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Keywords:

  • epidemiology;
  • Guillain−Barré syndrome;
  • incidence

Abstract

  1. Top of page
  2. Abstract
  3. Introduction
  4. Materials and methods
  5. Results
  6. Discussion
  7. Acknowledgements and funding
  8. Disclosure of conflicts of interest
  9. References

Background and purpose

It is important to have an estimate of the incidence of Guillain−Barré syndrome (GBS) because of the expansion of vaccination programs and the associated risks of vaccine-related GBS. Incidence information in Asia, especially in China, is scarce. This study attempts to describe GBS incidence in large Chinese populations located in three geographically different and moderately distant areas of the same province.

Methods

The surveyed areas were Nanjing, Yancheng and Xuzhou, which are three cities in Jiangsu province in China. Nanjing is in the south of Jiangsu province, Yancheng is in the middle and Xuzhou is in the north. The survey was carried out in regions that might have received patients meeting the case definition from 2008 to 2010. The population numbers came from the local Bureau of Statistics. Data analysis was conducted in 2011.

Results

The incidence of GBS was 0.59 cases per 100 000 person-years. The GBS incidence increased with age amongst people <80 years old. Males had a higher incidence of GBS than females. GBS incidence in Nanjing was the highest amongst the three regions.

Conclusions

The incidence rates in parts of Jiangsu province were lower than those in Europe and North America. There was one peak in incidence amongst older adults (70–80 years). Geographical differences in GBS incidence rates may be related to socioeconomic status. There were no significant seasonal variations of incidence in Jiangsu.


Introduction

  1. Top of page
  2. Abstract
  3. Introduction
  4. Materials and methods
  5. Results
  6. Discussion
  7. Acknowledgements and funding
  8. Disclosure of conflicts of interest
  9. References

Guillain−Barré syndrome (GBS) is a polyneuropathy with an acute or sub-acute onset of varying degrees of weakness in the limbs or cranial-nerve-innervated muscles and is characterized by decreased or absent deep tendon reflexes [1]. Diagnostic criteria for GBS were developed in 1978 [2]. More recently, it has become clear that the clinical spectrum of GBS is pathophysiologically diverse [3]. Currently, it is known that the type of preceding event and specific host factors determine the form and severity of GBS [4].

In addition to a known association with infections [5], vaccinations have also been suggested to increase the risk of GBS, although the biological mechanisms of this association remain ambiguous. A sudden increase in cases was seen following a US swine flu vaccination campaign in 1976 [6]. More recently, scientists have postulated an association between the quadrivalent meningococcal conjugate vaccine and GBS [7]. However, in 2011, a European research study based on five countries’ databases showed that the risk of the occurrence of GBS does not increase after pandemic influenza vaccine [8]. Contrary to this finding, a meta-analysis and an international study found an increased risk following the 2009 H1N1 vaccination [9].

In recent years, an Expanded Program on Immunization (EPI) was carried out in China. The type and number of vaccines administered to citizens were expanded. Although there is a low probability of having an abnormal reaction such as GBS to vaccines, the occurrence of such reactions increased after the EPI, causing widespread public concern. When judging whether GBS has a causal association with vaccination or when evaluating the risk of vaccines leading to GBS, epidemiological characteristics and baseline population-level incidence rates, in addition to clinical features and disease diagnosis, must be assessed. A firm measure of the incidence of GBS is increasingly important.

A recent comprehensive systematic literature review by Sejvar et al. summarized data from papers worldwide describing the incidence of GBS [10]. However, the data used were mainly from North America and Europe; incidence information from Asia, in particular China, was scarce. This study attempts to describe GBS incidence in a selection of large Chinese populations located in three geographically different and moderately distant areas of the same province.

Materials and methods

  1. Top of page
  2. Abstract
  3. Introduction
  4. Materials and methods
  5. Results
  6. Discussion
  7. Acknowledgements and funding
  8. Disclosure of conflicts of interest
  9. References

Study population

GBS cases were selected from 1 January 2008 to 31 December 2010. The surveyed areas were Nanjing, Yancheng and Xuzhou, which are three cities in Jiangsu province in China. Each city contains both urban and rural populations. Age-specific and gender-specific population numbers from 2008 to 2010 were from the local Bureau of Statistics. The population denominator excluded the migratory labor population, which does not officially reside in the area. The populations covered in this research and the geographical locations of the three cities are shown in Table 1 and Fig. 1.

Table 1. Age-, sex- and place-related variations in GBS incidence
VariableNumber of casesPopulationIncidence × 100 000RR
Point95% CI
  1. Deviance 124; degrees of freedom 82.

Sex
Males27638 399 6370.721.591.31–1.92
Females16536 307 6200.451.00
Age groups
0–4 years153 947 1220.380.880.39–2.02
5–9 years113 089 4820.360.800.33–1.92
10–14 years104 606 2760.220.500.20–1.23
15–19 years295 855 8130.501.100.52–2.33
20–24 years266 323 5330.410.910.42–1.94
25–29 years296 473 3750.450.990.47–2.10
30–34 years336 276 5370.531.150.55–2.41
35–39 years296 134 6950.471.030.49–2.18
40–44 years435 462 2110.791.730.84–3.54
45–49 years315 165 4800.601.320.63–2.78
50–54 years304 707 0710.641.410.67–2.97
55–59 years434 275 1081.012.261.10–4.64
60–64 years323 913 5250.821.840.88–3.85
65–69 years262 762 1220.942.050.96–4.38
70–74 years272 188 4611.232.691.27–5.73
75–79 years181 597 3361.132.461.11–5.48
>80 years91 929 1120.471.00
Population
Nanjing18121 837 2170.831.611.28–2.02
Xuzhou13124 216 3300.540.930.73–1.19
Yancheng12928 653 7100.451.00
image

Figure 1. Geographical location of Jiangsu province in China (1, Jiangsu) and the study population in Jiangsu (2, Xuzhou; 3, Yancheng; 4, Nanjing).

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Medical and pediatric services

In China, most people have access to medical technology and specialized neurological care provided by public hospitals. Generally, patients with suspected GBS are hospitalized as emergencies and, soon after, hospital neurologists become involved in their care. Residents under the age of 16 years who are affected by neurological disorders usually attend pediatric hospitals.

Case definition

Search criteria included ‘Guillain−Barré syndrome, GBS’, ‘acute inflammatory demyelinating polyradiculopathy, AIDP’, ‘chronic inflammatory demyelinating polyradiculopathy, CIDP’, ‘acute motor-axonal neuropathy, AMAN’, ‘acute motor-sensory axonal neuropathy, AMSAN’ and ‘Miller−Fisher syndrome, MFS’.

Case selection

Cases from all hospitals that may have treated GBS patients were searched and reviewed. Within these hospitals, any sections that might have received patients meeting the case definition were included, including neurology, pediatrics, internal medicine and inpatient wards. Some hospitals had hospital information systems (HISs), in which case the HIS was searched for relevant information. Otherwise, the inpatient medical records were manually reviewed. In total, 2 173 220 records were searched by electronic databases and 271 375 records were searched by manual chart review. The kappa coefficient was used to assess inter-rater reliability.

Guillain−Barré syndrome cases were confirmed by neurologists from clinical data, such as clinical manifestations, electromyography, magnetic resonance imaging and cerebrospinal fluid examinations, and a clear and widely accepted case definition for GBS was used [2], i.e. the case definition developed by Asbury and Cornblath [11].

Some of the cases were from foreign cities. Because these cases would affect the accuracy of local incidence assessment they were excluded. The Poisson model was used to calculate the point values and 95% confidence intervals (CIs) of the rate ratio (RR) for sex, age and place. The research protocol was approved by the institutional review board of the Jiangsu Provincial Center for Disease Control and Prevention. All analyses were conducted in 2011.

Results

  1. Top of page
  2. Abstract
  3. Introduction
  4. Materials and methods
  5. Results
  6. Discussion
  7. Acknowledgements and funding
  8. Disclosure of conflicts of interest
  9. References

In total, 104 hospitals and 2 444 595 records in the three cities were surveyed. From these records, 534 GBS cases were found in the study population. Of these 534 cases, 93 cases were excluded due to residence outside the geographical areas of study. Four hundred and forty-one cases were included in the incidence counts. The incidence was 0.59 cases per 100 000 person-years.

Variation with age

Age- and sex-specific incidences of GBS are shown in Fig. 2, and the corresponding age-specific RRs, controlling for the effect of sex and location, are shown in Table 1. The age-specific GBS rates increased from 0.37/100 000/year in children (0–10 years) to 1.19/100 000/year amongst 70-year-olds, and decreased to 0.47/100 000/year in the highest age group of ≥80 years.

image

Figure 2. Age- and sex-specific GBS incidence between 2008 and 2010.

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Gender variation

The incidence rate found for GBS in males was 0.72/100 000/year, which is higher than that in females (0.45/100 000/year) (Table 1). The sex differential proved statistically significant, indicating that GBS incidence was 59% higher amongst men than amongst women.

Geographical variation

The variations in incidence by location, adjusted for age and sex, were 1.73-fold. The incidence rate in Nanjing was 0.83/100 000/year, with the highest RR (1.61, 95% CI 1.28–2.02). The incidence for both sexes in Xuzhou was close to the incidence rate in Yancheng (Fig. 3).

image

Figure 3. Sex-specific GBS incidence in Nanjing, Xuzhou and Yancheng.

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Seasonal variation

New cases of GBS occurred during each month throughout the year. The highest incidences were seen amongst males in June and females in April (Fig. 4). The highest risk of acquiring GBS for young populations (under 40 years) was in April and, for older populations, was in May (Fig. 5). There was no significant difference in incidence by seasonal variation. Cases with preceding infections were clustered in spring/summer for the young group, whilst there was no significant difference amongst older patients (Fig. 6).

image

Figure 4. Monthly distribution of sex-specific GBS incidence.

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image

Figure 5. Monthly distribution of GBS incidence in individuals aged below 39 years and above 40 years.

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image

Figure 6. Pattern of antecedent infections amongst individuals aged below 39 years and above 40 years.

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Discussion

  1. Top of page
  2. Abstract
  3. Introduction
  4. Materials and methods
  5. Results
  6. Discussion
  7. Acknowledgements and funding
  8. Disclosure of conflicts of interest
  9. References

This study found that incidence rates in three cities within Jiangsu province were lower than those in Europe and North America (which were estimated to be between 1.1/100 000/year and 1.8/100 000/year) [12], were similar to those of Harbin [13, 14] and Hong Kong [15] and were lower than those of Beijing and Hebei [16]. A recent study in Heilongjiang province, which is located in northern China, found that the overall incidence rate was 0.45/100 000/year, a little lower than that in Jiangsu [17].

Contrasting the bimodal shape of the data observed in Sweden, with one valley at 35–39 years of age and one peak at 70–74 years of age [18], our data revealed one peak in incidence amongst older adults (70–80 years). This finding was similar to data observed in Spain [19]. Within our study, children below 15 years of age had a lower risk of GBS than similarly aged children in Harbin [13] and in other countries studied except for Finland [20]. It is more difficult to diagnose GBS in younger patients, especially children, which may cause under-diagnosis of GBS in younger populations [21]. The lower incidence of GBS in older age groups may reflect a survivor bias, in which individuals surviving into their 80s and 90s are less likely to develop GBS, although there is no biological evidence to support this hypothesis [10]. van der Maas et al. have also suggested that people with GBS in nursing homes may not be included in existing data sets [22].

Our study found that males had a higher risk of GBS; the male to female ratio was 1.59. This finding has been consistently demonstrated in many published studies [10]. It is also similar to observations of multifocal motor neuropathy with conduction blocks, another autoimmune disorder of the peripheral nervous system [23]. Such male predominance is unusual for an autoimmune disease, which may imply that estrogen has a protective effect operating at the level of susceptibility to infection or control of an autoimmune response [24]. In general, older women and men with motor ailments may be differentially referred from their households or homes to hospitals. A male to female incidence ratio that changes with advanced age may suggest differential referral, detection or access to a neurologist.

When comparing geographical patterns of incidence in Jiangsu, the highest incidence was found in Nanjing. This result may be related to the level of economic development. Concerning the level of economic development, Nanjing has a higher level of economic development than Yancheng and Xuzhou. In poorer areas, there is less access to healthcare, fewer doctors, fewer neurologists and perhaps a greater rate of misdiagnosis. In Nanjing, the temperature is usually 2–3°C higher than that in Xuzhou, which may increase gastroenterological infection rates. Compared with neighboring areas, Jiangsu has a higher level of economic development and better hospital treatment. Additionally, the proportion of residents from surrounding areas treated in the hospitals of Jiangsu is much higher than the proportion of Jiangsu residents treated in hospitals in neighboring areas.

An absence of seasonal variation in GBS incidence was also found in northern Italy [25]. This finding was different from Shijiazhuang [26] and Dezhou [27], two cities in north China, which had a higher risk in summer and autumn. GBS is thought to be an autoimmune condition triggered by a preceding infection in two-thirds of cases, most frequently respiratory or gastrointestinal infections [28]. The lack of obvious seasonal variation in incidence may be because the infections found most frequently to trigger this disease, respiratory and enteric infections, occur in different seasons around the globe [29].

Our study has several limitations. The duration of our survey was too short to discover long-term trends in the incidence rate of GBS. Some cases may have been admitted to hospitals in regions outside the surveyed areas and, as a result, the incidence would have been underestimated. However, because the medical conditions of the three cities are better than those of the surrounding areas, the number of these cases might be very small. After reviewing 63 papers, McGrogan et al. noted that the overall incidence rates found by prospective studies and database studies that did not review cases were higher than those found by retrospective studies that reviewed medical records [12]. The range of incidence rates found by retrospective studies produced slightly lower incidence rates, which indicates that some cases may have been missed by these studies. This may also contribute to an underestimate of the incidence.

Our findings provide a rough estimate of baseline GBS incidence in three large populations in parts of Jiangsu province in China and provide information for further studies assessing the effects of potential risk factors, such as immunization, infection or putative causal exposure. Our findings also provide useful information for potential epidemiological surveillance of GBS, which will be carried out in the near future. Future investigators should carry out studies for a longer period of time to ensure the discovery of a long-term trend in the incidence rate of GBS.

Acknowledgements and funding

  1. Top of page
  2. Abstract
  3. Introduction
  4. Materials and methods
  5. Results
  6. Discussion
  7. Acknowledgements and funding
  8. Disclosure of conflicts of interest
  9. References

This work was supported by a grant from the China-Australia Project, the epidemiology disciplines of science and education (LJ201150) and the Science-Education Project of the Jiangsu Center for Disease Control and Prevention (CDC) (JKRC2011023). The authors greatly appreciated the fieldwork of the following institutions: the Nanjing CDC, Yancheng CDC and Xuzhou CDC. The authors have also greatly benefited from the China CDC.

Disclosure of conflicts of interest

  1. Top of page
  2. Abstract
  3. Introduction
  4. Materials and methods
  5. Results
  6. Discussion
  7. Acknowledgements and funding
  8. Disclosure of conflicts of interest
  9. References

The authors declare no financial or other conflicts of interest.

References

  1. Top of page
  2. Abstract
  3. Introduction
  4. Materials and methods
  5. Results
  6. Discussion
  7. Acknowledgements and funding
  8. Disclosure of conflicts of interest
  9. References
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