***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: The efficacy of artemether and artemether followed by mefloquine was evaluated in 45 pregnant women with drug resistant Plasmodium falciparum malaria during the second and third trimesters . There was prompt clinical response to both treatment regimens . The parasite and fever clearance times and the cure rate were similar in both groups . Except for the correlation between initial parasite density and fever clearance time in the artemether-mefloquine group , there was no correlation between initial parasite density and parasite or fever clearance times in the two groups . Similarly , there was no correlation between parasite and fever clearance . Both treatment regimens were well tolerated . All newborn babies of the participating women were normal at birth . Physical and neurodevelopmental assessment of the newborn babies followed up for a period varying between 6 and 36 months were within normal limits . Artemether alone or with mefloquine are effective and do not produce undue deleterious effects in pregnant patients with drug-resistant falciparum malaria during the second and third trimesters BACKGROUND Adherence to antimalarial drug regimens is improved by simple dosing . If the fixed antimalarial drug combination artemether-lumefantrine ( AL ) could be given once daily , this should improve adherence and thus effectiveness and lower the risk of selecting for resistance . METHODS In an open r and omized study , 43 patients with uncomplicated falciparum malaria were given equivalent doses of AL with 200 ml flavoured milk either as the conventional twice-daily regimen or as a single daily dose for 3 days . The primary end point was a comparison of the areas under the plasma lumefantrine concentration-time curves ( AUC ) . Secondary end points were the day 42 polymerase chain reaction (PCR)-adjusted cure rates and the tolerability profiles . RESULTS Lumefantrine pharmacokinetic profiles were obtained for 36 patients . The AUC((0 - ->infinity ) ) of the once-daily regimen was 30 % lower than that in the conventional regimen ( P = 0.011 ) with a median ( range ) value of 306 ( 114 - 5781 ) microg/ml h , compared with 432 ( 308 - 992 ) microg/ml h. There was no significant difference in the peak plasma concentrations reached . PCR-adjusted cure rate estimates at day 42 of follow-up were 94 % ( 95 % CI : 84 - 100 ) in the six-dose arm and 85 % ( 70 - 100 ) in the three-dose arm ( P = 0.3 ) . CONCLUSION Artemether-lumefantrine  efficacy is reduced by once-daily dosing , because absorption of lumefantrine is dose limited . At currently recommended doses , this antimalarial should be given twice daily in a 3-day regimen , with food containing fat Background To date no comparative trials have been done , to our knowledge , of fixed-dose artemisinin combination therapies ( ACTs ) for the treatment of Plasmodium falciparum malaria in pregnancy . Evidence on the safety and efficacy of ACTs in pregnancy is needed as these drugs are being used increasingly throughout the malaria-affected world . The objective of this study was to compare the efficacy , tolerability , and safety of artemether-lumefantrine , the most widely used fixed ACT , with 7 d artesunate monotherapy in the second and third trimesters of pregnancy . Methods and Findings An open-label r and omised controlled trial comparing directly observed treatment with artemether-lumefantrine 3 d ( AL ) or artesunate monotherapy 7 d ( AS7 ) was conducted in Karen women in the border area of northwestern Thail and who had uncomplicated P. falciparum malaria in the second and third trimesters of pregnancy . The primary endpoint was efficacy defined as the P. falciparum PCR-adjusted cure rates assessed at delivery or by day 42 if this occurred later than delivery , as estimated by Kaplan-Meier survival analysis . Infants were assessed at birth and followed until 1 y of life . Blood sampling was performed to characterise the pharmacokinetics of lumefantrine in pregnancy . Both regimens were very well tolerated . The cure rates ( 95 % confidence interval ) for the intention to treat ( ITT ) population were : AS7 89.2 % ( 82.3%–96.1 % ) and AL 82.0 % ( 74.8%–89.3 % ) , p = 0.054 ( ITT ) ; and AS7 89.7 % ( 82.6%–96.8 % ) and AL 81.2 % ( 73.6%–88.8 % ) , p = 0.031 ( per- protocol population ) . One-third of the PCR-confirmed recrudescent cases occurred after 42 d of follow-up . Birth outcomes and infant ( up to age 1 y ) outcomes did not differ significantly between the two groups . The pharmacokinetic study indicated that low concentrations of artemether and lumefantrine were the main contributors to the poor efficacy of AL . Conclusion The current st and ard six-dose artemether-lumefantrine regimen was well tolerated and safe in pregnant Karen women with uncomplicated falciparum malaria , but efficacy was inferior to 7 d artesunate monotherapy and was unsatisfactory for general deployment in this geographic area . Reduced efficacy probably results from low drug concentrations in later pregnancy . A longer or more frequent AL dose regimen may be needed to treat pregnant women effectively and should now be evaluated . Parasitological endpoints in clinical trials of any antimalarial drug treatment in pregnancy should be extended to delivery or day 42 if it comes later . Trial Registration : Current Controlled Trials IS RCT Background Safety data regarding exposure to artemisinin-based combination therapy in pregnancy are limited . This prospect i ve cohort study conducted in Zambia evaluated the safety of artemether-lumefantrine ( AL ) in pregnant women with malaria . Methods Pregnant women attending antenatal clinics were assigned to groups based on the drug used to treat their most recent malaria episode ( AL vs. sulphadoxine-pyrimethamine , SP ) .  Safety was assessed using st and ard and pregnancy-specific parameters . Post-delivery follow-up was six weeks for mothers and 12 months for live births . Primary outcome was perinatal mortality ( stillbirth or neonatal death within seven days after birth ) . Results Data from 1,001 pregnant women ( AL n = 495 ; SP n = 506 ) and 933 newborns ( AL n = 466 ; SP n = 467 ) showed : perinatal mortality ( AL 4.2 % ; SP 5.0 % ) , comprised of early neonatal mortality ( each group 2.3 % ) , stillbirths ( AL 1.9 % ; SP 2.7 % ) ; preterm deliveries ( AL 14.1 % ; SP 17.4 % of foetuses ) ; and gestational age-adjusted low birth weight ( AL 9.0 % ; SP 7.7 % ) . Infant birth defect incidence was 1.8 % AL and 1.6 % SP , excluding umbilical hernia . Abortions prior to antenatal care could not be determined : abortion occurred in 4.5 % of women treated with AL during their first trimester ; none were reported in the 133 women exposed to SP and /or quinine during their first trimester . Overall development ( including neurological assessment ) was similar in both groups . Conclusions These data suggest that exposure to AL in pregnancy , including first trimester , is not associated with particular safety risks in terms of perinatal mortality , malformations , or developmental impairment . However , more data are required on AL use during the first trimester Background . There is some consensus that malaria in pregnancy may negatively affect  infant 's mortality and malaria morbidity  , but there is less evidence concerning the factors involved . Methods . A total of 1030 Mozambican pregnant women were enrolled in a r and omized , placebo-controlled trial of intermittent preventive treatment with sulfadoxine-pyrimethamine , and their infants were followed up throughout infancy . Overall mortality and malaria morbidity rates were recorded . The association of maternal and fetal risk factors with infant mortality and malaria morbidity was assessed . Results . There were 58 infant deaths among 997 live-born infants .  The risk of dying during infancy was increased among infants born to women with acute placental infection ( odds ratio [ OR ] , 5.08 [ 95 % confidence interval ( CI ) , 1.77–14.53 ) ] , parasitemia in cord blood ( OR , 19.31 [ 95 % CI , 4.44–84.02 ] ) , low birth weight ( OR , 2.82 [ 95 % CI , 1.27–6.28 ] ) or prematurity ( OR , 3.19 [ 95 % CI , 1.14–8.95 ] ) . Infants born to women who had clinical malaria during pregnancy ( OR , 1.96 [ 95 % CI , 1.13–3.41 ] ) or acute placental infection ( OR , 4.63 [ 95 % CI , 2.10–10.24 ] ) had an increased risk of clinical malaria during infancy . Conclusions . Malaria infection at the end of pregnancy and maternal clinical malaria negatively impact survival and malaria morbidity in infancy . Effective clinical management and prevention of malaria in pregnancy may improve infant 's health and survival Background Prompt use of an effective anti-malarial drug is essential for controlling malaria and its adverse effects in pregnancy . The World Health Organization recommends an artemisinin-based combination therapy as the first-line treatment of uncomplicated malaria in the second and third trimesters of pregnancy . The study objective was to determine the degree to which presumed episodes of uncomplicated symptomatic malaria in pregnancy were treated with a recommended anti-malarial regimen in a region of Ug and a. Methods Utilizing a population -based r and om sample , we interviewed women living in Jinja , Ug and a who had been pregnant in the past year . Results Self-reported malaria during the index pregnancy was reported among 67 % ( n = 334 ) of the 500 participants . Among the 637 self-reported episodes of malaria , an anti-malarial drug was used for treatment in 85 % of the episodes . Use of a currently recommended treatment in the first trimester was uncommon ( 5.6 % ) . A contraindicated anti-malarial drug ( sulphadoxine-pyrimethamine and /or artemether-lumefantrine ) was involved in 70 % of first trimester episodes . Recommended anti-malarials were used according to the guidelines in only 30.1 % of all second and third trimester episodes . Conclusions Self-reported malaria was extremely common in this population and adherence to treatment guidelines for the management of malaria in pregnancy was poor . Use of artemether-lumefantrine combined with non-recommended anti-malarials was common practice . Overuse of anti-malarial drugs , especially ones that are no longer recommended , undermines malaria control efforts by fueling the spread of drug resistance and delaying appropriate treatment of non-malarial febrile illnesses . Improved diagnostic capacity is essential to ultimately improving the management of malaria-like symptoms during pregnancy and appropriate use of currently available anti-malarials Background Maternal mortality is a major health problem concentrated in re source -poor regions . Accurate data on its causes using rigorous methods is lacking , but is essential to guide policy-makers and health professionals to reduce this intolerable burden . The aim of this study was to accurately describe the causes of  maternal  death in order to contribute to its reduction , in one of the regions of the world with the highest maternal mortality ratios . Methods and Findings We conducted a prospect i ve study between October 2002 and December 2004 on the causes of  maternal death  in a tertiary-level referral hospital in Maputo , Mozambique , using  complete autopsies with histological examination . HIV detection was done by virologic and serologic tests , and malaria was diagnosed by histological and parasitological examination . During 26 mo there were 179 maternal deaths , of which 139 ( 77.6 % ) had a complete autopsy and formed the basis of this analysis . Of those with test results , 65 women ( 52.8 % ) were HIV-positive .  Obstetric complications accounted for 38.2 % of deaths ; haemorrhage was the most frequent cause ( 16.6 % ) . Nonobstetric conditions accounted for 56.1 % of deaths ; HIV/AIDS , pyogenic bronchopneumonia , severe malaria , and pyogenic meningitis were the most common causes ( 12.9 % , 12.2 % , 10.1 % and 7.2 % respectively ) . Mycobacterial infection was found in 12 ( 8.6 % ) maternal deaths . Conclusions In this tertiary hospital in Mozambique , infectious diseases accounted for at least half of all maternal deaths , even though effective treatment is available for the four leading causes , HIV/AIDS , pyogenic bronchopneumonia , severe malaria , and pyogenic meningitis . These observations highlight the need to implement effective and available prevention tools , such as intermittent preventive treatment and insecticide-treated bed-nets for malaria , antiretroviral drugs for HIV/AID 
    Output:
    
In the second and third trimesters , AL was not associated with increased adverse pregnancy outcomes as compared with quinine or sulphadoxine-pyrimethamine , showed improved tolerability relative to quinine , and its efficacy was non-inferior to quinine .
There is evidence to suggest that the pharmacokinetics of anti-malarial drugs may change in pregnancy , although the impact on efficacy and safety needs to be studied further , especially since the majority of studies report high cure rates and adequate tolerability .