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Radzuan Razali -et al., IJSIT, 2013, 2(5),359-366

ESTIMATION OF THE REPRODUCTION NUMBER OF THE NOVEL
INFLUENZA A, H1N1 IN MALAYSIA
Radzuan Razali* and SamsulAriffin Abdul Karim
Fundamental and Applied Sciences Department, UniversitiTeknologiPetronas, Bandar Seri Iskandar, 31750
Tronoh, Perak DarulRidzuan, Malaysia.

ABSTRACT

In June 2009, the World Health Organization (WHO) confirmed that the novel influenza A, H1N1 as a
pandemic. After six months, as of December 29, 2009, it was reported by WHO that more than 208 countries
and territories were affected by the pandemic accounting for about 150,000 infected cases and at least 11,516
death. In Malaysia, during the first wave, there are about 14,912 cases were reported from May, 15, 2009
until June, 4, 2010 and a total number of 88 deaths were recorded across the country in 2010. The aim of this
study is to assess the transmissibility of this pandemic in Malaysia by estimating the basic reproduction
number, Ro, which is the average number of secondary cases generated by a single primary case. The value of
Ro is a summary measure of the transmission potential in a given epidemic setting and has been estimated to
range from 1.4 – 1.6 in Mexico, from 2.0 – 2.6 in Japan, 1.96 in New Zealand and 1.68 in China for this current
pandemic.

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Radzuan Razali -et al., IJSIT, 2013, 2(5),359-366

INTRODUCTION
In June 2009, WHO raised the influenza pandemic alert level from phase 5 to phase 6, declaring that
the influenza A, H1N1 had reached pandemic levels. As of December 29, 2009, it was reported by WHO that
more than 208 countries and territories were affected by the pandemic accounting for about 150,000 infected
cases and at least 11,516 death [1]. In Malaysia, during the first wave, there are about 14,912 cases were
reported from May, 15, 2009 until June, 4, 2010 and a total number of 88 deaths were recorded across the
country in 2010[2].
The H1N1 pandemic calls for action and the various mathematical models have been constructed to
study the spread and control of H1N1. The transmissibility of the disease can be shown quantitatively by
calculating basic reproduction number which is the average number of individuals directly infected by a
primary infected case during infectious period without any preventive measure during the epidemic and
when the infected person enters a totally susceptible population. It is a key concept in epidemiology and is
inarguably one of the foremost and most valuable ideas that mathematical thinking has brought to epidemic
theory [3]. This index is useful in assessing the necessary preventive measures and needs assessment for
prevention and prediction for future. If Ro less than 1, it shows that the disease will eventually die out.
However, if Ro is equal to 1, the disease is endemic and when Ro is greater than 1, then there will be an

epidemic and increasing number of infected persons [4]. This threshold behavior is the most
important and useful aspect of the Ro concept. In an endemic infection, the control measures and at
what magnitude, would be most effective in reducing Ro below one can be determined and this will
provide important guidance for public health initiatives [5].
The estimation of the basic reproduction number Ro in Mexico is in the range of 1.4 – 1.6 [6]. For
Japan, the reproduction number Ro was estimated in the range 2.0 – 2.6[7]; 1.96 for New Zealand [8]; and
1.68 in China [9]. The main aim of this study is to calculate and determine the estimation of the reproduction
number, Ro for Malaysia.

MATERIAL AND METHODS
During the first wave of influenza A, H1N1, 5,496 cases were reported between July, 26, 2009 and
August 20, 2009 and a total number of 77 deaths in Malaysia as in Table 1 and the Figure 1 and Figure 2 [10a.
10b. 10c.]. All patients were referred to public and private hospital.

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Radzuan Razali -et al., IJSIT, 2013, 2(5),359-366

Confirmed Cases in Malaysia

Death Cases in Malaysia

26/7/2009

1124

26/7/2009

2

27/7/2009

1219

27/7/2009

3

2/8/2009

1429

2/8/2009

6

3/8/2009

1460

3/8/2009

8

5/8/2009

1476

5/8/2009

12

6/8/2009

1492

6/8/2009

14

10/8/2009

1983

10/8/2009

32

11/8/2009

2250

11/8/2009

38

14/8/2009

2253

14/8/2009

56

16/8/2009

3857

16/8/2009

62

17/8/2009

4225

17/8/2009

64

20/8/2009

5496

20/8/2009

68

Table 1: The number of confirmed and death cases in Malaysia

Figure 1: Confirmed cases in Malaysia

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Radzuan Razali -et al., IJSIT, 2013, 2(5),359-366

Figure 2: Death cases in Malaysia
During that time the study was conducted to develop a proposed mathematical modeling of this
disease using SEIR model [11], where S is susceptible, E is exposed, I is infectious and R is recovered. The
least-square fitting procedure in MATLAB using the build-in routine cftoolsin the optimization toolbox is
implemented to the data and model can be estimated. Two models were fitted to the data for each case as in
the Table 2 and Table 3.

Boltzmann Model :
f (x)






2

3  2.0421 , and x0  12.441

The coefficient
of determination,

f (x)1exp(2 x)3exp(4 x)

1

1exp(( x1x0 ) / 
 1  10744 ,  2  1214.1 ,

Parameters
estimation

R

1

Double Exponent Model:

)
3

 1  1088, 

2

0.03448 ,

3  120.4 , and 4 0.3075

0.977

0.976

2

Table 2: The models for confirmed cases in Malaysia

Based on Table 2, because the R2 for Boltzmann model is greater than double exponent model then
the fitting model for confirmed cases is a Boltzmann model as in the figure 3.

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Radzuan Razali -et al., IJSIT, 2013, 2(5),359-366

Boltzmann Model :
f (x)1

Rational Function Model:

21
1exp(( x1x0 ) / 3 )

1 x   2 x
3

f (x)

2

 3 x   4

x 2  1 x 

2

 1  69.521 ,  2  3.175 ,

The coefficient of
determination, R

 1  1.582 ,  2 12.69 ,

3  1.235 and x07.591

Parameters
estimation

3  51.41 , 4  188.8 ,
 1 21.3 and  2 156.3

0.999

0.992

2

Table 3: The models for death cases in Malaysia

Figure 3: Fitting model for confirmed cases in Malaysia
Where x axis is the time and f(x) or y axis is the confirmed cases estimation

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Radzuan Razali -et al., IJSIT, 2013, 2(5),359-366
While based on Table 4, the fitting model for the death cases is a rational function since the R2 for
Boltzmann model is greater than rational function as shown in the figure 4.

Figure 4: Fitting model for death cases in Malaysia
Where x axis is the time and f(x) or y axis is the death cases estimation.
The data from this study was use in estimation of reproduction number. There are different methods
to calculate the basic reproduction number which the simplest method using SIR model is given by [12]:

R o




(1)

where
is the probability of the disease transmission from an infected person to a healthy person
and is the recovery rate or one divided by average period of infection.
The second method for calculation of Ro using SEIR model is given by [13],

Ro 




(2)

whereis the probability of the disease transmission from an infected person to a healthy person,
is the recovery rate or one divided by average period of infection and is the mortality rate which is
calculated by the following formula [13]:

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Radzuan Razali -et al., IJSIT, 2013, 2(5),359-366

WhereCFP is the mean case fatality proportion.
The third method for calculation of Ro using the complex SEIR model is given by [13],

In our previous study, we proposed the model SEIR as our appropriate mathematical model for
influenza A, H1N1 in Malaysia. So we will use the equation (2) and (4) to estimate the basic reproduction of
the influenza A, H1N1 in Malaysia.

RESULT AND DISCUSSION
According to the data obtained in the first wave of influenza A, H1N1 in Malaysia, it is founded that
the probability of the disease transmission from an infected person to a healthy person,  is 0.35. The
recovery rate or one divided by average period of infection,  is 1/6 days, and the mean case fatality
proportion (CFP) is 0.003 hence the mortality rate, is 0.0005.
From equation (2), the basic reproduction number, Ro is 2.1. However if we use equation (4), the
basic reproduction number, Ro is 3.1. So the range of basic reproduction number, Ro forMalaysia can be
concluded is between 2.1 and 3.1. A value of Ro is determined which minimized the sum of squares
differences between the simulated and observed data. The median estimate for Ro is 2.6. It is interesting to
note that in this study, one of the most careful and a recent investigation of Ro in the literature, the result is
relied on a very simple simulation and least squares fitting. Based on theory of reproduction number, if Ro >1,
then the pathogen is able to invade the susceptible population. This threshold behavior is the most important
and useful aspect of the Ro concept to determine which control measures and at what magnitude would be
most effective in reducing Ro < 1, and providing important guidance for public health initiatives.

REFERENCES
1.

World Health Organization (WHO).(2009). Global surveillance during an influenza pandemic. Version
1. Updated April 2009. Available at:
http://www.who.int.csr/disease/swineflu/global_pandemic_influenza_surveilance_apr2009.pdf

2.

Ministry of Health (MOH). (2010). Public Health Crisis Management: The Malaysian Scenario. Disease
Control Division, 17 June 2010.

IJSIT (www.ijsit.com), Volume 2, Issue 5, September-October 2013

365
Radzuan Razali -et al., IJSIT, 2013, 2(5),359-366
3.

Heesterbeek, J.A.P and K. Dietz (1996). The concept of Ro in epidemic theory. StatisticaNeerlandica
50:89-110.

4.

Giesecke J. Modern Infectious disease epidemiology. Arnold Company. 2nd. Edition 2002; page: 119132.

5.

Heffernan J.M , Smith R.J, Wahl L.M. (2005).Perspectives on the basic reproduction ratio. Journal
Royal Society Interface, 2(4): page: 281-293.

6.

Fraser C., et al.:(2009): Pandemic potential of a strain of influenza A (H1N1): Early findings. Science,
324: 1557-1561.

7.

Nishiura H, Castillo-Chaves C, Safan M, and Chowell G (2009): Transmission potential of the new
influenza A (H1N1) virus and its age-specificity in Japan. Eurosurveillance, 14: page: 11-15.

8.

Hiroshi N, Wilson N, and Baker M.G. (2009). Estimating the reproduction number of the novel
influenza A virus (H1N1) in a southern Hemisphere setting: preliminary estimate in New Zealand.
Journal New Zealand Medical Association, 122: page: 73-77

9.

Zhen Jin et al. (2011). Modeling and analysis of influenza A(H1N1) on networks. Biomedical Central
Ltd. 11: S1-S9

10. H1N1 situation in Malaysia, (2009).Chronicles: bengodomon.com
11. H1N1 situation in Malaysia (Part 2), (2009).Chronicles: bengodomon.com
12. H1N1 situation in Malaysia (Part 3), (2009).Chronicles: bengodomon.com
13. Karim S.A.A. and Razali, R (2011). Mathematical modeling for Influenza A, H1N1 in Malaysia. Journal
of Applied Sciences, Vol. 11, No. 7, page: 1457-1480.
14. Favier C et al. (2006). Early determination of the reproduction number for vector borne diseases: the
case of dengue in Brazil. Trop. Med. Int. Health, 11: page: 332-340.
15. Chowel G, Nishiura H, Bettencourt L.M. (2009).Comparative estimation of the reproduction number
for pandemic influenza from daily case notification data. Journal Royal Society Interface, 4: page:
155-166.

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ESTIMATION OF THE REPRODUCTION NUMBER OF THE NOVEL INFLUENZA A, H1N1 IN MALAYSIA

  • 1. Radzuan Razali -et al., IJSIT, 2013, 2(5),359-366 ESTIMATION OF THE REPRODUCTION NUMBER OF THE NOVEL INFLUENZA A, H1N1 IN MALAYSIA Radzuan Razali* and SamsulAriffin Abdul Karim Fundamental and Applied Sciences Department, UniversitiTeknologiPetronas, Bandar Seri Iskandar, 31750 Tronoh, Perak DarulRidzuan, Malaysia. ABSTRACT In June 2009, the World Health Organization (WHO) confirmed that the novel influenza A, H1N1 as a pandemic. After six months, as of December 29, 2009, it was reported by WHO that more than 208 countries and territories were affected by the pandemic accounting for about 150,000 infected cases and at least 11,516 death. In Malaysia, during the first wave, there are about 14,912 cases were reported from May, 15, 2009 until June, 4, 2010 and a total number of 88 deaths were recorded across the country in 2010. The aim of this study is to assess the transmissibility of this pandemic in Malaysia by estimating the basic reproduction number, Ro, which is the average number of secondary cases generated by a single primary case. The value of Ro is a summary measure of the transmission potential in a given epidemic setting and has been estimated to range from 1.4 – 1.6 in Mexico, from 2.0 – 2.6 in Japan, 1.96 in New Zealand and 1.68 in China for this current pandemic. IJSIT (www.ijsit.com), Volume 2, Issue 5, September-October 2013 359
  • 2. Radzuan Razali -et al., IJSIT, 2013, 2(5),359-366 INTRODUCTION In June 2009, WHO raised the influenza pandemic alert level from phase 5 to phase 6, declaring that the influenza A, H1N1 had reached pandemic levels. As of December 29, 2009, it was reported by WHO that more than 208 countries and territories were affected by the pandemic accounting for about 150,000 infected cases and at least 11,516 death [1]. In Malaysia, during the first wave, there are about 14,912 cases were reported from May, 15, 2009 until June, 4, 2010 and a total number of 88 deaths were recorded across the country in 2010[2]. The H1N1 pandemic calls for action and the various mathematical models have been constructed to study the spread and control of H1N1. The transmissibility of the disease can be shown quantitatively by calculating basic reproduction number which is the average number of individuals directly infected by a primary infected case during infectious period without any preventive measure during the epidemic and when the infected person enters a totally susceptible population. It is a key concept in epidemiology and is inarguably one of the foremost and most valuable ideas that mathematical thinking has brought to epidemic theory [3]. This index is useful in assessing the necessary preventive measures and needs assessment for prevention and prediction for future. If Ro less than 1, it shows that the disease will eventually die out. However, if Ro is equal to 1, the disease is endemic and when Ro is greater than 1, then there will be an epidemic and increasing number of infected persons [4]. This threshold behavior is the most important and useful aspect of the Ro concept. In an endemic infection, the control measures and at what magnitude, would be most effective in reducing Ro below one can be determined and this will provide important guidance for public health initiatives [5]. The estimation of the basic reproduction number Ro in Mexico is in the range of 1.4 – 1.6 [6]. For Japan, the reproduction number Ro was estimated in the range 2.0 – 2.6[7]; 1.96 for New Zealand [8]; and 1.68 in China [9]. The main aim of this study is to calculate and determine the estimation of the reproduction number, Ro for Malaysia. MATERIAL AND METHODS During the first wave of influenza A, H1N1, 5,496 cases were reported between July, 26, 2009 and August 20, 2009 and a total number of 77 deaths in Malaysia as in Table 1 and the Figure 1 and Figure 2 [10a. 10b. 10c.]. All patients were referred to public and private hospital. IJSIT (www.ijsit.com), Volume 2, Issue 5, September-October 2013 360
  • 3. Radzuan Razali -et al., IJSIT, 2013, 2(5),359-366 Confirmed Cases in Malaysia Death Cases in Malaysia 26/7/2009 1124 26/7/2009 2 27/7/2009 1219 27/7/2009 3 2/8/2009 1429 2/8/2009 6 3/8/2009 1460 3/8/2009 8 5/8/2009 1476 5/8/2009 12 6/8/2009 1492 6/8/2009 14 10/8/2009 1983 10/8/2009 32 11/8/2009 2250 11/8/2009 38 14/8/2009 2253 14/8/2009 56 16/8/2009 3857 16/8/2009 62 17/8/2009 4225 17/8/2009 64 20/8/2009 5496 20/8/2009 68 Table 1: The number of confirmed and death cases in Malaysia Figure 1: Confirmed cases in Malaysia IJSIT (www.ijsit.com), Volume 2, Issue 5, September-October 2013 361
  • 4. Radzuan Razali -et al., IJSIT, 2013, 2(5),359-366 Figure 2: Death cases in Malaysia During that time the study was conducted to develop a proposed mathematical modeling of this disease using SEIR model [11], where S is susceptible, E is exposed, I is infectious and R is recovered. The least-square fitting procedure in MATLAB using the build-in routine cftoolsin the optimization toolbox is implemented to the data and model can be estimated. Two models were fitted to the data for each case as in the Table 2 and Table 3. Boltzmann Model : f (x)    2 3  2.0421 , and x0  12.441 The coefficient of determination, f (x)1exp(2 x)3exp(4 x) 1 1exp(( x1x0 ) /   1  10744 ,  2  1214.1 , Parameters estimation R 1 Double Exponent Model: ) 3  1  1088,  2 0.03448 , 3  120.4 , and 4 0.3075 0.977 0.976 2 Table 2: The models for confirmed cases in Malaysia Based on Table 2, because the R2 for Boltzmann model is greater than double exponent model then the fitting model for confirmed cases is a Boltzmann model as in the figure 3. IJSIT (www.ijsit.com), Volume 2, Issue 5, September-October 2013 362
  • 5. Radzuan Razali -et al., IJSIT, 2013, 2(5),359-366 Boltzmann Model : f (x)1 Rational Function Model: 21 1exp(( x1x0 ) / 3 ) 1 x   2 x 3 f (x) 2  3 x   4 x 2  1 x  2  1  69.521 ,  2  3.175 , The coefficient of determination, R  1  1.582 ,  2 12.69 , 3  1.235 and x07.591 Parameters estimation 3  51.41 , 4  188.8 ,  1 21.3 and  2 156.3 0.999 0.992 2 Table 3: The models for death cases in Malaysia Figure 3: Fitting model for confirmed cases in Malaysia Where x axis is the time and f(x) or y axis is the confirmed cases estimation IJSIT (www.ijsit.com), Volume 2, Issue 5, September-October 2013 363
  • 6. Radzuan Razali -et al., IJSIT, 2013, 2(5),359-366 While based on Table 4, the fitting model for the death cases is a rational function since the R2 for Boltzmann model is greater than rational function as shown in the figure 4. Figure 4: Fitting model for death cases in Malaysia Where x axis is the time and f(x) or y axis is the death cases estimation. The data from this study was use in estimation of reproduction number. There are different methods to calculate the basic reproduction number which the simplest method using SIR model is given by [12]: R o   (1) where is the probability of the disease transmission from an infected person to a healthy person and is the recovery rate or one divided by average period of infection. The second method for calculation of Ro using SEIR model is given by [13], Ro    (2) whereis the probability of the disease transmission from an infected person to a healthy person, is the recovery rate or one divided by average period of infection and is the mortality rate which is calculated by the following formula [13]: IJSIT (www.ijsit.com), Volume 2, Issue 5, September-October 2013 364
  • 7. Radzuan Razali -et al., IJSIT, 2013, 2(5),359-366 WhereCFP is the mean case fatality proportion. The third method for calculation of Ro using the complex SEIR model is given by [13], In our previous study, we proposed the model SEIR as our appropriate mathematical model for influenza A, H1N1 in Malaysia. So we will use the equation (2) and (4) to estimate the basic reproduction of the influenza A, H1N1 in Malaysia. RESULT AND DISCUSSION According to the data obtained in the first wave of influenza A, H1N1 in Malaysia, it is founded that the probability of the disease transmission from an infected person to a healthy person,  is 0.35. The recovery rate or one divided by average period of infection,  is 1/6 days, and the mean case fatality proportion (CFP) is 0.003 hence the mortality rate, is 0.0005. From equation (2), the basic reproduction number, Ro is 2.1. However if we use equation (4), the basic reproduction number, Ro is 3.1. So the range of basic reproduction number, Ro forMalaysia can be concluded is between 2.1 and 3.1. A value of Ro is determined which minimized the sum of squares differences between the simulated and observed data. The median estimate for Ro is 2.6. It is interesting to note that in this study, one of the most careful and a recent investigation of Ro in the literature, the result is relied on a very simple simulation and least squares fitting. Based on theory of reproduction number, if Ro >1, then the pathogen is able to invade the susceptible population. This threshold behavior is the most important and useful aspect of the Ro concept to determine which control measures and at what magnitude would be most effective in reducing Ro < 1, and providing important guidance for public health initiatives. REFERENCES 1. World Health Organization (WHO).(2009). Global surveillance during an influenza pandemic. Version 1. Updated April 2009. Available at: http://www.who.int.csr/disease/swineflu/global_pandemic_influenza_surveilance_apr2009.pdf 2. Ministry of Health (MOH). (2010). Public Health Crisis Management: The Malaysian Scenario. Disease Control Division, 17 June 2010. IJSIT (www.ijsit.com), Volume 2, Issue 5, September-October 2013 365
  • 8. Radzuan Razali -et al., IJSIT, 2013, 2(5),359-366 3. Heesterbeek, J.A.P and K. Dietz (1996). The concept of Ro in epidemic theory. StatisticaNeerlandica 50:89-110. 4. Giesecke J. Modern Infectious disease epidemiology. Arnold Company. 2nd. Edition 2002; page: 119132. 5. Heffernan J.M , Smith R.J, Wahl L.M. (2005).Perspectives on the basic reproduction ratio. Journal Royal Society Interface, 2(4): page: 281-293. 6. Fraser C., et al.:(2009): Pandemic potential of a strain of influenza A (H1N1): Early findings. Science, 324: 1557-1561. 7. Nishiura H, Castillo-Chaves C, Safan M, and Chowell G (2009): Transmission potential of the new influenza A (H1N1) virus and its age-specificity in Japan. Eurosurveillance, 14: page: 11-15. 8. Hiroshi N, Wilson N, and Baker M.G. (2009). Estimating the reproduction number of the novel influenza A virus (H1N1) in a southern Hemisphere setting: preliminary estimate in New Zealand. Journal New Zealand Medical Association, 122: page: 73-77 9. Zhen Jin et al. (2011). Modeling and analysis of influenza A(H1N1) on networks. Biomedical Central Ltd. 11: S1-S9 10. H1N1 situation in Malaysia, (2009).Chronicles: bengodomon.com 11. H1N1 situation in Malaysia (Part 2), (2009).Chronicles: bengodomon.com 12. H1N1 situation in Malaysia (Part 3), (2009).Chronicles: bengodomon.com 13. Karim S.A.A. and Razali, R (2011). Mathematical modeling for Influenza A, H1N1 in Malaysia. Journal of Applied Sciences, Vol. 11, No. 7, page: 1457-1480. 14. Favier C et al. (2006). Early determination of the reproduction number for vector borne diseases: the case of dengue in Brazil. Trop. Med. Int. Health, 11: page: 332-340. 15. Chowel G, Nishiura H, Bettencourt L.M. (2009).Comparative estimation of the reproduction number for pandemic influenza from daily case notification data. Journal Royal Society Interface, 4: page: 155-166. IJSIT (www.ijsit.com), Volume 2, Issue 5, September-October 2013 366