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%), followed 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.
Adult ; Animals ; Antimalarials/adverse effects ; Antimalarials/therapeutic use ; Female ; Humans ; Korea/epidemiology ; Malaria, Falciparum/drug therapy ; Malaria, Falciparum/epidemiology ; Malaria, Falciparum/parasitology ; Male ; Middle Aged ; Plasmodium falciparum/drug effects ; Plasmodium falciparum/isolation & purification ; Retrospective Studies ; Travel

Peripheral gangrene, characterized by distal ischemia of the extremities, is a rare complication in patients with falciparum malaria. Patients with this complication have generally undergone early amputation of the affected areas. In this report, we describe 3 adult Thai patients presented at the Hospital for Tropical Diseases, Bangkok, with high grade of fever ranged 6-9 days, jaundice, acute renal failure, respiratory failure, alteration of consciousness and shock. Two patients had gangrene developed at the lower extremities on day 1 of hospitalization and 1 patient had gangrene developed on day 3. Blood smears revealed hyperparasitemia with Plasmodium falciparum. These patients were diagnosed as having severe malaria with peripheral gangrene. The resolution of gangrene was successfully achieved by treatment with artesunate and conservative treatment in 2 of 3 cases.
Middle Aged ; Male ; Malaria, Falciparum/complications ; Malaria, Falciparum/drug therapy ; Humans ; Gangrene/etiology ; Female ; Antimalarials/therapeutic use ; Adult

With increasing travel to tropical area, the number of patients with imported malaria in this country is increasing. RBC exchange transfusion has proposed as a adjunct therapy for very severe falciparum malaria to reduce the parasite load rapidly. We report a patient with severe Plasmodium falciparum infection with 26% of erythrocyte parasitized, treated with RBC exchange transfusion in addition to conventional chemotherapy. The exchange of 1200 mL of red blood cells was carried out with 7 packed red cells using automatic cell separator. This patients recovered from his disease despite respiratory distress syndrome and acute renal failure. We conclude that RBC exchange is a useful adjunct to conventional chemotherapy and should be considered in patients with severe and complicated falciparum malaria.
Acute Kidney Injury ; Drug Therapy ; Erythrocytes ; Humans ; Malaria ; Parasite Load ; Plasmodium falciparum* ; Plasmodium*

Pyronaridine and artesunate have been shown to be effective in falciparum malaria treatment. However, pyronaridine is rarely used in Hainan Island clinically, and artesunate is not widely used as a therapeutic agent. Instead, conventional antimalarial drugs, chloroquine and piperaquine, are used, explaining the emergence of chloroquine-resistant Plasmodium falciparum. In this article, we investigated the sensitivity of P. falciparum to antimalarial drugs used in Hainan Island for rational drug therapy. We performed in vivo (28 days) and in vitro tests to determine the sensitivity of P. falciparum to antimalarial drugs. Total 46 patients with falciparum malaria were treated with dihydroartemisinin/piperaquine phosphate (DUO-COTECXIN) and followed up for 28 day. The cure rate was 97.8%. The mean fever clearance time (22.5+/-10.6 hr) and the mean parasite clearance time (27.3+/-12.2 hr) showed no statistical significance with different genders, ages, temperatures, or parasite density (P>0.05). The resistance rates of chloroquine, piperaquine, pyronarididine, and artesunate detected in vitro were 71.9%, 40.6%, 12.5%, and 0%, respectively (P<0.0001). The resistance intensities decreased as follows: chloroquine>piperaquine>pyronarididine>artesunate. The inhibitory dose 50 (IC50) was 3.77x10(-6) mol/L, 2.09x10(-6) mol/L, 0.09x10(-6) mol/L, and 0.05x10(-6) mol/L, and the mean concentrations for complete inhibition (CIMC) of schizont formation were 5.60x10(-6) mol/L, 9.26x10(-6) mol/L, 0.55x10(-6) mol/L, and 0.07x10(-6) mol/L, respectively. Dihydroartemisinin showed a strong therapeutic effect against falciparum malaria with a low toxicity.
Adolescent ; Adult ; Aged ; Antimalarials/pharmacology ; Antimalarials/therapeutic use ; Child ; Child, Preschool ; China ; Female ; Humans ; Inhibitory Concentration 50 ; Malaria, Falciparum/drug therapy ; Malaria, Falciparum/parasitology ; Male ; Middle Aged ; Parasitic Sensitivity Tests ; Plasmodium falciparum/drug effects ; Treatment Outcome ; Young Adult

The parasite Plasmodium falciparum causes severe malaria and is the most dangerous to humans. However, it exhibits resistance to their drugs. Farnesyltransferase has been identified in pathogenic protozoa of the genera Plasmodium and the target of farnesyltransferase includes Ras family. Therefore, the inhibition of farnesyltransferase has been suggested as a new strategy for the treatment of malaria. However, the exact functional mechanism of this agent is still unknown. In addition, the effect of farnesyltransferase inhibitor (FTIs) on mitochondrial level of malaria parasites is not fully understood. In this study, therefore, the effect of a FTI R115777 on the function of mitochondria of P. falciparum was investigated experimentally. As a result, FTI R115777 was found to suppress the infection rate of malaria parasites under in vitro condition. It also reduces the copy number of mtDNA-encoded cytochrome c oxidase III. In addition, the mitochondrial membrane potential (DeltaPsim) and the green fluorescence intensity of MitoTracker were decreased by FTI R115777. Chloroquine and atovaquone were measured by the mtDNA copy number as mitochondrial non-specific or specific inhibitor, respectively. Chloroquine did not affect the copy number of mtDNA-encoded cytochrome c oxidase III, while atovaquone induced to change the mtDNA copy number. These results suggest that FTI R115777 has strong influence on the mitochondrial function of P. falciparum. It may have therapeutic potential for malaria by targeting the mitochondria of parasites.
Antimalarials/pharmacology ; Enzyme Inhibitors/pharmacology ; Farnesyltranstransferase/antagonists & inhibitors ; Farnesyltranstransferase/genetics ; Farnesyltranstransferase/metabolism ; Humans ; Malaria, Falciparum/drug therapy ; Malaria, Falciparum/parasitology ; Mitochondria/drug effects ; Mitochondria/metabolism ; Plasmodium falciparum/drug effects ; Plasmodium falciparum/enzymology ; Plasmodium falciparum/genetics ; Protozoan Proteins/antagonists & inhibitors ; Protozoan Proteins/genetics ; Protozoan Proteins/metabolism ; Quinolones/pharmacology

While imported falciparum malaria has been increasingly reported in recent years in Korea, clinicians have difficulties in making a clinical diagnosis as well as in having accessibility to effective anti-malarial agents. Here we describe an unusual case of imported falciparum malaria with severe hemolytic anemia lasting over 2 weeks, clinically mimicking a coinfection with babesiosis. A 48-year old Korean man was diagnosed with severe falciparum malaria in France after traveling to the Republic of Benin, West Africa. He received a 1-day course of intravenous artesunate and a 7-day course of Malarone (atovaquone/proguanil) with supportive hemodialysis. Coming back to Korea 5 days after discharge, he was readmitted due to recurrent fever, and further treated with Malarone for 3 days. Both the peripheral blood smears and PCR test were positive for Plasmodium falciparum. However, he had prolonged severe hemolytic anemia (Hb 5.6 g/dl). Therefore, 10 days after the hospitalization, Babesia was considered to be potentially coinfected. A 7-day course of Malarone and azithromycin was empirically started. He became afebrile within 3 days of this babesiosis treatment, and hemolytic anemia profiles began to improve at the completion of the treatment. He has remained stable since his discharge. Unexpectedly, the PCR assays failed to detect DNA of Babesia spp. from blood. In addition, during the retrospective review of the case, the artesunate-induced delayed hemolytic anemia was considered as an alternative cause of the unexplained hemolytic anemia.
Anemia, Hemolytic/chemically induced ; Anemia, Hemolytic/etiology ; Anemia, Hemolytic/pathology ; Anti-Bacterial Agents/therapeutic use ; Antimalarials/therapeutic use ; Artemisinins/adverse effects ; Artemisinins/therapeutic use ; Atovaquone/therapeutic use ; Azithromycin/therapeutic use ; Babesiosis/complications ; Babesiosis/diagnosis ; Babesiosis/drug therapy ; Babesiosis/pathology ; Benin ; Blood/parasitology ; Coinfection/diagnosis ; Coinfection/pathology ; Drug Combinations ; France ; Humans ; Korea ; Malaria, Falciparum/complications ; Malaria, Falciparum/diagnosis ; Malaria, Falciparum/drug therapy ; Malaria, Falciparum/pathology ; Male ; Middle Aged ; Plasmodium falciparum/isolation & purification ; Proguanil/therapeutic use ; Travel ; Treatment Outcome

Artemisinin-based combination therapy (ACT) is currently promoted as a strategy for treating both uncomplicated and severe falciparum malaria, targeting asexual blood-stage Plasmodium falciparum parasites. However, the effect of ACT on sexual-stage parasites remains controversial. To determine the clearance of sexual-stage P. falciparum parasites from 342 uncomplicated, and 217 severe, adult malaria cases, we reviewed and followed peripheral blood sexualstage parasites for 4 wk after starting ACT. All patients presented with both asexual and sexual stage parasites on admission, and were treated with artesunate-mefloquine as the standard regimen. The results showed that all patients were asymptomatic and negative for asexual forms before discharge from hospital. The percentages of uncomplicated malaria patients positive for gametocytes on days 3, 7, 14, 21, and 28 were 41.5, 13.1, 3.8, 2.0, and 2.0%, while the percentages of gametocyte positive severe malaria patients on days 3, 7, 14, 21, and 28 were 33.6, 8.2, 2.7, 0.9, and 0.9%, respectively. Although all patients were negative for asexual parasites by day 7 after completion of the artesunate-mefloquine course, gametocytemia persisted in some patients. Thus, a gametocytocidal drug, e.g., primaquine, may be useful in combination with an artesunate-mefloquine regimen to clear gametocytes, so blocking transmission more effectively than artesunate alone, in malaria transmission areas.
Adolescent ; Adult ; Animals ; Antimalarials/pharmacology ; Antimalarials/therapeutic use ; Artemisinins/pharmacology ; Artemisinins/therapeutic use ; Drug Evaluation ; Drug Therapy, Combination ; Female ; Follow-Up Studies ; Germ Cells/drug effects ; Germ Cells/growth & development ; Humans ; Malaria, Falciparum/drug therapy ; Malaria, Falciparum/parasitology ; Male ; Mefloquine/pharmacology ; Mefloquine/therapeutic use ; Plasmodium falciparum/drug effects ; Plasmodium falciparum/growth & development ; Severity of Illness Index ; Thailand ; Treatment Outcome

Genetic characteristics of Plasmodium falciparum may play a role in the treatment outcome of malaria infection. We have studied the association between diversity at the merozoite surface protein-1 (msp-1), msp-2, and glutamate-rich protein (glurp) loci and the treatment outcome of uncomplicated falciparum malaria patients along the Thai-Myanmar border who were treated with artemisinin derivatives combination therapy. P. falciparum isolates were collected prior to treatment from 3 groups of patients; 50 cases of treatment failures, 50 recrudescences, and 56 successful treatments. Genotyping of the 3 polymorphic markers was analyzed by nested PCR. The distribution of msp-1 alleles was significantly different among the 3 groups of patients but not the msp-2 and glurp alleles. The allelic frequencies of K1 and MAD20 alleles of msp1 gene were higher while RO33 allele was significantly lower in the successful treatment group. Treatment failure samples had a higher median number of alleles as compared to the successful treatment group. Specific genotypes of msp-1, msp-2, and glurp were significantly associated with the treatment outcomes. Three allelic size variants were significantly higher among the isolates from the treatment failure groups, i.e., K1270-290, 3D7610-630, G650-690, while 2 variants, K1150-170, and 3D7670-690 were significantly lower. In conclusion, the present study reports the differences in multiplicity of infection and distribution of specific alleles of msp-1, msp-2, and glurp genes in P. falciparum isolates obtained from treatment failure and successful treatment patients following artemisinin derivatives combination therapy.
Adult ; Antigens, Protozoan/genetics ; Antimalarials/therapeutic use ; Artemisinins/therapeutic use ; Female ; Gene Frequency ; Genetic Variation ; Genotype ; Humans ; Malaria, Falciparum/drug therapy ; Malaria, Falciparum/parasitology ; Male ; Merozoite Surface Protein 1/genetics ; Myanmar ; Plasmodium falciparum/classification ; Plasmodium falciparum/genetics ; Plasmodium falciparum/isolation & purification ; Polymerase Chain Reaction ; Protozoan Proteins/genetics ; Thailand ; Treatment Failure

Cerebral malalria is a life-threatening complication of Plasmodium falciparum infection. RBC exchange transfusion (RCE) can reduce the burden of parasitemia in this situation. We have experienced two cases of cerebral malaria treated with automated RBC exchange as an adjunct to standard chemotherapy. Case 1: A 42-year-old male was referred to the emergency room with a history of 3 days of fever after having returned from Congo. Peripheral blood smear showed the P. falciparum parasitemia of 70-80%. Quinidine and doxycycline were administered but, mental state started to deteriorate. He underwent RCE on hospital day 2 to reduce the parasitemia to 10% after 8 hours. No parasite could be found on day 3 after the RCE. Case 2: A 62-year-old male was referred to the emergency room with a history of 3 days of fever after having returned from Cameroon. P. falciparum parasitemia was 10% on peripheral blood smear. Quinidine and doxycycline were immediately started but headache developed abruptly and he underwent RCE on hospital day 3. After 8 hours following the completion of RCE, parasitemia decreased to less than 1%. Automated RBC exchange transfusion can rapidly reduce the burden of parasitemia and achieve improvement of neurologic symptom and sign in patients with cerebral malaria.
Adult ; Cameroon ; Congo ; Doxycycline ; Drug Therapy ; Emergency Service, Hospital ; Fever ; Headache ; Humans ; Malaria, Cerebral* ; Male ; Middle Aged ; Neurologic Manifestations ; Parasitemia ; Parasites ; Plasmodium falciparum ; Quinidine

In recent years, the incidence of imported cases infested with Plasmodium falciparum has been increasing in Korea due to marked increase in travel to malarious area without adequate prophylaxis. Cerebral malaria is an encephalopathy, occasionally associated with infestation of P. falciparum, which can complicate some patients infected with Plasmodium falciparum leading to significant mortality. We experienced a case of 45 year-ld male with cerebral malaria, complicated with disseminated intravascular coagulation and acute renal failure. The patient was thought to be infected in travel to Indonesia, Laos, and Bangkok. Blood smear showed typical multiple intra-rythrocytic ring form trophozoites and banana-haped gametocytes of Plasmodium falciparum. The patient died after comatose state with respiration failure for 24 days despite treatment with exchange transfusion, hemodialysis and chemotherapy. We report this case with a review of the literature.
Acute Kidney Injury ; Coma ; Disseminated Intravascular Coagulation ; Drug Therapy ; Humans ; Incidence ; Indonesia ; Korea ; Laos ; Malaria, Cerebral* ; Male ; Mortality ; Plasmodium falciparum* ; Plasmodium* ; Renal Dialysis ; Renal Insufficiency* ; Respiration ; Trophozoites