Modern Hematology Analyzers Are Very Useful for Diagnosis of Malaria and, Crucially, May Help Avoid Misdiagnosis

LETTER

Mathison and Pritt provide an excellent update on the optimal test utilization for the diagnosis of malaria (1). Their review is directed toward affluent settings where malaria is not endemic, such as the United States or Europe. Here, the main problem in diagnosis is limited experience and poor proficiency in microscopy, further compounded by the fact that many requests are made out of hours, when more experienced staff may not be available (2).

The diagnostic difficulties are not limited to the laboratory, though. Malaria tests are only performed when “malaria is suspected based on clinical findings and exposure history,” as indicated in Mathison and Pritt's algorithm (1). But what happens in the absence of clinical suspicion? In countries where malaria is not endemic, this may be a more common problem than usually thought. In Canada, 59% of malaria patients were missed on first presentation and 16% had three or more physician contacts before malaria smears were ordered (3). In the United States, one study showed that 16% of diagnoses were missed on first presentation (4) while another study found that of 60 patients with fatal malaria, 40% were not diagnosed on first presentation (5).

Fortunately, in the kind of setting that Mathison and Pritt's update addresses (1), a battery of other laboratory tests is a common standard in the work-up of a febrile patient, including a complete blood count (CBC). The incidental finding that Cell-Dyn hematology analyzers detect malaria pigment (hemozoin) during routine CBC determination permits the diagnosis of malaria with remarkably good sensitivity and specificity (6). Even more importantly, it has led to the diagnosis of several clinically unsuspected cases of malaria (7). Modern hematology analyzers are very sophisticated instruments. Based on flow cytometric principles, they produce a myriad of highly accurate and precise measurements. Not too astonishingly then, instruments from other manufacturers (which do not detect hemozoin) also detect malaria, usually after combining several parameters into a screening algorithm (6). Indeed, the European Inventor Award 2017 has just been awarded for a method where the Advia 2120i hematology system can run malaria tests automatically as part of a CBC measurement (http://nltimes.nl/2017/06/16/new-malaria-test-earns-dutch-hematologist-european-inventor-award).

One can argue that other common laboratory parameters should be part of a useful algorithm (8), including the information from the hematology analyzer. Perhaps creating such an algorithm on the level of the laboratory information system would likely have the biggest impact. A positive flag would encourage staff to read slides more carefully and longer. Most important, though, it would allow for automatic “reporting” of a malaria diagnosis even if it is not requested by a clinician.

It looks like a missed opportunity if affluent countries and those where malaria is not endemic, which are fortunate enough to have access to all laboratory tests, limit the diagnostic work-up to the use of specific malaria-diagnostic tests—especially when novel, highly valuable information from modern hematology analyzers may aid substantially in the diagnosis of this potentially fatal disease.