Expedito José de Albuquerque Luna

Visceral leishmaniasis in Brazil: trends and challenges

The urbanization of visceral leishmaniasis in Brazil has been related to environmental changes, migration, interaction and spread of sylvatic reservoirs and infected dogs to areas with no transmission, and adaptation of the vector Lutzomyia longipalpis to the peridomiciliary environment. From 1980 to 2005, Brazil recorded 59,129 cases of visceral leishmaniasis, 82.5% of which in the Northeast region. Visceral leishmaniasis gradually spread to other regions of the country: in 1998 these other regions reported 15% of all cases, but by 2005 this proportion had increased to 44%. From 1998 to 2005, indigenous cases were reported in 1,904 different municipalities of the country (34.2%). Reservoir and vector control pose major challenges for disease control, since there is a need for better knowledge of vector behavior in urban areas, and control activities involve high operational costs. In recent years the Brazilian Ministry of Health has supported research on the laboratory diagnosis of infection and disease in humans and dogs, treatment of patients, evaluation of the effectiveness of control strategies, and development of new technologies that could contribute to the surveillance and control of visceral leishmaniasis in the country.

Mecanismos alternativos de transmissão do Trypanosoma cruzi no Brasil e sugestões para sua prevenção

INTRODUCTION: Following advances in the control of vector and blood transfusion transmission of Chagas disease, alternative mechanisms of transmission have become more relevant. This article discusses the importance of each one of these alternative mechanisms and the measures to prevent them. METHODS: A review was conducted of the scientific literature concerning alternative transmission mechanisms of Trypanosoma cruzi occurring in Brazil and the measures to prevent them. PubMed and BVS databases were consulted. RESULTS: Twenty-five publications describing alternative mechanisms of transmission of Chagas disease were identified. CONCLUSIONS: Oral transmission, through ingestion of contaminated food items has been the most frequent mode of transmission in Brazil in recent years. Other alternative mechanisms of transmission occur less frequently. It is important to understand these occurrences, especially now that vector transmission of the parasite is under control. Preventive measures have been presented, according to each of the situations considered, in line with current knowledge.

Microbial Translocation Is Associated with Extensive Immune Activation in Dengue Virus Infected Patients with Severe Disease

Background Severe dengue virus (DENV) disease is associated with extensive immune activation, characterized by a cytokine storm. Previously, elevated lipopolysaccharide (LPS) levels in dengue were found to correlate with clinical disease severity. In the present cross-sectional study we identified markers of microbial translocation and immune activation, which are associated with severe manifestations of DENV infection. Methods Serum samples from DENV-infected patients were collected during the outbreak in 2010 in the State of São Paulo, Brazil. Levels of LPS, lipopolysaccharide binding protein (LBP), soluble CD14 (sCD14) and IgM and IgG endotoxin core antibodies were determined by ELISA. Thirty cytokines were quantified using a multiplex luminex system. Patients were classified according to the 2009 WHO classification and the occurrence of plasma leakage/shock and hemorrhage. Moreover, a (non-supervised) cluster analysis based on the expression of the quantified cytokines was applied to identify groups of patients with similar cytokine profiles. Markers of microbial translocation were linked to groups with similar clinical disease severity and clusters with similar cytokine profiles. Results Cluster analysis indicated that LPS levels were significantly increased in patients with a profound pro-inflammatory cytokine profile. LBP and sCD14 showed significantly increased levels in patients with severe disease in the clinical classification and in patients with severe inflammation in the cluster analysis. With both the clinical classification and the cluster analysis, levels of IL-6, IL-8, sIL-2R, MCP-1, RANTES, HGF, G-CSF and EGF were associated with severe disease. Conclusions The present study provides evidence that both microbial translocation and extensive immune activation occur during severe DENV infection and may play an important role in the pathogenesis.

Immunogenicity and reactogenicity of 2009 influenza A (H1N1) inactivated monovalent non-adjuvanted vaccine in elderly and immunocompromised patients.

Background Immunosuppressed individuals present serious morbidity and mortality from influenza, therefore it is important to understand the safety and immunogenicity of influenza vaccination among them. Methods This multicenter cohort study evaluated the immunogenicity and reactogenicity of an inactivated, monovalent, non-adjuvanted pandemic (H1N1) 2009 vaccine among the elderly, HIV-infected, rheumatoid arthritis (RA), cancer, kidney transplant, and juvenile idiopathic arthritis (JIA) patients. Participants were included during routine clinical visits, and vaccinated according to conventional influenza vaccination schedules. Antibody response was measured by the hemagglutination-inhibition assay, before and 21 days after vaccination. Results 319 patients with cancer, 260 with RA, 256 HIV-infected, 149 elderly individuals, 85 kidney transplant recipients, and 83 with JIA were included. The proportions of seroprotection, seroconversion, and the geometric mean titer ratios postvaccination were, respectively: 37.6%, 31.8%, and 3.2 among kidney transplant recipients, 61.5%, 53.1%, and 7.5 among RA patients, 63.1%, 55.7%, and 5.7 among the elderly, 59.0%, 54.7%, and 5.9 among HIV-infected patients, 52.4%, 49.2%, and 5.3 among cancer patients, 85.5%, 78.3%, and 16.5 among JIA patients. The vaccine was well tolerated, with no reported severe adverse events. Conclusions The vaccine was safe among all groups, with an acceptable immunogenicity among the elderly and JIA patients, however new vaccination strategies should be explored to improve the immune response of immunocompromised adult patients. (ClinicalTrials.gov, NCT01218685)

Serum angiopoietin-2 and soluble VEGF receptor 2 are surrogate markers for plasma leakage in patients with acute dengue virus infection.

BACKGROUND Endothelial cell dysfunction is believed to play an important role in the pathogenesis of plasma leakage in patients with acute dengue virus (DENV) infection. Several factors, produced by activated endothelial cells, have been associated with plasma leakage or severe disease in patients with infectious diseases. OBJECTIVES The aim of this study was to investigate which of these markers could serve as a surrogate marker for the occurrence of plasma leakage in patients with acute DENV infection. STUDY DESIGN A case-control study was performed in patients with acute DENV infection in Santos, Brazil. Plasma leakage was detected with X-ray and/or ultrasound examination at admission. Serum levels of soluble endoglin, endothelin-1, angiopoietin-2, VEGF, soluble VEGFR-2, MMP-2, MMP-9, TIMP-1 and TIMP-2 were determined using commercially available ELISAs. RESULTS Increased levels of angiopoietin-2, endothelin-1 and MMP-2 and decreased levels of soluble VEGFR-2 were significantly associated with the occurrence of plasma leakage. An unsupervised cluster analysis confirmed that angiopoietin-2 and soluble VEGFR-2 were strongly associated with clinical apparent vascular leakage. CONCLUSION Angiopoietin-2 and soluble VEGFR-2 can serve as surrogate markers for the occurrence of plasma leakage in patients with acute DENV infection.

Household survey of hepatitis B vaccine coverage among Brazilian children.

We conducted a multi-stage household cluster survey to calculate hepatitis B vaccine coverage among children 18-30 months of age in 27 Brazilian cities. Hepatitis B vaccine is administered at birth, 1 month and 6 months of age by Brazils national immunization program. Among 17,749 children surveyed, 40.2% received a birth dose within one day of birth, 94.8% received at least one dose of hepatitis B vaccine, and 86.7% completed the three-dose series by 12 months of age. Increased coverage with the birth dose and administration of hepatitis B in combination with diphtheria-tetanus-pertussis-Haemophilus influenzae type b antigens could improve protection against hepatitis B.

Case-control study of an outbreak of acute toxoplasmosis in an industrial plant in the state of São Paulo, Brazil

Foodborne diseases represent operational risks in industrial restaurants. We described an outbreak of nine clustered cases of acute illness resembling acute toxoplasmosis in an industrial plant with 2300 employees. These patients and another 36 similar asymptomatic employees were diagnosed with anti-T. gondii IgG titer and avidity by ELISA. We excluded 14 patients based on high IgG avidity and chronic toxoplasmosis: 13 from controls and one from acute disease other than T. gondii infection. We also identified another three asymptomatic employees with T.gondii acute infection and also anti-T. gondii IgM positive as remaining acute cases. Case control study was conducted by interview in 11 acute infections and 20 negative controls. The ingestion of green vegetables, but not meat or water, was observed to be associated with the incidence of acute disease. These data reinforce the importance of sanitation control in industrial restaurants and also demonstrate the need for improvement in quality control regarding vegetables at risk for T. gondii oocyst contamination. We emphasized the accurate diagnosis of indexed cases and the detection of asymptomatic infections to determine the extent of the toxoplasmosis outbreak.

Effectiveness of the Brazilian influenza vaccination policy, a systematic review

Since 1999, Brazil has undertaken annual influenza vaccine campaigns, free of charge, targeting the elderly population, health professionals, and immune-deficient patients. We conducted a systematic review of literature in order to evaluate the effectiveness of the initiative. We used the keywords influenza, vaccine, Brazil and effectiveness to search the main databases. Thirty-one studies matched our inclusion and exclusion criteria. Influenza vaccine coverage among the elderly is high, though not as high as suggested by the official figures. Estimates on effectiveness are scarce. The majority come from ecological studies that show a modest reduction in mortality and hospital admissions due to influenza-related causes. Such reduction is not evident in the North and Northeastern states of Brazil, a finding that is probably related to the different seasonal pattern of influenza in equatorial and tropical regions. Brazilian epidemiologists still owe society better-designed studies addressing the effectiveness of influenza vaccine campaigns.

Seleção das doenças de notificação compulsória: critérios e recomendações para as três esferas de governo

Apresenta-se neste trabalho uma revisão referente ao Sistema Nacional de Vigilância Epidemiológica, principalmente, quanto ao processo de revisão e seleção de doenças de Notificação Compulsória. Foi elaborada uma proposta da Lista Brasileira de Doenças de Notificação Compulsória, fruto de um exercício de seleção baseado na avaliação de doenças com relação a 13 critérios e de debates com técnicos de áreas específicas do Ministério da Saúde, das Secretarias Estaduais/Municipais de Saúde, de institições acadêmicas e da Organização Pan-Americana da Saúde. Várias recomendações são feitas, úteis para as três esferas do governo no processo de definição das doenças e agravos de notificação compulsória, levando-se em consideração o principal objetivo desse instrumento fornecer informação de forma rápida e ágil, servir de base para a tomada de decisões e implementação de ações de controle e/ou prevenção.

Evaluation of real-time PCR assay to detect Schistosoma mansoni infections in a low endemic setting

BackgroundSchistosomiasis constitutes a major public health problem, and 200 million people are estimated to be infected with schistosomiasis worldwide. In Brazil, schistosomiasis has been reported in 19 states, showing areas of high and medium endemicity and a wide range of areas of low endemicity (ALE). Barra Mansa in Rio de Janeiro state has an estimated prevalence of 1%. ALE represent a new challenge for the helminth control because about 75% of infected individuals are asymptomatic and infections occur with a low parasite load (<100 eggs per gram of feces), causing a decrease in sensitivity of stool parasitological techniques, which are a reference for the laboratory diagnosis of this helminth. The objective of this study was to evaluate the performance of a TaqMan quantitative polymerase chain reaction (qPCR) technique in serum and feces DNA samples using the techniques of Kato-Katz (KK), Hoffman, Pons and Janer (HH) as references, during an epidemiological survey using fecal samples and sera from randomized residents from an ALE.MethodsA cross-sectional study conducted from April to December 2011 using a probabilistic sampling that collected 572 fecal and serum samples. The laboratory diagnostic techniques used were: KK, HH and qPCR (feces and serum).ResultsWe obtained the following results using the different diagnostic techniques: KK and HH, 0.9% (n =5); qPCR-feces, 9.6% (n =55); and qPCR-serum, 1.4% (n =8). The qPCR-feces presented the highest positivity, whereas the techniques of HH and KK were the least sensitive to detect infections (0.8%). Compared to HH and KK, qPCR-feces showed a statistically significant difference in positivity (p <0.05), although with poor agreement.ConclusionThe positivity rate presented by the qPCR approach was far higher than that obtained by parasitological techniques. The lack of adequate surveillance in ALE of schistosomiasis indicates a high possibility of these areas being actually of medium and high endemicity. This study presents a control perspective, pointing to the possibility of using combined laboratory tools in the diagnosis of schistosomiasis in ALE.