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The case of a new sequence type 7 serogroup X Neisseria meningitidis infection in China: may capsular switching change serogroup profile?
International Journal of Infectious Diseases 29 (2014) 62–64
Contents lists available at ScienceDirect
International Journal of Infectious Diseases journal homepage: www.elsevier.com/locate/ijid
Case Report
The case of a new sequence type 7 serogroup X Neisseria meningitidis infection in China: may capsular switching change serogroup profile? Jinren Pan a, Pingping Yao a, Heng Zhang b, Xiaoyu Sun c, Hanqing He a, Shuyun Xie a,* a
Zhejiang Provincial Center for Disease Control and Prevention, Hangzhou, Zhejiang Province 310051, China Changsha Center for Disease Control and Prevention, Changsha, Hunan Province, China c Wenzhou Center for Disease Control and Prevention, Wenzhou, Zhejiang Province, China b
A R T I C L E I N F O
Article history: Received 21 October 2013 Received in revised form 17 March 2014 Accepted 30 July 2014 Corresponding Editor: Maria RodriguezBarradas, Texas, USA
S U M M A R Y
Neisseria meningitidis remains the leading cause of bacterial meningitis and septicemia worldwide. We describe a case of invasive meningococcal infection caused by serogroup X N. meningitidis with a unique sequence type (ST-7) in China. The strain may have arisen from locally prevalent hypervirulent serogroup A clones by capsular switching events. ß 2014 The Authors. Published by Elsevier Ltd on behalf of International Society for Infectious Diseases. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/bync-nd/3.0/).
Keywords: Neisseria meningitidis Serogroup X Multilocus sequence typing (MLST)
1. Introduction
2. Case report
Neisseria meningitidis remains the leading cause of bacterial meningitis and septicemia worldwide. Based on the different capsular polysaccharide structures, 13 different serogroups of N. meningitidis have been identified, and the majority of cases are caused by six of these serogroups (A, B, C, W, X, and Y).1 In China, the morbidity rate of meningococcal disease has declined sharply since the introduction of a national immunization campaign starting in the 1980s with a serogroup A polysaccharide-based vaccine. Since the year 2000, the rate has been maintained at below 0.2 per 100 000 population. Serogroups C and B N. meningitidis have been the prevalent strains isolated in recent years, whereas only one case of invasive infection with meningococcal serogroup X (MenX) has been reported in China.2 We report a case of invasive meningococcal disease caused by a serogroup X strain with a unique sequence type (ST-7) in Zhejiang Province, China.
The case was a 19-year-old female who experienced sudden high fever, chills, and faintness on the morning of May 13, 2013. These symptoms were followed by the onset of hemorrhagic rashes and petechiae at around 5:00 p.m. on the same day. Later that day she presented to a local hospital; blood tests taken at that time revealed a leukocyte count of 13.39 109/l, with a 92% proportion of neutrophils. She was immediately transferred and admitted to a municipal hospital without any treatment. During the admission process, the patient vomited once, complained of a headache, and more petechiae were observed. A physical examination revealed her body temperature to be 38.5 8C, and a blood pressure reading was 60/40 mmHg. She also presented the symptom of a stiff neck, and Kernig’s sign was elicited. A blood culture from the sample that was drawn on May 13 during the admission was found to be N. meningitidis-positive. The isolated bacterial strain was submitted to the Laboratory of Zhejiang Provincial Center for Disease Control and Prevention and it was subsequently identified as serogroup X N. meningitidis by slide agglutination test with a specific antiserum (Remel, Dartford, Kent, UK). In addition, it was further confirmed positive for serogroup X by serogroup-specific real-time PCR assays. Culture of cerebrospinal fluid (CSF) obtained on May 17, after antibiotics had been administered, was negative.
* Corresponding author. Tel./fax: +86 571 87115171. E-mail address: [email protected] (S. Xie).
http://dx.doi.org/10.1016/j.ijid.2014.07.022 1201-9712/ß 2014 The Authors. Published by Elsevier Ltd on behalf of International Society for Infectious Diseases. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/3.0/).
J. Pan et al. / International Journal of Infectious Diseases 29 (2014) 62–64
Antibiotic susceptibility testing was performed by Etest (AB bioMe´rieux, Solna, Stockholm, Sweden). The minimum inhibitory concentrations (MICs) for ampicillin, azithromycin, ceftriaxone, chloramphenicol, ciprofloxacin, levofloxacin, meropenem, minocycline, penicillin, and rifampin were 1.0 mg/ml, 1.5 mg/ml, <0.016 mg/ml, 0.75 mg/ml, 0.19 mg/ml, 0.19 mg/ml, 0.032 mg/ml, 0.75 mg/ml, 0.125 mg/ml, and 0.047 mg/ml, respectively. Thus the
63
isolate was sensitive to most of the antibiotics, except penicillin and ciprofloxacin. This isolate was moderately sensitive to penicillin and ciprofloxacin. The patient received pressor therapy (dopamine and norepinephrine injection) at admission, followed by anti-infection and supportive treatments. She recovered fully and was discharged 19 days later without observable sequelae. The patient was a
Figure 1. The eBURST population structure of Neisseria meningitidis isolates from the PubMLST database (825 isolates obtained since the year 2000 with assigned sequence type (ST) numbers): (A) serogroup X; (B) serogroup A. Each circle represents a single ST, with the area proportional to the number of isolates of that type. Black numbers represent STs found only in carriers, green numbers represent STs found only in invasive cases, and blue numbers represent STs found in both of them. The black lines represent single-locus variants.
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J. Pan et al. / International Journal of Infectious Diseases 29 (2014) 62–64
factory worker who lived in a six-person dormitory room. She did not report other identifiable risk factors before the occurrence of the disease, such as an epidemiological contact history. Anti-HIV antibody testing was negative and the immunization history of the patient with regard to the meningococcal vaccine was unknown. The isolate was assayed by multilocus sequence typing (MLST) method as per the protocols specified on the Neisseria MLST website (http://pubmlst.org/neisseria/). Alleles, sequence type (ST), and clonal complex were queried and assigned by comparison to the PubMLST database on the website. The ST of this isolate was identified as ST-7 (a member of the subgroup III/ST-5 clonal complex). It is the first strain of ST-7 serogroup X in the database so far. In order to explore the correlations between the different strains of MenX, eBURST v. 3.0 (http://eburst.mlst.net/) was used to display the population snapshot of the strains from the PubMLST database. ST-7 was demonstrated as a singleton; in fact it was found to share no more than two common alleles with any other serogroup X strain (a total seven alleles were analyzed).
(Figure 1). According to the definition of ‘capsular switching’ in a meningococcal isolate, it is expected to occur when the ST of a serogroup is not generally associated with the clonal complex observed;3 thus we hypothesize that the ST-7 serogroup X strain we isolated may have arisen from locally prevalent hypervirulent serogroup A clones. A study by Zhou et al.4 reported that the ST-7 clone emerged in China in the late 1980s, and it replaced the ST-5 clone as the dominant lineage circulating in China from 2000. Capsular switching could explain the recent appearance of the ST-7 serogroup C strains in China as well. Capsular switching is deemed the result of horizontal genetic exchange by transformation and recombination in the locus of serogroup-specific capsule biosynthesis genes.5 It is a mechanism of escape from protective immunity induced by vaccine or natural infection. This phenomenon has attracted a certain amount of attention already, as it will reduce the effectiveness of capsulebased vaccination programs. Further epidemiological and microbiological surveillance is needed to monitor the changing trend in serogroup profile of meningococcal diseases.
3. Discussion
Acknowledgements
In the past, serogroup X N. meningitidis has been considered a rare cause of invasive cases, but in the last decade, the number of outbreaks has increased in the African meningitis belt. In China, only a few serogroup X strains have been isolated from carriers so far, and the case reported here is only the second case in our country to date. The first reported case caused by serogroup X N. meningitidis in China was a 14-year-old boy in Beijing and the ST number was newly assigned as ST-5944 in January 2007.2 In the PubMLST database, serogroup X strains comprise only a minor proportion of the whole N. meningitidis isolates (1%, 267/ 25 667, as on October 18, 2013), but they exhibit genetic complexity. On October 18, 2013, with the most stringent group definition, 84 of 259 strains (32%) that had been assayed and had an assigned ST number were singletons. They cannot be classified into any eBURST group (i.e., they differ at three or more loci from every other strain in the dataset). The ST-7 strain we report here is the only one of the serogroup X strain and the eBURST analysis did not show close correlations with any other serogroup X strains
We would like to thank Sanbao Li and his colleagues for their help in the case investigation. Conflict of interest: There are no funding sources or conflicts of interest to declare. References 1. Xie O, Pollard AJ, Mueller JE, Norheim G. Emergence of serogroup X meningococcal disease in Africa: need for a vaccine. Vaccine 2013;31:2852–61. 2. Chen C, Zhang TG, He JG, Wu J, Chen LJ, Liu JF, et al. A first meningococcal meningitis case caused by serogroup X Neisseria meningitidis strains in China. Chinese Medical Journal 2008;121:664–6. 3. Harrison LH, Shutt KA, Schmink SE, Marsh JW, Harcourt BH, Wang X, et al. Population structure and capsular switching of invasive Neisseria meningitidis isolates in the pre-meningococcal conjugate vaccine era—United States, 20002005. J Infect Dis 2010;201:1208–24. 4. Zhou H, Gao Y, Xu L, Li M, Li Q, Li Y, et al. Distribution of serogroups and sequence types in disease-associated and carrier strains of Neisseria meningitidis isolated in China between 2003 and 2008. Epidemiol Infect 2011;140:1296–303. 5. Nadine GR, David SS. Neisseria meningitidis: biology, microbiology, and epidemiology. In: Christodoulides M, editor. Neisseria meningitidis: advanced methods and protocols. New York: Humana Press; 2012. p. 1–20.
Contents lists available at ScienceDirect
International Journal of Infectious Diseases journal homepage: www.elsevier.com/locate/ijid
Case Report
The case of a new sequence type 7 serogroup X Neisseria meningitidis infection in China: may capsular switching change serogroup profile? Jinren Pan a, Pingping Yao a, Heng Zhang b, Xiaoyu Sun c, Hanqing He a, Shuyun Xie a,* a
Zhejiang Provincial Center for Disease Control and Prevention, Hangzhou, Zhejiang Province 310051, China Changsha Center for Disease Control and Prevention, Changsha, Hunan Province, China c Wenzhou Center for Disease Control and Prevention, Wenzhou, Zhejiang Province, China b
A R T I C L E I N F O
Article history: Received 21 October 2013 Received in revised form 17 March 2014 Accepted 30 July 2014 Corresponding Editor: Maria RodriguezBarradas, Texas, USA
S U M M A R Y
Neisseria meningitidis remains the leading cause of bacterial meningitis and septicemia worldwide. We describe a case of invasive meningococcal infection caused by serogroup X N. meningitidis with a unique sequence type (ST-7) in China. The strain may have arisen from locally prevalent hypervirulent serogroup A clones by capsular switching events. ß 2014 The Authors. Published by Elsevier Ltd on behalf of International Society for Infectious Diseases. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/bync-nd/3.0/).
Keywords: Neisseria meningitidis Serogroup X Multilocus sequence typing (MLST)
1. Introduction
2. Case report
Neisseria meningitidis remains the leading cause of bacterial meningitis and septicemia worldwide. Based on the different capsular polysaccharide structures, 13 different serogroups of N. meningitidis have been identified, and the majority of cases are caused by six of these serogroups (A, B, C, W, X, and Y).1 In China, the morbidity rate of meningococcal disease has declined sharply since the introduction of a national immunization campaign starting in the 1980s with a serogroup A polysaccharide-based vaccine. Since the year 2000, the rate has been maintained at below 0.2 per 100 000 population. Serogroups C and B N. meningitidis have been the prevalent strains isolated in recent years, whereas only one case of invasive infection with meningococcal serogroup X (MenX) has been reported in China.2 We report a case of invasive meningococcal disease caused by a serogroup X strain with a unique sequence type (ST-7) in Zhejiang Province, China.
The case was a 19-year-old female who experienced sudden high fever, chills, and faintness on the morning of May 13, 2013. These symptoms were followed by the onset of hemorrhagic rashes and petechiae at around 5:00 p.m. on the same day. Later that day she presented to a local hospital; blood tests taken at that time revealed a leukocyte count of 13.39 109/l, with a 92% proportion of neutrophils. She was immediately transferred and admitted to a municipal hospital without any treatment. During the admission process, the patient vomited once, complained of a headache, and more petechiae were observed. A physical examination revealed her body temperature to be 38.5 8C, and a blood pressure reading was 60/40 mmHg. She also presented the symptom of a stiff neck, and Kernig’s sign was elicited. A blood culture from the sample that was drawn on May 13 during the admission was found to be N. meningitidis-positive. The isolated bacterial strain was submitted to the Laboratory of Zhejiang Provincial Center for Disease Control and Prevention and it was subsequently identified as serogroup X N. meningitidis by slide agglutination test with a specific antiserum (Remel, Dartford, Kent, UK). In addition, it was further confirmed positive for serogroup X by serogroup-specific real-time PCR assays. Culture of cerebrospinal fluid (CSF) obtained on May 17, after antibiotics had been administered, was negative.
* Corresponding author. Tel./fax: +86 571 87115171. E-mail address: [email protected] (S. Xie).
http://dx.doi.org/10.1016/j.ijid.2014.07.022 1201-9712/ß 2014 The Authors. Published by Elsevier Ltd on behalf of International Society for Infectious Diseases. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/3.0/).
J. Pan et al. / International Journal of Infectious Diseases 29 (2014) 62–64
Antibiotic susceptibility testing was performed by Etest (AB bioMe´rieux, Solna, Stockholm, Sweden). The minimum inhibitory concentrations (MICs) for ampicillin, azithromycin, ceftriaxone, chloramphenicol, ciprofloxacin, levofloxacin, meropenem, minocycline, penicillin, and rifampin were 1.0 mg/ml, 1.5 mg/ml, <0.016 mg/ml, 0.75 mg/ml, 0.19 mg/ml, 0.19 mg/ml, 0.032 mg/ml, 0.75 mg/ml, 0.125 mg/ml, and 0.047 mg/ml, respectively. Thus the
63
isolate was sensitive to most of the antibiotics, except penicillin and ciprofloxacin. This isolate was moderately sensitive to penicillin and ciprofloxacin. The patient received pressor therapy (dopamine and norepinephrine injection) at admission, followed by anti-infection and supportive treatments. She recovered fully and was discharged 19 days later without observable sequelae. The patient was a
Figure 1. The eBURST population structure of Neisseria meningitidis isolates from the PubMLST database (825 isolates obtained since the year 2000 with assigned sequence type (ST) numbers): (A) serogroup X; (B) serogroup A. Each circle represents a single ST, with the area proportional to the number of isolates of that type. Black numbers represent STs found only in carriers, green numbers represent STs found only in invasive cases, and blue numbers represent STs found in both of them. The black lines represent single-locus variants.
64
J. Pan et al. / International Journal of Infectious Diseases 29 (2014) 62–64
factory worker who lived in a six-person dormitory room. She did not report other identifiable risk factors before the occurrence of the disease, such as an epidemiological contact history. Anti-HIV antibody testing was negative and the immunization history of the patient with regard to the meningococcal vaccine was unknown. The isolate was assayed by multilocus sequence typing (MLST) method as per the protocols specified on the Neisseria MLST website (http://pubmlst.org/neisseria/). Alleles, sequence type (ST), and clonal complex were queried and assigned by comparison to the PubMLST database on the website. The ST of this isolate was identified as ST-7 (a member of the subgroup III/ST-5 clonal complex). It is the first strain of ST-7 serogroup X in the database so far. In order to explore the correlations between the different strains of MenX, eBURST v. 3.0 (http://eburst.mlst.net/) was used to display the population snapshot of the strains from the PubMLST database. ST-7 was demonstrated as a singleton; in fact it was found to share no more than two common alleles with any other serogroup X strain (a total seven alleles were analyzed).
(Figure 1). According to the definition of ‘capsular switching’ in a meningococcal isolate, it is expected to occur when the ST of a serogroup is not generally associated with the clonal complex observed;3 thus we hypothesize that the ST-7 serogroup X strain we isolated may have arisen from locally prevalent hypervirulent serogroup A clones. A study by Zhou et al.4 reported that the ST-7 clone emerged in China in the late 1980s, and it replaced the ST-5 clone as the dominant lineage circulating in China from 2000. Capsular switching could explain the recent appearance of the ST-7 serogroup C strains in China as well. Capsular switching is deemed the result of horizontal genetic exchange by transformation and recombination in the locus of serogroup-specific capsule biosynthesis genes.5 It is a mechanism of escape from protective immunity induced by vaccine or natural infection. This phenomenon has attracted a certain amount of attention already, as it will reduce the effectiveness of capsulebased vaccination programs. Further epidemiological and microbiological surveillance is needed to monitor the changing trend in serogroup profile of meningococcal diseases.
3. Discussion
Acknowledgements
In the past, serogroup X N. meningitidis has been considered a rare cause of invasive cases, but in the last decade, the number of outbreaks has increased in the African meningitis belt. In China, only a few serogroup X strains have been isolated from carriers so far, and the case reported here is only the second case in our country to date. The first reported case caused by serogroup X N. meningitidis in China was a 14-year-old boy in Beijing and the ST number was newly assigned as ST-5944 in January 2007.2 In the PubMLST database, serogroup X strains comprise only a minor proportion of the whole N. meningitidis isolates (1%, 267/ 25 667, as on October 18, 2013), but they exhibit genetic complexity. On October 18, 2013, with the most stringent group definition, 84 of 259 strains (32%) that had been assayed and had an assigned ST number were singletons. They cannot be classified into any eBURST group (i.e., they differ at three or more loci from every other strain in the dataset). The ST-7 strain we report here is the only one of the serogroup X strain and the eBURST analysis did not show close correlations with any other serogroup X strains
We would like to thank Sanbao Li and his colleagues for their help in the case investigation. Conflict of interest: There are no funding sources or conflicts of interest to declare. References 1. Xie O, Pollard AJ, Mueller JE, Norheim G. Emergence of serogroup X meningococcal disease in Africa: need for a vaccine. Vaccine 2013;31:2852–61. 2. Chen C, Zhang TG, He JG, Wu J, Chen LJ, Liu JF, et al. A first meningococcal meningitis case caused by serogroup X Neisseria meningitidis strains in China. Chinese Medical Journal 2008;121:664–6. 3. Harrison LH, Shutt KA, Schmink SE, Marsh JW, Harcourt BH, Wang X, et al. Population structure and capsular switching of invasive Neisseria meningitidis isolates in the pre-meningococcal conjugate vaccine era—United States, 20002005. J Infect Dis 2010;201:1208–24. 4. Zhou H, Gao Y, Xu L, Li M, Li Q, Li Y, et al. Distribution of serogroups and sequence types in disease-associated and carrier strains of Neisseria meningitidis isolated in China between 2003 and 2008. Epidemiol Infect 2011;140:1296–303. 5. Nadine GR, David SS. Neisseria meningitidis: biology, microbiology, and epidemiology. In: Christodoulides M, editor. Neisseria meningitidis: advanced methods and protocols. New York: Humana Press; 2012. p. 1–20.