Recent developments on Junin virus, a causative agent for Argentine haemorrhagic fever.

Junin virus consists of ribonucleic acid as the genome and is responsible for a rapidly changing tendency of the virus. The virus is accountable for ailments in the human body and causes Argentine Haemorrhagic Fever (AHF). The infection is may be transmitted through contact between an infected animal/host and a person, and later between person to person. Prevention of outbreaks of AHF in humans can be a tough practice, as their occurrence is infrequent and unpredictable. In this review, recent information from the past 5 years available on the Junin virus including the risk of its emergence, infectious agents, its pathogenesis in humans, available diagnostic and therapeutic approaches, and disease management has been summarised. Altogether, this article would be highly significant in understanding the mechanistic basis behind virus interaction and other processes during the life cycle. Currently, no specific therapeutic options are available to treat the Junin virus infection. The information covered in this review could be important for finding possible treatment options for Junin virus infections.

Immune response during hantavirus diseases: implications for immunotherapies and vaccine design.

Orthohantaviruses, previously named hantaviruses, cause two emerging zoonotic diseases: haemorrhagic fever with renal syndrome (HFRS) in Eurasia and hantavirus cardiopulmonary syndrome (HCPS) in the Americas. Overall, over 200 000 cases are registered every year worldwide, with a fatality rate ranging between 0·1% and 15% for HFRS and between 20% and 40% for HCPS. No specific treatment or vaccines have been approved by the U.S. Food and Drug Administration (FDA) to treat or prevent hantavirus-caused syndromes. Currently, little is known about the mechanisms at the basis of hantavirus-induced disease. However, it has been hypothesized that an excessive inflammatory response plays an essential role in the course of the disease. Furthermore, the contributions of the cellular immune response to either viral clearance or pathology have not been fully elucidated. This article discusses recent findings relative to the immune responses elicited to hantaviruses in subjects suffering HFRS or HCPS, highlighting the similarities and differences between these two clinical diseases. Also, we summarize the most recent data about the cellular immune response that could be important for designing new vaccines to prevent this global public health problem.

Socio-demographic inequalities in the clinical characteristics of dengue haemorrhagic fever in the city of Rio de Janeiro, Brazil, 2007-2008.

In 2007-2008, the city of Rio de Janeiro underwent an epidemiological change, with increases in the incidence in children and in severe forms of dengue. To describe the clinical profile and spatial distribution of dengue we performed an ecological study based on dengue surveillance data using the Brazilian classification (2005): dengue fever, dengue haemorrhagic fever (DHF) and dengue with complications. χ 2 test was used to describe the clinical and socio-demographic variables (P < 0.05). Spatial distribution of incidence and case-fatality was explored with thematic maps, Moran and Geary indices (P < 0.05). Of the total of 151 527 dengue cases, 38 808 met the inclusion criteria; 42.4% <18 years; 22.9% dengue with complications and 2.7% DHF. Case-fatality was higher in infants (1.4%) and in DHF (7.7%). Bleeding was more frequent in adolescents and adults while plasma leakage was more common in preschoolers and schoolchildren. The highest incidence was found in the West Zone of the city, in a different area from that of the worst case-fatality (P < 0.05). Although the incidence of DHF was higher in schoolchildren, infants showed higher case-fatality. The area with the highest case-fatality did not present the highest incidence, which suggests problems in the organization of health services.

Comorbidities increase in-hospital mortality in dengue patients in Brazil

Dengue remains an unmet public health burden. We determined risk factors for dengue in-hospital mortality in Brazil. Of 326,380 hospitalised dengue cases in 9-45-year-old individuals, there were 971 deaths. Risk of dying was 11-times higher in the presence of underlying common comorbidities (renal, infectious, pulmonary disease and diabetes), similar to the risk of dying from severe dengue and much higher with the combination. Ensuring access to integrated dengue preventative measures in individuals aged ≥ 9 years including those with comorbidities may help achieve the WHO objective of 50% reduction in mortality and 25% reduction in morbidity due to dengue by 2020.

Fiebre amarilla: revisión concisa ante el actual escenario epidemiológico / Yellow fever: A concise review given the current epidemiological scenario

Resumen: La fiebre amarilla es una infección viral ictérico-hemorrágica trasmitida por mosquitos del género Haemagogus en su ciclo selvático y Aedes aegypti en el urbano. En México hubo brotes y epidemias en puertos del Golfo de México y del litoral del Pacífico desde la Colonia hasta mediados del siglo XX. El médico cubano Carlos J Finlay en 1881 expuso la posibilidad de trasmisión por medio de vectores, lo que se corroboró en 1890 y en México, en 1903, se iniciaron trabajos de erradicación de vectores logrando el control de la enfermedad con el último caso urbano en 1923 y selvático en 1959. Sin embargo, ante el resurgimiento en nuestro continente es importante la revisión de la enfermedad y estar alertas ante la posible aparición de casos importados o autóctonos en nuestro país.

Abstract: Mosquitoes transmit yellow fever, a viral infection characterised by haemorrhage and jaundice. Currently, it is endemic in African and South American countries whereas our country has been declared free of the disease since 1959 following the latest outbreaks and epidemics occurred in coastal cities from both the Gulf of Mexico and the Pacific coast that were registered from the Colony until the middle of century XX. In 1881, Carlos J Finlay, who was a Cuban physician, exposed the hypothesis concerning the transmission of yellow fever by vectors; such theory was corroborated in 1890. In 1903, Mexico started working to eradicate the disease through control of mosquitoes. Finally, in 1923 Mexico achieved the control of the disease with the last urban case registered, whereas the last jungle case was recorded in 1959. However, due to the resurgence of the disease in our continent, it is important to provide the clinician with a comprehensive review of the disease and to raise awareness of the possible occurrence of imported or autochthonous cases in our territory.

Primary dengue haemorrhagic fever in patients from northeast of Brazil is associated with high levels of interferon-β during acute phase

Dengue is an acute febrile disease caused by the mosquito-borne dengue virus (DENV) that according to clinical manifestations can be classified as asymptomatic, mild or severe dengue. Severe dengue cases have been associated with an unbalanced immune response characterised by an over secretion of inflammatory cytokines. In the present study we measured type I interferon (IFN-I) transcript and circulating levels in primary and secondary DENV infected patients. We observed that dengue fever (DF) and dengue haemorrhagic fever (DHF) patients express IFN-I differently. While DF and DHF patients express interferon-α similarly (52,71 ± 7,40 and 49,05 ± 7,70, respectively), IFN- β were associated with primary DHF patients. On the other hand, secondary DHF patients were not able to secrete large amounts of IFN- β which in turn may have influenced the high-level of viraemia. Our results suggest that, in patients from our cohort, infection by DENV serotype 3 elicits an innate response characterised by higher levels of IFN- β in the DHF patients with primary infection, which could contribute to control infection evidenced by the low-level of viraemia in these patients. The present findings may contribute to shed light in the role of innate immune response in dengue pathogenesis.

Primary dengue virus infections induce differential cytokine production in Mexican patients

Severe dengue pathogenesis is not fully understood, but high levels of proinflammatory cytokines have been associated with dengue disease severity. In this study, the cytokine levels in 171 sera from Mexican patients with primary dengue fever (DF) and dengue haemorrhagic fever (DHF) from dengue virus (DENV) 1 (n = 116) or 2 (n = 55) were compared. DF and DHF were defined according to the patient’s clinical condition, the primary infections as indicated by IgG enzymatic immunoassay negative results, and the infecting serotype as assessed by real-time reverse transcription-polymerase chain reaction. Samples were analysed for circulating levels of interleukin (IL)-12p70, interferon (IFN)-γ, tumour necrosis factor (TNF)-α, IL-6, and IL-8 using a commercial cytometric bead array. Significantly higher IFN-γ levels were found in patients with DHF than those with DF. However, significantly higher IL-12p70, TNF-α, and IL-6 levels were associated with DHF only in patients who were infected with DENV2 but not with DENV1. Moreover, patients with DF who were infected with DENV1 showed higher levels of IL-12p70, TNF-α, and IL-6 than patients with DHF early after-fever onset. The IL-8 levels were similar in all cases regardless of the clinical condition or infection serotype. These results suggest that the association between high proinflammatory cytokine levels and dengue disease severity does not always stand, and it once again highlights the complex nature of DHF pathogenesis.

Factors associated with death from dengue in the state of Minas Gerais, Brazil: historical cohort study.

OBJECTIVES: To analyse the clinical and epidemiological profiles of dengue haemorrhagic fever (DHF), dengue shock syndrome (DSS) and complicated dengue cases and deaths from 2008 to 2010 that occurred in the state of Minas Gerais, south-eastern Brazil, and to identify factors associated with death from dengue. METHODS: Historical cohort study using data from the Brazilian Information System for Notifiable Diseases. A descriptive analysis of the DHF, DSS and complicated dengue cases and deaths was performed; the incidence, mortality and case-fatality rates were estimated. Logistic regression analysis was used to identify factors associated with death from dengue. Comorbidities were not included in the analysis because the information system does not contain such data. RESULTS: During the study period, 2214 DHF, DSS and complicated dengue cases were reported, including 156 deaths. The annual case-fatality rates for DHF/DSS and complicated dengue cases in the period of 2008-2010 were 7.3%, 4.8% and 7.9%, respectively. The factors associated with death from dengue included residence in a municipality with a population of fewer than 100,000 inhabitants [odds ratio (OR) 2.46; 95% confidence interval (CI) 1.71-3.55], age over 65 years (OR 3.05; 95% CI 1.99-4.68) and plasma leakage (OR 1.69; 95% CI 1.16-2.46). CONCLUSIONS: The results support the importance of plasma leakage as a warning sign associated with death from dengue as well as the signs and symptoms that allow the diagnosis of DHF. Moreover, our findings suggest that increased attention is necessary for individuals over 65 years of age and in municipalities with populations under 100,000 inhabitants to ensure a better quality of care during the management of severe patients of dengue in these locations. Differences in the interpretation of the DHF definition have hindered the comparison of data from different countries; it can improve from the WHO 2009 dengue classification.

[Phenotypic markers of attenuation in Junin virus strains recently isolated from individuals vaccinated with Junin Candid#1 strain]. / Marcadores fenotípicos de atenuación en cepas de virus Junín recuperadas de individuos vacunados con la cepa Junín Candid#1.

Argentine hemorrhagic fever is a severe acute disease caused by Junin virus. For prevention of this disease an effective vaccine called Candid#1 has been developed, composed of a live attenuated Junin virus strain. During a clinical trial conducted at Instituto Nacional de Enfermedades Virales Humanas (INEVH) in 2005, Junin virus was isolated from two vaccinated volunteers by co-culture of peripheral mononuclear blood cells. The aim of this study was to compare the strains isolated from these human volunteers with Candid#1 strain regarding phenotypic characteristics of attenuation according to the indicators developed by Contigiani and Sabattini in 1977. The three strains were lethal to suckling mice but not to 10-12 days old mice and guinea pigs. Surviving guinea pigs from primary infection were protected when challenged by intra-muscular inoculation with lethal doses of a virulent strain. Infection and protection rates indicate that these strains are highly infective and protective in the hosts studied herein. These results demonstrate that Junin virus strains isolated from volunteers immunized with Candid#1 maintain the same attenuated phenotype of Candid#1 vaccine after one passage in humans.

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.

Fiebre manchada de las montañas rocosas: ni tan manchada ni tan montañosa como pensábamos / Rocky Mountain Spotted Fever: not as spotted

La fiebre manchada de las Montañas Rocosas es una infección producida por Rickettsia rickettsii, un cocobacilo polimorfo perteneciente a la familia Rickettsiaceae. A pesar de que ha pasado más de un siglo desde que fue descrita, continúa siendo una de las zoonosis más importantes en todo el mundo. Aunque los casos se presentan de manera focal y esporádica, en los últimos años se ha notado un incremento de su incidencia en los Estados Unidos y parece estar resurgiendo en varios países de Suramérica. En Colombia, poco se sabía de la enfermedad desde 1937, cuando fue descrita por primera vez, pero, en los últimos años se han presentado nuevos casos con alta tasa de mortalidad. Dado que los hallazgos clínicos y de laboratorio son inespecíficos, la fiebre manchada de las Montañas Rocosas debe incluirse en el diagnóstico diferencial de los síndromes febriles de causa no clara. A continuación se presenta una revisión de la literatura, señalando los aspectos más importantes del resurgimiento de la enfermedad en Colombia y se resaltan su etiopatogenia, manifestaciones clínicas, diagnóstico y tratamiento, con el objeto de mejorar el conocimiento local de esta infección, probablemente subdiagnosticada, que puede curarse fácilmente con unas cuantas dosis de antibióticos por vía oral.

Rocky Mountain Spotted Fever (RMSF) is an infection caused by Rickettsia rickettsii, a pleomorphic cocobacillae which belongs to the Rickettsiaceae family. Although it has been more than a century since its first description, this disease is still one of the most important zoonosis in the world. Usually cases occur in focal and sporadic form, but an unusual increase in the frequency of cases during the last few years has drawn the attention of surveillance systems in United States and some South American countries. Little was known about the disease in Colombia when it was first described in 1937, but in recent years new cases have been reported showing high mortality rates. Since clinical and laboratory findings have not been specific, the RMSF must be included in the differential diagnosis of febrile syndromes of unknown origin. A literature review follows herein, pointing out the most important features of the cases diagnosed in Colombia and highlighting their pathogenesis, clinical manifestations, diagnosis, and treatment, and attempting to improve local knowledge of this infection. The disease is probably under-diagnosed and could be treated with a few doses of PO antibiotics.

Neisseria meningitidis: a neglected cause of infectious haemorrhagic fever in the amazon rainforest

Neisseria meningitidis has not been seen as a significant cause of infectious haemorrhagic fever in the Amazon inlands; most reported cases are from the city of Manaus, the capital of the State of Amazonas. This picture is sustained by the lack of reliable microbiology laboratories, the perception of the health care workers, and the difficult to reach medical assistance; thus the number of confirmed cases is even lower with no reference of the strains phenotype. We report here the investigation of a case of suspected meningococcemia and his close contacts in a rural community in the Coari Lake, up the Amazon River.

Crimean-Congo haemorrhagic fever in ostriches: could it be a public health risk? / Febre hemorrágica Crimean-Congo em avestruzes: poderá ser um risco de saúde pública?

Crimean-Congo haemorrhagic fever is a zoonose caused by a virus of nairovirus genera, which maybe transmitted by ixodides ticks. The ostriches among other domestic and wild birds species are refractory to CCHF, but in humans the disease have shown to be lethal in 30% of the cases. The disease is disserninated in A ia, Africa and east of Europe. In the past few year in South Africa The first country to produce and export ostriches, many cases of such disease were reported in people who work in slaughterhouses, as weU a people who deal with ostriches and/or diagnostic laboratory technician.

A doença conhecida como febre hemorrágica Crimean-Congo é uma zoonose causada por um vírus do gênero Nairovirus, que pode er transmitida por carrapato ixodídeos e argasídeos. Os avestruzes, entre outras espécies de ave doméstica e silvestres, são considerados refratários à doença, mas no humanos a doença apresentou-se fatal em 30% dos casos. A doença está amplamente disseminada na Ásia, África e leste da Europa. Nos últimos anos, na África do Sul - país pioneiro na produção e exportação de avestruzes, foram reportados alguns surtos da doença em humanos que trabalhavam em abatedouro, manipulavam essa espécie animal e/ou trabalhavam em laboratórios de diagnóstico.

Crimean-Congo haemorrhagic fever in ostriches: could it be a public health risk? / Febre hemorrágica Crimean-Congo em avestruzes: poderá ser um risco de saúde pública?

Crimean-Congo haemorrhagic fever is a zoonose caused by a virus of nairovirus genera, which maybe transmitted by ixodides ticks. The ostriches among other domestic and wild birds species are refractory to CCHF, but in humans the disease have shown to be lethal in 30% of the cases. The disease is disserninated in A ia, Africa and east of Europe. In the past few year in South Africa The first country to produce and export ostriches, many cases of such disease were reported in people who work in slaughterhouses, as weU a people who deal with ostriches and/or diagnostic laboratory technician.

A doença conhecida como febre hemorrágica Crimean-Congo é uma zoonose causada por um vírus do gênero Nairovirus, que pode er transmitida por carrapato ixodídeos e argasídeos. Os avestruzes, entre outras espécies de ave doméstica e silvestres, são considerados refratários à doença, mas no humanos a doença apresentou-se fatal em 30% dos casos. A doença está amplamente disseminada na Ásia, África e leste da Europa. Nos últimos anos, na África do Sul - país pioneiro na produção e exportação de avestruzes, foram reportados alguns surtos da doença em humanos que trabalhavam em abatedouro, manipulavam essa espécie animal e/ou trabalhavam em laboratórios de diagnóstico.