Genetic Control of Malaria and Dengue

Zach N. Adelman

• Publisher: Academic Press
• Year: 2015
• ISBN:
  9780128004050
• Topic: Medicina
• Subtopic: Microbiologia medica e parassitologia

Genetic Control of Malaria and Dengue focuses on the knowledge, technology, regulation and ethics of using genetically modified mosquitoes to interrupt the transmission of important vector-borne diseases including Malaria. It contains coverage of the current state of knowledge of vector-borne diseases and how they are currently controlled; vaccine, drug and insecticide development; various strategies for altering the genome of mosquitoes in beneficial ways; and the regulatory, ethical and social environment concerning these strategies.

For more than five decades, the prospect of using genetically-modified mosquitoes to control vector-borne disease transmission has been a purely hypothetical scenario. We simply did not have the technology or basic knowledge to be able to do it. With the explosion of field trials and potential interventions in development, Genetic Control of Malaria and Dengue provides a comprehensive overview of research in genetics, microbiology, virology, and ecology involved in the development and implementation of genetic modification programs for virus and disease control. This book is meant to provide a practical guide to researchers, regulators and the general public about how this technology actually works, how it can be improved, and what is still unknown.

• Includes coverage of vectorial capacity, critical to understanding vector-borne disease transmission
• Provides a summary of the concepts of both population suppression and population replacement
• Contains pivotal coverage of ethical and ecological ramifications of genetics-based control strategies

Chapter 1

Transgenic Pests and Human Health

A Short Overview of Social, Cultural, and Scientific Considerations*

Tim Antonelli¹, Amanda Clayton², Molly Hartzog³, Sophia Webster⁴ and Gabriel Zilnik⁴, ¹Department of Mathematics, Worcester State University, Worcester, MA, USA, ²Department of Economics, North Carolina State University, Raleigh, NC, USA, ³Department of Communication, Rhetoric, and Digital Media, North Carolina State University, Raleigh, NC, USA, ⁴Department of Entomology, North Carolina State University, Raleigh, NC, USA

Abstract

Tropical disease mitigation is a multifaceted, complex issue that spans many disciplines within the natural sciences, social sciences, and humanities. Effective control and prevention of diseases like malaria and dengue fever requires integrated research in order to understand these problems within their social and cultural contexts. This type of interdisciplinary research was recently endorsed by the American Academy of Arts and Sciences (2013) as critical for developing effective solutions for the world’s problems. Adopting such an interdisciplinary approach, we discuss various social, cultural, and ethical issues related to the control of dengue fever and malaria, especially those pertaining to the potential use of transgenic technologies.

Keywords

Dengue; malaria; Aedes aegypti; Anopheles; vector control; genetic engineering; ethics; communication; community engagement; treatment

Introduction

The global problems of dengue fever and malaria are multifaceted, complex issues that span many disciplines, including human health, ecology, economics and urban development, health and environmental policy, social work, and risk analysis. Effective disease control and prevention therefore requires integrated research from all of these disciplines in order to understand the problem from as many angles as possible and within its social and cultural contexts. This type of interdisciplinary approach that integrates perspectives from the natural sciences, social sciences, and humanities was recently endorsed by the American Academy of Arts and Sciences as critical for developing effective solutions for the world’s problems [1]. Adopting this approach, we introduce the ethical, regulatory, social, and economic aspects of control programs for dengue fever and malaria, relating to both currently used control techniques as well as the emerging technologies involving genetically modified organisms (GMOs).

The goal of this chapter is not to offer a definitive stance on whether or not genetically modified (GM) technologies should be used to control mosquito-borne diseases, but rather to offer a cursory look at the complex issues that span multiple disciplines, governmental and nongovernmental organizations, and community interests. In conclusion, we argue that a discussion of whether or not to implement GM technologies should be conducted within the larger discussion of national, regional, and global disease control strategies. These control plans should consider an integration of multiple control strategies and adapt to suit differing social and cultural contexts based on the area under consideration.

Current State of GMOs

In 1996, agriculture experienced a genetic revolution. Before the planting season, the United States Environmental Protection Agency (EPA) had approved the commercial sale of what would become the most widespread transgenic cultivars. Recombinant DNA technology has revolutionized biological sciences with practical impacts in fields ranging from medicine to agriculture [2]. New crops and modified organisms would soon come to be known as GMOs. Crops carried genes from bacteria conferring resistance to Roundup™ (glyphosate) weed killer and to certain insect species. Bacteria were engineered to produce human insulin. With regard to pest management, the impact of transgenics remains acutely felt in agriculture. Entire agricultural systems were constructed around new transgenic cultivars; new industries were born, while old ones failed. Land-grant institutions around the country helped research the impacts of these new varieties. Fields from the applied life sciences produced thousands of articles in biochemistry, molecular biology, conservation biology, ecology, evolution, plant science, weed science, environmental resource management, and many more regarding the efficacy and safety of transgenic cultivars [3]. Yet, this technology has its detractors. Many groups such as Union of Concerned Scientists and Gene Watch point to issues with regulatory systems in assessing safety or environmental concerns related to transgenic organisms.

Controlling pests with transgenic technology is predominantly accomplished with δ-endotoxins (Cry toxins) from strains of Bacillus thuringiensis. Commonly known as Bt crops, the plants have a host of attractive features. Most notable is the narrow spectrum of pests that each Cry toxin affects. At the time of this writing, varieties of Bt crops primarily target lepidopteran, dipteran, and coleopteran pests. Furthermore, a single gene encodes each Cry toxin making the combination of toxins, known as stacking, relatively straightforward [4]. Growers have found these crops extremely useful; in 2014, transgenic Bt crops constituted 84% of cotton and 80% of corn grown in the United States [5]. Developing countries such as India, China, South Africa, Brazil, and Argentina have seen explosive growth in transgenic crop adoption. Those five countries accounted for nearly 50% of transgenic crops (including herbicide tolerant cultivars) grown worldwide in 2011 [6]. However, these crops are not without their drawbacks. While the primary pests of these crops have been controlled, a surge of secondary piercing–sucking pests such as stink bugs and aphids has become a problem in some regions of the world [7]. Consequently, the increase in insecticide use to control secondary pests may offset the decreased insecticide applications for the primary pests now controlled by Bt. Thus, detailed knowledge of the pest assemblage is useful when approaching transgenic control through direct modification. Similarly, in thinking about GM mosquitoes to combat dengue and malaria, detailed knowledge of the transmission cycle and host assemblage is required to know how the system might respond to genetic control of a single species.

While transgenic crops are widespread in much of North America and Asia, this is not necessarily the case around much of the globe. For example, many nations in Europe restrict transgenic cultivars and in some cases have even seen a decline in field trials of these cultivars [6]. Concern over the safety of these crops remains intense, but as it stands now, no credible scientific evidence has been presented demonstrating adverse effects associated with consumption of transgenic crops [8]. However, the moral and ethical arguments against transgenic crops seem to have the most traction and these arguments are more difficult to resolve with scientific data alone. Below we discuss some of the ethical implications surrounding transgenic insects, which are derived from literature surrounding transgenic cultivars.

Dengue Fever and Malaria

The WHO provides fact sheets (available online) on both dengue and malaria that are straightforward and highly informative. Here, we provide a summary and comparison of the two diseases focusing on their global prevalence, symptom severity, and vector characteristics. We also discuss briefly the availability and efficacy of existing treatment and prevention methods for both diseases. Table 1.1 displays a summary of the key facts for both diseases.

Table 1.1

Key Facts About Dengue and Malaria [9–12]

	Dengue	Malaria
Vector	Aedes aegypti, Aedes albopictus (secondary)	About 20 species from the Anopheles genus
Strains	Four virus serotypes from the Flavivirus genus	Four parasite species from the Plasmodium genus
Severity	Contracting a second serotype results in a higher likelihood of experiencing severe dengue	Prevalence and severity varies with parasite (Plasmodium falciparum is the most common and deadly)
Immunity	Contracting one serotype provides permanent immunity to that strain and temporary immunity to the others	Partial immunity is accumulated over time and provides protection against severe disease
Diagnosis	ELISA tests for antigens (IgM & IgG), PCR	Rapid diagnostic tests for antigens, microscopy, PCR
Symptoms	Classic: fever, rash, headache, muscle aches, retro-orbital pain, vomiting	Classic: fever, headache, chills, vomiting
	Severe: internal hemorrhaging, severe abdominal pain and vomiting, respiratory distress	Severe: anemia, respiratory distress, cerebral malaria, organ failure
Mortality	Without treatment: about 20% mortality rate	About 627,000 deaths in 2012
	With treatment: less than 1% mortality rate	About 90% of deaths were from Africa, mostly among children
Global burden	WHO [9]: 50–100 million cases per year	WHO [10]: about 207 (473–789) million cases in 2012
	Bhatt et al. [12]: about 390 million cases per year, including asymptomatic
Risk groups	Children, elderly, imunocompromised	Children, elderly, imunocompromised, tourists and immigrants
Vaccines	In development but not yet available	In development but not yet available
Treatment	Classic: fluids, pain medication, rest	Antimalarial medications (parasite resistance is a continuing issue)
	Severe: fluid replacement therapy, blood transfusion
Common vector control	Container control, IRS of insecticides, larvicide packets in collected water	LLINs, indoor residual spraying of insecticides

Dengue Fever

Dengue is caused by at least four independent viruses that are all transmitted primarily by the mosquito Aedes aegypti. The most typical form of the disease is commonly called dengue fever and its symptoms include fever, rash, headache, and joint and retro-orbital pain. The severe form of the disease, called severe dengue or dengue hemorrhagic fever (DHF), can result in vomiting, internal hemorrhaging, and even death [13].

The WHO estimates that there are 50–100 million dengue infections each year, mostly in tropical regions, though a more recent estimate is nearer to 400 million due to the large number of asymptomatic and unreported cases [12]. Despite its high incidence, dengue fever is one of seventeen diseases classified as a neglected tropical disease (NTD) [14]. In terms of human health impact, NTDs are often compared to “the big three”: malaria, HIV/AIDS, and tuberculosis, which receive significantly more attention in funding, research, and social welfare projects than the 17 NTDs. T...