Comparison of Imported Plasmodium ovale curtisi and P. ovale wallikeri Infections among Patients in Spain, 2005–2011

Gerardo Rojo-Marcos

, José Miguel Rubio-Muñoz, Germán Ramírez-Olivencia, Silvia García-Bujalance, Rosa Elcuaz-Romano, Marta Díaz-Menéndez, María Calderón, Isabel García-Bermejo, José Manuel Ruiz-Giardín, Francisco Jesús Merino-Fernández, Diego Torrús-Tendero, Alberto Delgado-Iribarren, Mónica Ribell-Bachs, Juan Arévalo-Serrano, and Juan Cuadros-González

Author affiliations: Príncipe de Asturias University Hospital, Madrid, Spain (G. Rojo-Marcos, J. Arévalo-Serrano, J. Cuadros-González,);Instituto de Salud Carlos III, Madrid (J.M. Rubio-Muñoz); Carlos III Hospital, Madrid (G. Ramírez-Olivencia); La Paz University Hospital, Madrid (S García-Bujalance); Doctor Negrín University Hospital, Las Palmas de Gran Canaria, Spain (R. Elcuaz-Romano);Ramón y Cajal Hospital, Madrid (M. Díaz-Menéndez); Gregorio Marañón University Hospital, Madrid (M. Calderón); Getafe University Hospital, Madrid (I. García-Bermejo); University Hospital of Fuenlabrada, Madrid (J. M. Ruiz-Giardín); Severo Ochoa University Hospital, Madrid (F.J. Merino-Fernández); University General Hospital of Alicante, Alicante, Spain (D. Torrús-Tendero);University Hospital Fundación Alcorcón, Madrid (A. Delgado-Iribarren); Hospital General de Granollers, Barcelona, Spain (M. Ribell-Bachs).

Abstract

Sequencing data from Plasmodium ovale genotypes co-circulating in multiple countries support the hypothesis that P. ovale curtisi and P. ovale wallikeri are 2 separate species. We conducted a multicenter, retrospective, comparative study in Spain of 21 patients who had imported P. ovale curtisi infections and 14 who had imported P. ovale wallikeri infections confirmed by PCR and gene sequencing during June 2005–December 2011. The only significant finding was more severe thrombocytopenia among patients with P. ovale wallikeriinfection than among those with P. ovale curtisi infection (p = 0.031). However, we also found nonsignificant trends showing that patients with P. ovale wallikeri infection had shorter time from arrival in Spain to onset of symptoms, lower level of albumin, higher median maximum core temperature, and more markers of hemolysis than did those with P. ovale curtisi infection. Larger, prospective studies are needed to confirm these findings.

Malaria caused by Plasmodium ovale infection has been considered a low-prevalence disease with limited geographic distribution, benign clinical course, and easy treatment; therefore, little attention has been paid to it. Diagnosis of P. ovale malaria can be difficult because of low parasitemia levels, mixed infections with other Plasmodium species, and false negatives from malaria rapid diagnostic tests (RDTs) (1). However, recent epidemiologic studies conducted by using PCR techniques have found P. ovale infections in most of sub-Saharan Africa, Southeast Asia, and the Indian subcontinent (2–5), including prevalence as high as 15% according to results of cross-sectional studies conducted in rural Nigeria (6) and Papua New Guinea (7). In addition, severe complications such as spleen rupture, severe anemia, or acute respiratory distress syndrome (ADRS) (8) may occur in patients with P. ovale malaria. Thus, the global burden of P. ovale infection might have been underestimated.

On the basis of differences in its gene sequences, P. ovale was considered to be dimorphic or to comprise 2 subspecies (2,3,9,10). This difference has hampered molecular diagnosis in some cases because of lack of DNA amplification by PCR with gene-specific primers for the small subunit ribosomal RNA (ssrRNA) (10). These subspecies had been named classic and variant P. ovale, but a comprehensive study recently described differences between these subspecies in at least 6 genes (4). These findings demonstrate that P. ovale actually consists of 2 subspecies that co-circulate in Africa and Asia and that are unable to recombine genetically; the differences seem to be explained by real biological factors, rather than ecologic or geographic factors (11).P. ovale curtisi and P. ovale wallikeri were the names proposed for these species (4).

Scant information is available on differences in clinical and analytical features, relapse profile, or accuracy of RDT results between these proposed species. Relatively high parasitemia levels were found in some patients with P. ovale wallikeri infection in Thailand (12), Vietnam (13), and Flores Island (14). A study published from a disease-endemic area of Bangladesh reported on the clinical features and degree of parasitemia in 13 patients with P. ovale wallikeri infection and 10 with P. ovale curtisi infection (5). These infections were diagnosed by PCR; only 4 of the 23 patients were symptomatic. Another recent study compared parasitemia levels, RDT results, and patient country of origin for 31 patients from Côte d’Ivoire and the Comoros Islands with imported P. ovale wallikeri infection and 59 with P. ovale curtisi infection, but no clinical data were provided (15). Clearly, information on these infections is limited.

Growth in international travel and migration has increased the incidence of imported malaria in industrialized countries. P. ovale infection may represent up to 8% of imported malaria cases, according to some published series of patients primarily from West Africa (16,17), where the proportion of sub-Saharan immigrants is high and PCR has been systematically performed. Yet, it is difficult to gather a substantial number of cases with clinico-epidemiologic correlation and molecular data. To identify clinical or analytical differences between P. ovale wallikeri and P. ovale curtisi infections and expand data on these infections, we conducted a multicenter, retrospective, comparative study of imported P. ovale infections diagnosed in Spain during 2005–2011.