Mathematical model of the Population Dynamics of a of

Staphylococcus aureus with dual-transmission pathways in the

presence of Antibiotic-based Therapy
1. Introduction:
Staphylococcus aureus (staph) is a member of the staphylococcaceae family that contains
more than 50 species (Jawetz et. al, 2010, Ochei and Kolhatkar, 2008). The staph is a leading
opportunistic Gram-positive pathogen in human and animal medicine, causing a wide array
of hard-to-treat infections ranging from superficial skin and soft tissue infections (SSTIs) to
life-threating invasive diseases such as brain abscess, pneumonia, endophthalmitis and sepsis
(bloodstream) infection (Leonard and Markey, 2007). Besides this, infertility, sexual
dysfunction, impotency (Esmail Khani et al. 2018) and staphylococcal food poisoning
remain some of the immediate consequences of staph in humans, accounting for 68.2% of
seminal fluid infection in male and female alike (Gupta and Probha, 2012). Meanwhile, staph
primary exists as a human commensal, mostly in the anterior nares, from whence it’s able to
seed infection, colonizing about a third of the world’s population (Col et.al 2001).
The individuals most vulnerable to staphylococcal infections are children and adults of all
age who are immune compromised or who have invasive medical devices. (Cunnion, 2003).
Transmission of infection can however be spread from skin-to-skin by having direct contact
with individuals who are appropriate carriers (Straskova et. al, 2009). Sexual transfer of S-
aureus is evidently a new trend of transmission which has not been widely explored.
Nevertheless, S-aureus still ranks second as the major cause of nosocomial blood stream
infection that leads to increased mortality, morbidity, hospital stay and lost (Gravel et. al,
2009; Klevens et. al, 2007).
The adaptability of S-aureus to antibiotics is a significant characteristics that led to the
emergence of methicillin –Resistant staphylococcus aureus (MRSA) in 1961 in the UK
(Patrick et. al 2013). The ability of S-aureus to acquire mecA gene offers then resistance to
all -lactam antibiotics. Patients infected with a methicillin-Resistant strains are twice likely to
die compared with to those infected with a methicillin-susceptible strains. Nevertheless,
antibiotics remain the only available option for treating staphylococcus aureus infection till
date (Francois et al., 2017).
The dynamics of the staphylococcal infections are complicated by the multiple interactions
between the human hosts, pathogens (bacteria) and the environment (Strastkova et. al, 2009);
which contribute to both 76direct human –to-human and indirect environment –to-human
pathways. Mathematical modelling, simulation and analysis will offer a promising way to
look into the nature of the staphylococcal infection dynamics. Beanparlant and Smith (2016)
developed a metapopulation model for the spread of MRSA in correctional facilities. They
consider a population within two patches with infections modelled standard insistence
function in hotspots.
Hogea et al. (2014) presented a basic dynamic transmission model of staphylococcus aureus
in the US population. The model is dynamic and accounts for the US population growth with
MRSA and MSSA strains and illustrated the population-level impact of indirect using an
assumed S-aureus vaccination.

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 Wang and Ruan (2017) proposed a models that explicitly accounted for the environmental
component (bacteria concentration) in a hospital setting between patients and health care
workers (HCW).
Batina et al. (2016) provide conditions for elimination and epidemic potential of MRSA in
nursing homes. They formulated the deterministic model on a single strain of S-aurus using
density dependent transmission approach with decolonization as a control strategy.
All these models have their own strategy and weakness; some models only track the human
population dynamics directly with nosocomial infection process. Whereas, others focus on
environment components while neglecting direct human to human transmission. Meanwhile,
most of the models formulated on S-aureus are purely based on hospital and nosocomial
transmission. Therefore, the present study intend to propose a unified S-aureus model that
allows a general non-linear incidence factors for both sexually human to human and bacteria
transmission pathways with antibiotic therapy without concentrating on hospital setting.

1.2 Statement of the problem

Antimicrobial drugs resistance over the decades has been a major public health challenge
on a global scale in the fight against staph. This problem originated from antibiotic
pressure and drugs misuse. Staphylococcal infections were curable with the introduction
of Penicillin, but decades of misuse and frequent blind prescription of antibiotics offered
resistance to Penicillin. This is similarly experienced in the treatment cases using
Methicillin and Vancomycin drugs. Culturing and sensitivity testing has been imperative
in order to aid medical prescription process of antibiotics, for the users, since antibiotics
remain the treatment option for staph infection till date. Unfortunately, mathematical
models as tools for suggesting treatment regimens for staphylococcal infections in non-
hospital based setting are very few and not widely explored. To this end, we intend to
formulate a generalized mathematical model of staphylococcal infection with dual-
transmission pathways in the presence of culture and Antibiotics Susceptibility Testing
(AST).

1.3 Aim and objectives of the study

The aim of the study is to formulate a mathematical model of staphylococcus aureus with
dual-transmission pathways in the presence of antibiotic-based therapy. The specific
objectives of the study are to:
• Develop a mathematical model for the population dynamics of a
staphylococcal infection with dual-transmission pathways in the presence of
Antibiotics Susceptibility Testing.
• Analyze for the stability otherwise the equilibrium states of the proposed
model
• Compute and analyze the basic reproduction number
• Carry out the sensitivity analysis of the parameters of the proposed model

2
 • Conduct the numerical simulation of the proposed model using Matlab
package
1.4 Significance of the study
The study will shade more light on the population dynamics of the staphylococcus aureus
with dual transmission pathways in the presence of antibiotics base therapy.
1.5 Justification of the Study:
Staphylococcus aureus (S. Aureus) is one of the most common etiological agents of
community – acquired and nosocomial bacteria infections (Mohammed 2005). S. Aureus
has emerged as one of the most important human pathogens and has over the past decades
been a leading cause of community acquired infections (Lowy, 2003). The spread of
methicillin resistant strain of staphylococcus aureus (MRSA) in healthcare settings has
become increasingly difficult to control and has since been able to spread in the general
community which cause outbreaks (Bean Parlant and Robert Smith 2016). The
characterization of S. aureus and monitoring of antimicrobial susceptibility patterns are
important for clinicians in selecting empiric antimicrobial therapy will provide useful
information on the surveillance of this important pathogen. The mathematical model of a
population dynamics of staphylococcus aureus with dual transmission pathways in the
presence of antibiotics base therapy will serve as a powerful tool for better understating
of epidemiology of the pathogen and for establishing appropriate and effective control
measures.
2.0 The model formulation
We construct the staphylococcal infection dynamics based on the combination of a
regular SIR model and an environmental component using the Beanparlant and Smith
(2016) model as a motivation. It helps us in developing a generalized S-aureus
transmission model without special reference to hotspots areas and hospital setting.
2.1 The proposed model
The following assumptions on the state variables are taken into consideration with the
definition of parameters given in table 1;
i. Infected individuals become susceptible at the rate through decolonization
ii. Transmission can occur through contact with infected individuals using standard
incidence function
iii. Uncolonized (susceptible) can also acquire infection through dirty environment
using saturated incidence function
The figure below shows the interaction between the components

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The figure below shows the interaction between the components’

Figure 1: Schematic description of the Model

Table 1: State variables and parameters of the proposed model

Variable Description
S (t ) Number of uncolonized (susceptible) individuals at time t
C( t) Number of colonized (susceptible) individuals at time t
I ( t) Number of infectious individuals at time t
B (t) S-aureus bacteria concentration in the dirty environment at time t
T A (t) Number of treated individuals at time t
R(t) Number of recovered individuals at time t
βs Infection rate from environment to humans
βh Rate of infection due to sexual transmissions
K Saturated concentration of the bacteria
ω Rate of decolonization
α Progression rate from C to I
ρ Treatment rate due to antibiotic based therapy
γ Rate of recovery for those treated
r1 Treatment failure resulting to persistently infected individuals
r2 Reactivation of the bacteria after recovery
d1 Diseased induced death rate
d2 Rate of disinfection of the bacteria concentration
μ Natural death rate

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 }
dS
= Λ−( f B+ λh ) S+ωC−μS
dt
dC
=( f B + λh ) S−( α+ω + μ ) C−μS +r 1 T A
dt
dI
=αC + r 2 R−( ρ+ μ+d 1 ) I ,(1)
dt
d TA
=ρI −( r 1 +γ + μ ) T A
dt
dR
=γ T A−( r 2+ μ ) R
dt

where

f B (C , I , B )=β s

λ =β (
h
I + ηC
h
N )
}
( KB+B ) (2)

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