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.

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.

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.

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.

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.

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.

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.

Doenças exantemáticas e primeira epidemia de dengue ocorrida em Manaus, Amazonas, no período de 1998-1999 / Exanthematous diseases and the first epidemic of dengue to occur in Manaus, Amazonas State, Brazil, during 1998-1999

Em 1998, a Fundação de Medicina Tropical/Instituto de Medicina Tropical do Amazonas implementou o sistema de vigilância para síndromes febris agudas indiferenciadas, com o propósito de manter vigilância ativa e passiva na Amazônia Ocidental, Brasil, permitindo identificar e diagnosticar os agentes etiológicos causadores de febres agudas. O diagnóstico foi realizado através de estudos sorológicos para a detecção de anticorpos IgM, utilizando-se técnicas de ELISA (Enzyme-linked-immunosorbent assay) e kits ELISA comerciais. Foram analisadas 8.557 amostras de soros de pacientes com suspeita clínica de dengue, 40 por cento dos soros foram ELISA positivos para o vírus da dengue e 26 por cento dos soros foram ELISA positivos para outras doenças exantemáticas virais como rubéola, sarampo, parvovírus, oropouche e mayaro.

Dengue hemorrhagic fever and acute hepatitis: a case report

Dengue fever is the world's most important viral hemorrhagic fever disease, the most geographically wide-spread of the arthropod-born viruses, and it causes a wide clinical spectrum of disease. We report a case of dengue hemorrhagic fever complicated by acute hepatitis. The initial picture of classical dengue fever was followed by painful liver enlargement, vomiting, hematemesis, epistaxis and diarrhea. Severe liver injury was detected by laboratory investigation, according to a syndromic surveillance protocol, expressed in a self-limiting pattern and the patient had a complete recovery. The serological tests for hepatitis and yellow fever viruses were negative. MAC-ELISA for dengue was positive.

Non-planed urbanization as a contributing factor for malaria incidence in Manaus-Amazonas, Brazil

OBJETIVOS: Estudio de la dinámica de malaria en Manaos y su relación con la expansión urbana de la ciudad y los factores ambientales relacionados con la enfermedad. El objetivo es analizar como la forma de ocupación de la ciudad, la urbanización y factores relacionados al ambiente contribuyen en la instalación, aumento y/o manutención de la malaria en el área urbana de Manaus-Amazonas, Brasil. METODOLOGÍA: Se realizó un estudio retrospectivo sobre la epidemiología de la malaria en el período de 1986 a 1997: levantamiento de datos sobre la evolución y expansión urbana de la ciudad de Manaus. Los datos fueron analizados descriptivamente, buscando relación con aspectos ambientales de la urbanización y la forma de crecimiento de la ciudad de Manaos, y cómo contribuyó en la epidemiología de la malaria en la ciudad. RESULTADOS: Los resultados apuntan a la importancia que tiene el ambiente en el mantenimiento de la endemia de malaria, y también, la influencia de las intervenciones humanas en los cambios del ecosistema, dejando el ambiente urbano con las condiciones favorables para la proliferación del Anopheles, transmisor del parásito. CONCLUSIÓN: La asociación de estos elementos favorecen el mantenimiento de la endemia de malaria en el área urbana de Manaos.

Febre hemorrágica do dengue em lactentes: relato de dois casos / Dengue hemorrhagic fever in infants: report of two cases

Dois casos de lactentes atendidos na Fundação de Medicina Tropical do Amazonas, com síndrome febril exantemática aguda, extravasamento capilar e manifestações hemorrágicas de pequena magnitude, caracterizando quadro de febre hemorrágica do dengue. O diagnóstico etiológico foi confirmado pelo MAC-ELISA e pelo ELISA de inibição para IgG, realizados nos lactentes e nas respectivas mães.

Malaria during pregnancy in a reference centre from the Brazilian Amazon: unexpected increase in the frequency of Plasmodium falciparum infections

Malaria remains globally the most important parasitic disease of man. Data on its deleterious effects during pregnancy have been extensively documented in hyperendemic, holoendemic, and mesoendemic areas from Africa and Asia where Plasmodium falciparum is responsible for almost all infections. However, knowledge about malaria during pregnancy in areas where transmission is unstable and P. vivax is the most prevalent species, such as the Brazilian Amazon, is scarce. Here, we report a preliminary cross sectional descriptive study, carried out at the Fundação de Medicina Tropical do Amazonas, a reference centre for diagnosis and treatment of tropical diseases in the west-Amazon (Manaus, Brazil). A total of 1699 febrile childbearing age women had positive thick blood smears to Plasmodium species, between January and November 1997: 1401 (82.5 percent) were positive for P. vivax , 286 (16.8 percent) for P. falciparum and 12 (0.07 percent) carried mixed infections. From the malarious patients, 195 were pregnant. The ratio of P. falciparum to P. vivax infections in the group of non-pregnant infected women was 1:5.6 while it was 1:2.3 in that of pregnant infected ones. Similar rates or even proportionally more vivax infections during pregnancy were expected to occur, in function of the contraindication of primaquine with the resulting increased P. vivax relapse rates. Such an observation suggests that the mechanism of resistance/susceptibility to infection and/or malaria pathogenesis in pregnant women may differ according to Plasmodium species and that the extensively described increase in the frequencies of malaria infection during pregnancy may be specifically due to P. falciparum infection.

Registro da ocorrência de Aedes albopictus em área urbana do município de Manaus, Amazonas / Registration of the ocurrence of Aedes albopictus in an urban zone in Manaus, Amazonas, Brazil

A partir de exemplares de Aedes albopictus coletados em área urbana no município de Manaus, AM, Brasil, e das informações sobre a presença desse mosquito em vários municípios do Estado do Amazonas, registra-se pela primeira vez a introduçäo dessa espécie nesse Estado.

Fauna de Culicidae em municípios da zona rural do estado do Amazonas, com incidência de febre amarela / Culicidae insect fauna from rural zone in Amazonas State with incidence of sylvatic yellow fever

Em 1996, foi realizado um levantamento da fauna de Culicidae (coleta de adultos e imaturos) em cinco dos dez municípios onde foram registrados 14 casos de febre amarela silvestre (Rio Preto da Eva, Iranduba, Manacapuru, Manaquiri e Careiro). Os mosquitos foram coletados utilizando-se armadilhas de luz CDC, inspeções domiciliares e captura com tubos coletores para isca humana. Foram identificadas entre adultos e imaturos 36 espécies de Culicidae, entre estas, nove foram encontradas apenas na fase imatura. Dentre os adultos, coletou-se espécies de Haemagogus janthinomys, Ha. leucocelaenus e Aedes fulvus, incluídas entre os vetores de febre amarela silvestre

Tratamento de crianças com malária pelo Plasmodium falciparum com derivados da artemisinina / Treatment of children with malaria Plasmodium falciparum with derivatives artemisinin

No período compreendido entre janeiro de 1996 e dezembro de 1998, administramos derivados da artemisinina em 108 crianças com malária por Plasmodium falciparum, para avaliar a resposta clínica e terapêutica. Foram incluídas apenas crianças com clínica de malária moderada ou grave. No Grupo I, incluímos 62 pacientes e administramos artesunate por via endovenosa. Clinicamente, 50,8 por cento tinham malária moderada e 49,2 por cento malária grave; a parasitemia foi baixa em 53,2 por cento, média em 22,6 por cento e alta em 24,2 por cento; no D2 a parasitemia estava negativa em 58,1 por cento. No Grupo II,incluímos 46 pacientes que receberam artemeter (Paluter®) intramuscular. Clinicamente, 67,4 por cento apresentavam malária moderada e 32,6 por cento malária grave; a parasitemia foi baixa em 52,2 por cento, média em 36,2 por cento e alta em 15,2 por cento; em D2, 56,5 por cento apresentaram negativaçäo da parasitemia. Nos dois grupos, a melhora clínica e evoluçäo da parasitemia näo mostraram diferença estatística; no D7 havia clareada a parasitemia em todos os pacientes. Para evitar recrudescência usamos mefloquina ou clindamicina

Febre tifóide: recaída por resistência antimicrobiana. Relato de caso / Typhoid fever: relapse due to antimicrobial resistance. Case report

Relatamos pela primeira vez na Amazônia Brasileira um paciente com febre tifóide, com resistência clínica e laboratorial ao cloranfenicol, droga de escolha para esta doença em nossa regiäo. A recaída foi observada no 7° dia após o término do tratamento e a paciente foi tratada com ciprofloxacina