Aetiology of acute meningoencephalitis in Cambodian children, 2010-2013

Abstract

Acute meningoencephalitis (AME) is associated with considerable morbidity and mortality in children in developing countries. Clinical specimens were collected from children presenting with AME at two Cambodian paediatric hospitals to determine the major aetiologies associated with AME in the country. Cerebrospinal fluid (CSF) and blood samples were screened by molecular and cell culture methods for a range of pathogens previously associated with AME in the region. CSF and serum (acute and convalescent) were screened for antibodies to arboviruses such as Japanese encephalitis virus (JEV), dengue virus (DENV), and chikungunya virus (CHIKV). From July 2010 through December 2013, 1160 children (one month to 15 years of age) presenting with AME to two major paediatric hospitals were enroled into the study. Pathogens associated with AME were identified using molecular diagnostics, cell culture and serology. According to a diagnostic algorithm, a confirmed or highly probable aetiologic agent was detected in 35.0% (n=406) of AME cases, with a further 9.2% (total: 44.2%, n=513) aetiologies defined as suspected. JEV (24.4%, n=283) was the most commonly identified pathogen followed by Orientia tsutsugamushi (4.7%, n=55), DENV (4.6%, n=53), enteroviruses (3.5%, n=41), CHIKV (2.0%, n=23) and Streptococcus pneumoniae (1.6%, n=19). The majority of aetiologies identified for paediatric AME in Cambodia were vaccine preventable and/or treatable with appropriate antimicrobials.

Figure 1

The diagnostic algorithm used for the study.

Figure 2

A decision tree used in the study to prioritize the importance of results in determining the final conclusion for aetiology. Ranking of the primacy of results is from left (most reliable) to right (least reliable). ^aDetection of CMV or EBV in the CSF was categorized as ‘highly probable’ due to the possibility of reactivation of latent virus. ^bIgM detection was considered positive when the optical density (OD) of the samples was greater than the mean OD of three negative control samples plus 3 standard deviations. ^cIgM detection in the CSF was only considered positive when the CSF IgM titre was higher than blood IgM titre for the corresponding virus. ^dAn acute infection was defined as a significant increase in OD measured for IgM by ELISA between admission and discharge sera.

Figure 3

Population-adjusted attack rates (cases per 100 000 pop, using 2012 population) of Japanese encephalitis virus for the 2010–2012 study period (A) and 2013 study period (B) mapped using ArcGIS 10 (Esri, Redlands, CA, USA), by year and patient’s province of residence, to assess the time and geographical distribution of ‘confirmed’ and ‘highly probable’ cases. Population density across Cambodia was also mapped, using villages as a proxy for population (each village being represented as one dot). Note: The number of hospitals participating in the surveillance system differed between the two periods. The maps therefore use different scales to illustrate the relative incidence and burden of JEV by province during those periods rather than absolute incidence values.

Figure 4

Representation of Japanese encephalitis virus cases by month with mean rainfall data estimated by satellite teledetection (Tropical Rainfall Measuring Mission, NASA, USA, http://trmm.gsfc.nasa.gov/) and adjusted for surface of province of residence.