Current strategies to avoid misdiagnosis of malaria

Abstract

Malaria remains the most important parasitic disease, and tens of thousands of cases are imported into non-endemic countries annually. However, any single institution may see only a very few cases-this is probably the reason why laboratory and clinical misdiagnosis may not be uncommon. In the laboratory, unfamiliarity with microscopic diagnosis may be the main reason, considering the large number of laboratory staff who provide on-call services, often without expert help at hand, as well as the difficulty in detecting cases with low-level parasitemia. Staff should therefore be provided with continuing microscopic training to maintain proficiency. The complementary use of immunochromatographic rapid detection tests (RDTs) may be useful, especially during on-call hours, although, in order to ensure correct interpretation, their inherent limitations have to be well known. Diagnosis based on the polymerase chain reaction is still unsuitable for routine use, due to its long turnaround time, its cost, and its unavailability outside regular hours, although it may be helpful in selected cases. Once the alert clinician has considered the possibility of malaria, and suspicion continues to be high, malaria can be excluded by repeat smears or RDTs. However, the absence of clinical suspicion may not be infrequent, and may have more serious consequences. Depending on the local number of malaria cases seen, laboratory staff should have a low threshold for the decision to perform unsolicited malaria diagnostic tests on suspicious samples, especially if other laboratory tests are abnormal (e.g. thrombocytopenia, presence of atypical lymphocytes, or raised lactate dehydrogenase). The detection of intraleukocytic hemozoin during automated full blood counts is a promising new way to avoid misdiagnosis of clinically unsuspected malaria.

Evaluation of the Immunoquick+4 malaria rapid diagnostic test in a non-endemic setting

“…In resource-poor endemic settings, there may be problems related to equipment, expertise and workload, whereas in non-endemic settings in industrialised countries, there may be a lack of routine among the laboratory staff, resulting in low expertise [1]. In these circumstances, the use of malaria rapid diagnostic tests (MRDTs) can be valuable in the diagnosis of malaria [1,2]. MRDTs detect antigens specific to one or more of the Plasmodium species.…”

Real-Time PCR for Detection and Identification of Plasmodium spp

“…95% of the deaths due to malaria (33). The current standard for diagnosis is the microscopic examination of Giemsa-stained thick and thin blood smears (12,16,21,22,28). This procedure is time-consuming to prepare, read, and interpret the slides.…”

“…This procedure is time-consuming to prepare, read, and interpret the slides. Previous studies have shown that even with experienced microscopists, misdiagnosis occurs, particularly in cases of mixed infection or low parasitemia (12,28). Immunochromatographic assays based on antigen detection have been developed but are also relatively insensitive in cases of low parasitemia (22,24,30).…”

“…In addition, antigenemia may persist weeks beyond the actual infection, leading to the false diagnosis of malaria parasitemia (6,22). Molecular detection for Plasmodium diagnosis using PCR has resulted in increased sensitivity and species discrimination compared to either microscopic or immunochromatographic diagnosis of malaria (2,4,12,14,22,23,25,27). However, most published PCR assays are gel based with (4,5,15) or without (2, 3, 9, 23, 25-27, 29, 31, 35, 36) subsequent probe hybridizations, resulting in a lengthy procedure not optimal for clinical use.…”

Comparison of Three Molecular Methods for the Detection and Speciation of Five Human Plasmodium Species

“…In fact, even experienced microscopists have been found to misdiagnose cases involving low parasitemia or mixed infections. [7][8][9] Moreover, morphological similarities between P. knowlesi and P. malariae often result in misdiagnosis. 10 Although RDTs are generally specific for detecting P. falciparum and P. vivax infections, they are non-specific for other malaria species.…”