Perspective Received: 17 May 2013
Revised: 23 October 2013
Accepted article published: 31 October 2013
Published online in Wiley Online Library: 19 November 2013
(wileyonlinelibrary.com) DOI 10.1002/ps.3676
Vector population manipulation for control of arboviruses – a novel prospect for India BP Niranjan Reddy,a∗ Bhavna Guptab and B Prasad Raoa Abstract India, the seventh largest country in the world, has diverse geographical and climatic regions with vast rural and peri-urban areas. Many are experiencing an escalation in the spread and intensity of numerous human diseases transmitted by insects. Classically, the management of these vector-borne diseases is underpinned by either chemical insecticides and/or environmental management targeted at the vector. However, these methods or their present implementation do not offer acceptable levels of control, and more effective and sustainable options are now available. Genetic strategies for the prevention of arbovirus transmission are most advanced for dengue and chikungunya, targeting their primary vector, Aedes aegypti. The national burden in terms of morbidity and mortality as a direct consequence of dengue virus in India is considered to be the largest worldwide, over 4 times that of any other country. Presently, new genetic technologies are undergoing field evaluation of their biosafety and efficacy in several countries. This paper discusses the merits of these approaches and argues for fair and transparent appraisal in India as a matter of urgency. Identification of any associated risks and their appropriate mitigation are fundamental to that process. c 2013 Society of Chemical Industry Keywords: genetic control; genetically modified; India; public health; arbovirus; dengue; chikungunya
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INTRODUCTION
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∗
Correspondence to: BP Niranjan Reddy, School of Studies in Biotechnology, Jiwaji University, Gwalior, Madhya Pradesh 474011, India. E-mail: [email protected]
a School of Studies in Biotechnology, Jiwaji University, Gwalior, Madhya Pradesh, India b Agriculture Department, Gole Pully, Talab Tillo, Jammu, India
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India has diverse physiogeographical conditions that provide habitats for a wealth of insect species whose distributions are closely linked to regional temperatures, rainfall and humidity.1 A number of these species are responsible for the transmission of human diseases by acting as vectors for viruses, nematodes and parasites.2 There are six major vector-borne diseases (VBDs) that currently present a direct threat to Indian public health:3 malaria (Anopheles culicifacies, Anopheles stephensi, Anopheles dirus, Anopheles fluviatilis, Anopheles minimus and Anopheles sundaicus), dengue (Aedes aegypti and Aedes albopictus), lymphatic filariasis (Culex quinquefasciatus and Culex tritaeniorhynchus), kala-azar (Phlebotomus argentipes), Japanese encephalitis (Culex tritaeniorhynchus, Culex vishnui and Culex pseudovishnui) and Chikungunya (Ae. aegypti and Ae. albopictus). As in many countries, VBD control in India is primarily focused on targeting the transmission of the diseases by suppressing vector populations. Historically, vector populations have been suppressed through the integrated use of insecticides, public engagement, including health education, and the reduction in vector breeding sites through environmental management. Such strategies have at times proven to be effective, for example in facilitating a dramatic reduction in malaria cases from India during the 1960s and the earlier eradication of yellow fever mosquito, Ae. aegypti, from Brazil and other Latin American countries.4,5 Unfortunately, these conventional strategies have also frequently proven to be difficult to implement successfully owing to a variety of factors, including failed public engagement, resulting in low levels of local compliance, problems related to effective application of chemical insecticides or the biological adaptation of insect populations to withstand increased doses of insecticides.6 The latter, known as insecticide resistance, has been referred to as the single greatest
threat to the sustainability of chemical control.7 Furthermore, mapping of VBDs shows that the burden of disease is significantly skewed towards poorer, rural or marginalised communities which are less able to protect themselves with repellents, insecticidetreated bed nets (ITNs) or other safeguarding measures against mosquito bites.8 The intricacies of VBD management are clearly reflected in the failures of control strategies and thus raise the need to develop and deploy more effective, environmentally friendly and species-specific approaches.6 Novel control methods that could alleviate much of the morbidity and mortality associated with VBDs by reducing or replacing the vector population are already available, and these are described later.9 Numerous countries where diseases are endemic have begun the possibly lengthy process of actively assessing the potential of novel methods for enhancing existing control.10 The introduction of novel technologies should always be underpinned by appropriate risk assessments and risk mitigation, and where appropriate should be accompanied with public scientific debate. This paper intends to contribute to this discussion by focusing on the available genetic insect control techniques for combating the spread of dengue viruses and their primary vector, Ae. aegypti, thereby challenging whether such approaches possess genuine potential for advancing the management of pests of public health importance in India.
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2 HISTORY OF MOSQUITO CONTROL USING GENETIC TECHNOLOGIES IN INDIA During the 1960s, owing primarily to the use of dichlorodiphenyltrichloroethane (DDT), coupled with community engagement and environmental management for source reduction of mosquito populations, it was possible to reduce the incidence of malaria in India from 75 million cases to 0.05–0.1 million cases per annum through the near-elimination of the insects responsible for transmission from large swathes of the country.4,11 During subsequent decades, probably owing to a combination of ecological changes promoting higher pest densities, such as increasing levels of insecticide resistance in vector populations, urban development, deforestation and increased human travel and trade, containment attempts failed and malaria was evident with increasing severity from the mid-1960s onwards.11,12 Consequently, a collaborative research project was developed between the World Health Organisation (WHO) and the Indian Council of Medical Research (ICMR), aiming to control vector species of dengue and malaria by the sterile insect technique (SIT).13 The project was focused on three mosquito species (Cx. quinquefasciatus, Ae. aegypti and An. stephensi) in an attempt to understand the key biological determinants for their successful genetic control. Culex spp. and Aedes spp. were chosen for investigations of aspects of species biology and for an examination of the practical constraints on effective reductions in dengue and malaria transmission rates. Preliminary field studies releasing Culex mosquitoes were undertaken,13 but no field trials targeting disease suppression were possible.14,15 Major reasons for failure of the SIT programme included the presence of unidentified species complexes, migration of already inseminated female mosquitoes with fertile semen from the surrounding areas and low mating competitiveness of the irradiated mosquitoes.14 – 16 In addition, only partial completion of the project was possible in view of illiteracy and the hysteria engendered by false accusations that the project was intended to collect data on biological warfare.17 – 19 Rumours were also spread about possible health hazards, specifically that mosquito bites could cause sterility.19,20 Since these early attempts, genetic tools and technologies have progressed rapidly, and novel techniques have come to the fore that now present a real opportunity to advance and potentially revolutionise VBD control. With a national population estimated at over 1.2 billion (https://www. http://moud.gov.in/urbanscenario), India has more people at risk of daily exposure to the primary vectors of dengue and chikungunya (Aedes spp.) than any other country, and is home to 12 of the 19 dominant Anopheles vectors of human malaria that occur in the Asia-Pacific region.21 With these numbers in mind, technical and regulatory assessments of contemporary genetic control strategies in a national context may even be considered to be overdue.
3 PRESENTLY AVAILABLE NOVEL STRATEGIES FOR VECTOR CONTROL
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The novel strategies that are presently available for vector control may be classified into two broad categories, namely genetically modified (RIDL, female-specific RIDL and Medea-based refractory gene drive systems) and non-genetically modified (SIT, Wolbachiacentred biopesticide strategies) (Fig. 1). The classical sterile insect technique (SIT), modified SIT (RIDL-Ox513A and RIDL-Ox3604C female-specific flightless phenotypes) and Wolbachia-male-only releases are examples of population suppression strategies (Fig. 1B) aimed at reducing the number of wild mosquitoes, ideally to
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BP Niranjan Reddy, B Gupta, BP Rao below the levels required for sustained virus transmission.9 Near or complete replacement of wild vector populations with modified insects is exemplified by releases of mosquitoes carrying transgenes for refractoriness against human pathogens (for example, Medea driven) (Fig. IC). In addition, the deliberate invasion of the wild population through releases of Wolbachiainfected refractory mosquitoes, called the ‘biopesticide strategy’, is considered to be another strategy to manage vector-borne diseases.22 3.1 Sterile insect technique SIT has been successfully used over decades to control and/or eradicate several pests and disease vectors.23 Male insects of the target species that have been previously sterilised using irradiation treatments are released to compete against wild males to breed with wild females. If large enough numbers of reproductively competitive males are used, the reproductive capacity of the wild population is reduced. If such releases are repeated over a sustained period, this technique has the potential to suppress the wild population and may lead to localised eradication. However, a number of associated concerns have inhibited the integration of SIT as a prominent management tool for public health pests, including safe disposal and health hazards associated with the irradiation process and technical challenges associated with its application.24 Implementation of SIT is a labour- and resourceintensive process, which, without sufficient planning, support and ongoing management, can quickly lead to erroneous and/or inconclusive data. SIT field studies for mosquitoes are limited in number and are variable in terms of results. The most positive reports concern the eradication of the southern house mosquito, Culex quinquefasciatus, from a Florida island and from Okpo (Myanmar, Mandalay),25 and the New-World malaria mosquito, Anopheles albimanus, from El Salvador.24 Since then, in spite of numerous initiatives to implement SIT in mosquito control, unfortunately the biological impact of irradiation on the relatively delicate adults and the complexities of mate and food-source location in an urban (as opposed to agricultural) setting appear to have conspired against mosquito SIT initiatives.26,27 Recently, a semi-field pilot study conducted on Reunion Island to test the mating efficiency of irradiated Ae. albopictus males revealed a twofold reduction in wild-type fertility.28 Other open field trials have been conducted to reduce the Ae. albopictus population in Italian urban areas, but with as yet unconclusive results.26,29 To date, there are at least as many reports of failure as there are reports of unequivocal success.10,24,30 3.2 Release of insects carrying dominant lethal (RIDL) genes The Ae. aegypti-specific RIDL technology is based on a dominantly inherited lethal gene that is artificially inserted into the mosquito genome.31,32 The lethal phenotype is expressed only in immature stages. RIDL mosquitoes are therefore autocidal in that mating of RIDL adult males with wild females results in the death of 97% of heterozygous F1 progeny. The system is repressible, so progeny are unaffected if reared in the presence of tetracycline, an antidote. RIDL technology is in some ways analogous to conventional SIT, although a number of advantages of RIDL over conventional SIT have been purported.33 These include a less-compromised level of fitness in the released male insects, as there is no requirement for irradiation, a procedure that has been shown to cause variable degrees of sublethal damage.34,35 In practical terms, such fitness costs are manifest in reduced efficiencies and/or performance,
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Figure 1. Vector control methods categorised as conventional, population suppression and population replacement strategies. Note that, although present methods of chemical usage (A) to control vector populations fall under the population suppression heading, they are depicted separately from other methods (B) in order to show that chemical methods, at least in theory, fail to reduce the population below a certain level (vertical space between the blue line and the x-axis in diagram A. Diagram B represents population suppression strategies that include conventional non-GM SIT, GM-based RIDL, flightless RIDL and Wolbachia-driven biopesticide strategies. The diagram shows two downward-trend lines to represent the reduction in wild vector populations in response to the suppression treatments, where the primary (blue) line represents population reduction to a maximum level while the secondary (red) line represents post-suppression releases to maintain the population suppression. Diagram C presents a theoretical paradigm of population invasion/replacement, where release of a pathogen-specific refractory strain into the wild population results in disease transmission blockage. Note that two different Wolbachia-based strategies are mentioned in diagram C: Wolbachia used as a biopesticide to invade the wild vector populations, and a second, GM-based method where Wolbachia is exploited as a mere gene drive mechanism to introduce the refractory gene into the wild population.
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these results owing to the high fitness cost of the RIDL-Ox3604C males (ca 97%).40 The first open field suppression trials using genetically modified RIDL-Ox513A Ae. aegypti were conducted on Grand Cayman Islands by Oxitec Limited (UK). The selected field site was within a small town and had a population of ca 3000 people. The study was conducted from May to October 2010, during which time 3.3 million sterile males were released, reducing the wild Ae. aegypti population by ca 80%.30,31 Although this study successfully demonstrated suppression of a wild population, and in doing so confirmed the utility of the inherent marker, some of the other perceived benefits will require longer-term studies to enable verification. Further trials in a range of countries (Brazil, India, Panama, Malaysia, the United States) are completed, under way or in the process of gaining regulatory approval.10 3.3 Wolbachia pipientis Wolbachia pipientis (hereafter referred to as Wolbachia) is a rickettsia-like bacterial endosymbiont present in a significant proportion of insect species. Estimations vary, but a recent report suggests that globally it is present in approximately 76% of species.41 Wolbachia has recently received much needed attention, especially from scientists and programme managers, on account
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and correspondingly higher production and release numbers are required in an attempt to mitigate these effects.33 A further suggested benefit of RIDL over SIT is the late-acting lethality during the larval phase. In contrast to sterile or Wolbachiamediated population reduction, where F1 generation eggs fail to hatch, F1 RIDL progeny indeed hatch and develop through to the later immature stages (L3 pupae), thereby offering densitydependent competition with developing wild-type progeny. This is thought to contribute a significant additive effect in terms of population suppression.36 Other benefits include the inherent genetic marking system, which facilitates fast and accurate identification of RIDL insects and the potential to develop genetic sexing strains in which female-specific phenotypes (e.g. lethality) offer simple and precise sexing techniques.31 Laboratory, semifield and field assessment of RIDL-Ox513A Ae. aegypti mosquitoes for various fitness parameters and practical aspects have yielded encouraging results, demonstrating equivalent or near-equivalent dispersal and mating competitiveness.37,38 In contrast, studies on another form of RIDL, the Ox3604C female-specific flightless phenotype strain, showed excellent results in laboratory-based simulation studies aimed at eliminating a cage population.39 However, experiments in semi-field conditions failed to repeat
www.soci.org of its extraordinary ability to modify the host’s reproductive behaviour in favour of its spread.42 In fact, this is why Wolbachia is one of the most successful bacteria at forming symbiotic relationships with a wide range of insect species.41,42 Wolbachia is found to modify the host’s behaviour by inducing a range of reproductive phenotypes, namely cytoplasmic incompatibility, feminisation, induction of male-only mosquitoes, parthenogenesis, etc.41 – 43 Nonetheless, it has been established that a mutant of Wolbachia from Drosophila melanogaster restricts the growth of otherwise harmful pathogens to the host by its unusual replication behaviour. This strain (wMelPop) is popularly known as ‘Popcorn’ in view of its exceptional multiplicative behaviour in the host’s brain tissues.42 Another interesting phenotype observed in Drosophila is that some of the strains are found to reduce the active life span of the infected adults.44 Together, all these phenotypes make Wolbachia especially important to those involved in management of vector-borne diseases. Interestingly, Wolbachia is also found to be widely distributed in disease-spreading mosquitoes; however, it is conspicuous by its absence from the primary dengue vector Ae. aegypti. It is this absence that has opened the door to approaches exploiting the side effects of artificially infecting wild Ae. aegypti populations with Wolbachia. A reproductive phenomenon known as cytoplasmic incompatibility (CI) underpins Wolbachia-mediated biocontrol of Ae. aegypti and facilitates the prevention of virus transmission. Wolbachia infections impart a reproductive deficit in uninfected females, whereby wild females mated by an infected male cannot produce offspring.25 Wolbachia-infected males can therefore be used in a similar manner to conventional SIT, in that eggs laid by mated wild females fail to hatch, and repeated releases can serve to suppress the wild population. Wolbachia infections are only inherited maternally, so releases of Wolbachia-infected females can result in a mechanism by which infection can be driven through a population.45,46 One particular control strategy utilises this characteristic to infect all wild Ae. aegypti in a given area with a life-shortening strain of Wolbachia.47 A second strategy uses the CI mechanism to drive a Wolbachia infection throughout all members of the wild population, as it has been shown to inhibit pathogen (including dengue virus) transmission dramatically.22 It is presently being more widely evaluated (e.g. Australia, Indonesia, Brazil and Vietnam) by using wMel-Wolbachia strain in Ae. aegypti, and initial data from Australia have shown it to be extremely effective, with complete and stable infection rates achieved.48 However, more studies are warranted in light of the finding that, upon cessation of release of Wolbachia-infected mosquitoes, the local population is susceptible to reversal, i.e. to an increase in bacteria-free mosquitoes.48 Although there is no evidence for such reversal in the case of wMel-Wolbachia releases,48 it could be possible with the Popcorn strain, given its high fitness costs to the host. Also, studies on the impact of Wolbachia on dengue transmission in field conditions are required.
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Critical consideration of the safety and application of control strategies is a prerequisite for their development, and a number of discussions and studies have addressed the hypothetical environmental risks posed by releasing genetically modified organisms. The ethical, legal and social issues associated with genetic engineering, relevant to technologies such as RIDL, are under fierce debate in many parts of the world.49 – 51 A fundamental consideration pertinent to any environmental assessment is the degree of permanency that is being imposed.
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BP Niranjan Reddy, B Gupta, BP Rao Control regimes that offer a benefit in the short to medium term (decades) can evidently be advantageous, but the impact of longterm or permanent changes on the environment are inherently difficult to predict; they cause uncertainty and justifiable concern. Assuming that implementation is correct, genetic strategies based on population reduction (i.e. SIT, Wolbachia-infected male releases and RIDL) generally offer a temporary reduction or localised elimination of vector populations, and their species specificity and short- to medium-term persistence leave a minimal ecological footprint.52,53 Strategies aimed at population replacement, such as self-driving Medea-genetic-element-infected female releases.43 have the potential to impose permanent change on the wild vector populations and additionally spread through non-target areas. This may be a cause of concern in a regulatory context, as risk mitigation is fundamentally more challenging.
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PROSPECTS FOR NON-GENETIC CONTROL
Increasingly stringent regulatory frameworks and soaring developmental costs have progressively constrained the discovery and registration of novel pesticide molecules over recent decades. In conjunction with this, the available chemical classes are being exhausted, reducing the chances of finding active ingredients (AIs) with new modes of action.7 Disappointingly, the public health sector has rarely been the focus of pesticide discovery, as the agrochemical market is far more lucrative. This has resulted in a shortage of available AIs, subsequent overreliance on specific chemical classes and the consequent development of insecticide resistance. Resistance to key chemical classes, such as pyrethroids and organophosphates, is now ubiquitous in Ae. Aegypti.54 With no evidence of change in the foreseeable future, increasing political and social condemnation of pesticide use in developed countries and a track record of resistance development, chemical control would appear to be an unlikely source for a novel, environmentally acceptable and sustainable solution to vector control. Partially treatable diseases such as microfilariasis and untreatable diseases such as chikungunya and dengue are inflicting extreme socioeconomic losses to communities of rural origin. In addition, in spite of intense efforts and progress in vaccine research for VBDs such as malaria and dengue, effective vaccines are neither available nor imminent.55 Another problem that arises in controlling such diseases using therapeutic preparations is the adaptation of parasites in the form of drug resistance. The targeted organisms can adapt as a consequence of selection pressures imposed by sublethal doses of a drug, in combination with their own high genomic plasticity. An illustrative example is P. falciparum, one of the most devastating human malaria parasite species. P. falciparum has developed resistance to almost all types of therapeutic drug currently being used to combat malaria.56 Drug resistance is also emerging in other human pathogens, e.g. leishmaniasis and sleeping sickness.57,58
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COMMUNITY ENGAGEMENT
Ethical, legal and social issues (ELSIs) are considered to be more important than technological innovations and even the intended primary objectives of the project.17,42,49,59 – 63 Public education and community engagement are considered to be final steps in the lengthy evaluation process of bringing lab-to-field translation of innovations; nevertheless, these are also acknowledged as momentous in implementing novel technologies for vector control.50,63 Historically there have been serious repercussions
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from the lack of a proper approach, planning and execution of public education, which may prove disastrous in delivering success to a project.17,49,59 Experience also shows that improper, incorrect or inappropriate dissemination of project objectives and goals and technological background information may even lead to a halt in a project at any time during the course of its evaluation.59 – 61 Thus, when preparing the communication strategy, it is imperative to consider the various socioeconomic strata of local communities, including the involvement and participation of various stakeholders. Besides ELSIs, there are many other nation- or region-specific issues and challenges related to the development and deployment of genetic technologies for the control of human diseases (for example, political commitment).64,65 Those issues and their solutions need to be known beforehand for the successful and effective development of the technology.
7 ISSUES AND CHALLENGES, AND JUSTIFICATION OF USING NOVEL VECTOR CONTROL METHODS IN INDIA
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LOGISTICS AND RECOMMENDATIONS
When evaluating the efficacy of these novel technologies, it would be advisable to proceed with caution and to consider some important points. Firstly, India already has a well-established hierarchical public health system for dealing with vector-borne diseases. Hence it is logical to consult, apprise, involve and acquire the support of the health system for any new initiative right from the beginning of the project.50,64 Health care in India is state run rather than federally governed, and hence it is important to obtain permission to conduct feasibility studies from the state as well as from local government. Secondly, trials should start in hamlets or at study sites of similar size, requiring minimal logistics and operational costs before progressing to large-scale area-wide implementation.43,72,73 Preferably, these studies should be regarded as a prelude to obtaining novel information on public and community responses, government and policy-makers’ support, political will and other scientific parameters that could be locally influenced by change in geography and climate.42,43,64 Thirdly, serious attention should be paid to the experiences and mistakes of others.19,49,50,59 In other words, lessons must be learnt from the findings of similar experiments in countries where diseases are endemic, mostly in south-east Asia and Latin America, which have similar, if not identical, socioeconomic conditions and living standards, including demography and population densities, for example RIDL trials in the Grand Cayman Islands50 and in Brazil (www.Oxitec.com) and Wolbachia-based biocontrol trials in Vietnam.74
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CONCLUSION
VBDs are a huge burden on many societies throughout the world, and in the case of dengue viruses they are rapidly increasing both in terms of geographical spread and rates of morbidity and mortality. Owing to constraints associated with the use of chemical insecticides, coupled with the lack of any treatment or vaccine in the foreseeable future, there is a clear need for alternate approaches. Vector control strategies that are effective, that in theory are sustainable and that have a defined ecological footprint are now available. The complexities of regulation, public education or scientific accreditation should not be insurmountable barriers preventing their independent and rigorous assessment. An evaluation in this context is merely an appraisal of safety and worth, although in the longer term it may also prove to be the seed of better social well-being and large-scale social development. These sometimes politically charged technologies present new challenges for the political and regulatory bodies, and in some cases their innovation may require new regulatory frameworks to be put in place. They demand a level of transparency at all stages of the evaluation process, and cooperation at the community level is vitally important. With the nation’s well-being at the fore, the political and regulatory authorities are duty bound to act in the public’s interest, and the potential for major advances in public
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The vast geography and diverse climatic profile of India make adoption of such techniques a challenging task. However, with a well-prepared strategy and step-by-step evaluation of potential technologies, coupled with proper project management and communication strategies, the seemingly daunting task is certainly not an impossible one.50,51 For obvious reasons, such as geographical and demographic changes due to pursuit of economic ambitions, the dynamics of disease vector population is ever changing (www.nvbdcp.org), especially in the case of vectors that favour urban dwellings. Furthermore, India is home to different ethnic communities with diverse traditions and cultural practices that are tightly linked to their socioeconomic status.66,67 In addition to the above-mentioned complexities, another major issue with India is the size of the population. As a result of globalisation, the urban population of India is expanding unexpectedly into poor or ill-planned cities, where basic amenities and sanitary conditions are lacking, and the local environment is deteriorating day by day.68 One report on population migration suggests that, in the coming decade, ∼400 million people will leave rural villages in pursuit of a livelihood in urban settings (http://www.urbanindia.nic.in). Already under severe stress from a lack of sufficient basic amenities, the additional population burden on the cities, in reality, will pose a serious threat to the viability of existing or any new innovative vector control measures. All these issues present a great challenge when novel methods are being incorporated into existing vector control programmes. Paradoxically, these issues are among the strongest arguments for the testing of novel controls that basically require minimal intervention because of their greater species specificity9 and ecofriendliness, coupled with their low operating costs once established, for example self-driven Wolbachia-mediated biological control.42 For the time being, in theory at least, there is no better option than community engagement and unequivocal support and involvement in the control of vectorborne diseases that are spreading, in particular, in urban areas where the sprawling population is adopting a more complex living environment in which ‘vertical’ living is the norm.69,70 These are some of the issues contributing to failure of existing urban vector management strategies such as source reduction with environmental management, source treatment
using larvicides and insecticide fogging during epidemics. One of the greatest examples can be drawn from the recent failure of the Delhi government to control dengue disease during the 2010 Commonwealth Games,71 in spite of the mobilisation of all possible resources, from political will to exploiting the experience of vector control experts and programme managers, and a similar situation is evident with year-on-year malaria in metropolitan cities like Mumbai, Kolkata and Chennai (www.nvbdcp.gov.in).
www.soci.org health should not be overlooked. As the country at the top of the world rankings in terms of numbers of dengue cases, with a recent estimate of over 32 million per annum,75 should not India be leading the way in the pursuit of an effective, sustainable solution?
ACKNOWLEDGEMENTS BPNR thanks the council of scientific and industrial research (CSIR) for a senior research fellowship. The authors are grateful two anonymous reviewers for their valuable comments on a previous version of the manuscript.
REFERENCES
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1 Patz JA, Campbell-Lendrum D, Holloway T and Foley JA, Impact of regional climate change on human health. Nature 438:310–317 (2005). 2 Reddy BPN, Labbe´ P and Corbel V, Culex genome is not just another genome for comparative genomics. Parasites Vectors 5:1–4 (2012). 3 Lobo DA, Velayudhan R, Chatterjee P, Kohli H and Hotez PJ, The neglected tropical diseases of India and South Asia: review of their prevalence, distribution, and control or elimination. PLoS Negl Trop Dis 5:e1222 (2011). 4 Dash AP, Adak T, Raghavendra K and Singh OP, The biology and control of malaria vectors. Curr Sci 92:1571–1578 (2007). 5 Soper FL, The elimination of urban yellow fever in the Americas through the eradication of Aedes aegypti. Am J Publ Hlth Nation’s Hlth 53:7–16 (1963). 6 Zaim M and Guillet P, Alternative insecticides: an urgent need. Trends Parasitol 18:161–163 (2002). 7 Gorman K, Editorial – Resistance 2011. Pest Manag Sci 69:149 (2013). 8 Ault SK, Pan American Health Organization’s regional strategic framework for addressing neglected diseases in neglected populations in Latin America and the Caribbean. Mem Inst Oswaldo Cruz 102:99–107 (2007). 9 Alphey L, Benedict M, Bellini R, Clark GG, Dame DA, Service MW et al, Sterile-insect methods for control of mosquito-borne diseases: an analysis. Vector-Borne Zoonotic Dis 10:295–311 (2010). 10 McGraw EA and O’Neill SL, Beyond insecticides: new thinking on an ancient problem. Nat Rev Microbiol 11:181–193 (2013). 11 Sharma GK, Review of malaria and its control in India. Proc Indo-UK Workshop on Malaria, Malaria Research Centre, Delhi, India, pp. 13–40 (1984). 12 Kumar A, Valecha N, Jain T and Dash AP, Burden of malaria in India: retrospective and prospective view. Am J Trop Med Hyg 77:69–78 (2007). 13 Gratz NG, Emerging and resurging vector-borne diseases. Annu Rev Entomol 44:51–75 (1999). 14 Curtis C, Review of Previous Applications of Genetics to Vector Control. Springer, Dordrecht, The Netherlands (2006). 15 Curtis C, Brooks G, Ansari M, Grover K, Krishnamurthy B, Rajagopalan P et al, A field trial on control of Culex quinquefasciatus by release of males of a strain integrating cytoplasmic incompatibility and a translocation. Entomol Exp Applic 31:181–190 (1982). 16 Yasuno M, Macdonald WW, Curtis CF, Grover KK, Rajagopalan PK, Sharma LS et al, A control experiment with chemosterilized male Culex pipiens fatigans Wiedemann in a village near Delhi surrounded by a breeding-free zone. Jpn J Sanit Zool 29:325–343 (1975). 17 Sehgal NK, Doubts over US in India. Nature 251:177–178 (1974). 18 Powell K and Jayaraman KS, Mosquito researchers deny plotting secret biowarfare test. Nature 419:867 (2002). 19 WHO-supported collaborative research projects in India: the facts. WHO Chron 30:131–139 (1976). 20 Davidson G, Curtis CF, White GB and Rawlings P, Mosquito war games. Nature 296:700 (1982). 21 Hay SI, Sinka ME, Okara RM, Kabaria CW, Mbithi PM, Tago CC et al, Developing global maps of the dominant Anopheles vectors of human malaria. PLoS Med 7:e1000209 (2010). 22 Moreira LA, Iturbe-Ormaetxe I, Jeffery JA, Lu G, Pyke AT, Hedges LM et al, A Wolbachia symbiont in Aedes aegypti limits infection with Dengue, Chikungunya, and Plasmodium. Cell 139:1268–1278 (2009).
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BP Niranjan Reddy, B Gupta, BP Rao 23 Dyck V, Hendrichs J and Robinson AS, Sterile Insect Technique: Principles and Practice in Area-wide Integrated Pest Management. International Atomic Energy Agency, The Netherlands (2005). 24 Vreysen MJ, Robinson AS and Hendrichs J, Area-wide Control of Insect Pests: from Research to Field Implementation. Springer, Dordrecht, The Netherlands (2007). 25 Laven H, Eradication of Culex pipiens fatigans through cytoplasmic incompatibility. Nature 216:383–384 (1967). 26 Bellini R, Calvitti M, Medici A, Carrieri M, Celli G and Maini S, Use of the sterile insect technique against Aedes albopictus in Italy: first results of a pilot trial, in Area-wide Control of Insect Pests, ed. by Vreysen MJB, Robinson AS and Hendrichs J. Springer, Dordrecht, The Netherlands, pp. 505–515 (2007). 27 Dame DA, Woodard DB, Ford HR and Weidhaas DE, Field behavior of sexually sterile Anopheles quadrimaculatus males. Mosquito News 24:6–16 (1964). 28 Oliva CF, Jacquet M, Gilles J, Lemperiere G, Maquart PO, Quilici S et al, The sterile insect technique for controlling populations of Aedes albopictus (Diptera: Culicidae) on Reunion Island: mating vigour of sterilized males. PloS One 7:e49414 (2012). 29 Bellini R, Medici A, Puggioli A, Balestrino F and Carrieri M, Pilot field trials with Aedes albopictus irradiated sterile males in Italian urban areas. J Med Entomol 50:317–325 (2013). 30 Dyck VA, Hendrichs J and Robinson A, Sterile Insect Technique: Principles and Practice in Area-wide Integrated Pest Management. Springer, Dordrecht, The Netherlands (2005). 31 Thomas DD, Donnelly CA, Wood RJ and Alphey LS, Insect population control using a dominant, repressible, lethal genetic system. Science 287:2474–2476 (2000). 32 Alphey L, Baker P, Burton RS, Condon GC, Condon KC, Dafa’alla TH, Epton MJ, Fu G, Gong P, Jin L, Labbe´ G, Morrison NI, Nimmo DD, O’Connell S, Phillips CE, Plackett A, Scaife S and Woods A, Genetic technologies to enhance the Sterile Insect Technique (SIT). Fruit Flies of Economic Importance: From Basic to Applied Knowledge Proceedings of the 7th International Symposium on Fruit Flies of Economic Importance 10–15 September 2006, Salvador, Brazil pp. 319–326. 33 Black IV WC, Alphey L and James AA, Why RIDL is not SIT. Trends Parasitol 27:362–370 (2011). 34 Raghavendra K, Barik TK, Reddy BPN, Sharma P and Dash AP, Malaria vector control: from past to future. Parasitol Res 108:757–779 (2011). 35 Catteruccia F, Crisanti A and Wimmer EA, Transgenic technologies to induce sterility. Malar J 8:S7 (2009). 36 Phuc HK, Andreasen MH, Burton RS, Vass C, Epton MJ, Pape G et al, Late-acting dominant lethal genetic systems and mosquito control. BMC Biol 5:11 (2007). 37 Lee HL, Joko H, Nazni WA and Vasan SS, Comparative life parameters of transgenic and wild strains of Aedes aegypti in the laboratory. Dengue Bull 33:103–314 (2009). 38 Bargielowski I, Nimmo D, Alphey L and Koella JC, Comparison of life history characteristics of the genetically modified Ox513a line and a wild type strain of Aedes aegypti. PLoS One 6:e20699 (2011). 39 Wise de Valdez MR, Nimmo D, Betz J, Gong H-F, James AA, Alphey L et al., Genetic elimination of dengue vector mosquitoes. Proc Natl Acad Sci USA 108:4772–4775 (2011). 40 Facchinelli L, Valerio L, Ramsey JM, Gould F, Walsh RK, Bond G et al, Field cage studies and progressive evaluation of geneticallyengineered mosquitoes. PLoS Neglected Trop Dis 7:e2001 (2013). 41 Jeyaprakash A and Hoy MA, Long PCR improves Wolbachia DNA amplification: wsp sequences found in 76% of sixty-three arthropod species. Insect Mol Biol 9:393–405 (2000). 42 Iturbe-Ormaetxe I, Walker T and O’Neill S, Wolbachia and the biological control of mosquito-borne disease. EMBO Rep 12:508–518 (2011). 43 Hoffmann AA, Montgomery BL, Popovici J, Iturbe-Ormaetxe I, Johnson PH, Muzzi F et al., Successful establishment of Wolbachia in Aedes populations to suppress dengue transmission. Nature 476:454–457 (2011). 44 Min K-T and Benzer S, Wolbachia, normally a symbiont of Drosophila, can be virulent, causing degeneration and early death. Proc Natl Acad Sci USA 94:10 792–10 796 (1997). 45 Adak T, Singh OP, Nanda N, Sharma VP and Subbarao SK, Isolation of a Plasmodium vivax refractory Anopheles culicifacies strain from India. Trop Med Int Hlth 11:197–203 (2006).
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46 Adams MD, Celniker SE, Holt RA, Evans CA, Gocayne JD, Amanatides PG et al, The genome sequence of Drosophilamelanogaster. Science 287:2185–2195 (2000). 47 McMeniman CJ, Lane RV, Cass BN, Fong AWC, Sidhu M, Wang YF et al, Stable introduction of a life-shortening Wolbachia infection into the mosquito Aedes aegypti. Science 323:141–144 (2009). 48 Hoffmann AA, Montgomery BL, Popovici J, Iturbe-Ormaetxe I, Johnson PH, Muzzi F et al, Successful establishment of Wolbachia in Aedes populations to suppress dengue transmission. Nature 476:454–457 (2011). 49 Subbaraman N, Science snipes at Oxitec transgenic-mosquito trial. Nature Biotechnol 29:9–11 (2011). 50 Reeves RG, Denton JA, Santucci F, Bryk J and Reed FA, Scientific standards and the regulation of genetically modified insects. PLoS Neglected Trop Dis 6:e1502 (2012). 51 Mumford JD, Science, regulation, and precedent for genetically modified insects. PLoS Neglected Trop Dis 6:e1504 (2012). 52 Beech CJ, Nagaraju J, Vasan SS, Rose RI, Othman RY, Pillai V et al, Risk analysis of a hypothetical open field release of a self-limiting transgenic Aedes aegypti mosquito strain to combat dengue. Asia Pacif J Mol Biol Biotechnol 17:99–111 (2009). 53 Beech CJ, Koukidou M, Morrison NI and Alphey L, Genetically modified insects: science, use, status and regulation. Colln Biosaf Rev 6:66–124 (2012). 54 Bariami V, Jones CM, Bisset JA, Rodrigquez M, Vontas J and Hilary Ranson, The molecular basis of pyrethroid resistance in Aedes aegypti from the Caribbean. PLoS Negl Trop Dis 6:e1692 (2012). 55 Vaughan AM and Kappe SH, Malaria vaccine development: persistent challenges. Curr Opin Immunol 24:324–331 (2012). 56 Hayton K and Su X, Drug resistance and genetic mapping in Plasmodium falciparum. Curr Genet 54:223–239 (2008). 57 Croft SL, Sundar S and Fairlamb AH, Drug resistance in Leishmaniasis. Clin Microbiol Rev 19:111–126 (2006). 58 M¨aser P, Luscher A and Kaminsky R, Drug transport and drug ¨ resistance in African trypanosomes. Drug Resist Updates 6:281–290 (2003). 59 Jayaraman KS, Pest research centres: foreign labs shut. Nature 296:104–105 (1982). 60 Jayaraman KS, Consortium aims to revive sterile-mosquito project. Nature 389:6 (1997). 61 Opinion. Oh, New Delhi; oh, Geneva. Nature 256:355–357 (1975). 62 Pal R and Whitten MJ, WHO/ICMR programme of genetic control of mosquitoes in India, in The Use of Genetics in Insect Control. Elsevier/North Holland, Amsterdam, The Netherlands, pp. 73–95 (1974).
63 Macer D, Ethical, legal and social issues of genetically modified disease vectors in public health. UNDP/World Bank/WHO Special Program for Research and Training in Tropical Diseases (TDR). [Online]. WHO, Geneva (2003). Available: http://www.who. int/tdr/publications/documents/seb_topic1.pdf. [5 May 2010]. 64 Progress and prospects for the use of genetically modified mosquitoes to inhibit disease transmission. Report on Planning Meeting 1: Technical Consultation on Current Status and Planning for Future Development of Genetically Modified Mosquitoes for Malaria and Dengue Control 2009. [Online]. WHO, Geneva (2009). Available: http://whqlibdoc.who.int/publications/2010/9789241599238_ eng.pdf [6 March 2013]. 65 Pal R and Whitten MJ, The Use of Genetics in Insect Control. Elsevier/North-Holland, Amsterdam, The Netherlands (1974). 66 Chhokar JS, India: diversity and complexity in action, in Culture and Leadership across the World: the GLOBE Book of In-depth Studies of 25 Societies. Psychology Press, New York, NY, pp. 971–1020 (2008). 67 Majumder PP, People of India: Biological Diversity and Affinities. University Press, Hyderabad, India (1998). 68 King RA, Rathi S and Sudhira HS, An approach to regional planning in India. Int J Syst Syst Eng 3:117–128 (2012). 69 Gubler DJ, Resurgent vector-borne diseases as a global health problem. Emerging Infectious Dis 4:442–450 (1998). 70 Beaty BJ, Genetic manipulation of vectors: a potential novel approach for control of vector-borne diseases. Proc Natl Acad Sci USA 97:10 295–10 297 (2000). 71 Shaw M, Leggat PA and Chatterjee S, Travelling to India for the Delhi XIX Commonwealth Games 2010. Travel Med Infectious Dis 8:129–138 (2010). 72 Harris AF, Nimmo D, McKemey AR, Kelly N, Scaife S, Donnelly CA et al, Field performance of engineered male mosquitoes. Nat Biotechnol 29:1034–1037 (2011). 73 Harris AF, McKemey AR, Nimmo D, Curtis Z, Black I, Morgan SA et al, Successful suppression of a field mosquito population by sustained release of engineered male mosquitoes. Nat Biotechnol 30:828-30 (2012). 74 Tri NGuyen Island Field Trial Update. [Online]. 2013. Available: http://www.eliminatedengue.com/library/publication/document/ field_trial_update/tni_trial_update/2013.09.03_tni_trial_update_ english_final.pdf [5 September 2013]. 75 Bhatt S, Gething PW, Brady OJ, Messina JP, Farlow AW, Moyes CL et al, The global distribution and burden of dengue. Nature 496(7446):504–507 (2013).
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Revised: 23 October 2013
Accepted article published: 31 October 2013
Published online in Wiley Online Library: 19 November 2013
(wileyonlinelibrary.com) DOI 10.1002/ps.3676
Vector population manipulation for control of arboviruses – a novel prospect for India BP Niranjan Reddy,a∗ Bhavna Guptab and B Prasad Raoa Abstract India, the seventh largest country in the world, has diverse geographical and climatic regions with vast rural and peri-urban areas. Many are experiencing an escalation in the spread and intensity of numerous human diseases transmitted by insects. Classically, the management of these vector-borne diseases is underpinned by either chemical insecticides and/or environmental management targeted at the vector. However, these methods or their present implementation do not offer acceptable levels of control, and more effective and sustainable options are now available. Genetic strategies for the prevention of arbovirus transmission are most advanced for dengue and chikungunya, targeting their primary vector, Aedes aegypti. The national burden in terms of morbidity and mortality as a direct consequence of dengue virus in India is considered to be the largest worldwide, over 4 times that of any other country. Presently, new genetic technologies are undergoing field evaluation of their biosafety and efficacy in several countries. This paper discusses the merits of these approaches and argues for fair and transparent appraisal in India as a matter of urgency. Identification of any associated risks and their appropriate mitigation are fundamental to that process. c 2013 Society of Chemical Industry Keywords: genetic control; genetically modified; India; public health; arbovirus; dengue; chikungunya
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INTRODUCTION
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∗
Correspondence to: BP Niranjan Reddy, School of Studies in Biotechnology, Jiwaji University, Gwalior, Madhya Pradesh 474011, India. E-mail: [email protected]
a School of Studies in Biotechnology, Jiwaji University, Gwalior, Madhya Pradesh, India b Agriculture Department, Gole Pully, Talab Tillo, Jammu, India
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India has diverse physiogeographical conditions that provide habitats for a wealth of insect species whose distributions are closely linked to regional temperatures, rainfall and humidity.1 A number of these species are responsible for the transmission of human diseases by acting as vectors for viruses, nematodes and parasites.2 There are six major vector-borne diseases (VBDs) that currently present a direct threat to Indian public health:3 malaria (Anopheles culicifacies, Anopheles stephensi, Anopheles dirus, Anopheles fluviatilis, Anopheles minimus and Anopheles sundaicus), dengue (Aedes aegypti and Aedes albopictus), lymphatic filariasis (Culex quinquefasciatus and Culex tritaeniorhynchus), kala-azar (Phlebotomus argentipes), Japanese encephalitis (Culex tritaeniorhynchus, Culex vishnui and Culex pseudovishnui) and Chikungunya (Ae. aegypti and Ae. albopictus). As in many countries, VBD control in India is primarily focused on targeting the transmission of the diseases by suppressing vector populations. Historically, vector populations have been suppressed through the integrated use of insecticides, public engagement, including health education, and the reduction in vector breeding sites through environmental management. Such strategies have at times proven to be effective, for example in facilitating a dramatic reduction in malaria cases from India during the 1960s and the earlier eradication of yellow fever mosquito, Ae. aegypti, from Brazil and other Latin American countries.4,5 Unfortunately, these conventional strategies have also frequently proven to be difficult to implement successfully owing to a variety of factors, including failed public engagement, resulting in low levels of local compliance, problems related to effective application of chemical insecticides or the biological adaptation of insect populations to withstand increased doses of insecticides.6 The latter, known as insecticide resistance, has been referred to as the single greatest
threat to the sustainability of chemical control.7 Furthermore, mapping of VBDs shows that the burden of disease is significantly skewed towards poorer, rural or marginalised communities which are less able to protect themselves with repellents, insecticidetreated bed nets (ITNs) or other safeguarding measures against mosquito bites.8 The intricacies of VBD management are clearly reflected in the failures of control strategies and thus raise the need to develop and deploy more effective, environmentally friendly and species-specific approaches.6 Novel control methods that could alleviate much of the morbidity and mortality associated with VBDs by reducing or replacing the vector population are already available, and these are described later.9 Numerous countries where diseases are endemic have begun the possibly lengthy process of actively assessing the potential of novel methods for enhancing existing control.10 The introduction of novel technologies should always be underpinned by appropriate risk assessments and risk mitigation, and where appropriate should be accompanied with public scientific debate. This paper intends to contribute to this discussion by focusing on the available genetic insect control techniques for combating the spread of dengue viruses and their primary vector, Ae. aegypti, thereby challenging whether such approaches possess genuine potential for advancing the management of pests of public health importance in India.
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2 HISTORY OF MOSQUITO CONTROL USING GENETIC TECHNOLOGIES IN INDIA During the 1960s, owing primarily to the use of dichlorodiphenyltrichloroethane (DDT), coupled with community engagement and environmental management for source reduction of mosquito populations, it was possible to reduce the incidence of malaria in India from 75 million cases to 0.05–0.1 million cases per annum through the near-elimination of the insects responsible for transmission from large swathes of the country.4,11 During subsequent decades, probably owing to a combination of ecological changes promoting higher pest densities, such as increasing levels of insecticide resistance in vector populations, urban development, deforestation and increased human travel and trade, containment attempts failed and malaria was evident with increasing severity from the mid-1960s onwards.11,12 Consequently, a collaborative research project was developed between the World Health Organisation (WHO) and the Indian Council of Medical Research (ICMR), aiming to control vector species of dengue and malaria by the sterile insect technique (SIT).13 The project was focused on three mosquito species (Cx. quinquefasciatus, Ae. aegypti and An. stephensi) in an attempt to understand the key biological determinants for their successful genetic control. Culex spp. and Aedes spp. were chosen for investigations of aspects of species biology and for an examination of the practical constraints on effective reductions in dengue and malaria transmission rates. Preliminary field studies releasing Culex mosquitoes were undertaken,13 but no field trials targeting disease suppression were possible.14,15 Major reasons for failure of the SIT programme included the presence of unidentified species complexes, migration of already inseminated female mosquitoes with fertile semen from the surrounding areas and low mating competitiveness of the irradiated mosquitoes.14 – 16 In addition, only partial completion of the project was possible in view of illiteracy and the hysteria engendered by false accusations that the project was intended to collect data on biological warfare.17 – 19 Rumours were also spread about possible health hazards, specifically that mosquito bites could cause sterility.19,20 Since these early attempts, genetic tools and technologies have progressed rapidly, and novel techniques have come to the fore that now present a real opportunity to advance and potentially revolutionise VBD control. With a national population estimated at over 1.2 billion (https://www. http://moud.gov.in/urbanscenario), India has more people at risk of daily exposure to the primary vectors of dengue and chikungunya (Aedes spp.) than any other country, and is home to 12 of the 19 dominant Anopheles vectors of human malaria that occur in the Asia-Pacific region.21 With these numbers in mind, technical and regulatory assessments of contemporary genetic control strategies in a national context may even be considered to be overdue.
3 PRESENTLY AVAILABLE NOVEL STRATEGIES FOR VECTOR CONTROL
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The novel strategies that are presently available for vector control may be classified into two broad categories, namely genetically modified (RIDL, female-specific RIDL and Medea-based refractory gene drive systems) and non-genetically modified (SIT, Wolbachiacentred biopesticide strategies) (Fig. 1). The classical sterile insect technique (SIT), modified SIT (RIDL-Ox513A and RIDL-Ox3604C female-specific flightless phenotypes) and Wolbachia-male-only releases are examples of population suppression strategies (Fig. 1B) aimed at reducing the number of wild mosquitoes, ideally to
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BP Niranjan Reddy, B Gupta, BP Rao below the levels required for sustained virus transmission.9 Near or complete replacement of wild vector populations with modified insects is exemplified by releases of mosquitoes carrying transgenes for refractoriness against human pathogens (for example, Medea driven) (Fig. IC). In addition, the deliberate invasion of the wild population through releases of Wolbachiainfected refractory mosquitoes, called the ‘biopesticide strategy’, is considered to be another strategy to manage vector-borne diseases.22 3.1 Sterile insect technique SIT has been successfully used over decades to control and/or eradicate several pests and disease vectors.23 Male insects of the target species that have been previously sterilised using irradiation treatments are released to compete against wild males to breed with wild females. If large enough numbers of reproductively competitive males are used, the reproductive capacity of the wild population is reduced. If such releases are repeated over a sustained period, this technique has the potential to suppress the wild population and may lead to localised eradication. However, a number of associated concerns have inhibited the integration of SIT as a prominent management tool for public health pests, including safe disposal and health hazards associated with the irradiation process and technical challenges associated with its application.24 Implementation of SIT is a labour- and resourceintensive process, which, without sufficient planning, support and ongoing management, can quickly lead to erroneous and/or inconclusive data. SIT field studies for mosquitoes are limited in number and are variable in terms of results. The most positive reports concern the eradication of the southern house mosquito, Culex quinquefasciatus, from a Florida island and from Okpo (Myanmar, Mandalay),25 and the New-World malaria mosquito, Anopheles albimanus, from El Salvador.24 Since then, in spite of numerous initiatives to implement SIT in mosquito control, unfortunately the biological impact of irradiation on the relatively delicate adults and the complexities of mate and food-source location in an urban (as opposed to agricultural) setting appear to have conspired against mosquito SIT initiatives.26,27 Recently, a semi-field pilot study conducted on Reunion Island to test the mating efficiency of irradiated Ae. albopictus males revealed a twofold reduction in wild-type fertility.28 Other open field trials have been conducted to reduce the Ae. albopictus population in Italian urban areas, but with as yet unconclusive results.26,29 To date, there are at least as many reports of failure as there are reports of unequivocal success.10,24,30 3.2 Release of insects carrying dominant lethal (RIDL) genes The Ae. aegypti-specific RIDL technology is based on a dominantly inherited lethal gene that is artificially inserted into the mosquito genome.31,32 The lethal phenotype is expressed only in immature stages. RIDL mosquitoes are therefore autocidal in that mating of RIDL adult males with wild females results in the death of 97% of heterozygous F1 progeny. The system is repressible, so progeny are unaffected if reared in the presence of tetracycline, an antidote. RIDL technology is in some ways analogous to conventional SIT, although a number of advantages of RIDL over conventional SIT have been purported.33 These include a less-compromised level of fitness in the released male insects, as there is no requirement for irradiation, a procedure that has been shown to cause variable degrees of sublethal damage.34,35 In practical terms, such fitness costs are manifest in reduced efficiencies and/or performance,
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Figure 1. Vector control methods categorised as conventional, population suppression and population replacement strategies. Note that, although present methods of chemical usage (A) to control vector populations fall under the population suppression heading, they are depicted separately from other methods (B) in order to show that chemical methods, at least in theory, fail to reduce the population below a certain level (vertical space between the blue line and the x-axis in diagram A. Diagram B represents population suppression strategies that include conventional non-GM SIT, GM-based RIDL, flightless RIDL and Wolbachia-driven biopesticide strategies. The diagram shows two downward-trend lines to represent the reduction in wild vector populations in response to the suppression treatments, where the primary (blue) line represents population reduction to a maximum level while the secondary (red) line represents post-suppression releases to maintain the population suppression. Diagram C presents a theoretical paradigm of population invasion/replacement, where release of a pathogen-specific refractory strain into the wild population results in disease transmission blockage. Note that two different Wolbachia-based strategies are mentioned in diagram C: Wolbachia used as a biopesticide to invade the wild vector populations, and a second, GM-based method where Wolbachia is exploited as a mere gene drive mechanism to introduce the refractory gene into the wild population.
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these results owing to the high fitness cost of the RIDL-Ox3604C males (ca 97%).40 The first open field suppression trials using genetically modified RIDL-Ox513A Ae. aegypti were conducted on Grand Cayman Islands by Oxitec Limited (UK). The selected field site was within a small town and had a population of ca 3000 people. The study was conducted from May to October 2010, during which time 3.3 million sterile males were released, reducing the wild Ae. aegypti population by ca 80%.30,31 Although this study successfully demonstrated suppression of a wild population, and in doing so confirmed the utility of the inherent marker, some of the other perceived benefits will require longer-term studies to enable verification. Further trials in a range of countries (Brazil, India, Panama, Malaysia, the United States) are completed, under way or in the process of gaining regulatory approval.10 3.3 Wolbachia pipientis Wolbachia pipientis (hereafter referred to as Wolbachia) is a rickettsia-like bacterial endosymbiont present in a significant proportion of insect species. Estimations vary, but a recent report suggests that globally it is present in approximately 76% of species.41 Wolbachia has recently received much needed attention, especially from scientists and programme managers, on account
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and correspondingly higher production and release numbers are required in an attempt to mitigate these effects.33 A further suggested benefit of RIDL over SIT is the late-acting lethality during the larval phase. In contrast to sterile or Wolbachiamediated population reduction, where F1 generation eggs fail to hatch, F1 RIDL progeny indeed hatch and develop through to the later immature stages (L3 pupae), thereby offering densitydependent competition with developing wild-type progeny. This is thought to contribute a significant additive effect in terms of population suppression.36 Other benefits include the inherent genetic marking system, which facilitates fast and accurate identification of RIDL insects and the potential to develop genetic sexing strains in which female-specific phenotypes (e.g. lethality) offer simple and precise sexing techniques.31 Laboratory, semifield and field assessment of RIDL-Ox513A Ae. aegypti mosquitoes for various fitness parameters and practical aspects have yielded encouraging results, demonstrating equivalent or near-equivalent dispersal and mating competitiveness.37,38 In contrast, studies on another form of RIDL, the Ox3604C female-specific flightless phenotype strain, showed excellent results in laboratory-based simulation studies aimed at eliminating a cage population.39 However, experiments in semi-field conditions failed to repeat
www.soci.org of its extraordinary ability to modify the host’s reproductive behaviour in favour of its spread.42 In fact, this is why Wolbachia is one of the most successful bacteria at forming symbiotic relationships with a wide range of insect species.41,42 Wolbachia is found to modify the host’s behaviour by inducing a range of reproductive phenotypes, namely cytoplasmic incompatibility, feminisation, induction of male-only mosquitoes, parthenogenesis, etc.41 – 43 Nonetheless, it has been established that a mutant of Wolbachia from Drosophila melanogaster restricts the growth of otherwise harmful pathogens to the host by its unusual replication behaviour. This strain (wMelPop) is popularly known as ‘Popcorn’ in view of its exceptional multiplicative behaviour in the host’s brain tissues.42 Another interesting phenotype observed in Drosophila is that some of the strains are found to reduce the active life span of the infected adults.44 Together, all these phenotypes make Wolbachia especially important to those involved in management of vector-borne diseases. Interestingly, Wolbachia is also found to be widely distributed in disease-spreading mosquitoes; however, it is conspicuous by its absence from the primary dengue vector Ae. aegypti. It is this absence that has opened the door to approaches exploiting the side effects of artificially infecting wild Ae. aegypti populations with Wolbachia. A reproductive phenomenon known as cytoplasmic incompatibility (CI) underpins Wolbachia-mediated biocontrol of Ae. aegypti and facilitates the prevention of virus transmission. Wolbachia infections impart a reproductive deficit in uninfected females, whereby wild females mated by an infected male cannot produce offspring.25 Wolbachia-infected males can therefore be used in a similar manner to conventional SIT, in that eggs laid by mated wild females fail to hatch, and repeated releases can serve to suppress the wild population. Wolbachia infections are only inherited maternally, so releases of Wolbachia-infected females can result in a mechanism by which infection can be driven through a population.45,46 One particular control strategy utilises this characteristic to infect all wild Ae. aegypti in a given area with a life-shortening strain of Wolbachia.47 A second strategy uses the CI mechanism to drive a Wolbachia infection throughout all members of the wild population, as it has been shown to inhibit pathogen (including dengue virus) transmission dramatically.22 It is presently being more widely evaluated (e.g. Australia, Indonesia, Brazil and Vietnam) by using wMel-Wolbachia strain in Ae. aegypti, and initial data from Australia have shown it to be extremely effective, with complete and stable infection rates achieved.48 However, more studies are warranted in light of the finding that, upon cessation of release of Wolbachia-infected mosquitoes, the local population is susceptible to reversal, i.e. to an increase in bacteria-free mosquitoes.48 Although there is no evidence for such reversal in the case of wMel-Wolbachia releases,48 it could be possible with the Popcorn strain, given its high fitness costs to the host. Also, studies on the impact of Wolbachia on dengue transmission in field conditions are required.
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Critical consideration of the safety and application of control strategies is a prerequisite for their development, and a number of discussions and studies have addressed the hypothetical environmental risks posed by releasing genetically modified organisms. The ethical, legal and social issues associated with genetic engineering, relevant to technologies such as RIDL, are under fierce debate in many parts of the world.49 – 51 A fundamental consideration pertinent to any environmental assessment is the degree of permanency that is being imposed.
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BP Niranjan Reddy, B Gupta, BP Rao Control regimes that offer a benefit in the short to medium term (decades) can evidently be advantageous, but the impact of longterm or permanent changes on the environment are inherently difficult to predict; they cause uncertainty and justifiable concern. Assuming that implementation is correct, genetic strategies based on population reduction (i.e. SIT, Wolbachia-infected male releases and RIDL) generally offer a temporary reduction or localised elimination of vector populations, and their species specificity and short- to medium-term persistence leave a minimal ecological footprint.52,53 Strategies aimed at population replacement, such as self-driving Medea-genetic-element-infected female releases.43 have the potential to impose permanent change on the wild vector populations and additionally spread through non-target areas. This may be a cause of concern in a regulatory context, as risk mitigation is fundamentally more challenging.
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PROSPECTS FOR NON-GENETIC CONTROL
Increasingly stringent regulatory frameworks and soaring developmental costs have progressively constrained the discovery and registration of novel pesticide molecules over recent decades. In conjunction with this, the available chemical classes are being exhausted, reducing the chances of finding active ingredients (AIs) with new modes of action.7 Disappointingly, the public health sector has rarely been the focus of pesticide discovery, as the agrochemical market is far more lucrative. This has resulted in a shortage of available AIs, subsequent overreliance on specific chemical classes and the consequent development of insecticide resistance. Resistance to key chemical classes, such as pyrethroids and organophosphates, is now ubiquitous in Ae. Aegypti.54 With no evidence of change in the foreseeable future, increasing political and social condemnation of pesticide use in developed countries and a track record of resistance development, chemical control would appear to be an unlikely source for a novel, environmentally acceptable and sustainable solution to vector control. Partially treatable diseases such as microfilariasis and untreatable diseases such as chikungunya and dengue are inflicting extreme socioeconomic losses to communities of rural origin. In addition, in spite of intense efforts and progress in vaccine research for VBDs such as malaria and dengue, effective vaccines are neither available nor imminent.55 Another problem that arises in controlling such diseases using therapeutic preparations is the adaptation of parasites in the form of drug resistance. The targeted organisms can adapt as a consequence of selection pressures imposed by sublethal doses of a drug, in combination with their own high genomic plasticity. An illustrative example is P. falciparum, one of the most devastating human malaria parasite species. P. falciparum has developed resistance to almost all types of therapeutic drug currently being used to combat malaria.56 Drug resistance is also emerging in other human pathogens, e.g. leishmaniasis and sleeping sickness.57,58
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COMMUNITY ENGAGEMENT
Ethical, legal and social issues (ELSIs) are considered to be more important than technological innovations and even the intended primary objectives of the project.17,42,49,59 – 63 Public education and community engagement are considered to be final steps in the lengthy evaluation process of bringing lab-to-field translation of innovations; nevertheless, these are also acknowledged as momentous in implementing novel technologies for vector control.50,63 Historically there have been serious repercussions
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from the lack of a proper approach, planning and execution of public education, which may prove disastrous in delivering success to a project.17,49,59 Experience also shows that improper, incorrect or inappropriate dissemination of project objectives and goals and technological background information may even lead to a halt in a project at any time during the course of its evaluation.59 – 61 Thus, when preparing the communication strategy, it is imperative to consider the various socioeconomic strata of local communities, including the involvement and participation of various stakeholders. Besides ELSIs, there are many other nation- or region-specific issues and challenges related to the development and deployment of genetic technologies for the control of human diseases (for example, political commitment).64,65 Those issues and their solutions need to be known beforehand for the successful and effective development of the technology.
7 ISSUES AND CHALLENGES, AND JUSTIFICATION OF USING NOVEL VECTOR CONTROL METHODS IN INDIA
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LOGISTICS AND RECOMMENDATIONS
When evaluating the efficacy of these novel technologies, it would be advisable to proceed with caution and to consider some important points. Firstly, India already has a well-established hierarchical public health system for dealing with vector-borne diseases. Hence it is logical to consult, apprise, involve and acquire the support of the health system for any new initiative right from the beginning of the project.50,64 Health care in India is state run rather than federally governed, and hence it is important to obtain permission to conduct feasibility studies from the state as well as from local government. Secondly, trials should start in hamlets or at study sites of similar size, requiring minimal logistics and operational costs before progressing to large-scale area-wide implementation.43,72,73 Preferably, these studies should be regarded as a prelude to obtaining novel information on public and community responses, government and policy-makers’ support, political will and other scientific parameters that could be locally influenced by change in geography and climate.42,43,64 Thirdly, serious attention should be paid to the experiences and mistakes of others.19,49,50,59 In other words, lessons must be learnt from the findings of similar experiments in countries where diseases are endemic, mostly in south-east Asia and Latin America, which have similar, if not identical, socioeconomic conditions and living standards, including demography and population densities, for example RIDL trials in the Grand Cayman Islands50 and in Brazil (www.Oxitec.com) and Wolbachia-based biocontrol trials in Vietnam.74
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CONCLUSION
VBDs are a huge burden on many societies throughout the world, and in the case of dengue viruses they are rapidly increasing both in terms of geographical spread and rates of morbidity and mortality. Owing to constraints associated with the use of chemical insecticides, coupled with the lack of any treatment or vaccine in the foreseeable future, there is a clear need for alternate approaches. Vector control strategies that are effective, that in theory are sustainable and that have a defined ecological footprint are now available. The complexities of regulation, public education or scientific accreditation should not be insurmountable barriers preventing their independent and rigorous assessment. An evaluation in this context is merely an appraisal of safety and worth, although in the longer term it may also prove to be the seed of better social well-being and large-scale social development. These sometimes politically charged technologies present new challenges for the political and regulatory bodies, and in some cases their innovation may require new regulatory frameworks to be put in place. They demand a level of transparency at all stages of the evaluation process, and cooperation at the community level is vitally important. With the nation’s well-being at the fore, the political and regulatory authorities are duty bound to act in the public’s interest, and the potential for major advances in public
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The vast geography and diverse climatic profile of India make adoption of such techniques a challenging task. However, with a well-prepared strategy and step-by-step evaluation of potential technologies, coupled with proper project management and communication strategies, the seemingly daunting task is certainly not an impossible one.50,51 For obvious reasons, such as geographical and demographic changes due to pursuit of economic ambitions, the dynamics of disease vector population is ever changing (www.nvbdcp.org), especially in the case of vectors that favour urban dwellings. Furthermore, India is home to different ethnic communities with diverse traditions and cultural practices that are tightly linked to their socioeconomic status.66,67 In addition to the above-mentioned complexities, another major issue with India is the size of the population. As a result of globalisation, the urban population of India is expanding unexpectedly into poor or ill-planned cities, where basic amenities and sanitary conditions are lacking, and the local environment is deteriorating day by day.68 One report on population migration suggests that, in the coming decade, ∼400 million people will leave rural villages in pursuit of a livelihood in urban settings (http://www.urbanindia.nic.in). Already under severe stress from a lack of sufficient basic amenities, the additional population burden on the cities, in reality, will pose a serious threat to the viability of existing or any new innovative vector control measures. All these issues present a great challenge when novel methods are being incorporated into existing vector control programmes. Paradoxically, these issues are among the strongest arguments for the testing of novel controls that basically require minimal intervention because of their greater species specificity9 and ecofriendliness, coupled with their low operating costs once established, for example self-driven Wolbachia-mediated biological control.42 For the time being, in theory at least, there is no better option than community engagement and unequivocal support and involvement in the control of vectorborne diseases that are spreading, in particular, in urban areas where the sprawling population is adopting a more complex living environment in which ‘vertical’ living is the norm.69,70 These are some of the issues contributing to failure of existing urban vector management strategies such as source reduction with environmental management, source treatment
using larvicides and insecticide fogging during epidemics. One of the greatest examples can be drawn from the recent failure of the Delhi government to control dengue disease during the 2010 Commonwealth Games,71 in spite of the mobilisation of all possible resources, from political will to exploiting the experience of vector control experts and programme managers, and a similar situation is evident with year-on-year malaria in metropolitan cities like Mumbai, Kolkata and Chennai (www.nvbdcp.gov.in).
www.soci.org health should not be overlooked. As the country at the top of the world rankings in terms of numbers of dengue cases, with a recent estimate of over 32 million per annum,75 should not India be leading the way in the pursuit of an effective, sustainable solution?
ACKNOWLEDGEMENTS BPNR thanks the council of scientific and industrial research (CSIR) for a senior research fellowship. The authors are grateful two anonymous reviewers for their valuable comments on a previous version of the manuscript.
REFERENCES
522
1 Patz JA, Campbell-Lendrum D, Holloway T and Foley JA, Impact of regional climate change on human health. Nature 438:310–317 (2005). 2 Reddy BPN, Labbe´ P and Corbel V, Culex genome is not just another genome for comparative genomics. Parasites Vectors 5:1–4 (2012). 3 Lobo DA, Velayudhan R, Chatterjee P, Kohli H and Hotez PJ, The neglected tropical diseases of India and South Asia: review of their prevalence, distribution, and control or elimination. PLoS Negl Trop Dis 5:e1222 (2011). 4 Dash AP, Adak T, Raghavendra K and Singh OP, The biology and control of malaria vectors. Curr Sci 92:1571–1578 (2007). 5 Soper FL, The elimination of urban yellow fever in the Americas through the eradication of Aedes aegypti. Am J Publ Hlth Nation’s Hlth 53:7–16 (1963). 6 Zaim M and Guillet P, Alternative insecticides: an urgent need. Trends Parasitol 18:161–163 (2002). 7 Gorman K, Editorial – Resistance 2011. Pest Manag Sci 69:149 (2013). 8 Ault SK, Pan American Health Organization’s regional strategic framework for addressing neglected diseases in neglected populations in Latin America and the Caribbean. Mem Inst Oswaldo Cruz 102:99–107 (2007). 9 Alphey L, Benedict M, Bellini R, Clark GG, Dame DA, Service MW et al, Sterile-insect methods for control of mosquito-borne diseases: an analysis. Vector-Borne Zoonotic Dis 10:295–311 (2010). 10 McGraw EA and O’Neill SL, Beyond insecticides: new thinking on an ancient problem. Nat Rev Microbiol 11:181–193 (2013). 11 Sharma GK, Review of malaria and its control in India. Proc Indo-UK Workshop on Malaria, Malaria Research Centre, Delhi, India, pp. 13–40 (1984). 12 Kumar A, Valecha N, Jain T and Dash AP, Burden of malaria in India: retrospective and prospective view. Am J Trop Med Hyg 77:69–78 (2007). 13 Gratz NG, Emerging and resurging vector-borne diseases. Annu Rev Entomol 44:51–75 (1999). 14 Curtis C, Review of Previous Applications of Genetics to Vector Control. Springer, Dordrecht, The Netherlands (2006). 15 Curtis C, Brooks G, Ansari M, Grover K, Krishnamurthy B, Rajagopalan P et al, A field trial on control of Culex quinquefasciatus by release of males of a strain integrating cytoplasmic incompatibility and a translocation. Entomol Exp Applic 31:181–190 (1982). 16 Yasuno M, Macdonald WW, Curtis CF, Grover KK, Rajagopalan PK, Sharma LS et al, A control experiment with chemosterilized male Culex pipiens fatigans Wiedemann in a village near Delhi surrounded by a breeding-free zone. Jpn J Sanit Zool 29:325–343 (1975). 17 Sehgal NK, Doubts over US in India. Nature 251:177–178 (1974). 18 Powell K and Jayaraman KS, Mosquito researchers deny plotting secret biowarfare test. Nature 419:867 (2002). 19 WHO-supported collaborative research projects in India: the facts. WHO Chron 30:131–139 (1976). 20 Davidson G, Curtis CF, White GB and Rawlings P, Mosquito war games. Nature 296:700 (1982). 21 Hay SI, Sinka ME, Okara RM, Kabaria CW, Mbithi PM, Tago CC et al, Developing global maps of the dominant Anopheles vectors of human malaria. PLoS Med 7:e1000209 (2010). 22 Moreira LA, Iturbe-Ormaetxe I, Jeffery JA, Lu G, Pyke AT, Hedges LM et al, A Wolbachia symbiont in Aedes aegypti limits infection with Dengue, Chikungunya, and Plasmodium. Cell 139:1268–1278 (2009).
wileyonlinelibrary.com/journal/ps
BP Niranjan Reddy, B Gupta, BP Rao 23 Dyck V, Hendrichs J and Robinson AS, Sterile Insect Technique: Principles and Practice in Area-wide Integrated Pest Management. International Atomic Energy Agency, The Netherlands (2005). 24 Vreysen MJ, Robinson AS and Hendrichs J, Area-wide Control of Insect Pests: from Research to Field Implementation. Springer, Dordrecht, The Netherlands (2007). 25 Laven H, Eradication of Culex pipiens fatigans through cytoplasmic incompatibility. Nature 216:383–384 (1967). 26 Bellini R, Calvitti M, Medici A, Carrieri M, Celli G and Maini S, Use of the sterile insect technique against Aedes albopictus in Italy: first results of a pilot trial, in Area-wide Control of Insect Pests, ed. by Vreysen MJB, Robinson AS and Hendrichs J. Springer, Dordrecht, The Netherlands, pp. 505–515 (2007). 27 Dame DA, Woodard DB, Ford HR and Weidhaas DE, Field behavior of sexually sterile Anopheles quadrimaculatus males. Mosquito News 24:6–16 (1964). 28 Oliva CF, Jacquet M, Gilles J, Lemperiere G, Maquart PO, Quilici S et al, The sterile insect technique for controlling populations of Aedes albopictus (Diptera: Culicidae) on Reunion Island: mating vigour of sterilized males. PloS One 7:e49414 (2012). 29 Bellini R, Medici A, Puggioli A, Balestrino F and Carrieri M, Pilot field trials with Aedes albopictus irradiated sterile males in Italian urban areas. J Med Entomol 50:317–325 (2013). 30 Dyck VA, Hendrichs J and Robinson A, Sterile Insect Technique: Principles and Practice in Area-wide Integrated Pest Management. Springer, Dordrecht, The Netherlands (2005). 31 Thomas DD, Donnelly CA, Wood RJ and Alphey LS, Insect population control using a dominant, repressible, lethal genetic system. Science 287:2474–2476 (2000). 32 Alphey L, Baker P, Burton RS, Condon GC, Condon KC, Dafa’alla TH, Epton MJ, Fu G, Gong P, Jin L, Labbe´ G, Morrison NI, Nimmo DD, O’Connell S, Phillips CE, Plackett A, Scaife S and Woods A, Genetic technologies to enhance the Sterile Insect Technique (SIT). Fruit Flies of Economic Importance: From Basic to Applied Knowledge Proceedings of the 7th International Symposium on Fruit Flies of Economic Importance 10–15 September 2006, Salvador, Brazil pp. 319–326. 33 Black IV WC, Alphey L and James AA, Why RIDL is not SIT. Trends Parasitol 27:362–370 (2011). 34 Raghavendra K, Barik TK, Reddy BPN, Sharma P and Dash AP, Malaria vector control: from past to future. Parasitol Res 108:757–779 (2011). 35 Catteruccia F, Crisanti A and Wimmer EA, Transgenic technologies to induce sterility. Malar J 8:S7 (2009). 36 Phuc HK, Andreasen MH, Burton RS, Vass C, Epton MJ, Pape G et al, Late-acting dominant lethal genetic systems and mosquito control. BMC Biol 5:11 (2007). 37 Lee HL, Joko H, Nazni WA and Vasan SS, Comparative life parameters of transgenic and wild strains of Aedes aegypti in the laboratory. Dengue Bull 33:103–314 (2009). 38 Bargielowski I, Nimmo D, Alphey L and Koella JC, Comparison of life history characteristics of the genetically modified Ox513a line and a wild type strain of Aedes aegypti. PLoS One 6:e20699 (2011). 39 Wise de Valdez MR, Nimmo D, Betz J, Gong H-F, James AA, Alphey L et al., Genetic elimination of dengue vector mosquitoes. Proc Natl Acad Sci USA 108:4772–4775 (2011). 40 Facchinelli L, Valerio L, Ramsey JM, Gould F, Walsh RK, Bond G et al, Field cage studies and progressive evaluation of geneticallyengineered mosquitoes. PLoS Neglected Trop Dis 7:e2001 (2013). 41 Jeyaprakash A and Hoy MA, Long PCR improves Wolbachia DNA amplification: wsp sequences found in 76% of sixty-three arthropod species. Insect Mol Biol 9:393–405 (2000). 42 Iturbe-Ormaetxe I, Walker T and O’Neill S, Wolbachia and the biological control of mosquito-borne disease. EMBO Rep 12:508–518 (2011). 43 Hoffmann AA, Montgomery BL, Popovici J, Iturbe-Ormaetxe I, Johnson PH, Muzzi F et al., Successful establishment of Wolbachia in Aedes populations to suppress dengue transmission. Nature 476:454–457 (2011). 44 Min K-T and Benzer S, Wolbachia, normally a symbiont of Drosophila, can be virulent, causing degeneration and early death. Proc Natl Acad Sci USA 94:10 792–10 796 (1997). 45 Adak T, Singh OP, Nanda N, Sharma VP and Subbarao SK, Isolation of a Plasmodium vivax refractory Anopheles culicifacies strain from India. Trop Med Int Hlth 11:197–203 (2006).
c 2013 Society of Chemical Industry
Pest Manag Sci 2014; 70: 517–523
Novel control methods of mosquitoes in India
www.soci.org
46 Adams MD, Celniker SE, Holt RA, Evans CA, Gocayne JD, Amanatides PG et al, The genome sequence of Drosophilamelanogaster. Science 287:2185–2195 (2000). 47 McMeniman CJ, Lane RV, Cass BN, Fong AWC, Sidhu M, Wang YF et al, Stable introduction of a life-shortening Wolbachia infection into the mosquito Aedes aegypti. Science 323:141–144 (2009). 48 Hoffmann AA, Montgomery BL, Popovici J, Iturbe-Ormaetxe I, Johnson PH, Muzzi F et al, Successful establishment of Wolbachia in Aedes populations to suppress dengue transmission. Nature 476:454–457 (2011). 49 Subbaraman N, Science snipes at Oxitec transgenic-mosquito trial. Nature Biotechnol 29:9–11 (2011). 50 Reeves RG, Denton JA, Santucci F, Bryk J and Reed FA, Scientific standards and the regulation of genetically modified insects. PLoS Neglected Trop Dis 6:e1502 (2012). 51 Mumford JD, Science, regulation, and precedent for genetically modified insects. PLoS Neglected Trop Dis 6:e1504 (2012). 52 Beech CJ, Nagaraju J, Vasan SS, Rose RI, Othman RY, Pillai V et al, Risk analysis of a hypothetical open field release of a self-limiting transgenic Aedes aegypti mosquito strain to combat dengue. Asia Pacif J Mol Biol Biotechnol 17:99–111 (2009). 53 Beech CJ, Koukidou M, Morrison NI and Alphey L, Genetically modified insects: science, use, status and regulation. Colln Biosaf Rev 6:66–124 (2012). 54 Bariami V, Jones CM, Bisset JA, Rodrigquez M, Vontas J and Hilary Ranson, The molecular basis of pyrethroid resistance in Aedes aegypti from the Caribbean. PLoS Negl Trop Dis 6:e1692 (2012). 55 Vaughan AM and Kappe SH, Malaria vaccine development: persistent challenges. Curr Opin Immunol 24:324–331 (2012). 56 Hayton K and Su X, Drug resistance and genetic mapping in Plasmodium falciparum. Curr Genet 54:223–239 (2008). 57 Croft SL, Sundar S and Fairlamb AH, Drug resistance in Leishmaniasis. Clin Microbiol Rev 19:111–126 (2006). 58 M¨aser P, Luscher A and Kaminsky R, Drug transport and drug ¨ resistance in African trypanosomes. Drug Resist Updates 6:281–290 (2003). 59 Jayaraman KS, Pest research centres: foreign labs shut. Nature 296:104–105 (1982). 60 Jayaraman KS, Consortium aims to revive sterile-mosquito project. Nature 389:6 (1997). 61 Opinion. Oh, New Delhi; oh, Geneva. Nature 256:355–357 (1975). 62 Pal R and Whitten MJ, WHO/ICMR programme of genetic control of mosquitoes in India, in The Use of Genetics in Insect Control. Elsevier/North Holland, Amsterdam, The Netherlands, pp. 73–95 (1974).
63 Macer D, Ethical, legal and social issues of genetically modified disease vectors in public health. UNDP/World Bank/WHO Special Program for Research and Training in Tropical Diseases (TDR). [Online]. WHO, Geneva (2003). Available: http://www.who. int/tdr/publications/documents/seb_topic1.pdf. [5 May 2010]. 64 Progress and prospects for the use of genetically modified mosquitoes to inhibit disease transmission. Report on Planning Meeting 1: Technical Consultation on Current Status and Planning for Future Development of Genetically Modified Mosquitoes for Malaria and Dengue Control 2009. [Online]. WHO, Geneva (2009). Available: http://whqlibdoc.who.int/publications/2010/9789241599238_ eng.pdf [6 March 2013]. 65 Pal R and Whitten MJ, The Use of Genetics in Insect Control. Elsevier/North-Holland, Amsterdam, The Netherlands (1974). 66 Chhokar JS, India: diversity and complexity in action, in Culture and Leadership across the World: the GLOBE Book of In-depth Studies of 25 Societies. Psychology Press, New York, NY, pp. 971–1020 (2008). 67 Majumder PP, People of India: Biological Diversity and Affinities. University Press, Hyderabad, India (1998). 68 King RA, Rathi S and Sudhira HS, An approach to regional planning in India. Int J Syst Syst Eng 3:117–128 (2012). 69 Gubler DJ, Resurgent vector-borne diseases as a global health problem. Emerging Infectious Dis 4:442–450 (1998). 70 Beaty BJ, Genetic manipulation of vectors: a potential novel approach for control of vector-borne diseases. Proc Natl Acad Sci USA 97:10 295–10 297 (2000). 71 Shaw M, Leggat PA and Chatterjee S, Travelling to India for the Delhi XIX Commonwealth Games 2010. Travel Med Infectious Dis 8:129–138 (2010). 72 Harris AF, Nimmo D, McKemey AR, Kelly N, Scaife S, Donnelly CA et al, Field performance of engineered male mosquitoes. Nat Biotechnol 29:1034–1037 (2011). 73 Harris AF, McKemey AR, Nimmo D, Curtis Z, Black I, Morgan SA et al, Successful suppression of a field mosquito population by sustained release of engineered male mosquitoes. Nat Biotechnol 30:828-30 (2012). 74 Tri NGuyen Island Field Trial Update. [Online]. 2013. Available: http://www.eliminatedengue.com/library/publication/document/ field_trial_update/tni_trial_update/2013.09.03_tni_trial_update_ english_final.pdf [5 September 2013]. 75 Bhatt S, Gething PW, Brady OJ, Messina JP, Farlow AW, Moyes CL et al, The global distribution and burden of dengue. Nature 496(7446):504–507 (2013).
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