INTRODUCTIONChloroquine, in combination with primaquine, is used as the firstline treatment for uncomplicated P. vivax malaria in Thailand. In view of the declining efficacy of chloroquine in many P. vivax endemic areas, the possibility of emergence of chloroquine- resistant P. vivax in Thailand is a concern. The aim of this study was to assess the trends in therapeutic efficacy of chloroquine and primaquine for the treatment of uncomplicated P. vivax malaria and to assess the utility of parasite clearance times as a measure of efficacy.

MATERIALS AND METHODSThis study consisted of: 1) review of medical records of patients who were hospitalised for a period during their treatment for uncomplicated P. vivax malaria at the Hospital for Tropical Diseases, Bangkok, Thailand between 2004 and 2013. Treatment consisted of chloroquine (1500 mg base administered over 3 days) or chloroquine (as before) plus primaquine (15 to 30 mg base/daily for 14 days from day 2); and 2) systematic review of the literature in English to assess current standards in the reporting of parasite clearance times.

RESULTSThe 28-day cure rate was 99.1%. The range of median parasite clearance time over the 10-year period was 46 to 59 hours, and there was statistical evidence for an increasing trend in parasite clearance times between 2009 and 2013. Heterogeneity was noted among previous chloroquine efficacy studies in the measurement and reporting of parasite clearance.

CONCLUSIONThe treatment of P. vivax infection with a combination of chloroquine and primaquine has remained efficacious in Thailand. Increasing rates of parasite clearance in a population over time may be a useful early warning mechanism for the emergence of chloroquine resistance. The utility of monitoring time-trends in parasite clearance to detect resistance may be enhanced if parasite clearance measurements are standardised.

Antimalarials ; therapeutic use ; Chloroquine ; therapeutic use ; Drug Resistance, Microbial ; Drug Therapy, Combination ; Humans ; Malaria, Vivax ; drug therapy ; Plasmodium vivax ; Primaquine ; therapeutic use ; Thailand ; Time Factors ; Treatment Outcome

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

Malarial infection is one of the most important tropical diseases, but also increasing in the temperate regions. Severe malaria with organ dysfunction is commonly associated with Plasmodium falciparum, but rarely with Plasmodium vivax. Malarial hepatitis is also unusual in P. falciparum and very rare in P. vivax. Only 3 cases of malarial hepatitis caused by P. vivax have been reported in the world. Because the presence of hepatitis in malaria indicates a more severe illness with higher incidence of other complications and poor prognosis, malarial patients should be meticulously monitored for hepatic dysfunction with or without jaundice. We report here a case of malarial hepatitis caused by P. vivax that was presented by fever, general ache, nausea, fatigue, and significant elevation of aminotransferase and bilirubin.
Abdomen/ultrasonography ; Antimalarials/therapeutic use ; Erythrocytes/immunology/parasitology ; Fatigue/etiology ; Hepatitis/*diagnosis/etiology/ultrasonography ; Humans ; Malaria, Vivax/complications/*diagnosis/drug therapy ; Male ; Mefloquine/therapeutic use ; Nausea/etiology ; Plasmodium vivax/isolation & purification ; Primaquine/therapeutic use ; Young Adult

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

Splenic infarction is a rare complication in malaria cases, and is caused primarily by Plasmodium falciparum. Recently in South Korea, only P. vivax has prevailed since 1993. Although the probability that symptomatic splenic infarction may occur in vivax malaria cases is considered relatively high, there have never been any case reports describing the occurrence of symptomatic splenic infarction in cases of vivax malaria. A 34-year-old man presented with fever that had persisted for 5 days. P. vivax infection was verified using a peripheral blood smear, and chloroquine was utilized to treat the fever successfully. Six days later, the patient developed pain in the left upper abdomen, which was diagnosed as splenic infarction by computed tomography.
Adult ; Animals ; Humans ; Malaria, Vivax/blood/*complications/drug therapy ; Male ; Plasmodium vivax/*isolation & purification ; Primaquine/therapeutic use ; Splenic Infarction/blood/*parasitology

Splenic infarction is a rare complication in malaria cases, and is caused primarily by Plasmodium falciparum. Recently in South Korea, only P. vivax has prevailed since 1993. Although the probability that symptomatic splenic infarction may occur in vivax malaria cases is considered relatively high, there have never been any case reports describing the occurrence of symptomatic splenic infarction in cases of vivax malaria. A 34-year-old man presented with fever that had persisted for 5 days. P. vivax infection was verified using a peripheral blood smear, and chloroquine was utilized to treat the fever successfully. Six days later, the patient developed pain in the left upper abdomen, which was diagnosed as splenic infarction by computed tomography.
Adult ; Animals ; Humans ; Malaria, Vivax/blood/*complications/drug therapy ; Male ; Plasmodium vivax/*isolation & purification ; Primaquine/therapeutic use ; Splenic Infarction/blood/*parasitology

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

Vivax malaria was endemic on the Korean peninsula for many centuries until the late 1970's when the Republic of Korea (ROK) was declared "malaria free". Since its re-emergence in 1993, the number of malaria cases in the military increased exponentially through 2000 near the demilitarized zone. Chemoprophylaxis with chloroquine and primaquine has been used in the ROK Army since 1997 in an attempt to reduce the number of the malaria cases throughout the ROK. Data show that chemoprophylaxis contributed, in part, to the decrease in the number of malaria cases among military personnel. However, mass chemoprophylaxis on a large scale in the ROK Army is unprecedented and extensive supervision and monitoring is warranted to determine its effectiveness and to monitor the appearance of chloroquine tolerant/resistant strains of Plasmodium vivax.
Antimalarials/therapeutic use ; Chemoprevention/methods/statistics and numerical data ; Chloroquine/*therapeutic use ; Disease Outbreaks/*prevention and control/*statistics and numerical data ; Humans ; Incidence ; Korea/epidemiology ; Malaria, Vivax/*epidemiology/*prevention and control ; Military Personnel/*statistics and numerical data ; Outcome Assessment (Health Care) ; Prevalence ; Primaquine/*therapeutic use ; Research Support, Non-U.S. Gov't ; Risk Assessment/methods ; Risk Factors ; Treatment Outcome