanol. By preventing the adult mosquitoes’ reproductive cycle, it also reduces the population rate. Researchers used 3-, 24-, and 25-trihydroxycycloartane and beddomeilactone with ethyl acetate-extracted Dysoxylum malabaricum to measure the larvicidal, pupicidal, and adulticidal activities against Anopheles stephensi. Three, twenty-four, and twenty-five trihydroxycycloartane and beddomeilactone, both of which limit Anopheles stephensi’s growth, had a 90% larval mortality rate at 10 ppm concentration (Masur et al., 2014).

Khaya senegalensis

Khaya senegalensis is also known as Khaya wood and African Mahogany. The plant’s seeds are extracted using acetone, ethanol, hexane, and methanol, among other solvents (Shaalan et al., 2006). The effectiveness of these extracts against Culex annulirostris was investigated. At varied concentrations, various seed extracts were used, including acetone (12 mg/L), ethanol (5.1), hexane (5.08), and methanol (7.62). At a concentration of 100 mg/L with LC50, these extracts have a 100% death rate (Mukaila et al., 2021).

Ficus benghalensis

Banyan, also known as Ficus benghalensis, is toxic to Culex quinquefasciatus and Anopheles stephensi mosquito species (Govindarajan et al., 2011b). This plant has been shown to be larvicidal against various Culex and Anopheles mosquito larval stages. Chi-square test was used to obtain the 95% confidence limits for the data at LC50 and LC90 values. Early, second, third, and fourth instar larvae of Culex quinquefasciatus and Anopheles stephensi are resistant to the methanolic extracts of Ficus benghalensis, which are used as larvicides (Khaliq and Abdul Khaliq, 2017).

Lansium domesticum

Lansium domesticum is also known as langsat. Aqueous solution is used to extract parts of this plant, and the resulting substance has larvicidal effects on Culex quinquefasciatus (Klungsupya et al., 2015).

Moschosma polystachyum

The mosquito species Culex quinquefasciatus was used to assess the herb Moschosma polystachyum’s toxicity (Maheswaran and Ignacimuthu, 2013). At concentrations of 1.0 and 2.5 mg/cm², the active ingredient octacosane provided protection for 85.2±1.7 min and 54.6±2.3 min, respectively. Octacosane’s overall percentage of protection was 96.2±0.9 at a concentration of 2.5 mg/cm² and 86.4±1.3 at a concentration of 1.0 mg/cm² (Govindarajan et al., 2011a).

Ocimum sanctum

Utilizing mosquito bioassay-guided fractionation, the hexane extract of Ocimum sanctum was examined and produced components 1 and 2 (Kelm and Nair, 1998). NMR spectral data from the 1H and 13C bands were used to determine the structures of these substances. The substances eugenol (1) and (E)-6-hydroxy-4,6-dimethyl-3-heptene-2-one (2) demonstrated mosquitocidal effect on fourth-instar Aedes aegyptii larvae at 200 and 6.25 g mL−1 in 24 h, respectively (Rahuman et al., 2008).

Magnolia salicifolia

Six mosquitocidal chemicals were obtained from Magnolia salicifolia after bioassay-guided isolation and purification. When separated from the bark, geranial and neral caused 100 ppm in 24 h of 100% mortality in 4th instar Aedes aegypti (Kishore et al., 2014). At 20 ppm in 24 h, trans-anethole from the leaves showed 100% death in Aedes aegypti 4th instars. Methyl eugenol from the leaves and isomethyl eugenol isolated from leaves, fruits, and flowers, respectively, both demonstrated 100% death in 4th instar Aedes aegypti after 24 h at 60 and 80 ppm. The sesquiterpene lactone costunolide, which was first discovered in the fruits of Magnolia salicifolia, caused Aedes aegypti of the fourth instar to die completely within 24 h (Tamaki et al., 2018; Tsuruga et al., 1984).

Triphyophyllum peltatum

The root bark of Triphyophyllum peltatum yielded the novel naphthylisoquinoline alkaloid 5′-O-demethyldioncophylline A (Bringmann et al., 1998). A bromination-benzylation process substantially aided in its ordinarily challenging separation from the primary alkaloid, dioncophylline A, which was the dominant component. The resulting derivative made it possible to conduct an anomalous X-ray diffraction crystal structure research, which verified the novel alkaloid’s entire absolute stereostructure. The validity of the structure was further strengthened by a partial synthesis from dioncopeltine A. It was demonstrated that the natural product has antimalarial effects on erythrocytic Plasmodium falciparum (Li et al., 2017).

Microcos paniculata

An innovative alkaloid (N-methyl-6 beta-(deca-1′,3′,5′-trienyl)-3 beta-methoxy-2 beta-methylpiperidine) discovered in the stem bark of Microcos paniculata has demonstrated effective insecticidal activity against Aedes aegypti second instar larvae (Abdullah Aziz et al., 2013).

S. curtisii

A new pentacyclic Stemona alkaloid with a pyrido[1,2-a]azepine A,B-ring system named stemocurtisinol and the well-known pyrrolo[1,2-a]azepine alkaloid oxyprotostemonine have been discovered from a root extract of Stemona curtisii. X-ray crystallography and spectral data interpretation were used to identify the structure and relative stereochemistry of stemocurtisinol. Its C-4 and C-19 positions are in the opposite configuration as oxystemokerrin, of which it is a diastereoisomer. On mosquito larvae, the various alkaloid components had a considerable larvicidal effect (IC(50) 4–39 ppm) (Anopheles minimus HO) (Mungkornasawakul et al., 2004; Online Research Online, 2005).

Piper longum

After 24 h, it was discovered that a methanol extract of Piper longum fruit was effective at 10 microg/ml against Culex pipiens pallens mosquito larvae. This activity was discovered to be caused by the piperidine alkaloid pipernonaline, whose 24-h median lethal dose (LD50) was 0.21 mg/liter. The three organophosphorous insecticides malathion, chlorpyrifos-methyl, and pirimiphos-methyl, which were utilized for comparison in this investigation, had LD50 values that were not significantly greater than those of pipernonaline (Rahuman et al., 2008).

Pisonia alba

Pisonia alba leaf extracts were examined for their ability to kill mosquitoes such as Aedes aegypti, Anopheles stephensi, and Culex quinquefasciatus (Baranitharan et al., 2019). The 24-h LC50 values of the Pisonia alba extracts were evaluated by Probit analysis after 25 early fourth instar larvae of Anopheles stephensi, Culex quinquefasciatus, and Aedes aegypti (Anopheles stephensi, Culex quinquefasciatus, and Aedes aegypti) were exposed to various concentrations (50–250,106) (Thakur et al., 2017).

Terminalia chebula

Hexane, benzene, ethyl acetate, methanol, and chloroform extracts of Terminalia chebula were tested for their toxicity against these three key vector mosquitoes (Culex quinquefasciatus, Anopheles stephensi, Aedes aegypti) (Veni et al., 2017). Larval mortality was seen 24 h after exposure. The Terminalia chebula methanol extract had LC50 values of 87.13, 93.24, and 111.98 ppm against the larvae of Anopheles stephensi, Aedes aegypti, and Culex quinquefasciatus, respectively. All extracts demonstrated a modest larvicidal effect (Thanigaivel et al., 2017).

Mechanism of action of phytochemicals in target insect body

Secondary metabolites that have evolved to defend plants from herbivores typically make up the poisonous active components in plant extracts. As the insects consume these secondary metabolites, they may be exposed to toxic substances that have relatively nonspecific effects on a range of molecular targets. Proteins (including receptors, enzymes, signaling molecules, structural proteins, and ion channels) are some of these targets, along with biomembranes, nucleic acids, and other cellular components (Wink, 2008). The main one of them is anomalies in the nervous system, which in turn has a variety of consequences on insect physiology at various receptor sites (such as in neurotransmitter synthesis, storage, release, binding, and re-uptake, receptor activation and function, enzymes involved in signal transduction pathway). The mechanism of action of plant secondary metabolites on insect body discovered numerous physiological disturbances, such as acetylecholinesterase inhibition (by essential oils), GABA-gated chloride channel (by thymol), disruption of sodium and potassium ion exchange (by pyrethrin), and inhibition of cellular respiration (by rotenone) (Hussain et al., 2019). Aside from hormonal imbalance, mitotic poisoning (azadirachtin), disruption of the molecular events of morphogenesis, alteration of the cholinergic system’s behavior and memory (by essential oil), blockage of calcium channels (by ryanodine), inhibition of nerve cell membrane action (by sabadilla), blockage of octopamine receptors (by thymol), etc., this disruption also includes alteration of the hormones and their balance. Acetylcholinesterase (AChE) is a crucial enzyme that stops the transmission of nerve impulses through the synaptic pathway, and it has been observed that AChE is resistant to organophosphorus and carbamates. It is generally known that one of the primary resistance mechanisms in insect pests is a modification in the AChE gene (Nahak, 2015; Tehri and Singh, 2015).

Epidemiology

Medical and veterinary entomologists provide major contributions to multidisciplinary programs that study, track, and manage parasites transmitted by vectors and are essential to comprehending the epidemiology of diseases transmitted by vectors. Medical entomology is essential to public health during times of large outbreaks, war, starvation, or natural calamities that devastate communities and increase exposure to vectors (Barker and Reisen, 2018). Because neither the invaders nor the indigenous population were immune to the new parasites they were exposed to, massive movements of populations (such as military personnel) into regions where vector-borne diseases are common have had devastating effects on both. An increase in the spread of parasites and their vectors into new geographic regions has been caused by recent changes in international travel health regulations, affordable and accessible rapid transportation, and the recent expansion of global trade, putting at risk populations of people and other animals that had not previously been exposed to them (Eder et al., 2018). Emerging infectious diseases are a group of pathogen outbreaks that have been spreading across the globe. Vector-borne parasites are responsible for a sizable portion of newly emerging infectious diseases, either as a result of anthropogenic (human-induced) changes that have given vectors or parasites opportunities to expand their distribution in time or space or because the parasites have evolved into more virulent or drug-resistant forms (Chan et al., 1999).

Epidemiology developed became a science through the examination of infectious disease epidemics. The natural history and spread of diseases among human and animal populations are the focus of the contemporary academic area of epidemiology (etymology: epi ¼ upon, demos ¼ people, logos ¼ study). Arthropod vectors, vertebrate hosts, and parasites are the basic causes of vector-borne illnesses (Keeling et al., 2011). Because an arthropod is necessary for the transfer of the parasite to uninfected hosts as well as interactions between the parasite and its vertebrate host, the spread of diseases by arthropods is particularly complicated. Environmental factors such as temperature and rainfall have an effect on these processes by affecting the rate of parasite maturation within the arthropod host as well as the abundance of arthropod and vertebrate hosts throughout time and space (O’Dwyer et al., 2020).

To comprehend the epidemiology of arthropod-borne diseases, one must have a thorough grasp of the biology of parasites, vectors, and hosts as well as how they interact in varied ecosystems. The frequency of interaction between vertebrate hosts and vectors varies, ranging from infrequent (such as with mosquitoes) to intimate and constant (e.g., sucking lice). The host frequently provides the vector with a home and food in the form of blood or other tissues (Mills et al., 2010). The vector, vertebrate host, and parasite are brought together in time and place by the vector’s blood feeding, which has the potential to transmit parasites from infected to vulnerable vertebrate hosts. A vector normally needs to eat two blood meals for the parasite to spread over the course of its lifetime—the first to become infected and the second to do so. Blood meals provide the arthropod with the nutrients it requires for metabolism, metamorphosis, and/or reproduction (Lefèvre and Thomas, 2008).

WHO guidelines for vector-borne diseases

The global vector control response 2017–30, which was created over the course of an intense consultation process that began in June 2016, is anticipated to be approved by the seventieth World Health Assembly in May 2017. The response was developed in close collaboration with numerous experts and partners from all over the world under the overall direction of Pedro Alonso, Director of the Global Malaria Programme, Dirk Engels, Director of the Department of Control of Neglected Tropical Diseases, and John Reeder, Director of the Special Programme for Research and Training in Tropical Diseases (World Health Organization, 2018).

Millions of individuals throughout the world are infected by viruses, parasites, and bacteria that are spread by mosquitoes, flies, bugs, and other vectors. Numerous illnesses are brought on by them, including those caused by the Zika virus, leishmaniases, Chagas disease, and malaria. To improve vector management globally, the World Health Organization (WHO) has created a new strategy. At the 2017 World Health Assembly, Member States applauded this integrated approach and endorsed a resolution in favor of the plan (WHO, 2022; Zinszer et al., 2020).

Since 2014, there have been significant outbreaks of the diseases zika virus, yellow fever, dengue, malaria, and chikungunya due to social, demographic, and environmental reasons. If vector control is properly done, the majority of vector-borne diseases can be avoided. Strong political and financial commitment has significantly reduced the prevalence of Chagas disease, onchocerciasis, and malaria (Fritzell et al., 2016). Vector control has not yet been utilized to its fullest extent or had its greatest influence on other vector-borne diseases. This condition can be improved by realigning programs to maximize the delivery of interventions that are pertinent to the local context. This solution requires for improved sectoral and intersectoral cooperation, improved community involvement in vector management, reinforced monitoring systems, greater public health entomology (and malarialogy) expertise, and novel interventions with proven efficacy (Moise et al., 2021).

Future prospects

Many infectious diseases are spread through the use of arthropod vectors. More than three billion individuals are currently exposed to vector-borne infections because they live in endemic regions. It is extremely difficult to forecast the prevalence of vector-borne diseases in the future due to significant changes in the biology of arthropod vectors. However, the ecology and distribution of arthropod vectors are significantly impacted by both urbanization and climate change. Such processes frequently cause a nonrandom process of biodiversity loss that homogenizes species biotically (Githeko et al., 2000). The data now available demonstrate a trend toward progressive rises in the prevalence and quantity of human-associated vectors that may thrive in urban environments, raising the possibility that these vectors will come into contact with human hosts. We anticipate a rise in the prevalence of vector-borne diseases as a result. We believe that resources ought to be made accessible and should be focused on integrated vector management plans that use tried-and-true vector control tools. In addition, adhering to environmental regulations and establishing fundamental sanitary infrastructure at the beginning of IVM’s development would significantly save expenditures. This might improve IVM’s ability to lessen social health determinants and social injustices brought on by exposure to vectors (Campbell-Lendrum et al., 2015; Martens et al., 1995).

Climate change is one of the largest threats to human health in the 21st century. The climate directly influences health through climatic extremes, air quality, sea-level rise, and other effects on food production systems and water supplies. Infectious diseases are influenced by climate, and these diseases have had a major impact on the development of civilizations throughout history as well as the expansion of humankind into new lands (Schaffner et al., 2021). Our analysis focuses on significant regional shifts in the distribution of vectors and pathogens that have been noticed recently in temperate, peri-Arctic, Arctic, and tropical highland regions. These changes were predicted by experts around the world. If we do not mitigate and adapt to climate change, there will probably be more alterations in the future. A few of the significant factors that affect the spread and severity of human diseases include the movement of people, animals, and goods; current control measures; the availability of effective medications; the standard of public health services; human behavior; and political stability and conflicts. Due to the rise in medication and insecticide resistance, significant funding and research efforts must be maintained to continue the battle against current and new diseases, especially those that are vector-borne (Caminade et al., 2019; Schaffner et al., 2021).

Compounds that are insecticidal, acaricidal, and repellant have a sizable and expanding industry worldwide. For instance, the global market for insect repellents was worth 3.2 billion US dollars in 2016 and is anticipated to grow to 5 billion by 2022. This market might be more lucrative for some companies than vaccinations, which would decrease support for and interest in ectoparasite control vaccines (Jain et al., 2020). It is possibly one of the factors that prevented BM86-based vaccines from finding success on the market despite their efficacy. It has long been accepted that combining vaccination with other preventative therapies, such as insecticides, acaricides, and repellents, is the most effective way to manage ectoparasite vectors. Vaccines should be seen as an alternative and complementary intervention to insecticides and acaricides in order to effectively control ectoparasites. This will increase demand for vaccines while reducing the need for these chemicals (Medlock and Leach, 2015).

When creating vaccinations to manage ectoparasite vectors, security and cost-effectiveness are crucial considerations. To address these issues, research should focus on effective formulations with cutting-edge adjuvants for oral vaccination delivery and nanoparticle-based vaccines (Parham et al., 2015).

In general, vaccines for ectoparasite vector control in people and companion animals are thought to prevent infestations and the spread of infections. Based on the knowledge currently available, it might be possible to create vaccinations that stop the spread of bacteria and protozoan parasites, which take hours to days to spread when a vector feeds on blood. However, the majority of viruses spread quickly after a vector bite, making transmission prevention more challenging (Khan, 2015). In order to affect the life cycle of the vector and transmit illnesses, various biological processes rely on interaction with the ectoparasite; as a result, the immune response to vaccination (such as antibodies) cannot prevent vector attachment or feeding. One open question is how to combine vector- and pathogen-derived antigens to target both of them with a single vaccination (Merino et al., 2013). Two further innovative strategies have been proposed to control illnesses with alpha-Gal on their surface and tick vector infestations: developing vaccines based on alpha-Gal glycoproteins and glycolipids and targeting tick galactosyltransferases. However, these options still require validation (Otranto and Wall, 2008).

Food-grade nanoparticles are one type of nanotechnology that can be used to overcome mosquito drug and insecticide resistance that has developed as a result of traditional treatment methods used to halt dengue and malaria outbreaks. When contrast to metallic nanoparticles, food-grade nanoparticles have no adverse effects (Estrada-Peña et al., 2012). They respect both people and the environment. Transgenic (genetically altered) mosquitoes and a medication cocktail have been tested to address difficulties. These techniques provide difficulties because multidrugs are present in mosquito bodies and trans-genes are destroyed. Nanomedicines are predictable and may help with the treatment of dengue and malaria. The use of nanoparticles in a multidrug combination may have promising results. Special consideration should be given to biodegradable nanoparticles with various drug encapsulating, food-grade nanoparticles like curcumin, and metallic nanoparticles like ZnO in order to stop the evolution. Future advancements in food-based nanoparticles, which are safer than metallic pharmaceuticals, multidrugs, and biodrugs, may help Pakistan and other developing countries eradicate vector-borne diseases. More investigation is required to determine the larvicidal efficacy of food-based nanoparticles against the mosquito larvae that transmit malaria and dengue disease (Hromníková et al., 2022; Tsao, 2009).

Current trends, opportunities, and knowledge gaps in vector-borne diseases management with botanical products

The use of natural and synthetic repellents, available in many pharmaceutical forms, is rising rapidly as a result of the advent of vector-borne illnesses like Dengue, Zika, Chikungunya, Yellow Fever, and Malaria. The formulation choice will be influenced by the type of repellent active (natural or synthetic), pharmacological forms (spray, lotion, cream, gel), action time length (short or long), environment of exposure, and the user (adult, pregnant women, children, newborn) (Lee, 2018). Essential oils, DEET, IR3535 (ethyl butylacetylaminopropionate), icaridin (Picaridin), and DEET are the most widely used repellents. Each of these compounds has benefits and drawbacks. DEET is the industry standard since it is the most effective and oldest insect repellent on the market. Due of this, a variety of traditional formulations with DEET in spray and lotion form are readily accessible on the market. However, DEET is contraindicated in pregnant women and children up to 6 months old due to its toxicity. DEET has been a choice along with other popular items like IR3535 and icaridin (picaridin), which are made of less dangerous components. The best choice due to the lower levels of toxicity exhibited is IR3535, which may be given for children over 6 months of age and pregnant women. Children older than 6 months old and pregnant women may be taken IR3535 because it has the lowest level of toxicity of the three alternatives (Anoopkumar and Aneesh, 2022; Raveen et al., 2017).

Icaridin has the advantage of having the longest-lasting effect among the aforementioned repellents and is as effective as DEET while being less harmful. Controlled release technologies have served as the foundation for the novel formulations (CRS). Among the CRSs for repellents are polymer micro/nanocapsules, micro/solid lipid nanoparticles, nanoemulsions/microemulsions, liposomes/niosomes, nanostructured hydrogels, and cyclodextrins. To extend the duration of the repellent activity and reduce penetration and, consequently, systemic toxicity, numerous formulations based on micro- and nanocapsules with DEET and essential oils exist. Unexplored in terms of research is the creation of new IR3535 and icaridin formulations. The current trend is to use natural repellent actives like essential oils, which have a short-lived repellent effect after being applied to the skin but are low toxic and environmentally benign. Natural repellents have been transported by CRSs to enhance long-lasting repellent efficacy, lessen skin permeability, and limit systemic effects (Messenger and Rowland, 2017; Tavares et al., 2018).

Due to their effectiveness, affordability, and environmental friendliness, plant-based pesticides have recently attracted a lot of interest. Plants produce a variety of phytochemicals, which are defense compounds that can be employed to control insect outbreaks. Chemical ecology examines the role that particular chemicals (allele chemicals) play in how organisms interact with one another and their environments (Senthil-Nathan, 2015). These defense mechanisms, known as allelochemicals, affect a wide range of molecular targets, including as cellular proteins, enzymes, nervous system signal transduction (neurotransmitter synthesis, storage, and release, as well as receptor binding), as well as herbivore or microbe metabolic processes (Mpumi et al.,