In Plasmodium vivax and Plasmodium ovale malaria, some of the liver stage parasites remain dormant. The activation of these dormant forms (called hypnozoite) can give rise to relapse weeks, months or years after the initial infection. To prevent relapses, a course of primaquine may be given as terminal prophylaxis to patients. Different strains of Plasmodium vivax vary in their sensitivity to primaquine and, recently, cases of relapse of Plasmodium vivax after this standard primaquine therapy were reported from various countries. We reported a case of primaquine resistant malaria which initially was thought to be relapsed caused by loss of terminal prophylaxis.
Animal ; Antimalarials/therapeutic use* ; Case Report ; Chloroquine/therapeutic use ; Drug Resistance ; Human ; Malaria, Vivax/parasitology ; Malaria, Vivax/drug therapy* ; Male ; Middle Age ; Plasmodium vivax/growth & development ; Plasmodium vivax/drug effects ; Primaquine/therapeutic use* ; Recurrence

OBJECTIVETo compare the applicability of the SYBR Green-I assay with the standard schizont maturation assay, for determination of sensitivity of Plasmodium vivax (P. vivax) to chloroquine and a new antifolate WR 99210.

METHODSThe study was conducted at Mae Tao Clinic for migrant workers, Tak Province during April 2009 to July 2010. A total of 64 blood samples (1 mL blood collected into sodium heparinized plastic tube) were collected from patients with mono-infection with P. vivax malaria prior to treatment with standard regimen of a 3-day chloroquine. In vitro sensitivity of P. vivax isolates was evaluated by schizont maturation inhibition and SYBR Green-I assays.

RESULTSA total of 30 out of 64 blood samples collected from patients with P. vivax malaria were successfully analyzed using both the microscopic schizont maturation inhibition and SYBR Green-I assays. The failure rates of the schizont maturation inhibition assay (50%) and the SYBR Green-I assay (54%) were similar (P=0.51). The median IC10s, IC50s and IC90s of both chloroquine and WR99210 were not significantly different from the clinical isolates of P. vivax tested. Based on the cut-off of 100 nM, the prevalences of chloroquine resistance determined by schizont maturation inhibition and SYBR Green-I assays were 19 and 11 isolates, respectively. The strength of agreement between the two methods was very poor for both chloroquine and WR99210.

CONCLUSIONSOn the basis of this condition and its superior sensitivity, the microscopic method appears better than the SYBR Green-I Green assay for assessing in vitro sensitivity of fresh P. vivax isolates to antimalarial drugs.

Antimalarials ; pharmacology ; Chloroquine ; pharmacology ; Humans ; Inhibitory Concentration 50 ; Malaria, Vivax ; parasitology ; Organic Chemicals ; Parasitemia ; parasitology ; Parasitic Sensitivity Tests ; Plasmodium vivax ; drug effects ; isolation & purification ; Schizonts ; drug effects

The annual incidence of Plasmodium vivax malaria that reemerged in the Republic of Korea (ROK) in 1993 increased annually, reaching 4,142 cases in 2000, decreased to 864 cases in 2004, and once again increased to reach more than 2,000 cases by 2007. Early after reemergence, more than two-thirds of the total annual cases were reported among military personnel. However, subsequently, the proportion of civilian cases increased consistently, reaching over 60% in 2006. P. vivax malaria has mainly occurred in the areas adjacent to the Demilitarized Zone, which strongly suggests that malaria situation in ROK has been directly influenced by infected mosquitoes originating from the Democratic People's Republic of Korea (DPRK). Besides the direct influence from DPRK, local transmission within ROK was also likely. P. vivax malaria in ROK exhibited a typical unstable pattern with a unimodal peak from June through September. Chemoprophylaxis with hydroxychloroquine (HCQ) and primaquine, which was expanded from approximately 16,000 soldiers in 1997 to 200,000 soldiers in 2005, contributed to the reduction in number of cases among military personnel. However, the efficacy of the mass chemoprophylaxis has been hampered by poor compliance. Since 2000, many prophylactic failure cases due to resistance to the HCQ prophylactic regimen have been reported and 2 cases of chloroquine (CQ)-resistant P. vivax were reported, representing the first-known cases of CQ-resistant P. vivax from a temperate region of Asia. Continuous surveillance and monitoring are warranted to prevent further expansion of CQ-resistant P. vivax in ROK.
Antimalarials/administration & dosage ; Chemoprevention ; *Disease Outbreaks ; Drug Resistance ; Humans ; Malaria, Vivax/drug therapy/*epidemiology/parasitology/prevention & control ; Military Personnel ; Plasmodium vivax/drug effects/*physiology ; Republic of Korea/epidemiology

Liver function tests were performed in 61 vivax, 54 malariae and 15 ovale malaria patients who were admitted to Bangkok Hospital for Tropical Diseases between 2001 and 2004. The objective of the study was to evaluate changes in hepatic biochemical indices before and after treatment with artemisinin derivatives. On admission and prior to treatment, hepatic dysfunction was found among the 3 groups. Serum liver function tests and physical examinations were performed weekly during the 28-day follow-up period. Initially elevated serum bilirubin and diminished albumin returned to normal within 2 weeks of treatment. Serum alkaline phosphatase and aminotransferases returned to within normal limits within 3 weeks. We conclude that patients with Plasmodium vivax, P. malariae and P. ovale infections had slightly elevated serum bilirubin, aminotransferase and alkaline phosphatase levels, and hypoalbuminemia. These minor abnormalities returned to normal within a few weeks after treatment with therapies based on artemisinin derivatives.
Treatment Outcome ; Sesquiterpenes/*therapeutic use ; Serum Albumin ; Plasmodium vivax/*drug effects/pathogenicity ; Plasmodium ovale/*drug effects/pathogenicity ; Plasmodium malariae/*drug effects/pathogenicity ; Middle Aged ; Male ; Malaria, Vivax/drug therapy/parasitology/physiopathology ; Malaria/*drug therapy/parasitology/physiopathology ; Liver Function Tests ; Liver/*physiopathology ; Humans ; Female ; Bilirubin/blood ; Artemisinins/*therapeutic use ; Anti-Infective Agents/therapeutic use ; Animals ; Alanine Transaminase/blood ; Adult ; Adolescent

We conducted a study to compare the safety and tolerability of anti-relapse drugs elubaquine and primaquine against Plasmodium vivax malaria. After standard therapy with chloroquine, 30 mg/kg given over 3 days, 141 patients with P. vivax infection were randomized to receive primaquine or elubaquine. The 2 treatment regimens were primaquine 30 mg once daily for 7 days (group A, n = 71), and elubaquine 25 mg once daily for 7 days (group B, n = 70). All patients cleared parasitemia within 7 days after chloroquine treatment. Among patients treated with primaquine, one patient relapsed on day 26; no relapse occurred with elubaquine treatement. Both drugs were well tolerated. Adverse effects occurred only in patients with G6PD deficiency who were treated with primaquine (group A, n = 4), whose mean hematocrit fell significantly on days 7, 8 and 9 (P = 0.015, 0.027, and 0.048, respectively). No significant change in hematocrit was observed in patients with G6PD deficiency who were treated with elubaquine (group B, n = 3) or in patients with normal G6PD. In conclusion, elubaquine, as anti-relapse therapy for P. vivax malaria, was as safe and well tolerated as primaquine and did not cause clinically significant hemolysis.
Thailand ; Prospective Studies ; Primaquine/adverse effects/*analogs & derivatives/therapeutic use ; *Plasmodium vivax ; Middle Aged ; Male ; Malaria, Vivax/*drug therapy ; Humans ; Female ; Chloroquine/therapeutic use ; Antimalarials/*adverse effects/therapeutic use ; Animals ; Adult ; Adolescent

The aim of the study was to explore the possible molecular markers of chloroquine resistance in Plasmodium vivax isolates in Thailand. A total of 30 P. vivax isolates were collected from a malaria endemic area along the Thai-Myanmar border in Mae Sot district of Thailand. Dried blood spot samples were collected for analysis of Pvmdr1 and Pvcrt-o polymorphisms. Blood samples (100 mul) were collected by finger-prick for in vitro chloroquine susceptibility testing by schizont maturation inhibition assay. Based on the cut-off IC50 of 100 nM, 19 (63.3%) isolates were classified as chloroquine resistant P. vivax isolates. Seven non-synonymous mutations and 2 synonymous were identified in Pvmdr1 gene. Y976F and F1076L mutations were detected in 7 (23.3%) and 16 isolates (53.3%), respectively. Analysis of Pvcrt-o gene revealed that all isolates were wild-type. Our results suggest that chloroquine resistance gene is now spreading in this area. Monitoring of chloroquine resistant molecular markers provide a useful tool for future control of P. vivax malaria.
Amino Acid Substitution ; Antimalarials/*pharmacology ; Chloroquine/*pharmacology ; *Drug Resistance ; Humans ; Inhibitory Concentration 50 ; Malaria, Vivax/*parasitology ; Membrane Transport Proteins/*genetics ; Multidrug Resistance-Associated Proteins/*genetics ; Mutation, Missense ; Myanmar ; Parasitic Sensitivity Tests ; Plasmodium vivax/*drug effects/genetics ; Protozoan Proteins/*genetics ; Thailand

The aim of the study was to explore the possible molecular markers of chloroquine resistance in Plasmodium vivax isolates in Thailand. A total of 30 P. vivax isolates were collected from a malaria endemic area along the Thai-Myanmar border in Mae Sot district of Thailand. Dried blood spot samples were collected for analysis of Pvmdr1 and Pvcrt-o polymorphisms. Blood samples (100 mul) were collected by finger-prick for in vitro chloroquine susceptibility testing by schizont maturation inhibition assay. Based on the cut-off IC50 of 100 nM, 19 (63.3%) isolates were classified as chloroquine resistant P. vivax isolates. Seven non-synonymous mutations and 2 synonymous were identified in Pvmdr1 gene. Y976F and F1076L mutations were detected in 7 (23.3%) and 16 isolates (53.3%), respectively. Analysis of Pvcrt-o gene revealed that all isolates were wild-type. Our results suggest that chloroquine resistance gene is now spreading in this area. Monitoring of chloroquine resistant molecular markers provide a useful tool for future control of P. vivax malaria.
Amino Acid Substitution ; Antimalarials/*pharmacology ; Chloroquine/*pharmacology ; *Drug Resistance ; Humans ; Inhibitory Concentration 50 ; Malaria, Vivax/*parasitology ; Membrane Transport Proteins/*genetics ; Multidrug Resistance-Associated Proteins/*genetics ; Mutation, Missense ; Myanmar ; Parasitic Sensitivity Tests ; Plasmodium vivax/*drug effects/genetics ; Protozoan Proteins/*genetics ; Thailand

Changing patterns of the reemerging Plasmodium vivax malaria in the Republic of Korea (South Korea) during the period 1993 to 2005 are briefly analyzed with emphasis on the control measures used and the effects of meteorological and entomological factors. Data were obtained from the Communicable Diseases Monthly Reports published by the Korea Center for Disease Control and Prevention, and webpages of World Health Organization and United Nations. Meteorological data of Kangwon-do (Province) were obtained from local weather stations. After its first reemergence in 1993, the prevalence of malaria increased exponentially, peaking in 2000, and then decreased. In total, 21,419 cases were reported between 1993 and 2005 in South Korea. In North Korea, a total of 916,225 cases were reported between 1999 and 2004. The occurrence of malaria in high risk areas of South Korea was significantly (P<0.05) correlated with the mosquito population but not with temperature and rainfall. Control programs, including early case detection and treatment, mass chemoprophylaxis of soldiers, and international financial aids to North Korea for malaria control have been instituted. The situation of the reemerging vivax malaria in the Republic of Korea is remarkably improving during the recent years, at least in part, due to the control activities undertaken in South and North Korea.
Seasons ; Plasmodium vivax/drug effects ; Military Personnel/statistics & numerical data ; Malaria, Vivax/*epidemiology/parasitology/*prevention & control ; Korea/epidemiology ; Incidence ; Humans ; Disease Outbreaks/*prevention & control ; Communicable Diseases, Emerging/*epidemiology/parasitology/*prevention & control ; Chloroquine/administration & dosage ; Antimalarials/administration & dosage ; Anopheles/parasitology ; Animals

Chloroquine remains the drug of choice for the treatment of vivax malaria in Thailand. Mixed infections of falciparum and vivax malaria are also common in South-East Asia. Laboratory confirmation of malaria species is not generally available. This study aimed to find alternative regimens for treating both malaria species by using falciparum antimalarial drugs. From June 2004 to May 2005, 98 patients with Plasmodium vivax were randomly treated with either artemether-lumefantrine (n = 47) or chloroquine (n = 51). Both treatments were followed by 15 mg of primaquine over 14 days. Adverse events and clinical and parasitological outcomes were recorded and revealed similar in both groups. The cure rate was 97.4% for the artemether-lumefantrine treated group and 100% for the chloroquine treated group. We concluded that the combination of artemether-lumefantrine and primaquine was well tolerated, as effective as chloroquine and primaquine, and can be an alternative regimen for treatment of vivax malaria especially in the event that a mixed infection of falciparum and vivax malaria could not be ruled out.
Adolescent ; Aged ; Animals ; Antimalarials/adverse effects/*therapeutic use ; Artemisinins/adverse effects/*therapeutic use ; Chloroquine/adverse effects/*therapeutic use ; Drug Therapy, Combination ; Ethanolamines/adverse effects/*therapeutic use ; Female ; Fluorenes/adverse effects/*therapeutic use ; Humans ; Malaria, Vivax/*drug therapy ; Male ; Middle Aged ; Parasitemia ; Plasmodium vivax/drug effects ; Primaquine/therapeutic use ; Thailand ; Treatment Outcome

Resistance of Plasmodium spp. to anti-malarial drugs is the primary obstacle in the fight against malaria, and molecular markers for the drug resistance have been applied as an adjunct in the surveillance of the resistance. In this study, we investigated the prevalence of mutations in pvmdr1, pvcrt-o, pvdhfr, and pvdhps genes in temperate-zone P. vivax parasites from central China. A total of 26 isolates were selected, including 8 which were previously shown to have a lower susceptibility to chloroquine in vitro. For pvmdr1, pvcrt-o, and pvdhps genes, no resistance-conferring mutations were discovered. However, a highly prevalent (69.2%), single-point mutation (S117N) was found in pvdhfr gene. In addition, tandem repeat polymorphisms existed in pvdhfr and pvdhps genes, which warranted further studies in relation to the parasite resistance to antifolate drugs. The study further suggests that P. vivax populations in central China may still be relatively susceptible to chloroquine and sulfadoxine-pyrimethamine.
Antimalarials/*pharmacology ; China ; Chloroquine/pharmacology ; DNA, Protozoan/chemistry/genetics ; Drug Resistance/*genetics ; Folic Acid Antagonists/pharmacology ; Genotype ; Humans ; Malaria, Vivax/epidemiology/*parasitology ; Plasmodium vivax/drug effects/*genetics/isolation & purification ; Point Mutation ; Polymorphism, Single Nucleotide/*genetics ; Prevalence ; Protozoan Proteins/genetics ; Sequence Analysis, DNA ; Tandem Repeat Sequences/*genetics