Lecture 1: Infectious disease pt 1 Flashcards
1) What causes communicable disease?
2) When was it the leading cause of death and disability?
1) Bacteria, viruses, parasites.
2) Until antibiotics and vaccines
What is R0/ R naught?
Average number of infections produced by an infected individual
Differentiate between incubation period and latent period
1) Incubation = time interval from infection to symptom onset
2) Latent = time interval from infection to becoming infectious
What are the R0s for the following communicable diseases?: measles, mumps, HIV, SARS, ebola, & hep C
1) Measles: 18
2) Mumps: 10
3) HIV: 4
4) SARS: 4
5) Ebola: 2
6) Hep C: 2
List 2 things that can impact R0
1) Route of transmission
2) Period of communicability
1) Who designed criteria to establish a relationship between a microbe and a disease?
2) What two diseases did this person study?
1) Robert Hermann Koch
2) Cholera and TB
List the 4 criteria of Koch’s postulates
1) The organism must be present in every case of the disease
2) The organism must be isolated and grown in the laboratory
3) When injected with the laboratory-grown culture, susceptible test animals must develop the disease
4) The organism must be isolated from the newly infected animals and the process repeated
What are the 3 modifies Koch’s postulates criteria?
1) Association
2) Isolation
3) Transmission
1) Define endemic
2) Define epidemic
3) Define pandemic
1) Transmissions occur, but number of cases remains constant
2) Number of cases increases
3) When epidemics occur on several continents (a global epidemic)
Describe the two steps of case finding for diseases
1) Confidential interviewing
-can be challenging due to social stigmas
2) Epidemiological Treatment: treatment of contacts
1) Where should certain positive disease cases be reported?
2) Whose responsibility is it to report?
3) Who has a list of reportable diseases?
1) Local health department
2) Provider responsibility to report (not the patient)
3) CDC
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slide 19
What did Koch say abt the burden of TB?
If the importance of a disease for mankind is measured by the number of fatalities it causes, then tuberculosis must be considered much more important than those most feared infectious diseases, plague, cholera and the like. One in seven of all human beings die from tuberculosis. If one only considers the productive middle-age groups, tuberculosis carries away one-third, and often more.
1) From the 1700s-1900s how many deaths occurred due to TB?
2) Koch demonstrated __________ are a contributory cause of disease, but other factors are needed
3) What are these other factors? (3)
1) 1 billion
2) bacilli
3) Reduced immunity, poor nutrition, genetic factors
List 3 major victories in public health that contributed towards fighting TB
1) Isolation in sanitariums
2) Vaccine development
3) Screening with PPD skin tests and chest xrays
1) What important discovery regarding TB occurred in the 1940s?
2) What two things advanced the fight against TB in the 50s?
3) What occurred regarding TB in the 60s?
1) Streptomycin
2) Isoniazid (INH) and Para-aminosalicyclic acid
3) Success prompted closures of sanitoriums and cut backs on screening; “Eradication”
1) When did active TB resurface and why?
2) What era did DOT (directly observed therapy) and adherence to effective treatment occur?
3) How does TB spread? [method of transmission]
1) 1980s; AIDS epidemic & drug resistance increased
2) 1990s
3) Aerosolized droplets
What is the national goal for TB treatment completion rates?
95%
1) What is the number one cause of death from infectious disease in the world?
2) What is the the number one killer of people with HIV?
1) TB
2) TB
Describe the 3 steps to contracting TB
1) Person w active pulmonary TB coughs on you.
2) You breathe droplets containing mycobacterium tuberculosis into lungs.
3) TB bacilli travel to alveoli & proliferate.
1) For infection to occur, about ______ TB bacilli need to reach the lungs
2) Is this high or low relative to other diseases?
3) Once in the lungs, the bacilli are _______________ by __________________ in the lung
1) 10
2) Very low
3) phagocytosed; macrophages
List the infectious doses for:
1) E. coli
2) Vibrio cholera
3) Campylobacter
4) TB
5) Entamoeba coli
1) 10^6 – 10^8
2) 10^4 – 10^6
3) 500
4) 10-50
5) 10
6) 1
What happens after TB bacilli are phagocytosed by macrophages in the lungs?
Instead of being killed, the TB bacilli proliferate in the macrophages for 2-12 weeks until there are thousands of them
1) What happens after TB bacilli proliferate in macrophages until there are thousands?
2) Does this involve antibodies and B cells?
1) Enough antigen has been produced to cause a cellular immune response
2) No; this is different from the humoral response involving antibodies and B cells
What cells are involved in a cellular immune reposne?
CD4 and CD8 T cells attempt to contain the infection and/or kill infected cells
After a cellular immune response is initiated, one of two things can happen; what are they?
1) Latent TB: Infection is contained in Granulomas
OR
2) Active TB: Spreads
Define the 3 types of TB infections
1) Primary: asymptomatic or symptomatic
2) Latent: inactive, non-communicable
3) Reactivation: prior containment
____% of the time, primary TB infection results in latent infection
90%
1) The primary mechanism the immune system has for controlling TB is what?
2) Why?
3) When is a person infected with TB considered to be healthy for all intents and purposes?
1) Walling it off in granulomas
2) Primarily bc of a healthy CD4 and CD8 T-cell response
3) As long the immune system keeps the TB inside granulomas
1) Define granuloma
2) What is a caseating granuloma?
3) Define caseum
1) A rim of healthy macrophages and T cells that act as a wall
2) A granuloma w areas of caseation (areas of necrosis w complete loss of tissue architecture)
3) Soft, dead cell mush
The granuloma is a rim of healthy
macrophages and T cells that are walling off what 4 things?
1) Infected macrophages
2) Dead and dying infected cells
3) Free bacteria
4) Matrix
Why do we care about latent infection? (2 reasons)
1) 5% reactivate in the first 1.5 years after infection
2) 5% reactivate over the remaining lifetime
List the 3 most critical TB symptoms
1) Coughing up blood
2) Unintended weight loss
3) Night sweats
If a pt feels fine, under what circumstances should they be tested for TB?
1) Are they from somewhere where TB is endemic?
2) Is risk of reactivation high?
- Do they have have HIV?
- Otherwise (or about to be) immunosuppressed?
(e.g. on chemotherapy, on TNF inhibitors,
getting HD)
Describe how a Tuberculin skin test (TST) is done
By injecting 0.1 ml of tuberculin purified protein derivative (PPD) intradermally into the inner surface of the forearm.
After the administration of a TB test, 48-72 hours later, the diameter of what is measured?
Induration (NOT erythema)
How do you read a TB test?
By diameter of induration:
1) 5 mm is positive for: HIV+, organ transplant, other immunosuppressed people
2) 10 mm is positive for: recent immigrants from areas with high TB incidence, health care workers, the homeless, and people with hematologic or head/neck malignancies, renal failure, or diabetes
3) 15 mm is positive for: people with no known risk factors
What are the two types of Interferon gamma release assay (IGRA)? What is measured in both?
Quantiferon and T spot; interferon gamma.
Explain how Quantiferon and T spot TB tests work
T cells in a patient’s blood sample are stimulated with tuberculosis-specific peptides and the activity of the T cells is approximated by measuring interferon gamma.
True or false: T cells only bind to antigens presented by antigen presenting cells
True
Why does nothing happen inside the test tube of an IGRA test for someone without latent TB?
There won’t be any effector T cells in the blood specific for TB (bc this person hasn’t been exposed to it before)
1) What is produced inside the test tube of an IGRA test for someone without latent TB?
2) Why?
1) Interferon gamma
2) Effector T cell re-encounters the TB antigen
For TST TB testing:
1) Describe how it’s performed
2) How many visits does it require?
3) When are results available?
4) Can it cause a boosted reaction?
5) Is the interpretation of this test subjective?
6) Can BCG vaccination cause a false positive?
7) Does a negative reaction to the test exclude the diagnosis of LTBI or TB disease?
TST:
1) Tuberculin is injected under the skin and produces a delayed-type hypersensitivity reaction if the person has been infected withM. tuberculosis
2) Requires two or more patient visits to conduct the test
3) Results are available 48 to 72 hours later
4) Yes, can cause
5) Yes; reading by HCW may be subjective
6) BCG vaccination can cause false-positive result
7) No, does not exclude
For IGRA TB testing:
1) Describe how it’s performed
2) How many visits does it require?
3) When are results available?
4) Can it cause a boosted reaction?
5) Is the interpretation of this test subjective?
6) Can BCG vaccination cause a false positive? What about infection with most nontuberculous mycobacteria?
7) Does a negative reaction to the test exclude the diagnosis of LTBI or TB disease?
1) Blood is drawn for testing; test measures the immune response to the TB bacteria in whole blood
2) One
3) 24 hours depending on lab batching + transport time
4) Does not cause boosted rxn
5) No, not affected by perception
6) BCG vaccination doesnotcause
false-positive result, neither does infection with most nontuberculous mycobacteria
7) No, does not exclude
If a pt has has hemoptysis, night sweats, and weight loss, how would you test them for TB?
1) Sputum:
-AFB stain
-Culture for M. Tb
-Nucleic acid amplication (PCR) for M. Tb
2) Imaging:
-Chest X ray or CT
How would you perform an AFB (Acid fast bacilli stain) for TB?
Typically collect 3 smears, 8 hours apart.
-Ideally one smear is first thing in the morning.
Xray Findings for TB may include what? (4 things)
1) Parenchymal infiltrates
2) Hilar Adenopathy
3) Cavitation
4) Pleural effusion
What may TB progress to?
Miliary TB
Why can cavitations and hemoptysis occur with TB?
1) Cell necrosis leads to destruction of lung tissue and cavitations
2) This lung destruction is what leads to hemoptysis
How would you Dx extrapulmonary TB?
The principles of diagnosis are the same:
Get tissue (biopsy); get CSF, tissue, fluid, etc; and send AFB smear(s), culture, and PCR on the sample
Give 3 examples of extrapulmonary TB locations
1) Pott’s disease (spine)
2) Ileum
3) Miliary TB in spleen
You should always rule out active TB (via CXR) before starting treatment for latent TB. Why?
If you give a latent TB regimen (monotherapy) to someone with active TB, you risk development of drug resistant TB
42 year old man, recently emigrated from Vietnam and found to have a positive screening TST. He denies weight loss, night sweats, cough/hemoptysis, or any other symptoms of illness. Your exam and a chest X ray are normal. He does mention that prior to moving to the US, he was living with his grandfather who had active, pulmonary TB. He is otherwise healthy.
What do you do? What is your Dx and plan?
Dx: Latent TB
-Get CXR to rule out active TB before starting treatment for latent TB. If you give a latent TB regimen (monotherapy) to someone with active TB, you risk development of drug resistant TB
OPTIONS:
1. Isoniazid (INH) x 9 months
2. Rifampin x 4 months
3. Isoniazid and rifapentin x 3 months
1) For LTBI (latent TB) therapy, how often should you see the pt?
2) What questions should you ask the pt?
3) What labs should you monitor?
1) Monthly follow up
2) Nausea, anorexia, icterus, rash, paresthesias
3) ALT, AST, Total Bilirubin (INH and rifampin can cause hepatitis)
Under what conditions should you stop LTBI therapy?
1) Asymptomatic >5 fold increase above upper-limit of normal (ULN) AST
2) Symptomatic >3 fold increase above ULN AST
3) Baseline abnormal >3 fold increase above ULN AST
What are the 4 medications of active TB treatment? (there’s a mnemonic to remember these)
R - Rifampin
I - Isoniazid
P - Pyrazinamide
E - Ethambutol
1) How long is the intensive phase of active TB treatment? Which medication can be stopped early if drug susceptibilities return before 2 months confirming pan-sensitivity?
2) How long is the continuation phase? What medications are used?
1) 2 months; ethambutol
2) 4 months of rifampin isoniazide (RI) alone
What are the exceptions to the general active TB treatment plan?
1) Extend continuation phase (7 months) in patients with cavitary pulmonary TB and ongoing M. Tb in sputum samples at 2 months
2) In extrapulmonary TB, continuation phase is 9-12 months
Describe TB drug action:
1) Which drug is the most early bactericidal?
2) Which is the best for long term sterilizing (bacilli w short metabolism periods)?
3) Which is best for resistance prevention? (actively growing bacilli)
1) INH (> EMB > RIF > PZA)
2) RIF (> PZA > INH > EMB)
3) INH (> RIF > EMB > PZA)
Describe TB treatment in patients with HIV
Treatment regimen is the same but a few important things to consider:
1. There are often drug-drug interactions between TB medications and antiretrovirals – check before prescribing
2. Duration of treatment is longer for patients with HIV not on HAART(Highly Active Retroviral Treatment) (the continuation phase is extended to 7 months)
3. Remember that TB can look different in HIV: extrapulmonary and CNS TB are much more common and symptoms can progress more quickly
1) What did Edward Jenner do in 1796?
2) What characteristics allowed smallpox to be eradicated?
1) Create the first smallpox vaccine (leading to smallpox eradication)
2)
-No animal reservoir
-Short persistence in environment
-Absence of a long-term carrier state
-Long-term immunity
-Vaccination also establishes long-term immunity
-Herd Immunity
-Easily identified
-Post exposure vaccination
1) HIV infection in humans came from a type of ______________ in Central Africa.
2) Studies show that HIV may have jumped from this species to humans as far back as the late ___________
1) chimpanzee
2) 1800s
Give the timeline of HIV in 1981
1) June 5: First official reporting of what will be known as AIDS.
-A report described Pneumocystis pneumonia in previously healthy, gay men in LA.Link to the first official report of what will be known as the AIDS epidemic
2) June: CDC forms Task Force on Kaposi’s Sarcoma and Opportunistic Infections.
-About 30 Epidemic Intelligence Service officers and staff participated.
3) July 3: Report of Kaposi’s Sarcoma and Pneumocystis pneumonia in 26 homosexual men in New York and California
Give the timeline of HIV in 1982
1) September 24: CDC uses the term “AIDS” for the first time and releases the first case definition for AIDS.
2) December 10: Report of AIDS likely from blood transfusion.
-CDC reports a case of AIDS in an infant who received a blood transfusion.
3) December 17: Reports of AIDS hinting of perinatal transmission.
-MMWR reports 22 cases of unexplained immunodeficiency and opportunistic infections in infants.
1) When was needle-sharing identified as transmission method of HIV?
2) When did project SIDA begin in Africa? What is this project?
1) July 13 1984: CDC states that avoiding injection drug use and reducing needle-sharing “should also be effective in preventing transmissions of the virus.”
2)1984; CDC, along with colleagues from Zaire and Belgium, establishes Project SIDA, which would become the largest HIV/AIDS research project in Africa in the 1980s.
October 22 1986, Surgeon General, C. Everett Koop, issued the Surgeon General’s Report on AIDS.
What did this report make clear?
That HIV cannot be spread casually and calls for a nationwide education campaign (including early sex education in schools), increased use of condoms, and voluntary HIV testing.
Describe the timeline of HIV in 1987
1) August 14: CDC issues Perspectives in Disease Prevention and Health Promotion: Public Health Service Guidelines for Counseling and Antibody Testing to Prevent HIV Infections and AIDS.
2) CDC launches first AIDS-related public service announcement, “America Responds to AIDS.”
3) CDC expands work in Africa.
-CDC begins working in Côte d’Ivoire, establishing a field station in Abidjan and launching the Retrovirus Côte d’Ivoire (CDC Retro-CI)
The brochure “Understanding AIDS” was sent to every household in the US—107 million copies in all. When did this occur?
1988
Describe the timeline of HIV in 1990-94
1) HIV transmission from healthcare worker reported. CDC issues recommendations for healthcare workers with HIV and for organ transplantation.
2) AIDS deaths increase.
3) CDC expands prevention efforts into businesses, labor, and community organizations.
Describe HIV in 1995-1999
1) Guidelines issued to prevent opportunistic infections (OIs) and for the use of antiretroviral therapy.
2) Highly active antiretroviral therapy (HAART) introduced; AIDS deaths decline.
3) US racial/ethnic disparities are notable.
4) Africa efforts expand.
Describe HIV in 2000-2004
Global AIDS programs and funding increase as economic concerns over pandemic increase; US emphasizes HIV prevention with people living with HIV.
Describe HIV in 2005-2009
CDC issues recommendations on HIV prevention and testing, releases new incidence estimates, launches new HIV prevention campaigns for general public and healthcare providers. Global programs grow.
Describe HIV in 2010-2014
1) Non-US citizens living with HIV can enter US, CDC announced High Impact Prevention and focuses funding where the US HIV burden is greatest.
2) Preexposure prophylaxis (PrEP) shown to prevent HIV transmission, as does reducing viral load through treatment.
3) Racial/ethnic disparities persist
Describe HIV in 2015-present
Co-infections addressed, more data about transmission, HIV diagnoses data show progress and challenges, PrEP holds promise
How is HIV transmitted?
1) Blood transfusions/contaminated needles
2) Intercourse (unprotected anal intercourse most common)
List 5 common Public Health Interventions to prevent HIV
1) Proper use of latex condoms
2) Abstinence programs
3) Aggressive treatment at early stages
4) Safe practices for pregnancy and breast-feeding
5) Safe needle practices
1) Are most patients with HIV symptomatic or asymptomatic?
2) List the symptoms of HIV
1) Asymptomatic
2) Sore throat, fever, swollen lymph nodes, rash, muscle aches, fatigue, chills, mouth ulcers, night sweats
Describe each of the 3 stages of an HIV infection
1) Stage 1: Acute HIV Infection
-Very contagious
-Flu-like symptoms
2) Stage 2: Chronic HIV Infection
-Asymptomatic
-HIV still replicates
**If treatment is started, they may stay in this stage and viral load is reduced
3) Stage 3: Acquired Immunodeficiency Syndrome (AIDS)
-Severe stage
-High viral load possible
-Opportunistic infections
1) What 3 types of cells does HIV infect?
2) What type of immunity is lost?
3) How long can it remain dormant?
1) Helper T cells, macrophages and dendritic cells
-CD4+ T cells
2) Cell-mediated immunity
3) 10 years from primary infection
What is the first step of HIV diagnosis? What should you do if negative? What about if positive?
Step 1: HIV Antibody test
-If negative, retest in 2-4 weeks
-If Positive: Go to Step 2
What is the second step of HIV diagnosis? What should you do if negative? What about if positive?
Step 2: HIV Discriminatory Assay (Multispot)
-If Negative, go to Step 3
-If positive: Start Combination Antiretroviral Therapy
What is the third step of HIV diagnosis? What should you do if negative? What about if positive?
Step 3: NRNA Nucleic Acid Amplification Test
If Negative, Retest in 2-4 weeks
If positive, Start Combination Antiretroviral Therapy.
What is the sensitivity and specificity of the NRNA Nucleic Acid Amplification Test for HIV?
100% Sensitive; 97.4% Specific
List the 2 most important related labs for HIV patients
CD4 Cell Count
Viral Load
List 10 other labs you should get from an HIV patient
1) CD4 Cell Count
2) Viral Load
3) Tuberculin Skin Test
4) Toxoplasmosis Titer
5) Cytomegalovirus Serology
6) Pap Smears
7) High rates of cervical cancer
8) Syphilis
9) Hepatitis
10) Chlamydia/Gonorrhea
1) What should you obtain before starting HIV therapy?
2) What increase compliance with HIV therapy?
1) Genotypic Antiretroviral Resistance Testing (GART)
2) Combination pills
Regarding HIV treatment:
1) Adherence of 95% to drug regimen: ___% success rate
2) Adherence of 90-95% to drug regimen: ___% success rate
3) Adherence of 80-90% to drug regimen: ___% success rate
4) Adherence of 70-80% to drug regimen: ___% success rate
5) Adherence of <70% to drug regimen: ___% success rate
1) 81%
2) 64%
3) 50%
4) 24%
5) 6%
List Nucleotide-Nucleoside Reverse Transcriptase Inhibitors (nRTI) used in HIV treatment
Many end in -ine (don’t need to know specifics):
1) Abacavir
2) Didanosine
3) Emtricitabine
4) Lamivudine
5) Stavudine
6) Zalcitabine
7) Zidovudine
8) Tenofovir
List Nonnucleoside Reverse Transcriptase Inhibitor (NNRTI) used in HIV treatment
Many also end in -ine
1) Delavirdine
2) Efavirenz
3) Etravirine
4) Nevirapine
5) Rilpivirine
List Protease Inhibitors used in HIV treatment
All end in -avir:
-Amprenavir
-Atazanavir
-Darunavir
-Fosamprenavir
-Indinavir
-Lopinavir
-Nelfinavir
-Ritonavir
-Saquinavir
-Saquinavir Mesylate
-Tiprinavir
1) What Entry Inhibitor is used in HIV treatment?
2) What fusion inhibitor is used?
1) Maraviroc
2) Enfuvirtide
List 4 Integrase Strand Transfer Inhibitors (InSTI) used in HIV treatment
1) Raltegravir
2) Elvitegravir
3) Dolutegravir
4) Bictegravir
List 6 categories of drugs used in HIV treatment
1) Nucleotide-Nucleoside Reverse Transcriptase Inhibitors (nRTI)
2) Nonnucleoside Reverse Transcriptase Inhibitor (NNRTI)
3) Protease Inhibitor
4) Entry inhibitor
5) Fusion inhibitor
6) Integrase Strand Transfer Inhibitor (InSTI)
What is the most common combo of HIV medications used?
Triple Therapy: Bictegravir AND Tenofovir AND Emtricitabine
When does HIV become Acquired Immunodeficiency Syndrome (AIDS)?
If:
1) CD 4 cell count drops below 200 cells per mL of blood
OR
2) Develop Opportunistic Infections
Give 5 examples of opportunistic infections that can be found in pts with AIDS
Candidiasis
Coccidioidomycosis
Cryptococcosis
Histoplasmosis
Karposi Sarcoma
Give 2 examples of communicable diseases the WHO has impacted the transmission of
Malaria and TB
