BME 301

Lecture Three

Review of Lecture Two

Developing countries Leading causes of mortality: ages

15-44 Developing world

1. HIV/AIDS2. Road Accidents3. Interpersonal violence

Developed world1. Road accidents2. Self-inflicted injuries3. Interpersonal violence

Overview of Lecture 3 What are the major health problems

worldwide? Leading causes of mortality by age

Developed world Developing world

Global health challenges

Leading Causes of Mortality Ages 45-60

Developing World1. Heart Disease - ARF2. Cerebrovascular Disease3. Tuberculosis

Developed World1. Heart Disease – IHD2. Respiratory Cancers3. Cerebrovascular Disease

Epidemiology: ARF United States

1940: mortality was 20.6/100,000 population

1982: mortality was 2.2/100,000 population Occasionally outbreaks in localized areas of

US (Salt Lake City, Pittsburgh in the 1980s) Developing countries

Still a significant health problem 15-20 million new cases a year

Risk factors Low standard of living Crowding

ARF – Clinical Course Begins with group A strep infection

“strep throat” resolves (NOT SERIOUS) Small group (3%) of propel go on to

develop rheumatic fever (CAN BE VERY SERIOUS)

Cause not fully understood Heightened immunologic reactivity to

streptococcal antigens; makes antibodies that are cross-reactive to human tissue antigens

Individual develops autoimmune reaction induced by strep infection

ARF – Clinical Course Initial attack

1-5 weeks after strep throat infection

Migratory polyarthritis and fever

One joint after another becomes painful and swollen for a few days and then gets better

Carditis – inflammation of lining of the heart, can induce heart arrythmias. Usually heals

Prognosis for first attack is usually quite good, 1% die

ARF – Clinical Course

Subsequent attacks Increased vulnerability to reactivation of

disease with subsequent strep infections Same symptoms with each attack Carditis worsens with each attack Heart valves are frequently deformed

(mitral) Hear failure develops after decades

Long Term Consequences: ARF

Healing of rheumatic valvitis can lead to valvular stenosis

Heart pumps against a closed valve with stenosis and/or regurgitation

heart pumps against an open valve with regurgitation Can lead to heart failure Can lead to death

My Uncle Gene

Treatment: ARF

Treat first strep throat infection with penicillin

Treat other manifestations symptomatically

Prophylactic long term anti-strep therapy given to anyone who has had RF

Ischemic Heart Disease: Epidemiology

United States 11 million people have coronary artery disease Causes more deaths, disability and economic

cost than any other illness Risk factors

Positive family history Diabetes Hyperlipidemia Hypertension Smoking

Ischemic Heart Disease: Pathogenesis

Atherosclerosis Causes a decrease in myocardial perfusion

Stable angina Typically a 50-60 yo man or 65-75 yo woman Heaviness, pressure, squeezing, smothering or

choking Localized to chest Lasts 1-5 minutes Radiates to left shoulder and both arms

Unstable angina Patients with angina that is:

New onset and severe and frequent Accelerating Angina at rest

Ischemic Heart Disease: Diagnosis

Usually made by history Physical exam may reveal other

disorders Lipid disorders Hypertension Diabetes

Testing EKG Stress Testing Coronary arteriography

http://www.columbiasurgery.org/divisions/cardiac/images/novartis_207B.jpg

Ischemic Heart Disease: Treatment

Medical management Nitrates

Increase myocardial oxygen supply, systemic vasodilation

Beta blockers Inhibit increases in heart rate and contractility Decrease myocardial oxygen demand

Calcium channel agonists Coronary vasodilators

CABG PTCA

CABG PTCA

Cerebrovascular Disease: Epidemiology

Third leading cause of death in the US

Most prevalent neurologic disorder Morbidity Mortality

Cerebrovascular Disease: Stroke

Abrupt onset with focal neurologic deficit Usually mini-event or warning signs

5-20% transient ischemic attacks Reversible ischemia

Some lasting 24-72 hours Completed stroke

Maximal deficit within hours Often patient awakens with completed stroke Usually preceded by TIA Progressive stroke Ischemia worsens min. to min. or hour to hour

Cerebrovascular Disease: Pathogenesis

Causes of stroke: Blood vessel supplying the brain is

blocked Thrombosis (clot in vessel) Embolism (clot breaks off and lodges in

blood vessel in brain) Vasoconstriction or spasm Venous collapse

Cerebrovascular Disease: Diagnosis

History Exam Imaging

CT Scan MRI CT/MR Angiography

Cerebrovascular Disease: Treatment

Thrombolysis Rehabilitation Experimental

Angioplasty Heparin Coumarin Aspirin

Lung Cancer: Epidemiology

United States 99,000 males die per year 78,000 females die per year Five year survival: 14% Only 15% of patients are diagnosed with

localized disease Risk factors

Smoking Actively: increases relative risk 13X Passively: increases relative risk 1.5X

Lung Cancer: Clinical Manifestations

Signs and symptoms Coughing, wheezing, difficulty breathing,

recurrent pneumonia Diagnosis:

Screening: Trials of CXR, sputum cytology, NOT SUCCESSFUL

Diagnostic: CXR CT directed biopsy Bronchoscopically directed biopsy

Staging: concept of localized vs. distant disease

Lung Cancer: Treatment

Localized Small: Possibly surgery Large: Chemo or XRT + surgery

Metastatic: Chemo + XRT

Tuberculosis: Epidemiology

Reported cases: 3.8 million new cases per year reported to

WHO 90% occur in developing world Probably underreported

Likely 9 million new cases per year 3 million deaths per year (98%) in developing

world

Tuberculosis: Pathogenesis

Bacterial infection of the lungs Drug susceptible TB is curable If untreated, results in death in 5 years

in half of all cases

Tuberculosis: Clinical Manifestations

Primary disease Results from initial infection Usually occurs in children Lesion in lower or middle lungs Heals spontaneously, may leave calicified

scar Secondary disease

Endogenous reactivation of latent infection May involve massive amounts of lung

1/3 of patients: cavity formation liquefied necrosis spills into airway pneumonia

2/3 of patients: spontaneous remission chronic, progressively debilitating course ‘consumption’

Tuberculosis: Clinical Manifestations

Symptoms Fever Night sweats Weight loss Weakness Coughs (productive with bloody sputum)

Tuberculosis: Diagnosis CXR

Shows nodules Sputum culture

Tuberculosis: Treatment

Chemotherapy with streptomycin Four new drugs available for oral

therapy NPR Story: TB and AIDS

http://www.npr.org/rundowns/segment.php?wfId=1520699

Global Health Challenges

$200 million medical research initiative Grand challenges in global health Bill and Melinda Gates Foundation Encourage scientific and technological

solutions to diseases that disproportionately affect the developing world

Announced in January 2003

What is a grand challenge? Scientific or technical innovation that:

Removes a critical barrier to solving an important health problem in developing world

High likelihood of global impact and feasibility Different than:

Simple statement of a “big problem” in global health

HIV/AIDS, malnutrition, lack of access to medical care, lack of resources

Meant to: Direct investigators to specific breakthrough

that provides solution to a significant health problem(s)

Call for Grand Challenges

Call For Ideas I (May 2003) 1048 submissions from scientists and

institutions in 75 countries Scientific Board heard proposals

(August 2003) Problem Roadblock (obstacle to progress) Challenge List of potential benefits

Goals and Grand Challenges Seven Long Range Goals 14 Grand Challenges Heavily oriented toward infectious

disease Infectious diseases account for the most

profound discrepancies between advanced and developing economies

Causes of infectious diseases are well-known Can more easily formulate technical and

scientific obstacles to progress Results reported in Science (Oct 17,

2003)

Goals and Grand Challenges Improve childhood vaccines

GC1-Create effective, single dose vaccines that can be used soon after birth

GC2-Prepare vaccines that do not require refrigeration

GC3-Develop needle-free delivery systems for vaccines

Create new vaccines GC4-Devise reliable tests in model systems to

evaluate live attenuated vaccines GC5-Solve how to design antigens for effective

protective immunity GC6-Learn which immunological responses

provide protective immunity

Goals and Grand Challenges Control insects that transmit infectious disease

GC7-Develop a genetic strategy to deplete or incapacitate a disease-transmitting insect population

GC8-Develop a chemical strategy to deplete or incapacitate a disease-transmitting insect population

Improve nutrition to promote health GC9-Create a full range of optimal bioavailable

nutrients in a single staple plant species Improve drug treatment of infectious disease

GC10-Discover drugs and delivery systems that minimize the likelihood of drug-resistant organisms

Goals and Grand Challenges Cure latent and chronic infections

GC11-Create therapies that can cure latent infections

GC12-Create immunologic methods that can cure chronic infections

Measure disease and health status accurately in economically in poor countries GC13-Develop technologies that permit

quantitative assessment of population health status

GC14-Develop technologies that allow assessment of individuals for multiple conditions or pathogens at point-of-care

Next Steps

NIH issues request for proposals to address challenges Grants of up to $20M over five years of

less Due June 2004 Awards in October 2004

Summary of Lecture Three

Leading causes of mortality: ages 45-60

Developing World1. Heart Disease - ARF2. Cerebrovascular Disease3. Tuberculosis

Developed World1. Heart Disease – IHD2. Respiratory Cancers3. Cerebrovascular Disease

Global health challenges

Assignments Due Next Time

WA2 Poll on Global Attitudes