INTRODUCTION: Data on sexual violence (SV) prevalence in Nigeria is limited; however, 2014 data indicate that 24.8% of females aged 18-24 years experienced SV in childhood and only 3.5% received any form of services. Initiation of post-exposure prophylaxis (PEP) to prevent HIV acquisition following SV is most effective when started immediately and is not recommended after 72 hours. Police stations are often entry points for survivors; however, lengthy processes may result in delays and missed PEP opportunities. Using an ongoing phased approach, we introduced PEP into selected police stations in Nigeria's Federal Capital Territory in order to explore expanding access to time-sensitive HIV prevention within non-health services. METHODS: Our intervention phase consisted of the provision of training of police officers and the provision of PEP starter packs coupled with linkage to referral facilities. During two time periods (pre-intervention: January-March 2023) and (during intervention: July-September 2023), we evaluated routinely reported programme data from 27 U.S. Centers for Disease Control and Prevention-supported health facilities for changes in the provision of SV services and PEP initiation. We used geospatial mapping to assess the proximity of participating health facilities to police stations and to see changes in both SV and PEP service provision. The statistical significance of the difference in PEP uptake proportion during the two periods was determined using the Wilcoxon signed rank test at a 0.05 level of significance. RESULTS: Of the total 27 health facilities, 24 were within a 5-km radius of a participating police station. Total SV service provision increased from 114 cases to 218 cases, representing a 91.2% increase and with most of this increase seen among females. PEP initiation increased by 289.3% at the two time points, with 56 initiations pre-intervention to 218 PEP initiations during the intervention. CONCLUSIONS: Our findings showed promise in increasing immediate access to PEP in non-health services and highlighted the feasibility of police stations and health facilities collaboration to address urgent health needs. There was an overall increase in PEP initiations by referral and non-referral facilities which could be the result of demand creation and increased access at police stations.

Large-scale programmes using micronutrient powders (MNPs) may not achieve maximum impact due to limited/inappropriate MNP coverage, consumption, and use. We identify predictors of MNP coverage, maternal knowledge of appropriate use, and child MNP consumption in Nepal. A cross-sectional survey was conducted in 2,578 mother-child pairs representative of children 6-23 months in two districts that were part of the post-pilot, scale-up of an integrated infant and young child feeding-MNP (IYCF-MNP) programme. Children aged 6-23 months were expected to receive 60 MNP sachets every 6 months from a female community health volunteer (FCHV) or health centre. Outcomes of interest were MNP coverage (ever received), maternal knowledge of appropriate use (correct response to seven questions), repeat coverage (receipt >/= twice; among children 12-23 months who had received MNP at least once, n = 1342), and high intake (child consumed >/=75% of last distribution, excluding those with recent receipt/insufficient time to use 75% at recommended one-sachet-per-day dose, n = 1422). Multivariable log-binomial regression models were used to identify predictors of the four outcomes. Coverage, knowledge of appropriate use, and repeat coverage were 61.3%, 33.5%, and 45.9%, respectively. Among MNP receivers, 97.9% consumed MNP at least once and 38.9% of eligible children consumed >/=75% of last distribution. FCHV IYCF-MNP counselling was positively associated with knowledge, coverage, repeat coverage, and high intake; health worker counselling with knowledge and coverage indicators; and radio messages with coverage indicators only. FCHV counselling had the strongest association with knowledge, coverage, and high intake. Community-based counselling may play a vital role in improving coverage and intake in MNP programmes.

BACKGROUND: Artemisinin-based combination therapy (ACT) is recommended for uncomplicated Plasmodium vivax malaria in areas of emerging chloroquine resistance. We undertook a systematic review and individual patient data meta-analysis to compare the efficacies of dihydroartemisinin-piperaquine (DP) and artemether-lumefantrine (AL) with or without primaquine (PQ) on the risk of recurrent P. vivax. METHODS AND FINDINGS: Clinical efficacy studies of uncomplicated P. vivax treated with DP or AL and published between January 1, 2000, and January 31, 2018, were identified by conducting a systematic review registered with the International Prospective Register of Systematic Reviews (PROSPERO): CRD42016053310. Investigators of eligible studies were invited to contribute individual patient data that were pooled using standardised methodology. The effect of mg/kg dose of piperaquine/lumefantrine, ACT administered, and PQ on the rate of P. vivax recurrence between days 7 and 42 after starting treatment were investigated by Cox regression analyses according to an a priori analysis plan. Secondary outcomes were the risk of recurrence assessed on days 28 and 63. Nineteen studies enrolling 2,017 patients were included in the analysis. The risk of recurrent P. vivax at day 42 was significantly higher in the 384 patients treated with AL alone (44.0%, 95% confidence interval [CI] 38.7-49.8) compared with the 812 patients treated with DP alone (9.3%, 95% CI 7.1-12.2): adjusted hazard ratio (AHR) 12.63 (95% CI 6.40-24.92), p < 0.001. The rates of recurrence assessed at days 42 and 63 were associated inversely with the dose of piperaquine: AHRs (95% CI) for every 5-mg/kg increase 0.63 (0.48-0.84), p = 0.0013 and 0.83 (0.73-0.94), p = 0.0033, respectively. The dose of lumefantrine was not significantly associated with the rate of recurrence (1.07 for every 5-mg/kg increase, 95% CI 0.99-1.16, p = 0.0869). In a post hoc analysis, in patients with symptomatic recurrence after AL, the mean haemoglobin increased 0.13 g/dL (95% CI 0.01-0.26) for every 5 days that recurrence was delayed, p = 0.0407. Coadministration of PQ reduced substantially the rate of recurrence assessed at day 42 after AL (AHR = 0.20, 95% CI 0.10-0.41, p < 0.001) and at day 63 after DP (AHR = 0.08, 95% CI 0.01-0.70, p = 0.0233). Results were limited by follow-up of patients to 63 days or less and nonrandomised treatment groups. CONCLUSIONS: In this study, we observed the risk of P. vivax recurrence at day 42 to be significantly lower following treatment with DP compared with AL, reflecting the longer period of post-treatment prophylaxis; this risk was reduced substantially by coadministration with PQ. We found that delaying P. vivax recurrence was associated with a small but significant improvement in haemoglobin. These results highlight the benefits of PQ radical cure and also the provision of blood-stage antimalarial agents with prolonged post-treatment prophylaxis.

BACKGROUND: Malaria causes a reduction in haemoglobin that is compounded by primaquine, particularly in patients with glucose-6-phosphate dehydrogenase (G6PD) deficiency. The aim of this study was to determine the relative contributions to red cell loss of malaria and primaquine in patients with uncomplicated Plasmodium vivax. METHODS: A systematic review identified P. vivax efficacy studies of chloroquine with or without primaquine published between January 2000 and March 2017. Individual patient data were pooled using standardised methodology, and the haematological response versus time was quantified using a multivariable linear mixed effects model with non-linear terms for time. Mean differences in haemoglobin between treatment groups at day of nadir and day 42 were estimated from this model. RESULTS: In total, 3421 patients from 29 studies were included: 1692 (49.5%) with normal G6PD status, 1701 (49.7%) with unknown status and 28 (0.8%) deficient or borderline individuals. Of 1975 patients treated with chloroquine alone, the mean haemoglobin fell from 12.22 g/dL [95% CI 11.93, 12.50] on day 0 to a nadir of 11.64 g/dL [11.36, 11.93] on day 2, before rising to 12.88 g/dL [12.60, 13.17] on day 42. In comparison to chloroquine alone, the mean haemoglobin in 1446 patients treated with chloroquine plus primaquine was - 0.13 g/dL [- 0.27, 0.01] lower at day of nadir (p = 0.072), but 0.49 g/dL [0.28, 0.69] higher by day 42 (p < 0.001). On day 42, patients with recurrent parasitaemia had a mean haemoglobin concentration - 0.72 g/dL [- 0.90, - 0.54] lower than patients without recurrence (p < 0.001). Seven days after starting primaquine, G6PD normal patients had a 0.3% (1/389) risk of clinically significant haemolysis (fall in haemoglobin > 25% to < 7 g/dL) and a 1% (4/389) risk of a fall in haemoglobin > 5 g/dL. CONCLUSIONS: Primaquine has the potential to reduce malaria-related anaemia at day 42 and beyond by preventing recurrent parasitaemia. Its widespread implementation will require accurate diagnosis of G6PD deficiency to reduce the risk of drug-induced haemolysis in vulnerable individuals. TRIAL REGISTRATION: This trial was registered with PROSPERO: CRD42016053312. The date of the first registration was 23 December 2016.

There is limited research on integrated infant and young child feeding (IYCF) and micronutrient powders (MNPs) programmes operating at scale, despite widespread implementation. This study uses cross-sectional baseline (n = 2,542) and endline (n = 2,578) surveys representative of children 6-23 months in two districts in Nepal that were part of a post-pilot scale-up of a IYCF-MNP programme. Multivariable log-binomial regression models were used to estimate prevalence ratios (PRs) for stunting (length-for-age z-score <-2), wasting (weight-for-length z-score <-2), underweight (weight-for-age z-score <-2), anaemia (altitude-adjusted haemoglobin <110 mug/L), moderate or severe anaemia (altitude-adjusted haemoglobin <100 g/L), iron deficiency (inflammation-adjusted ferritin <12 mug/L), and iron deficiency anaemia (iron deficiency + anaemia [IDA]) at endline versus baseline and also to compare children in the endline survey based on frequency of mothers' interactions with female community health volunteers (FCHVs; >1x per month or monthly vs. <1x per month) and MNP coverage (1 or >/=2 distributions vs. none among children 12-23 months). Endline children were significantly less likely to be stunted than baseline children in both districts (multivariable-adjusted PR [95% CI]: 0.77 [0.69, 0.85], P < 0.001 and 0.82 [0.75, 0.91], P < 0.001 in Kapilvastu and Achham, respectively); however, only Achham had significantly lower prevalences of underweight, moderate/severe anaemia, iron deficiency, and IDA at endline. At endline, 53.5% and 71.4% of children had tried MNP in Kapilvastu and Achham districts, respectively, consuming an average of 24 sachets from the last distribution. Frequent maternal-FCHV interactions were associated with a reduced risk of stunting and underweight at endline, whereas repeat MNP coverage was associated with reduced risk of anaemia and IDA. Future research using experimental designs should verify the potential of integrated IYCF-MNP programmes to improve children's nutritional status.

BACKGROUND: Chloroquine remains the mainstay of treatment for Plasmodium vivax malaria despite increasing reports of treatment failure. We did a systematic review and meta-analysis to investigate the effect of chloroquine dose and the addition of primaquine on the risk of recurrent vivax malaria across different settings. METHODS: A systematic review done in MEDLINE, Web of Science, Embase, and Cochrane Database of Systematic Reviews identified P vivax clinical trials published between Jan 1, 2000, and March 22, 2017. Principal investigators were invited to share individual patient data, which were pooled using standardised methods. Cox regression analyses with random effects for study site were used to investigate the roles of chloroquine dose and primaquine use on rate of recurrence between day 7 and day 42 (primary outcome). The review protocol is registered in PROSPERO, number CRD42016053310. FINDINGS: Of 134 identified chloroquine studies, 37 studies (from 17 countries) and 5240 patients were included. 2990 patients were treated with chloroquine alone, of whom 1041 (34.8%) received a dose below the target 25 mg/kg. The risk of recurrence was 32.4% (95% CI 29.8-35.1) by day 42. After controlling for confounders, a 5 mg/kg higher chloroquine dose reduced the rate of recurrence overall (adjusted hazard ratio [AHR] 0.82, 95% CI 0.69-0.97; p=0.021) and in children younger than 5 years (0.59, 0.41-0.86; p=0.0058). Adding primaquine reduced the risk of recurrence to 4.9% (95% CI 3.1-7.7) by day 42, which is lower than with chloroquine alone (AHR 0.10, 0.05-0.17; p<0.0001). INTERPRETATION: Chloroquine is commonly under-dosed in the treatment of vivax malaria. Increasing the recommended dose to 30 mg/kg in children younger than 5 years could reduce substantially the risk of early recurrence when primaquine is not given. Radical cure with primaquine was highly effective in preventing early recurrence and may also improve blood schizontocidal efficacy against chloroquine-resistant P vivax. FUNDING: Wellcome Trust, Australian National Health and Medical Research Council, and Bill & Melinda Gates Foundation.

Background: Three-quarters of the >/=50 programs that use micronutrient powders (MNPs) integrate MNPs into infant and young child feeding (IYCF) programs, with limited research on impacts on IYCF practices. Objective: This study assessed changes in IYCF practices in 2 districts in Nepal that were part of a post-pilot scale-up of an integrated IYCF-MNP program. Methods: This analysis used cross-sectional surveys (n = 2543 and 2578 for baseline and endline) representative of children aged 6-23 mo and their mothers in 2 districts where an IYCF program added MNP distributions through female community health volunteers (FCHVs) and health workers (HWs). Multivariable log-binomial models estimated prevalence ratios comparing reported IYCF at endline with baseline and at endline on the basis of exposure to different sources of IYCF information. Mothers who received FCHV-IYCF counseling with infrequent (</=1 time/mo) and frequent (>1 time/mo) interactions were compared with mothers who never received FCHV-IYCF counseling. The receipt of HW-IYCF counseling and receipt of MNPs from an FCHV (both yes or no) were also compared. Results: The prevalence of minimum dietary diversity (MDD) and minimum acceptable diet (MAD) was significantly higher at endline than at baseline. In analyses from endline, compared with mothers who never received FCHV counseling, only mothers in the frequent FCHV-IYCF counseling group were more likely to report feeding the minimum meal frequency (MMF) and MAD, with no difference for the infrequent FCHV-IYCF counseling group in these indicators. HW-IYCF counseling was not associated with these indicators. Mothers who received MNPs from their FCHV were more likely to report initiating solid foods at 6 mo and feeding the child the MDD, MMF, and MAD compared with mothers who did not, adjusting for HW- and FCHV-IYCF counseling and demographic covariates. Conclusions: Incorporating MNPs into the Nepal IYCF program did not harm IYCF and may have contributed to improvements in select practices. Research that uses experimental designs should verify whether integrated IYCF-MNP programs can improve IYCF practices.

BACKGROUND: Assessing micronutrient powder (MNP) consumption is the key for monitoring program performance; no gold standard exists for assessing consumption in nutrition programs. OBJECTIVE: To compare estimates of MNP consumption assessed by maternal report versus observed unopened MNP sachets in the household. METHODS: Cross-sectional household surveys of children aged 6 to 23 months were conducted to assess an MNP project in Nepal; eligible children received 60 sachets per distribution. Mothers reported the number of sachets consumed and showed unused sachets. Directly observed difference (DOD) of MNP consumption was calculated by subtracting the number of observed unopened sachets from 60. Spearman correlation coefficient, categories of MNP consumption, and end digit preference were assessed. RESULTS: A total of 205 mothers did not show remaining unopened sachets despite reporting that all were not consumed. For the remaining 605 children, median consumption was 60.0 sachets by DOD and maternal report; the correlation coefficient was 0.91. With consumption grouped into categories of 0 to 14, 15 to 29, 30 to 44, and 45 to 60 sachets, the percent categorized into the same groupings by DOD and maternal report was 100%, 80.6%, 80.7%, and 91.2%, respectively. Excluding those who consumed 60 sachets, 16.9% and 8.0% by report and 14.2% and 6.1% DOD, ended with 0 and 5, respectively. CONCLUSION: Had the observation of unused sachets been used alone to assess MNP consumption, 205 children would not have been assessed. Estimates of MNP consumption by DOD and maternal report were similar in this population with high intake adherence.

Many children in low- and middle-income countries may have inadequate intake of vitamin B12 and folate; data confirming these inadequacies are limited. We used biochemical, demographic, behavioral and anthropometric data to describe the folate and vitamin B12 concentrations among six- to 23-month-old Nepalese children. Vitamin B12 (serum B12 < 150 pmol/L) and folate deficiencies (red blood cell (RBC) folate < 226.5 nmol/L) were assessed. We used logistic regression to identify predictors of vitamin B12 deficiency. The vitamin B12 geometric mean was 186 pmol/L; 30.2% of children were deficient. The mean RBC folate concentration was 13,612 nmol/L; there was no deficiency. Factors associated with vitamin B12 deficiency included: (a) age six to 11 months (adjusted odds ratio (aOR) 1.51; 95% confidence interval (CI): 1.18, 1.92) or 12-17 months (aOR 1.38; 95% CI: 1.10, 1.72) compared to 18-23 months; (b) being stunted (aOR 1.24; 95% CI: 1.03, 1.50) compared to not being stunted; (c) and not eating animal-source foods (aOR 1.85; 95% CI: 1.42, 2.41) compared to eating animal-source foods the previous day. There was a high prevalence of vitamin B12 deficiency, but no folate deficiency. Improving early feeding practices, including the consumption of rich sources of vitamin B12, such as animal-source foods and fortified foods, may help decrease deficiency.

BACKGROUND AND OBJECTIVE: Little is known about purchasing micronutrient powders (MNP) for children 2-5 years. We describe acceptability for purchasing and price points for MNP for children 2-5 years among caregivers living in districts where free MNP are distributed for children 6-23 months. METHODS AND STUDY DESIGN: Crosssectional surveys conducted 3 months after MNP program implementation in 2 districts; 15 months after implementation in 2 different districts. Chi square tests and logistic regression describe associations among sociodemographics and program exposure factors and acceptability of purchasing MNP among 1,261 mothers of children 6-23 months who had heard of MNP. RESULTS: Overall, 77.5% and 86.1% of mothers reported acceptability for purchasing MNP in the 3 and 15 month surveys, respectively. Positive pricing attitude (PPA) about paying 150 Nepali rupees for 60 sachets of MNP was reported by 66.3% and 73.4% of mothers. Acceptability for purchasing MNP in both time periods increased with higher wealth quintile and higher maternal education; PPA increased with higher maternal education. Controlling for socio-demographics, program exposure factors associated with acceptability for purchasing MNP included: lack of perceived barriers to MNP intake and health worker counselling (3 month surveys); knowledge of benefits of MNP intake and lack of perceived barriers to MNP intake (15 month surveys). CONCLUSIONS: Mothers reported acceptability for purchasing MNP and PPA for older children in Nepal. Differences in acceptability were found across socio-demographics and program exposures. Use of these results and further exploration into actual purchasing behaviour can inform future MNP distribution methods in Nepal.

Integrated infant and young child feeding (IYCF)/micronutrient powder (MNP) programs are increasingly used to address poor IYCF practices and micronutrient deficiencies in low-income settings; however, little is known about how MNP use may affect IYCF practices. We describe how MNP use was associated with IYCF practices in a pilot program in select districts of Nepal where free MNP for children 6-23 months were added to an existing IYCF platform. Representative cross-sectional surveys were conducted in pilot districts with mothers of eligible children at 3 months (plains ecozone, n=1054) or 15 months (hill ecozone, rural only, n=654) after implementation of an integrated MNP/IYCF program. We used logistic regression to assess how IYCF practices varied by MNP use (none, 1-30, 30-60 sachets). At both time points, consuming 30-60 MNP sachets vs. none was associated with achieving minimum dietary diversity and minimum acceptable diet. In the 3 month survey consuming 30- 60 MNP sachets vs none was also associated with achieving minimum meal frequency and continued breastfeeding at 2 years. In this setting, addition of MNP to an existing platform of IYCF messaging did not appear detrimental to IYCF practices.; Publisher: Abstract available from the publisher.; chi

OBJECTIVE: Poor adherence to recommended intake protocols is common and a top challenge for micronutrient powder (MNP) programmes globally. Identifying modifiable predictors of intake adherence could inform the design and implementation of MNP projects. DESIGN: We assessed high MNP intake adherence among children who had received MNP ≥2 months ago and consumed ≥1 sachet (n 771). High MNP intake adherence was defined as maternal report of child intake ≥45 sachets. We used logistic regression to assess demographic, intervention components and perception-of-use factors associated with high MNP intake. SETTING: Four districts of Nepal piloting an integrated infant and young child feeding and MNP project. SUBJECTS: Children aged 6-23 months were eligible to receive sixty MNP sachets every 6 months with suggested intake of one sachet daily for 60 d. Cross-sectional surveys representative of children aged 6-23 months were conducted. RESULTS: Receiving a reminder card was associated with increased odds for high intake (OR=2.18, 95 % CI 1.14, 4.18); exposure to other programme components was not associated with high intake. Mothers perceiving ≥1 positive effects in their child after MNP use was also associated with high intake (OR=6.55, 95 % CI 4.29, 10.01). Perceiving negative affects was not associated; however, the child not liking the food with MNP was associated with lower odds of high intake (OR=0.12, 95 % CI 0.08, 0.20). CONCLUSIONS: Behaviour change intervention strategies tailored to address these modifiable predictors could potentially increase MNP intake adherence.

BACKGROUND: Artemisinin-resistant Plasmodium falciparum has emerged in the Greater Mekong sub-region and poses a major global public health threat. Slow parasite clearance is a key clinical manifestation of reduced susceptibility to artemisinin. This study was designed to establish the baseline values for clearance in patients from Sub-Saharan African countries with uncomplicated malaria treated with artemisinin-based combination therapies (ACTs). METHODS: A literature review in PubMed was conducted in March 2013 to identify all prospective clinical trials (uncontrolled trials, controlled trials and randomized controlled trials), including ACTs conducted in Sub-Saharan Africa, between 1960 and 2012. Individual patient data from these studies were shared with the WorldWide Antimalarial Resistance Network (WWARN) and pooled using an a priori statistical analytical plan. Factors affecting early parasitological response were investigated using logistic regression with study sites fitted as a random effect. The risk of bias in included studies was evaluated based on study design, methodology and missing data. RESULTS: In total, 29,493 patients from 84 clinical trials were included in the analysis, treated with artemether-lumefantrine (n = 13,664), artesunate-amodiaquine (n = 11,337) and dihydroartemisinin-piperaquine (n = 4,492). The overall parasite clearance rate was rapid. The parasite positivity rate (PPR) decreased from 59.7 % (95 % CI: 54.5-64.9) on day 1 to 6.7 % (95 % CI: 4.8-8.7) on day 2 and 0.9 % (95 % CI: 0.5-1.2) on day 3. The 95th percentile of observed day 3 PPR was 5.3 %. Independent risk factors predictive of day 3 positivity were: high baseline parasitaemia (adjusted odds ratio (AOR) = 1.16 (95 % CI: 1.08-1.25); per 2-fold increase in parasite density, P <0.001); fever (>37.5 degreeC) (AOR = 1.50 (95 % CI: 1.06-2.13), P = 0.022); severe anaemia (AOR = 2.04 (95 % CI: 1.21-3.44), P = 0.008); areas of low/moderate transmission setting (AOR = 2.71 (95 % CI: 1.38-5.36), P = 0.004); and treatment with the loose formulation of artesunate-amodiaquine (AOR = 2.27 (95 % CI: 1.14-4.51), P = 0.020, compared to dihydroartemisinin-piperaquine). CONCLUSIONS: The three ACTs assessed in this analysis continue to achieve rapid early parasitological clearance across the sites assessed in Sub-Saharan Africa. A threshold of 5 % day 3 parasite positivity from a minimum sample size of 50 patients provides a more sensitive benchmark in Sub-Saharan Africa compared to the current recommended threshold of 10 % to trigger further investigation of artemisinin susceptibility.

Many countries implement micronutrient powder (MNP) programmes to improve the nutritional status of young children. Little is known about the predictors of MNP coverage for different delivery models. We describe MNP coverage of an infant and young child feeding and MNP intervention for children aged 6-23 months comparing two delivery models piloted in rural Nepal: distributing MNPs either by female community health volunteers (FCHVs) or at health facilities (HFs). Cross-sectional household cluster surveys were conducted in four pilot districts among mothers of children 6-23 months after starting MNP distribution. FCHVs in each cluster were also surveyed. We used logistic regression to describe predictors of initial coverage (obtaining a batch of 60 MNP sachets) at 3 months and repeat coverage (≥2 times coverage among eligible children) at 15 months after project launch. At 15 months, initial and repeat coverage were higher in the FCHV model, although no differences were observed at 3 months. Attending an FCHV-led mothers' group meeting where MNP was discussed increased odds of any coverage in both models at 3 months and of repeat coverage in the HF model at 15 months. Perceiving ≥1 positive effects in the child increased odds of repeat coverage in both delivery models. A greater portion of FCHV volunteers from the FCHV model vs. the HF model reported increased burden at 3 and 15 months (not statistically significant). Designing MNP programmes that maximise coverage without overburdening the system can be challenging and more than one delivery model may be needed.

Adequate clinical and parasitologic cure by artemisinin combination therapies relies on the artemisinin component and the partner drug. Polymorphisms in the Plasmodium falciparum chloroquine resistance transporter (pfcrt) and P. falciparum multidrug resistance 1 (pfmdr1) genes are associated with decreased sensitivity to amodiaquine and lumefantrine, but effects of these polymorphisms on therapeutic responses to artesunate-amodiaquine (ASAQ) and artemether-lumefantrine (AL) have not been clearly defined. Individual patient data from 31 clinical trials were harmonized and pooled by using standardized methods from the WorldWide Antimalarial Resistance Network. Data for more than 7,000 patients were analyzed to assess relationships between parasite polymorphisms in pfcrt and pfmdr1 and clinically relevant outcomes after treatment with AL or ASAQ. Presence of the pfmdr1 gene N86 (adjusted hazards ratio = 4.74, 95% confidence interval = 2.29 - 9.78, P < 0.001) and increased pfmdr1 copy number (adjusted hazards ratio = 6.52, 95% confidence interval = 2.36-17.97, P < 0.001: were significant independent risk factors for recrudescence in patients treated with AL. AL and ASAQ exerted opposing selective effects on single-nucleotide polymorphisms in pfcrt and pfmdr1. Monitoring selection and responding to emerging signs of drug resistance are critical tools for preserving efficacy of artemisinin combination therapies; determination of the prevalence of at least pfcrt K76T and pfmdr1 N86Y should now be routine.