Skip to main content
Top
Published in: BMC Infectious Diseases 1/2019

Open Access 01-12-2019 | Human Alphaherpesvirus 3 | Research article

The etiology of acute meningitis and encephalitis syndromes in a sentinel pediatric hospital, Shenzhen, China

Authors: Hongwei Shen, Chunqing Zhu, Xiaorong Liu, Dongli Ma, Chunli Song, Lintao Zhou, Zuer Wang, Yongxuan Ou, Wen Ma, Xianghui Shi, Xuejun Ma, Yiwen Zhou

Published in: BMC Infectious Diseases | Issue 1/2019

Login to get access

Abstract

Background

Acute meningitis and encephalitis syndromes (AMES) is a severe neurological infection which causes high case fatality and severe sequelae in children. To determine the etiology of childhood AMES in Shenzhen, a hospital-based study was undertaken.

Methods

A total of 240 cerebrospinal fluid (CSF) samples from 171 children meeting the case definition were included and screened for 12 common causative organisms. The clinical data and conventional testing results were collected and analyzed. Whole genome sequencing was performed on a Neisseria meningitidis isolate.

Results

A pathogen was found in 85 (49.7%) cases; Group B Streptococcus (GBS) was detected in 17 cases, Escherichia coli in 15, Streptococcus pneumoniae in 14, enterovirus (EV) in 13, herpes simplex virus (HSV) in 3, N. meningitidis in 1, Haemophilus influenzae in 1, and others in 23. Notably, HSV was found after 43 days of treatment. Twelve GBS and 6 E. coli meningitis were found in neonates aged less than 1 month; 13 pneumococcal meningitis in children aged > 3 months; and 12 EV infections in children aged > 1 year old. The multilocus sequence typing of serogroup B N. meningitidis isolate was ST-3200/CC4821. High resistance rate to tetracycline (75%), penicillin (75%), and trimethoprim/sulfamethoxazole (75%) was found in 4 of S. pneumoniae isolates; clindamycin (100%) and tetracycline (100%) in 9 of GBS; and ampicillin (75%) and trimethoprim/sulfamethoxazole (67%) in 12 of E. coli.

Conclusions

The prevalence of N. meningitidis and JEV was very low and the cases of childhood AMES were mainly caused by other pathogens. GBS and E. coli were the main causative organisms in neonates, while S. pneumoniae and EV were mainly found in older children. HSV could be persistently found in the CSF samples despite of the treatment. A better prevention strategy for GBS, the introduction of pneumococcal vaccine, and incorporation of PCR methods were recommended.
Literature
1.
go back to reference Edmond K, Clark A, Korczak VS, Sanderson C, Griffiths UK, Rudan I. Global and regional risk of disabling sequelae from bacterial meningitis: a systematic review and meta-analysis. Lancet Infect Dis. 2010;10(5):317–28.PubMedCrossRef Edmond K, Clark A, Korczak VS, Sanderson C, Griffiths UK, Rudan I. Global and regional risk of disabling sequelae from bacterial meningitis: a systematic review and meta-analysis. Lancet Infect Dis. 2010;10(5):317–28.PubMedCrossRef
2.
go back to reference Thigpen MC, Whitney CG, Messonnier NE, Zell ER, Lynfield R, Hadler JL, Harrison LH, Farley MM, Reingold A, Bennett NM, et al. Bacterial meningitis in the United States, 1998-2007. N Engl J Med. 2011;364(21):2016–25.PubMedCrossRef Thigpen MC, Whitney CG, Messonnier NE, Zell ER, Lynfield R, Hadler JL, Harrison LH, Farley MM, Reingold A, Bennett NM, et al. Bacterial meningitis in the United States, 1998-2007. N Engl J Med. 2011;364(21):2016–25.PubMedCrossRef
3.
go back to reference Li Y, Yin Z, Shao Z, Li M, Liang X, Sandhu HS, Hadler SC, Li J, Sun Y, Li J, et al. Population-based surveillance for bacterial meningitis in China, September 2006-December 2009. Emerg Infect Dis. 2014;20(1):61–9.PubMedPubMedCentralCrossRef Li Y, Yin Z, Shao Z, Li M, Liang X, Sandhu HS, Hadler SC, Li J, Sun Y, Li J, et al. Population-based surveillance for bacterial meningitis in China, September 2006-December 2009. Emerg Infect Dis. 2014;20(1):61–9.PubMedPubMedCentralCrossRef
4.
go back to reference Granerod J, Ambrose HE, Davies NW, Clewley JP, Walsh AL, Morgan D, Cunningham R, Zuckerman M, Mutton KJ, Solomon T, et al. Causes of encephalitis and differences in their clinical presentations in England: a multicentre, population-based prospective study. Lancet Infect Dis. 2010;10(12):835–44.CrossRefPubMed Granerod J, Ambrose HE, Davies NW, Clewley JP, Walsh AL, Morgan D, Cunningham R, Zuckerman M, Mutton KJ, Solomon T, et al. Causes of encephalitis and differences in their clinical presentations in England: a multicentre, population-based prospective study. Lancet Infect Dis. 2010;10(12):835–44.CrossRefPubMed
5.
go back to reference Zheng Y, Li M, Wang H, Liang G. Japanese encephalitis and Japanese encephalitis virus in mainland China. Rev Med Virol. 2012;22(5):301–22.PubMedCrossRef Zheng Y, Li M, Wang H, Liang G. Japanese encephalitis and Japanese encephalitis virus in mainland China. Rev Med Virol. 2012;22(5):301–22.PubMedCrossRef
6.
go back to reference Wang H, Li Y, Liang X, Liang G. Japanese encephalitis in mainland China. Jpn J Infect Dis. 2009;62(5):331–6.PubMed Wang H, Li Y, Liang X, Liang G. Japanese encephalitis in mainland China. Jpn J Infect Dis. 2009;62(5):331–6.PubMed
7.
go back to reference Gao X, Li X, Li M, Fu S, Wang H, Lu Z, Cao Y, He Y, Zhu W, Zhang T, et al. Vaccine strategies for the control and prevention of Japanese encephalitis in mainland China, 1951-2011. PLoS Negl Trop Dis. 2014;8(8):e3015.PubMedPubMedCentralCrossRef Gao X, Li X, Li M, Fu S, Wang H, Lu Z, Cao Y, He Y, Zhu W, Zhang T, et al. Vaccine strategies for the control and prevention of Japanese encephalitis in mainland China, 1951-2011. PLoS Negl Trop Dis. 2014;8(8):e3015.PubMedPubMedCentralCrossRef
8.
go back to reference Li J, Shao Z, Liu G, Bai X, Borrow R, Chen M, Guo Q, Han Y, Li Y, Taha MK, et al. Meningococcal disease and control in China: findings and updates from the global meningococcal initiative (GMI). J Inf Secur. 2018;76(5):429–37. Li J, Shao Z, Liu G, Bai X, Borrow R, Chen M, Guo Q, Han Y, Li Y, Taha MK, et al. Meningococcal disease and control in China: findings and updates from the global meningococcal initiative (GMI). J Inf Secur. 2018;76(5):429–37.
9.
go back to reference Li J, Li Y, Shao Z, Li L, Yin Z, Ning G, Xu L, Luo H. Prevalence of meningococcal meningitis in China from 2005 to 2010. Vaccine. 2015;33(8):1092–7.PubMedCrossRef Li J, Li Y, Shao Z, Li L, Yin Z, Ning G, Xu L, Luo H. Prevalence of meningococcal meningitis in China from 2005 to 2010. Vaccine. 2015;33(8):1092–7.PubMedCrossRef
10.
go back to reference Xie Y, Tan Y, Chongsuvivatwong V, Wu X, Bi F, Hadler SC, Jiraphongsa C, Sornsrivichai V, Lin M, Quan Y. A population-based acute meningitis and encephalitis syndromes surveillance in Guangxi, China, may 2007-June 2012. PLoS One. 2015;10(12):e0144366.PubMedPubMedCentralCrossRef Xie Y, Tan Y, Chongsuvivatwong V, Wu X, Bi F, Hadler SC, Jiraphongsa C, Sornsrivichai V, Lin M, Quan Y. A population-based acute meningitis and encephalitis syndromes surveillance in Guangxi, China, may 2007-June 2012. PLoS One. 2015;10(12):e0144366.PubMedPubMedCentralCrossRef
11.
go back to reference Sacchi CT, Fukasawa LO, Goncalves MG, Salgado MM, Shutt KA, Carvalhanas TR, Ribeiro AF, Kemp B, Gorla MC, Albernaz RK, et al. Incorporation of real-time PCR into routine public health surveillance of culture negative bacterial meningitis in Sao Paulo, Brazil. PLoS One. 2011;6(6):e20675.PubMedPubMedCentralCrossRef Sacchi CT, Fukasawa LO, Goncalves MG, Salgado MM, Shutt KA, Carvalhanas TR, Ribeiro AF, Kemp B, Gorla MC, Albernaz RK, et al. Incorporation of real-time PCR into routine public health surveillance of culture negative bacterial meningitis in Sao Paulo, Brazil. PLoS One. 2011;6(6):e20675.PubMedPubMedCentralCrossRef
12.
go back to reference Chiba N, Murayama SY, Morozumi M, Nakayama E, Okada T, Iwata S, Sunakawa K, Ubukata K. Rapid detection of eight causative pathogens for the diagnosis of bacterial meningitis by real-time PCR. J Infect Chemother. 2009;15(2):92–8.PubMedCrossRef Chiba N, Murayama SY, Morozumi M, Nakayama E, Okada T, Iwata S, Sunakawa K, Ubukata K. Rapid detection of eight causative pathogens for the diagnosis of bacterial meningitis by real-time PCR. J Infect Chemother. 2009;15(2):92–8.PubMedCrossRef
13.
go back to reference Saha SK, Darmstadt GL, Yamanaka N, Billal DS, Nasreen T, Islam M, Hamer DH. Rapid diagnosis of pneumococcal meningitis: implications for treatment and measuring disease burden. Pediatr Infect Dis J. 2005;24(12):1093–8.PubMedCrossRef Saha SK, Darmstadt GL, Yamanaka N, Billal DS, Nasreen T, Islam M, Hamer DH. Rapid diagnosis of pneumococcal meningitis: implications for treatment and measuring disease burden. Pediatr Infect Dis J. 2005;24(12):1093–8.PubMedCrossRef
14.
go back to reference Qin Y, Mei S, Xie X, Kong D, Tang X. Analysis of the epidemiological characteristics of epidemic cerebrospinal meningitis in Shenzhen during 2005-2015. J Dis Monitor Control. 2016;10(11):874–5 (in Chinese). Qin Y, Mei S, Xie X, Kong D, Tang X. Analysis of the epidemiological characteristics of epidemic cerebrospinal meningitis in Shenzhen during 2005-2015. J Dis Monitor Control. 2016;10(11):874–5 (in Chinese).
15.
go back to reference Xu L, Xie J, Li Y. Analysis on epidemic characteristics of epidemic encephalitis B in Baoan District of Shenzhen. Pract Prev Med. 2009;16(1):64–5 (in Chinese). Xu L, Xie J, Li Y. Analysis on epidemic characteristics of epidemic encephalitis B in Baoan District of Shenzhen. Pract Prev Med. 2009;16(1):64–5 (in Chinese).
16.
go back to reference Z-j S, Xu L, Gao Y. Epidemiologic trend of serogroup switching of Neisseria meningitidis strains in China [J]. Chin J Vaccines Immunization. 2007;6:012 (in Chinese). Z-j S, Xu L, Gao Y. Epidemiologic trend of serogroup switching of Neisseria meningitidis strains in China [J]. Chin J Vaccines Immunization. 2007;6:012 (in Chinese).
17.
18.
go back to reference Chiou CS, Liao JC, Liao TL, Li CC, Chou CY, Chang HL, Yao SM, Lee YS. Molecular epidemiology and emergence of worldwide epidemic clones of Neisseria meningitidis in Taiwan. BMC Infect Dis. 2006;6:25.PubMedPubMedCentralCrossRef Chiou CS, Liao JC, Liao TL, Li CC, Chou CY, Chang HL, Yao SM, Lee YS. Molecular epidemiology and emergence of worldwide epidemic clones of Neisseria meningitidis in Taiwan. BMC Infect Dis. 2006;6:25.PubMedPubMedCentralCrossRef
19.
go back to reference Okike IO, Johnson AP, Henderson KL, Blackburn RM, Muller-Pebody B, Ladhani SN, Anthony M, Ninis N, Heath PT, neoMen Study G. Incidence, etiology, and outcome of bacterial meningitis in infants aged <90 days in the United Kingdom and Republic of Ireland: prospective, enhanced, national population-based surveillance. Clin Infect Dis. 2014;59(10):e150–7.PubMedCrossRef Okike IO, Johnson AP, Henderson KL, Blackburn RM, Muller-Pebody B, Ladhani SN, Anthony M, Ninis N, Heath PT, neoMen Study G. Incidence, etiology, and outcome of bacterial meningitis in infants aged <90 days in the United Kingdom and Republic of Ireland: prospective, enhanced, national population-based surveillance. Clin Infect Dis. 2014;59(10):e150–7.PubMedCrossRef
20.
go back to reference Heath PT, Balfour G, Weisner AM, Efstratiou A, Lamagni TL, Tighe H, O'Connell LA, Cafferkey M, Verlander NQ, Nicoll A, et al. Group B streptococcal disease in UK and Irish infants younger than 90 days. Lancet. 2004;363(9405):292–4.PubMedCrossRef Heath PT, Balfour G, Weisner AM, Efstratiou A, Lamagni TL, Tighe H, O'Connell LA, Cafferkey M, Verlander NQ, Nicoll A, et al. Group B streptococcal disease in UK and Irish infants younger than 90 days. Lancet. 2004;363(9405):292–4.PubMedCrossRef
21.
go back to reference Zhang J, Zhao R, Dong Y, Zheng Y. Invasive group B streptococcal infection in infants in Shenzhen, China. Int J Clin Exp Med. 2015;8(2):2939–43.PubMedPubMedCentral Zhang J, Zhao R, Dong Y, Zheng Y. Invasive group B streptococcal infection in infants in Shenzhen, China. Int J Clin Exp Med. 2015;8(2):2939–43.PubMedPubMedCentral
22.
go back to reference Cho HK, Lee H, Kang JH, Kim KN, Kim DS, Kim YK, Kim JS, Kim JH, Kim CH, Kim HM, et al. The causative organisms of bacterial meningitis in Korean children in 1996-2005. J Korean Med Sci. 2010;25(6):895–9.PubMedPubMedCentralCrossRef Cho HK, Lee H, Kang JH, Kim KN, Kim DS, Kim YK, Kim JS, Kim JH, Kim CH, Kim HM, et al. The causative organisms of bacterial meningitis in Korean children in 1996-2005. J Korean Med Sci. 2010;25(6):895–9.PubMedPubMedCentralCrossRef
23.
go back to reference Chen Y, Deng W, Wang SM, Mo QM, Jia H, Wang Q, Li SG, Li X, Yao BD, Liu CJ, et al. Burden of pneumonia and meningitis caused by Streptococcus pneumoniae in China among children under 5 years of age: a systematic literature review. PLoS One. 2011;6(11):e27333.PubMedPubMedCentralCrossRef Chen Y, Deng W, Wang SM, Mo QM, Jia H, Wang Q, Li SG, Li X, Yao BD, Liu CJ, et al. Burden of pneumonia and meningitis caused by Streptococcus pneumoniae in China among children under 5 years of age: a systematic literature review. PLoS One. 2011;6(11):e27333.PubMedPubMedCentralCrossRef
24.
go back to reference Ma X, Zhao R, Ma Z, Yao K, Yu S, Zheng Y, Yang Y. Serotype distribution and antimicrobial resistance of Streptococcus pneumoniae isolates causing invasive diseases from Shenzhen Children's hospital. PLoS One. 2013;8(6):e67507.PubMedPubMedCentralCrossRef Ma X, Zhao R, Ma Z, Yao K, Yu S, Zheng Y, Yang Y. Serotype distribution and antimicrobial resistance of Streptococcus pneumoniae isolates causing invasive diseases from Shenzhen Children's hospital. PLoS One. 2013;8(6):e67507.PubMedPubMedCentralCrossRef
25.
go back to reference Miller E, Andrews NJ, Waight PA, Slack MP, George RC. Effectiveness of the new serotypes in the 13-valent pneumococcal conjugate vaccine. Vaccine. 2011;29(49):9127–31.PubMedCrossRef Miller E, Andrews NJ, Waight PA, Slack MP, George RC. Effectiveness of the new serotypes in the 13-valent pneumococcal conjugate vaccine. Vaccine. 2011;29(49):9127–31.PubMedCrossRef
26.
go back to reference Michos AG, Syriopoulou VP, Hadjichristodoulou C, Daikos GL, Lagona E, Douridas P, Mostrou G, Theodoridou M. Aseptic meningitis in children: analysis of 506 cases. PLoS One. 2007;2(7):e674.PubMedPubMedCentralCrossRef Michos AG, Syriopoulou VP, Hadjichristodoulou C, Daikos GL, Lagona E, Douridas P, Mostrou G, Theodoridou M. Aseptic meningitis in children: analysis of 506 cases. PLoS One. 2007;2(7):e674.PubMedPubMedCentralCrossRef
27.
go back to reference Abel L, Plancoulaine S, Jouanguy E, Zhang SY, Mahfoufi N, Nicolas N, Sancho-Shimizu V, Alcais A, Guo Y, Cardon A et al: Age-dependent Mendelian predisposition to herpes simplex virus type 1 encephalitis in childhood. J Pediatr 2010, 157(4):623–629, 629 e621.CrossRef Abel L, Plancoulaine S, Jouanguy E, Zhang SY, Mahfoufi N, Nicolas N, Sancho-Shimizu V, Alcais A, Guo Y, Cardon A et al: Age-dependent Mendelian predisposition to herpes simplex virus type 1 encephalitis in childhood. J Pediatr 2010, 157(4):623–629, 629 e621.CrossRef
28.
go back to reference Whitley RJ, Gnann JW. Viral encephalitis: familiar infections and emerging pathogens. Lancet. 2002;359(9305):507–13.PubMedCrossRef Whitley RJ, Gnann JW. Viral encephalitis: familiar infections and emerging pathogens. Lancet. 2002;359(9305):507–13.PubMedCrossRef
29.
go back to reference Azzari C, Moriondo M, Indolfi G, Massai C, Becciolini L, de Martino M, Resti M. Molecular detection methods and serotyping performed directly on clinical samples improve diagnostic sensitivity and reveal increased incidence of invasive disease by Streptococcus pneumoniae in Italian children. J Med Microbiol. 2008;57(Pt 10):1205–12.PubMedPubMedCentralCrossRef Azzari C, Moriondo M, Indolfi G, Massai C, Becciolini L, de Martino M, Resti M. Molecular detection methods and serotyping performed directly on clinical samples improve diagnostic sensitivity and reveal increased incidence of invasive disease by Streptococcus pneumoniae in Italian children. J Med Microbiol. 2008;57(Pt 10):1205–12.PubMedPubMedCentralCrossRef
30.
go back to reference Gillespie BE, Oliver SP. Simultaneous detection of mastitis pathogens, Staphylococcus aureus, Streptococcus uberis, and Streptococcus agalactiae by multiplex real-time polymerase chain reaction. J Dairy Sci. 2005;88(10):3510–8.PubMedCrossRef Gillespie BE, Oliver SP. Simultaneous detection of mastitis pathogens, Staphylococcus aureus, Streptococcus uberis, and Streptococcus agalactiae by multiplex real-time polymerase chain reaction. J Dairy Sci. 2005;88(10):3510–8.PubMedCrossRef
31.
go back to reference Maheux AF, Bissonnette L, Boissinot M, Bernier JL, Huppe V, Picard FJ, Berube E, Bergeron MG. Rapid concentration and molecular enrichment approach for sensitive detection of Escherichia coli and Shigella species in potable water samples. Appl Environ Microbiol. 2011;77(17):6199–207.PubMedPubMedCentralCrossRef Maheux AF, Bissonnette L, Boissinot M, Bernier JL, Huppe V, Picard FJ, Berube E, Bergeron MG. Rapid concentration and molecular enrichment approach for sensitive detection of Escherichia coli and Shigella species in potable water samples. Appl Environ Microbiol. 2011;77(17):6199–207.PubMedPubMedCentralCrossRef
32.
go back to reference Corless CE, Guiver M, Borrow R, Edwards-Jones V, Fox AJ, Kaczmarski EB. Simultaneous detection of Neisseria meningitidis, Haemophilus influenzae, and Streptococcus pneumoniae in suspected cases of meningitis and septicemia using real-time PCR. J Clin Microbiol. 2001;39(4):1553–8.PubMedPubMedCentralCrossRef Corless CE, Guiver M, Borrow R, Edwards-Jones V, Fox AJ, Kaczmarski EB. Simultaneous detection of Neisseria meningitidis, Haemophilus influenzae, and Streptococcus pneumoniae in suspected cases of meningitis and septicemia using real-time PCR. J Clin Microbiol. 2001;39(4):1553–8.PubMedPubMedCentralCrossRef
33.
go back to reference Flekna G, Stefanic P, Wagner M, Smulders FJ, Mozina SS, Hein I. Insufficient differentiation of live and dead campylobacter jejuni and listeria monocytogenes cells by ethidium monoazide (EMA) compromises EMA/real-time PCR. Res Microbiol. 2007;158(5):405–12.PubMedCrossRef Flekna G, Stefanic P, Wagner M, Smulders FJ, Mozina SS, Hein I. Insufficient differentiation of live and dead campylobacter jejuni and listeria monocytogenes cells by ethidium monoazide (EMA) compromises EMA/real-time PCR. Res Microbiol. 2007;158(5):405–12.PubMedCrossRef
34.
go back to reference Uchida K, Shinohara M, Shimada S, Segawa Y, Doi R, Gotoh A, Hondo R. Rapid and sensitive detection of mumps virus RNA directly from clinical samples by real-time PCR. J Med Virol. 2005;75(3):470–4.PubMedCrossRef Uchida K, Shinohara M, Shimada S, Segawa Y, Doi R, Gotoh A, Hondo R. Rapid and sensitive detection of mumps virus RNA directly from clinical samples by real-time PCR. J Med Virol. 2005;75(3):470–4.PubMedCrossRef
35.
go back to reference Kessler HH, Muhlbauer G, Rinner B, Stelzl E, Berger A, Dorr HW, Santner B, Marth E, Rabenau H. Detection of herpes simplex virus DNA by real-time PCR. J Clin Microbiol. 2000;38(7):2638–42.PubMedPubMedCentral Kessler HH, Muhlbauer G, Rinner B, Stelzl E, Berger A, Dorr HW, Santner B, Marth E, Rabenau H. Detection of herpes simplex virus DNA by real-time PCR. J Clin Microbiol. 2000;38(7):2638–42.PubMedPubMedCentral
36.
go back to reference Shirato K, Miyoshi H, Kariwa H, Takashima I. Detection of West Nile virus and Japanese encephalitis virus using real-time PCR with a probe common to both viruses. J Virol Methods. 2005;126(1–2):119–25.PubMedCrossRef Shirato K, Miyoshi H, Kariwa H, Takashima I. Detection of West Nile virus and Japanese encephalitis virus using real-time PCR with a probe common to both viruses. J Virol Methods. 2005;126(1–2):119–25.PubMedCrossRef
37.
38.
go back to reference Heim A, Ebnet C, Harste G, Pring-Akerblom P. Rapid and quantitative detection of human adenovirus DNA by real-time PCR. J Med Virol. 2003;70(2):228–39.PubMedCrossRef Heim A, Ebnet C, Harste G, Pring-Akerblom P. Rapid and quantitative detection of human adenovirus DNA by real-time PCR. J Med Virol. 2003;70(2):228–39.PubMedCrossRef
39.
go back to reference Weidmann M, Meyer-Konig U, Hufert FT. Rapid detection of herpes simplex virus and varicella-zoster virus infections by real-time PCR. J Clin Microbiol. 2003;41(4):1565–8.PubMedPubMedCentralCrossRef Weidmann M, Meyer-Konig U, Hufert FT. Rapid detection of herpes simplex virus and varicella-zoster virus infections by real-time PCR. J Clin Microbiol. 2003;41(4):1565–8.PubMedPubMedCentralCrossRef
Metadata
Title
The etiology of acute meningitis and encephalitis syndromes in a sentinel pediatric hospital, Shenzhen, China
Authors
Hongwei Shen
Chunqing Zhu
Xiaorong Liu
Dongli Ma
Chunli Song
Lintao Zhou
Zuer Wang
Yongxuan Ou
Wen Ma
Xianghui Shi
Xuejun Ma
Yiwen Zhou
Publication date
01-12-2019
Publisher
BioMed Central
Published in
BMC Infectious Diseases / Issue 1/2019
Electronic ISSN: 1471-2334
DOI
https://doi.org/10.1186/s12879-019-4162-5

Other articles of this Issue 1/2019

BMC Infectious Diseases 1/2019 Go to the issue