cgp-56697 and Drug-Related-Side-Effects-and-Adverse-Reactions

The purpose of the study was to compare the safety of artemether-lumefantrine (AL) with other artemisinin-based combinations in children.. A search of EMBASE (from 1974 to April 2013), MEDLINE (from 1946 to April 2013) and the Cochrane library of registered controlled trials for randomized controlled trials (RCTs) which compared AL with other artemisinin-based combinations was done. Only studies involving children ≤ 17 years old in which safety of AL was an outcome measure were included.. Four thousand, seven hundred and twenty six adverse events (AEs) were recorded in 6,000 patients receiving AL. Common AEs (≥ 1/100 and <1/10) included: coryza, vomiting, anaemia, diarrhoea, vomiting and abdominal pain; while cough was the only very commonly reported AE (≥ 1/10). AL-treated children have a higher risk of body weakness (64.9%) than those on artesunate-mefloquine (58.2%) (p = 0.004, RR: 1.12 95% CI: 1.04-1.21). The risk of vomiting was significantly lower in patients on AL (8.8%) than artesunate-amodiaquine (10.6%) (p = 0.002, RR: 0.76, 95% CI: 0.63-0.90). Similarly, children on AL had a lower risk of vomiting (1.2%) than chlorproguanil-dapsone-artesunate (ACD) treated children (5.2%) (p = 0.002, RR: 0.63, 95% CI: 0.47-0.85). The risk of serious adverse events was significantly lower for AL (1.3%) than ACD (5.2%) (p = 0.002, RR: 0.45, 95% CI: 0.27-0.74).. Artemether-lumefantrine combination is as safe as ASAQ and DP for use in children. Common adverse events are cough and gastrointestinal symptoms. More studies comparing AL with artesunate-mefloquine and artesunate-azithromycin are needed to determine the comparative safety of these drugs.

Topics: Adolescent; Antimalarials; Artemether, Lumefantrine Drug Combination; Artemisinins; Child; Child, Preschool; Cough; Drug Combinations; Drug-Related Side Effects and Adverse Reactions; Dyspepsia; Ethanolamines; Fluorenes; Humans; Infant; Infant, Newborn; Randomized Controlled Trials as Topic

Malaria during pregnancy, particularly Plasmodium falciparum malaria, has been linked to increased morbidity and mortality, which must be reduced by both preventive measures and effective case management. The World Health Organization (WHO) recommends artemisinin-based combination therapy (ACT) to treat uncomplicated falciparum malaria during the second and third trimesters of pregnancy, and quinine plus clindamycin during the first trimester. However, the national policies of many African countries currently recommend quinine throughout pregnancy. Therefore, the aim of this article is to provide a summary of the available data on the safety and efficacy of artemether-lumefantrine (AL) in pregnancy. An English-language search identified 16 publications from 1989 to October 2011 with reports of artemether or AL exposure in pregnancy, including randomized clinical trials, observational studies and systematic reviews. Overall, there were 1,103 reports of AL use in pregnant women: 890 second/third trimester exposures; 212 first trimester exposures; and one case where the trimester of exposure was not reported. 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. As there are fewer reports of AL safety in the first trimester, additional data are required to assess the potential to use AL in the first trimester. Though the available safety and efficacy data support the use of AL in the second and third trimesters, there is still a need for further information. These findings reinforce the WHO recommendation to treat uncomplicated falciparum malaria with quinine plus clindamycin in early pregnancy and ACT in later pregnancy.

Topics: Antimalarials; Artemether, Lumefantrine Drug Combination; Artemisinins; Drug Combinations; Drug-Related Side Effects and Adverse Reactions; Ethanolamines; Female; Fluorenes; Humans; Malaria, Falciparum; Pregnancy; Pregnancy Complications, Infectious; Pyrimethamine; Quinine; Sulfadoxine; Treatment Outcome

Plasmodium knowlesi is reported increasingly across Southeast Asia and is the most common cause of malaria in Malaysia. No randomized trials have assessed the comparative efficacy of artemether-lumefantrine (AL) for knowlesi malaria.. A randomized controlled trial was conducted in 3 district hospitals in Sabah, Malaysia to compare the efficacy of AL against chloroquine (CQ) for uncomplicated knowlesi malaria. Participants were included if they weighed >10 kg, had a parasitemia count <20000/μL, and had a negative rapid diagnostic test result for Plasmodium falciparum histidine-rich protein 2. Diagnosis was confirmed by means of polymerase chain reaction. Patients were block randomized to AL (total target dose, 12 mg/kg for artemether and 60 mg/kg for lumefantrine) or CQ (25 mg/kg). The primary outcome was parasite clearance at 24 hours in a modified intention-to-treat analysis.. From November 2014 to January 2016, a total of 123 patients (including 18 children) were enrolled. At 24 hours after treatment 76% of patients administered AL (95% confidence interval [CI], 63%-86%; 44 of 58) were aparasitemic, compared with 60% administered CQ (47%-72%; 39 of 65; risk ratio, 1.3 [95% CI, 1.0-1.6]; P = .06). Overall parasite clearance was shorter after AL than after CQ (median, 18 vs 24 hours, respectively; P = .02), with all patients aparasitemic by 48 hours. By day 42 there were no treatment failures. The risk of anemia during follow-up was similar between arms. Patients treated with AL would require lower bed occupancy than those treated with CQ (2414 vs 2800 days per 1000 patients; incidence rate ratio, 0.86 [95% CI, .82-.91]; P < .001). There were no serious adverse events.. AL is highly efficacious for treating uncomplicated knowlesi malaria; its excellent tolerability and rapid therapeutic response allow earlier hospital discharge, and support its use as a first-line artemisinin-combination treatment policy for all Plasmodium species in Malaysia.. NCT02001012.

Topics: Adolescent; Adult; Aged; Antimalarials; Artemether, Lumefantrine Drug Combination; Child; Child, Preschool; Chloroquine; Drug-Related Side Effects and Adverse Reactions; Female; Humans; Malaria; Malaysia; Male; Middle Aged; Plasmodium knowlesi; Treatment Outcome; Young Adult

This study assessed the safety of the new World Health Organization (WHO) recommendation of adding a single low-dose of primaquine (PQ) to standard artemisinin-based combination therapy (ACT), regardless of individual glucose-6-phosphate dehydrogenase (G6PD) status, for treatment of acute uncomplicated Plasmodium falciparum malaria in Tanzania.. Men and non-pregnant, non-lactating women aged ≥1 year with uncomplicated P. falciparum malaria were enrolled and randomized to either standard artemether-lumefantrine (AL) regimen alone or with a 0.25 mg/kg single-dose of PQ. PQ was administered concomitantly with the first AL dose. All drug doses were supervised. Safety was evaluated between days 0 and 28. G6PD status was assessed using rapid test (CareStart™) and molecular genotyping. The primary endpoint was mean percentage relative reduction in haemoglobin (Hb) concentration (g/dL) between days 0 and 7 by genotypic G6PD status and treatment arm.. Overall, 220 patients, 110 per treatment arm, were enrolled, of whom 33/217 (15.2 %) were phenotypically G6PD deficient, whereas 15/110 (13.6 %) were genotypically hemizygous males, 5/110 (4.5 %) homozygous females and 22/110 (20 %) heterozygous females. Compared to genotypically G6PD wild-type/normal [6.8, 95 % confidence interval (CI) 4.67-8.96], only heterozygous patients in AL arm had significant reduction in day-7 mean relative Hb concentration (14.3, 95 % CI 7.02-21.55, p=0.045), however, none fulfilled the pre-defined haemolytic threshold value of ≥25 % Hb reduction. After adjustment for baseline parasitaemia, Hb, age and sex the mean relative Hb reduction was not statistically significant in both heterozygous and hemizygous/homozygous patients in both arms. A majority of the adverse events (AEs) were mild and unrelated to the study drugs. However, six (4.4 %) episodes, three per treatment arm, of acute haemolytic anaemia occurred between days 0 and 7. Three occurred in phenotypically G6PD deficient patients, two in AL and one in AL + PQ arm, but none in genotypically hemizygous/homozygous patients. All patients with acute haemolytic anaemia recovered without medical intervention.. The findings support that the WHO recommendation of adding a single low-dose of PQ to standard AL regimen is safe for the treatment of acute uncomplicated P. falciparum malaria regardless of G6PD status in Tanzania. Trial registration number NCT02090036.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Antimalarials; Artemether, Lumefantrine Drug Combination; Artemisinins; Child; Child, Preschool; Drug Combinations; Drug-Related Side Effects and Adverse Reactions; Ethanolamines; Female; Fluorenes; Genotyping Techniques; Glucosephosphate Dehydrogenase; Hemoglobins; Humans; Infant; Malaria, Falciparum; Male; Middle Aged; Primaquine; Single-Blind Method; Tanzania; Young Adult

Artemether-lumefantrine and artesunate-amodiaquine are first-line treatment for uncomplicated malaria in Cameroon. No study has yet compared the efficacy of these drugs following the WHO recommended 42-day follow-up period. The goal of this study was to compare the clinical efficacy, tolerability and safety of artesunate-amodiaquine (ASAQ), artemether-lumefantrine (AL) and dihydroartemisinin piperaquine (DHAP) among children aged less than ten years in two malaria-endemic ecological regions of Cameroon.. A three-arm, randomized, controlled, non-inferiority trial was conducted among children of either gender aged six months (>5 kg) to ten years (n = 720) with acute uncomplicated Plasmodium falciparum infection. Parents/guardians of children provided consent prior to randomization to receive ASAQ, DHAP or AL in the ratio of 2:2:1, respectively. Treatment outcome was assessed based on standard WHO 2003 classification after 42 days of follow-up. The primary outcome was PCR-corrected day-42 cure rates. The non-inferiority, one-sided, lower limit asymptotic 97.5% confidence interval (CI) on the difference in PCR-corrected cure rates of ASAQ and DHAP when compared to AL was accepted if the lower limit of the CI was greater than -10%. Secondary outcomes were parasite and fever clearances and day 7 haemoglobin changes.. PCR-corrected PP cure rates of 96.7, 98.1 and 96.3, respectively, for AL, ASAQ and DHAP was observed. The lower bound of the one-sided 97.5% CI calculated around the difference between day-42 cure rate point estimates in AL and ASAQ groups, AL and DHAP groups were, -6% and -4% respectively. There were no statistical significant differences in parasite or fever clearance times between treatments, although fever clearance pattern was different between ASAQ and DHAP. No statistical significant differences were observed in the occurrence of adverse events among treatment groups.. ASAQ and DHAP are considered safe and tolerable and are not inferior to AL in the treatment of uncomplicated P. falciparum malaria in Cameroonian children.. NCT01845701.

Topics: Amodiaquine; Antimalarials; Artemether, Lumefantrine Drug Combination; Artemisinins; Cameroon; Child; Child, Preschool; Drug Combinations; Drug-Related Side Effects and Adverse Reactions; Ethanolamines; Fluorenes; Humans; Infant; Malaria, Falciparum; Male; Quinolines; Treatment Outcome

The burden of malaria remains high for children in parts of Africa despite the use of insecticide-treated bed nets (ITNs). Chemoprevention has the potential of reducing the malaria burden; however, limited data exist on the efficacy and safety of anti-malarial therapy in the setting of chemoprevention.. 600 children 4-5 months of age were enrolled in Tororo, Uganda, an area of high transmission intensity. Participants were given ITNs, and caregivers instructed to bring their child to a study clinic whenever they were ill. Starting at six months of age, 579 were randomized to no chemoprevention, monthly sulphadoxine-pyrimethamine (SP), daily trimethoprim-sulphamethoxazole (TS), or monthly dihydroartemisinin-piperaquine (DP). Study drugs were administered unsupervised at home until 24 months of age. Episodes of uncomplicated malaria were treated with artemether-lumefantrine (AL) with active follow-up for 28 days. The cumulative risk of recurrent malaria within 84 days and the risk of adverse events within 28 days were compared across study arms using a Cox proportional hazards model and generalized estimating equations, respectively.. A total of 1007, 919, 736, and 451 episodes of malaria were treated in the no chemoprevention, SP, TS, and DP arms, respectively. Only 19 (0.6%) treatments were for severe malaria. Early response to therapy with AL was excellent with 96.5% fever clearance and 99.4% parasite clearance by day 3. However, over 50% of AL treatments were followed by recurrent parasitaemia within 28 days. Compared to the no chemoprevention arm, the cumulative risk of recurrent malaria within 84 days following treatment of uncomplicated malaria with AL was significantly lower in the DP arm (HR = 0.77, 95% CI 0.63-0.95, p = 0.01) but not the SP or TS arms. Compared to the no chemoprevention arm, none of the chemopreventive regimens were associated with an increased risk of adverse events following treatment of malaria with AL.. The risk of severe malaria was very low in this cohort of young children living in a high transmission setting. In the setting of chemoprevention, treatment of uncomplicated malaria with AL was safe and efficacious, with moderate protection against recurrent malaria among children assigned monthly DP.. ClinicalTrials.gov NCT00948896 .

Topics: Antimalarials; Artemether, Lumefantrine Drug Combination; Artemisinins; Chemoprevention; Child, Preschool; Drug Combinations; Drug-Related Side Effects and Adverse Reactions; Ethanolamines; Female; Fluorenes; Humans; Infant; Malaria; Male; Recurrence; Treatment Outcome; Uganda

Artemether-lumefantrine (AL) dispersible formulation was developed for the treatment of uncomplicated Plasmodium falciparum malaria in infants and children weighing 5 to <35 kg. However, there are no clinical studies with artemisinin-based combination therapy in infants <5 kg.. This multicentre, open-label, single-arm study evaluated the efficacy, safety and pharmacokinetics of AL dispersible in infants aged >28 days and <5 kg of body weight, who were treated with one AL dispersible tablet (20 mg artemether/120 mg lumefantrine) given twice-daily for three days and followed up for six weeks (core follow-up) and at 12 months of age (long-term follow-up).. A total of 20 patients were enrolled and completed the six-week core study follow-up. In the per protocol population, PCR-corrected cure rate at days 28 and 42 was 100% (95% CI: 79.4, 100). AL dispersible was well tolerated with reported adverse events of mild to moderate severity. Pharmacokinetic data showed that lumefantrine levels were similar, however, artemether and dihydroartemisinin levels were on average two- to three-fold greater than historical values in infants and children ≥5 kg.. A three-day regimen of AL dispersible formulation was efficacious and generally well tolerated in infants weighing <5 kg with uncomplicated P. falciparum malaria, but artemether and dihydroartemisinin exposures could not be supported by the preclinical safety margins for neurotoxicity. Hence, dosing recommendations cannot be made in infants <5 kg as implications for toxicity are unknown.. Clinicaltrials.gov NCT01619878.

Topics: Antimalarials; Artemether, Lumefantrine Drug Combination; Artemisinins; Drug Combinations; Drug-Related Side Effects and Adverse Reactions; Ethanolamines; Female; Fluorenes; Humans; Infant; Malaria, Falciparum; Male; Treatment Outcome

The recommendation of artemisinin combination therapy (ACT) as first-line treatment for uncomplicated falciparum malaria is supported by a plethora of high quality clinical trials. However, their recommendation for the treatment of mixed-species malaria and the large-scale use for the treatment of non-falciparum malaria in endemic regions is based on anecdotal rather than systematic clinical evidence.. This study prospectively observed the efficacy of artemether-lumefantrine for the treatment of uncomplicated non-falciparum or mixed-species malaria in two routine district hospitals in the Central African country of Gabon.. Forty patients suffering from uncomplicated Plasmodium malariae, Plasmodium ovale or mixed-species malaria (including Plasmodium falciparum) presenting at the hospital received artemether-lumefantrine treatment and were followed up. All evaluable patients (n=38) showed an adequate clinical and parasitological response on Day 28 after oral treatment with artemether-lumefantrine (95% confidence interval: 0.91,1). All adverse events were of mild to moderate intensity and completely resolved by the end of study.. This first systematic assessment of artemether-lumefantrine treatment for P. malariae, P. ovale and mixed-species malaria demonstrated a high cure rate of 100% and a favourable tolerability profile, and thus lends support to the practice of treating non-falciparum or mixed-species malaria, or all cases of malaria without definite species differentiation, with artemether-lumefantrine in Gabon.. ClinicalTrials.gov Identifier: NCT00725777.

Topics: Adolescent; Adult; Antimalarials; Artemether, Lumefantrine Drug Combination; Artemisinins; Child; Child, Preschool; Coinfection; Drug Combinations; Drug-Related Side Effects and Adverse Reactions; Ethanolamines; Female; Fluorenes; Gabon; Humans; Malaria; Male; Middle Aged; Plasmodium falciparum; Plasmodium malariae; Plasmodium ovale; Prospective Studies; Treatment Outcome; Young Adult

Artemisinin combination therapies such as artemether-lumefantrine (AL) are effective for first-line treatment of uncomplicated acute Plasmodium falciparum malaria. However, the safety profile of AL in large populations has not been fully assessed. The objective of this study was to establish the safety of AL in public health facilities in Tanzania using the Cohort Event Monitoring (CEM) method.. Patients who presented to public health facilities in four regions of Tanzania who were prescribed AL were enrolled in a CEM study, a prospective, observational cohort study to establish a profile of adverse events (AEs) for the medicine when used in routine clinical practice. Pre- and post-treatment forms were used to record baseline information and new health events before and 7 days after treatment.. A total of 8040 patients were enrolled in the study, of whom 6147 were included in the analysis. Following treatment initiation, a total of 530 AEs were reported in 6% (383) of the patients. The most frequent post-treatment AEs were in alimentary system (42%), including vomiting, nausea, diarrhoea, abdominal pain and anorexia, followed by AEs in the neurological system (25%). Causality assessment of the events showed that 51.9% (275/530) were possibly related to AL. There was a significant difference in the frequency of AEs by age-group with an increase in the number of AEs as age increased (P < 0.001). There was no statistically significant difference in the frequency of the events between males and females (P = 0.504). The AE profile was consistent with the AEs reported in the product information and in other studies; no new adverse drug reactions were identified. The majority of the reported AEs were the same as the symptoms of malaria and therefore indistinguishable from the underlying disease.. The safety profile of AL for treatment of malaria continues to be favourable. CEM as a pharmacovigilance tool has proven to provide reliable safety data in a short period.

Topics: Adolescent; Adult; Antimalarials; Artemether, Lumefantrine Drug Combination; Artemisinins; Child; Child, Preschool; Cohort Studies; Drug Combinations; Drug Monitoring; Drug-Related Side Effects and Adverse Reactions; Ethanolamines; Female; Fluorenes; Health Facilities; Humans; Infant; Malaria; Male; Middle Aged; Nausea; Prospective Studies; Tanzania; Vomiting; Young Adult

Countries remain reluctant to adopt the 2012 World Health Organization recommendation for single low-dose (0.25 mg/kg) primaquine (SLD PQ) for Plasmodium falciparum transmission-blocking due to concerns over drug-related haemolysis risk, especially among glucose-6-phosphate dehydrogenase-deficient (G6PDd) people, without evidence demonstrating that it can be safely deployed in their settings. Pharmacovigilance methods provide a systematic way of collecting safety data and supporting the rollout of SLD PQ.. The Primaquine Roll Out Monitoring Pharmacovigilance Tool (PROMPT), comprising: (1) a standardized form to support the surveillance of possible adverse events following SLD PQ treatment; (2) a patient information card to enhance awareness of known adverse drug reactions of SLD PQ use; and (3) a database compiling recorded information, was developed and piloted. Data on patient characteristics, malaria diagnosis and treatment are collected. Blood samples are taken to measure haemoglobin (Hb) and test for G6PD deficiency. Active follow-up includes a repeat Hb measurement and adverse event monitoring on or near day 7. A 13-month prospective pilot study in two hospital facilities in Swaziland alongside the introduction of SLD PQ generated preliminary evidence on the feasibility and acceptability of PROMPT.. PROMPT was well received by nurses as a simple, pragmatic approach to active surveillance of SLD PQ safety data. Of the 102 patients enrolled and administered SLD PQ, none were G6PDd. 93 (91.2 %) returned on or near day 7 for follow-up. Four (4.6 %) patients had falls in Hb ≥25 % from baseline, none of whom presented with signs or symptoms of anaemia. No patient's Hb fell below 7 g/dL and none required a blood transfusion. Of the 11 (11 %) patients who reported an adverse event over the study period, three were considered serious and included two deaths and one hospitalization; none were causally related to SLD PQ. Four non-serious adverse events were considered definitely, probably, or possibly related to SLD PQ.. Improved pharmacovigilance to monitor and promote the safety of the WHO recommendation is needed. The successful application of PROMPT demonstrates its potential as an important tool to rapidly generate locally acquired safety data and support pharmacovigilance in resource-limited settings.

Topics: Adolescent; Adult; Aged; Antimalarials; Artemether, Lumefantrine Drug Combination; Artemisinins; Child; Child, Preschool; Drug Combinations; Drug-Related Side Effects and Adverse Reactions; Eswatini; Ethanolamines; Female; Fluorenes; Humans; Infant; Malaria, Falciparum; Male; Middle Aged; Pharmacovigilance; Pilot Projects; Primaquine; Product Surveillance, Postmarketing; Prospective Studies; Young Adult

Unsweetened natural cocoa has antimalarial properties. Unsweetened natural cocoa powder (UNCP), obtained as a result of the removal of cocoa butter from a cocoa bean protects against malaria episodes. Cocoa powder, which is prepared after removal of the cocoa butter, contains about 1.9 % theobromine and 0.21 % caffeine. Concomitant consumption of cocoa and artemether/lumefantrine (A/L) is a common practice in Ghana, West Africa. This study seeks to determine the elemental composition of UNCP and its protective effect on the heart and kidney against (A/L) administration.. Energy dispersive x-ray fluorescence spectroscopy was used to detect the quality and quantity of the elemental composition in UNCP. Thereafter, 30 nonmalarious male guinea pigs were divided into five groups of six animals each. One group was administered with 75 mg/kg body weight A/L only and another group distilled water (control group). The rest received 300 mg/kg, 900 mg/kg and 1500 mg/kg body weight UNCP for 14 days orally and A/L for the last 3 days (ie day 11 to day 14). Biochemical and histopathological examinations were carried out after euthanisation of the animals.. A total of thirty-eight (38) micro and macro elements were detected with the ED-XRF. Macro elements like sodium (Na), magnesium (Mg), aluminium (Al), phosphorus (P), chlorine (Cl), potassium (K), calcium (Ca), manganese (Mn) and iron (Fe) and micro elements like chromium (Cr), copper (Cu), zinc (Zn), arsenic (As), and lead (Pb) were identified and evaluated. Biochemical analysis revealed increases in HDL levels (p>0.05) while there were decreases in LDL levels (p>0.05), creatine kinase and AST levels (P<0.05) in animals that received UNCP compared to A/L only administered group. Urea levels reduced significantly by 53 % (p<0.05) in group that received 1500 mg/kg UNCP. Histopathological examinations of the heart and kidney buttressed the protective effects of cocoa administration.. The percentage of recommended daily allowance of UNCP for chromium is 3750 % for men and 5250 % for women while % RDA for copper corresponds to 103.6 % in both sexes. UNCP proved to possess cardioprotective and renoprotective potential during artemether-lumefantrine administration.

Topics: Animals; Antimalarials; Artemether, Lumefantrine Drug Combination; Artemisinins; Cacao; Creatine Kinase; Drug Combinations; Drug-Related Side Effects and Adverse Reactions; Ethanolamines; Fluorenes; Guinea Pigs; Kidney; Lipids; Male; Plant Preparations

Anti-malarial drug resistance continues to be a leading threat to malaria control efforts and calls for continued monitoring of waning efficacy of artemisinin-based combination therapy (ACT). Artesunate + sulfadoxine/pyrimethamine (AS + SP) is used for the treatment of uncomplicated Plasmodium falciparum malaria in India. However, resistance against AS + SP is emerged in northeastern states. Therefore, artemether-lumefantrine (AL) is the recommended first line treatment for falciparum malaria in north eastern states. This study investigates the therapeutic efficacy and safety of AL for the treatment of uncomplicated falciparum malaria in three malaria-endemic states in India. The data generated through this study will benefit the immediate implementation of second-line ACT as and when required.. This was a one-arm prospective evaluation of clinical and parasitological responses for uncomplicated falciparum malaria using WHO protocol. Patients diagnosed with uncomplicated mono P. falciparum infection were administered six-dose regimen of AL over 3 days and subsequent follow-up was carried out up to 28 days. Molecular markers msp-1 and msp-2 were used to differentiate recrudescence and re-infection and K13 propeller gene was amplified and sequenced covering the codon 450-680.. A total of 402 eligible patients were enrolled in the study from all four sites. Overall, adequate clinical and parasitological response (ACPR) was 98 % without PCR correction and 99 % with PCR correction. At three study sites, ACPR rates were 100 %, while at Bastar, cure rate was 92.5 % on day 28. No early treatment failure was found. The PCR-corrected endpoint finding confirmed that one late clinical failure (LCF) and two late parasitological failures (LPF) were recrudescences. The PCR corrected cure rate was 96.5 %. The mean fever clearance time was 27.2 h ± 8.2 (24-48 h) and the mean parasite clearance time was 30.1 h ± 11.0 (24-72 h). Additionally, no adverse event was recorded. Analysis of total 186 samples revealed a mutation in the k13 gene along with non-synonymous mutation at codon M579T in three (1.6 %) samples.. AL is an efficacious drug for the treatment of uncomplicated falciparum malaria. However, regular monitoring of AL is required in view of malaria elimination initiatives, which will be largely dependent on therapeutic interventions, regular surveillance and targeted vector control.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Antigens, Protozoan; Antimalarials; Artemether, Lumefantrine Drug Combination; Artemisinins; Child; Child, Preschool; Drug Combinations; Drug-Related Side Effects and Adverse Reactions; Ethanolamines; Fluorenes; Humans; India; Infant; Malaria, Falciparum; Merozoite Surface Protein 1; Middle Aged; Plasmodium falciparum; Prospective Studies; Protozoan Proteins; Sequence Analysis, DNA; Treatment Outcome; Young Adult

The World Health Organization presently recommends Artemisinin-based combination therapy (ACT) as first-line therapy for uncomplicated P. falciparum malaria. Many malaria-endemic countries, including Rwanda, have adopted these treatment guidelines. The Artemisinin derivative Artemether, in combination with lumefantrine, is currently used in Rwanda for malaria during the second and third trimesters of pregnancy. Safety data on the use of ACT in pregnancy are still limited though and more data are needed.. In this pharmacovigilance study, the exposed group (pregnant women with malaria given artemether-lumefantrine), and a matched non-exposed group (pregnant women without malaria and no exposure to artemether-lumefantrine) were followed until delivery. Data were collected at public health centres all over Rwanda during acute malaria, routine antenatal visits, after hospital delivery or within 48 hours after home delivery. Information gathered from patients included routine antenatal and peri-partum data, pregnancy outcomes (abortions, stillbirths, at term delivery), congenital malformations and other adverse events through history taking and physical examination of both mothers and newborns.. The outcomes for the total sample of 2,050 women were for the treatment (n=1,072) and control groups (n=978) respectively: abortions: 1.3% and 0.4%; peri-natal mortality 3.7% and 2.8%; stillbirth 2.9% and 2.4%; neonatal death [less than or equal to]7 days after birth 0.5% and 0.4%; premature delivery 0.7% and 0.3%; congenital malformations 0.3% and 0.3%. A total of 129 obstetric adverse events in 127 subjects were reported (7.3% in the treatment group, 5.0% in the control group). In a multivariate regression model, obstetric complications were more frequent in the treatment group (OR (95% CI): 1.38 (0.95, 2.01)), and in primigravidae (OR (95% CI) 2.65 (1.71, 4.12) and at higher age (OR per year: 1.05 (1.01-1.09).. There were no specific safety concerns related to artemether-lumefantrine treatment for uncomplicated falciparum malaria in pregnancy. However, more obstetric complications were observed in the treatment group. These increased occurrence of complications could, however, be caused by the malaria episode itself, but further assessment is required.

Topics: Adolescent; Adult; Antimalarials; Artemether, Lumefantrine Drug Combination; Artemisinins; Cohort Studies; Drug Combinations; Drug-Related Side Effects and Adverse Reactions; Ethanolamines; Female; Fluorenes; Humans; Malaria; Middle Aged; Pharmacovigilance; Pregnancy; Pregnancy Complications, Infectious; Rwanda; Young Adult

Topics: Acetamides; Antibodies, Monoclonal; Antimalarials; Artemether, Lumefantrine Drug Combination; Artemisinins; Azepines; Benzazepines; Benzhydryl Compounds; Benzyl Alcohol; Benzylamines; Cyclams; Cyclopropanes; Drug Combinations; Drug Therapy; Drug-Related Side Effects and Adverse Reactions; Ethanolamines; Everolimus; Febuxostat; Fluorenes; Fluoroquinolones; Gout Suppressants; Heterocyclic Compounds; Humans; Immunosuppressive Agents; Indoles; Lacosamide; Milnacipran; Oligopeptides; Phenols; Selective Serotonin Reuptake Inhibitors; Sirolimus; Tapentadol; Thiazoles; Tolvaptan; Triazoles