Comparison of an assumed versus measured leucocyte count in parasite density calculations in Papua New Guinean children with uncomplicated malaria

Background:The accuracy of the World HealthOrganization method of estimating malaria parasite density from thick bloodsmears by assuming a white blood cell (WBC) count of 8,000/μL has been questioned in several studies. Since epidemiologicalinvestigations, anti-malarial efficacy trials and routine laboratory reportingin Papua New Guinea (PNG) have all relied on this approach, its validity wasassessed as part of a trial of artemisinin-based combination therapy, whichincluded blood smear microscopy and automated measurement of leucocytedensities on Days 0, 3 and 7.

Results:168 children with uncomplicated malaria(median (inter-quartile range) age 44 (39–47) months) were enrolled, 80.3% with Plasmodium falciparum monoinfection,14.9% with Plasmodium vivax monoinfection, and 4.8% with mixed P. falciparum/P. vivax infection.All responded to allocated therapy and none had a malaria-positive slide on Day3. Consistent with a median baseline WBC density of 7.3 (6.5-7.8) × 109/L, there was no significant difference inbaseline parasite density between the two methods regardless of Plasmodium species. BlandAltman plots showed that, for both species, the mean difference between pairedparasite densities calculated from assumed and measured WBC densities was closeto zero. At parasite densities <10,000/μL by measured WBC, almost all between-method differences werewithin the 95% limits of agreement. Above this range, there was increasing scatterbut no systematic bias.

Conclusions:Diagnostic thresholds and parasiteclearance assessment in most PNG children with uncomplicated malaria arerelatively robust, but accurate estimates of a higher parasitaemia, as aprognostic index, requires formal WBC measurement.