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1.
Cochrane Database Syst Rev ; 8: CD012656, 2020 08 19.
Artigo em Inglês | MEDLINE | ID: mdl-32816320

RESUMO

BACKGROUND: Plasmodium vivax liver stages (hypnozoites) may cause relapses, prolonging morbidity, and impeding malaria control and elimination. The World Health Organization (WHO) recommends three schedules for primaquine: 0.25 mg/kg/day (standard), or 0.5 mg/kg/day (high standard) for 14 days, or 0.75 mg/kg once weekly for eight weeks, all of which can be difficult to complete. Since primaquine can cause haemolysis in individuals with glucose-6-phosphate dehydrogenase (G6PD) deficiency, clinicians may be reluctant to prescribe primaquine without G6PD testing, and recommendations when G6PD status is unknown must be based on an assessment of the risks and benefits of prescribing primaquine. Alternative safe and efficacious regimens are needed. OBJECTIVES: To assess the efficacy and safety of alternative primaquine regimens for radical cure of P vivax malaria compared to the standard or high-standard 14-day courses. SEARCH METHODS: We searched the Cochrane Infectious Diseases Group Specialized Register; the Cochrane Central Register of Controlled Trials (CENTRAL); MEDLINE (PubMed); Embase (Ovid); LILACS (BIREME); WHO International Clinical Trials Registry Platform and ClinicalTrials.gov up to 2 September 2019, and checked the reference lists of all identified studies. SELECTION CRITERIA: Randomized controlled trials (RCTs) of adults and children with P vivax malaria using either chloroquine or artemisinin-based combination therapy plus primaquine at a total adult dose of at least 210 mg, compared with the WHO-recommended regimens of 0.25 or 0.5 mg/kg/day for 14 days. DATA COLLECTION AND ANALYSIS: Two review authors independently assessed trial eligibility and quality, and extracted data. We calculated risk ratios (RRs) with 95% confidence intervals (CIs) for dichotomous data. We grouped efficacy data according to length of follow-up, partner drug, and trial location. We analysed safety data where included. MAIN RESULTS: 0.5 mg/kg/day for seven days versus standard 0.25 mg/kg/day for 14 days There may be little or no difference in P vivax recurrences at six to seven months when using the same total dose (210 mg adult dose) over seven days compared to 14 days (RR 0.96, 95% CI 0.66 to 1.39; 4 RCTs, 1211 participants; low-certainty evidence). No serious adverse events were reported. We do not know if there is any difference in the number of adverse events resulting in discontinuation of primaquine (RR 1.04, 95% CI 0.15 to 7.38; 5 RCTs, 1427 participants) or in the frequency of anaemia (RR 3.00, 95% CI 0.12 to 72.91, 1 RCT, 240 participants) between the shorter and longer regimens (very low-certainty evidence). Three trials excluded people with G6PD deficiency; two did not provide this information. Pregnant and lactating women were either excluded or no details were provided. High-standard 0.5 mg/kg/day for 14 days versus standard 0.25 mg/kg/day for 14 days There may be little or no difference in P vivax recurrences at six months with 0.5 mg/kg/day primaquine for 14 days compared to 0.25 mg/kg/day for 14 days (RR 0.84 (95% CI 0.49 to 1.43; 2 RCTs, 677 participants, low-certainty evidence). No serious adverse events were reported. We do not know whether there is a difference in adverse events resulting in discontinuation of treatment with the high-standard dosage (RR 4.19, 95% CI 0.90 to 19.60; 1 RCT, 778 participants, very low-certainty evidence). People with G6PD deficiency and pregnant or lactating women were excluded. 0.75 mg/kg/week for eight weeks versus high-standard 0.5 mg/kg/day for 14 days We do not know whether weekly primaquine increases or decreases recurrences of P vivax compared to high-standard 0.5 mg/kg/day for 14 days, at 11 months' follow-up (RR 3.18, 95% CI 0.37 to 27.60; 1 RCT, 122 participants; very low-certainty evidence). No serious adverse events and no episodes of anaemia were reported. G6PD-deficient patients were not randomized but included in the weekly primaquine group (only one patient detected). 1 mg/kg/day for seven days versus high standard 0.5 mg/kg/day for 14 days There is probably little or no difference in P vivax recurrences at 12 months between 1.0 mg/kg/day primaquine for seven days and the high-standard 0.5 mg/kg/day for 14 days (RR 1.03, 95% CI 0.82 to 1.30; 2 RCTs, 2526 participants; moderate-certainty evidence). There may be moderate to large increase in serious adverse events in the 1.0 mg/kg/day primaquine for seven days compared with the high-standard 0.5 mg/kg/day for 14 days, during 42 days follow-up (RR 12.03, 95% CI 1.57 to 92.30; 1 RCT, 1872 participants, low-certainty evidence). We do not know if there is a difference between 1.0 mg/kg/day primaquine for seven days and high-standard 0.5 mg/kg/day for 14 days in adverse events that resulted in discontinuation of treatment (RR 2.50, 95% CI 0.49 to 12.87; 1 RCT, 2526 participants, very low-certainty evidence), nor if there is difference in frequency of anaemia by 42 days (RR 0.93, 95% CI 0.62 to 1.41; 2 RCTs, 2440 participants, very low-certainty evidence). People with G6PD deficiency were excluded. Other regimens Two RCTs evaluated other rarely-used doses of primaquine, one of which had very high loss to follow-up. Adverse events were not reported. People with G6PD deficiency and pregnant or lactating women were excluded. AUTHORS' CONCLUSIONS: Trials available to date do not detect a difference in recurrence between the following regimens: 1) 0.5 mg/kg/day for seven days versus standard 0.25 mg/kg/day for 14 days; 2) high-standard 0.5 mg/kg/day for 14 days versus standard 0.25 mg/kg/day for 14 days; 3) 0.75 mg/kg/week for eight weeks versus high-standard 0.5 mg/kg/day for 14 days; 4) 1 mg/kg/day for seven days versus high-standard 0.5 mg/kg/day for 14 days. There were no differences detected in adverse events for Comparisons 1, 2 or 3, but there may be more serious adverse events with the high seven-day course in Comparison 4. The shorter regimen of 0.5 mg/kg/day for seven days versus standard 0.25 mg/kg/day for 14 days may suit G6PD-normal patients. Further research will help increase the certainty of the findings and applicability in different settings.


Assuntos
Antimaláricos/uso terapêutico , Malária Vivax/tratamento farmacológico , Primaquina/uso terapêutico , Adulto , Antimaláricos/administração & dosagem , Antimaláricos/efeitos adversos , Criança , Esquema de Medicação , Glucosefosfato Desidrogenase , Humanos , Malária Vivax/enzimologia , Primaquina/administração & dosagem , Primaquina/efeitos adversos , Ensaios Clínicos Controlados Aleatórios como Assunto , Recidiva , Prevenção Secundária
2.
PLoS Negl Trop Dis ; 14(7): e0008526, 2020 07.
Artigo em Inglês | MEDLINE | ID: mdl-32735631

RESUMO

Each year, 4.3 million pregnant women are exposed to malaria risk in Latin America and the Caribbean. Plasmodium vivax causes 76% of the regional malaria burden and appears to be less affected than P. falciparum by current elimination efforts. This is in part due to the parasite's ability to stay dormant in the liver and originate relapses within months after a single mosquito inoculation. Primaquine (PQ) is routinely combined with chloroquine (CQ) or other schizontocidal drugs to supress P. vivax relapses and reduce the risk of late blood-stage recrudescences of parasites with low-grade CQ resistance. However, PQ is contraindicated for pregnant women, who remain at increased risk of repeated infections following CQ-only treatment. Here we apply a mathematical model to time-to-recurrence data from Juruá Valley, Brazil's main malaria transmission hotspot, to quantify the extra burden of parasite recurrences attributable to PQ ineligibility in pregnant women. The model accounts for competing risks, since relapses and late recrudescences (that may be at least partially prevented by PQ) and new infections (that are not affected by PQ use) all contribute to recurrences. We compare recurrence rates observed after primary P. vivax infections in 158 pregnant women treated with CQ only and 316 P. vivax infections in non-pregnant control women, matched for age, date of infection, and place of residence, who were administered a standard CQ-PQ combination. We estimate that, once infected with P. vivax, 23% of the pregnant women have one or more vivax malaria recurrences over the next 12 weeks; 86% of these early P. vivax recurrences are attributable to relapses or late recrudescences, rather than new infections that could be prevented by reducing malaria exposure during pregnancy. Model simulations indicate that weekly CQ chemoprophylaxis extending over 4 to 12 weeks, starting after the first vivax malaria episode diagnosed in pregnancy, might reduce the risk of P. vivax recurrences over the next 12 months by 20% to 65%. We conclude that post-treatment CQ prophylaxis could be further explored as a measure to prevent vivax malaria recurrences in pregnancy and avert their adverse effects on maternal and neonatal health.


Assuntos
Antimaláricos/uso terapêutico , Malária Vivax/prevenção & controle , Plasmodium vivax , Complicações Parasitárias na Gravidez/prevenção & controle , Primaquina/administração & dosagem , Adolescente , Adulto , Brasil , Estudos de Casos e Controles , Criança , Cloroquina/administração & dosagem , Cloroquina/uso terapêutico , Feminino , Humanos , Malária Vivax/tratamento farmacológico , Modelos Biológicos , Gravidez , Primaquina/uso terapêutico , Recidiva , Adulto Jovem
3.
Am J Trop Med Hyg ; 103(3): 1094-1099, 2020 09.
Artigo em Inglês | MEDLINE | ID: mdl-32524950

RESUMO

Plasmodium vivax and Plasmodium ovale form dormant liver hypnozoites that can reactivate weeks to months following initial infection. Malaria recurrences caused by relapses are an important cause of morbidity and source of transmission. To estimate the proportions of P. vivax malaria recurrences caused by relapses in different geographical locations, we systematically reviewed clinical efficacy studies of uncomplicated P. vivax malaria, in which patients were randomized to treatment with or without radical cure primaquine regimens and were followed up for 1 year. The minimum proportion of recurrences caused by relapses was estimated for each study site by assuming primaquine prevented all relapses and did not augment blood-stage efficacy. Of the 261 studies identified, six were eligible enrolling 4,092 patients from 14 treatment arm comparisons across seven countries. Of the 2,735 patients treated with primaquine, 24.3% received low dose (2.5 to < 5.0 mg/kg total) and 75.7% received high-dose primaquine (≥ 5.0 mg/kg total). The overall pooled incidence rate ratio of P. vivax relapses for patients treated with primaquine versus no primaquine was 0.15 (95% CI: 0.10-0.21; I 2 = 83.3%), equating to a minimum of 79% of recurrences attributable to relapse. Country-specific incidence rate ratios ranged from 0.05 (95% CI: 0.01-0.34; one estimate) in Pakistan to 0.34 in Nepal (95% CI: 0.12-0.83; one estimate) and Afghanistan (95% CI: 0.22-0.51; three estimates). Relapses account for a very high proportion of recurrent infections following schizontocidal treatment of acute P. vivax malaria across diverse geographic locations. This emphasizes the importance of implementing hypnozoitocidal treatment.


Assuntos
Antimaláricos/uso terapêutico , Malária Vivax/tratamento farmacológico , Malária/tratamento farmacológico , Plasmodium vivax/efeitos dos fármacos , Primaquina/uso terapêutico , Geografia , Humanos , Malária/parasitologia , Malária Vivax/parasitologia , Recidiva
4.
Am J Trop Med Hyg ; 103(1): 415-420, 2020 07.
Artigo em Inglês | MEDLINE | ID: mdl-32394882

RESUMO

Failures of primaquine for the treatment of relapsed Plasmodium vivax malaria is a serious challenge to malaria elimination in Ethiopia, where P. vivax accounts for up to 40% of malaria infections. We report here occurrence of a total of 15 episodes of primaquine treatment failure for radical cure in three historical P. vivax malaria patients from Gambella, Ethiopia, during 8-16 months of follow-up in 1985-1987. The total primaquine doses received were 17.5 mg/kg, 25.8 mg/kg, and 35.8 mg/kg, respectively. These total doses are much higher than in previous reports of patients with treatment failure in Ethiopia and East Africa. The possibility of new infection was excluded for these cases as the treatment and follow-up were carried out in Addis Ababa, a malaria-free city. Recrudescences were unlikely, considering the short duration pattern of the recurrences. The cytochrome P450 2D6 (CYP2D6) status for these patients is unknown, but polymorphisms have been described in Ethiopia and may have contributed to primaquine treatment failures. It is suggested that further studies be carried out in Ethiopia to determine the prevalence and distribution of primaquine treatment failures in different ethnic groups, considering the impact of CYP2D6 polymorphisms and the potential value of increasing the primaquine dose to avoid relapse.


Assuntos
Antimaláricos/uso terapêutico , Cloroquina/uso terapêutico , Malária Vivax/tratamento farmacológico , Primaquina/uso terapêutico , Adulto , Quimioprevenção , Etiópia , Humanos , Malária Vivax/prevenção & controle , Masculino , Pessoa de Meia-Idade , Carga Parasitária , Plasmodium vivax , Retratamento , Falha de Tratamento
5.
Am J Trop Med Hyg ; 103(2): 756-759, 2020 08.
Artigo em Inglês | MEDLINE | ID: mdl-32394887

RESUMO

Clinical failure of primaquine (PQ) has been demonstrated in people with CYP450 2D6 genetic polymorphisms that result in reduced or no enzyme activity. The distribution of CYP2D6 genotypes and predicted phenotypes in the Cambodian population is not well described. Surveys in other Asian countries have shown an approximate 50% prevalence of the reduced activity CYP2D6 allele *10, which could translate into increased risk of PQ radical cure failure and repeated relapses, making interruption of transmission and malaria elimination difficult to achieve. We determined CYP2D6 genotypes from 96 volunteers from Oddor Meanchey Province, Cambodia, an area endemic for Plasmodium vivax. We found a 54.2% frequency of the *10 allele, but in approximately half of our subjects, it was paired with a normal activity allele, either *1 or *2. The prevalence of *5, a null allele, was 9.4%. Overall predicted phenotype percentages were normal metabolizers, 46%; intermediate metabolizers, 52%; and poor metabolizers, 1%.


Assuntos
Antimaláricos/uso terapêutico , Citocromo P-450 CYP2D6/genética , Malária Vivax/tratamento farmacológico , Primaquina/uso terapêutico , Artemisininas/uso terapêutico , Grupo com Ancestrais do Continente Asiático/genética , Camboja , Quimioterapia Combinada , Doenças Endêmicas , Frequência do Gene , Genótipo , Humanos , Variantes Farmacogenômicos , Fenótipo , Plasmodium vivax , Polimorfismo Genético , Quinolinas/uso terapêutico , Recidiva , Falha de Tratamento
6.
Brasília; s.n; 14 maio 2020.
Não convencional em Português | LILACS, BRISA/RedTESA, PIE | ID: biblio-1097392

RESUMO

Essa é uma produção do Departamento de Ciência e Tecnologia (Decit) da Secretaria de Ciência, Tecnologia, Inovação e Insumos Estratégicos em Saúde (SCTIE) do Ministério da Saúde (Decit/SCTIE/MS), que tem como missão promover a ciência e tecnologia e o uso de evidências científicas para a tomada de decisão do SUS, tendo como principal atribuição o incentivo ao desenvolvimento de pesquisas em saúde no Brasil, de modo a direcionar os investimentos realizados em pesquisa pelo Governo Federal às necessidades de saúde pública. Informar sobre as principais evidências científicas descritas na literatura internacional sobre tratamento farmacológico para a COVID-19. Além de resumir cada estudo identificado, o informe apresenta também uma avaliação da qualidade metodológica e a quantidade de artigos publicados, de acordo com a sua classificação metodológica (revisões sistemáticas, ensaios clínicos randomizados, entre outros). Foram encontrados 15 artigos.


Assuntos
Humanos , Pneumonia Viral/tratamento farmacológico , Infecções por Coronavirus/tratamento farmacológico , Progressão da Doença , Betacoronavirus/efeitos dos fármacos , Primaquina/uso terapêutico , Ivermectina/uso terapêutico , Inibidores da Enzima Conversora de Angiotensina/uso terapêutico , Vacina BCG/administração & dosagem , Oxigenação por Membrana Extracorpórea/instrumentação , Cloroquina/uso terapêutico , Azitromicina/uso terapêutico , Ritonavir/uso terapêutico , Losartan/uso terapêutico , Terapia Antirretroviral de Alta Atividade/instrumentação , Combinação de Medicamentos , Oseltamivir/uso terapêutico , Lopinavir/uso terapêutico , Darunavir/uso terapêutico , Telmisartan/uso terapêutico , Hidroxicloroquina/uso terapêutico , Anticoagulantes/uso terapêutico
7.
Am J Trop Med Hyg ; 103(1): 334-343, 2020 07.
Artigo em Inglês | MEDLINE | ID: mdl-32342855

RESUMO

The Deployment and Travel Medicine Knowledge, Attitudes, Practices, and Outcomes Study (KAPOS) examines the integrated relationship between provider and patient inputs and health outcomes associated with travel and deployments. This study describes malaria chemoprophylaxis prescribing patterns by medical providers within the U.S. Department of Defense's Military Health System and its network of civilian healthcare providers during a 5-year period. Chemoprophylaxis varied by practice setting, beneficiary status, and providers' travel medicine expertise. Whereas both civilian and military facilities prescribe an increasing proportion of atovaquone-proguanil, doxycycline remains the most prevalent antimalarial at military facility based practices. Civilian providers dispense higher rates of mefloquine than their military counterparts. Within military treatment facilities, travel medicine specialists vary their prescribing pattern based on service member versus beneficiary status of the patient, both in regards to primary prophylaxis, and use of presumptive anti-relapse therapy (PQ-PART). By contrast, nonspecialists appear to carry over practice patterns developed under force health protection (FHP) policy for service members, into the care of beneficiaries, particularly in high rates of prescribing doxycycline and PQ-PART compared with both military travel medicine specialists and civilian comparators. Force health protection policy plays an important role in standardizing and improving the quality of care for deployed service members, but this may not be the perfect solution outside of the deployment context. Solutions that broaden both utilization of decision support tools and travel medicine specialty care are necessary.


Assuntos
Antimaláricos/uso terapêutico , Quimioprevenção/estatística & dados numéricos , Malária/prevenção & controle , Medicina Militar , Militares , Padrões de Prática Médica/estatística & dados numéricos , Adolescente , Adulto , Idoso , Atovaquona/uso terapêutico , Cloroquina/uso terapêutico , Doxiciclina/uso terapêutico , Combinação de Medicamentos , Feminino , Humanos , Masculino , Mefloquina/uso terapêutico , Pessoa de Meia-Idade , Primaquina/uso terapêutico , Proguanil/uso terapêutico , Estados Unidos , Adulto Jovem
8.
PLoS One ; 15(2): e0228190, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32023293

RESUMO

BACKGROUND: Mass administrations of antimalarial drugs (MDA) have reduced the incidence and prevalence of P. falciparum infections in a trial in the Greater Mekong Subregion. Here we assess the impact of the MDA on P. vivax infections. METHODS: Between May 2013 and July 2017, four villages in each Myanmar, Vietnam, Cambodia and Lao PDR were selected based on high prevalence of P. falciparum infections. Eight of the 16 villages were randomly assigned to receive MDA consisting of three-monthly rounds of three-day courses of dihydroartemisinin-piperaquine and, except in Cambodia, a single low-dose of primaquine. Cross-sectional surveys were conducted at quarterly intervals to detect Plasmodium infections using ultrasensitive qPCR. The difference in the cumulative incidence between the groups was assessed through a discrete time survival approach, the difference in prevalence through a difference-in-difference analysis, and the difference in the number of participants with a recurrence of P. vivax infection through a mixed-effect logistic regression. RESULTS: 3,790 (86%) residents in the intervention villages participated in at least one MDA round, of whom 2,520 (57%) participated in three rounds. The prevalence of P. vivax infections fell from 9.31% to 0.89% at month 3 but rebounded by six months to 5.81%. There was no evidence that the intervention reduced the cumulative incidence of P.vivax infections (95% confidence interval [CI] Odds ratio (OR): 0.29 to 1.36). Similarly, there was no evidence of MDA related reduction in the number of participants with at least one recurrent infection (OR: 0.34; 95% CI: 0.08 to 1.42). CONCLUSION: MDA with schizontocidal drugs had a lasting effect on P. falciparum infections but only a transient effect on the prevalence of P. vivax infections. Radical cure with an 8-aminoquinoline will be needed for the rapid elimination of vivax malaria.


Assuntos
Antimaláricos/uso terapêutico , Artemisininas/uso terapêutico , Malária Falciparum/tratamento farmacológico , Malária Vivax/tratamento farmacológico , Primaquina/uso terapêutico , Quinolinas/uso terapêutico , Adolescente , Adulto , Camboja/epidemiologia , Criança , Feminino , Humanos , Malária Falciparum/epidemiologia , Malária Vivax/epidemiologia , Masculino , Administração Massiva de Medicamentos , Mianmar/epidemiologia , Prevalência , Recidiva , Resultado do Tratamento , Vietnã/epidemiologia , Adulto Jovem
9.
PLoS One ; 15(1): e0228207, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32004348

RESUMO

BACKGROUND: Primaquine is an approved radical cure treatment for Plasmodium vivax malaria but treatment can result in life-threatening hemolysis if given to a glucose-6-phosphate dehydrogenase deficient (G6PDd) patient. There is a need for reliable point-of-care G6PD diagnostic tests. OBJECTIVES: To evaluate the performance of the CareStart™ rapid diagnostic test (RDT) in the hands of healthcare workers (HCWs) and village malaria workers (VMWs) in field settings, and to better understand user perceptions about the risks and benefits of PQ treatment guided by RDT results. METHODS: This study enrolled 105 HCWs and VMWs, herein referred to as trainees, who tested 1,543 healthy adult male volunteers from 84 villages in Cambodia. The trainees were instructed on G6PD screening, primaquine case management, and completed pre and post-training questionnaires. Each trainee tested up to 16 volunteers in the field under observation by the study staff. RESULTS: Out of 1,542 evaluable G6PD volunteers, 251 (16.28%) had quantitative enzymatic activity less than 30% of an adjusted male median (8.30 U/g Hb). There was no significant difference in test sensitivity in detecting G6PDd between trainees (97.21%), expert study staff in the field (98.01%), and in a laboratory setting (95.62%) (p = 0.229); however, test specificity was different for trainees (96.62%), expert study staff in the field (98.14%), and experts in the laboratory (98.99%) (p < 0.001). Negative predictive values were not statistically different for trainees, expert staff, and laboratory testing: 99.44%, 99.61%, and 99.15%, respectively. Knowledge scores increased significantly post-training, with 98.7% willing to prescribe primaquine for P.vivax malaria, an improvement from 40.6% pre-training (p < 0.001). CONCLUSION: This study demonstrated ability of medical staff with different background to accurately use CareStart™ RDT to identify G6PDd in male patients, which may enable safer prescribing of primaquine; however, pharmacovigilance is required to address possible G6PDd misclassifications.


Assuntos
Testes Diagnósticos de Rotina , Deficiência de Glucosefosfato Desidrogenase/diagnóstico , Primaquina/efeitos adversos , Características de Residência , Adulto , Camboja , Feminino , Glucosefosfato Desidrogenase/metabolismo , Deficiência de Glucosefosfato Desidrogenase/metabolismo , Humanos , Malária Vivax/tratamento farmacológico , Masculino , Sistemas Automatizados de Assistência Junto ao Leito , Primaquina/uso terapêutico , Medição de Risco , Adulto Jovem
10.
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
11.
N Z Med J ; 133(1508): 123-126, 2020 01 17.
Artigo em Inglês | MEDLINE | ID: mdl-31945049

RESUMO

Methotrexate monotherapy is a common management strategy in rheumatoid arthritis (RA). Treatment with immunosuppression can lead to opportunistic infections such as Pneumocystis jirovecii pneumonia (PJP). The treatment options for PJP include cotrimoxazole, clindamycin-primaquine and dapsone. Though these drugs are generally well tolerated, they can result in potentially severe adverse effects. Sometimes several undesired events may occur in a single patient, reminding us of Murphy's law. Herein, we report a case which exemplifies this adage. A 50-year-old female developed PJP, while on methotrexate therapy for RA and was treated with cotrimoxazole. The latter resulted in painful peripheral neuropathy, which improved after cotrimoxazole was stopped. Salvage therapy for PJP with primaquine-clindamycin, lead to another serious adverse event, methemoglobinemia. Withdrawing the offending drug resulted in dramatic improvement.


Assuntos
Aplicação da Lei/métodos , Metemoglobinemia/induzido quimicamente , Doenças do Sistema Nervoso Periférico/induzido quimicamente , Pneumonia por Pneumocystis/tratamento farmacológico , Antibacterianos/efeitos adversos , Antibacterianos/uso terapêutico , Antimaláricos/efeitos adversos , Antimaláricos/uso terapêutico , Clindamicina/efeitos adversos , Clindamicina/uso terapêutico , Dapsona/efeitos adversos , Dapsona/uso terapêutico , Quimioterapia Combinada/métodos , Feminino , Humanos , Pessoa de Meia-Idade , Nova Zelândia/epidemiologia , Pneumonia por Pneumocystis/complicações , Primaquina/efeitos adversos , Primaquina/uso terapêutico , Combinação Trimetoprima e Sulfametoxazol/efeitos adversos , Combinação Trimetoprima e Sulfametoxazol/uso terapêutico , Suspensão de Tratamento
12.
Malar J ; 19(1): 4, 2020 Jan 03.
Artigo em Inglês | MEDLINE | ID: mdl-31900172

RESUMO

BACKGROUND: Trials to assess the efficacy of the radical cure of Plasmodium vivax malaria with 8-aminoquinolines require that most post-treatment relapses are identified, but there is no consensus on the optimal duration of follow-up in either symptomatic or asymptomatic vivax malaria. The efficacy of a 14-day course of primaquine on the cumulative incidence of recurrent asymptomatic P. vivax infections detected by ultrasensitive quantitative PCR (uPCR) as a primary endpoint was assessed. METHODS: A randomized, placebo-controlled, single-blind trial was conducted in four villages of the Lao PDR during 2016-2018 nested in a larger project evaluating mass drug administrations (MDA) with dihydroartemisinin-piperaquine (DP) and a single low-dose primaquine to clear Plasmodium falciparum infections. In the nested sub-study, eligible participants with mono- or mixed P. vivax infections detected by uPCR were randomized to receive either 14 days of primaquine (0.5 mg/kg/day) or placebo during the last round of MDA (round 3) through directly observed therapy. Participants were checked monthly for 12 months for parasitaemia using uPCR. The primary outcome was cumulative incidence of participants with at least one recurrent episode of P. vivax infection. RESULTS: 20 G6PD-normal participants were randomized in each arm. 5 (29%) of 20 participants in the placebo arm experienced asymptomatic, recurrent P. vivax infections, resulting in a cumulative incidence at month 12 of 29%. None of the 20 participants in the intervention arm had recurrent infections (p = 0.047 Fisher's exact test). Participants with recurrent P. vivax infections were found to be parasitaemic for between one and five sequential monthly tests. The median time to recurrence of P. vivax parasitaemia was 178 days (range 62-243 days). CONCLUSIONS: A 14-day course of primaquine in addition to a DP-MDA was safe, well-tolerated, and prevented recurrent asymptomatic P. vivax infections. Long follow-up for up to 12 months is required to capture all recurrences following the treatment of asymptomatic vivax infection. To eliminate all malarias in settings where P. vivax is endemic, a full-course of an 8-aminoquinolines should be added to MDA to eliminate all malarias. Trial registration This study was registered with ClinicalTrials.gov under NCT02802813 on 16th June 2016. https://clinicaltrials.gov/ct2/show/NCT02802813.


Assuntos
Antimaláricos/uso terapêutico , Malária Vivax/tratamento farmacológico , Reação em Cadeia da Polimerase/métodos , Primaquina/uso terapêutico , Adolescente , Adulto , Artemisininas/uso terapêutico , Infecções Assintomáticas , Feminino , Humanos , Laos , Masculino , Administração Massiva de Medicamentos , Plasmodium vivax , Primaquina/administração & dosagem , Quinolinas/uso terapêutico , Recidiva , Fatores de Tempo , Adulto Jovem
13.
Am J Trop Med Hyg ; 102(1): 156-158, 2020 01.
Artigo em Inglês | MEDLINE | ID: mdl-31701865

RESUMO

We herein report the first case of Mediterranean glucose-6-phosphate dehydrogenase (G6PD) variant from Bangladesh. A boy had been admitted to hospital and was diagnosed with uncomplicated Plasmodium vivax infection and treated with 30 mg/kg body weight (BW) chloroquine for 3 days and 4.8 mg/kg BW primaquine (PQ) to be taken over 14 days. The boy was discharged but represented 4 days later with severe hemoglobinuria and fatigue. Hemoglobin was measured at 6.0 g/dL and serum bilirubin was at 5.6 mg/dL, although malaria microscopy was negative. The boy had taken the 4-fold recommended daily dose of PQ and was treated with two fresh blood transfusions. Subsequent molecular analysis showed the boy to have the Mediterranean G6PD variant and a G6PD activity of 0.93 U/gHb.


Assuntos
Cloroquina/uso terapêutico , Deficiência de Glucosefosfato Desidrogenase , Hemoglobinúria/induzido quimicamente , Malária/tratamento farmacológico , Primaquina/efeitos adversos , Primaquina/uso terapêutico , Antimaláricos/efeitos adversos , Antimaláricos/uso terapêutico , Transfusão de Sangue , Criança , Cloroquina/administração & dosagem , Deficiência de Glucosefosfato Desidrogenase/genética , Hemoglobinúria/terapia , Humanos , Masculino
14.
Am J Trop Med Hyg ; 102(1): 147-150, 2020 01.
Artigo em Inglês | MEDLINE | ID: mdl-31746312

RESUMO

All Plasmodium cases have declined over the last decade in northwestern Thailand along the Myanmar border. During this time, Plasmodium vivax has replaced Plasmodium falciparum as the dominant species. The decline in P. falciparum has been shadowed by a coincidental but delayed decline in P. vivax cases. This may be due to early detection and artemisinin-based therapy, species-specific diagnostics, and bed net usage all of which reduce malaria transmission but not P. vivax relapse. In the absence of widespread primaquine use for radical cure against P. vivax hypnozoites, the decline in P. vivax may be explained by decreased hypnozoite activation of P. vivax relapses triggered by P. falciparum. The observed trends in this region suggest a beneficial effect of decreased P. falciparum transmission on P. vivax incidence, but elimination of P. vivax in a timely manner likely requires radical cure.


Assuntos
Antimaláricos/uso terapêutico , Malária Vivax/epidemiologia , Primaquina/uso terapêutico , Humanos , Plasmodium vivax , Estudos Retrospectivos , Tailândia/epidemiologia
15.
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
16.
JCI Insight ; 4(24)2019 12 19.
Artigo em Inglês | MEDLINE | ID: mdl-31852843

RESUMO

Despite an unprecedented 2 decades of success, the combat against malaria - the mosquito-transmitted disease caused by Plasmodium parasites - is no longer progressing. Efforts toward eradication are threatened by the lack of an effective vaccine and a rise in antiparasite drug resistance. Alternative approaches are urgently needed. Repurposing of available, approved drugs with distinct modes of action are being considered as viable and immediate adjuncts to standard antimicrobial treatment. Such strategies may be well suited to the obligatory and clinically silent first phase of Plasmodium infection, where massive parasite replication occurs within hepatocytes in the liver. Here, we report that the widely used antidiabetic drug, metformin, impairs parasite liver stage development of both rodent-infecting Plasmodium berghei and human-infecting P. falciparum parasites. Prophylactic treatment with metformin curtails parasite intracellular growth in vitro. An additional effect was observed in mice with a decrease in the numbers of infected hepatocytes. Moreover, metformin provided in combination with conventional liver- or blood-acting antimalarial drugs further reduced the total burden of P. berghei infection and substantially lessened disease severity in mice. Together, our findings indicate that repurposing of metformin in a prophylactic regimen could be considered for malaria chemoprevention.


Assuntos
Antimaláricos/farmacologia , Malária/prevenção & controle , Metformina/farmacologia , Plasmodium berghei/efeitos dos fármacos , Plasmodium falciparum/efeitos dos fármacos , Animais , Antimaláricos/uso terapêutico , Células Cultivadas , Modelos Animais de Doenças , Avaliação Pré-Clínica de Medicamentos , Reposicionamento de Medicamentos , Quimioterapia Combinada/métodos , Hepatócitos , Humanos , Concentração Inibidora 50 , Fígado/citologia , Fígado/efeitos dos fármacos , Fígado/parasitologia , Malária/sangue , Malária/tratamento farmacológico , Malária/parasitologia , Masculino , Mefloquina/farmacologia , Mefloquina/uso terapêutico , Metformina/uso terapêutico , Camundongos , Carga Parasitária , Testes de Sensibilidade Parasitária , Plasmodium berghei/isolamento & purificação , Plasmodium falciparum/isolamento & purificação , Primaquina/farmacologia , Primaquina/uso terapêutico , Cultura Primária de Células
17.
Nat Commun ; 10(1): 5595, 2019 12 06.
Artigo em Inglês | MEDLINE | ID: mdl-31811128

RESUMO

Relapses arising from dormant liver-stage Plasmodium vivax parasites (hypnozoites) are a major cause of vivax malaria. However, in endemic areas, a recurrent blood-stage infection following treatment can be hypnozoite-derived (relapse), a blood-stage treatment failure (recrudescence), or a newly acquired infection (reinfection). Each of these requires a different prevention strategy, but it was not previously possible to distinguish between them reliably. We show that individual vivax malaria recurrences can be characterised probabilistically by combined modelling of time-to-event and genetic data within a framework incorporating identity-by-descent. Analysis of pooled patient data on 1441 recurrent P. vivax infections in 1299 patients on the Thailand-Myanmar border observed over 1000 patient follow-up years shows that, without primaquine radical curative treatment, 3 in 4 patients relapse. In contrast, after supervised high-dose primaquine only 1 in 40 relapse. In this region of frequent relapsing P. vivax, failure rates after supervised high-dose primaquine are significantly lower (∼3%) than estimated previously.


Assuntos
Antimaláricos/uso terapêutico , Malária Vivax/tratamento farmacológico , Malária Vivax/epidemiologia , Plasmodium vivax/genética , Primaquina/uso terapêutico , Adolescente , Adulto , Antimaláricos/administração & dosagem , Criança , Pré-Escolar , Feminino , Humanos , Lactente , Malária Vivax/sangue , Malária Vivax/parasitologia , Masculino , Pessoa de Meia-Idade , Modelos Teóricos , Mianmar/epidemiologia , Plasmodium vivax/efeitos dos fármacos , Plasmodium vivax/patogenicidade , Primaquina/administração & dosagem , Recidiva , Tailândia/epidemiologia , Resultado do Tratamento , Adulto Jovem
18.
Sci Rep ; 9(1): 19060, 2019 12 13.
Artigo em Inglês | MEDLINE | ID: mdl-31836757

RESUMO

Although WHO recommends mass drug administration (MDA) for malaria elimination, further evidence is required for understanding the obstacles for the optimum implementation of MDA. Just before the long rain in 2016, two rounds of MDA with artemisinin/piperaquine (Artequick) and low-dose primaquine were conducted with a 35-day interval for the entire population of Ngodhe Island (~500 inhabitants) in Lake Victoria, Kenya, which is surrounded by areas with moderate and high transmission. With approximately 90% compliance, Plasmodium prevalence decreased from 3% to 0% by microscopy and from 10% to 2% by PCR. However, prevalence rebounded to 9% by PCR two months after conclusion of MDA. Besides the remained local transmission, parasite importation caused by human movement likely contributed to the resurgence. Analyses of 419 arrivals to Ngodhe between July 2016 and September 2017 revealed Plasmodium prevalence of 4.6% and 16.0% by microscopy and PCR, respectively. Risk factors for infection among arrivals included age (0 to 5 and 11 to 15 years), and travelers from Siaya County, located to the north of Ngodhe Island. Parasite importation caused by human movement is one of major obstacles to sustain malaria elimination, suggesting the importance of cross-regional initiatives together with local vector control.


Assuntos
Ilhas , Malária/tratamento farmacológico , Malária/epidemiologia , Administração Massiva de Medicamentos , Anemia/complicações , Animais , Antimaláricos/efeitos adversos , Antimaláricos/farmacologia , Antimaláricos/uso terapêutico , Geografia , Hemoglobinas/metabolismo , Humanos , Quênia/epidemiologia , Malária/parasitologia , Administração Massiva de Medicamentos/efeitos adversos , Adesão à Medicação , Parasitos/efeitos dos fármacos , Prevalência , Primaquina/efeitos adversos , Primaquina/farmacologia , Primaquina/uso terapêutico , Recidiva , Fatores de Risco
19.
PLoS Med ; 16(12): e1002992, 2019 12.
Artigo em Inglês | MEDLINE | ID: mdl-31834890

RESUMO

BACKGROUND: To reduce the risk of drug-induced haemolysis, all patients should be tested for glucose-6-phosphate dehydrogenase (G6PD) deficiency (G6PDd) prior to prescribing primaquine (PQ)-based radical cure for the treatment of vivax malaria. This systematic review and individual patient meta-analysis assessed the utility of a qualitative lateral flow assay from Access Bio/CareStart (Somerset, NJ) (CareStart Screening test for G6PD deficiency) for the diagnosis of G6PDd compared to the gold standard spectrophotometry (International Prospective Register of Systematic Reviews [PROSPERO]: CRD42019110994). METHODS AND FINDINGS: Articles published on PubMed between 1 January 2011 and 27 September 2019 were screened. Articles reporting performance of the standard CSG from venous or capillary blood samples collected prospectively and considering spectrophotometry as gold standard (using kits from Trinity Biotech PLC, Wicklow, Ireland) were included. Authors of articles fulfilling the inclusion criteria were contacted to contribute anonymized individual data. Minimal data requested were sex of the participant, CSG result, spectrophotometry result in U/gHb, and haemoglobin (Hb) reading. The adjusted male median (AMM) was calculated per site and defined as 100% G6PD activity. G6PDd was defined as an enzyme activity of less than 30%. Pooled estimates for sensitivity and specificity, unconditional negative predictive value (NPV), positive likelihood ratio (LR+), and negative likelihood ratio (LR-) were calculated comparing CSG results to spectrophotometry using a random-effects bivariate model. Of 11 eligible published articles, individual data were available from 8 studies, 6 from Southeast Asia, 1 from Africa, and 1 from the Americas. A total of 5,815 individual participant data (IPD) were available, of which 5,777 results (99.3%) were considered for analysis, including data from 3,095 (53.6%) females. Overall, the CSG had a pooled sensitivity of 0.96 (95% CI 0.90-0.99) and a specificity of 0.95 (95% CI 0.92-0.96). When the prevalence of G6PDd was varied from 5% to 30%, the unconditional NPV was 0.99 (95% CI 0.94-1.00), with an LR+ and an LR- of 18.23 (95% CI 13.04-25.48) and 0.05 (95% CI 0.02-0.12), respectively. Performance was significantly better in males compared to females (p = 0.027) but did not differ significantly between samples collected from capillary or venous blood (p = 0.547). Limitations of the study include the lack of wide geographical representation of the included data and that the CSG results were generated under research conditions, and therefore may not reflect performance in routine settings. CONCLUSIONS: The CSG performed well at the 30% threshold. Its high NPV suggests that the test is suitable to guide PQ treatment, and the high LR+ and low LR- render the test suitable to confirm and exclude G6PDd. Further operational studies are needed to confirm the utility of the test in remote endemic settings.


Assuntos
Testes Diagnósticos de Rotina , Deficiência de Glucosefosfato Desidrogenase/diagnóstico , Glucosefosfato Desidrogenase/genética , Primaquina/uso terapêutico , Testes Diagnósticos de Rotina/métodos , Doenças Endêmicas , Feminino , Deficiência de Glucosefosfato Desidrogenase/tratamento farmacológico , Humanos , Malária/tratamento farmacológico , Malária/epidemiologia , Malária Vivax/epidemiologia , Masculino , Sistemas Automatizados de Assistência Junto ao Leito , Primaquina/efeitos adversos , Sensibilidade e Especificidade
20.
Mikrobiyol Bul ; 53(4): 472-479, 2019 Oct.
Artigo em Turco | MEDLINE | ID: mdl-31709945

RESUMO

In spite of the fact that Plasmodium vivax is the leading causative agent of malaria in our country, imported malaria cases have been reported, recently. In this report, two malaria cases originated from sub-Saharan Africa, and their diagnostic and therapeutic approaches were aimed to be presented. First case, 45-year-old male, who has been working in Republic of Ghana, was admitted to Hacettepe University Hospitals Emergency Service with complaints of fever, sweating and shivering, after returning to Turkey. On admission, his general condition was fine and his physical examination revealed no pathological finding. After his admission, a fever episode occured and his blood tests revealed anemia, trombocytopenia and increased alkaline phosphatase level. Second case, 39-year-old-male admitted to the emergency service with the complaints of fever, shivering and myalgia. His physical examination revealed decreased breath sounds and splenomegaly, his laboratory tests resulted in pansitopenia and elevated liver enzymes. In the thick blood smears of the patients ring formed young trophozoites are detected and in the thin films multiple ring forms demonstrated in one erythrocyte with the absence of mature trophozoites and schizont forms, which were compatible with falciparum malaria. The rapid antigen test (Digamed, Belgium) of the second case found to be positive for both Plasmodium falciparum and P.vivax and this patient followed-up in intensive care unit due to his deterioration of general condition, respiratory distress, hematuria and change of consciousness. Neither cases were commenced on malaria prophylaxis. Both patients have been in countries which chloroquine resistance is commonly seen, they were treated with artemether/lumefantrine as current World Health Organization recommended. Targeting hypnozoites of P.vivax, primaquine was added to the therapy of the second patient. Both patients resulted in cure. In conclusion, while travelling to endemic countries, people should be informed about the importance of malaria prophylaxis and prophylaxis should be commenced immediately and continued appropriately. Additionally, malaria should always be considered in the differential diagnosis of high fever for the patients who admitted to the hospital with a travelling history to these countries.


Assuntos
Antimaláricos , Combinação Arteméter e Lumefantrina , Malária , Primaquina , Adulto , África ao Sul do Saara , Antimaláricos/uso terapêutico , Combinação Arteméter e Lumefantrina/uso terapêutico , Doenças Transmissíveis Importadas/diagnóstico , Doenças Transmissíveis Importadas/tratamento farmacológico , Doenças Transmissíveis Importadas/parasitologia , Doenças Transmissíveis Importadas/prevenção & controle , Humanos , Malária/diagnóstico , Malária/tratamento farmacológico , Malária/parasitologia , Malária/prevenção & controle , Masculino , Pessoa de Meia-Idade , Plasmodium falciparum , Plasmodium vivax , Primaquina/uso terapêutico , Viagem , Resultado do Tratamento , Turquia
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