it has been claimed that tertian malaria had been completely eradicated in the latter part of 1970 in korea .
but since 1993 , this tertian malaria has reemerged to infect soldiers and civilians living near the armistice line , resulting in 1,724 cases in 1997 . also , imported malaria from an overseas trip has become a medical problem to the extent of calling attention .
reports have appeared calling attention to what has been termed primaquine resistance in plasmodium vivax in korea .
we present a case of primaquine resistant tertian malaria which was thought to be relapsed because of loss of radical cure at initial treatment .
a 50-year - old man presented on november , 1997 with high fever , chills and splenomegaly .
three weeks before admission , he had traveled to ethiopia where he had remained for 10 days without prophylactic chemotherapy against malaria .
the temperature was 39c , the pulse was 100/min and the respiration rates were 22/min .
a physical examination was normal , except for a nontender , firm splenomegaly exceeding 5 cm below the costal margin .
laboratory examinations showed hemoglobin 16.1 gm / dl , white blood cell count 7,510/mm , platelet count 49,100/mm , alkaline phosphatase 248 iu / l , alanine aminotransferase 165 iu / l , aspartate aminotransferase 89 iu / l . at that time , microscopic examination of a blood smear was said to show malaria ( p.vivax ) and a diagnosis of malaria was made .
after treatment with chloroquine ( 750 mg as a loading dose and then 350 mg each 6 , 24 , 48 hours later ) , he felt well but subsequently did not receive primaquine because of the physician s mistake .
laboratory examinations showed hemoglobin 16.5 gm / dl , white blood cell count 4,150/mm , platelet count 26,300/mm .
microscopic examination of a stained blood smear for malarial organism ( 38,180/l ) was positive .
the patient was given a conventional three - day course of chloroquine with relapsed malaria .
on the following day , he became afebrile and reevaluation of blood smears showed decrease in the number of parasite counts(3,480/l ) .
he subsequently was given primaquine ( 15 mg base daily for 14 days ) with improvement .
the test of g-6pdh ( glucose-6-phosphate dehydrogenase ) deficiency was negatived(11.7 u / g ) .
about three months after the first relapse , however , he revisited the hospital with fever , headache and chills .
physical examination showed no change , except that the spleen was felt 4 cm below the costal margin .
the patient was treated with chloroquine in the same dose as the in first attack . on the next day
he subsequently received primaquine ( 22.5 mg daily for 21 days ) without side effects from the drug .
although it has been eradicated from temperate zones , increasing numbers of travelers from temperate areas each year visit tropical countries where the disease remains a major cause of morbidity and death .
relapse occurs with p.vivax infections because delayed developmental forms of the parasite , called hypnozoites , are present in the liver .
hypnozoites can mature months to years later to cause clinical disease . after maturing and multiplying in the liver ,
a radical cure is achieved for p.vivax infections by the use of both blood - stage antimalarial drugs and primaquine , which is the only available drug that can destroy hypnozoites . to provide radical cure of p.vivax malaria , treatment
must be prescribed to eliminate the liver stage of the parasites , otherwise intermittent relapses with clinical symptoms will continue . usually , after acute phase therapy with chloroquine , patients with p.vivax are treated with the standard course of primaquine , i.e. 15 mg base / day for 14 days , as curative therapy .
primaquine - resistant strains have been reported from papua new guinea , south - east asia and central and south america .
cases of primaquine treatment failure have also been reported in patients who visited kenya , sudan and ethiopia .
the interval between primary infection and relapse varies with differing strains of p.vivax-chesson strain from papua new guinea relapsing rapidly , at intervals of 28 days ; strains from southern china may relapse on an approximately annual basis .
such strains appear to show intrinsic differences in sensitivity to 8-aminoquinolines , the agents most commonly used to eradicate the liver stage .
studies carried out in the western pacific region soon after world warii , and predominantly involving the chesson strains , indicated that a regimen of primaquine base 15 mg / day for 14 days led to failure in over 30 % of cases .
it would appear that this investigation regimen was selected solely on the basis of limiting potential toxicity .
common practice over subsequent decades within this region has been to use a regimen of primaquine base 22.530 mg / day for 14 days to ensure a high chance of parasite eradication .
in contrast , however , studies during the vietnam war determined that strains from south - east asia were more primaquine - sensitive and were almost entirely eradicated with primaquine base 15 mg / day for 14 days .
strains from south - east asia and central and south america have also been reported to relapse after standard regimens of primaquine .
most authorities agree that it is reasonable to treat patients who acquire their infections from these areas with a higher dose regimen .
to reduce side effects , a regimen of 15 mg daily of primaquine base for 28 days has been used instead of 30 mg base daily for 14 days , under the assumption that it is the total , cumulative dose of primaquine that is important in eliminating hypnozoites . unfortunately , there are no data to support the longer duration regimen .
human and animal studies have only used total doses scheduled over a shorter time interval ( 60 mg base daily for 7 days versus 30 mg base daily for 14 days ) in showing equivalent cure rates .
it is curious that primaquine resistance emanates from areas where higher doses of primaquine have been used for longer periods . whether this increased anti -
animal and human studies of sub - therapeutic doses of primaquine in p.vivax infections resulted only in resistance in the erythrocytic stages of the life cycle . while it has been suggested that the apparent increasing resistance to primaquine in p.vivax actually reflects unrecognized chloroquine - resistance in this parasite , at present , recurrence of vivax parasitemia after primaquine therapy and > 28 days from initial infection more often represents primaquine rather than chloroquine failure .
cause of the first relapse in our patient is thought to be inadequate regimen rather than chloroquine resistance : primaquine was not prescribed at initial infection .
second attack was due to primaquine resistance , since the peripheral blood smear of our patient was normal up to three days after the treatment ( chloroquine ) and relapse took place after three months .
primaquine may cause nausea and abdominal pain , particularly if taken on an empty stomach and , more important , oxidant hemolysis with methemglobinemia , anemia and , sometimes , hemoglobinuria .
patients with a deficiency of glucose-6-phosphate dehydrogenase are particularly vulnerable to oxidant hemolysis , and primaquine is contraindicated in patients with severe form of the deficiency . in places
where mild variants of glucose-6-phosphate dehydrogenase deficiency are common , primaquine ( 0.8 mg of base per kilogram ; adult dose , 45 mg ) should be given once a week for six weeks for a radical cure .
it is imperative to establish the most appropriate regimen with primaquine for the curative treatment of relapsed vivax malaria after the completion of chloroquine - primaquine therapy .
 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 . 
INTRODUCTION
CASE REPORT
DISCUSSION