On 29 December 2006, a 57-year old man, suffering from pulmonary tuberculosis was admitted with hemoptysis to the emergency room of a tertiary hospital in Korea. Fourteen days after admission, the patient developed the first fever episode. This developed into a high fever with concomitant anemia, thrombocytopenia, and increased bilirubin levels. Because these symptoms were similar to those of malaria, a peripheral blood smear was requested, and the patient was diagnosed as falciparum malaria with 18% parasitemia. Despite treatment with 750 mg mefloquine on 23 January 2007, the patient died from severe malaria on 24 January 2007.

On 24 December, 2006, 5 days before the admission of Case 1, a 59-year old Greek man entered through Incheon International Airport of Korea. He had traveled in Nigeria and Congo for 3 months before entry into Korea. He developed fever 2 days before entry into Korea and was admitted to a primary hospital complaining fever, cough, and muscle pain on 25 December 2006. Because of ingravescence of symptoms he was transferred to the emergency room of this hospital, which is 2 km away from the first hospital, on 30 December 2009. He was diagnosed as severe complicated falciparum malaria with 40% parasitemia. The patient stayed in the emergency room and received immediate attention with blood examination, but died 9 hr later on the same day.

After the diagnosis of falciparum malaria was confirmed in Case 1, an intensive investigation on how he acquired the infection was initiated. The patient lived in Yangsan city in a southern part of Korea. Neither he, nor his family, traveled to any area in or out of the country where malaria is endemic. Case 1 was in Vietnam from February 1970 to February 1971, but had never been out of the country since then. The patient suffered from the after-effects of dioxine. Because of this, he stayed at home, or was in hospital, since 2006. He did not reside near a harbor or an airport. Although Anopheles sinensis, Anopheles kleini, Anopheles lesteri, and Anopheles pullus are vectors for vivax malaria in Korea [7-9], the vector mosquito responsible for falciparum malaria has never been found in Korea. In addition, it has never been associated with the airport, so the possibility of luggage malaria was excluded. Furthermore, this malaria case occurred during the winter season when temperatures ranged from 0 to 10℃, which is not suitable for mosquito survival.

Case 1 had undergone transfusions 3 times (22 September 2006; 19 January 2007; 21 January 2007), but the serologic and PCR examinations of the blood had no indication of malaria. There was no history of intravenous drug use which was confirmed through the family interviews. After reviewing all medical records from the hospital, we found that these 2 falciparum malaria cases were hospitalized in the emergency room at the same time. They were in the same emergency room for 9 hr and were given several emergency diagnostic and therapeutic treatments. The 2 patients were approximately 7 m apart. Case 1 received intravenous fluid via a peripheral vein and his gastrostomy incision site was disinfected and the dressing was changed. The interventions of Case 2 consisted of blood examination, central vein catheter insertion, intubation, mechanical ventilation, and cardiac massage. It is possible that several emergency room and internal medicine staff managed both patients. We interviewed 28 hospital staffs on the procedures used to prepare and administer intravenous medication and manipulate intravenous devices. From the interviews, we found that 3 nurses and 1 emergency rescuer handled both patients. However, the evidence was not very clear and most of the staffs interviewed did not remember the Korean patient. No emergency room staff had symptoms of malaria in the succeeding weeks. Further investigation of blood samples from the 36 staffs and 34 patients who were in the emergency room were negative for malaria, as determined by PCR amplification of P. falciparum 18s rRNA gene [10] and indirect immunofluorescence assay.

To confirm this possible nosocomial transmission, sequence analysis of parasites was performed. Genomic DNA as prepared from a 3-ml blood sample from Case 1 using a DNA extraction kit (Macherey-Nargal, Düren, Germany). DNA from 2 thin Giemsa films from Case 2 was isolated using DNAzol (Invitrogen, Carlsbad, California, USA). We amplified the P. falciparum MSP-1 gene block 2 region with the allele-specific primer sets, K2F, M2F, and R2F as the forward, and C3R as the reverse (AF061126 226-579). We amplified the block 17 region with K16F and M16F as the forward and C3flaR as the reverse (AB276005 4662-5057) by PCR, as described previously [11]. PCR amplifications for the 2 patients were performed separately at different laboratories to avoid contamination. To compare the sequence of the 2 patients' P. falciparum samples and to demonstrate that there was no contamination, each of the PCR amplifications was performed with DNA from a frozen P. falciparum blood sample from Myanmar as the positive control.