A 7-day in vivo test system was applied to assess the parasitological response to chloroquine treatment in patients with falciparum malaria in the Central Province and National Capital District of Papua New Guinea. 30 patients were investigated but only 23 took a full course of chloroquine and were completely followed up. Of the 23 patients, 13 (57%) were negative for malaria parasites on day 2, 4 (17%) had significantly reduced parasitaemia by day 2 and cleared parasites by day 7, and 1 (4%) showed a partial response (R2). In 5 (22%) of the patients resistance at the R3 level was observed. The indication from this study is that chloroquine should continue to be the first-line drug for the treatment of uncomplicated falciparum malaria. However, judicious use of chloroquine in uncomplicated falciparum malaria is required to halt the spread of chloroquine-resistant strains of Plasmodium falciparum.
Antimalarials - therapeutic use ; Chloroquine - therapeutic use ; Drug Resistance ; Malaria, Falciparum - drug therapy ; Malaria, Falciparum - parasitology

Antimalarials ; therapeutic use ; Artemisinins ; therapeutic use ; Child ; Drug Therapy, Combination ; Humans ; Malaria, Falciparum ; drug therapy

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/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*

*Asia, Southeastern ; *Chloroguanide ; *Chloroquine ; *Drug Resistance, Microbial ; *Drug Therapy ; *Malaria ; *Plasmodium falciparum ; *Pyrimethamine ; *Quinacrine ; *Quinine ; *Statistics ; *Adolescent ; *Child

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/genetics/*metabolism ; Humans ; Malaria, Falciparum/drug therapy/*parasitology ; Mitochondria/*drug effects/metabolism ; Plasmodium falciparum/drug effects/*enzymology/genetics ; Protozoan Proteins/*antagonists & inhibitors/genetics/metabolism ; Quinolones/*pharmacology

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/*therapeutic use ; Child ; Child, Preschool ; China ; Female ; Humans ; Inhibitory Concentration 50 ; Malaria, Falciparum/*drug therapy/parasitology ; Male ; Middle Aged ; Parasitic Sensitivity Tests ; Plasmodium falciparum/*drug effects ; Treatment Outcome ; Young Adult

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/*therapeutic use ; Child ; Child, Preschool ; China ; Female ; Humans ; Inhibitory Concentration 50 ; Malaria, Falciparum/*drug therapy/parasitology ; Male ; Middle Aged ; Parasitic Sensitivity Tests ; Plasmodium falciparum/*drug effects ; Treatment Outcome ; Young Adult

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/therapeutic use ; Female ; Humans ; Korea/epidemiology ; Malaria, Falciparum/drug therapy/epidemiology/*parasitology ; Male ; Middle Aged ; Plasmodium falciparum/drug effects/isolation & purification ; Retrospective Studies ; *Travel

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