1. DEVELOPMENT IN THE PRODUCTION AND EFFECTIVENESS OF ARTEMISININ Background Information Currently, there is an epidemic of malaria in third world countries, particularly sub-Saharan Africa and Southeast Asia, affecting 200 million people and putting 300 billion at risk worldwide. Even in developed countries, people are at risk of contracting malaria because the world is globalized, and people can travel internationally. For this reason, scientists are trying to find a way to eradicate malaria. Treatment options right now include quinine and chloroquine, but in certain areas, the Plasmodium falciparum that causes malaria is showing a significant amount of resistance to these drugs. To combat the resistance, research is turning to the drug artemisinin as the first line of treatment, as it works faster, is more effective, prevents transmission of the parasite, and overcomes the bacteria’s resistance. Artemisinin is a plant- derived antimalarial medicine with the chemical formula C 15 H 22 O 5. Artemisinin-based combination therapy (ACT) seems especially promising as a treatment option since there is even less resistance to it. However, issues arise with production of artemisinin. Even if artemisinin were to be isolated and produced in large amounts, resistance has already started to occur against artemisinin. That is why another investigation being conducted is determining which drugs to combine with artemisinin in order to delay widespread resistance. Finding the solution will rid the world of malaria before the time comes where parasites do not respond to ACT’s either. ACT’s Artemisinin-based Combination Therapies Pairing artemisinin with another substance Prevents the parasite from resisting the treatment Uses extra substance as a “mask” Malaria does not notice that Artemisinin is part of the compound Many types such as Artekin No reports of resistance Artekin Dihydroartemisinin-piperaquine (Artekin) is a more recently discovered ACT with several benefits compared to other treatments. It is tolerated by patients more than other medicines. For example, in one study, Artekin had an effectiveness of about 70%, while the drug combination artemether-lumefantrine was approximately 50% effective. More tolerance means more lives saved and less people experiencing side effects. Furthermore, it only needs to be administered once every day. This reduces the amount of forgetfulness in patients because they will not have to remember to receive the treatment more than once per day. Sustainability The developed resistance of malaria against artemisinin is discouraging. Deciding to continue research on the medicine by itself could turn out to be a waste of time and resources. However, when paired with another substance in the form of an ACT, it has the ability to fight malaria without experiencing and resistance. This fact, along with several others, makes ACT’s a sustainable choice for malarial treatment with artemisinin. Artekin has a high level of effectiveness and must only be administered to patients once every day. This means that not as much artekin must be produced when compared to other ACT’s, which saves resources. The sustainability of pACT is even better. By using the Artemisia annua leaves as treatment, no lab procedure must be conducted to extract the medicine. In addition, the efficiency of it is higher because there is not a percent yield like there is in a chemical laboratory. In many cases, pACT has a high success rate of terminating the bacterial disease. No signs of resistance have been reported for ACT’s, and their efficiency and effectivity rates are higher than any other medicine. Focusing research on these combination therapies is a sustainable decision that will eventually help numerous people around the world. Method of Elimination Artemisinin attacks the parasite in malaria in a unique way. The drug does not go straight for the core of the disease. It does its job by depolarizing the mitochondrial membrane. When artemisinin comes in contact with the parasite, the endoperoxide bridge splits from artemisinic substance. This causes a rapid formation of reactive oxygen species. Those species then react with the mitochondrial membrane, through depolarization, causing a loss in the membrane potential of the mitochondria, which decreases the parasite’s energy, thus decreasing its effectiveness. This disruption leads to an interference with the electron transport chain of the cell, making the malarial parasite more sensitive to the artemisinic treatment. By weakening the cell’s energy source, artemisinin is then able to attack and kill it. Every ACT and artemisinin-related medicine has an endoperoxide bridge, which allows it to bypass the resistance of malaria and eliminate the infection. Endopero xide Bridge pACT Plant-based Cost-efficient High yield No co-drug eAN Lab extraction Expensive Low yield Requires co- drug