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BIOE 301

BIOE 301. Lecture Three: Leading Causes of Mortality, Ages 15-44. Geoff Preidis MD/PhD candidate Baylor College of Medicine preidis@post.harvard.edu. Review of Lecture Two: Leading Causes of Mortality, Birth-Age 4. Developing world Perinatal conditions Lower respiratory infections

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BIOE 301

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  1. BIOE 301 Lecture Three: Leading Causes of Mortality, Ages 15-44 Geoff Preidis MD/PhD candidate Baylor College of Medicine preidis@post.harvard.edu

  2. Review of Lecture Two:Leading Causes of Mortality, Birth-Age 4 • Developing world • Perinatal conditions • Lower respiratory infections • Diarrheal diseases • Malaria • Developed world • Perinatal conditions • Congenital anomalies • Lower respiratory infections • Unintentional injuries

  3. 1. Perinatal Conditions • Question: What is the #1 way to prevent septicemia in a newborn in the developing world?

  4. 1. Perinatal Conditions http://www.path.org/projects/clean-delivery_kit.php

  5. 2. Lower Respiratory Infections • Question: How can a busy health worker (or a parent) quickly screen for pneumonia in a child?

  6. 2. Lower Respiratory Infections

  7. 3. Diarrheal Diseases • Question: What is the #1 way to prevent diarrheal illness in a newborn?

  8. 3. Diarrheal Diseases

  9. 4. Malaria • Questions: 1. Why has malaria been eradicated from the southern U.S.? How can these principles be applied to less developed countries?

  10. 4. Malaria • Reduced human/insect contact • Prevent mosquito breeding • Use insect repellents, mats, coils • Residual treatment of interior walls • Wear long sleeves/pants • Insecticide-treated mosquito bed nets • Treatment of those who have malaria prevent its spread! • Questions: 2. What are the challenges for implementing this technology in developing countries?

  11. 4. Malaria • What are the challenges for implementing this technology in developing countries? • Mapping areas that are difficult to access • Poor communication • Direction – Transfer of vector control efforts from malaria control authorities to local primary health care center • Financial support – decreased standard of living from wars, environmental factors, migration • Corruption, graft • Questions: 3. Where is the malaria vaccine?

  12. 4. Malaria • Where is the malaria vaccine? • Funding • Thousands of antigens presented to the human immune system -> which ones are useful targets? • Plasmodium has many life stages -> different antigens at each stage • Plasmodium has several strategies to confuse, hide, and misdirect the human immune system • Multiple malaria infections of the different species and different strains of the same species may occur in one host! http://www.cdc.gov/malaria/images/graphs/malaria_lifecycle.gif • Questions: 4. How does Chloroquine protect you when you travel?

  13. 4. Malaria http://sickle.bwh.harvard.edu

  14. Leading Causes of Mortality Ages 15-44 • Developing World • HIV/AIDS • Unintentional injuries • Cardiovascular diseases • Tuberculosis • Developed World • Unintentional injuries • Cardiovascular diseases • Cancer • Self-inflicted injuries

  15. 1. HIV/AIDS • Burden of HIV/AIDS • Pathophysiology of HIV • Clinical course of HIV/AIDS • Highly Active Antiretroviral Therapy • Historical Perspective of HIV/AIDS • Discussion: Is HAART really feasible in developing countries?

  16. Burden of HIV/AIDS • Worldwide • 39.5 million people are living with HIV/AIDS • 20 million people have been killed by the disease • 2006: • 2.9 million deaths • 4.3 million new HIV infections (400,000 more than in 2004) • 40% of new infections occurred in young people (ages 15-24) • 2/3 of those with AIDS and 3/4 of all AIDS deaths are in sub-Saharan Africa • In the past 2 years, the number of HIV-infected people rose in every region in the world Source: 2006 AIDS Epidemic Update, UNAIDS/WHO

  17. AIDS has Reduced Life Expectancy

  18. Burden of HIV/AIDS • United States • 1.2 million people have HIV/AIDS (prevalence) • 30,000-40,000 new infections per year (incidence) • Only 7 countries in the world have more people living with HIV than the U.S. • Routes of transmission: • Unsafe sex between men (44%) • Unprotected heterosexual intercourse (34%) • Non-sterile drug injection equipment (17%)

  19. Burden of HIV/AIDS in the U.S. • Racial and ethnic minorities are disproportionately affected: • 50% of AIDS diagnoses are in African-Americans (12% pop) • 20% of AIDS diagnoses are in Hispanics (14% pop) • The rate of new HIV diagnoses was 21x higher in African-American women than in white women • Women are increasingly affected: • The proportion of of women among new HIV/AIDS diagnoses have risen from 15% to 27% in 10 years • Question: Why is the total number of HIV infected people in the U.S. continuing to increase?

  20. Burden of HIV/AIDS in the U.S. • Anti-retroviral therapy has accounted for an 80% decrease in AIDS death rates in the last decade • Annual cost to treat: $15 billion

  21. Pathophysiology of HIV/AIDS HIV Structure Envelope Proteins gp120 Envelope gp41 Matrix Proteins p17 Core Proteins p14 RT RNA Integrase Protease http://bayloraids.org/curriculum/

  22. Pathophysiology of HIV/AIDS http://bayloraids.org/curriculum/

  23. Pathophysiology of HIV/AIDS http://bayloraids.org/curriculum/

  24. Clinical Course of HIV/AIDS • HIV Infection • Spread by sexual contact with infected person or sharing needles with infected person or by transmission from mother to child • Virus deposited on mucosal surface • Acute infection (flu like symptoms) • Viral dissemination • HIV-specific immune response • Replication of virus • Destruction of CD4+ lymphocytes • Rate of progression is correlated with viral load • Latent Period

  25. Clinical Course of HIV/AIDS

  26. Clinical Course of HIV/AIDS http://hivinsite.ucsf.edu/topics/aids_basics

  27. Clinical Course of HIV/AIDS http://bayloraids.org/curriculum/

  28. Clinical Course of HIV/AIDS • AIDS • Immunologic dysregulation • Opportunistic infections and cancers • Risk of infections is correlated with number of CD4+ lymphocytes • Average patient with AIDS dies in 1-3 years • Within 10 years of infection (w/o Rx): • 50% of patients develop AIDS • 40% develop illness associated with HIV • 5-10% remain asymptomatic

  29. Clinical Course of HIV/AIDS

  30. HIV/AIDS Therapy • Reverse Transcriptase Inhibitor enzymes (1987) • Enzyme is specific to HIV • Combinations of RTIs appear effective • HIV Protease Inhibitors (1995) • HIV proteases are distinct from mammalian proteases • Most significant advance in HIV therapy yet • Highly Active Antiretroviral Therapy (HAART) • Combination of three or more drugs • Fusion inhibitors (2003) • Subject of new research

  31. HIV/AIDS Therapy • HIV can rapidly mutate to quickly develop resistance to a single drug • Resistance develops much more slowly to drug combinations • Goal of HAART: • Reduce viral levels to undetectable levels • Has reduced death rate in US and Europe by 80%

  32. HIV/AIDS Therapy http://www.aids-ed.org

  33. 6 million people living with AIDS in developing countries are in need of HAART. 90% are in just 34 countries http://www.npr.org/templates/story/story.php?storyId=4724368

  34. HIV/AIDS Therapy • Prevention of Mother to Child Transmission (PMTCT) • 3 routes of transmission: • Parentally (during pregnancy) • Perinatally (during delivery) • Breast feeding (through milk) • 4 Core interventions: • HIV testing and counseling • ARV prophylaxis (ZDV, NVP) • Safer delivery practices • Safer infant-feeding practices • Reduces transmission from 30-40% to 4-6%

  35. HIV/AIDS Historical Perspective • 1981 • CDC reported unexplained PCP in 5 previously healthy, homosexual men • CDC reported Kaposi’s sarcoma in 26 previously healthy, homosexual men • 1981-1982 • Increased association with IV drug use, recipients of blood transfusions, hemophiliacs • 1983 • Virus isolated

  36. HIV/AIDS Historical Perspective • August 23, 1982 • “‘Homosexual Plague’ Strikes New Victims” • Cites evidence from the CDC • “The 4-H Club”

  37. HIV/AIDS Historical Perspective • 1985 • ELISA approved, began screening U.S. blood supply • 1987 • AZT (RTI) approved by FDA, costs $12,000 per year • 1995 • First Protease Inhibitor approved, makes HAART possible • 2003 • First Fusion Inhibitor approved • 2005 • NIH funds CHAVI (Center for HIV/AIDS Vaccine Immunology) • Today • NRTIs, NNRTIs, Protease Inhibitors, Fusion Inhibitors • Integrase Inhibitors??? Vaccine development???

  38. Discussion “For the average AIDS patient in developing countries… therapy is an inaccessible dream, and merely a diversion for developing country health ministries from more pressing concerns which threatens more cost-effective programs against HIV.... Since nothing will likely bridge this gap between poor and rich countries, only prevention and a vaccine will likely make a real difference for the poor in the battle against HIV/AIDS.” --Hirschel B, Francioli P. Progress and problems in the fight against AIDS. NEJM 1998 Mar 26;338(13):853-60.

  39. 2. Unintentional Injuries

  40. 2. Unintentional Injuries • Burden of Unintentional Injuries • Accident Physics • Slowed Driver Reaction Time • Prevention of Road Accidents

  41. Burden of Unintentional Injuries • More than 1.25 million people ages 15-44 die from unintentional injuries each year • 1 million deaths in developing countries, 1/4 million in developed countries • 40x this number are injured • Major cause of disability • Leading cause is road accidents: • 500,000 deaths per year in this age group • 90% of these deaths occur in developing countries

  42. Burden of Road Accidents in the US • Rates declining steadily • A leading cause of potential years of life lost • 2004: • 42,636 Americans killed • 2,788,000 Americans injured • Fatal accident rates >4X higher for males than for females • Motorcycles: 40X higher death rate per mile traveled • 39% of fatalities related to alcohol use

  43. Accident Physics • Newton’s 2nd Law: • F = m a • a = dv/dt • a = initial velocity/time to come to rest • In a crash: • Velocity slows to zero in a very short time • Generates large forces • How can we reduce these forces? • Reduce initial velocity of impact • Extend time that it takes passengers to come to rest

  44. Accident Physics 1. Reduce initial velocity of impact • Excessive speed contributes to: • 30% of deaths in developed countries • 50% of deaths in developing countries

  45. Slowed Driver Reaction Time • When drivers anticipate a crash, they have time to brake and reduce initial velocity • Factors which slow driver reaction time: • Alcohol use • Mobile phone use • Poor visibility • Driver inexperience

  46. Slowed Driver Reaction Time • Alcohol impaired drivers have 17X increased risk of being in fatal crash • Alcohol use increases risk more in younger drivers • 1 in 5 Americans will be involved in an alcohol-related crash at some time in their lives • TX BAC limit: • 0.08+ g/dl is illegal • Approx 3 drinks in a 140 lb individual • Significant driving impairment at just 0.04 BAC!

  47. Slowed Driver Reaction Time • Mobile phone use: • At any given daylight moment in US: • 10% of drivers are using a cell phone • Increases driver reaction time by 0.5-1.5 sections • Risk of crash is 4X higher when using a mobile phone • Same as driving with a BAC of 0.09 g/ dl • 4 states and D.C. have banned use of hand held phones while driving (NY, NJ, CT, CA) • Partial bans in AR, AZ, FL, GA, IL, ME, MA, MN, NH, NM, OH, PA, TN, VA

  48. Prevention of Road Accidents 2. Extending Time to Come to Rest: • Crumple zones • Allow passengers additional time to decelerate • Seat belts • Keep occupants in the passenger compartment • Stretch during impact • Reduce risk of death in crash by 40-60% • http://www.regentsprep.org/Regents/physics/phys01/accident/nobelt.htm • http://www.regentsprep.org/Regents/physics/phys01/accident/withbelt.htm • Air bags • When combined with seat belts, reduce risk of serious and fatal injuries by 40-65% • http://www.nhtsa.dot.gov/staticfiles/DOT/NHTSA/Communication%20&%20Consumer%20Information/Multimedia/Associated%20Files/crashdum2.ram • http://www.accidentreconstruction.com/movies/5thper.mov • Child restraints: • Reduce risk of infant death by 71% and toddler death by 54% • http://www.nhtsa.dot.gov/staticfiles/DOT/NHTSA/Communication%20&%20Consumer%20Information/Multimedia/Associated%20Files/crashdum3.ram

  49. Prevention of Road Accidents • Legislation: • Speed • Seat belts, Car seats, Air Bags • Alcohol use • Motorcycle helmets • Engineering: • Restraints • Safety standards • Education: • Seat belts, Car seats, Air Bags • Alcohol use

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