Ivo Castelo Branco Coelho

In vitro and in vivo Leishmanicidal activity of 2‐hydroxy‐3‐(3‐methyl‐2‐butenyl)‐1,4‐naphthoquinone (lapachol)

This study aims to evaluate the in vitro and in vivo leishmanicidal activity of lapachol, a naphthoquinone found in the seeds and heartwood of certain tropical plants, and to compare its efficacy with a reference drug, sodium stibogluconate (Pentostam®). These compounds (0.0125–4.0 mg/mL) were evaluated in vitro against intracellular amastigotes of Leishmania (Viannia) braziliensis (LVb), then tested in an animal model (hamster) to try to reproduce the leishmanicidal activity. In vitro, lapachol exhibited an anti‐amastigote effect, whereas in vivo it did not prevent the development of LVb‐induced lesions at an oral dose of 300 mg/kg/day for 42 days. Pentostam® demonstrated a significant anti‐amastigote effect in vitro for LVb and apparent clinical cure in vivo (60 mg/kg/day). However, it could not completely eradicate parasites from the tissues of infected animals. The observation that lapachol exerts leishmanicidal activity in vitro without offering significant protection against LVb‐infected lesions in hamsters suggests that lapachol in vivo might possibly inhibit the microbicidal functioning of macrophages. Alternatively, it might be transformed into an inactive metabolite(s) or neutralized, losing its leishmanicidal activity. It is also possible that an optimal and sustained plasma level of the drug could not be achieved at the dose used in this study. Copyright

Controle do calazar canino: comparação dos resultados de um programa de eliminação rápida de cães sororreagentes por ensaio imuno-enzimático com outro de eliminação tardia de cães sororreagentes por teste de imunofluorescência indireta de eluato de papel filtro

The kala-azar control program, adopted by the Fundação Nacional de SaúdeFNS (National Health Foundation) has not been able to reduce to an acceptable level the incidence of human cases. The diagnostic method utilized is a blood eluate immunofluorescence. A dogs diagnosed as infected is eliminated a mean of eighty days after the blood collection. The low sensitivity of the test used and the continuing residence of the infected dog in the region due to the elimination delay may be critical in the lack of success of this program. In this study, the FNS standard canine control method is compared to a strategy based on ELISA identification of infected dog and elimination within 7 days. In both study areas the canine seroprevalence was noted ten months before and ten months after the intervention. In the routine FNS area a 9% decrease in seroprevalence was noted, compared to statistically significant greater 27%, reduction (p = 0.0015) in the ELISA intervention area. Key-words: Visceral leishmaniasis. Kala-azar. Epidemiologic control. Reservoir. Canine kala-azar control: aftermath comparison of a fast deletion program of serum-reactive dogs by immuno-enzimatic essay with another of late deletion program of serum-reactive dogs by indirect immunofluorescence of filter paper eluate Marcus Davis Machado Braga, Ivo Castelo Branco Coêlho, Margarida Maria Lima Pompeu, Thomas G. Evans, Isabel Tavares MacAullife, Maria Jania Teixeira e José Wellington de Oliveira Lima Revista da Sociedade Brasileira de Medicina Tropical 31:419-424, set-out, 1998. 420 No Brasil a leishmaniose visceral é causada pela Leishmania chagasi 6 22, e transmitida ao homem através da picada de um psicodídeo, a Lutzomya longipalpis 6 9 13 14. Duas espécies de mamíferos já foram incriminadas como reservatório deste parasita, uma silvestre, a raposa12, e outra doméstica, o cão1 2 3 10 11. A leishmaniose visceral humana e canina são endêmicas no Brasil, principalmente no Nordeste6 18. Nesta região, e mais especificamente, no Estado do Ceará, em humanos a doença apresenta uma prevalência de 10,08/100.000 habitantes17. O Ministério da Saúde do Brasil, desde o início da década de 60, através da então Superintendência de Campanhas de Saúde Pública (SUCAM), e mais recentemente, da Fundação Nacional de Saúde (FNS), vem desenvolvendo atividades de controle da infecção canina, em vários estados da Federação, incluindo o Ceará2 20. Este controle inclui medidas para diminuir a densidade populacional do vetor, e a identificação e eliminação de cães infectados6 20 22. Ao longo destes anos, em função da necessidade de se utilizar técnicas cada vez mais sensíveis, diferentes métodos de identificação de cães infectados têm sido propostos. Inicialmente, foi utilizado o exame parasitológico da pele e/ou vísceras3, outra técnica utilizada foi a detecção de anticorpos antileishmania, por reação de fixação do complemento8. A partir de 1982, vêm-se usando a técnica de imunofluorescência realizada em eluato de sangue colhido em papel filtro6 22. Embora a introdução da imunofluorescência ainda represente um grande avanço, esta técnica, quando realizada em eluato de papel filtro, apresenta uma sensibilidade muito baixa, quando comparada com ELISA realizada no soro4 15. Após 5 anos de atividades de controle do reservatório canino, utilizando a imunofluorescência no eluato para detectar cães infectados, observou-se que é possível reduzir a prevalência da infecção no cão até certo limite, em torno de 0,5 a 1%. Esta redução, no entanto, não se acompanha necessariamente de uma interrupção da transmissão ao homem21. Acreditamos que, entre outros fatores, a baixa sensibilidade do teste de IFI no eluato, e o tempo decorrido entre a coleta de sangue e a eliminação do cão infectado, sejam responsáveis pela permanência de cães infectados e pela manutenção da transmissão da infecção. Neste trabalho, avalia-se o impacto que a eliminação precoce de cães infectados, detectados por uma técnica de diagnóstico mais sensível, possa ter na prevalência da infecção do cão pela L. chagasi, comparando esta estratégia com aquela adotada pelo programa de controle da leishmaniose visceral, na qual cães infectados são detectados pela IFI no eluato e eliminados, em média, 80 dias depois.The kala-azar control program, adopted by the Fundacao Nacional de Saude- FNS (National Health Foundation) has not been able to reduce to an acceptable level the incidence of human cases. The diagnostic method utilized is a blood eluate immunofluorescence. A dogs diagnosed as infected is eliminated a mean of eighty days after the blood collection. The low sensitivity of the test used and the continuing residence of the infected dog in the region due to the elimination delay may be critical in the lack of success of this program. In this study, the FNS standard canine control method is compared to a strategy based on ELISA identification of infected dog and elimination within 7 days. In both study areas the canine seroprevalence was noted ten months before and ten months after the intervention. In the routine FNS area a 9% decrease in seroprevalence was noted, compared to statistically significant greater 27%, reduction (p = 0.0015) in the ELISA intervention area.The kala-azar control program, adopted by the Fundação Nacional de Saúde-FNS (National Health Foundation) has not been able to reduce to an acceptable level the incidence of human cases. The diagnostic method utilized is a blood eluate immunofluorescence. A dogs diagnosed as infected is eliminated a mean of eighty days after the blood collection. The low sensitivity of the test used and the continuing residence of the infected dog in the region due to the elimination delay may be critical in the lack of success of this program. In this study, the FNS standard canine control method is compared to a strategy based on ELISA identification of infected dog and elimination within 7 days. In both study areas the canine seroprevalence was noted ten months before and ten months after the intervention. In the routine FNS area a 9% decrease in seroprevalence was noted, compared to statistically significant greater 27%, reduction (p = 0.0015) in the ELISA intervention area.

Concurrent infection with dengue virus type-2 and DENV-3 in a patient from Ceará, Brazil

Dengue outbreaks have occurred in several regions in Brazil and cocirculating dengue virus type 1 (DENV-1), DENV-2, and DENV-3 have been frequently observed. Dual infection by DENV-2 and DENV-3 was identified by type-specific indirect immunofluorescence assay and confirmed by reverse transcription polymerase chain reaction in a patient in Ceará with a mild disease. This is the first documented case of simultaneous infection with DENV-2 and DENV-3 in Brazil. Sequencing confirmed DENV-2 and DENV-3 (South-East/American) genotype III and (SriLanka/India), genotype III respectively.

Clinical-Epidemiological Features of 13 Cases of Melioidosis in Brazil

ABSTRACT The aim of this work was to catalog the clinical and ecoepidemiological characteristics of melioidosis in Brazil. The clinical-epidemiological features of melioidosis in Ceará are similar to those in other regions where the disease is endemic. These findings support the inclusion of this Brazilian state as part of the zone of endemicity for melioidosis.

Involvement of the central nervous system in dengue fever: three serologically confirmed cases from Fortaleza, Ceará, Brazil

Three cases of dengue fever involving the central nervous system (CNS) are reported. All occurred in 1994 during a dengue (DEN) epidemic caused by serotypes DEN-1 and DEN-2. The first case examined was a 17-year-old girl who complained of fever, nuchal rigidity and genital bleeding. Three blood samples were positive by anti-dengue IgM ELISA and showed hemagglutination-inhibition (HI) test titers > or = 1,280. The second case concerned a 86-year-old women with fever, muscle and joint pains, altered consciousness, syncope, nuchal rigidity and meningismus. Her blood sample showed an HI titer of 1:320 for flaviviruses, and an IgM ELISA positive for dengue. The third case was a 67-year-old women with fever, abnormal behaviour, seizures, tremor of extremities, thrombocytopenia, increased hematocrit and leukopenia. The patient suffered a typical case of dengue hemorrhagic fever with ensuing shock and a fatal outcome. A single blood sample showed HI antibodies of > or = 1,280 and an IgM ELISA positive for dengue. No virus could be isolated from any patient by inoculation of blood into C6/36 cells and suckling mice. No other agent of disease was encountered in the patient.

Evaluation of the WHO classification of dengue disease severity during an epidemic in 2011 in the state of Ceará, Brazil

In 2009, the World Health Organization (WHO) issued a new guideline that stratifies dengue-affected patients into severe (SD) and non-severe dengue (NSD) (with or without warning signs). To evaluate the new recommendations, we completed a retrospective cross-sectional study of the dengue haemorrhagic fever (DHF) cases reported during an outbreak in 2011 in northeastern Brazil. We investigated 84 suspected DHF patients, including 45 (53.6%) males and 39 (46.4%) females. The ages of the patients ranged from five-83 years and the median age was 29. According to the DHF/dengue shock syndrome classification, 53 (63.1%) patients were classified as having dengue fever and 31 (36.9%) as having DHF. According to the 2009 WHO classification, 32 (38.1%) patients were grouped as having NSD [4 (4.8%) without warning signs and 28 (33.3%) with warning signs] and 52 (61.9%) as having SD. A better performance of the revised classification in the detection of severe clinical manifestations allows for an improved detection of patients with SD and may reduce deaths. The revised classification will not only facilitate effective screening and patient management, but will also enable the collection of standardised surveillance data for future epidemiological and clinical studies.

Dengue infection in children and adolescents: Clinical profile in a reference hospital in northeast Brazil

INTRODUCTION This study aimed to describe the clinical spectrum of dengue in children and adolescents from a hyperendemic region who were admitted for hospitalization. METHODS A retrospective study was conducted on patients diagnosed with dengue infection upon admission to a reference center in Fortaleza, Brazil. RESULTS Of the 84 patients included, 42 underwent confirmatory testing. The main symptoms were fever, abdominal pain and vomiting. The median level of serum aspartate aminotransferase was 143.5±128mg/dL. CONCLUSIONS A peculiar clinical profile was evident among children and adolescents with dengue infection in a reference center in northeast Brazil, including gastrointestinal symptoms and liver involvement.

Reações adversas em pacientes com doença de Chagas tratados com benzonidazol, no Estado do Ceará

INTRODUCTION Chagas disease is caused by Trypanosoma cruzi and treated with benznidazole (BNZ). This drug has the troublesome features of presenting partial effectiveness and high toxicity ranging from hypersensitivity reactions to medullary aplasia. The objective here was to describe and evaluate the occurrence of adverse reactions in Chagas disease patients treated with benznidazole in Fortaleza, Ceará. METHODS This was a prospective descriptive study involving 32 chronic Chagas patients treated with benznidazole between January 2005 and April 2006. Sociodemographic and clinical data were collected through questionnaires, interviews and laboratory tests. Blood samples were collected before treatment and after 30 and 60 days of treatment. RESULTS Adverse reactions were reported in 28 patients (87.5%) patients and the most frequent of these were pruritus (50%), prickling (43.8%), muscle weakness (37.5%) and skin rash (31.3%). Out of the 28 patients with adverse reactions, eight (28.57%) discontinued their treatment. The adverse reactions that culminated with discontinuation of the treatment were prickling (7; 87.5%) or skin eruptions (5; 62.5%). There was a slight increase in aminotransferase levels during the treatment in 9.4% of the patients. CONCLUSIONS Following up the drug therapy administered to Chagas patients is of great importance for prevention and early detection of adverse reactions to drugs.

Manifestações mucocutâneas da dengue

Dengue fever is a systemic viral disease that occurs epidemically in tropical and subtropical regions of Asia, Americas and Africa. The dengue virus belongs to the genus Flavivirus of the family Flaviviridae (group B arbovirus). Aedes aegypti is the major vector and the true reservoir for the virus. Classic dengue fever lasts for two-five days, with severe headache, intense myalgia, arthralgia and retro-orbital pain. Cutaneous alterations include several findings such as a diffuse morbilliform rash that may be pruritic and heals with desquamation, and minor bleeding phenomena such as epistaxis, petechiae, and gingival bleeding. Diffuse capillary leakage of plasma is responsible for the hemoconcentration and thrombocytopenia that characterize dengue hemorrhagic fever. Cutaneous manifestations of dengue hemorrhagic fever include many disseminated hemorrhagic lesions such as petechiae and ecchymoses, but also hemodynamic instability with filiform pulse, narrowing of pulse pressure, cold extremities, mental confusion, and shock.

Clinical and serological evolution in chronic Chagas disease patients in a 4-year pharmacotherapy follow-up: a preliminary study

INTRODUCTION The role of trypanocidal therapy in the chronic phase of Chagas disease remains controversial. METHODS A total of 13 patients with chronic Chagas disease were treated with benznidazole (5mg/kg/day/60 days) and surveyed via antibody measurement and conventional electrocardiogram over the course of 4 years. RESULTS The antibody titers were significantly reduced after 4 years (p<0.05). Most of the patients showed maintenance of the initial clinical picture (electrocardiographic), with the exception of 4 cases. CONCLUSIONS Although trypanocidal therapy in the chronic phase of Chagas disease was of limited effectiveness, we believe that it is beneficial in treating these patients.