Declining Guillain-Barré syndrome after campylobacteriosis control, New Zealand, 1988-2010.
ABSTRACT Infection with Campylobacter spp. commonly precedes Guillain-Barré syndrome (GBS). We therefore hypothesized that GBS incidence may have followed a marked rise and then decline in campylobacteriosis rates in New Zealand. We reviewed records for 1988-2010: hospitalization records for GBS case-patients and campylobacteriosis case-patients plus notifications of campylobacteriosis. We identified 2,056 first hospitalizations for GBS, an average rate of 2.32 hospitalizations/100,000 population/year. Annual rates of hospitalization for GBS were significantly correlated with rates of notifications of campylobacteriosis. For patients hospitalized for campylobacteriosis, risk of being hospitalized for GBS during the next month was greatly increased. Three years after successful interventions to lower Campylobacter spp. contamination of fresh poultry meat, notifications of campylobacteriosis had declined by 52% and hospitalizations for GBS by 13%. Therefore, regulatory measures to prevent foodborne campylobacteriosis probably have an additional health and economic benefit of preventing GBS.
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ABSTRACT: Since the eradication of polio in most parts of the world, Guillain-Barré syndrome (GBS) has become the most common cause of acute flaccid paralysis. GBS is an autoimmune disorder of the peripheral nervous system characterized by weakness, usually symmetrical, evolving over a period of several days or more. Since laboratories began to isolate Campylobacter species from stool specimens some 20 years ago, there have been many reports of GBS following Campylobacter infection. Only during the past few years has strong evidence supporting this association developed. Campylobacter infection is now known as the single most identifiable antecedent infection associated with the development of GBS. Campylobacter is thought to cause this autoimmune disease through a mechanism called molecular mimicry, whereby Campylobacter contains ganglioside-like epitopes in the lipopolysaccharide moiety that elicit autoantibodies reacting with peripheral nerve targets. Campylobacter is associated with several pathologic forms of GBS, including the demyelinating (acute inflammatory demyelinating polyneuropathy) and axonal (acute motor axonal neuropathy) forms. Different strains of Campylobacter as well as host factors likely play an important role in determining who develops GBS as well as the nerve targets for the host immune attack of peripheral nerves. The purpose of this review is to summarize our current knowledge about the clinical, epidemiological, pathogenetic, and laboratory aspects of campylobacter-associated GBS.Clinical Microbiology Reviews 08/1998; 11(3):555-67. · 17.31 Impact Factor
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ABSTRACT: New Zealand's campylobacteriosis epidemic reached a new peak in May 2006 with the annualised national notification rate exceeding 400 per 100,000 for the first time, the highest national rate reported in the literature. The epidemic is estimated to cause at least 1 fatality a year, >800 hospitalisations, and >100,000 cases in the community, and cost the New Zealand economy 75 million dollars per annum. There is overwhelming epidemiological and laboratory evidence that fresh chicken is the dominant source of human infection. The seriousness of this epidemic justifies rapid, decisive action to reduce human exposure to this pathogen. There is good international evidence to support removal of fresh chicken from the food supply, with its reintroduction only when it can be shown to pose a very low risk to human health. Because freezing can substantially reduce Campylobacter levels, frozen chicken could be substituted to allow continued consumption of this popular food. Efforts to reduce Campylobacter colonisation of poultry flocks and contamination during chicken processing and distribution, along with continued consumer education, are important, but do not appear sufficient to control this epidemic in the short to medium term.The New Zealand medical journal 01/2006; 119(1243):U2264.
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ABSTRACT: Beginning in the 1980s, New Zealand experienced rising annual rates of campylobacteriosis that peaked in 2006. We analyzed notification, hospitalization, and other data to explore the 2007-2008 drop in campylobacteriosis incidence. Source attribution techniques based on genotyping of Campylobacter jejuni isolates from patients and environmental sources were also used to examine the decline. In 2008, the annual campylobacteriosis notification rate was 161.5/100,000 population, representing a 54% decline compared with the average annual rate of 353.8/100,000 for 2002-2006. A similar decline was seen for hospitalizations. Source attribution findings demonstrated a 74% (95% credible interval 49%-94%) reduction in the number of cases attributed to poultry. These reductions coincided with the introduction of a range of voluntary and regulatory interventions to reduce Campylobacter spp. contamination of poultry. The apparent success of these interventions may inform approaches other countries could consider to help control foodborne campylobacteriosis.Emerging Infectious Diseases 06/2011; 17(6):1007-15. · 6.79 Impact Factor
Infection with Campylobacter spp. commonly precedes
Guillain-Barré syndrome (GBS). We therefore hypothesized
that GBS incidence may have followed a marked rise and
then decline in campylobacteriosis rates in New Zealand.
We reviewed records for 1988–2010: hospitalization
records for GBS case-patients and campylobacteriosis
case-patients plus notifi cations of campylobacteriosis. We
Author affi liations: University of Otago, Wellington, New Zealand
(M.G. Baker, A. Kvalsvig, J. Zhang, A. Sears, N. Wilson); and
Institute of Environmental Science and Research, Christchurch,
New Zealand (R. Lake)
identifi ed 2,056 fi rst hospitalizations for GBS, an average
rate of 2.32 hospitalizations/100,000 population/year.
Annual rates of hospitalization for GBS were signifi cantly
correlated with rates of notifi cations of campylobacteriosis.
For patients hospitalized for campylobacteriosis, risk
of being hospitalized for GBS during the next month
was greatly increased. Three years after successful
interventions to lower Campylobacter spp. contamination
of fresh poultry meat, notifi cations of campylobacteriosis
had declined by 52% and hospitalizations for GBS by
13%. Therefore, regulatory measures to prevent foodborne
campylobacteriosis probably have an additional health and
economic benefi t of preventing GBS.
Declining Guillain-Barré S yndrome
after Campylobac teriosis Control,
New Zealand, 1988–2010
Michael G. Baker, Amanda Kvalsvig, Jane Zhang, Rob Lake, Ann Sears, and Nick Wilson
226 Emerging Infectious Diseases • www.cdc.gov/eid • Vol. 18, No. 2, February 2012
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Upon completion of this activity, participants will be able to:
• Distinguish the infection most closely associated with GBS
• Analyze the temporal relationship between campylobacteriosis and GBS
• Assess differences in the association between campylobacteriosis and GBS based on age
• Evaluate the effect of infection-control measures on rates of campylobacteriosis and GBS
P. Lynne Stockton, VMD, MS, ELS(D), Technical Writer/Editor, Emerging Infectious Diseases. Disclosure: P. Lynne Stockton,
VMD, MS, ELS(D), has disclosed no relevant fi nancial relationships.
Charles P. Vega, MD, Health Sciences Clinical Professor; Residency Director, Department of Family Medicine, University of
California, Irvine. Disclosure: Charles P. Vega, MD, has disclosed no relevant fi nancial relationships.
Michael G. Baker, MBChB, DPH, FNZCPHM; Amanda Kvalsvig, MBChB; Jane Zhang, MSc; Rob Lake, PhD; Ann Sears,
MBChB, MPH; and Nick Wilson, MBChB, MPH, FNZCPHM, have disclosed no relevant fi nancial relationships.
Guillain-Barré Syndrome and Campylobacteriosis
Patients typically describe ascending weakness and
sensory disturbance that evolve over several days; during
this acute phase, approximately one third of patients
require ventilatory support. The condition is generally self-
limiting, but for 3%–10% of patients, it is fatal (1).
An estimated 40%–70% of patients with GBS had
an infection before GBS onset; for 6%–39% of these
patients, the infection affected the gastrointestinal system
(2). Campylobacteriosis is the most commonly identifi ed
antecedent infection; several studies have shown that in
industrialized countries (Europe, North and South America,
Japan, and Australia), Campylobacter spp. infection
preceded GBS for 20%–50% of patients (3,4).
During 1980–2006 in New Zealand, incidence of
campylobacteriosis steadily increased. The notifi cation
rate in 2006 (379 cases/100,000 population) remains
the highest national rate reported in the literature
(5,6). In 2006, in response to this high incidence,
New Zealand introduced an array of voluntary and
regulatory interventions to reduce contamination of
poultry with Campylobacter spp. (7). By 2008, the rate
of campylobacteriosis notifi cations had dropped to 157
cases/100,000 population, a decrease of 59% over 2
years (7); this decline has persisted (8). Given the known
association between Campylobacter spp. infection and
GBS and the marked recent changes in reported rates of
campylobacteriosis in New Zealand, we examined GBS
hospitalization data for evidence of responsiveness to
trends in campylobacteriosis incidence.
uillain-Barré syndrome (GBS) is an autoimmune
condition that affects the peripheral nervous system.
Identifi cation of GBS Incidence
Because GBS is a serious illness that nearly always
results in hospitalization, hospitalization data provided the
most accurate available measure of GBS incidence. We
obtained national hospital discharge data for the 23-year
period 1988–2010 in New Zealand. To estimate the case-
fatality proportion, we also obtained data on deaths from
GBS for 1988–2008 (the most recent year available). Both
datasets are collated and maintained by the New Zealand
Ministry of Health.
Although hospitalization data are available for earlier
years, we used 1988 as the starting point because that is
when use of unique patient identifi ers, the National Health
Index (NHI), became universal in New Zealand. Use of
the NHI enables identifi cation and removal of repeat GBS
hospitalizations for the same patient, thereby identifying
the fi rst GBS hospitalization for each case (hereafter called
GBS hospitalization), which provides an estimate of the
number of incident cases of GBS.
We selected all cases from 1988 on that had Inter-
national Classifi cation of Diseases, 9th and 10th Revisions,
Clinical Modifi cation and Australian Modifi cation, codes
for GBS (ICD-9 CM 357.0 and ICD-10 AM G61.0)
recorded as the principal or additional diagnosis. Records
of patients who had been transferred between hospitals
were merged to create 1 hospitalization event. We identifi ed
repeat hospitalizations for the current year and for previous
years, i.e., case-patients with the same NHI number
previously admitted in the same or a previous year. Some
patients were readmitted before universal use of the NHI
in 1988, so the calculation needed to take these estimated
repeat hospitalizations into account. (See online Technical
Appendix Tables 1, 2, wwwnc.cdc.gov/EID/pdfs/11-1126-
Techapp.pdf, for a description of how estimated repeat
hospitalizations and incident cases were calculated.)
Identifi cation of Campylobacteriosis Incidence
Since 1980, campylobacteriosis has been a notifi able
disease in New Zealand. Medical practitioners are required
to report all identifi ed and suspected cases to the local
medical offi cer of health. These data are in turn collated
nationally by the Institute of Environmental Science and
Research for the New Zealand Ministry of Health. We
used published annual totals of notifi cations (9) as well as
anonymized datasets of notifi ed cases. Most cases were
culture confi rmed (>96% during 1997–2008 ), although
the case defi nition also allows for cases epidemiologically
linked to a confi rmed case.
Hospitalizations for campylobacteriosis are recorded in
hospital discharge data, which are electronically available
for a similar period. However, a specifi c diagnostic code
for Campylobacter spp. infection was not introduced until
July 1995. Hospitalizations for campylobacteriosis were
defi ned as those with ICD-9 CM code 008.43 from July
1995 on and ICD-10 AM code A04.5 from July 1999 on. To
create a dataset of incident cases, we included principal or
additional diagnoses, merged records for those transferred
with records from preceding hospitalizations, and removed
repeat hospitalizations in the current and previous years.
Analysis of Hospitalizations for GBS
To assess the association between the 2 conditions,
we investigated the incidence
patients hospitalized for campylobacteriosis. Because
campylobacteriosis was only specifi cally identifi ed in
hospitalization data from July 1995, this analysis focused
on the period starting in July 1995. To allow a follow-up
period for GBS cases to emerge, we continued the inclusion
period through December 2008.
For those cases identifi ed, we fi rst analyzed the
time from hospital admission for campylobacteriosis to
of GBS among
Emerging Infectious Diseases • www.cdc.gov/eid • Vol. 18, No. 2, February 2012 227
admission for GBS. For epidemiologic purposes, the risk
period for GBS after Campylobacter spp. infection is ≈2
months (10); neurologic signs of GBS usually develop
1–3 weeks after a preceding infection (3). In our dataset,
a clear trend was seen toward a close temporal association
between hospitalization dates: for most (34/35, 97.1%)
patients, hospitalizations for GBS and campylobacteriosis
were concurrent (patients were discharged with a diagnosis
of both), or hospitalization for GBS occurred within 1
month of hospitalization for campylobacteriosis.
To assess the risk for GBS associated with
campylobacteriosis, we calculated GBS hospitalization
rates for comparison conditions, notably other infections
that might be associated with an elevated risk for GBS.
We used the GBS rate in the total New Zealand population
as our reference rate for calculating age-standardized
rate ratios for GBS after campylobacteriosis and other
conditions of interest.
We also evaluated which age groups might be more
vulnerable to development of GBS. To do so, we compared
the age distributions of all patients hospitalized for GBS
and those associated with campylobacteriosis with the
age distributions for those with campylobacteriosis alone
(hospitalized or with notifi ed case).
Because of marked changes in campylobacteriosis
disease incidence and some changes in case identifi cation
during the 23-year study period, some outcomes were
measured over a shorter time. The periods associated
with implementation of the Campylobacter spp. control
interventions used a baseline period similar to that used in
a previous study (7).
Data were analyzed by using Stata version 11.0
(StataCorp LP, College Station, TX, USA) and SAS
version 9.1 (SAS Institute, Cary, NC, USA). CIs are given
at the 95% level throughout. We used well-documented
methods for calculating adjusted rates, rate ratios (RRs),
and 95% CIs (11). Rates were calculated by using
mean population estimates published by Statistics New
denominators. To calculate age-standardized rates, we used
the population age structure determined by the New Zealand
2006 Census of Population and Dwellings (www.stats.govt.
This study identifi ed 2,056 fi rst hospitalizations for
GBS that occurred during 1988–2010, resulting in an
average rate of 2.32 hospitalizations/100,000 population/
year (online Technical Appendix Table 1). Incidence
was not stable over the period of the study (Figure). The
minimum recorded rate was 1.53 hospitalizations/100,000
population/year in 1989; the maximum was 2.93 in 2005.
During 1989–2008, a total of 56 deaths from GBS were
recorded; case-fatality proportion (56 deaths/1,873 cases)
Changes in GBS and Campylobacteriosis Incidence
For 1988–2010, there was a signifi cant direct
correlation between annual rates of hospitalization for
GBS and annual rates of notifi cation of campylobacteriosis
cases (Spearman ρ = 0.52, p = 0.012). During 1988–2006,
incidence of campylobacteriosis notifi cations and of
GBS hospitalizations increased (Figure; online Technical
Appendix Table 3). Subsequently, campylobacteriosis
notifi cations then decreased markedly, and GBS
hospitalizations decreased, although less dramatically.
The fall in campylobacteriosis notifi cations followed the
introduction of countrywide campylobacteriosis control
measures focused on reducing contamination levels in
fresh poultry meat (7).
228 Emerging Infectious Diseases • www.cdc.gov/eid • Vol. 18, No. 2, February 2012
campylobacteriosis notifi cation rates,
by year, New Zealand, 1988–2010.
*Per 100,000 population.
Guillain-Barré Syndrome and Campylobacteriosis
Table 1 summarizes the changes between the 2
periods: 1) 2002–2006, the baseline period, when rising
campylobacteriosis rates became an urgent public health
concern, and 2) 2008–2010, the postintervention period,
after implementation of wide-ranging control measures.
The transition year, 2007, was excluded.
During the postintervention period, notifi cations and
hospitalizations decreased by ≈50% (online Technical
Appendix Tables 3, 4). Incidence of GBS declined by
13%, which was statistically signifi cant (RR 0.87, 95% CI
0.81–0.93), suggesting that ≈25% of GBS was caused by
GBS among Patients Hospitalized
for Campylobacteriosis or Other Conditions
During 1995–2008, among the 8,448 patients
hospitalized for campylobacteriosis, 35 were also
hospitalized for GBS. The frequency distribution of
time delays is shown in Table 2. These data show that
most (29) of these 35 patients had diagnoses of GBS and
campylobacteriosis at time of hospital discharge. Another 5
patients were hospitalized for GBS within 4 weeks of being
hospitalized for campylobacteriosis. The time difference
for the remaining patient was >1,500 days (this patient
was excluded from subsequent analyses). This striking
distribution further supports a causative association
between campylobacteriosis and GBS in New Zealand.
We calculated the rate of GBS hospitalizations among
the cohort of patients hospitalized for campylobacteriosis
and compared this with rates of GBS hospitalization among
other patient cohorts hospitalized for infectious diseases
(Table 3). This analysis used the overall rate of GBS
hospitalizations among the New Zealand population as a
reference for calculating age-standardized RRs.
The age-standardized rate of GBS was 810.0
41.4–1,578.7) in the month after hospitalization for
campylobacteriosis. The RR, compared with the rate of
GBS hospitalizations among the New Zealand population,
was 319.4 (95% CI 201.5–506.4). This rate was markedly
higher than rates for the other patient cohorts examined
Patients with GBS (median age 52.5 years)
were signifi cantly older than those hospitalized for
campylobacteriosis (median 41 years), who in turn were
signifi cantly older than those with campylobacteriosis
notifi cations (median 31 years) (Tables 4, 5). The age of
the subpopulation of patients with GBS associated with
campylobacteriosis was similar (median 54 years) to that
of the total population with GBS.
This study shows how the incidence of an acute
infectious disease, campylobacteriosis, can infl uence
incidence of a serious neurologic condition, GBS. At the
population level, hospitalizations for GBS were signifi cantly
correlated with notifi cations of campylobacteriosis for the
same year. At the individual level, compared with rates for
the New Zealand population as a whole, hospitalizations
for campylobacteriosis were associated with an almost
320-fold increased risk for subsequent hospital admission
for GBS in the next month.
Results also show that food safety measures to reduce
contamination of fresh poultry meat with Campylobacter
spp. not only reduced incidence of campylobacteriosis but
also were associated with reduced incidence of GBS. In
the 3 years after introduction of these control measures,
campylobacteriosis notifi cations and hospitalizations
decreased by ≈50%, and GBS hospitalizations dropped
by 13%. These fi ndings suggest that in New Zealand,
Campylobacter spp. infection may be responsible for
≈25% of GBS cases, which is consistent with data from
other industrialized countries (3).
A recent systematic review (12) summarized attempts
to quantify the association between campylobacteriosis
and GBS incidence. There is general agreement that
measuring GBS population rates is useful, for example,
for monitoring vaccine adverse effects (13,14). However,
Emerging Infectious Diseases • www.cdc.gov/eid • Vol. 18, No. 2, February 2012 229
Table 1. Incidence of campylobacteriosis and GBS before and after intervention to reduce Campylobacter spp. in poultry, New
Before intervention, 2002–2006
Total no. Average/year Rate‡
GBS hospitalizations¶ 513 103 2.6
*GBS, Guillain-Barré syndrome.
†Excludes 2007, which was a transitional year.
‡Annual no. cases/100,000 person-years at risk. Denominator populations based on mean population estimates published by Statistics New Zealand
(www.stats.govt.nz/browse_for_stats/population/estimates_and_projections/national-pop-estimates.aspx). Campylobacteriosis and Guillan-Barré
syndrome hospitalizations used age-standardized rates based on the age structure of the New Zealand 2006 Census of Population and Dwellings
§Published campylobacteriosis notification data (9).
¶Hospitalization data from New Zealand Ministry of Health.
After intervention, 2008–2010†
Total no. Average/year
Rate ratio (95% CI)
<0.0001 69,207 13,841 339.4
4,669 934 23.2 1,603 534 12.2 0.53 (0.51–0.54) <0.0001
290 97 2.2 0.87 (0.81–0.93) 0.0496
to our knowledge, no similar population-based analysis
of the relationship between GBS and campylobacteriosis
has been conducted for other countries, probably because
few countries collect similarly detailed national-level
hospitalization data. An earlier population-based study
in New Zealand did not show an association between
notifi cations for campylobacteriosis and GBS incidence
(15). However, that study was over a shorter period and did
not use a correction factor to account for undetected repeat
hospitalizations in the early years of the observation period,
which would have made it harder to detect an association
between incidence rates for the 2 conditions.
Compared with global estimates, rates of GBS in
New Zealand are high. In a review of reported GBS rates
during 1980–2000, worldwide incidence varied between
1.0 and 1.8 cases/100,000 population/year (2). The average
reported rate for New Zealand during this period was at the
upper end of this range (1.8/100,000). A more recent study
from the United States estimated that annual hospitalization
rates for GBS varied between 1.65 and 1.79/100,000 during
2000–2004 (16). In New Zealand during the same period,
the annual hospitalization rates varied between 1.8 and
The 320-fold increased risk for GBS in the month after
hospitalization for campylobacteriosis found in this study
is higher than that previously reported. In a case–control
study of GBS and potential antecedent infections in the
United Kingdom, Tam et al. reported that persons with
Campylobacter enteritis had a 38-fold increased risk that
GBS would develop in the next 2 months (17). However,
when they added a correction factor to account for under-
ascertainment of campylobacteriosis, the risk increased to
60-fold. Similarly, a population-based study in Sweden
estimated that patients with laboratory-confi rmed C. jejuni
infection had a 100-fold increased risk that GBS would
develop in the next 2 months (10). We used a 1-month risk
period because the GBS cases we identifi ed subsequent to
hospitalizations for campylobacteriosis were confi ned to
this period. Using a 2-month risk period would have halved
our estimated age-standardized RR, but the elevated risk
would still be higher than that reported elsewhere.
The proportion of GBS cases attributable to preceding
Campylobacter spp. infection estimated for New Zealand
(≈25%) is within the range described elsewhere. Studies
from other countries and regions have reported serologic
evidence of previous C. jejuni infection in 13%–72%
of GBS case-patients (18). A systematic review, based
on 32 eligible studies, estimated that 31% of GBS cases
were attributable to Campylobacter spp. infection (12).
230 Emerging Infectious Diseases • www.cdc.gov/eid • Vol. 18, No. 2, February 2012
Table 2. Hospitalization for Guillain-Barré syndrome during or
after hospitalization for campylobacteriosis, New Zealand, July
Interval, d No. (%) persons hospitalized
Concurrent 29 (82.9)
1–7 2 (5.7)
8–28 3 (8.6)
1,524 (4.2 y) 1 (2.9)
Total 35 (100)
Table 3. Incidence of GBS after hospitalization for campylobacteriosis and other infectious diseases compared with total population
incidence rate for GBS, New Zealand, July 1995–December 2008*
(ICD chapter 1)
rate¶ (95% CI)
480–488 J09–J18 250,399 19 (82) 91.1
77,793 6 (21) 93.3
Campylobacteriosis 8,448 5 (29) 710.2 810.0
population GBS rate
*GBS, Guillain-Barré syndrome; ICD, International Classification of Diseases; ICD-9, ICD 9th Revision; ICD-10, ICD 10th Revision; NA, not applicable.
†Denominator population based on either 1) incident hospitalizations for specific condition (number of acute and arranged first overnight hospitalizations
as principal or additional diagnosis); or 2) total New Zealand population person-years for July 1995– December 2008 for calculating the New Zealand
population GBS rate.
‡First hospitalization of GBS either 1) among those with a previous hospitalization in the preceding 30 d and excluding those with concurrent diagnoses
(numbers in parentheses); or 2) in the total New Zealand population for July 1995–December 2008.
§Rate per 100,000 person-years at risk. For GBS hospitalizations after specific conditions, monthly rate has been multiplied by 12 to convert to annual
¶Standard population is population of New Zealand according to the New Zealand 2006 Census of Population and Dwellings
#Excluding campylobacteriosis and salmonellosis.