Acute Rheumatic Fever and Rheumatic Heart Disease: Incidence and Progression in The Northern Territory of Australia 1997 - 2010

DOI: 10.1161/CIRCULATIONAHA.113.
001477
Acute Rheumatic Fever and Rheumatic Heart Disease: Incidence and
Progression in the Northern Territory of Australia 1997 -2010
Running title: Lawrence et al.; Rheumatic heart disease: Lessons from the register
Joanna G. Lawrence, BHB, MBCHB, FRACP1; Jonathan R. Carapetis, MBBS, FRACP, PhD2,3,4;
Downloaded from http://circ.ahajournals.org/ by guest on July 3, 2018
Kalinda Griffiths, BBMSci, MPH3, 5; Keith Edwards, MBBS, DCH, FRCP(Edin), FRCPCH
FRACP2; John R. Condon, FAFPHM PhD3
1
Dept
De
ept of
of Paediatrics,
Paed
Pa ediaatric
ed trics,
cs Royal Children’s Hospital,
l, M elbourne; 2Paediatric
Melbourne; Paaed
e iaatrricc and Infectious Diseases
Dept
De
Depts,
ep s, Royal
Roy
oyaal
al Darwin
Dar
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Address for Correspondence:

Joanna Lawrence, BHB, MBCHB, FRACP
Royal Children’s Hospital
Flemington Road
Parkville, Victoria Australia 3052
Tel: +61 3 9345 4351
Fax: +61 3 9345 4751
E-mail: joanna.lawrence@rch.org.au
Journal Subject Code: Etiology:[8] Epidemiology
1
DOI: 10.1161/CIRCULATIONAHA.113.001477
Abstract:
Background—Although Acute Rheumatic Fever (ARF) and its sequel Rheumatic Heart Disease
(RHD) continue to cause a large burden of morbidity and mortality in disadvantaged populations,
most studies investigating the effectiveness of control programs date from the 1950s. A control
program, including a disease register, in the Northern Territory (NT) of Australia where the
Indigenous population has high rates of ARF and RHD, allowed us to examine current disease
incidence and progression.

Methods and Results—ARF and RHD incidence rates, ARF recurrence rates, progression rates
from ARF to RHD to heart failure, and RHD survival and mortality rates were calculated
caalc
lcul ated for
u ated NT
for N T
residents
esidents from 1997 to 2010. For Indigenous people, ARF incidence was highest in the 5-14 year
age-group
ag
ge-
e-gr oup (males
grooup
gr (m ess 162,
6 , females 228 per 100,000).
162 0)). There
100,000) There was little
lee evidence
dennce that the incidence of
eviide
ARF or RHD hhad

ARF a ddeclined.
ad ecli
ecl ned
ned.
d. Th
Thee AR
ARF recurrence
F re rate
ate ddeclined
ecurrrence ra by 99%
ecliineed by
ecli % pe year.
per ye
yeaa r. A
ar. Afterer a ffirst
fter
ft irst
ir stt
ARF
AR ddiagnosis,
RF di ag
gno
nosi s, 661%
sis, 1% ddeveloped
ev
vel
elopped
dRRHD
H w
HD within
ithi
ithinn te
hi yyears.
tenn yea After
earss. After
ft RHD
er RHD ddiagnosis,
iagn
gnos
nosis
is,, 27
is 227%
% ddeveloped
evvellope
lopeed
heart failure within

w th
wi t in five
ve years.
fiv yeear s For
ars. For Indigenous
Ind
n ig
igen
enou
en ouss RHD
ou RHD patients
p ti
pa tients the
ents
en the relative
rellativee survival
ativ
iv surv
su r iv
rv al rate
ival atee was 88.4%
rat %
ten years after diagnosis and the standardized mortality ratio was 1.56 (95% CI 1.23-1.96).
Conclusions—For Indigenous Australians in the NT, ARF and RHD incidence and associated
mortality remain very high. The reduction in ARF recurrence indicates that the RHD control
program has improved secondary prophylaxis; a decline in RHD incidence is expected to follow.
Key words: Acute Rheumatic Fever, Recurrence, Indigenous Australians, rheumatic heart
disease, incidence
2
Background
Acute Rheumatic Fever (ARF) is an autoimmune phenomenon following infection with Group A
streptococcus. Inflammation of the joints, heart and brain result in the common clinical
manifestations of arthritis, carditis and chorea. Although now rare in developed countries, ARF
maintains a note-worthy presence in economically disadvantaged populations driven by factors
including household overcrowding and poor hygiene. 1 The major morbidity and mortality result
from cardiac involvement known as Rheumatic Heart Disease (RHD).
Compared with primary prevention or treatment of established carditis, secondary

prophylaxis (in the form off two to four-weekly intramuscular benzathine

benzathine penicillinn G)
G has
has been
bee
eenn
RHD
RH D. 2
proven to be the most cost-effective intervention in the management of ARF andd RHD.
Unfortunately,
y delivery of regular doses remains suboptimal in most countries, and many
patients
pa
ati
tieentts suf
suffer
uffe
ferr re
fe repe
repeat
peat
pe at eepisodes
piso
pi sode
so d s of A
de ARF
RF aand
nd cconsequently
onse
on s qu
quentlly de
deve
develop
v lo
op po
pote
potentially
tent
nttia
i llyy av
avoi
avoidable
oida
oi dabl
blee
progressive
pr r ssive heart
roggre hearrt damage.
he dam
mage.
Despite
Desp
De causing
spitte caus
usin llarge
ing a la rg burden
ge bu rden ooff di
burd disease
dise globally,
seasse glob
obal
ally
ly, th morbidity
thee mo
orb
rbid
idit
i y an mortality
andd mo
mort
tallit relating
ityy re
ela
lati
ting
ng to
ARF
AR F remain
rema
re in ppoorly
main oorl
oo understood.
rlyy un
unde
ders
rsto
tood
od Th
Thee mo st ccomprehensive
most ompr
ompreh
eheens
nsiv longitudinal
ivee lo
long
ngit
itud
udin al sstudy
inal tudy
tudy aaddressing
ddre
dd ress
ssin disease
ingg di
dise
seas
asee
progression dates from 1965, almost half a century ago. 3 In 2005, only one country in which
RHD occurs at high rates (New Zealand) was felt to have reliable cause-specific mortality data
relating to RHD.4 Similarly, little is known of the morbidity due to cardiac involvement or the
time course of disease progression from ARF to RHD and heart failure. A large burden of
disease exists in developing countries, where there is little scope for detailed epidemiological
analysis.5 However, in some high-income countries there are population groups that live in
poverty and have high rates of ARF and RHD, including the Indigenous populations of northern
and central Australia and New Zealand. Longitudinal studies in these populations will give
3
insights into morbidity and mortality that may be extrapolated to low and middle income
countries, albeit with appropriate adjustment for rates of disease and access to medical care.
The Aboriginal population living in the Northern Territory of Australia (NT) has the
highest documented incidence rate of ARF in the world. 6 Since the NT Rheumatic Heart
Disease Control Program established a computerised register in 1997, all known cases of ARF
(including recurrent episodes) and RHD in the NT have been recorded. The register is used by
RHD program coordinators to collect demographic data, send reminders for secondary
prophylaxis and facilitate specialist clinical care. This confidential password-protected database
covers a population of over 225,000 people scattered over an area of 1,346,000 square kilometers
anging from coastal tropics in the north to desert in the south.7 Of this population,
ranging populatiion,,
approximately 64,000 (30%) is Indigenous (Aboriginal or Torres Strait Islander), the majority of
whom
wh om live
live
ive in small,
sma
malll,
ma ll, very isolated remote communities
commu
mu
uni
n ties characterized
characteriz
izzed
e bby
y ppoor
oor quality,
over
overcrowded
ercr
c owded ho
hou
housing
usingg an
usin and
nd wi
wide
widespread
desp
de spre
r ad
re y. 8
a ppoverty.
overrty
There
Ther
Th eree are
er are currently
curren
curr entl
tlyy approximately
ap
ppr
prox
oxim
ox imat
imattelly 2,500
2, 00 people
2,50 peop
peo le
op le rrecorded
ecor
ec orrde
d d on tthe
he rregister
he egis
eg iste
is teer an
andd th
the
he
Rheumatic Heart
Heear
artt Disease
Dise
Di seeasse Control
Cont
Co n ro
roll Program
Prog
Pr og
gra
r m staff
staf
st afff consider
af con
onsi
s deer th
si that
a ssince
incee 11997
in 9977 th
99 thee re
regi
g st
gi ster
registerer iiss almost
complete (ie, contains almost all people diagnosed with ARF or RHD) with incomplete data on
cases for several years before that.9 These data have been used to date to report predominantly
on incidence of ARF and prevalence of RHD, but not to look at longitudinal outcomes.10,11 The
data collected offered an opportunity to explore the epidemiology, mortality and morbidity of
ARF and RHD in a population with very high rates of disease.
Methods
The NT RHD register includes data on patient demographics and diagnoses, clinical features of
4
ARF episodes, reviews by doctors and secondary prophylaxis administration. De-identified data
were extracted from the register in May 2011, assessed for data quality and analysed using
STATA software (STATA Corporation, College Station, Texas). The study was approved by the
Human Research Ethics Committee of the NT Department of Health and the Menzies School of
Health Research. Access to register data was approved by the RHD Steering Committee and the
register’s data custodian. No contact with registered patients was required.
Data quality assessment and exclusions
People registered with a diagnosis of unconfirmed ARF or RHD, or no diagnosis at all, were
excluded, as were people with missing demographic data such as sex and Indigenous status.
Diagnosis and clinical review data were analysed for inconsistencies (such as cli
clinical
linnica
nica reviews
c l re
revi
view
vi ewss for
ew
RHD before the RHD diagnosis date); inconsistent data were resolved where possible or cases
excluded
ex
xcl
clud ed ((see
uded
ud Results
s e Re
se esu l s for details).
sult
The study
dy population
sttud populaati
pop on was
tion was defined
def ned ass NT
e in NT residents
ressideents who
who were
re registered
were
we regiiste
tere ith a cconfirmed
redd wi
re with onnfirm
firm
rmeed
first
fi
irsst AR
ARF episode
F ep
epis
isod
od RHD
de or R HD ddiagnosis
HD iagn
iagn
nos is ooccurring
osis ccur
ccurri
ur ring
ri weeen 1stt JJanuary
g bbetween
etw anua
anuaary
y 11997
99
97 an
and 3 stt D
nd 31 December
ecem
embe
emberr
2010. In the Northern

Nor
orth
th
her
ernn Territory,
T rrrit
Te itor
ory,
or y,, the
the diagnosis
diaagn
gnos
osis
os iss of
of ARF
ARF was
was based
base
ba sedd onn the
se the 1992
199
9922 updated
upda
update
datedd Jones
te
Criteria19 until the 2005 Australian guidelines became available.12 RHD was diagnosed by
specialist physician and confirmed by echocardiography. A first episode of ARF was defined as
an ARF episode within the study period, where there was no previous record of an ARF or RHD
diagnosis. An ARF recurrence was defined as a second or subsequent ARF episode occurring in
a person with a first ARF episode in the study period. Only recurrences in those who presented
with ARF were used (ie. subsequent episodes of ARF in those who first presented with RHD,
presumed to have missed first episode of ARF, were not included) in order to allow measurement
of time to recurrence. The date of diagnosis of RHD was defined as the date of diagnosis
5
recorded on the register, unless there were clinical reviews for RHD prior to the recorded
diagnosis date, in which case the date of first review was used as a surrogate.
Statistical analysis
Univarate and multivariate analyses of several outcome measures were performed, most
stratified by sex, age at diagnosis and year of diagnosis. The following outcome measures were
analysed:
1. demographic characteristics of people diagnosed with ARF and/or RHD
2. clinical manifestations of ARF: restricted to first ARF episodes between 2/10/2007 and
31/12/2010 because recording of clinical manifestations was incomplete before 2007.
3. age-specific and age-adjusted incidence rates for first ARF episode, totall A
ARF
RF eepisodes,
piso
pi soddes,
so des,
and RHD diagnosis
4.. negative
ne
ega tivee binomial
gati
ti binomial
in regression analysis off ARF
AR and RHD incidence;
in
nci ncee; independent variables
c deenc
were
w re Indigenous
erre ouss status,
Indigenou us, gender,
sttattus gend
ge nder
nd er,, age
er ge at diagnosis
ag diagnnossis and
and year
yeaar of
of diagnosis.
dia
iaggnosis.. The
gn sis The model
deel for
mode
mo for RHD
RH
HD
incidence
nci
cide n e also
denc
de nc alsso
al so included
ludeed an interaction
incllude int
ntera
nt ract
ra ctio
ct ionn term
io term for
forr Indigenous
Indig
gen ouss status
nou stat
atus
at uss by
by age
ge at diagnosis
ag dia
iagn
gnoosi
gn is bbecause
osis ecau
ec se tthe
ause h
he
effect of agee was

was found
foun
fo undd to be
un be different
diiff
ffer e t for
e en
er f r Indigenous
fo Indi
In dige
di geno
ge u than
nous
no us hann non-Indigenous
tha
ha non-
no n In
n- I di
dige
geno
ge nous
no us people.
peo
opl e. Negative
ple. Neg
e ative
binomial regression was used because incidence data were found to be over-dispersed.
5. RHD prevalence on 31 December in 2000, 2005 and 2010
6. rate of ARF recurrence after a first ARF episode in people diagnosed with their first ARF
episode between 1/1/1997 and 31/12/2010, calculated as the number of second ARF episodes per
100 person-years.
7. rate of progression from ARF to RHD: proportional hazards regression analysis of the
incidence of RHD in people who had a first ARF episode between 1/1/1997 and 31/12/2010;
independent variables were indigenous status, gender, age at diagnosis, year of diagnosis and the
6
presence of chorea at the first ARF episode.
8. rate of progression from RHD to heart failure: proportional hazards regression analysis of
the incidence of heart failure in people diagnosed with RHD between 1/1/2004 and 31/12/2010.
Independent variables were Indigenous status, gender, age at diagnosis and year of diagnosis.
9. relative survival rate (RSR) and standardised mortality ratio (SMR) for people diagnosed
with RHD in 1997-2010, which measure excess mortality due to RHD.
For measures 6, 7 and 8, the follow-up time was censored at the earliest of: date of
diagnosis (of second ARF episode, or RHD, or heart failure, respectively); date of death; or
31/12/2010. Since 2004 the NT RHD Control Program has classified severity of carditis to guide
appropriate medical follow up.12 Patients are classified as “Priority 1” if they have:
hav
av
ve:: established
est
stab
st abli
ablish
lished
sh ed
RHD with severe valve lesions; moderate to severe valve lesions where left ventricular function
iss impaired;
imp
mpai
aire
ai reed; increased
incre
reeased
ase left ventricular size; shortness
shorttne
n ss of breath, tire
tiredness,
redneess
re ss,, oedema, angina or
syncope;
yncope;
ncc or ha
had
ad an
any
ny su
surgical
urg
gic
ical
al iintervention
nterv
nte rveent
ention onn ttheir
heirr vvalves.
alv
vess. W
Wee uused
sed tthe
he ddate
atee of
at of cclassification
laasssif
ific
icat
icattion
ion aass
“Priority
“P
Pri
rior i y 1” to
orrit indicate
to in catte the
ndiica the ddate
a e of diagnosis
at dia
iaggnos
gnos is of
osis of heart
heearrt failure.
faillur
fail uree. Analysis
A al
An a ys i of
ysis
is of progression
p og
pr ogre
ress
re ionn too heart
sssio hea
earrt
failure was re
rest
restricted
s ri
st r ct
cted
ed tto
o thee 64
6455 ca
case
cases
sees of R
RHD
HD di
ddiagnosed
agno
agnoseed si
no sinc
since
n e th
nc the pr
prio
priority
iori
iority
ri ty cclassification
laass
ssif
ific
ificcat
atio
i n was
introduced.
Relative survival analysis was used to estimate mortality due to RHD because: cause of
death data was not available to for cause-specific analysis; and a comparison cohort of people
without RHD was not available for comparison of all-cause mortality in people with and without
disease. Relative survival estimates mortality due to RHD by comparing the observed with the
expected all-causes mortality rate for the RHD cohort; the expected rate is based on general
population all-cause mortality rates matched by age, sex, year and Indigenous status. Relative
survival rates and standardized mortality ratios was calculated by the method described by
7
Dickman et. al. using the ‘strs’ commands in Stata.13 Life-tables for the total Australian
population were used to calculate expected probability of death (by age, sex and year) for non-
Indigenous cases.14 Life-tables for the total NT Indigenous population (by age, sex and year)
were calculated from NT Indigenous population mortality rates.
The number of non-Indigenous subjects was small (e.g. only 15 of 615 first ARF
episodes), so comparisons of Indigenous with non-Indigenous subjects was limited; for some
outcome measures multivariate analyses were restricted to Indigenous cases only. The Estimated
Resident Population of the NT by five-year age-group, sex, Indigenous status and year as
published by the Australian Bureau of Statistics was used as the denominator for calculation of
population-based incidence rates.
Results
Resu
Re sult
su ltss
lt
Datta
ta quality aassessment
Data sssesssm
men
nt an
andd ex
excl
c usi
clusions
exclusions
The
Th
he re
regi
register
gist
gi ster
er ccontained
onttaiined
on ined
d iinformation
nform
nfo mattio
ionn on 22,837
,8837 ind
individuals,
ndiv
nd iv
vid
duaals
ls,, with
wi h a ttotal
ottal ooff 3,92
33,920
,9220 di
ddiagnoses
agnnose
ag sees an
andd
20,890 clinica
caal co
clinical cont
ntac
ntacts
acts..
ts
contacts.
84 people were documented as having a RHD diagnosis date before the date of their first
ARF episode. The first ARF diagnosis date was changed to the RHD diagnosis date if there was
less than 30 days difference (29 subjects) and otherwise excluded from analysis of ‘first ARF
episode’ on the basis that this was unlikely to have been their first presentation (55 subjects).
1,372 individuals were excluded from analysis because: they had no recorded diagnosis details
(528 people, 222 of whom had died before 1997, 115 died between 1997 and 2010, 119 had an
indication that they had an episode of unconfirmed ARF); they had been diagnosed with RHD
before 1/1/1997 (495) or diagnosed with ARF before 1/1/1997 and had not been diagnosed with
8
RHD (197); or they were interstate residents (141). 1,469 individuals met the inclusion criteria
for the study, four of whom were excluded from analysis because of missing data on Indigenous
status (1) or gender (3), leaving 1,465 individuals in the analysis dataset (Figure 1).
The final dataset included a total of 1,465 subjects with 1,149 diagnoses of RHD and 615
first diagnoses of ARF between 1st January 1997 and 31st December 2010.
Acute Rheumatic Fever
Of the 615 people with a first episode of ARF between 1997 and 2010, 600 (97.6%) were
Indigenous (Table 1). The proportion of females was similar for Indigenous and non-
Indigenous cases. The median age of first presentation was 12 years old for Indigenous subjects
egardless of gender. Non-Indigenous cases were older by 6 years for males (median
regardless (m
med
edia
iaan age
ag
ge 18
years) and 3 years for females (median age 15 years). Incidence of first ARF episode was
hi
igh
ghes
esst in tthe
highest he 5-1
-1
14 yyear
5-14 ear age-group for both Indig
gen
e ous and non-I
Indigenous Ind
n ig
gen
nous
ou people (Figure 2).
non-Indigenous
T hee in
The iincidence
cidencee ra
atee inn In
rate Indi
dige
di geno
nous
no
Indigenous us ppeople
eople age
eop ed 5-144 yyears
aged eaars
a rs was 19
was 1944 pe
perr 10
1100,000
0,00
0, 0000 ov
00 over
e al
erall,
l, 162
overall, 62 iin
n
ma
ale
l s an
males aand
d 228
228 inn females.
fem
emaalees.
es Incidence
Incid
ncid
iden
encce
en ce in
in non-Indigenous
nonn-In
no In
ndi
d geno
genous
u ppeople
us eopl
eopl
plee wa
wass mu
mucch llower
ch
much ower
ow e iin
er n aall
lll ag
ge-
age-
groups than for

fo
or Indigenous
In
ndi
dige
geno
ge nouss people.
no peo
e pl
ple.
e
e.
In multivariate analysis, the incidence of first ARF episode was 69 times higher for
Indigenous than non-Indigenous people, adjusted for age, sex and year of diagnosis (Table 2);
however, this is not a precise estimate because of the low number of non-Indigenous cases (the
lower bound of the confidence interval being a 40-fold increased risk). In analysis restricted to
Indigenous people only, ARF incidence was 49% higher in females than males, and there was no
evidence of a decrease in incidence between 1997 and 2010 (Table 2).
Clinical manifestations at the first diagnosis of ARF
149 people were registered with their first episode of ARF between 2 October 2007 (when the
9
register commenced uniform collection of data on clinical manifestations of ARF) and 31
December 2010. Of the major manifestations, joint involvement was the most common
presenting feature, recorded in 77% of total presentations (Table 3). Amongst those with joint
involvement, 63.5% had polyarthritis, 7.0% had polyarthralgia and 29.6% had mono-arthritis, the
latter two considered major manifestations in high risk populations in Australia.12 Carditis was
present in 27.5% and chorea in 19.5%. As the rates of carditis were much lower than expected, a
subgroup analysis was performed. Rates of carditis were found to be significantly lower
(14.6%) in a subgroup where diagnosis was based on chorea or less stringent criteria for arthritis
(ie. monoarthritis or arthralgia). In the subgroup with more classical features, carditis was
present in a higher proportion (43.3%). The most common minorr manifestation

nw a a rise
as
was ris
isee in
nflammatory markers (74%). Fever was present in 53%.

inflammatory
Choorea
Ch orea
Chorea
Twenty-nine
T weenty-nine
en (19.
(1
(19.5%)
9 5%) off tthe
he 1149
49 ppatients
49 attie
iennts
nts dia
diagnosed
agnoseed af
agn after
fter
ter 2/
2/10/2007
/100/2
/20007
007 ha
hhad
d ch
cho
chorea
orea
ore
ea aass a
ma
ani
nife
fest
fe stat
atio
manifestationionn of th
io heir fir
heir
their irrst A
first RF eepisode.
ARF pissod
pi sode.
de C horrea
ho e w
Chorea a am
as
was ore co
ore
more ccommon
mmon
mm on mani
nife
fest
fe s attio
st
manifestationionn ooff a ffirst
irrstt
ARF episodee in females

fem
emal
alles (22
(22 of
of 88,
88, 25%)
2 %) than
25 tha
hann males
male
ma lees (7
( of
of 61,
61, 11%)
11%) and
and in
in those
thos
th osse aged
aged <20 years
(28 of 123, 23%) than those aged 20 and over (1 of 26, 4%). In multivariate logistic regression
analysis (adjusted for diagnosis age (<20 or 20+), sex and diagnosis year, the associations with
age (OR 0.90, CI 0.81-0.99) and sex (OR 3.21 , CI 1.2-8.4) were significant.
Those with chorea were less likely to have concurrent arthritis (31% compared to 88%),
raised inflammatory markers (38% compared to 83%) or fever (21% compared to 29%). Rates
of carditis in the initial episode were similar; of those with chorea, 49.5% were documented as
developing RHD sometime during the study period, compared to 51.5% of non-chorea patients.
Evidence of the development of heart failure was less likely in chorea (3.7%) compared to non-
10
chorea patients (26.4%).
Rheumatic Heart Disease
There were 1,149 people registered as having been diagnosed with RHD between 1997-2010,
1,066 (92.8%) of whom were Indigenous and 756 (65.8%) female (Table 1). Males presented at
a younger age than females and Indigenous patients were much younger (males 19 years,
females 23 years) at diagnosis than non-Indigenous patients (males 46.5yrs, females 51 years).
Figure 3 shows an increasing prevalence of RHD amongst the Indigenous population
with time. However, 71% of RHD cases recorded on the register were diagnosed after the
register commenced (1997-2010), 25% of whom were aged 40 years and over when diagnosed.
This indicates that although efforts were made to collect data on cases diagnosed
d pprior
r orr tto
ri 1997,
o 19
1997
97,
data collection was incomplete then. The lower prevalence in 2000 and 2005 is therefore at least
inn part
artt because
par beca
beca usse of more
caus more recent diagnosis of long-standing
g standing RHD cases.
long-
g- a es.. In
cas In 2010 the peak
prevalence
prev a ence was
val as in
in the
he 45-64
th 64 year
455-6
-64 year age
ge group
age group (3.1%).
(33.1%
%).
For thee NT IIndigenous

For th nddig
gen population,
enouus po
popu
pula
pu lattion
tion
on,, RH
RHD iincidence
D inc
ncid
cidenc
denc was
as hhighest
ncee wa igh
ghes
gh n tthe
e t in
es he 55-14
-144 age
-1 aage-group
ge-gr
e-gr
grou
oupp for
fo
males and in
n tthe
he 115-24
5 244 aage-group
5- gee-g r up ffor
gro o ffemales,
or emal
emales
al es,, an
es wass hi
andd wa
w hhigher
er ffor
gher
gh o ffemales
or emal
em es tthan
ales
al h n ma
ha males
male
less in all age-
le
groups except 65+ (Figure 4). For the non-Indigenous population, the incidence rate was highest
in the oldest age-group, and was much lower in all age-groups than for Indigenous people.
In multivariate analysis, RHD incidence was 64 times higher for Indigenous than non-
Indigenous people, adjusted for age, sex and year of diagnosis (Table 4) with the lower bound of
the confidence interval being a 43-fold increased risk. RHD incidence for females was almost
twice that for males.
Recurrences of ARF
There were 846 total episodes of ARF registered in 1997-2010. This includes 94 recurrent
11
episodes in 77 of the 615 people who had their first episode in that period. Sixteen of these 77
had two or more recurrences. The recurrence rate was highest in the first year after the first ARF
episode and decreased to zero by ten years after the first episode (Figure 5).
Among Indigenous people, the recurrence rate in the first year after diagnosis was 4.5%
and the five-year recurrence rate was 12.5%. In multivariate analysis, the recurrence rate
decreased by 9% per year following the date of diagnosis of the first episode (Table 5). The
recurrence rate also decreased with older age at initial presentation (by 7% per year of age).
Although the point estimates suggested a possible association of female gender and Indigenous
status with recurrence rate, the confidence intervals for both these associations included 1.0.
Disease Progression:
ARF to RHD
Inn m
multivariate
ulti
ul tiva
ti vaari ate analysis
riat
at an alysis the only factor strongly associated
naly a sociated with RH
as RHD
R incidence
D in
incci
cidence was age at first
ARF episode (risk

ARF (ris
(r decreased
iskk de
is deccreease
ease by 22%
sedd by per
% pe year
ar ooff ag
er yea age)
ge) (Table
(Ta
Tabl
Tablee 6).
6) There
There was
Ther wa a suggestion
suugg
ggeesti
tion
tionn that
hatt the
tha the
risk
isk of
of developing
deve
de veelo
lopi ng RHD
pinng RHD after
f err an
aft an ARF
ARF diagnosis
diag
di agnnosi
ag siss w
si was
as hhigher
ighe
ig herr fo
he IIndigenous
forr Indi
ndi
dige
g nous
ge nous tthan non-Indigenous
hann no
ha nonn-In
ndiige
geno
nouus
us
people and for

forr females
fema ess than
mal thaan males,
m le
ma s but
les,
s, butt the
the confidence
con
onffid
den c iintervals
ence
ce nter
nt erva
er v ls ffor
va or bboth
othh ha
ot hazard
z rd rratios
haza
za atio
at ioss included
io
1.0. Among Indigenous subjects, 35% developed RHD by one year after first ARF episode and
61% by 10 years (Figure 6).
RHD to Heart Failure
Overall, 28% of those diagnosed with RHD developed heart failure at some stage between
diagnosis and the end of the study period (31 December 2010). Fourteen percent had heart
failure at diagnosis. This increased to 21% at one year after diagnosis and 27% at five years
after diagnosis (Figure 6). In multivariate analysis there was little or no evidence of an
association between Indigenous status, gender, age at diagnosis or year of diagnosis and risk of
12
developing heart failure (Table 7).
Mortality
During 1997 to 2010, 79 individuals (6.9%) from the cohort diagnosed with RHD (1149
subjects) died; 3 non-Indigenous (3.6% of non-Indigenous cases) with a median age of 51 years
and 76 Indigenous (7.1% of Indigenous cases) with a median age of 22 years.
There was no excess mortality from RHD among non-Indigenous cases relative to the
general population of the NT of the same age and sex; relative survival was greater than 100% at
5, 10 and 14 years after diagnosis.

Amongst the Indigenous cohort, the crude all-cause survival rate was 96.1% at five years
after diagnosis and 88.4% at ten years after diagnosis. The relative survival rate for
for Indigenous
Ind
ndig
igen
igenou
eno s
ou
cases (i.e. survival rate of Indigenous people with RHD compared to the total Indigenous
population)
po
opu
pula
lati
lation
ti was
onn) w 98.9%
ass 98
98.9 97.4-100.1),
. % at five years (95%CI 97.4 lower
4-100.1), but lowe
4-1 thereafter:
wer th
we her
ereeafter: 95.3% at ten
yyears
rs (92.3-97.8)
ear
ars (92.3-97 8) and
7.8 and 90.5%
90 5% at 14
0.5% 14 years
years (83.9-95.6).
yea (833.99-95..6). This
Thiis indicates
indicaatees that
ndica hat Indigenous
tha Indi
Indi
dige
geno us RHD
nouus RHD patients
patie
at ents
suffer
uff err little
ffer lit tlee if any
ittl any excess
exc ess mortality
xceess mort
mo r al
rt ityy compared
alit
it comp
comp
mpar ed to
ared
ar the
to th general
he ge rall NT IIndigenous
eneera nddig
igen
en ppopulation
nous popu
opu
pula tionn inn the
laati the first
firs
fi rt
after
five years aft er ttheir
fter RHD
heeir R H ddiagnosis,
HD iagn
ia nos but
o iss, bu
ut th
that
a th
at ey ssuffer
they considerable
u feer co
uf cons
n id
ns ider
e ab
er blee eexcess
xces
xc mortality
esss mo
es mort
r al
rt a it
i y in
subsequent years. This is consistent with the all-cause death rates of Indigenous RHD cases that
increase with time after diagnosis, particularly more than four years after diagnosis (Figure 7).
Among Indigenous people diagnosed during or after 2004 (when the clinical priority
classification was introduced), those with a first clinical assessment of severe disease had a
five-year relative survival rate of 89.7% (95%CI 79.5-95.8), while those assessed as having
moderate, mild or inactive disease had five-year survival close to 100% (99.6%-103.7%).
The Standardised Mortality Ratio (SMR) among Indigenous cases was 1.56 (95% CI
1.23-1.96) indicating the number of deaths was 56% higher than expected compared to the NT
13
Indigenous population, whereas for non-Indigenous cases the SMR was 0.63 (0.13-1.85), which
is consistent with their relative survival rates greater than 100%.
Discussion
This is the first time that longitudinal data collected from an RHD registry have been used to
evaluate disease burden and patterns of disease evolution in a high-incidence population.
This audit demonstrates that the incidence rate and at-risk population for first episode of ARF
has not changed significantly over the past 14 years. Those most at risk continue to be
Indigenous children, aged 5-14 years.
The incidence rates of first episodes of ARF reported here in Indigenouss 5-14
5-14
5-1 year
14 eaar olds
year olds
(228
228 and 162 per 100,000 in females and males, respectively) are similar to previously
documented
do
ocu
cume
ment
me ed rates
nted
nt ess of
rates of 250-300 per 100,000 in thee same populationn.6,10 T
me population.
sam The
he slightly lower rates
he
ffound
ound
unn in this audit
auddit are
au arre most
most likely
lik
ikel
elyy due
due too thee fact
fact tthat
hat we iincluded
nclludeed on
only
nly ffirst
irs
rstt ep
epis
episodes
isod
odees
od es ((whereas
wher
wh ereeas
e as
the previous
he pr
prev
e io
ev us sstudy
ious dy iincluded
tuddy
tu ncclu
lude aalll ep
dedd al episodes),
epis
isoode
is ) aass we
odes),
es), well u sstrict
ll ass our
ur triictt in
tr iinclusion
c us
clusio ccriteria
i n crit
io eriaa rresulting
riteeria ng iin
esuultin
es ul ng n the
t he
exclusion off a number

num
mbe
b r of
o documented
doc
ocum
umen
umente
en tedd cases
te case
ca sess with
se w th
wi h insufficient
ins
nsuf
u fi
fici
c en
ci entt di
diag
diagnostic
a no
ag nost
stic
st ic iinformation
nfor
nf o ma
or mati
tion
ti on eeither
ither
recorded or present (the latter represents ‘possible’ ARF).
It is unlikely that increased awareness and notification are responsible for the ongoing
high rates of ARF in this population, as the disease became notifiable in the NT in 1996 (prior to
this study period) and campaigns to increase awareness have been present since WHO
recommendations in 1994.15 The more recent broadening of the definition of joint involvement,
with the inclusion of polyarthralgia and monoarthritis in the diagnostic criteria, as well as the
inclusion of subclinical carditis12 may account for increased numbers of diagnoses. However, it
is likely that the rates remain high due to a failure to adequately address the socio-economic
14
determinants of health driving the high rates of infection in our remote Indigenous population.
This therefore remains a significant public health concern worthy of further attention.
RHD has a similar demographic profile to ARF, with higher incidences occurring in the
Indigenous population, females and those living remotely. No decrease in incidence of RHD
was demonstrated over the past 14 years. Because there was incomplete recording of cases prior
to the register commencing in 1997, there has been a continual increase in prevalence due to the
steady incidence of new cases combined with the long duration of incident cases. With the
completeness of data collection over this period, the recent prevalence rates are likely to be
nearing the true prevalence of disease in this population. Our reported prevalence rates, with a
peak of 3.1% in the 45-64 year old group are consistent with previously reportedd rates
t s in the
raate the
Northern Territory.6,10 As efforts to reduce recurrence rates of ARF appear to be having an
ef
ffeect
ct,, and
effect, and th
thee pe
ers
rsis
i tently high incidence of ARF
persistently RF may partly be eexplained
may x laain
xp ineed by the recent
inclusion
ncllus
u ion of milder
millder cases
case
ca sess with
with a lower
lo
ower
wer incidence
in
nciddence of
of clinical
clini
nica
ni call carditis
caard
rdiitiis (a
(ass a re
result
esul
sult
lt ooff ex
expansion
xpa
pans
nssio
ionn of
of
diagnostic
diag
di agno
agnost
no stic
ic criteria
cri
rite
teri
riia to include
incclu
lude
de subclinical
subc
su bcli
bc lini
linica
caal ca
car
carditis,
rd tis
rditis,, mo
m
monoarthritis
nooar
arth
thrriti
th tiss and
ti and po
ppolyarthralgia
lyaarth
arth
hra
r lg
lgia
iaa aass maj
m
major
ajor
jor
nss12),
manifestations ) tthe
h iincidence
he n id
nc den
ence
cee ooff RH
R
RHD
D ca
cann be eexpected
xpec
xp e teed to rreduce
ec educ
ed u e in ccoming
uc omin
omingg ye
in year
years.
a s.
ar s
Females were 1.5 times more likely to present with ARF, and significantly more likely to
develop RHD. An increased risk of RHD in females has been found in almost all populations.5,16
Interestingly, females were less likely than males to have a recurrence which may relate to
willingness to receive medical care including secondary prophylaxis. This suggests that gender
susceptibility may be related either to an innate predilection for cardiac damage or to a greater
risk of exposure to Group A Streptococcus (as females tend to be more involved in child rearing)
rather than limited access to prevention.
Although cases of ARF may be mild or even asymptomatic,17,18 ongoing presentations
15
with RHD in the absence of a history of ARF suggest that detection, accurate diagnosis and
notification of ARF remains suboptimal. Contributing factors may include lack of training or
awareness among health staff, transient health professional staffing in remote areas, poor access
to medical services and lack of health service utilization due to many factors including
inadequate cultural safety.
The most promising finding of this audit was the evidence of a reduction in the
recurrence rate by 9% per year since 1997. This suggests that primary health care services in the
NT, with support from the NT RHD Control Program, are having success in improving the
delivery of secondary prophylaxis.
The true number of ARF recurrences is larger than measured in our stud
study only
dy ass onl
nlyy
nl
recurrences
ecurrences amongst those presenting with a first episode off ARF since 1997 were included
(therefore
theere
refo
fore
fo ree missing
mis ng rrecurrences
issing ecurrences in those diagnosed with
ed with ARF before
befo r 1997
ore 9997 or whose first
199
presentation
pres
sen was
e tation w RHD).
ass RHD).. Th
HD is ddefinition
This efi
fini
niti
ni on wass rrequired
t on equuirred in oorder
rdeer
rd o aanalyse
er to lysee ttime
naly
na ly im between
me be
betw
twee
tw episode
e n ep
ee epis
isod
ode
od
and
an recurrence
nd re
ecu
c rr
rren ce bbut
encce
en utt iiss llikely
kely to uunderestimate
ikkel nder
nd eres
er esti
t ma
ti te the
mate the total
otaal burden
tot burd
bu en of
rdeen
rd rrecurrences.
of re curr
curreence
ences.
s.
World
ld Health
Worl H al
He th Organization
alth Org
r an
aniz ionn recommendations
izattio
iz r co
re omm
mmen
enda
end ti
da onss regarding
t on reg
egar
egardi
arding
di ng tthe
hee dduration
urat
ur atio
ationn of ssecondary
io econ
econda
on d ry
prophylaxis19 are based on old studies, with no recent data on recurrence rates related to age or
duration since the last ARF episode. Our finding of high rates of recurrence in the first year
following diagnosis (4.5%) reducing to zero by 10 years support the current Australian
guidelines for administration of prophylaxis for a minimum duration of 10 years in those without
severe carditis.12 Moreover, we demonstrated that recurrence rates are highest in the first three
to four years after diagnosis, suggesting that secondary prophylaxis efforts should concentrate on
this critical period. We also found that recurrences are more common in younger patients,
supporting for now the Australian recommendation of continuing prophylaxis until a minimum
16
of 21 years even in those diagnosed at a very young age. At present, our data are not strong
enough to determine if these young patients retain an elevated risk of recurrence after 10 years
(e.g. between ages 15 and 21 years in those whose first episode occurred at age 5); ongoing data
collection will allow us to re-evaluate this recommendation in coming years. As compliance in
adolescence is often problematic, this would be an important consideration.
The 2005 Australian Guidelines were used for prioritisation and follow up. These
guidelines, and the 2012 updated version20 outline the importance of echocardiography in routine
clinical care for RHD, particularly in Aboriginal people living in remote areas of Australia. As
history taking in this population is often impaired by cultural and language barriers, the use of
echocardiography allows more accurate monitoring of progression of valvular di

disseas
a e,
disease,e, aand
nd
detection of severely affected patients to be targeted for intervention.
Of those
tho
hosee with
wit
ith ARF, 35% developed RHD
D within
within 1 year an
nd 61
and 1% by
61% b 10 years. Although
ome
me of these ca
some case
es wi
cases w th
withh ddelayed
elay
el ayed
ay ed ddevelopment
eveloopmeent off R
eve HD
RHDDm ay rrepresent
ay
may epre
ep rese
sent
nt na
atur
urral eevolution
natural voolu
uti
tioon of
of in
init
ittial
initial
mi
ild or
mild or subclinical
subc
su bcli
bc lini
niccall cardiac
carrdia
ca rdia
i c damage,
daama
mage
ge,, most
ge mo
ost are
are
re likely
like
lik ly
ke ly tto
o bee ddue
ue tto
ue o AR
ARFF rec
rrecurrences
ecurrren
e ce
c s ca
aussin
ingg
causing
cumulative heart
hea
eart
r valve
rt val
alve
vee damage.
dam
mag
age.. The
The risk
riisk of
of developing
dev
evel
e op
el opin
ingg RHD
RHD decreased
decr
de crea
ease
ea sedd wi
se with
t ttime
th im
me si
sinc
n e
since
diagnosis and with older age at initial diagnosis. These data provide further evidence that
secondary prophylaxis is critical and that, although important in all patients, enhanced efforts are
needed to deliver secondary prophylaxis in younger patients and in the initial few years after
diagnosis of ARF.
Heart failure developed in 28% of RHD cases, half of which was present at diagnosis,
with almost all of the remaining cases presenting within five years. To our knowledge, these are
the only recent data on this most important clinical manifestation of ARF or RHD. It is essential
to validate these data with ongoing surveillance, and in other populations, because they are
17
critical for informing estimates of disability due to ARF and RHD. Reassuringly, when
compared to older natural history studies from the 1950s, when almost a third of children died in
the two decades following diagnosis, morbidity and mortality appear much improved.21
Patients were reviewed and offered medical and surgical treatment as required.
Although the data analyzed for this report did not allow us to quantify access to or acceptance of
medical care, others have found many barriers to Aboriginal people receiving optimal medical
and surgical care for chronic diseases, related to health care systems and remoteness, as well as
cultural factors. 22, 23 In the case of RHD, there is the added complication that cardiac surgery is
not available in the Northern Territory, so surgical intervention involves travel to cities many
thousands
housands of kilometres away. If outcomes for RHD are to be improved in simi
similar
ilaar se
ssettings,
ttin
ttin
ings
gs,,
gs
health care services must improve the capacity of the health workforce, availability of specialist
ca
care,
aree, systems
syst
stem
tem
emss fo
for
or delivering
de care to patients with
h complex,
complex, chronic
chroniic diseases,
dise
seeas
ases, and mechanisms to
ad
address
ddres
dre s cultur
cultural
rall iimpediments
mped
mped
edim
men
ents
tss tto
o up
upt
uptake
tak
akee ooff W
Western
esterrn
rn me
medical
edical
edi
icall ccare.
aree.
ar
The burden
The b rd
bu n of
den of mortality
mortal
mort i y is likely
allit likelly to be
ikel be under-estimated
u der
un der-esti
estiima teed due
mate due to the
thee limitation
lim
mittat on of our
a io ur study
ouur studdy
dy
period (14 years).

yeaars
rs).
) Amongst
). Amo
mong
ng
gst the
thee Indigenous
I di
In d geeno
nous
us cohort,
coh
o or
ort,
t relative
t, rel
elat
ativ
at iv
ve survival
suurv
rviv
ival
a rate
al rat
atee de
decr
decreased
crrea
ease
sedd wi
se w
with
th time
following diagnosis. With longer follow-up this may become even more pronounced. The
excess mortality was calculated to be 56% higher amongst those with RHD compared to non-
affected individuals of the same age and gender. These results confirm the large burden of
mortality associated with RHD among Indigenous Northern Territory residents and highlight the
progressive nature of the disease. RHD is likely to play a significant causative role in this
24,25
excess mortality, as is demonstrated in other studies. As mortality due to RHD should be
preventable through secondary prophylaxis and better clinical care, these data reinforce the
importance of treatment and prevention programs for RHD in this population. The non-
18
Indigenous cohort, consisting predominantly of older individuals with most likely long-standing
RHD, was too small to infer any significant trends.
Although the clinical presentation of ARF in the Northern Territory has many similarities
to classic descriptions over the past half-century 26-28, there are some striking differences. While
joint manifestations were the most common manifestation (77% of cases, similar to reported
rates of 65-85%29), we found that more than a third of these (23% of all cases) had mono-
arthritis. This has been reported previously in a retrospective case series in the NT30, in other
parts of Australia31, and in the Pacific32. Our data support the inclusion of monoarthritis as a
major manifestation in ARF diagnostic criteria, as has been the case in Australia since 2006.12
We also found a remarkably low proportion off cases (28%) with carditiss ddocumented.
occum
men
ente
ted.
te d.
This is substantially lower than previously reported in the NT33, as well as other studies from
di
ifffer
eren
entt pa
en
different part
rts
ts off tthe
parts he world, which uniformly repo
he portt rates of 50-60
po
report % 322 This
0%.
50-60%. Th may potentially be
explained
ex
xplai
a ned by tthe
h in
he inclusion
nclu
nclu
lusi
sion
on ooff pol
ppolyarthralgia
olya
yarrth
rthralgiaa an
and
nd mo
mono
monoarthritis
oar
arth
thrriti
ri is inn the
the diagnostic
diag
di gno
ost
stiic
ic ccriteria
r teeriia re
ri resu
resulting
sult
l ing
in
inn the
the detection
det
etec
eccti on of
tion of milder
er cases
millde
mi lder casses of
of ARF,
F, less
A F,
AR esss likely
les liike ly to
k ly to have
have cardiac
car diiacc involvement.
ardi inv
nvol
olvvem
vement
ment
n.
The pr
prop
proportion
opor
op orti
or tion
ti on ooff ca
case
cases
ses wi
se w
with
th
h cho
chorea
hore
ho reaa (1
re (19.5%)
19.
9 5%
5%)) is
i ssomewhat
omew
omewha
ewhatt lo
ha lower
owe
werr th
than
a tthe
an he 228%
8% previouslyy
found in NT Aboriginal people30, but still higher than the proportion found in most other
populations.17 The reasons for particular ethnic or regional susceptibility to this manifestation
of ARF are not clear. Given the striking presentation of chorea it is unlikely that cases have
gone undetected. More likely, the slight decrease in the proportion of cases presenting with
chorea, may be due to an increase in the detection of other presentations of ARF, particularly
those with mono-arthritis, related to increased awareness because of education campaigns.
Although RHD was just as commonly diagnosed in chorea as non-chorea cases, evidence of
heart failure was less likely in chorea (3.7%) compared to non-chorea patients (26.4%),
19
supporting the hypothesis that chorea is associated with less severe carditis. Currently the data
are not strong enough to support lessening surveillance in this cohort. As chorea is a late
manifestation, the finding of a lack of acute inflammatory manifestations was expected.
This population had access to high quality medical care including active outreach
services by specialist clinicians and echocardiography. This provides a higher level of care than
is available in most developing countries where RHD exists in high numbers. We believe that
the diagnoses and confirmation of severity of RHD are reliable due to easy access to
echocardiogram. Therefore, this study is unique in that it documents real-life outcomes of a

whole population with high rates of RHD, carefully followed with specialist review and
echocardiography
To our knowledge the only high quality population based data on the health outcomes of
RHD
RH
HD ar
aree fr
from NZ
om N aand
Z an Northern
d Australia. In the Northe
ern
r TTerritory feel
erritory we fe
eel wee hhave
e w ave reached a point
where
w er we are identifying
heere ide y ngg most
denntiffyi ost presentations
most entationss ooff RH
preese
pr esent RHD n tthe
HD in hee aabsence
bsen
bs ce ooff ro
encce routine
out
utin screening.
inee sc
in scre
reen
re enin
ening.
ing.. Th
Thee
same
me may
ame y not
may o be
not be true
trrue in
in developing
deveelop
de ingg countries
pin co
oun
ntr ies that
trie
ie thatt lack
lackk the
the capacity
caapaccitty to
t establish
esstab
stab l sh rregisters
bli egiisteerss oon
eg na
large
arge scale an
andd maintain
main
ma inta
in taain high
n hig
ighh qu
ig quality
uali
lity surveillance
ty sur
u ve
ur veil
illa
illaanc individual
n e of in
indi
divi
di vidu
vi dual
du al ccases
e oover
ases
as es verr th
ve tthee lo
long
ong tterm.
e m. In
er
these countries, screening echocardiography may act as a tool to both understand disease burden
but also to identify cases that might otherwise not present for routine care.34
This analysis informs disease prevention and control efforts in the NT, but also provides
insights into pathogenesis and disease burden that may be useful in other populations as well.
We call for similar analyses of other RHD registers around the world, and for establishment of
RHD registers where they don’t already exist, as part of control programs in developing
countries where ARF and RHD are common.
Conflict of Interest Disclosures: None.
20
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Table
blee 1.
Tabl 1. Demographic
Demo
De mogr
g aphic characteristic
aphi ch
har
a ac
acte
teristic off ARF
rist ARF and HD ccases,
nd RHD ases
ases, NT 11997-2010.
997-
997 20
20100.
ARF
ARF RHD
RHD
Indigenous non-Indigenous Indigenous non-Indigenous
Number of cases 600 15 600 15
Female (%) 58.5 60.0 65.4 71.1
Age-group at diagnosis (%)
0-4 years 2.7 0.0 1.4 0.0
5-9 27.2 13.3 11.3 2.4
10-14 36.8 26.7 18.5 1.2
15-24 19.7 20.0 23.4 6.0
25-34 8.7 13.3 18.4 12.0
35-44 3.8 26.7 13.2 15.7
45+ 1.2 0.0 13.9 62.7
Median age at diagnosis (years) 12 18 22 51
Year of diagnosis (%)
1997-2000 22.7 46.7 20.6 18.1
2001-2005 42.5 20.0 44.7 63.9
2006-2010 34.8 33.3 34.6 18.1
23
Table 2. Multivariate analysis of ARF incidence, NT 1997-2010
All subjects Indigenous only

IRR* p-value 95% CI IRR* p-value 95% CI
Indigenous status 68.82 0.000 40.1-118.1 na† na† na†
Female gender 1.50 0.004 1.1- 2.0 1.49 0.007 1.12-1.99
Age (year) 0.95 0.00 0.94- 0.96 0.94 <0.001 0.93-0.95
Year 0.98 0.497 0.95- 1.02 0.99 0.669 0.96-1.03
* incidence rate ratio.
† not applicable
Table 3. Clinical manifestations at initial presentation of ARF, NT 2007-2010
Manifestation Number %
Major
Carditis 41 27.5
Chorea 29 19.5
19.5
Joint Manifestations 115 77.2
77 .2
Polyarthritis 73
Monoarthritis 34
P
Polyarthralgia
olya
ol yart
ya rthr
rt hraalgiia
hr 8
S
Sub
Subcutaneous
ubcutaneo
bc ous
us nnodules
o ul
od ules
ess 1 0.77
0.
Er
Erythema
ryt
y hema mar marginatum
argginnatu
tumm 1 00.7
0. 7
M
Minor
innor
no
Raais
ised
Raiseded iinflammatory
nfla
nf lamm
la mmmattor
oryy ma
markr errs (E
markers (ESR
SR// CR
(ESR/ CRP)
P) 11
10
110 73 .8
73.88
Prolonged
Prol
Pr olon
ol onge
on gedd PR interval
ge int
nter
erva
ervall on ECG
va ECG 41 27.5
27.55
Fever 79 53
Total people 149 100.0
Table 4. Multivariate analysis of RHD Incidence, NT 1997-2010
All subjects Indigenous only

IRR* p-value 95% CI IRR* p-value 95% CI
Indigenous status 63.65 <0.01 43.0-94.2 na‡ na‡ na‡
Female gender 1.94 <0.01 1.64-2.32 1.84 <0.01 1.53-2.21
Age at diagnosis† 1.05 <0.01 1.03-1.06 1.00 0.68 0.99-1.00
Year † 1.00 0.81 0.98-1.02 1.00 0.83 0.98-1.03
Indigenous by age 0.95 <0.01 0.94-0.97 na
* incidence rate ratio.
† IRR for a one year increase
‡ not applicable.
24
Table 5. Recurrence of ARF, multivariate analysis of recurrence rate, NT 1997-2010
Hazards Ratio* p-value 95% CI

Indigenous status 1.92 0.52 0.27-13.9
Female gender 0.79 0.30 0.50-1.23
Age at first ARF episode † 0.93 <0.01 0.90-0.97
Year 0.91 0.01 0.84-0.97
* hazard ratio (proportional hazard regression).
† per single year.
Table 6. Progression to RHD, multivariate analysis of incidence of RHD after a first episode of
ARF, NT 1997-2010
Hazards Ratio* p-value 95% CI


Female gender 1.19 0.13 0.95
0.95-1.50
9 1.50
Age at first ARF episode † 0.98 <0.01 0.96-0.99
0.96
0. 96-0
96 -0.9
-0 .999
.9
Year 1.03 0.10 0.99
0. 99-1
99 -1.0
0.99-1.06.006
Chorea ‡ 0.85 0.29 0.62-1.15
* hazard ratio (proportional
(pr
p opportional hazard regression).
† per
per single
sing
si le yyear.
ngle
ng earr.
ea
‡ presence
pressen
pres c of
ence of chorea
ch ea asas a clinical
cllin
i ical manifestation
ical maani
nifesttat on at the first
a io fir ARF
i st A episode
RF epi
piso
sode
de
Table
Taabl
blee 7.
7 Pro
Progression
ro
ogr
g es
essiion to
to cardiac
card
rd
dia
iacc fa
fail
failure,
illur
uree, m
multivariate
ulttivvari
ul var ate
ate an
analysis
nalys
alysiis off in
inc
incidence
cidenc
ncee of
nc of hheart
eart
ea rt ffailure
ailu
uree aafter
ftterr
diagnosis
diag
di agno
nosi
no siss of R
si RHD,
HD,, NT 22004-2010
HD 0 4--20
00 2010
10
H
Hazards
a arrds
az ds Ratio*
Rat
atio
io**
io p-va
p-
p-value
valu
aluee 95% CI
95% CI
Female gender 0.86 0.37 0.63-1.19
Age at RHD diagnosis† 1.01 0.25 1.00-1.02
Year 1.06 0.18 0.97-1.16
* hazard ratio (proportional hazard regression).
† per single year.
Figure Legends:
Figure 1. Application of Exclusion Criteria.
Figure 2. Age-specific incidence of first episodes of ARF 1997-2010.
25
Figure 3. RHD prevalence at three time points* by age-group, NT Indigenous only. *prevalence
per 100 at 30 June in each year.
Figure 4. Age-specific incidence of RHD, NT 1997-2010.
Figure 5. ARF recurrence rate* by time since first episode. * number of recurrences per 100
person-years after a first ARF episode in 1997-2010, with 95% confidence interval.
Figure 6. Progression of ARF to RHD and cardiac failure among Indigenous subjects.
Figure 7. Death rate by 2 year period since diagnosis (Indigenous only).
26
Figure 1
Figure 2
Figure 3
Figure 4
Figure 5
Figure 6
Figure 7
Acute Rheumatic Fever and Rheumatic Heart Disease: Incidence and Progression in the
Northern Territory of Australia 1997-2010
Joanna G. Lawrence, Jonathan R. Carapetis, Kalinda Griffiths, Keith Edwards and John R. Condon
Circulation. published online June 21, 2013;

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Acute Rheumatic Fever and Rheumatic Heart Disease: Incidence and Progression in The Northern Territory of Australia 1997 - 2010

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DOI: 10.1161/CIRCULATIONAHA.113.

Acute Rheumatic Fever and Rheumatic Heart Disease: Incidence and

Progression in the Northern Territory of Australia 1997 -2010

FRACP2; John R. Condon, FAFPHM PhD3

Address for Correspondence:

Journal Subject Code: Etiology:[8] Epidemiology

incidence and progression.

ARF or RHD hhad

heart failure within

maintains a note-worthy presence in economically disadvantaged populations driven by factors

from cardiac involvement known as Rheumatic Heart Disease (RHD).

Compared with primary prevention or treatment of established carditis, secondary

prophylaxis (in the form off two to four-weekly intramuscular benzathine

ARF and RHD in a population with very high rates of disease.

register’s data custodian. No contact with registered patients was required.

Data quality assessment and exclusions

2010. In the Northern

1. demographic characteristics of people diagnosed with ARF and/or RHD

31/12/2010 because recording of clinical manifestations was incomplete before 2007.

and RHD diagnosis

effect of agee was

5. RHD prevalence on 31 December in 2000, 2005 and 2010

presence of chorea at the first ARF episode.

with RHD in 1997-2010, which measure excess mortality due to RHD.

were calculated from NT Indigenous population mortality rates.

population-based incidence rates.

Acute Rheumatic Fever

groups than for

evidence of a decrease in incidence between 1997 and 2010 (Table 2).

Clinical manifestations at the first diagnosis of ARF

register commenced uniform collection of data on clinical manifestations of ARF) and 31

present in a higher proportion (43.3%). The most common minorr manifestation

nflammatory markers (74%). Fever was present in 53%.

ARF episodee in females

chorea patients (26.4%).

Rheumatic Heart Disease

Figure 3 shows an increasing prevalence of RHD amongst the Indigenous population

For thee NT IIndigenous

twice that for males.

ARF episode (risk

people and for

61% by 10 years (Figure 6).

RHD to Heart Failure

developing heart failure (Table 7).

and 76 Indigenous (7.1% of Indigenous cases) with a median age of 22 years.

5, 10 and 14 years after diagnosis.

is consistent with their relative survival rates greater than 100%.

evaluate disease burden and patterns of disease evolution in a high-incidence population.

Indigenous children, aged 5-14 years.

exclusion off a number

recorded or present (the latter represents ‘possible’ ARF).

Northern Territory.6,10 As efforts to reduce recurrence rates of ARF appear to be having an

rather than limited access to prevention.

Although cases of ARF may be mild or even asymptomatic,17,18 ongoing presentations

inadequate cultural safety.

delivery of secondary prophylaxis.

collection will allow us to re-evaluate this recommendation in coming years. As compliance in

adolescence is often problematic, this would be an important consideration.

echocardiography allows more accurate monitoring of progression of valvular di

detection of severely affected patients to be targeted for intervention.

period (14 years).

RHD, was too small to infer any significant trends.

those with mono-arthritis, related to increased awareness because of education campaigns.