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Malaria Facts • Where malaria is common the average life span is 30 YOA. This is not all due to malaria but malaria and trypanosomiasis do play their part! Malaria Facts • Where malaria is common the average life span is 30 YOA. This is not all due to malaria but malaria and trypanosomiasis do play their part! • Malaria has protected Western Africa from European colonization! Malaria has Been Significant Enough to Make the World Different! • Being sent to Gambia, Serra Leon, etc. was considered a death sentence because of the probability of contracting malaria! Malaria has Been Significant Enough to Make the World Different! • Being sent to Gambia, Serra Leon, etc. was considered a death sentence because of the probability of contracting malaria! • 1880 was when Plasmodium was fist discovered. Malaria has Been Significant Enough to Make the World Different! • Being sent to Gambia, Serra Leon, etc. was considered a death sentence because of the probability of contracting malaria! • 1880 was when Plasmodium was fist discovered. • 1897: the vector host was discovered by Ronald Ross. But it did not matter since there was no attempt to control it! Malaria in History • Ancient references – China, Assyria, India – 500 BC Hippocrates gives first clinical description Malaria in History • Ancient references – China, Assyria, India – 500 BC Hippocrates gives first clinical description • Historical Impacts – 413 BC Fall of Greek empire – 323 BC Alexander the Great died of malaria – The Roman Empire: Malaria is generally considered to have played a role in the decline of Rome, a city located in marshland, where malaria is transmitted History • 1800’s 20-40% of people hospitalized in New Orleans had malaria History • 1800’s 20-40% of people hospitalized in New Orleans had malaria • 1861-1865 Civil War. Savannah, GA 878 men had 3313 cases of malaria in a 14 month period. History • 1800’s 20-40% of people hospitalized in New Orleans had malaria • 1861-1865 Civil War. Savannah, GA 878 men had 3313 cases of malaria in a 14 month period. • 1880 Plasmodium discovered as etiological agent History • 1800’s 20-40% of people hospitalized in New Orleans had malaria • 1861-1865 Civil War. Savannah, GA 878 men had 3313 cases of malaria in a 14 month period. • 1880 Plasmodium discovered as etiological agent • 1900’s Sir Ronald Ross discovers mosquitoes are vectors History • 1800’s 20-40% of people hospitalized in New Orleans had malaria • 1861-1865 Civil War. Savannah, GA 878 men had 3313 cases of malaria in a 14 month period. • 1880 Plasmodium discovered as etiological agent • 1900’s Sir Ronald Ross discovers mosquitoes are vectors • 1930’s malaria diminished in U.S. except for southeast. Conversion of swamp to agriculture. 1882 1912 1934 History • World War II. In 1942, 2678 cases from 1,000 men; Ran out of drug for treatment. History • Gen. Douglas MacArthur in May 1943: "Doctor," he said, "this will be a long war if for every division I have facing the enemy I must count on a second division in hospital with malaria and a third division convalescing from this debilitating disease!" The general was not at all worried about defeating the Japanese, but he was greatly concerned about the failure up to that time to defeat the Anopheles mosquito. History • Lost five times more men to malaria than in Battle! History • Lost five times more men to malaria than in Battle! • Brought about chemical insecticides. – DDT was a result of WWII – And a few year later there were only 50/1000 History • Lost five times more men to malaria than in Battle! • Brought about chemical insecticides. – DDT was a result of WWII – And a few year later there were only 50/1000 • So after the war there was a false hope of eradicating malaria from the world! History • 1946. WHO initiates program to “eradicate malaria”. • History • 1946. WHO initiates program to “eradicate malaria”. • 1961: A parasitology textbook is quoted as saying “with present prospects, malaria WILL soon be treated as an uncommon/non-existent disease. History • 1946. WHO initiates program to “eradicate malaria”. • 1961: A parasitology textbook is quoted as saying “with present prospects, malaria WILL soon be treated as an uncommon/non-existent disease. • 1970. Malaria decreased dramatically. Eradication of Malaria • So why did the campaign fail? • 1) Insecticides (DDT) – Environmental damage! Eradication of Malaria • So why did the campaign fail? • 1) Insecticides (DDT) – Environmental damage! Pesticide Resistance • Rapid Reproduction • Selection DDT Pesticide Resistance • Rapid Reproduction • Selection DDT Eradication of Malaria • 2) Plasmodium – Wide use of chloroquine has led to drug resistant strains! Eradication of Malaria • 3) Social/Political Reasons – Emerging nations in Africa were trying to be free from external (Western European nations) domination; much of the monetary resources stopped flowing in! There are some general genotypes that are resistant to malaria • Genetic resistance to Plasmodium • 2 examples Duffy Blood Group • Noticed in military groups in Vietnam. • African Americans had less severe cases or no cases of malaria! Genetic Resistance • Plasmodium vivax • Duffy blood groups – Proteins on cell surface – 3 alleles • A Dominant • B Dominant • y recessive A= B= y = no proteins Genetic Resistance • Plasmodium vivax • Duffy blood groups – Proteins on cell surface – 3 alleles A= B= y = no proteins By • A Dominant • B Dominant • y recessive AA BB AB Ay yy Genetic Resistance • yy genotype has advantage – P. vivax malaria resistance – Only advantageous if P. vivax malaria endemic • 40% people of W. African decent • 0.1% people of non-African decent • P. vivax keeps the allele common in Africa. Genetic Resistance • Sickle celled anemia • Codominant trait (Allele “A” and “B”) – AA have sickle celled anemia – AB have both types of cells • Sickle cells don’t support species of Plasmodium well. • Resistance to infection Genetic Resistance • AA selected against – Sickle celled anemia • AB selected for – Both sickle and normal cells • BB selected against – Normal cells • If malaria is not endemic, what alleles will be selected for? Against? • Allele for sickle cells maintained in the population even though strongly disadvantageous to have both alleles. Genetic Resistance Sickle Celled Anemia • In the US, 10% of African Americans have this allele! Other forms of Resistance to Malaria • Babies get antibodies from their moms breast milk; they are protected until weaned. • Once weaned becomes susceptible again! • What you need to have malaria spread within a population! Epidemiological Models Habitat Behavior Infected People contact Mosquitoes contact Source of Plasmodium Uninfected People Source of New Hosts Climate Habitat Food Breaking the Chain Habitat Behavior Infected People contact Mosquitoes contact Source of Plasmodium Uninfected People Source of New Hosts Climate Habitat Food Eliminating Mosquitoes • Mosquito Life Cycle Eliminating Mosquitoes Eliminating Mosquitoes • Destroy habitat • Insecticides • Biological control Eliminating Mosquitoes • • • • Destroy habitat Insecticides Biological control Why don’t these methods work? Pesticide Resistance • Rapid Reproduction • Natural selection Getting rid of the source of Plasmodium Getting rid of the source of Plasmodium • Drug treatment • Transgenic mosquitoes Getting rid of the source of Plasmodium • Drug treatment • Transgenic mosquitoes • Why don’t these work? Getting rid of the source of Plasmodium • Drug treatment • Transgenic mosquitoes • Why don’t these work? – Availability of drugs • Money • Medical staff – – – – – Recrudescense Drug resistance Reservoir hosts? Transgenic mosquitoes not a reality Expensive How can we protect the uninfected population? • Vaccines • Prophylactic drugs How can we protect the uninfected population? • Vaccines • Prophylactic drugs • Why don’t these work? How can we protect the uninfected population? • Vaccines • Prophylactic drugs • Why don’t these work? – Vaccines unsuccessful – Prophylactic drugs expensive – Prophylactic drugs unpleasant How can we prevent contact between people and mosquitoes? • • • • • Insecticides Mosquito nets Long clothing Behavior Avoid mosquito habitat • Screens on houses How can we prevent contact between people and mosquitoes? • • • • • Insecticides Mosquito nets Long clothing Behavior Avoid mosquito habitat • Screens on houses • Why don’t these work? How can we prevent contact between people and mosquitoes? • • • • • Insecticides Mosquito nets Long clothing Behavior Avoid mosquito habitat • Screens on houses • Why don’t these work? – Money – Availability of materials – Human behavior difficult to change • "Everything about malaria is so molded by local conditions that it becomes a thousand epidemiological puzzles." Hackett (1937) Roll Back Malaria (RBM) Strategy • Early diagnosis and prompt treatment Roll Back Malaria (RBM) Strategy • Early diagnosis and prompt treatment • Prevention – insecticide-treated materials – vector control measures • indoor spraying • larvicide • environmental management Roll Back Malaria (RBM) Strategy • Early diagnosis and prompt treatment • Prevention – insecticide-treated materials – vector control measures • indoor spraying • larvicide • environmental management • Prevention of malaria in pregnancy Roll Back Malaria (RBM) Strategy • Early diagnosis and prompt treatment • Prevention – insecticide-treated materials – vector control measures • indoor spraying • larvicide • environmental management • Prevention of malaria in pregnancy • Monitoring for epidemics – Rapid response Roll Back Malaria (RBM) Strategy • Early diagnosis and prompt treatment • Prevention – insecticide-treated materials – vector control measures • indoor spraying • larvicide • environmental management • Prevention of malaria in pregnancy • Monitoring for epidemics – Rapid response • New methods and tools Roll Back Malaria (RBM) Strategy • Early diagnosis and prompt treatment • Prevention – insecticide-treated materials – vector control measures • indoor spraying • larvicide • environmental management • Prevention of malaria in pregnancy • Monitoring for epidemics – Rapid response • New methods and tools • Improvement in existing tools through research and development Roll Back Malaria (RBM) Strategy • Early diagnosis and prompt treatment • Prevention – insecticide-treated materials – vector control measures • indoor spraying • larvicide • environmental management • Prevention of malaria in pregnancy • Monitoring for epidemics – Rapid response • New methods and tools • Improvement in existing tools through research and development • Coordinated action through establishing partnerships that utilize an optimal mix of measures adapted to local situations.