Imperfect Vaccines: An Agent-Based Modeling Approach

Stanley Wang

Duke University: Math 196S, Professor Layton

9 December 2010
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0) Abstract

Vaccines are not all created equal. Some potential HIV vaccines, for example, are

effective for only a limited amount of time. Others are only effective for about 30% of the

population (Mclean, 1993). Although there are many models that use systems of differential

equations to model vaccination and herd immunity within an infected population, this paper

uses probabilistic agent-based modeling to analyze the path and variance of vaccine

effectiveness. Such a model confirms the importance of long-lasting vaccines and shows how

difficult it is to measure the effectiveness of imperfect vaccines. McLean’s model matches the

agent-based approach, but only under specific assumptions that can make or break both

models. In particular, this paper will both reinforce many of McLean’s results and unveil new

complications for public health authorities.

1) Introduction – Public Health

A vaccine is a substance that induces an immune response against an actual infection

(Cancer Vaccine Institute). Since the first successful vaccine for smallpox was made from

cowpox, vaccines have been used to drastically reduce the number of infections for a variety of

diseases, including smallpox (Scott, 1996).

A recent example is the use of vaccines to combat measles in Canada. Before the

introduction of such a vaccine in 1963, measles outbreaks occurred in 2 to 3 year cycles. During

those years, an estimated 300,000 to 400,000 cases appeared annually and continued to grow

in number each year. Since the introduction of vaccine, the incidence has declined markedly:
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Figure 1: Measles in Canada

*(Measles Reported Incidence)

However, this story is did not end there. The measles vaccine that was so effective is not

perfect. It does not work for at least 10% of children. Between 2001 and 2005, the number of

measles cases reported each year ranged from 6 (in 2005) to 34 (in 2001). Most recently in

2007, there was a minor outbreak that reversed the downtrend of cases:

Figure 2

*(Measles Reported Incidence)

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In an ideal world, diseases would have vaccines that work for everybody, completely

cure diseases, and last a lifetime. Public health authorities could focus on developing and

implementing such a vaccine for every disease. However, diseases like HIV and malaria break

this mold. There are many potential vaccines for each that are incomplete in one way or

another. A non-ideal vaccine is still better than none at all, so given a multitude of partially

effective vaccines (all deficient in some way), how can these different imperfect vaccines be

compared to each other? If there are resources (time or money) to develop one or another,

which imperfections would be less significant?

1.1) Malaria

Every year, nearly one million people (mostly in sub-Saharan Africa) die from malaria. A

mosquito-borne parasitic disease, malaria can be prevented with insecticides and bed nets to

prevent mosquito bites. Plasmodium falciparum is the variant of malaria that causes the vast

majority of cases and deaths and is therefore the strain that is the most researched (Griffin,

2010). Recently, there have been major advances in both the diagnosing and treating of malaria:

Rapid Diagnostic Tests (RDTs) need only a drop of blood to test for infection and artemisinin-

based combination therapy (ACT) uses drugs to remove infection. The ability to perform these

tests in nearly all of areas (not just hospitals) allows for quick and simple identification of who is

infected and who is not. Artemisinin-based combination therapies have been effective, but

some of the parasites have become resistant and the Word Health Organization now suggests

using ACT in combination with other drugs (WHO, 2010). As more parasites become resistant,

the usefulness of this particular approach (currently the best available) may decrease

considerably.
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1.2) HIV/AIDS

Human immunodeficiency virus (HIV) is a virus that weakens the human immune system.

In the resulting condition, acquired immunodeficiency syndrome (AIDS), opportunistic

infections that would otherwise not lead to illness can kill (Weiss, 1993). There is currently no

cure/vaccine for HIV (Cohen, 2009). A major area of research is the search for, and replication

of, effective antibodies against multiple strains of HIV. Cohen’s 2009 paper in Science refers to

two of the most promising antibodies, called PG9 and PG16, which had a 70% prevention rate

out of 162 viral strains test. The antibodies were collected from 1800 HIV-positive people in

Africa, of which even those with the most resistant antibodies still developed AIDS. The fact

that a 70% protection rate can “Spark Vaccine Hopes” (Cohen, 2009) only further demonstrates

the severity of the situation. In 2007, 33.2 million people worldwide lived with HIV, and HIV

caused more deaths than any other infectious disease (Klimas, 2008).

1.3) Imperfect vaccines & McLean

In 1993, A.R. McLean and S.M. Blower compared different types of imperfect vaccines

to find that different imperfect vaccines may actually be equivalent in results. Within the

context of HIV vaccines, McLean examined herd immunity and the resulting characteristics of

vaccines necessary for eradication of the disease from a given population. A main example

result is that a perfect vaccine that protects with a half-life of 10 years is only as good as a

permanent vaccine that works in 30 % of people. The models were based on the male

homosexual population of San Francisco that split people into four types: susceptible,

vaccinated, infectious, and AIDS patients. On the other hand, imperfect vaccines were split
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according to three variables: “take” (% of people for which it works), “degree” (reduction in

probability of infection given exposure), and “duration” (protection decrease over time).

McLean used differential equations to model the population according to the splits

above, using the equations to quantify infection/curing/mortality. The rate of change for

susceptible men, for example, accounts for vaccinated men whose protection wears off,

infection probability, and the fraction of the community that is infected (McLean, 1993). This

last factor accounts for the higher susceptibility of people by proximity. McLean eventually

found that the critical point necessary for eradication depends on three major input variables

(adjusted for constants and normalization). This result allowed McLean to calculate the

equivalence mentioned above, and in essence created a framework for quantifying the

tradeoffs between different types of imperfect vaccines. A basic layout summarizing the

interactions of the above types is below:

Figure 3
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In this case, the arrows and symbols represent transitions and probabilities for

transitions. Variables such as epsilon, N, beta represent the input variables to the model, of

which a subset will be modeled for this project.

For reference, McLean derived a formula to quantify the effectiveness of a vaccine:

Vaccine impact = take * degree * rate of natural death

duration + rate of natural death

Take is the proportion of immunizations that are accepted by the patient’s body, degree is how

effective the vaccination is at reducing infection, and duration is how long the protection lasts.

Vaccine impact is used to determine whether a vaccine successfully eradicates an illness or not,

and allows for total effectiveness to be summarized in one number. These are the main

variables for this experiment, and along with the vaccine impact formula form part of the

experiment setup (section 2).

From this equation and clinical data, McLean shows that duration outweighs take and

degree in determining the final result of a vaccine. That fact that duration is on the

denominator summarizes McLean’s derivation and analysis (McLean, 1993). At the same time,

take and degree have equivalent effects on whether the impact is sufficient to completely

eliminate an infection.

1.4) Agent-based modeling

Agent-based modeling (ABM) has been described as more “a mindset than technology”

(Bonabeau, 2002). The modeling of a system using autonomous decision-making “agents” to

simulate relationships, ABM also serves as a counterpoint to the common usage of differential
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equations. ABM is the bottom-up/micro view versus the differential equation/macro view of

mathematical models.

The origins of agent-based modeling extend to the 1960sm with John von Neumann’s

“self-replicating” machines thought experiment (von Neumann J, 1966). Often referred to as

Von Neumann machines, these miniature robots can build exact copies of themselves. Starting

from a few individuals, these machines could easily become a population with collective

behaviors.

The benefits of this modeling approach include emergent phenomena, natural

descriptions, and flexibility (Bonabeau, 2002). Emergent phenomena are behaviors or results

where the whole is more than the sum of its parts. Analyzing a population using differential

equations requires that aggregate behavior can be explicitly stated beforehand. This is often

valid, but for certain situations, especially in the social sciences, it is this aggregate behavior

that is the characteristic in question. ABM provides a possible solution to this.

Secondly, agent-based modeling provides a more natural method to describe systems. A

population does not decide to grow at 3.5% a year; millions of separate families have a child

each year, and the overall population change is a statistic that summarizes all of these decisions.

Modeling such a scenario using ABM is a far better approximation of the inner workings of

population change than equations alone.

Another advantage of ABM is the ability to change behavior at will. A traffic model can

have different car speeds and traffic light timings often by changing a single variable in the

model. NetLogo, the program used for this project, allows users to add an individual attribute

with a single word. This project itself uses an existing AIDS model as a starting point.
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However, agent-based modeling is not perfect. Like other tools, ABM still falls under the

garbage-in, garbage-out principle in computer science. Not everything can or should be

modeled using individual agents. Creating an agent for every cell in the human body is most

likely not going to be useful or predictive for modeling the process of walking. A mathematical

model that usually seeks to isolate behavior would be hindered by unrelated details. The model

created for this project is affected by this as well – the simplifying assumptions that McLean

makes to analyze infection by construction do not specify the implementation at the individual

level. This will be discussed at the end of section 4 and in section 5.

At the same time, applications in fields such as the social sciences can be difficult to

implement. An ABM approach may be able to extend individual decisions to a group (a benefit

in the introduction), but individual behavior still needs to be well-defined. A person may buy a

product at a certain price, but the reason and variability of such choices are difficult to model.

Markets, whether it is for iPods or stocks, requires ideas such as value and utility that are

difficult to define and quantify. This is why this project focuses on the quantifiable aspects of

policy, not necessarily the notions of equity or utility that policy makers adhere to.

Models and interactions should accurately summarize the behaviors of individual agents,

and in particular a model that generates data based on qualitative and relative metrics should

not be interpreted quantitatively and in an absolute basis. For example, a model designed to

test equivalence (such as this project) should not be interpreted on absolute basis. Two sets of

inputs that both result in 30% infection rate in the model, for example, does not necessarily

mean that 30% is the rate that would result from real-world implementation. It can only mean

that the two sets of inputs are equivalent. This project will attempt to mitigate this problem by
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analyzing results relative to each other and other papers. It will not attempt to find the precise

inputs necessary to eradicate infection (whether it is HIV or another disease).

Much of the above background is confirmed by and taught at the Santa Fe Institute, a

research institute dedicated to the study of complex systems. From economic to quantum

mechanical models, the Santa Fe Institute attempts to address current questions from an

agent-based modeling approach.

1.5) NetLogo

NetLogo was first created in 1999 by Uri Wilensky as the next generation of StarLogoT (a

similar modeling program). A Java-based program built around ABM, it has been under

continuous development since then at the Center for Connected Learning and Computer-Based

Modeling (now at Northwestern University) (Wilensky, 2010). There is an updated website at

<http://ccl.northwestern.edu/netlogo/>, where the complete programming and testing

environment can be downloaded for free and experimented with. There is a 458-page manual

and multiple sample models that cover everything from the flocking of birds to traffic lights in a

miniature city.

The model itself uses the 4.1.1 version of NetLogo version (the most recent) and

simulates hundreds of people getting vaccinated, getting sick, or dying. Specifically, the model

uses NetLogo’s ability to create independently interacting agents and have them make

decisions in real time. The speed of the simulation can be altered with each trial run to save

time or examine interactions more closely, as desired. Given certain starting conditions, the

program can run without further input, allowing different entities to interact with each other.
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The picture below shows part of the current model setup. Pressing the setup button

initializes the program and people; pressing go once starts a full trial. The simulation stops

when either all people are dead or there are not more infected. There is a physical plane on

which agents move graphically, and it is shown below in section 3.4:

Figure 4

Information &
Control

Variables to be
tested

Non-tested
variables

2) Experiment Setup

The first part of this project simulated McLean’s scenario setup using NetLogo

(described above), where participants infect one or another probabilistically. The variables

tested (from McLean’s article) include “take” (not effective in some people), “degree” (only

reduce probability of infection) and “duration” (protection weakens over time). As discussed
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above, McLean shows that certain permutations of the above variables are equivalent in results.

The model replicated such results in terms of the complete eradication of the disease.

Apart from the three major variables introduced above, there are seven other variables

that affect the behavior of agents. The screenshot at the end of section one shows these

variables, which are used to calibrate the model. Vaccinationrate is the proportion of natural

births that are vaccinated; on the other hand, birthrate and deathrate determines how many

people die or get born each time-step as a proportion of the current population. On the right

side, infectstart determines how many people of the original population begin infected. It can

also serve as proxy for how far along the epidemic is. Vaccinationstart is the same as

vaccinationrate except for the initial population. Infectchance is the probability of a susceptible

people getting infected by an infected person. The values shown above is the base case scenario

that is near the tipping point for all three of the key variables.

Simulation will consist of multiple agents (representing people) making decisions

independently to move around in a space at a preset distance and having the same four states

that McLean described above. Prior to running the simulation, 500 people will be generated

with the three variables below as attributes. When two entities touch physically, there will be a

probability of infection if one of the entities is infected. Vaccinations will be simulated by a

setup button that creates both susceptible and vaccinated people. The simulation will be split

up into a series of time-steps. Although they are called weeks, each time-step is not designed to

have an equivalent unit outside the model.

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Figure 5: Agent states

The yellow arrows represent entries and exits from the four states. They are in essence

natural births and deaths for the current population. The calibration variable vaccinationrate

determines the percentage of natural births that are vaccinated (as if they were immunized at

birth). Take affects both the setup and the natural births by discounting the actual number of

vaccinations by probability (1-take).

This diagram is very similar to the one in McLean’s, but is split into two major versions.

The first includes only the turquoise arrows between the boxes and the turquoise arrow. This is

to simulate an isolated population that includes both infected and vaccinated people in the

beginning. On the other hand, the inclusion of the yellow arrows is a closer approximation of

McLean’s model. The reason why the first version is the primary model for this project is shown

is discussed in section 4.2.

2.1) Variable 1 – “take” (not effective in some people)

Each agent receives a vaccine when entering the population. Whether the person is one

of the initial people or part of the additional people, he or she has a certain probability of

receiving the vaccination. If selected for vaccination, only a certain percentage of those
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vaccinated (take) actually receive protection. The same is true for any births or additional

entrants to the population.

2.2) Variable 2 - “degree” (only reduce probability of infection)

For each time-step, everyone agent moves one step in a random direction. When two

agents are close to each the same spot in the graphics area, an infected member of the pair (if

any) has a certain percentage to infect his partner if that partner is susceptible or vaccinated.

This percentage is a global variable (infectrate, from above); If a vaccinated person meets an

infected person, the vaccinated person as infectrate * (1-degree) chance of getting infected..

2.4) Variable 3 - “duration” (protection weakens over time)

This variable is implemented globally as a single protection weakening rate. In each

time-step, each vaccinated agent has probability (100 * (1 - exp ((ln 0.5) / duration))) of losing

vaccination. This formula results in half the vaccinated population losing protection after the

number of time-steps specified in duration. As such, duration is effectively a percentage of the

currently vaccinated population (as in McLean’s model), but through the mathematics of

compounding the input box actually takes in the number of time-steps. This nonlinear version

was chosen over a linear version (vaccines where off after ) in order to better approximate

McLean’s experiment. The use of an individual time-keeper or a constant percentage actually

had little effect on results, so the actual implementation does not affect the conclusions below.

2.5) Disease specifics – malaria and HIV

Although malaria is spread by mosquitos, physical proximity will approximate the spread

of disease for this experiment. HIV, which is spread through physical contact between two

people, is accurately portrayed according in this model. At the same time, this model is general
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enough to apply to infectious diseases as a whole. The actual method of infection can be

approximated by physical proximity and movement of the agents.

3) Results and conclusions

Although this experiment began with multiple trials, the actual variation in most results

was negligible. The sample set below is representative of different variations of the three

variables. Any significant variation seen is discussed below along with repeated trial data for

such cases. This experiment will have multiple trials to test the equivalence conditions that in

the McLean article. The final result is 10 scenarios that not only varied all three key variables,

but crossed the tipping point of eradication for all three. Reference graphs (see picture of

NetLogo above) accompany the most significant runs, showing the maximum percentage

infected, and the size of the uninfected (susceptible).

To calibrate the model, the variables not directly related to imperfect vaccines were

specifically set so that the base case (defined below) just barely eradicates the infection.

Although this reverse approach is somewhat arbitrary, early attempts to exactly replicate the

constants used by McLean did not succeed because of the fundamental nature of agent-based

modeling. The essentially limitless ways to modify agent interactions (such as agent speed and

infectrate) produced unexpected ambiguities. For example, the speed of an agent moving

around mimics human movement but inevitably misses on the daily actions of people. Not

having them move would defeat the purpose of such an experiment, but moving them is at best

a crude approximation for methods of infection. The fundamental difference between

differential equations and agent-based modeling is the ability to replicate individual action.
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However, the ability to manipulate every single characteristic also requires the calibration of

every characteristic. From the speed of turtles to physical location, there are many variables

inherent in this agent-based model that McLean’s model does not specify. This is why the

analysis of this model focuses on relative comparisons.

Base case:

Initial-people Take Degree Duration

500 1.00 1.00 500 (weeks)

Figure 6: Result of base case

The graph on the right includes an additional feature of the AIDS model – testing for HIV

(red and blue lines). This feature is off for the actual experimental runs. Later graphs will only

contain the green line – the above is for reference. Because comparisons are more relative, the

graphs above omit the most of the markings and gridlines. Specific numbers are shown in the

output boxes (see figure 4). The graphs above are meant to capture large differences in the

progression of the infection and vaccine over different levels of take, degree and duration. As a

result, fully calibrating an agent-based model to have the exact results is not only difficult but

not guaranteed to be unique or informative.

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Raw data:

As discussed above, the above raw data points are single samples. In practice, average

data looks essentially the same, except for the end population and time to eradication variables.

These last two variables are discussed in section 3.2 and 3.4.

3.1) Mean tipping point & boundary conditions for eradication (equivalences)

The trials tested whether McLean’s equivalences hold up in this simulation, and if not, at

which input combinations do the vaccines become effective and at which points do the

vaccines become completely ineffective. McLean speaks of “vaccine impact” as a proxy for this
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(McLean, 1993). This is helpful in public health, where a top priority is that the vaccine

eradicates the disease, not just slows it down. The existence of such tipping points at all for all

three major variables in this ABM confirms McLean’s viewpoints. Absolute percentages do not

need to match, only the existence of relationships and equivalences that parallel (qualitatively)

those in McLean’s model.

Duration does play the largest role in the agent-based model, confirming another of

McLean’s conclusions. A permanent vaccine has not only the lowest maximum infected

percentage (88.1%), it actually keeps the most people alive (49). Such a large duration means

no one leaves the vaccine population. In practice, an infinite duration just means that a person

is protected until death by natural causes. Since natural causes of death are not considered in

this model, this serves to confirm the validity of the results in relative, not absolute terms.

Figure 7: Duration comparison

Permanent Vaccine 50-week half-life

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The important takeaways from these two sets of graphs are not the specific values but

the importance of reaching 100% infected or not. The latter reached 100% infection (from the

data set above), and the entire population dies. This is because this model assumes the only

deaths are from infection. The top right graph drops vertically to zero as everyone is dead.

At the same time, the different tipping points in take and degree show that take is more

effective. The data set above shows that 0.2 take does eradicate the disease, but a 0.2 degree

does not. Because the actual values are not highly useful for this model, this relative

comparison is the most informative. One explanation for this is that the actual equivalence

relative to eradication is dependent on infection rate and the movement of people. In this

scenario, each pairing of people that includes one infected member has a 10% probability of

infecting the other. The overall rate of infection for the entire population is different than this,

however, because the rate and direction of movement directly affects how quickly or random

infection is. Different values for any of these factors result in drastically different tipping points.

3.2) Mean of maximum infection % and time to eradication of the population in general

The maximum infection rate provides another way to compare equivalent points

between this model and McLean’s model. Even though certain combinations are the

boundaries for whether a disease is eradicated or not, how much of the population could get

infected before eradication, and how long would such a process take (using time-steps as

weeks or months)? Public health authorities could use this as a further differentiator in order to

decide on which projects to fund and also as real-time check for vaccines once used. If the

model is predicting that no more than 10% of the population should get sick given a successful

vaccination, a population that reaches 20% in infections can serve as a warning signal to
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authorities that something is wrong given certain inputs, or that the disease is different from

what is assumed in the model.

Because the model is calibrated to be near the tipping point between success and

failure, the value of the maximum percentage is unsurprisingly in the 90%-99% range. What is

unexpected is the diminishing benefit of a greater take and greater degree. Saturation seems to

be a limiting factor in take and degree’s effectiveness. Apart from this, duration is still the most

effective relative to take and degree. With the fastest eradication time and lowest maximum

infected, a permanent vaccine saves more lives than one that fully protects a person for a

period of time:

Figure 8

Permanent vaccine Fifty-week half-life

0.2 take, 1.0 degree 1.0 take, 1.0 degree

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3.3) Variance of results

Starting with 5 trials for the base case, how much do the results change due to

randomness? Do the equivalences seen in the beginning hold in the face of randomness, or are

the equivalence points actually equivalence areas where randomness determines effectiveness?

This actually helps to interpret the max % infected variable above, as a rudimentary

understanding of how much a specific trial may vary from the mean can prevent over or

underestimation of the vaccine’s effectiveness. In terms of public health, this provides a further

comparison point between vaccines: is a vaccine whose results vary widely but on average is

more effective than a constantly less effective vaccine? This is a social and ethical question, but

this model may give another tool to evaluate the alternatives.

The actual experiment resulted in less variance than expected. For the base case, the

maximum infection percentage never changed more than 5% from the mean:

On the other hand, the time it takes to completely eradicate the virus can vary wildly

(especially as a percentage of any of the times). The implication is that the proportion of

infections can be estimated, but the timing of eradication can be highly unpredictable. This is

reasonable considering the random nature of movement in this experiment. When more and

more people die, it is less likely in each time-step for an infection to occur. This process is also
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reasonable in actual outbreaks, given that as more people die the infected become both less

numerous and more dispersed.

For public policy, this means that the top of the cycle is easier to predict and analyze

relative to how quickly the all illness is gone. Now, the actual percentage depends both on the

properties of the vaccine (take, degree, duration) as well as the details of the infection. The

probability of infection given contact and method for transmission can result in vastly difficult

max percentages. Regardless of the actual value, the authorities can use this maximum

percentage of infected as a baseline to see how effective a vaccine is. The generality and

flexibility of the model is intended to make this a general property of imperfect vaccines, not

just relative to HIV and malaria.

3.4) Path taken

NetLogo allows for the creation of real-time graphs that plot variables as they change

over time. By running multiple trials and comparing the proportion of infected over time, this

project attempted to discern a reasonable path for vaccine programs to take. Possible

outcomes include a logistic-like graph and a quadratic curve that reaches a maximum of 100%.

Because of the many simplifying assumptions in this model, it may be the case that qualitative

comparisons are the most useful. Authorities can use this to plot the progress of a specific

event versus the average: is this vaccine working as it should? If the rate of infection should

decrease exponentially over time, is that the case in a live test?

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The extreme calibration of the model made each trial similar a race between infection

and vaccine. If one attribute reached a certain critical level, the other would eventually be

pushed out. In this case, the graph of percentage infected over time is a bell shape whose right

side often lags:

Figure 9: Sample run and physical plane (right)

This is actually because at the beginning of the pandemic, infections dominate. With

only a small percentage of the population (2% in this case) infected (blue agents), the infectious

inevitably (and frequently) move near many uninfected (green agents). Infections therefore

began in the shape of a logistic function, exponential-like at first but slowing in growth as the

population becomes more saturated with infection.

However, as more and more people start getting infected, more and more people

transition to the AIDS stage and start dying. The key difference in this model that makes it seem

like AIDS is that nobody survives AIDS and rejoins the susceptible population. This is accurate

for AIDS, a fatal disease. This assumption also approximates infections that can only happen

once per person, such as chickenpox. After getting AIDS, people either die or exit the
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susceptible population. Both cases reduce the susceptible population so that infection rates

after saturation are eventually overtaken by death rates. This lowers the infection percentage

of the population while simultaneously reducing the population size drastically. As discussed in

the previous section, the often elongated right tail is due to the fewer people alive.

3.5) Comparison to McLean’s work

Because of the difficulty of modeling the McLean’s exact assumptions and changes,

comparisons were made on a relative and qualitative basis. At the most fundamental level, do

similar equivalent conditions even exist when using agent-based modeling? Given randomness,

how do McLean’s assertions hold up? Are differences between the two models a product of

ABM being a fundamentally different approach or of yet another important dimension to the

imperfect vaccine problem?

The two duration graphs in figure 7 show that the tipping point is directly related to the

maximum percent infected – even with a permanent vaccine, most of the population gets

infected and subsequently dies. It is the ability of the few to hold out that keeps the population

alive. Duration is so effective that even the 200-week half-life version eradicates the infection

while saving more lives than any combination of take or degree with shorter durations.

At the same time, take and degree have a different relationship in this approach when

compared to McLean’s model. Although McLean acknowledges that similar reductions in take

or degree will yield different levels of infection within vaccinated populations, her paper asserts

that the level of vaccination required for eradication remains the same. As shown above, this is

not the case in this experiment (see raw data). This may indicate a sensitivity to starting
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conditions, whether it is the presence of continuing inflows of susceptible and vaccinated

people in McLean’s model or a different death rate in this one.

Apart from the above comparisons, the use of probability in this paper’s model did not

contradict McLean’s work. Instead, it added another useful data point – variability. Variables

not directly related to time, such as eradication and maximum infection percentage, did not

vary with repeated runs. However, time-dependent variables such as time to eradication did

have significant variation relative to mean values (see section 3.3).

4) Extended results

The first portion of this experiment, as discussed above, recreates a version of McLean’s

results in a stochastic and agent-based model. After the initial base case, further variations of

the model attempted to both further replicate McLean’s results as well as extend them to

Gandon’s setups. Theses extensions are intended as starting points for further research.

4.1) Gandon – varying virulence

The first extension is the evolution of pathogens (from Gandon article). Imperfect

vaccines that do not work all the time or for the entire population can introduce complications.

In fact, imperfect vaccines can select for more virulent strains of viruses so that vaccines that

can save only a few or slow down the progression of the virus can actually increase the overall

mortality rate of a population.

Increasing the probability of infection (given physical proximity) produced the

hypothesized effect in the model. The original infection probability was 10% (bold is base case

from above), and the chart below is for when infectchance = 50%:
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Varying virulence (base case is bold):

Figure 10: All other variables set to the base case in section 3

This above data set compares (hypothetical) different versions of the virus that are

more or less virulent. Gandon’s article on vaccines asserts that with different types of viruses,

imperfect vaccines can only leave the more virulent strains to infect others, such that the

population mortality can remain constant or even increase. Allowing for infection rates to vary

over time produced the results above, but the current model is not capable of supporting two

different infections at once.

Nonetheless, the data shows a distinct difference from all the cases in the previous

section. In particular, the presence of a second hump in the infection percentage chart shows a

resurgence in infection percentage even with far fewer people alive. This suggests that in a

head to head competition between two strains of varying virulence, the introduction of an

imperfect vaccine would change the composition of the infected. Specifically, the infected
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would be composed more of the virulent strains. This would be similar to the superbug problem

with antibiotics, where overuse of antibiotics has inadvertently selected for drug-resistant

strains of diseases.

4.2) Natural entries and exits allowed

The original model created for this project included both natural birth and death of

agents. Each new set of entrants included some who were vaccinated. Exactly how much

depended on the take variable and the vaccinationstart parameter. At the same time, a natural

way for death allowed agents to die even if they were not infected. The total probability of

death is therefore deathrate + deathrateaids. Below is a sample run using the same base case

from section 3 with total population as an addition to the population chart:

Figure 11

For the case above, 2% of the initial population joins and 2% of the current population

dies each time-step. The introduction of new people in each time-step forces the equilibrium

percentage to a range between 20 and 40% for the base case and increases the variability of

results. The population size also remains roughly between 600 and 800.
 Wang 28

At the same time, this model dampens the effects of changes to the three variables

being tested. None of the scenarios show in section 3 results in complete eradication or full

infection. Instead, the chart is range-bound for infection percentage and populations, and

changes only shift the entire graph shift up or down. A variable change that increases a

vaccine’s overall effectiveness shifts both graphs up, and a corresponding decrease has the

opposite effect.

These additional flows were taken out of the main experiment because of realism and

simplicity. In particular, the constant addition of new people makes the result highly dependent

on the composition of such flows. One can shift birth rates or death rates to be high or low

enough to create a growing or dying population, but that is equivalent to turning one of them

off. To make finer comparisons, it is faster and simpler to turn such flows off for this project.

5) Discussion of results and connections to other methods

Although this paper focuses on the uses of vaccines to eradicate disease in populations,

public health authorities can use a variety of other methods. From efficient detection and

quarantining to bed nets, conventional methods are often enough to contain potential

pandemics and reduce the amount infected in a population. Is there a point where imperfect

vaccines, combined with certain conventional methods, are just as effective as permanent

vaccines? Such cost benefit analysis is well beyond the scope of this paper, but it is exactly what

public health officials may consider in responding to pandemics and epidemics. Depending on

the results, the equivalences found above may be skewed in favor of certain imperfect vaccines

over others.
 Wang 29

5.1) Other methods for malaria

Jamie Griffin, in “Reducing Plasmodium falciparum Malaria Transmission in Africa,”

shows that through a combination of indoor insecticide spraying, long-lasting insecticide nets,

and “mass screening and treatment,” the public can reduce malaria transmission considerably.

In particular, a stochastic model of these three factors reduced the parasite prevalence to 1%

given settings in Africa over 25 years (Griffin, 2010). Assuming such results can be reasonably

reproduced in real, the urgency of imperfect vaccines may be reduced. Resources could be

diverted to permanent vaccines that could reach the last 1% instead of people in general.

5.2) Other methods for HIV

Social attitudes and education with respect to safety and physical contact can be just as

effective as a vaccine. Early and effective HIV testing and screening can reduce the transmission

rate, indirectly reducing the infection percentage rate variable above. At the same time,

antiretroviral therapies can lengthen lifespans for the already infected (not a variable

considered above), but similar to other drug-based approaches drug resistance will continue to

be an issue (Klimas, 2008).

5.3) Applications for public health authorities

From all this, this project hopes to give more fine-tuned data for public health

authorities with respect to researching and administrating responses to epidemics, from

malaria to beyond. In particular, by determining which types of vaccines are more effective

given the characteristics of certain diseases (malaria in this case), it can help authorities

determine placement of vaccines, which vaccines to focus on given the current status of

infections and other factors. At the very least, this model will provide another metric by which
 Wang 30

to evaluate strategies to contain diseases. There may also purely physical methods

(quarantining) that sidestep the expensive research necessary for vaccines, and may serve as

yet another alternative. After all, why use a needle when soap will do?

5.4) Limitations of this model

Prior to actual testing, it became clear that because of the multiple variables and highly

flexible platform for this project, it is very possible to assume the project to a desired

conclusion. In other words, there are enough internal parameters in addition to the explicit

inputs that the experiment can over-fit the scenario and essentially produce data that is too

artificial and not representative of imperfect vaccines. The key is to generalize the analysis as

much as possible so as to not be so dependent on the specific implementation of McLean’s

scenario. This is the reason for the focus on relative versus absolute results.

This project attempted to do so by comparing infection percentage paths and time to

eradication near the boundaries of eradiation. There was no shortage of data or results; in fact,

there are many more combinations and base case scenarios that may yield completely different

results. This tipping point chosen for this experiment is not unique – changes in the non-key

variables result in many more. The one chosen was simply the closets matching one to

McLean’s scenario. There are many opportunities for further investigation even within the

current model.

5.5) Later study

The time differential between an outbreak and introduction of a vaccine can be

modeled and analyzed for effectiveness. Perhaps after a certain point in the outbreak, is it
 Wang 31

better to go with permanent but less widely compatible vaccines rather than temporary

vaccines that are widely compatible with patients?

Another part of the simulation to study can be to test different types of infections.

Whereas the first part changed the effectiveness of vaccines, there are hundreds of diseases

with enough literature to fit this model to. The original diseases here are HIV (from McLean)

and malaria (Gandon), but they were very loosely followed in order to get meaningful results.

Indeed, Tom Smith’s critique of Gandon’s evolutionary model demonstrates that competition

between different strains/versions of a disease is difficult to model – what happens if another

parasite attempts to infect an already infected patient?

6) Conclusion

Using multi-agent models of imperfect vaccinations, this project both reconfirmed and

extended the work of McLean and Gandon. By analyzing both the results (mortality percentage)

with different types of imperfect vaccines and the path taken to such results, this project was

able to rank the relative importance of duration, take and degree. Most importantly, this agent-

based model demonstrated the highly sensitive-nature of such models to starting conditions

and assumptions. Although this model and other models does give public health authorities a

tool to evaluate imperfect vaccines, the specific recommendations and interpretations of these

models depend just as much on take, degree and duration as the infection probability and

many other factors. While this sensitivity and lack of robustness does weaken the specificity of

the model. The dominance of duration and comparable effects of take and degree are general

enough to be directly useful to the public. (I affirm the Duke Community Standard)
 Wang 32

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