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A dynamical analysis of
tuberculosis in the Philippines
King James B. Villasin1, Angelyn R. Lao2, and Eva M. Rodriguez*,1
1
Department of Mathematics, School of Sciences and Engineering, University of Asia and the Pacific,
Pasig City, Philippines
2
Mathematics Department, De La Salle University, Manila, Philippines
T
uberculosis (TB), an infection obtained from KEYWORDS
Mycobacterium, is the fourth leading cause of death
in the Philippines. It remains to be a problem tuberculosis (TB), dynamics analysis, stability analysis,
especially in developing countries, even after prevalence rate, incidence rate, TB control, Philippines
following guidelines and achieving some of the
targets set by the World Health Organization (WHO) for TB INTRODUCTION
elimination. Inspired by the TB transmission model developed
Tuberculosis is the infection of Mycobacterium tuberculosis,
by Trauer et al. (2014), we propose a model for TB transmission
acquired through inhaling and causing infection in the lungs
in the Philippines and validated it using Philippine-based data (NIAID, 2009). There are two main kinds of tuberculosis: latent
for TB incidence and prevalence rates in 2003-2013 (WHO, and active. Latent tuberculosis is the inactive infection in which
2014). Using the Theorem of van den Driessche & Watmough the body’s immune system can only control the growth of the
(2002) we show that our proposed Philippine TB model has a bacteria but cannot eradicate them. This makes the infection
locally asymptotically stable endemic equilibrium, with basic non-contagious and asymptomatic. After latency, active TB can
occur and M. tuberculosis can populate, infect and destroy the
reproduction number R0 = 0.4516 and an unstable free-disease
defense mechanism of the body, making the TB contagious
equilibrium, with R0 = 3.8896. Moreover, our projected (NIAID, 2009). Treatments and drugs have already been
simulations show that improving partial immunity, treatment developed, but these drugs have side effects and the treatment
success, treatment duration and case detection in the Philippines can last for at least 6 months thus, costly and open to possibility
will significantly reduce the TB incidence and prevalence rates. of failure (WHO, 2010b). Moreover, treatment failure could
Interestingly, we found that improving vaccine coverage would result in the development of the multi-drug-resistant TB or
not significantly reduce the projected TB incidence and MDR-TB.
prevalence rates. These results can help the Philippines in
Although the World Health Organization (WHO) and countries
improving its TB programs and develop new strategies to affected by TB have set guidelines and targets for TB
eliminate tuberculosis in the country. elimination, some countries are far from achieving them (WHO,
2014a). The Philippines is one of the TB high-burden countries
and is listed as the 13th highest TB-related death rate, 8th highest
TB incidence, and 7th highest TB prevalence as of 2013 (WHO,
2014a). This paper aims to contribute to the Philippines in its
effort to control TB by understanding its dynamics in the country
*Corresponding author through mathematical modelling.
Email Address: eva.rodriguez@uap.asia
Mathematical modelling of disease transmission is a tool for
Received: January 11, 2016
studying an epidemic and can be used for designing epidemic
Revised: July 12, 2016
control strategies and for predicting the effects of certain
Accepted: August 3, 2016
strategies (Abu-Raddad et al., 2009). We want to make sense out
of the data and provide meaning to the model (Wolkenhauer et
et al. (2014) based on the TB incidence and prevalence data for undergo fast progression to active TB at rate ε or slow
the Philippines as reported by the World Health Organization progression and go to L group at rate k. Those in L could
B B
(WHO) for 2003-2013. Our proposed model will be analyzed for develop active TB with rate v, or acquire additional infection and
stability and used to determine factors which can significantly go to “slow” latency group L with force of infection 𝜆 . Those
A d
reduce TB in the country. Conclusions of this study can give who develop active TB but are undetected could be cured
important insights for the development and implementation of without medical treatment at rate 𝛾 or be detected by the national
more effective and efficient TB programs in the Philippines. TB program at rate 𝛿. Those detected are assumed to be treated
immediately. Those who are treated are cured at rate 𝜂𝜑, where
4
THE MODEL 𝜂 is the treatment success rate and is the duration of TB
5
treatment. They could also miss treatment at rate w (default rate).
In this study, we propose a TB transmission model for the
Philippine setting based on the work of Trauer and colleagues All parameters are assumed to be positive since the model only
for the Asia Pacific Region (2014). Restricted by the data that is
deals with positive rates. The values of i, h and 𝜌 range from 0
available for validation, we revised the model of Trauer et al. in
to 1 since they represent ratios. Moreover, since the variables
three ways. First, in order to focus this study only on drug-
represent numbers of individuals, their values are also
susceptible TB, we omitted the drug-resistant compartments in
nonnegative. Given the model in Figure 1, we obtain the
the model. This omission could not significantly affect our study
following system of equations:
since drug-resistant TB in the Philippines is still relatively low
– about 4,000 persons or a prevalence of 4 per 100,000
population as of 2013 (WHO, 2014b). Second, while the model
of Trauer et al. assumed that birth rate is proportional to the total
population, we assumed the birth rate to be constant. This was
done in order to focus the cause of changing population on the
disease. This method of using constant birth rate was also used
by Liu et al. (2011) in their analysis of the TB dynamics in
Guangdong, China. Third, because treatment success rate is an
important element in TB dynamics, we incorporated it in our
model.
Free-disease Equilibrium
We denoted the free-disease equilibrium as xo = (LAo, LBo, Io, To,
SAo, SBo). In the free-disease state, the system has no infection.
Thus, we have the following formulations for prevalence and Thus, we have
incidence rates, respectively
LAo = LBo = Io = To = 𝜆 = 𝜆d = 0. (Eq. 27)
o o
Solving for SA and SB , we arrived at the free-disease
equilibrium:
4NO 𝚲 O𝚲
𝐱 M = 0,0,0,0, + . (Eq. 28)
Q Q
Using Philippine data for prevalence and incidence rates Endemic Equilibrium
obtained from the World Health Organization Report for 2003
We denoted the endemic equilibrium as x* = (LA*, LB*, I*, T*, SA*,
to 2013 (WHO, 2015), values for parameters obtained from
SB*). To describe the endemic state of the system, we considered
literature, and assuming initial values for 𝐿; , 𝐿= , 𝐼, 𝑇, 𝑆; , 𝑆= the force of infection
we estimated the effective contact rate 𝛽 for the model using
Matlab and found it to be 11.5. All simulations in this paper were #$(& ∗ ( )* ∗ )
𝜆* = . (Eq. 29)
also done in Matlab. ,
As shown in Figure 2, the fitted values follow the same Since N = SA* + SB* + LA* + LB* + I* + T*, equation (29) can be
decreasing behaviour of the actual values of the incidence and expressed as
prevalence rates of TB in the Philippines. The discrepancies are
within the error bars. Hence, we can say that our model is valid 𝜆*SA* + 𝜆*SB* + 𝜆*LA* + 𝜆*LB* + 𝜆*I* + 𝜆*T* − 𝛽𝜌I* −𝛽𝜌hT* = 0.
and is able to describe the TB dynamics in the Philippines, (Eq. 30)
particularly the TB incidence and prevalence rates in the country.
Substituting the expressions for SA*, SB*, LA*, LB*, I* and T* in
terms of 𝜆* and the parameters, equation (30) resulted into a
polynomial equation of the form
We determined the free-disease and endemic equilibrium points Basic Reproduction number R0
and analyzed their stability. To calculate an equilibrium point x ,0 The basic reproduction number R0 is the average secondary
we equated each of the differential equations (1) − (6) to zero infection produced by an infectious individual in a fully
and solved for the respective variables. Thus we have, susceptible population.
and this gave eigenvalues which all have negative real parts.
Moreover, computing for the basic reproduction number we
obtained R = 3.8896 > 1. By the van den Driessche and
0
J(x ) and obtained eigenvalues which all have negative real parts.
*
Theorem of van den Driessche and Watmough Projected simulations of the incidence and prevalence rates were
Let x be an equilibrium point of a system ẋ = f(x) and X =
0 S based on our proposed TB model for the Philippines in terms of
{x ≥ 0∣x = 0, i = 1, 2, …, m} be the set of all disease-free
i case detection rate, vaccination coverage, partial immunity,
states. duration of treatment and treatment success rate for the years
2013 to 2023. Assuming the initial conditions LA2013(0), L (0), B
2013
− +
Moreover, let F(x), V(x), V (x) and V (x), as defined above, I (0), T (0), S (0), S (0), and N (0) to be the 2013
2013 2013 A B 2013
2013 2013
satisfy the following assumptions: projected values of the system, we calibrated the case detection
1. If x ≥ 0, then F (x), V (x), V (x) ≥ 0, for i = 1, 2, …, n.
− +
i i i
rate, vaccination coverage, partial immunity, duration of
2. If x = 0, V (x) = 0 for i = 1, 2, …, n.
i i
−
treatment and treatment success rate and simulated the projected
In particular, if x ∈ X then V (x) = 0 for i = 1, 2, …, S i
−
incidence and prevalence rates using default parameter values
m. without any adjustments. These were compared with simulations
of projected incidence and prevalence rates made using the
3. F (x) = 0 if i > m.
i calibrated values of each parameter (as shown in Figures 3 and
4. Both F (x) = 0 and V (x) = 0 if x ∈ X for i = 1, 2, …, m.
+ 4).
i i S
prevalence in the first two years, and maintains slower but equilibrium which is unstable and an endemic equilibrium which
significant decrease in the next years, as shown in Figure 4D. is locally and asymptotically stable. This implies a continued
challenge to control TB in the Philippines.
There is no conflict of interest among the authors. Liu, Y., Sun, Z., Sun, G., Zhong, Q., Jiang, L., Zhou, L& Jia, Z.
(2011). Modeling Transmission of Tuberculosis with MDR
CONTRIBUTIONS OF INDIVIDUAL AUTHORS and Undetected Cases. Discrete Dynamics in Nature and
Society, 12. http://doi.org/10.1155/2011/296905
KJV performed the modeling and wrote the first draft of the
manuscript. AL and ER supervised the work and contributed to Mathematica. Wolfram.
the writing and editing of the manuscript.
Matlab. MathWorks.
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S2 → − −i k w 𝛾 𝜆 𝚲 𝜇 − i w 𝛾 ϵ 𝜆 𝚲 𝜇 − i k w 𝛾 𝚲 𝜇2 − i w 𝛾 ϵ 𝚲 𝜇2 − i w 𝛾 𝜆 𝚲 𝜇2 − i w 𝛾 𝚲 𝜇3 − i k v w 𝜆 𝚲 𝜇1 −
i v w ϵ 𝜆 𝚲 𝜇1 − i k v w 𝚲 𝜇 𝜇1 − i v w ϵ 𝚲 𝜇 𝜇1 − i k w 𝜆 𝚲 𝜇 𝜇1 − i v w 𝜆 𝚲 𝜇 𝜇1 − i w ϵ 𝜆 𝚲 𝜇 𝜇1 −
i k w 𝚲 𝜇2 𝜇1 − i v w 𝚲 𝜇2 𝜇1 − i w ϵ 𝚲 𝜇2 𝜇1 − i w 𝜆 𝚲 𝜇2 𝜇1 − i w 𝚲 𝜇3 𝜇1 − i k v 𝛿 𝜆 𝚲 𝜇2 − i v 𝛿 ϵ 𝜆 𝚲 𝜇2 −
i k v 𝛿 𝚲 𝜇 𝜇2 − i v 𝛿 ϵ 𝚲 𝜇 𝜇2 − i k 𝛾 𝜆 𝚲 𝜇 𝜇2 − i v 𝛿 𝜆 𝚲 𝜇 𝜇2 − i 𝛾 ϵ 𝜆 𝚲 𝜇 𝜇2 −
i 𝛿 ϵ 𝜆 𝚲 𝜇 𝜇2 − i k 𝛾 𝚲 𝜇2 𝜇2 − i k 𝛿 𝚲 𝜇2 𝜇2 − i v 𝛿 𝚲 𝜇2 𝜇2 − i 𝛾 ϵ 𝚲 𝜇2 𝜇2 − i 𝛿 ϵ 𝚲 𝜇2 𝜇2 − i 𝛾 𝜆 𝚲 𝜇2 𝜇2 −
i 𝛿 𝜆 𝚲 𝜇2 𝜇2 − i 𝛾 𝚲 𝜇3 𝜇2 − i 𝛿 𝚲 𝜇3 𝜇2 − i k v 𝜆 𝚲 𝜇1 𝜇2 − i v ϵ 𝜆 𝚲 𝜇1 𝜇2 − i k v 𝚲 𝜇 𝜇1 𝜇2 −
i v ϵ 𝚲 𝜇 𝜇1 𝜇2 − i k 𝜆 𝚲 𝜇 𝜇1 𝜇2 − i v 𝜆 𝚲 𝜇 𝜇1 𝜇2 − i ϵ 𝜆 𝚲 𝜇 𝜇1 𝜇2 − i k 𝚲 2% 𝜇1 𝜇2 − i v 𝚲 𝜇2 𝜇1 𝜇2 −
i ϵ 𝚲 𝜇2 𝜇1 𝜇2 − i 𝜆 𝚲 𝜇2 𝜇1 𝜇2 − i 𝚲 𝜇3 𝜇1 𝜇2 − k v 𝛿 𝜂 𝜆 𝚲 𝜙 − v 𝛿 ϵ 𝜂 𝜆 𝚲 𝜙 − i k v 𝛿 𝜂 𝚲 𝜇 𝜙 −
iv𝛿ϵ𝜂𝚲𝜇𝜙−ik𝛾𝜂𝜆𝚲𝜇𝜙−ik𝛿𝜂𝜆𝚲𝜇𝜙−iv𝛿𝜂𝜆𝚲𝜇𝜙−i𝛾ϵ𝜂𝜆𝚲𝜇𝜙−𝛿ϵ𝜂𝜆𝚲𝜇𝜙−
i k 𝛾 𝜂 𝚲 𝜇2 𝜙 − i k 𝛿 𝜂 𝚲 𝜇2 𝜙 − i v 𝛿 𝜂 𝚲 𝜇2 𝜙 − i 𝛾 ϵ 𝜂 𝚲 𝜇2 𝜙 − i 𝛿 ϵ 𝜂 𝚲 𝜇2 𝜙 − i 𝛾 𝜂 𝜆 𝚲 𝜇2 𝜙 −
i 𝛿 𝜂 𝜆 𝚲 𝜇2 𝜙 − i 𝛾 𝜂 𝚲 𝜇3 𝜙 − i 𝛿 𝜂 𝚲 𝜇3 𝜙 − i k v 𝜂 𝜆 𝚲 𝜇1 𝜙 − i v ϵ 𝜂 𝜆 𝚲 𝜇1 𝜙 − i k v 𝜂 𝚲 𝜇 𝜇1 𝜙 −
i v ϵ 𝜂 𝚲 𝜇 𝜇1 𝜙 − i k 𝜂 𝜆 𝚲 𝜇 𝜇1 𝜙 − i v 𝜂 𝜆 𝚲 𝜇 𝜇1 𝜙 − i ϵ 𝜂 𝜆 𝚲 𝜇 𝜇1 𝜙 − i k 𝜂 𝚲 𝜇2 𝜇1 𝜙 − i v 𝜂 𝚲 𝜇2 𝜇1 𝜙 −
i ϵ 𝜂 𝚲 𝜇2 𝜇1 𝜙 − i 𝜂 𝜆 𝚲 𝜇2 𝜇1 𝜙 − i 𝜂 & 𝜇3 𝜇1 𝜙 − i w 𝛾 𝜆2 𝚲 𝜇𝝌 − i w 𝛾 𝜆 𝚲 𝜇2 𝝌 − i w ϵ 𝜆2 𝚲 𝜇1 𝝌 −
i w ϵ 𝜆 𝚲 𝜇 𝜇1 𝝌 − i w 𝜆2 𝚲 𝜇 𝜇1 𝝌 − i w 𝜆 𝚲 𝜇2 𝜇1 𝝌 − i 𝛿 ϵ 𝜆2 𝚲 𝜇2 𝝌 − i 𝛿 ϵ 𝜆 𝚲 𝜇 𝜇2 𝝌 − i 𝛾 𝜆2 𝚲 𝜇 𝜇2 𝝌 −
i 𝛿 𝜆2 𝚲 𝜇 𝜇2 𝝌 − i 𝛾 𝜆 𝚲 𝜇2 𝜇2 𝝌 − i 𝛿 𝜆 𝚲 𝜇2 𝜇2 𝝌 − i ϵ 𝜆2 𝚲 𝜇1 𝜇2 𝝌 − i ϵ 𝜆 𝚲 𝜇 𝜇1 𝜇2 𝝌 − i 𝜆2 𝚲 𝜇 𝜇1 𝜇2 𝝌 −
i 𝜆 𝚲 𝜇2 𝜇1 𝜇2 𝝌 − 𝛿 ϵ 𝜂 𝜆2 𝚲 𝜙 𝝌 − i 𝛿 ϵ 𝜂 𝜆 𝚲 𝜇 𝜙 𝝌 − i 𝛾 𝜂 𝜆2 𝚲 𝜇 𝜙 𝝌 − i 𝛿 𝜂 𝜆2 𝚲 𝜇 𝜙 𝝌 − i 𝛾 𝜂 𝜆 𝚲 𝜇2 𝜙 𝝌 −
i 𝛿 𝜂 𝜆 𝚲 𝜇2 𝜙 𝝌 − i ϵ 𝜂 𝜆2 𝚲 𝜇1 𝜙 𝝌 − i ϵ 𝜂 𝜆 𝚲 𝜇 𝜇1 𝜙 𝝌 − i 𝜂 𝜆2 𝚲 𝜇 𝜇1 𝜙 𝝌 − i 𝜂 𝜆 𝚲 𝜇2 𝜇1 𝜙 𝝌
(𝜆 + 𝜇) k w 𝛾 𝜇2 + w 𝛾 ϵ 𝜇2 + w 𝛾 𝜇3 + k v w 𝜇 𝜇1 + v w ϵ 𝜇 𝜇1 + k w 𝜇2 𝜇1 + v w 𝜇2 𝜇1 + w ϵ 𝜇2 𝜇1 +
w 𝜇3 𝜇1 + k v 𝛿 𝜇 𝜇2 + v 𝛿 ϵ 𝜇 𝜇2 + k 𝛾 𝜇2 𝜇2 + k 𝛿 𝜇2 𝜇2 + v 𝛿 𝜇2 𝜇2 + 𝛾 ϵ 𝜇2 𝜇2 + 𝛿 ϵ 𝜇2 𝜇2 +
𝛾 𝜇3 𝜇2 + 𝛿 𝜇3 𝜇2 + k v 𝜇 𝜇1 𝜇2 + v ϵ 𝜇 𝜇1 𝜇2 + k 𝜇2 𝜇1 𝜇2 + v 𝜇2 𝜇1 𝜇2 + ϵ 𝜇2 𝜇1 𝜇2 + 𝜇3 𝜇1 𝜇2 +
k v 𝛿 𝜂 𝜇 𝜙 + v 𝛿 ϵ 𝜂 𝜇 𝜙 + k 𝛾 𝜂 𝜇2 𝜙 + k 𝛿 𝜂 𝜇2 𝜙 + v 𝛿 𝜂 𝜇2 𝜙 + 𝛾 ϵ 𝜂 𝜇2 𝜙 + 𝛿 ϵ 𝜂 𝜇2 𝜙 + 𝛾 𝜂 𝜇3 𝜙 +
𝛿 𝜂 𝜇3 𝜙 + k v 𝜂 𝜇 𝜇1 𝜙 + v ϵ 𝜂 𝜇 𝜇1 𝜙 + k 𝜂 𝜇2 𝜇1 𝜙 + v 𝜂 𝜇2 𝜇1 𝜙 + ϵ 𝜂 𝜇2 𝜇1 𝜙 + 𝜂 𝜇3 𝜇1 𝜙 +
k w 𝛾 𝜆 𝜇 𝝌 + w 𝛾 ϵ 𝜆 𝜇 𝝌 + 2 w 𝛾 𝜆 𝜇2 𝝌 + k v w 𝜆 𝜇1 𝝌 + v w ϵ 𝜆 𝜇1 𝝌 + k w 𝜆 𝜇 𝜇1 𝝌 + v w 𝜆 𝜇 𝜇1 𝝌 +
2 w ϵ 𝜆 𝜇 𝜇1 𝝌 + 2 w 𝜆 𝜇2 𝜇1 𝝌 + k v 𝛿 𝜆 𝜇2 𝝌 + v 𝛿 ϵ 𝜆 𝜇2 𝝌 + k 𝛾 𝜆 𝜇 𝜇2 𝝌 + k 𝛿 𝜆 𝜇 𝜇2 𝝌 +
v 𝛿 𝜆 𝜇 %2 𝝌 + 𝛾 ϵ 𝜆 𝜇 𝜇2 𝝌 + 2 𝛿 ϵ 𝜆 𝜇 𝜇2 𝝌 + 2 𝛾 𝜆 𝜇2 𝜇2 𝝌 + 2 𝛿 𝜆 𝜇2 𝜇2 𝝌 + k v 𝜆 𝜇1 𝜇2 𝝌 +
v ϵ 𝜆 𝜇1 𝜇2 𝝌 + k 𝜆 𝜇 𝜇1 𝜇2 𝝌 + v 𝜆 𝜇 𝜇1 𝜇2 𝝌 + 2 ϵ 𝜆 𝜇 𝜇1 𝜇2 𝝌 + 2 𝜆 𝜇2 𝜇1 𝜇2 𝝌 + k 𝛾 𝜂 𝜆 𝜇 𝜙 𝝌 +
k 𝛿 𝜂 𝜆 𝜇 ' 𝝌 + v 𝛿 𝜂 𝜆 𝜇 𝜙 𝝌 + 𝛾 ϵ 𝜂 𝜆 𝜇 𝜙 𝝌 + 𝛿 ϵ 𝜂 𝜆 𝜇 𝜙 𝝌 + 2 𝛾 𝜂 𝜆 𝜇2 𝜙 𝝌 + 2 𝛿 𝜂 𝜆 𝜇2 𝜙 𝝌 +
k v 𝜂 𝜆 𝜇1 𝜙 𝝌 + v ϵ 𝜂 𝜆 𝜇1 𝜙 𝝌 + k 𝜂 𝜆 𝜇 𝜇1 𝜙 𝝌 + v 𝜂 𝜆 𝜇 𝜇1 𝜙 𝝌 + 2 ϵ 𝜂 𝜆 𝜇 𝜇1 𝜙 𝝌 + 2 𝜂 𝜆 𝜇2 𝜇1 𝜙 𝝌 +
w 𝛾 𝜆2 𝜇 𝝌2 + w ϵ 𝜆2 𝜇1 𝝌2 + w 𝜆2 𝜇 𝜇1 𝝌2 + 𝛿 ϵ 𝜆2 𝜇2 𝝌2 + 𝛾 𝜆2 𝜇 𝜇2 𝝌2 + 𝛿 𝜆2 𝜇 𝜇2 𝝌2 +
ϵ 𝜆2 𝜇1 𝜇2 𝝌2 + 𝜆2 𝜇 𝜇1 𝜇2 𝝌2 + 𝛾 𝜂 𝜆2 𝜇 𝜙 𝝌2 + 𝛿 𝜂 𝜆2 𝜇 𝜙 𝝌2 + ϵ 𝜂 𝜆2 𝜇1 𝜙 𝝌2 + 𝜂 𝜆2 𝜇 𝜇1 𝜙 𝝌2 ,
L1 → 𝜆 𝚲 𝜇 − i 𝜆 𝚲 𝜇 + 𝜆2 𝚲 𝝌 + i 𝜆 𝚲 𝜇 𝝌 (w 𝛾 𝜇 + v w 𝜇1 + w 𝜇 𝜇1 + v 𝛿 𝜇2 + 𝛾 𝜇 𝜇2 + 𝛿 𝜇 𝜇2 +
v 𝜇1 𝜇2 + 𝜇 𝜇1 𝜇2 + v 𝛿 𝜂 𝜙 + 𝛾 𝜂 𝜇 𝜙 + 𝛿 𝜂 𝜇 𝜙 + v 𝜂 𝜇1 𝜙 + 𝜂 𝜇 𝜇1 𝜙 + w 𝛾 𝜆 𝝌 +
w 𝜆 𝜇1 𝝌 + 𝛾 𝜆 𝜇2 𝝌 + 𝛿 𝜆 𝜇 2 𝝌 + 𝜆 𝜇1 𝜇 2 𝝌 + 𝛾 𝜂 𝜆 𝜙 𝝌 + 𝛿 𝜂 𝜆 𝜙 𝝌 + 𝜂 𝜆 𝜇1 𝜙 𝝌)
(𝜆 + 𝜇) k w 𝛾 𝜇2 + w 𝛾 ϵ 𝜇2 + w 𝛾 𝜇3 + k v w 𝜇 𝜇1 + v w ϵ 𝜇 𝜇1 + k w 𝜇2 𝜇1 + v w 𝜇2 𝜇1 + w ϵ 𝜇2 𝜇1 +
w 𝜇3 𝜇1 + k v 𝛿 𝜇 𝜇2 + v 𝛿 ϵ 𝜇 𝜇2 + k 𝛾 𝜇2 𝜇2 + k 𝛿 𝜇2 𝜇2 + v 𝛿 𝜇2 𝜇2 + 𝛾 ϵ 𝜇2 𝜇2 + 𝛿 ϵ 𝜇2 𝜇2 + 𝛾 𝜇3 𝜇2 +
𝛿 𝜇3 𝜇2 + k v 𝜇 𝜇1 𝜇2 + v ϵ 𝜇 𝜇1 𝜇2 + k 𝜇2 𝜇1 𝜇2 + v 𝜇2 𝜇1 𝜇2 + ϵ 𝜇2 𝜇1 𝜇2 + 𝜇3 𝜇1 𝜇2 + k v 𝛿 𝜂 𝜇 𝜙 +
v 𝛿 ϵ 𝜂 𝜇 𝜙 + k 𝛾 𝜂 𝜇2 𝜙 + k 𝛿 𝜂 𝜇2 𝜙 + v 𝛿 𝜂 𝜇2 𝜙 + 𝛾 ϵ 𝜂 𝜇2 𝜙 + 𝛿 ϵ 𝜂 𝜇2 𝜙 + 𝛾 𝜂 𝜇3 𝜙 + 𝛿 𝜂 𝜇3 𝜙 + k v 𝜂 𝜇 𝜇1 𝜙 +
v ϵ 𝜂 𝜇 𝜇1 𝜙 + k 𝜂 𝜇2 𝜇1 𝜙 + v 𝜂 𝜇2 𝜇1 𝜙 + ϵ 𝜂 𝜇2 𝜇1 𝜙 + 𝜂 𝜇3 𝜇1 𝜙 + k w 𝛾 𝜆 𝜇 𝝌 + w 𝛾 ϵ 𝜆 𝜇 𝝌 + 2 w 𝛾 𝜆 𝜇2 𝝌 +
k v w 𝜆 𝜇1 𝝌 + v w ϵ 𝜆 𝜇1 𝝌 + k w 𝜆 𝜇 𝜇1 𝝌 + v w 𝜆 𝜇 𝜇1 𝝌 + 2 w ϵ 𝜆 𝜇 𝜇1 𝝌 + 2 w 𝜆 𝜇2 𝜇1 𝝌 + k v 𝛿 𝜆 𝜇2 𝝌 +
v 𝛿 ϵ 𝜆 𝜇2 𝝌 + k 𝛾 𝜆 𝜇 𝜇2 𝝌 + k 𝛿 𝜆 𝜇 𝜇2 𝝌 + v 𝛿 𝜆 𝜇 𝜇2 𝝌 + 𝛾 ϵ 𝜆 𝜇 𝜇2 𝝌 + 2 𝛿 ϵ 𝜆 𝜇 𝜇2 𝝌 + 2 𝛾 𝜆 𝜇2 𝜇2 𝝌 +
2 𝛿 𝜆 𝜇2 𝜇2 𝝌 + k v 𝜆 𝜇1 𝜇2 𝝌 + v ϵ 𝜆 𝜇1 𝜇2 𝝌 + k 𝜆 𝜇 𝜇1 𝜇2 𝝌 + v 𝜆 𝜇 𝜇1 𝜇2 𝝌 + 2 ϵ 𝜆 𝜇 𝜇1 𝜇2 𝝌 +
2 𝜆 𝜇2 𝜇1 𝜇2 𝝌 + k 𝛾 𝜂 𝜆 𝜇 𝜙 𝝌 + k 𝛿 𝜂 𝜆 𝜇 𝜙 𝝌 + v 𝛿 𝜂 𝜆 𝜇 𝜙 𝝌 + 𝛾 ϵ 𝜂 𝜆 𝜇 𝜙 𝝌 + 𝛿 ϵ ( 𝜆 𝜇 𝜙 𝝌 + 2 𝛾 𝜂 𝜆 𝜇2 𝜙 𝝌 +
2 𝛿 𝜂 𝜆 𝜇2 𝜙 𝝌 + k v 𝜂 𝜆 𝜇1 𝜙 𝝌 + v ϵ 𝜂 𝜆 𝜇1 𝜙 𝝌 + k 𝜂 𝜆 𝜇 𝜇1 𝜙 𝝌 + v 𝜂 𝜆 𝜇 𝜇1 𝜙 𝝌 + 2 ϵ 𝜂 𝜆 𝜇 𝜇1 𝜙 𝝌 +
2 𝜂 𝜆 𝜇2 𝜇1 𝜙 𝝌 + w 𝛾 𝜆2 𝜇 𝝌2 + w ϵ 𝜆2 𝜇1 𝝌2 + w 𝜆2 𝜇 𝜇1 𝝌2 + 𝛿 ϵ 𝜆2 𝜇2 𝝌2 + 𝛾 𝜆2 𝜇 𝜇2 𝝌2 + 𝛿 𝜆2 𝜇 𝜇2 𝝌2 +
ϵ 𝜆2 𝜇1 𝜇2 𝝌2 + 𝜆2 𝜇 𝜇1 𝜇2 𝝌2 + 𝛾 𝜂 𝜆2 𝜇 𝜙 𝝌2 + 𝛿 𝜂 𝜆2 𝜇 𝜙 𝝌2 + ϵ 𝜂 𝜆2 𝜇1 𝜙 𝝌2 + 𝜂 𝜆2 𝜇 𝜇1 𝜙 𝝌2 ,