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Funding Information: This paper was funded by the Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq, Brazil) (404067/2012-3 and 2020/00433-8), the European and Developing Countries Clinical Trials Partnership (EDCTP) (RIA2017T-2018), the Fundação de Amparo *a Pesquisa do Estado de mInas Gerais (FAPEMIG) (CBB-APQ 00952-16) and the Fundação para a Ciência e Tecnologia (FCT, Portugal) (SFRH/BD/142860/2018). Funding Information: L Pernaute-Lau is a recipient of a fellowship from BioSys PhD program PD65‐2012 (Ref SFRH/BD/142860/2018) from Fundação para a Ciência e Tecnologia (FCT, Portugal). JP Gil, M Camara and U Morris were partially supported by the European Developing Countries Clinical Trial Partnership (EDCTP2) programme supported by the European Union (Grant number RIA2017T-2018 – WANECAM 2). T Nóbrega de Sousa is a recipient of a Senior Research Scholarships from Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq, Brazil). Funded by Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPqants number 404,067/2012-3, 2020/00433-8), and the Fundação de Amparo à Pesquisa do Estado de mInas Gerais (FAPEMIG), grant number CBB-APQ 00952-16). MU Ferreira was funded by Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPqants number 404,067/2012-3, 2020/00433-8), and the Fundação de Amparo à Pesquisa do Estado de mInas Gerais (FAPEMIG), grant number CBB-APQ 00952-16). The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed. Publisher Copyright: © 2022 The Author(s). Published by Informa UK Limited, trading as Taylor & Francis Group. Introduction: Artemisinin-based combination therapies (ACTs) are recommended first-line antimalarials for uncomplicated Plasmodium falciparum malaria. Pharmacokinetic/pharmacodynamic variation associated with ACT drugs and their effect is documented. It is accepted to an extent that inter-individual variation is genetically driven, and should be explored for optimized antimalarial use. Areas covered: We provide an update on the pharmacogenetics of ACT antimalarial disposition. Beyond presently used antimalarials, we also refer to information available for the most notable next-generation drugs under development. The bibliographic approach was based on multiple Boolean searches on PubMed covering all recent publications since our previous review. Expert opinion: The last 10 years have witnessed an increase in our knowledge of ACT pharmacogenetics, including the first clear examples of its contribution as an exacerbating factor for drug–drug interactions. This knowledge gap is still large and is likely to widen as a new wave of antimalarial drug is looming, with few studies addressing their pharmacogenetics. Clinically useful pharmacogenetic markers are still not available, in particular, from an individual precision medicine perspective. A better understanding of the genetic makeup of target populations can be valuable for aiding decisions on mass drug administration implementation concerning region-specific antimalarial drug and dosage options. publishersversion published

The authors describe the baseline malaria prevalence and arbovirus seroprevalence among 467 subjects in an ongoing cohort study in rural Amazonia. Most subjects (72.2%) reported one or more previous episodes of malaria, and 15.6% had been hospitalized for malaria, but only 3.6% of individuals five years or older had malaria parasites detected by microscopy (10 with Plasmodium vivax and 4 with P. falciparum). Antibodies to Alphavirus, Orthobunyavirus, and/or Flavivirus were detected by hemagglutination inhibition (HI) in 42.6% of subjects aged five years or older, with a higher seropositivity rate among males (49.2%) than females (36.2%). Since 98.9% of subjects had been immunized for yellow fever, the presence of cross-reactive antibodies to dengue and other Flaviviruses cannot be ruled out, but at least 12 subjects (3.3%) with IgM antibodies to dengue virus detected by ELISA had a putative recent exposure to this virus. Descrevem-se aqui dados de prevalência de malária e soroprevalência de arboviroses na linha de base de um estudo de coorte, envolvendo 467 indivíduos, atualmente em curso na Amazônia rural. A maioria (72,2%) dos indivíduos relatou um ou mais episódios maláricos prévios, tendo 15,6% deles tido pelo menos uma internação hospitalar motivada pela malária, mas somente 3,6% dos indivíduos com idade igual ou superior a cinco anos tinham plasmódios (Plasmodium vivax em dez e P. falciparum em quatro) diagnosticados por microscopia. Detectaram-se anticorpos contra Alphavirus, Orthobunyavirus e Flavivirus, pelo teste de inibição de hemaglutinação, em 42,6% dos indivíduos com idade igual ou superior a cinco anos, com uma taxa de soropositividade maior entre indivíduos do sexo masculino (49,2%) do que os do feminino (36,2%). Como 98,9% dos indivíduos entrevistados tinham sido previamente vacinados contra a febre amarela, a presença de reações cruzadas com o vírus do dengue e outros Flavivirus não pode ser descartada, mas a exposição recente ao vírus do dengue foi evidenciada pela detecção de anticorpos IgM por ELISA em 12 indivíduos (3,3%).

We have compared Duffy blood group genotype distribution, as determined by polymerase chain reaction with allele-specific primers, in 68 Plasmodium vivax-infected patients and 59 non-vivax malaria controls from Rondônia, Brazil. Homozygosity for the allele Fy, which abolishes Duffy antigen expression on erythrocytes, was observed in 12% non-vivax controls but in no P. vivax patient. However, no significant association was found between Fy heterozygosity and protection against P. vivax. The Fy x allele, which has recently been associated with very weak erythrocyte expression of Duffy antigen, was not found in local P. vivax patients. Compara-se neste trabalho a distribuição de genótipos do sistema sangüíneo Duffy, determinados através de reação em cadeia da polimerase com oligonucleotídeos iniciadores alelo-específicos, em 68 pacientes com infecção por Plasmodium vivax e em 59 controles com malária não-vivax de Rondônia, Brasil. Nenhum paciente infectado com P. vivax, mas 12% dos controles não-vivax, eram homozigotos para o alelo Fy, que abole a expressão do antígeno Duffy em hemácias. No entanto, não se observou evidência de proteção significativa contra P. vivax entre indivíduos heterozigotos para Fy. O alelo Fy x, que tem sido recentemente associado com a expressão eritrocitária muito fraca do antígeno Duffy, não foi encontrado entre pacientes locais com infecção por P. vivax.

We have compared results of Plasmodium species identification obtained with conventional on-site microscopy of Giemsa-stained thick smears (GTS) and a semi-nested polymerase chain reaction (PCR) in 96 malaria patients from Rondônia, Western Brazilian Amazon. Mixed-species infections were detected by PCR in 30% patients, but no such case had been found on GTS. Moreover, P. malariae infections were detected in 9 of 96 patients (10%) by PCR, but were not identified by local microscopists. The potential impact of species misidentification on malaria treatment and control is discussed. Comparam-se neste trabalho resultados de identificação de espécie de Plasmodium obtidos com a microscopia convencional de gotas espessas coradas pelo Giemsa, realizada no local, e um protocolo semi-aninhado de reação em cadeia da polimerase (PCR) em 96 pacientes maláricos de Rondônia, Amazônia Ocidental Brasileira. Infecções envolvendo mais de uma espécie foram detectadas através de PCR em 30% dos pacientes, mas nenhum caso havia sido encontrado pelo exame de gotas espessas. Além disso, encontraram-se infecções por P. malariae por PCR em 9 dos 96 pacientes (10%), mas nenhuma havia sido encontrada pelos microscopistas locais. Discute-se o potencial impacto de erros de identificação de espécie sobre o tratamento e o controle da malária.

This work was supported by grants from the UNDP/World Bank/World Health Organization Special Program for Research and Training in Tropical Diseases, the Program for Malaria Contrai in the Amazon (PCMAM) of the National Health Foundation (Brazilian Ministry of Health), and the Fundacao para o Amparo a Pesquisa do Estado de Sao Paulo (FAPESP), Brazil. Universidade de S?o Paulo. Instituto de Ci?ncias Biom?dicas. Departamento de Parasitologia. S?o Paulo, SP, Brazil. Universidade de S?o Paulo. Instituto de Ci?ncias Biom?dicas. Departamento de Parasitologia. S?o Paulo, SP, Brazil. Minist?rio da Sa?de. Funda??o Nacional de Sa?de. Instituto Evandro Chagas. Bel?m, PA, Brasil. Universidade de S?o Paulo. Instituto de Ci?ncias Biom?dicas. Departamento de Parasitologia. S?o Paulo, SP, Brazil. A critical role has been proposed for cytophilic IgOl and IgOJ subclass antibodies and monocytes and macrophages in antimalarial immunity. Here we compared lhe isotype composition and avidity of naturally acquired antibodies, as measured by enzyme immunoassay against a detergent-soluble extract of Plasmodium falciparum schizonts, in clinically immune Senegalese adults (n = 33) and semi-immune, adult Amazonian patients (n = 25). Plasma were collected during an acute symptomatic P. falciparum attack and two months later, and in the absence of recrudescence or reinfection. Specific IgO, IgM, IgA, and IgO subclass antibodies were assessed. The results are summarized as follows: 1) high-avidity cytophilic antibodies predorninated in clinically immune Senegalese subjects; 2) acutely ill Amazonian patients produced high levels of low-avidity cytophilic antibody; 3) such a response was shonlived, since two months later, the concentrations of cytophilic antibodies were significantly lower; 4) however, affinity maturation of IgO antibodies was observed in Amazonian patients two months after the acute malaria attack. A considerable proponion (35-46%) of anti-P. falciparum IgOI antibodies produced by African and Amazonian patients was shown to recognize periodate-sensitive carbohydrate epitopes. The potential impact of these findings on the design and evaluation of antimalarial vaccines is discussed.