What are the most common signs and symptoms of malaria?

Uncomplicated malaria is characterized by fever, chills, sweats, headaches, muscle pains, nausea, vomiting, and general malaise. Patients with severe, or complicated, malaria can experience confusion, coma, seizures, severe anemia, and respiratory difficulties.

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How many people die of malaria each year, and who are they?

Approximately one to three million people die of malaria each year, the vast majority of whom are children in sub-Saharan Africa. Nearly 90 percent of all deaths due to malaria occur in sub-Saharan Africa.¹ Those without naturally acquired immunity to the disease, such as young children and travelers, and pregnant women are at particularly great risk.

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Where is malaria most common?

Malaria is one of the most prevalent infectious diseases worldwide.² There are currently 107 malaria-endemic countries throughout Africa, Asia, Latin America, the Middle East and the South Pacific.³ Although malaria occasionally occurs in other countries, such as in the United States, this is much less common. It is important to note that although malaria has been virtually eradicated from Western countries, it was prevalent in these places as recently as 50 years ago. The disease was eliminated in these countries through economic, environmental, and public health efforts.

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Is malaria suddenly a big problem or has it always been so?

Malaria is an ancient disease, documented for almost 4,000 years and most likely existing for an even longer period of time. Its name is Italian in origin and means “bad air;" it was given this name because it was common in marshy areas outside of ancient Rome. Malaria was recognized as a significant problem in Greece by the 4th century B.C., where it was responsible for population decreases in many city-states.⁴

Malaria remained a significant global health threat - particularly in warm, moist climates - until the Second World War. In the first half of the 20th century several scientific breakthroughs, such as the identification of the mosquito as the parasite's host, allowed significant control efforts to be put in place. Efforts to curb the disease in the United States were initiated in 1914; by 1951 the transmission of the disease was eradicated from the U.S. through the use of insecticides and other vector control methods.⁵

In 1955, the World Health Organization (WHO) set forth an ambitious proposal for the eradication of malaria worldwide. These efforts focused on house spraying with residual insecticides and antimalarial drug treatment. The program was successful in some areas, particularly in nations with temperate climates. Some countries, such as India, saw temporary sharp reductions in the number of cases as a result of the program, but infection rates returned to their original levels once efforts ceased. Other nations experienced negligible progress, while yet others – including most sub-Saharan African states - were excluded completely from the eradication campaign.⁶

Today, malaria remains a tremendous public health problem world-wide. Although some countries, such as the United States, have remained malaria-free since implementing eradication strategies, drug and insecticide resistance and other factors have exacerbated the problem in many areas of the world. Fortunately, malaria has received renewed attention from the global health community in the past few years, largely due to efforts by private organizations such as the Bill & Melinda Gates Foundation.

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Why is malaria still prevalent?

Problems such as the emergence of drug and insecticide resistance, the lack of a malaria vaccine, difficulties in obtaining sustained funding from donor countries, poverty, population growth, and the lack of community involvement have exacerbated malaria's prevalence in many countries. Parasite resistance to traditional antimalarials such as chloroquine, coupled with misuse and overuse of certain treatments, has presented a tremendous challenge. In 1980, chloroquine was cheap and effective; today resistance has rendered it useless in many parts of the world. At present, artemisinin combination therapies (ACTs) are considered to be the most effective treatments due to their efficacy and the total lack of clinical parasite resistance. Unfortunately, the treatments are not widely available and are currently too expensive for most of the people who are infected with malaria annually.⁷

The Plasmodium parasite has a complex lifecycle and mutates frequently, complicating efforts to develop effective vaccines. While there are some vaccines that are currently undergoing preclinical and clinical trials, it is not likely that an effective vaccine will be approved and ready for deployment for several years. Additionally, proper and thorough deployment presents a significant challenge in many countries, particularly those that are extremely poor or politically unstable.

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What are currently the most viable solutions to this global health problem?

The most viable strategies for controlling and eradicating malaria worldwide today are multifaceted. These include new medicines, combination therapies of both new and old medicines to decrease parasite resistance, efficacious vaccines with appropriate deployment, vector control, and social and behavioral change.

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Why aren't preventive measures enough?

Malaria control strategies focused upon the prevention of infection play an important role in addressing the epidemic. These preventive measures include the use of insecticides, bednets, other vector control strategies, and prophylactic drug therapies in at-risk populations, among others. Unfortunately, preventive measures are extremely difficult to implement on a broad scale, and adequate global coverage is nearly impossible. Some researchers argue that, at best, prevention alone may reduce the incidence of clinical disease by half.⁸

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Why don't we just spray insecticides to kill the mosquitos?

There are currently two major methods of using insecticides to contol malaria - source reduction and indoor residual spraying (IRS). Source reduction involves many non-chemical methods, and also includes spraying mosquito habitats and breeding areas with insecticides such as DDT. IRS involves coating the walls and other surfaces of a home with residual insecticides. Unfortunately, it is economically and logistically impossible (and generally not considered environmentally sound) to use insecticides on a scale large enough to kill all Anopheles mosquitos in malaria-endemic areas. Insecticides and other vector control methods remain an important component of malaria control, but do not represent a complete solution to the problem.

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Why isn't everyone using bednets for their children?

Recent research has demonstrated that insecticide-treated nets (ITNs), or bednets, constitute a simple, low-cost, and appropriate method with enormous potential to prevent malaria and decrease childhood mortality and morbidity from the disease.⁹ Due to a variety of complex social and economic issues, not all families currently use bednets in malaria-endemic areas.

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What is the state of development of a vaccine to prevent malaria?

There is much interest in the development of malaria vaccines, but thus far, field testing of candidate vaccines has shown only a limited degree of protection. An ideal vaccine would target multiple stages of the malaria parasite's development. Several different malaria vaccine candidates are now in human clinical trials in Africa, Asia, Europe, and the United States. Although vaccine development is progressing, it could be years before an effective vaccine is licensed and deployed.

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Why is semi-synthetic artemisinin a solution?

Artemisinin based combination therapies (ACTs) have been heralded by the international malaria community as an excellent option for the treatment of malaria. They have been shown to be safe and efficacious for the treatment of both uncomplicated and severe malaria. Additionally, while the disease-causing Plasmodium parasite has become increasingly resistant to traditional antimalarial therapies such as chloroquine, it has not yet shown any clinical resistance to artemisinin and its derivatives. Unfortunately, although ACTs are recommended as preferential therapies in areas with drug-resistant malaria parasites,¹⁰A.annua, the plant from which this important compound is derived. The development of semi-synthetic artemisinin is expected to provide a consistent, reliable, and cheap source of this key active pharmaceutical ingredient for companies around the world. Ultimately, this would improve affordable access to antimalarial treatments, even in the most impoverished areas.

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Who first discovered artemisinin as an antimalarial?

Chinese traditional healers are credited with first discovering the antimalarial properties of the annual herb Artemisia annua, known colloquially as sweet wormwood. In China, where A.annua was first described, it is known as qinghao, and the active ingredient artemisinin is termed qinghaosu. Although it has been used as an antimalarial in traditional Chinese medicine for many years, artemisinin was first isolated in 1972 by scientists working for the Chinese military (People’s Liberation Army).¹¹

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How long has artemisinin been used to treat malaria?

Artemisia annua, the plant from which artemisinin is derived, has been used by the Chinese to treat fevers and malaria for over 2,000 years. Studies in the 1970s first led to the scientific characterization of artemisinin as an antimalarial compound.¹²

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Are artemisinin derivatives safe to use in pregnant women?

There are limited reports on the use of artemisinin and its derivatives during pregnancy. Currently, the World Health Organization (WHO) recommends the use of artemisinin derivatives in pregnant women with severe malaria. Additionally, they are recommended for use in pregnant women with uncomplicated malaria in the second and third trimester of pregnancy in areas of multiple drug resistance. Due to a lack of data, the use of artemisinin derivatives in the first trimester of pregnancy is not recommended.¹³

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Are artemisinin derivatives safe to use in children?

The WHO has stated that artemisinins are safe for use in infants and children.¹⁴ Even so, there presently are few high-quality, licensed, and regulated sources of pediatric formulations of ACTs.

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Who makes ACTs?

Currently there are a few select pharmaceutical companies manufacturing high-quality ACTs. An example is Novartis, the manufacturer of Coartem^tm, currently the most widely used combination therapy. This project is not focused on creating a new ACT drug, but will instead develop an alternative source of artemisinin, the key ingredient in ACTs. This product would be sold to other pharmaceutical companies to be incorporated into life-saving treatments. The Artemisinin Project will help ensure that these pharmaceutical companies have a consistent, reliable, and inexpensive source of artemisinin.

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What is each partner's role in this project?

UC Berkeley will apply their breakthroughs in synthetic biology to produce a precursor to artemisinin in the lab. Amyris Biotechnologies will collaborate with UC Berkeley to build better microbes for fermentation and develop novel chemical processes. OneWorld Health will lead the drug development strategy, perform appropriate regulatory work, and provide overall project management.

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What are the goals of this project?

The goal of the partnership is to produce semi-synthetic artemisinin the key pharmaceutical compound in currently preferred treatments for malaria (artemisinin combination therapies, or ACTs). We anticipate that bulk production of this important compound will significantly reduce the price of these life-saving medicines, making them accessible to the hundreds of millions of impoverished people who contract malaria each year. Additionally, the development of a consistent, reliable source of artemisinin could help drug manufacturers avoid global shortages in the future.

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What do you anticipate your product costing?

The project aims to complete, optimize, and scale-up semi-synthetic artemisinin production systems to make bulk artemisinin available to pharmaceutical companies at a price much lower than the current cost. We anticipate that this would greatly reduce the cost of currently marketed ACTs, which are currently available to countries at a price of approximately $2.20 per adult course of treatment through the WHO.

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How can I get involved?

Individuals and organizations interested in supporting the project are invited to contact any of the three partners.

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