***TASK*** the task is to summarize an input biomedical literature in six sentences 
    ***INPUT*** the input is a biomedical literature 
    ***OUTPUT*** the output is the summary of an input biomedical literature in six sentences 
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    Input: To determine if iron chelation therapy has activity against human malaria , we administered desferrioxamine B in amounts of 100 mg/kg per day by continuous 72-hour subcutaneous infusions to 28 volunteers with asymptomatic Plasmodium falciparum infection in a r and omized , double-blind , placebo-controlled crossover trial . Peripheral blood concentrations of P falciparum ring forms were determined at 12-hour intervals in all subjects and serum concentrations of desferrioxamine B + ferrioxamine  ( the iron complex of desferrioxamine B ) were measured in 26 subjects . Geometric mean concentrations of asexual intraerythrocytic parasites decreased with both chelator and placebo treatment , but the decrement with desferrioxamine B was significantly greater than that with placebo ( P less than .006 ) during both the initial and crossover periods . Compared with placebo , desferrioxamine B treatment was associated with an almost 10-fold enhancement of the rate of parasite clearance during both phases of the trial ( P less than .007 ) . Mean + /- SEM steady state concentrations of desferrioxamine B + ferrioxamine were 6.90 + /- 0.60 mumol/L at 36 hours and 7.72 + /- 0.68 mumol/L at 72 hours ; in vitro , the ID50 has been reported to be approximately 4 to 20 mumol/L. No drug toxicity was detected . Parasitemia recurred in 19 of 24 participants followed-up over 1 to 6 months . We conclude that desferrioxamine B enhances the clearance of P falciparum parasitemia and that iron chelation may provide a new strategy to be developed for the treatment of malaria While the parenteral iron-chelating agent desferrioxamine B has anti-malarial activity in humans , the usefulness of an orally active chelator for this indication has not been investigated previously in vivo . We conducted a prospect i ve , double-blind , placebo-controlled , cross-over trial of deferiprone ( L1 ; CP20 ; 1,2-dimethyl-3-hydroxypyridin-4-one ) in 25 adult Zambians with asymptomatic Plasmodium falciparum parasitemia .  Deferiprone was administered daily for three or four days in divided doses of 75 or 100 mg/kg of body weight , dosages that are effective for treating iron overload . No reduction in asexual intra-erythrocytic parasites was observed during or after deferiprone treatment . The mean peak plasma concentration of deferiprone ( 108.9 + /- 24.9 micromol/L ) achieved was within the range demonstrated to inhibit the growth of P. falciparum in vitro , but the systemic exposure as determined by the 24-hr plasma concentration-time curve would not be predicted inhibit growth in vivo . No evidence of deferiprone-associated  hematological toxicity was noted in this short-term study of these subjects , all of whom had clinical evidence of normal body iron stores . Because of the risk of neutropenia and other adverse effects with higher doses or prolonged use of the chelator , additional trials of deferiprone as a sole anti-malarial agent would not seem to be justified . In contrast , further efforts are needed to develop other orally active iron-chelating agents specifically for their anti-malarial action BACKGROUND Cerebral malaria is a severe complication of Plasmodium falciparum infection in children , with a mortality rate of 15 to 50 percent despite antimalarial therapy . METHODS To determine whether combining iron chelation with quinine therapy speeds the recovery of consciousness , we conducted a r and omized , double-blind , placebo-controlled trial of the iron chelator deferoxamine in 83 Zambian children with cerebral malaria . To be enrolled , patients had to be less than six years old , have P. falciparum parasitemia , have normal cerebrospinal fluid without evidence of bacterial infection , and be in a coma from which they could not be aroused .  Deferoxamine ( 100 mg per kilogram of body weight per day , infused intravenously for 72 hours ) or placebo was added to st and ard therapy with quinine and sulfadoxine-pyrimethamine . The time to the recovery of full consciousness , time to parasite clearance , and mortality were examined with Cox proportional-hazards regression analysis . RESULTS The rate of recovery of full consciousness among the 42 patients given deferoxamine was 1.3 times that among the 41 given placebo ( 95 percent confidence interval , 0.7 to 2.3 ) ; the median time to recovery was 20.2 hours in the deferoxamine group and 43.1 hours in the placebo group ( P = 0.38 ) . Among 50 patients with deep coma , the rate of recovery of full consciousness was increased 2.2-fold with deferoxamine ( 95 percent confidence interval , 1.1 to 4.7 ) , decreasing the median recovery time from 68.2 to 24.1 hours ( P = 0.03 ) . Among 69 patients for whom data on parasite clearance were available , the rate of clearance with deferoxamine was 2.0 times that with placebo ( 95 percent confidence interval , 1.2 to 3.6 ) . Among all 83 patients , mortality was 17 percent in the deferoxamine group and 22 percent in the placebo group ( P = 0.52 ) . CONCLUSIONS Iron chelation therapy may hasten the clearance of parasitemia and enhance recovery from deep coma in cerebral malaria The incidence of infections was studied in 137 iron-deficient Somali nomads , 67 of whom were treated with placebo and 71 with iron .  Seven episodes of infection occurred in the placebo group and 36 in the group treated with iron ; these 36 episodes included activation of pre-existing malaria , brucellosis , and tuberculosis . This difference suggested that host defence against these infections was better during iron deficiency than during iron repletion . Iron deficiency among Somali nomads may be part of an ecological compromise , permitting optimum co-survival of host and infecting agent During the Central African ( Sahelian ) drought , attacks of falciparum malaria were common in patients and their relatives shortly after their arrival in a hospital in Eastern Niger . A prospect i ve study of 72 adult patients not admitted for malaria and 109 accompanying relatives was undertaken to investigate this observation . 23 attacks occurred in patients and 51 in relatives , with a peak frequency five days after arrival . On arrival , parasitaemia was low but reached a maximum by five days . Serum-iron and percentage saturation of transferrin were moderately increased initially , rose dramatically within forty-eight hours with near maximum saturation , and were falling by the fifth day . It is suggested that the early hyperferraemia , apparently related to refeeding , led to rapid multiplication of existing parasites and attacks of malaria . The results of experimental malarial infection of Wistar rats , half of which had been given intramuscular iron , supported this hypothesis To examine the effect of iron chelation on mortality in cerebral malaria , we enrolled 352 children in a trial of deferoxamine in addition to st and ard quinine therapy at 2 centres in Zambia , one rural and one urban . Entrance criteria included age < 6 years , Plasmodium falciparum parasitaemia , normal cerebral spinal fluid , and unrousable coma .  Deferoxamine ( 100 mg/kg/d infused for a total of 72 h ) or placebo was added to a 7 d regimen of quinine that included a loading dose . Mortality overall was 18.3 % ( 32/175 ) in the deferoxamine group and 10.7 % ( 19/177 ) in the placebo group ( adjusted odds ratio 1.8 ; 95 % confidence interval 0.9 - 3.6 ; P = 0.074 ) . At the rural study site , mortality was 15.4 % ( 18/117 ) with deferoxamine compared to 12.7 % ( 15/118 ) with placebo ( P = 0.78 , adjusted for covariates ) . At the urban site , mortality was 24.1 % ( 14/58 ) with deferoxamine and 6.8 % ( 4/59 ) with placebo ( P = 0.061 , adjusted for covariates ) . Among survivors , there was a non-significant trend to faster recovery from coma in the deferoxamine group ( adjusted odds ratio 1.2 ; 95 % confidence interval 0.97 - 1.6 ; P = 0.089 ) . Hepatomegaly was significantly associated with higher mortality , while splenomegaly was associated with lower mortality . This study did not provide evidence for a beneficial effect on mortality in children with cerebral malaria when deferoxamine was added to quinine , given in a regimen that included a loading dose BACKGROUND & OBJECTIVES Mortality due to Plasmodium falciparum infection remains high in India , hence any modality of treatment which can improve the outcome of this disease is worth exploring . The present study was undertaken to see whether addition of an oral iron chelator , deferiprone ( L1 ) to the conventional treatment regime for P. falciparum infection improves the clinical course and final outcome . METHODS In this prospect i ve , r and omised double blind trial , 45 consecutive patients with P. falciparum infection were r and omised into two groups . Patients in Group I ( control group , 21 patients ) received st and ard quinine and doxycycline therapy along with supportive therapy and placebo capsules for 10 days . Patients in Group II ( 24 patients ) received the same treatment as Group I but in place of placebo capsule received deferiprone capsules 75 mg/kg/day in 12 hourly divided doses . The parameters evaluated included the time taken in resolution of parasitaemia , fever and coma , differences in final outcome i.e. , death or other severe complications , and side effects and deferiprone tolerance . RESULTS Four patients in Group I and two in Group II died ( P > 0.05 ) . The resolution of fever and coma was significantly faster in Group II ( P < 0.05 ) and parasitaemia cleared 24 h earlier in this Group . The drug was well tolerated and had no side effects . INTERPRETATION & CONCLUSION Deferiprone ( L1 ) seems to be a promising agent as an adjuvant in the treatment for severe P. falciparum malaria infection Desferrioxamine B ( DFO , Desferal ) , an iron chelator , was earlier shown to be active against Plasmodium falciparum in vitro and in vivo . The present open pilot study served to assess its clinical tolerability and efficacy in human malaria under hospital conditions . Continuous intravenous DFO was administered to 28 Thai males at a dose of 100 mg/kg over 24 h for 3 consecutive days . No other antimalarial therapy was administered unless recrudescence had occurred . The first 14 patients had symptomatic Plasmodium vivax ( P.v . ) malaria , while the other 14 patients were suffering from uncomplicated Plasmodium falciparum malaria ( P.f . ) . Both groups were treated in Bangkok , where malaria transmission does not take place , and followed up , on the ward , for 3 weeks ( P.v . group ) or 4 weeks ( P.f . group ) after the start of therapy . In both groups DFO reduced the parasitaemia to zero within 106 and 57 h respectively . The fever clearance time was 55 and 60 h , respectively . The overall tolerability of DFO was good but 4 P.v . and 5 P.f . patients had transient visual blurring . Recrudescences were observed on average 15 , respectively 10 days after the start of therapy . Only 2 P.v . patients and none of the P.f . patients remained free of recrudescences during the observation period . There was no apparent gametocytocidal effect of DFO on P.f The administration of 0.5 g ( IM ) of desferrioxamine every 12 hr for 3 days with 25 mg/kg ( total dose for three days ) of chloroquine  abated the parasitemia of Plasmodium falciparum infected individuals more rapidly than chloroquine alone . Two patients with in vitro evidence of total or  partial resistance to  chloroquine also were successfully treated with the combination of drugs , and were free of parasitized red cells by day 7 . Further clinical trials and development of desferrioxamine in the treatment of P. falciparum are warranted To examine the effect of iron chelation against human malaria , 37 Zambians with asymptomatic Plasmodium falciparum infections were r and omly assigned to 72-hr infusions of desferrioxamine B or placebo .  Mean concentrations of ring forms decreased significantly with desferrioxamine B ( P < 0.001 ) but not with a placebo . Over seven days of observation , mean parasite concentrations remained at the initial levels in six individuals originally given placebo , but decreased promptly with administration of desferrioxamine B ( P = 0.001 ) . Mean parasitemia was significantly lower for up to four weeks in 16 subjects treated with desferrioxamine B when compared with the 
    Output:
    
Many adverse effects were more common in participants treated with desferrioxamine .
REVIEW ER 'S CONCLUSIONS Trends suggestive of both harm ( death ) and potential benefit ( fewer seizures ) are demonstrated in this review .