Class 8- TB and HIV

Question 1

TB’s History

Answer 1

• Tuberculosis is an ancient disease
  
  • Thought to have first appeared more than 1 million years ago in soil
• TB’s many aliases include
  
  • Consumption
  • King’s evil
  • Scorfula
  • Potts disease
• Respiratory infection by the gram positive bacteria Mycobacterium tuberculosis

Question 2

TB history (1950-1990’s)

Answer 2

• In the 1950s and 60s new Tx were discovered
  
  • Leading many in medical communities to assume TB was on the path towards eradication
  • Caused a lag in anti-mycobacterial drug research
• What happened in the early 1980s?
  
  • HIV started appearing
  • WHO declared TB a global emergency in 1993
    
    • Primary strategy relies heavily on DOTS (Directly observed therapy, short course)

Question 3

TB Epidemiology

Answer 3

• Over 2.2 billion people, roughly 1/3 of the world’s total population, are infected with M. tuberculosis
• ¨Every second someone is newly infected with TB
• 1.4 million people died in 2010 of TB

Question 4

The difference between active TB infections and Latent TB infections (LTBI)

Answer 4

• Only 5-10% of the 1/3 will ever activate.
• You are at your greatest risk of TB activation within the first 2 years after exposure
• HIV increases your risk of activation due to a compromised immune system
• Ninety-five percent of all tuberculosis cases in the world occur in developing countries.
  
  • Tuberculosis is highly prevalent in Russia, India, Southeast Asia, sub-Saharan Africa, and parts of Latin America.
    
    • Countries with a high prevalence of HIV infection have the greatest tuberculosis burden.

Question 5

TB Route of Exposure/Site of Infection

Answer 5

• Tuberculosis always begins as a latent infection
• Route of exposure is almost always inhalation
  
  • Why does this matter?
    
    • TB first infects the lungs and airway.
    • TB can spread to other organs, which is known as extrapulmonary or disseminated tuberculosis
      
      • Extrapulmonary - rarely infectious, but still deadly
• Why does the site of infection matter?
  
  • If you have a pulmonary infection then you are much more contagious because you are spreading the infection with every exhalation

Question 6

Extrapulmonary TB

Answer 6

• More commonly found in children and HIV infected individuals
• Causes fatigue and weight loss, but symptoms are usually specific to the affected organ system
• Most frequent sides include
  
  • pleura, pericardium, larynx, lymph nodes, skeleton (primarily the spine), genitourinary tract, eyes, meninges, gastrointestinal tract, adrenal glands, and skin. Can results in Systemic infection in essentially every organ
• Infections have occurred after autopsies of infected tissue

Question 7

Active TB transmission and symptoms

Answer 7

• Infected Droplet nuclei are released into the air.
  
  • Smaller the particles can penetrate your lungs deeper
    
    • However incredibly small particles are of minimal risk because your will expel them quickly
• Symptoms include
  
  • Fatigue
  • Extreme weight loss
  • Sputum producing cough
  • Fever

Question 8

TB Stages

Answer 8

Step 1: 90-95 % of primary infections remain in the LTBI phase

Step 2: Several years later, members from the LTBI group may reactivate – creating a new set of infected TB cases (step 3)

Step 3: 5 – 10 % of the primary infections may progress to active infection (Step 4) within the first two years of exposure, the rest will enlarge the pool of latent infections (Step 1)

Step 4: Active TB infections will infect an average of 10 contacts (Step 3) of which a subset will progress to Step 4, the rest will enlarge latent pool

Question 9

Tests used to diagnose Active TB

Answer 9

• Signs and symptoms overlap with a number of other pulmonary and systemic diseases
• Chest radiographs are critically important in diagnosing pulmonary TB
• Cavitation (shown in picture) commonly occurs in HIV infected
  
  • Causes holes in lungs
  • Rarely occurs with primary infection, commonly found in reactivation of infection years later
• Diagnosis involves a synthesis of both
  
  • Clinical – symptoms and x-rays
  • Laboratory findings – afb smears
• Laryngeal TB is particularly infectious
  
  • All exhalations are forced through infected tissue

Question 10

Issues with TB vaccine/surveillance

Answer 10

• Complications of the Bacille Calmette–Guérin, (BCG) vaccine, roughly 60% affective in preventing TB
  
  • BCG vaccinated individuals will often come up positive because they have antibodies.​
    
    • Influences surveillance/screening

Question 11

Risk Factors Associated with TB

Answer 11

• Time since infection
  
  • Most likely to activate within first 2 years
• Age
  
  • Men at a higher risk at young and old ages
  • Women at a higher risk in middle age
• Gender
  
  • Risk by gender changes over life time
• Genetics
• Nutrition
• Occupation
  
  • Silicosis in miners
• Smoking
• Diabetes
• HIV

Question 12

TB in Eskimos

Answer 12

Study of active TB in Alaskan Eskimos, found individuals with AB and B blood types were three times more likely to have moderate to severe tuberculosis compared to blood types O and A

Question 13

TB in Prisons

Answer 13

• Lack of access to care
• HIV co-infection
• Spread of multi drug resistance strains of TB (MDR)
• Overcrowding
  
  • Increased risk of transmission
  • Less serious prisoners are more likely to be released
    
    • Results in infected prisoners bringing TB home

Question 14

WHO DOTS program

Answer 14

Key strategy to reduce morbidity, mortality, and drug resistance

Downside- expensive and relies on countries ability to detect cases

Question 15

TB Treatment

Answer 15

• TB drugs can be very hard on the liver
  
  • All of the drugs create liver toxicity
• In the study we conducted we found elderly with LTBI were more likely to have a hepatic event than elderly with Active TB, why do you think that’s the case?
  
  • Don’t have someone checking on them every day like with DOTS

Question 16

Origin of HIV

Answer 16

• Human Immunodeficiency Virus (HIV) was thought to have entered the human population within the past 100 years
  
  • Simian immunodeficiency virus (SIV) jumped host from Cameroon chimps sometime before 1931 through the ‘bushmeat’ trade. (the most common scientific theory*)
• Why did we not see a HIV pandemic until the early 1980s?
  
  • Central African Isolation

Question 17

What Role did roads play in the spread of HIV?

Answer 17

• Transporting disease across boarders
  
  • Introducing the HIV virus to naïve populations
• Risks associated with Trucking industry in Africa in the 1960s
  
  • Prostitution at truck stops drastically influenced the spread of disease

Question 18

HIV from Africa to the America

Answer 18

• HIV-1 was first introduced into Haiti from West Africa
  
  • Haiti has strong cultural ties to West Africa
• Spread from Haiti to the DR
  
  • Active sex destination for MSM populations in the 1960s and 1970s
• Gaetan Dugas
  
  • Canadian flight attendant who was falsely dubbed as patient-zero for HIV introduction to North America

Question 19

Early AIDS mortality

Answer 19

• Prior to the HAART era median time to AIDS in the US was 9.5 years – 11 years
  
  • Survival as 10.5 years to 11.8 years post infection
    
    • Only lived 1 - 2.3 years after HIV converted to AIDS
  • In Thailand median survival was 7.4-8.4 years post infection
    
    • Much higher prevalence of infectious diseases that can act as comorbidity

Question 20

Difference between HIV and AIDS?

Answer 20

HIV transitions to AIDS when CD4 cell count gets below 200/µl (microliter)

Question 21

Viral “set point”

Answer 21

The higher the level during the latent period, the sooner you will die. A lower viral “set point” during latency means you will live longer before infection becomes fatal.

Question 22

HIV Epi terminology

Answer 22

Generalized – when the HIV prevalence among the general population is greater than 1%

Concentrated – when the HIV prevalence is under 1% in the general population but greater than 5% in higher risk subpopulations

Nascent (just coming into existence and beginning to display signs of future potential) – in countries with some HIV infections but with prevalence less than 5% in high risk populations

Question 23

Epidemiology of HIV/AIDS

Answer 23

• People living with HIV/AIDS
  
  • 34-40 million
• Mortality 1.7 million die every year
  
  • 1.2 million of the deaths occur in Sub-Saharan Africa
    
    • Sub-Saharan Africa accounts for 68% of people living with HIV world wide.
    • Africa accounts for 70% of new infections

Question 24

HIV/AIDS Definitions and Modes of Transmission

Answer 24

• HIV- Human Immunodeficiency Virus
• AIDS-Acquired Immunodeficiency Syndrome
• Acquired through the transfer of blood, semen, vaginal fluid, pre-ejaculate, and breast milk.
• Modes of Transmission:
  
  • Sexual intercourse (75-80% of cases)
  • Intravenous drug use (15-25% of cases)
  • The following account for all other cases of HIV
    
    • Blood transfusions
    • Vertical transmission – Mother to child
    • Accidental needle pricks (very low risk)

Question 25

Heroin’s impact on HIV

Answer 25

* Lower rates of HIV observed in West coast IDUs than east coast. * Type of heroin thought to play major role * West Coast – black tar heroin has to be cooked at a higher temperature and clogs up needles more often, forcing syringes to be cleaned out between use

Question 26

HIV/AIDS Clinical manifestation

Answer 26

* The virus directly infects and kills white blood cells -CD4+T, macrophages, and dendritic cells * Concerns of Co-infections and Co-morbidities * TB, Pneumonia, KS, HIV wasting syndrome, HPV * Difference between HIV and AIDS- its all in how we label the disease * Classification is based on CD4+T cell counts * lower than 200 cells per microliter = AIDS * Or the occurrence of specific diseases associated with HIV infection * How you are classified as either HIV or AIDS can influence insurance and cost… * If you are ever below 200/µl then you are always considered to have AIDS; even if you go above 200/µl in the future.

Question 27

Progression of Opportunistic infections

Answer 27

* Opportunistic infections (TB, thrush, PCP pneumonia) are normally controlled by the immune system * At the dentist, they check you for Thrush and Oral Hairy Leukoplakia

Question 28

HIV and vision

Answer 28

* 70% of advanced AIDs patients experience eye disorders * Cytomegalovirus (CMV) occurs in 20 to 30 % of patients with AIDS * CMV is a concern in newborns and HIV/AIDS patients * 5/1000 live births are infected, with 5 % of those births developing multiple handicaps. * CMV is usually easily controlled by the immune system, however in HIV/AIDS patients it can cause vision problems * Floating spots or “spider-webs” * flashing lights * blind spots or blurred vision * detached retina

Question 29

HIV - 1 recombinants

Answer 29

* Three groups M, N, and O (HIV – 2 not included) * M is almost everyone * N has only had 10 cases * O stands for “outliers” * Group M strains are responsible for all HIV-1 * 11 genetic subtypes A-K * Co-infection with multiple subtypes can be common

Question 30

Who's at risk for HIV and available treatments

Answer 30

* Who’s at risk for HIV? * Intravenous drug users (High prevalence in at risk group in Eastern Europe) * Sexually active adults * Children born to HIV infected mothers * Health care personal (accidental needle sticks) * Treatment * PrEP- Pre-exposure Prophylaxis (preventative) * ART- Anti-retroviral therapy * AZT and others needed to be taken multiple times a day at different time intervals * Some must be taken with food, some without * Many of the drugs are to address the adverse effects associated with Anti-retroviral medications. * Highly Active ART (HAART)

Question 31

Downside to HAART

Answer 31

* HIV infected patients appear to have elevated risks of many chronic diseases * Diabetes * CVD * Cancer * Neurologic decline * Smoking, drug use, and specific Opportunistic infections increases risks

Question 32

HIV prevention

Answer 32

* PEP and PREP * Post Exposure Prophylaxis * Pre-exposure Prophylaxis * More emphasis placed on viral suppression * The ABCs * Abstinence * Be monogamous * Condom use * Male medical circumcision * TasP (Treatment as Prevention) * Harm reduction programs * Needle exchange * Microbicides and HIV prevention * Prevention of Mother to Child transmission (MTCT) * Structural approach to treating underlying factors of HIV * poverty, gender inequality and power dynamics, policy changes * Early detection and Tx of infected individuals

Question 33

Mines, Migration, and HIV/AIDS in Southern Africa

Answer 33

* Swaziland and Lesotho have the highest HIV prevalence in the world. * Many men were migrant workers in the South African mines * Months away from home = active sex industry. * You are 15 % more likely to be HIV positive, if you are a Miner in South Africa * Women married to miners are 8% more likely to become infected * The association is heavily linked to the combination of migration and mining * There is no significant association between mining and HIV in Zimbabwe, where the majority of workers are local.

Question 34

Why its called tuberculosis?

Answer 34

* Granulomas form in the infected tissue and undergo necrosis in the center, hardening into tubercule shapes * It changes the pH of the environment killing the mycobacteria. * The scarring of the lungs is a result of our own immune system fighting the disease * You tend to see less scarring in HIV patients due to a weaker immune response.

Question 35

Test to check TB exposure

Answer 35

* A Tuberculine skin test uses Purified Protein Derivatives (PPD) to check TB exposure * Over 100 different proteins isolated from mycobacterium strains * If you’ve been infected by any forms of mycobacterium, antibodies developed from that exposure will attack the purified proteins.