Etiological and epidemiological features of acute meningitis or encephalitis in China: a nationwide active surveillance study

Abstract

Background: Acute meningitis or encephalitis (AME) results from a neurological infection causing high case fatality and severe sequelae. AME lacked comprehensive surveillance in China.

Methods: Nation-wide surveillance of all-age patients with AME syndromes was conducted in 144 sentinel hospitals of 29 provinces in China. Eleven AME-causative viral and bacterial pathogens were tested with multiple diagnostic methods.

Findings: Between 2009 and 2018, 20,454 AME patients were recruited for tests. Based on 9,079 patients with all-four-virus tested, 28.43% (95% CI: 27.50%‒29.36%) of them had at least one virus-positive detection. Enterovirus was the most frequently determined virus in children <18 years, herpes simplex virus and Japanese encephalitis virus were the most frequently determined in 18-59 and ≥60 years age groups, respectively. Based on 6,802 patients with all-seven-bacteria tested, 4.43% (95% CI: 3.94%‒4.91%) had at least one bacteria-positive detection, Streptococcus pneumoniae and Neisseria meningitidis were the leading bacterium in children aged <5 years and 5-17 years, respectively. Staphylococcus aureus was the most frequently detected in adults aged 18-59 and ≥60 years. The pathogen spectrum also differed statistically significantly between northern and southern China. Joinpoint analysis revealed age-specific positive rates, with enterovirus, herpes simplex virus and mumps virus peaking at 3-6 years old, while Japanese encephalitis virus peaked in the ≥60 years old. As age increased, the positive rate for Streptococcus pneumoniae and Escherichia coli statistically significantly decreased, while for Staphylococcus aureus and Streptococcus suis it increased.

Interpretation: The current findings allow enhanced identification of the predominant AME-related pathogen candidates for diagnosis in clinical practice and more targeted application of prevention and control measures in China, and a possible reassessment of vaccination strategy.

Funding: China Mega-Project on Infectious Disease Prevention and the National Natural Science Funds.

Keywords: China; encephalitis; etiology; meningitis; sentinel surveillance.

Figure 1

The flowchart of patient recruit and sorting procedures. This flow diagram summarizes the number of AME patients subject to each analysis in this study.

Figure 2

Joinpoint regression analysis of the positive rates by age of the patient. (a) EV; (b) JEV; (c) HSV; (d) MuV. EV, Enterovirus; JEV, Japanese encephalitis virus; HSV, Herpes simplex virus; MuV, Mumps virus. Red points indicate the mean positive rate of patients in terms of age and the colored curves indicate fitted patterns by age groups. The annual percent change (APC) value of each fitted curves is given for each virus. *indicates that the APC is statistically significantly different from zero at P<0.05.

Figure 3

Joinpoint regression analysis of the annual positive rates for four viruses. (a) EV; (b) JEV; (c) HSV; (d) MuV. EV, Enterovirus; JEV, Japanese encephalitis virus; HSV, Herpes simplex virus; MuV, Mumps virus. Red points indicate the mean positive rate of tested viruses in terms of year. The colored curves indicate fitted patterns by the red points. Legends give the annual percent change (APC) value of each fitted curve for each virus. *indicates that the APC is statistically significantly different from zero at P<0.05.