1. © 2004 Aeras Global TB Vaccine Foundation Clinical Infectious Diseases 2 Clinical Research Practice

2. © 2004 Aeras Global TB Vaccine Foundation 2 Objectives Differentiate between infection and disease. Differentiate between infection and disease. Describe why poor health status makes one more susceptible to infectious disease. Describe why poor health status makes one more susceptible to infectious disease. Identify routes of transmission for TB, HIV and Malaria. Identify routes of transmission for TB, HIV and Malaria. Describe the disease cycle in humans for TB, HIV and Malaria. Describe the disease cycle in humans for TB, HIV and Malaria.

3. © 2004 Aeras Global TB Vaccine Foundation 3 Objectives Differentiate between active and passive immunity. Differentiate between active and passive immunity. Describe how a vaccine works. Describe how a vaccine works. Describe the need for a new TB vaccine. Describe the need for a new TB vaccine. Describe the role of public health measures in curtailing the spread of TB, HIV and Malaria. Describe the role of public health measures in curtailing the spread of TB, HIV and Malaria.

4. © 2004 Aeras Global TB Vaccine Foundation 4 Infectious Disease Review Health: A state of wellbeing without disease. Illness: A state of being unable to function normally.

5. © 2004 Aeras Global TB Vaccine Foundation 5 Types Of Disease There are two main types of disease: Non-infectious diseases do not spread from a sick person to a healthy person. Non-infectious diseases do not spread from a sick person to a healthy person. Infectious diseases are spread from person to person. Infectious diseases are spread from person to person.

6. © 2004 Aeras Global TB Vaccine Foundation 6 Infectious Diseases These diseases are mainly caused by tiny organisms called: Bacteria Bacteria Viruses Viruses Parasites Parasites These are called germs or microorganisms.

7. © 2004 Aeras Global TB Vaccine Foundation 7 How Do Infection and Disease Differ? Infection An invasion and multiplication of microorganisms in body tissues. An invasion and multiplication of microorganisms in body tissues. The infection may not be evident in a way that affects one’s health or well-being. The infection may not be evident in a way that affects one’s health or well-being. Disease The debilitating effects on a host after infection by a microorganism. The debilitating effects on a host after infection by a microorganism. Microorganism causes enough harm to the body to cause physiological impairment. Microorganism causes enough harm to the body to cause physiological impairment.

8. © 2004 Aeras Global TB Vaccine Foundation 8

9. 9 Your Body’s Defenses 1 st Line of Defence: Skin, mucous membranes with tiny hairs (in your nose and throat) and tears. Skin, mucous membranes with tiny hairs (in your nose and throat) and tears. When a harmful microbe is present they: When a harmful microbe is present they: Prevent the microbes from entering your body. Prevent the microbes from entering your body. Wash them away. Wash them away.

10. © 2004 Aeras Global TB Vaccine Foundation 10 Your Body’s Defenses 2 nd Line of Defence: The immune system is a complex system that works to clear infection from the body. The immune system is a complex system that works to clear infection from the body. When a harmful microbe is present: When a harmful microbe is present: White blood cells destroy the foreign microbes and call on other defences to fight them. Antibodies might be created to go after the microorganisms.

11. © 2004 Aeras Global TB Vaccine Foundation 11 Why Do We Still Get Disease? Certain factors weaken our immune system and make us prone to disease: Age Age Other illness Other illness Malnutrition Malnutrition Medication Medication Life style Life style Environment Environment

12. © 2004 Aeras Global TB Vaccine Foundation 12 Impact of Infectious Disease Infectious diseases are among the top seven biggest killers worldwide - with TB, malaria, hepatitis, and, HIV/AIDS all listed. Infectious diseases are among the top seven biggest killers worldwide - with TB, malaria, hepatitis, and, HIV/AIDS all listed. High rates of infectious disease require many resources and affect a nation’s economy, health, even national security. High rates of infectious disease require many resources and affect a nation’s economy, health, even national security. Monitoring levels of disease is important to allocating international and national resources. Monitoring levels of disease is important to allocating international and national resources.

13. © 2004 Aeras Global TB Vaccine Foundation 13 Tuberculosis or TB TB is caused by Mycobacterium tuberculosis. TB is caused by Mycobacterium tuberculosis. Primarily affects the body by causing problems with the lungs. Primarily affects the body by causing problems with the lungs. Not everyone exposed will become infected. Not everyone exposed will become infected. Not everyone infected, become diseased. Not everyone infected, become diseased.

14. © 2004 Aeras Global TB Vaccine Foundation 14 Global Impact of TB In 2002, there were 8.8 million new cases of TB. In 2002, there were 8.8 million new cases of TB. TB is a treatable disease, yet 2 million people with TB died in 2002. TB is a treatable disease, yet 2 million people with TB died in 2002. TB is the leading cause of death in people who are HIV positive. TB is the leading cause of death in people who are HIV positive. In South Africa, about 60% of adult TB patients are HIV positive. In South Africa, about 60% of adult TB patients are HIV positive. Information from the World Health Organization Global TB Report 2004 available at: http://www.who.int/tb/publications/global_report/2004/en/http://www.who.int/tb/publications/global_report/2004/en/

15. © 2004 Aeras Global TB Vaccine Foundation 15 TB: Global Incidence 25 - 49 50 - 99 100 - 300 0 - 9 10 - 24 300 or more No Estimate Rate per 100 000 Information from the World Health Organization Global TB Report 2004 available at: http://www.who.int/tb/publications/global_report/2004/en/ http://www.who.int/tb/publications/global_report/2004/en/

16. © 2004 Aeras Global TB Vaccine Foundation 16 TB Transmission Tuberculosis is an infection caused by a bacterium called Mycobacterium tuberculosis. Tuberculosis is an infection caused by a bacterium called Mycobacterium tuberculosis. The bacterium is also sometimes called the “tubercle bacillus”. The bacterium is also sometimes called the “tubercle bacillus”. Tuberculosis spreads from person to person through air as a person with active tuberculosis coughs, sneezes or expels air. Tuberculosis spreads from person to person through air as a person with active tuberculosis coughs, sneezes or expels air.

17. © 2004 Aeras Global TB Vaccine Foundation 17 TB Disease Cycle Smaller TB droplets enter air sacks of lung. TB Infection Immune system contains infection. Immune system fails. TB disease develops and person is infectious. People exposed to TB droplets.

18. © 2004 Aeras Global TB Vaccine Foundation 18 TB Review Where is TB a health problem? Where is TB a health problem? What are the routes of TB transmission? What are the routes of TB transmission? Describe the TB disease cycle. Describe the TB disease cycle.

19. © 2004 Aeras Global TB Vaccine Foundation 19HIV HIV = human immunodeficiency virus. Spread from one human being to another through body fluids. Slowly attacks and destroys the body’s immune system. The body responds by producing antibodies, although they are not able to stop the course of the disease. Antibodies to HIV can be detected by a blood test.

20. © 2004 Aeras Global TB Vaccine Foundation 20 Global HIV Epidemic Information from the UNAIDS 2004 Report on the Global AIDS Epidemic available at: http://www.unaids.org/bangkok2004/report.html http://www.unaids.org/bangkok2004/report.html

21. © 2004 Aeras Global TB Vaccine Foundation 21 Why do you think the HIV rate in South Africa is so high?

22. © 2004 Aeras Global TB Vaccine Foundation 22 HIV Transmission Requires: 1) Infected body fluids: Blood, semen, vaginal secretions and breast milk. Blood, semen, vaginal secretions and breast milk. 2) Entry into the body: Mucous membrane: anal, oral or vaginal sex Mucous membrane: anal, oral or vaginal sex Blood to blood: needle (body piercing, tattooing) or broken skin Blood to blood: needle (body piercing, tattooing) or broken skin Period around birth: In uterus, during birth or breastfeeding Period around birth: In uterus, during birth or breastfeeding

23. © 2004 Aeras Global TB Vaccine Foundation 23 HIV Disease Cycle Stage 1 First 6-12 weeks after the virus gets into the body. First 6-12 weeks after the virus gets into the body. Flu-like symptoms may occur. Flu-like symptoms may occur. Window period: The HIV antibody test may show a negative result during these first 6-12 weeks because not enough antibodies are formed to show positive results, but the person HAS the virus and can give it to other people! Window period: The HIV antibody test may show a negative result during these first 6-12 weeks because not enough antibodies are formed to show positive results, but the person HAS the virus and can give it to other people!

24. © 2004 Aeras Global TB Vaccine Foundation 24 Stage 2 The phase with no symptoms, also called silent phase. The virus has taken up residence and is slowly destroying components of the immune system. The phase with no symptoms, also called silent phase. The virus has taken up residence and is slowly destroying components of the immune system. This phase can last anything from 3-7 years, sometimes even longer! This phase can last anything from 3-7 years, sometimes even longer! This time period is much shorter in children. This time period is much shorter in children.

25. © 2004 Aeras Global TB Vaccine Foundation 25 Stage 3 The immune system gets weaker and a number of symptoms will occur, like weight loss. The immune system gets weaker and a number of symptoms will occur, like weight loss. Stage 4 Usually 5-8 years after infection. Usually 5-8 years after infection. More severe illnesses start to appear like tuberculosis and chronic diarrhea. More severe illnesses start to appear like tuberculosis and chronic diarrhea.

26. © 2004 Aeras Global TB Vaccine Foundation 26 Stage 5: AIDS (Acquired Immunodeficiency Syndrome) The final and most serious stage that is followed by death. The final and most serious stage that is followed by death. Many illnesses and cancers may appear in this stage. Many illnesses and cancers may appear in this stage.

27. © 2004 Aeras Global TB Vaccine Foundation 27 HIV Review Where is HIV a health problem? Where is HIV a health problem? What are the routes of HIV transmission? What are the routes of HIV transmission? Describe the HIV disease cycle. Describe the HIV disease cycle.

28. © 2004 Aeras Global TB Vaccine Foundation 28 Activity Discuss in your groups the TOP 5 Causes of Death for: 1. Men 2. Women 3. Children >5

29. © 2004 Aeras Global TB Vaccine Foundation 29 Malaria Malaria (“bad air”) is an infectious disease. Malaria (“bad air”) is an infectious disease. Malaria is caused by four parasites species of the genus Plasmodium. Malaria is caused by four parasites species of the genus Plasmodium. P. falciparum is the most widespread and dangerous of the four: untreated it can lead to fatal cerebral malaria. P. falciparum is the most widespread and dangerous of the four: untreated it can lead to fatal cerebral malaria.

30. © 2004 Aeras Global TB Vaccine Foundation 30 Impact of Malaria Worldwide prevalence of the disease is estimated to be in order of 300-500 million cases per year. Worldwide prevalence of the disease is estimated to be in order of 300-500 million cases per year. More than 90% of all cases are in sub- Saharan Africa. More than 90% of all cases are in sub- Saharan Africa. Mortality due to malaria is estimated to be over 1 million deaths each year. Mortality due to malaria is estimated to be over 1 million deaths each year.

31. © 2004 Aeras Global TB Vaccine Foundation 31 Malaria Transmission Malaria is transmitted by certain types of mosquitoes. Malaria is transmitted by certain types of mosquitoes. The female mosquito gets the parasite when it bites a person who is infected. The female mosquito gets the parasite when it bites a person who is infected. The mosquito then spreads malaria when biting other people. The mosquito then spreads malaria when biting other people. Mosquitoes bite during nighttime hours, from dusk to dawn. Mosquitoes bite during nighttime hours, from dusk to dawn.

32. © 2004 Aeras Global TB Vaccine Foundation 32 Malaria Life Cycle 1. An infected female mosquito bites, injecting parasites into the blood. 2. They pass quickly into the liver where they multiply. 3. Parasites burst from the liver cells to invade red blood cells and multiply. 4. Mosquito feeds on this patient, parasites will multiply in her stomach wall. 5. The mosquito inoculates another human.

33. © 2004 Aeras Global TB Vaccine Foundation 33 Malaria Review Where is malaria a health problem? Where is malaria a health problem? What are the routes of malaria transmission? What are the routes of malaria transmission? Describe the malaria disease cycle. Describe the malaria disease cycle.

34. © 2004 Aeras Global TB Vaccine Foundation 34 How Do We Fight The Spread Of Disease? Public health activities: Public health activities: Health promotion Health promotion Health needs assessment Health needs assessment Screening Screening Vaccination Vaccination Can you think of any other measures?

35. © 2004 Aeras Global TB Vaccine Foundation 35 How Does A Vaccine Work? A vaccine is made to prevent you from becoming sick from a particular disease. A vaccine is made to prevent you from becoming sick from a particular disease. Vaccines make the body thinks it is being invaded by a specific microorganism, and the body reacts by producing antibodies. Vaccines make the body thinks it is being invaded by a specific microorganism, and the body reacts by producing antibodies. After a vaccination, your body will be able to fight off that disease in the future. After a vaccination, your body will be able to fight off that disease in the future.

36. © 2004 Aeras Global TB Vaccine Foundation 36 Different Types Of Vaccines: Toxins produced by the bacteria of a certain disease are made harmless. Toxins produced by the bacteria of a certain disease are made harmless. Sometimes the bacteria may be killed and then injected. Sometimes the bacteria may be killed and then injected. A weak and therefore harmless strain of a virus or bacteria may be used as a vaccine. A weak and therefore harmless strain of a virus or bacteria may be used as a vaccine. Use an organism which is similar to the virulent organism but that does not cause serious disease. Use an organism which is similar to the virulent organism but that does not cause serious disease. BCG vaccine made this way !

37. © 2004 Aeras Global TB Vaccine Foundation 37 Immunity and Protection Through Vaccines Immunity may be passive or active. Immunity may be passive or active. Passive acquired immunity results when antibodies produced by another animal or human are given to someone to prevent or treat disease. Passive acquired immunity results when antibodies produced by another animal or human are given to someone to prevent or treat disease. For example, administering tetanus antitoxin or rabies immune globulin to someone is a way of conferring passive immunity. For example, administering tetanus antitoxin or rabies immune globulin to someone is a way of conferring passive immunity. This type of immunization is effective very quickly, but since it lasts only a short time. This type of immunization is effective very quickly, but since it lasts only a short time.

38. © 2004 Aeras Global TB Vaccine Foundation 38 Immunity and Protection Through Vaccines Active acquired immunity occurs when the person is exposed to a microorganism, develops the disease, and becomes immune as a result of the primary immune response. Active acquired immunity occurs when the person is exposed to a microorganism, develops the disease, and becomes immune as a result of the primary immune response. This immunity can be induced by a vaccine, a substance that contains the antigen. This immunity can be induced by a vaccine, a substance that contains the antigen. A vaccine stimulates a primary response against the antigen without causing symptoms of the disease. A vaccine stimulates a primary response against the antigen without causing symptoms of the disease.

39. © 2004 Aeras Global TB Vaccine Foundation 39 TB Prevention By Vaccination The present TB vaccine is a made from a bacterium discovered in 1921 by Profs Calmette and Guerin called BCG. The present TB vaccine is a made from a bacterium discovered in 1921 by Profs Calmette and Guerin called BCG. In South Africa BCG is given at birth. In South Africa BCG is given at birth. Experts agree that BCG prevents serious TB in children. Experts agree that BCG prevents serious TB in children. Experts disagree about the effectiveness of BCG in preventing adult TB. Experts disagree about the effectiveness of BCG in preventing adult TB. Aeras Global TB Vaccine Foundation and others are doing research to find more effective TB vaccines. Aeras Global TB Vaccine Foundation and others are doing research to find more effective TB vaccines.

40. © 2004 Aeras Global TB Vaccine Foundation 40 How Do We Fight Disease In The Community? Government measures Government measures Housing, safe environment, clinical research, immunization Housing, safe environment, clinical research, immunization Community measures Community measures NGO,TAC, ATICC, NGO,TAC, ATICC, Individual measures Individual measures Lifestyle changes, regular health check- ups, Lifestyle changes, regular health check- ups,

41. © 2004 Aeras Global TB Vaccine Foundation 41 Review Infection is the invasion and multiplication of microorganisms in body tissues. Disease occurs when the microorganisms causes enough harm to cause physiological impairment. Infection is the invasion and multiplication of microorganisms in body tissues. Disease occurs when the microorganisms causes enough harm to cause physiological impairment. Certain factors weaken our immune system and make us prone to disease. Certain factors weaken our immune system and make us prone to disease.

42. © 2004 Aeras Global TB Vaccine Foundation 42Review Tuberculosis is caused by the Mycobacterium tuberculosis bacteria which is spread from person to person via droplets. Tuberculosis is caused by the Mycobacterium tuberculosis bacteria which is spread from person to person via droplets. A person infected with TB bacteria may not necessarily get TB disease. A person infected with TB bacteria may not necessarily get TB disease. HIV is transmitted through body fluids. HIV is transmitted through body fluids. A person infected with HIV goes through different stages in the disease process which eventually leads to AIDS. A person infected with HIV goes through different stages in the disease process which eventually leads to AIDS.

43. © 2004 Aeras Global TB Vaccine Foundation 43 Review Malaria is caused by a parasite carried by certain species of female mosquitoes. Malaria is caused by a parasite carried by certain species of female mosquitoes. The malaria parasite causes damage to the human liver, red blood cells and brain which could lead to death. The malaria parasite causes damage to the human liver, red blood cells and brain which could lead to death. There are different ways in which to fight disease, i.e. natural defenses of the body, immunization and public health measures. There are different ways in which to fight disease, i.e. natural defenses of the body, immunization and public health measures. Immunity could be actively acquired (immunization and the production of antibodies) or passively acquired (antiserum which contains antibodies). Immunity could be actively acquired (immunization and the production of antibodies) or passively acquired (antiserum which contains antibodies).

44. © 2004 Aeras Global TB Vaccine Foundation 44 Review Vaccines make the body think it is being invaded by a specific microorganisms, and the body reacts by producing antibodies. Vaccines make the body think it is being invaded by a specific microorganisms, and the body reacts by producing antibodies. Experts disagree on the effectiveness of BCG vaccine against adult TB and many are searching for a more effective vaccine. Experts disagree on the effectiveness of BCG vaccine against adult TB and many are searching for a more effective vaccine. Public health efforts play an important role in fighting the spread of infectious diseases such as TB, HIV and Malaria. Public health efforts play an important role in fighting the spread of infectious diseases such as TB, HIV and Malaria.

45. © 2004 Aeras Global TB Vaccine Foundation 45 This presentation is produced by Aeras Global TB Vaccine Foundation SM in collaboration with the University of Cape Town and the South African Tuberculosis Vaccine Initiative. A special thanks to Professor Greg Hussey, Professor Maurice Kibel, Marie Buchanan, Marijke Geldenhuys, MSHS CRA, Marwou De Kock, B.Tec., Dr. Sylvia Silver, D.A., and Jen Page, M.Ed. for their contributions and support for this presentation. Clinical Infectious Disease 2