Malaria in the State of Amazonas: a typical Brazilian tropical disease influenced by waves of economic development.

In Brazil, more than 99% of malaria cases are reported in the Amazon, and the State of Amazonas accounts for 40% of this total. However, the accumulated experience and challenges in controlling malaria in this region in recent decades have not been reported. Throughout the first economic cycle during the rubber boom (1879 to 1912), malaria was recorded in the entire state, with the highest incidence in the villages near the Madeira River in the Southern part of the State of Amazonas. In the 1970s, during the second economic development cycle, the economy turned to the industrial sector and demanded a large labor force, resulting in a large migratory influx to the capital Manaus. Over time, a gradual increase in malaria transmission was observed in peri-urban areas. In the 1990s, the stimulation of agroforestry, particularly fish farming, led to the formation of permanent Anopheline breeding sites and increased malaria in settlements. The estimation of environmental impacts and the planning of measures to mitigate them, as seen in the construction of the Coari-Manaus gas pipeline, proved effective. Considering the changes occurred since the Amsterdam Conference in 1992, disease control has been based on early diagnosis and treatment, but the development of parasites that are resistant to major antimalarial drugs in Brazilian Amazon has posed a new challenge. Despite the decreased lethality and the gradual decrease in the number of malaria cases, disease elimination, which should be associated with government programs for economic development in the region, continues to be a challenge.

Malaria in the State of Amazonas: a typical Brazilian tropical disease influenced by waves of economic development

In Brazil, more than 99% of malaria cases are reported in the Amazon, and the State of Amazonas accounts for 40% of this total. However, the accumulated experience and challenges in controlling malaria in this region in recent decades have not been reported. Throughout the first economic cycle during the rubber boom (1879 to 1912), malaria was recorded in the entire state, with the highest incidence in the villages near the Madeira River in the Southern part of the State of Amazonas. In the 1970s, during the second economic development cycle, the economy turned to the industrial sector and demanded a large labor force, resulting in a large migratory influx to the capital Manaus. Over time, a gradual increase in malaria transmission was observed in peri-urban areas. In the 1990s, the stimulation of agroforestry, particularly fish farming, led to the formation of permanent Anopheline breeding sites and increased malaria in settlements. The estimation of environmental impacts and the planning of measures to mitigate them, as seen in the construction of the Coari-Manaus gas pipeline, proved effective. Considering the changes occurred since the Amsterdam Conference in 1992, disease control has been based on early diagnosis and treatment, but the development of parasites that are resistant to major antimalarial drugs in Brazilian Amazon has posed a new challenge. Despite the decreased lethality and the gradual decrease in the number of malaria cases, disease elimination, which should be associated with government programs for economic development in the region, continues to be a challenge.

Construindo consensos para o SUS / Building consensus for SUS

Em julho de 2015, durante dois dias, o CONASS realizou o Seminário para a Construção de Consensos, desenvolvendo uma programação previamente aprovada pela Assembleia realizada em junho na cidade de João Pessoa, quando foi mencionada a importância da participação dos secretários, o que de fato realmente ocorreu.

O papel das Secretarias Estaduais de Saúde na Construção da Hemorrede Pública: uma reflexão sobreo compartilhamento de responsabilidades em face aodesafio do fornecimento de plasma à Hemobrás / The role of State Health Departments in the construction of Hemorrede: a reflection on sharing responsibilities in meeting the challenge of providing plasma to Hemobrás

O Brasil vem implantando sua hemorrede nacional, levando assistência hemoterápica aos serviços de saúde. A implantação das hemorredes estaduais estabeleceu a participação dos Estados no esforço de consolidar a Política Nacional de Sangue, Componentese Hemoderivados, implementada pelo Sistema Nacional do Sangue – SINASAN. Garantir atendimento hemoterápico é responsabilidade das hemorredes estaduais, que agora passam o fornecimento de plasma à Hemobrás, com qualidade e em quantidade suficiente. A hemorrede tem dificuldades para obter sangue de doadores voluntários. Ações integradase mais investimentos para a melhoria da sua qualificação técnica e gerencial são necessários. Nessa perspectiva, este trabalho apresenta uma reflexão das relações intergovernamentais na gestão da hemoterapia, das dificuldades das hemorredes e o esforço da gestãocompartilhada para o fornecimento do plasma qualificado à Hemobrás.

Brazil has been implementing its National Hemorrede, taking hemotherapy care to health services. The deployment of regional Hemorredes established the participation of statesin efforts to consolidate the National Policy on Blood, Blood Components and Blood Products, implemented by the National Blood System – SINASAN. Ensuring hemotherapeutic complianceis the responsibility of regional Hemorredes, who now supply plasma to Hemobrás, with quality and in sufficient quantity. The Hemorrede have trouble getting blood from volunteer donors.Integrated actions and investments are needed to improve their technical and managerial. In this perspective, it presents a reflection of the intergovernmental relations in the management of hemotherapeudic, the difficulties of Hemorredes and the effort of shared management to supply of plasma qualified to Hemobrás.

Comparative study of serologic tests for the diagnosis of asymptomatic visceral leishmaniasis in an endemic area.

Serologic tests have been widely used for the diagnosis of asymptomatic visceral leishmaniasis. This study evaluated five serologic tests used for the diagnosis of asymptomatic infection: enzyme-linked immunosorbent assay (ELISA) using promastigote antigen (ELISAp), ELISA using recombinant K39 (ELISA rK39), and K26 (ELISA rK26) antigens, an indirect immunofluorescence test using Leishmania (Leishmania) amazonensis promastigote antigen (IIFT), and an immunochromatographic test using rK39 antigen (TRALd). As a reference regarding the performance of the tests, patients with classic visceral leishmaniasis originating from Minas Gerais, Brazil (N = 36), were defined as the positive group and samples of healthy individuals from nonendemic areas (Argentina) (N = 127) were used as negative controls. Patients with other diseases such as cutaneous leishmaniasis (N = 53) and malaria (N = 56) were also studied to evaluate the chance of cross-reactivity in these tests. Finally, subjects from an area endemic for visceral leishmaniasis in Brazil (Porteirinha, northern Minas Gerais) (N = 1241) were screened for asymptomatic infection with Leishmania and Chagas disease. The sensitivity of the serologic tests was 50% (18/36), 66.7% (24/36), 69.4% (25/36), 83.3% (30/36), and 88.9% (32/36) for ELISAp, ELISA rK26, ELISA rK39, IIFT, and TRALd, respectively. Specificity, calculated using the truly negative group, was 96% (122/127) for TRALd, 97.6% (124/127) for ELISAp and IIFT, and 100% (127/127) for ELISA rK39 and rK26. Positivity in at least one test employing recombinant antigen was observed in 24 (45%) patients with cutaneous leishmaniasis and 47 (82.4%) with malaria. In the visceral leishmaniasis-endemic area, the positivity of the serologic tests ranged from 3.9% to 37.5%. The enzyme-linked immunosorbent assay (ELISA) tests using recombinant antigens were more frequently positive in subjects with a history of exposure to human or canine visceral leishmaniasis (ELISArK39: 14.6% [149/1017] versus 37.5% [84/224]; ELISA rK26: 12.7% [129/1017] versus 21.4% [48/224], P < 0.001 for both). Kappa agreement was low, with a maximum value of 0.449 between ELISAp and IIFT. In addition, among the 112 IIFT-positive subjects, 75 (67%) also presented positive serology for Chagas disease. In conclusion, IIFT and TRALd presented the best performance to diagnose classic cases of visceral leishmaniasis in an endemic area. Cross-reactivity of the tests with Chagas disease, cutaneous leishmaniasis, and malaria should be taken into account. However, the differences in the positivity of the tests used, together with the low agreement between results, do not permit to select the best test for the diagnosis of asymptomatic Leishmania infection.

Glucose-6-phosphate dehydrogenase deficiency in an endemic area for malaria in Manaus: a cross-sectional survey in the Brazilian Amazon.

BACKGROUND: There is a paucity of information regarding glucose-6-phosphate dehydrogenase (G6PD) deficiency in endemic areas for malaria in Latin America. METHODOLOGY/PRINCIPAL FINDINGS: This study determined the prevalence of the G6PD deficiency in 200 male non-consanguineous individuals residing in the Ismail Aziz Community, on the outskirts of Manaus (Brazilian Amazon). Six individuals (3%) were deficient using the qualitative Brewer's test. Gel electrophoresis showed that five of these patients were G6PD A(-). The deficiency was not associated with the ethnic origin (P = 0.571). In a multivariate logistic regression analysis, G6PD deficiency protected against three or more episodes of malaria (P = 0.049), independently of the age, and was associated with a history of jaundice (P = 0.020) and need of blood transfusion (P = 0.045) during previous treatment for malarial infection, independently of the age and the previous malarial exposure. CONCLUSIONS/SIGNIFICANCE: The frequency of G6PD deficiency was similar to other studies performed in Brazil and the finding of a predominant G6PD A(-) variant will help the clinical management of patients with drug-induced haemolysis. The history of jaundice and blood transfusion during previous malarial infection may trigger the screening of patients for G6PD deficiency. The apparent protection against multiple malarial infections in an area primarily endemic for Plasmodium vivax needs further investigation.

Night and crepuscular mosquitoes and risk of vector-borne diseases in areas of piassaba extraction in the middle Negro River basin, state of Amazonas, Brazil.

A study of crepuscular and night-biting mosquitoes was conducted at remote settlements along the Padauiri River, middle Negro River, state of Amazonas, Brazil. Collections were performed with human bait and a CDC-light trap on three consecutive days per month from June 2003-May 2004. In total, 1,203 h of collection were performed, of which 384 were outside and 819 were inside houses. At total of 11,612 specimens were captured, and Anophelinae (6.01%) were much less frequent than Culicinae (93.94%). Anopheles darlingi was the most frequent Anophelinae collected. Among the culicines, 2,666 Culex (Ae.) clastrieri Casal & Garcia, 2,394 Culex. (Mel.) vomerifer Komp, and 1,252 Culex (Mel.) eastor Dyar were the most frequent species collected. The diversity of insects found reveals the receptivity of the area towards a variety of diseases facilitated by the presence of vectors involved in the transmission of Plasmodium, arboviruses and other infectious agents.

Night and crepuscular mosquitoes and risk of vector-borne diseases in areas of piassaba extraction in the middle Negro River basin, state of Amazonas, Brazil

A study of crepuscular and night-biting mosquitoes was conducted at remote settlements along the Padauiri River, middle Negro River, state of Amazonas, Brazil. Collections were performed with human bait and a CDC-light trap on three consecutive days per month from June 2003-May 2004. In total, 1,203 h of collection were performed, of which 384 were outside and 819 were inside houses. At total of 11,612 specimens were captured, and Anophelinae (6.01 percent) were much less frequent than Culicinae (93.94 percent). Anopheles darlingi was the most frequent Anophelinae collected. Among the culicines, 2,666 Culex (Ae.) clastrieri Casal & Garcia, 2,394 Culex. (Mel.) vomerifer Komp, and 1,252 Culex (Mel.) eastor Dyar were the most frequent species collected. The diversity of insects found reveals the receptivity of the area towards a variety of diseases facilitated by the presence of vectors involved in the transmission of Plasmodium, arboviruses and other infectious agents.

[Molecular diagnosing of malaria in a tertiary care center in the Brazilian Amazon region]. / Diagnóstico molecular da malária em uma unidade de atenção terciária na Amazônia Brasileira.

The routine test for diagnosing malaria is still the thick blood smear, despite its known decreased sensitivity and specificity in situations of low parasite density and mixed infections. The polymerase chain reaction is increasingly being used for molecular detection and identification of Plasmodium species, due to its higher sensitivity and specificity. Nested PCR was performed on whole-blood samples from 344 patients with acute febrile syndrome who came to a tertiary healthcare center in Manaus (State of Amazonas) for diagnostic confirmation of malaria. No malaria cases caused by Plasmodium malariae were detected through the blood smear or PCR. Co-positivity of 96.7%, co-negativity of 62.2% and kappa coefficient of 0.44 were observed between PCR and thick blood smear for Plasmodium falciparum. For Plasmodium vivax, co-positivity of 100%, co-negativity of 78.1% and kappa coefficient of 0.56 were observed. For mixed infection, co-positivity of 100%, co-negativity of 84.9% and kappa coefficient of 0.26 were observed. Polymerase chain reaction detected a high number of mixed infections in the samples analyzed, but its routine use for diagnosing malaria still deserves further discussion.

Diagnóstico molecular da malária em uma unidade de atenção terciária na Amazônia Brasileira / Molecular diagnosing of malaria in a tertiary care center in the Brazilian Amazon region

O exame de rotina para o diagnóstico da malária continua sendo a gota espessa, apesar da comprovada diminuição da sensibilidade e especificidade em situações de densidade parasitária baixa e infecções mistas. A reação em cadeia da polimerase vem sendo cada vez mais utilizada para a detecção molecular e identificação das espécies de plasmódio, por apresentar maior sensibilidade e especificidade. Foi realizada a nested-PCR em amostras de sangue total de 344 pacientes com síndrome febril aguda que se apresentaram para o diagnóstico de malária, em uma unidade terciária de saúde, em Manaus (Amazonas). Nenhum caso de malária por Plasmodium malariae foi diagnosticado à gota espessa ou PCR. Observou-se co-positividade de 96,7 por cento, co-negatividade de 62,2 por cento e coeficiente kappa de 0,44 entre PCR e gota espessa para Plasmodium falciparum. Para Plasmodium vivax, co-positividade de 100 por cento, co-negatividade de 78,1 por cento e coeficiente kappa de 0,56. Na detecção da malária mista, co-positividade de 100 por cento, co-negatividade de 84,9 por cento e coeficiente kappa de 0,26. A reação em cadeia da polimerase detectou alto número de infecções mistas nas amostras analisadas, mas seu uso rotineiro no diagnóstico da malária merece ainda ampla discussão.

The routine test for diagnosing malaria is still the thick blood smear, despite its known decreased sensitivity and specificity in situations of low parasite density and mixed infections. The polymerase chain reaction is increasingly being used for molecular detection and identification of Plasmodium species, due to its higher sensitivity and specificity. Nested PCR was performed on whole-blood samples from 344 patients with acute febrile syndrome who came to a tertiary healthcare center in Manaus (State of Amazonas) for diagnostic confirmation of malaria. No malaria cases caused by Plasmodium malariae were detected through the blood smear or PCR. Co-positivity of 96.7 percent, co-negativity of 62.2 percent and kappa coefficient of 0.44 were observed between PCR and thick blood smear for Plasmodium falciparum. For Plasmodium vivax, co-positivity of 100 percent, co-negativity of 78.1 percent and kappa coefficient of 0.56 were observed. For mixed infection, co-positivity of 100 percent, co-negativity of 84.9 percent and kappa coefficient of 0.26 were observed. Polymerase chain reaction detected a high number of mixed infections in the samples analyzed, but its routine use for diagnosing malaria still deserves further discussion.

[Association of methemoglobinemia and glucose-6-phosphate dehydrogenase deficiency in malaria patients treated with primaquine]. / Associação de metemoglobinemia e deficiência de glicose-6-fosfato desidrogenase em pacientes com malária tratados com primaquina.

This study had the aim of investigating occurrences of methemoglobinemia among individuals with glucose-6-phosphate dehydrogenase deficiency during treatment for malaria infection using primaquine. Patients with a diagnosis of malaria caused by Plasmodium vivax or the V+F mixture (Plasmodium vivax + Plasmodium falciparum) were selected. Group 1 consisted of 74 individuals with a clinical diagnosis of methemoglobinemia and Group 2 consisted of 161 individuals without a clinical diagnosis of methemoglobinemia. The glucose-6-phosphate dehydrogenase deficiency rates (numbers of enzymopenic individuals) in Groups 1 and 2 were 51.3% (38) and 8.7% (14) respectively. These data demonstrated a statistically significant association with methemoglobinemia only among the individuals in Group 1 (p<0.05). Investigation of the relationship between methemoglobinemia and glucose-6-phosphate dehydrogenase deficiency showed that there was a possible association such that enzymopenic individuals may develop methemoglobinemia more frequently.

Associação de metemoglobinemia e deficiência de glicose-6-fosfato desidrogenase em pacientes com malária tratados com primaquina / Association of methemoglobinemia and glucose-6-phosphate dehydrogenase deficiency in malaria patients treated with primaquine

Este estudo teve como objetivo verificar a ocorrência de metemoglobinemia em indivíduos deficientes da glicose-6-fosfato desidrogenase durante o tratamento da infecção malárica com primaquina. Foram selecionados pacientes com diagnóstico para malária por Plasmodium vivax ou mista V+F (Plasmodium vivax + Plasmodium falciparum), Grupo 1: com 74 indivíduos com diagnóstico clínico de metemoglobinemia e Grupo 2: 161 indivíduos sem diagnóstico clínico de metemoglobinemia. Quanto à deficiência da G6PD, nos Grupos 1 e 2, houveram 51,3 por cento (38) e 8,7 por cento (14) de indivíduos enzimopênicos, respectivamente, demonstrando através de tais dados, significância estatística na associação com a metemoglobinemia somente nos indivíduos do Grupo 1 (p<0,05). A comparação da relação da metemoglobinemia à deficiência da G6PD mostrou haver uma possível associação de indivíduos enzimopênicos desenvolverem metemoglobinemia com maior freqüência.

This study had the aim of investigating occurrences of methemoglobinemia among individuals with glucose-6-phosphate dehydrogenase deficiency during treatment for malaria infection using primaquine. Patients with a diagnosis of malaria caused by Plasmodium vivax or the V+F mixture (Plasmodium vivax + Plasmodium falciparum) were selected. Group 1 consisted of 74 individuals with a clinical diagnosis of methemoglobinemia and Group 2 consisted of 161 individuals without a clinical diagnosis of methemoglobinemia. The glucose-6-phosphate dehydrogenase deficiency rates (numbers of enzymopenic individuals) in Groups 1 and 2 were 51.3 percent (38) and 8.7 percent (14) respectively. These data demonstrated a statistically significant association with methemoglobinemia only among the individuals in Group 1 (p<0.05). Investigation of the relationship between methemoglobinemia and glucose-6-phosphate dehydrogenase deficiency showed that there was a possible association such that enzymopenic individuals may develop methemoglobinemia more frequently.

In vitro inhibition of Plasmodium falciparum by substances isolated from Amazonian antimalarial plants.

In the present study, a quassinoid, neosergeolide, isolated from the roots and stems of Picrolemma sprucei (Simaroubaceae), the indole alkaloids ellipticine and aspidocarpine, isolated from the bark of Aspidosperma vargasii and A. desmanthum (Apocynaceae), respectively, and 4-nerolidylcatechol, isolated from the roots of Pothomorphe peltata (Piperaceae), all presented significant in vitro inhibition (more active than quinine and chloroquine) of the multi-drug resistant K1 strain of Plasmodium falciparum. Neosergeolide presented activity in the nanomolar range. This is the first report on the antimalarial activity of these known, natural compounds. This is also the first report on the isolation of aspidocarpine from A. desmanthum. These compounds are good candidates for pre-clinical tests as novel lead structures with the aim of finding new antimalarial prototypes and lend support to the traditional use of the plants from which these compounds are derived.

In vitro inhibition of Plasmodium falciparum by substances isolated from Amazonian antimalarial plants

In the present study, a quassinoid, neosergeolide, isolated from the roots and stems of Picrolemma sprucei (Simaroubaceae), the indole alkaloids ellipticine and aspidocarpine, isolated from the bark of Aspidosperma vargasii and A. desmanthum (Apocynaceae), respectively, and 4-nerolidylcatechol, isolated from the roots of Pothomorphe peltata (Piperaceae), all presented significant in vitro inhibition (more active than quinine and chloroquine) of the multi-drug resistant K1 strain of Plasmodium falciparum. Neosergeolide presented activity in the nanomolar range. This is the first report on the antimalarial activity of these known, natural compounds. This is also the first report on the isolation of aspidocarpine from A. desmanthum. These compounds are good candidates for pre-clinical tests as novel lead structures with the aim of finding new antimalarial prototypes and lend support to the traditional use of the plants from which these compounds are derived.

[Evaluation of the Optimal-IT and ICT P.f./P.v. rapid dipstick tests for diagnosing malaria within primary healthcare in the municipality of Manaus, Amazonas]. / Avaliação dos testes rápidos Optimal-IT e ICT P.f./P.v. para o diagnóstico da malária, na Atenção Básica de Saúde, no município de Manaus, Amazonas.

Malaria is routinely diagnosed using the thick blood smear test. However, this technique requires the training of microscopists and may be time-consuming. A concordance study was conducted on two dipstick tests (Optimal-IT and ICT P.f./P.v.) and the thick blood smear test, within primary healthcare in Manaus.

Avaliação dos testes rápidos Optimal-IT® e ICT P.f./P.v.® para o diagnóstico da malária, na Atenção Básica de Saúde, no município de Manaus, Amazonas / Evaluation of the Optimal-IT® and ICT Pf/Pv® rapid dipstick tests for diagnosing malaria within primary healthcare in the municipality of Manaus, Amazonas

O diagnóstico da malária é realizado rotineiramente pelo exame da gota espessa, entretanto, esta técnica requer o treinamento de microscopistas e pode consumir muito tempo. Foi realizado um estudo de concordância de dois testes rápidos (Optimal-IT® e ICT P.f./P.v.®) com a gota espessa, na atenção básica de saúde, em Manaus.

Malaria is routinely diagnosed using the thick blood smear test. However, this technique requires the training of microscopists and may be time-consuming. A concordance study was conducted on two dipstick tests (Optimal-IT® and ICT P.f./P.v.®) and the thick blood smear test, within primary healthcare in Manaus.