Animal models Flashcards
(109 cards)
1
Q
What types of animals are covered under EU Directive 2010/63 for animal experiments?
A
Live vertebrate animals, including independently feeding larvae and fetal forms in the last third of gestation.
2
Q
When is an experiment considered an “Animal Experiment” under EU Directive 2010/63? (3)
A
When it involves any invasive or non-invasive use of a live vertebrate animal for scientific or educational purposes, causing pain, discomfort, or distress.
3
Q
What are some examples of animal experiments under EU Directive 2010/63? (4)
A
Drug administration, surgical procedures, disease induction, and behavioral studies causing discomfort.
4
Q
What key information about objectives should be provided to the Ethical Committee (DEC) for an animal experiment? (3)
A
A clear primary objective, including long-term goals and specific research questions for the next five years.
5
Q
What must be included in the description of procedures for an ethical review? (6)
A
Type of procedure
Frequency and duration
Recovery and aftercare
Impact severity classification
Control groups and experimental design
6
Q
How should the use of animals be justified for an ethical review?
A
By explaining why non-animal alternatives cannot be used and why animal models are necessary.
7
Q
What is the role of the Three R’s in an ethical review?
A
Replacement: Why non-animal methods can’t be used.
Reduction: How animal numbers will be minimized.
Refinement: How animal suffering will be reduced.
8
Q
What outcome parameters should be included for the Ethical Committee? (5)
A
Primary outcome: The main result or effect that the experiment aims to measure, such as tumor size, behavioral changes, or survival rate.
Secondary outcomes: Additional effects that will be measured, like biochemical markers, side effects, or histological analysis.
Causal link: Demonstration of a cause-effect relationship between the intervention (e.g., drug administration, surgery) and the observed outcomes.
Correlation with human relevance: Explanation of how the outcomes observed in the animal model relate to the expected outcomes in humans (if applicable).
Time frame for outcomes: When and how often measurements will be taken to observe the effects, ensuring that outcomes are measurable and timed appropriately for valid data.een variables.
9
Q
What are some pros of using experimental animals in research? (4)
A
Controlled variables - genetics, environment, previous exposure. Allows for precise manipulation of variables
Animal models: modification of animals to mimic human disease
Invasive studies or long-term studies - ie. surgeries or drug testing, not as easy in humans
Ethical feasibility - some experiments may not be ethical to perform on humans (i.e. toxicity or severe disease models)
10
Q
What are some cons of using experimental animals in research? (4)
A
Species differences - can limit relevance to humans
Ethical concerns - Cannot consent, may suffer pain and discomfort
High costs and time consumption - require specialized facilities, care, regulatory compliance
Publication bias - negative results are often unreported, leading to repeats and unnecessary use of animals
11
Q
What are pros of using human beings in research? (4)
A
-Direct relevance to human physiology and health
-Informed consent - voluntary participation and ethical transparency
-No species differences
-Diverse data including genetic, environmental and lifestyle background (may be relevant to human disease)
12
Q
What are cons of using human beings in experiments? (4)
A
Ethical limitations: limitations in types of invasive or harmful procedures, restricts research scope
High variability: due to genetic, environmental and lifestyle variability - harder to control for confounding factors
Limited long-term of invasive studies
Higher risks that are hard to manage due to requirement of strict oversight
13
Q
Why are human studies often more variable than animal studies?
A
Humans have high genetic and environmental variability, making it harder to control for confounding factors.
14
Q
What is the definition of an animal model in research?
A
A living organism used to induce a pathological process for the purpose of investigating human biology and diseases, often mimicking human responses for research.
15
Q
What are some of the main uses of animal models in research? (4)
A
- Characterizing pathogens
- Studying mechanisms of diseases
- Testing intervention strategies
- Understanding biological processes
16
Q
What makes animal models controversial yet valuable?
A
Animal models are controversial due to ethical concerns about animal use in research, but they remain highly valuable if experiments are conducted with precision, following ethical guidelines and regulations.
17
Q
What are the three (3) key responsibilities a researcher must have when conducting animal experiments?
A
- Knowledge of regulations
- Practical skills to conduct experiments
- Awareness of animal welfare and ethical considerations
18
Q
What is the process of applying for permission to conduct animal experiments? (4)
A
- Writing a detailed proposal for a Central Commission for Animal Experiments (CCD) license.
- Receiving feedback from the Animal Welfare Body (ABB).
- Submitting the proposal to a national project evaluation body (DEC).
- Revising and resubmitting until the experiment is approved.
19
Q
What are the 3 R’s that researchers should consider when designing an animal experiment?
A
Replacement: Can the experiment be conducted without using animals?
Reduction: Can fewer animals be used while still obtaining valid results?
Refinement: Can procedures be refined to minimize discomfort and enhance animal welfare?
20
Q
What are the ARRIVE guidelines?
A
A set of standards that detail how animal experiments should be designed and reported to ensure that they can be reproduced and validated by other researchers.
21
Q
What are some factors to consider when choosing an animal model?
A
- Species: Which species is most appropriate for the research question?
- Age, Sex, and Genetics: Does the age, sex, or genetic background affect the results?
- Microbiological Status: Are the animals pathogen-free, or do they have relevant infections/co-morbidities?
- Behavior: How does the behavior of the species affect the outcome?
22
Q
What are some commonly used animal models for studying human coronaviruses? (4)
A
Non-human primates: Used for their similarity to humans, though expensive and ethically sensitive.
Ferrets: Often used for respiratory viruses like influenza and SARS-CoV.
Hamsters: Commonly used for SARS-CoV-2 studies due to their ability to mimic human respiratory symptoms.
Transgenic mice: Genetically modified to express human receptors like ACE2 to study SARS-CoV and SARS-CoV-2.
23
Q
What factors influence the outcome of animal experiments studying coronaviruses? (4)
A
Age: Older animals may show more severe symptoms.
Sex: Male animals often exhibit more severe outcomes than females.
Comorbidities: Conditions like obesity, diabetes, and immune deficiencies influence disease severity.
Species: The choice of species affects how closely the model mimics human responses.
24
Q
What are the complexities of designing an animal experiment for zoonotic coronaviruses? (4)
A
- Host-virus interactions: The receptor diversity between species can impact susceptibility.
- Viral strain: Different strains of a virus can have different levels of infectivity and pathogenicity.
- Immune response: Host immune responses vary across species and can affect the disease outcome.
- Transmission pathways: Designing models that accurately replicate natural transmission is challenging.
25
What components make up an animal model to study a disease? (4)
An animal model includes not only the (1) animal species but also (2) the specific aspect of the disease being studied, (3) the pathogen, and the (4) methodology (e.g., dose and inoculation route).
26
Why are ferrets the animal species of choice to study the pathogenesis of influenza viruses? (4)
Ferrets are (1) highly susceptible to both human and zoonotic influenza viruses, (2) show similar disease progression and symptoms to humans, and (3) have similar lung anatomy and virus-associated pathological changes. (4) They also have comparable receptor distribution for flu virus attachment.
27
What are important criteria to consider when selecting the components of an animal model?
Key criteria include (1) the susceptibility of the species to the pathogen, (2) anatomical and histological similarities, (3) immune response, (4) the aspect of the disease being studied, (5) pathogen characteristics (e.g., wild-type vs. recombinant), and (6) methodological considerations like dose and time points.
28
How does the methodology impact the design of an animal model?
Methodology, such as the inoculation dose and route, affects where the infection occurs (e.g., upper vs. lower respiratory tract), the severity of the disease, and the reproducibility of results. Adjustments are made to ensure consistent infection and to match the study's research goals.
29
What is a common methodological adjustment made when designing animal models for respiratory infections?
In respiratory infection models, researchers often choose intratracheal inoculation to ensure the virus reaches the lower respiratory tract, especially when studying pneumonia. Intranasal inoculation may be used for studies focused on upper respiratory tract infections or transmission studies.
30
Why is it important to adjust the dose of the pathogen in animal experiments?
A higher dose is often used in animal studies to ensure all subjects are infected, which is crucial for statistical significance, especially when studying vaccine protection or other interventions.
31
What factors influence the selection of time points for sample collection in animal experiments?
Time points are selected based on the progression of the disease in both humans and animals. Acute diseases like flu may require earlier time points, while slower-progressing diseases may need later points to capture key stages of pathology and immune response.
32
What factors influence the selection of time points for sample collection in animal experiments?
Time points are selected based on the progression of the disease in both humans and animals. Acute diseases like flu may require earlier time points, while slower-progressing diseases may need later points to capture key stages of pathology and immune response.
33
What makes ferrets a reliable model for both human and zoonotic influenza viruses? (3)
Ferrets share similar (1) virus attachment patterns, (2) receptor distribution, and (3) lung pathology with humans, making them reliable for studying natural infections without the need for viral adaptation, which is often required in other species like mice.
34
Why is it important to align an animal model, like the ferret model, to a specific research question in disease studies?
An animal model must be aligned to the research question to effectively mimic the aspect of the disease being studied, such as airborne transmission between humans, ensuring the model provides relevant and accurate insights.
35
What are the three key principles of the 3R approach in animal experiments?
Refinement: Improving the methods to reduce suffering and improve data quality.
Reduction: Using fewer animals while obtaining quality data.
Replacement: Using alternatives to animal testing where possible.
36
What are some positive aspects of the ferret model for studying influenza transmission?
The ferret model is useful because ferrets are susceptible to natural infections, have similar airway anatomy and pathology to humans, and exhibit virus attachment patterns akin to humans, making it a reliable model for airborne transmission studies.
37
What is a potential limitation of using ferrets for studying contact transmission of diseases?
Ferrets are very social animals and in experiments tend to stay close together, which may not accurately reflect human behavior during contact transmission, leading to less realistic outcomes for human disease modeling.
38
How does humidity affect virus transmission in the guinea pig model?
Transmission efficiency of influenza viruses in guinea pigs varies with humidity. It is more efficient at low humidity, decreases at around 50%, and increases again at very high humidity, illustrating how environmental factors influence transmission.
39
What did air sampling studies in ferrets reveal about the infectious period for influenza?
Air sampling studies showed that peak airborne virus shedding occurs around day two after infection and drops quickly, suggesting that even though a ferret may still be PCR positive, it may not remain contagious throughout the entire sickness period.
40
How do small and large aerosol particles differ in their role in virus transmission?
Small aerosols can remain airborne for longer periods, allowing them to travel further distances, while large droplets tend to fall to the ground more quickly due to gravity, limiting their role in distant airborne transmission.
41
How was the concept of virus transmission by fur tested in ferrets?
Researchers vaccinated ferrets to prevent nasal infection, applied a virus to their fur, and found that transmission still occurred, suggesting that fur contamination could contribute to virus spread even without respiratory infection.
42
What are the advantages and challenges of using guinea pigs as models for influenza transmission studies?
Guinea pigs are easier to handle, less likely to bite, and require smaller spaces, but they are less experienced as models, and their pathogenesis differs from that of ferrets, presenting a challenge for studying transmission dynamics.
43
What did experiments testing SARS-CoV-2 transmission in ferrets reveal about airborne transmission?
Experiments showed that SARS-CoV-2 could be transmitted via the air in ferrets, similar to H1N1 influenza, suggesting that the virus can remain infectious while airborne over a distance greater than one meter.
44
What is Pharmacokinetics?
The study of how a drug moves through the body, specifically how the organism affects the drug, including absorption, distribution, metabolism, and excretion.
45
What is Pharmacodynamics?
Refers to the study of how the drug affects the organism, focusing on the biological and physiological effects of the drug and its mechanism of action.
46
How are PK and PD related in the context of drug therapy?
PK describes the drug’s journey through the body, while PD describes the drug’s effects on the body. Together, they help understand the drug’s therapeutic and toxic effects to optimize dosing.
47
Why are Pharmacokinetics (PK) and Pharmacodynamics (PD) important in dosing pharmaceutical drugs?
PK and PD are crucial in determining the optimal dose to maximize therapeutic effects and minimize side effects or resistance, ensuring drugs are delivered in the right amount at the right time.
48
In PK studies, what does the AUC (Area Under the Curve) represent?
AUC represents the total exposure of the drug in the body over time, helping to measure the drug's absorption and clearance.
49
What is the importance of the MIC (Minimum Inhibitory Concentration) in PK/PD?
MIC is the lowest concentration of a drug that inhibits visible bacterial growth. It’s crucial for determining the dose and frequency needed to keep drug levels above MIC to effectively treat infections.
50
How would you design an in vivo experiment to study Pharmacokinetics (PK)?
Administer a drug to an animal model, then measure the drug concentrations in the plasma over time at multiple intervals to generate a concentration-time curve. This helps calculate parameters like Cmax, AUC, and half-life.
51
How would you design an in vivo experiment to study Pharmacodynamics?
Administer varying doses of a drug to an infected animal model, then measure the bacterial load or therapeutic effect over time. Compare these results to the dose given to determine the drug’s efficacy.
52
When time above MIC is important for drug efficacy, how should dosing be adjusted?
Dosing should be more frequent to ensure that the drug concentration stays above the MIC for a longer period.
53
What is the goal of combining PK and PD studies?
The goal is to find the PK/PD index that correlates best with efficacy, such as AUC/MIC, Cmax/MIC, or time above MIC, to determine the most effective dosing regimen.
54
Why is it important to dose frequently for time-dependent antibiotics?
For time-dependent antibiotics, like β-lactams, the drug's effectiveness depends on the duration the concentration stays above the MIC. Frequent dosing ensures that drug levels remain consistently above the MIC, maximizing bacterial killing.
55
What is the bacteriostatic dose?
The bacteriostatic dose is the dosage of an antibiotic that inhibits bacterial growth but does not kill the bacteria. It results in no growth or killing of bacteria but prevents further proliferation.
56
What is the bactericidal dose?
The bactericidal dose is the dosage of an antibiotic that actively kills bacteria, reducing the bacterial load significantly. It is important in treating severe infections.
57
What is the purpose of using a neutropenic mouse model in PK/PD studies?
A neutropenic mouse model is used to mimic immunocompromised patients, such as those undergoing chemotherapy. By inducing neutropenia (low white blood cells), researchers can study infections and drug effects in a controlled environment where the immune system has minimal influence.
58
How do you determine the dosing frequency of a drug?
Dosing frequency is often based on the drug's half-life. Drugs with a short half-life need to be dosed more frequently to maintain therapeutic levels, while drugs with a long half-life can be dosed less frequently.
59
What are the advantages of in vitro PK/PD studies? (3)
In vitro PK/PD studies are:
Cheap and fast
Allow precise control over conditions
Can model specific bacterial growth environments
60
What is the probability of target attainment (PTA) in PK/PD?
The probability of target attainment (PTA) refers to the likelihood that a specific dosing regimen will achieve the pharmacodynamic target (e.g., AUC/MIC or T>MIC) necessary to effectively treat an infection in a patient population.
61
Why is the time above MIC (T>MIC) important in antibiotic treatment?
The time above the Minimum Inhibitory Concentration (T>MIC) represents how long the drug concentration remains above the MIC, which is crucial for time-dependent antibiotics like β-lactams. The longer the drug stays above the MIC, the more effective it is at killing bacteria.
62
What are the 3Rs of animal research?
The 3Rs are Refinement, Reduction, and Replacement. These principles guide researchers in improving animal welfare by refining procedures, reducing the number of animals used, and replacing animals with alternatives when possible.
63
Why is there a push to replace animal models in research?
There are ethical concerns about animal welfare, high costs associated with animal experiments, and the poor translational efficiency of animal models to humans (with a translation rate of about 8%).
64
What are organotypic models?
Organotypic models are human-based systems like organoids and organ-on-a-chip models that mimic certain functions of human organs, allowing for the study of diseases and drug testing without using animals.
65
What makes viruses obligate intracellular parasites?
Viruses rely on the host cell’s machinery for replication because they cannot carry all the components they need to replicate on their own. This makes studying viruses in human cells essential for understanding their behavior.
66
Why are stem cells used in organoid models?
Stem cells can differentiate into any cell type, allowing scientists to recreate human tissues and organs in the lab. These models are closer to human physiology than traditional animal models.
67
What is the significance of humanized animal models?
Humanized animal models involve modifying animals (like mice) to carry human traits. However, these models still have limitations compared to fully human-derived systems, such as organoids, because they do not account for all human-specific cellular and molecular interactions.
68
What are brain organoids and how are they used in research?
Brain organoids are 3D models made from stem cells that mimic the structure and function of a developing human brain. They are used to study diseases like viral encephalitis and to understand how viruses affect the central nervous system (CNS).
69
How do organoids help in studying viral infections like Paracovirus?
Organoids can replicate human tissues like the airway, gut, and brain, allowing researchers to study how viruses infect these areas, what cell types they target, and how the body responds, providing more relevant insights than animal models.
70
What is external validity, and why is it important in organoid models?
External validity refers to how well the results from an experiment translate to real-world clinical situations. In the context of organoid models, high external validity means the model accurately predicts how a human will respond to a treatment or infection.
71
What is the role of organoid models in personalized medicine?
Organoid models derived from patient cells can be used to test how specific drugs will affect an individual, leading to personalized treatments that are more effective and tailored to the patient’s unique biology.
72
What challenges exist in replacing animal models entirely?
While organoid models offer many advantages, challenges include the complexity of developing these models, the time it takes to generate them (e.g., brain organoids take 6–9 months), and ensuring they fully replicate the functions of human organs.
73
Why are non-human primates (NHPs) sometimes selected as experimental animal species despite ethical concerns? (2)
NHPs are selected because they (1) closely mimic human biology, making them valuable for studying diseases or vaccines where other animals (like rodents) are not susceptible or fail to replicate human disease progression. They also (2) offer higher translational value for certain biologics and vaccines.
74
What is the most commonly used primate in infectious disease research?
The most commonly used primates are rhesus macaques and Cynomogus macaques. Chimpanzees are no longer used due to ethical and legal restrictions.
75
What factors influence the selection of the virus inoculation route in primate research?
The route of inoculation affects where the virus replicates in the body. For example, intranasal inoculation targets the upper respiratory tract, intratracheal inoculation targets the lower respiratory tract, and aerosol exposure affects both. The chosen route impacts disease development and the research objective (e.g., studying natural infection vs. disease progression).
76
How does the dose of virus inoculation affect experimental outcomes in primates? (2)
(1) Higher doses of virus typically lead to quicker infection and replication, while lower doses result in longer incubation periods. (2) The dose also affects the likelihood of finding infected cells in early stages of the disease.
77
What clinical specimens are typically collected in infectious disease studies using NHPs?
Clinical specimens include throat swabs, nose swabs, bronchoalveolar lavage (BAL) fluid, blood, tear fluid, lymph node biopsies, and sometimes skin biopsies or feces and urine (if feasible).
78
What is bronchoalveolar lavage (BAL), and why is it used in primate research?
BAL involves inserting a small catheter into the trachea, injecting saline into the lungs, and then recovering it to collect lung cells and fluids. It is used to detect viral replication in the lungs.
79
Why are genetically modified organisms (GMOs), such as recombinant viruses, sometimes used in NHP research?
GMOs, like recombinant viruses that express reporter proteins (e.g., GFP), allow researchers to visualize viral infection in tissues and track viral replication and spread in vivo. However, strict biosafety regulations apply when using GMOs.
80
How does measles virus cause immune suppression, and why is this significant?
Measles virus depletes immune cells, particularly memory lymphocytes, leading to immune suppression. This increases susceptibility to secondary infections, which is a key factor in measles-related mortality.
81
What are the advantages of aerosol delivery of viruses in NHP models?
Aerosol delivery allows virus particles to enter both the upper and lower respiratory tracts, providing a more natural and comprehensive infection route. It also ensures that a high dose reaches the lungs, critical for studying lower respiratory tract infections.
82
How does the 3Rs principle apply to non-human primate research?
The 3Rs principle (Refinement, Reduction, Replacement) applies by ensuring that NHPs are only used when absolutely necessary (Replacement), improving experimental techniques to minimize animal suffering (Refinement), and using the fewest number of animals possible to achieve valid results (Reduction).
83
What are the ethical and practical challenges of using non-human primates in research?
Ethical challenges include the close evolutionary relationship to humans, raising concerns about their welfare. Practical challenges include the high cost of purchasing and housing NHPs, as well as their need for specialized care.
84
What are the 3Rs in animal research, and why are they important?
The 3Rs stand for Replacement, Reduction, and Refinement. They are important because they aim to minimize the use of animals in research, reduce the number of animals needed for experiments, and refine procedures to minimize animal suffering and improve welfare.
85
What is the concept of "Replacement" in the 3Rs framework?
Replacement refers to using alternative methods to avoid or replace the use of animals in research, such as in vitro models, human volunteers, or computational (in silico) methods.
86
What does "Reduction" mean in the 3Rs framework?
Reduction involves designing experiments to use the fewest number of animals possible while still obtaining valid and statistically significant data.
87
What is "Refinement" in the context of the 3Rs
Refinement means improving experimental techniques and animal care to reduce suffering, stress, and discomfort. This includes using non-invasive methods, better housing, and behavioral enrichment.
88
What are some critical factors to consider when developing animal models?
Key factors include the species and strain of animals, microbial status, availability of reagents, anesthesia methods, route of administration, disease measurement, and ensuring experimental reproducibility.
89
Why is species selection important when developing animal models?
Different species may have varying susceptibility to diseases, immune responses, and genetic backgrounds. Choosing the right species is critical to ensure the model accurately represents human disease conditions.
90
Why is the microbial status of animals important in research?
Microbial status affects the health and immune response of animals. SPF (specific pathogen-free) animals are often used to ensure consistent and controlled experimental conditions.
91
What are the PREPARE guidelines in animal research?
PREPARE guidelines provide a framework for planning animal experiments. They help researchers design studies that consider animal welfare, appropriate methodology, and reproducibility before the experiment begins.
92
What are the ARRIVE guidelines, and why are they important?
The ARRIVE (Animal Research: Reporting of In Vivo Experiments) guidelines ensure that animal research is reported transparently and comprehensively. This improves the reproducibility and ethical standards of published studies.
93
Why is reproducibility a critical factor in animal research?
Reproducibility ensures that the results of animal studies can be reliably replicated. This is vital for the validity of scientific findings and helps reduce unnecessary repetition of experiments.
94
Why are animal models necessary in TB research?
They allow researchers to study drug safety, pharmacokinetics, drug interactions, and efficacy, which cannot be fully assessed in vitro or directly in humans due to ethical and practical limitations.
95
Why can't TB drug regimens be tested directly in humans without prior animal studies?
Ethical concerns prevent testing potentially less effective drug regimens in humans without extensive preclinical data from animal models to ensure safety and efficacy.
96
What role do animal models play in preclinical TB drug development?
Animal models provide crucial data on the safety, effectiveness, and duration of TB treatments before they can be ethically tested in human clinical trials.
97
Why are mouse models commonly used in TB research?
Mice are commonly used because they are genetically uniform, easy to handle, and have demonstrated predictive value for translating TB treatment findings to humans.
98
What factors must be considered when selecting a Mycobacterium tuberculosis strain for a mouse TB model?
Researchers must consider the strain’s virulence, drug susceptibility, and whether it is a lab reference strain (e.g., H37RV) or a clinical isolate.
99
What are the most common mouse strains used in TB research, and why?
BellopC mice are most commonly used because they are immune-competent and widely studied, but other strains like C3H mice may be used for more human-like lung pathology.
100
What are the main types of mouse models used in TB research?
The main types are the acute model, chronic model, and latent TB model, each designed to study different aspects of infection and treatment.
101
What’s the difference between an acute and a chronic TB model in mice?
In the acute model, mice are infected with a high bacterial load and treatment starts early, while in the chronic model, mice control the infection, simulating latent TB before treatment starts.
102
How does the timing of treatment initiation impact TB model outcomes?
Starting treatment early in the acute model allows researchers to study bactericidal activity, while delaying treatment in the chronic model helps study sterilizing activity and long-term infection control.
103
What does bactericidal activity measure in a TB mouse model?
Bactericidal activity measures the change in bacterial load in the lungs during treatment, indicating the drug's ability to kill or inhibit the growth of TB bacteria.
104
What does sterilizing activity measure in TB mouse studies?
Sterilizing activity measures the proportion of mice that are culture-negative (i.e., free of detectable bacteria) three to six months after treatment has stopped, used to assess the effectiveness of treatment in eliminating infection.
105
Why is drug exposure (pharmacokinetics) important in mouse models of TB treatment?
Correct drug exposure levels in mice must mimic those in humans to ensure the findings are translatable and the drug's activity in mice reflects what might happen in human clinical trials.
106
How does the experimental setup influence the outcome of a TB study in mice?
Factors such as the infection dose, treatment duration, and strain of mice can affect the results, including the drug’s observed effectiveness, leading to varying outcomes across different models.
107
How does the choice of model affect the interpretation of TB study outcomes?
Different models (acute vs. chronic) can show varying levels of drug activity. A drug might show no activity in an acute model but could still be effective in a chronic model where the bacteria behave differently.
108
Why aren't more human-like mouse models (like C3H mice) always used for TB treatment studies?
Human-like models with complex pathology (e.g., cavitations) can add variability to the study, requiring more animals and complicating the interpretation of treatment efficacy, whereas simpler models can still provide predictive data.
109
What should be considered when selecting a mouse model for TB treatment studies?
The specific research question (e.g., bactericidal vs. sterilizing activity), the nature of the infection (acute, chronic, or latent), and the pharmacokinetics of the drug must all be considered to choose the appropriate model.
