Bio 418 Exam 2

What causes antibiotic resistance (generally)

use and misuse of antibiotics

What pathogen causes TB?

Mycobacterium tuberculosis

Where can Mycobacterium tuberculosis exist in the environment

Soil and water,

What are some symptoms of TB

Coughing, fever, coughing blood, weakness, weight loss, tubercles

Why can TB be hard to diagnosis based on the symptoms

They’re nonspecific and can resemble other diseases

Where does a TB infection usually start

The lungs

What did Laennec identify that helped him connect all the vague symtpoms of TB

the tubercle

What is a tubercle

clump of mycobacterium surrounded by immune cells, forming a lump

What are risk factors of TB

• repeated exposure

• being immunocompromised

• poor health/nutrition/body condition

• HIV co-infection

• residents in a long term facility

• children

T/F Someone who is healthy won’t have a severe case of TB

True

Why did it take so long for people to understand how TB was spread

People thought it was hereditary since it usually clustered in families, and if you came in contact with someone who had TB you probably wouldn’t get it

What happens to TB in a fully healthy person

bacteria enters the body, macrophages attack and destroy it

What happens to TB in a mildly healthy person

bacteria enters the body, macrophages can’t destroy it so they create a sphere around it to cut off nutrients, bacteria becomes dormant, enters a latent period

What happens to TB in an unhealthy person

Bacteria enters the body, replicates and spreads to other areas of the body

Describe the latent period of a TB infection

Immune system is holding the TB dormant, which is costing a lot of energy, if something else comes along (different infection, period of malnutrition, etc) that would redirect the immune systems energy, TB will become active again

What % of people will get TB with an active infection following exposure?

10% (aka very few)

Compare and contrast a latent vs asymptomatic TB infection

Latent

• Not dividing

• Not replicating

• Not infectious

Asymptomatic

• Shedding TB

• Transmitting TB

What makes mycobacterium so resilient

It’s protective wall

What characteristics make the TB wall so effective

The wall is hydrophobic and the peptidoglycan layer is very hardy

What did Koch’s postulates prove

That a disease was caused by a pathogen

What are each of Koch’s postulates

• Suspected pathogen is present in diseased individuals but absent from healthy ones 

• Suspected pathogen must be grown in pure culture  

• Cells from a pure culture of the suspected pathogen must cause disease in a healthy individual  

• Suspected pathogen must be isolated and shown to be the original pathogen 

Why was it hard to prove mycobacterium caused TB with Koch’s postulates?

Because it grows so slowly

What did Koch discover from TB

Tuberculin, a purified protein derivative of TB

Make sure you know the difference between tuberculin vs tubercles

Tuberculin is the protein from TB, tubercles are the bumps that a TB infection will cause

How is tuberculin used for TB diagnostics

It is placed under the skin to see if your immune system has a response

What does a response to tuberculin tell you

The immune system has seen TB before

What some reasons you can elicit a response to a tuberculin test

1. You’ve been exposed to TB

2. You’ve had the TB vaccine

3. You’ve had too many tuberculin tests

Describe how you can get false positives or false negatives with a tuberculin test

False positive

• You’ve already had the TB vaccine

• You’ve had the tuberculin test multiple times before

False negative

• Immunocompromised people won’t have a response but are susceptible to TB

• Test is too early after exposure

T/F A tuberculin test tells you if you have a latent or active infection

False, it just tells you that you’re immune system has seen TB somewhere before

Why is the tuberculin test still used if it’s not that great

It’s cheap

Besides tuberculin what other exposure test can you use to diagnose TB

Blood test, expose blood to TB antigen to see if they release interferons

What are the definitive diagnostics for TB

• Culture

• DNA detection

What are the drawbacks for definitive diagnostics for TB

Culture

• TB grows slowly

• takes months to see if it’s drug resistance

DNA detection

• Much quicker

• Doesn’t have drug resistance detection

• Expensive

What are the two ways to get a drug resistant strain of TB

1. have TB → misuse treatment → acquire drug resistance

2. Healthy individual → exposed to drug resistance TB→ get drug resistant TB

What’s happening to the amount of drug resistance strains of TB

They’re increasing

T/F There are more drugs to treat TB than resistance strains

False, it’s hard to discover new TB drugs

What are the four targets for TB drugs

• cell wall synthesis

• energy metabolism

• replication + transcription

• translation

T/F Drug resistant strains are more effective at proliferating

False, they’re worse since they had to adapt to the pressure/drugs

What is drug cocktail therapy

Combining multiple drugs that target different aspects of a pathogen

Why is it important to know if someone has drug resistant TB when treating them

If it’s drug resistant it will need a specific combo of treatment to make sure it’s actually working

How accessible is TB treatment

Not very, it’s super expensive, requires daily doses for months, hard on the body

Describe the ethical dilemma of public health vs private rights as it relates to TB

• people with drug resistant TB could infect others and sentence them to a life with TB if they’re taken out of isolation

• people with TB are still people, so isolating them from family and the rest of the world can be cruel

What happened to TB treatments during COVID (like every other pathogen)

Loss of gains

What’s the other dilemma with where TB funding should be focused

If it should be spent on preventative care or diagnosis/treatment, is it better to focus on people from getting sick or treating them when they do get sick

Describe the BCG TB vaccine generally

It’s mid

What are some issues with the TB vaccine

• it spikes the immune system, but not specifically against TB (not antigen specific)

• it’s really only used for kids in areas of high prevalence

• it’s not effective at preventing pulmonary TB

• needs a cold chain

• percutaneous injection

• doesn’t have a long lived effect

Describe the political conditions in the 70s and 80s that led to higher rates of TB

• Nixon’s war on drugs led to large number of incarcerations

• Reagan’s cuts to public health funding

What demographic was particularly affected by Reagan/Nixon’s political policies

Young people of color in urban areas

T/F If you clear TB and don’t change your lifestyle you’ll likely get TB again

True, if the conditions in which you got TB the first time are the same you’ll likely get it again

As new drugs for TB _____, new drug resistant strains of TB also ____

arise/discovered

Why do prisons have higher rates of TB

• confined space leading to frequent exposure

• poor health conditions

• poor ventilation

• lack of adequate access to health care

• late diagnosis

What are some of the ongoing struggles with TB

• Personal rights vs public health  

• Economic balance between research innovation with disease specific funding  

• Timeline tradeoff between need and safety of new drugs  

• Addressing systemic problems that lead to poor health  

• Incremental changes in TB related treatments/vaccines

What type of pathogen is malaria

a macro parasite

Where are the majority of malaria cases globally

Sub-saharan Africa (95% of cases)

T/F The localized burden for malaria is high

True, 11 countries have the highest burden of malaria

What’s the mortality demographic for malaria

Kids under 5

T/F If a kid gets malaria and survives, they’re going to live a happy health life

False, they will probably succumb to another illness since their RBCs are destroyed and they have anemia

List risk factors for malaria

• Children  

• Fetuses 

• Patients with HIV/AIDS 

• Non immune migrants, mobile populations 

• Chronic or repeated infections  

Describe the malaria life cycle generally

infected mosquito takes blood meal → infects human → red blood cells are infected → another mosquito takes blood meal and becomes infected

What is the vector for malaria

Anopheles mosquitoes

What are the two dominant species of mosquitos that transmit malaria

A. falciparum and A. vivax

Which species of anopheles is found primarily in Africa? Outside Africa?

Africa: falciparum (aFrica like Falciparum)

Everywhere else: vivax (eVerywhere else like Vivax)

Where do sporozoites go in the body?

To the liver

Where do merozoites go in the body?

red blood cells

What two paths can merozoites follow

1. Become gametes and get taken up by another mosquito to finish the lifecycle

2. Enter ring stage where they continue replicating, entering the schizont stage to release more merozoites

How long does it take for sporozoites to reach the liver and become merozoites

~1 week

How long does it take for merozoites to reach red blood cells after leaving the liver

~2 days

What does the plasmodium eat? Why is that an issue?

Hemoglobin in red blood cells, means that RBC can’t carry oxygen anymore and the host becomes anemic

Why do people get fevers and fever spikes from malaria

They coincide with the merozoites rupturing the RBC, which causes an immune response (fever)

T/F The malaria parasite has a circadian rhythm

True, that’s why night sweats from fever spikes are so common

List some general symptoms of malaria

• Chills  

• Night Sweats 

• Enlarged spleen

• Struggling liver 

• Malaise 

T/F The malaria parasite can be transmitted by any mosquito

False, it has to be an anopheles, since they so evolved together

List aspects of anopheles bionomics that should are important

• takes one blood meal per clutch of eggs

• eats at night

• breed in shallow, still, fresh, water

• live about a month

• takes two weeks to be malaria competent

Describe the malaria poverty cycle

Countries spend a huge chunk of their budget to prevent/treat malaria, that doesn’t have a huge economic return so they’re stuck in cycle of allocating money towards malaria instead of other economically promising thigns

T/F Most malaria interventions aren’t cost efficient

False, they’re very cost efficient

What are the three effective and cheap malaria interventions

1. insecticide treated bed nets

2. rapid diagnostics tests

3. treatment for malaria

Define sequestration for malaria

The tendency for infected red blood cells to cling to the endothelium of capillaries 

What did Ronald Ross do for malaria

Proved mosquitoes as the vector for malaria

Describe how the US got malaria under control in the 20th century

Bombed the environment with DDT

What does DDT do to insects

Neurologically impairs arthropods, causing death

Why was the US able to use DDT to eliminate malaria but other countries who also used DDT couldn’t

The US used DDT quickly and thoroughly which prevented resistance, other countries used it more slowly or not as throughly so resistance arose

What’s another major class of insecticides used for malaria vector control

pyrethroids

Will resistance to pyrethroids impair the effectiveness of a bed net sprayed with pyrethroids?

No, since the bed net is still stopping the mosquito

Why are bed nets so effective against anopheles

since they’re night biters, and bed nets are used at night

What is the main compound used to mitigate malaria in human hosts

quinine/chloroquine

What does quinine interfere with

trophozoite digestion of red blood cells

Chloroquine/quinine is most effective when used with ____ therapy

combination

What is the duffy negative phenotype

Mutation that doesn’t let the malaria parasite gain entry to the blood cells

Where would the duffy negative phenotype be most common

In sub-saharan Africa, in the areas with the highest burden of malaria

The duffy negative phenotype will be in areas with which anopheles mosquito

falciparum

What do the vaccines for malaria target

Proteins on the sporozoites

T/F The malaria vaccines are best used reduce the severity of malaria

True, it reduces uncomplicated malaria, child mortality, and severe disease

Describe the components of the malaria vaccines

• four doses over 5 months

• protection wanes after a few years

• needs to be kept at -70

• intramuscular injection

T/F The malaria vaccines should be used as a stand alone interventions

False, it’s best used as a layered approach

T/F once you eliminate malaria from a region there’s no chance it’ll return

False, imported cases can reintroduce malaria

In a country: if intensity of transmission is low, and frequency of importation is low, is elimination possible?

Yes

In a country: if intensity of transmission is low, and frequency of importation is high, is elimination possible?

it’s worth assessing

In a country: if intensity of transmission is high, and frequency of importation is low, is elimination possible?

it’s worth assessing

In a country: if intensity of transmission is high, and frequency of importation is high, is elimination possible?

Probably not

What genus is dengue part of

Flavivirus