© 2004 aeras global tb vaccine foundation clinical infectious diseases 2 clinical research practice

© 2004 Aeras Global TB Vaccine © 2004 Aeras Global TB Vaccine FoundationFoundation

Clinical Infectious Diseases 2Clinical Infectious Diseases 2

Clinical Research PracticeClinical Research Practice

22

© 2004 Aeras Global TB Vaccine Foundation© 2004 Aeras Global TB Vaccine Foundation

ObjectivesObjectives Differentiate between infection and Differentiate between infection and

disease.disease. Describe why poor health status Describe why poor health status

makes one more susceptible to makes one more susceptible to infectious disease.infectious disease.

Identify routes of transmission for TB, Identify routes of transmission for TB, HIV and Malaria.HIV and Malaria.

Describe the disease cycle in humans Describe the disease cycle in humans for TB, HIV and Malaria.for TB, HIV and Malaria.

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ObjectivesObjectives Differentiate between active and Differentiate between active and

passive immunity.passive immunity. Describe how a vaccine works.Describe how a vaccine works. Describe the need for a new TB Describe the need for a new TB

vaccine.vaccine. Describe the role of public health Describe the role of public health

measures in curtailing the spread of measures in curtailing the spread of TB, HIV and Malaria.TB, HIV and Malaria.

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Infectious Disease ReviewInfectious Disease Review

Health:Health:A state of wellbeing A state of wellbeing without disease.without disease.

Illness: Illness: A state of being A state of being unable to function unable to function normally.normally.

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Types Of Disease Types Of Disease

There are two main types of disease:There are two main types of disease:

Non-infectious Non-infectious diseases do not diseases do not spread from a sick person to a spread from a sick person to a healthy person.healthy person.

InfectiousInfectious diseases are spread from diseases are spread from person to person.person to person.

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Infectious DiseasesInfectious Diseases

These diseases are mainly These diseases are mainly caused by tiny organisms caused by tiny organisms called: called:

Bacteria Bacteria

VirusesViruses

ParasitesParasites

These are called germs or These are called germs or microorganisms.microorganisms.

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How Do Infection and Disease How Do Infection and Disease Differ?Differ?

InfectionInfection An invasion and An invasion and

multiplication of multiplication of microorganisms in body microorganisms in body tissues.tissues.

The infection may not be The infection may not be evident in a way that evident in a way that affects one’s health or affects one’s health or well-being. well-being.

DiseaseDisease The debilitating The debilitating

effects on a host effects on a host afterafter infection by a infection by a microorganism .microorganism .

Microorganism causes Microorganism causes enough harm to the enough harm to the body to cause body to cause physiological physiological impairment.impairment.

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Your Body’s DefensesYour Body’s Defenses

11stst Line of Defence: Line of Defence: Skin, mucous membranes Skin, mucous membranes

with tiny hairs (in your nose with tiny hairs (in your nose and throat) and tears. and throat) and tears.

When a harmful microbe is When a harmful microbe is present they:present they: Prevent the microbes from Prevent the microbes from

entering your body.entering your body. Wash them awayWash them away..

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Your Body’s DefensesYour Body’s Defenses22ndnd Line of Defence: Line of Defence:

The immune system is The immune system is a complex system a complex system that works to clear infection from the body.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 White blood cells destroy the foreign

microbes and call on other defences to microbes and call on other defences to fight them.fight them.

Antibodies might be created to go after Antibodies might be created to go after the microorganisms. the microorganisms.

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Why Do We Still Get Why Do We Still Get Disease?Disease?

Certain factors weaken our Certain factors weaken our immune system and make us immune system and make us prone to disease:prone to disease:

AgeAge Other illness Other illness MalnutritionMalnutrition MedicationMedication Life styleLife style EnvironmentEnvironment

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Impact of Infectious DiseaseImpact of Infectious Disease Infectious diseases are among the top Infectious diseases are among the top

seven biggest killers worldwide - with TB, seven biggest killers worldwide - with TB, malaria, hepatitis, and, HIV/AIDS all listed.malaria, hepatitis, and, HIV/AIDS all listed.

High rates of infectious disease require High rates of infectious disease require many resources and affect a nation’s many resources and affect a nation’s economy, health, even national security.economy, health, even national security.

Monitoring levels of disease is important to Monitoring levels of disease is important to allocating international and national allocating international and national resources.resources.

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Tuberculosis or TBTuberculosis or TB TB is caused by TB is caused by MycobacteriumMycobacterium

tuberculosistuberculosis.. Primarily affects the body by causing Primarily affects the body by causing

problems with the lungs.problems with the lungs. Not everyone exposed will become Not everyone exposed will become

infected. infected. Not everyone infected, become Not everyone infected, become

diseased.diseased.

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Global Impact of TBGlobal Impact of TB

In 2002, there were 8.8 million new cases In 2002, there were 8.8 million new cases of TB.of TB.

TB is a treatable disease, yet 2 million TB is a treatable disease, yet 2 million people with TB died in 2002.people with TB died in 2002.

TB is the leading cause of death in people TB is the leading cause of death in people who are HIV positive.who are HIV positive.

In South Africa, about 60% of adult TB In South Africa, about 60% of adult TB patients are HIV positive.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/

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TB: Global IncidenceTB: Global Incidence

25 - 4950 - 99100 - 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/

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TB TransmissionTB Transmission Tuberculosis is an infection Tuberculosis is an infection

caused by a bacterium called caused by a bacterium called Mycobacterium tuberculosisMycobacterium tuberculosis..

The bacterium is also The bacterium is also sometimes called the sometimes called the “tubercle bacillus”.“tubercle bacillus”.

Tuberculosis spreads from Tuberculosis spreads from person to person through air person to person through air as a person with active as a person with active tuberculosis coughs, sneezes tuberculosis coughs, sneezes or expels air.or expels air.

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TB Disease CycleTB Disease CycleSmaller TB Smaller TB

droplets enter droplets enter air sacks of lung.air sacks of lung.

TB disease TB disease develops anddevelops and

person is infectious.person is infectious.

People exposed People exposed to TB droplets.to TB droplets.

Immune Immune system fails.system fails.

Immune system Immune system contains infection.contains infection.

TB InfectionTB Infection

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TB ReviewTB Review

Where is TB a health problem?Where is TB a health problem?

What are the routes of TB What are the routes of TB transmission?transmission?

Describe the TB disease cycle.Describe the TB disease cycle.

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HIVHIV 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.

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Global HIV EpidemicGlobal HIV Epidemic

0 0 0 0 2 - E - 4 – 1 D e c e m b e r 2 0 0 3

A d u l t s a n d c h i l d r e n e s t i m a t e d t o b e l i v i n g A d u l t s a n d c h i l d r e n e s t i m a t e d t o b e l i v i n g w i t h H I V / A I D S a s o f e n d 2 0 0 3w i t h H I V / A I D S a s o f e n d 2 0 0 3

T o t a l : 3 4 – 4 6 m i l l i o n

W e s t e r n E u r o p e5 2 0 0 0 0 5 2 0 0 0 0 –– 6 8 0 0 0 06 8 0 0 0 0

N o r t h A f r i c a & M i d d l e E a s t4 7 0 0 0 0 4 7 0 0 0 0 –– 7 3 0 0 0 07 3 0 0 0 0

S u b - S a h a r a n A f r i c a2 5 . 0 2 5 . 0 –– 2 8 . 2 m i l l i o n2 8 . 2 m i l l i o n

E a s t e r n E u r o p e & C e n t r a l A s i a1 . 2 1 . 2 –– 1 . 8 m i l l i o n1 . 8 m i l l i o n

S o u t h & S o u t h - E a s t A s i a

4 . 6 4 . 6 –– 8 . 2 m i l l i o n8 . 2 m i l l i o n

A u s t r a l i a & N e w Z e a l a n d

1 2 0 0 0 1 2 0 0 0 –– 1 8 0 0 01 8 0 0 0

N o r t h A m e r i c a7 9 0 0 0 0 7 9 0 0 0 0 –– 1 . 2 m i l l i o n1 . 2 m i l l i o n

C a r i b b e a n3 5 0 0 0 0 3 5 0 0 0 0 –– 5 9 0 0 0 05 9 0 0 0 0

L a t i n A m e r i c a1 . 3 1 . 3 –– 1 . 9 m i l l i o n1 . 9 m i l l i o n

E a s t A s i a & P a c i f i c7 0 0 0 0 0 7 0 0 0 0 0 –– 1 . 3 m i l l i o n1 . 3 m i l l i o n

Information from the UNAIDS 2004 Report on the Global AIDS Epidemic available at: http://www.unaids.org/bangkok2004/report.html

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Why do Why do youyou think the HIV think the HIV rate in South Africa is so rate in South Africa is so high?high?

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HIV Transmission Requires:HIV Transmission Requires:

1) Infected body fluids:1) Infected body fluids: Blood, semen, vaginal secretions and breast Blood, semen, vaginal secretions and breast

milk. milk.

2) Entry into the body:2) Entry into the body: Mucous membrane: anal, oral or vaginal sexMucous membrane: anal, oral or vaginal sex Blood to blood: needle (body piercing, Blood to blood: needle (body piercing,

tattooing) or broken skintattooing) or broken skin Period around birth: In uterus, during birth or Period around birth: In uterus, during birth or

breastfeedingbreastfeeding

2323


HIV Disease CycleHIV Disease Cycle

Stage 1Stage 1 First 6-12 weeks after the virus gets First 6-12 weeks after the virus gets

into the body.into the body. Flu-like symptoms may occur.Flu-like symptoms may occur. Window period: Window period: The HIV antibody The HIV antibody

test may show a negative result during test may show a negative result during these first 6-12 weeks because not these first 6-12 weeks because not enough antibodies are formed to show enough antibodies are formed to show positive results, but the person HAS the positive results, but the person HAS the virus and can give it to other people!virus and can give it to other people!

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Stage 2Stage 2

The phase with no symptoms, The phase with no symptoms, also called silent phase. The also called silent phase. The virus has taken up residence virus has taken up residence and is slowly destroying and is slowly destroying components of the immune components of the immune systemsystem. .

This phase can last anything This phase can last anything from 3-7 years, sometimes from 3-7 years, sometimes even longer!even longer!

This time period is much This time period is much shorter in children.shorter in children.

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Stage 3Stage 3

The immune system gets weaker and a The immune system gets weaker and a number of symptoms will occur, like weight number of symptoms will occur, like weight loss.loss.

Stage 4Stage 4

Usually 5-8 years after infection.Usually 5-8 years after infection. More severe illnesses start to appear like More severe illnesses start to appear like

tuberculosis and chronic diarrhea.tuberculosis and chronic diarrhea.

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Stage 5: AIDS (Acquired Stage 5: AIDS (Acquired Immunodeficiency Syndrome)Immunodeficiency Syndrome)

The final and most serious stageThe final and most serious stagethat is followed by death.that is followed by death.

Many illnesses and cancers mayMany illnesses and cancers mayappear in this stage.appear in this stage.

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HIV ReviewHIV Review

Where is HIV a health problem?Where is HIV a health problem?

What are the routes of HIV What are the routes of HIV transmission?transmission?

Describe the HIV disease cycle.Describe the HIV disease cycle.

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ActivityActivity

Discuss in your groups the TOP 5 Discuss in your groups the TOP 5 Causes of Death for:Causes of Death for:

1.1. MenMen

2.2. WomenWomen

3.3. Children >5Children >5

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MalariaMalaria

Malaria (“bad air”) is an infectious Malaria (“bad air”) is an infectious disease. disease.

Malaria is caused by four parasites Malaria is caused by four parasites species of the genus species of the genus PlasmodiumPlasmodium..

P. falciparumP. falciparum is the most widespread is the most widespread and dangerous of the four: untreated and dangerous of the four: untreated it can lead to fatal cerebral malaria.it can lead to fatal cerebral malaria.

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Impact of MalariaImpact of Malaria

Worldwide prevalence of the disease Worldwide prevalence of the disease is estimated to be in order of 300-is estimated to be in order of 300-500 million cases per year.500 million cases per year.

More than 90% of all cases are in More than 90% of all cases are in sub-Saharan Africa.sub-Saharan Africa.

Mortality due to malaria is estimated Mortality due to malaria is estimated to be over 1 million deaths each to be over 1 million deaths each year.year.

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Malaria TransmissionMalaria Transmission

Malaria is transmitted by certain Malaria is transmitted by certain types of mosquitoes.types of mosquitoes.

The female mosquito gets the The female mosquito gets the parasite when it bites a person who parasite when it bites a person who is infected.is infected.

The mosquito then spreads malaria The mosquito then spreads malaria when biting other people. when biting other people.

Mosquitoes bite during nighttime Mosquitoes bite during nighttime hours, from dusk to dawn.hours, from dusk to dawn.

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Malaria Life CycleMalaria Life Cycle1.1. An infected female mosquito An infected female mosquito

bites, injecting parasites into bites, injecting parasites into the blood.the blood.

2.2. They pass quickly into the liver They pass quickly into the liver where they multiply.where they multiply.

3.3. Parasites burst from the liver Parasites burst from the liver cells to invade red blood cells cells to invade red blood cells and multiply.and multiply.

4.4. Mosquito feeds on this patient, Mosquito feeds on this patient, parasites will multiply in her parasites will multiply in her stomach wall.stomach wall.

5.5. The mosquito inoculates The mosquito inoculates another human.another human.

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Malaria ReviewMalaria Review

Where is malaria a health problem?Where is malaria a health problem?

What are the routes of malaria What are the routes of malaria transmission?transmission?

Describe the malaria disease cycle.Describe the malaria disease cycle.

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How Do We Fight The Spread How Do We Fight The Spread Of Disease?Of Disease?

Public health activities:Public health activities: Health promotionHealth promotion Health needs assessmentHealth needs assessment ScreeningScreening VaccinationVaccination

Can you think of any other measures?Can you think of any other measures?

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How Does A Vaccine Work?How Does A Vaccine Work? A A vaccinevaccine is made to prevent is made to prevent

you from becoming sick from a you from becoming sick from a particular disease. particular disease.

Vaccines make the body thinks Vaccines make the body thinks it is being invaded by a specific it is being invaded by a specific microorganism, and the body microorganism, and the body reacts by producing antibodies. reacts by producing antibodies.

After a vaccination, your body After a vaccination, your body will be able to fight off that will be able to fight off that disease in the future.disease in the future.

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Different Types Of Vaccines:Different Types Of Vaccines: Toxins produced by the bacteria of a Toxins produced by the bacteria of a

certain disease are made harmless.certain disease are made harmless. Sometimes the bacteria may be killed and Sometimes the bacteria may be killed and

then injected.then injected. A weak and therefore harmless strain of a A weak and therefore harmless strain of a

virus or bacteria may be used as a virus or bacteria may be used as a vaccine.vaccine.

Use an organism which is similar to the Use an organism which is similar to the virulent organism but that does not cause virulent organism but that does not cause serious disease.serious disease.

BCG vaccine made this wayBCG vaccine made this way!!

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Immunity and Protection Immunity and Protection Through VaccinesThrough Vaccines

Immunity may be passive or active. Immunity may be passive or active. Passive acquired immunityPassive acquired immunity results when results when

antibodies produced by another animal or antibodies produced by another animal or human are given to someone to prevent human are given to someone to prevent or treat disease. or treat disease.

For example, administering tetanus For example, administering tetanus antitoxin or rabies immune globulin to antitoxin or rabies immune globulin to someone is a way of conferring passive someone is a way of conferring passive immunity. immunity.

This type of immunization is effective very This type of immunization is effective very quickly, but since it lasts only a short quickly, but since it lasts only a short time. time.

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Immunity and Protection Immunity and Protection Through VaccinesThrough Vaccines

Active acquired immunityActive acquired immunity occurs when occurs when the person is exposed to a the person is exposed to a microorganism, develops the disease, and microorganism, develops the disease, and becomes immune as a result of the becomes immune as a result of the primary immune response. primary immune response.

This immunity can be induced by a This immunity can be induced by a vaccine, a substance that contains the vaccine, a substance that contains the antigen. antigen.

A vaccine stimulates a primary response A vaccine stimulates a primary response against the antigen without causing against the antigen without causing symptoms of the disease. symptoms of the disease.

3939


TB Prevention By TB Prevention By VaccinationVaccination

The present TB vaccine is a made from a The present TB vaccine is a made from a bacterium discovered in 1921 by Profs bacterium discovered in 1921 by Profs Calmette and Guerin called BCG.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 Experts agree that BCG prevents serious

TB in children.TB in children. Experts disagree about the effectiveness Experts disagree about the effectiveness

of BCG in preventing adult TB.of BCG in preventing adult TB. Aeras Global TB Vaccine FoundationAeras Global TB Vaccine Foundation and and

others are doing research to find more others are doing research to find more effective TB vaccines. effective TB vaccines.

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How Do We Fight Disease In How Do We Fight Disease In The Community?The Community?

Government measuresGovernment measures Housing, safe environment, clinical Housing, safe environment, clinical

research, immunizationresearch, immunization

Community measures Community measures NGO,TAC, ATICC, NGO,TAC, ATICC,

Individual measures Individual measures Lifestyle changes, regular health Lifestyle changes, regular health

check-ups, check-ups,

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ReviewReview

Infection is the invasion and Infection is the invasion and multiplication of microorganisms in multiplication of microorganisms in body tissues. Disease occurs when the body tissues. Disease occurs when the microorganisms causes enough harm microorganisms causes enough harm to cause physiological impairment.to cause physiological impairment.

Certain factors weaken our immune Certain factors weaken our immune system and make us prone to disease.system and make us prone to disease.

4242


ReviewReview Tuberculosis is caused by the Tuberculosis is caused by the

Mycobacterium tuberculosisMycobacterium tuberculosis bacteria bacteria which is spread from person to person via which is spread from person to person via droplets.droplets.

A person infected with TB bacteria may A person infected with TB bacteria may not necessarily get TB disease.not necessarily get TB disease.

HIV is transmitted through body fluids.HIV is transmitted through body fluids. A person infected with HIV goes through A person infected with HIV goes through

different stages in the disease process different stages in the disease process which eventually leads to AIDS.which eventually leads to AIDS.

4343


ReviewReview Malaria is caused by a parasite carried by Malaria is caused by a parasite carried by

certain species of female mosquitoes. certain species of female mosquitoes. The malaria parasite causes damage to the The malaria parasite causes damage to the

human liver, red blood cells and brain human liver, red blood cells and brain which could lead to death.which could lead to death.

There are different ways in which to fight There are different ways in which to fight disease, i.e. natural defenses of the body, disease, i.e. natural defenses of the body, immunization and public health measures.immunization and public health measures.

Immunity could be actively acquired Immunity could be actively acquired (immunization and the production of (immunization and the production of antibodies) or passively acquired antibodies) or passively acquired (antiserum which contains antibodies).(antiserum which contains antibodies).

4444


ReviewReview Vaccines make the body think it is being Vaccines make the body think it is being

invaded by a specific microorganisms, and invaded by a specific microorganisms, and the body reacts by producing antibodies. the body reacts by producing antibodies.

Experts disagree on the effectiveness of Experts disagree on the effectiveness of BCG vaccineBCG vaccine against adult TB and many against adult TB and many are searching for a more effective vaccine.are searching for a more effective vaccine.

Public health efforts play an important role Public health efforts play an important role in fighting the spread of infectious in fighting the spread of infectious diseases such as TB, HIV and Malaria.diseases such as TB, HIV and Malaria.

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This presentation is produced by Aeras Global TB Vaccine FoundationSM 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 2Clinical Infectious Disease 2

© 2004 aeras global tb vaccine foundation clinical infectious diseases 2 clinical research practice

Documents

spread of tb

new tb vaccine

disease cycle

main types of disease

sick person

healthy person

noninfectious diseases

ones health