• 1.

    Centers for Disease Control and Prevention, 2013. Incidence and trends of infection with pathogens transmitted commonly through food—foodborne diseases active surveillance network, 10 U.S. sites, 1996–2012. MMWR Morb Mortal Wkly Rep 62: 283287.

    • Search Google Scholar
    • Export Citation
  • 2.

    Young KT, Davis LM, Dirita VJ, 2007. Campylobacter jejuni: molecular biology and pathogenesis. Nat Rev Microbiol 5: 665679.

  • 3.

    Blaser MJ, Berkowitz ID, LaForce FM, Cravens J, Reller LB, Wang WL, 1979. Campylobacter enteritis: clinical and epidemiologic features. Ann Intern Med 91: 179185.

    • Search Google Scholar
    • Export Citation
  • 4.

    Coker AO, Isokpehi RD, Thomas BN, Amisu KO, Obi CL, 2002. Human campylobacteriosis in developing countries. Emerg Infect Dis 8: 237244.

  • 5.

    McCarthy N, Giesecke J, 2001. Incidence of Guillain–Barre syndrome following infection with Campylobacter jejuni. Am J Epidemiol 153: 610614.

    • Search Google Scholar
    • Export Citation
  • 6.

    van Doorn PA, Ruts L, Jacobs BC, 2008. Clinical features, pathogenesis, and treatment of Guillain–Barre syndrome. Lancet Neurol 7: 939950.

  • 7.

    Guillain–Barre Syndrome Study Group, 2000. Guillain–Barre syndrome: an Italian multicentre case-control study. Neurol Sci 21: 229234.

    • Search Google Scholar
    • Export Citation
  • 8.

    Hadden RD 2001. Preceding infections, immune factors, and outcome in Guillain–Barre syndrome. Neurology 56: 758765.

  • 9.

    Jacobs BC, Rothbarth PH, van der Meche FG, Herbrink P, Schmitz PI, de Klerk MA, van Doorn PA, 1998. The spectrum of antecedent infections in Guillain–Barre syndrome: a case-control study. Neurology 51: 11101115.

    • Search Google Scholar
    • Export Citation
  • 10.

    Krauer F, Riesen M, Reveiz L, Oladapo OT, Martinez-Vega R, Porgo TV, Haefliger A, Broutet NJ, Low N, 2017. Zika virus infection as a cause of congenital brain abnormalities and Guillain–Barre syndrome: systematic review. PLoS Med 14: e1002203.

    • Search Google Scholar
    • Export Citation
  • 11.

    Vieira MA, Romano AP, Borba AS, Silva EV, Chiang JO, Eulalio KD, Azevedo RS, Rodrigues SG, Almeida-Neto WS, Vasconcelos PF, 2015. West Nile virus encephalitis: the first human case recorded in Brazil. Am J Trop Med Hyg 93: 377379.

    • Search Google Scholar
    • Export Citation
  • 12.

    McGrogan A, Madle GC, Seaman HE, de Vries CS, 2009. The epidemiology of Guillain–Barre syndrome worldwide. A systematic literature review. Neuroepidemiology 32: 150163.

    • Search Google Scholar
    • Export Citation
  • 13.

    Mishu B, Ilyas AA, Koski CL, Vriesendorp F, Cook SD, Mithen FA, Blaser MJ, 1993. Serologic evidence of previous Campylobacter jejuni infection in patients with the Guillain–Barre syndrome. Ann Intern Med 118: 947953.

    • Search Google Scholar
    • Export Citation
  • 14.

    Saida T, Kuroki S, Hao Q, Nishimura M, Nukina M, Obayashi H, 1997. Campylobacter jejuni isolates from Japanese patients with Guillain–Barre syndrome. J Infect Dis 176 (Suppl 2): S129S134.

    • Search Google Scholar
    • Export Citation
  • 15.

    Vriesendorp FJ, Mishu B, Blaser MJ, Koski CL, 1993. Serum antibodies to GM1, GD1b, peripheral nerve myelin, and Campylobacter jejuni in patients with Guillain–Barre syndrome and controls: correlation and prognosis. Ann Neurol 34: 130135.

    • Search Google Scholar
    • Export Citation
  • 16.

    Schmidt-Ott R, Schmidt J, Feldmann S, Brass F, Krone B, Gross U, 2006. Improved serological diagnosis stresses the major role of Campylobacter jejuni in triggering Guillain–Barré syndrome. Clin Vaccine Immunol 13: 779783.

    • Search Google Scholar
    • Export Citation
  • 17.

    da Silva Quetz J, Lima IF, Havt A, de Carvalho EB, Lima NL, Soares AM, Mota RM, Guerrant RL, Lima AA, 2010. Campylobacter jejuni and Campylobacter coli in children from communities in northeastern Brazil: molecular detection and relation to nutritional status. Diagn Microbiol Infect Dis 67: 220227.

    • Search Google Scholar
    • Export Citation
  • 18.

    Fernandez H, Toledo MR, Fagundes Neto U, Trabulsi LR, 1985. Occurrence of Campylobacter jejuni in diarrhoeic and non-diarrhoeic children in Sao Paulo, Brazil. Rev Inst Med Trop São Paulo 27: 102104.

    • Search Google Scholar
    • Export Citation
  • 19.

    Fernández H, 2011. Campylobacter y campylobacteriosis: una mirada desde Amereica del Sur. Rev Peru Med Exp Salud Publica 28: 7.

  • 20.

    Walgaard C, Lingsma HF, Ruts L, van Doorn PA, Steyerberg EW, Jacobs BC, 2011. Early recognition of poor prognosis in Guillain–Barre syndrome. Neurology 76: 968975.

    • Search Google Scholar
    • Export Citation

 

 

 

 

 

Serological Markers of Recent Campylobacter jejuni Infection in Patients with Guillain–Barré Syndrome in the State of Piauí, Brazil, 2014–2016

View More View Less
  • 1 Department of Bacteriology and Mycology, Evandro Chagas Institute, Ananindeua, Pará, Brazil;
  • 2 Natan Portella Institute of Tropical Medicine, Piauí State Health Secretariat, Teresina, Piauí, Brazil;
  • 3 Department of Health Surveillance, Teresina Municipal Health Secretariat, Teresina, Piauí, Brazil;
  • 4 Post-graduation Program in Virology, Evandro Chagas Institute, Ananindeua, Pará, Brazil;
  • 5 Department of Health Surveillance, Piauí State Health Secretariat, Teresina, Piauí, Brazil;
  • 6 Novafapi University, Medicine School, Teresina, Piauí, Brazil;
  • 7 Department of Health Surveillance, Piauí State University Hospital, Teresina, Piauí, Brazil;
  • 8 Department of Arbovirology and Haemorrhagic Fevers, Evandro Chagas Institute, Ananindeua, Pará, Brazil;
  • 9 Department of Mother and Child Health, Federal University of Piauí, Teresina, Piauí, Brazil

In countries where poliomyelitis has been eradicated, Guillain–Barré syndrome (GBS) is the leading cause of acute flaccid paralysis. The range of infections that precede GBS in Brazil is unknown. Campylobacter jejuni infection is the most frequent trigger of GBS worldwide. Given the lack of systematic surveillance of diarrheal diseases, particularly in adults, the incidence of enteritis caused by C. jejuni in developing countries is unknown. From 2014 to 2016, pretreatment serum samples from 63 GBS patients were tested by immunoglobulin M (IgM) enzyme-linked immunosorbent assay for C. jejuni. Campylobacter jejuni IgM antibodies were detected in 17% (11/63) of the samples. There was no association between serological positivity (IgM) for C. jejuni and the occurrence of diarrhea among the investigated cases (P = 0.36). Hygiene measures, basic sanitation, and precautions during handling and preparation of food of animal origin may help prevent acute flaccid paralysis.

Campylobacter jejuni is the leading cause of bacterial diarrhea in developed countries, where the rate of this infection is higher than that with Shigella sp. and Salmonella sp.1 Campylobacter jejuni is a Gram-negative microaerophilic bacillus that is transmitted to humans by the ingestion of contaminated and undercooked meat, untreated water, and unpasteurized milk. Contact with animals with diarrhea and handling of raw meat (particularly poultry meat) are also implicated in its transmission.2 Most cases of C. jejuni enteritis (CJE) have a benign and self-limited course and occur in small sporadic outbreaks. Acute infection is characterized by fever, myalgia, vomiting, abdominal pain, and inflammatory diarrhea with different combinations of symptoms.3 Acute complications such as dehydration, peritonitis, and sepsis may occur in infants, elderly individuals, and immunocompromised individuals. In addition, rare late complications have been described, including reactive arthritis, hemolytic uremic syndrome, and Guillain–Barré syndrome (GBS).2,3

The incidence of CJE in developing countries is unknown because usually there is no systematic surveillance of diarrheal diseases. The available estimates in Brazil are based on surveys of samples from a few laboratory or hospital services, where the reported positivity rates for C. jejuni in diarrheal stool are 5–20%.4

Campylobacter jejuni infection is the most common precipitating factor for GBS. A study estimated that in CJE patients, the risk of developing GBS within 2 months after developing symptomatic CJE was 100 times higher than that in the general population, and approximately 0.03% of CJE patients developed GBS.5 GBS is the leading cause of acute flaccid paralysis in children and adults in countries where poliomyelitis has been eradicated.6 As a rule, two-thirds of individuals affected by GBS report symptoms of previous and recent infection of the respiratory or gastrointestinal tract. Cytomegalovirus, Epstein–Barr virus, and Mycoplasma pneumoniae are also involved in GBS trigger, as reported in prevalence and case–control studies conducted in several countries.79 In January 2017, the World Health Organization concluded that there are causal relationships between the Zika epidemic and the increase in the number of GBS cases in several countries.10 To date, the range of infections associated with the onset of GBS in Brazil is unknown.

The Health Department of Piauí State, Brazil, initiated a hospital-based program for the active surveillance of infectious, parainfectious, and postinfectious cases of neurological syndromes. In 2014, the surveillance of neurological syndromes was intensified because of the detection of the first case of a severe neuroinvasive disease caused by the West Nile virus (WNV) in Brazil, in Aroeiras do Itaim municipality (Piauí, Brazil).11 Since then, cases of aseptic meningitis, encephalitis, and acute flaccid paralysis (including those involving adult patients) have been reported and investigated.

From 2014 to 2016, 73 patients were diagnosed with GBS in Piauí (0.83 cases per 100,000 patients per year). The annual incidence of GBS in this period was lower than the global estimate of one to two cases per 100,000 inhabitants per year,12 but the surveillance program evaluated only hospitalized patients. Sixty-three samples were collected from 63 GBS patients in the acute phase of the disease, before the administration of hyperimmune human immunoglobulin. The samples were analyzed in the Bacteriology Section of the Evandro Chagas Institute. Serum immunoglobulin M (IgM) antibodies specific for C. jejuni were determined by using commercial enzyme-linked immunosorbent assay (ELISA) kits (Serion ELISA Classic, Institut Virion/Serion, Wurzburg, Germany), using a preparation of the outer membrane of C. jejuni, according to the manufacturer’s recommendations. None of the evaluated samples were positive for WNV by in-house antibody capture IgM-ELISA or reverse transcription–polymerase chain reaction in real time.

Of the 63 screened patients, 38 (60%) were men and 25 (40%) were women, and their mean age was 43 years. Only 11 (17%) patients lived in rural areas. The GBS report forms registered the occurrence of diarrheal symptoms in 10 (16%) patients (Table 1). The GBS cases were classified in accordance with the diagnostic certainty of the Brighton Collaboration Criteria case definitions for GBS, as follows: 11 (17%) patients met level 1, 43 (69%) met level 2, and 9 (14%) met level 3 of diagnostic certainty. Campylobacter jejuni IgM antibodies were detected in 17% (11/63) of the serum samples. In other countries, serological surveys of patients with GBS using a variety of methods and control groups have shown that a significant proportion of GBS patients have antibodies against C. jejuni antigens8,9,1315 (Table 2). The wide range of levels of positivity could reflect local population characteristics, fine specificities of the assay, different criteria for positivity, and timing of the serum sample collection. The present study used the presence of IgM against C. jejuni as evidence of a recent infection. IgG was not used as a criterion because high IgG reactivity against C. jejuni may persist for months or years after infection. However, the detection of short-lived C. jejuni-specific IgM in GBS patients strongly indicates that the infection occurred within the previous weeks.16

Table 1

Association between serological positivity (IgM ELISA) for Campylobacter jejuni and the report of diarrhea in patients with Guillain–Barré syndrome

IgM ELISA for C. jejuniReport of diarrheaTotal
Present (n)Absent (n)
Positive3811 (17%)
Negative74552 (83%)
Total10 (16%)53 (84%)63 (100%)

ELISA = enzyme-linked immunosorbent assay; IgM = immunoglobulin M. P = 0.36, by Fisher’s exact test.

Table 2

Prevalence of serological markers of recent infection with Campylobacter jejuni in serum samples of patients in the acute phase of Guillain–Barré syndrome (GBS), reported in the five largest studies conducted in other countries

Authors and year of publicationStudy periodCountriesStudy designSample size (GBS cases)Positivity criteriaPrevalence of C. jejuni antibodies indicating recent infection
Mishu et al., 19931983–1990USACase control118Detection of IgG, IgA, or IgM36%
Vriesendorp et al., 19931985–1991USACase control58Detection of two or more immunoglobulin classes (IgG, IgA, and/or IgM)17%
Saida et al., 19971990–1996JapanCase control205Detection of two or more immunoglobulin classes (IgG, IgA, and/or IgM) or high titer of IgA or IgM45%
Jacobs et al., 19981986–1996The NetherlandsCase control154Detection of IgM, IgA, or high titer IgG32%
Hadden et al., 20011993–1995Australia, Europe, and North AmericaPrevalence229Detection of two or more immunoglobulin classes (IgG, IgA, and/or IgM), or one class and recent diarrhea23%

IgA = immunoglobulin A; IgG = immunoglobulin G; IgM = immunoglobulin M.

There was no association between serological positivity (IgM) for C. jejuni and the reporting of diarrhea among the investigated cases (P = 0.36, by Fisher’s exact test) (Table 1). Two studies performed in Brazil used bacterial genome assays and coproculture tests and reported that the prevalence of C. jejuni in the stool was similar between symptomatic and asymptomatic individuals (5.8–9.6% in patients with diarrhea and 4.9–7.2% in patients without diarrhea).17,18 In developing countries, symptomatic presentations are more common in children, whereas subclinical infections are more usual in adults.19 Subclinical C. jejuni infections may be associated with GBS, and IgM antibodies may remain detectable for up to 90 days in the serum of infected individuals. Some IgM-negative samples may have been collected from patients who had diarrhea caused by microorganisms of high incidence in the country, such as norovirus and rotavirus.17 The GBS report form did not indicate whether the onset of diarrheal symptoms occurred before or concomitantly with neurological symptoms or it occurred as a result of complications during hospitalization. In addition, the available sample size provided inadequate statistical power to demonstrate a difference in the prevalence of diarrhea between the IgM-positive and IgM-negative subgroups.

Campylobacter jejuni infections are associated with more severe types of GBS, with axonal involvement rather than demyelinating peripheral nervous system involvement.20 Meanwhile, no differences were found between the electrophysiological pattern and the outcome among the C. jejuni IgM-positive and IgM-negative subgroups of the present study. However, there was no homogeneity between the proportion of patients submitted to electromyography in each subgroup, and the sample included only hospitalized patients. Therefore, patients who showed mild GBS and did not require hospitalization were not included in this study.

The gold-standard method for the detection of C. jejuni infection is coproculture using specific media.3 However, most GBS patients present neurological symptoms after the resolution of diarrheal symptoms, when C. jejuni is no longer detectable or isolated in their stool samples. This study was based on the epidemiological surveillance investigation of GBS cases in Piauí. Therefore, the control group was not available for comparing the frequency of serological positivity in the evaluated cases.

This study is the first to investigate the presence of serological markers (IgM antibodies) of recent C. jejuni infection in a case series of hospitalized GBS patients in Brazil. Additional studies are necessary to assess the role of CJE in diarrheal diseases in Brazil and in GBS onset in other Brazilian states, with longer duration, larger sample size, and control groups. The search for other infections associated with GBS, particularly of those with epidemic potential, gains relevance in the current epidemiological scenario in Brazil, wherein several arboviruses are present. The results of the present study demonstrate the possible epidemiological importance of C. jejuni as a pathogen associated with GBS. Therefore, the use of strategies to prevent the transmission of CJE in Brazil, including the adoption of hygiene measures, basic sanitation, and precautions during handling and preparation of food of animal origin, may help prevent acute flaccid paralysis.

Acknowledgments:

We thank Amaríles Borba, Amparo Salmito, Célia Regina, and Lidianny Lauritzen for their help with the epidemiological surveillance procedures, and Gildevane Vieira, Joana Lima, and Juana Sousa for their help with packaging, storing, and shipping of the biological samples.

REFERENCES

  • 1.

    Centers for Disease Control and Prevention, 2013. Incidence and trends of infection with pathogens transmitted commonly through food—foodborne diseases active surveillance network, 10 U.S. sites, 1996–2012. MMWR Morb Mortal Wkly Rep 62: 283287.

    • Search Google Scholar
    • Export Citation
  • 2.

    Young KT, Davis LM, Dirita VJ, 2007. Campylobacter jejuni: molecular biology and pathogenesis. Nat Rev Microbiol 5: 665679.

  • 3.

    Blaser MJ, Berkowitz ID, LaForce FM, Cravens J, Reller LB, Wang WL, 1979. Campylobacter enteritis: clinical and epidemiologic features. Ann Intern Med 91: 179185.

    • Search Google Scholar
    • Export Citation
  • 4.

    Coker AO, Isokpehi RD, Thomas BN, Amisu KO, Obi CL, 2002. Human campylobacteriosis in developing countries. Emerg Infect Dis 8: 237244.

  • 5.

    McCarthy N, Giesecke J, 2001. Incidence of Guillain–Barre syndrome following infection with Campylobacter jejuni. Am J Epidemiol 153: 610614.

    • Search Google Scholar
    • Export Citation
  • 6.

    van Doorn PA, Ruts L, Jacobs BC, 2008. Clinical features, pathogenesis, and treatment of Guillain–Barre syndrome. Lancet Neurol 7: 939950.

  • 7.

    Guillain–Barre Syndrome Study Group, 2000. Guillain–Barre syndrome: an Italian multicentre case-control study. Neurol Sci 21: 229234.

    • Search Google Scholar
    • Export Citation
  • 8.

    Hadden RD 2001. Preceding infections, immune factors, and outcome in Guillain–Barre syndrome. Neurology 56: 758765.

  • 9.

    Jacobs BC, Rothbarth PH, van der Meche FG, Herbrink P, Schmitz PI, de Klerk MA, van Doorn PA, 1998. The spectrum of antecedent infections in Guillain–Barre syndrome: a case-control study. Neurology 51: 11101115.

    • Search Google Scholar
    • Export Citation
  • 10.

    Krauer F, Riesen M, Reveiz L, Oladapo OT, Martinez-Vega R, Porgo TV, Haefliger A, Broutet NJ, Low N, 2017. Zika virus infection as a cause of congenital brain abnormalities and Guillain–Barre syndrome: systematic review. PLoS Med 14: e1002203.

    • Search Google Scholar
    • Export Citation
  • 11.

    Vieira MA, Romano AP, Borba AS, Silva EV, Chiang JO, Eulalio KD, Azevedo RS, Rodrigues SG, Almeida-Neto WS, Vasconcelos PF, 2015. West Nile virus encephalitis: the first human case recorded in Brazil. Am J Trop Med Hyg 93: 377379.

    • Search Google Scholar
    • Export Citation
  • 12.

    McGrogan A, Madle GC, Seaman HE, de Vries CS, 2009. The epidemiology of Guillain–Barre syndrome worldwide. A systematic literature review. Neuroepidemiology 32: 150163.

    • Search Google Scholar
    • Export Citation
  • 13.

    Mishu B, Ilyas AA, Koski CL, Vriesendorp F, Cook SD, Mithen FA, Blaser MJ, 1993. Serologic evidence of previous Campylobacter jejuni infection in patients with the Guillain–Barre syndrome. Ann Intern Med 118: 947953.

    • Search Google Scholar
    • Export Citation
  • 14.

    Saida T, Kuroki S, Hao Q, Nishimura M, Nukina M, Obayashi H, 1997. Campylobacter jejuni isolates from Japanese patients with Guillain–Barre syndrome. J Infect Dis 176 (Suppl 2): S129S134.

    • Search Google Scholar
    • Export Citation
  • 15.

    Vriesendorp FJ, Mishu B, Blaser MJ, Koski CL, 1993. Serum antibodies to GM1, GD1b, peripheral nerve myelin, and Campylobacter jejuni in patients with Guillain–Barre syndrome and controls: correlation and prognosis. Ann Neurol 34: 130135.

    • Search Google Scholar
    • Export Citation
  • 16.

    Schmidt-Ott R, Schmidt J, Feldmann S, Brass F, Krone B, Gross U, 2006. Improved serological diagnosis stresses the major role of Campylobacter jejuni in triggering Guillain–Barré syndrome. Clin Vaccine Immunol 13: 779783.

    • Search Google Scholar
    • Export Citation
  • 17.

    da Silva Quetz J, Lima IF, Havt A, de Carvalho EB, Lima NL, Soares AM, Mota RM, Guerrant RL, Lima AA, 2010. Campylobacter jejuni and Campylobacter coli in children from communities in northeastern Brazil: molecular detection and relation to nutritional status. Diagn Microbiol Infect Dis 67: 220227.

    • Search Google Scholar
    • Export Citation
  • 18.

    Fernandez H, Toledo MR, Fagundes Neto U, Trabulsi LR, 1985. Occurrence of Campylobacter jejuni in diarrhoeic and non-diarrhoeic children in Sao Paulo, Brazil. Rev Inst Med Trop São Paulo 27: 102104.

    • Search Google Scholar
    • Export Citation
  • 19.

    Fernández H, 2011. Campylobacter y campylobacteriosis: una mirada desde Amereica del Sur. Rev Peru Med Exp Salud Publica 28: 7.

  • 20.

    Walgaard C, Lingsma HF, Ruts L, van Doorn PA, Steyerberg EW, Jacobs BC, 2011. Early recognition of poor prognosis in Guillain–Barre syndrome. Neurology 76: 968975.

    • Search Google Scholar
    • Export Citation

Author Notes

Address correspondence to Marcelo A. C. S. Vieira, Department of Neurology, Natan Portella Institute of Tropical Medicine, Rua Governador Artur de Vasconcelos, 151 Sul, Teresina, Piauí, Brazil. E-mail: macsvieira@superig.com.br

Ethics committee approval: This study was approved by the Piauí State University Ethics Committee (CAAE 68445817.9.0000.5613).

Financial support: The Instituto Evandro Chagas provided a grant for this study, as well as Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq) and Fundação de Amparo à Pesquisa do Estado do Piauí (FAPEPI).

Authors’ addresses: Cintya O. Souza and Leni C. R. Monteiro, Department of Bacteriology and Mycology, Evandro Chagas Institute, Ananindeua, Pará, Brazil, E-mails: cintyaoliveira@iec.pa.gov.br and lenimonteiro@iec.pa.gov.br. Marcelo A. C. S. Vieira, Department of Neurology, Natan Portella Institute of Tropical Medicine, Teresina, Piauí, Brazil, E-mail: macsvieira@superig.com.br. Ana C. R. Cruz and Raimunda S. S. Azevedo, Department of Arbovirology and Haemorrhagic Fevers, Evandro Chagas Institute, Ananindeua, Pará, Brazil, E-mails: anacecilia@iec.pa.gov.br and raimundaazevedo@iec.pa.gov.br. Francisca M. A. Batista, Department of Health Surveillance, Piauí State Health Secretariat, Teresina, Piauí, Brazil, E-mail: mirianearaujo@hotmail.com. Laís C. Sá, Department of Health Surveillance, Piauí State University Hospital, Teresina, Piauí, Brazil, E-mail: laiscarvalhodesa@hotmail.com. Kelsen D. Eulálio and Walfrido S. Almeida-Neto, Department of Infectious Diseases, Natan Portella Institute of Tropical Medicine, Teresina, Piauí, Brazil, E-mails: kelsendeulalio@yahoo.com.br and walfridomed@hotmail.com. Jéssica M. M. Neves, Medicine School, Novafapi University, Teresina, Piauí, Brazil, E-mail: milenamoura80@hotmail.com. Dorcas L. Costa, Department of Mother and Child Health, Federal University of Piauí, Teresina, Piauí, Brazil, E-mail: dorcas.lc@gmail.com.

These two authors contributed equally to this article.

Save