Hematologic Abnormalities Improve The Clinical Suspicion Of Malaria In Non-Endemic Countries
Authors: Pereira Marta I , Marques Gilberto P , Pontes Celeste , Ribeiro Graça 
Published: October 2019

Malaria is one of the most frequent hemoparasitic infections in developing countries, responsible for a high health burden; with increasing world travel, growing numbers of patients present with malaria in non-endemic areas. While the clinical presentation of malaria is well characterized in the literature, it is non-specific, and suspicion is often raised simply by a fever and a report of a recent stay in an endemic area. Due to the connection of Europe with its former colonies, with bilateral migratory patterns, this anamnestic suspicion is frequent.
To determine whether the addition of classic malaria hematology findings (thrombocytopenia, anemia and increased serum lactate dehydrogenase – LDH - levels) can improve clinical suspicion in patients presenting in non-endemic countries, We reviewed all malaria testing resulting from emergency room (ER) visits between 01-01-2000 and 06-30-2013. Repeated tests related to the same ER visit were analysed together; patients with more than one unrelated ER visit with suspected malaria were treated as separate subjects.

Results
1357 subjects (69.0% male) fulfilled our criteria (median of 96 per year); the percentage of yearly Positive results varied between 2.6 and 17.0%, with no discernible temporal pattern, for an overall average of 9.5% of Positives.
The monthly distribution of testing was balanced, with each month accounting for 6.4 to 10.2% of yearly tests; however, the percentage of Positives had a bimodal distribution, with two significant peaks in April (14.3% positivity) and December (16.5%); males were twice as likely to be Positive (11.0 vs 6.2%, p=0.005).
There was a significant decrease in the mean haemoglobin of malaria-Positive patients (12.8±2.6 vs 13.5±2.2 g/dL, p<0.001), leading to a higher incidence of anemia (39.8 vs 18.6%, p<0.001). The positivity for malaria in anemic patients was 18.6% (vs the overall 9.5%).
Mean platelet counts decreased in Positives (102.2±82.8 vs 227.1±91.8 G/L, p<0.001), leading to an increase in thrombocytopenia from 16.1 to 80.6%, p<0.001. Malaria-positivity in thrombocytopenic patients was 34.9%, rising to 36.6% when anemia was also present.
Mean leukocyte counts decreased in Positives (5.5±2.4 vs 8.3±4.2 G/L, p<0.001), affecting all lineages, with overt leukopenia present in 20.9 vs 6.8%, p<0.001. Positivity for malaria in leukopenic patients was 20.9%. Leukocytosis was more frequent in suspicious patients without malaria (38.0 vs 17.8%, p<0.001), as was an elevated erythrocyte sedimentation rate (30.8±38.1 vs 16.5±16.8 mm, p=0.005).
Serum LDH increased in Positives from 263±287 to 414±201 U/L, p=0.003, with values over the upper limit of normal being more likely in Positives (78.7 vs 35.8%, p<0.001); however, among Positives, high LDH was as likely to be found in patients with anemia as without (87.5 vs 74.2%, p=NS). Malaria-positivity was 19.5% in the presence of high LDH, rising to 35.9% with concomitant anemia or 53.1% with thrombocytopenia.
The simultaneous presence of thrombocytopenia, anemia and high LDH (irrespective of leukopenia) resulted in 62% of Positive results, although only 10% of malaria patients fulfilled these criteria. Only 1.8% of patients who were normal on all three counts had malaria, and only 3% of malaria patients were negative for all three.
We found that malaria was suspected more often in males, who were in fact more likely to have a positive result. Although suspicion was spread out across the year, there were two seasonal peaks of positive diagnoses, around Easter and Christmas, temporally coinciding with the migratory movements of expatriates and their families.
Compared to patients with a clinical suspicion of malaria but without infection, patients who tested positive were more likely to be anemic, thrombocytopenic or leukopenic and to present with elevated LDH levels (irrespective of anemia). Patients with normal haemoglobin, platelets and LDH had a very low likelihood of malaria.
The incorporation of these laboratory findings into the clinical scenario improved on clinical suspicion nearly 6-fold (with the percentage of positivity rising from just under 10% to over 60%), although at a high cost of false-negatives.
In patients presenting at the ER in non-endemic countries with a fever and recent travel, the presence of combinations of anemia, thrombocytopenia and high LDH greatly increased the likelihood of malaria, although their absence should not impede testing.

Disclosures:
No relevant conflicts of interest to declare.