Assessment of chemokine and cytokine signatures in patients with dengue infection: A hospital-based study in Kolkata, India.

Dengue fever is an acute viral infection transmitted by arthropods but may evolve to severe clinical manifestations. Descriptions of the role of circulating immune modulators such as cytokines or chemokines in dengue immunopathogenesis have largely relied on data from South-east Asia and America, while India is poorly represented. This study characterizes dengue cases from West Bengal, eastern India, with respect to clinical profile and pro-inflammatory and inflammatory cytokines. We evaluated the profile of both inflammatory and anti-inflammatory cytokines (IFNγ, IL6, IL10, IL12 and TGFß) and chemokines (IL8, CXCL9, CXCL10 and RANTES) in 100 hospitalized NS1/IgM confirmed Dengue patients during the epidemic in West Bengal during 2017. Additionally, all necessary blood investigations of the study subjects were performed. The patients mostly hailed from Kolkata, followed by Nadia, 24 Parganas (North and South), Murshidabad and Midnapore. The most common presentations apart from fever and bodyache were gastrointestinal symptoms. An elevated levels of cytokines IL6 and IL10 chemokine IL8 and CXCL10 along with decreased RANTES were found in the patients with Severe Dengue as compared to mild forms of dengue (p < 0.0001) during 3-6 days of infections. A significant association was obtained between most of cytokine and increased SGPT, haematocrit, albumin and decreased platelet count, whereas a negative correlation with the level of RANTES to haematocrit (r=-0.220 with p = 0.029) was found in severe dengue cases with altered liver function parameters. This is the first study demonstrating cytokine and chemokine association with dengue severity from the eastern part of India. Taken together, this study demonstrated that the altered expression levels of IL6, IL10, IL8, CXCL10 and RANTES had significant associations with dengue severity parameters.

Assessment of World Health Organization definition of dengue hemorrhagic fever in North India.

BACKGROUND: Classification of symptomatic dengue according to current World Health Organization (WHO) criteria is not straightforward. In this prospective study of dengue infection during an epidemic in India in 2004, we applied the WHO classification of dengue to assess its usefulness for our patients. METHODOLOGY: The study included 145 clinically suspected cases of dengue infection of all ages. Dengue was confirmed by serological methods (IgM ELISA and HI test). WHO criteria were applied to classify dengue positive patients into Dengue Fever (DF), Dengue Hemorrhagic Fever (DHF) and Dengue Shock Syndrome (DSS). Clinical and laboratory parameters were compared between dengue patients with bleeding and those without bleeding. RESULTS: Out of the 50 serologically positive cases of dengue enrolled in the study, only 3 met the WHO criteria for DHF and 1 met the criteria for DSS; however, 21 (42%) cases had one or more bleeding manifestations. CONCLUSION: By using WHO criteria of DHF on Indian patients, all severe cases of dengue cannot be correctly classified. A new definition of DHF that considers geographic and age-related variations in laboratory and clinical parameters is urgently required.

Consecuencias del dengue hemorrágico en niños / Impact of dengue hemorrhagic fever in children

En los niños, el dengue se presenta con una variabilidad sintomática caracterizado por manifestaciones de extravasación vascular que pueden conllevar a consecuencias severas en términos de mortalidad y de costos. Estudio prospectivo y descriptivo realizado en Pediatría Médica Infecciosa (PMI) del hospital Universitario de Caracas (HUC), en niños de un mes a 12 años, con criterios de dengue hemorrágico (DH) y evidencia por laboratorio de infección aguda o reciente, que ingresaron entre enero 2000 y junio 2008, con el objetivo de evaluar las consecuencias en términos de mortalidad y costos por hospitalización. De 4 386/930 hospitalizados que ingresaron con diagnóstico de dengue, 453 cumplieron con los criterios de inclusión representando el 10 por ciento de las hospitalizaciones en PMI. El DH se presentó con mayor frecuencia entre los 5 y 9 años de edad y en el segundo semestre de cada año. El promedio de hospitalización fue de 6 días. Las consecuencias se evaluaron en términos de pérdidas de vidas (3 niños), con una tasa de letalidad 0,6 por ciento y egresos monetarios por concepto de hospitalización (exceptuando de la definición, costos/medicamentos y pruebas de laboratorio). Los gastos/hospitalización/día oscilaron entre 100 y 350$. Un 15 por ciento de los pacientes recibieron antibióticos por diagnósticos diferenciales. Ha habido un incremento progresivo de hospitalizaciones por DH en PMI, desde el 2000, predominando en la época de lluvia, con registros de casos fatales. Se generaron costos hospitalarios elevados por hospitalización que pudieran ser derivados a campañas de prevención.

Understanding dengue pathogenesis: implications for vaccine design.

In the second half of the twentieth century dengue spread throughout the tropics, threatening the health of a third of the world's population. Dengue viruses cause 50-100 million cases of acute febrile disease every year, including more than 500,000 reported cases of the severe forms of the disease--dengue haemorrhagic fever and dengue shock syndrome. Attempts to create conventional vaccines have been hampered by the lack of suitable experimental models, the need to provide protection against all four serotypes simultaneously and the possible involvement of virus-specific immune responses in severe disease. The current understanding of dengue pathogenesis is outlined in this review, with special emphasis on the role of the immune response. The suspected involvement of the immune system in increased disease severity and vascular damage has raised concerns about every vaccine design strategy proposed so far. Clearly more research is needed on understanding the correlates of protection and mechanisms of pathogenesis. There is, however, an urgent need to provide a solution to the escalating global public health problems caused by dengue infections. Better disease management, vector control and improved public health measures will help reduce the current disease burden, but a safe and effective vaccine is probably the only long-term solution. Although concerns have been raised about the possible safety and efficacy of both conventional and novel vaccine technologies, the situation is now so acute that it is not possible to wait for the perfect vaccine. Consequently the careful and thorough evaluation of several of the current candidate vaccines may be the best approach to halting the spread of disease.