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Centro Nacional de Desarrollo e Investigacin en Tecnologas Libres (CENDITEL)

Revista Electrnica Conocimiento Libre y Licenciamiento (CLIC) Mrida !ene"#ela


I$$N% &&''()'&*
Analysis of an SEIR-SEI four-strain epidemic
dengue model with primary and secondary
infections
received% &+,-.,&-/'
acce0ted% -',-1,&-/'
0ages% * )
Ra2l Isea
3#ndacin Instit#to de Est#dios 4van"ados
5oyo de la 6#erta
7ar#ta8 Re02blica 7olivariana de !ene"#ela
risea@idea.gob.ve
Abstract We propose an SEIR model for the populations
and an SEI model for the vector to describe the transmission
dynamics of a four-strain model with both primary and
secondary dengue infections. In order to accomplish this we
propose and obtain an analytic solution of a system of !" coupled
differential e#uations. $his would be the most complete epidemic
model proposed to describe the dengue epidemic.
Keywords: Dengue; SEIR; SEI; epidemic model
I9 INTR:D;CTI:N
Deng#e is a viral disease8 <o#nd in tro0ical and s#b(tro0ical
regions o< t=e 0lanet >=ere it is estimated t=at bet>een &.--
and *--- million 0eo0le are at ris? o< contracting t=e disease
@/A9 In <act8 since /++B t=e Corld 5ealt= :rgani"ation (C5:)
=as listed deng#e as t=e tent= leading ca#se o< deat= among all
in<ectio#s diseases t=at are 0revalent in t=e >orld @&A9
Deng#e is transmitted 0rimarily by t=e bite o< in<ected
<emale mosD#itoes Aedes aegypti8 b#t it also =as been
associated >it= ot=er s0ecies s#c= as Ae. albopictus8 Ae.
polynesiensis8 and Ae. scutellaris @*A9 Deng#e =as <o#r strains
denoted by Deng#e I(I! @/8&A9 T=e most common <orm is t=e
classic deng#e or deng#e <ever t=at can o<ten be ca#sed by one
strain9 In addition8 severe deng#e =emorr=agic <ever <ormerly
associated >it= a secondary in<ection is ca#sed by antibody(
de0endent en=ancement 0rocesses @/8&A9
T=e <irst case o< deng#e oc#rred in 4#stralia in /+.' and
similar o#tbrea?s >ere observed in t=e 6=ili00ines and
s#bseD#ently s0read to !ietnam8 T=ailand and ot=er 4sian
co#ntries @'A9 T=e <irst e0idemic o< deng#e in t=e 4mericas
occ#rred in C#ba in /+B/ >=ic= >as ca#sed by an 4sian strain
o< Deng#e seroty0e(II @.A9
D#e to t=e lac? o< e<<ective dr#gs and vaccines against
deng#e <ever t=ere =as been a lac? o< e<<ective 0rograms to
=el0 control t=e disease8 and <or t=is reason8 a >ide range o<
mat=ematical models to describe and c=aracteri"e t=e
dynamics o< deng#e transmission =as been develo0ed @1(BA9
T=e classic eEam0le is t=e $IR model >=ic= indicates t=at
t=ere are t=ree signi<icant 0o0#lations to be eEamined9 T=ey are
t=e 0o0#lation t=at is s#sce0tible to a given disease ($)8 t=e
0o0#lation t=at is in<ected >it= t=e disease (I) and t=e
0o0#lation t=at recovers <rom t=e disease (R)9 4g#ilar et. al. @+A
described an eEtension to n#merically resolve deng#e
e0idemics >it= <o#r strains8 em0loying a $IR model9
In t=e case o< vir#ses8 t=e mat=ematical model m#st incl#de
t=e inc#bation or latency 0eriod >=ic= occ#rs F#st be<ore
in<ection9 In t=is case8 t=e model is called t=e $EIR model
>=ere E re0resents t=e 0o0#lation t=at is eE0osed to t=e
disease9 In t=e case o< deng#e8 t=e eE0os#re time is
a00roEimately B(+ days be<ore mani<estation o< t=e disease
once it is transmitted by an in<ected mosD#ito @/-A9
:#r model 0ro0oses an analytic sol#tion o< a system o< ')
di<<erential eD#ation t=at describes t=e dynamics o< deng#e
transmission >it= <o#r strains9 In addition >e ta?e into acco#nt
0rimary and secondary in<ections em0loying t=e $EIR model
<or t=e 0o0#lations and t=e $EI model <or vectorG it is an
eEtension o< t=e model o< Hanre#ng and C=inviriyasit 0#blis=ed
in &-/' @//A9 Ce believe t=is to be t=e most com0lete analytical
analysis o< t=e transmission o< deng#e9
II9 M4T5EM4TIC4L M:DEL
T=e model is initially based on t=e recent model 0ro0osed
by Hanre#ng and C=inviriyasit @//A >=o resolved a system >it=
/) di<<erential eD#ations9 In t=is model (3ig9 /)8 t=e =ost
0o0#lation (N) is s#bseD#ently s#bdivided into m#lti0le
0o0#lations based on t=e <ollo>ing ass#m0tions%
(T=e model ass#mes a =omogeneo#s miEt#re o< t=e
0o0#lations o< bot= =#mans (=ost) and vectors (mosD#ito) so
t=at eac= mosD#ito bite is as li?ely to transmit t=e vir#s to
=#mans regardless o< t=e ty0e o< t=e vir#s9
*
Centro Nacional de Desarrollo e Investigacin en Tecnologas Libres (CENDITEL)
Revista Electrnica Conocimiento Libre y Licenciamiento (CLIC) Mrida !ene"#ela
I$$N% &&''()'&*
3ig9 /9 T=e com0artmental model o< =ost(vector 0o0#lation em0loyed in o#r
model (see t=e teEt <or t=e nomenclat#re)9
(T=e total =#man 0o0#lation at time t is divided into *B
s#b0o0#lations9 T=is means t=at t=e s#sce0tible 0o0#lation >ill
be eE0osed to an in<ection by one strain denoted by E
i9
8 >=ere
iI / to ' is t=e indeE to indicate t=e <o#r strains9 $#bseD#ently8
t=e 0o0#lations >ill become in<ected (denoted I
i
)9 T=e
secondary in<ection occ#rs >=en an individ#al is rein<ected
>it= anot=er strain8 and in t=is case8 t=e 0o0#lation t=at is
eE0osed to t=e second in<ection >ill be denoted as E
iF
9 T=e
in<ected 0o0#lation >ill be identi<ied as I
iF
(t=e second indeE
re0resents t=e second in<ection >=ile t=e <irst indeE re0resents
t=e 0rimary in<ection8 >it= t=e condition iJF)9 3inally t=e
=#man 0o0#lation t=at recovered is indicated >it= R9 T=e total
0o0#lation (N) >ill be eD#al%
N I $KE
/
KE
&
KE
*
KE
'
KI
/
KI
&
KI
*
KI
'
K$
/
K$
&
K$
*
K$
'
K
E
/&
KE
/*
KE
/'
KE
&/
KE
&*
KE
&'
KE
*/
KE
*&
KE
*'
K
E
'/
KE
'&
KE
'*
KI
/&
KI
/*
KI
/'
KI
&/
KI
&*
KI
&'
KI
*/
KI
*&
KI
*'
K
I
'/
KI
'&
KI
'*
KR
(T=e total mosD#ito (vector) 0o0#lation is denoted by M
and is divided into + classes9 T=e <irst is $
v
>=ic= re0resents
t=e mosD#ito 0o0#lation s#sce0tible to carry t=e vir#s9 T=e neEt
<o#r are t=e mosD#itoes t=at are eE0osed to t=e deng#e vir#s
and are denoted by E
vi
9 T=e last <o#r8 corres0onding to in<ected
mosD#itoes8 are denoted by I
vi
9 $o
M I $
v
KE
v/
KE
v&
KE
v*
KE
v'
KI
v/
KI
v&
KI
v*
KI
v'
( It >as also considered t=at t=e mosD#itoes t=at >ere
eE0osed to t=e <o#r vir#s ty0es at di<<erent times8 once in<ected8
cannot recover as =as been already establis=ed in t=e scienti<ic
literat#re @+8//A9
3inally8 >e model t=e system >it= a set o< ') ordinary
di<<erential eD#ations >=ic= are >ritten as%
dS
dt
=( NS)

i=/
'
S

N
I
vi
(/)
dE
i
dt
=S

N
I
vi
( +) E
i
(&)
d I
i
dt
= E
i
( +) I
i
(*)
d S
i
dt
= I
i
S
i

N

j=/
i j
'
I
vj
S
i
(')
d E
ij
dt
=S
i

N
I
vj
( +) E
ij
(.)
d I
ij
dt
= E
ij
( +) I
ij
(1)
d
dt
=

j=/
i j
'
I
ij

())
d S
v
dt
=!S
v

v
N
(

i=/
'
I
i
+"

j=/
i j
'
I
ij
)
S
v
(B)
d E
vi
dt
=S
v

v
N
(
I
i
+"

j=/
i j
'
I
ij
)
(
v
+
v
) E
vi
(+)
d I
vi
dt
=
v
E
vi
(
v
+
v
) I
vi
(/-)
>=ere i re0resent eac= strain >it= iI / to '8 and is t=e rate o<
secondary in<ections contrib#ting to intensity o< t=e disease
@/&A9 :< co#rse8 t=e best val#e o< is calc#lated according to
t=e n#mber o< o#tbrea?s o< e0idemics observed in eac=
geogra0=ical area9
'
Centro Nacional de Desarrollo e Investigacin en Tecnologas Libres (CENDITEL)
Revista Electrnica Conocimiento Libre y Licenciamiento (CLIC) Mrida !ene"#ela
I$$N% &&''()'&*
III9 RE$;LT$
T=e e0idemiologically relevant bioregion t=at is
symboli"ed >it= L @+8//8/&A is given by
MIN ($8E/8E&8E*8E'8I/8I&8I*8I'8$/8$&8$*8$'8E/&8E/*8E/'8
E&/8E&*8E&'8E*/8E*&8E*'8E'/8E'&8E'*8I/&8 I/*8I/'8
I&/8I&*8I&'8I*/8I*&8I*'8I'/8I'&8I'*8R8$v8Ev/8Ev&8Ev*8Ev'8
Iv/8Iv&8Iv*8 Iv' ) O - P
T=e sol#tion o< t=is system o< eD#ations #ses t=e same
met=odology as eE0lained and 0#blis=ed by Hanre#g and
C=inviriyasit @//A9 T=e sol#tion o< o#r system o< eD#ations
s#ggests t=at t=ere are t>o 0oints o< eD#ilibri#m t=at >e call
6oint / and 6oint &9
6oint /% T=is 0oint corres0ond a disease <ree eD#ilibri#m
analogo#s to t=at <o#nd in @//A eD#al to%
($QIN,8-8-8-8-8-8-8-8-8-8-8-8-8-8-8-8-8-8-8-8-8-8-8
-8-8-8-8-8-8-8-8-8-8-8-8-8-8-8$QvIM,v8-8-8-8-8-8-8-8-)
and8
6oint &% t=is is an endemic eD#ilibri#m 0oint eD#al to%
($Q8EQ/8EQ&8EQ*8EQ'8IQ/8IQ&8IQ*8IQ'8$Q/8$Q&8$Q*8$Q'8EQ/&8EQ/*8EQ/'8
EQ&/8EQ&*8EQ&'8EQ*/8EQ*&8EQ*'8EQ'/8EQ'&8EQ'*8IQ/&8
IQ/*8IQ/'8IQ&/8IQ&*8IQ&'8IQ*/8IQ*&8IQ*'8IQ'/8IQ'&8IQ'*8
RQ8$Qv8EQv/8EQv&8EQv*8EQv'8 IQv/8IQv&8IQv*8 IQv' )
T=e sol#tion is <o#nd >it= t=e same mat=ematical
met=odology 0#blis=ed in @//A8 and does contrib#te anyt=ing
abo#t ne>9 T=e sol#tion <o#nd is eD#al to%
S
#
=
N
&
$
&
(//)
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.
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[
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#
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I
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#
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(/B)
I
vi
#
=
!
v

v
$
'
$
.
$
1
[
I
i
#
+ "

j =/
j i
'
I
ij
#
]
(/+)
In t=is case8 t=e constants are%
$
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&+
$
&
&N+
[

i=/
'
I
vi
#
]
$
*
&+ ' $
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&
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T=e most critical val#e in t=e e0idemic model is t=e basic
re0rod#ction val#e (R-) and is t=e res#lting =ig=er val#e o< t=e
eigenval#es o< t=e Hacobian o< t=e ') di<<erential eD#ations
>=en eval#ated <or eac= critical 0oint (ie98 6oint / and 6oint &)G
t=e analysis is di<<ic#lt to 0er<orm and >ill 0#blis=ed in t=e
<#t#re9
3inally8 >e >ill eEamine t>o cases o< >=ic= t=e <irst res#lts
<rom t=e consideration o< a single strain and t=e second res#lts
<rom t=e consideration o< t>o strains9
Model /9 $ingle(strain model
In t=e case o< a single strain iI/8 so
S
i
#
=-8 E
ij
#
=-8 I
ij
#
=-9 T=ere<ore t=e sol#tion is%
.
Centro Nacional de Desarrollo e Investigacin en Tecnologas Libres (CENDITEL)
Revista Electrnica Conocimiento Libre y Licenciamiento (CLIC) Mrida !ene"#ela
I$$N% &&''()'&*
S # =
N
&
N+ I
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=
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Model &9 T>o(strains model9
In t=is case8 t=e val#es i are / and & and t=e terms t=at are
not "ero are $Q8EQ/8EQ&8IQ/8IQ&88$Q/8$Q&8EQ/&8EQ&/8IQ/&8IQ&/8RQ8$Qv8EQv/8EQv&8
IQv/ and IQv& >=ose eD#ations are res0ectively%
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In t=is case8 t=e constants are%
%
/
#
&(I
v,
#
+I
v)
#
) + N
%
*
#
&
v
N +
v
( I
/
+I
&
+"(I
/&
+I
&/
))
T=e constants C' and C1 ?ee0 t=eir original de<initions9
N#merical sim#lations%
In Table / lists t=e n#merical val#es are listed o< t=e
0arameters #sed in t=e sim#lation t=at >ere obtained <rom
0revio#s 0#blication @//A9 T=e time series 0lot is s=o>n in 3ig9
&(a) <or t=e case o< <o#r strains <or t=e time interval o< *- days9
T=e sol#tion >it= t>o strains is s=o>n in 3ig9 &(b)9 T=e res#lts
o< bot= sim#lations are very similar9
1
Centro Nacional de Desarrollo e Investigacin en Tecnologas Libres (CENDITEL)
Revista Electrnica Conocimiento Libre y Licenciamiento (CLIC) Mrida !ene"#ela
I$$N% &&''()'&*
I!9 C:NCL;$I:N$
Ce =ave develo0ed an $EIR($EI model o< t=e transmission
dynamics o< <o#r(strains o< deng#e model considering 0rimary
and secondary in<ections8 >=ic= is an eEtension o< t=e 0revio#s
model 0ro0osed in t=e literat#re b#t only only considering t>o
strains9 Ce <o#nd t=at t=is model =as t>o eD#ilibri#m 0oints%
t=e disease <ree eD#ilibri#m (called 6oint /) and 6oint & >=ic=
is t=e endemic eD#ilibri#m o< t=e system9 It is interesting to
indicate t=at t=e model t=at analy"ing t=e e0idemic >it= <o#r
strains is very similar >it= to t=e model >it= t>o strains (3ig9
&)8 and t=ere<ore >e concl#de t=at it is #nnecessary to 0er<orm
analytical st#dies >it= <o#r strains o< deng#e8 since it is
s#<<icient to consider a sol#tion >it= t>o di<<erent strains9
4CRN:CLEDSMENT
T=e a#t=or >is=es to eE0ress =is sincere t=an?s to 6ro<9
Rarl Lonngren and Ho=an 5oebe?e <or t=eir #nconditional =el0
and t=e comments concerning t=e man#scri0t9
3ig9 &9 T=e n#merical sol#tion o< t=is model >it= (a) <o#r strains8 and (b) t>o
strains according to Table / val#es9 $ re0resent t=e s#sce0tible
0o0#lation8 I is eD#al to t=e s#m o< I
/
KI
&
KI
*
KI
'
9 $
/
is t=e =#mans
eE0osed >it= strain /8 and <inally $
v
is t=e total 0o0#lation o<
mosD#itoes s#sce0tible to any strains9
RE3ERENCE$
@/A I9 R#rane and T9 Ta?asa?i8 TDeng#e <ever and deng#e =emorr=agic
<ever% c=allenges o< controlling an enemy still at large8U Rev9 Med9 !irol9
!ol9 //8 009 *-/(*// (&--/)9
@&A 49 $eiFo8 TEl deng#e como 0roblema de sal#d 02blica8U 4rc=9 4rgent
6ediatr98 vol9 ++8 009 ./-(.&/ (&--/)9
@*A L9 49 5ill8 H9 79 Davis8 S9 5a0good8 69 I9 C=elan8 S9 49 $mit=8 $9 49
Ritc=ie8 R9 D9 Coo0er8 and 4939 van den 5#r?8 TRa0id Identi<ication o<
4edes albo0ict#s8 4edes sc#tellaris8 and 4edes aegy0ti Li<e $tages
;sing Real(time 6olymerase C=ain Reaction 4ssays8U 4m9 H9 Tro09
Med9 5yg98 vol9 )+(1)8 009 B11B). (&--B)9
@'A $979 5alstead8 TT=e VVt= Cent#ry deng#e 0andemic% need <or
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