Global spread of dengue virus types: Mapping the 70 year history

Abstract

Since the first isolation of dengue virus (DENV) in 1943, four types have been identified. Global phenomena such as urbanization and international travel are key factors in facilitating the spread of dengue. Documenting the type-specific record of DENV spread has important implications for understanding patterns in dengue hyperendemicity and disease severity as well as vaccine design and deployment strategies. Existing studies have examined the spread of DENV types at regional or local scales, or described phylogeographic relationships within a single type. Here we summarize the global distribution of confirmed instances of each DENV type from 1943 to 2013 in a series of global maps. These show the worldwide expansion of the types, the expansion of disease hyperendemicity, and the establishment of an increasingly important infectious disease of global public health significance.

Full text

Global
spread
of
dengue
virus
types:
mapping
the
70
year
history
Jane
P.
Messina
1
,
Oliver
J.
Brady
1
,
Thomas
W.
Scott
2,3
,
Chenting
Zou
1
,
David
M.
Pigott
1
,
Kirsten
A.
Duda
1
,
Samir
Bhatt
1
,
Leah
Katzelnick
4
,
Rosalind
E.
Howes
1
,
Katherine
E.
Battle
1
,
Cameron
P.
Simmons
5,6,7
,
and
Simon
I.
Hay
1,3
1
Spatial
Ecology
and
Epidemiology
Group,
Department
of
Zoology,
University
of
Oxford,
South
Parks
Road,
Oxford
OX1
3PS,
UK
2
Department
of
Entomology,
University
of
California
Davis,
Davis,
California
95616,
USA
3
Fogarty
International
Center,
National
Institutes
of
Health,
Bethesda,
Maryland
20892,
USA
4
Department
of
Zoology,
University
of
Cambridge,
Cambridge,
CB2
3EJ,
UK
5
Oxford
University
Clinical
Research
Unit,
Hospital
for
Tropical
Diseases,
Ho
Chi
Minh
City,
Vietnam
6
Centre
for
Tropical
Medicine,
University
of
Oxford,
Churchill
Hospital,
Oxford
OX3
7LJ,
UK
7
Nossal
Institute
of
Global
Health,
University
of
Melbourne,
Parkville,
Victoria,
Australia
Since
the
first
isolation
of
dengue
virus
(DENV)
in
1943,
four
types
have
been
identified.
Global
phenomena
such
as
urbanization
and
international
travel
are
key
factors
in
facilitating
the
spread
of
dengue.
Documenting
the
type-
specific
record
of
DENV
spread
has
important
implica-
tions
for
understanding
patterns
in
dengue
hyperende-
micity
and
disease
severity
as
well
as
vaccine
design
and
deployment
strategies.
Existing
studies
have
examined
the
spread
of
DENV
types
at
regional
or
local
scales,
or
described
phylogeographic
relationships
within
a
single
type.
Here
we
summarize
the
global
distribution
of
con-
firmed
instances
of
each
DENV
type
from
1943
to
2013
in
a
series
of
global
maps.
These
show
the
worldwide
expan-
sion
of
the
types,
the
expansion
of
disease
hyperendemi-
city,
and
the
establishment
of
an
increasingly
important
infectious
disease
of
global
public
health
significance.
Early
spread
and
typing
of
DENV
DENV
are
members
of
the
Flavivirus
genus
(see
Glossary),
related
to
other
medically
important
arboviruses
such
as
yellow
fever
and
Japanese
encephalitis
viruses.
There
are
four
phylogenetically
and
antigenically
distinct
dengue
viruses
(DENV1–4),
and
although
infection
with
one
type
confers
long-term
immunity,
it
is
to
that
type
only
and
not
to
the
other
three
[1].
The
ancestor
of
these
viruses
has
been
postulated
to
have
emerged
about
1
000
years
ago
in
an
infectious
cycle
involving
non-human
primates
and
mosquitoes,
with
transmission
to
humans
having
occurred
independently
for
all
four
virus
types
only
a
few
hundred
years
ago
[2,3].
Although
outbreaks
of
disease
clinically
consistent
with
dengue
have
been
reported
for
centuries,
it
was
not
until
1943
in
Japan
and
1945
in
Hawaii
that
the
first
two
dengue
viruses
were
isolated
(named
DENV1
and
DENV2,
respectively)
[4].
At
this
point,
epidemics
of
den-
gue
illness
were
being
reported
across
the
region
spanning
from
India
to
the
Pacific
Islands.
In
the
latter
half
of
the
20th
century,
DENV
transmission
followed
the
spread
of
its
principal
mosquito
vector,
Aedes
aegypti
[5],
and
was
likely
accelerated
by
urbanization
and
globalization
[6,7].
The
collapse
of
the
Ae.
aegypti
eradication
campaign
in
the
Americas
in
the
1970s
was
also
important
in
marking
the
beginning
of
transport
of
Asian
dengue
viruses
to
the
Americas,
followed
by
the
rapid
re-introduction
of
the
principal
mosquito
vector
throughout
both
continents
[8].
A
need
for
type-specific
global
maps
Spatial
patterns
in
concurrent
and/or
sequential
circula-
tion
of
DENV1–4
should
be
considered
along
with
virus
and
host
genetics
as
potentially
important
population-level
risk
factors
for
severe
dengue
illness
[9,10]
because
sec-
ondary
infection
with
a
heterologous
DENV
type
may
increase
the
probability
of
severe
disease
[11–14].
Despite
this,
no
study
has
systematically
reviewed
all
documented
spatially
explicit
evidence
of
the
global
spread
of
the
four
DENV
types
since
the
first
isolation
in
1943.
Rather,
the
majority
of
existing
studies
have
focused
on
the
evolution
of
individual
DENV
types
at
regional
or
local
scales
[15–
20].
Global
descriptions
of
type-specific
DENV
distribution
are
few
in
number,
lacking
spatial
and
temporal
precision,
and
are
presented
in
a
non-systematic
manner
[8].
Reported
cases
do
not
comprise
the
entire
range
of
each
DENV
type
at
any
given
time,
meaning
that
a
lack
of
reporting
for
a
specific
type
at
any
time
or
place
does
not
indicate
its
certain
absence.
This
is
due
to
spatial
Review
Glossary
Flavivirus:
a
family
of
single-stranded
RNA
viruses
transmitted
primarily
by
ticks
and
mosquitoes.
Medical
Subject
Headings
(MeSH)
terminology:
a
wide-ranging
and
regulated
vocabulary
for
the
purpose
of
indexing
and
searching
for
journal
articles
and
books
in
the
life
sciences;
created
by
the
US
National
Library
of
Medicine.
Sylvatic:
denoting
certain
diseases
contracted
by
and
affecting
wild
animals,
and
the
pathogens
causing
them.
0966-842X/$
–
see
front
matter
ß
2014
Elsevier
Ltd.
All
rights
reserved.
http://dx.doi.org/10.1016/j.tim.2013.12.011
Corresponding
author:
Messina,
J.P.
(jane.messina@zoo.ox.ac.uk).
Keywords:
dengue;
serotypes.
138
Trends
in
Microbiology,
March
2014,
Vol.
22,
No.
3

variability
in
several
factors,
namely
in
the
degree
of
sampling,
proportion
of
infections
having
been
typed,
relia-
bility
of
typing
methods,
and
finally
reporting
of
these
types.
That
said,
the
use
of
more
advanced
typing
methods
has
expanded
significantly
across
the
globe
since
their
development,
and
a
thorough
description
of
confirmed
presences
of
each
DENV
type
is
needed
if
we
are
to
gain
a
better
understanding
of
the
global
dispersal
of
the
four
viruses
and
track
changes
moving
forward.
Here
we
pro-
vide
this
baseline
depiction,
also
highlighting
those
geo-
graphic
areas
lacking
in
information
about
the
specific
DENV
type(s)
responsible
for
dengue
occurrence.
Brady
et
al.
[21]
recently
outlined
the
definitive
extents
of
dengue
presence
globally,
and
their
work
was
followed
by
that
of
Bhatt
et
al.
[22]
which
generated
high
spatial-
resolution
(5
km

5
km)
estimates
of
contemporary
global
dengue
risk
and
burden
in
2010.
Our
efforts
here
provide
further
insight
into
the
global
distribution
of
dengue
by
reviewing
the
individual
DENV
types
responsible
for
reported
occurrence
throughout
the
past
seven
decades.
Our
aim
is
to
complement
phylogenetic
and
disease
occur-
rence
analyses
by
presenting
the
sub-national
distribution
of
reported
confirmed
instances
of
human
infection
with
each
DENV
type
globally
from
1943
to
2013.
We
provide
a
more
spatially
and
temporally
detailed
picture
of
the
spread
of
each
individual
DENV
type
than
was
previously
available,
also
presenting
contemporary
maps
of
the
num-
ber
of
DENV
types
ever
reported
in
an
area
to
elucidate
global
patterns
in
their
co-circulation
and
establishment
of
hyperendemicity.
Compiling
a
global
database
of
DENV
type
reporting
We
compiled
an
extensive
database
by
extracting
DENV
type
and
locational
information
from
published
literature
and
case
reports
spanning
the
period
1943–2013.
In
brief,
searches
were
conducted
in
PubMed
(http://www.ncbi.nlm/
pubmed)
using
the
terms
‘dengue’
and
‘serotype’
or
‘type,’
and
all
pseudonyms
were
automatically
included
using
the
Medical
Subject
Headings
(MeSH)
terminology.
No
lan-
guage
restrictions
were
placed
on
these
searches;
however,
only
those
citations
with
a
full
title
and
abstract
were
retrieved.
In-house
language
skills
allowed
processing
of
all
English,
French,
Portuguese,
and
Spanish
articles.
We
were
unable
to
extract
information
from
a
small
number
of
Turkish,
Polish,
Hebrew,
Italian,
German,
and
Chinese
articles.
ProMED
reports
(http://www.promedmail.org)
were
also
searched
using
the
terms
‘dengue’
and
‘serotype’
or
‘type’,
and
all
DENV
type
data
that
could
be
linked
to
a
location
were
extracted,
resulting
in
a
search
of
1
912
unique
articles
or
reports.
DENV
type
data
from
national
Ministry
of
Health
websites
were
included
where
avail-
able,
resulting
in
294
additional
sources
of
information.
Finally,
DENV
envelope
protein
gene
sequences
were
extracted
from
GenBank
(http://www.ncbi.nlm.nih.gov/
genbank),
providing
another
1
070
sources
for
a
total
of
3
276
sources
from
which
type
and
geographical
coordinate
information
was
ultimately
extracted.
References
for
these
sources
are
available
upon
request.
Geo-positioning
was
performed
to
the
finest
level
of
detail
possible
(e.g.,
country,
province,
district,
or
city/
town).
In
the
case
of
a
returning
traveler
report,
we
recorded
the
location
visited
as
the
site
of
the
occurrence.
The
database
was
last
updated
on
4
October
2013.
The
sources
we
used
to
create
our
initial
database
often
described
the
occurrence
of
more
than
one
DENV
type
at
a
time
and/or
spanned
multiple
years.
Conversely,
it
was
often
the
case
that
multiple
sources
were
referring
to
the
same
outbreak.
To
account
for
these
concerns
we
derived
a
standard
definition
of
an
occurrence
as
the
following:
one
or
more
reports
of
confirmed
infection(s)
from
a
specific
DENV
type
in
a
given
unique
location
within
a
single
year.
Accordingly,
if
multiple
reports
confirmed
the
presence
of
a
DENV
type
in
the
same
location
within
the
same
calendar
year,
they
were
considered
as
a
single
occurrence
record.
It
is
thus
important
to
stress
that
our
definition
of
a
type-
specific
occurrence
does
not
relate
to
the
actual
number
of
cases
reported
(this
information
was
not
consistently
avail-
able),
but
rather
to
the
presence
of
that
DENV
type
in
a
given
area
and
year.
For
mapping
and
descriptive
purposes,
province-
or
state-level
administrative
units
(Admin1)
served
as
our
unique
locations.
When
information
was
only
available
at
the
country
(Admin0)
level
in
a
particular
year,
it
was
included
in
the
database
for
those
countries
smaller
in
area
than
Queensland,
Australia
(the
largest
Admin1
unit
in
our
database
at
1.7
million
km
2
).
From
this
final
Admin1-
level
occurrence
database,
a
series
of
global
maps
were
created
for
each
DENV
type
across
six
time-periods
between
1943
and
2013.
We
also
present
the
number
of
DENV
types
ever
reported
in
a
given
area
across
these
time-periods.
Graphs
displaying
yearly
occurrences
by
world
region
and
country
were
also
created
(Figures
S1–
S12
in
the
supplementary
material
online).
Although
reports
of
suspected
cases
were
excluded
from
the
database,
no
restrictions
were
made
regarding
the
specific
diagnostic
typing
method
used
to
confirm
the
DENV
type(s)
responsible
for
an
occurrence
because
not
all
sources
specified
this
information.
This
was
particularly
true
for
ProMED
reports
that
often
simply
reported
cases
as
confirmed
without
specifying
the
method
of
confirma-
tion;
however,
for
comprehensiveness
in
our
database,
the
following
identification
method(s)
were
recorded:
(i)
virus
isolation,
(ii)
PCR,
(iii)
plaque-reduction
neutralization
test
(PRNT),
(iv)
not
specified/other.
The
frequency
of
occurrences
confirmed
by
each
of
these
methods
is
described
in
Table
S1
in
the
supplementary
material
online.
In
some
cases,
immunoglobulin
M
(IgM),
immuno-
globulin
G
(IgG),
or
hemagglutination
inhibition
(HI)
assays
were
used
to
confirm
infection
with
DENV,
but
used
alone
these
methods
are
not
useful
for
type-specific
DENV
determination
owing
to
DENV
type
cross-reactivity
[23].
As
such,
these
were
included
in
the
not
specified/other
category.
Mapping
DENV
spread
A
total
of
1
956
DENV1
occurrences,
1
931
DENV2
occur-
rences,
1
631
DENV3
occurrences,
and
1
000
DENV4
occurrences
were
mapped
at
the
Admin1
and
small
Admin0
level
across
the
entire
study
period.
An
additional
1
811
confirmed
DENV
occurrences
were
not
attributable
to
a
specific
type
due
to
lack
of
testing
and/or
reporting.
Review Trends
in
Microbiology
March
2014,
Vol.
22,
No.
3
139

Our
maps
describe
the
reporting
history
of
each
DENV
type
for
the
periods
1943–1959,
1960–1969,
1970–1979,
1980–1989,
1990–1999,
and
2000–2013
as
presented
in
Figures
1–4.
These
figures
are
complemented
by
additional
graphs
(Figures
S1–S12
in
the
supplementary
material
online)
that
further
break
down
the
yearly
distribution
of
occur-
rences
for
each
DENV
type
by
region
(Africa,
the
Americas,
and
Asia)
and
by
country
within
those
regions.
To
simplify
the
number
of
categories
presented
in
the
supplementary
material
online,
the
Americas
were
considered
to
include
North,
Central,
and
South
America,
whereas
Africa
includes
the
African
continent
as
well
as
Yemen
and
Saudi
Arabia.
The
Asia
region
additionally
includes
Oceania
and
the
Pacific
Islands.
The
supplementary
material
also
con-
tains
the
summary
of
available
information
on
type-spe-
cific
diagnostic
methods
(Table
S1
in
the
supplementary
material
online).
Again,
this
is
provided
for
descriptive
purposes
only
because
any
occurrence
described
as
con-
firmed
was
included
in
our
database,
regardless
of
diag-
nostic
method,
to
obtain
the
most
comprehensive
picture
of
DENV
type
distributions.
DENV1
Figure
1
displays
the
global
spatial
distribution
of
con-
firmed
DENV1
occurrences
by
time
period.
DENV1
was
first
reported
in
1943
in
French
Polynesia
and
Japan,
followed
by
reports
in
Hawaii
in
1944
and
1945.
It
was
not
until
the
late
1950s,
however,
that
reporting
of
DENV1
in
the
Asian
region
constantly
increased
over
time.
It
was
first
reported
in
Africa
in
1984
in
Sudan,
and
has
been
sporadically
reported
in
the
region
ever
since,
with
more
continuous
periods
of
reporting
in
Saudi
Arabia
between
the
mid-1990s
and
mid-2000s,
as
well
as
several
years
of
reporting
in
Reunion
in
the
mid-to-late
2000s.
DENV1
was
not
reported
in
the
Americas
until
1977,
when
it
was
recorded
in
Barbados,
Cuba,
French
Antilles,
Grenada,
Paraguay,
and
Puerto
Rico.
After
these
first
recorded
occurrences,
reporting
increased
persistently
across
the
region
over
the
next
few
decades,
with
near-continuous
reporting
in
Brazil,
Mexico,
and
Puerto
Rico
in
particular.
Several
other
countries
in
the
region
began
having
more
sustained
reports
in
the
1980s
and
1990s,
including
Colom-
bia,
Costa
Rica,
French
Guiana,
Paraguay,
Peru,
and
Venezuela.
Reporting
of
DENV1
peaked
in
2005–2006,
primarily
attributable
to
recorded
occurrences
in
the
Americas.
Since
1983,
the
Pan
American
Health
Organiza-
tion
(PAHO),
in
collaboration
with
the
US
Centers
for
Disease
Control
(CDC)
Dengue
Branch
in
Puerto
Rico,
provided
technical
assistance
for
developing
laboratory
surveillance
networks
in
several
countries
in
the
region,
and
this
may
partially
explain
increased
reporting
of
all
DENV
types
since
this
time.
DENV2
DENV2
was
first
reported
in
1944
in
Papua
New
Guinea
and
Indonesia,
followed
by
the
Philippines
in
1954
and
1956.
Malaysia
and
Thailand
have
reported
many
conse-
cutive
years
of
DENV2
occurrence
since
the
early
1960s,
as
well
as
Indonesia
since
the
early
1970s
and
China,
India,
the
Philippines,
Sri
Lanka,
and
Singapore
since
the
1980s.
Continuous
reporting
did
not
occur
in
Cambodia
and
1943−1959
1960−1969 1990−1999
2000−2013
1970−1979
1980−1989
TRENDS in Microbiology
Figure
1.
Spatial
distribution
of
reported
confirmed
cases
of
DENV1
since
1943.
Darker-colored
areas
represent
cases
that
were
confirmed
in
the
given
decade
under
consideration,
whereas
lighter-colored
areas
represent
cases
that
had
been
previously
reported
but
not
in
the
current
decade.
Review Trends
in
Microbiology
March
2014,
Vol.
22,
No.
3
140

Vietnam
until
the
1990s.
In
Africa,
DENV2
was
reported
in
Nigeria
multiple
times
between
1964
and
1968,
but
has
not
since
been
reported
there.
However,
several
sporadic
occurrences
have
since
been
reported
in
the
African
region,
with
the
most
recent
reports
being
from
Gabon
in
2010
and
Kenya
in
2013.
DENV2
was
reported
in
the
Americas
as
early
as
1953
in
Trinidad
and
Tobago,
but
continuous
reporting
in
the
region
did
not
begin
until
the
late
1960s
and
early
1970s,
most
notably
in
Puerto
Rico.
Since
this
time,
more
and
more
Latin
American
countries
have
begun
frequent
reporting
of
DENV2,
with
continuous
reporting
in
Brazil
in
particular
since
1984
accounting
for
the
majority
of
reporting
of
this
type
globally.
In
the
1990s,
there
was
an
increase
in
the
number
of
the
more
severe
hemorrhagic
fever
(DHF)
cases
in
the
Americas,
possibly
due
to
the
replacement
of
the
American
DENV2
genotype
with
an
imported
and
more
virulent
Asian
one
[24–27].
This
increase
in
DHF
cases
may
be
responsible
for
the
notice-
able
rise
in
DENV2
reporting
in
this
region
since
that
time,
as
seen
in
Figure
2.
The
largest
number
of
occurrences
reported
to
date
was
in
2005,
with
over
100
Admin1
and
small
Admin0
areas
worldwide
reporting
DENV2
pre-
sence,
primarily
in
the
Americas.
DENV3
DENV3
was
first
reported
in
1953
in
the
Philippines
and
Thailand,
and
has
been
reported
in
Asia
every
year
since
1962.
Although
many
countries
in
Asia
have
reported
DENV3
throughout
the
study
period,
Thailand
most
nota-
bly
reported
DENV3
every
year
between
1973
and
2010,
with
the
most
widespread
reporting
occurring
between
1999
and
2002.
Malaysia
and
Indonesia
have
also
reported
DENV3
frequently
since
the
1970s,
as
well
as
Sri
Lanka
since
the
early
1980s.
Records
of
DENV3
in
China,
Viet-
nam,
Cambodia,
and
Singapore
have
been
fairly
consistent
since
the
mid-1990s.
The
first
reports
in
the
Americas
were
in
Puerto
Rico
in
1963,
which
continued
to
report
DENV3
until
1978,
and
then
again
from
1994
to
2008
owing
to
the
introduction
of
a
new
DENV3
genotype
from
Asia
[28].
The
majority
of
other
countries
in
the
Americas
did
not
start
reporting
the
type
until
between
the
late
1980s
and
early
2000s.
Particularly
widespread
reporting
occurred
in
Bra-
zil
in
the
mid-2000s.
In
Africa,
overall
very
little
DENV3
has
been
reported
since
the
first
reports
in
1984–1985
in
Mozambique,
and
occurrence
has
mostly
been
sporadic,
with
the
exception
of
more
frequent
reporting
between
1994
and
2009
in
Saudi
Arabia.
DENV4
DENV4
was
reported
first
in
1953
in
the
Philippines
and
Thailand.
Since
this
time
the
region
has
reported
DENV4
yearly,
most
frequently
in
Thailand
whose
most
wide-
spread
reporting
occurred
between
1999
and
2002.
Sri
Lanka
has
also
reported
DENV4
almost
yearly
since
1978.
Although
reporting
by
country
has
not
been
as
consistent
as
for
other
DENV
types,
periods
of
more
fre-
quent
reporting
have
occurred
in
the
Indochina
region
as
well
as
Indonesia,
India,
Myanmar,
and
French
Polynesia.
DENV4
was
not
reported
in
the
Americas
until
1981,
when
it
was
reported
in
Brazil,
Cuba,
Dominica,
Puerto
Rico,
and
the
US
Virgin
Islands.
Since
this
date,
reporting
has
occurred
yearly
in
the
region,
with
particularly
frequent
1943−1959
1960−1969
1970−1979
1990−1999
2000−2013
1980−1989
TRENDS in Microbiology
Figure
2.
Spatial
distribution
of
reported
confirmed
cases
of
DENV2
since
1943.
Darker-colored
areas
represent
cases
that
were
confirmed
in
the
given
decade
under
consideration,
whereas
lighter-colored
areas
represent
cases
that
had
been
previously
reported
but
not
in
the
current
decade.
Review Trends
in
Microbiology
March
2014,
Vol.
22,
No.
3
141

1943−1959
1960−1969
1970−1979
1990−1999
2000−2013
1980−1989
TRENDS in Microbiology
Figure
3.
Spatial
distribution
of
reported
confirmed
cases
of
DENV3
since
1943.
Darker-colored
areas
represent
cases
that
were
confirmed
in
the
given
decade
under
consideration,
whereas
lighter-colored
areas
represent
cases
that
had
been
previously
reported
but
not
in
the
current
decade.
1943−1959
1960−1969
1970−1979
1990−1999
2000−2013
1980−1989
TRENDS in Microbiology
Figure
4.
Spatial
distribution
of
reported
confirmed
cases
of
DENV4
since
1943.
Darker-colored
areas
represent
cases
that
were
confirmed
in
the
given
decade
under
consideration,
whereas
lighter-colored
areas
represent
cases
that
had
been
previously
reported
but
not
in
the
current
decade.
Review Trends
in
Microbiology
March
2014,
Vol.
22,
No.
3
142

reporting
in
Puerto
Rico
since
the
1980s–1990s,
Venezuela
and
Colombia
since
the
1990s,
and
Nicaragua,
Brazil,
and
Peru
since
the
late
1990s–mid
2000s.
Co-circulation
of
DENV
types
Figure
5
displays
the
cumulative
number
of
DENV
types
having
been
reported
in
any
given
Admin1
and
small
Admin0
area
by
decade,
and
highlights
the
fact
that,
until
the
1980s,
the
majority
of
areas
had
only
reported
one
or
two
types
of
DENV.
This
figure
allows
the
observation
of
potential
increases
in
co-circulation
of
the
four
viruses,
which
may
serve
as
a
key
indicator
of
progression
toward
hyperendemic
transmission
[29].
In
the
late
1980s,
the
number
of
types
having
been
reported
within
a
single
area
began
to
increase
as
more
cost-effective
and
less
labor-
intensive
type-specific
diagnostic
tests
(e.g.,
PCR)
were
developed
for
dengue
[30].
This
may
also
explain
increases
in
global
reporting
of
specific
DENV
types
at
this
time,
although
the
number
of
reported
DENV
types
has
since
continued
to
increase
in
many
areas
across
Latin
America
and
the
Caribbean
islands,
as
well
as
in
Southeast
Asia,
the
Indian
subcontinent,
Indonesia,
and
Australia.
This
is
particularly
noticeable
in
the
map
representing
2000–
2013,
by
which
time
the
majority
of
Brazilian
provinces
as
well
as
much
of
Mexico,
India,
and
Indonesia
had
reported
every
DENV
type.
Although
few
areas
in
Africa
have
reported
all
four
DENV
types,
by
the
2000s
several
areas
had
reported
three.
However,
it
is
unclear
whether
these
all
represent
the
persistently
transmitted
epidemic
form
of
the
virus,
or
are
only
sporadic
overspills
from
the
sylvatic
transmission
cycle.
Exponential
growth
in
DENV
type
reporting
Reporting
of
DENV
type
is
irregular
and
affected
by
many
types
of
bias,
in
particular
in
locations
with
less
virological
diagnostic
capacity,
and
thus
our
database
represents
an
opportunistic
sample
of
occurrence.
As
such,
it
is
important
to
remember
that
an
absence
of
reporting
for
one
DENV
type
is
not
synonymous
with
an
absence
of
its
occurrence.
It
is
also
important
to
remember
that
our
definition
of
a
type
occurrence
does
not
relate
to
the
actual
number
of
cases
reported,
but
rather
to
the
presence
of
the
DENV
type
in
a
given
area
and
year.
Furthermore,
because
our
definition
of
a
type
occurrence
does
not
relate
to
the
actual
number
of
cases
reported,
but
rather
the
presence
of
the
DENV
type
in
a
given
area
and
year,
it
is
impossible
to
make
inferences
about
the
relative
prevalence
of
each
type
in
any
given
location.
That
said,
the
records
that
support
this
review
comprise
the
most
comprehensive
type-specific
DENV
database
to
date,
and
its
breadth
allows
a
much
more
detailed
depiction
of
spread
than
was
previously
available.
Although
there
is
general
agreement
that
several
fac-
tors
have
led
to
an
expansion
of
the
geographic
range
of
dengue
over
our
study
period,
and
particularly
in
the
latter
half
of
the
20th
century
[6,31–36],
the
variability
in
report-
ing
practices
over
time
as
well
as
by
region
and
country
1943−1959
1960−1969
1970−1979
1990−1999
2000−2013
Number of reported DENV types
1
Key:
2
3
4
1980−1989
TRENDS in Microbiology
Figure
5.
DENV
Co-circulation.
Cumulative
number
of
DENV
types
reported
by
decade
since
1943.
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in
Microbiology
March
2014,
Vol.
22,
No.
3
143

must
be
considered
alongside
apparent
patterns
of
expan-
sion
[37].
Improvements
in
reporting
capacity
over
time
will
have
had
a
significant
effect
on
the
number
of
cases
being
reported,
compounded
by
the
fact
that
increasing
co-
circulation
of
DENV
types
may
be
associated
with
more
severe
disease
outcomes
which
are
therefore
more
likely
to
be
reported.
However,
this
study
makes
it
clear
that
den-
gue
detection
has
increased
dramatically
across
the
globe
since
1943,
with
some
DENV
types
being
newly
reported
in
particular
areas
more
rapidly
than
others.
DENV1
was
reported
to
occur
the
most
times
during
this
70
year
study
period,
followed
by
DENV2,
DENV3,
and
DENV4.
The
overall
number
of
confirmed
type-specific
DENV
events
particularly
escalated
in
the
1990s,
primarily
comprising
increases
in
DENV1
and
DENV2
detection
in
the
Americas
owing
to
the
availability
of
rapid
diagnostic
tests.
In
Asia,
although
DENV2
reporting
has
increased
rapidly,
DENV3
reporting
has
surpassed
that
of
DENV1.
The
greatest
increase
in
reporting
of
DENV3
occurred
in
the
1990s,
predominantly
in
the
Americas.
DENV4
reporting
spread
the
least
rapidly
during
the
70
year
period,
although
it
has
been
consistently
reported
in
ever-greater
numbers
since
the
1980s,
particularly
in
Asia
and
the
Americas.
Although
documenting
dramatic
increases
in
DENV
reporting
across
Asia
and
the
Americas,
our
review
also
underscores
the
fact
that
there
still
remains
a
dearth
of
type-specific
DENV
information
in
many
parts
of
Africa
–
where
our
understanding
of
the
evolutionary
history
and
current
dynamic
of
DENV
transmission
and
spread
is
also
poorest.
Both
research
efforts
and
numbers
of
reports
have
remained
relatively
low
here
compared
to
Asia
and
the
Americas,
although
several
arboviral
studies
have
been
conducted
in
the
region
since
the
1980s
[38–56].
This
problem
is
made
worse
by
the
lack
of
DENV
type-specific
information
in
the
few
countries
where
occurrence
reports
are
available.
This
is
particularly
true
in
the
countries
of
east
Africa
where
evidence
for
dengue
presence
is
high
[21],
but
little
information
exists
about
the
specific
location(s)
within
these
countries
where
DENV
has
occurred
or
about
the
DENV
type(s)
responsible
for
occurrence.
Research
outlook
Additional
research
questions
can
be
explored
with
use
of
the
database
presented
here,
such
as
those
surrounding
the
importance
of
travel,
migration,
and
commercial
trade
in
the
spread
of
dengue,
the
introduction
of
novel
DENV
types
(and/or
genotypes)
into
locations
where
DENV
is
or
is
not
already
present
[57],
and
DENV
population
structure
and
evolution,
as
well
as
casting
light
on
how
human
immunity
mediates
DENV
transmission
at
the
micro
and
macro
scales
(Box
1)
[58].
The
ability
to
answer
these
questions
will
complement
phylogenetic
studies,
and
may
even
be
integrated
with
phylogeographic
studies
of
DENV
evolution
and
dispersal
on
a
regional
and
global
scale
[59–
61].
The
comprehensive
database
that
has
been
compiled
will
be
made
publicly
available
(via
http://figshare.com
[62])
such
that
it
can
be
directly
referred
to
in
order
to
facilitate
DENV
type
identification
in
historic
samples,
thereby
providing
information
about
what
specific
viruses
were
circulating
in
an
area
at
a
particular
time.
Tracking
the
spread
of
DENV
types
also
has
important
implications
for
ongoing
research
[15]
analyzing
changes
in
dengue
endemicity
in
a
given
area
over
time.
Continuing
spread
has
global
implications
Although
international
transmission
of
disease
is
not
new,
it
is
notable
that
airline
passenger
numbers
have
increased
by
9%
annually
since
1960,
enabling
infected
human
hosts
to
move
the
viruses
long
distances
more
quickly
[27,63].
Increased
urbanization
along
with
substandard
housing,
unreliable
water
supply,
and
poor
sanitation
provide
an
environment
for
Ae.
aegypti
proliferation
in
close
proximity
to
human
hosts.
In
the
Americas,
this
may
have
been
exacerbated
by
the
collapse
of
the
Ae.
aegypti
eradication
program
in
the
1970s
[8].
Increases
in
the
size
of
resource-
poor
urban
populations
in
Latin
America
and
the
Carib-
bean
in
the
late
1980s
and
early
1990s
may
have
supported
the
establishment
and
spread
of
all
four
DENV
types
in
the
Americas
[64].
According
to
the
United
Nations
Population
Division,
between
2000
and
2030,
Africa
and
Asia
together
are
expected
to
account
for
four-fifths
of
all
urban
growth
in
the
world
(see
http://esa.un.org/unpd/wpp/Documentation/
pdf/WPP2012_Volume-I_Comprehensive-Tables.pdf).
Therefore,
it
is
essential
that
we
closely
monitor
the
ongoing
and
future
spread
of
DENV
types
in
these
regions
to
understand,
detect,
and
respond
better
to
the
global
burden
of
dengue
disease.
Finally,
because
our
maps
have
underscored
the
ability
of
all
four
DENV
types
to
expand
into
new
territories,
the
crucial
need
for
a
DENV
vaccine
which
protects
against
all
four
known
types
is
made
ever
more
apparent
[64].
It
is
also
important
to
note
the
recent
suggestion
of
a
fifth
DENV
type
[65]
which,
if
found
to
be
as
transmissible
as
the
other
four
DENV
types,
might
follow
a
similar
pattern
of
geographical
spread
as
seen
with
these
types
over
the
past
two
decades.
If
sustained
transmission
of
a
fifth
type
did
occur
in
human
populations,
this
would
be
an
addi-
tional
consideration
for
vaccine
development
efforts
[64,66],
and
an
up-to-date
map
of
the
spread
of
DENV
types
would
be
essential.
Concluding
remarks
In
sum,
this
review
offers
the
most
contemporary
under-
standing
of
DENV
type-specific
geographic
distributions
from
1943
to
2013,
providing
a
starting
point
and
rationale
for
charting
the
ongoing
global
spread
of
each
DENV
type.
Specifically,
the
increasing
co-circulation
of
types
in
most
regions
of
the
world
–
particularly
in
Latin
America
and
Box
1.
Outstanding
questions

How
can
we
quantify
the
importance
of
travel,
migration,
and
commercial
trade
in
the
global
spread
and
evolution
of
DENV
types?

Does
co-circulation
of
DENV
types
increase
the
incidence
of
more
severe
disease
outcomes
in
a
given
area?
A
greater
number
of
seroprevalence
studies
involving
active
surveillance
are
required
to
answer
this
question.

What
is
the
distribution
of
DENV
types
in
Africa?
Although
returning
traveler
reports
are
useful
for
establishing
the
presence
of
certain
types
in
some
African
countries,
these
reports
are
currently
infrequent
and
sporadic.
Greater
surveillance
efforts
are
needed
in
Africa.
Review Trends
in
Microbiology
March
2014,
Vol.
22,
No.
3
144

Asia
–
has
important
implications
for
patterns
in
disease
severity
and
hyperendemicity,
as
well
as
for
ongoing
vac-
cine
efforts.
It
also
highlights
a
paucity
of
DENV
type-
specific
geographic
information
in
many
locations
across
the
globe
that
needs
to
be
urgently
addressed.
Appendix
A.
Supplementary
data
Supplementary
data
associated
with
this
article
can
be
found,
in
the
online
version,
at
http://dx.doi.org/10.1016/
j.tim.2013.12.011.
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