This case may represent either a relapse due to dormant liver hypnozoites or a reinfection during the same trip. The absence of radical cure in the previous episode supports the relapse hypothesis.

Plasmodium ovale is often overlooked due to its low parasitemia and morphological resemblance to P. vivax, frequently leading to misdiagnosis. Traditional microscopy, despite being widely used, has limitations in differentiating P. ovale from other Plasmodium species, often leading to incorrect treatment initiation, as seen in this case [8, 9]. Distinctive features of P. ovale include oval-shaped infected red blood cells with fimbriated edges and Schüffner’s stippling, which can help differentiate it from P. vivax. However, these characteristics may not always be apparent, reinforcing the importance of molecular techniques such as real-time PCR and nested PCR for species-specific identification [10, 11].

A key feature of P. ovale is its ability to form dormant liver-stage hypnozoites, which can reactivate months or even years after the initial infection. This long incubation period poses a challenge in identifying the origin of infection, especially in travelers who may not immediately present symptoms upon returning from endemic regions [12, 13]. In some reported cases, P. ovale has demonstrated incubation periods of up to two years before clinical presentation, necessitating thorough travel history assessments in febrile patients [14].

Accurate microscopic recognition of Plasmodium species is critical for achieving a definitive diagnosis and guiding appropriate treatment. Misidentification can lead to suboptimal management and potential disease progression. In this case, the initial misclassification as P. falciparum illustrates the diagnostic challenges posed by P. ovale, which has morphological similarities with P. vivax but distinct features that, when properly identified, can aid in differentiation [8, 9].

Microscopic differentiation of malaria species relies on key morphological characteristics observed in blood smears [10, 11]. P. falciparum predominantly presents as ring-stage trophozoites with a high parasitemia, often lacking mature schizonts in peripheral blood, and its gametocytes appear as crescent-shaped forms [12]. P. vivax displays larger, ameboid trophozoites and Schüffner’s stippling, with infected erythrocytes appearing enlarged [13]. P. malariae is characterized by band-form trophozoites and compact schizonts within normal-sized erythrocytes. P. ovale, as seen in this case, is distinguished by oval-shaped infected red blood cells, fimbriated edges, and prominent Schüffner’s stippling [14]. Table 1 provides a structured comparison of the key morphological characteristics that distinguish Plasmodium species, assisting in species identification and treatment selection. Recognizing these distinguishing features is essential to ensuring species-specific management and avoiding unnecessary exposure to drugs intended for P. falciparum, such as artemisinin-based therapies [15, 16].

Treatment strategies for P. ovale follow protocols similar to P. vivax, with chloroquine serving as the first-line therapy for acute infection, and primaquine used to eradicate latent hepatic stages and prevent relapse. However, before initiating primaquine, screening for glucose-6-phosphate dehydrogenase (G6PD) deficiency is imperative to prevent hemolytic anemia [15]. An alternative therapy, tafenoquine, has recently been approved for radical cure and offers a single-dose regimen compared to the 14-day primaquine course [16].

Given that Colombia is a non-endemic country for P. ovale, awareness of imported cases is crucial among healthcare providers. Routine malaria rapid diagnostic tests (RDTs), commonly used in clinical settings, may not always detect P. ovale due to its lower antigen levels or genetic variations affecting test performance [17, 18]. As a result, combining microscopic evaluation with molecular assays is strongly recommended for confirming species identification. Furthermore, blood donors with a history of travel to endemic areas should be screened rigorously, as long incubation periods may allow for asymptomatic transmission through transfusions [19, 20].

This case underscores the importance of accurate microscopic evaluation to differentiate Plasmodium species, particularly in non-endemic regions where P. ovale may be less recognized. The addition of molecular techniques, such as PCR, enhances species identification, guiding appropriate treatment and preventing relapses associated with latent hypnozoites in the liver.