Splenic Infarction in Plasmodium vivax Infection in South Korea

Malaria is a protozoan disease that is found in many regions globally.¹ Malarial infection can be complicated by cerebral malaria, pulmonary edema, acute kidney injury, spontaneous bleeding, shock, anemia, liver failure, hypoglycemia, metabolic acidosis, and death.² Although splenic infarction, splenic rupture, cyst, hemorrhage, torsion, and hypersplenism can develop in vivax malaria,³ the incidence of splenic complications can be easily underestimated because they should be confirmed through computed tomography (CT) or ultrasonography (US). Currently, there are only a few studies on the incidence and clinical signs of splenic infarction in vivax malaria,⁴ so we analyzed the incidence and characteristics of splenic infarction in patients with vivax malaria in Korea.

This study was approved by the Institutional Review Board of Inha University Hospital. The study was retrospectively conducted on in- and outpatients with vivax malaria, diagnosed in an 860-bed university hospital (Incheon, South Korea) and enrolled from January 2005 to December 2017. The diagnosis was confirmed by peripheral blood smear examination, which was performed by an expert. In Korea, Plasmodium vivax is the only prevalent species, so patients with malaria without a history of travel abroad undoubtedly have vivax malaria, even if there is no molecular evidence.⁵ Patients who had a history of travel abroad within 6 months from the start of the study and children aged < 15 years were excluded. We reviewed the abdominal CT or US findings of the enrolled patients with vivax malaria.

A total of 273 patients with vivax malaria were included in this study. Of these patients, 92 underwent abdominal CT or US. Twelve patients presented with splenic infarction (Table 1). Among the 12 patients with splenic infarction, six had localized pain in the upper left abdomen on the day of visit, whereas the remaining six patients did not present with abdominal pain at the time of hospital visit. Eight patients had anemia (hemoglobin level < 12 mg/dL). All patients were treated with chloroquine (a total of 2,500 mg in 2 days) and primaquine (15–30 mg, once daily, for 14 days) and recovered spontaneously without any surgery or intervention. In the univariate analysis (Mann–Whitney U test), anemia and prolonged fever were risk factors for splenic infarction (Table 2). However, there were insufficient patients to perform multivariate analysis. Notably, a patient had splenic rupture but improved without any surgery or intervention. No deaths occurred in the present study.

A previous study revealed that splenic infarction and rupture were more frequently reported in vivax than in falciparum malaria, which is contradictory to other complications.⁶ However, there is doubt as to whether these differences of incidence by region are related to the malaria species. Previous studies on splenic infarction were conducted primarily in France, India, and Korea.^4,6–10 These countries have better medical settings than other endemic areas, which can increase the accessibility of patients to radiologic examinations. In particular, South Korea has an extremely low cost burden when CT is performed because of the well-established national health insurance system. The accessibility of these imaging tests can lead to frequent screening and can be a source of the high splenic infarction rate. Moreover, low partial immunity of Korean individuals can be considered as a cause of high incidence of splenic infarction in malaria. Most Korean individuals have low partial immunity to vivax malaria because there has been re-emergence of malaria in South Korea since 1993. Low frequency of exposure can be related to low partial immunity, and there is a possibility that the low partial immunity caused more frequent splenic complications in South Korea.⁵

The pathophysiology of splenic infarction is poorly known. The literature indicates the following possibilities: hypercoagulopathy (due to decreased levels of antithrombin III, protein C, and protein S and increased levels of von Willebrand factor and plasminogen activator inhibitor),^11,12 vascular congestion and occlusion (due to cytoadhesion of infected red blood cells [RBCs] and splenic cellular hyperplasia), and hypoxemia (due to anemia).^4,10 In this study, there were more patients with splenic infarction and anemia than those without splenic infarction. Red blood cell destruction can cause an increased release of vasoactive cytokines or microthrombus.¹³ Patients with low immunity to malaria can be assumed to have more severe reactions because of infected RBCs or RBC lysis, but there is no study regarding this theory, and further research is needed. The median duration of fever in patients with splenic infarction was 10 days, which was longer than that in patients without splenic infarction. In this study, there was no statistically significant relationship between hypoxemia and splenic infarction. In patients with underlying risk of splenic infarction (e.g., cardiovascular disease, malignancy, and coagulopathy), there is a possibility that hypoxemia may cause splenic infarction. However, patients with malaria in South Korea are generally young, so most patients have no comorbidity.

It is interesting to note that six of the 12 patients had no abdominal pain. The diagnosis of splenic infarction may be difficult without imaging because it can be asymptomatic. However, splenic rupture was noted in one patient who had splenic infarction. Although the association between splenic infarction and rupture remains unclear, splenic rupture is a fatal complication. Therefore, patients with upper left abdominal pain or those with risk factors for splenic infarction need to be closely monitored.

The present study has several limitations. First, it was performed in a single center and was retrospective. Second, the number of splenic complications was insufficient to analyze the risk. Last, many patients did not undergo CT or US, so the incidence of splenic complications in the present study could be underestimated.

Therefore, in our study, splenic infarction caused by P. vivax showed a relatively high incidence in South Korea. Because splenic infarction may be often asymptomatic, careful observation is needed. In this study, prolonged fever and anemia were risk factors, and further study is needed in the pathogenesis of splenic infarction in vivax malaria.