New Perspectives on Emerging Diseases, Biocomplexity and

Teaching for ContextFrom Microbial Threats to Health

Institute of Medicine, 2003

Emerging diseases/ Biocomplexity

http://www.nsf.gov/od/lpa/forum/bordogna/jb01sarnoff/sld012.htm

Policy Forum ScienceScience, , 4/23/044/23/04:Scientific Teaching

“Science education should be founded on“scientific teaching.”

Scientific teaching involves activelearning strategies to engage students in the process of science and teachingmethods that have been systematically testedand shown to reach diverse students.”

How?• Implementing change in lectures so that

students are learning actively• Engaging students with important questions• Empowering students as investigators, both

in their reading/ problem formulation and in the laboratory

• RESOURCE LIST with Science Policy Report 4/23/04

Beloit College Mindset ListBeloit College Mindset List

http://www.beloit.edu/~pubaff/releases/mindset_2007.html

Most students entering college last fall were born in 1985:

1. John Kennedy and John Lennon have always been dead.2. Iraq has always been a problem.3. Genetic testing and DNA screening have always been available4. Paul Newman has always made salad dressing.5. The "evil empire" has moved from Moscow to a setting in a distant galaxy far, far away. 6. Bert and Ernie are old enough to be their parents.7. An automatic is a weapon, not a transmission.8. There has always been a screening test for AIDS.9. Computers have always fit in their backpacks

Microbiology Student Mindset List

They have never worried about polio and always worried about AIDS.

Anthrax is a weapon not a soil microbe.Chlamydia has always been an STD threat.Magic Johnson has been “cured” of AIDS.Ebola has always been known.DNA is easily copied and sequenced.Warnings for Toxic Shock Syndrome are in all tampon

boxes.Hasn’t drug design always been rational?

Recent newsRare Infection Threatens to Spread in Blood SupplyBy DONALD G. McNEIL Jr. New York Times Published: November 18, 2003

Dr. David A. Leiby, a Chagas' disease expert, says the risk of getting a transfusion of

infected blood in the United States is about 1 in 25,000. But in 1998 in Miami it was found to be 1 in 9,000, he said, and in Los Angeles the same year, he measured it at 1 in 5,400, up from 1 in 9,850 only two years earlier.

530 Hepatitis Cases Linked to Pa. EateryBy THE ASSOCIATED PRESS Published: November 19, 2003

PITTSBURGH (AP) -- The number of cases of hepatitis A linked to a Mexican restaurant rose to 530 Wednesday, but state health officials said the outbreak has slowed considerably since last week, when dozens of new cases were being reported daily.

Secretary of Health Calvin Johnson said officials still haven't determined whether tainted green onions are behind the outbreak at the Chi-Chi's restaurant, but were continuing to investigate.

germ disease

“Germ theory” of disease

agent

environment

host

Epidemiological model of disease

Chagas Disease in the Blood Supply

• Chagas is American trypanosomiasis- no treatment, chronic heart disease, colon blockage

• Caused by protist, usually transmitted by arthropods

• Adapted to new technologies- can survive in blood supply

WHO’s warning

• The risk of infection with Chagas disease is directly related to poverty: the blood-sucking triatomine bug which transmits the parasite finds a favourable habitat in crevices in the walls and roofs of poor houses in rural areas and in the peripheral urban slums.

• The rural/urban migration movements that occurred in Latin America in the 1970's and 1980's changed the traditional epidemiological pattern of Chagas disease and transformed it into an urban infection that can be transmitted by blood transfusion.

• The figures of infection of blood in blood banks in some selected cities of the continent vary between 3.0 and 53.0 % thus showing that the prevalence of T.cruzi-infected blood is higher than that of HIV infection and Hepatitis B and C.

How has the oranism changed?Is it genotypic or phenotypic?

Hepatitis A

• Viral, acute disease• No carrier state• Spread by food, fecal contamination• Mortality rate 1%• Vaccination available for health care workers,

travelers• Green onions from Mexico implicated in ourbreak,

not employees who didn’t wash their hands…• Will Chi-Chi’s survive this outbreak?

Reasons for disease emergence-Chi Chi’s outbreak

• Eating out?• Young workers?• Imported produce?• Changing food preferences?• Immunocompromised eaters?• What is the process of tracking disease?

– Viral subtyping– Epidemiological analysis

Factors in Disease Emergence 1992

• Microbial adaptation and change

• Economic development and land use

• Human demographics and behavior

• International travel and commerce

• Technology and industry

• Breakdown of public health measures

Factors in Disease Emergence 2003Factors in Disease Emergence 2003• Microbial adaptation and change

• Human susceptibility to infection

• Climate and weather

• Changing ecosystems

• Economic development and land use

• Human demographics and behavior

• International travel and commerce

• Technology and industry

Breakdown of public health measures

Poverty and social inequality

• War and famine

• Lack of political will

• Intent to do harm

from

Microbial Threats to Health

Institute of Medicine, 2003

Factors in Disease Emergence 2003Factors in Disease Emergence 2003• Microbial adaptation and change AGENT

• Human susceptibility to infection HOST

• Climate and weather ENVIRONMENT

• Changing ecosystems ENVIRONMENT

• Economic development and land use ENVIRONMENT

• Human demographics and behavior ENVIRONMENT

• International travel and commerce ENVIRONMENT

• Technology and industry ENVIRONMENT

• Breakdown of public health measures ENVIRONMENT

• Poverty and social inequality Structural Violence

• War and famine Structural Violence

• Lack of political will Structural Violence

• Intent to do harm Structural Violence

Diseaseemergence

Structural factors

agent

environmenthost

Decresed immunity

Public health

warPolitical will

Microbial evolution

technology

climate

travel

Land use

Diseaseemergence

Structural factors

agent environment

host

susceptibility

Public health

Political will

War and famine

Microbial evolution

technology

climate

travel

Land use

Human behavior

Diseaseemergence

Structural factors

agent environment

host

susceptibility

Public health

Political will

War and famine

Microbial evolution

technology

climate

travel

Land use

Human behavior

While pathogenesis is related to factors of agent and host, the

emergence of new diseases is an environmental and political

phenomenon as well

Microbial adaptation and change

• Microbes have enormous evolutionary potential, undergoing changes in pathogenicity and ability to avoid immune system-

• Have ability to share traits for virulence

• Evolutionary pressures to adapt are enhanced by human activities

The challenge of influenza

• New strains develop frequently because of mixing of strains from pigs, chickens and wild birds

• Factory farming practices increase risks

• Fear that new strain could have impact of 1918 influenza

• Could this happen now?

http://www.civil.kyushu-u.ac.jp/suiken/kawamura/seminar/earthstature/

Functional Motions of Influenza Virus Hemagglutinin (HA): A Structure-Based Analytical Approach

Isin B, Doruker P and Bahar I. Biophys J.  2002; 82(2):569-81

http://www.ccbb.pitt.edu/CCBBResearchFunMotInf.htm

What makes a “Killer flu”?How do mutations affect vaccine effectiveness?

Microbial adaptation and change

Microbial adaptations• Rapid reproduction- some bacteria have 20

minute generation cycles• Horizontal gene transfer• Frequent mutations, especially in RNA viruses

like HIV, influenza• Microbes may become resistant to drugs but less

“fit”- when drugs not used, will revert • What is the time/ space scale of microbial

evolution?

Surveillance of H. pylori antibiotic resistance in England and Wales, 2003

http://www.hpa.org.uk/infections/topics_az/helicobacter/data.htm

Human susceptibility to infection

• Impaired host immunity- HIV, transplants, aging• Malnutrition and effect on host resistance to

infection– 150 million children under 5– Impaired phagocyte activity, cytokines, mucous

membranes– Effects of specific nutrients, copper, vit A

• Genetic polymorphisms– Sickle cell anemia and thalessemia– Glucose 6 phosphate dehydrogenase deficiency

http://www.worldbank.org/html/extdr/hnp/sector_strategy/hnpmaps.htm

Climate and weather

• Vectors, animal reservoirs, microbes and humans

• Hanta virus and El Nino weather in AZ

• Cholera

• Arthropod borne diseases like malaria, yellow fever and dengue

• Mosquitoes in Beloit!!!

Changing ecosystems

• Forest growth reduces evaporation,• Crops increase local humidity• These change range of vectors• Dengue in Arizona- swamp coolers..• Reservoir abundance (mice and Hanta)• Moving mosquitoes

– Culex like drier seasons (St Louis enchepal.)

– Aedes aegypti, breed in containers Dengue

http://www.usgcrp.gov/usgcrp/Library/nationalassessment/overviewhealth.htm

Why is dengue a greater problem in Mexico than Texas?

Economic development and land use

• Suburban development, species diversity and Lyme disease

• Dams and schistosomiasis- Nile and Yangtse

Snail fever outbreak hits China- ----------------------------------China has vowed stronger measures to contain the spread of a potentially lethal parasitic worm, carried by freshwater snails, that attacks the blood and liver of humans, state media has reported. The Government hopes research in its fight against the disease, known as shistosomiasis, or snail fever, will help identify infection sources and develop new prevention methods, the China Daily reported. It is believed that more than one million Chinese are infected with the disease, but, given the current prevalence of the carrier snail, a total of 65 million Chinese are in danger of being infected, previous reports said. In 2003 alone, 843 000 Chinese were infected, most of them living in frequently flooded areas along the Yangtze River, where the carrier snail has an ideal habitat, according to the paper. By the 1980s, China thought that it had effectively controlled snail fever, but a mixture of natural disasters, and human error, has facilitated its return. After a massive deluge along the Yangtze 6 years ago, the disease moved on to large, previously unaffected areas. The disease has been allowed to spread due to public ignorance and the erosion of China's healthcare system, the report said.

ProMED, Vol 2004, #223, June 14, 2004

Human demographics and behavior

• Child care• Population growth and limited infrastructure

response• Aging of population- decreased immune response• Immunocompromised populations• Women’s rights• Risky behaviors

HIV Prevalence in Teenagers in Kisumu, Kenya 1999

10%32%19

3%24%18

5%30%17

0%18%16

0%9%15

BOYSGIRLSAge

Technology and industry

• Chi-chi’s and the food industry

• Blood supply and safety

• Organ transplantation, xenotransplantation

• Animal husbandry- pig farms and chicken coops, aquaculture -– Antibiotics– Waste management

Transplant disaster

• CDC reported in 11/2001 the story of a 23 year old man who received bone cartilage during reconstructive knee surgery and developed a fatal infection with Clostridium sordellii, an anaerobic spore and toxin forming organism

• Several days later a man in Illinois received an infection from tissue from the same cadaver.

• CDC investigators found 19 other tissues taken from the donor

International Travel and Commerce

• Humans• Food

– 95% of green onions in US imported from Mexico

• Cruise ships (what a great environment)– Elderly passengers– Frequent new environments– Employees who can be carriers– Contaminated food and water – Some ships offer medical care

and dialysis

Breakdown of public health measures

• Tuberculosis in Russian jails- is the problem drug resistant TB or just poor treatment in poor environments?

• Potential for spread of vaccine preventable diseases

• Fear of loss of fertility with Polio vaccine in Muslim countries?

How do you treatHIV/AIDS from a clinic like this?

In Kenya you begin tostudy the role of nutrition because you can makean impact without manyresources

Poverty and social inequality

• Is this biological? How?

War and famine

• Most deaths in modern wars are not soldiers but civilians

• Most deaths are not direct but indirect- result from destruction of water supply, malnutrition, loss of access to medical care

• Increased migrations• Rape as a weapon of war• Famine- in war and as consequence of HIV

Intent to do harm

• Role of individual vs nation state in political arena• Potential of genetically altered weapons

– How much information should be available in the scientific literature? Should science be censored

• Changing scenario of attack-– Terrorist scenario vs large attack

– Characteristics of bioweapons- what do we need to know?

Political will

• When the choice is 87 billion in Iraq or 3 billion to stop AIDS…

• Countries that spend money on armies cut money to health services

• Lost windows of opportunity-– Could countries have acted to stop AIDS?– Why was the response to SARS so rapid?

HIV storiesMbeki’s stance “How can a virus cause

a syndrome”vs Achmat’s activism

Politics of drugsWho is Zackie Achmat?

Political will and future scientists

• Engaging students with science that matters will increase students who want to study science

• Only if our students understand the context of what they are doing will they become ethical scientists