RESUMO
OBJECTIVES: New point-of-care (POC) quantitative G6PD testing devices developed to provide safe radical cure for Plasmodium vivax malaria may be used to diagnose G6PD deficiency in newborns at risk of severe neonatal hyperbilirubinaemia, improving clinical care, and preventing related morbidity and mortality. METHODS: We conducted a mixed-methods study analysing technical performance and usability of the 'STANDARD G6PD' Biosensor when used by trained midwives on cord blood samples at two rural clinics on the Thailand-Myanmar border. RESULTS: In 307 cord blood samples, the Biosensor had a sensitivity of 1.000 (95% CI: 0.859 to 1.000) and a specificity of 0.993 (95% CI: 0.971 to 0.999) as compared with gold-standard spectrophotometry to diagnose G6PD-deficient newborns using a receiver operating characteristic (ROC) analysis-derived threshold of ≤4.8 IU/gHb. The Biosensor had a sensitivity of 0.727 (95% CI: 0.498 to 0.893) and specificity of 0.933 (95% CI: 0.876 to 0.969) for 30%-70% activity range in girls using ROC analysis-derived range of 4.9-9.9 IU/gHb. These thresholds allowed identification of all G6PD-deficient neonates and 80% of female neonates with intermediate phenotypes.Need of phototherapy treatment for neonatal hyperbilirubinaemia was higher in neonates with deficient and intermediate phenotypes as diagnosed by either reference spectrophotometry or Biosensor.Focus group discussions found high levels of learnability, willingness, satisfaction and suitability for the Biosensor in this setting. The staff valued the capacity of the Biosensor to identify newborns with G6PD deficiency early ('We can know that early, we can counsel the parents about the chances of their children getting jaundice') and at the POC, including in more rural settings ('Because we can know the right result of the G6PD deficiency in a short time, especially for the clinic which does not have a lab'). CONCLUSIONS: The Biosensor is a suitable tool in this resource-constrained setting to identify newborns with abnormal G6PD phenotypes at increased risk of neonatal hyperbilirubinaemia.
Assuntos
Deficiência de Glucosefosfato Desidrogenase , Hiperbilirrubinemia Neonatal , Malária Vivax , Oxibato de Sódio , Humanos , Recém-Nascido , Feminino , Deficiência de Glucosefosfato Desidrogenase/diagnóstico , Sangue Fetal , Oxibato de Sódio/uso terapêutico , Malária Vivax/tratamento farmacológicoRESUMO
Introduction: Malaria infection is still a public health problem in Indonesia. One of the problems in combating malaria in Indonesia is the limited kind of antimalarial drugs provided by the government. Sambiloto (Andrographis paniculata) extract has been shown to have antimalarial activity in human clinical trials. Aim: To assess the ability of a single A. paniculata ethanolic extract capsule to treat malaria in humans caused by Plasmodium falciparum or P. vivax alone or mixed infections of both. Methods: An open clinical trial was conducted in Batubara District, Sumatra Utara Province, Indonesia, a malaria-endemic area. Sixty-nine malaria patients found in the field were diagnosed microscopically as malaria vivax, malaria falciparum, and mixed infections uncomplicated malaria with 12 years old and above. Previously all patients signed informed consent. All patients have been treated with A. paniculata ethanolic extract capsules 250 mg thrice a day for five days. Parasite density was calculated from D0, D1, D2, D3, D7, D14, and D28. Results: The efficacy of A . paniculata ethanolic extract capsules 250 mg thrice a day for five days against malaria vivax, malaria falciparum, and mixed malaria patients was 94.2%. There are no side effects were found during treatment. Conclusion: A. paniculata ethanolic extract can be used as an alternative antimalarial candidate derived from native Indonesian medicinal plants or as an adjunct in standard treatment for malaria.
Assuntos
Antimaláricos , Coinfecção , Malária Falciparum , Malária Vivax , Malária , Humanos , Criança , Antimaláricos/uso terapêutico , Indonésia , Andrographis paniculata , Coinfecção/induzido quimicamente , Coinfecção/tratamento farmacológico , Malária/tratamento farmacológico , Malária/induzido quimicamente , Malária/parasitologia , Malária Falciparum/tratamento farmacológico , Malária Falciparum/induzido quimicamente , Malária Falciparum/parasitologia , Malária Vivax/induzido quimicamente , Malária Vivax/tratamento farmacológico , Malária Vivax/parasitologia , Extratos Vegetais/uso terapêuticoRESUMO
BACKGROUND: Reduced artemisinin susceptibility and artemisinin-based combination therapy (ACT)-resistance against Plasmodium falciparum and chloroquine (CQ)-resistant P. vivax malaria has been reported in Vietnam. Two therapeutic efficacy studies were conducted in Thuan Bac District (Ninh Thuan Province, Vietnam) in 2015 and 2016 to determine the extent of reduced artemisinin susceptibility and ACT resistant falciparum malaria, and CQ-resistant vivax malaria were present. METHODS: Twenty-seven patients with falciparum malaria were randomized to receive artesunate alone (AS ~ 4 mg/kg/day) for 4 days followed by dihydroartemisinin (DHA) (2.2 mg/kg)-piperaquine (PPQ) (18 mg/kg) daily for 3 days or artemether (AM) (1.7 mg/kg)-lumefantrine (LUM) (12 mg/kg) twice daily for 3 days. Sixteen subjects with vivax malaria received CQ (total 25 mg/kg over 3 days). The therapeutic efficacy study for treating falciparum malaria was complemented with molecular analysis for artemisinin and piperaquine resistance, and in vitro drug susceptibility testing. Patient's drug exposure following both falciparum and vivax treatment studies was determined. RESULTS: Twenty-five of 27 patients treated with the artemisinin regimens completed the 42-day follow-up period. None had parasites present on day 3 after commencing treatment with no incidence of recrudescence (100% curative rate). One patient on AS + DHA-PPQ was lost to follow-up and one patient had Plasmodium falciparum and Plasmodium vivax infection on day 0 by PCR. Of the vivax patients, 15 of 16 completed CQ treatment and two had a recurrence of vivax malaria on day 28, a failure rate of 13.3% (2/15). No mutations in the Pfkelch-13 gene for artemisinin resistance or exo-E415G gene polymorphism and amplification in plasmepsins 2 and 3 for piperaquine resistance were observed. In vitro testing of patient's falciparum parasites indicated susceptibility (low IC50 nM values) to dihydroartemisinin, lumefantrine, piperaquine and pyronaridine. Patient's drug exposure to artesunate and lumefantrine was comparable to published data, however, blood CQ concentrations were lower. CONCLUSIONS: Clinical findings, molecular analysis and in vitro testing revealed that the falciparum parasites at Phuoc Chien Commune were artemisinin susceptible. The clinical failure rate of the 15 vivax patients who completed CQ treatment was 13%. Further studies are required to determine whether CQ-resistant vivax malaria is present at the commune.
Assuntos
Antimaláricos/uso terapêutico , Cloroquina/uso terapêutico , Malária Falciparum/tratamento farmacológico , Malária Vivax/tratamento farmacológico , Plasmodium falciparum/efeitos dos fármacos , Plasmodium vivax/efeitos dos fármacos , Adolescente , Adulto , Idoso , Antimaláricos/farmacologia , Criança , Pré-Escolar , Cloroquina/farmacologia , Resistência a Múltiplos Medicamentos/genética , Etanolaminas/farmacologia , Etanolaminas/uso terapêutico , Feminino , Fluorenos/farmacologia , Fluorenos/uso terapêutico , Humanos , Masculino , Testes de Sensibilidade Microbiana , Pessoa de Meia-Idade , Quinolinas/farmacologia , Quinolinas/uso terapêutico , Reação em Cadeia da Polimerase em Tempo Real , Vietnã/epidemiologia , Adulto JovemRESUMO
Primaquine is the only drug available to prevent relapse in vivax malaria. The main adverse effect of primaquine is erythrocyte age and dose-dependent acute haemolytic anaemia in individuals with glucose-6-phosphate dehydrogenase deficiency (G6PDd). As testing for G6PDd is often unavailable, this limits the use of primaquine for radical cure. A compartmental model of the dynamics of red blood cell production and destruction was designed to characterise primaquine-induced haemolysis using a holistic Bayesian analysis of all published data and was used to predict a safer alternative to the currently recommended once weekly 0.75 mg/kg regimen for G6PDd. The model suggests that a step-wise increase in daily administered primaquine dose would be relatively safe in G6PDd. If this is confirmed, then were this regimen to be recommended for radical cure patients would not require testing for G6PDd in areas where G6PDd Viangchan or milder variants are prevalent.
Assuntos
Anemia Hemolítica/prevenção & controle , Antimaláricos/efeitos adversos , Deficiência de Glucosefosfato Desidrogenase/tratamento farmacológico , Malária Vivax/tratamento farmacológico , Modelos Estatísticos , Primaquina/efeitos adversos , Anemia Hemolítica/induzido quimicamente , Anemia Hemolítica/diagnóstico , Antimaláricos/administração & dosagem , Teorema de Bayes , Morte Celular/efeitos dos fármacos , Eritrócitos/efeitos dos fármacos , Feminino , Deficiência de Glucosefosfato Desidrogenase/complicações , Deficiência de Glucosefosfato Desidrogenase/parasitologia , Deficiência de Glucosefosfato Desidrogenase/patologia , Hemólise/efeitos dos fármacos , Humanos , Malária Vivax/complicações , Malária Vivax/parasitologia , Malária Vivax/patologia , Masculino , Plasmodium vivax/efeitos dos fármacos , Plasmodium vivax/crescimento & desenvolvimento , Primaquina/administração & dosagem , RecidivaRESUMO
There is an urgent need to make drug discovery cheaper and faster. This will enable the development of treatments for diseases currently neglected for economic reasons, such as tropical and orphan diseases, and generally increase the supply of new drugs. Here, we report the Robot Scientist 'Eve' designed to make drug discovery more economical. A Robot Scientist is a laboratory automation system that uses artificial intelligence (AI) techniques to discover scientific knowledge through cycles of experimentation. Eve integrates and automates library-screening, hit-confirmation, and lead generation through cycles of quantitative structure activity relationship learning and testing. Using econometric modelling we demonstrate that the use of AI to select compounds economically outperforms standard drug screening. For further efficiency Eve uses a standardized form of assay to compute Boolean functions of compound properties. These assays can be quickly and cheaply engineered using synthetic biology, enabling more targets to be assayed for a given budget. Eve has repositioned several drugs against specific targets in parasites that cause tropical diseases. One validated discovery is that the anti-cancer compound TNP-470 is a potent inhibitor of dihydrofolate reductase from the malaria-causing parasite Plasmodium vivax.
Assuntos
Desenho de Fármacos , Reposicionamento de Medicamentos , Doenças Raras/tratamento farmacológico , Tecnologia Farmacêutica/tendências , Algoritmos , Antineoplásicos/uso terapêutico , Automação , Avaliação Pré-Clínica de Medicamentos , Humanos , Malária Vivax/tratamento farmacológico , Modelos Estatísticos , Plasmodium vivax/efeitos dos fármacos , Relação Quantitativa Estrutura-Atividade , Análise de Regressão , Reprodutibilidade dos Testes , Software , Medicina TropicalRESUMO
There remains a need for new drugs to prevent relapse of Plasmodium vivax or P. ovale infection. The relapsing primate malaria P. cynomolgi has been used for decades to assess drugs for anti-hypnozoite activity. After sporozoite inoculation and blood-stage cure of initial parasitemia with chloroquine, rhesus macaques were treated on subsequent relapses with chloroquine in conjunction with test regimens of approved drugs. Tested drugs were selected for known liver or blood-stage activity and were tested alone or in conjunction with low-dose primaquine. Tinidazole and pyrazinamide prevented relapse when used in conjunction with chloroquine and low-dose primaquine. Triamterene and tinidazole administered without primaquine achieved radical cure in some animals. All other tested drugs or combinations failed to prevent relapse. The rhesus macaque-P. cynomolgi model remains a useful tool for screening drugs with anti-hypnozoite activity. Tinidazole and pyrazinamide require further investigation as agents to enable dose reduction of primaquine.
Assuntos
Antimaláricos/uso terapêutico , Macaca mulatta/parasitologia , Malária Vivax/tratamento farmacológico , Plasmodium cynomolgi/efeitos dos fármacos , Plasmodium cynomolgi/patogenicidade , Animais , Cloroquina/uso terapêutico , Modelos Animais de Doenças , Avaliação Pré-Clínica de Medicamentos , Malária Vivax/prevenção & controle , Parasitemia/prevenção & controle , Plasmodium vivax/crescimento & desenvolvimento , Plasmodium vivax/patogenicidade , Primaquina/uso terapêutico , Pirazinamida/uso terapêutico , Prevenção Secundária , Esporozoítos/efeitos dos fármacos , Tinidazol/uso terapêutico , Triantereno/uso terapêuticoAssuntos
Malária Vivax/diagnóstico , Auditoria Médica , Militares , Campanha Afegã de 2001- , Afeganistão , Animais , Antimaláricos/uso terapêutico , Celulite (Flegmão)/complicações , Celulite (Flegmão)/diagnóstico , Cloroquina/uso terapêutico , Diagnóstico Diferencial , Humanos , Malária Vivax/complicações , Malária Vivax/tratamento farmacológico , Masculino , Entorpecentes/efeitos adversos , Ópio/efeitos adversos , Sepse/diagnóstico , Sepse/tratamento farmacológico , Sepse/etiologia , Síndrome de Abstinência a Substâncias/diagnóstico , Inquéritos e Questionários , Reino Unido , Adulto JovemRESUMO
A regular implementation of prophylactic and therapeutic decision trees was organized on a consensus basis in Cayenne, French Guiana in 1990, 1995 and 2002. The updated recommendations were based on the knowledge of the in vitro chemosensitivity profiles of the local isolates, mainly coming from big rivers (Maroni and Oyapock, frontiers with Suriname and Brazil, respectively; and more recently Approuague). Most of the patients infected by Plasmodium falciparum were followed by the medical staff of the main hospitals (Cayenne and Saint-Laurent) and of the peripheral health centers in remote areas. Consequently the epidemiological situation and evolution of chemoresistance have been widely observed on a long-term (since 1994) basis in the Maroni region. Yet, we have only partial information coming from the Oyapock valley, even though an important (most of the time) illegal immigration has been developing since the 90s' leading to a notable modification of the epidemiological status of malaria in this eastern region, including a regular increase of P. vivax infections. Presently very little P. vivax chloroquine (and mefloquine) resistance has been identified but this result could lead to a real public health problem in a near future. As such, the National Reference Center on Plasmodium Chemoresistance in the French West Indies and Guiana (CNRCP-AG in French) is a unique observatory of malaria chemoresistance in the Guyanese shield which works with research laboratories of the Institut Pasteur, Paris. This network strategy offers a very attractive perspective for applications of modern tools, including the validation of chemoresistance molecular markers, for malaria control at both medical and public health levels. Some examples related to chloroquine and artemether resistance are given.
Assuntos
Antimaláricos/farmacologia , Resistência a Medicamentos , Malária Falciparum/epidemiologia , Malária Vivax/epidemiologia , Plasmodium falciparum/efeitos dos fármacos , Plasmodium vivax/efeitos dos fármacos , Sistema de Registros , Animais , Antimaláricos/uso terapêutico , Surtos de Doenças , Resistência a Medicamentos/genética , Resistência a Múltiplos Medicamentos/genética , Doenças Endêmicas , França , Guiana Francesa/epidemiologia , Guiana/epidemiologia , Humanos , Centros de Informação/organização & administração , Cooperação Internacional , Malária Falciparum/tratamento farmacológico , Malária Falciparum/parasitologia , Malária Vivax/tratamento farmacológico , Malária Vivax/parasitologia , Fitoterapia , Plasmodium falciparum/genética , Plasmodium vivax/genética , Saúde Pública , Suriname/epidemiologiaRESUMO
INTRODUCTION: Malaria, anemia and intestinal parasitism can co-exist in certain populations of Colombian children. The effects of retinol supplementation and anti-intestinal parasite treatment in children with malaria is unknown. Changes after this treatment of with respect to hemoglobin, retinol, ferritin and C reactive protein levels have not been previously monitored. OBJECTIVE: The effect of simultaneous intervention with antimalarial, retinol supplementation and anti-intestinal parasites treatment will be monitored by examining levels of hemoglobin, ferritin, retinol and C reactive protein in children with malaria. MATERIALS AND METHODS: A non-blind experimental study was conducted in 93 children with malaria, aged 4-10 years. Each was randomly allocated to one of the following groups: (1) treatment with antimalarial and retinol supplement (Group MA); (2) treatment with antimalarialretinol supplement and anti-parasitic drug (Group MAP); (3) treatment with antimalarial and antiparasitic drug (Group MP), and (4) treatment only with antimalarials (Group M). The groups were observed for 30 days, with haemoglobin, ferritin, retinol and C reactive protein evaluated on days 0, 8 and 30 after treatment. RESULTS: Mean values for the children at day 0 were as follows: hemoglobin 10.3 +/- 1.6 g/dL, retinol 19.1 +/- 6.0 microg/dL, C reactive protein 75 +/- 63 mg/L and ferritin 213 +/- 203 microg/L. On day 30 after treatment, hemoglobin and plasma retinol concentrations increased in 1.4 +/- 1.4 g/dL and 11.5 +/- 8.1 microg/dL, whereas the C reactive protein and ferritin concentrations decreased to 66 +/- 60 mg/L, and 184 +/- 203 microg/L, respectively. No statistically significant differences appeared among the groups. On day 8, significant differences between the groups were observed in hemoglobin concentrations Group MAP was higher when compared to other groups. CONCLUSION: On day 30, hemoglobin and retinol were high, whereas C reactive protein was low. Simultaneous administration of a retinol supplement and anti-parasite treatment prevented hemoglobin reduction observed on day 8 without changes in other variables.
Assuntos
Albendazol/uso terapêutico , Antimaláricos/uso terapêutico , Ferritinas/sangue , Hemoglobinas/análise , Malária Falciparum/sangue , Malária Falciparum/tratamento farmacológico , Malária Vivax/sangue , Malária Vivax/tratamento farmacológico , Vitamina A/sangue , Vitamina A/uso terapêutico , Albendazol/administração & dosagem , Anemia/epidemiologia , Anemia/etiologia , Anemia/prevenção & controle , Antimaláricos/administração & dosagem , Proteína C-Reativa , Criança , Pré-Escolar , Colômbia/epidemiologia , Comorbidade , Quimioterapia Combinada , Feminino , Hemorragia Gastrointestinal/complicações , Hemorragia Gastrointestinal/parasitologia , Humanos , Inflamação/sangue , Inflamação/epidemiologia , Enteropatias Parasitárias/complicações , Enteropatias Parasitárias/tratamento farmacológico , Enteropatias Parasitárias/epidemiologia , Malária Falciparum/epidemiologia , Malária Vivax/epidemiologia , Masculino , Contagem de Ovos de Parasitas , Deficiência de Vitamina A/tratamento farmacológico , Deficiência de Vitamina A/epidemiologiaRESUMO
Preclinical animal models informing antimalarial drug development are scarce. We have used asexual erythrocytic Plasmodium cynomolgi infections of rhesus macaques to model Plasmodium vivax during preclinical development of compounds targeting parasite phospholipid synthesis. Using this malaria model, we accumulated data confirming highly reproducible infection patterns, with self-curing parasite peaks reproducibly preceding recrudescence peaks. We applied nonlinear mixed-effect (NLME) models, estimating treatment effects in three drug studies: G25 (injected) and the bisthiazolium prodrugs TE4gt and TE3 (oral). All compounds fully cured P. cynomolgi-infected macaques, with significant effects on parasitemia height and time of peak. Although all three TE3 doses tested were fully curative, NLME models discriminated dose-dependent differential pharmacological antimalarial activity. By applying NLME modeling treatment effects are readily quantified. Such drug development studies are more informative and contribute to reduction and refinement in animal experimentation.
Assuntos
Antimaláricos/uso terapêutico , Malária Vivax/tratamento farmacológico , Plasmodium cynomolgi , Administração Oral , Animais , Relação Dose-Resposta a Droga , Avaliação Pré-Clínica de Medicamentos , Feminino , Injeções Intramusculares , Macaca mulatta , Malária Vivax/parasitologia , Masculino , Modelos Estatísticos , Pró-Fármacos/uso terapêutico , Pirrolidinas/uso terapêuticoRESUMO
Chloroquine (CQ) is an effective treatment of choice for vivax malaria in most settings, but with the spread of CQ-resistant Plasmodium falciparum, many countries now use artemisinin-based combination therapy for treatment of falciparum malaria. In areas co-endemic for falciparum and vivax malaria incorrect differential diagnosis is always a risk. In Afghanistan the adoption of sulfadoxine-pyrimethamine plus artesunate (SP+AS) as first-line falciparum treatment raises the prospect of a significant proportion of vivax malaria being misdiagnosed and treated with the combination. SP is considered to have limited efficacy against vivax malaria, and the efficacy of SP+AS against Plasmodium vivax has not been established in areas that are using SP+AS. A randomised, non-inferiority trial comparing SP+AS with CQ monotherapy was undertaken on 190 vivax malaria patients in eastern Afghanistan. Standard WHO procedures for in vivo evaluation of antimalarial drugs were followed. A total of 180 individuals completed the trial to day 42. Using a per protocol analysis, both regimens resulted in > or =96% treatment success at 28 d, but significantly more cases failed in the CQ arm (46%) than in the SP+AS arm (24%) by day 42. In areas where vivax infections might be misdiagnosed as falciparum infections and treated with SP+AS, patient management would be as good, or better than, with the standard CQ treatment.
Assuntos
Antimaláricos/uso terapêutico , Artemisininas/uso terapêutico , Cloroquina/uso terapêutico , Malária Falciparum/tratamento farmacológico , Malária Vivax/tratamento farmacológico , Pirimetamina/uso terapêutico , Sesquiterpenos/uso terapêutico , Sulfadoxina/uso terapêutico , Adolescente , Afeganistão/epidemiologia , Artesunato , Criança , Combinação de Medicamentos , Resistência a Medicamentos , Quimioterapia Combinada , Doenças Endêmicas , Humanos , Malária Falciparum/epidemiologia , Malária Vivax/epidemiologia , Resultado do TratamentoRESUMO
BACKGROUND: The burden of Plasmodium vivax infections has been underappreciated, especially in southeast Asia where chloroquine resistant strains have emerged. Our aim was to compare the safety and efficacy of dihydroartemisinin-piperaquine with that of artemether-lumefantrine in patients with uncomplicated malaria caused by multidrug-resistant P falciparum and P vivax. METHODS: 774 patients in southern Papua, Indonesia, with slide-confirmed malaria were randomly assigned to receive either artemether-lumefantrine or dihydroartemisinin-piperaquine and followed up for at least 42 days. The primary endpoint was the overall cumulative risk of parasitological failure at day 42 with a modified intention-to-treat analysis. This trial is registered with ClinicalTrials.gov, trial number 00157833. FINDINGS: Of the 754 evaluable patients enrolled, 466 had infections with P falciparum, 175 with P vivax, and 113 with a mixture of both species. The overall risk of failure at day 42 was 43% (95% CI 38-48) for artemether-lumefantrine and 19% (14-23) for dihydroartemisinin-piperaquine (hazard ratio=3.0, 95% CI 2.2-4.1, p<0.0001). After correcting for reinfections, the risk of recrudescence of P falciparum was 4.4% (2.6-6.2) with no difference between regimens. Recurrence of vivax occurred in 38% (33-44) of patients given artemether-lumefantrine compared with 10% (6.9-14.0) given dihydroartemisinin-piperaquine (p<0.0001). At the end of the study, patients receiving dihydroartemisinin-piperaquine were 2.0 times (1.2-3.6) less likely to be anaemic and 6.6 times (2.8-16) less likely to carry vivax gametocytes than were those given artemether-lumefantrine. INTERPRETATION: Both dihydroartemisinin-piperaquine and artemether-lumefantrine were safe and effective for the treatment of multidrug-resistant uncomplicated malaria. However, dihydroartemisinin-piperaquine provided greater post-treatment prophylaxis than did artemether-lumefantrine, reducing P falciparum reinfections and P vivax recurrences, the clinical public-health importance of which should not be ignored.
Assuntos
Antimaláricos/administração & dosagem , Artemisininas/administração & dosagem , Artemisininas/uso terapêutico , Etanolaminas/uso terapêutico , Fluorenos/uso terapêutico , Malária Falciparum/tratamento farmacológico , Malária Vivax/tratamento farmacológico , Quinolinas/administração & dosagem , Sesquiterpenos/administração & dosagem , Adolescente , Adulto , Anemia/etiologia , Antimaláricos/efeitos adversos , Combinação Arteméter e Lumefantrina , Artemisininas/efeitos adversos , Criança , Pré-Escolar , Diarreia/induzido quimicamente , Esquema de Medicação , Combinação de Medicamentos , Resistência a Múltiplos Medicamentos/efeitos dos fármacos , Feminino , Humanos , Indonésia , Lactente , Malária Falciparum/complicações , Malária Vivax/complicações , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Quinolinas/efeitos adversos , Recidiva , Sesquiterpenos/efeitos adversos , Resultado do Tratamento , Urticária/induzido quimicamente , Vômito/induzido quimicamenteRESUMO
The standard adult treatment regimen for Plasmodium vivax malaria is chloroquine (1500 mg over 3 d) plus primaquine (15 or 30 mg daily for 14 d), but patient compliance tends to be poor with the lengthy course. Preliminary observations are reported on the efficacy of a shorter treatment course - artesunate (200mg twice a day for 2 d) plus primaquine (22.5mg base twice a day for 7 d) - given to 28 adult patients infected with P. vivax in Viet Nam. All patients responded quickly to treatment with mean (SD) parasite and fever clearance times of 14.2 (4.0) and 18.6 (8.4) h, respectively. The high dose of primaquine was generally well tolerated, and only one patient (3.6%) had a recurrence of parasitaemia during 28 d of follow-up. As most patients infected with Southeast Asian strains of P. vivax have their first relapse within 28 d after treatment with rapidly eliminated blood schizonticides, the absence of parasitaemia in the remaining 27 patients suggests that this drug regimen was active against both blood and liver stages. Further studies are needed to confirm that this rapidly acting, short artesunate-primaquine regimen can result in better patient compliance and treatment outcomes than the chloroquine-primaquine regimen.
Assuntos
Antimaláricos/uso terapêutico , Artemisininas/uso terapêutico , Malária Vivax/tratamento farmacológico , Primaquina/uso terapêutico , Sesquiterpenos/uso terapêutico , Administração Oral , Adolescente , Adulto , Animais , Antimaláricos/administração & dosagem , Artemisininas/administração & dosagem , Artesunato , Quimioterapia Combinada , Feminino , Humanos , Malária Vivax/sangue , Masculino , Primaquina/administração & dosagem , Prevenção Secundária , Sesquiterpenos/administração & dosagemRESUMO
OBJECTIVES: To compare the efficacy and tolerability of dihydroartemisinin-piperaquine (DHA-PQP) with that of a 3-day regimen of mefloquine and artesunate (MAS3) for the treatment of uncomplicated falciparum malaria in Cambodia. METHOD: Randomized open-label non-inferiority study over 64 days. RESULTS: Four hundred and sixty-four patients were included in the study. The polymerase chain reaction genotyping-adjusted cure rates on day 63 were 97.5% (95% confidence interval, CI, 93.8-99.3) for DHA-PQP and 97.5% (95% CI, 93.8-99.3) for MAS3, P = 1. There were no serious adverse events, but significantly more episodes of vomiting (P = 0.03), dizziness (P = 0.002), palpitations (P = 0.04), and sleep disorders (P = 0.03) reported in the MAS3 treatment group, consistent with the side-effect profile of mefloquine. CONCLUSIONS: DHA-PQP was as efficacious as MAS3, but much better tolerated, making it more appropriate for use in a routine programme setting. This highly efficacious, safe and more affordable fixed-dose combination could become the treatment of choice for Plasmodium falciparum malaria in Cambodia.
Assuntos
Antimaláricos/uso terapêutico , Artemisininas/uso terapêutico , Malária Falciparum/tratamento farmacológico , Quinolinas/uso terapêutico , Sesquiterpenos/uso terapêutico , Adolescente , Adulto , Idoso , Anemia/complicações , Anemia/epidemiologia , Antimaláricos/efeitos adversos , Artemisininas/efeitos adversos , Artesunato , Camboja/epidemiologia , Criança , Pré-Escolar , Quimioterapia Combinada , Feminino , Genoma de Protozoário , Humanos , Lactente , Malária Falciparum/epidemiologia , Malária Falciparum/parasitologia , Malária Vivax/tratamento farmacológico , Malária Vivax/epidemiologia , Malária Vivax/parasitologia , Masculino , Mefloquina/uso terapêutico , Pessoa de Meia-Idade , Quinolinas/efeitos adversos , Recidiva , Sesquiterpenos/efeitos adversos , Resultado do TratamentoRESUMO
Liver function tests were performed in 61 vivax, 54 malariae and 15 ovale malaria patients who were admitted to Bangkok Hospital for Tropical Diseases between 2001 and 2004. The objective of the study was to evaluate changes in hepatic biochemical indices before and after treatment with artemisinin derivatives. On admission and prior to treatment, hepatic dysfunction was found among the 3 groups. Serum liver function tests and physical examinations were performed weekly during the 28-day follow-up period. Initially elevated serum bilirubin and diminished albumin returned to normal within 2 weeks of treatment. Serum alkaline phosphatase and aminotransferases returned to within normal limits within 3 weeks. We conclude that patients with Plasmodium vivax, P. malariae and P. ovale infections had slightly elevated serum bilirubin, aminotransferase and alkaline phosphatase levels, and hypoalbuminemia. These minor abnormalities returned to normal within a few weeks after treatment with therapies based on artemisinin derivatives.
Assuntos
Artemisininas/uso terapêutico , Fígado/fisiopatologia , Malária/tratamento farmacológico , Plasmodium malariae/efeitos dos fármacos , Plasmodium ovale/efeitos dos fármacos , Plasmodium vivax/efeitos dos fármacos , Sesquiterpenos/uso terapêutico , Adolescente , Adulto , Alanina Transaminase/sangue , Animais , Anti-Infecciosos/uso terapêutico , Bilirrubina/sangue , Feminino , Humanos , Testes de Função Hepática , Malária/parasitologia , Malária/fisiopatologia , Malária Vivax/tratamento farmacológico , Malária Vivax/parasitologia , Malária Vivax/fisiopatologia , Masculino , Pessoa de Meia-Idade , Plasmodium malariae/patogenicidade , Plasmodium ovale/patogenicidade , Plasmodium vivax/patogenicidade , Albumina Sérica , Resultado do TratamentoRESUMO
BACKGROUND: Delivering drugs in a fixed combination is essential to the success of the strategy of artemisinin-based combination therapy. This prevents one drug being taken without the protection of the other, reducing the chance of emergence and spread of drug resistant strains of Plasmodium falciparum. A lower tablet burden should also facilitate adherence to treatment. A new fixed combination of mefloquine plus artesunate has been developed. This was compared with the conventional regimen of separate tablets for the treatment of uncomplicated multidrug-resistant falciparum malaria. METHODS: On the north-western border of Thailand 500 adults and children with uncomplicated falciparum malaria were randomized to receive either the new fixed combination or separate tablets. They were followed up weekly for 63 days. RESULTS: The day 63 polymerase chain reaction-adjusted cure rates were 91.9% (95% CI 88.2-95.6) in the fixed combination group and 89.2% (85.0-93.4) in the loose tablets group (P=0.3). There was a lower incidence of early vomiting in the group receiving the fixed combination. CONCLUSION: This new fixed combination of mefloquine and artesunate was efficacious, well tolerated and convenient to administer.
Assuntos
Antimaláricos/administração & dosagem , Artemisininas/administração & dosagem , Resistência a Múltiplos Medicamentos , Malária Falciparum/tratamento farmacológico , Mefloquina/administração & dosagem , Sesquiterpenos/administração & dosagem , Adolescente , Adulto , Idoso , Antimaláricos/efeitos adversos , Artemisininas/efeitos adversos , Artesunato , Criança , Pré-Escolar , Combinação de Medicamentos , Quimioterapia Combinada , Feminino , Humanos , Lactente , Malária Falciparum/epidemiologia , Malária Vivax/tratamento farmacológico , Malária Vivax/epidemiologia , Masculino , Mefloquina/efeitos adversos , Pessoa de Meia-Idade , Controle de Qualidade , Sesquiterpenos/efeitos adversos , Comprimidos , Tailândia/epidemiologia , Resultado do TratamentoRESUMO
BACKGROUND: Early diagnosis and treatment with artesunate-mefloquine combination therapy (MAS) have reduced the transmission of falciparum malaria dramatically and halted the progression of mefloquine resistance in camps for displaced persons along the Thai-Burmese border, an area of low and seasonal transmission of multidrug-resistant Plasmodium falciparum. We extended the same combination drug strategy to all other communities (estimated population 450,000) living in five border districts of Tak province in northwestern Thailand. METHODS AND FINDINGS: Existing health structures were reinforced. Village volunteers were trained to use rapid diagnostic tests and to treat positive cases with MAS. Cases of malaria, hospitalizations, and malaria-related deaths were recorded in the 6 y before, during, and after the Tak Malaria Initiative (TMI) intervention. Cross-sectional surveys were conducted before and during the TMI period. P. falciparum malaria cases fell by 34% (95% confidence interval [CI], 33.5-34.4) and hospitalisations for falciparum malaria fell by 39% (95% CI, 37.0-39.9) during the TMI period, while hospitalisations for P. vivax malaria remained constant. There were 32 deaths attributed to malaria during, and 22 after the TMI, a 51.5% (95% CI, 39.0-63.9) reduction compared to the average of the previous 3 y. Cross-sectional surveys indicated that P. vivax had become the predominant species in Thai villages, but not in populations living on the Myanmar side of the border. In the displaced persons population, where the original deployment took place 7 y before the TMI, the transmission of P. falciparum continued to be suppressed, the incidence of falciparum malaria remained low, and the in vivo efficacy of the 3-d MAS remained high. CONCLUSIONS: In the remote malarious north western border area of Thailand, the early detection of malaria by trained village volunteers, using rapid diagnostic tests and treatment with mefloquine-artesunate was feasible and reduced the morbidity and mortality of multidrug-resistant P. falciparum.
Assuntos
Antimaláricos/uso terapêutico , Artemisininas/uso terapêutico , Malária Falciparum/diagnóstico , Malária Falciparum/tratamento farmacológico , Mefloquina/uso terapêutico , Complicações Parasitárias na Gravidez/tratamento farmacológico , Sesquiterpenos/uso terapêutico , Adulto , Idoso , Artesunato , Estudos Transversais , Quimioterapia Combinada , Diagnóstico Precoce , Feminino , Mortalidade Hospitalar , Hospitalização , Humanos , Incidência , Malária Falciparum/epidemiologia , Malária Falciparum/prevenção & controle , Malária Vivax/diagnóstico , Malária Vivax/tratamento farmacológico , Masculino , Pessoa de Meia-Idade , Programas Nacionais de Saúde , Testes de Sensibilidade Parasitária , Gravidez , Complicações Parasitárias na Gravidez/diagnóstico , Prevalência , Refugiados , Tailândia/epidemiologia , Clima TropicalRESUMO
Households in eleven geographically and ethnically distinct areas in Loreto, Peru, were interviewed about their knowledge and use of plants, for the treatment of malaria and leishmaniasis. The survey resulted in 988 use records representing 118 plant-taxa for malaria and 289 use-records representing 85 plant-taxa for leishmaniasis. In both cases the 10 most frequently reported taxa accounted for about half of all the use-records. Plant material was collected and extracts were screened for in vitro inhibition of Plasmodium and Leishmania parasites. In the case of Plasmodium, extracts of 11 of the 13 most frequently reported plants showed significant growth inhibitory activity, while only a few plant extracts inhibited the growth of Leishmania parasites.
Assuntos
Antimaláricos/farmacologia , Fitoterapia , Extratos Vegetais/farmacologia , Plantas Medicinais , Plasmodium vivax/efeitos dos fármacos , Animais , Antimaláricos/administração & dosagem , Antimaláricos/uso terapêutico , Antiprotozoários/administração & dosagem , Antiprotozoários/farmacologia , Antiprotozoários/uso terapêutico , Humanos , Leishmania/efeitos dos fármacos , Leishmaniose/tratamento farmacológico , Leucócitos Mononucleares/efeitos dos fármacos , Malária Vivax/tratamento farmacológico , Medicina Tradicional , Testes de Sensibilidade Parasitária , Peru , Extratos Vegetais/administração & dosagem , Extratos Vegetais/uso terapêuticoRESUMO
Liver function tests were performed in 61 vivax, 54 malariae and 15 ovale malaria patients who were admitted to Bangkok Hospital for Tropical Diseases between 2001 and 2004. The objective of the study was to evaluate changes in hepatic biochemical indices before and after treatment with artemisinin derivatives. On admission and prior to treatment, hepatic dysfunction was found among the 3 groups. Serum liver function tests and physical examinations were performed weekly during the 28-day follow-up period. Initially elevated serum bilirubin and diminished albumin returned to normal within 2 weeks of treatment. Serum alkaline phosphatase and aminotransferases returned to within normal limits within 3 weeks. We conclude that patients with Plasmodium vivax, P. malariae and P. ovale infections had slightly elevated serum bilirubin, aminotransferase and alkaline phosphatase levels, and hypoalbuminemia. These minor abnormalities returned to normal within a few weeks after treatment with therapies based on artemisinin derivatives.
Assuntos
Pessoa de Meia-Idade , Masculino , Humanos , Feminino , Animais , Adulto , Adolescente , Resultado do Tratamento , Sesquiterpenos/uso terapêutico , Albumina Sérica , Plasmodium vivax/efeitos dos fármacos , Plasmodium ovale/efeitos dos fármacos , Plasmodium malariae/efeitos dos fármacos , Malária Vivax/tratamento farmacológico , Malária/tratamento farmacológico , Testes de Função Hepática , Fígado/fisiopatologia , Bilirrubina/sangue , Artemisininas/uso terapêutico , Anti-Infecciosos/uso terapêutico , Alanina Transaminase/sangueRESUMO
The gametocidal activities of chloroquine and artesunate were compared. The relative risk (RR) of having detectable gametocytes appear after treatment initiation was lower in artesunate-treated patients (n = 792) than in chloroquine-treated patients (n = 695) (RR = 0.29; 95% CI = 0.2 to 0.40; P < 0.0001). The duration and magnitude of gametocyte carriage were also lower for artesunate than chloroquine. By reducing the transmission of Plasmodium vivax to the vector, artesunate could therefore reduce the incidence of P. vivax malaria.