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1.
Rev Soc Bras Med Trop ; 54: e05362020, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33605379

RESUMO

INTRODUCTION: Artemisinin-based combination therapy (ACT), such as artemisinin-piperaquine (AP), dihydroartemisinin-piperaquine (DP), and artemether-lumefantrine (AL), is the first-line treatment for malaria in many malaria-endemic areas. However, we lack a detailed evaluation of the cardiotoxicity of these ACTs. This study aimed to analyze the electrocardiographic effects of these three ACTs in malaria patients. METHODS: We analyzed the clinical data of 89 hospitalized patients with falciparum malaria who had received oral doses of three different ACTs. According to the ACTs administered, these patients were divided into three treatment groups: 27 treated with AP (Artequick), 31 with DP (Artekin), and 31 with AL (Coartem). Electrocardiograms and other indicators were recorded before and after the treatment. The QT interval was calculated using Fridericia's formula (QTcF) and Bazett's formula (QTcB). RESULTS: Both QTcF and QTcB interval prolongation occurred in all three groups. The incidence of such prolongation between the three groups was not significantly different. The incidence of both moderate and severe prolongation was not significantly different between the three groups. The ΔQTcF and ΔQTcB of the three groups were not significantly different. The intra-group comparison showed significant prolongation of QTcF after AL treatment. CONCLUSIONS: Clinically recommended doses of DP, AL, and AP may cause QT prolongation in some malaria patients but do not cause torsades de pointes ventricular tachycardia or other arrhythmias.


Assuntos
Antimaláricos , Artemisininas , Malária Falciparum , Malária , Antimaláricos/efeitos adversos , Artemeter/uso terapêutico , Combinação Arteméter e Lumefantrina/uso terapêutico , Artemisininas/efeitos adversos , Combinação de Medicamentos , Eletrocardiografia , Humanos , Malária/tratamento farmacológico , Malária Falciparum/tratamento farmacológico , Quinolinas
2.
Cochrane Database Syst Rev ; 1: CD004529, 2021 01 15.
Artigo em Inglês | MEDLINE | ID: mdl-33459345

RESUMO

BACKGROUND: The World Health Organization (WHO) in 2015 stated atovaquone-proguanil can be used in travellers, and is an option in malaria-endemic areas in combination with artesunate, as an alternative treatment where first-line artemisinin-based combination therapy (ACT) is not available or effective. This review is an update of a Cochrane Review undertaken in 2005. OBJECTIVES: To assess the efficacy and safety of atovaquone-proguanil (alone and in combination with artemisinin drugs) versus other antimalarial drugs for treating uncomplicated Plasmodium falciparum malaria in adults and children. SEARCH METHODS: The date of the last trial search was 30 January 2020. Search locations for published trials included the Cochrane Infectious Diseases Group Specialized Register, CENTRAL, MEDLINE, Embase, and LILACS. To include recently published and unpublished trials, we also searched ClinicalTrials.gov, the metaRegister of Controlled Trials and the WHO International Clinical Trials Registry Platform Search Portal. SELECTION CRITERIA: Randomized controlled trials (RCTs) reporting efficacy and safety data for atovaquone-proguanil or atovaquone-proguanil with a partner drug compared with at least one other antimalarial drug for treating uncomplicated Plasmodium falciparum infection. DATA COLLECTION AND ANALYSIS: For this update, two review authors re-extracted data and assessed certainty of evidence. We meta-analyzed data to calculate risk ratios (RRs) with 95% confidence intervals (CI) for treatment failures between comparisons, and for safety outcomes between and across comparisons. Outcome measures include unadjusted treatment failures and polymerase chain reaction (PCR)-adjusted treatment failures. PCR adjustment differentiates new infection from recrudescent infection. MAIN RESULTS: Seventeen RCTs met our inclusion criteria providing 4763 adults and children from Africa, South-America, and South-East Asia. Eight trials reported PCR-adjusted data to distinguish between new and recrudescent infection during the follow-up period. In this abstract, we report only the comparisons against the three WHO-recommended antimalarials which were included within these trials. There were two comparisons with artemether-lumefantrine, one trial from 2008 in Ethiopia with 60 participants had two failures with atovaquone-proguanil compared to none with artemether-lumefantrine (PCR-adjusted treatment failures at day 28). A second trial from 2012 in Colombia with 208 participants had one failure in each arm (PCR-adjusted treatment failures at day 42). There was only one comparison with artesunate-amodiaquine from a 2014 trial conducted in Cameroon. There were six failures with atovaquone-proguanil at day 28 and two with artesunate-amodiaquine (PCR-adjusted treatment failures at day 28: 9.4% with atovaquone-proguanil compared to 2.9% with artesunate-amodiaquine; RR 3.19, 95% CI 0.67 to 15.22; 1 RCT, 132 participants; low-certainty evidence), although there was a similar number of PCR-unadjusted treatment failures (9 (14.1%) with atovaquone-proguanil and 8 (11.8%) with artesunate-amodiaquine; RR 1.20, 95% CI 0.49 to 2.91; 1 RCT, 132 participants; low-certainty evidence). There were two comparisons with artesunate-mefloquine from a 2012 trial in Colombia and a 2002 trial in Thailand where there are high levels of multi-resistant malaria. There were similar numbers of PCR-adjusted treatment failures between groups at day 42 (2.7% with atovaquone-proguanil compared to 2.4% with artesunate-mefloquine; RR 1.15, 95% CI 0.57 to 2.34; 2 RCTs, 1168 participants; high-certainty evidence). There were also similar PCR-unadjusted treatment failures between groups (5.3% with atovaquone-proguanil compared to 6.6% with artesunate-mefloquine; RR 0.8, 95% CI 0.5 to 1.3; 1 RCT, 1063 participants; low-certainty evidence). When atovaquone-proguanil was combined with artesunate, there were fewer treatment failures with and without PCR-adjustment at day 28 (PCR-adjusted treatment failures at day 28: 2.16% with atovaquone-proguanil compared to no failures with artesunate-atovaquone-proguanil; RR 5.14, 95% CI 0.61 to 43.52; 2 RCTs, 375 participants, low-certainty evidence) and day 42 (PCR-adjusted treatment failures at day 42: 3.82% with atovaquone-proguanil compared to 2.05% with artesunate-atovaquone-proguanil (RR 1.84, 95% CI 0.95 to 3.56; 2 RCTs, 1258 participants, moderate-certainty evidence). In the 2002 trial in Thailand, there were fewer treatment failures in the artesunate-atovaquone-proguanil group compared to the atovaquone-proguanil group at day 42 with PCR-adjustment. Whilst there were some small differences in which adverse events were more frequent in the atovaquone-proguanil groups compared to comparator drugs, there were no recurrent associations to suggest that atovaquone-proguanil is strongly associated with any specific adverse event. AUTHORS' CONCLUSIONS: Atovaquone-proguanil was effective against uncomplicated P falciparum malaria, although in some instances treatment failure rates were between 5% and 10%. The addition of artesunate to atovaquone-proguanil may reduce treatment failure rates. Artesunate-atovaquone-proguanil and the development of parasite resistance may represent an area for further research.


Assuntos
Antimaláricos/uso terapêutico , Atovaquona/uso terapêutico , Malária Falciparum/tratamento farmacológico , Proguanil/uso terapêutico , Adulto , Amodiaquina/uso terapêutico , Combinação Arteméter e Lumefantrina/uso terapêutico , Artemisininas/uso terapêutico , Camarões , Criança , Colômbia , Combinação de Medicamentos , Etiópia , Humanos , Mefloquina/uso terapêutico , Ensaios Clínicos Controlados Aleatórios como Assunto , Tailândia , Falha de Tratamento
3.
BMC Res Notes ; 13(1): 497, 2020 Oct 27.
Artigo em Inglês | MEDLINE | ID: mdl-33109270

RESUMO

OBJECTIVE: Nigeria bears 25% of global malaria burden despite concerted efforts towards its control and elimination. The emergence of drug resistance to first line drugs, artemisinin combination therapies (ACTs), indicates an urgent need for continuous molecular surveillance of drug resistance especially in high burden countries where drug interventions are heavily relied on. This study describes mutations in Plasmodium falciparum genes associated with drug resistance in malaria; Pfk13, Pfmdr1, PfATPase6 and Pfcrt in isolates obtained from 83 symptomatic malaria patients collected in August 2014, aged 1-61 years old from South-west Nigeria. RESULTS: Two Pfmdr1, N86 and Y184 variants were present at a prevalence of 56% and 13.25% of isolates respectively. There was one synonymous (S679S) and two non-synonymous (M699V, S769M) mutations in the PATPase6 gene, while Pfcrt genotype (CVIET), had a prevalence of 45%. The Pfk13 C580Y mutant allele was suspected by allelic discrimination in two samples with mixed genotypes although this could not be validated with independent isolation or additional methods. Our findings call for robust molecular surveillance of antimalarial drug resistance markers in west Africa especially with increased use of antimalarial drugs as prophylaxis for Covid-19.


Assuntos
Combinação Arteméter e Lumefantrina/uso terapêutico , ATPases Transportadoras de Cálcio/genética , Malária Falciparum/tratamento farmacológico , Proteínas de Membrana Transportadoras/genética , Proteínas Associadas à Resistência a Múltiplos Medicamentos/genética , Mutação , Plasmodium falciparum/efeitos dos fármacos , Proteínas de Protozoários/genética , Adolescente , Adulto , Antimaláricos/uso terapêutico , Artemisininas/uso terapêutico , Criança , Pré-Escolar , Infecções por Coronavirus/epidemiologia , Infecções por Coronavirus/prevenção & controle , Resistência a Medicamentos/genética , Feminino , Expressão Gênica , Genótipo , Humanos , Lactente , Malária Falciparum/epidemiologia , Malária Falciparum/parasitologia , Pessoa de Meia-Idade , Epidemiologia Molecular , Nigéria/epidemiologia , Pandemias/prevenção & controle , Plasmodium falciparum/genética , Plasmodium falciparum/crescimento & desenvolvimento , Pneumonia Viral/epidemiologia , Pneumonia Viral/prevenção & controle
4.
Am J Trop Med Hyg ; 103(4): 1681-1690, 2020 10.
Artigo em Inglês | MEDLINE | ID: mdl-32876007

RESUMO

The main objective of this study was to assess the management of childhood infections in high-density poorly planned urban areas of Kampala and Wakiso districts in Uganda, to develop a strategy to deliver integrated community case management (iCCM) of childhood illness services. A total of 72 private healthcare facilities were surveyed (36 drug shops, eight pharmacies, 27 private clinics, and one herbal clinic); supplemented by focus group discussions with village health teams (VHTs), drug shops, and private clinic providers. The majority of drug shops (96.4%, 27/28), pharmacies (100%, 8/8), and (68%, private clinics 17/27) were registered; however, supervision was poor. The majority of patients (> 77%) who visited private health facilities were children aged < 5 years. Furthermore, over 80% (29/64) of the children with uncomplicated malaria were reported to have been given artemether-lumefantrine, and 42% with difficulty breathing were given an antibiotic. Although > 72% providers said they referred children with severe illnesses, taking up referral was complicated by poverty, long distances, and the perception that there were inadequate drugs at referral facilities. Less than 38% of all the facilities had malaria treatment guidelines; < 15% had iCCM guidelines; 6% of the drug shops had iCCM guidelines; and < 13% of the facilities had pneumonia and diarrhea treatment guidelines. Village health teams existed in the study areas, although they had little knowledge on causes and prevention of pneumonia. In conclusion, this study found that quality of care was poor and introduction of iCCM delivered through VHTs, drug shops, and private clinics may, with proper training and support, be a feasible intervention to improve care.


Assuntos
Antimaláricos/uso terapêutico , Combinação Arteméter e Lumefantrina/uso terapêutico , Administração de Caso/normas , Pessoal de Saúde/educação , Malária/tratamento farmacológico , Qualidade da Assistência à Saúde , Criança , Redes Comunitárias , Feminino , Humanos , Masculino , Farmácias , Instalações Privadas , Encaminhamento e Consulta , Uganda
5.
Int J Infect Dis ; 99: 437-440, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32805422

RESUMO

OBJECTIVES: At the end of November 2019, a novel coronavirus responsible for respiratory tract infections (COVID-19) emerged in China. Despite drastic containment measures, this virus, known as severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), spread in Asia and Europe. The pandemic is ongoing with a particular hotspot in Southern Europe and America; many studies predicted a similar epidemic in Africa, as is currently seen in Europe and the United States of America. However, reported data have not confirmed these predictions. One of the hypotheses that could explain the later emergence and spread of COVID-19 pandemic in African countries is the use of antimalarial drugs to treat malaria, and specifically, artemisinin-based combination therapy (ACT). METHODS: The antiviral activity of fixed concentrations of ACT at concentrations consistent with those observed in human plasma when ACT is administered at oral doses for uncomplicated malaria treatment was evaluatedin vitro against a clinically isolated SARS-CoV-2 strain (IHUMI-3) in Vero E6 cells. RESULTS: Mefloquine-artesunate exerted the highest antiviral activity with % inhibition of 72.1 ± 18.3 % at expected maximum blood concentration (Cmax) for each ACT drug at doses commonly administered in malaria treatment. All the other combinations, artesunate-amodiaquine, artemether-lumefantrine, artesunate-pyronaridine, or dihydroartemisinin-piperaquine, showed antiviral inhibition in the same ranges (27.1 to 34.1 %). CONCLUSIONS: Antimalarial drugs for which concentration data in the lungs are available are concentrated from 10 to 160 fold more in the lungs than in blood. Thesein vitro results reinforce the hypothesis that antimalarial drugs could be effective as an anti-COVID-19 treatment.


Assuntos
Amodiaquina/uso terapêutico , Antimaláricos/uso terapêutico , Combinação Arteméter e Lumefantrina/uso terapêutico , Artemisininas/uso terapêutico , Betacoronavirus/efeitos dos fármacos , Infecções por Coronavirus/tratamento farmacológico , Mefloquina/uso terapêutico , Pneumonia Viral/tratamento farmacológico , Replicação Viral/efeitos dos fármacos , Amodiaquina/farmacologia , Animais , Antimaláricos/farmacologia , Combinação Arteméter e Lumefantrina/farmacologia , Artemisininas/farmacologia , Chlorocebus aethiops , Combinação de Medicamentos , Humanos , Malária/epidemiologia , Malária Falciparum/tratamento farmacológico , Mefloquina/farmacologia , Pandemias , Células Vero
6.
Am J Trop Med Hyg ; 103(1): 485-493, 2020 07.
Artigo em Inglês | MEDLINE | ID: mdl-32372751

RESUMO

Tropical splenomegaly is often associated with malaria and schistosomiasis. In 2014 and 2015, 145 Congolese refugees in western Uganda diagnosed with splenomegaly during predeparture medical examinations underwent enhanced screening for various etiologies. After anecdotal reports of unresolved splenomegaly and complications after U.S. arrival, patients were reassessed to describe long-term clinical progression after arrival in the United States. Post-arrival medical information was obtained through medical chart abstraction in collaboration with state health partners in nine participating states. We evaluated observed splenomegaly duration and associated clinical sequelae between 130 case patients from eastern Congo and 102 controls through adjusted hierarchical Poisson models, accounting for familial clustering. Of the 130 case patients, 95 (73.1%) had detectable splenomegaly after arrival. Of the 85 patients with records beyond 6 months, 45 (52.9%) had persistent splenomegaly, with a median persistence of 14.7 months (range 6.0-27.9 months). Of the 112 patients with available results, 65 (58.0%) patients had evidence of malaria infection, and the mean splenomegaly duration did not differ by Plasmodium species. Refugees with splenomegaly on arrival were 43% more likely to have anemia (adjusted relative risk [aRR]: 1.43, 95% CI: 1.04-1.97). Those with persistent splenomegaly were 60% more likely (adjusted relative risk [aRR]: 1.60, 95% CI: 1.15-2.23) to have a hematologic abnormality, particularly thrombocytopenia (aRR: 5.53, 95% CI: 1.73-17.62), and elevated alkaline phosphatase (aRR: 1.57, 95% CI: 1.03-2.40). Many patients experienced persistent splenomegaly, contradicting literature describing resolution after treatment and removal from an endemic setting. Other possible etiologies should be investigated and effective treatment, beyond treatment for malaria and schistosomiasis, explored.


Assuntos
Anemia/epidemiologia , Eosinofilia/epidemiologia , Malária/epidemiologia , Refugiados , Esquistossomose/epidemiologia , Esplenomegalia/epidemiologia , Trombocitopenia/epidemiologia , Adolescente , Adulto , Fosfatase Alcalina/sangue , Anemia/sangue , Anti-Helmínticos/uso terapêutico , Antimaláricos/uso terapêutico , Combinação Arteméter e Lumefantrina/uso terapêutico , Estudos de Casos e Controles , Criança , Pré-Escolar , Estudos de Coortes , República Democrática do Congo/etnologia , Progressão da Doença , Eosinofilia/sangue , Feminino , Hepatite A/epidemiologia , Hepatite B/epidemiologia , Hepatite C/epidemiologia , Humanos , Imunoglobulina M , Lactente , Malária/complicações , Malária/diagnóstico , Malária/tratamento farmacológico , Masculino , Pessoa de Meia-Idade , Reação em Cadeia da Polimerase , Praziquantel/uso terapêutico , Esquistossomose/complicações , Esquistossomose/tratamento farmacológico , Esplenomegalia/sangue , Esplenomegalia/etiologia , Trombocitopenia/sangue , Estados Unidos/epidemiologia , Adulto Jovem
7.
Lancet ; 395(10233): 1361-1373, 2020 04 25.
Artigo em Inglês | MEDLINE | ID: mdl-32334702

RESUMO

BACKGROUND: In low malaria-endemic settings, screening and treatment of individuals in close proximity to index cases, also known as reactive case detection (RACD), is practised for surveillance and response. However, other approaches could be more effective for reducing transmission. We aimed to evaluate the effectiveness of reactive focal mass drug administration (rfMDA) and reactive focal vector control (RAVC) in the low malaria-endemic setting of Zambezi (Namibia). METHODS: We did a cluster-randomised controlled, open-label trial using a two-by-two factorial design of 56 enumeration area clusters in the low malaria-endemic setting of Zambezi (Namibia). We randomly assigned these clusters using restricted randomisation to four groups: RACD only, rfMDA only, RAVC plus RACD, or rfMDA plus RAVC. RACD involved rapid diagnostic testing and treatment with artemether-lumefantrine and single-dose primaquine, rfMDA involved presumptive treatment with artemether-lumefantrine, and RAVC involved indoor residual spraying with pirimiphos-methyl. Interventions were administered within 500 m of index cases. To evaluate the effectiveness of interventions targeting the parasite reservoir in humans (rfMDA vs RACD), in mosquitoes (RAVC vs no RAVC), and in both humans and mosquitoes (rfMDA plus RAVC vs RACD only), an intention-to-treat analysis was done. For each of the three comparisons, the primary outcome was the cumulative incidence of locally acquired malaria cases. This trial is registered with ClinicalTrials.gov, number NCT02610400. FINDINGS: Between Jan 1, 2017, and Dec 31, 2017, 55 enumeration area clusters had 1118 eligible index cases that led to 342 interventions covering 8948 individuals. The cumulative incidence of locally acquired malaria was 30·8 per 1000 person-years (95% CI 12·8-48·7) in the clusters that received rfMDA versus 38·3 per 1000 person-years (23·0-53·6) in the clusters that received RACD; 30·2 per 1000 person-years (15·0-45·5) in the clusters that received RAVC versus 38·9 per 1000 person-years (20·7-57·1) in the clusters that did not receive RAVC; and 25·0 per 1000 person-years (5·2-44·7) in the clusters that received rfMDA plus RAVC versus 41·4 per 1000 person-years (21·5-61·2) in the clusters that received RACD only. After adjusting for imbalances in baseline and implementation factors, the incidence of malaria was lower in clusters receiving rfMDA than in those receiving RACD (adjusted incidence rate ratio 0·52 [95% CI 0·16-0·88], p=0·009), lower in clusters receiving RAVC than in those that did not (0·48 [0·16-0·80], p=0·002), and lower in clusters that received rfMDA plus RAVC than in those receiving RACD only (0·26 [0·10-0·68], p=0·006). No serious adverse events were reported. INTERPRETATION: In a low malaria-endemic setting, rfMDA and RAVC, implemented alone and in combination, reduced malaria transmission and should be considered as alternatives to RACD for elimination of malaria. FUNDING: Novartis Foundation, Bill & Melinda Gates Foundation, and Horchow Family Fund.


Assuntos
Antimaláricos/uso terapêutico , Combinação Arteméter e Lumefantrina/uso terapêutico , Malária Falciparum/prevenção & controle , Administração Massiva de Medicamentos/métodos , Controle de Mosquitos , Antimaláricos/administração & dosagem , Combinação Arteméter e Lumefantrina/administração & dosagem , Análise por Conglomerados , Humanos , Malária Falciparum/epidemiologia , Controle de Mosquitos/métodos , Namíbia/epidemiologia , Plasmodium falciparum , Estudos Soroepidemiológicos
8.
Malar J ; 19(1): 144, 2020 Apr 08.
Artigo em Inglês | MEDLINE | ID: mdl-32268901

RESUMO

BACKGROUND: While there is increasing evidence on the safety of artemisinin-based combination therapy (ACT) for the case management of malaria in early pregnancy, little is known about the association between exposure to ACT during the first trimester and the effect on fetal growth. METHODS: Data were analysed from prospective studies of pregnant women enrolled in Mozambique, Burkina Faso and Kenya designed to determine the association between anti-malarial drug exposure in the first trimester and pregnancy outcomes, including low birth weight (LBW) and small for gestational age (SGA). Exposure to anti-malarial drugs was ascertained retrospectively by record linkage using a combination of data collected from antenatal and adult outpatient clinic registries, prescription records and self-reported medication usage by the women. Site-level data synthesis (fixed effects and random effects) was conducted as well as individual-level analysis (fixed effects by site). RESULTS: Overall, 1915 newborns were included with 92 and 26 exposed to ACT (artemether-lumefantrine) and quinine, respectively. In Burkina Faso, Mozambique and Kenya at recruitment, the mean age (standard deviation) was 27.1 (6.6), 24.2 (6.2) and 25.7 (6.5) years, and the mean gestational age was 24.0 (6.2), 21.2 (5.7) and 17.9 (10.2) weeks, respectively. The LBW prevalence among newborns born to women exposed to ACT and quinine (QNN) during the first trimester was 10/92 (10.9%) and 7/26 (26.9%), respectively, compared to 9.5% (171/1797) among women unexposed to any anti-malarials during pregnancy. Compared to those unexposed to anti-malarials, ACT and QNN exposed women had the pooled LBW prevalence ratio (PR) of 1.13 (95% confidence interval (CI) 0.62-2.05, p-value 0.700) and 2.03 (95% CI 1.09-3.78, p-value 0.027), respectively. Compared to those unexposed to anti-malarials ACT and QNN-exposed women had the pooled SGA PR of 0.85 (95% CI 0.50-1.44, p-value 0.543) and 1.41 (95% CI 0.71-2.77, p-value 0.322), respectively. Whereas compared to ACT-exposed, the QNN-exposed had a PR of 2.14 (95% CI 0.78-5.89, p-value 0.142) for LBW and 8.60 (95% CI 1.29-57.6, p-value 0.027) for SGA. The level of between sites heterogeneity was moderate to high. CONCLUSION: ACT exposure during the first trimester was not associated with an increased occurrence of LBW or SGA. However, the data suggest a higher prevalence of LBW and SGA for children born to QNN-exposed pregnancies. The findings support the use of ACT (artemether-lumefantrine) for the treatment of uncomplicated malaria during the first trimester of pregnancy.


Assuntos
Antimaláricos/uso terapêutico , Combinação Arteméter e Lumefantrina/uso terapêutico , Recém-Nascido de Baixo Peso , Recém-Nascido Pequeno para a Idade Gestacional , Malária/prevenção & controle , Quinina/uso terapêutico , Adulto , Burkina Faso/epidemiologia , Feminino , Humanos , Quênia/epidemiologia , Malária/epidemiologia , Moçambique/epidemiologia , Gravidez , Primeiro Trimestre da Gravidez , Prevalência , Estudos Retrospectivos , Fatores de Risco , Adulto Jovem
9.
Lancet ; 395(10233): 1345-1360, 2020 04 25.
Artigo em Inglês | MEDLINE | ID: mdl-32171078

RESUMO

BACKGROUND: Artemisinin and partner-drug resistance in Plasmodium falciparum are major threats to malaria control and elimination. Triple artemisinin-based combination therapies (TACTs), which combine existing co-formulated ACTs with a second partner drug that is slowly eliminated, might provide effective treatment and delay emergence of antimalarial drug resistance. METHODS: In this multicentre, open-label, randomised trial, we recruited patients with uncomplicated P falciparum malaria at 18 hospitals and health clinics in eight countries. Eligible patients were aged 2-65 years, with acute, uncomplicated P falciparum malaria alone or mixed with non-falciparum species, and a temperature of 37·5°C or higher, or a history of fever in the past 24 h. Patients were randomly assigned (1:1) to one of two treatments using block randomisation, depending on their location: in Thailand, Cambodia, Vietnam, and Myanmar patients were assigned to either dihydroartemisinin-piperaquine or dihydroartemisinin-piperaquine plus mefloquine; at three sites in Cambodia they were assigned to either artesunate-mefloquine or dihydroartemisinin-piperaquine plus mefloquine; and in Laos, Myanmar, Bangladesh, India, and the Democratic Republic of the Congo they were assigned to either artemether-lumefantrine or artemether-lumefantrine plus amodiaquine. All drugs were administered orally and doses varied by drug combination and site. Patients were followed-up weekly for 42 days. The primary endpoint was efficacy, defined by 42-day PCR-corrected adequate clinical and parasitological response. Primary analysis was by intention to treat. A detailed assessment of safety and tolerability of the study drugs was done in all patients randomly assigned to treatment. This study is registered at ClinicalTrials.gov, NCT02453308, and is complete. FINDINGS: Between Aug 7, 2015, and Feb 8, 2018, 1100 patients were given either dihydroartemisinin-piperaquine (183 [17%]), dihydroartemisinin-piperaquine plus mefloquine (269 [24%]), artesunate-mefloquine (73 [7%]), artemether-lumefantrine (289 [26%]), or artemether-lumefantrine plus amodiaquine (286 [26%]). The median age was 23 years (IQR 13 to 34) and 854 (78%) of 1100 patients were male. In Cambodia, Thailand, and Vietnam the 42-day PCR-corrected efficacy after dihydroartemisinin-piperaquine plus mefloquine was 98% (149 of 152; 95% CI 94 to 100) and after dihydroartemisinin-piperaquine was 48% (67 of 141; 95% CI 39 to 56; risk difference 51%, 95% CI 42 to 59; p<0·0001). Efficacy of dihydroartemisinin-piperaquine plus mefloquine in the three sites in Myanmar was 91% (42 of 46; 95% CI 79 to 98) versus 100% (42 of 42; 95% CI 92 to 100) after dihydroartemisinin-piperaquine (risk difference 9%, 95% CI 1 to 17; p=0·12). The 42-day PCR corrected efficacy of dihydroartemisinin-piperaquine plus mefloquine (96% [68 of 71; 95% CI 88 to 99]) was non-inferior to that of artesunate-mefloquine (95% [69 of 73; 95% CI 87 to 99]) in three sites in Cambodia (risk difference 1%; 95% CI -6 to 8; p=1·00). The overall 42-day PCR-corrected efficacy of artemether-lumefantrine plus amodiaquine (98% [281 of 286; 95% CI 97 to 99]) was similar to that of artemether-lumefantrine (97% [279 of 289; 95% CI 94 to 98]; risk difference 2%, 95% CI -1 to 4; p=0·30). Both TACTs were well tolerated, although early vomiting (within 1 h) was more frequent after dihydroartemisinin-piperaquine plus mefloquine (30 [3·8%] of 794) than after dihydroartemisinin-piperaquine (eight [1·5%] of 543; p=0·012). Vomiting after artemether-lumefantrine plus amodiaquine (22 [1·3%] of 1703) and artemether-lumefantrine (11 [0·6%] of 1721) was infrequent. Adding amodiaquine to artemether-lumefantrine extended the electrocardiogram corrected QT interval (mean increase at 52 h compared with baseline of 8·8 ms [SD 18·6] vs 0·9 ms [16·1]; p<0·01) but adding mefloquine to dihydroartemisinin-piperaquine did not (mean increase of 22·1 ms [SD 19·2] for dihydroartemisinin-piperaquine vs 20·8 ms [SD 17·8] for dihydroartemisinin-piperaquine plus mefloquine; p=0·50). INTERPRETATION: Dihydroartemisinin-piperaquine plus mefloquine and artemether-lumefantrine plus amodiaquine TACTs are efficacious, well tolerated, and safe treatments of uncomplicated P falciparum malaria, including in areas with artemisinin and ACT partner-drug resistance. FUNDING: UK Department for International Development, Wellcome Trust, Bill & Melinda Gates Foundation, UK Medical Research Council, and US National Institutes of Health.


Assuntos
Antimaláricos/uso terapêutico , Artemisininas/uso terapêutico , Malária Falciparum/tratamento farmacológico , Adolescente , Adulto , Amodiaquina/administração & dosagem , Amodiaquina/uso terapêutico , Antraquinonas/administração & dosagem , Antraquinonas/uso terapêutico , Antimaláricos/administração & dosagem , Combinação Arteméter e Lumefantrina/administração & dosagem , Combinação Arteméter e Lumefantrina/uso terapêutico , Artemisininas/administração & dosagem , Resistência a Medicamentos , Quimioterapia Combinada , Feminino , Humanos , Masculino , Mefloquina/administração & dosagem , Mefloquina/uso terapêutico , Plasmodium falciparum/efeitos dos fármacos , Reação em Cadeia da Polimerase , Quinolinas/administração & dosagem , Quinolinas/uso terapêutico , Resultado do Tratamento , Adulto Jovem
10.
BMC Med ; 18(1): 47, 2020 02 25.
Artigo em Inglês | MEDLINE | ID: mdl-32098634

RESUMO

BACKGROUND: The majority of Plasmodium falciparum malaria cases in Africa are treated with the artemisinin combination therapies artemether-lumefantrine (AL) and artesunate-amodiaquine (AS-AQ), with amodiaquine being also widely used as part of seasonal malaria chemoprevention programs combined with sulfadoxine-pyrimethamine. While artemisinin derivatives have a short half-life, lumefantrine and amodiaquine may give rise to differing durations of post-treatment prophylaxis, an important additional benefit to patients in higher transmission areas. METHODS: We analyzed individual patient data from 8 clinical trials of AL versus AS-AQ in 12 sites in Africa (n = 4214 individuals). The time to PCR-confirmed reinfection after treatment was used to estimate the duration of post-treatment protection, accounting for variation in transmission intensity between settings using hidden semi-Markov models. Accelerated failure-time models were used to identify potential effects of covariates on the time to reinfection. The estimated duration of chemoprophylaxis was then used in a mathematical model of malaria transmission to determine the potential public health impact of each drug when used for first-line treatment. RESULTS: We estimated a mean duration of post-treatment protection of 13.0 days (95% CI 10.7-15.7) for AL and 15.2 days (95% CI 12.8-18.4) for AS-AQ overall. However, the duration varied significantly between trial sites, from 8.7-18.6 days for AL and 10.2-18.7 days for AS-AQ. Significant predictors of time to reinfection in multivariable models were transmission intensity, age, drug, and parasite genotype. Where wild type pfmdr1 and pfcrt parasite genotypes predominated (<=20% 86Y and 76T mutants, respectively), AS-AQ provided ~ 2-fold longer protection than AL. Conversely, at a higher prevalence of 86Y and 76T mutant parasites (> 80%), AL provided up to 1.5-fold longer protection than AS-AQ. Our simulations found that these differences in the duration of protection could alter population-level clinical incidence of malaria by up to 14% in under-5-year-old children when the drugs were used as first-line treatments in areas with high, seasonal transmission. CONCLUSION: Choosing a first-line treatment which provides optimal post-treatment prophylaxis given the local prevalence of resistance-associated markers could make a significant contribution to reducing malaria morbidity.


Assuntos
Amodiaquina/uso terapêutico , Antimaláricos/uso terapêutico , Combinação Arteméter e Lumefantrina/uso terapêutico , Artemisininas/uso terapêutico , Malária Falciparum/tratamento farmacológico , Plasmodium falciparum/patogenicidade , Amodiaquina/farmacologia , Antimaláricos/farmacologia , Combinação Arteméter e Lumefantrina/farmacologia , Artemisininas/farmacologia , Pré-Escolar , Combinação de Medicamentos , Feminino , Humanos , Lactente , Masculino
11.
Malar J ; 19(1): 66, 2020 Feb 11.
Artigo em Inglês | MEDLINE | ID: mdl-32046718

RESUMO

BACKGROUND: Day 7 plasma lumefantrine concentration is suggested as a predictor for malaria treatment outcomes and a cut-off of ≥ 200 ng/ml is associated with day 28 cure rate in the general population. However, day 7 lumefantrine plasma concentration can be affected by age, the extent of fever, baseline parasitaemia, and bodyweight. Therefore, this study assessed the usefulness of day 7 lumefantrine plasma concentration as a predictor of malaria treatment outcome in under-fives children treated with generic or innovator drug-containing artemether-lumefantrine (ALu) in Tanzania. METHODS: This study was nested in an equivalence prospective study that aimed at determining the effectiveness of a generic ALu (Artefan®) in comparison with the innovator's product (Coartem®). Children with uncomplicated malaria aged 6-59 months were recruited and randomized to receive either generic or innovator's product. Children were treated with ALu as per World Health Organization recommendations. The clinical and parasitological outcomes were assessed after 28 days of follow up. PCR was performed to distinguish recrudescence and re-infections among children with recurrent malaria. Analysis of day 7 lumefantrine plasma concentration was carried out using a high-performance liquid chromatographic method with UV detection. RESULTS: The PCR corrected cure rates were 98.7% for children treated with generic and 98.6% for those treated with the innovator product (p = 1.00). The geometric mean (± SD) of day 7 plasma lumefantrine concentration was 159.3 (± 2.4) ng/ml for the generic and 164 (± 2.5) ng/ml for the innovator groups, p = 0.87. Geometric mean (± SD) day 7 lumefantrine plasma concentration between cured and recurrent malaria was not statistically different in both treatment arms [158.5 (± 2.4) vs 100.0 (± 1.5) ng/ml, (p = 0.28) for generic arm and 158.5 (± 2.3) vs 251.2 (± 4.2) ng/ml, (p = 0.24) for innovator arm]. Nutritional status was found to be a determinant of recurrent malaria (adjusted hazardous ratio (95% confidence interval) = 3(1.1-8.2), p = 0.029. CONCLUSION: Using the recommended cut-off point of ≥ 200 ng/ml, day 7 plasma lumefantrine concentration failed to predict malaria treatment outcome in children treated with ALu in Tanzania. Further studies are recommended to establish the day 7 plasma lumefantrine concentration cut-off point to predict malaria treatment outcome in children.


Assuntos
Antimaláricos/uso terapêutico , Combinação Arteméter e Lumefantrina/uso terapêutico , Lumefantrina/sangue , Malária/tratamento farmacológico , Fatores Etários , Peso Corporal , Pré-Escolar , Feminino , Hemoglobinas/análise , Humanos , Lactente , Modelos Lineares , Malária/sangue , Malária/epidemiologia , Masculino , Estado Nutricional , Parasitemia/parasitologia , Reação em Cadeia da Polimerase , Recidiva , Fatores Sexuais , Tanzânia/epidemiologia , Resultado do Tratamento
12.
Am J Trop Med Hyg ; 102(5): 1056-1063, 2020 05.
Artigo em Inglês | MEDLINE | ID: mdl-32100686

RESUMO

Artemether-lumefantrine (AL) is the first-line treatment for uncomplicated Plasmodium falciparum infection in Colombia. To assess AL efficacy for uncomplicated falciparum malaria in Quibdo, Choco, Colombia, we conducted a 28-day therapeutic efficacy study (TES) following the WHO guidelines. From July 2018 to February 2019, febrile patients aged 5-65 years with microscopy-confirmed P. falciparum mono-infection and asexual parasite density of 250-100,000 parasites/µL were enrolled and treated with a supervised 3-day course of AL. The primary endpoint was adequate clinical and parasitological response (ACPR) on day 28. We attempted to use polymerase chain reaction (PCR) genotyping to differentiate reinfection and recrudescence, and conducted genetic testing for antimalarial resistance-associated genes. Eighty-eight patients consented and were enrolled; four were lost to follow-up or missed treatment doses. Therefore, 84 (95.5%) participants reached a valid endpoint: treatment failure or ACPR. No patient remained microscopy positive for malaria on day 3, evidence of delayed parasite clearance and artemisinin resistance. One patient had recurrent infection (12 parasites/µL) on day 28. Uncorrected ACPR rate was 98.8% (83/84) (95% CI: 93.5-100%). The recurrent infection sample did not amplify during molecular testing, giving a PCR-corrected ACPR of 100% (83/83) (95% CI: 95.7-100%). No P. falciparum kelch 13 polymorphisms associated with artemisinin resistance were identified. Our results support high AL efficacy for falciparum malaria in Choco. Because of the time required to conduct TESs in low-endemic settings, it is important to consider complementary alternatives to monitor antimalarial efficacy and resistance.


Assuntos
Antimaláricos/uso terapêutico , Combinação Arteméter e Lumefantrina/uso terapêutico , Malária Falciparum/tratamento farmacológico , Adolescente , Adulto , Fatores Etários , Idoso , Antimaláricos/administração & dosagem , Combinação Arteméter e Lumefantrina/administração & dosagem , Criança , Pré-Escolar , Colômbia , Resistência a Medicamentos/genética , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Plasmodium falciparum/efeitos dos fármacos , Plasmodium falciparum/genética , Polimorfismo de Nucleotídeo Único/genética , Resultado do Tratamento , Adulto Jovem
13.
Malar J ; 19(1): 8, 2020 Jan 06.
Artigo em Inglês | MEDLINE | ID: mdl-31906948

RESUMO

BACKGROUND: Artemisinin-based combination therapy (ACT) is recommended to improve malaria treatment efficacy and limit drug-resistant parasites selection in malaria endemic areas. 5 years after they were adopted, the efficacy and safety of artemether-lumefantrine (AL) and artesunate-amodiaquine (ASAQ), the first-line treatments for uncomplicated malaria were assessed in Burkina Faso. METHODS: In total, 440 children with uncomplicated Plasmodium falciparum malaria were randomized to receive either AL or ASAQ for 3 days and were followed up weekly for 42 days. Blood samples were collected to investigate the ex vivo susceptibility of P. falciparum isolates to lumefantrine, dihydroartemisinin (the active metabolite of artemisinin derivatives) and monodesethylamodiaquine (the active metabolite of amodiaquine). The modified isotopic micro test technique was used to determine the 50% inhibitory concentration (IC50) values. Primary endpoints were the risks of treatment failure at days 42. RESULTS: Out of the 440 patients enrolled, 420 (95.5%) completed the 42 days follow up. The results showed a significantly higher PCR unadjusted cure rate in ASAQ arm (71.0%) than that in the AL arm (49.8%) on day 42, and this trend was similar after correction by PCR, with ASAQ performing better (98.1%) than AL (91.1%). Overall adverse events incidence was low and not significantly different between the two treatment arms. Ex vivo results showed that 6.4% P. falciparum isolates were resistant to monodesthylamodiaquine. The coupled in vivo/ex vivo analysis showed increased IC50 values for lumefantrine and monodesethylamodiaquine at day of recurrent parasitaemia compared to baseline values while for artesunate, IC50 values remained stable at baseline and after treatment failure (p > 0.05). CONCLUSION: These findings provide substantial evidence that AL and ASAQ are highly efficacious for the treatment of uncomplicated malaria in children in Burkina Faso. However, the result of P. falciparum susceptibility to the partner drugs advocates the need to regularly replicate such surveillance studies. This would be particularly indicated when amodiaquine is associated in seasonal malaria chemoprophylaxis (SMC) mass drug administration in children under 5 years in Burkina Faso. Trial registration clinicaltrials, NCT00808951. Registered 05 December 2008,https://clinicaltrials.gov/ct2/show/NCT00808951?cond=NCT00808951&rank=1.


Assuntos
Amodiaquina/uso terapêutico , Combinação Arteméter e Lumefantrina/uso terapêutico , Artemisininas/uso terapêutico , Quimioterapia Combinada/métodos , Malária Falciparum/tratamento farmacológico , Adolescente , Amodiaquina/administração & dosagem , Amodiaquina/análogos & derivados , Antimaláricos/uso terapêutico , Combinação Arteméter e Lumefantrina/administração & dosagem , Artemisininas/administração & dosagem , Artesunato/uso terapêutico , Burkina Faso , Criança , Pré-Escolar , Combinação de Medicamentos , Feminino , Humanos , Lactente , Concentração Inibidora 50 , Lumefantrina/uso terapêutico , Masculino , Administração Massiva de Medicamentos , Plasmodium falciparum/efeitos dos fármacos , Plasmodium falciparum/isolamento & purificação , Falha de Tratamento , Resultado do Tratamento
14.
Malar J ; 19(1): 40, 2020 Jan 22.
Artigo em Inglês | MEDLINE | ID: mdl-31969155

RESUMO

BACKGROUND: The Sustainable Development Goals (SDG) call for increased gender equity and reduction in malaria-related mortality and morbidity. Plasmodium vivax infections in pregnancy are associated with maternal anaemia and increased adverse perinatal outcomes. Providing radical cure for women with 8-aminoquinolines (e.g., primaquine) is hindered by gender-specific complexities. CASE PRESENTATION: A symptomatic episode of vivax malaria at 18 weeks of gestation in a primigravid woman was associated with maternal anaemia, a recurrent asymptomatic P. vivax episode, severe intra-uterine growth restriction with no other identifiable cause and induction to reduce the risk of stillbirth. At 5 months postpartum a qualitative glucose-6-phosphate dehydrogenase (G6PD) point-of-care test was normal and radical cure with primaquine was prescribed to the mother. A 33% fractional decrease in haematocrit on day 7 of primaquine led to further testing which showed intermediate phenotypic G6PD activity; the G6PD genotype could not be identified. Her infant daughter was well throughout maternal treatment and found to be heterozygous for Mahidol variant. CONCLUSION: Adverse effects of vivax malaria in pregnancy, ineligibility of radical cure for pregnant and postpartum women, and difficulties in diagnosing intermediate levels of G6PD activity multiplied morbidity in this woman. Steps towards meeting the SDG include prevention of malaria in pregnancy, reducing unnecessary exclusion of women from radical cure, and accessible quantitative G6PD screening in P. vivax-endemic settings.


Assuntos
Equidade em Saúde/estatística & dados numéricos , Malária Vivax/epidemiologia , Complicações Parasitárias na Gravidez/epidemiologia , Adolescente , Aminoquinolinas/uso terapêutico , Anemia/tratamento farmacológico , Anemia/etiologia , Antimaláricos/uso terapêutico , Combinação Arteméter e Lumefantrina/uso terapêutico , Feminino , Retardo do Crescimento Fetal/etiologia , Retardo do Crescimento Fetal/terapia , Deficiência de Glucosefosfato Desidrogenase/diagnóstico , Humanos , Recém-Nascido Pequeno para a Idade Gestacional , Transtornos da Lactação/etiologia , Transtornos da Lactação/parasitologia , Malária Vivax/tratamento farmacológico , Malária Vivax/mortalidade , Gravidez , Complicações Parasitárias na Gravidez/tratamento farmacológico , Complicações Parasitárias na Gravidez/mortalidade , Resultado da Gravidez , Primaquina/uso terapêutico
15.
J Infect Dis ; 221(6): 948-955, 2020 03 02.
Artigo em Inglês | MEDLINE | ID: mdl-30852586

RESUMO

BACKGROUND: Plasmodium malariae is considered a minor malaria parasite, although its global disease burden is underappreciated. The aim of this study was to develop an induced blood-stage malaria (IBSM) model of P. malariae to study parasite biology, diagnostic assays, and treatment. METHODS: This clinical trial involved 2 healthy subjects who were intravenously inoculated with cryopreserved P. malariae-infected erythrocytes. Subjects were treated with artemether-lumefantrine after development of clinical symptoms. Prior to antimalarial therapy, mosquito-feeding assays were performed to investigate transmission, and blood samples were collected for rapid diagnostic testing and parasite transcription profiling. Serial blood samples were collected for biomarker analysis. RESULTS: Both subjects experienced symptoms and signs typical of early malaria. Parasitemia was detected 7 days after inoculation, and parasite concentrations increased until antimalarial treatment was initiated 25 and 21 days after inoculation for subjects 1 and 2 respectively (peak parasitemia levels, 174 182 and 50 291 parasites/mL, respectively). The parasite clearance half-life following artemether-lumefantrine treatment was 6.7 hours. Mosquito transmission was observed for 1 subject, while in vivo parasite transcription and biomarkers were successfully profiled. CONCLUSIONS: An IBSM model of P. malariae has been successfully developed and may be used to study the biology of, diagnostic testing for, and treatment of this neglected malaria species. CLINICAL TRIALS REGISTRATION: ACTRN12617000048381.


Assuntos
Antimaláricos/uso terapêutico , Combinação Arteméter e Lumefantrina/uso terapêutico , Malária/sangue , Malária/parasitologia , Plasmodium malariae/genética , Adolescente , Animais , Anopheles/parasitologia , Comportamento Alimentar , Humanos , Malária/patologia , Masculino , Parasitemia/sangue , Parasitemia/tratamento farmacológico , Parasitemia/parasitologia , Plasmodium malariae/fisiologia , Transcriptoma , Adulto Jovem
16.
Am J Trop Med Hyg ; 102(3): 598-604, 2020 03.
Artigo em Inglês | MEDLINE | ID: mdl-31833468

RESUMO

The emergence of artemisinin-resistant Plasmodium falciparum in the Greater Mekong Subregion threatens both the efficacy of artemisinin-based combination therapy (ACT), the first-line treatment for malaria, and prospects for malaria elimination. Monitoring of ACT efficacy is essential for ensuring timely updates to elimination policies and treatment recommendations. In 2014-2015, we assessed the therapeutic efficacies of artemether-lumefantrine (AL) and dihydroartemisinin-piperaquine (DP) for the treatment of uncomplicated P. falciparum at three study sites in Rakhine, Shan, and Kachin states in Myanmar. Patients presenting with uncomplicated P. falciparum malaria were enrolled, treated, and followed up for 28 days for AL or 42 days for DP. Both AL and DP demonstrated good therapeutic efficacy at all three study sites. The 28-day cure rate for AL was > 96% across all study sites, and the 42-day cure rate for DP was 100%. Parasitemia on day 3 was detected in 0%, 3.3%, and 3.6% of participants treated with AL at the Rakhine, Shan, and Kachin sites, respectively. No participants treated with DP were parasitemic on day 3. No evidence of P. falciparum k13 mutations was found at the Rakhine study site. A high prevalence of k13 mutations associated with artemisinin resistance was observed at the Kachin and Shan state study sites. These results confirm that ACT efficacy has been resilient in therapeutic efficacy study (TES) sentinel sites in Myanmar, despite the presence at some sites of k13 mutations associated with resistance. Studies are ongoing to assess whether this resilience persists.


Assuntos
Combinação Arteméter e Lumefantrina/uso terapêutico , Artemisininas/uso terapêutico , Malária Falciparum/tratamento farmacológico , Plasmodium falciparum/efeitos dos fármacos , Quinolinas/uso terapêutico , Adolescente , Adulto , Antimaláricos/administração & dosagem , Antimaláricos/uso terapêutico , Artemisininas/administração & dosagem , Criança , Combinação de Medicamentos , Feminino , Genótipo , Humanos , Malária Falciparum/epidemiologia , Masculino , Pessoa de Meia-Idade , Mianmar/epidemiologia , Plasmodium falciparum/genética , Quinolinas/administração & dosagem , Adulto Jovem
17.
Ann Parasitol ; 66(4): 561-571, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33789028

RESUMO

The purpose of this study was to update efficacy data of Artesunate-Amodiaquine (AS+AQ) and Artemether-Lumefantrine (AL) used as first-line malaria treatment in Côte d'Ivoire since 2005. This was an open-label, randomized trial conducted in patients older than 6 months with uncomplicated P. falciparum malaria at six sentinel sites. The WHO 2009 protocol on surveillance of anti-malaria drug efficacy was used with primary outcomes as ACPR corrected by PCR at day 42. Secondary endpoints were parasite and fever clearance times and safety. From January to July 2016, 712 patients were included in the trial. 353 and 359 patients were randomly assigned respectively to the AS+AQ and AL arm. Day 42 PCR-adjusted ACPR in the per-protocol analysis was 99.4% and 98.8% in AS+AQ and AL arm respectively. Delayed parasite clearance was observed in six patients at Abidjan and Yamousssoukro sites. Both ACTs were well tolerated. Both ACTs remain efficacious for uncomplicated P. falciparum malaria treatment in Côte d'Ivoire. But regarding delayed parasite clearance observed in this study, a close monitoring and supervision for ACT resistance are essential for future malaria treatment and control strategies in Côte d'Ivoire.


Assuntos
Antimaláricos , Artemisininas , Malária Falciparum , Malária , Amodiaquina/uso terapêutico , Antimaláricos/uso terapêutico , Artemeter/uso terapêutico , Combinação Arteméter e Lumefantrina/uso terapêutico , Artemisininas/uso terapêutico , Costa do Marfim/epidemiologia , Combinação de Medicamentos , Etanolaminas/uso terapêutico , Fluorenos/uso terapêutico , Humanos , Lactente , Malária/tratamento farmacológico , Malária/epidemiologia , Malária Falciparum/tratamento farmacológico , Malária Falciparum/epidemiologia , Resultado do Tratamento
18.
S Afr Med J ; 111(1): 13-16, 2020 11 23.
Artigo em Inglês | MEDLINE | ID: mdl-33403998

RESUMO

As September marks the start of the malaria season in South Africa (SA), it is essential that healthcare professionals consider both COVID- 19 and malaria when a patient who lives in or has recently travelled to a malaria area presents with acute febrile illness. Early diagnosis of malaria by either a rapid diagnostic test or microscopy enables prompt treatment with the effective antimalarial, artemether-lumefantrine, preventing progression to severe disease and death. Intravenous artesunate is the preferred treatment for severe malaria in both children and adults. Adding single low-dose primaquine to standard treatment is recommended in endemic areas to block onward transmission. Use of the highly effective artemisinin-based therapies should be limited to the treatment of confirmed malaria infections, as there is no clinical evidence that these antimalarials can prevent or treat COVID-19. Routine malaria case management services must be sustained, in spite of COVID-19, to treat malaria effectively and support SA's malaria elimination efforts.


Assuntos
Antimaláricos/uso terapêutico , Malária/diagnóstico , Malária/tratamento farmacológico , Administração Intravenosa , Antígenos de Protozoários/sangue , Combinação Arteméter e Lumefantrina/uso terapêutico , Artesunato/uso terapêutico , Diagnóstico Precoce , Intervenção Médica Precoce , Humanos , Malária/transmissão , Malária Falciparum/diagnóstico , Malária Falciparum/tratamento farmacológico , Malária Falciparum/transmissão , Microscopia , Testes Imediatos , Primaquina/uso terapêutico , Proteínas de Protozoários/sangue , Índice de Gravidade de Doença , África do Sul
19.
Malar J ; 18(1): 424, 2019 Dec 16.
Artigo em Inglês | MEDLINE | ID: mdl-31842893

RESUMO

BACKGROUND: Malaria remains a major public health problem, affecting mainly low-and middle-income countries. The management of this parasitic disease is challenged by ever increasing drug resistance. This study, investigated the therapeutic efficacy, tolerability and safety of artemether-lumefantrine (AL) and artesunate-amodiaquine (AS-AQ), used as first-line drugs to treat uncomplicated malaria in Lambaréné, Gabon. METHODS: A non-randomized clinical trial was conducted between October 2017 and March 2018 to assess safety, clinical and parasitological efficacy of fixed-doses of AL and AS-AQ administered to treat uncomplicated Plasmodium falciparum malaria in children aged from 6 months to 12 years. After 50 children were treated with AL, another 50 children received ASAQ. The 2009 World Health Organization protocol for monitoring of the efficacy of anti­malarial drugs was followed. Molecular markers msp1 and msp2 were used to differentiate recrudescence and reinfection. For the investigation of artemisinin resistant markers, gene mutations in Pfk13 were screened. RESULTS: Per-protocol analysis on day 28 showed a PCR corrected cure rate of 97% (95% CI 86-100) and 95% (95% CI 84-99) for AL and AS-AQ, respectively. The most frequent adverse event in both groups was asthenia. No mutations in the kelch-13 gene associated with artemisinin resistance were identified. All participants had completed microscopic parasite clearance by day 3 post-treatment. CONCLUSION: This study showed that AL and AS-AQ remain efficacious, well-tolerated, and are safe to treat uncomplicated malaria in children from Lambaréné. However, a regular monitoring of efficacy and a study of molecular markers of drug resistance to artemisinin in field isolates is essential. Trial registration ANZCTR, ACTRN12616001600437. Registered 18 November, http://www.anzctr.org.au/TrialSearch.aspx?searchTxt=ACTRN12616001600437p&isBasic=True.


Assuntos
Amodiaquina/uso terapêutico , Antimaláricos/uso terapêutico , Combinação Arteméter e Lumefantrina/uso terapêutico , Artemisininas/uso terapêutico , Monitoramento de Medicamentos/estatística & dados numéricos , Malária Falciparum/tratamento farmacológico , Criança , Pré-Escolar , Combinação de Medicamentos , Feminino , Gabão , Humanos , Lactente , Masculino , Plasmodium falciparum/efeitos dos fármacos , Plasmodium falciparum/isolamento & purificação , Proteínas de Protozoários/genética
20.
Malar J ; 18(1): 398, 2019 Dec 04.
Artigo em Inglês | MEDLINE | ID: mdl-31801562

RESUMO

BACKGROUND: The efficacy and safety of artemether-lumefantrine (AL) and dihydroartemisinin-piperaquine (DP) against asexual parasites population has been documented. However, the effect of these anti-malarials on sexual parasites is still less clear. Gametocyte clearance following treatment is essential for malaria control and elimination efforts; therefore, the study sought to determine trends in gametocyte clearance after AL or DP treatment in children from a malaria-endemic site in Kenya. METHODS: Children aged between 0.5 and 12 years from Busia, western Kenya with uncomplicated Plasmodium falciparum malaria were assigned randomly to AL or DP treatment. A total of 334 children were enrolled, and dried blood spot samples were collected for up to 6 weeks after treatment during the peak malaria transmission season in 2016 and preserved. Plasmodium falciparum gametocytes were detected by qRT-PCR and gametocyte prevalence, density and mean duration of gametocyte carriage were determined. RESULTS: At baseline, all the 334 children had positive asexual parasites by microscopy, 12% (40/334) had detectable gametocyte by microscopy, and 83.7% (253/302) children had gametocytes by RT-qPCR. Gametocyte prevalence by RT-qPCR decreased from 85.1% (126/148) at day 0 to 7.04% (5/71) at day 42 in AL group and from 82.4% (127/154) at day 0 to 14.5% (11/74) at day 42 in DP group. The average duration of gametocyte carriage as estimated by qRT-PCR was slightly shorter in the AL group (4.5 days) than in the DP group (5.1 days) but not significantly different (p = 0.301). CONCLUSION: The study identifies no significant difference between AL and DP in gametocyte clearance. Gametocytes persisted up to 42 days post treatment in minority of individuals in both treatment arms. A gametocytocidal drug, in combination with artemisinin-based combination therapy, will be useful in blocking malaria transmission more efficiently.


Assuntos
Antimaláricos/uso terapêutico , Combinação Arteméter e Lumefantrina/uso terapêutico , Artemisininas/uso terapêutico , Malária Falciparum/prevenção & controle , Plasmodium falciparum/efeitos dos fármacos , Quinolinas/uso terapêutico , Criança , Pré-Escolar , Feminino , Humanos , Lactente , Quênia/epidemiologia , Malária Falciparum/epidemiologia , Masculino , Prevalência
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