Alan J. Magill

Plasmodium falciparum is responsible for most of the mortality in travelers related to imported malaria. Problems that occur during travel include the inaccuracy of a microscopic diagnosis of malaria, both false positives and false negatives, when ill travelers seek care while abroad. A false positive diagnosis can result in unnecessary parenteral injections that carry a risk of transmission of blood-borne pathogens, receipt of potentially dangerous drugs such as halofantrine, or receipt of fake, counterfeit drugs. Increased morbidity and mortality are associated with delays in diagnosis and initiation of prompt treatment for falciparum malaria. Availability of expert microscopy to confirm the diagnosis of malaria is limited. The presence of splenomegaly and thrombocytopenia are strongly associated with malaria and would justify empiric treatment. The availability of atovaquone-proguanil, a safe and well tolerated oral drug, should prompt a reconsideration of current treatment recommendations that discourage empiric treatment on clinical suspicion alone.

Enumeration of parasites by microscopic examination of blood smears is the only method available for quantifying parasitemia in infected blood. However, the sources and scale of error inherent in this technique have not been systematically investigated. Here we use data collected in outpatient clinics in Peru and Thailand to elucidate important sources of variation in parasite density measurements. We show that discrepancies between readings from two independent microscopists and multiple readings from a single microscopist are inversely related to the density of the infection. We present an example of how differences in reader technique, specifically the number of white blood cells counted, can contribute to the differences between readings. We discuss the implications of this analysis for field studies and clinical trials.