Long COVID-19 syndrome associated with Omicron XBB.1.5 infection: a case report

BACKGROUND There is interest in lingering non-specific symptoms after severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, referred to as Long coronavirus disease 2019 (Long COVID-19). It remains unknown whether the risk of Long COVID-19 is associated with pre-existing comorbidities or initial COVID-19 severity, including infections due to new Omicron lineages which predominated in 2023. OBJECTIVES The aim of this case report was to characterize the clinical features of acute XBB.1.5 infection followed by Long COVID-19. METHODS We followed a 73-year old female resident of Rio de Janeiro with laboratory-confirmed SARS-CoV-2 during acute infection and subsequent months. The SARS-CoV-2 lineage was determined by genome sequencing. FINDINGS The participant denied comorbidities and had completed a two-dose vaccination schedule followed by two booster doses eight months prior to SARS-CoV-2 infection. Primary infection by viral lineage XBB.1.5. was clinically mild, but the participant subsequently reported persistent fatigue. MAIN CONCLUSIONS This case demonstrates that Long COVID-19 may develop even after mild disease due to SARS-CoV-2 in fully vaccinated and boosted individuals without comorbidities. Continued monitoring of new SARS-CoV-2 lineages and associated clinical outcomes is warranted. Measures to prevent infection should continue to be implemented including development of new vaccines and antivirals effective against novel variants.

Fatal Brazilian spotted fever in a healthy military man during field training in Rio de Janeiro city, southeastern Brazil

ABSTRACT Brazilian spotted fever, a zoonotic disease transmitted by ticks, is caused by Rickettsia rickettsii. We report a fulminant case of this zoonosis in a healthy 46-year-old military man in the urban region of Rio de Janeiro city, in October, 2021. Ticks and capybaras (Amblyomma sculptum, Hydrochoerus hydrochaeris, respectively) were identified in the military fields, pointing to the participation of this large synanthropic rodent, recognized as an efficient amplifier host of Rickettsia rickettsii in Brazil. As the military population is considered a risk group for spotted fever, it is necessary to alert health professionals to the importance of the early detection of the disease and its adequate management, mainly in populations that are particularly at risk of exposure to ticks, in order to avoid fatal outcomes.

Neurodevelopment in the third year of life in children with antenatal ZIKV-exposure

ABSTRACT We report cognitive, language and motor neurodevelopment, assessed by the Bayley-III test, in 31 non-microcephalic children at age 3 with PCR-confirmed maternal Zika virus exposure (Rio de Janeiro, 2015-2016). Most children had average neurodevelopmental scores, however, 8 children (26%) presented delay in some domain. Language was the most affected: 7 children (22.6%) had a delay in this domain (2 presenting severe delay). Moderate delay was detected in the cognitive (3.2%) and motor (10%) domains. Maternal illness in the third trimester of pregnancy and later gestational age at birth were associated with higher Bayley-III scores. Zika-exposed children require long-term follow-up until school age.

SARS-CoV-2 variant N. 9 identified in Rio de Janeiro, Brazil

BACKGROUND The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) B.1.1.33-derived lineage named N.9 was described recently in Brazil and it's considered a potential variant of interest (VOI) due to the presence of E484K substitution at the receptor-binding domain (RBD) of the Spike (S) protein. OBJECTIVE To describe the first detection of variant N.9 in Rio de Janeiro State. METHODS SARS-CoV-2 N.9 was confirmed by quantitative reverse transcription polymerase chain reaction (qRT-PCR), whole-genome sequencing and phylogenetic analysis. FINDINGS Here, we report two SARS-CoV-2 N.9 lineage strains in Rio de Janeiro. One of them had only the E484K substitution of the six N.9 lineage-defining mutations. Other three strains pre-defined as N.9 have the same genomic profile. These four strains are grouped within the B.1.1.33 lineage and basal to the N.9 lineage in our phylogenetic analysis, and we call them "N.9-like/B.1.1.33 + E484K". MAIN CONCLUSIONS The phylogenetic analysis shows four independent introductions of N.9 in the state of Rio de Janeiro in October and December 2020, January and March 2021. SARS-CoV-2 N.9 dissemination in the Rio de Janeiro could have been limited by the emergence and dominance of other variants, mainly by the lineage P.2 VOI Zeta that emerged in the same period and co-circulated with N.9, as observed in the neighboring State of São Paulo.

A populational-based birth cohort study in a low-income urban area in Rio de Janeiro, Brazil: implementation and description of the characteristics of the study / Um estudo de coorte de nascimento de base populacional em uma área urbana desfavorecida no Rio de Janeiro, Brasil: implementação e descrição das características do estudo / Estudio de una cohorte de nacimientos de base poblacional en un área urbana desfavorecida de Río de Janeiro, Brasil: implementación y descripción de las características del estudio

Abstract: A comprehensive cohort study including an entomological surveillance component can contribute to our knowledge of clinical aspects and transmission patterns of arbovirosis. This article describes the implementation of a populational-based birth cohort study that included an entomological surveillance component, and its associated challenges in a low-income community of Rio de Janeiro, Brazil. The participants were recruited in two periods: from 2012 to 2014, and from 2015 to 2017. The children had scheduled pediatric consultations and in case of fever. Epidemiological, clinical data and biological samples were collected at pediatric visits. Active febrile surveillance was performed by telephone calls, social networking, message apps, and household visits. A total of 387 newborns and 332 new children were included during the first and second recruitment periods, respectively. By July 2017, there were 451 children on follow-up. During the study, 2,759 pediatric visits were performed: 1,783 asymptomatic and 976 febrile/rash consultations. The number of febrile or rash consultations increased 3.5-fold after the use of media tools for surveillance. No temporal pattern, seasonality or peak of febrile cases was observed during the study period. A total of 10,105 adult mosquitoes (including 3,523 Aedes spp. and 6,582 Culex quinquefasciatus) and 46,047 Aedes eggs were collected from households, schools, and key sites. Although challenging, this structured sentinel populational-based birth cohort is relevant to the knowledge of risks and awareness of emerging pathogens.

Resumo: Estudos de coorte com um componente de vigilância epidemiológica podem contribuir para nosso conhecimento dos aspectos clínicos e dos padrões de transmissão de arboviroses. Este artigo descreve a implementação de um estudo de coorte de nascimento de base populacional que incluiu um componente de vigilância entomológica e desafios relacionados numa comunidade desfavorecida do Rio de Janeiro, Brasil. Os participantes foram recrutados em dois períodos: de 2012-2014 e de 2015-2017. As crianças tiveram consultas pediátricas agendadas e em caso de febre. Dados epidemiológicos, clínicos e amostras biológicas foram coletadas nas visitas pediátricas. A vigilância ativa febril foi realizada por meio de ligações telefônicas, redes sociais, aplicativos de mensagens e visitas domiciliares. Um total de 387 recém-nascidos e 332 novas crianças foram incluídas durante o primeiro e segundo períodos de recrutamento, respectivamente. Em Julho de 2017, havia 451 crianças em seguimento. Durante o estudo, foram realizadas 2.759 visitas pediátricas: 1.783 assintomáticas e 976 consultas por febre/exantema. O número de consultas por febre ou exantema aumentou 3,5 vezes após uso de ferramentas de mídia para vigilância. Nenhum padrão temporal, sazonalidade ou pico de casos de febre foi observado durante o período do estudo. Um total de 10.105 mosquitos adultos (incluindo 3.523 Aedes spp. e 6.582 Culex quinquefasciatus) e 46.047 ovos foram coletados de domicílios, escolas, e pontos estratégicos. Apesar dos desafios, esta coorte de nascimento sentinela de base populacional é relevante para o conhecimento dos riscos e de patógenos emergentes.

Resumen: Un estudio completro de cohorte que incluya una vigilancia entomológica puede contribuir a nuestro conocimiento de aspectos clínicos y patrones de transmisión de arbovirosis. Este artículo describe la implementación de un estudio poblacional de cohorte de nascimientos que incluyó el componente de vigilancia entomológica y los desafios asociados en una comunidad desfavorecida de Río de Janeiro, Brasil. Los participantes fueron captados en dos periodos: de 2012 a 2014 y de 2015 a 2017. Los niños tenían fijadas consultas pediátrica regulares y por fiebre. Durante las visitas pediátricas, se recogieron datos epidemiológicos y clínicos, así como muestras biológicas. Se realizó una vigilancia activa de la fiebre mediante llamadas telefónicas, redes sociales, aplicaciones de mensajes, y visitas a domicilio. Un total de 387 recién nacidos y 332 nuevos niños fueron incluidos durante el primer y segundo período de reclutamiento, respectivamente. En julio de 2017 se había realizado un seguimiento a 451 niños. Durante el estudio, se realizaron 2.759 visitas pediátricas: 1.783 asintomáticas y 976 por fiebre/urgencias. El número de consultas por fiebre o urgencias aumentó 3.5-veces tras el uso de herramientas de comunicación para la viglancia. No se observaron patrones temporales, estacionalidad o casos de picos de fiebre durante el periodo de estudio. Un total of 10.105 mosquitos adultos (incluyendo 3.523 Aedes spp. y 6.582 Culex quinquefasciatus) y 46.047 huevos fueron recogidos de viviendas, escuelas, y lugares estratégicos. A pesar de los retos, esta cohorte de nacimiento estructurada y supervisada, basada en población es relevante para el conocimiento de los riesgos y la concienciación sobre patógenos emergentes.

Lack of quadruple and quintuple mutant alleles associated with sulfadoxine-pyrimethamine resistance in Plasmodium vivax isolates from Brazilian endemic areas

BACKGROUND AND OBJECTIVE Brazil is responsible for a large number of Plasmodium vivax cases in America. Given the emergence of P. vivax parasites resistant to chloroquine and the effectiveness of antifolates in vivax malaria treatment together with a correlation between mutations in P. vivax dhfr and dhps genes and SP treatment failure, the point mutations in these genes were investigated. METHODS Blood samples from 54 patients experiencing vivax malaria symptomatic episodes in the Amazonian Region were investigated. Genomic DNA was extracted using a DNA extraction kit (QIAGENTM). Nested polymerase chain reaction (PCR) amplification was carried out followed by Sanger sequencing to detect single nucleotide polymorphisms (SNPs). FINDINGS All tested isolates showed non-synonymous mutations in pvdhfr gene: 117N (54/54, 100%) and 58R (25/54, 46%). Double mutant allele 58R/117N (FRTNI, 28%) was the most frequent followed by triple mutant alleles (58R/117N/173L, FRTNL, 11%; 58R/61M/117N, FRMNI, 5% 117N/173L, FSTNL, 4%) and quadruple mutant allele (58R/61M/117N/173L, FRMNL, 2%). A single mutation was observed at codon C383G in pvdhps gene (SGKAV, 48%). CONCLUSION No evidence of molecular signatures associated with P. vivax resistance to SP was observed in the Brazilian samples.

Surveillance of deaths caused by arboviruses in Brazil: from dengue to chikungunya

Did death occur DUE TO dengue, or in a patient WITH dengue virus infection? It seems a matter of semantics, but in fact, it underscores how challenging it is to distinguish whether the disease contributed to death, or was itself the underlying cause of death. Can a death be attributed to chikungunya virus, when some deaths occur after the acute phase? Did the virus decompensate the underlying diseases, leading to death? Did prolonged hospitalisation lead to infection, resulting in the patient's progression to death? Were there iatrogenic complications during patient care? The dengue question, for which there has not yet been a definitive response, resurfaces prominently under the chikungunya surveillance scenario. We are facing an epidemic of a disease that seems to be more lethal than previously thought. The major challenge ahead is to investigate deaths suspected of occurring due to arbovirus infections and to understand the role of each infection in the unfavourable outcome.

Zika puzzle in Brazil: peculiar conditions of viral introduction and dissemination: a review

This article discusses the peculiar conditions that favoured the unexpected introduction of Zika virus into the poorest northeastern region of Brazil in 2015, its speed of transmission to other Brazilian states, other Latin American countries and other regions, and the severity of related neurological disorders in newborns and adults. Contrasting with evidence that Zika had so far caused only mild cases in humans in the last six decades, the epidemiological scenario of this outbreak in Brazil indicates dramatic health effects: in 2015, an increase of 20-fold in notified cases of microcephaly and/or central nervous system (CNS) alterations suggestive of Zika congenital infection, followed by an exponential increase in 2016, with 2366 cumulative cases confirmed in the country by the end of December 2016. A significant increase in Guillain-Barré syndrome in adults has also been reported. Factors involved in viral dissemination, neural pathogenesis and routes of transmission in Brazil are examined, such as the role of social and environmental factors and the controversies involved in the hypothesis of antibody-dependent enhancement, to explain the incidence of congenital Zika syndrome in Brazil. Responses to the Zika outbreak and the development of new products are also discussed.

Trombose venosa profunda e vírus chicungunha / Deep venous thrombosis and chikungunya virus

Resumo Algumas infecções virais sistêmicas podem estar relacionadas ao desenvolvimento de trombose venosa profunda e/ou embolia pulmonar. Essa associação já está bem descrita em pacientes com infeções pelo vírus da imunodeficiência humana (HIV), hepatite C ou influenza. Recentemente introduzido no continente americano, o vírus chicungunha, agente etiológico da febre de chicungunha, ainda não tem essa relação bem sedimentada, mas com o aumento progressivo de sua incidência e pelo fato dessa infecção causar, muitas vezes, uma restrição severa da locomoção por poliartralgia e uma possível lesão endotelial direta, casos de tromboembolismo venoso podem começar a ser descritos. Neste relato de caso, descrevemos um paciente que desenvolveu trombose de veia poplítea direita durante internação para tratamento de febre por infecção por vírus chicungunha e poliartralgia severa.

Abstract Some systemic viral infections can be linked to development of deep venous thrombosis and/or pulmonary embolism. This association has already been well described in patients infected by human immunodeficiency virus (HIV), hepatitis C, and influenza. The chikungunya virus is the etiologic agent of chikungunya fever and it has recently been introduced to the American continent. As yet, there is no firm foundation for a relationship between chikungunya and thromboembolism, but the progressive increase in its incidence, the fact that this infection very often causes severe locomotion restrictions due to polyathralgia, and the possibility of direct endothelial injury suggest that cases of venous thromboembolism may begin to be described. In this case report, we describe a patient who developed thrombosis of the right popliteal vein after being admitted for treatment of severe polyathralgia and fever caused by chikungunya virus infection.

Clinical and laboratory signs associated to serious dengue disease in hospitalized children / Sinais clínicos e laboratoriais para o dengue com evolução grave em crianças hospitalizadas

Abstract Objective: To evaluate the validity of clinical and laboratory signs to serious dengue disease in hospitalized children. Methods: Retrospective cohort of children (<18 years) hospitalized with dengue diagnosis (2007-2008). Serious dengue disease was defined as death or use of advanced life support therapy. Accuracy measures and area under the receiver operating characteristic curve were calculated. Results: Of the total (n = 145), 53.1% were female, 69% aged 2-11 years, and 15.9% evolved to the worse outcome. Lethargy had the best accuracy (positive likelihood ratio >19 and negative likelihood ratio <0.6). Pleural effusion and abdominal distension had higher sensitivity (82.6%). History of bleeding (epistaxis, gingival or gastrointestinal bleeding) and severe hemorrhage (pulmonary or gastrointestinal bleeding) in physical examination were more frequent in serious dengue disease (p < 0.01), but with poor accuracy (positive likelihood ratio = 1.89 and 3.89; negative likelihood ratio = 0.53 and 0.60, respectively). Serum albumin was lower in serious dengue forms (p < 0.01). Despite statistical significance (p < 0.05), both groups presented thrombocytopenia. Platelets count, hematocrit, and hemoglobin parameters had area under the curve <0.5. Conclusions: Lethargy, abdominal distension, pleural effusion, and hypoalbuminemia were the best clinical and laboratorial markers of serious dengue disease in hospitalized children, while bleeding, severe hemorrhage, hemoconcentration and thrombocytopenia did not reach adequate diagnostic accuracy. In pediatric referral hospitals, the absence of hemoconcentration does not imply absence of plasma leakage, particularly in children with previous fluid replacement. These findings may contribute to the clinical management of dengue in children at referral hospitals.

Resumo Objetivo Avaliar a validade dos sinais clínicos e laboratoriais para o dengue com evolução grave em crianças hospitalizadas. Métodos Coorte retrospectivo de crianças (<18 anos) internadas com dengue (2007-2008). Evolução grave foi definida como óbito ou pelo uso de terapia de suporte avançado de vida. Foram calculadas medidas de acurácia e área sob a curva ROC. Resultados Do total (n = 145), 53,1% casos eram do sexo feminino, 69% de 2 a 11 anos e 15,9% evoluíram para gravidade. Letargia obteve a melhor acurácia (razão de verossimilhança positiva RVP > 19 e RV negativa RVN < 0,6). Derrame pleural e distensão abdominal apresentaram maior sensibilidade (se = 82,6%). Relato de sangramentos (epistaxe, gengivorragia ou gastrointestinal) e hemorragia grave (pulmonar ou gastrointestinal) presente no exame físico foi mais frequente nos casos com evolução grave (p <0,01), porém com baixa acurácia (RVP = 1,89 e 3,89; RVN = 0,53 e 0,60, respectivamente). Os níveis de albumina sérica foram mais baixos nas formas graves (p <0,01). Ambos os grupos apresentaram trombocitopenia, apesar da diferença estatística (p <0,05). Contagem de plaquetas, hematócrito e hemoglobina apresentaram área sob a curva ROC < 0,5. Conclusões Letargia, distensão abdominal, derrame pleural e hipoalbuminemia foram os melhores marcadores clínicos e laboratoriais de dengue com evolução grave em crianças hospitalizadas, enquanto sangramento, hemorragia grave, hemoconcentração e trombocitopenia não tiveram boa acurácia diagnóstica. Em hospitais de referência pediátricos, a ausência de hemoconcentração não implica ausência de extravasamento plasmático, particularmente quando há reposição anterior de volume. Esses resultados podem contribuir para o manejo clínico do dengue em crianças em hospitais de referência.

DENGUE DURING PREGNANCY: ASSOCIATION WITH LOW BIRTH WEIGHT AND PREMATURITY

The aim of this study was to evaluate the effects of dengue virus infection during pregnancy and its correlation with low birth weight, prematurity, and asphyxia. A non-concurrent cohort study reveals the association of dengue during pregnancy with prematurity and low birth weight, when birth occurred during the maternal-fetal viremia period (p = 0.016 and p < 0.0001, respectively).

First report of acute Chagas disease by vector transmission in Rio de Janeiro State, Brazil / Primeiro relato de doença de Chagas aguda por transmissão vetorial no Estado do Rio de Janeiro, Brasil

SUMMARYChagas disease (CD) is an endemic anthropozoonosis from Latin America of which the main means of transmission is the contact of skin lesions or mucosa with the feces of triatomine bugs infected by Trypanosoma cruzi. In this article, we describe the first acute CD case acquired by vector transmission in the Rio de Janeiro State and confirmed by parasitological, serological and PCR tests. The patient presented acute cardiomyopathy and pericardial effusion without cardiac tamponade. Together with fever and malaise, a 3 cm wide erythematous, non-pruritic, papule compatible with a "chagoma" was found on his left wrist. This case report draws attention to the possible transmission of CD by non-domiciled native vectors in non-endemic areas. Therefore, acute CD should be included in the diagnostic workout of febrile diseases and acute myopericarditis in Rio de Janeiro.

RESUMOA doença de Chagas é antropozoonose endêmica na América Latina que tem como principal mecanismo de transmissão humana o contato da pele lesada ou da mucosa com as fezes de triatomíneos infectados por Trypanosoma cruzi. Neste artigo descrevemos o primeiro caso de doença de Chagas aguda adquirida no Estado do Rio de Janeiro por transmissão vetorial com confirmação parasitológica, sorológica e pela PCR. O paciente apresentou miocardite aguda e derrame pericárdico de evolução benigna. Juntamente com as manifestações sistêmicas da fase aguda, foi notada pápula eritematosa de três cm de diâmetro compatível com chagoma em punho esquerdo. Este relato de caso chama a atenção para a possibilidade de transmissão da doença de Chagas por vetores nativos não domiciliados e em áreas consideradas indenes. Portanto, a doença de Chagas aguda deve ser incluída entre os diagnósticos diferenciais de doenças febris e miopericardites agudas no Rio de Janeiro.

Tradução e adaptação transcultural do instrumento da Organização Mundial da Saúde sobre o uso de sinais de alarme para dengue por profissionais de saúde / Translation and cross-cultural adaptation of the World Health Organization staff questionnaire on dengue warning signs for use in Brazil / Traducción y adaptación cultural del instrumento de la Organización Mundial de la Salud para el uso de signos de alarma sobre dengue por parte de profesionales de la salud

A identificação precoce de sinais de alarme e o tratamento de dengue grave são as principais estratégias para reduzir a letalidade da doença, principalmente em crianças, usualmente oligosintomáticas e com rápida progressão para o choque. O objetivo foi elaborar a versão brasileira do instrumento proposto pela Organização Mundial da Saúde (OMS) para avaliar o uso de sinais de alarme para dengue grave. Tradução e retrotradução do instrumento original em inglês, seguidas de um painel de especialistas, pré-teste (n = 13) e estudo piloto (n = 20) da versão preliminar. A comparação do instrumento original com a retrotradução mostrou que apenas 8 de 49 itens foram julgados como muito ou completamente alterados, três dos quais foram revistos. O painel de especialistas incluiu os sinais preconizados pelo Ministério da Saúde do Brasil. Na versão final do questionário, o item "classificação dos sinais de alarme" foi reformulado e a opção de resposta "não sei" foi excluída. A versão brasileira do instrumento da OMS permite avaliar o uso dos sinais de alarme, preconizados nos recentes manuais de dengue.

Early recognition of warning signs and treatment of severe dengue cases is the main strategy for reducing case-fatality, especially in children, who usually present few symptoms and can progress rapidly to dengue shock syndrome. The objective of this study was to elaborate the Brazilian version of the World Health Organization (WHO) staff questionnaire on the use and value of dengue warning signs, through translation and back-translation of the WHO questionnaire, followed by an expert panel consensus, pretest (n = 13), and pilot study (n = 20) of the preliminary version. Comparison of the original questionnaire in English and the back-translation showed that 8 of the 49 items had been extensively or completely altered, and three were rephrased. The expert panel added the warning signs listed by the Brazilian Ministry of Health. In the final version of the questionnaire, the item "ranking of warning signs" was rephrased and the answer option "do not know" was excluded. The Brazilian version of the WHO staff questionnaire allows assessing health professionals' experience and perceptions regarding the use of warning signs included in the recent dengue guidelines.

La detección precoz de los signos de alarma y el tratamiento de los casos graves de dengue constituyen la principal estrategia para reducir la letalidad, especialmente en niños, comúnmente oligosintomáticos y con rápida progresión hacia choques clínicos. El objetivo fue elaborar la versión brasileña del cuestionario de la Organización Mundial de la Salud (OMS), con el fin de evaluar el uso de los signos de alarma de dengue grave. Se realizó una traducción y retrotraducción del cuestionario en inglés, revisión por un panel de expertos, preprueba (n = 13) y un estudio piloto (n = 20) de la versión preliminar. La comparación del original con la retrotraducción mostró que 8 de los 49 ítems fueron considerados muy o completamente modificados, tres de los cuales fueron revisados. El panel de expertos incluyó los signos de alarma del Ministerio de Salud de Brasil. En la versión final, el ítem "ranking de los signos de alarma" fue revisado y se suprimió la opción de respuesta "no lo sé". La versión brasileña del cuestionario de la OMS permite evaluar el uso de los signos de alarma, recomendado en los actuales manuales sobre el dengue.

Malaria in Brazil: what happens outside the Amazonian endemic region

Brazil, a country of continental proportions, presents three profiles of malaria transmission. The first and most important numerically, occurs inside the Amazon. The Amazon accounts for approximately 60% of the nation’s territory and approximately 13% of the Brazilian population. This region hosts 99.5% of the nation’s malaria cases, which are predominantly caused by Plasmodium vivax (i.e., 82% of cases in 2013). The second involves imported malaria, which corresponds to malaria cases acquired outside the region where the individuals live or the diagnosis was made. These cases are imported from endemic regions of Brazil (i.e., the Amazon) or from other countries in South and Central America, Africa and Asia. Imported malaria comprised 89% of the cases found outside the area of active transmission in Brazil in 2013. These cases highlight an important question with respect to both therapeutic and epidemiological issues because patients, especially those with falciparum malaria, arriving in a region where the health professionals may not have experience with the clinical manifestations of malaria and its diagnosis could suffer dramatic consequences associated with a potential delay in treatment. Additionally, because the Anopheles vectors exist in most of the country, even a single case of malaria, if not diagnosed and treated immediately, may result in introduced cases, causing outbreaks and even introducing or reintroducing the disease to a non-endemic, receptive region. Cases introduced outside the Amazon usually occur in areas in which malaria was formerly endemic and are transmitted by competent vectors belonging to the subgenus Nyssorhynchus (i.e., Anopheles darlingi, Anopheles aquasalis and species of the Albitarsis complex). The third type of transmission accounts for only 0.05% of all cases and is caused by autochthonous malaria in the Atlantic Forest, located primarily along the southeastern Atlantic Coast. They are caused by parasites that seem to be (or to be very close to) P. vivax and, in a less extent, by Plasmodium malariae and it is transmitted by the bromeliad mosquito Anopheles (Kerteszia) cruzii. This paper deals mainly with the two profiles of malaria found outside the Amazon: the imported and ensuing introduced cases and the autochthonous cases. We also provide an update regarding the situation in Brazil and the Brazilian endemic Amazon.

Malaria in the state of Rio de Janeiro, Brazil, an Atlantic Forest area: an assessment using the health surveillance service

The lethality of malaria in the extra-Amazonian region is more than 70 times higher than in Amazonia itself. Recently, several studies have shown that autochthonous malaria is not a rare event in the Brazilian southeastern states in the Atlantic Forest biome. Information about autochthonous malaria in the state of Rio de Janeiro (RJ) is scarce. This study aims to assess malaria cases reported to the Health Surveillance System of the State of Rio de Janeiro between 2000-2010. An average of 90 cases per year had parasitological malaria confirmation by thick smear. The number of malaria notifications due to Plasmodium falciparum increased over time. Imported cases reported during the period studied were spread among 51% of the municipalities (counties) of the state. Only 35 cases (4.3%) were autochthonous, which represents an average of 3.8 new cases per year. Eleven municipalities reported autochthonous cases; within these, six could be characterised as areas of residual or new foci of malaria from the Atlantic Forest system. The other 28 municipalities could become receptive for transmission reintroduction. Cases occurred during all periods of the year, but 62.9% of cases were in the first semester of each year. Assessing vulnerability and receptivity conditions and vector ecology is imperative to establish the real risk of malaria reintroduction in RJ.

From primary care to hospitalization: clinical warning signs of severe dengue fever in children and adolescents during an outbreak in Rio de Janeiro, Brazil / Da atenção primária à hospitalização: sinais clínicos de alarme para dengue grave em crianças e adolescentes durante uma epidemia no Rio de Janeiro, Brasil / De la atención primaria a la hospitalización: señales clínicas de alarma del dengue grave en niños y adolescentes durante una epidemia en Río de Janeiro, Brasil

We analyzed factors associated with severe cases of dengue in children and adolescents hospitalized during the 2007/2008 epidemic in Rio de Janeiro, Brazil. This is a retrospective case-control study that covers 88 cases of severe dengue in patients admitted to four tertiary care children's hospitals. Controls consisted of 22 children with non-severe dengue living in the same neighborhood as the patients with severe dengue. Differences in prevalence of the clinical signs - abdominal pain, breathing difficulty, drowsiness or irritability - emerged on the third day after the onset of symptoms, in the febrile stage. Cases and controls received first medical care at the same clinical stage of disease. However, hospital admission of severe cases occurred later, on average between the third and fourth day after the onset of the disease. Early discharge of patients with fever whose condition could have progressed to severe dengue may have been a consequence of the type of medical assistance provided by primary care units, suggesting deficiencies both in the use of the risk classification protocol and patient triage.

Foram avaliados fatores associados à ocorrência de casos graves de dengue em crianças/adolescentes hospitalizados durante a epidemia de 2007/2008 no Rio de Janeiro, Brasil. Trata-se de estudo caso-controle retrospectivo com 88 casos graves de dengue, admitidos em quatro hospitais de atenção terciária infantil. Os controles foram 22 crianças com dengue não grave residentes na vizinhança dos casos. Foram observadas diferenças na prevalência de sinais clínicos - dor abdominal, dificuldade respiratória, sonolência/irritabilidade - a partir do terceiro dia do início dos sintomas, ainda na presença da febre. Casos e controles receberam o primeiro atendimento médico no mesmo estágio clínico da doença. Contudo, as hospitalizações dos casos graves ocorreram mais tardiamente, em média entre o terceiro e quarto dia da doença. A liberação precoce de pacientes com quadro febril e potencialmente graves pode ter sido consequência do atendimento médico prestado nas unidades de atenção primária, sugerindo deficiências na aplicação do protocolo de classificação de risco de dengue e triagem de pacientes.

Fueron evaluados factores asociados a la ocurrencia de casos graves de dengue en niños/adolescentes hospitalizados, durante la epidemia de 2007/2008 en Río de Janeiro, Brasil. Se trata de un estudio caso-control retrospectivo con 88 casos graves de dengue, admitidos en cuatro hospitales de atención terciaria infantil. Los controles se efectuaron con 22 niños con dengue no grave, residentes en los alrededores de los casos. Se observaron diferencias en la prevalencia de señales clínicas -dolor abdominal, dificultad respiratoria, somnolencia/irritabilidad- a partir del tercer día del inicio de los síntomas, todavía con presencia de fiebre. Casos y controles recibieron la primera atención médica en la misma fase clínica de la enfermedad. No obstante, las hospitalizaciones de los casos graves se produjeron más tardíamente, en media entre el tercer y cuarto día de la enfermedad. El alta precoz de pacientes con cuadro febril, y potencialmente graves, puede haber sido consecuencia de la atención médica prestada en las unidades de atención primaria, sugiriendo deficiencias en la aplicación del protocolo de clasificación de riesgo de dengue y selección de pacientes.

HLA-A*01 allele: a risk factor for dengue haemorrhagic fever in Brazil's population

Severe forms of dengue, such as dengue haemorrhagic fever (DHF) and dengue shock syndrome, are examples of a complex pathogenic mechanism in which the virus, environment and host immune response interact. The influence of the host's genetic predisposition to susceptibility or resistance to infectious diseases has been evidenced in several studies. The association of the human leukocyte antigen gene (HLA) class I alleles with DHF susceptibility or resistance has been reported in ethnically and geographically distinct populations. Due to these ethnic and viral strain differences, associations occur in each population, independently with a specific allele, which most likely explains the associations of several alleles with DHF. As the potential role of HLA alleles in the progression of DHF in Brazilian patients remains unknown, we then identified HLA-A alleles in 67 patients with dengue fever and 42 with DHF from Rio de Janeiro, Brazil, selected from 2002-2008 by the sequence-based typing technique. Statistical analysis revealed an association between the HLA-A*01 allele and DHF [odds ratio (OR) = 2.7, p = 0.01], while analysis of the HLA-A*31 allele (OR = 0.5, p = 0.11) suggested a potential protective role in DHF that should be further investigated. This study provides evidence that HLA class I alleles might be important risk factors for DHF in Brazilian patients.

Diagnóstico tardio de malária em área endêmica de dengue na extra-Amazônia Brasileira: experiência recente de uma unidade sentinela no estado do Rio de Janeiro / Delayed diagnosis of malaria in a dengue endemic area in the Brazilian extra-Amazon: recent experience of a malaria surveillance unit in state of Rio de Janeiro

INTRODUÇÃO: A letalidade da malária na região extra-amazônica é cerca de 80 vezes maior do que na Amazônia, que concentra 99,8 por cento dos casos do país. Em áreas de transmissão de dengue, como o Rio de Janeiro, o atraso no diagnóstico e tratamento da malária dos pacientes com febre, provenientes de áreas endêmicas de malária, pode ser, entre outros fatores, devido à confusão entre o diagnóstico das duas doenças pelos generalistas da rede de assistência médica. Neste trabalho, apresentamos as consequências do atraso diagnóstico em três pacientes com malária por Plasmodium falciparum; P. malariae e P. vivax, que, após o périplo habitual para tratamento de dengue, procuraram a nossa instituição onde foram corretamente diagnosticados e submetidos aos tratamentos adequados. MÉTODOS: Descrição de três casos de malária diagnosticada tardiamente e encaminhados ao IPEC/ FIOCRUZ, entre os anos de 2007 e 2008. RESULTADOS: uma brasileira proveniente de Moçambique, primo-infectada por P. falciparum, com malária diagnosticada após 6 dias do início da febre, morreu com malária cerebral e choque. Outro paciente com malária por P. malariae teve um curso grave e prolongado, mas ficou curado após o tratamento específico. A terceira paciente diagnosticada tardiamente apresentou malária por P. vivax adquirida na região de Mata Atlântica no Estado do Rio. CONCLUSÕES: Os profissionais de saúde do Rio devem ser treinados para aperfeiçoar a vigilância e o tratamento oportuno da malária e evitar desfechos mórbidos e fatais. Sugere-se que uma investigação de focos de malária autóctone em áreas de mata no estado seja realizada.

INTRODUCTION: The mortality of malaria in the extra-Amazon region is about 80 times higher than in the Amazon region, where malaria is concentrated (99.8 percent of cases). In areas of dengue transmission, delay in the diagnosis and treatment of malaria in patients with fever who reside in areas of malaria transmission can be due to the confusion between the clinical diagnoses of both diseases by nonspecialist doctors, among other factors. This work presents some of the consequences of delayed diagnosis in three patients with malaria by Plasmodium falciparum, P. malariae and P. vivax, who, after following the usual route for Dengue treatment, sought our institution, where they were correctly diagnosed and adequately treated. METHODS: Description of three cases of malaria with delayed diagnosed malaria referred to the Outpatient Clinic for Acute Febrile Diseases, IPEC/FIOCRUZ-RJ, between 2007 and 2008. RESULTS: A Brazilian from Mozambique, primo-infected with P. falciparum was diagnosed with malaria six days after the onset of fever and died of cerebral malaria and shock. Another patient with P.malariae malaria presented a severe and prolonged course, but was cured after specific treatment. A third patient, with delayed diagnosis of P. vivax malaria, acquired it in the Atlantic Forest region in the State of Rio. CONCLUSIONS: Health professionals from non-endemic areas for malaria should be trained to optimize the surveillance and early treatment of malaria and prevent morbid and fatal outcomes. An investigation of outbreaks of autochthonous malaria in the State of Rio de Janeiro is suggested.