Current World Health Organization (WHO) Ebola virus disease case definitions are suboptimal at identifying cases in both community and clinical triage settings, according to a review recently published in The Lancet.

The Ebola case definition acts as a crucial surveillance tool for detection of suspected cases and as a screening tool to support admission and laboratory testing decisions at Ebola health facilities. Unfortunately, WHO Ebola case definitions have long been a source of concern due to their poor performance and inability to distinguish Ebola from other common diseases, including malaria and typhoid fever.

In response, organizations involved in the Ebola response have estimated the sensitivity and specificity of the WHO case definitions and developed alternative definitions and risk scores that could predict infection under outbreak conditions. The discordance has resulted in community disengagement and a delay in outbreak control in some African countries. Furthermore, the operational use and performance of those definitions and risk scores has not been rigorously evaluated, which is needed to help guide both communities and public health practitioners to improve the effectiveness and efficiency of identification and management of suspected cases during Ebola virus disease responses. This systemic review assessed the performance of WHO Ebola case definitions and other screening scores.

Currently published studies that estimated the sensitivity and specificity of WHO Ebola case definitions, clinical and epidemiological characteristics, including symptoms at admission and contact history, and predictive risk scores against the reference standard, were searched for on PubMed, Embase, and Web of Science. In total, 14 studies from Sierra Leone, Guinea, Liberia, and Angola, published between 2010 and 2019, were included in the analysis. These studies included 12,021 people with suspected disease, of whom 4874 were confirmed positive for Ebola infection. Bivariate and hierarchical summary receiver operating characteristics were used to calculate summary estimates of sensitivity and specificity when 4 or more studies provided data; random-effects meta-analysis was used when less than 4 studies provided data.


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Results demonstrate that current WHO Ebola case definitions sub-optimally identify cases at both the community level and during triage. In 6 of the studies included, the performance of WHO case definitions was explored in non-pediatric populations, and, in all of these studies, suspected and probable cases were combined and could not be disaggregated for analysis. Among these studies, investigators found a pooled sensitivity of 81.5% (95% CI, 74.1-87.2) and a pooled specificity of 35.7% (95% CI, 28.5-43.6).

A history of contact or an epidemiological link was a key predictor for the WHO case definitions (7 studies) and for risk scores (6 studies). Intense fatigue, assessed in 7 studies, was found to be the most sensitive symptom (79%; 95% CI, 74.4-83.0) and could be used at the community level to facilitate early referral of suspected cases and prevent community transmission. Pain behind the eyes, assessed in 3 studies, was found to be the least sensitive symptom (1%; 95% CI, 0.0-7.0). Results of a random-effects analysis demonstrated that a fever threshold ³38.5°C had a pooled specificity of 25% (95% CI, 17.0-33.0) and a sensitivity of 80% (95% CI, 69.0-90.0). When the WHO case sub-definition did not include fever as a mandatory criterion, sensitivity was 100%.

The researchers noted that “[a] range of contextual factors related to study setting will affect the performance of Ebola…case definitions,” suggesting that these factors will limit the generalizability of findings to other settings. They also note that only 2 of the recommended risk scores were externally validated and added that further exploration is needed in pediatric populations and among pregnant women. 

 “[The] inclusion of intense fatigue as a key symptom could improve the sensitivity, the primary requirement for community-based screening, of WHO and alternative case definitions,” the researchers concluded. “Implementation of these changes will require effective collaboration with, and trust of, affected communities.”

Reference

Caleo G, Theocharaki F, Lokuge K, et al. Clinical and epidemiological performance of WHO Ebola case definitions: A systemic review and meta-analysis [published online June 25, 2020]. Lancet Infect Dis. doi:10.1016/S1473-3099(20)30193-6