***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: Abstract Objective : Atovaquone plus proguanil is a new , well-tolerated and highly effective antimalarial drug . In order to protect it from the development of resistance , it may be deployed in combination with an artemisinin derivative . To investigate whether artesunate affects the pharmacokinetics of atovaquone plus proguanil , and to provide preliminary information regarding the tolerability of the triple drug combination ( artesunate plus atovaquone plus proguanil ) , a cross over study was conducted in adult volunteers . Methods : Twelve healthy Karen adults were r and omised to receive atovaquone-proguanil ( 1000/400 mg ) with or without artesunate ( 250 mg ) and , at least 90 days later , the study was repeated . Blood was sample d over a 10-day period . Results : The three-drug combination was well tolerated . Artesunate did not alter the pharmacokinetic properties of atovaquone and proguanil ( maximum plasma concentrations : 13.02 μg/ml and 742 ng/ml ; elimination half-lives : 42.2 h and 14.4 h ; oral plasma clearance estimates : 90 ml/h/kg and 710 ml/h/kg ; and apparent volumes of distribution : 4.9 l/kg and 14.5 l/kg , respectively ) . There was also no effect of artesunate on the biotransformation of proguanil to cycloguanil . The pharmacokinetic variables were similar to those reported previously for the individual drugs . Conclusion : Artesunate does not influence atovaquone or proguanil pharmacokinetics . The triple-drug combination of atovaquone and proguanil and artesunate was well tolerated 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 To compare the effectiveness and safety of quinine sulfate and artesunate with mefloquine for treating second trimester pregnancy in women who suffered from Plasmodium falciparum malaria . The prospect i ve study was done in Srisangwal Hospital , Mae Hong Son , Thail and . Sixty , second to third trimester pregnant patients with P. falciparum infection , were recruited at r and om . They received either quinine sulfate 10 mg/kg/day for at least 7 days , 29 women ( group I ) , or oral artesunate 2 mg/kg as the first dose , 1 mg/kg every 12 hours orally for at least 5 days together with split doses of mefloquine , 15 mg/kg and 6 hours later 10 mg/kg orally 1 day after artesunate was stopped , 28 women ( group II ) . Three cases ( 5 % ) were lost to follow-up before delivery , one case in group I and two cases in group II . After treatment , the mean hematocrit of group I was significantly less than group II ( p = 0.000 ) . The PCT ( parasite clearance time ) and FCT ( fever clearance time ) of group II were significantly shorter than group I ( p = 0.000 ) . None of the patients in both groups had recrudescences within 28 days . Group I had more adverse effects than group II . No adverse neurological effects in pregnancy were found in both groups . The calcification of placenta and IUGR ( Intrauterine growth retard ) were not different between the two groups ( p = 0.964 , 0.363 respectively ) . The PCT was not different between the calcified placenta group and normal placenta group ( p = 0.058 ) , but the TTPP ( Total time of parasite presentation ) was ( p = 0.000 ) . TTPP related to low birth weight and low apgar score at 1 minute might be the cause ( p = 0.000 , 0.000 F = 5.261 , 21.627 respectively ) . TTPP and PCT related to neonatal blood pH and caused low neonatal blood pH ( p = 0.000 , 0.001 F = 24.351 , 11.162 respectively ) . The physical and neurological development of the babies at 2 , 4 , 6 and 12 months follow-up , were normal and there were no congenital abnormalities in either group . TTPP relating to fetal outcome , the longer the TTPP , the worse the fetal outcome , so we should diagnose early and treat P. falciparum malaria in pregnancy to prevent fetal jeopardy . Artesunate with mefloquine could shorten the PCT more than quinine sulfate in pregnancy , so the fetal outcome was better than that of quinine sulfate . In cases of prolonged infection before treatment , artesunate might be the alternative treatment of P. falciparum malaria in pregnancy . However , its safety should be carefully studied further with a larger sample size Objective New anti-malarial regimens are urgently needed in sub-Saharan Africa because of the increase in drug resistance . We investigated the safety and efficacy of azithromycin or artesunate combined with sulfadoxine-pyrimethamine used for treatment of malaria in pregnant women in Blantyre , Malawi . Methods / Findings This was a r and omized open-label clinical trial , conducted at two rural health centers in Blantyre district , Malawi . A total of 141 pregnant women with uncomplicated Plasmodium falciparum malaria were recruited and r and omly allocated to 3 treatment groups : sulfadoxine-pyrimethamine ( SP ; 3 tablets , 500 mg sulfadoxine and 25 mg pyrimethamine per tablet ) ; SP plus azithromycin ( 1 g/day × 2 days ) ; or SP plus artesunate ( 200 mg/day × 3 days ) . Women received two doses administered at least 4 weeks apart . Heteroduplex tracking assays were performed to distinguish recrudescence from new infections . Main outcome measures were incidence of adverse outcomes , parasite and fever clearance times and recrudescence rates . All treatment regimens were well tolerated . Two women vomited soon after ingesting azithromycin . The parasite clearance time was significantly faster in the SP-artesunate group . Recrudescent episodes of malaria were less frequent with SP-azithromycin [ Hazard Ratio 0.19 ( 95 % confidence interval 0.06 to 0.63 ) ] and SP-artesunate [ Hazard Ratio 0.25 ( 95 % confidence interval 0.10 to 0.65 ) ] compared with SP monotherapy . With one exception ( an abortion in the SP-azithromycin group ) , all adverse pregnancy outcomes could be attributed to known infectious or obstetrical causes . Because of the small sample size , the effect on birth outcomes , maternal malaria or maternal anemia could not be evaluated . Conclusions Both SP-artesunate and SP-azithromycin appeared to be safe , well tolerated and efficacious for the treatment of malaria during pregnancy . A larger study is needed to determine their safety and efficacy in preventing poor birth outcomes . Trial Registration ClinialTrials.gov OBJECTIVE : To investigate the pharmacokinetics , safety and efficacy of the recommended 3-day treatment regimen of Malarone in third-trimester pregnant women with acute uncomplicated falciparum malaria . METHODS : Twenty-six pregnant women in their third trimester ( gestational age : 24–34 weeks ) with acute uncomplicated Plasmodium falciparum malaria who fulfilled the enrollment criteria were recruited from the antenatal clinics of Mae Sot Hospital , Tak Province , Thail and , ( n=8 ) and the Tropical Diseases Research Centre , Ndola , Zambia ( n=18 ) . Patients were treated with four Malarone tablets ( GlaxoSmithKline : each tablet contains 250 mg atovaquone and 100 mg proguanil ) once daily for 3 consecutive days . Blood sample s were taken for pharmacokinetic investigations of atovaquone , proguanil , and cycloguanil up to 288 h ( day 14 ) after the last dose . Urine sample s were collected for the evaluation of proguanil and cycloguanil 0–8 , 8–16 , 16–24 and 24–48 h after the last dose . Efficacy assessment s included the clinical and parasitological evaluation of mothers and newborns . Adverse events were evaluated at each visit to the antenatal clinics . RESULTS : Malarone appeared to be effective and well tolerated when used for the treatment of falciparum malaria in pregnant women . All patients showed prompt clinical improvement and the disappearance of parasitaemia after treatment . There were no serious adverse effects or unexpected adverse effects and no stillbirths or spontaneous abortions . The plasma concentration-time profiles of atovaquone and proguanil in most cases were best characterised by the two-compartment open model with zero-order input with/without absorption lag time and first-order elimination . There were no significant differences in any of the pharmacokinetic parameters of atovaquone , proguanil or cycloguanil between patients from Thail and and Zambia . For atovaquone , a Cmax of 1.33–8.33 μg/ml was reached at 2.0–9.3 h after the last dose on day 2 . V/F , CL/F and t1/2β were 6.9–39.5 l/kg , 83–384 ml/h/kg , and 57.8–130.8 h , respectively . The Cmax and tmax values for proguanil versus cycloguanil were 383–918 versus 0–129 ng/ml and 3.3–8.6 versus 3–12 h , respectively . V/F , CL/F , and t1/2β values for proguanil were 10.7–34.0 l/kg , 431–1,662 ml/h/kg and 11.2–30.3 h. The CLR-CG , t1/2z , CG , proguanil/cycloguanil metabolic ratios , AUC ratios for proguanil to cycloguanil ( AUCPG/CG ) were 107.2–1,001 ml/h/kg , 5–95 ml/h/kg , 7.8–20.7 h , 5–57 , and 4.7–20.2 , respectively . CONCLUSION : The pharmacokinetics of atovaquone and cycloguanil appeared to be influenced by the pregnancy status , result ing in an decrease in the Cmax and AUC of approximately twofold Malaria during pregnancy is associated with maternal and fetal morbidity and mortality . In order to minimize the burden , sulfadoxine – pyrimethamine ( SP ) is widely used in Africa as an intermittent preventive treatment of malaria in pregnancy ( IPTp ) . However , only limited data are available on the pharmacokinetics of sulfadoxine and pyrimethamine during pregnancy . We conducted a prospect i ve , self‐matched , multicenter study of 98 pregnant women in four African countries in order to determine the effects of pregnancy on SP pharmacokinetics . After adjusting for the effects of potential confounders , blood concentrations ( associated with therapeutic efficacy ) of pyrimethamine were higher ( geometric mean ratio ( GMR ) 1.33 ; 95 % confidence interval ( CI ) 1.18–1.51 ; P < 0.001 ) and those of sulfadoxine were lower ( GMR 0.91 ; 95 % CI 0.84–0.98 ; P = 0.013 ) on day 7 after SP administration during pregnancy than after the postpartum period . SP pharmacokinetic parameters differed significantly among the study sites . Given the inconsistency of changes in pharmacokinetic parameters between sulfadoxine and pyrimethamine as well as among the study sites , it is not possible to recommend any dose adjustment to prolong the therapeutic life span of the fixed dose combination of SP for IPTp on the basis of our study findings BACKGROUND There is no safe , practical , and effective treatment for pregnant women infected with multidrug-resistant Plasmodium falciparum . METHODS We recruited pregnant Karen women in the second or third trimesters of pregnancy who had uncomplicated falciparum malaria for a r and omized , open-label trial with a restricted sequential trial design of 7 days of supervised quinine ( 
    Output:
    
Comparison of the available studies showed lower maximum concentrations ( Cmax ) and exposure ( AUC ) of dihydroartemisinin , the active metabolite of all artemisinin derivatives , after oral administration of artemether , artesunate and dihydroartemisinin in pregnant women .
Low day 7 concentrations were commonly seen in lumefantrine studies , indicating a low exposure and possibly reduced efficacy .
The influence of pregnancy on amodiaquine and piperaquine seemed not to be clinical ly relevant .
Sulfadoxine plasma concentration was significantly reduced and clearance rates were higher in pregnancy , while pyrimethamine and mefloquine need more research as no general conclusion can be drawn based on the available evidence .
For atovaquone , the available data showed a lower maximum concentration and exposure .
Finally , the maximum concentration of cycloguanil , the active metabolite of proguanil , was significantly lower , possibly compromising the efficacy .
Conclusion These findings suggest that re assessment of the dose of the artemisinin derivate and some components of ACT are necessary to ensure the highest possible efficacy of malaria treatment in pregnant women .