Oral Artemether-lumefantrine Research Articles

Severe complicated malaria caused by Plasmodium falciparum in a female traveler returning from Zanzibar

A 25-year-old female outpatient presenting with fever and micro-hematuria was treated for urinary tract infection. Her condition worsened over 3 days at home. After experiencing multiple falls caused by leg weakness and mental confusion, she was admitted to a hospital with high fever. Initial laboratory findings showed hemolytic anemia, pancytopenia, and acute kidney injury, suggesting hemolytic uremic syndrome. However, a detailed fever evaluation revealed her recent return from Afrika. This prompted amalaria test, which confirmed Plasmodium falciparum infection with 80 % parasitemia. Despite the quick reduction of parasitemia following treatment with intravenous administered artesunate and oral Artemether-Lumefantrine, her condition worsened, leading to a septic shock. This required renal replacement and kinetic ventilation therapy, as well as blood transfusions due to persistent hemolysis until the laboratory values normalized after 48 days post-admission. The evaluation of fever is often challenging, but most often a detailed patient history is key to early diagnosis and treatment preventing deathly outcomes in severe cases.

Prophylaxis Failure and Successful Management of Delayed-Onset Malaria with Renal Complications: A Case Report with Oral Artemether-Lumefantrine Treatment

This case report presents a critical clinical scenario involving a 55-year-old patient who developed severe Plasmodium falciparum malaria with renal complications despite receiving doxycycline prophylaxis while traveling in a malaria-endemic region. The case emphasizes the potential failure of doxycycline prophylaxis and highlights the importance of considering malaria in patients with a history of travel to endemic areas, even if they have adhered to prophylactic treatment. The patient’s clinical presentation included fever, extreme fatigue, and loss of consciousness, leading to hospitalization. Laboratory findings revealed severe anemia, elevated liver enzymes, and impaired renal function, consistent with the criteria for severe malaria. The diagnosis was confirmed by the presence of Plasmodium falciparum parasites on thin blood smears. Due to limited access to parenteral antimalarial medications in Kosovo, the patient received oral artemether-lumefantrine, resulting in clinical improvement. Supportive care and dialysis played a vital role in the patient’s recovery. This case report underscores the need for increased awareness of prophylaxis failure, the challenges of managing severe malaria in non-endemic countries, and the importance of timely and appropriate interventions to improve outcomes in severe malaria cases, particularly those with renal involvement.

Imported severe Plasmodium falciparum infection in the first trimester of pregnancy complicated by post-artemisinin delayed hemolysis and intrauterine fetal death, a case report

BackgroundPost-artemisinin delayed hemolysis (PADH) is a serious complication in patients who recover from severe malaria after receiving artemisinin-based combined therapy (ACT), including artemether-lumefantrine. In Japan, among the antimalarial drugs recommended by the World Health Organization (WHO) guideline for severe malaria, intravenous quinine gluconate is available only in 29 designated hospitals, and intravenous artesunate is unavailable. Therefore, oral artemether-lumefantrine is occasionally administered as an alternative, even though it may be a suboptimal treatment. In non-endemic settings like Japan, a lack of knowledge of malaria and the side effects, such as post-artemisinin delayed hemolysis caused by the ACT, can have critical consequences. Like our patient, being a primigravida in the early stages of pregnancy is a serious risk factor for severe malaria and must be carefully monitored.Case presentationThis report describes a severe case of imported Plasmodium falciparum malaria complicated by fetal loss and prolonged anemia, requiring frequent blood transfusions. The patient was a previously healthy pregnant Japanese female in her 30 s. She developed a high fever 2 days after returning from Nigeria. The patient fulfilled the severe malaria criteria by WHO. On arrival, an abdominal ultrasound incidentally revealed a fetus of 5 week gestational age with a heartbeat in the uterus. Given her pregnancy and the severity of the disease, she was administered intravenous quinine 16 mg/kg as a loading dose. However, the second dose of quinine was not administered due to frequent vomiting and QTc prolongation. We initiated treatment with oral artemether-lumefantrine, and clearance of parasitemia was confirmed by microscopic observation on day 4. Miscarriage was noted on day 6 after admission. Moreover, the patient became feverish again up to 39 °C, and from days 14 to 22, the patient required multiple blood transfusions due to PADH. On day 40, follow-up was discontinued as the hemoglobin level exceeded 10 g/dL.ConclusionsIn patients who recover from severe malaria after ACT treatment, monitoring the hemoglobin level for at least a month is strongly recommended for prompt identification of PADH. Travelers to malaria-endemic countries, especially primigravida women, should be provided with adequate information on the risk and prevention of infection.

Prevalence, trends and associated factors of malaria in the Shai-Osudoku District Hospital, Ghana

BackgroundEven though malaria is easily preventable and treatable, it continues to have a devastating impact on people’s health and livelihoods around the world. Sub-Saharan Africa carries a disproportionately high share of the global malaria burden. This study seeks to assess the prevalence, trends and factors associated with malaria in the Shai-Osudoku District Hospital, Ghana.MethodsA cross-sectional study was conducted to determine the prevalence, trend, and factors associated with malaria in the Shai-Osudoku District Hospital; a 10-month secondary data was extracted from February to November 2020. The extracted data were entered into Epi Data version 6 and analysed using STATA version 16. Descriptive analysis was performed to determine the prevalence, trend and socio-demographic characteristics of study participants. Simple logistic regression at a 95% confidence level was performed to investigate socio-demographic factors associated with malaria infection. Tables and charts with summary statistics were used to present the results.ResultsSecondary data from 3896 individuals were included in the study. The age of the participants range from 0.8 to 101 years with a mean age of 32.5. The estimated prevalence of malaria during the study period is 20.9%. A majority (79.1%) of the participants who presented signs and symptoms of malaria were negative after testing. The prevalence of malaria cases increased progressively from 6.7 to 55.4% across the ten months. The simple logistic regression at a 95% confidence level revealed that age group, sex, residential status, religion, occupation and marital status were statistically significantly associated with malaria. The results shows that persons who tested positive for malaria were mostly treated with artemether-lumefantrine (46.1%), some malaria positive cases were given artesunate injection (11.6%), dihydroartemisinin-piperaquine (16.2%) and oral artemether-lumefantrine (6.5%). Surprisingly 19.6% of the malaria-positive cases were not given any form of malaria medication.ConclusionFactors found to influence malaria infection in the Shai-Osudoku District Hospital include participant’s age, sex, residential status, religious affiliation occupation and marital status. The findings of this study showed that malaria remains a serious public health problem in the Shai Osudoku District Hospital. The information obtained from this study can guide the implementation of malaria prevention, control and elimination strategies in Ghana.

Prolongation of QT Interval as a Result of Combination Therapy of Oral Artemether-Lumefantrine: A Cross-Sectional Study

Aim: To determine the frequency of prolongation of QT interval as a result of combination therapy of oral Artemether-Lumefantrine Study design: A cross-sectional study Place and Duration: This study was conducted at Karachi Institute of Heart Diseases Karachi Pakistan from June 2020 to June 2021. Methodology: The study included a total of 120 participants. Participants were selected by a consecutive sampling method. All the patients were adults and had been diagnosed with malaria by positive blood smear for plasmodium falciparum. The patients had not taken any antimalarial therapy for the last seven days of reporting to the hospital. The treatment was given in six doses of AL combination therapy. The strength of one dose was 80 mg Artemether and 480 mg of Lumefantrine. The QT interval was calculated before and after the therapy administration. Bazett’s formula (Qtc (s) = QT interval / √ RR interval) was used for the calculation of the corrected QT interval (Qtc) Results: The mean age of the patients was 30 ± 2.96 years. A total of 85 (70.83%) were male and 35 (29.17%) were female. According to the age distribution, 31 (25.83%) patients were between the age of 20 years and 30 years. A total of 42 (35%) patients were between the age of 31 and 40 years. 36 (30%) were in the age range of 41 and 50 years. A total of 11 (9.17%) were above the age of 50 years All the patients were analyzed for QT interval prolongation and the QT interval was not prolonged in any of the participants. Conclusion: As QT interval prolongation was not observed in any of the patients, oral AL can be considered a safe combination therapy for the treatment of malaria caused by plasmodium falciparum. Keywords: Artemether, Lumefantrine, QT prolongation, Malaria, Plasmodium Falciparum

Arterolane–piperaquine–mefloquine versus arterolane–piperaquine and artemether–lumefantrine in the treatment of uncomplicated Plasmodium falciparum malaria in Kenyan children: a single-centre, open-label, randomised, non-inferiority trial

SummaryBackgroundTriple antimalarial combination therapies combine potent and rapidly cleared artemisinins or related synthetic ozonides, such as arterolane, with two, more slowly eliminated partner drugs to reduce the risk of resistance. We aimed to assess the safety, tolerability, and efficacy of arterolane–piperaquine–mefloquine versus arterolane–piperaquine and artemether–lumefantrine for the treatment of uncomplicated falciparum malaria in Kenyan children.MethodsIn this single-centre, open-label, randomised, non-inferiority trial done in Kilifi County Hospital, Kilifi, coastal Kenya, children with uncomplicated Plasmodium falciparum malaria were recruited. Eligible patients were aged 2–12 years and had an asexual parasitaemia of 5000–250 000 parasites per μL. The exclusion criteria included the presence of an acute illness other than malaria, the inability to tolerate oral medications, treatment with an artemisinin derivative in the previous 7 days, a known hypersensitivity or contraindication to any of the study drugs, and a QT interval corrected for heart rate (QTc interval) longer than 450 ms. Patients were randomly assigned (1:1:1), by use of blocks of six, nine, and 12, and opaque, sealed, and sequentially numbered envelopes, to receive either arterolane–piperaquine, arterolane–piperaquine–mefloquine, or artemether–lumefantrine. Laboratory staff, but not the patients, the patients' parents or caregivers, clinical or medical officers, nurses, or trial statistician, were masked to the intervention groups. For 3 days, oral artemether–lumefantrine was administered twice daily (target dose 5–24 mg/kg of bodyweight of artemether and 29–144 mg/kg of bodyweight of lumefantrine), and oral arterolane–piperaquine (arterolane dose 4 mg/kg of bodyweight; piperaquine dose 20 mg/kg of bodyweight) and oral arterolane–piperaquine–mefloquine (mefloquine dose 8 mg/kg of bodyweight) were administered once daily. All patients received 0·25 mg/kg of bodyweight of oral primaquine at hour 24. All patients were admitted to Kilifi County Hospital for at least 3 consecutive days and followed up at day 7 and, thereafter, weekly for up to 42 days. The primary endpoint was 42-day PCR-corrected efficacy, defined as the absence of treatment failure in the first 42 days post-treatment, of arterolane–piperaquine–mefloquine versus artemether–lumefantrine, and, along with safety, was analysed in the intention-to-treat population, which comprised all patients who received at least one dose of a study drug. The 42-day PCR-corrected efficacy of arterolane–piperaquine–mefloquine versus arterolane–piperaquine was an important secondary endpoint and was also analysed in the intention-to-treat population. The non-inferiority margin for the risk difference between treatments was −7%. The study is registered in ClinicalTrials.gov, NCT03452475, and is completed.FindingsBetween March 7, 2018, and May 2, 2019, 533 children with P falciparum were screened, of whom 217 were randomly assigned to receive either arterolane–piperaquine (n=73), arterolane–piperaquine–mefloquine (n=72), or artemether–lumefantrine (n=72) and comprised the intention-to-treat population. The 42-day PCR-corrected efficacy after treatment with arterolane–piperaquine–mefloquine (100%, 95% CI 95–100; 72/72) was non-inferior to that after treatment with artemether–lumefantrine (96%, 95% CI 88–99; 69/72; risk difference 4%, 95% CI 0–9; p=0·25). The 42-day PCR-corrected efficacy of arterolane–piperaquine–mefloquine was non-inferior to that of arterolane–piperaquine (100%, 95% CI 95–100; 73/73; risk difference 0%). Vomiting rates in the first hour post-drug administration were significantly higher in patients treated with arterolane–piperaquine (5%, 95% CI 2–9; ten of 203 drug administrations; p=0·0013) or arterolane–piperaquine–mefloquine (5%, 3–9; 11 of 209 drug administrations; p=0·0006) than in patients treated with artemether–lumefantrine (1%, 0–2; three of 415 drug administrations). Upper respiratory tract complaints (n=26 for artemether–lumefantrine; n=19 for arterolane–piperaquine–mefloquine; n=23 for arterolane–piperaquine), headache (n=13; n=4; n=5), and abdominal pain (n=7; n=5; n=5) were the most frequently reported adverse events. There were no deaths.InterpretationThis study shows that arterolane–piperaquine–mefloquine is an efficacious and safe treatment for uncomplicated falciparum malaria in children and could potentially be used to prevent or delay the emergence of antimalarial resistance.FundingUK Department for International Development, The Wellcome Trust, The Bill & Melinda Gates Foundation, Sun Pharmaceutical Industries

Quality of care for adult in-patients with malaria in a tertiary hospital in Uganda

BackgroundPrompt detection and appropriate treatment of malaria prevents severe disease and death. The quality of care for adult malaria in-patients is not well documented in sub-Saharan Africa, particularly in Uganda. The study sought to describe the patterns of malaria diagnosis and treatment among adult in-patients admitted to the medical and gynaecological wards of Uganda’s 1790-bed Mulago National Referral Hospital from December 2013 to April 2014.MethodsA prospective cohort of 762 consented in-patients aged ≥ 18 years was assembled. Proportions of in-patients who received preadmission and in-hospital anti-malarials, missed Day 1 dosing of hospital-initiated anti-malarials and/or had malaria microscopy done were determined. Multivariable logistic regression was used to identify risk-factors for missed Day 1 dosing of anti-malarials.ResultsOne in five (19%, 146/762) in-patients had an admission or discharge malaria diagnosis or both; with median age of 29 years (IQR, 22–42 years). Microscopy was requested in 77% (108/141) of in-patients with an admission malaria diagnosis; results were available for 46% (50/108), of whom 42% (21/50) tested positive for Plasmodium falciparum malaria parasitaemia. Only 13% (11/83) of in-patients who received in-hospital injectable artesunate (AS) or quinine (Q) received follow-up oral artemether-lumefantrine (AL); 2 of 18 severe malaria cases received follow-up oral AL. Injectable AS only (47%, 47/100) was the most frequent hospital-initiated anti-malarial treatment followed by injectable Q only (23%, 23/100) amongst in-patients who received in-hospital anti-malarials. A quarter (25%, 25/100; 95% CI: 17–35%) of in-patients missed Day 1 dosing of hospital-initiated anti-malarials. Each additional admission diagnosis was more than two-fold likely to increase the odds of missed Day 1 dosing of in-hospital anti-malarials (aOR = 2.6, 95% CI: 1.52–4.56; P-value = 0.001).ConclusionsHalf the malaria microscopy results were not available; yet, the rate of testing was high. The majority of in-patients initiated on injectable AS or Q did not receive the recommended follow-up oral AL. One in four in-patients delayed to initiate hospital anti-malarials by at least one calendar day. The hospital should encourage prompt availability of malaria test-results to promote the timely initiation and completion of anti-malarial treatment, thereby improving the quality of care for hospitalized malaria patients in Uganda.

A Phase II Pilot Trial to Evaluate CoBaT-Y017 Safety and Efficacy against Uncomplicated Falciparum Malaria versus Artemether-Lumefantrine in Benin Subjects.

Background. Considering the promising results of Phase I clinical trials with herbal medicine CoBaT-Y017, a Phase II study was conducted with Plasmodium falciparum malaria‐infected patients, for efficacy and safety evaluation of CoBaT-Y017 compared with Artemether‐Lumefantrine used as a positive control. Methods. A single‐blind randomized trial was conducted on 25 eligible males aged 18–40 years randomly assigned to two treatment groups: CoBaT-Y017 or Artemether‐Lumefantrine. The first group received 35 ml of CoBaT-Y017 in 1.5 L mineral water administered daily for four consecutive days; the second group received oral Artemether‐Lumefantrine, using WHO‐recommended therapeutic dose regimens. For both drugs, efficacy for parasite clearance and safety were evaluated clinically, haematologically, and biochemically on days 1–4, 7, 14, 21, and 28. Clinical‐ and laboratory‐adverse events (AEs) were recorded until day 28. Results. 13 and 12 patients were randomized into CoBaT-Y017 arm and Artemether‐Lumefantrine arm, respectively. In all patients, parasitaemia was adequately neutralized with CoBaT-Y017 group patients’ parasite clearance lagging slightly behind that of Artemether‐Lumefantrine’s group, but without a statistically significant difference (HR = 1.08, 95% CI 0.47–2.51, P = 0.85). Physical and laboratory examinations did not show any significant changes in vital signs, biochemical, and haematological parameters. In the Artemether‐Lumefantrine arm, 100% (12/12) of patients experienced, at least, one adverse event versus 61.5% (8/13) in the CoBaT-Y017 arm. Conclusion. CoBaT-Y017 exhibited similar antimalarial efficacy against P. falciparum to that of Artemether‐Lumefantrine, with good tolerability and safety.

QT PROLONGATION WITH THE USE OF ORAL ARTEMETHER-LUMEFANTRINE COMBINATION THERAPY

Objective: To determine the frequency of patients developing QT prolongationwith the use of oral Artemether-Lumefantrine (AL) combination therapy. Methodology: This cross sectional study was conducted in general medicinedepartment of Khyber Teaching Hospital from January to December 2018. A totalof 133 patients were selected on basis of consecutive (non-probability)sampling. All adult patients (irrespective of gender) presenting with high gradefever having positive blood smear (thick and thin blood films) for plasmodiumfalciparum and not taken any antimalarial treatment in the preceding seven dayswere included in the study. All information was entered in pre designed proforma. Results: Total 133 patients were including. Mean age was 30 ± 3.18 years.About 72% patients were males while 28% patients were female. Prolongcorrected QT interval among 133 patients were analyzed, and no patient withprolonged corrected QT interval was observed. Conclusion: It can be concluded that AL is a safe drug combination for thetreatment of falciparummalaria with negligible adverse effects on QT profile. Key Words: QT Prolongation, Plasmodium falciparum, Malaria, Artemether,Lumefentarine.

Preconceptional factors associated with haemoglobin concentration in early pregnancy: a community-based cohort study in rural northeastern Tanzania.

Maternal anaemia in early pregnancy is associated with poor pregnancy outcomes. Furthermore, preconceptional health can influence the health during pregnancy. The aim of this study was to investigate which preconceptional factors were associated with haemoglobin (Hb) concentration in early pregnancy. In Tanzania, 226 women were followed at preconception and during early pregnancy. Red blood cell (RBC) morphology, serum micronutrient concentration, demographic characteristics and health status were assessed in preconception and in early pregnancy. The association between preconceptional factors and Hb concentration in early pregnancy was investigated using simple and multiple linear regression analyses stratified by preconceptional anaemia status. Mean Hb was 123 and 119g/l before conception and during early pregnancy (median gestational age 53days) respectively. Preconceptional mid-upper arm circumference (MUAC) (adjusted coefficient (AC) 0.35 95% CI 0.9-0.61) and preconceptional Hb concentration (AC 0.45 95% CI 0.36-0.54) were positively associated with early pregnancy Hb concentration, whereas preconceptional microcytic hypochromic RBC morphology (AC -6.00 95% CI -9.56 to -2.44) was negatively associated with early pregnancy Hb concentration. In addition, treatment of preconceptional malaria was positively associated with early pregnancy Hb concentration (AC 6.45 95% CI 0.74-12.2) among women with preconceptional anaemia. In contrast, among preconceptional non-anaemic women, only preconceptional Hb concentration and medium socio-economic status was positively associated with early pregnancy Hb concentration. Mid-upper arm circumference (MUAC) and Hb measurements in preconception can help to detect women at increased risk of low Hb concentration in early pregnancy.

Chloroquine Resistance in a Case with Uncomplicated Plasmodium vivax Malaria: An Evolving Threat

Introduction: Chloroquine resistance is an emerging phenomenon in uncomplicated Plasmodium vivax malaria. Presentation of Case: This case report describes a 21 year old forest worker who was diagnosed to have Plasmodium vivax malaria on blood film microscopy and it was confirmed on molecular real-time polymerase chain reaction analysis. He was treated with conventional oral chloroquine of optimal dosage in which he failed to respond appropriately. His blood film parasite count increased on day 3 of treatment despite adequate chloroquine therapy. He was then commenced on oral artemether-lumefantrine (Riamet) combination therapy in which he responded clinically and microscopically. He was discharged from the hospital after completing a 14-day course of oral primaquine. His serial blood films were negative for more than three consecutive days whilst in hospital. On subsequent weekly follow ups at the specialist clinic for a duration of 28 days, his blood films remained negative for malaria parasites. Conclusion: Chloroquine resistance is now an emerging threat in many middle and low income countries globally. Case Study Kasinathan; BJAST, 13(2): 1-4, 2016; Article no.BJAST.22553 2

Pharmacokinetics of a novel sublingual spray formulation of the antimalarial drug artemether in African children with malaria.

The pharmacokinetics of sublingual artemether (ArTiMist) was investigated in 91 young African children with severe malaria or who could not tolerate oral antimalarial therapy. Each received 3.0 mg/kg of body weight of artemether at 0, 8, 24, 36, 48, and 60 h or until the initiation of oral treatment. Few blood samples were drawn postdose. Plasma artemether and dihydroartemisinin (DHA) levels were measured using liquid chromatography-mass spectrometry, and the data were analyzed using established population compartmental pharmacokinetic models. Parasite clearance was prompt (median parasite clearance time, 24 h), and there were no serious adverse events. Consistent with studies in healthy adults (S. Salman, D. Bendel, T. C. Lee, D. Templeton, and T. M. E. Davis, Antimicrob Agents Chemother 59:3197-3207, 2015, http://dx.doi.org/10.1128/AAC.05013-14), the absorption of sublingual artemether was biphasic, and multiple dosing was associated with the autoinduction of the metabolism of artemether to DHA (which itself has potent antimalarial activity). In contrast to studies using healthy volunteers, pharmacokinetic modeling indicated that the first absorption phase did not avoid first-pass metabolism, suggesting that the drug is transferred to the upper intestine through postdose fluid/food intake. Simulations using the present data and those from an earlier study in older Melanesian children with uncomplicated malaria treated with artemether-lumefantrine tablets suggested that the bioavailability of sublingual artemether was at least equivalent to that after conventional oral artemether-lumefantrine (median [interquartile range] areas under the concentration-time curve for artemether, 3,403 [2,471 to 4,771] versus 3,063 [2,358 to 4,514] μg · h/liter, respectively; and for DHA, 2,958 [2,146 to 4,278] versus 2,839 [1,812 to 3,488] μg · h/liter, respectively; P ≥ 0.42). These findings suggest that sublingual artemether could be used as prereferral treatment for sick children before transfer for definitive management of severe or moderately severe malaria.

Haemolytic anaemia after oral artemether–lumefantrine treatment in a patient affected by severe imported falciparum malaria

Artemisinin and its derivatives are essential components of artemisinin-based combination therapies for treating severe falciparum malaria. In this paper, we describe the occurrence of haemolysis after oral artemether-lumefantrine treatment. To the best of our knowledge, this is the second reported case of a patient affected by severe falciparum malaria with haemolytic anaemia that is likely associated with oral artemether-lumefantrine treatment.

Efficacy of artemether-lumefantrine, the nationally-recommended artemisinin combination for the treatment of uncomplicated falciparum malaria, in southern Laos

BackgroundThe Lao Government changed the national policy for uncomplicated Plasmodium falciparum malaria from chloroquine to artemether-lumefantrine (AL) in 2005. Since then, no information on AL efficacy has been reported. With evidence of resistance to artemisinin derivatives in adjacent Cambodia, there has been a concern as to AL efficacy. Monitoring of AL efficacy would help the Lao Government to make decisions on appropriate malaria treatment.MethodsThe efficacy of a three-day, twice daily oral artemether-lumefantrine for the treatment of uncomplicated falciparum malaria in Xepon District, Savannakhet Province, southern Laos was studied over 42 days follow-up. This was part of a trial of thiamin supplementation in falciparum malaria.ResultsOf 630 patients with P. falciparum enrolled in the trial of thiamin treatment, 549 (87%, 357 children ≤15 years and 192 adults) were included in this study. The per protocol 42-day cure rates were 97% (524/541) [96% (337/352) for children and 99% (187/189) for adults, p = 0.042]. By conventional intention-to-treat analysis, the 42-day cure rates adjusted for re-infection, were 97% (532/549) [96% (342/357) in children and 99% (190/192) in adults, p = 0.042]. The proportion of patients who remained parasitaemic at day 1 after treatment was significantly higher in children [33% (116/356)] compared to adults [15% (28/192)] (p < 0.001) and only one adult patient had detectable parasitaemia on day 2. There were no serious adverse events. Potential side effects after treatment were reported more commonly in adults (32%) compared to children (15%) (p < 0.001). Patients with recrudescent infections were significantly younger, had longer mean time to fever clearance, and had longer median time to parasite clearance compared to those who were cured.ConclusionsThe current nationally-recommended anti-malarial treatment (artemether-lumefantrine) remains highly efficacious for the treatment of uncomplicated falciparum malaria five years after introduction in Laos. Regular monitoring is required in case artemisinin-resistant P. falciparum parasites should appear.Trial registrationISRCTN85411059.

Haemolytic anaemia in an HIV-infected patient with severe falciparum malaria after treatment with oral artemether-lumefantrine

Intravenous (i.v.) artesunate is now the recommended first-line treatment of severe falciparum malaria in adults and children by WHO guidelines. Nevertheless, several cases of haemolytic anaemia due to i.v. artesunate treatment have been reported. This paper describes the case of an HIV-infected patient with severe falciparum malaria who was diagnosed with haemolytic anaemia after treatment with oral artemether-lumefantrine.The patient presented with fever, headache, and arthromyalgia after returning from Central African Republic where he had been working. The blood examination revealed acute renal failure, thrombocytopaenia and hypoxia. Blood for malaria parasites indicated hyperparasitaemia (6%) and Plasmodium falciparum infection was confirmed by nested-PCR. Severe malaria according to the laboratory WHO criteria was diagnosed. A treatment with quinine and doxycycline for the first 12 hours was initially administered, followed by arthemeter/lumefantrine (Riamet®) for a further three days. At day 10, a diagnosis of severe haemolytic anaemia was made (Hb 6.9 g/dl, LDH 2071 U/l). Hereditary and autoimmune disorders and other infections were excluded through bone marrow aspiration, total body TC scan and a wide panel of molecular and serologic assays. The patient was treated by transfusion of six units of packed blood red cell. He was discharged after complete remission at day 25. At present, the patient is in a good clinical condition and there is no evidence of haemolytic anaemia recurrence.This is the first report of haemolytic anaemia probably associated with oral artemether/lumefantrine. Further research is warranted to better define the adverse events occurring during combination therapy with artemisinin derivatives.

A comparative, randomized clinical trial of artemisinin/naphtoquine twice daily one day versus artemether/lumefantrine six doses regimen in children and adults with uncomplicated falciparum malaria in Côte d'Ivoire

BackgroundDrug resistance in Plasmodium falciparum poses a major threat to malaria control. Combination anti-malarial therapy, including artemisinins, has been advocated to improve efficacy and limit the spread of resistance. The fixed combination of oral artemether-lumefantrine (AL) is highly effective and well-tolerated. Artemisinin/naphtoquine (AN) is a fixed-dose ACT that has recently become available in Africa.The objectives of the study were to compare the efficacy and safety of AN and AL for the treatment of uncomplicated falciparum malaria in a high transmission-intensity site in Ivory Coast.MethodsWe enrolled 122 participants aged 6 months or more with uncomplicated falciparum malaria. Participants were randomized to receive either artemisinin/naphtoquine or artemether/lumefantrine with variable dose according to their weight. Primary endpoints were the risks of treatment failure within 28 days, either unadjusted or adjusted by genotyping to distinguish recrudescence from new infection.ResultsAmong 125 participants enrolled, 123 (98.4%) completed follow-up. Clinical evaluation of the 123 participants showed that cumulative PCR-uncorrected cure rate on day 28 was 100% for artemisinin/naphtoquine and 98.4% for artemether/lumefantrine. Both artemisinin-based combinations effected rapid fever and parasite clearance.InterpretationThese data suggest that Arco® could prove to be suitable for use as combination antimalarial therapy. Meanwhile, pharmacokinetic studies and further efficacy assessment should be conducted before its widespread use can be supported.

A randomized trial of artemether-lumefantrine versus mefloquine-artesunate for the treatment of uncomplicated multi-drug resistant Plasmodium falciparum on the western border of Thailand.

BackgroundThe use of antimalarial drug combinations with artemisinin derivatives is recommended to overcome drug resistance in Plasmodium falciparum. The fixed combination of oral artemether-lumefantrine, an artemisinin combination therapy (ACT) is highly effective and well tolerated. It is the only registered fixed combination containing an artemisinin. The trial presented here was conducted to monitor the efficacy of the six-dose regimen of artemether-lumefantrine (ALN) in an area of multi-drug resistance, along the Thai-Myanmar border.MethodsThe trial was an open-label, two-arm, randomized study comparing artemether-lumefantrine and mefloquine-artesunate for the treatment of uncomplicated falciparum malaria with 42 days of follow up. Parasite genotyping by polymerase chain reaction (PCR) was used to distinguish recrudescent from newly acquired P. falciparum infections. The PCR adjusted cure rates were evaluated by survival analysis.ResultsIn 2001–2002 a total of 490 patients with slide confirmed uncomplicated P. falciparum malaria were randomly assigned to receive artemether-lumefantrine (n = 245) or artesunate and mefloquine (n = 245) and were followed for 42 days. All patients had rapid initial clinical and parasitological responses. In both groups, the PCR adjusted cure rates by day 42 were high: 98.8% (95% CI 96.4, 99.6%) for artemether-lumefantrine and 96.3% (95% CI 93.1, 98.0%) for artesunate-mefloquine. Both regimens were very well tolerated with no serious adverse events observed attributable to either combination.ConclusionOverall, this study confirms that these two artemisinin-based combinations remain highly effective and result in equivalent therapeutic responses in the treatment of highly drug-resistant falciparum malaria.