The effect of iron supplementation on maternal iron deficiency anemia does not differ by baseline anemia type among Tanzanian pregnant women without severe iron deficiency anemia.

PURPOSE: Whether anemia type modifies the risk of pregnancy and newborn outcomes and the effectiveness of iron supplementation is unclear. We examined the association of iron deficiency anemia (IDA) and non-iron deficiency anemia (NIDA) on the risks of these outcomes and the extent to which anemia type modifies the impact of prenatal iron supplementation. METHODS: This was a secondary analysis of a placebo-controlled trial of iron supplementation among 1450 HIV-negative women in Tanzania. Eligibility criteria included gestational age < 27 weeks, hemoglobin > 85 g/L, and ferritin > 12 µg/L. Individuals were categorized as non-anemia, IDA or NIDA using hemoglobin, ferritin and CRP. Analyses were conducted using regression models and likelihood ratio tests. RESULTS: Compared to the non-anemia group, delivery hemoglobin was lower by 15 g/L (95% CI 10.9, 19.3) in the baseline IDA group, and 7.3 g/L (95% CI 3.1, 11.5) in the baseline NIDA group. The RRs of anemia severity, iron deficiency, placental malaria, stillbirths, perinatal mortality, birthweight, and preterm birth were not different among women in the baseline NIDA group (vs. non-anemia) compared to the baseline IDA group (vs. non-anemia). The difference in the mean delivery hemoglobin for iron supplementation and placebo arms was 8 g/L (95% CI 6, 11) in the non-anemia group, 7 g/L (95% CI 2, 13) in the NIDA group, and 16 g/L (95% CI 10, 22) in the IDA group. CONCLUSION: Iron supplementation is effective even among pregnant women with NIDA. TRIAL REGISTRATION: NCT01119612 (May 7, 2010).

Prenatal Zinc and Vitamin A Reduce the Benefit of Iron on Maternal Hematologic and Micronutrient Status at Delivery in Tanzania.

BACKGROUND: Zinc and vitamin A supplementation have both been shown to affect iron status, hemoglobin (Hb) concentration, and anemia in animal and human studies. However, evidence on their combined use in pregnancy, in the context of iron-folic acid (IFA) supplementation, remains limited. OBJECTIVE: This study determined the effects of prenatal zinc, vitamin A, and iron supplementation on maternal hematologic and micronutrient status at delivery in Tanzania. METHODS: We analyzed 2 large randomized controlled trials, using generalized estimating equations, and examined the effect of daily zinc (25 mg) and vitamin A (2500 IU) supplementation starting in the first trimester of pregnancy compared with placebo (n = 2500), and separately evaluated the safety and efficacy of daily iron (60 mg) supplementation among iron-replete pregnant women (n = 1500). Blood samples from baseline and delivery were tested for Hb, serum ferritin, soluble transferrin receptor, plasma zinc, and zinc protoporphyrin. RESULTS: Zinc and vitamin A supplementation were associated with lower Hb concentrations at delivery of  -0.26 g/dL (95% CI: -0.50, -0.02 g/dL) and -0.25 g/dL (95% CI: -0.49, -0.01 g/dL), respectively. Vitamin A increased mean ferritin concentrations at delivery (14.3 µg/L, 95% CI: 1.84, 29.11 µg/L), but was associated with increased risk of severe anemia (RR: 1.41; 95% CI: 1.06, 1.88). Among women who were iron replete at baseline, iron supplementation reduced the risk of iron depletion at delivery by 47% (RR: 0.53; 95% CI: 0.43, 0.65). There was no effect of zinc or iron supplements on plasma zinc concentrations. CONCLUSIONS: Our findings support existing WHO guidelines on prenatal iron, vitamin A, and zinc supplementation among pregnant women. In this setting, scaling uptake of prenatal iron supplements is warranted, but prenatal zinc and vitamin A supplementation did not benefit maternal hematologic status at delivery. In settings where vitamin A deficiency is endemic, the efficacy and safety of the WHO recommended prenatal vitamin A supplementation require further evaluation.

Metabolic syndrome and its predictors in an urban population in Kenya: A cross sectional study.

BACKGROUND: The metabolic syndrome (MetS) is a clustering of interrelated risk factors which doubles the risk of cardio-vascular disease (CVD) in 5-10 years and increases the risk of type 2 diabetes 5 fold. The identification of modifiable CVD risk factors and predictors of MetS in an otherwise healthy population is necessary in order to identify individuals who may benefit from early interventions. We sought to determine the prevalence of MetS as defined by the harmonized criteria and its predictors in subjectively healthy black Africans from various urban centres in Kenya. METHOD: We used data collected from healthy black Africans in Kenya as part of a global study on establishing reference intervals for common laboratory tests. We determined the prevalence of MetS and its components using the 2009 harmonized criterion. Receiver operator characteristic (ROC) curve analysis was used to determine the area under the curves (AUC) for various predictors of MetS. Youden index was used to determine optimum cut-offs for quantitative measurements such as waist circumference (WC). RESULTS: A total of 528 participants were included in the analysis. The prevalence of MetS was 25.6% (95% CI: 22.0%-29.5%). Among the surrogate markers of visceral adiposity, lipid accumulation product was the best predictor of MetS with an AUC of 0.880 while triglyceride was the best predictor among the lipid parameters with an AUC of 0.816 for all participants. The optimal WC cut-off for diagnosing MetS was 94 cm and 86 cm respectively for males and females. CONCLUSIONS: The prevalence of MetS was high for a healthy population highlighting the fact that one can be physically healthy but have metabolic derangements indicative of an increased CVD risk. This is likely to result in an increase in the cases of CVD and type 2 diabetes in Kenya if interventions are not put in place to reverse this trend. We have also demonstrated the inappropriateness of the WC cut-off of 80 cm for black African women in Kenya when defining MetS and recommend adoption of 86 cm.

Epidemiology of malaria in a village in the Rufiji River Delta, Tanzania: declining transmission over 25 years revealed by different parasitological metrics.

BACKGROUND: Assessments of the epidemiology of malaria over time are needed to understand changes in transmission and guide control and elimination strategies. METHODS: A longitudinal population study was established in 1985 in Nyamisati village in the Rufiji River Delta, Tanzania. A physician and research team lived in the village 1984-2000. Parasite prevalence by microscopy and two PCR methods, spleen rates and haemoglobin levels were measured in repeated cross-sectional surveys between 1985 and 2010. Passive surveillance of malaria cases was maintained until end 1999. Bed nets were distributed after the surveys 1993, 1999 and 2010. RESULTS: In 1985, overall parasite prevalence by microscopy was 70% (90% in children ages two to nine years). The prevalence decreased gradually by microscopy (38.9% 1994, 26.7% 1999) and msp2-PCR (58.7% 1994, 44.8% 1999), whereas real-time PCR prevalence remained higher throughout the 1990s (69.4% 1994, 64.8% 1999). In 2010, parasite prevalence was 17.8% by real-time PCR and 16.3% by msp2-PCR, and estimated to 4.8% by microscopy. Spleen rates in children ages two to nine years decreased earlier than parasite prevalence, from >75 to 42% in the 1980s, to nil during the 1990s. The prevalence of severe and moderate anaemia decreased from 41.1 to 13.1%. No deaths at the time of acute malaria were recorded when the research team lived in the village. CONCLUSIONS: A marked decline in malaria transmission was observed over 25 years. The decrease was detected after the arrival of the research team and continued gradually both before and after distribution of bed nets. Spleen rates and microscopy identified early changes when transmission was still intense, whereas real-time PCR was a more sensitive metric when transmission was reduced. The study provides historical data on malaria within a closely monitored rural village and contributes to the understanding of changing epidemiology in sub-Saharan Africa.

Exploration of in vivo efficacy of artemether-lumefantrine against uncomplicated Plasmodium falciparum malaria in under fives in Tabora region, Tanzania.

BACKGROUND: Tanzania adopted artemether-lumefantrine (AL) as first-line drug for uncomplicated malaria in 2006. Recently, there was an anecdotal report on high malaria recurrence rate following AL treatment in in the (urban and peri-urban), western part of Tanzania. The current report is an exploratory study to carefully and systematically assess AL efficacy in the area. METHODS: Between June and August 2011, a total of 1,126 patients were screened for malaria, 33 had malaria, of which 20 patients met inclusion criteria and were enrolled and treated with standard dose of AL as recommended in the WHO protocol. Treated patients were followed up for 28 days to assess treatment responses. Before treatment (Day 0) and post-treatment (Day 7) plasma lumefantrine levels were determined to assess prior AL use and ascertain parasites exposure to adequate plasma leveles of lumefantrine, respectively. RESULTS: The cure rate was 100%. All Day 0 plasma lumefantrine were below HPLC detectable level. The median Day 7 lumefantrine concentration was 404, (range, 189-894 ng/ml). Six out of 20 patients (30%) were gametocytaemic and all cleared gametocytes by Day 14. One patient showed an increase in gametocytes from four on Day 0 to 68, per 500 WBC on Day 2. CONCLUSION: Artemether lumefantrine is highly efficacious against uncomplicated Plasmodium falciparum malaria. The elevation of gametocytaemia despite AL treatment needs to be evaluated in a larger study.

Community screening and treatment of asymptomatic carriers of Plasmodium falciparum with artemether-lumefantrine to reduce malaria disease burden: a modelling and simulation analysis.

BACKGROUND: Asymptomatic carriers of Plasmodium falciparum serve as a reservoir of parasites for malaria transmission. Identification and treatment of asymptomatic carriers within a region may reduce the parasite reservoir and influence malaria transmission in that area. METHODS: Using computer simulation, this analysis explored the impact of community screening campaigns (CSC) followed by systematic treatment of P. falciparum asymptomatic carriers (AC) with artemether-lumefantrine (AL) on disease transmission. The model created by Okell et al (originally designed to explore the impact of the introduction of treatment with artemisinin-based combination therapy on malaria endemicity) was modified to represent CSC and treatment of AC with AL, with the addition of malaria vector seasonality. The age grouping, relative distribution of age in a region, and degree of heterogeneity in disease transmission were maintained. The number and frequency of CSC and their relative timing were explored in terms of their effect on malaria incidence. A sensitivity analysis was conducted to determine the factors with the greatest impact on the model predictions. RESULTS: The simulation showed that the intervention that had the largest effect was performed in an area with high endemicity (entomological inoculation rate, EIR > 200); however, the rate of infection returned to its normal level in the subsequent year, unless the intervention was repeated. In areas with low disease burden (EIR < 10), the reduction was sustained for over three years after a single intervention. Three CSC scheduled in close succession (monthly intervals) at the start of the dry season had the greatest impact on the success of the intervention. CONCLUSIONS: Community screening and treatment of asymptomatic carriers with AL may reduce malaria transmission significantly. The initial level of disease intensity has the greatest impact on the potential magnitude and duration of malaria reduction. When combined with other interventions (e.g. long-lasting insecticide-treated nets, rapid diagnostic tests, prompt diagnosis and treatment, and, where appropriate, indoor residual spraying) the effect of this intervention can be sustained for many years, and it could become a tool to accelerate the reduction in transmission intensity to pre-elimination levels. Repeated interventions at least every other year may help to prolong the effect. The use of an effective diagnostic tool and a highly effective ACT, such as AL, is also vital. The modelling supports the evaluation of this approach in a prospective clinical trial to reduce the pool of infective vectors for malaria transmission in an area with marked seasonality.

Treatment of asymptomatic carriers with artemether-lumefantrine: an opportunity to reduce the burden of malaria?

BACKGROUND: Increased investment and commitment to malaria prevention and treatment strategies across Africa has produced impressive reductions in the incidence of this disease. Nevertheless, it is clear that further interventions will be necessary to meet the international target of a reversal in the incidence of malaria by 2015. This article discusses the prospective role of an innovative malaria control strategy - the community-based treatment of asymptomatic carriers of Plasmodium falciparum, with artemisinin-based combination therapy (ACT). The potential of this intervention was considered by key scientists in the field at an Advisory Board meeting held in Basel, in April 2009. This article summarizes the discussions that took place among the participants. PRESENTATION OF THE HYPOTHESIS: Asymptomatic carriers do not seek treatment for their infection and, therefore, constitute a reservoir of parasites and thus a real public-health risk. The systematic identification and treatment of individuals with asymptomatic P. falciparum as part of a surveillance intervention strategy should reduce the parasite reservoir, and if this pool is greatly reduced, it will impact disease transmission. TESTING THE HYPOTHESIS: This article considers the populations that could benefit from such a strategy and examines the ethical issues associated with the treatment of apparently healthy individuals, who represent a neglected public health risk. The potential for the treatment of asymptomatic carriers to impair the development of protective immunity, resulting in a 'rebound' and age escalation of malaria incidence, is also discussed.For policymakers to consider the treatment of asymptomatic carriers with ACT as a new tool in their malaria control programmes, it will be important to demonstrate that such a strategy can produce significant benefits, without having a negative impact on the efficacy of ACT and the health of the target population. IMPLICATIONS OF THE HYPOTHESIS: The treatment of asymptomatic carriers with ACT is an innovative and essential tool for breaking the cycle of infection in some transmission settings. Safe and effective medicines can save the lives of children, but the reprieve is only temporary so long as the mosquitoes can become re-infected from the asymptomatic carriers. With improvements in rapid diagnostic tests that allow easier identification of asymptomatic carriers, the elimination of the pool of parasites is within reach.

Hemoglobin and hepcidin have good validity and utility for diagnosing iron deficiency anemia among pregnant women.

BACKGROUND/OBJECTIVES: Screening and diagnosis of iron deficiency anemia (IDA) is cumbersome as it may require testing for hemoglobin, ferritin, and an inflammatory biomarker. The aim of this study was to compare the diagnostic capacity of hematologic biomarkers to detect IDA among pregnant women in Tanzania. SUBJECTS/METHODS: We pooled data from an iron supplementation trial of 1500 iron-replete pregnant woman and a prospective cohort of 600 iron-deficient pregnant women. Receiver operating characteristic curves (ROC) for hematologic biomarkers were used to assess the sensitivity, specificity, and area under the curve (AUC) for iron deficiency (ID) and iron deficiency anemia (IDA), crude, or corrected for inflammation. Regression models assessed the relationship of baseline biomarker categories (gestational age <27 weeks) and IDA at delivery. RESULTS: Hemoglobin had the largest AUC for crude ID (0.96), while hepcidin had the largest AUC for corrected ID (0.80). The optimal hepcidin cutoff for the diagnosis of corrected IDA based on maximal sensitivity and specificity was ≤1.6 µg/L. An hepcidin cutoff of <4.3 µg/L had a sensitivity of 95% for regression-corrected ID. Among iron-replete women who did not receive iron, the association of baseline hemoglobin >110 g/L with IDA at delivery (RR = 0.73; 95% CI: 0.47, 1.13) was attenuated. Baseline hepcidin >1.6 µg/L was associated with reduced risk of anemia at delivery by 49% (95% CI: 27%, 45%). CONCLUSIONS: Ascertaining hemoglobin and hepcidin levels may improve the targeting of iron supplementation programs in resource-limited countries, though hepcidin's high costs may limit its use.

Coartem: the journey to the clinic.

Artemisinin, from which the artemether component of Coartem (artemether/lumefantrine, AL) is derived, is obtained from the plant sweet wormwood (Artemisia annua) which has been used for over 2,000 years as a Chinese herbal remedy. Artemisinin was first identified by Chinese researchers as the active anti-malarial constituent of A. annua and its derivatives were found to be the most potent of all anti-malarial drugs. Artemether acts rapidly, reducing the infecting parasite biomass by approximately 10,000-fold per asexual life cycle. Lumefantrine, the other active constituent of AL, acts over a longer period to eliminate the residual 100-100,000 parasites that remain after artemether is cleared from the body and thus minimizes the risk of recrudescence. The two agents have different modes of action and act at different points in the parasite life cycle and show a synergistic action against Plasmodium falciparum in vitro. The combination of artemether and lumefantrine reduces the risk of resistance developing to either agent, and to date there are no reports of resistance to AL combined therapy in the malaria parasite that infects humans. Following a unique partnership agreement between Chinese authorities and Novartis, the manufacturer of AL, over 20 sponsored clinical studies have been undertaken in various malaria endemic regions and in travellers. These trials have involved more than 3,500 patients (including over 2,000 children), and led to identification of a six-dose, three-day regimen as the optimal dosing strategy for AL in uncomplicated falciparum malaria. AL has consistently shown 28-day polymerase chain (PCR)-corrected cure rates greater than 95% in the evaluable population, meeting WHO recommendations. More recently, Novartis and the Medicines for Malaria Venture have worked in partnership to develop Coartem Dispersible, a new formulation designed specifically to meet the specific needs of children with malaria. The dispersible tablets have shown similar high response rates to those observed with crushed standard tablets of AL. A partnership agreement between Novartis and WHO has seen over 250 million AL (Coartem) treatments (75% for children) being distributed to malaria patients in developing countries without profit, supported by training programmes and educational resources.

The content of African diets is adequate to achieve optimal efficacy with fixed-dose artemether-lumefantrine: a review of the evidence.

A fixed-dose combination of artemether-lumefantrine (AL, Coartem(R)) has shown high efficacy, good tolerability and cost-effectiveness in adults and children with uncomplicated malaria caused by Plasmodium falciparum. Lumefantrine bioavailability is enhanced by food, particularly fat.As the fat content of sub-Saharan African meals is approximately a third that of Western countries, it raises the question of whether fat consumption by African patients is sufficient for good efficacy. Data from healthy volunteers have indicated that drinking 36 mL soya milk (containing only 1.2 g of fat) results in 90% of the lumefantrine absorption obtained with 500 mL milk (16 g fat). African diets are typically based on a carbohydrate staple (starchy root vegetables, fruit [plantain] or cereals) supplemented by soups, relishes and sauces derived from vegetables, pulses, nuts or fish. The most important sources of dietary fat in African countries are oil crops (e.g. peanuts, soya beans) and cooking oils as red palm, peanut, coconut and sesame oils. Total fat intake in the majority of subSaharan countries is estimated to be in the range 30-60 g/person/day across the whole population (average 43 g/person/day). Breast-feeding of infants up to two years of age is standard, with one study estimating a fat intake of 15-30 g fat/day from breast milk up to the age of 18 months. Weaning foods typically contain low levels of fat, and the transition from breast milk to complete weaning is associated with a marked reduction in dietary fat. Nevertheless, fat intake >10 g/day has been reported in young children post-weaning. A randomized trial in Uganda reported no difference in the efficacy of AL between patients receiving supervised meals with a fixed fat content (~23 g fat) or taking AL unsupervised, suggesting that fat intake at home was sufficient for optimal efficacy. Moreover, randomized trials in African children aged 5-59 months have shown similar high cure rates to those observed in older populations, indicating that food consumption is adequate post-weaning. In conclusion, it appears that only a very small amount of dietary fat is necessary to ensure optimal efficacy with AL and that the fat content of standard meals or breast milk in sub-Saharan Africa is adequate.

A randomized control trial comparing train of four ratio > 0.9 to clinical assessment of return of neuromuscular function before endotracheal extubation on critical respiratory events in adult patients undergoing elective surgery at a tertiary hospital in Nairobi.

BACKGROUND: There is increasing evidence that the incidence of postoperative residual paresis after using neuromuscular blockers ranges from 24 to 50% in post anaesthesia care unit (PACU) and is associated with postoperative complications such as critical respiratory events as evidenced by hypoxia, hypoventilation and upper airway obstruction. Quantitative neuromuscular monitoring (such as the assessment of Train of four (TOF) ratio) and reversal of neuromuscular blockers has been shown to reduce postoperative residual paresis. There are very few outcome studies on effect of residual paresis in PACU. There is a paucity of published randomized controlled trials investigating whether using a TOF ratio ≥0.9 before endotracheal extubation compared to clinical assessment of return of neuromuscular function reduces the incidence of critical respiratory events in PACU. OBJECTIVE: To determine whether using TOF ratio ≥ 0.9 compared to clinical assessment of return of neuromuscular function before endotracheal extubation reduces the incidence of critical respiratory events in PACU. METHODS: Onehundred sixty eight adult patients in ASA physical status I and II requiring general anaesthesia for elective surgery with cisatracurium as the muscle relaxant were randomized into 2 groups of 84 each. Group 1 were patients who required a TOF ratio of ≥0.9 before extubation. Group 2 patients were extubated based on clinical assessment of return of adequate neuromuscular function by the anaesthetist as is the standard of practice at the Aga Khan University hospital Nairobi. General anaesthesia was standardized in both groups. Both the investigators and patients were blinded during the study.Once the patient was transferred to PACU, oxygen saturation (SP02), respiratory rate and any signs of upper airway obstruction as demonstrated by stridor, laryngospasms or requirement of any airway manipulation was recorded for the first 30 minutes. Duration of anaesthesia and surgery was also recorded. Patient demographics were recorded and analyzed. RESULTS: There was no statistical difference between the 2 groups in terms of patient demographics, duration of surgery and anaesthesia and duration since last muscle relaxant was given. In terms of hypoxia on arrival in PACU, the incidence of mild hypoxia (SPO2 90-93%) was 11% in clinical assessment groupversus 5% in TOF group P-value 0.149 while severe hypoxia (SPO2 <90%) was 19% versus 10% P-value 0.078. During the first 30 minutes in PACU, the incidence of mild hypoxia (SPO2 90-93%) was statistically significant between the 2 groups (12% in clinical assessment group versus 1% in TOF group, P-value 0.005) while severe hypoxia (SPO2 <90%) was 7% versus 5%, P-value 0.373. The incidence of upper airway obstruction was statistically significant between the two groups (45% in clinical assessment group versus 14% in TOF group P-value<0.0001 for patients requiring airway maneuver, 21% versus 2% P-value <0.0001 for those who required tactile stimulation and 31% versus 12% were snoring, P-value 0.003. Logistic regression analysis revealed TOF group was less likely associated with mild hypoxia (OR 0.09 95% CI 0.01-0.71 P-value 0.023), tactile stimulation (OR 0.09 95% CI 0.02-0.40 P-value 0.002), airway maneuver (OR 0.20 95% CI 0.10-0.43 P-value <0.001) and snoring (OR 0.30 95% CI 0.13-0.68 P-value 0.04). CONCLUSION: Among this population, there is a lower incidence of critical respiratory events in PACU with the use of neuromuscular monitoring using TOF ratio ≥0.9 to assess neuromuscular function before endotracheal extubation compared with the use of clinical assessment methods.

Pre-referral rectal artesunate in severe malaria: flawed trial.

BACKGROUND: Immediate injectable treatment is essential for severe malaria. Otherwise, the afflicted risk lifelong impairment or death. In rural areas of Africa and Asia, appropriate care is often miles away. In 2009, Melba Gomes and her colleagues published the findings of a randomized, placebo-controlled trial of rectal artesunate for suspected severe malaria in such remote areas. Enrolling nearly 18,000 cases, the aim was to evaluate whether, as patients were in transit to a health facility, a pre-referral artesunate suppository blocked disease progression sufficiently to reduce these risks. The affirmative findings of this, the only trial on the issue thus far, have led the WHO to endorse rectal artesunate as a pre-referral treatment for severe malaria. In the light of its public health importance and because its scientific quality has not been assessed for a systematic review, our paper provides a detailed evaluation of the design, conduct, analysis, reporting, and practical features of this trial. RESULTS: We performed a checklist-based and an in-depth evaluation of the trial. The evaluation criteria were based on the CONSORT statement for reporting clinical trials, the clinical trial methodology literature, and practice in malaria research. Our main findings are: The inclusion and exclusion criteria and the sample size justification are not stated. Many clearly ineligible subjects were enrolled. The training of the recruiters does not appear to have been satisfactory. There was excessive between center heterogeneity in design and conduct. Outcome evaluation schedule was not defined, and in practice, became too wide. Large gaps in the collection of key data were evident. Primary endpoints were inconsistently utilized and reported; an overall analysis of the outcomes was not done; analyses of time to event data had major flaws; the stated intent-to-treat analysis excluded a third of the randomized subjects; the design-indicated stratified or multi-variate analysis was not done; many improper subgroups were analyzed in a post-hoc fashion; the analysis and reporting metric was deficient. There are concerns relating to patient welfare at some centers. Exclusion of many cases from data analysis compromised external validity. A bias-controlled reanalysis of available data does not lend support to the conclusions drawn by the authors. CONCLUSIONS: This trial has numerous serious deficiencies in design, implementation, and methods of data analysis. Interpretation and manner of reporting are wanting, and the applicability of the findings is unclear. The trial conduct could have been improved to better protect patient welfare. The totality of these problems make it a flawed study whose conclusions remain subject to appreciable doubt.

Efficacy and safety of artemether-lumefantrine in the treatment of acute, uncomplicated Plasmodium falciparum malaria: a pooled analysis.

Randomized trials have confirmed the efficacy and safety of artemether-lumefantrine (AL) for treatment of uncomplicated Plasmodium falciparum malaria. Data from seven studies supported by Novartis (1996-2007), including 647 adults (> 16 years of age, 83.3% completed the study) and 1,332 children (≤ 16 years of age, 89.3% completed the study) with microscopically confirmed uncomplicated P. falciparum malaria and treated with the recommended regimen of AL, were pooled. The 28-day polymerase chain reaction-corrected parasitologic cure rate (primary efficacy endpoint) was 97.1% (495 of 510) in adults and 97.3% (792 of 814) in children (evaluable population). Gametocytemia prevalence after day was 4.2% (23 of 554) in adults and 0.9% (8 of 846) in children. No noteworthy safety signals were observed. Serious adverse events occurred in 1.4% of the adults and 1.3% of the children. This study is the largest data set to date assessing AL therapy for treatment of acute uncomplicated P. falciparum malaria. Artemether-lumefantrine showed high cure rates and rapid resolution of parasitemia, fever, and gametocytemia in adults and children, and showed an excellent safety and tolerability profile.