Babesiosis is a worldwide emerging tick-borne disease from an infection induced by the genus Babesia, which is transmitted by ixodid ticks. More than 100 species of Babesia can infect different domestic and wild animals [1], but only a few species infect humans [2,3], including B. microti, B. divergens, B. duncani, B. venatorum, B. crassa-like agents, Babesia sp. MO1, and B. motasi-like agents. The majority of human babesiosis cases in the USA are induced by B. microti, which causes about 1,500 cases per year. It is endemic to the northeastern and midwestern regions of the USA, and babesiosis occurrences have risen and expanded geographically between 2011 and 2015 [3].

Clinical symptoms of babesiosis range from asymptomatic to fulminant. The most typical symptoms of human babesiosis include fever, fatigue, chills, headache, and myalgia. Babesiosis has malaria-like symptoms [4], requiring a differential diagnosis from malaria. Babesiosis diagnoses can be verified by the identification of intraerythrocytic parasites on a blood smear or confirmation of Babesia DNA using polymerase chain reaction (PCR) [5].

Since the initial report of human babesiosis in the Republic of Korea in 1988 [6], 14 additional cases of babesiosis have been revealed. Most of these cases were imported [7,8], and only 2 were known to be locally transmitted, which were infected with Babesia sp. KO-1 and B. motasi-like agents [9,10].

This research reports 2 patients with a travel history to babesiosis-endemic regions of the USA. Blood smears and/or PCR tests found the Babesia pathogen.

The prevalence rates and geographic occurrence of human babesiosis have been rising globally. In the USA, human babesiosis is prevalently induced by B. microti and occasionally by Babesia WA1. In Europe, most cases were found in France and Ireland and were induced by B. divergens [3,4]. In Asia, multiple species of Babesia have been discovered in China and the Republic of Korea, including B. venatorum (China), Babesia sp. KO-1, and B. motasi-like agent (Republic of Korea) [9–11]. Human babesiosis is induced by the asexual reproduction of Babesia parasites in host erythrocytes, causing red blood cell hemolysis [12]. Consequently, several clinical manifestations reflective of the parasitemia level are revealed. The incubation period of babesiosis is typically 1–6 weeks after a tick bite, depending on the host’s general condition and the infecting Babesia strain [4]. Confirmation of particular tick bites for both of our patients could not be identified. However, considering that both patients had recently visited babesiosis-endemic regions of the USA and their clinical symptoms aligned with those commonly presenting within the general babesiosis incubation period, a diagnosis of babesiosis was identified.

Morphologically, Babesia species commonly appear as round-, oval-, or pear-shaped within red blood cells. The ring form is the most prevalent morphological characteristic of Babesia, which can be misconstrued with the features of P. falciparum. The tetrad form (called “Maltese cross”) is the pathognomonic form for babesiosis but is rarely found. Babesia was historically classified by the morphology of the intraerythrocytic forms, which can be divided into small (trophozoite measurement: 1–2.5 μm; included species: B. microti, B. gibsoni, and B. rodhaini) and large (trophozoite measurement: 2.5–5.0 μm; included species: B. bovis, B. caballi, and B. canis) Babesia [1,13]. In the first case of our research, we found tetrads of Babesia sp., which are a feature of babesiosis, prompting the babesiosis diagnosis. However, in the second case, only ring forms were found in blood smears, which were confusing to differentiate from P. falciparum. There is limited accuracy in depending on these morphological characteristics as comparable or identical species can not be distinguished [14]. Morphological classification methods are gradually being supplanted by more recent molecular biological methods, which are more helpful in differentiating between related species and verifying distinctions based on subjective characteristics.

On a species-level classification, recent molecular studies demonstrated that the B. microti group is a complex species involving 4 groups, including the US, Munich, Kobe, and Hobetsu types [1,15]. Under the B. microti group, the US type is the main and most common type of babesiosis within the northeastern and midwestern regions of the USA [16]. In the present studies, both patients visited babesiosis-endemic regions of the USA and reported clinical symptoms within babesiosis incubation time. In the second case, the identification of the Babesia strain as the most often occurring strain in the USA was at a molecular level of evidence. This result aligns with the patient’s travel history to the endemic region and related clinical symptoms of babesiosis. These cases of travel-acquired human babesiosis diagnosed in the Republic of Korea highlight the crucial consideration required for returning travelers from babesiosis-endemic countries, such as the USA, and European countries. Additionally, diagnosis via PCR with sequence analysis is crucial for determining specific Babesia species. These data are essential to comprehending the epidemiology and origin of pathogens.

Given the rising number of travelers returning from babesiosis-endemic countries, the risk of travel-acquired babesiosis is increasing. Although babesiosis was described as a notifiable disease by the Sentinel surveillance system in the Republic of Korea in 2011, awareness among physicians remains insufficient. As a result, some babesiosis descriptions, including molecular phylogeny and morphological analyses, are incomplete. Babesiosis diagnosis in non-endemic areas requires knowledge of the disease. Furthermore, surveillance of vectors having babesias, including ticks, and mammals, is required to understand changes in babesiosis distribution or the introduction of new Babesia spp. in naïve areas.