In March 2001, a 75-year-old woman was admitted to the Hospital Príncipe de Asturias in Madrid with a history of intermittent fever for 1 week and no obvious infection. Intravenous treatment with ciprofloxacin was prescribed to treat provisionally diagnosed pyelonephritis. While in hospital, the patient had two episodes of high fever (39°C–40°C) separated by 48-hour intervals with hypoxemia and deterioration of her general condition. On day 7 of fever, the hematologist advised the physician of the presence of rings inside the patient’s erythrocytes (parasitemia rate <1 %). A rapid antigen detection test (HRP2 detection; ICT Diagnostics, Amrad Corporation, Victor, Australia) was done; the test returned negative results for Plasmodium falciparum and P. vivax. The sample was later identified as P. ovale through microscopy and molecular studies at a reference malaria laboratory. Initial treatment with chloroquine followed by primaquine eliminated the infection successfully, and the patient recovered fully without complications.

P. ovale was confirmed by semi-nested multiplex polymerase chain reaction (PCR) (8). DNA isolation was carried out with Chelex (9) and the total DNA with the QIAamp DNA Blood Mini Kit (QIAGEN GmbH, Hilden, Germany); the sample was amplified, and a 499-bp fragment compatible with P. ovale was determined. PCR was repeated by using primers at two different temperatures, and the presence of P. ovale fragments was confirmed. The P. ovale fragments, initially embedded in the agarose gel, were then extracted with the help of the column for DNA purification. The rDNA was also amplified by using four specific primers (two forward and two reverse) at two different temperatures to obtain a large quantity of DNA for posterior sequencing. The product of amplification was sequenced in the ABISPRISM 377 XL DNA automatic sequencer (PE Applied Biosystems, Foster City, CA). Afterwards, sequences were sent to the GenBank database; in all the cases, 100% homology for the small subunit of the P. ovale rRNA gene was confirmed.

This case is the first locally acquired P. ovale infection connected with Europe. The infection may have been transmitted by an odyssean vector. The patient lives 4 and 18 km away from international airports, within the radius of other previously reported airport malaria cases (4,12). The case may also have been transmitted by a local mosquito (introduced malaria) (5). In Spain, a possible vector for local infection is An. atroparvus, since this species has shown receptivity to P. vivax (10) and possibly could be receptive to P. ovale as well. The infection could have also been transmitted by an odyssean African vector such as An. gambiae (4). Surprisingly, the illness began when cold temperatures started. Thus, the disease could have been a relapse from hepatic hypnozoite or a primoinfection produced by the bite of an inhouse hibernating infected Anopheles spp. female (11). Whatever the mechanism, the diagnosis was complicated by the fact that the disease occurred during the winter.

Spain hosts a growing number of migrant workers from west and central Africa traveling through the Gibraltar Strait. Tourism and international flights to and from tropical countries have multiplied in recent years (12). All these factors can account for occasional or epidemic reintroduction of malaria into the country.

Although some studies indicate that indigenous mosquitoes such as An. labranquiae and An. atroparvus are not susceptible to the afrotropical P. falciparum strains (2,10), these species of anophelines are probably fully susceptible to infection by P. vivax and P. ovale strains imported from Africa. In addition, Asian or American P. falciparum strains may also be imported.

In Europe, malaria transmission can also occur in urban settings given the appropriate conditions. Malaria should be considered in patients with a fever of unknown origin, even if they have never traveled to malaria-endemic areas. Increased attention should be given to persons who work or live close to international airports or in areas with high population of new foreign residents from malarious areas. Hospital laboratories should be ready to detect malaria parasitemia on a 24-hour basis (thick films or antigen detection if microscopy expert is unavailable) on a physician’s request. Likewise, PCR techniques should be used to detect retrospectively low parasitemias and confirm the species diagnosis. We suggest that epidemiologic and clinical attention should be given to travelers and newly arrived foreign residents from malaria-endemic countries to prevent secondary cases (13). Simple, easy access to health care for recently arrived migrant workers should be implemented to assess risk factors and screen for malaria if necessary.