Soluble triggering receptor expressed on myeloid cells-1 (sTREM-1) and other inflammatory mediators in malaria by Plasmodium vivax during enteroparasites coinfection.

Malaria is a major health issue with more than 200 million cases occurring annually. Moreover, in Malaria endemic area are frequently observed Malaria-enteroparasite co-infections associated with the modulation of inflammatory response. In this aspect, biomarkers play an important role in the disease prognosis. This study aimed to evaluate inflammatory mediators in malaria during coinfection with enteroparasites. A subset of serum samples already collected was analyzed and divided into four groups: Malaria (n = 34), Co-infected (n = 116), Enteroparasite (n = 120) and Control (n = 95). The serum levels of sTREM-1 and IL-6 were measured by ELISA. TNF-α, and IL-10 levels were previously carried out by flow cytometry. Higher serum levels of sTREM-1 and IL-6 were showed in malaria patients compared to healthy controls. In co-infected malarial patients sTREM-1 serum levels were similar to control group. Interestingly, co-infected malaria patients showed IL-6 serum levels decreased compared to individuals only infected with P. vivax. However, in Malaria patients and co-infected there was a positive correlation between the IL-6 and IL-10 levels (P < 0.0001). This is the first report of sTREM-1 levels in P. vivax infected. Moreover, the results revealing a divergent effect of co-infection with the increased balance between pro-and anti-inflammatory cytokines and reduced IL-6 levels but increases the anemia occurrence. The results also highlight the potential use of IL-6 as a biomarker for P. vivax and enteroparasites coinfection.

Contributing to Elimination of Cross-Border Malaria Through a Standardized Solution for Case Surveillance, Data Sharing, and Data Interpretation: Development of a Cross-Border Monitoring System.

BACKGROUND: Cross-border malaria is a significant obstacle to achieving malaria control and elimination worldwide. OBJECTIVE: This study aimed to build a cross-border surveillance system that can make comparable and qualified data available to all parties involved in malaria control between French Guiana and Brazil. METHODS: Data reconciliation rules based on expert knowledge were defined and applied to the heterogeneous data provided by the existing malaria surveillance systems of both countries. Visualization dashboards were designed to facilitate progressive data exploration, analysis, and interpretation. Dedicated advanced open source and robust software solutions were chosen to facilitate solution sharing and reuse. RESULTS: A database gathering the harmonized data on cross-border malaria epidemiology is updated monthly with new individual malaria cases from both countries. Online dashboards permit a progressive and user-friendly visualization of raw data and epidemiological indicators, in the form of time series, maps, and data quality indexes. The monitoring system was shown to be able to identify changes in time series that are related to control actions, as well as differentiated changes according to space and to population subgroups. CONCLUSIONS: This cross-border monitoring tool could help produce new scientific evidence on cross-border malaria dynamics, implementing cross-border cooperation for malaria control and elimination, and can be quickly adapted to other cross-border contexts.

Malária na fronteira do Brasil com a Guiana Francesa: a influência dos determinantes sociais e ambientais da saúde na permanência da doença / Malaria in the borders between Brazil and French Guiana: social and environmental health determinants and their influence on the permanence of the disease

Resumo O objetivo deste artigo é analisar a influência dos determinantes socioambientais da saúde na incidência de malária por Plasmodium vivax na fronteira franco-brasileira. O estudo foi realizado entre 2011 e 2015, no município de Oiapoque (AP), na Amazônia brasileira. Foram incluídos na amostra 253 indivíduos de ambos os sexos, de 10 a 60 anos de idade. Houve predominância de 63,64% (161/253) de casos de malária em adultos do sexo masculino. A faixa etária mais acometida foi de 20 a 29 anos, com 30% (76/253); 84,6% (214/253) dos pacientes não concluíram o ensino médio, e 29,6% (75/253) não concluíram o ensino primário. No aspecto ambiental, houve correlação negativa entre as precipitações pluviométricas e a incidência da malária por P. vivax (p=0,0026). Em termos de mobilidade, constatou-se considerável proporção de migrantes provenientes dos estados do Pará e do Maranhão (55,73%; 141/253). Por fim, os dados apontaram que 31,23% (79/253) dos casos de malária foram importados da Guiana Francesa. Em síntese, a transmissão da malária na fronteira franco-brasileira envolve fatores ecológico-ambientais, biológicos e sociais que se expressam na elevada vulnerabilidade social da população que vive e circula na zona fronteiriça, favorecendo a ocorrência de surtos e a permanência da enfermidade.

Abstract This study analyzes the influence of socio-environmental health determinants on the maintenance of Plasmodium vivax malaria at the borders between French Guiana and Brazil. This study was carried out between 2011 and 2015 in the city of Oiapoque, Amapá, situated in the Brazilian Amazon region. The sample included 253 individuals of both sexes aged between 10 and 60 years. The disease was predominant in 63.64% (161/253) adult males. The most affected age group was 20 to 29 years old, with 30% (76/253). About 84.6% did not complete high school, while 29.6% (75/253) of the cases had not finished the first degree. Concerning the environmental aspect, negative correlation was observed between rainfall and the incidence of P. vivax malaria (p=0.0026). In terms of mobility, there was a considerable influx of migrants from the states of Pará and Maranhão, with 55.73% (141/253). Lastly, the data indicated that 31.23% (79/253) of malaria cases were imported from French Guiana. In summary, the transmission of malaria in these particular borders involved ecological, environmental, biological and social factors, which are expressed in the high social vulnerability of the population living and circulating in the border zone, favoring the occurrence of outbreaks and the maintenance of the disease.

Enteroparasite and vivax malaria co-infection on the Brazil-French Guiana border: Epidemiological, haematological and immunological aspects.

Malaria-enteroparasitic co-infections are known for their endemicity. Although they are prevalent, little is known about their epidemiology and effect on the immune response. This study evaluated the effect of enteroparasite co-infections with malaria caused by Plasmodium vivax in a border area between Brazil and French Guiana. The cross sectional study took place in Oiapoque, a municipality of Amapá, on the Amazon border. Malaria was diagnosed using thick blood smears, haemoglobin dosage by an automated method and coproparasitology by the Hoffman and Faust methods. The anti-PvMSP-119 IgG antibodies in the plasma were evaluated using ELISA and Th1 (IFN-γ, TNF-α and IL-2), and Th2 (IL-4, IL-5 and IL-10) cytokine counts were performed by flow cytometry. The participants were grouped into those that were monoinfected with vivax malaria (M), vivax malaria-enteroparasite co-infected (CI), monoinfected with enteroparasite (E) and endemic controls (EC), who were negative for both diseases. 441 individuals were included and grouped according to their infection status: [M 6.9% (30/441)], [Cl 26.5% (117/441)], [E 32.4% (143/441)] and [EC 34.2% (151/441)]. Males prevailed among the (M) 77% (23/30) and (CI) 60% (70/117) groups. There was a difference in haemoglobin levels among the different groups under study for [EC-E], [EC-Cl], [E-M] and [Cl-M], with (p < 0.01). Anaemia was expressed as a percentage between individuals [CI-EC (p < 0.05)]. In terms of parasitaemia, there were differences for the groups [CI-M (p < 0.05)]. Anti-PvMSP-119 antibodies were detected in 51.2% (226/441) of the population. The level of cytokines evaluation revealed a large variation in TNF-α and IL-10 concentrations in the co-infected group. In this study we did not observe any influence of coinfection on the acquisition of IgG antibodies against PvMSP119, as well as on the profile of the cytokines that characterize the Th1 and Th2 patterns. However, co-infection increased TNF-α and IL-10 levels.

Prevalência de uropatógenos no laboratório de saúde pública de Macapá ­ AP entre 2009 e 2012 / Uropathogens prevalence in public health laboratory Macapá ­ AP between 2009 and 2012

Objetivo: Investigar a prevalência de uropatógenos de usuários atendidos no Laboratório Central de Saúde Pública de Macapá no período de 2009 a 2012. Métodos: Trata-se de um estudo retrospectivo de corte transversal, realizado no Laboratório Central de Saúde Públicade Macapá no período de 2009 a 2012, identificando os principais microrganismos responsáveis por infecções do trato urinário. O universo amostral foi composto pela população ambulatorial e hospitalar atendida no laboratório, sendo realizado o teste qui-quadrado. Os resultados foram expressos em números absolutos e em porcentagens utilizando-se o Programa Bioestat (5.0) e Excel Windows (2010). Resultados: Os resultados foram avaliados pela frequência das variáveis e analisados pelo teste qui-quadrado, destacando-se comocritérios: ocorrência, gênero, idade e o tipo de microrganismo causador e apresentados por meio de tabelas e gráficos. Das 10.026 (100%) uroculturas, observaram-se 7.758 (77,38%) com resultado negativo e 2.268 (22,62%) com resultado positivo. Os casos positivos foram separados em quatro grandes grupos: Enterobactérias ­ 1.422 (62,70%); Cocos Gram positivos ­ 663 (29,23%); Bacilo Gram negativo não fermentador ­102 (4,50%) e Fungo ­ 81 (3,57%). Os patógenos isolados mais prevalentes foram: Escherichia coli ­ 67,09%, Staphylococcus coagulase negativa ­ 20,8%, Acinetobacter baumanii ­ 38,23% e Candida albicans ­ 44,45%. Conclusão: O perfil epidemiológico de microrganismos e suas variáveis torna-se uma ferramenta imprescindível às investigações direcionadas à população susceptível. Tal conhecimento é relevante para a Saúde prestar maior assistência aos pacientes contribuindo para o planejamento, execução e avaliação das ações de prevenção, controle e tratamento

Objective: To investigate the prevalence of uropathogens of users served at the Central Laboratory of Public Health Macapá the period 2009 to 2012. Methods: This is a retrospective cross-sectional study, carried out at the Central Laboratory of Public Health Macapá the period 2009 to 2012, identifying key microorganisms responsible for urinary tract infections. The sample was composed of the Universe out patient population treated at the hospital and laboratory, which performed the chi-square test. Results were expressed in absolute numbers and in percentage using the Program Bioestat (5.0) and Windows Excel (2010). Results: The results were evaluated by variable frequency and analyzed by chi-square test, especially as criteria: occurrence, gender, age and type of causative microorganism and were presented descriptively and analytically through tables and graphs. Of 10.026 (100%) urine culture, there was 7.758 (77.38%) with negative and 2.268 (22.62%) with positive results. Positive cases were separated into four groups: Enterobacteria 1.422 (62.70%); Cocos Gram positive 663 (29.23%), Gram negative bacillus not fermentor 102 (4.50%) and Fungus 81 (3, 57%). The most prevalent pathogens isolated were Escherichia coli ­ 67.09%, 20.8% coagulase-negative Staphylococcus, Acinetobacter baumannii ­ 38.23% and 44.45% Candida albicans. Conclusion: The epidemiological profile of microorganisms and their variables becomes an indispensable tool for investigations directed at susceptible population. Such knowledge is relevant to health provide greater patient care by contributing to the planning, implementation and evaluation of prevention, control and treatment

Recurrence of Plasmodium falciparum after treatment with quinine and doxycycline in the Amazon basin.

OBJECTIVE: To investigate whether the recurrence of infection by Plasmodium falciparum in patients from the Brazilian Amazon was caused by an inadequate exposure to quinine. METHODS: A retrospective study was carried out using blood samples from patients with slide-confirmed infection by P. falciparum, classified according to the parasitological response after 28 days of follow-up. Quinine and doxycycline were measured in plasma samples by high-performance liquid chromatography. A statistical model was used to estimate parasite clearance rates. RESULTS: Six of 40 patients who met the criteria for inclusion in the study showed recurrence of parasitaemia within 28 days after the commencement of treatment. A group of six patients with adequate parasitological response was formed to avoid bias when the variables were compared. Parasitaemia at admission was similar in both groups. Plasma quinine concentrations were similar in both groups on days 1, 2 and 3 and ranged from 1.07 to 4.35 µg/ml in cured patients and from 1.1 to 3.2 µg/ml in patients with parasite recurrence. Concentrations of doxycycline were similar in both groups on day 3. The parasite clearance rate constant was 0.131 ± 0.16 h in the cured patients and 0.117 ± 0.02 h in those showing recurrence. The slope half-life in the cured patients was 4.8 h and 5.4 h in recurrence cases. The hillslope of the cured group (14.24) increased sharply compared to the recurrence group (4.13). CONCLUSION: There is evidence of a decreased in vivo sensitivity to quinine of P. falciparum strains in the Brazilian Amazon basin.

Patient age does not affect mefloquine concentrations in erythrocytes and plasma during the acute phase of falciparum malaria

Abstract Objective To evaluate whether patient age has a significant impact on mefloquine concentrations in the plasma and erythrocytes over the course of treatment for uncomplicated falciparum malaria. Methods A total of 20 children aged between 8 and 11 years and 20 adult males aged between 22 and 41 years with uncomplicated falciparum malaria were enrolled in the study. Mefloquine was administered to patients in both age groups at a dose of 20 mg kg−1. The steady-state drug concentrations were measured by reversed-phase high performance liquid chromatography. Results All patients had an undetectable mefloquine concentration on day 0. In adults, the plasma mefloquine concentrations ranged from 770 to 2930 ng mL−1 and the erythrocyte concentrations ranged from 2000 to 6030 ng mL−1. In children, plasma mefloquine concentrations ranged from 881 to 3300 ng mL−1 and erythrocyte concentrations ranged from 3000 to 4920 ng mL−1. There was no significant correlation between mefloquine concentrations in the plasma and erythrocytes in either adults or children. Conclusion In the present study, we observed no effect of patient age on the steady-state concentrations of mefloquine in the plasma and erythrocytes. We found that the mefloquine concentration in the erythrocytes was approximately 2.8-times higher than in the plasma. There were no significant correlations between mefloquine concentrations in the erythrocytes and plasma for either age group.

EVALUATION OF CIRCUMSPOROZOITE PROTEIN OF Plasmodium vivax TO ESTIMATE ITS PREVALENCE IN OIAPOQUE , AMAPÁ STATE, BRAZIL, BORDERING FRENCH GUIANA.

Malaria is a major health problem for people who live on the border between Brazil and French Guiana. Here we discuss Plasmodium vivax distribution pattern in the town of Oiapoque, Amapá State using the circumsporozoite (CS) gene as a marker. Ninety-one peripheral blood samples from P. vivax patients have been studied. Of these, 64 individuals were from the municipality of Oiapoque (Amapá State, Brazil) and 27 patients from French Guiana (August to December 2011). DNA extraction was performed, and a fragment of the P. vivax CS gene was subsequently analyzed using PCR/RFLP. The VK210 genotype was the most common in both countries (48.36% in Brazil and 14.28% in French Guiana), followed by the P. vivax-like (1.10% in both Brazil and French Guiana) and VK247 (1.10% only in Brazil) in single infections. We were able to detect all three CS genotypes simultaneously in mixed infections. There were no statistically significant differences either regarding infection site or parasitaemia among individuals with different genotypes. These results suggest that the same genotypes circulating in French Guiana are found in the municipality of Oiapoque in Brazil. These findings suggest that there may be a dispersion of parasitic populations occurring between the two countries. Most likely, this distribution is associated with prolonged and/or more complex transmission patterns of these genotypes in Brazil, bordering French Guiana.

Patient age does not affect mefloquine concentrations in erythrocytes and plasma during the acute phase of falciparum malaria.

OBJECTIVE: To evaluate whether patient age has a significant impact on mefloquine concentrations in the plasma and erythrocytes over the course of treatment for uncomplicated falciparum malaria. METHODS: A total of 20 children aged between 8 and 11 years and 20 adult males aged between 22 and 41 years with uncomplicated falciparum malaria were enrolled in the study. Mefloquine was administered to patients in both age groups at a dose of 20mgkg(-1). The steady-state drug concentrations were measured by reversed-phase high performance liquid chromatography. RESULTS: All patients had an undetectable mefloquine concentration on day 0. In adults, the plasma mefloquine concentrations ranged from 770 to 2930ngmL(-1) and the erythrocyte concentrations ranged from 2000 to 6030ngmL(-1). In children, plasma mefloquine concentrations ranged from 881 to 3300ngmL(-1) and erythrocyte concentrations ranged from 3000 to 4920ngmL(-1). There was no significant correlation between mefloquine concentrations in the plasma and erythrocytes in either adults or children. CONCLUSION: In the present study, we observed no effect of patient age on the steady-state concentrations of mefloquine in the plasma and erythrocytes. We found that the mefloquine concentration in the erythrocytes was approximately 2.8-times higher than in the plasma. There were no significant correlations between mefloquine concentrations in the erythrocytes and plasma for either age group.

[Methemoglobinemia in patients with Plasmodium vivax receiving oral therapy with primaquine]. / Metemoglobinemia em pacientes com malária por Plasmodium vivax em uso oral de primaquina.

INTRODUCTION: Primaquine can produce adverse reactions as toxicity to blood when used in the treatment of vivax malaria. This work aimed to determine methemoglobinemia in patients with vivax malaria receiving oral therapy with primaquine. METHODS: Spectrophotometric quantification of methemoglobinemia and qualitative assay for glucose-6-phosphate dehydrogenase. RESULTS: Methemoglobinemia ranged from 2.85 to 5.45% in male patients and 3.77 to 7.34% in female patients. CONCLUSIONS: A statistically significant increase in methemoglobinemia was observed following oral therapy with primaquine, with no clinical manifestations, and independent of sex and the qualitative expression of glucose-6-phosphate dehydrogenase.

Metemoglobinemia em pacientes com malária por Plasmodium vivax em uso oral de primaquina / Methemoglobinemia in patients with Plasmodium vivax receiving oral therapy with primaquine

INTRODUÇÃO: A primaquina pode acarretar sérios eventos adversos, com destaque para a toxicidade ao sangue. O objetivo deste trabalho é determinar a metemoglobinemia de 20 pacientes com malária por Plasmodium vivax tratados com primaquina, comparando-os segundo o sexo e a expressão da glicose-6-fosfato desidrogenase. MÉTODOS: Quantificação da metemoglobina por espectrofotometria visível e avaliação qualitativa da glicose-6-fosfato desidrogenase. RESULTADOS: A metemoglobinemia variou de 2,85 a 5,45 por cento nos pacientes do sexo masculino e de 3,77 a 7,34 por cento no feminino. CONCLUSÕES: A instituição da terapia aumentou de maneira significativa os teores de metemoglobina, sem manifestação clínica evidente e independente do sexo e da atividade enzimática.

INTRODUCTION: Primaquine can produce adverse reactions as toxicity to blood when used in the treatment of vivax malaria. This work aimed to determine methemoglobinemia in patients with vivax malaria receiving oral therapy with primaquine. METHODS: Spectrophotometric quantification of methemoglobinemia and qualitative assay for glucose-6-phosphate dehydrogenase. RESULTS: Methemoglobinemia ranged from 2.85 to 5.45 percent in male patients and 3.77 to 7.34 percent in female patients. CONCLUSIONS: A statistically significant increase in methemoglobinemia was observed following oral therapy with primaquine, with no clinical manifestations, and independent of sex and the qualitative expression of glucose-6-phosphate dehydrogenase.