Comparative efficacy of two poeciliid fish in indoor cement tanks against chikungunya vector Aedes aegypti in villages in Karnataka, India

<p>Abstract</p> <p>Background</p> <p>In 2006, severe outbreaks of <it>Aedes aegypti</it>-transmitted chikungunya occurred in villages in Karnataka, South India. We evaluated the effectiveness of combined information, education and communication (IEC) campaigns using two potential poeciliid larvivorous fish guppy (<it>Poecilia reticulata</it>) and mosquitofish (<it>Gambusia affinis</it>), in indoor cement tanks for <it>Aedes </it>larval control.</p> <p>Methods</p> <p>Trials were conducted in two villages (Domatmari and Srinivaspura) in Tumkur District from March to May 2006 for <it>Poecilia </it>and one village (Balmanda) in Kolar District from July to October 2006 for <it>Gambusia</it>. A survey on knowledge, attitude and practice (KAP) on chikungunya was initially conducted and IEC campaigns were performed before and after fish release in Domatmari (IEC alone, followed by IEC + <it>Poecilia</it>) and Balmanda (IEC + <it>Gambusia</it>). In Srinivaspura, IEC was not conducted. Larval surveys were conducted at the baseline followed by one-week and one-month post-intervention periods. The impact of fish on <it>Aedes </it>larvae and disease was assessed based on baseline and post-intervention observations.</p> <p>Results</p> <p>Only 18% of respondents knew of the role of mosquitoes in fever outbreaks, while almost all (<it>n </it>= 50 each) gained new knowledge from the IEC campaigns. In Domatmari, IEC alone was not effective (OR 0.54; <it>p </it>= 0.067). Indoor cement tanks were the most preferred <it>Ae. aegypti </it>breeding habitat (86.9%), and had a significant impact on <it>Aedes </it>breeding (Breteau Index) in all villages in the one-week period (<it>p </it>< 0.001). In the one-month period, the impact was most sustained in Domatmari (OR 1.58, <it>p </it>< 0.001) then Srinivaspura (OR 0.45, <it>p </it>= 0.063) and Balmanda (OR 0.51, <it>p </it>= 0.067). After fish introductions, chikungunya cases were reduced by 99.87% in Domatmari, 65.48% in Srinivaspura and 68.51% in Balmanda.</p> <p>Conclusions</p> <p><it>Poecilia </it>exhibited greater survival rates than <it>Gambusia </it>(86.04 <it>vs</it>.16.03%) in cement tanks. Neither IEC nor <it>Poecilia </it>alone was effective against <it>Aedes </it>(<it>p </it>> 0.05). We conclude that <it>Poecilia </it>+ IEC is an effective intervention strategy. The operational cost was 0.50 (US$0.011, 1 US$= 47) per capita per application. Proper water storage practices, focused IEC with <it>Poecilia </it>introductions and vector sanitation involving the local administration and community, is suggested as the best strategy for <it>Aedes </it>control.</p

Post-Epidemic Chikungunya Disease on Reunion Island: Course of Rheumatic Manifestations and Associated Factors over a 15-Month Period

Although the acute manifestations of Chikungunya virus (CHIKV) illness are well-documented, few data exist about the long-term rheumatic outcomes of CHIKV-infected patients. We undertook between June and September 2006 a retrospective cohort study aimed at assessing the course of late rheumatic manifestations and investigating potential risk factors associated with the persistence of these rheumatic manifestations over 15 months. 147 participants (>16 yrs) with laboratory-confirmed CHIKV disease diagnosed between March 1 and June 30, 2005, were identified through a surveillance database and interviewed by telephone. At the 15-month-period evaluation after diagnosis, 84 of 147 participants (57%) self-reported rheumatic symptoms. Of these 84 patients, 53 (63%) reported permanent trouble while 31 (37%) had recurrent symptoms. Age ≥45 years (OR = 3.9, 95% CI 1.7–9.7), severe initial joint pain (OR = 4.8, 95% CI 1.9–12.1), and presence of underlying osteoarthritis comorbidity (OR = 2.9, 95% CI 1.1–7.4) were predictors of nonrecovery. Our findings suggest that long-term CHIKV rheumatic manifestations seem to be a frequent underlying post-epidemic condition. Three independent risk factors that may aid in early recognition of patients with the highest risk of presenting prolonged CHIKV illness were identified. Such findings may be particularly useful in the development of future prevention and care strategies for this emerging virus infection

Sequential Adaptive Mutations Enhance Efficient Vector Switching by Chikungunya Virus and Its Epidemic Emergence

The adaptation of Chikungunya virus (CHIKV) to a new vector, the Aedes albopictus mosquito, is a major factor contributing to its ongoing re-emergence in a series of large-scale epidemics of arthritic disease in many parts of the world since 2004. Although the initial step of CHIKV adaptation to A. albopictus was determined to involve an A226V amino acid substitution in the E1 envelope glycoprotein that first arose in 2005, little attention has been paid to subsequent CHIKV evolution after this adaptive mutation was convergently selected in several geographic locations. To determine whether selection of second-step adaptive mutations in CHIKV or other arthropod-borne viruses occurs in nature, we tested the effect of an additional envelope glycoprotein amino acid change identified in Kerala, India in 2009. This substitution, E2-L210Q, caused a significant increase in the ability of CHIKV to develop a disseminated infection in A. albopictus, but had no effect on CHIKV fitness in the alternative mosquito vector, A. aegypti, or in vertebrate cell lines. Using infectious viruses or virus-like replicon particles expressing the E2-210Q and E2-210L residues, we determined that E2-L210Q acts primarily at the level of infection of A. albopictus midgut epithelial cells. In addition, we observed that the initial adaptive substitution, E1-A226V, had a significantly stronger effect on CHIKV fitness in A. albopictus than E2-L210Q, thus explaining the observed time differences required for selective sweeps of these mutations in nature. These results indicate that the continuous CHIKV circulation in an A. albopictus-human cycle since 2005 has resulted in the selection of an additional, second-step mutation that may facilitate even more efficient virus circulation and persistence in endemic areas, further increasing the risk of more severe and expanded CHIK epidemics

Recombinant Modified Vaccinia Virus Ankara Expressing Glycoprotein E2 of Chikungunya Virus Protects AG129 Mice against Lethal Challenge

Chikungunya virus (CHIKV) infection is characterized by rash, acute high fever, chills, headache, nausea, photophobia, vomiting, and severe polyarthralgia. There is evidence that arthralgia can persist for years and result in long-term discomfort. Neurologic disease with fatal outcome has been documented, although at low incidences. The CHIKV RNA genome encodes five structural proteins (C, E1, E2, E3 and 6K). The E1 spike protein drives the fusion process within the cytoplasm, while the E2 protein is believed to interact with cellular receptors and therefore most probably constitutes the target of neutralizing antibodies. We have constructed recombinant Modified Vaccinia Ankara (MVA) expressing E3E2, 6KE1, or the entire CHIKV envelope polyprotein cassette E3E26KE1. MVA is an appropriate platform because of its demonstrated clinical safety and its suitability for expression of various heterologous proteins. After completing the immunization scheme, animals were challenged with CHIV-S27. Immunization of AG129 mice with MVAs expressing E2 or E3E26KE1 elicited neutralizing antibodies in all animals and provided 100% protection against lethal disease. In contrast, 75% of the animals immunized with 6KE1 were protected against lethal infection. In conclusion, MVA expressing the glycoprotein E2 of CHIKV represents as an immunogenic and effective candidate vaccine against CHIKV infections

Macrophage-derived proinflammatory factors contribute to the development of arthritis and myositis after infection with an arthrogenic alphavirus

Alphaviruses, such as chikungunya virus and Ross River virus (RRV), are associated with outbreaks of infectious rheumatic disease in humans worldwide. Using an established mouse model of disease that mimics RRV disease in humans, we showed that macrophage‐derived factors are critical in the development of striated muscle and joint tissue damage. Histologic analyses of muscle and ankle joint tissues demonstrated a substantial reduction in inflammatory infiltrates in infected mice depleted of macrophages (i.e., “macrophage‐depleted mice”). Levels of the proinflammatory factors tumor necrosis factor–α, interferon–γ, and macrophage chemoattractant protein–1 were also dramatically reduced in tissue samples obtained from infected macrophage‐depleted mice, compared with samples obtained from infected mice without macrophage depletion. These factors were also detected in the synovial fluid of patients with RRV‐induced polyarthritis. Neutralization of these factors reduced the severity of disease in mice, whereas blocking nuclear factor κB by treatment with sulfasalazine ameliorated RRV inflammatory disease and tissue damage. To our knowledge, these findings are the first to demonstrate that macrophage‐derived products play important roles in the development of arthritis and myositis triggered by alphavirus infection.Brett A. Lidbury, Nestor E. Rulli, Andreas Suhrbier, Paul N. Smith, Shaun R. McColl, Anthony L. Cunningham, Andrej Tarkowski, Nico van Rooijen, Robert J. Fraser and Suresh Mahalinga