Vacinas contra a dengue: o que sabemos, o que tem sido feito, mas o que nos reserva o futuro?

Dengue, a disease caused by any of the four serotypes of dengue viruses, is the most important arthropod-borne viral disease in the world in terms of both morbidity and mortality. The infection by these viruses induces a plethora of clinical manifestations ranging from asymptomatic infections to severe diseases with involvement of several organs. Severe forms of the disease are more frequent in secondary infections by distinct serotypes and, consequently, a dengue vaccine must be tetravalent. Although several approaches have been used on the vaccine development, no vaccine is available against these viruses, especially because of problems on the development of a tetravalent vaccine. Here, we describe briefly the vaccine candidates available and their ability to elicit a protective immune response. We also discuss the problems and possibilities of any of the vaccines in final development stage reaching the market for human use.Dengue, doença causada por qualquer um dos quatro sorotipos dos vírus dengue, é atualmente a mais importante doença viral transmitida por artrópodos em todo o mundo, tanto em termos de morbidade como de mortalidade. A infecção por estes vírus causa grande variedade de manifestações clínicas, desde infecções assintomáticas até doenças graves com envolvimento de diversos órgãos. As formas graves da dengue são mais frequentes em infecções secundárias por sorotipos diferentes e, por esta razão, a vacina contra a dengue deve ser tetravalente. Embora várias estratégias tenham sido usadas no desenvolvimento de vacinas contra a dengue, não há ainda nenhuma vacina disponível, particularmente por problemas no desenvolvimento de uma vacina tetravalente. Aqui, descreve-se brevemente os candidatos vacinais disponíveis e a capacidade de eles induzirem resposta imune protetora contra novas infecções. Ainda, discutimos os problemas e as possibilidades de liberação, para uso em seres humanos, de qualquer uma das vacinas em fase final de desenvolviment

Epidemiologia da infecção pela dengue em Ribeirão Preto, SP, Brasil

OBJECTIVE: To assess dengue transmission in a correctional facility for juvenile delinquents in Ribeirão Preto, state of São Paulo, Brazil. METHODS: A serological and virology investigation was carried out among inmates and employees of a correctional facility for juvenile delinquents in Ribeirão Preto, Brazil. The study population consisted of 105 inmates and 91 employees representing 89% of the exposed. The collected blood was stored and processed using MAC-ELISA and virus isolation. A questionnaire was applied to each subject at the time of blood collection. RESULTS: Of the total of blood samples collected (n=196), 42 (21.4%) were positive for IgM antibodies and 43 (21.9%) for IgG antibodies; of which, 15 were both IgM and IgG positive and 28 (14.3%) were IgG positive only. Serotype 1 dengue virus was isolated in 5 samples. Out of 42 IgM positive samples, 14 (33.0%) subjects did not have any physical complaints. The incidence rate was 23.8% and 18.6% among inmates and employees, respectively. The first cases in the facility were reported in 1997 and the last ones in March 1997 though results are suggestive of an earlier onset of transmission. CONCLUSIONS: The high incidence rate of dengue infection can be explained by the high population density of the facility, high Aedes aegypti infestation, high numbers of asymptomatic subjects, and a higher transmission of disease in a closed setting.OBJETIVO: Avaliar a transmissão de dengue em uma instituição correcional de adolescentes localizada em Ribeirão Preto, SP, Brasil. MÉTODOS: Foi realizado um inquérito sorológico e virológico da população de internos e funcionários de uma instituição correcional de adolescentes infratores localizada em Ribeirão Preto, SP, Brasil. A população de estudo consistiu em 105 menores e 91 funcionários que representavam 89% do total de pessoas expostas. O sangue coletado da população estudada foi armazenado e processado para avaliação pelas técnicas de MAC-Elisa e de isolamento viral. Cada participante respondeu a um questionário aplicado na ocasião da coleta de sangue. RESULTADOS: Do total de amostras de sangue coletadas (n=196), 42 (21,4%) foram positivas para anticorpos da classe IgM, e 43 (21,9%), para anticorpo IgG; destes, 15 com IgM e IgG positivas e 28 (14,3%) com apenas IgG positiva. Em cinco amostras, foram isolados vírus da dengue, sorotipo 1. Dos 42 casos com IgM positiva, 14 (33,4%) não relataram sintomas característico de dengue. A incidência entre os internos foi de 23,8% e, entre funcionários, de 18,6%. Os primeiros casos foram notificados em fevereiro de 1997, e os últimos, em março do mesmo ano, embora os resultados mostrem a possibilidade de a transmissão ter se iniciado bem antes de ser detectada. CONCLUSÕES: A alta incidência observada pode ser explicada pela grande densidade populacional na instituição, alta infestação do vetor Aedes aegypti, alta taxa de assintomáticos e transmissão favorecida pelo fato de a comunidade ser fechada

Malaria and other febrile diseases among travellers: the experience of a reference centre located outside the Brazilian Amazon Region

Abstract\ud \ud Background\ud Malaria is endemic in countries located in tropical and sub-tropical regions. The increasing flow of domestic and international travellers has made malaria a relevant health problem even in non-endemic regions. Malaria has been described as the main diagnosis among travellers presenting febrile diseases after returning from tropical countries. In Brazil, malaria transmission occurs mainly in the Amazon region. Outside this area, malaria transmission is of low magnitude.\ud \ud \ud Methods\ud This cross-sectional study aimed to describe the experience in the diagnosis of malaria in a reference centre located outside the Brazilian Amazon Region, emphasizing the differences in clinical and laboratory markers between cases of malaria and those of other febrile diseases (OFD). Medical charts from adult patients (≥18 years) who underwent a thick smear test (TST) for malaria, between January 2001 and December 2014, were retrospectively reviewed.\ud \ud \ud Results\ud A total of 458 cases referred to perform the TST were included. Malaria was diagnosed in 193 (42 %) episodes. The remaining 265 episodes (58 %) were grouped as OFD. The majority of malaria episodes were acquired in the Brazilian Amazon Region. The median time between the onset of symptoms and the TST was 7 days. Only 53 (11.5 %) episodes were tested within the first 48 h after symptom onset. Comparing malaria with OFD, jaundice, nausea, vomiting, and reports of fever were more prevalent in the malaria group. Low platelet count and elevated bilirubin levels were also related to the diagnosis of malaria.\ud \ud \ud Conclusions\ud The results indicate that outside the endemic area travellers presenting febrile disease suspected of being malaria underwent diagnostic test after considerable delay. The reporting of fever combined with a recent visit to an endemic area should promptly evoke the hypothesis of malaria. In these cases, specific diagnostic tests for malaria should be a priority. For cases that jump this step, the presence of elevated bilirubin or thrombocytopaenia should also indicate a diagnosis of malaria.This work was supported by the Grant # 2014/05337-6, São Paulo Research Foundation (FAPESP)

Seroprevalence and Seroconversion of Dengue and Implications for Clinical Diagnosis in Amazonian Children

This study aimed to evaluate the prevalence of serum IgG dengue in children in an Amazonian population, to assess the seroconversion rate in 12 months, and to estimate how many seropositive children had a prior clinical diagnosis of dengue. We conducted a population-based study between 2010 and 2011, with children aged 6 months to 12 years that were living in the urban area of a small town in the Brazilian Amazon. The prevalence of IgG antibodies against dengue antigens was determined by indirect ELISA technique, and seronegative children were reexamined after 12 months to determine seroconversion rates. Results showed seroprevalence of IgG antibodies against dengue type of 2.9%, with no significant association between age, race, and sex. In seropositive children, only 8.4% had received a clinical diagnosis of dengue, and the ratio of clinically diagnosed cases and subclinical cases was 1 : 11. The seroconversion rate between 2010 and 2011 was 1.4% (CI 3.8% to 35.1%). The seroprevalence of dengue in this pediatric population was low, and the vast majority of cases were not clinically detected, suggesting a difficulty in making the clinical diagnosis in children and a high frequency of asymptomatic infections

Dengue vaccines: what we know, what has been done, but what does the future hold?

Dengue, a disease caused by any of the four serotypes of dengue viruses, is the most important arthropod-borne viral disease in the world in terms of both morbidity and mortality. The infection by these viruses induces a plethora of clinical manifestations ranging from asymptomatic infections to severe diseases with involvement of several organs. Severe forms of the disease are more frequent in secondary infections by distinct serotypes and, consequently, a dengue vaccine must be tetravalent. Although several approaches have been used on the vaccine development, no vaccine is available against these viruses, especially because of problems on the development of a tetravalent vaccine. Here, we describe briefly the vaccine candidates available and their ability to elicit a protective immune response. We also discuss the problems and possibilities of any of the vaccines in final development stage reaching the market for human use

Will Mayaro virus be responsible for the next outbreak of an arthropod-borne virus in Brazil?

Mayaro virus is an alphavirus from the Togaviridae family and is transmitted mainly by Hemagogus mosquitoes. This virus circulates in high-density tropical forests or rural areas of Central and South America causing a disease characterized by high-grade fever, maculopapular skin rash and marked arthralgia that, in some patients, can persist for long periods after infection and may be misinterpreted as chikungunya. Although only a few outbreaks involving this virus have been reported, in the last years the number of Mayaro virus infections has increased in the central and northern regions of Brazil. In this review, we describe the reported prevalence of this infection over the years and discuss the circumstances that can contribute to the establishment of an urban mayaro virus epidemic in Brazil and the problems encountered with the specific diagnosis, especially the antigenic cross-reactivity of this pathogen with other viruses of the same family. Keywords: Mayaro virus, Alphavirus, Chikungunya virus, Epidemiology, Outbreak

Will Mayaro virus be responsible for the next outbreak of an arthropod-borne virus in Brazil?

Mayaro virus is an alphavirus from the Togaviridae family and is transmitted mainly by Hemagogus mosquitoes. This virus circulates in high-density tropical forests or rural areas of Central and South America causing a disease characterized by high-grade fever, maculopapular skin rash and marked arthralgia that, in some patients, can persist for long periods after infection and may be misinterpreted as chikungunya. Although only a few outbreaks involving this virus have been reported, in the last years the number of Mayaro virus infections has increased in the central and northern regions of Brazil. In this review, we describe the reported prevalence of this infection over the years and discuss the circumstances that can contribute to the establishment of an urban mayaro virus epidemic in Brazil and the problems encountered with the specific diagnosis, especially the antigenic cross-reactivity of this pathogen with other viruses of the same family

Sensitivity and detection of chikungunya viral genetic material using several PCR-based approaches

Abstract INTRODUCTION: Chikungunya fever is a condition resulting from infection by chikungunya virus (CHIKV), an Aedes sp.-transmitted virus. This disease has been diagnosed in thousands of cases in the Americas, particularly in Brazil, in recent years, and there is an ongoing epidemic of chikungunya fever in Brazil that began in 2014. Clinical diagnosis is difficult; only a few cases have been confirmed by laboratory tests due to the low number of specific, efficient tests available for virus or antibody detection. Here, we aimed to evaluate different polymerase chain reaction (PCR) approaches for detection of CHIKV genetic material. METHODS: Specific primers and probes within the viral capsid gene region were designed for this work. To evaluate the analytic sensitivity of detection, human sera were spiked with serial dilutions of the viral stock. Several PCR protocols were performed to investigate the sensitivity of CHIKV RNA detection in serum dilutions ranging from 106 to 1 PFU equivalents. RESULTS: The technique showing the greatest sensitivity was a real-time PCR assay using specific probes that could detect the genetic material of the virus at all dilutions, followed by conventional PCR. Digital PCR showed low sensitivity and was much more expensive than other technologies. Digital PCR should be used for specific purposes other than clinical diagnosis. CONCLUSIONS: Although quantitative PCR using probes was more expensive than the use of intercalating dyes or conventional PCR, it had the highest sensitivity out of all tested PCR approaches

Chloroquine use improves dengue-related symptoms

Dengue is the most important arboviral disease in the world. As chloroquine, an antimalarial agent, has shown some antiviral effects, this study evaluated its effect in patients with dengue. A randomised, double-blind study was performed by administering chloroquine or placebo for three days to 129 patients with dengue-related symptoms. Of these patients, 37 were confirmed as having dengue and completed the study; in total, 19 dengue patients received chloroquine and 18 received placebo. There was no significant difference in the duration of the disease or the degree and days of fever. However, 12 patients (63%) with confirmed dengue reported a substantial decrease in pain intensity and a great improvement in their ability to perform daily activities (p = 0.0004) while on the medication and the symptoms returned immediately after these patients stopped taking the medication. The same effect was not observed in patients with diseases other than dengue. Therefore, this study shows that patients with dengue treated with chloroquine had an improvement in their quality of life and were able to resume their daily activities. However, as chloroquine did not alter the duration of the disease or the intensity and days of fever, further studies are necessary to confirm the clinical effects and to assess the side effects of chloroquine in dengue patients