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The Brigham and Women's Hospital, Boston, Massachusetts
Blantyre Malaria Project, University of Malawi College of Medicine
Malawi/Liverpool/Wellcome Trust Clinical Research Programme, Blantyre, Malawi
College of Osteopathic Medicine, Michigan State University, East Lansing
We appreciate the comments from White and Silamut [1]. We did not cite Raja's original study [2] in our article [3], because Raja's study is a report of 4 cases in which smears of brain tissue from patients dying of malaria are compared with the gross appearance of the brain and not with histological appearance. Our own experience has shown that the gross appearance of the brain is not always "classic" (i.e., with a slate gray cerebral cortex and petechial hemorrhages) (figure 1). Raja's use of brain smears is, however, a good example of using the technique in the context we suggestthat is, when histological analyses are not possible. We do not claim to have discovered a new technique, but we hope that our validation will help to expand its use.
We did not compare intensity, stage distribution, and intervessel variance of sequestration in smears versus histological sections, because our goal was to validate a practical tool for nonpathologists and nonscientists. We did establish that brain smears obtained from a single site (the frontal lobe) could be used to identify patients with significant sequestration as reliably as when the more laboriously obtained histological sections (which require opening of the skull; fixing, embedding, and staining of the tissue; and interpretation by a pathologist) are used. We believe that our validation establishes that brain smears are a sound method for confirming the presence of cerebral sequestration when histological analyses are not possible. In our recent study of fatal malaria in children [4], cases lacking cerebral sequestration of parasites invariably had an additional pathological explanation for death.
Our goal was to expand the capacity to identify significant cerebral sequestration of parasitized red blood cells to clinicians working in malaria-endemic areas where autopsies and histological analyses are not possible. Because the standard clinical case definition lacks specificity and positive predictive value, this additional information may be useful, both in the context of individual case diagnoses and in interpretation of findings from research studies.
References
1. White NJ, Silamut K. Postmortem brain smear assessment of fatal malaria . J Infect Dis 2005; 192:547 (in this issue). First citation in article
2. Raja RN. Post-mortem examination in cerebral malaria: a new simple method of demonstrating parasites in the capillaries of the brain. Ind Med Gaz 1922; 57:29899. First citation in article
3. Milner DA Jr, Dzamalala CP, Liomba NG, Molyneux ME, Taylor TE. Sampling of supraorbital brain tissue after death: improving on the clinical diagnosis of cerebral malaria. J Infect Dis 2005; 191:8058. First citation in article
4. Taylor TE, Fu WJ, Carr RA, et al. Differentiating the pathologies of cerebral malaria by postmortem parasite counts. Nat Med 2004; 10:1435. First citation in article