Etiology of acute meningitis and encephalitis from hospital-based surveillance in South Kazakhstan oblast, February 2017-January 2018

Abstract

Encephalitis and meningitis (EM) are severe infections of the central nervous system associated with high morbidity and mortality. The etiology of EM in Kazakhstan is not clearly defined, so from February 1, 2017 to January 31, 2018 we conducted hospital-based syndromic surveillance for EM at the Shymkent City Hospital, in the South Kazakhstan region. All consenting inpatients meeting a standard case definition were enrolled. Blood and cerebrospinal fluid (CSF) samples were collected for bacterial culture, and CSF samples were additionally tested by PCR for four bacterial species and three viruses using a cascading algorithm. We enrolled 556 patients. Of these, 494 were of viral etiology (including 4 probable rabies cases), 37 were of bacterial etiology, 19 were of unknown etiology and 6 were not tested. The most commonly identified pathogens included enterovirus (73%, n = 406 cases), herpes simplex virus (12.8%, n = 71), and Neisseria meningitidis (3.8%, n = 21). The incidence rates (IRs) for enteroviral and meningococcal EM were found to be 14.5 and 0.7 per 100,000 persons, respectively. The IR for bacterial EM using both PCR and culture results was 3-5 times higher compared to culture-only results. Antibacterial medicines were used to treat 97.2% (480/494) of virus-associated EM. Incorporation of PCR into routine laboratory diagnostics of EM improves diagnosis, pathogen identification, ensures IRs are not underestimated, and can help avoid unnecessary antibacterial treatment.

Fig 1. Flow chart for the diagnostic algorithm performed with associated test results.

546 CSF samples and 517 blood samples were taken from 556 patients. Out of 546 collected CSF samples, all 546 were tested in molecular assays and 331 were tested for bacterial culture. In molecular assays 494/546 samples were positive for viruses, 33/546 samples were positive for bacteria, and one sample was positive for both. 15/531 CSF samples and 2/517 blood samples were positive for bacterial culture. Nineteen CSF samples remained negative. ^a15 cases with mild symptoms had less than 1ml cerebrospinal fluid collected and culture was not conducted. ^bOne sample was positive for both N. meningitidis and Hib. ^cOne sample was positive for both N. meningitidis (tested at the earlier step) and VZV.

Fig 2. Incidence rates of meningococcal and pneumococcal EM by age group.

Children <1-year-old had the highest IRs for bacterial EM; 4.2 and 2.8 per 100,000 children for pneumococcal and meningococcal EM, respectively. The IR of pneumococcal EM among children < 1 yr. of age was 8 times higher than the IR among children aged 1–14 years. No significant difference by age was observed for meningococcal EM.

Fig 3. Viral and bacterial etiologies of acute encephalitis/meningitis in adults and children.

(A) In children (< 15 years old) the largest proportion of EM was caused by enteroviruses (86%; 362/422), herpes simplex viruses (12%; 49/422), varicella-zoster virus (2%; 10/422) and probable rabies (0.2%; 1/422). (B) For adults (≥ 15 years old), the proportion of enterovirus cases was lower at 61% (44/72), and herpes simplex virus infections higher at 31% (22/72). (C) For bacterial etiologies in children, the largest proportion of cases was caused by N. meningitidis at 61% (16/26), followed by S. pneumoniae at 31% (8/26). (D) In adults, bacterial etiology due to N. meningitidis was lower than children but remained the largest bacterial etiologic agent at 46% (5/11).

Fig 4. Epidemiological curves of laboratory-confirmed acute encephalitis/meningitis in South Kazakhstan oblast, February 2017—January 2018.

The viral etiology epidemiological curve shows an increase in enterovirus cases in March 2017 that peaked the first week of May and stayed high until the end of June. Cases then gradually decreased until early October. A second wave starting the first week of October was observed, peaking at the end of the month at a level half that of the first upsurge. Meningococcal meningitis cases were identified throughout the whole year.