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BACKGROUND: Perennial malaria chemoprevention (PMC) aims to protect children at risk from severe malaria by the administration of anti-malarial drugs to children of defined ages throughout the year. Sulfadoxine-pyrimethamine (SP) has been widely used for chemoprevention in Africa and a child-friendly dispersible tablet formulation has recently become available. METHODS: This qualitative non-interventional observational study was conducted in Benin, Côte d'Ivoire, and Mozambique between February and June 2022. Prototype blister packs, dispensing boxes and job aids designed to support dispersible SP deployment for PMC were evaluated using focus group discussions (FGD) and semi-structured in-depth individual interviews (IDI) with health authorities, health personnel, community health workers (CHWs) and caregivers. The aim was to evaluate knowledge and perceptions of malaria and chemoprevention, test understanding of the tools and identify gaps in understanding, satisfaction, user-friendliness and acceptability, and assess the potential role of CHWs in PMC implementation. Interviews were transcribed and imported to ATLAS.ti for encoding and categorization. Thematic content analysis used deductive and inductive coding with cross-referencing of findings between countries and participants to enrich data interpretation. Continuous comparison across the IDI and FGD permitted iterative, collaborative development of materials. RESULTS: Overall, 106 participants completed IDIs and 70 contributed to FGDs. Malaria was widely recognised as the most common disease affecting children, and PMC was viewed as a positive intervention to support child health. The role of CHWs was perceived differently by the target groups, with caregivers appreciating their trusted status in the community, whereas health authorities preferred clinic-based deployment of PMC by health professionals. Empirical testing of the prototype blister packs, dispensing boxes and job aids highlighted the context-specific expectations of respondents, such as familiar situations and equipment, and identified areas of confusion or low acceptance. A key finding was the need for a clear product identity reflecting malaria. CONCLUSION: Simple modifications profoundly affected the perception of PMC and influenced acceptability. Iterative quantitative investigation resulted in PMC-specific materials suited to the local context and socio-cultural norms of the target population with the aim of increasing access to chemoprevention in children most at risk of severe malaria.
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Antimaláricos , Quimioprevención , Combinación de Medicamentos , Malaria , Pirimetamina , Mozambique , Benin , Malaria/prevención & control , Antimaláricos/administración & dosificación , Antimaláricos/uso terapéutico , Quimioprevención/métodos , Quimioprevención/estadística & datos numéricos , Humanos , Côte d'Ivoire , Pirimetamina/administración & dosificación , Pirimetamina/uso terapéutico , Sulfadoxina/administración & dosificación , Sulfadoxina/uso terapéutico , Preescolar , Femenino , Masculino , Embalaje de Medicamentos/métodos , Lactante , Niño , AdultoRESUMEN
AIMS: The rare yeast species Lodderomyces elongisporus, Kodamaea ohmeri, Cyberlindnera fabianii, and Wickerhamomyces anomalus are increasingly implicated in severe mycoses in immunocompromised patients. This study aimed to assess the prevalence of uncommon yeast species in Côte d'Ivoire. METHODS: The yeast isolates from superficial samples, mainly vaginal swabs, were collected at the Pasteur Institute of Abidjan in a study on the molecular epidemiology of clinical yeast species. Identification relied on MALDI-TOF MS and ITS sequence analysis. Antifungal susceptibility testing was performed using the CLSI method. RESULTS: Of the 315 strains analysed from 227 outpatients, 14 belonged to 4 uncommon species: Lodderomyces elongisporus, Kodamaea ohmeri, Cyberlindnera fabianii, and Wickerhamomyces anomalus. None exhibited elevated fluconazole, amphotericin B, caspofungin, ketoconazole, or flucytosin MIC. CONCLUSIONS: The presence of these rare yeasts represents a risk in immunocompromised people. Their adequate and timely identification is a priority. Overall, enhancing the mycoses diagnostic capacities in Côte d'Ivoire, and more generally in African clinical laboratories with limited resources is a critical aim.
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Hongos , Micosis , Femenino , Humanos , Côte d'Ivoire/epidemiología , Levaduras , Micosis/epidemiologíaRESUMEN
Background: Porcine cysticercosis is an endemic parasitic zoonosis in many developing countries. The objective of this study was to estimate the seroprevalence of porcine cysticercosis in traditional pig farms in the departments of Dabou, Aboisso and Agboville. Methods: Blood samples were taken from pigs and analyzed by ELISA (IgG) and western blot. Data on farming practices and pig characteristics were collected. Multivariate logistic regression models were constructed to identify risk factors. Results: A total of 668 pigs were sampled from 116 farms and 639 samples were analyzed. The seroprevalence of cysticercosis was estimated at 13.2%. Overweight [OR = 2.6; 95%CI (1.3-4.9)] and fat pigs [OR = 2.3; 95%CI (1.0-4.8)] were twice as likely to be seropositive for cysticercosis. This risk was increased in farms using well water for drinking [OR = 2.5; 95%CI (1.0-6.3)] as well as those reporting veterinary care of the animals (OR = 2.9; 95%CI (1.2-7.3)). Conclusions: This study demonstrated the circulation of Taenia solium in pig farms in southern Côte d'Ivoire.
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The combinations of artemether-lumefantrine (AL) and artesunate-amodiaquine (ASAQ) are used as first-line treatments for uncomplicated malaria in the Ivory Coast. Different studies document the efficacy of two artemisinin-based combination therapies (ACTs) (AL and ASAQ) in the Ivory Coast. However, there is no meta-analysis examining the data set of these studies. The purpose of this work was to determine the prevalence of malaria treatment failure cases in randomized control trials with two artemisinin-based combination therapies (AL versus ASAQ) in the Ivory Coast between 2009 to 2016. This study is a meta-analysis of data from the results of four previous multicenter, open-label, randomized clinical trial studies evaluating the clinical and parasitological efficacy of artemether-lumefantrine and artesunate-amodiaquine conducted between 2009 and 2016 following World Health Organization (WHO) protocol at sentinel sites in the Ivory Coast. These drug efficacy data collected between 2009 and 2016 were analyzed. During these studies, to distinguish between recrudescence and new infection, molecular genotyping of genes encoding merozoite surface protein 1 and 2 was carried out using nested polymerase chain reaction (PCR). A total of 1575 patients enrolled in the four studies, including 768 in the AL arm and 762 in the ASAQ arm, which were fully followed either for 28 days or 42 days according to WHO protocol. The adequate clinical and parasitological response (ACPR) was higher than 95% in the two groups (intention to treat (ITT): AL = 96.59% and ASAQ = 96.81; Per Protocol (PP): AL = 99.48% and ASAQ = 99.61%) after PCR correction at day 28. Aggregate data analysis (2009-2016) showed that at day 28, the proportions of patients with recurrent infection was higher in the AL group (ITT: 3.79%, PP: 3.9%) than in the ASAQ group (ITT: 2.17%, PP: 2.23%). After PCR correction, most treatment failures were classified as new infections (AL group (ITT: 0.13%, PP: 0.13%); ASAQ group (ITT: 0.39%, PP: 0.39%). The recrudescent infections rate was high, at 0.39% compared to 0.13% for ASAQ and AL, respectively, for both ITT and PP, no significant difference. However, the Kaplan-Meier curve of cumulative treatment success showed a significant difference between the two groups after PCR from 2012-2013 (p = 0.032). Overall, ASAQ and AL have been shown to be effective drugs for the treatment of uncomplicated P. falciparum malaria in the study areas, 14 years after deployment of these drugs.
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Anopheles gambiae and An. coluzzii are very closely related and recently differentiated species representing the main malaria vectors in the Afrotropical region and responsible of up to >3 infective bites/person/night in Côte D'Ivoire, where prevention and control has stagnated in recent years. The aim of the present study was to genetically and ecologically characterize An. gambiae and An. coluzzii populations from two villages of Côte D'Ivoire, lying in the coastal forest belt and 250â¯km inland in the Guinean savannah mosaic belt, respectively. Results reveal high frequencies of both species in both study sites and high frequencies of hybrids (4-33%) along the whole year of sampling. Consistently with observations for the well-known high hybridization zone at the far-west of the species range, hybrid frequencies were higher in the coastal village and highest when the two species occurred at more balanced frequencies, supporting the "frequency-dependent hybridization" ecological speciation theory. Pilot genotyping revealed signatures of genomic admixture in both chromosome-X and -3. Coupled with previous reports of hybrids in the region, the results point to the coastal region of Côte D'Ivoire as a possible regions of high hybridization. Preliminary characterization of parameters relevant for malaria transmission and control (e.g. possibly higher sporozoite rates and indoor biting preferences in hybrids than in the parental species) highlight the possible relevance of the breakdown of reproductive barriers between An. gambiae and An. coluzzii not only in the field of ecological evolution, but also in malaria epidemiology and control.
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Distribución Animal , Anopheles/genética , Hibridación Genética , Mosquitos Vectores/genética , Animales , Côte d'Ivoire , Femenino , MalariaRESUMEN
BACKGROUND: Placental malaria (PM) is associated with increased risk of both maternal and neonatal adverse outcomes. The objective of this study was to assess risks factors associated with PM including intermittent preventive treatment with sulfadoxine-pyrimethamine (IPTp-SP). METHODS: A cross-sectional study was conducted at Ayame hospital in the southern region of Cote d'Ivoire between August 2016 and March 2017. Sociodemographic baseline characteristic and antenatal data were obtained from the mother's antenatal card and included timing and number of IPTp-SP doses. Newborn characteristics were recorded.Peripheral blood as well as placental and cord blood were used to prepare thick and thin blood films. In addition, pieces of placental tissues were used to prepare impression smears. Regression logistics were used to study factors associated with PM and low birth weight (LBW) (<2.500 g). RESULTS: Three hundred delivered women were enrolled in the study. The mean age of the participants was 25 ± 6.5 years and most participants were multigravida (52.8%). The coverage rate of IPTp-SP with the full three doses recommended was 27.8%. Overall, 7.3% (22/300) of women examined had PM detected by microscopy using impression smear (22/300). Multivariate analysis showed that significant risks factors of PM were maternal peripheral parasitemia at delivery (P < 0.0001), residence (P = 0.03), and not sleeping under long-lasting insecticide treated nets (LLINs) (P = 0.006). LBW infants were born to 22.7% (5/22) of women with PM and 13.3% (37/278) of women without PM (P = 0.47). Only primiparous was associated with LBW in the multivariable analysis (P = 0.04). CONCLUSION: The prevalence of PM was 7.3%. Low parity, residence and not using LLINs and maternal peripheral parasitemia were identified as risks factors. PM was associated with LBW. Implementation of IPTp-SP should be improved by the National Malaria Control Program in rural settings.
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INTRODUCTION: Parasite clearance is useful to detect artemisinin resistance. The aim of this study was to investigate parasite clearance in patients treated with artesunate + amodiaquine (AS + AQ) and artemether + lumefantrine (AL): the two artemisinin-based combination therapies (ACTs) recommended in the first-line treatment of uncomplicated malaria in Côte d'Ivoire. METHODS: This study was conducted in Bouaké, Côte d'Ivoire, from April to June 2016. Patients aged at least 6 months with uncomplicated malaria and treated with AS + AQ or AL were hospitalized for 3 days, and follow-up assessments were performed on days 3, 7, 14, 21, 28, 35, and 42. Blood smears were collected at the time of screening, pre-dose, and 6-hour intervals following the first dose of administration until two consecutive negative smears were recorded, thereafter at day 3 and follow-up visits. Parasite clearance was determined using the Worldwide Antimalarial Resistance Network's parasite clearance estimator. The primary end points were parasite clearance rate and time. RESULTS: A total of 120 patients (57 in the AS + AQ group and 63 in the AL group) were randomized among 298 patients screened. The median parasite clearance time was 30 hours (IQR, 24-36 hours), for each ACT. The median parasite clearance rate had a slope half-life of 2.36 hours (IQR, 1.85-2.88 hours) and 2.23 hours (IQR, 1.74-2.63 hours) for AS + AQ and AL, respectively. The polymerase chain reaction-corrected adequate clinical and parasitological response was 100% and 98.07% at day 42 for AS + AQ and AL, respectively. CONCLUSION: Patients treated with AS + AQ and AL had cleared parasites rapidly. ACTs are still efficacious in Bouaké, Côte d'Ivoire, but continued efficacy monitoring of ACTs is needed.
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BACKGROUND: Administration of artemisinin-based combination therapy (ACT) to infant and young children can be challenging. A formulation with accurate dose and ease of administration will improve adherence and compliance in children. The fixed-dose combination dispersible tablet of arterolane maleate (AM) 37.5 mg and piperaquine phosphate (PQP) 187.5 mg can make dosing convenient in children. METHODS: This multicenter (India and Africa), comparative, parallel-group trial enrolled 859 patients aged 6 months to 12 years with Plasmodium falciparum malaria. Patients were randomized in a ratio of 2:1 to AM-PQP (571 patients) once daily and artemether-lumefantrine (AL) (288 patients) twice daily for 3 days and followed for 42 days. RESULTS: The cure rate (ie, polymerase chain reaction-corrected adequate clinical and parasitological response) in the per-protocol population at day 28 was 100.0% and 98.5% (difference, 1.48% [95% confidence interval {CI}, .04%-2.91%]) in the AM-PQP and AL arms, respectively, and 96.0% and 95.8% (difference, 0.14% [95% CI, -2.68% to 2.95%]) in the intention-to-treat (ITT) population. The cure rate was comparable at day 42 in the ITT population (AM-PQP, 94.4% vs AL, 93.1%). The median parasite clearance time was 24 hours in both the arms. The median fever clearance time was 6 hours in AM-PQP and 12 hours in the AL arm. Both the treatments were found to be safe and well tolerated. Overall, safety profile of both the treatments was similar. CONCLUSIONS: The efficacy and safety of fixed-dose combination of AM and PQP was comparable to AL for the treatment of uncomplicated P. falciparum malaria in pediatric patients. CLINICAL TRIALS REGISTRATION: CTRI/2014/07/004764.
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Antimaláricos/uso terapéutico , Artemisininas/uso terapéutico , Etanolaminas/uso terapéutico , Fluorenos/uso terapéutico , Compuestos Heterocíclicos con 1 Anillo/uso terapéutico , Malaria Falciparum/tratamiento farmacológico , Peróxidos/uso terapéutico , Quinolinas/uso terapéutico , Compuestos de Espiro/uso terapéutico , África , Antimaláricos/efectos adversos , Antimaláricos/sangre , Antimaláricos/farmacocinética , Combinación Arteméter y Lumefantrina , Artemisininas/efectos adversos , Artemisininas/sangre , Artemisininas/farmacocinética , Niño , Preescolar , Combinación de Medicamentos , Etanolaminas/efectos adversos , Etanolaminas/sangre , Etanolaminas/farmacocinética , Femenino , Fluorenos/efectos adversos , Fluorenos/sangre , Fluorenos/farmacocinética , Compuestos Heterocíclicos con 1 Anillo/efectos adversos , Compuestos Heterocíclicos con 1 Anillo/sangre , Compuestos Heterocíclicos con 1 Anillo/farmacocinética , Humanos , India , Lactante , Malaria Falciparum/mortalidad , Masculino , Peróxidos/efectos adversos , Peróxidos/sangre , Peróxidos/farmacocinética , Quinolinas/efectos adversos , Quinolinas/sangre , Quinolinas/farmacocinética , Compuestos de Espiro/efectos adversos , Compuestos de Espiro/sangre , Compuestos de Espiro/farmacocinética , Análisis de Supervivencia , ComprimidosRESUMEN
BACKGROUND: Artemisinins, which are derived from plants, are subject to risk of supply interruption due to climatic changes. Consequently, an effort to identify a new synthetic antimalarial was initiated. A fixed-dose combination of arterolane maleate (AM), a new synthetic trioxolane, with piperaquine phosphate (PQP), a long half-life bisquinoline, was evaluated in patients with uncomplicatedPlasmodium falciparummalaria. METHODS: In this multicenter, randomized, double-blind, comparative, parallel-group trial, 1072 patients aged 12-65 years withP. falciparummonoinfection received either AM-PQP (714 patients) once daily or artemether-lumefantrine (A-L; 358 patients) twice daily for 3 days. All patients were followed up until day 42. RESULTS: Of the 714 patients in the AM-PQP group, 638 (89.4%) completed the study; of the 358 patients in the A-L group, 301(84.1%) completed the study. In both groups, the polymerase chain reaction corrected adequate clinical and parasitological response (PCR-corrected ACPR) on day 28 in intent-to-treat (ITT) and per-protocol (PP) populations was 92.86% and 92.46% and 99.25% and 99.07%, respectively. The corresponding figures on day 42 in the ITT and PP populations were 90.48% and 91.34%, respectively. After adjusting for survival ITT, the PCR-corrected ACPR on day 42 was >98% in both groups. The overall incidence of adverse events was comparable. CONCLUSIONS: AM-PQP showed comparable efficacy and safety to A-L in the treatment of uncomplicatedP. falciparummalaria in adolescent and adult patients. AM-PQP demonstrated high clinical and parasitological response rates as well as rapid parasite clearance. CLINICAL TRIALS REGISTRATION: India. CTRI/2009/091/000101.
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Antimaláricos/administración & dosificación , Artemisininas/administración & dosificación , Etanolaminas/administración & dosificación , Fluorenos/administración & dosificación , Compuestos Heterocíclicos con 1 Anillo/administración & dosificación , Malaria Falciparum/tratamiento farmacológico , Malaria Falciparum/parasitología , Peróxidos/administración & dosificación , Quinolinas/administración & dosificación , Compuestos de Espiro/administración & dosificación , Adolescente , Adulto , África/epidemiología , Anciano , Antimaláricos/uso terapéutico , Arteméter , Artemisininas/uso terapéutico , Asia/epidemiología , Niño , Método Doble Ciego , Quimioterapia Combinada , Etanolaminas/uso terapéutico , Femenino , Fluorenos/uso terapéutico , Semivida , Compuestos Heterocíclicos con 1 Anillo/uso terapéutico , Humanos , India/epidemiología , Lumefantrina , Malaria Falciparum/epidemiología , Masculino , Persona de Mediana Edad , Peróxidos/uso terapéutico , Plasmodium falciparum/efectos de los fármacos , Quinolinas/uso terapéutico , Compuestos de Espiro/uso terapéutico , Adulto JovenRESUMEN
BACKGROUND: The World Health Organization (WHO) recommends artemisinin combination therapy (ACT) for the treatment of uncomplicated Plasmodium falciparum malaria. The present study investigated the efficacy and safety of fixed dose combination (FDC) of arterolane maleate 37.5 mg and piperaquine phosphate (PQP) 187.5 mg dispersible tablets in paediatric patients aged 6 months to 12 years. METHODS: Male and female patients aged 6 months to 12 years who were confirmed cases of P. falciparum mono-infection with fever or documented history of fever in the previous 24 h were included. The patients were administered FDC of arterolane maleate and PQP as single daily doses for three consecutive days based on their age. The primary efficacy outcome was proportion of patients with polymerase chain reaction (PCR)-corrected adequate clinical and parasitological response (ACPR) on day 28. Safety was analysed based on adverse events (AE), laboratory abnormalities and abnormalities on electrocardiograph. RESULTS: A total of 141 eligible paediatric patients received FDC of arterolane maleate and PQP in a 42-day follow-up study. All the enrolled patients (141) were included in intention to treat (ITT) and safety analyses, and 126 patients were considered in per protocol (PP) population. The PCR-corrected ACPR on day 28 was achieved in all patients (100 %; 95 % CI 97.11-100) included in PP population. The median parasite clearance time (PCT) and fever clearance time (FCT) were 24 h (95 % CI 18.0-24.0) and 10 h (95 % CI 4.0-18.0), respectively. The most frequently reported clinical AE was vomiting. Majority of the AEs were mild to moderate in severity and resolved without sequelae. No patient was discontinued for any QTc (corrected QT interval) prolongation. No deaths or serious AEs were reported during the study. CONCLUSION: The findings from this study showed that FDC of arterolane maleate and PQP effectively cures P. falciparum malaria and attains acceptable level of cure by day 28 in paediatric patients. The efficacy and safety results observed in children warrants further studies on FDC of arterolane maleate and PQP dispersible tablets. TRIAL REGISTRATION: Clinical Trial Registry India: CTRI/2009/091/000531.
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Compuestos Heterocíclicos con 1 Anillo/uso terapéutico , Malaria Falciparum/tratamiento farmacológico , Malaria/tratamiento farmacológico , Peróxidos/uso terapéutico , Quinolinas/uso terapéutico , Compuestos de Espiro/uso terapéutico , Antimaláricos/efectos adversos , Antimaláricos/farmacología , Antimaláricos/uso terapéutico , Niño , Preescolar , Côte d'Ivoire , Combinación de Medicamentos , Femenino , Compuestos Heterocíclicos con 1 Anillo/efectos adversos , Compuestos Heterocíclicos con 1 Anillo/farmacología , Humanos , India , Lactante , Recién Nacido , Masculino , Peróxidos/efectos adversos , Peróxidos/farmacología , Plasmodium falciparum/efectos de los fármacos , Quinolinas/efectos adversos , Quinolinas/farmacología , Rwanda , Compuestos de Espiro/efectos adversos , Compuestos de Espiro/farmacología , ComprimidosRESUMEN
INTRODUCTION: There are growing concerns about the emergence of resistance to artemisinin-based combination therapies (ACTs). Since the widespread adoption of ACTs, there has been a decrease in the systematic surveillance of antimalarial drug resistance in many malaria-endemic countries. The aim of this work was to test whether data on travellers returning from Africa with malaria could serve as an additional surveillance system of local information sources for the emergence of drug resistance in endemic-countries. METHODOLOGY: Data were collected from travellers with symptomatic Plasmodium falciparum malaria returning from Senegal (n = 1,993), Mali (n = 2,372), Cote d'Ivoire (n = 4,778) or Cameroon (n = 3,272) and recorded in the French Malaria Reference Centre during the period 1996-2011. Temporal trends of the proportion of parasite isolates that carried the mutant genotype, pfcrt 76T, a marker of resistance to chloroquine (CQ) and pfdhfr 108N, a marker of resistance to pyrimethamine, were compared for travellers and within-country surveys that were identified through a literature review in PubMed. The in vitro response to CQ was also compared between these two groups for parasites from Senegal. RESULTS: The trends in the proportion of parasites that carried pfcrt 76T, and pfdhfr 108N, were compared for parasites from travellers and patients within-country using the slopes of the curves over time; no significant differences in the trends were found for any of the 4 countries. These results were supported by in vitro analysis of parasites from the field in Senegal and travellers returning to France, where the trends were also not significantly different. CONCLUSION: The results have not shown different trends in resistance between parasites derived from travellers or from parasites within-country. This work highlights the value of an international database of drug responses in travellers as an additional tool to assess the emergence of drug resistance in endemic areas where information is limited.
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Antimaláricos/farmacología , Cloroquina/farmacología , Resistencia a Medicamentos , Malaria Falciparum/diagnóstico , Malaria Falciparum/epidemiología , Plasmodium falciparum/efectos de los fármacos , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Niño , Preescolar , ADN Protozoario/genética , Femenino , Marcadores Genéticos , Humanos , Lactante , Recién Nacido , Malaria Falciparum/tratamiento farmacológico , Masculino , Proteínas de Transporte de Membrana/genética , Persona de Mediana Edad , Plasmodium falciparum/genética , Plasmodium falciparum/aislamiento & purificación , Reacción en Cadena de la Polimerasa , Vigilancia de la Población , Pronóstico , Proteínas Protozoarias/genética , Senegal/epidemiología , Adulto JovenRESUMEN
BACKGROUND: Children are most vulnerable to malaria. A pyronaridine-artesunate pediatric granule formulation is being developed for the treatment of uncomplicated Plasmodium falciparum malaria. METHODS: This phase III, multi-center, comparative, open-label, parallel-group, controlled clinical trial included patients aged ≤12 years, bodyweight ≥5 to <25 kg, with a reported history of fever at inclusion or in the previous 24 h and microscopically-confirmed uncomplicated P. falciparum malaria. Patients were randomized (2:1) to pyronaridine-artesunate granules (60/20 mg) once daily or artemether-lumefantrine crushed tablets (20/120 mg) twice daily, both dosed by bodyweight, orally (liquid suspension) for three days. RESULTS: Of 535 patients randomized, 355 received pyronaridine-artesunate and 180 received artemether-lumefantrine. Day-28 adequate clinical and parasitological response (ACPR), corrected for re-infection using polymerase chain reaction (PCR) genotyping (per-protocol population) was 97.1% (329/339; 95% CI 94.6, 98.6) for pyronaridine-artesunate; 98.8% (165/167; 95% CI 95.7, 99.9) for artemether-lumefantrine. The primary endpoint was achieved: pyronaridine-artesunate PCR-corrected day-28 ACPR was statistically significantly >90% (P < .0001). Pyronaridine-artesunate was non-inferior to artemether-lumefantrine: treatment difference -1.8% (95% CI -4.3 to 1.6). The incidence of drug-related adverse events was 37.2% (132/355) with pyronaridine-artesunate, 44.4% (80/180) with artemether-lumefantrine. Clinical biochemistry results showed similar mean changes versus baseline in the two treatment groups. From day 3 until study completion, one patient in each treatment group had peak alanine aminotransferase (ALT) >3 times the upper limit of normal (ULN) and peak total bilirubin >2xULN (i.e. within the Hy's law definition). CONCLUSIONS: The pyronaridine-artesunate pediatric granule formulation was efficacious and was non-inferior to artemether-lumefantrine. The adverse event profile was similar for the two comparators. Pyronaridine-artesunate should be considered for inclusion in paediatric malaria treatment programmes. TRIAL REGISTRATION: ClinicalTrials.gov: identifier NCT00541385.
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Antimaláricos/administración & dosificación , Artemisininas/administración & dosificación , Etanolaminas/administración & dosificación , Fluorenos/administración & dosificación , Malaria Falciparum/tratamiento farmacológico , Naftiridinas/administración & dosificación , Antimaláricos/efectos adversos , Combinación Arteméter y Lumefantrina , Artesunato , Niño , Preescolar , Formas de Dosificación , Combinación de Medicamentos , Femenino , Humanos , Lactante , Malaria Falciparum/parasitología , Masculino , Carga de Parásitos , Recurrencia , Comprimidos , Resultado del TratamientoRESUMEN
PURPOSE: Artemisin-based combination therapies became the recommended therapy in Côte-d'Ivoire in 2005, but both chloroquine (CQ) and sulfadoxine/pyrimethamine (SP) have been heavily used for many decades. Despite this long history, little is known about the geographical distribution of drug resistance-conferring genotypes outside the capital city of Abidjan. In this work, we compared the prevalence of drug-resistant genotypes in Bonoua, an urban area, and Samo, a rural agricultural area, in southeastern Côte-d'Ivoire, about 59 km from Abidjan. PATIENTS AND METHODS: Samples were collected from symptomatic patients in both sites during the rainy season in 2005. Genomic DNA was isolated and codons associated with resistance to CQ and SP were analyzed: pfcrt codons Cys-72-Ser, Val-73-Val, Met-74-Ile, Arg-75-Glu, Lys-76-Thr; pfdhfr codons Ala-16-Val, Arg-51-Ile, Cys-59-Arg, Ser-108-Arg/Thr, and Ile-164-Leu; pfdhps codons Ser-436-Ala, Ala-437-Gly, Lys-540-Glu, Ala-581-Gly, and Ala-613-Thr/Ser. RESULTS: A limited number of genotypes were found in Bonoua compared with Samo. In both sites, the triple-mutant allele CVIET of pfcrt predominated: 100% in Bonoua and 86.2% in Samo. The wild-type allele, NCSI of pfdhfr, was common - 50% in Bonoua and 38.7% in Samo - but the triple-mutant IRNI and double-mutant NRNI were also frequent (IRNI, 32.6% in Bonoua and 19.4% in Samo; NRNI, 15.2% in Bonoua and 9.7% in Samo). In Samo, a wide range of different genotypes of Pfdhps was observed, with alleles carrying the Gly-437 codon fixed in Bonoua and comprising 73% of the isolates in Samo. CONCLUSION: Although these two sites are only 8 km apart, they belonged to very different ecological environments. The overall prevalence of alleles of single-nucleotide polymorphisms associated with resistance to CQ and SP in both locations was among the highest of the region by 2005, although the more rural site showed a more diverse set of alleles and mixed infections. Continued surveillance of these markers will be a useful tool for drug policy, as both CQ and SP are still frequently used years after withdrawal, and SP is recommended by the World Health Organization for intermittent preventive therapy for pregnant women and infants. Data analyzed herein are among the first to be generated during the year of artemisin-based combination-therapy introduction in Côte-d'Ivoire and could be of some interest for malaria policy-makers.
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OBJECTIVE: To compare, in a phase IV trial, the efficacy and tolerability of artesunate-amodiaquine (Camoquin plus) dosed at 300 and 600 mg of amodiaquine per tablet to artemether-lumefantrine (Coartem) for the treatment of Plasmodium falciparum uncomplicated malaria in Ivory Coast and Senegal. METHOD: Multisite, randomised, open-labelled study in patients over the age of 7 years. The primary endpoint for efficacy was adequate clinical and parasitological response (ACPR) at day 28. The secondary endpoints were fever and parasite clearance and gametocyte carriage in each treatment group. Drug tolerability was assessed comparing adverse events and modification of biological parameters between D0 and D7. Data were analysed on an intention-to-treat and per protocol basis. RESULTS: We included 322 patients; 316 patients completed the monitoring to D28 (155 in AS + AQ group and 161 in AL group). In ITT analysis, an ACPR corrected rate of 97.4% was observed in AS + AQ group versus 97% in AL group (P = 0.99). No parasite recrudescence was observed in AS + AQ arm. All patients in both groups had a fever and parasite clearance at D2. Gametocytes had disappeared by D14 in the AL group and by D21 in the AS + AQ group. No serious adverse events were observed. Minor adverse events were significantly more frequent in the AS + AQ arm. Biological parameters between D0 and D7 did not show any significant statistical variations except for anaemia. CONCLUSION: This study demonstrates the efficacy and tolerability of AS + AQ for uncomplicated Plasmodium falciparum malaria treatment in African patients over the age of 7 years.