Geographical information system (GIS) modeling territory receptivity to strengthen entomological surveillance: Anopheles (Nyssorhynchus) case study in Rio de Janeiro State, Brazil.

BACKGROUND: Extra-Amazonian malaria mortality is 60 times higher than the Amazon malaria mortality. Imported cases correspond to approximately 90% of extra-Amazonian cases. Imported malaria could be a major problem if it occurs in areas with receptivity, because it can favor the occurrence of outbreaks or reintroductions of malaria in those areas. This study aimed to model territorial receptivity for malaria to serve as an entomological surveillance tool in the State of Rio de Janeiro, Brazil. Geomorphology, rainfall, temperature, and vegetation layers were used in the AHP process for the receptivity stratification of Rio de Janeiro State territory. RESULTS: The model predicted five receptivity classes: very low, low, medium, high and very high. The 'very high' class is the most important in the receptivity model, corresponding to areas with optimal environmental and climatological conditions to provide suitable larval habitats for Anopheles (Nyssorhynchus) vectors. This receptivity class covered 497.14 km2 or 1.18% of the state's area. The 'high' class covered the largest area, 17,557.98 km2, or 41.62% of the area of Rio de Janeiro State. CONCLUSIONS: We used freely available databases for modeling the distribution of receptive areas for malaria transmission in the State of Rio de Janeiro. This was a new and low-cost approach to support entomological surveillance efforts. Health workers in 'very high' and 'high' receptivity areas should be prepared to diagnose all febrile individuals and determine the cause of the fever, including malaria. Each malaria case must be treated and epidemiological studies must be conducted to prevent the reintroduction of the disease.

Dispensing and determinants of non-adherence to treatment for non complicated malaria caused by Plasmodium vivax and Plasmodium falciparum in high-risk municipalities in the Brazilian Amazon.

BACKGROUND: In Brazil, 99.7 % of malaria cases occur in the Amazon region. Although the number of cases is decreasing, the country accounted for almost 60 % of cases in the Americas Region, in 2013. Novel approaches for malaria treatment open the possibility of eliminating the disease, but suboptimal dispensing and lack of adherence influence treatment outcomes. The aim of this paper is to show the results on dispensing practices, non-adherence and determinants of non-adherence to treatment of non-complicated malaria. METHODS: The study was conducted in six high-risk municipalities with Plasmodium vivax and Plasmodium falciparum transmission in the Brazilian Amazon and based on the theoretical framework of the Mafalda Project, which included investigation of dispensing and adherence. The World Health Organization Rapid Evaluation Method has been used to estimate sample size. Individuals over 15 years of age with malaria were approached at health facilities and invited to participate through informed consent. Data was collected in chart review forms focusing on diagnosis, Plasmodium type, prescribing, and dispensing (kind, quantity, labelling and procedures). Follow-up household interviews complemented data collection at health facility. Non-adherence was measured during the implementation phase, by self-reports and pill-counts. Analysis was descriptive and statistical tests were carried out. Determinants of non-adherence and quality of dispensing were assessed according to the literature. RESULTS: The study involved 165 patients. Dispensing was done according to the national guidelines. Labelling was adequate for P. vivax but inadequate for P. falciparum medicines. Non-adherent patients were 12.1 % according to self-reports and 21.8 % according to pill-counts. Results point to greater non-adherence among all P. falciparum patients and among malaria non-naîve patients. More patients informed understanding adverse effects than 'how to use' anti-malarials. CONCLUSIONS: Non-adherent patients were mostly those with a P. falciparum diagnosis and those in their second or more malaria episode. New taxonomies and concepts on adherence stress the importance of focusing on the individual patient. Interventions targeted to and tailored for malaria patients must be addressed by health policy and implemented by managers and clinicians.

Simian malaria in the Brazilian Atlantic forest: first description of natural infection of capuchin monkeys (Cebinae subfamily) by Plasmodium simium.

BACKGROUND: In Brazil, two species of Plasmodium have been described infecting non-human primates, Plasmodium brasilianum and Plasmodium simium. These species are morphologically, genetically and immunologically indistinguishable from the human Plasmodium malariae and Plasmodium vivax parasites, respectively. Plasmodium simium has been observed naturally infecting monkeys of the genera Alouatta and Brachyteles in a restricted area of the Atlantic Forest in the south and southeast regions of Brazil. However, its reported geographical distribution and the diversity of its vertebrate hosts may be underestimated, since available data were largely based on analyses by microscopic examination of peripheral blood, a method with limited sensitivity, considering the potential sub-patent feature of these infections. The present study describes, for the first time, the natural infection of P. simium in capuchin monkeys from the Brazilian Atlantic Forest. METHODS: Blood samples from 30 non-human primates belonging to nine species kept in the Primate Centre of Rio de Janeiro were collected. Fragments of spleen and liver from one dead monkey found in the neighborhoods of the Primate Centre were also analysed. Molecular diagnosis was performed by nested PCR (18SSU rRNA) and the amplified fragment was sequenced. RESULTS: Thirty per cent of the captive animals were infected with P. simium and/or P. brasilianum. The dead monkey tested positive for DNA of P. simium. For the first time, Cebinae primates (two specimens of genus Cebus and two of genus Sapajos) were found naturally infected by P. simium. The infection was confirmed by sequencing a small fragment of 18SSU rRNA. CONCLUSION: The results highlight the possibility of infection by P. simium in other species of non-human primates whose impact could be significant for the malaria epidemiology among non-human primates and, if it becomes clear that this P. simium is able to infect monkeys and, eventually, man, also for the maintenance of transmission of human malaria in the context of a zoonosis in areas under influence of the Atlantic Forest.

Pharmaceutical services for endemic situations in the Brazilian Amazon: organization of services and prescribing practices for Plasmodium vivax and Plasmodium falciparum non-complicated malaria in high-risk municipalities.

BACKGROUND: In spite of the fact that pharmaceutical services are an essential component of all malaria programmes, quality of these services has been little explored in the literature. This study presents the first results of the application of an evaluation model of pharmaceutical services in high-risk municipalities of the Amazon region, focusing on indicators regarding organization of services and prescribing according to national guidelines. METHODS: A theoretical framework of pharmaceutical services for non-complicated malaria was built based on the Rapid Evaluation Method (WHO). The framework included organization of services and prescribing, among other activities. The study was carried out in 15 primary health facilities in six high-risk municipalities of the Brazilian Amazon. Malaria individuals ≥ 15 years old were approached and data was collected using specific instruments. Data was checked by independent reviewers and fed to a data bank through double-entry. Descriptive variables were analyzed. RESULTS: A copy of the official treatment guideline was found in 80% of the facilities; 67% presented an environment for receiving and prescribing patients. Re-supply of stocks followed a different timeline; no facilities adhered to forecasting methods for stock management. No shortages or expired anti-malarials were observed, but overstock was a common finding. On 86.7% of facilities, the average of good storage practices was 48%. Time between diagnosis and treatment was zero days. Of 601 patients interviewed, 453 were diagnosed for Plasmodium vivax; of these, 99.3% received indications for the first-line scheme. Different therapeutic schemes were given to Plasmodium falciparum patients. Twenty-eight (4.6%) out of 601 were prescribed regimens not listed in the national guideline. Only 5.7% individuals received a prescription or a written instruction of any kind. CONCLUSIONS: The results show that while diagnostic procedure is well established and functioning in the Brazilian malaria programme, prescribing is still an activity that is actually not performed. The absence of physicians and poor integration between malaria services and primary health services make for the lack of a prescription or written instruction for malaria patients throughout the Brazilian Amazon. This fact may lead to a great number of problems in rational use and in adherence to medication.

Variants in the toll-like receptor signaling pathway and clinical outcomes of malaria.

BACKGROUND: Malaria is one of the most significant infectious diseases in the world and is responsible for a large proportion of infant deaths. Toll-like receptors (TLRs), key components of innate immunity, are central to countering infection. Variants in the TLR-signaling pathway are associated with susceptibility to infectious diseases. METHODS: We genotyped single nucleotide polymorphisms (SNPs) of the genes associated with the TLR-signaling pathway in patients with mild malaria and individuals with asymptomatic Plasmodium infections by means of polymerase chain reaction. RESULTS: Genotype distributions for the TLR-1 I602S differed significantly between patients with mild malaria and persons with asymptomatic infection. The TLR-1 602S allele was associated with an odds ratio (OR) of 2.2 (P= .003; P(corrected)= .015) for malaria among patients with mild malaria due to any Plasmodium species and 2.1 (P= .015; P(corrected)= .75) among patients with mild malaria due to Plasmodium falciparum only. The TLR-6 S249P SNP showed an excess of homozygotes for the TLR-6 249P allele in asymptomatic persons, compared with patients with mild malaria due to any Plasmodium species (OR 2.1; 95% confidence interval [CI], 1.1- 4.2; P= .01; P(corrected)= .05), suggesting that the TLR-6 249S allele may be a risk factor for malaria (OR, 2.0; 95% CI, 1.1-3.7; P=0.01; P(corrected)= .05). The TLR-9 -1486C allele showed a strong association with high parasitemia (P< .001). CONCLUSIONS: Our findings indicate that the TLR-1 and TLR-6 variants are significantly associated with mild malaria, whereas the TLR-9-1486C/T variants are associated with high parasitemia. These discoveries may bring additional understanding to the pathogenesis of malaria.

Cross sectional study reveals a high percentage of asymptomatic Plasmodium vivax infection in the Amazon Rio Negro area, Brazil.

A parasitological, clinical, serological and molecular cross-sectional study carried out in a highly endemic malaria area of Rio Negro in the Amazon State, Brazil, revealed a high prevalence of asymptomatic Plasmodium vivax infection. A total of 109 persons from 25 families were studied in five villages. Ninety-nine inhabitants (90.8%) had at least one previous episode of malaria. Serology showed 85.7% and 46.9% of positivity when P. falciparum antigens and P. vivax MSP-1, respectively, were used. Twenty blood samples were PCR positive for P. vivax (20.4%) and no P. falciparum infection was evidenced by this technique. No individual presenting positive PCR reaction had clinical malaria during the survey neither in the six months before nor after, confirming that they were cases of asymptomatic infection. Only one 12 year old girl presented a positive thick blood smear for P. vivax. This is the first description of asymptomatic Plasmodium infection in this area studied.

Cross sectional study reveals a high percentage of asymptomatic Plasmodium vivax infection in the Amazon Rio Negro area, Brazil

A parasitological, clinical, serological and molecular cross-sectional study carried out in a highly endemic malaria area of Rio Negro in the Amazon State, Brazil, revealed a high prevalence of asymptomatic Plasmodium vivax infection. A total of 109 persons from 25 families were studied in five villages. Ninety-nine inhabitants (90.8 percent) had at least one previous episode of malaria. Serology showed 85.7 percent and 46.9 percent of positivity when P. falciparum antigens and P. vivax MSP-1, respectively, were used. Twenty blood samples were PCR positive for P. vivax (20.4 percent) and no P. falciparum infection was evidenced by this technique. No individual presenting positive PCR reaction had clinical malaria during the survey neither in the six months before nor after, confirming that they were cases of asymptomatic infection. Only one 12 year old girl presented a positive thick blood smear for P. vivax. This is the first description of asymptomatic Plasmodium infection in this area studied.

Um estudo seccional parasitológico, clínico, sorológico e molecular, realizado em uma área altamente endêmica para malária, no Rio Negro, Estado do Amazonas, revela alta prevalência de infecção assintomática por Plasmodium vivax. Um total de 109 pessoas de 25 famílias residentes em cinco comunidades do Rio Padauiri, afluente do Rio Negro, foram estudadas. Noventa por cento dos habitantes (90,8 por cento) tinham tido pelo menos um episodio prévio de malária. A sorologia mostrou 85,7 por cento e 46,9 por cento de positividade quando antígenos de P. falciparum e P. vivax MSP-1, foram respectivamente usados. Vinte amostras de sangue submetidas ao PCR foram positivas para P. vivax (20,4 por cento), entretanto, nenhuma foi positiva para o P. falciparum por esta técnica. Nenhum paciente com PCR positivo durante o inquérito e seis meses antes ou depois teve manifestações clínicas de malária, portanto, podemos afirmar que eram assintomáticos. Somente uma criança de 12 anos de idade teve gota espessa positiva para P. vivax. Esta é a primeira descrição de infecção assintomática por Plasmodium na área estudada.

Processo Saúde-Doença na Amazônia: o caso da fronteira Brasil/Colômbia.

Arquivo de áudio contendo o debate que discutiu o processo saúde-doença na fronteira do Brasil com a Colômbia e teve como palestrantes Martha C. Suárez-Mutis (IOC), Paulo Peiter (EPSJV) e Claudia Mora, Mestranda em Saúde Pública pela ENSP. O objetivo do encontro é discutir soluções para os problemas de saúde pública existentes em áreas de fronteira, principalmente na Colômbia e Peru, onde, na maioria das vezes, não existe assistência à saúde adequada para as doenças predominantes nestas áreas. Paulo Peiter abriu os debates expondo algumas características peculiares às fronteiras, como a elevada incidências de atividades ilícitas, entre elas o tráfico de drogas e de armas; a migração e a exploração sexual; e um número significativo de população flutuante nas cidades gêmeas, que mesmo sem o porte de cidade grande, acaba enfrentando problemas iguais ou maiores do que nas grandes metrópoles. Segundo Paulo, a área de saúde apresenta problemas típicos em áreas de fronteira, como o controle e o monitoramento de doenças transmissíveis e a perda ou falta de informações e registros no acompanhamento de casos de longo tratamento. O palestrante destaca que o Trapézio Amazônico é composto por cerca de 100 mil pessoas distribuídas nas cidades de Tabatinga, Benjamim Constant e Atalaia do Norte no Brasil, Letícia na Colômbia e Santa Rosa e Islândia no Peru, e por serem zonas de fronteiras de interconexão de redes sociais de diferentes origens, tornam-se muito mais suscetíveis e vulneráveis. A segunda palestrante foi Claudia Mora, que apresentou uma análise do cenário das Doenças Sexualmente Transmissíveis (DST) na fronteira Brasil/Colômbia, relatando sua experiência na implementação de Políticas de saúde sexual e reprodutiva na cidade de Letícia. Como colaboradora de diversos projetos de pesquisa na fronteira, Paula falou sobre DST, malária, hepatite e o cólera, que são hoje, as principais doenças na região. Apresenta alguns indicadores epidemiológicos e comportamentais, como o inicio precoce da sexualidade nos jovens da fronteira, a dificuldade no acesso aos serviços de saúde e o narcotráfico. Cita os principais indicadores de incidência de doenças na região, principalmente as sexualmente transmissíveis. Ao final de suas exposições, Paula alerta que o problema é grave, mas se forem realizadas ações de controle das DSTs nessas áreas, a epidemia poderá ser evitada. A última palestrante do dia, Martha Suárez-Mutis, apresentou uma análise da incidência da malária e do Cólera na tríplice fronteira, salientando que, hoje, a malária aparece em áreas de colonização como garimpos, periferias urbanas, áreas indígenas, áreas de extrativismo, entre outras. Apresenta dados que mostram que na região do Alto Solimões, Benjamin Constant tem a menor Incidência Parasitária Anual (IPA), alguns casos identificados de malária em crianças e números de casos de cólera na tríplice fronteira, entre 1991 e 1992. A pesquisadora também fez uma exposição sobre o vírus da Hepatite B que é a causa infecciosa mais importante de doenças hepáticas agudas e crônicas no mundo, além de ser uma das principais responsáveis pelo câncer de fígado e pela cirrose. Ao final de sua apresentação, Martha destacou que as ações conjuntas entre os países são indispensáveis para melhorar o estado de saúde das populações na fronteira.