***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 
    ***DOCUMENTATION*** 
    ***EXAMPLES*** 
    Input: Emphasis on retaining chloroquine as the first-line therapy for Plasmodium falciparum infections in most of sub-Saharan Africa for as long as it remains effective has result ed in widespread reliance on chloroquine in areas where it can have little effect on P. falciparum parasitemia . To address this issue , clinical , parasitologic , and hematologic responses to chloroquine or pyrimethamine/sulfadoxine treatment were assessed among very young children in Malawi ( n = 153 ) and Kenya ( n = 73 ) . The median time to resumption of clinical symptoms in chloroquine-treated children was 13.5 days in Malawi and 9.5 days in Kenya . Children treated with pyrimethamine/sulfadoxine maintained clinical improvement and had greater increases in their hemoglobin concentration during the follow-up period than did children treated with chloroquine . Treatment with chloroquine failed to produce either a durable clinical improvement or optimal hematologic recovery . Consequently , chloroquine can no longer be considered adequately effective therapy of clinical P. falciparum malaria in very young children in these areas of Africa Background Little is known about the process of knowledge translation in low- and middle-income countries . We studied policymaking processes in Mozambique , South Africa and Zimbabwe to underst and the factors affecting the use of research evidence in national policy development , with a particular focus on the findings from r and omized control trials ( RCTs ) . We examined two cases : the use of magnesium sulphate ( MgSO4 ) in the treatment of eclampsia in pregnancy ( a clinical case ) ; and the use of insecticide treated bed nets and indoor residual household spraying for malaria vector control ( a public health case ) . Methods We used a qualitative case- study methodology to explore the policy making process . We carried out key informants interviews with a range of research and policy stakeholders in each country , review ed documents and developed timelines of key events . Using an iterative approach , we undertook a thematic analysis of the data . Findings Prior experience of particular interventions , local champions , stakeholders and international networks , and the involvement of research ers in policy development were important in knowledge translation for both case studies . Key differences across the two case studies included the nature of the evidence , with clear evidence of efficacy for MgSO4 and ongoing debate regarding the efficacy of bed nets compared with spraying ; local research er involvement in international evidence production , which was stronger for MgSO4 than for malaria vector control ; and a long-st and ing culture of evidence -based health care within obstetrics . Other differences were the importance of bureaucratic processes for clinical regulatory approval of MgSO4 , and regional networks and political interests for malaria control . In contrast to treatment policies for eclampsia , a diverse group of stakeholders with varied interests , differing in their use and interpretation of evidence , was involved in malaria policy decisions in the three countries . Conclusion Translating research knowledge into policy is a complex and context sensitive process . Research ers aim ing to enhance knowledge translation need to be aware of factors influencing the dem and for different types of research ; interact and work closely with key policy stakeholders , networks and local champions ; and acknowledge the roles of important interest groups In response to the spread of chloroquine-resistant Plasmodium falciparum , Malaŵi changed its first-line antimalarial drug in 1993 from chloroquine to sulfadoxine-pyrimethamine ( SP ) . Surveillance data has suggested that resistance to SP may be increasing . We compared the efficacy of SP with a potential successor , mefloquine ( MQ ) . By use of a modified World Health Organization in vivo protocol , children infected with P. falciparum were r and omized to receive SP ( sulfadoxine 25 mg/kg ) or MQ ( 15 mg/kg ) . We observed combined RII and RIII parasitologic failures of 20.0 and 22.0 % in the SP and MQ arms , respectively . Among those in the MQ arm , the relative hazard of failing with a Day 2 drug level < 500 ng/mL was 10.6 times higher than those with levels > or = 500 ng/mL. Given the decreased efficacy of the first-line antimalarial drug and the high failure rates of MQ at this lower dosage , Malaŵi should consider assessing the efficacy and feasibility of alternative drugs to treat uncomplicated falciparum malaria Abstract Objective To measure the efficacy of sulfadoxine-pyrimethamine treatment of falciparum malaria in Malawi from 1998 to 2002 , after a change from chloroquine to sulfadoxine-pyrimethamine as first line treatment in that country in 1993 . Design Prospect i ve open label drug efficacy study . Setting Health centre in large peri-urban township adjacent to Blantyre , Malawi . Participants People presenting to a health centre with uncomplicated Plasmodium falciparum malaria . Main outcome measures Therapeutic efficacy and parasitological resistance to st and ard sulfadoxine-pyrimethamine treatment at 14 days and 28 days of follow up . Results Therapeutic efficacy remained stable , with adequate clinical response rates of 80 % or higher throughout the five years of the study . Analysis of follow up to 28 days showed modest but significant trends towards diminishing clinical and parasitological efficacy over time within the study period . Conclusion Contrary to expectations , sulfadoxine-pyrimethamine has retained good efficacy after 10 years as the first line antimalarial drug in Malawi . African countries with very low chloroquine efficacy , high sulfadoxine-pyrimethamine efficacy , and no other immediately available alternatives may benefit from interim use of sulfadoxine-pyrimethamine while awaiting implementation of combination antimalarial treatments The use of combinations of inexpensive drugs for the treatment of malaria in Africa has been proposed as an interim policy while awaiting the widespread availability of more effective regimens . We compared sulfadoxine-pyrimethamine plus chloroquine or amodiaquine in three districts in Ug and a. Patients aged 6 months or greater with uncomplicated falciparum malaria were enrolled and r and omized to therapy . Safety , tolerability , and efficacy outcomes , adjusted by genotyping , were assessed over 28 days . Of 1,105 patients enrolled , 1,057 ( 96 % ) completed follow-up . For children less than 5 years old , the risk of clinical treatment failure adjusted by genotyping at the three sites ranged from 34 % to 67 % with chloroquine plus sulfadoxine-pyrimethamine and from 13 % to 35 % with amodiaquine plus sulfadoxine-pyrimethamine ( risk differences 21 - 32 % , P < 0.0001 at all sites ) . Serious adverse events were uncommon with both regimens . The risk of treatment failure with chloroquine plus sulfadoxine-pyrimethamine , the current st and ard in Ug and a , was unacceptably high . Amodiaquine plus sulfadoxine-pyrimethamine was significantly more efficacious ; however , existing levels of resistance raises concern about the useful therapeutic life-span of this regimen In March 1993 , sulphadoxine/pyrimethamine ( SP ) replaced chloroquine as the first line drug for malaria treatment in Malawi . Since then , the Ministry of Health has been receiving anecdotal and written reports of SP treatment failures in children . To determine whether treatment failure with SP was a widespread problem , children < 5 years of age with axillary temperature > 38.0 degrees C and parasite density > 2000/mm3 attending the outpatient clinics of the Mangochi and Karonga District Hospitals were enrolled in the study with parental consent . These were then followed for 28 days or until they failed clinical ly . Of 159 patients enrolled , 145 ( 91.2 % ) were followed for 28 days or until clinical failure . Of these , none had RII resistance and 3 ( 1.9 % ) had RIII resistance : 2/69 ( 2.9 % ) in Mangochi and 1/76 ( 1.3 % ) in Karonga ; 142/145 ( 97.9 % ) exhibited RI/sensitive patterns . Of those followed to day 28 or to clinical failure , 77.1 % had parasite clearance by day 3 and 98.6 % had parasite clearance by day 7 . Of those with temperature readings ( n = 140 ) , 129 ( 92.1 % ) clinical ly improved on day 3 and 98.6 % improved by day 7 . Other indicators of clinical improvement ( from day 0 to day 3 ) included , reported increased level of activity in 136 ( 97.1 % ) of the children , and mother 's impression of child 's improvement in 113 ( 80.7 % ) . Of the 14 patients not followed to day 28 or to clinical failure , 11 were lost to follow-up by day 7 . No allergic skin reactions were noted , and no deaths were observed . These data show that after one year of widespread use of SP in Malawi , Plasmodium falciparum parasite resistance remains very low , and therefore contradicts reports of widespread parasite resistance to SP 73 pregnant women in Malawi were given weekly antimalarial chemoprophylaxis under observation and were monitored for Plasmodium falciparum parasitaemia and placental infection . 3 of 19 women ( 16 % ) who were parasitaemic at the time they began chemoprophylaxis were infected with chloroquine-resistant P. falciparum . After clearance of initial infections , 25 % of the 73 women became parasitaemic while taking prophylaxis and 56 % had evidence of active or past placental infection at the time of delivery . None of the women who were parasitaemic at the time of enrollment , and only 11 % of those who had breakthrough parasitaemias while taking prophylaxis , had a history of fever and signs or symptoms that they recognized as malaria . Although the density of P. falciparum infection and rates of placental infection appeared to be lower among women taking regular chloroquine prophylaxis , this drug did not prevent P. falciparum infection among pregnant women BACKGROUND Chlorproguanil-dapsone exerts lower resistance pressure on Plasmodium falciparum than does sulfadoxine-pyrimethamine , but is rapidly eliminated . We aim ed to find out whether chlorproguanil-dapsone results in a higher retreatment rate for malaria than sulfadoxine-pyrimethamine . METHODS In a r and omised trial of paediatric out patients with uncomplicated falciparum malaria , patients received either chlorproguanil-dapsone or sulfadoxine-pyrimethamine  and were followed up for up to 1 year . Sites were in Kenya ( n=410 ) and Malawi ( n=500 ) . We used per- protocol analysis to assess the primary outcome of annual malaria incidence . FINDINGS Drop-outs were 117 of 410 ( 28.5 % ) in Kenya , and 342 of 500 ( 68.4 % ) in Malawi . Follow-up was for a median of 338 days ( IQR 128 - 360 ) and 342 days ( 152 - 359 ) in Kilifi ( chlorproguanil-dapsone and sulfadoxine-pyrimethamine , respectively ) , and for 120 days ( 33 - 281 ) and 84 days ( 26 - 224 ) in Blantyre . Mean annual malaria incidence was 2.5 versus 2.1 in Kenya ( relative risk 1.16 , 95 % CI 0.98 - 1.37 ) , and 2.2 versus 2.8 in Malawi ( 0.77 , 0.63 - 0.94 ) . 4.3 % versus 12.8 % , and 5.4 % versus 20.1 % , of patients were withdrawn for treatment failure in Kenya and Malawi , respectively . In Kenya haemoglobin concentration of 50 g/L or less caused exit in 6.9 % of chlorproguanil-dapsone patients and 1.5 % of sulfadoxine-pyrimethamine patients , but most anaemia occurred before re-treatment . In Malawi only one patient exited because of anaemia . INTERPRETATION Despite the rapid elimination of chlorproguanil-dapsone , children treated with this drug did not have a higher incidence of malaria episodes than those treated with sulfadoxine-pyrimethamine .  Treatment failure was more common with sulfadoxine-pyrimethamine . Cause of anaemia in Kenya was probably not adverse reaction to chlorproguanil-dapsone , but this observation requires further study OBJECTIVES To provide nationally relevant information on the antimalarial efficacy of chloroquine ( CQ ) , sulphadoxine-pyrimethamine ( SP ) and amodiaquine ( AQ ) in Sierra Leone , with a view to updating antimalarial policy in the country . METHODS Between October 2002 and May 2003 , st and ard WHO methodology for in vivo efficacy assessment was used in five sites to study the therapeutic response of 6 - 59 months old uncomplicated Plasmodium falciparum malaria cases treated with C 
    Output:
    
The views of key informants indicate that the switch from chloroquine to SP was justified based on local evidence despite unavailability of WHO ’s policy recommendations , while the switch to lumefantrine-artemether was uncomplicated as the country was following the recommendations from WHO .
Conclusion Ample evidence from Malawi influenced and justified the policy changes .
Therefore , locally generated evidence is vital for decision making during policy change