A second source of artemisinin, the key ingredient in World Health Organziation–recommended, artemisinin-based combination therapies will mean a more stable supply of antimalarial drugs and better access to care for those who need it most.

Photo credits: Photos 1-5 and 15, PATH/Elena Pantjushenko. Photos 6-14, PATH/Erika Amaya.

On World Malaria Day, we remember the 660,000 people killed by a mosquito’s bite each year and the hundreds of millions more who are sickened, some left crippled, by this disease. Thanks to major investment from the global community, particularly in the last two decades, over 90 countries today are malaria-free with an additional 26 en route to achieving that status. Since 2000, over 1.1 million lives have been saved, and global malaria mortality rates have decreased by 26 percent. For the first time in history, the goal of defeating malaria is within reach.

But the fight against malaria is not over. Approximately 3.3 billion people—about half the world’s population—still live at risk, and malaria remains a leading cause of death among young children. Recent gains against the disease are increasingly threatened by shortfalls in funding, and the resurgence of malaria will remain a persistent threat until the disease is stopped altogether.

It is important that we, as an international community, stay on course and maintain our collective focus in fighting malaria at this critical moment. With sustained investment and renewed commitment across sectors, we can continue making progress toward the 2015 Millennium Development Goal of halting and beginning to reverse the incidence of malaria.

PATH’s work in malaria

PATH is working to create a malaria-free world by tackling the disease from all sides. Our approach integrates:

1. Treatment, including the development of semisynthetic artemisinin, a key ingredient in WHO-recommended antimalarial drugs.
2. Case control, by developing and implementing strategies with national and global partners to create malaria-free zones village by village.
3. Prevention, including accelerating vaccine development, for the most effective results.

To learn more about malaria and PATH’s work to end the disease, take a look at the resources below:

World Malaria Day across PATH’s programs:

No more malaria

Making Malaria History

Malaria vaccine development: no longer a pipe dream?

A new way to make the most powerful malaria drug

Other resources:

The Roll Back Malaria Partnership website

World Health Organization malaria page

World Malaria Day website

Malaria toolkit

To learn more about the launch of industrial-scale production of semisynthetic artemisinin, read the full press release.

Photo credits: Photos 1-8, Sanofi. Photos 9-13, PATH/Ponni Subbiah.

Barrels of semisynthetic artemisinin derivatives at the Garessio launch.

Q. With the launch festivities wrapped up only a few hours ago, can you give us your highlights of the events today?

A. This morning, guests of Sanofi, our project partners, representatives of Roll Back Malaria and the Global Fund, and many other supporters gathered for a conference at Sanofi’s facility in Garessio, Italy, formally launching the industrial-scale production of semisynthetic artemisinin. Among the presenters at the conference was Dr. Jan Van Erps with Roll Back Malaria who spoke about the importance of semisynthetic artemsinin to ensure access to malaria care worldwide. The passion and dedication of the process development and manufacturing team at Sanofi was evident throughout today’s event. This included a tour in which we hopped aboard small trains (think of the train at Disneyland and you’ll have an idea of our ride!) for a tour of Sanofi’s new plant where semisynthetic artemisinin is produced. We saw the large photochemistry reactors where the final steps in the semisynthetic artemisinin production process occur and actual barrels of semisynthetic artemisinin ready to be shipped. The enthusiasm and excitement were contagious. One senior Sanofi colleague even indicated that this has been one of the most satisfying and fulfilling projects he has been involved in during his career.

I’m very grateful to Sanofi for hosting this event and bringing the partners together to commemorate this major milestone in the fight to eradicate malaria. Their hospitality has made this long-awaited celebration memorable.

Dr. Jan Van Erps from Roll Back Malaria speaks at the launch event.

Q. Nine years ago, the project was still an ambitious idea at UCB’s research lab in California. Today, you were standing on the factory floor at Sanofi’s plant in Italy, ready for large-scale production. What did it take to bring this innovative idea to scale?   

A. Strong partnership and cross-sector collaboration. From the original technology that provided the basis for this work, to the development of fermentation, chemistry, and scalable industrial manufacturing processes to get to semisynthetic artemisinin, our partners demonstrated ingenuity, scientific innovation, and willingness to work together toward a common goal of malaria eradication. We couldn’t have gotten here today without the talents and key contributions of each of the partners involved.

Dr. Ponni Subbiah (center) at Sanofi’s launch event.

Q. What was the role of OneWorld Health, PATH’s Drug Development program, in this project?

A. We led the partnership, providing overall program management and governance from research to commercialization. As the project grantee, we managed the interaction with the funder and facilitated communication between project partners; led strategy for product development, communications, and regulation; led the selection of the manufacturing partner; provided legal analysis for intellectual properties; and ensured that appropriate licenses and contracts were in place. We’ve also served as the public spokesperson for the project, keeping close contact with key stakeholders to ensure that the nonprofit nature of the project is well understood, and to promote the acceptance of this new technology and the smooth uptake of semisynthetic artemisinin.

Q. This project involved very diverse partners. What was it like working together despite varied institutional objectives and goals? 

A. The partnership included a diverse group of experts from the nonprofit, academic, biotech, and pharmaceutical sectors. As institutions, naturally, we have different ways to measure our success. Research scientists are rewarded for agility in research and publishing; an industry partner at a startup phase is rewarded for proof of concept of their technical platform; a pharma looks at commercial targets and getting products to market; and as a nonprofit, we strive to make a difference in public health. We realized our differences when we joined forces. At the onset of the project, we evaluated our differences and worked to harmonize them. We developed a set of shared standards for the project, identifying a common mission to keep our focus sharp.

Q. What was the most memorable moment of the launch event?

A. Seeing everyone together in one place celebrating this success—it really hit home the scale of what we have been able to do through our sustained cooperation, dedication, and most importantly our mutual respect for one another. Getting to see the fruits of that labor here in beautiful northern Italy, in Garessio, has been astonishing. What we have been able to accomplish—bringing semisynthetic artemisinin to fruition, first in the lab and then on an industrial scale—is truly incredible.

Dr. Subbiah and Dr. Wolfgang Laux from Sanofi tour the Garessio plant.

Q. What does it mean to you personally to see semisynthetic artemisinin enter the market?

A. When I worked at Mulago Hospital in Kampala, Uganda, I saw many patients suffering from malaria, including pregnant women and young children. I witnessed the critical need for meaningful treatment that would be accessible to patients, both in terms of supply and cost. Our work to diversify and strengthen production streams of artemisinin plays an important role in meeting that need. Semisynthetic artemisinin will strengthen the global market with an additional stream of high-quality product, giving ACT manufacturers a reliable supply they can depend on from year to year. By stabilizing the market against the fluctuating supply and pricing of botanical artemisinin, we’re making lifesaving treatments more available to vulnerable populations. This is the most fulfilling aspect of this work.

Read the full press release about the launch of industrial production of semisynthetic artemisinin.

Photo credits: PATH/Ponni Subbiah

I am thrilled to have been part of the Twitter contest, #LetsTalkDiarrhea, in March held by PATH’s Drug Development program (OneWorld Health)! I was excited to see such an important topic highlighted near World Water Day and that the efforts to do so reached so many people.

I like to think that I know my facts about water, sanitation, and hygiene (WASH), and I did know some of the answers off the bat. But I was also able to learn new things about WASH throughout the contest—did you know that when you eat a chocolate bar, you’re also eating something that is a micronutrient for diarrheal disease—zinc?! The team made all the questions engaging and pertinent to our own lives and our own practice. It was great to have questions teach me and remind me how diarrhea and pneumonia still kill more than 2 million children each year and how breastfeeding is actually one of the tools in fighting diarrheal disease in children.

Through this contest, I also learned more about other organizations doing work in WASH, like the partnership between PATH and the GAVI Alliance working toward providing all children with protection against rotavirus through vaccination and the new antidiarrheal drug called iOWH032 that could prevent dehydration and death from diarrheal disease!

I want to thank the team at PATH’s Drug Development program for the opportunity to be a part of their efforts on this very important topic. Through this Twitter contest, more and more people have seen the impacts of diarrheal disease on children around the world and the fact that the deaths caused by diarrhea are preventable through PATH’s and other organizations’ work!

—Jordan Teague, WASH Advocates
The George Washington University

Read up on drug development milestones, updates, and resources. Email us to receive future issues of A Healthy Dose.

In the 1970s, a new class of antimalarials—artemisinin derivatives—were first isolated and developed in China. Artemisinin is found naturally in the leaves of Artemisia annua (a plant used by Chinese healers as early as 168 B.C. to treat many illnesses), and its derivatives have proved highly potent against malaria parasites. Additionally, pairing artemisinin derivatives with a companion drug slows parasite resistance. In 2001, the World Health Organization (WHO) recommended the adoption of artemisinin-based combination therapies (ACTs) as the first-line treatment for uncomplicated malaria in Africa and Asia caused by the Plasmodium falciparum parasite, replacing older, less effective drugs.

Uncertain market

With growing global demand for ACTs, the world’s supply of artemisinin has not always kept pace. Currently, supply depends solely on the A. annua crop, which soars and plunges as prices for artemisinin fluctuate. Harvesting artemisinin from a plant, which is mostly cultivated in China and Vietnam, can take between 12 to 15 months from planting to extraction, and its yield and quality fluctuate due to environmental factors, competing crops, financial concerns, and/or political instability. Supply and demand volatility prevents antimalarial treatments from getting into the hands of the people who need them.

Creating a second source

To strengthen production of artemisinin, OneWorld Health (now PATH’s Drug Development program) collaborated with academic, biotech, and pharmaceutical partners to create a new, pharmaceutical manufacturing process using synthetic biology. Scientists first had to isolate the genes from the wormwood plant required to make artemisinic acid. Taking genes from the A. annua plant, they inserted them into bacteria and eventually into yeast. The yeast’s fermentation produced an intermediate product, artemisinic acid, which was then converted chemically into artemisinin. The artemisinin could then be used to make stable derivatives, appropriate for manufacturing several ACTs currently on the market. The entire manufacturing process takes approximately three months, less time than the botanical growing and harvesting cycle, and can be done in a controlled manufacturing setting to ensure high pharmaceutical consistency and quality.

Scaling industrial production to tons of material

Large-scale production of semisynthetic artemisinin will launch on April 11, with 35 metric tons of material aimed for production this year, which translates to approximately 70 million antimalarial treatments. Semisynthetic artemisinin will be produced at no profit, no loss, helping to keep the price at a fair market value. Providing the market with an additional source of high-quality artemisinin will complement the current plant-derived supply, ensure a more stable flow of artemisinin to ACT manufacturers, and secure greater availability of treatments to patients.

More than 650,000 people, mostly children, will die from malaria this year. Millions more will be sickened by the mosquito-borne illness, with some survivors crippled by its effects. The majority of people suffering from malaria live in sub-Saharan Africa, where each day a mosquito’s bite devastates families, threatens communities, and strains health resources. 

Photo credits, from top: PATH/Ponni Subbiah, PATH/Laura Newman, MMV Artemisinin Conference 2010

Drumroll, please! Without further ado, the winners are:

1st place: Jordan Teague (@jordanlteague)
2nd place: Grant Elijah Mattie (@TheGrantiChrist)
3rd place: Nikhil D. Patil (@npatil55)

Honorable mentions go to: Josh (@JoshFromCinci), Caitlin Garlow (@garlowc), Dr K Tangen-Steffins (@ktangensteffins), The Poop Project (@poop_project), and DEEJAY 3R3MY (DJ_3R3MY).

Contest questions and answers are listed in detail below.

1. Q:  In the past decade, global investments have led to great progress toward improving the health of children in developing countries. Yet, ____ and ____ still cause nearly one-third of all child deaths—over 2 million each year.
A:  In 2011 more than 2 million children died due to pneumonia and diarrheal disease. Episodes of diarrhea may predispose undernourished children to pneumonia. Tackling pneumonia and diarrhea simultaneously should be a global priority, especially because preventing both conditions involves overlapping forms of protection. Learn more.

2. Q: Severe diarrhea causes dehydration, and replacement of lost fluids is urgent to prevent symptoms from becoming fatal. If all caretakers could have access to this simple and effective treatment, diarrhea deaths would drop by 93%. What is it?
A: Oral rehydration solution (ORS)/oral rehydration treatment (ORT) is the cornerstone of diarrhea treatment in low-resource settings. Sugar, water, salt—this simple mixture has saved millions of lives and costs just pennies. Easy to prepare and administer in the home, ORT empowers caretakers with a first line of treatment for children suffering from diarrhea. If all parents could access and use ORS, diarrhea deaths would drop by a staggering 93%! Learn more.

3. Q:  What micronutrient for diarrheal disease treatment are you getting when you eat chocolate?
A: If you like to indulge in a piece of chocolate, you are also getting the micronutrient zinc. Treatment with zinc and other micronutrients is a critical new tool for treating episodes of diarrhea among children in developing countries. Zinc becomes depleted during diarrhea, but recent studies suggest that replenishing zinc with a 10- to 14-day course of treatment can reduce the duration and severity of diarrheal episodes and may also prevent future episodes for up to three months. Learn more.

4. Q: Rotavirus is the primary cause of severe childhood diarrhea and leads to more than one-third of all childhood deaths caused by diarrhea. PATH is working with ____ to ensure that all children can receive rotavirus vaccines, no matter where they live.
A: Although two rotavirus vaccines are currently available and recommended for global use by the World Health Organization, they are not yet widely available or affordable for low-resource countries, where 95% of rotavirus-related deaths occur. PATH is working with GAVI Alliance and other partners on two fronts—increasing access to and effectiveness of existing commercial rotavirus vaccines worldwide and speeding the development of safe, effective, and more affordable new rotavirus vaccines. PATH is also working on new vaccines against other two leading causes of diarrheal disease – enterotoxigenic Escherichia coli (ETEC), and Shigella. Learn more.

5. Q:  Almost 90% of diarrheal deaths could be prevented if everyone had access to _____.
A: Clean, fresh water is one of the best ways to treat and prevent diarrheal disease. More than 780 million lack access to it worldwide and 2.5 billion people don’t have basic sanitation. Eighty percent of childhood deaths from diarrheal disease are in Asia and Africa where access to safe water, sanitation and urgent medical care can be limited. Learn more.

6. Q:  What form of overlapping protection can new moms use to protect their newborns from diarrheal disease AND pneumonia?
A:  Breastfeeding is considered a pillar of child survival. It prevents death and stunting from malnutrition by providing ideal nourishment for the first six months of life and continues to provide essential nutrients through 24 months of age. Breast milk also helps develop the immune system, improving the response to vaccines and preventing infections, including diarrheal diseases. Learn more.

 BONUS QUESTIONS

 1. Q: Drugs for diarrhea will be an important addition to existing treatments. ____ is our program’s investigational drug candidate currently in clinical trials, designed to prevent dehydration and provide rapid relief of diarrhea symptoms before they become fatal. What is the drug called?
A: iOWH032 is our program’s investigational drug candidate for acute secretory diarrhea as a result of diseases such as cholera. A synthetic small molecule with novel biological activity, the drug is designed to prevent dehydration and provide rapid relief of diarrhea symptoms before they become fatal. In combination with greater access to safe water, new and improved vaccines, oral rehydration therapy, zinc supplementation, and improved nutrition, the development of antisecretory therapies like iOWH032 has the potential to reduce global mortality and morbidity rates associated with diarrhea. Learn more.

2. Q:  After nearly three years of research among low-income households in India, Cambodia, and parts of Africa, PATH developed what interface that allows users to shop for replacement filter elements (cartridges) on the open market?
A: PATH worked with product developers to design the C1 Common Interface—a standardized connection point between water filter devices and filter elements that allows interchangeability of parts between different household water filters. Safe water is critical for preventing diarrheal disease as well as pneumonia, but more than 780 million people lack access to it. Inadequate water, sanitation, and hygiene trigger 4 billion cases of diarrhea annually. Learn more.

Naturally-derived artemisinin is subject to volatile growing conditions, making the supply unstable from year to year.

In order to take on this monumental task, we needed a strong, dedicated, and dependable group of partners. UCB, Amyris, Inc., OneWorld Health (now PATH’s Drug Development program), and Sanofi aligned their biochemistry knowledge, global health expertise, and manufacturing savvy to lead the project from the research to commercialization phase. Partners worked together to refine the production process for semisynthetic artemisinin, set the stage for speedy regulatory approval, and ready the product for commercial distribution.

The floor of a Sanofi factory.

Through our collaboration, we succeeded in moving a synthetic biology innovation from the lab to the factory floor, launching industrial production of semisynthetic artemisinin in Northern Italy this spring. Having multiple sources of high-quality artemisinin will mean a steady global supply, stable price, and ultimately, greater availability of treatment to people suffering from malaria.

Advancing the product required willingness to take risks and work together across different institutional cultures, putting aside differences and focusing on the common mission of malaria eradication. It also required keeping one ear to the ground to develop a product that would be user-driven and readily incorporated into the supply chain.

The success of the partnership demonstrates that with a shared humanitarian goal—and the flexibility and perseverance of a dedicated team—collaboration across sectors can advance science to make a real impact in global health.

Photo credits, from top: PATH/Ponni Subbiah, Sanofi

An unsafe water supply and lack of sanitation are leading causes of diarrheal disease, killing more than 760,000 children each year. Globally, diarrhea is a leading cause of death in children under age five, second only to pneumonia.

Additionally, the effects of severe diarrhea linger far after the illness has passed. With each episode, children lose vital nutrients and become undernourished. Malnourishment can affect a child’s growth and cause developmental learning problems, perpetuating cycles of poverty. It can also leave children susceptible to other infections, including pneumonia. In 2011, pneumonia and diarrheal disease claimed the lives of nearly 2 million children worldwide.

PATH’s Drug Development program is committed to developing safe, effective, and affordable treatments for diarrheal disease. By preventing dehydration and providing rapid relief of diarrhea symptoms, our investigational drug, iOWH032, has the potential to help reduce global mortality and morbidity rates associated with acute secretory diarrhea. It also has the potential to bolster the efficacy of other therapies, including oral rehydration therapy (ORT), by hastening adoption and compliance. With phase 1 trials in 2012 confirming the drug’s safety and tolerability, iOWH032 is set to enter phase 2 clinical trials in Bangladesh this spring.

The United Nations’ declaration of 2013 as the Year of Water Cooperation illustrates our inter-connectedness in trying to solve the world’s water problems. Along with improving access to safe water; developing new vaccines and drugs; making ORT and zinc supplementation more accessible; and educating people about nutrition, sanitation, and hygiene; working together across sectors will be vital to paving the way forward with advancements in the treatment of diarrheal disease.

On World Water Day, we celebrate the accomplishments we’ve made so far. Thirteen years ago, with Millennium Development Goal (MDG) 7, the United Nations set out to halve, by 2015, the proportion of people who lack access to safe drinking water. As Bill Gates stated in his annual letter, the global community met that goal years ahead of the deadline. However, we’re still not on schedule to meet another urgent MDG—reducing by two-thirds the number of children who die before age five. While the number has dropped from nearly 12 million in 1990 to 6.9 million in 2011, we won’t meet the two-thirds target by 2015. By continuing to work in a spirit of unity, we can reduce further suffering and speed our progress toward that goal.

Photo credit: PATH