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1.
Am J Ther ; 21(3): 193-7, 2014.
Artículo en Inglés | MEDLINE | ID: mdl-22020083

RESUMEN

A simple method to estimate antimalarial drug-related fall in hematocrit (FIH) after treatment of Plasmodium falciparum infections in the field is described. The method involves numeric estimation of the relative difference in hematocrit at baseline (pretreatment) and the first 1 or 2 days after treatment begun as numerator and the corresponding relative difference in parasitemia as the denominator, and expressing it per 1000 parasites cleared from peripheral blood. Using the method showed that FIH/1000 parasites cleared from peripheral blood (cpb) at 24 or 48 hours were similar in artemether-lumefantrine and artesunate-amodiaquine-treated children (0.09; 95% confidence interval, 0.052-0.138 vs 0.10; 95% confidence interval, 0.069-0.139%; P = 0.75) FIH/1000 parasites cpb in patients with higher parasitemias were significantly (P < 0.0001) and five- to 10-fold lower than in patients with lower parasitemias suggesting conservation of hematocrit or red cells in patients with higher parasitemias treated with artesunate-amodiaquine or artemether-lumefantrine. FIH/1000 parasites cpb were similar in anemic and nonanemic children. Estimation of FIH/1000 parasites cpb is simple, allows estimation of relatively conserved hematocrit during treatment, and can be used in both observational studies and clinical trials involving antimalarial drugs.


Asunto(s)
Anemia/etiología , Antimaláricos/uso terapéutico , Hematócrito/métodos , Malaria Falciparum/tratamiento farmacológico , Amodiaquina/administración & dosificación , Amodiaquina/uso terapéutico , Anemia/epidemiología , Antimaláricos/administración & dosificación , Combinación Arteméter y Lumefantrina , Artemisininas/administración & dosificación , Artemisininas/uso terapéutico , Niño , Preescolar , Combinación de Medicamentos , Etanolaminas/administración & dosificación , Etanolaminas/uso terapéutico , Femenino , Fluorenos/administración & dosificación , Fluorenos/uso terapéutico , Humanos , Malaria Falciparum/complicaciones , Masculino , Parasitemia/tratamiento farmacológico , Plasmodium falciparum/aislamiento & purificación , Factores de Tiempo , Resultado del Tratamiento
2.
Am J Ther ; 20(1): 48-56, 2013 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-21192244

RESUMEN

The treatment efficacy of artesunate-amodiaquine (AQ) coformulated or copackaged, and the plasma and saliva concentrations of desethylamodiaquine (DEAQ), the active metabolite of AQ, were evaluated in 120 and 7 children, respectively, with uncomplicated Plasmodium falciparum malaria treated with oral daily doses of the 2 formulations for 3 days. All children recovered clinically. Fever clearance (1.1 ± 0.2 vs 1.0 ± 0 days) and parasite clearance times (21.1 ± 10.2 vs 19.0 ± 7.0 hours) in artesunate-AQ coformulated and artesunate-AQ copackaged treated children, respectively, were similar. All children remained aparasitemic for at least 28 days. Blood and saliva samples were collected over 35 days and DEAQ in plasma and saliva was determined by high-performance liquid chromatography. DEAQ was detectable in plasma and saliva within 40 minutes of oral administration of artesunate-AQ. DEAQ concentrations 7 days after the start of therapy were 247.8 and 125.1 ng/mL in plasma and saliva, respectively. The concentration-time curves of plasma and saliva in declining phases were approximately parallel giving a similar half-life of 169.1 ± 16.4 and 142.8 ± 6.5 hours in plasma and saliva, respectively. Clearance from plasma and saliva was also similar (335.6 and 443.4 mL·h·kg, respectively). Area under concentration-time curves (AUC0-35d) for plasma and saliva were 94,744.9 and 74,004.2 ng·mL·h, respectively. In general, Saliva-plasma concentration ratio was 0.25-0.4. DEAQ concentrations in saliva may be useful for monitoring therapy and for the evaluation of the disposition of AQ in children with falciparum malaria treated with AQ-based combination.


Asunto(s)
Amodiaquina/análogos & derivados , Antimaláricos/uso terapéutico , Artemisininas/uso terapéutico , Malaria Falciparum/tratamiento farmacológico , Saliva/química , Enfermedad Aguda , Administración Oral , Amodiaquina/análisis , Amodiaquina/sangre , Amodiaquina/farmacocinética , Amodiaquina/uso terapéutico , Antimaláricos/farmacocinética , Artemisininas/farmacocinética , Niño , Preescolar , Cromatografía Líquida de Alta Presión , Esquema de Medicación , Combinación de Medicamentos , Quimioterapia Combinada , Femenino , Estudios de Seguimiento , Semivida , Humanos , Lactante , Masculino , Tasa de Depuración Metabólica , Resultado del Tratamiento
3.
Am J Ther ; 19(4): e122-31, 2012 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-21519221

RESUMEN

A new dose regimen of artesunate and amodiaquine (NDRAA) based on age or body weight range was compared with standard dose regimen of artesunate and amodiaquine (SDRAA) calculated according to body weight and with fixed-dose artesunate-amodiaquine (FDAA) and artemether-lumefantrine (AL) in 304 children afflicted by malaria aged 15 years or younger. In initial comparison (n = 208), children on NDRAA received 1-3 times amodiaquine per kilogram of body weight and 1-1.5 times of artesunate per kilogram of body weight compared with those receiving SDRAA. Parasite but not fever clearance was significantly faster in children who received NDRAA (19.4 ± 8.4 hours vs. 24.6 ± 15.5 hours, P = 0.003). Polymerase chain reaction-uncorrected cure rates on days 28-42 were also significantly higher in children who received NDRAA (P < 0.02 in all cases). Therapeutic responses in children younger than 5 years (n = 96) treated with NDRAA, FDAA, and AL were similar. Changes in hematocrit values and reported adverse events after commencing therapy were similar in those who received NDRAA and SDRAA. All drug regimens were well tolerated. NDRAA based on age or body weight range is simple, is therapeutically superior to SDRAA calculated according to body weight, and is as efficacious as AL in children younger than 5 years.


Asunto(s)
Amodiaquina/uso terapéutico , Artemisininas/uso terapéutico , Etanolaminas/uso terapéutico , Fluorenos/uso terapéutico , Malaria Falciparum/tratamiento farmacológico , Administración Oral , Adolescente , Factores de Edad , Amodiaquina/administración & dosificación , Amodiaquina/efectos adversos , Antimaláricos/administración & dosificación , Antimaláricos/efectos adversos , Antimaláricos/uso terapéutico , Combinación Arteméter y Lumefantrina , Artemisininas/administración & dosificación , Artemisininas/efectos adversos , Peso Corporal , Niño , Preescolar , Relación Dosis-Respuesta a Droga , Combinación de Medicamentos , Etanolaminas/administración & dosificación , Etanolaminas/efectos adversos , Fluorenos/administración & dosificación , Fluorenos/efectos adversos , Estudios de Seguimiento , Humanos , Lactante , Reacción en Cadena de la Polimerasa , Resultado del Tratamiento
4.
J Trop Pediatr ; 58(2): 151-3, 2012 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-21622538

RESUMEN

The therapeutic efficacy, changes in haematocrit and declines in parasitaemias were evaluated in 56 children with uncomplicated falciparum hyperparasitaemia after oral artesunate-amodiaquine or artemether-lumefantrine. All children recovered clinically within 2 days and without progression to severe malaria. Falls in haematocrit in the first 3 days after treatment began were similar and <5%. Declines in parasitaemias were monoexponential with both treatments with an estimated half-life of 1 h.


Asunto(s)
Amodiaquina/uso terapéutico , Antimaláricos/uso terapéutico , Artemisininas/uso terapéutico , Etanolaminas/uso terapéutico , Fluorenos/uso terapéutico , Malaria Falciparum/tratamiento farmacológico , Combinación Arteméter y Lumefantrina , Niño , Preescolar , Combinación de Medicamentos , Femenino , Hematócrito , Humanos , Lactante , Malaria Falciparum/sangre , Malaria Falciparum/parasitología , Masculino , Nigeria , Parasitemia/tratamiento farmacológico , Plasmodium falciparum , Resultado del Tratamiento
5.
J Trop Pediatr ; 58(4): 263-8, 2012 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-22052702

RESUMEN

A dose regimen of artesunate and amodiaquine based on arm span- or age range (DRAAAS), derived from a study of 1674 children, was compared with standard dose regimen of the same drugs calculated according to body weight (SDRAA) in 68 malarious children. Children on DRAAAS received 0.8-1.0 of artesunate/kg and 0.9-1.2 times amodiaquine/kg compared with those receiving SDRAA. Parasite and fever clearance and fall in hematocrit in the first 3 days were similar; both regimens were well tolerated. DRAAAS is simple and is efficacious.


Asunto(s)
Amodiaquina/administración & dosificación , Antimaláricos/administración & dosificación , Artemisininas/administración & dosificación , Malaria Falciparum/tratamiento farmacológico , Adolescente , Distribución por Edad , Amodiaquina/uso terapéutico , Antimaláricos/uso terapéutico , Área Bajo la Curva , Brazo , Artemisininas/uso terapéutico , Artesunato , Peso Corporal , Niño , Preescolar , Relación Dosis-Respuesta a Droga , Femenino , Humanos , Malaria Falciparum/diagnóstico , Malaria Falciparum/parasitología , Masculino , Plasmodium falciparum/aislamiento & purificación , Evaluación de Programas y Proyectos de Salud , Resultado del Tratamiento
6.
BMC Infect Dis ; 11: 268, 2011 Oct 09.
Artículo en Inglés | MEDLINE | ID: mdl-21982211

RESUMEN

BACKGROUND: Hyperparasitaemia is a feature of childhood severe malaria but there is little information on the risk factors for hyperparasitaemia in malarious children METHODS: The risk factors associated with Plasmodium falciparum hyperparasitaemia, defined as asexual parasitaemia > 250,000/µl, at presentation were evaluated in 3338 malarious children enrolled prospectively between 2008 and 2010 in an endemic area of southwestern Nigeria. RESULTS: At enrolment, 97 (3%) of 3338 malarious children had hyperparasitaemia. In a multiple regression model, 3 factors were found to be independent risk factors for the presence of hyperparasitaemia at enrolment: an age ≤ 11 years (Adjusted odds ratio [AOR] = 2.85, 95% confidence interval [CI] 1.23-6.61, P = 0.014), fever (AOR = 2.02, 95% CI 1.23-3.29, P = 0.005), and enrolment after year 2008 (AOR = 0.42, 95% CI 0.24-0.73, P = 0.002). Duration of illness ≤ 3 d was associated with increased risk of hyperparasitaemia. There was no association between season and hyperparasitaemia. Compared to non-hyperparasitaemia, hyperparasitaemia was associated with an increased risk of progression to cerebral malaria (P < 0.0001). The risk of progression in hyperparasitaemic children was higher in < 5-year olds (P = 0.02). CONCLUSION: Young age and presence of fever are independent risk factors for hyperparasitaemia which is associated with an increased risk of progression to cerebral malaria. The findings have implications for case and community management of childhood hyperparasitaemia and for malaria control efforts in sub-Saharan Africa where severe malaria is relatively common.


Asunto(s)
Malaria Falciparum/patología , Parasitemia/epidemiología , Plasmodium falciparum/aislamiento & purificación , Adolescente , Niño , Preescolar , Femenino , Humanos , Lactante , Malaria Falciparum/parasitología , Masculino , Nigeria , Estudios Prospectivos , Factores de Riesgo
7.
Am J Ther ; 18(3): 190-7, 2011 May.
Artículo en Inglés | MEDLINE | ID: mdl-20683244

RESUMEN

To evaluate the effects of antimalarial drugs on Plasmodium falciparum malaria-associated anemia, we use the area under the curve (AUC) of anemia levels after treatment as an approach to combine their duration and magnitude. The method involves numeric estimation, by trapezoidal rule, of AUC from a plot of deficit in hematocrit levels from 30% (the lower threshold of normal) versus time in anemic children. Using the method, we evaluated, in randomized trials, the effects of artesunate-mefloquine versus mefloquine alone and artemether-lumefantrine versus amodiaquine-artesunate on the time course of recovery from malaria-associated anemia in 109 children. Anemia resolution times were similar (10.9 ± 6.2 [standard deviation] versus 13.3 ± 8.9 days, P = 0.2), but mean AUC was significantly lower in artesunate-mefloquine- compared with mefloquine-treated children (35.5 ± 7.1 [standard error of mean] versus 49.8 ± 11.3 %·h, P = 0.02) indicating larger exposure to anemia in mefloquine-treated children. In artemether-lumefantrine- and amodiaquine-artesunate-treated children, both anemia resolution times (8.6 ± 5.3 [standard deviation] versus 8.6 ± 4.8 days, P = 0.98) and mean AUC (57.1 ± 12.9 [standard error of mean] versus 46.3 ± 8.7 %·h, P = 0.74) were similar. Estimation of AUC appears more robust than estimation of anemia resolution time in evaluating antimalarial drug effects and can be used in both observational studies and clinical trials assessing the effects of therapies on malaria-associated anemia.


Asunto(s)
Anemia/tratamiento farmacológico , Antimaláricos/uso terapéutico , Área Bajo la Curva , Malaria/tratamiento farmacológico , Amodiaquina/farmacocinética , Amodiaquina/uso terapéutico , Anemia/complicaciones , Antimaláricos/farmacocinética , Combinación Arteméter y Lumefantrina , Artemisininas/farmacocinética , Artemisininas/uso terapéutico , Artesunato , Niño , Preescolar , Combinación de Medicamentos , Etanolaminas , Femenino , Fluorenos/farmacocinética , Fluorenos/uso terapéutico , Hematócrito , Humanos , Lactante , Malaria/complicaciones , Malaria Falciparum/tratamiento farmacológico , Masculino , Mefloquina/farmacocinética , Mefloquina/uso terapéutico , Nigeria , Plasmodium falciparum/efectos de los fármacos
8.
Chemotherapy ; 57(6): 497-504, 2011.
Artículo en Inglés | MEDLINE | ID: mdl-22261842

RESUMEN

BACKGROUND: Artemisinin-based combination treatments (ACTs) are the recommended first-line antimalarials globally, but their influence on the risk factors associated with gametocyte carriage has had little evaluation in endemic areas. METHODS: The risk factors associated with gametocytaemia at presentation and after ACTs were evaluated in 835 children assigned to artesunate, artesunate-amodiaquine, artesunate-mefloquine or artemether-lumefantrine. RESULTS: Gametocyte carriage at enrolment was 8.4%. During follow-up, 24 patients (2.8%) developed gametocytaemia, which in 83% (20 patients) had developed by day 7 following treatment. In a multiple regression model, 2 factors were independent risk factors for the presence of gametocytaemia at enrolment, namely age <3 years (adjusted odds ratio 2.03, 95% confidence interval 1.01-4.05; p = 0.04) and enrolment before 2009 (adjusted odds ratio 4.2, 95% confidence interval 2.09-8.44; p < 0.001). Haematocrit <25% and parasitaemia <50,000/µl blood were associated with an increased risk of gametocytaemia. Following treatment, 3 factors were independent risk factors for gametocytaemia, namely gametocytaemia at enrolment (adjusted odds ratio 46.39, 95% confidence interval 22.3-96.46; p < 0.0001) and treatment with artesunate (adjusted odds ratio 6.74, 95% confidence interval 1.79-25.27; p = 0.005) or artesunate-mefloquine (adjusted odds ratio 9.66, 95% confidence interval 2.87-32.46; p < 0.0.0001) relative to other ACTs. CONCLUSION: ACTs modified the risk factors associated with gametocyte carriage after use.


Asunto(s)
Antimaláricos/administración & dosificación , Artemisininas/administración & dosificación , Malaria Falciparum/tratamiento farmacológico , Adolescente , Aminoquinolinas/administración & dosificación , Niño , Preescolar , Quimioterapia Combinada , Femenino , Estudios de Seguimiento , Humanos , Lactante , Malaria Falciparum/genética , Malaria Falciparum/parasitología , Masculino , Factores de Riesgo
9.
Mem Inst Oswaldo Cruz ; 106(6): 685-90, 2011 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-22012222

RESUMEN

The effects of artemisinin-based combination therapies (ACTs) on transmission of Plasmodium falciparum were evaluated after a policy change instituting the use of ACTs in an endemic area. P. falciparum gametocyte carriage, sex ratios and inbreeding rates were examined in 2,585 children at presentation with acute falciparum malaria during a 10-year period from 2001-2010. Asexual parasite rates were also evaluated from 2003-2010 in 10,615 children before and after the policy change. Gametocyte carriage declined significantly from 12.4% in 2001 to 3.6% in 2010 (χ2 for trend = 44.3, p < 0.0001), but sex ratios and inbreeding rates remained unchanged. Additionally, overall parasite rates remained unchanged before and after the policy change (47.2% vs. 45.4%), but these rates declined significantly from 2003-2010 (χ2 for trend 35.4, p < 0.0001). Chloroquine (CQ) and artemether-lumefantrine (AL) were used as prototype drugs before and after the policy change, respectively. AL significantly shortened the duration of male gametocyte carriage in individual patients after treatment began compared with CQ (log rank statistic = 7.92, p = 0.005). ACTs reduced the rate of gametocyte carriage in children with acute falciparum infections at presentation and shortened the duration of male gametocyte carriage after treatment. However, parasite population sex ratios, inbreeding rates and overall parasite rate were unaffected.


Asunto(s)
Antimaláricos/uso terapéutico , Artemisininas/uso terapéutico , Cloroquina/uso terapéutico , Malaria Falciparum/tratamiento farmacológico , Parasitemia/tratamiento farmacológico , Plasmodium falciparum/efectos de los fármacos , Adolescente , Niño , Preescolar , Quimioterapia Combinada/métodos , Femenino , Humanos , Lactante , Malaria Falciparum/epidemiología , Malaria Falciparum/parasitología , Masculino , Nigeria , Parasitemia/parasitología , Plasmodium falciparum/crecimiento & desarrollo , Razón de Masculinidad
10.
Mem Inst Oswaldo Cruz ; 106(5): 562-9, 2011 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-21894377

RESUMEN

Anaemia in falciparum malaria is associated with an increased risk of gametocyte carriage, but its effects on transmission have not been extensively evaluated in malarious children. Plasmodium falciparum gametocyte carriage, emergence, clearance, population sex ratios (SR) (defined as the proportion of gametocytes that are male), inbreeding rates and temporal changes in SR were evaluated in 840 malarious children. Gametocyte carriage pre-treatment was at a level of 8.1%. Anaemia at enrolment was an independent risk factor for gametocyte carriage post-treatment. The emergence of gametocytes seven days post-treatment was significantly more frequent in anaemic children (7/106 vs. 10/696, p = 0.002). In the initially detected gametocytes, the proportion of children with a male-biased SR (MBSR) (> 0.5) was significantly higher in anaemic children (6/7 vs. 3/10, p = 0.027). Pre-treatment SR and estimated inbreeding rates (proportion of a mother's daughters fertilised by her sons) were similar in anaemic and non-anaemic children. Pre-treatment SR became more female-biased in non-anaemic children following treatment. However, in anaemic children, SR became male-biased. Anaemia was shown to significantly increase gametocyte emergence and may significantly alter the SR of emerging gametocytes. If MBSR is more infective to mosquitoes at low gametocytaemia, then these findings may have significant implications for malaria control efforts in endemic settings where malaria-associated anaemia is common.


Asunto(s)
Anemia/parasitología , Malaria Falciparum/parasitología , Plasmodium falciparum/citología , Antimaláricos/uso terapéutico , Preescolar , Femenino , Humanos , Malaria Falciparum/tratamiento farmacológico , Masculino , Plasmodium falciparum/efectos de los fármacos , Factores de Riesgo , Razón de Masculinidad
11.
Malar J ; 9: 335, 2010 Nov 22.
Artículo en Inglés | MEDLINE | ID: mdl-21092220

RESUMEN

BACKGROUND: Combination treatments, preferably containing an artemisinin derivative, are recommended to improve efficacy and prevent Plasmodium falciparum drug resistance. Artemether-lumefantrine (AL) and artesunate-amodiaquine (AA) are efficacious regimens that have been widely adopted in sub-Saharan Africa. However, most study designs ignore the effects of these regimens on peripheral parasitaemia in the first 24 hours of therapy. The study protocol was designed to evaluate more closely the early effects and the standard measures of efficacies of these two regimens. METHODS: In an open label, randomized controlled clinical trial, children aged 12 months to 132 months were randomized to receive AL (5-14 kg, one tablet; 15-24 kg, two tablets and 25-34 kg, three tablets twice daily) or artesunate (4 mg/kg daily) plus amodiaquine (10 mg/kg daily) for three days. Peripheral blood smears were made hourly in the first 4 hours, 8 h, 16 h, 24 h, and daily on days 2-7, and on days 7, 14, 21, 28, 35, and 42 for microscopic identification and quantification of Plasmodium falciparum. RESULTS: A total of 193 children were randomized to receive either AL (97) or AA (96). In children that received both medications, early response of peripheral parasitaemia showed that 42% of children who received AL and 36.7% of those who received AA had an immediate rise in peripheral parasitaemia (0-4 h after treatment) followed by a rapid fall. The rise in parasitaemia was significant and seems to suggest a mobilization of asexual parasites from the deep tissues to the periphery. Days 3, 7, 14, 28, and 42 cure rates in the per protocol (PP) population were > 90% in both groups of children. Both drug combinations were well tolerated with minimal side effects. CONCLUSION: The study showed the high efficacy of AL and AA in Nigerian children. In addition the study demonstrated the mobilisation of asexual parasites from the deep to the periphery in the early hours of commencing ACT treatment in a subset of patients in both study groups. It is unclear whether the early parasite dynamics discovered in this study play any role in the development of drug resistance and thus it is important to further evaluate this discovery. It may be useful for studies investigating delay in parasite clearance of artemisinin derivatives as a way of monitoring the development of resistance to artemisinin to assess the early effects of the drugs on the parasites.


Asunto(s)
Amodiaquina/administración & dosificación , Antimaláricos/administración & dosificación , Artemisininas/administración & dosificación , Etanolaminas/administración & dosificación , Fluorenos/administración & dosificación , Malaria Falciparum/tratamiento farmacológico , Malaria Falciparum/parasitología , Parasitemia , Plasmodium falciparum/aislamiento & purificación , Combinación Arteméter y Lumefantrina , Sangre/parasitología , Niño , Preescolar , Combinación de Medicamentos , Femenino , Humanos , Lactante , Masculino , Nigeria , Factores de Tiempo
12.
Malar J ; 9: 53, 2010 Feb 15.
Artículo en Inglés | MEDLINE | ID: mdl-20156350

RESUMEN

BACKGROUND: Drug resistance in Plasmodium falciparum is common in many endemic and other settings but there is no clear recommendation on when to change therapy when there is delay in parasite clearance after initiation of therapy in African children. METHODS: The factors contributing to delay in parasite clearance, defined as a clearance time > 2 d, in falciparum malaria were characterized in 2,752 prospectively studied children treated with anti-malarial drugs between 1996 and 2008. RESULTS: 1,237 of 2,752 children (45%) had delay in parasite clearance. Overall 211 children (17%) with delay in clearance subsequently failed therapy and they constituted 72% of those who had drug failure, i.e., 211 of 291 children. The following were independent risk factors for delay in parasite clearance at enrolment: age less than or equal to 2 years (Adjusted odds ratio [AOR] = 2.13, 95% confidence interval [CI]1.44-3.15, P < 0.0001), presence of fever (AOR = 1.33, 95% CI = 1.04-1.69, P = 0.019), parasitaemia >50,000/ul (AOR = 2.21, 95% CI = 1.77-2.75, P < 0.0001), and enrolment before year 2000 (AOR= 1.55, 95% CI = 1.22-1.96, P < 0.0001). Following treatment, a body temperature >or= 38 degrees C and parasitaemia > 20000/microl a day after treatment began, were independent risk factors for delay in clearance. Non-artemisinin monotherapies were associated with delay in clearance and treatment failures, and in those treated with chloroquine or amodiaquine, with pfmdr 1/pfcrt mutants. Delay in clearance significantly increased gametocyte carriage (P < 0.0001). CONCLUSION: Delay in parasite clearance is multifactorial, is related to drug resistance and treatment failure in uncomplicated malaria and has implications for malaria control efforts in sub-Saharan Africa.


Asunto(s)
Antimaláricos/uso terapéutico , Malaria Falciparum/tratamiento farmacológico , Parasitemia/tratamiento farmacológico , Plasmodium falciparum/aislamiento & purificación , Antimaláricos/farmacología , Niño , Preescolar , Resistencia a Medicamentos/efectos de los fármacos , Femenino , Estudios de Seguimiento , Humanos , Lactante , Malaria Falciparum/epidemiología , Malaria Falciparum/parasitología , Masculino , Proteínas de Transporte de Membrana/sangre , Proteínas Asociadas a Resistencia a Múltiples Medicamentos/sangre , Plasmodium falciparum/efectos de los fármacos , Polimorfismo de Nucleótido Simple , Estudios Prospectivos , Proteínas Protozoarias/sangre , Factores de Riesgo , Factores de Tiempo , Resultado del Tratamiento
13.
Malar J ; 8: 297, 2009 Dec 16.
Artículo en Inglés | MEDLINE | ID: mdl-20015395

RESUMEN

BACKGROUND: The gametocyte sex ratio of Plasmodium falciparum, defined as the proportion of gametocytes that are male, may influence transmission but little is known of the effects of mefloquine or artesunate-mefloquine on gametocyte sex ratio and on the sex ratio of first appearing gametocytes. METHODS: 350 children with uncomplicated P. falciparum malaria were enrolled in prospective treatment trial of mefloquine or artesunate-mefloquine between 2007 and 2008. Gametocytaemia was quantified, and gametocytes were sexed by morphological appearance, before and following treatment. The area under curve of gametocyte density versus time (AUCgm) was calculated by linear trapezoidal method. RESULTS: 91% and 96% of all gametocytes appeared by day 7 and day 14, respectively following treatment. The overall rate of gametocytaemia with both treatments was 31%, and was significantly higher in mefloquine than in artesunate-mefloquine treated children if no gametocyte was present a day after treatment began (25.3% v 12.8%, P = 0.01). Gametocyte clearance was significantly faster with artesunate-mefloquine (1.8 +/- 0.22 [sem] v 5.6 +/- 0.95 d; P = 0.001). AUCgm was significantly lower in the artesunate mefloquine group (P = 0.008). The pre-treatment sex ratio was male-biased, but post-treatment sex ratio or the sex ratio of first appearing gametocytes, was significantly lower and female-biased two or three days after beginning of treatment in children given artesunate-mefloquine. CONCLUSION: Addition of artesunate to mefloquine significantly modified the emergence, clearance, and densities of gametocytes and has short-lived, but significant, sex ratio modifying effects in children from this endemic area.


Asunto(s)
Artemisininas/uso terapéutico , Sangre/parasitología , Malaria Falciparum/tratamiento farmacológico , Malaria Falciparum/parasitología , Mefloquina/uso terapéutico , Plasmodium falciparum/citología , Plasmodium falciparum/aislamiento & purificación , Adolescente , Animales , Artesunato , Niño , Preescolar , Femenino , Humanos , Lactante , Masculino , Plasmodium falciparum/efectos de los fármacos , Estudios Prospectivos
14.
Am J Trop Med Hyg ; 91(5): 925-935, 2014 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-25246693

RESUMEN

The efficacy of 3-day regimens of artemether-lumefantrine and artesunate-amodiaquine were evaluated in 747 children < 5 years of age with uncomplicated malaria from six geographical areas of Nigeria. Fever clearance was significantly faster (P = 0.006) and the proportion of children with parasitemia 1 day after treatment began was significantly lower (P = 0.016) in artesunate-amodiaquine-compared with artemether-lumefantrine-treated children. Parasite clearance times were similar with both treatments. Overall efficacy was 96.3% (95% confidence interval [CI] 94.5-97.6%), and was similar for both regimens. Polymerase chain reaction-corrected parasitologic cure rates on Day 28 were 96.9% (95% CI 93.9-98.2%) and 98.3% (95% CI 96.1-99.3%) for artemether-lumefantrine and artesunate-amodiaquine, respectively. Gametocyte carriage post treatment was significantly lower than pretreatment (P < 0.0001). In anemic children, mean time to recovery from anemia was 10 days (95% CI 9.04-10.9) and was similar for both regimens. Both treatments were well tolerated and are safe and efficacious treatments of uncomplicated falciparum malaria in young Nigerian children.


Asunto(s)
Amodiaquina/uso terapéutico , Antimaláricos/uso terapéutico , Artemisininas/uso terapéutico , Etanolaminas/uso terapéutico , Fluorenos/uso terapéutico , Malaria Falciparum/tratamiento farmacológico , Anemia/complicaciones , Anemia/tratamiento farmacológico , Anemia/epidemiología , Combinación Arteméter y Lumefantrina , Preescolar , Combinación de Medicamentos , Femenino , Humanos , Malaria Falciparum/complicaciones , Masculino , Nigeria/epidemiología , Parasitemia/tratamiento farmacológico , Prevalencia , Resultado del Tratamiento
15.
Am J Trop Med Hyg ; 84(6): 936-43, 2011 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-21633031

RESUMEN

The therapeutic efficacies of 3-day regimens of artesunate-amodiaquine and artemether-lumefantrine during 5 years of adoption as first-line treatments were evaluated in 811 ≤ 12-year-old malarious children. Compared with artemether-lumefantrine, amodiaquine-artesunate significantly reduced the proportion of children with fever and parasitemia 1 day after treatment (day 1; P < 0.008 for both). The proportion of parasitemic children on day 2 and gametocytemia on presentation and carriage reduced significantly over the years (P < 0.000001 and P < 0.03, respectively; test for trend). Overall efficacy was 96.5% (95% confidence interval [CI] = 94.5-98.6) and remained unchanged over the years (P = 0.87; test for trend). Kinetics of parasitemias after treatments were estimated by a non-compartmental model. Declines of parasitemias were monoexponential, with a mean elimination half-life of 1.09 hours (95% CI = 1.0-1.16). Parasitemia half-lives and efficacy were similar for both regimens and in all ages. Artesunate-amodiaquine and artemether-lumefantrine remain efficacious treatments of uncomplicated falciparum malaria in Nigerian children 5 years after adoption.


Asunto(s)
Amodiaquina/uso terapéutico , Antimaláricos/uso terapéutico , Artemisininas/uso terapéutico , Fluorenos/uso terapéutico , Malaria Falciparum/tratamiento farmacológico , Análisis de Varianza , Combinación Arteméter y Lumefantrina , Niño , Preescolar , Combinación de Medicamentos , Etanolaminas , Femenino , Semivida , Humanos , Lactante , Malaria Falciparum/epidemiología , Masculino , Nigeria/epidemiología , Parasitemia/tratamiento farmacológico , Parasitemia/epidemiología , Plasmodium falciparum/efectos de los fármacos , Plasmodium falciparum/aislamiento & purificación , Estudios Prospectivos , Ensayos Clínicos Controlados Aleatorios como Asunto , Resultado del Tratamiento
16.
Am J Trop Med Hyg ; 84(5): 813-9, 2011 May.
Artículo en Inglés | MEDLINE | ID: mdl-21540395

RESUMEN

The therapeutic efficacy and effects of artemether-lumefantrine (AL) and artesunate-amodiaquine co-formulated (AAcf) or co-packaged (AAcp) on malaria-associated anemia (MAA) were evaluated in 285 children < 12 years of age with uncomplicated Plasmodium falciparum malaria randomized to receive one of the three drug combinations. Fever and parasite clearance times were similar in all treatment groups. Mean drug-attributable fall in hematocrit (DAFH), defined as difference between hematocrit values pre- and 3 d post-initiation of treatment, was low (< 4.5%) and rates of recovery from MAA were similar with all treatments. Mean areas under curve (AUCs) of the plot of deficit in hematocrit levels from 30% versus time in anemic children were similar in all groups. All regimens were well tolerated. AL, AAcf and AAcp cleared fever and parasitemia rapidly and had similar rates of resolution of MAA after treatment in malarious Nigerian children.


Asunto(s)
Amodiaquina/uso terapéutico , Anemia/tratamiento farmacológico , Antimaláricos/uso terapéutico , Artemisininas/uso terapéutico , Etanolaminas/uso terapéutico , Fluorenos/uso terapéutico , Malaria Falciparum/tratamiento farmacológico , Amodiaquina/farmacocinética , Anemia/etiología , Antimaláricos/farmacocinética , Área Bajo la Curva , Combinación Arteméter y Lumefantrina , Artemisininas/farmacocinética , Niño , Preescolar , Combinación de Medicamentos , Etanolaminas/farmacocinética , Fluorenos/farmacocinética , Humanos , Malaria Falciparum/complicaciones , Nigeria , Resultado del Tratamiento
18.
Mem. Inst. Oswaldo Cruz ; 106(6): 685-690, Sept. 2011. ilus, graf
Artículo en Inglés | LILACS | ID: lil-602051

RESUMEN

The effects of artemisinin-based combination therapies (ACTs) on transmission of Plasmodium falciparum were evaluated after a policy change instituting the use of ACTs in an endemic area. P. falciparum gametocyte carriage, sex ratios and inbreeding rates were examined in 2,585 children at presentation with acute falciparum malaria during a 10-year period from 2001-2010. Asexual parasite rates were also evaluated from 2003-2010 in 10,615 children before and after the policy change. Gametocyte carriage declined significantly from 12.4 percent in 2001 to 3.6 percent in 2010 (@@χ2 for trend = 44.3, p < 0.0001), but sex ratios and inbreeding rates remained unchanged. Additionally, overall parasite rates remained unchanged before and after the policy change (47.2 percent vs. 45.4 percent), but these rates declined significantly from 2003-2010 (@@χ2 for trend 35.4, p < 0.0001). Chloroquine (CQ) and artemether-lumefantrine (AL) were used as prototype drugs before and after the policy change, respectively. AL significantly shortened the duration of male gametocyte carriage in individual patients after treatment began compared with CQ (log rank statistic = 7.92, p = 0.005). ACTs reduced the rate of gametocyte carriage in children with acute falciparum infections at presentation and shortened the duration of male gametocyte carriage after treatment. However, parasite population sex ratios, inbreeding rates and overall parasite rate were unaffected.


Asunto(s)
Adolescente , Niño , Preescolar , Femenino , Humanos , Lactante , Masculino , Antimaláricos/uso terapéutico , Artemisininas/uso terapéutico , Cloroquina/uso terapéutico , Malaria Falciparum/tratamiento farmacológico , Parasitemia/tratamiento farmacológico , Plasmodium falciparum/efectos de los fármacos , Quimioterapia Combinada/métodos , Malaria Falciparum/epidemiología , Malaria Falciparum/parasitología , Nigeria , Parasitemia/parasitología , Plasmodium falciparum/crecimiento & desarrollo , Razón de Masculinidad
19.
Mem. Inst. Oswaldo Cruz ; 106(5): 562-569, Aug. 2011. graf, tab
Artículo en Inglés | LILACS | ID: lil-597716

RESUMEN

Anaemia in falciparum malaria is associated with an increased risk of gametocyte carriage, but its effects on transmission have not been extensively evaluated in malarious children. Plasmodium falciparum gametocyte carriage, emergence, clearance, population sex ratios (SR) (defined as the proportion of gametocytes that are male), inbreeding rates and temporal changes in SR were evaluated in 840 malarious children. Gametocyte carriage pre-treatment was at a level of 8.1 percent. Anaemia at enrolment was an independent risk factor for gametocyte carriage post-treatment. The emergence of gametocytes seven days post-treatment was significantly more frequent in anaemic children (7/106 vs. 10/696, p = 0.002). In the initially detected gametocytes, the proportion of children with a male-biased SR (MBSR) (> 0.5) was significantly higher in anaemic children (6/7 vs. 3/10, p = 0.027). Pre-treatment SR and estimated inbreeding rates (proportion of a mother's daughters fertilised by her sons) were similar in anaemic and non-anaemic children. Pre-treatment SR became more female-biased in non-anaemic children following treatment. However, in anaemic children, SR became male-biased. Anaemia was shown to significantly increase gametocyte emergence and may significantly alter the SR of emerging gametocytes. If MBSR is more infective to mosquitoes at low gametocytaemia, then these findings may have significant implications for malaria control efforts in endemic settings where malaria-associated anaemia is common.


Asunto(s)
Preescolar , Femenino , Humanos , Masculino , Anemia , Malaria Falciparum , Plasmodium falciparum , Antimaláricos , Malaria Falciparum , Plasmodium falciparum , Factores de Riesgo , Razón de Masculinidad
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