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B io Factsheet www.curriculum-press.co.uk Number 206 Malaria This Factsheet summarises: • The cause and means of transmission of malaria. • The worldwide distribution and importance of malaria. • The social, economic and biological factors significant in the prevention and control of malaria. Definitions Malaria is an infectious disease that threatens over one third of the world’s population. Up to 124 million people in Africa alone live in areas at risk of seasonal epidemics. This year, malaria is expected to kill one million individuals, 90% of them under age five, and the vast majority living in Africa. Host: An organism inside which the reproduction of another organism occurs. Humans act as a host for the malarial parasite. Vector: An organism responsible for the transmission or spread of a pathogen. In the case of malaria, the female mosquito is the vector as it transmits the Plasmodium parasite from human to human. Asexual reproduction: Reproduction with just one parent organism. Offspring are genetically identical, and are produced rapidly and in large numbers. What causes malaria? Sexual reproduction: Requires the fertilization of a male and female gamete to form a zygote. Offspring contain a combination of the genes of both gametes. Malaria is caused by 4 different species of the protoctist parasite Plasmodium. It is spread from human to human by female Anopheles mosquitoes as they feed on blood to obtain the protein they need to produce their eggs. Transmission of Malaria 1. Mosquito bites usually occur in the early evening. As the infected mosquito feeds, it injects saliva containing an anticoagulant to prevent the blood from clotting. 2. Malarial parasites known as sporozoites are injected along with the saliva and enter the human bloodstream where they migrate to the liver. The mosquito is therefore said to act as a vector of the malarial parasite. 3. In the liver cells the sporozoites multiply asexually, very rapidly increasing in number. 4. The liver cells burst open releasing many merozoites, which then invade the red blood cells. 5. These merozoites reproduce asexually again inside the red blood cells, causing the red blood cells to burst, releasing more merozoites which cause the characteristic fever and other symptoms of the disease. 6. Some of these merozoites develop into gametocytes (the male and female forms of the parasite) which are ingested by the female mosquito during feeding, and so complete the cycle of transmission between human and mosquito. 7. Once inside the female mosquito’s gut, the male and female gametocytes fuse to form sporozoites which migrate to the salivary glands ready to be injected into a new human host at the next blood meal. The diagram below summarizes the life cycle of the malarial parasite and is typical of many exam questions. Uninfected female mosquito feeds in the early evening and takes in mature sex cells with the blood Infected female mosquito feeds in the early evening and injetcs malarial parasites into the blood stream skin surface mature sex cells malarial parasites After 28 hours sex cells have matured blood system of human liver cell Immature sex cells malarial parasite Malarial parasite rapidly enters liver cell and changes form. New form ruptures liver cell, escapes into blood stream and infects red blood cells red blood cells 1 Every 48 hours, infected red blood cells burst, releasing more parasites and immature sex cells Bio Factsheet 206 Malaria www.curriculum-press.co.uk Controlling the Spread of Malaria Exam Hint: - Examiners often ask candidates to distinguish between the stage of sexual reproduction in the female mosquito, and the asexual stages in the liver and red blood cells of the human host, and to outline the advantages of each. Asexual reproduction is much more rapid and produces large numbers of offspring in a short space of time. At present, there is no vaccine for malaria, so prevention and control measures mainly focus on disrupting the breeding cycle of the mosquito in order to reduce the risk of mosquito bites. The female mosquito lays her eggs in the water where the larvae and pupae develop. • Draining swamps, marshes and other exposed areas of water removes potential breeding places for mosquitoes. Typical Exam Questions 1. Explain the importance of the female mosquito in the life cycle of the malarial parasite. 2. Explain why an infected person may feel feverish every two days in the early stages of malaria. 3. Describe and explain how Plasmodium is adapted to its way of life. Answers 1. Female acts as a vector/ transmits the parasite to humans; Fertilization of male and female gametocytes occurs in the female mosquito/ where sexual stage of life cycle occurs; 2. Infected red blood cells burst every 48 hours releasing more parasites into the bloodstream; 3. Has no locomotory structures because it is transported via the blood stream in humans and uses two hosts to transfer it from one stage to the next; Does not need an attachment mechanism as penetrates human host using mosquito vector; Has no need for a mechanism for regulating its water content because it lives inside cells; Avoids attack by host immune system by living inside host cells; Complex life cycle with several stages aids immune evasion; Sexual reproduction phase of life cycle allows for antigenic variation; Asexual reproduction phase of life cycle allows production of large numbers of offspring; Sprays containing the bacterium Bacillus thuringiensis can be used which kills mosquito larvae but is not toxic to other species. • Biological control by stocking permanent bodies of water with fish which feed on mosquito larvae. • Sleeping beneath mosquito nets which have been soaked in insecticides, and the use of insect repellents on the skin. • Keeping skin covered at dusk when mosquitoes are most likely to bite. • Sleeping with a dog or a pig! Local wisdom in New Guinea advises that mosquitoes much prefer animal blood to human blood. Mosquitoes cross national boundaries and so control programs must be co-coordinated between nations in order to be successful. The more recent problems of insecticide-resistant mosquitoes and drug-resistant strains of Plasmodium also hinder prevention and control. Many candidates’ knowledge of the malarial parasite’s life cycle is insufficient Some candidates do not show that they understand the need for rapid, asexual reproduction to produce sufficient numbers of parasites to ensure transmission to another host Few candidates mention the importance of the anticoagulant Some candidates are unsure of the sequence of stages within the human Exam Question The maps below show the pattern of annual rainfall in Africa and the incidence of malaria. Incidence of malaria Annual rainfall Describe and explain the relationship between annual rainfall in Africa and the incidence of malaria. /cm Under 25 25-50 50-100 100-150 Over 150 No malaria Low incidence Medium incidence High incidence Answer • • • Correlation between the incidence of malaria and rainfall; Malaria is spread by mosquitoes that breed in water; Rainfall causes puddles/pools/more breeding grounds; • Spreading oil over the surfaces of bodies of water suffocates the mosquito larvae and pupae by preventing them from coming to the surface to obtain oxygen. Many of these measures, however, are not always successful. Mosquitoes will breed in the tiniest bodies of water, such as puddles, making it difficult to treat or eliminate breeding places entirely. Other measures, such as mosquito nets and insecticides are expensive and logistically difficult to implement in remote areas. Civil war and unrest, along with poor infrastructure, prevents access to many endemic regions. Where do Students go wrong? • • 2 Bio Factsheet 206 Malaria www.curriculum-press.co.uk Anti-Malarial Drugs and Resistance In addition to the above measures, anti-malarial drugs such as quinine have been in use for many years. Modern anti-malarial drugs are often used as prophylaxis by tourists traveling to regions where malaria is endemic, to prevent infection occurring. These drugs can also be used to improve the condition of individuals who are already infected, reducing the number of parasites within their bodies and hence reducing the likelihood of the disease being passed on to others. Anti-malarial drugs, however, have drawbacks: • They are too expensive to be used in many developing countries where malaria is endemic. • Malarial parasites have developed resistance to the drugs, especially chloroquine. At present, there are some regions where no antimalarial drugs are effective due to the problem of resistance. Insecticides, Resistance and the DDT Story Malaria and Sickle Cell Anaemia In the 1950s, the World Health Organisation co-coordinated a worldwide program for the eradication of malaria. The program failed for two main reasons: 1. The emergence of drug-resistant strains of Plasmodium. 2. The emergence of insecticide-resistant strains of Anopheles mosquitoes. Sickle cell anaemia is a lethal condition in which the presence of the mutant allele HbS in place of the normal allele HbA results in an amino acid substitution at a critical position in the haemoglobin molecule. This causes the red blood cells to have a characteristic sickle shape, which leads to blockage of capillaries and severe anaemia. The frequency of the HbS allele is correlated with the distribution of malaria, being particularly prevalent in West Africa. This is because heterozygotes who are said to show sickle cell ‘trait’, have sufficient amounts of normal haemoglobin to prevent severe anaemia, however, the small percentage of sickled red blood cells confers an increased resistance to malaria giving them a selective advantage over ‘normal’ individuals as they less likely to die from malaria in childhood. In addition, the program itself became very unpopular with local communities. When constantly re-infected with malaria, individuals acquire resistance to infection that is lost if they are no longer in contact with the disease. The temporary eradication of malaria in some areas during the program caused locals to lose their immunity with many deaths and much suffering when the disease returned. Vaccination The diagram below shows the distribution of malaria and the sickle cell allele and is typical of many exam questions. Given the problems of drug resistance, the approach most likely to be successful in controlling malaria is the development of a vaccine. However, the production of a vaccine against malaria has so far proved difficult for a number of reasons: • Plasmodium is a protoctists parasite, therefore much larger and much more complex than viruses and bacteria. It has many surface antigens which differ between the several species of parasite that can cause malaria. • In order to survive inside the human host, Plasmodium evades the immune response by quickly entering and remaining “hidden” inside either red blood cells or liver cells for much of its time (antigen concealment). • Once inside host cells, antigens from the parasite are displayed on the cell surface to aid immune detection. Plasmodium can mutate and vary these antigens so that the immune system no longer recognizes them (antigenic drift). • Different stages in the life cycle display different proteins, and so a vaccine would ideally target multiple stages in order to be effective. Sickle cell allele Malaria Typical exam Question Typical Exam Question Explain why the sickle cell allele occurs at such high frequencies in some areas. Outline the difficulties associated with controlling the spread of malaria. Answer 1. Resistance of mosquitoes to insecticides such as DDT. 2. Difficulty in controlling breeding of mosquitoes as they can lay eggs in very small bodies of water. 3. Mosquitoes can quickly travel long distances making control difficult. 4. Mosquito control programs have been disrupted by war, poor infrastructure and lack of funds. 5. Resistance of Plasmodium to anti-malarial drugs such as chloroquine. 6. Large number of surface antigens/ antigenic variation and antigenic concealment within red blood cells and liver cells make it difficult for immune system to detect. 7. Different stages of the life cycle in the body make it difficult for immune system to operate. 8. No vaccine. 9. Poor primary health care makes detection and treatment difficult. 10. Lack of education over preventing mosquito bites. 1. Individuals homozygous for sickle cell allele die from sickle cell anaemia. 2. Individuals homozygous for normal allele are likely to die from malaria in childhood. 3. Sickle cell allele frequent in malarial areas. 4. Heterozygotes have a selective advantage because they are resistant to malaria. 5. So are more likely to survive and pass on sickle cell allele. Acknowledgements: This Factsheet was researched and written by Katrina Fox. Curriculum Press, Bank House, 105 King Street, Wellington, Shropshire, TF1 1NU. Bio Factsheets may be copied free of charge by teaching staff or students, provided that their school is a registered subscriber. No part of these Factsheets may be reproduced, stored in a retrieval system, or transmitted, in any other form or by any other means, without the prior permission of the publisher. ISSN 1351-5136 Answer 3