Lecture 4: Leading Causes of Mortality, 0-5 and 14-45 Years Flashcards
What are the leading causes of mortality in the developing world for ages 14-45?
- HIV/AIDS
- Unintentional injuries
- Cardiovascular diseases
- Tuberculosis
What are the leading causes of mortality in the developed world for ages 14-45?
- Unintentional injuries
- Cardiovascular diseases
- Cancer
- Self-inflicted injuries
What is the overall burden of AIDS?
Millions of people living with HIV/AIDS, highest number in Sub-Saharan Africa, leaving many children orphaned
What is the burden of AIDS in the US?
1.2 million people living with AIDS
$15 billion to treat a year
Affects ethnic minorities and women at a higher rate
What is a retrovirus?
A virus with a protein coat with RNA and important enzymes. Genetic flow is RNA –> DNA
Explain the steps of the Pathophysiology of HIV/AIDS
- Attachment and entry
- Reverse transcription
- Genome integration
- New viral RNA produces
- Budding using host cell membrane
- Virion maturation
- Infection of other cells
What is the clinical course of HIV/AIDS?
Infection –> Clinically latent period –> AIDS
without Rx 50% patients develop AIDS, 40% develop illness associated with HIV
What diagnostics tools are used for HIV/AIDS?
HIV Diagnostic Tech
• Antibodies (ELISA, Western Blots)
• Viral RNA (PCR)
• Number of rapid tests– need to be confirmed with Western Blots
AIDS diagnosis
• HIV positive from antibody tests • CD4+ T-cells ‹ 200 cells/ul
• Opportunistic infection(s)
What do HIV/AIDS therapies target?
- Fusion inhibitors
- Reverse transcriptase inhibitors
- Integration inhibitors
- Fusion inhibitors
What type of therapy is used for HIV/AIDS?
Highly Active Antiretroviral Therapy (HAART) - which is a combination of three drugs. This therapy is used to the the rapid mutation rate of HIV which can lead to drug resistance.
What are some of the barriers with HAART?
- Compliance
- Cost (10K)
- Access
- Reservoir outside of blood (brain tissue)
How has access to ART changed?
In the past 12 months there has been a 21% increase in the access to ART.
When can Mother to Child transmission of HIV occur?
During pregnancy or delivery and while breast feeding (through milk or blood)
How does Mother to Child transmission of HIV occur?
– RNA (cell-free viral particles)
– Proviral DNA (cell-associated virus integrated in latent T- cells)
– Intracellular RNA (cell-associated virus in activated producing T-cells).
What are the interventions used for Mother to Child Transmission of HIV?
– Antiretroviral prophylaxis
– Safer delivery practices
– Safer infant-feeding practices
What is the status of the HIV vaccine?
There have been various clinical trials although non so far have been very effective. The HVTN 505 clinical trial was promising due to a similar vaccine regimen used for SIV in rhesus macaques (large number of animals and strong immune response against the virus)
What are the issues and concerns about pre-exposure prophylaxis (PrEP)?
PrEP is not right for everyone, requires strict compliance and should only be used as an additional tool to other protective measures.
What is the burden on unintentional injuries?
Millions on unintentional injuries, leading cause is road accidents
What is the burden of tuberculosis?
Mycobacterium tuberculosis infects lung tissue, kills 600,00 people ages 15-15 each year.
1/3 of world infected with TB (greatest danger for those immunocompromised)
Follows poverty and urban crowding
Explain the pathophysiology of tuberculosis.
Transmission is airborne (sneezing 40,00 droplets, 1 droplet causes infection)
Inhaled bacilli ingested by alveolar macrophages which are later lysed by the bacteria that multiple in the endosome
What is the difference between latent and active TB?
Latent TB: granulomas can control infection bacteria becomes inactive
Active TB: granulomas become necrotic, bacteria spreads, lung tissue get destroyed –> hypoxia –> death
What is chronic TB?
10% develop, TB leaves the lung and infects other organs. Symptoms include fever, night sweets, weight loss, weakness and cough (bloody sputum)
What is the connection between TB and AIDS?
– People with AIDS are up to 34x more likely to develop active TB once infected
– TB is the leading cause of death among HIV positive individuals, accounting for 13% of AIDS deaths worldwide
What diagnostic tools are used for TB?
- Purified protein derivative (PPD)
- Serum test
- Sputum
- Chest X-ray
PPD (purified protein derivative)
Bacterial proteins are injected under patient’s skin
- false positive, immunocompromised may not have reaction
Serum test
– White blood cells of infected person will release
interferon-gamma (IGRA)
- Negative for vaccinations
- Cannot distinguish latent from active
Sputum
– Manybacteriawhenstainedlosetheir dye when exposed to acid.
– Acid-fast bacilli (M. tuberculosis) have a thick lipid membrane helping it to retain dye
Chest X-ray
– Showsnodules
– Used to confirm active infection
What treatments are available for TB? And what are some of the problems?
Antibiotics, although they must be taken for a long time as the do not disperse well intracellularly.
Problems include compliance, duration, and cost.
What is Directly Observed Therapy (DOT)?
A health care worker watches and helps as the patient swallows anti-TB medicines in his/her presence
• DOT shifts responsibility for cure from patient to health care system
• DOT works well in many developing countries
What different types of drug resistance occur with TB?
- Multi-Drug Resistant (MDR) TB - resistant to some first-line drugs
- Extensive Drug Resistant (XDR) TB - resistant to first-line drugs and 3 or more second-line drugs
