Korean J Parasitol. Vol. 47, No. 3: 299-302, September 2009 DOI: 10.3347/kjp.2009.47.3.299 BRIEF COMMUNICATION Imported Malaria in Korea: a 13-Year Experience in a Single Center
Hae Suk Cheong1,�, Ki-Tae Kwon2,�, Ji-Young Rhee3, Seong Yeol Ryu4, Dong Sik Jung5,
Sang Taek Heo6, Sang Yop Shin7, Doo Ryun Chung8, Kyong Ran Peck8,� and Jae-Hoon Song8,9
1Division of Infectious Diseases, Konkuk University Hospital, Konkuk University School of Medicine, Seoul 143-779, Korea; 2Division of InfectiousDiseases, Daegu Fatima Hospital, Daegu 701-600, Korea; 3Division of Infectious Diseases, Dankook University Hospital, Dankook University Schoolof Medicine, Cheonan 330-715, Korea; 4Division of Infectious Diseases, Keimyung University Dongsan Medical Center, Keimyung University Schoolof Medicine, Daegu 700-712, Korea; 5Division of Infectious Diseases, Dong-A University Medical Center, Dong-A University School of Medicine,Busan 602-715, Korea; 6Division of Infectious Diseases, Gyeongsang Institute of Health Sciences, Gyeongsang National University Hospital, Jinju660-702, Korea; 7Division of Infectious Diseases, Cheju National University Hospital, Cheju National University, Jeju 690-716, Korea; 8Division ofInfectious Diseases, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul 135-710, Korea; 9Asian-Pacific ResearchFoundation for Infectious Diseases (ARFID), Seoul 135-710, KoreaAbstract: The incidence of imported malaria has been increasing in Korea. We reviewed data retrospectively to evaluate the epidemiology, clinical features, and outcomes of imported malaria from 1995 to 2007 in a university hospital. All patients diagnosed with imported malaria were included. Imported malaria was defined as a positive smear for malaria that was acquired in a foreign country. A total of 49 patients (mean age, 35.7 year; M : F = 38 : 11) were enrolled. The predominant malarial species was Plasmodium falciparum (73.5%), and the most frequent area of acquisition was Africa (55.1%), fol- lowed by Southeast Asia (22.4%) and South Asia (18.4%). Fourteen-patients (30.6%) suffered from severe malaria caused by P. falciparum and 1 patient (2.0%) died of multiorgan failure. Most of the patients were treated with mefloquine (79.2%) or quinine (10.2%); other antimalarial agents had to be given in 13.2% treated with mefloquine and 44.4% with quinine due to adverse drug events (ADEs). P. falciparum was the most common cause of imported malaria, with the majority of cases acquired from Africa, and a significant number of patients had severe malaria. Alternative antimalarial agents with lower rates of ADEs might be considered for effective treatment instead of mefloquine and quinine.
Key words: Plasmodium, imported malaria, adverse drug events, mefloquine, quinine
Malaria is one of the most severe public health problems world-
ia-endemic counties for vacation or missionary works. About
wide. It is a leading cause of disease and death in many devel-
40-80 cases of imported malaria have been diagnosed in South
oping countries. An estimated 1 million deaths occur every year
Korea per year [4,5]. However, the above studies reported only
due to malaria [1]. Malaria due to Plasmodium vivax, the only
the clinical epidemiology of imported malaria in Korea [3,5].
naturally occurring human malaria in Korea, was endemic to
The clinical characteristics and treatment outcomes of import-
Korea until the late 1970s, when the country became malaria
ed malaria in South Korea have not been previously reported.
free. After its first reemergence in 1993, the prevalence of malar-
We therefore systematically reviewed the clinical characteristics
ia increased exponentially, peaking in 2000, and since then the
and treatment outcomes of imported malaria, and also assessed
rates of infection have been decreasing. In total, 21,419 cases
the frequency of adverse drug events (ADEs) associated with the
were reported between 1993 and 2005 in South Korea [2]. In
first line therapeutic anti-malarial regimens.
the 1960s and 1970s, many cases of imported malaria were
Imported malaria was defined as a positive smear for malaria
reported in Korea because of the participation of Korean troops
acquired in another country, outside of South Korea. The med-
in the Vietnamese War as Allied Forces in 1965 [3]. Recently,
ical records were retrospectively reviewed among all patients
an increasing number of Koreans have been traveling to malar-
with imported malaria diagnosed at the Samsung Medical Center(SMC) from January 1995 to December 2007. The diagnosiswas based on microscopic examination of thick and thin blood
● Received 14 November 2008, revised 17 April 2009, accepted 16 May 2009.
smears. Severe malaria was defined according to the World Health
* Corresponding author (krpeck@skku.edu)�HS Cheong and KT Kwon contributed equally to this study.
Organization (WHO) criteria [6]. We reviewed the electronic
Korean J Parasitol. Vol. 47, No. 3: 299-302, September 2009
database of medical records to analyze the travel history, use of
binemia over 3.0 mg/dl was detected in 13 patients (92.9%),
chemoprophylaxis, clinical features, species of Plasmodium detect-
disseminated intravascular coagulation (DIC) in 7 patients (50.0
ed, complications, treatment, and outcome. The time to defer-
%), pulmonary edema in 5 patients (35.7%) and parasitemia
vescence was defined as the interval from initiation of appro-
over 5% in 4 patients (28.6%) (Table 3). An exchange transfu-
priate antimalarial treatment until the documentation of nor-
sion was performed in 3 patients infected with P. falciparum. The
mal body temperature for more than 24 hr.
median number of days to defervescence was 3.6 days (range
During the study period, 49 patients were diagnosed with im-
2-7 days). All patients except 1 survived. Mefloquine was the
ported malaria in SMC. Thirty-five patients were infected with
most frequently prescribed medication (38/49, 77.6%). Quinine
only Plasmodium falciparum, while 8 patients were diagnosed with
was used in 9 patients (9/49, 18.4%) (Table 4). Among the
only P. vivax infection. There were 2 cases of mixed infections
mefloquine-treated patients, 7 had gastrointestinal symptoms,
with P. falciparum and P. vivax or P. falciparum and Plasmodium
such as nausea and vomiting. Among the quinine-treated
ovale. The exact species of the other cases (N = 4) were undeter-
patients, 5 developed cinchonism, seizures, and vomiting (Table
mined. There were 38 male and 11 female patients. Their agewas 35.7 ± 11.0 year (12-58 year). The epidemiological char-
Table 2. Clinical and laboratory findings at presentation
acteristics are described in Table 1. Africa appeared to be the most
common region of acquisition of infection (27/47, 55.1%).
Business (15/49, 30.6%) was the most common purpose of
travel, followed by missionary works (14/49, 28.6%). Table 2
shows the clinical and laboratory findings of the patients at pre-
sentation. In all cases, fever was the presenting symptom. At
presentation, 35 (71.4%) patients had abnormal liver enzyme
levels, and 30 (61.2%) had thrombocytopenia (i.e., platelets <
100,000/μl). According to the WHO severe malaria criteria, 14
patients were classified as having severe malaria: hyperbiliru-
Table 1. The characteristics of patients with imported malaria
AST, aspartate aminotransferase; ALT, alanine aminotransferase.
Table 3. Findings associated with severe malaria
aIncluding 2 mixed infection cases with P. falciparum and P. vivax or P.
aAll cases are Plasmodium falciparum infection. falciparum and P. ovale.
DIC, disseminated intravascular coagulation.
Cheong et al.: Imported malaria in Korea: experience in a single center 301
Table 4. Therapy and outcomes of patients with imported malaria
Table 5. Adverse events associated with mefloquine and quinine
malaria in adults. In order to use intravenous quinine and arte-
sunate, clinicians have to formally request these agents to the
National Medical Center. In our study, about 1/5 of the patients
who were taking mefloquine had gastrointestinal symptoms,
such as nausea and vomiting. ADEs leading to discontinuation
of treatment occurred in 13.2% of the patients treated with meflo-
quine. By contrast, Ki et al. [8] reported that mefloquine based
chemoprophylaxis was well tolerated in Korean patients; only
0.6% of patients receiving mefloquine had ADEs. This difference
in the frequency of ADEs with mefloquine treatment might be
Total number exceeds 49 because secondary treatment agents are in-cluded.
attributed to the difference in the doses used and the patient’sgeneral condition.
5). Five patients (13.2%) among the mefloquine-treated group
It is well known that multidrug-resistant falcifarum malaria
and 4 patients (44.4%) treated with quinine had to be treated
emerged in Southeast Asia, especially at the border between Thai-
with alternative antimalarial agents due to ADEs.
land and Myanmar or Thailand and Cambodia. Because many
P. falciparum infection accounted for 70.3% (N = 26) of cases
Koreans visit Thailand and Cambodia, healthcare-providers must
from Africa (all cases developed in sub-Saharan Africa), 16.2%
be aware of potential resistance when treating patients returning
(N = 6) from Southeast Asia, and 10.8% (N = 4) from South
from these areas [9]. With the increase in international travels,
Asia. These proportions were similar to the data from the Korean
imported malaria might become a more common problem for
Center for Disease Control and Prevention [4]. Severe malaria
healthcare providers. Improved educational programs for over-
attacks occurred in 14 patients infected with P. falciparum. Severe
seas travelers should help reduce the number of imported malar-
P. falciparum malaria accounted for 64.3% (N = 9), and 35.7%
ia cases in Korea. To reduce the morbidity and mortality related
(N = 5) of infections from Southeast or South Asia. Because
to imported malaria, travelers must be informed of the malaria
severe malaria is caused by P. falciparum, rapid diagnosis and
risks, the necessity of chemoprophylaxis, and the importance
of immediate medical care if fever develops.
Malaria caused by P. falciparum is becoming resistant to anti-
malarials. Multidrug resistant malaria is one of the most signif-
ACKNOWLEDGEMENTS
icant therapeutic problems in Africa and Southeast Asia. Mostof the imported malaria identified in this study developed after
A part of this study was presented at the 17th International
traveling to Africa or Southeast Asia (77.5%). Therefore, com-
Congress for Tropical Medicine and Malaria (ICTM), Jeju Island,
bination treatment is recommended for a first-line treatment of
falciparum malaria from Africa and Asia [7]. However, meflo-quine may be effective against imported malaria, especially aga-
REFERENCES
inst P. falciparum. In Korea, the oral agent atovaquone-proguanilwas introduced a few years ago for the treatment of imported
1. Center for Disease Control and Prevention, Republic of Korea. Korean J Parasitol. Vol. 47, No. 3: 299-302, September 2009
http://www.cdc.gov/malaria/impact/index.htm
status of malaria in Korea. Yonsei Rep Trop Med 1985; 16: 11-18.
2. Han ET, Lee DH, Park KD, Seok WS, Kim YS, Tsuboi T, Shin EH,
6. Severe and complicated malaria. World Health Organization,
Chai JY. Reemerging vivax malaria: changing patterns of annual
Division of Control of Tropical Diseases. Trans R Soc Trop Med
incidence and control programs in the Republic of Korea. Korean
7. Greenwood BM, Bojang K, Whitty CJ, Targett GA. Malaria. Lancet
3. Seo BS, Lee SH, Yoon JJ, Ryang YS. Parasitological studies of
Korean forces in South Vietnam. I. Examination of blood films
8. Ki HK, Kim YS, Jung SI, Kim S, Peck KR, Song JH. Incidence of
on malaria patients. Korean J Parasitol 1970; 8: 25-29.
mefloquine-related adverse reactions in Korean travelers. J Korean
4. Center for Disease Control and Prevention, Republic of Korea.
http://www.cdc.go.kr/kcdchome/jsp/home/information/had/IN
9. Miura T, Kimura M, Koibuchi T, Endo T, Nakamura H, Odawara
FOHAD0001 Detail.jsp?menuid=100053&appid=kcdchome&
T, Wataya Y, Nakamura T, Iwamoto A. Clinical characteristics of
content=/contents/information/had/b/6312_view.html
imported malaria in Japan: analysis at a referral hospital. Am J
5. Soh CT, Lee KT, Im KI, Min DY, Ahn MH, Kim JJ, Yong TS. Current
Armidale General Surgery Patient Information regarding Gastroscopy Gastroscopy Gastroscopy (also called endoscopy or OGD) is an examination of the inner lining of the oesophagus (gullet), stomach and duodenum using a thin flexible telescope (called an endoscope). A computer chip in the end of the endoscope sends the images to a monitor (TV screen). Air is blown into the stomach to