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TEACHER'S GUIDE: Background Information (optional class content) MALARIA AND ITS IMPACT Malaria is one of the world’s most devastating diseases. According to the World Health Organization (WHO), there are 300 to 500 million clinical cases of malaria each year that result in 1.5-2.7 million deaths. Malaria is caused by tiny parasites that are transmitted from person to person through a mosquito bite, genus Anopheles. Plasmodium falciparum is the most virulent form of the parasite and causes the majority of infections. Although P. falciparum can cause serious and deadly diseases, not all infections require medical treatment. Individuals that are most susceptible to severe infections are children and pregnant women, and travelers who have not previously experienced malaria. Whereas most malaria infections cause symptoms, such as a fever, tiredness, and headaches that have been compared to a very bad case of flu, the most serious disease complications include severe anemia (excessive loss of red blood cells) and cerebral malaria (coma from which one cannot be roused) and placental malaria (passed through placenta). These are known as complicated malaria. Cerebral and placental malaria can cause death if left untreated. Despite over a century of work to control and eradicate this disease, malaria continues to take its devastating toll, largely in developing nations where many parents are left childless. These deaths occur despite the fact that drugs exist to treat and cure infections. However, the emergence of insecticide-resistant mosquitoes and drug-resistant malarial parasites has put 40% of the world’s population at risk. Therefore, new approaches to eradicate mosquitoes, and new anti-malarial drugs, are desperately needed to prevent even more deaths. However, the ultimate malaria solution will require the development of vaccines to prevent infection and disease Liver Human Mosquito Sporozoites Life Cycle of the Malaria RBC P. falciparum parasites Ring the mosquito and the human. transmitted to humans when Life cycle of the Plasmodium parasite. Merozoites female anopheline mosquito feeds on human blood in Troph nutrients to produce eggs. sucking behavior is hardmosquitoes in order to ensure survival. At the same time Gametocytes mosquito is acquiring its Schizont spitting factors into the prevent blood clotting and that would interfere with mosquito thus acts as a syringe to deliver the parasite into the blood circulation. Parasite have two hosts, The parasite is a order to acquire Thus, bloodwired into their specie’s that the blood meal, it is human to other activities feeding. The Once in the bloodstream, parasites travel to and invade liver cells where they multiply up to 30,000-fold, eventually breaking out and infecting red blood cells (RBCs). Over 48 hours, the parasite in the RBC develops through the ring, trophozoite (troph), and schizont stages. When the schizont matures, it ruptures and releases new merozoites, which can then infect more RBCs, thus setting up a recurring cycle. It's these RBC stages that cause the pathology connected with malaria. At a low frequency, some parasites will begin to differentiate into male and female gametocytes shortly after entering RBCs. If ingested by an anopheline mosquito, the gametocytes fuse to form a zygote and proceed through mosquito developmental stages, culminating in infectious sporozoites in the mosquito’s salivary glands. Source, WHO Malaria parasites in the mosquito mid-gut. TEACHER'S GUIDE Key for Answers Assigned Student Role Tanzanian Doctor Questions: 1. How would you describe access to medical care in Tanzania? What role does the government play? What role does the private sector play? 2. How is malaria diagnosed? 3. Tetanus and polio are two examples of diseases that American children are vaccinated against. What is the nature of these vaccines? How do vaccines work, and how can malaria researchers use knowledge about existing vaccines to develop a malaria vaccine? 4. The following information should be included in the student answers. 1. Medical care is available through public and private facilities. The annual health budget of Tanzania works out to between $4 –7 per person per year. Medical care is available through a referral system that ranges from Village Health Services to Referral/Consultant Hospitals. 2. Diagnosis includes evaluation of symptoms and patient history, microscopic examination of blood, ELISA, and PCR. 3. Vaccines aim to prevent infection and disease by inducing specific immunity (B and T lymphocytes) that recognize the pathogen or its disease-causing products. Vaccines take different forms including 1) attenuated (weakened) bacterial or viral vaccine (example polio), purified antigens or “detoxified” toxins (example Tetanus), synthetic antigens. The polio vaccine is designed to induce an immune response against the polio virus, while a tetanus shot generates antibodies against the bacterial toxin that causes disease. 4. Students should consider impact on the doctor's family as dependents and caregivers, as well as lost income, and impact on health care system in the doctor's absence. If you were to contract malaria, what impact would it have on all those who depend on you? Health Care Worker 1. Plasmodium falciparum – life threatening illness may develop very rapidly, symptoms can include high fever & coma, spleen, brain, liver & kidney damage with a mortality rate of 4-20%. Plasmodium vivax – fever and chills, recurring fever, low mortality rate. Plasmodium malariae and Plasmodium ovale – least common, fever and chills, recurring fever, low mortality rate. 2. Treatment measures include rehydration, fever management and specific antimalarial medicines. Drug resistant strains of Plasmodium are common. 3. Vaccines can be delivered orally or by injection. SBRI is currently developing a genetically attenuated malaria vaccine, with the goal of injecting it through the bite of a mosquito! The per capita income of most countries that deal with malaria is extremely low. It is conceivable that government and charity organizations would need to assist in costs. 4. Students should consider impact on the Health Care Worker's family and his/her caregivers, lost income, and impact on health care system in the Health Care Worker's absence. Questions: 1. What are the symptoms of each of the four types of malaria? 2. How is malaria treated? 3. What are some ways that a malaria vaccine could be administered? Who would pay for it? 4. If you were to develop malaria, what impact would it have on all those who depend on you? Tanzanian Teacher 1. Protective traits have evolved in individuals living in parts of the world where malaria is endemic. Many of these beneficial traits impact the red blood cells in which the parasite lives. The Sickle Cell Trait is perhaps the most famous example and affects the type of hemoglobin that a person inherits. Inheriting one such gene can confer protection from malaria; inheriting two is actually more deadly. 2. From 1950-1972, a global effort to eradicate malaria was launched by a new organization called the Centers for Disease Control (CDC). The centerpiece of the targeted mosquito control utilized the pesticides such as DDT (dichlorodiphenyltrichloroethane). The application of this chemical on houses and mosquito breeding grounds resulted in a phenomenal drop in malaria cases in countries such as India. Prior to this campaign, even Seattleites battled malaria! In 1972 the US government banned crop spraying with DDT, and worldwide cases once again rose. Other efforts include vaccine research, antimalarial medications (including quinine, artemisinin, doxycycline, mefloquine, sulfacoxinepyrimethamine (SP) and malarone), and education. Thus far, none have been completely successful. The greatest hopes lie with a vaccine. (a,b). In 2007, the WHO has recommended the return of judicious application of DDT in high risk communities, and the implementation of affordable combination therapies (such as artemisinin & S-P). 3. Use mosquito control techniques including permethrin-impregnated bed nets, pesticides, avoid being outside during the time that mosquitoes are feeding. Education about control and vaccine development is important for society. Promote understanding that global health scourges are everyone’s responsibilities, and not merely the sufferers. 4. Students should consider impact on the teacher's family and his/her dependents, lost income, and impact on the education system in the teacher's absence. Questions: 1. Why is it that some people can be bitten by infected mosquitoes and never develop malaria, yet others readily develop the disease? 2. What efforts have been made to prevent the incidence and spread of malaria? In what ways have these efforts been successful? In what ways have they not failed? 3. What will be the most important things you can teach students to help control the spread of malaria? 4. If you were to develop malaria, what impact would it have on all those who depend on you? Mosquito 1. Female mosquitoes feed on blood to acquire nutrients in order to produce eggs (male mosquitoes have a “sweet tooth” and feed on nectar). Mosquitoes have evolved to recognize organisms that contain blood and have in-born blood-seeking behavior. Signals include emission of CO2, heat, and odors from bacteria that live on humans (also attracted to limburger cheese for the same reason). Anopheles mosquitoes transmit malaria. While there are over 1,000 species of Anopheles mosquitoes, only a handful of species can transmit malaria to man. These species inhabit different niches (i.e., some mosquitoes like to breed in sun-lit water, others in clear water, and some in cloudy water). Only some species of anopheline mosquitoes are known to transmit malaria to humans. In some, the parasite may not survive. In others, they prefer to feed on cattle blood rather than human. Some, like Anopheles Gambia, take many small blood meals, enhancing transmission, through the multiple skin wounds. 2. Although DDT is banned in many developed nations, it is still used as a recommended vector control method in some areas of the world that are severely impacted by malaria. Judicious amounts (< 0.5 kg) are now applied annually to the inside of dwellings—in comparison, during the 1950s, 100 hectare cotton fields used to receive >1,100 kilograms of DDT over 4 weeks. Some mosquitoes have developed resistance to DDT and other pesticides. The risks include dangers to other animal species and possible birth defects. These concerns weigh heavily upon the minds of policy makers—to the extent that many NGOs and funders will not fund multi-pronged malaria initiatives that include DDT in the response (including the World Bank and the International Monetary Fund agencies). 3. The Anopheles mosquito harbors a parasite of the Plasmodium genus. There are four species of Plasmodium, each capable of causing malaria in humans. The female anopheles mosquito must drink blood in order to lay eggs. When she injects her saliva into the host, to ensure a clogfree drink of blood, she will inject any parasites that she might be harboring in her salivary glands. The parasites in her salivary glands arrived there, by way of the mosquito gut, when she last took a blood meal from a person with malaria parasites in their blood. See life cycle of Plasmodium. 4. Students should consider the impact of the mosquito in the life cycle of other animals, such as birds. What would be the consequence of total eradication? This could affect bird species that help abate mosquito infestation and lead them to feed on an insect that is beneficial or plays a role in supporting crops. Questions: 1. What is the role of the mosquito in transmitting malaria? Why types of mosquitoes are involved? 2. Do the risks of DDT outweigh their benefit in controlling the spread of malaria? 3. What causes malaria? What role does the mosquito play in spreading this disease? 4. Is eradication the answer? How would this affect the environment? Mother Questions: 1. What is the mortality rate associated with malaria and which type has the highest mortality? 2. What effect might a malarial infection have on a developing fetus? 3. What effect might a malarial infection have on a woman while she is pregnant? 4. 1. Nearly all malaria deaths are attributable to P. falciparum. It has been estimated that nearly 20% of infections result in severe diseases and 10% in death. Malaria kills over 1 million people each year, about 3,000 people a day. In sub-Saharan Africa, malaria accounts for one in five of all childhood deaths. Malaria kills an African child every 30 seconds. 2. May cause death of fetus. In pregnant women, infected erythrocytes accumulate in the placenta. The placenta is the site where nutrients are passed between woman and fetus, and waste products are returned from fetus to woman. There may be direct effects of parasite accumulation in the placenta or indirect effects caused by immune abnormalities. Babies born to malaria-infected women have lower than normal birth weight. This is a risk factor for death whenever a child is born. Malaria infections can also cause miscarriages. 3. Women may develop immunity to malaria. Malaria infections can cause severe anemia (low red blood cell numbers) in mothers. It has been shown that pregnant women develop antibodies that protect against malaria. This helps to protect the fetus during subsequent pregnancies. SBRI researchers are studying why this response occurs in order to develop a vaccine that prevents malaria during pregnancy. 4. Students should consider impact on the woman’s family and her dependents, lost income, and social/economic impact of orphaned children. 1. Avoid being outdoors at dawn and from 5- 9 pm, use bed nets, use insect repellent, wear long clothing, use antimalarial medications before, during, and after visit, despite side effects. If you have a fever within a few weeks after your visit, see a doctor to rule out a malaria infection – be sure to tell them you have recently traveled to a malaria endemic area. 2. Possibilities include educating others, including peers, parents, and adults. Not-for-profit research institutes welcome volunteers to assist with community outreach and fund raising. Future scientists are needed and a research career could lead to future discoveries. 3. Yes! Children under the age of five are the population at highest risk for serious malaria. The complications due to anemia, high fever and poor digestions (recall that vomiting is malaria symptom in children) make mild infectious, deadly serious! 4. Because malaria is not commonly seen in the US, most people know very little about it. If not covered by health insurance, your illness could have a huge economic impact on your family. What would you need to know about the American doctors who are providing healthcare to other women in the village before you would consider participating in a malaria research study? American Teenager Visiting Tanzania Questions: 1. What preventative measures will you take to minimize the chances that you will contract malaria? 2. Even though you are a teenager, you are still influential and powerful in many ways. What will be your role in controlling the spread of malaria? 3. Are children at higher risk than adults of contracting malaria? Is the disease more severe in children or adults? 4. If you were to develop malaria, what impact would it have on all those who care for you? Researcher from SBRI 1. Infectious diseases can be transmitted from one person to another through contact (coughing, saliva, blood, etc.). Non-infectious diseases are not transmitted through contact (lung cancer). 2. The malaria parasite is very complex. It has a large genome; for example the human genome has approximately 35,000 genes and the malaria parasite 6,500. Malaria parasites have an estimated 5,000 proteins that are potential targets for a vaccine. The parasite has evolved very complex strategies to evade the immune response. These include extensive polymorphism (assuming various forms) of proteins that are exposed to the immune system. Thus, it is difficult to find good vaccine candidates that are conserved (the same) between different P. falciparum parasites. The parasite spends most of its life hidden from the immune system (known as sequestration) within a red blood cell where T and B lymphocytes cannot access it, but exposes parasite proteins on RBC surface (the target). 3. From the malaria genome project we got a “blueprint” or how-to manual for building the parasite. Just by examining the DNA sequence, scientists can learn things. For instance, scientists can discover which parasite proteins are different from humans. Unique proteins or metabolic pathways are potential drug targets. Different proteins are discovered by knowing the parasite DNA sequence, and these unique proteins and genes can then be targeted for an ideal drug or vaccine target—with less worry of harming the human patient. 4. There are many complicating factors in carrying out research based on data being collected in Tanzania. These include language barriers and the ethics of working with humans in another country. From a logistical standpoint there are extreme challenges in shipping equipment and time sensitive samples, problems with data storage for 1,000 participants and travel safety issues for the researchers traveling and working in Tanzania. Questions: 1. How would you define an infectious disease? A non-infectious disease? 2. Why is it so difficult to develop a vaccine for malaria? 3. How does knowing the genetic information (the sequence of DNA nucleotides) within the genome of Plasmodium help design a new treatment, vaccine or healthcare response (diagnosis)? 4. What are specific challenges in carrying out research based on participants in Tanzania? Park Ranger 1. The nature of the park ranger’s work, working mostly outdoors increases their chances of exposure, particularly when their work occurs during prime mosquito feeding times. 2. Factors include drug resistance of Plasmodium, insecticide resistance of mosquitoes, increasing poverty & malnutrition, political and social upheaval causing displacement of large groups of people, roads, dams, irrigation, and health budget constraints. 3. DDT was banned in the United States in 1972 and has been commonly banned since it was linked to reproductive dysfunction such as thin eggshells in birds. Also, some insects such as mosquitoes have become resistant to DDT while their natural predators were eradicated. Although DDT is banned in many developed nations, it is still used as a treatment of choice in some areas of the world that are severely impacted by malaria. 4. Students should consider impact on the ranger’s family and his/her caregivers, lost income, and impact on environmental protection in the ranger’s absence. Questions: 1. Is your risk of contracting malaria any greater than that of a teacher or doctor? 2. Why has the incidence of malaria increased? 3. What are the risks of DDT and do the risks outweigh their benefit in controlling the spread of malaria? 4. If you were to develop malaria, what impact would it have on all those who depend on you? Conference/Town Meeting Notes and Learner’s Summary—Teacher’s Guide Students take notes during class presentations in the Town Meeting. At the end of the Town Meeting, students should have a comprehensive, “8-character” view of the social, environmental, economic and political impact of Malaria. Students independently respond to questions 1-5, as homework. Mosquito What causes malaria? What role does the mosquito play in spreading this disease? Doctor Tetanus and polio are two examples of diseases that American children are vaccinated against. What is the nature of these vaccines? How do vaccines work, and how can malaria researchers use knowledge about existing vaccines to develop a malaria vaccine? Health Care Worker What are some ways that a malaria vaccine could be administered? Who would pay for it? Teacher What will be the most important things that your can teach students to help control the spread of malaria? Mother What effect might a malarial infection have on a woman while she is pregnant? American Teenager Are children at higher risk than adults of contracting malaria? Is the disease more severe in children or adults? SBRI Researcher How does knowing the genetic information (the sequence of DNA nucleotides) within the genome of Plasmodium help design a new treatment, vaccine or healthcare response (diagnosis)? Park Ranger Do the risks of DDT outweigh their benefit in controlling the spread of malaria?