Date Published: August 21, 2007
Publisher: Public Library of Science
Author(s): Nicholas M Anstey, Ric N Price
Abstract: The authors discuss a study by Philip Bejon et al. that adopted a new approach to balancing the sensitivity and specificity of criteria for defining severe malaria.
Partial Text: The lack of a “gold standard” definition for severe malaria has been a longstanding problem for both clinicians and researchers. The definitions currently used comprise a set of clinical and laboratory parameters associated with an increased risk of death [1,2], combined with the presence of Plasmodium falciparum parasitemia [2,3]. In young children, these criteria are predominantly altered consciousness, severe anemia, and respiratory distress [1,3]; a broader range of criteria is applicable to adolescents and adults .
What definition for severe malaria should be used when severe malaria is a study endpoint rather than an entry criterion? In vaccine trials or intervention studies designed to prevent severe disease, case definitions should reflect a balance between sensitivity and specificity. Neither of the definitions described above would be optimal. Ideally, a level of specificity would be adopted that ensures an accurate estimate of vaccine efficacy, without reducing the sensitivity to a level that requires a major increase in the sample size.
Bejon et al. have now demonstrated the utility of such methodology in identifying a case definition that appropriately balances sensitivity and specificity for severe malaria in coastal Kenya. Their definition provides a rational endpoint for future vaccine trials and other community-based malaria prevention trials at this site. The authors acknowledge that these findings are applicable to coastal Kenya and cannot necessarily be generalized to other settings. Nevertheless, the approach they have used will pave the way for others to derive locally applicable MAFs and test the generalizability of their findings. Indeed the derivation of MAFs should, where possible, become an intrinsic part of the planning of vaccine/intervention trials and epidemiology studies of severe malaria.