MATHS PORTFOLIO TYPE II

MODELLING THE COURSE OF A VIRUS AND ITS TREATMENT

INTRODUCTION
The portfolio tries to model the course of replication of a certain type of virus and how it can be treated.

Modeling infection 1
Consider n number of viral particles entering the body of human 1, in about 4 hours the number of viral particles would be 2n. Now consider human 2 with 2n viral particles entering the body, after 4 hours the number of viral particles would be 4n. Another human being human 3 is infected by 4n viral particles, after 4 hours the number of viral particles would be 8n. Supposing that the human beings above are clones and are kept at exactly the same conditions, it is noted that the number of viral particles doubles after 4 hours, quadruples after 8 hours and is 12 times after 12 hours. Table 1 below shows number of viral particles against time in hours expected. TABLE 1 Time in hours
0 4 8 12 16 20 24 28 32 10000 20000 40000 80000 160000 320000 640000 128000 0 320000

number of particles

Another table shown below is of t against lnn where t is time in hours and n is the number of viral particles. TABLE 2 T 0 4 8 12 16 20 24 28 32 Ln n 9.210340372 9.903487553 10.59663473 11.28979191 11.98292909 12.67607627 13.36922346 14.06237064 14.97866137

The graph below is that of the above data points from table 2.

The gradient of this line is 14.97866137-9.21034037232-0=ln3200000ln1000032=ln3232=0.108304247 The vertical line intercept is ln 10 000 =9.210340372 The equation of the line is therefore ln n= ln3232t + ln 10 000 And when simplifying we get lnn=ln(32132t10 000) This implies that n=(32132t10 000) which is our model in this case. The model definitely works for t=0 as 32132010 000=110 000=10 000. For t=4 we have that 32132410 000= 15422.10825

Oops! The model does not work in this case. The problem was found to be in 32 that raises 132t to a power. I will then modify this. Since we observed that n=a132t10 000 then the problem is to find a, by substituting any of the data points from table 1 we can find a. When substituting (4, 20 000) we get 20 000=a132410 000 We then divide both sides by 10 000 to get 2=a1324 When simplifying further we get that 2=a18 To solve for a we raise both sides to the power 8 and we have 28=a88 and therefore a= 28=256. The model is therefore n=(256132t10 000) and we simplify this further to get that n=(2832t10 000) which is equivalent to n=(2t410
000)

I will then check if the model works for t= 20, 24 and 28. For t= 20 we have that n=(220410 000)= 320 000 this is the same as the expected value shown on table 1. For t= 24 we have that n=(2t410 000= 640 000 this is also consistent with the expected value shown on table 1. For t= 28 we have that n=(228410 000= 1280 000 which is also consistent with the expected value shown on table 1. The model is therefore working correctly.

Below is a graph of the model:

When there are about 1 million viral particles in the body, the immune system starts to respond. From the graph above when the

number of viral particles is 1 million after approximately 26 hours. A more precise calculation is shown below: Since n=(2t410 000) Then 1000000=(2t410 000) Dividing both sides by 10 000 we have 100000010 000=2t4 This simplifies to 100=2t4 Taking natural logarithm both sides we have ln(100)=ln2t4 This simplifies to ln(100)= t4ln2 Solving for t we have that t= (ln100 ln2) 4= 26.57542476 hours This is approximately 26 hours and35 minutes. The bodys immune system would then begin to respond after 26 hours 35 minutes.

2
How long would it take the patient to die when the immune system has started responding but then there is no medication? The model below will deal with this task. The rise in temperature lowers the rate at which the virus replicates from 200% to 160%. This means that instead of doubling, the virus multiplies by a factor of 1.6 every 4 hours. The immune system removes 50 000 virus particles per hour. The model from number 1 is n=2t410 000 where 10 000 is the initial number of viral particles and 2 is the rate of replication. Suppose the viral particles just replicate by 1.6 without any elimination where the initial number of viral particles is 106, then the model would look as the one in part one but with this little modification as shown: n=1.6t4106. But we are given that the immune system removes 50 000 viral particles every hour, to account for that we carry the steps below:

We first look at t=1, we would have the number of viral particles after the immune system has removed some viral particles being: n=1.614106-50 000=1074682.65 For t=2, we would have that n=1074682.651.614-50 000=1158676.932 For t=3 we have that n=1158676.9321.614-50 000=1253143.842 For t=4 we have that n= 1253143.8421.614-50 000=1359389.138 I will then use the above results to account for a general model that would accommodate both the rate of replication and elimination. At t=1 we have that n=1.614106-50 000 At t=2 we have that n=(1.614106-50 000)1.614-50 000, At t=3 we have that n=((1.614106-50 000)1.614-50 000))1.614-50 000 At t=4 we have n=(((1.614106-50 000)1.614-50 000))1.614-50 000)1.614-50 000, For simplicity I will let k=1.614, y= 106, and z=50 000. Then for t=1 we have n=ky z At t=2 we would have n=(ky z)k z= k2y kz z which simplifies to n= k2y z(k +1) At t=3 we have n=(k2y kz z)k z= k3y k2z kz z, which is further simplified to get the result n= k3y z( k2 + k + 1) At t=4 we have that n= (k3y k2z kz z)k z= k4y k3z k2z kz z which when simplified reduces to n= k4y z(k3 + k2 + k + 1) From the above results we notice that the power of k which is multiplied by y equals the value of t and that the number of terms underlined equal the value of t. it is also noticed that the terms underlined follow a geometric sequence. I will then write the model using these observations: Kty z(kt-1+kt-2+kt-3+k+1), and this can also be rewritten as follows: Kty z(1+k+k2+k3kt-2+kt-1)

We then rewrite the series in the bracket using the geometric series sum formula
sn=u1(rn-1)r-1 where u1 is the first term, r is the common ratio and n

is the number of terms. The model will be n= Kty z(1(kt-1)k-1) We then re introduce the terms k, y and z into the model: We have that the model is n= 1.6t4 106 50 000(1.6t4 -1)1.614-1 I will then test the model to see if it is working correctly for t=1, t=2 and t=3. When t=1, n= 1.614 106 50 000(1.614 -1)1.614-1= 1074682.65, and this is the same as the expected value. When t=2, n=1.624 106 50 000(1.624 -1)1.614-1=1158676.932, which is consistent with the expected value of n. When t=3 n=1.634 106 50 000(1.634 -1)1.614-1=1253143.842, and this is consistent with the expected value of n for this value of t. I will then use model together with the answer from number 1 to get the time when the person dies: Using this model we have that 1012=1.6t4 106 50 000(1.6t4 -1)1.6141, We divide both sides by 50 000 to get 2107=201.6t4-(1.6t4 -1)1.614-1 We then multiply 201.6t4 by (1.614 -1)1.614-1 to get 2107=201.6t4(1.614 -1)1.614-1-(1.6t4 -1)1.614-1. We then open the brackets to get 2107= 201.6t41.614 -201.6t41.6t4+11.614-1, and then collect like terms and simplify to get: 2107= 1.6t4(201.614 -20-1)+11.614-1 I then multiply both sides by (1.614-1)to get: (2107)(1.614-1)= 1.6t4(201.614 -20-1)+1 [subtract 1 both sides] (2107)(1.614-1)-1=1.6t4(201.614 -20-1)[divide both sides by201.61420-1

And we get 2107(1.614-1)-1(201.614 -20-1)=1.6t4, we take natural logarithms both sides to get:
ln2107(1.614-1)-1(201.614 -20-1)=t4ln1.6, [multiply both sides by 4

and divide both sides by ln1.6] Then t= 4ln2107(1.614-1)-1(201.614 -20-1)1ln1.6=121.9397738 hours We add this value to 26.57542476 we got earlier in part 1 to get 121.9397738+26.57542476=148.5151986 hours. The person will therefore die after 148.5151986 hours if the virus is left untreated. The graph of the model is shown below:

3.
An antivirus can be administered as soon as the patient seeks medical attention. Together with the immune system, the antivirus removes 1.2 million viral particles per hour. I will use the model in number 2 to find why the antivirus must be taken before the number of viral particles reach between 9 to 10 million.

I will first modify the model and then solve a system of equations using technology. The model in number 2 is n= 1.6t4 106 50 000(1.6t4 -1)1.614-1, the 50 000 is the rate of elimination and the initial value is 106. We start by finding the initial value of viral particles for which n is constant, let this be y and the model would be n= 1.6t4 y 1.2106(1.6t4 -1)1.614-1. When t=x n would be the same as when t=x+1, x+2,x+3 We then create the following system of equations and solve for x and y using the equation solver from Microsoft math to get:

Solution array { y9624434.48495838, x0} The initial number of viral particles that should make n to be constant is 9624434.48495838 particles. I will then verify this result by multiplying by 1.60.25 and then subtracting 1.2106, I will do this three times so that I verify this result. 9624434.484958381.60.25 1.2106=9624434.485, is approximately the same result 9624434.4851.60.25 1.2106=9624434.485, is also approximately the same result 9624434.4851.60.25 1.2106=9624434.485, which is also the same result, therefore 9624434.485 particles is the critical value of the number of viral particles, if the initial number of viral particles is above this critical value when the patient takes medication, the patient will eventually die but if the number of viral particles is below this critical value the medication will eventually remove all the viral particles and the patient will reach a full recovery. But if

the number of viral particles is equal to the critical value the patient will not make full recovery instead the patient will suffer from fever and very high temperatures as we are told thats how the immune system would respond, and who knows the patient might eventually die of fever or high temperatures. 4. The antiviral medication is difficult for the body to adapt to, so it must initially be carefully introduced to the body over a four-hour time period of continuous intravenous dosing. This means the same amount of medication is entering the body at any given time during the first 4 hours. At the same time, however, the kidneys eliminate about 2.5 % of this medication per hour. The doctor has calculated that the patient needs at least 90 micrograms of medication to begin and maintain the rate of elimination of 1.2 million viral particles per hour. Let the medication that is needed for the 1 hour period be M, then at t =0 M is put into the patient. Therefore the medication follows the pattern shown in the table below: TABLE 3 Time/hours 0 1 2 Medication 0 M 0.025M (M 0.025M + M) 0.025(M 0.025M+M)
2M - 30.025M+ 0.0252M

(2M - 30.025M+ 0.0252M +M) 0.025(2M - 30.025M+ 0.0252M +M)

3M

-60.025M+40.0252M 0.0253M

(3M -60.025M+40.0252M 0.0253M+M) 0.025(3M -60.025M+40.0252M 0.0253M+M)

M(0.0254 -

50.0253+100.0252100.025+4)

For the four hour period the model was found to be M(0.0254 50.0253+100.0252-100.025+4), and we equate this to 90 to get : M(0.0254 - 50.0253+100.0252-100.025+4)=90, to solve for M we divide 90 by the number in the bracket and the calculator gives M=23.96056241 mg of medication.This is the amount that needs to be continuously given the patient during the 4 hour period. 5 In order to maintain a minimum of 90 micrograms within the patients body, at the time when the patient is taken of the intravenous phase there has to be an injection taken in immediately to avoid having micrograms of medication falling below 90. Therefore this will be (90 + D) where D is the Dosage. At the same time the kidneys are eliminating 2.5% of (90 + D) per hour and the medication should be at least 90mg 90mg after 4 hours. This is presented below: At t=1 we have that medication is (90 + D) 0.025(90 + D)=(10.025)(90+D) At t=2 we have that the medication is (1-0.025)(90+D) 0.025(10.025)(90+D) =(1-0.025)2(90+D) At t=3 we have that the medication is (1-0.025)2(90+D) 0.025(10.025)2(90+D) =(1-0.025)3(90+D) At t=4 we have that the medication is (1-0.025)3(90+D) 0.025(10.025)3(90+D) =(1-0.025)4(90+D) Therefore it is obvious that the medication at any given time after the intravenous phase is given by Mt=0.975t(90+D) To maintain at least 90mg of medication in the body the additional dosage must be:

90=0.9754(90+D), and we divide both sides by 0.9754 and then subtract 90 both sides to get that: D=900.9754-90=9.5919066mg, so an additional dosage of 9.5919066mg must be added so that the patient maintains at least 90mg in the body. 6 We found out from part1 of this portfolio that it takes 26.57542476 hours for the immune system to respond. From part 3 we found out that in order to make a full recovery the initial number of viral particles must be <9624434.485. What is the time then just before the viral particles reach 9624434.485? I will use the second model to find this time. Since 1.6t4 106 50 000(1.6t4 -1)1.614-1 as from part 2 of this portfolio then: 9624434.485<1.6t4 106 50 000(1.6t4 -1)1.614-1, we solve this using Microsoft maths:

Solution array {x23.270198299306} Then t must be less than 23.270198299306 hours. We add the value from part 1 with the 23.270198299306 hours we got to determine the last possible time from the onset of infection to start the regimen of medication. 23.270198299306 hours + 26.57542476 hours=49.84562306 hours. Then how long will it take to clear the viral particles from the patients system? I will then show a graph for the entire treatment regimen from the time treatment begins and this will allow me to find the time by which the number of viral particles reaches zero. From the spread sheet below, the following graph was drawn: Table 4 Time viral particles
0

96244 33

1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25

962443 3 962443 3 962443 3 962443 3 962443 3 962443 2 962443 2 962443 2 962443 2 962443 1 962443 1 962443 0 962443 0 962442 9 962442 9 962442 8 962442 7 962442 6 962442 5 962442 4 962442 3 962442 1 962442 0 962441 8 962441 6

26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50

962441 3 962441 1 962440 8 962440 4 962440 1 962439 6 962439 2 962438 6 962438 0 962437 3 962436 6 962435 7 962434 8 962433 7 962432 5 962431 1 962429 5 962427 8 962425 9 962423 7 962421 2 962418 4 962415 3 962411 8 962407 8

51 52 53 54 55 56 57 58 59 60 61 62 63 64 65 66 67 68 69 70 71 72 73 74 75

962403 4 962398 4 962392 8 962386 5 962379 4 962371 4 962362 4 962352 3 962340 9 962328 2 962313 8 962297 6 962279 4 962259 0 962237 0 962210 1 962181 0 962148 3 962111 5 962070 1 962023 6 961971 2 961912 4 961846 1 961771 7

76 77 78 79 80 81 82 83 84 85 86 87 88 89 90 91 92 93 94 95 96 97 98 99 100

961687 9 961593 7 961487 7 961368 6 961234 6 961083 8 960914 3 960723 7 960509 2 960268 1 959996 9 959691 8 959348 7 958962 9 958528 9 958040 8 957491 9 956874 5 956180 2 955399 3 954521 0 953533 2 952422 2 951172 7 949767 5

101 102 103 104 105 106 107 108 109 110 111 112 113 114 115 116 117 118 119 120 121 122 123 124 125

948186 2 946409 5 944410 3 942161 9 939633 1 936789 1 933590 4 929992 9 925946 9 921396 5 916278 6 910522 6 904049 0 896768 3 888579 7 879370 2 869012 4 857363 1 844261 4 829526 2 812953 7 794314 9 773352 2 749775 8 723259 9

126 127 128 129 130 131 132 133 134 135 136 137

693437 8 659897 5 622175 3 579749 7 532034 5 478369 9 418014 4 350133 5 273789 1 187925 8 913569 .4 172524

From the above graph when the number of viral particles is zero, the time in hours is approximately 136.5. The graph that summarizes all the models is shown below:

ANALYZING MODELS PART 1 MODEL When modeling the initial phase of the illness we assumed that all the human body response will be the same for all human beings but this is not actually true in reality, the immune systems of people may differ according to age and the diet that they take daily. The portfolio sheet mentioned that in about 4 hours the number of viral particles has doubled, the number of viral particles might have doubled even before the 4 hours or after four hours but in this model we assume it doubles every 4 hours. When modeling part 1 of this portfolio, the initial attempt gave the wrong model and this was because of the unreliability of the graphical analysis made, the

graph needed many set of values to give exactly the expected values for the modeling but few readings were used on by the spread sheet. Even though the initial model does not give us a clue into the second phase of the illness it allows us to determine the time by which a patient contracted the virus and we can therefore find out if medication is possible and hence calculate how much medication is needed for the patient. I did not prove the model because I only wanted to find a model that works for only a small number of readings. The results in this model are not so reliable since people might respond differently to the virus in the body and also due to the uncertainty of when exactly do viral particles double. The model is very effective in studying the rate at which a certain virus replicate and it makes it easier for me to come up with the best dosage model that can be used to clear out the viral particles from the patients system within a certain time. This model can also be modified used to determine how long it will take before the patient dies if the viral particles are left untreated. The model continues to assume that once a person is infected he will never get any viral particles from the outside environment; this is unlikely as at any time a person can get infected by yet another viral particle, which in any case will force the model to be altered. The model also does not specify which viral particle this is as this could have an effect on the study. This makes it difficult to apply this model in a real life. The model also assumes that the viral particles are not or will not be killed by the strain specific immune responses along the process. PART 2 MODEL We are told from the portfolio sheet that the immune system can only eliminate these particular viral particles at the rate of about 50 000 viral particles per hour but this does not necessarily mean it really does; it only has the ability to eliminate that amount but other factors in the body might affect the value. We had to assume that the immune systems of people are the same and will all eliminate that amount of viral particles in 4 hours. The model assumes that the effects of the immune response remain constant over time period of interest. While the assumption of constancy may be justified for a short-term period it may not be the case in the long-term. This model further assumes that once the person is infected he will not recover but in reality thats not the

case as the viral particles may be tampered by the healthy diet the person consumes. This model is very effective in showing the action of the immune system against the viral replication. This model can also be used to find how strong the virus is as compared to the rate at which it is eliminated and the rate at which it replicates. The model can also be used to estimate the last possible time the medication would still be effective if administered and the time in which it will be useless to administer the medication. PART 3 MODELS All the models in this section were based on assumptions made in part 1 and 2 of this portfolio. It is assumed that a person sees a doctor for treatment when they have observed fever from the time beginning when there are 1milion viral particles in their body. The models provided a valid reason why medication must be administered before the number of viral particles reached 9 million and they were able to determine the time by which the person would die if medication is not administered at the proper time. We cannot really rely on these models even though they give us some clue mainly because they are based on very little data. PART 4 MODEL The model is working correctly apart from the fact that it assumes that the rate of elimination of viral particles is the same for all people, it also assumes that all people need the same medication while in real life thats not the case. PART 5 MODEL The model here was an inequality which was derived using the principles of mathematical logic. We assumed that all people will respond the same to medication and will need the same medication. The answer to the model which was an inequality was therefore sensible apart from the fact that peoples kidneys wont behave the same to medication. The dosage that might be needed for a person with kidney problems might be less and putting too much medication that is needed in the body might harm our patient. The other assumption was that 90mg of medication is already in the body but that might differ according to peoples kidneys rate of elimination.

PART 6 MODELS In part 6 we used the models that we already have to calculate the last possible time from the onset of infection to start the regimen of medication and how long it will take to clear the viral particles from the patients system. This might mislead a bit because the medication might not work the same depending on peoples immune systems and kidneys response to medication. PART 7 APPLYING THE MODELS The immune system of an adult and a child are different, we will therefore have to accompany great changes for the models to work. For the initial phase of the illness the model is n=(2t410 000) We may multiply the model by a conversion factor where the conversion factor is the ratio of the strength of the immune system of a child to that of an adult, the model will therefore look like this
n=(2tRt410 000) where Rc is the ratio of the strength of the immune

system of a child to that of an adult. Rc may be expressed as a function of age so that it works more efficiently. The second model is n=1.6t4 106 50 000(1.6t4 -1)1.614-1and this may also be multiplied by Rc where Rc is expressed as a function of age, the model would be
1.6tRt4 106 50 000(1.6tRt4 -1)1.614-1

The other model in part 3 could be modified with the multiplication of the conversion factor such that the calculation of the critical value accompanies the Rt. In part 4 of the portfolio we may modify the model by multiplying the model by Rt and then multiplying again by the strength of the kidneys as a function of age Kt. The dosage in part 5 will differ from that of an adult and this will all result from applying all this models. In real life we know that the immune system of a child is much stronger that of an adult as studies reveal that the strength of the immune system decreases with age. The CD4 count of a child will therefore be more than that of an adult. The immune system of a child responds faster than that of an adult because the child has been less exposed to many diseases than an

adult, therefore for the first model where the person is infected with 10 000 viral particles I expect the childs immune system to respond when the viral particles are 500 000 and the time that it takes for the immune system of a child to respond would be: 0.5106=(2t410 000) and we take natural logarithms to base e both sides, multiply both sides by 4 and then divide both sides by ln2 to get t=4ln50ln2=22.57542476 hours. from here we can calculate the conversion factor Rc which is 22.5754247626.5742476=0.849485002. For the second model where the factor of viral replication is 1.6 the temperatures affects the viral particles the same way for a child and an adult, the same result will hold for both an adult and a child apart from the fact that the initial number of viral particles when the immune system starts to respond would be different and Rt would also make the times of death different. The strength of the kidneys of a child is weaker than that of an adult and the medication removed by a childs kidneys will be less than that removed by an adults kidneys. The dosage D added intravenously will thebe half of that of an adult as it is in real life cases and this would be 11.98028121mg. I expect the rate of viral removal by a childs kidneys to be sub-exponentially halve of that of an adult. The additional dosage in number 5 will therefore be less than that of an adult by about (10-e2)mg and would therefore be about 6.98mg.