Characterisation of pvmdr1 and pvdhfr genes associated with chemoresistance in Brazilian Plasmodium vivax isolates.

Plasmodium vivax control is now being hampered by drug resistance. Orthologous Plasmodium falciparum genes linked to chloroquine or sulfadoxine-pyrimethamine chemoresistance have been identified in P. vivax parasites, but few studies have been performed. The goal of the present work is to characterise pvmdr1 and pvdhfr genes in parasite isolates from a Brazilian endemic area where no molecular investigation had been previously conducted. The pvmdr1 analysis revealed the existence of single (85.7%) and double (14.3%) mutant haplotypes, while the pvdhfr examination showed the presence of double (57.2%) and triple (42.8%) mutant haplotypes. The implications of these findings are discussed.

Myocarditis associated with Plasmodium vivax malaria: a case report.

Malaria remains a major public health problem in Brazil where Plasmodium vivax is the predominant species, responsible for 82% of registered cases in 2013. Though benign, P. vivax infection may sometimes evolve with complications and a fatal outcome. Here, we report a severe case of P. vivax malaria in a 35-year-old Brazilian man from a malaria endemic area, who presented with reversible myocarditis.

Myocarditis associated with Plasmodium vivax malaria: a case report

Malaria remains a major public health problem in Brazil where Plasmodium vivax is the predominant species, responsible for 82% of registered cases in 2013. Though benign, P. vivax infection may sometimes evolve with complications and a fatal outcome. Here, we report a severe case of P. vivax malaria in a 35-year-old Brazilian man from a malaria endemic area, who presented with reversible myocarditis.

Cellular and humoral immune responses against the Plasmodium vivax MSP-119 malaria vaccine candidate in individuals living in an endemic area in north-eastern Amazon region of Brazil

Background: Plasmodium vivax merozoite surface protein-1 (MSP-1) is an antigen considered to be one of the leading malaria vaccine candidates. PvMSP-1 is highly immunogenic and evidences suggest that it is target for protective immunity against asexual blood stages of malaria parasites. Thus, this study aims to evaluate the acquired cellular and antibody immune responses against PvMSP-1 in individuals naturally exposed to malaria infections in a malaria-endemic area in the north-eastern Amazon region of Brazil. Methods: The study was carried out in Paragominas, Pará State, in the Brazilian Amazon. Blood samples were collected from 35 individuals with uncomplicated malaria. Peripheral blood mononuclear cells were isolated and the cellular proliferation and activation was analysed in presence of 19 kDa fragment of MSP-1 (PvMSP-119) and Plasmodium falciparum PSS1 crude antigen. Antibodies IgE, IgM, IgG and IgG subclass and the levels of TNF, IFN-?and IL-10 were measured by enzyme-linked immunosorbent assay. Results: The prevalence of activated CD4+ was greater than CD8+ T cells, in both ex-vivo and in 96 h culture in presence of PvMSP-119 and PSS1 antigen. A low proliferative response against PvMSP-119 and PSS1 crude antigen after 96 h culture was observed. High plasmatic levels of IFN-? and IL-10 as well as lower TNF levels were also detected in malaria patients. However, in the 96 h supernatant culture, the dynamics of cytokine responses differed from those depicted on plasma assays; in presence of PvMSP-119 stimulus, higher levels of TNF were noted in supernatant 96 h culture of malaria patients cells while low levels of IFN-? and IL-10 were verified. High frequency of malaria patients presenting antibodies against PvMSP-119 was evidenced, regardless class or IgG subclass. PvMSP-119-induced antibodies were predominantly on non-cytophilic subclasses. Conclusions: The results presented here shows that PvMSP-119 was able to induce a... (AU)

Malária falciparum com comprometimento renal (síndrome nefrótica - relato de caso / Falciparum malaria with renal impairment (nephrotic syndrome) - case report

Objetivo: apresentação de um caso de síndrome nefrótica por malária falciparum. Relato decaso: escolar, 8 anos, sexo feminino, admitida no Hospital Municipal de Tailândia, Pará, comquadro de febre alta, seguida de surgimento de edema, urina escura e oligúria.. Evoluiu comanúria e foi transferida para a Fundação Santa de Misericórdia do Pará (FSCM-PA), onderecebeu diagnóstico de síndrome nefrótica secundária à malária por Plasmodium falciparum,com base em dados de anamnese, exame físico e exames complementares. A paciente obteveboa resposta clínica e parasitológica com a terapêutica antimalárica, recebendo alta hospitalarpara controle no Programa de Ensaios Clínicos em Malária do Instituto Evandro Chagas eAmbulatório de Nefrologia. Considerações finais: o acometimento renal é uma dascomplicações graves da malária com possível evolução para insuficiência renal aguda (IRA), eque pode ser fatal. Desenvolvimento de estratégias preventivas de combate aos distúrbios renaisassociados à malária requer conhecimento dos aspectos clínicos e epidemiológicos da doença,diagnóstico precoce e correto, além de terapêutica antimalárica.

Objective: presentation of nephrotic syndrome case due to falciparum malaria. Case report:school child, 8 years old, female, admitted at Municipal Hospital of Tailândia, Pará, with historyof fever, edema, dark urine and oliguria. Because the patient evolved with anuria, she wastransferred to Fundação Santa Casa de Misericórdia do Pará (FSCM-PA), where she wasdiagnosed with nephrotic syndrome secondary to Plasmodium falciparum malaria, based onanamnesis, physical examination, and laboratory exams. The patient had clinical andparasitological response to antimalarial therapy, being discharged to control at Clinical EssayMalaria Program at Evandro Chagas Institute and in a Nephrology Outpatient Unit. Finalconsideration: renal involvement is one of the serious complications of malaria. It can progressto acute renal failure (ARF), and may be fatal. Development of preventive strategies againstkidney disorders due to malaria infection requires knowledge of epidemiological and clinicalfeatures of the disease, accurate and prompt diagnosis and antimalarial therapy.

Multifocal Electroretinography after High Dose Chloroquine Therapy for Malaria

Purpose: To investigate changes in multifocal electroretinography (mfERG) parameters associated with high dose chloroquine therapy for treatment of malaria in the Amazonia region of Brazil. Methods: Forty-eight subjects who had received chloroquine treatment for single or multiple malaria infections with a cumulative dose ranging from 1,050 to 27,000mg were included. The control group consisted of 37 healthy aged-matched subjects. Data was collected on amplitude and implicit time of the N1, P1 and N2 waves in the central macular hexagon (R1) and in five concentric rings at different retinal eccentriciti (R2-R6). Results: No significant difference was observed in any mfERG parameter between chloroquine treated patients and control subjects. A comparison with previous data obtained from patients with rheumatologic disorders in the same region of Brazil who had received larger cumulative doses of chloroquine and had displayed mfERG changes, indicated that retinal toxicity seems to be dependent on cumulative dose. Conclusion: Lack of mfERG changes in the current study suggests that intensive high dose chloroquine therapy for treatment of malaria is not associated with retinal toxicity. (AU)

Genetic polymorphism of the serine rich antigen N-terminal region in Plasmodium falciparum field isolates from Brazil.

In this work we investigated the frequency of polymorphism in exon II of the gene encoding most of the amino-terminal region of the serine rich antigen (SERA) in Plasmodium falciparum field samples. The blood samples were collected from P. falciparum infected individuals in three areas of the Brazilian Amazon. Two fragments have been characterized by polymerase chain reaction: one of 175 bp corresponding to the repeat region with 5 octamer units and one other of 199 bp related to the 6 repeat octamer units of SERA protein. The 199 bp fragment was the predominant one in all the studied areas. The higher frequency of this fragment has not been described before and could be explained by an immunological selection of the plasmodial population in the infected individuals under study. Since repeat motifs in the amino-terminal region of SERA contain epitopes recognized by parasite-inhibitor antibodies, data reported here suggest that the analysis of the polymorphism of P. falciparum isolates in different geographical areas is a preliminary stage before the final drawing of an universal vaccine against malaria can be reached.

Characterisation of pvmdr1 and pvdhfr genes associated with chemoresistance in Brazilian Plasmodium vivax isolates

Plasmodium vivax control is now being hampered by drug resistance. Orthologous Plasmodium falciparum genes linked to chloroquine or sulfadoxine-pyrimethamine chemoresistance have been identified in P. vivax parasites, but few studies have been performed. The goal of the present work is to characterise pvmdr1 and pvdhfr genes in parasite isolates from a Brazilian endemic area where no molecular investigation had been previously conducted. The pvmdr1 analysis revealed the existence of single (85.7 percent) and double (14.3 percent) mutant haplotypes, while the pvdhfr examination showed the presence of double (57.2 percent) and triple (42.8 percent) mutant haplotypes. The implications of these findings are discussed.

Fator de Necrose Tumoral Alfa eGravidade Clínica em Primoinfectadospelo Plasmodium Vivax / Tumor Necrosis Factor Alpha and Clinical Severity in Non-Immune Plasmodium Vivax

Avaliar a relação entre o FNT-α, a gravidade daapresentaçمo clيnica e a trombocitopenia, além da freqüênciado FNT2 e sua influência sobre os nيveis da citocina. Materiale Métodos: Foram avaliados pacientes primoinfectados peloP. vivax, ³ 15 anos, provenientes de Belém, Parل, com sintomashل £ 21 dias, atendidos e acompanhados clinicamente noInstituto Evandro Chagas (IEC) ou hospitalizados. A parasitemiafoi quantificada todos os dias até a negativaçمo. Adotou-se acloroquina e a primaquina por via oral, durante sete dias,como tratamento. Amostras sanguيneas foram coletadas emD0 e D7 para anلlises hematolَgicas e bioquيmicas, tيtulos doFNT-α e a freqüência do FNT2. Os programas Biostat 2.0 eExcel-Windows foram utilizados para as anلlises estatيsticasdas diferenças e das correlaçُes entre os parâmetros obtidos.Resultados: Oitenta e três pacientes foram atendidos eacompanhados clinicamente no D0, D1, D2, D3 e D7, defevereiro/2002 a março/2003. O FNT-α se correlacionoupositivamente e significativamente com a parasitemia (rs =0,33; p < 0,01) e com os escores clيnicos (rs = 0,48; p = 0,0001),porém negativamente com as plaquetas (rs = -0,48; p < 0,001)em D0. Os nيveis elevados de FNT-a foram responsلveis pelaintensidade das manifestaçُes clيnicas e pela trombocitopenianestes pacientes, porém o FNT2 nمo produziu tيtulos altos dacitocina. Conseqüentemente, tيtulos elevados de FNT-a forambenéficos na maioria dos casos, a plaquetopenia é um sinalde gravidade e outros fatores genéticos foram responsلveispelos nيveis elevados dessa citocina nesta amostra...

Evaluate the relationship between the TNF-a, theseverity of clinical presentation, the thrombocytopenia, thefrequency of TNF2 and its influence over cytokine levels.Material e Methods: We evaluated patients with first episodeof vivax malaria, ³ 15 years, with disease duration £ 21 days,coming from the city of Belém, Parل, attended at the InstitutoEvandro Chagas (IEC) or hospitalized. The parasitemia wasquantified every day till the negativation. The adoptedtreatment was cloroquine and primaquine PO, during sevendays. Blood samples were collected at D0 and D7 to realizequantification of hematological and biochemical parameters,TNF-a titles and TNF2 frequency. The programs Biostat 2.0and Excel for Windows were applied to analyze the differencesand correlations between the parameters. Results: Eighty threepatients were attended and accompanied clinically at D0, D1,D2, D3 and D7, from february/2002 till march/2003. TheTNF-a level correlated positively and significantly withparasitemia (rs = 0.33, p < 0.01) and clinical scores (rs = 0.48,p = 0.0001), but negatively with the platelets (rs = -0.48, p <0.0001) at D0. Consequently, high titles of TNF-a levels werebeneficial to the majority of the cases; the thrombocytopeniais a signal of severity, and others genetic factors were responsiblefor the high levels of this cytokine and phenotypicmanifestations on this sample...

Some aspects of the behavior of the hypothalamus-pituitary-adrenal axis in patients with uncomplicated Plasmodium falciparum malaria: cortisol and dehydroepiandrosterone levels

We studied the behavior of cortisol and dehydroepiandrosterone (DHEA) in 24 patients with uncomplicated Plasmodium falciparum malaria of the Evandro Chagas Institute, Belem, Para, Brazil. The patients were evaluated before treatment (Day 0), 24h after the beginning of medication (Day 1) and on Day 8 of follow-up (Day 7). Steroid levels were correlated with parasitemia, temperature and time of the disease. The levels of these hormones were found to be significantly higher on Day 0 than on Day 7, showing no correlation with parasitemia or temperature, but temperature had a positive effect on the correlation between cortisol and dehydroepiandrosterone. Cortisol was not correlated with the time of disease, but a significant negative correlation was observed between DHEA and time of disease on Day 7, suggesting a decline in the adrenal reserve of this steroid. In conclusion, an increase in cortisol and dehydroepiandrosterone is observed in patients with falciparum malaria, with these levels declining with decreasing parasitemia. The finding that temperature interfered with the correlation between cortisol and dehydroepiandrosterone suggests a common mechanism for the activation of these hormones in malaria...(AU)

Uma proposta de prevenção e controle da malária em pequenas comunidades / A proposal of prevention and control of the malaria in small communities

Objetivo: sugerir estratégias de prevenção e controle para diminuir a incidência da malária em comunidades do entorno do Lago do Reservatório da Usina Hidrelétrica de Tucuruí. Método: para fundamentar esta proposta, fez-se necessário uma revisão da literatura sobre aspectos da doença, prevenção em saúde e as contribuições da Psicologia necessárias ao desenvolvimento de tecnologias comportamentais em estudos de intervenção em saúde. Conclusão: a educação tem um papel relevante na busca de prevenção e controle da malária. A formação de agentes comunitários capacitados em analisar os fatores de riscos de transmissão da malária e treinados para desenvolver os problemas de acordo com os elementos estruturais do sistema de saúde nos níveis micro, meso e macro, pode favorecer a luta contra a malária em pequenas comunidades...(AU)

Genetic polymorphism of the serine rich antigen N-terminal region in Plasmodium falciparum field isolates from Brazil

In this work we investigated the frequency of polymorphism in exon II of the gene encoding most of the amino-terminal region of the serine rich antigen (SERA) in Plasmodium falciparum field samples. The blood samples were colleted from P. falciparum infected individuals in three areas of the Brazilian Amazon. Two fragments have been characterized by polymerase chain reaction: one of 175 bp corresponding to the repeat region with 5 octamer units and one other of 199 bp related to the 6 repeat octamer units of SERA protein. The 199 bp fragment was the predominant one in all the studied areas. The higher frequency of this fragment has not been described before and could be explained by an immunological selection of the plasmodial population in the infected individuals under study. Since repeat motifs in the amino-terminal region of SERA contain epitopes recognized by parasite-inhibitor antibodies, data reported here suggest that the analysis of the polymorphism of P. falciparum isolates in different geographical areas is a preliminary stage before the final drawing of an universal vaccine against malaria can be reached...(AU)

Genetic polymorphism of the serine rich antigen N-terminal region in Plasmodium falciparum field isolates from Brazil

In this work we investigated the frequency of polymorphism in exon II of the gene encoding most of the amino-terminal region of the serine rich antigen (SERA) in Plasmodium falciparum field samples. The blood samples were colleted from P. falciparum infected individuals in three areas of the Brazilian Amazon. Two fragments have been characterized by polymerase chain reaction: one of 175 bp corresponding to the repeat region with 5 octamer units and one other of 199 bp related to the 6 repeat octamer units of SERA protein. The 199 bp fragment was the predominant one in all the studied areas. The higher frequency of this fragment has not been described before and could be explained by an immunological selection of the plasmodial population in the infected individuals under study. Since repeat motifs in the amino-terminal region of SERA contain epitopes recognized by parasite-inhibitor antibodies, data reported here suggest that the analysis of the polymorphism of P. falciparum isolates in different geographical areas is a preliminary stage before the final drawing of an universal vaccine against malaria can be reached.

Epidemiological distribution of Plasmodium falciparum drug resistance in Brazil and its relevance to the treatment and controlof malaria

With the use of a simple formulary, field by health agents was ewstablished a monitoring programme for responses of P. falciparum to the antimalarial drugs. This monitoring programme is emphasized for knowledge of the epidemiology of the drug resistance and the control of malaria falciparum in Amazonan Basin where occurs more than 95% of Brazilian malaria cases every year. It was demonstrated that still now 4-aminoquinolines have a great importance for the mortality control in areas where just SUCAM (National Health Foundation - Health Ministry) agenst are present without any medical assistance. The results obtained permitted the simplification of malaria treatment in Brazil Important conclusions were established in the field of malaria drug resistance

Lipidemia de índios Kayapós primitivos habitando a Amazônia Brasileira

O teor sangüíneo de colesterol, triglicérides e lipoproteínas foi determinado em dezoito índios Kayapós saudáveis, não civilizados, habitantes das florestas da Amazônia brasileira. Os valores obtidos foram comparados ao de outros grupos residentes em Belém, a saber: militares (10 indivíduos), trabalhadores do porto (10), médicos sedentários (5), trabalhadores urbanos (5), futebolistas profissionais (5). Também foram estudados 10 trabalhadores rurais, exercendo atividades profissionais nas cercanias de Belém. Os índios Kayapós e os rurícolas apresentaram níveis de colesterol, triglicérides e lipoproteínas inferiores aos habitantes da cidade. O fator dietético (menor ingestão calórica, de gorduras e de hidratos de carbono de estrutura simples) é o mais importante na determinação desta diferença, embora outros possíveis fatores (como menor estresse, atividade física importante) possam ser considerados. Destaque-se o fato de que todos os grupos apresentaram alta ingestão protéica, especialmente sob forma de peixes.

Assessment of chloroquine single dose treatment of malaria due to Plasmodium vivax in Brazilian Amazon

Malaria regions of the Amazon basin have been characterized by difficult access and non-compliance of the patients to treatment. In an attempt to assess the schizonticide efficacy of chloroquine in a single dose of 600 mg, the authors realized a double-blind, placebo-controlled trial in 132 outpatients with vivax malaria. Patients were distributed into two groups: group CPLA, given chloroquine 600 mg (single dose) on the first day of treatment, and two doses of placebo on second and third days. Group CHLO, given chloroquine 600 mg on first day and 450 mg on second and third day. Geometric means of the parasite density during the follow-up was similar in both groups. No differences were observed in the parasitological cure between the two groups (p = 0.442). There was clinical and parasitological efficacy in treatment of patients given a single-dose of chloroquine. This suggests that its restricted use could be indicated in remote areas of Brazilian Amazon Region, nevertheless the inadequate response of three patients indicates the need for further studies.

A importância do perfil clínico-laboratorial no diagnóstico diferencial entre malária e hepatite aguda viral / Importance of clinical and laboratory profiles for the differential diagnosis of malaria and acute viral hepatitis

OBJETIVOS: Destacar o perfil clínico-laboratorial de malária e hepatite aguda viral em dois grupos de crianças, ressaltando semelhanças e diferenças entre os dois quadros; subsidiar o aumento da sensibilidade clínica de presunçäo diagnóstica precoce de malária na infância. MÉTODOS: Foram estudados dois grupos de 30 crianças, de dois a dez anos de idade, portadoras de primo infecçäo malárica ou hepatite viral aguda, confirmados pela pesquisa de plasmódio e pesquisa de marcadores virais de hepatite A e B. As crianças foram submetidas às seguintes avaliaçöes no primeiro dia de atendimento: hemograma, contagem de plaquetas, dosagem de enzimas hepáticas, uréia, creatinina e bilirrubinas. Os achados clínicos e laboratoriais foram descritos e comparados entre os dois grupos. Proporçöes de indivíduos com exames físicos alterados foram comparadas nos dois grupos, pelo teste exato de Fisher. RESULTADOS: A apresentaçäo clínica inicial da doença foi semelhante em todos os pacientes: febre, cefaléia, sintomas digestivos e colúria. Metade dos portadores de malária näo apresentou a tríade clássica, apesar de todos terem apresentado febre moderada ou alta, ao contrário dos portadores de hepatite. Na avaliaçäo laboratorial, os portadores de malária apresentaram mais anemia e plaquetopenia quando comparados aos portadores de hepatite. Foram marcantes, nos portadores de hepatite, as elevaçöes de bilirrubinas e enzimas hepáticas. CONCLUSÖES: A propedêutica detalhada e a avaliaçäo criteriosa dos exames laboratoriais inespecíficos constituem peças fundamentais para a diferenciaçäo clínica entre os dois diagnósticos, reforçando a identificaçäo precoce do parasita e, conseqüentemente, o tratamento rápido de malária em crianças