The Chikungunya virus infection zones have now quickly spread from Africa to parts of Asia, North America and Europe. Originally thought to trigger a disease of only mild symptoms, recently Chikungunya virus caused large-scale fatalities and widespread economic loss that was linked to recent virus genetic mutation and evolution. Due to the paucity of information on Chikungunya immunological progression, we investigated the serum levels of 13 cytokines/chemokines during the acute phase of Chikungunya disease and 6- and 12-month post-infection follow-up from patients of the Italian outbreak. We found that CXCL9/MIG, CCL2/MCP-1, IL-6 and CXCL10/IP-10 were significantly raised in the acute phase compared to follow-up samples. Furthermore, IL-1β, TNF-α, Il-12, IL-10, IFN-γ and IL-5 had low initial acute phase levels that significantly increased at later time points. Analysis of symptom severity showed association with CXCL9/MIG, CXCL10/IP-10 and IgG levels. These data give insight into Chikungunya disease establishment and subsequent convalescence, which is imperative to the treatment and containment of this quickly evolving and frequently re-emerging disease. Chikungunya virus (CHIKV) is transmitted by mosquitoes and causes a human disease clinically characterized by sudden appearance of high fever, rash, headache, nausea, and severe joint pain (the defining symptom). Chikungunya was identified in Africa and the word Chikungunya means that which bends up, describing the bent posture of CHIKV patients while in severe pain. CHIKV, a current problem in Africa, Indian Ocean region, and Southeast Asia, is now spreading to temperate regions of North America, France and Italy. Presently, the immune response for CHIKV infection remains largely uninvestigated and no treatment is available. We investigated cytokine profiles at diagnosis and follow-up of CHIKV infected patients during the Italian 2007 outbreak and associated cytokine levels with antibody level and symptom severity. Cytokines, important immune mediators, are often drug targets. Since CHIKV symptoms can persist for months or years following infection it is important to investigate possible drug targets to alleviate discomfort. We found cytokine profiles that describe the initial infection and recovery phase. We determined the cytokines CXCL9/MIG and CXCL10/IP-10 as well as antibody levels were associated with symptom severity. These results reflect previously unreported cytokine profiles which may be important for the development of future therapeutics for CHIKV outbreaks.

West Nile virus (WNV) is a mosquito-borne flavivirus in the Japanese encephalitis antigenic group. It was first isolated in 1937 from a febrile woman in Omogo in the West Nile district of Uganda [ 1 x 1 Hubalek, Z and Halouzka, J. West Nile fever—a reemerging mosquito‐borne viral disease in Europe. Emerg Infect Dis. 1999; 5: 643–650 Crossref | PubMed | Google Scholar See all References 1 ]. WNV has a natural transmission cycle in Culex spp. mosquitoes and wild and captive birds [ 2 x 2 Rossi, SL, Ross, TM, and Evans, JD. West Nile virus. Clin Lab Med. 2010; 30: 47–65 Abstract | Full Text | Full Text PDF | PubMed | Scopus (80) | Google Scholar See all References 2 ]. In contrast, humans and horses are incidental dead-end hosts [ 3 x 3 Kramer, LD, Li, J, and Shi, PY. West Nile virus. Lancet Neurol. 2007; 6: 171–181 Abstract | Full Text | Full Text PDF | PubMed | Scopus (185) | Google Scholar See all References 3 ]. The enzootic/epizootic cycle is strictly linked to the period of activity of the arthropod vectors, which, in Europe, results in a season of WNV activity that, depending on the different latitude, ranges from mid-June to mid-November [ 4 x 4 Angelini, P, Tamba, M, Finarelli, AC et al. West Nile virus circulation in Emilia‐Romagna, Italy: the integrated surveillance system 2009. Euro Surveill. 2010; 15: 19547 PubMed | Google Scholar See all References , 5 x 5 Reiter, P. West Nile virus in Europe: understanding the present to gauge the future. Euro Surveill. 2010; 15: 19508 PubMed | Google Scholar See all References ]. Since its first recognition in Uganda, the virus has gradually dispersed, via migratory birds, out of Africa to the more southerly regions of Europe, Asia, and Australasia [ 2 x 2 Rossi, SL, Ross, TM, and Evans, JD. West Nile virus. Clin Lab Med. 2010; 30: 47–65 Abstract | Full Text | Full Text PDF | PubMed | Scopus (80) | Google Scholar See all References 2 ]. This review highlights some of the most relevant aspects of WNV human infections in Europe.

Usutu virus (USUV) is a mosquito-borne flavivirus that emerged 2001 in Austria and caused deaths in wild birds. In Germany, 70,378 female mosquitoes were captured in 2009 and 2010 and assayed for USUV. Virus was isolated in cell culture from one pool of Culex pipiens pipiens mosquitoes trapped exclusively in August 2010 in Weinheim, Germany. Subsequent phylogenetic analysis demonstrated a close relationship between the isolated USUV strain from Germany and a USUV strain from Austria, which was detected in a dead blackbird in 2004.

We report a case of Usutu virus (USUV)-related illness in a patient that underwent an orthotropic liver transplant (OLT). Post transplant, the patient developed clinical signs of a possible neuroinvasive disease with a significant loss of cerebral functions. USUV was isolated in Vero E6 cells from a plasma sample obtained immediately before the surgery, and USUV RNA was demonstrated by RT-PCR and sequencing. This report enlarges the panel of emerging mosquito-borne flavivirus-related disease in humans.

After an outbreak of Chikungunya infection in Emilia-Romagna Region (North-eastern Italy), a survey was performed to estimate the seroprevalence of antibody to Chikungunya virus and the proportion of asymptomatic infections, to identify factors associated with infection, and evaluate the performance of the surveillance system. The method used was a survey on a random sample of residents of the village with the largest number of reported cases. The prevalence was 10.2% (33 of 325), being higher in older people and males, and lower when window screens and insect repellents were used. Only 18% of infected persons were fully asymptomatic, 85% of the 27 symptomatic confirmed cases satisfied the surveillance case definition, and 63% of the persons meeting the criteria for suspect case were identified by the active surveillance system. This study provides basic parameters for modeling the transmission potential of outbreaks and planning control measures for Chikungunya infection in temperate settings.

Originating from Africa, Usutu virus (USUV) first emerged in Europe in 2001. This mosquito-borne flavivirus caused high mortality rates in its bird reservoirs, which strongly resembled the introduction of West Nile virus (WNV) in 1999 in the United States. Mosquitoes infected with USUV incidentally transmit the virus to other vertebrates, including humans, which can result in neuroinvasive disease. USUV and WNV co-circulate in parts of southern Europe, but the distribution of USUV extends into central and northwestern Europe. In the field, both viruses have been detected in the northern house mosquito Culex pipiens, of which the potential for USUV transmission is unknown. To understand the transmission dynamics and assess the potential spread of USUV, we determined the vector competence of C. pipiens for USUV and compared it with the well characterized WNV. We show for the first time that northwestern European mosquitoes are highly effective vectors for USUV, with infection rates of 11% at 18 °C and 53% at 23 °C, which are comparable with values obtained for WNV. Interestingly, at a high temperature of 28 °C, mosquitoes became more effectively infected with USUV (90%) than with WNV (58%), which could be attributed to barriers in the mosquito midgut. Small RNA deep sequencing of infected mosquitoes showed for both viruses a strong bias for 21-nucleotide small interfering (si)RNAs, which map across the entire viral genome both on the sense and antisense strand. No evidence for viral PIWI-associated RNA (piRNA) was found, suggesting that the siRNA pathway is the major small RNA pathway that targets USUV and WNV infection in C. pipiens mosquitoes.