This study shows how the incidence of an acute infectious disease, campylobacteriosis, can influence incidence of a serious neurologic condition, GBS. At the population level, hospitalizations for GBS were significantly correlated with notifications 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 notifications and hospitalizations decreased by ≈50%, and GBS hospitalizations dropped by 13%. These findings 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, 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 notifications 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 2.7/100,000.

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-confirmed 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 identified subsequent to hospitalizations for campylobacteriosis were confined 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). The strength of the association with GBS may vary geographically, according to the neuropathic propensity of local Campylobacter strains. We would also expect the percentage contribution of preceding Campylobacter spp. infection to vary according to the incidence of this infection in the population and the incidence of other causal infections and exposures.

The results of our study suggest that risk for GBS may not be uniform for different degrees of campylobacteriosis severity. Our study found that risk for GBS was ≈1 in 1,690 (5 in 8,448) among patients hospitalized for campylobacteriosis and that ≈25% of GBS cases were caused by campylobacteriosis. On the basis of an annual incidence of ≈100 GBS cases, these data suggest that ≈42,000 cases of campylobacteriosis occur each year in New Zealand. Current estimates of total campylobacteriosis incidence are higher. Annual notifications remain at ≈7,000 cases. A study from the United Kingdom estimated that 9.3 cases of campylobacteriosis occurred in the community for every notified case (19); a study from Australia estimated this number to be 10 (20). Applied to New Zealand, these multipliers suggest an incidence among the population of 65,000 to 70,000 cases per year. These findings suggest that the causal association between campylobacteriosis and GBS is probably weaker for patients with less severe infections, who do not require hospitalization.

Analysis of the age distribution of patients with campylobacteriosis and GBS suggests that older age is a major risk factor for more severe outcomes (hospitalization and GBS) from this enteric infection. The rising incidence of GBS with increasing age in New Zealand is consistent with incidence observed in other countries (21).

One strength of this study is that it has been able to monitor a natural experiment in which campylobacteriosis incidence decreased by 50% within a few months, providing an unusual opportunity to assess the effect of this change on incidence of GBS. New Zealand’s comprehensive recording of national hospitalization data and use of a unique patient number also provided us with a consistent base for estimating population rates of GBS over a prolonged period. Although the spectrum of GBS includes extremely mild cases, studies elsewhere indicate that only ≈3.0%–5.8% of patients with GBS are not hospitalized (22,23). In addition, patients with Campylobacter-associated GBS are believed to experience more severe disease (24,25), which would minimize the number of Campylobacter-associated GBS cases missed by this investigation.

One limitation of this study is the group used to compare risk for GBS: the total New Zealand population. A variety of conditions and events have been identified as possible GBS triggers (1,24,26–29). Consequently, because it is not possible with current knowledge to identify a reference patient population with no additional GBS risk factors, we considered that the total population provided the most appropriate reference rate.

The association between campylobacteriosis and GBS in New Zealand needs further investigation. It will be useful to continue to follow the trends identified here to assess the stability of the decrease in GBS, which will eventually give greater precision to the estimated contribution of campylobacteriosis. Ongoing monitoring of GBS should be included in the comprehensive surveillance of infectious diseases (30). The hypothesis that patients not hospitalized for campylobacteriosis have a lower risk for GBS should be tested by investigation of incidence of GBS among these patients.

Our findings suggest the value of further research to identify other potentially preventable infectious causes of GBS. Table 3 shows a markedly elevated risk for GBS after hospitalization for infectious diseases in general. Investigating these associations in detail may identify other potentially preventable causes of GBS.

Findings of this study have relevant implications for food safety programs. Although GBS is rare, the toll it takes on the individual patient is often high (1). Even with treatment, 9%–17% of patients die or remain disabled (31), and repeat hospitalizations are common, representing ≈60% of total hospitalizations (Technical Appendix Table 1). Almost half of all patients report ongoing difficulties 3–6 years after GBS onset (32). Consequently, ongoing health care costs for each GBS patient are considerable. In New Zealand during 1988–2008, the GBS case-fatality proportion was 3.0%, and a recent article (33) estimated that 204 (13%) of 1,568 disability-adjusted life years for campylobacteriosis in New Zealand were caused by GBS.

This study shows that food safety programs that successfully lower rates of campylobacteriosis might have the additional benefit of preventing GBS. This finding adds to the health and economic arguments for such control measures. The justification for such interventions is particularly strong where a substantial proportion of human disease can be linked to a widely consumed food source, such as contaminated poultry products, as it is in New Zealand (7).

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1. Which of the following infections is most common prior to the development of Guillain-Barré syndrome (GBS)?A. Listeria monocytogenesB. Campylobacter jejuniC. Neisseria meningitidisD. Neisseria gonorrhoeae2. Which of the following statements best describes the temporal relationship between campylobacteriosis and GBS in the current study?A. Most patients had concurrent campylobacteriosis and GBSB. GBS followed infection with C. jejuni by an average of 2 monthsC. GBS followed infection with C. jejuni by an average of 6 monthsD. There was no temporal relationship between campylobacteriosis and GBS3. Which of the following age groups in the current study featured the strongest association between campylobacteriosis and GBS?A. <5 years oldB. 5–9 years oldC. 10–19 years oldD. 60–69 years old4. How did new food safety measures affect risks for campylobacteriosis and GBS in the current study?A. Food safety measures failed to significantly alter the prevalence of campylobacteriosis or GBSB. Food safety measures reduced the prevalence of campylobacteriosis onlyC. Food safety measures reduced the prevalence of GBS onlyD. Food safety measures reduced the prevalence of both campylobacteriosis and GBS