Sysmex Europe

Malaria vivax

Pathogen:Protozoa →Plasmodium vivax
Transmission:Female mosquitoes of the Anopheles genus
Geographical range:Tropical regions
Incidence:Over 130 million infections per year

Case history

A 35-year old woman living in Mumbai in India suffered the following flu-like symptoms for several days : fever accompanied by sudden chills, joint pain, fatigue, headache and occasional dry cough. After one week, when the symptoms did not resolve she decided to visit her general practitioner. The doctor examined the patient and considered her medical history, and thus decided to order a complete blood count with WBC differential and reticulocyte count to investigate the cause of her persisting symptoms and initiate the appropriate treatment.

Malaria pathophysiology and diagnostics

Each year there are around half a million reported deaths due to malaria (1). While malaria exists in more than 100 countries, it is mainly confined to poorer tropical areas of Africa, Asia and Latin America. More than 90% of malaria cases and the vast majority of malaria deaths occur in tropical Africa.

Malaria is a parasitic infection transmitted primarily by the bite of an infected female Anopheles mosquito. Malaria may also be transmitted via blood transfusion or congenitally between mother and foetus. In humans, parasites multiply exponentially in the liver and, after several developmental stages, infect red blood cells. Mosquitoes ingest parasites with a blood meal, upon which the parasites undergo another reproductive phase inside the mosquito before being passed on to another human host.

There are four species of Plasmodium that commonly infect humans - P. falciparum, P. vivax, P. ovale and P. malariae. P. falciparum accounts for the highest mortality. P. vivax (causes Malaria tertiana) is generally less virulent than P. falciparum, but can lead to severe disease progression, leading to death due to a severe splenomegaly (2,3).

The parasite is protected from the body's immune system because for most of its life cycle it resides within the liver and the red blood cells. The P. vivax blood levels are lower than with P. falciparum since only young erythrocytes are infected. The knob-like excrescences on the surface of infected red cells - known from P. falciparum infected cells - do not develop on infected RBCs and thus microvascular obstruction does not occur. Therefore, in terms of P. vivax infection, there is no damage to the brain, kidney, lung or other organs. The parasites form a dormant stage in liver cells called hypnozoites, which can become activated and cause a delayed infection of RBC or relapse. Relapse usually occurs within 6 months of an acute attack but the period of dormancy may be up to years.

A blood count is almost always requested as part of the routine investigation of febrile patients. The changes in RBC and WBC parameters are generally nonspecific and unlikely to directly suggest a diagnosis of malaria. Thrombocytopenia is often present in children and adults infected with malaria. A careful study of the results provided by automated haematology analysers in malaria patients has shown several changes, mainly related to abnormal WBC and RET scattergrams that could suggest malaria infection in these patients, without knowledge of their clinical status (4).

Peripheral smear examination for malarial parasites is the gold standard in confirming the diagnosis of malaria. Thick and thin smears prepared from peripheral blood are used for this purpose (5). The peripheral blood smear provides comprehensive information on the species, the stages and the density of parasitemia with a positive smear of low density of 80-200 parasites/μL of blood. However, the sensitivity of the ‘thick smear’ reference test is to be taken into account. Even in expert hands, ‘thick smears’ lack sensitivity, giving rise to false negative results (6).

Laboratory results

Case interpretation

The results of XN complete blood count analysis revealed populations of Plasmodium trophozoites and schizonts in the WDF scattergram, which triggered the parasite RBC flag (‘pRBC’) on the analyser.

Without the activated ‘pRBC’ license, which triggers the flag, the reported values can lead to incorrect results, such as false high neutrophil or eosinophil count when schizonts, gametocytes and/or trophozoites are present and overlap with these cells. Even a small number of infected RBCs with these larger forms may have a significant impact on the differential count, as the concentration of RBCs is a thousand-fold higher than WBCs and parasited RBCs (schizont inclusions increase fluorescence) are not completely lysed in the WDF channel. In the WNR scattergram the abnormal ghost population consisting also of cell debris of parasitized RBCs (a stronger lysis reagent than in WDF channel) did not interfere with the WBC population and thus the correct WBC count is reported from this channel.

In the presented case, WBC counts from the WDF channel are thus falsely higher (10.80 x 109/L – not reported) than the correct WBC count from the WNR channel (7.76 x 109/L – correct reported value). Due to the activation of the flag ‘pRBC’, the neutrophil and eosinophil counts (0.38 x 109/L without ‘pRBC’ flag – not reported; 0.08 x 109/L – correct reported value) are corrected to the accurate values.

The WDF pattern of the scattergram is typical for P. vivax infection of RBC cells, as P. vivax breaks down haemoglobin to haemozoin, a dark-brown haeme crystal, which increases side scatter and side fluorescence signal in the WDF scattergram of incompletely lysed parasited RBC.

In the RET scattergram parasitized RBC (trophozoites) of P. vivax can interfere with reticulocytes (in case of a high number of infected young RBCs). The ring form trophozoites interfere in the area of relatively immature reticulocytes (medium and high fluorescence ratio, MFR and HFR) and can lead to falsely increased values of RET (pseudo-reticulocytosis). This is not explicitly visible in our RET scattergram. However, a slightly increased absolute and relative RET count (RET# = 100 x109/L, RET% = 2.16) but normal-to-low MacroR value (=3.8%) could indicate a low interference from parasitized RBCs.

The final diagnosis of Malaria tertiana was confirmed by the microscopic examination of patient’s blood ‘thick smear’ and positive blood culture.


  1. World Health Organization (2015): Malaria
  2. Baird JK (2007): Neglect of Plasmodium vivax malaria. Trends in Parasitology 23 (11): 533–539.
  3. Anstey NM, Douglas NM, Poespoprodjo JR, Price RN (2012): Plasmodium vivax: clinical spectrum, risk factors and pathogenesis. Adv Parasitol.; 80:151-201.
  4. Bejon P, Andrews L, Hunt-Cooke A, Sanderson F, Gilbert SC, Hill VS (2006): Thick blood film examination for Plasmodium falciparum malaria has reduced sensitivity and underestimates parasite density. Malar J.; 5: 104.
  5. World Health Organization (2015): Guidelines for the treatment of malaria
  6. Dubreuil P, Pihet M, Cau S, Croquefer S, Deguigne PA, Godon A, Genevieve F, De Gentile L, Zandecki M (2014): Use of Sysmex XE-2100 and XE-5000 hematology analyzers for the diagnosis of malaria in a nonendemic country (France). Int J Lab Hematol. Apr;36(2):124-34.

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