Postepidemic Analysis of Rift Valley Fever Virus Transmission in Northeastern Kenya: A Village Cohort Study

RVFV infection causes significant disease in both human and animal populations, resulting in significant agricultural, economic and public health consequences. We conducted a cohort study on residents of a high-risk area to measure human anti-RVFV seroprevalence, to identify risk factors, and to estimate the durability of prior RVFV immunity. One hundred two individuals tested for RVFV exposure before the 2006–2007 RVF outbreak were restudied to determine interval anti-RVFV seroconversion and persistence of humoral immunity since 2006. Ninety-two additional subjects were enrolled from randomly selected households to help identify risk factors for current seropositivity. Seroprevalence in the region was high (23%). 1/85 at-risk individuals restudied in the follow-up cohort had seroconverted since early 2006. 29% of newly tested individuals were seropositive. After adjustment in multivariable logistic models, age, village, and drinking raw milk were significantly associated with RVFV seropositivity. Visual impairment (defined as ≤20/80) was much more likely in the RVFV-seropositive group. Among those with previous exposure, RVFV titers remained at protective levels (>1∶40) for more than 3 years. This study highlights the high seroprevalence among Northeastern Kenyans and the ongoing surge in seroprevalence with each RVF outbreak

Melting of a 2D Quantum Electron Solid in High Magnetic Field

The melting temperature ($T_m$) of a solid is generally determined by the pressure applied to it, or indirectly by its density ($n$) through the equation of state. This remains true even for helium solids\cite{wilk:67}, where quantum effects often lead to unusual properties\cite{ekim:04}. In this letter we present experimental evidence to show that for a two dimensional (2D) solid formed by electrons in a semiconductor sample under a strong perpendicular magnetic field\cite{shay:97} ($B$), the $T_m$ is not controlled by $n$, but effectively by the \textit{quantum correlation} between the electrons through the Landau level filling factor $\nu$=$nh/eB$. Such melting behavior, different from that of all other known solids (including a classical 2D electron solid at zero magnetic field\cite{grim:79}), attests to the quantum nature of the magnetic field induced electron solid. Moreover, we found the $T_m$ to increase with the strength of the sample-dependent disorder that pins the electron solid.Comment: Some typos corrected and 2 references added. Final version with minor editoriol revisions published in Nature Physic

Rift Valley Fever Virus Seroprevalence in Human Rural Populations of Gabon

Rift Valley fever (RVF) is a disease transmitted by a mosquito bite (Aedes). Humans can also be infected through direct contact with blood (aerosols) or tissues (placenta, stillborn) of infected animals. Although severe clinical cases can be observed, infection with RVF virus (RVFV) in humans in most cases causes a febrile illness without serious symptoms. In small ruminants RVFV mainly causes abortion and neonatal death. RVFV distribution has been poorly investigated in Central Africa. We conducted a large scale serological survey of RVF antibodies in rural populations in Gabon, involving 4,323 individuals from 212 randomly selected villages. The results showed an overall RVFV prevalence of 3.3%, with values of 2.9% in the forested zones, 2.2% in savannas and 8.3% in the lakes region. These findings strongly suggest for the first time the wide circulation of Rift valley fever virus in Gabon and the possible existence of a sylvan cycle of RVF virus in this country. The serological higher prevalence in the lake region suggests that this region is likely to have particular ecological conditions, especially mosquito vector species, favoring the circulation of this virus. In Gabon, human cases of RVF may occur but are either misdiagnosed or not reported

Broad Spectrum Antiviral Activity of Favipiravir (T-705): Protection from Highly Lethal Inhalational Rift Valley Fever

Background:Development of antiviral drugs that have broad-spectrum activity against a number of viral infections would be of significant benefit. Due to the evolution of resistance to currently licensed antiviral drugs, development of novel anti-influenza drugs is in progress, including Favipiravir (T-705), which is currently in human clinical trials. T-705 displays broad-spectrum in vitro activity against a number of viruses, including Rift Valley Fever virus (RVFV). RVF is an important neglected tropical disease that causes human, agricultural, and economic losses in endemic regions. RVF has the capacity to emerge in new locations and also presents a potential bioterrorism threat. In the current study, the in vivo efficacy of T-705 was evaluated in Wistar-Furth rats infected with the virulent ZH501 strain of RVFV by the aerosol route.Methodology/Principal Findings:Wistar-Furth rats are highly susceptible to a rapidly lethal disease after parenteral or inhalational exposure to the pathogenic ZH501 strain of RVFV. In the current study, two experiments were performed: a dose-determination study and a delayed-treatment study. In both experiments, all untreated control rats succumbed to disease. Out of 72 total rats infected with RVFV and treated with T-705, only 6 succumbed to disease. The remaining 66 rats (92%) survived lethal infection with no significant weight loss or fever. The 6 treated rats that succumbed survived significantly longer before succumbing to encephalitic disease.Conclusions/Significance:Currently, there are no licensed antiviral drugs for treating RVF. Here, T-705 showed remarkable efficacy in a highly lethal rat model of Rift Valley Fever, even when given up to 48 hours post-infection. This is the first study to show protection of rats infected with the pathogenic ZH501 strain of RVFV. Our data suggest that T-705 has potential to be a broad-spectrum antiviral drug. © 2014 Caroline et al

Randomized controlled field trial to assess the immunogenicity and safety of rift valley fever clone 13 vaccine in livestock

BACKGROUND:Although livestock vaccination is effective in preventing Rift Valley fever (RVF) epidemics, there are concerns about safety and effectiveness of the only commercially available RVF Smithburn vaccine. We conducted a randomized controlled field trial to evaluate the immunogenicity and safety of the new RVF Clone 13 vaccine, recently registered in South Africa. METHODS:In a blinded randomized controlled field trial, 404 animals (85 cattle, 168 sheep, and 151 goats) in three farms in Kenya were divided into three groups. Group A included males and non-pregnant females that were randomized and assigned to two groups; one vaccinated with RVF Clone 13 and the other given placebo. Groups B included animals in 1st half of pregnancy, and group C animals in 2nd half of pregnancy, which were also randomized and either vaccinated and given placebo. Animals were monitored for one year and virus antibodies titers assessed on days 14, 28, 56, 183 and 365. RESULTS:In vaccinated goats (N = 72), 72% developed anti-RVF virus IgM antibodies and 97% neutralizing IgG antibodies. In vaccinated sheep (N = 77), 84% developed IgM and 91% neutralizing IgG antibodies. Vaccinated cattle (N = 42) did not develop IgM antibodies but 67% developed neutralizing IgG antibodies. At day 14 post-vaccination, the odds of being seropositive for IgG in the vaccine group was 3.6 (95% CI, 1.5 - 9.2) in cattle, 90.0 (95% CI, 25.1 - 579.2) in goats, and 40.0 (95% CI, 16.5 - 110.5) in sheep. Abortion was observed in one vaccinated goat but histopathologic analysis did not indicate RVF virus infection. There was no evidence of teratogenicity in vaccinated or placebo animals. CONCLUSIONS:The results suggest RVF Clone 13 vaccine is safe to use and has high (>90%) immunogenicity in sheep and goats but moderate (> 65%) immunogenicity in cattle

Chemotactic and Inflammatory Responses in the Liver and Brain Are Associated with Pathogenesis of Rift Valley Fever Virus Infection in the Mouse

Rift Valley fever virus (RVFV) is a major human and animal pathogen associated with severe disease including hemorrhagic fever or encephalitis. RVFV is endemic to parts of Africa and the Arabian Peninsula, but there is significant concern regarding its introduction into non-endemic regions and the potentially devastating effect to livestock populations with concurrent infections of humans. To date, there is little detailed data directly comparing the host response to infection with wild-type or vaccine strains of RVFV and correlation with viral pathogenesis. Here we characterized clinical and systemic immune responses to infection with wild-type strain ZH501 or IND vaccine strain MP-12 in the C57BL/6 mouse. Animals infected with live-attenuated MP-12 survived productive viral infection with little evidence of clinical disease and minimal cytokine response in evaluated tissues. In contrast, ZH501 infection was lethal, caused depletion of lymphocytes and platelets and elicited a strong, systemic cytokine response which correlated with high virus titers and significant tissue pathology. Lymphopenia and platelet depletion were indicators of disease onset with indications of lymphocyte recovery correlating with increases in G-CSF production. RVFV is hepatotropic and in these studies significant clinical and histological data supported these findings; however, significant evidence of a pro-inflammatory response in the liver was not apparent. Rather, viral infection resulted in a chemokine response indicating infiltration of immunoreactive cells, such as neutrophils, which was supported by histological data. In brains of ZH501 infected mice, a significant chemokine and pro-inflammatory cytokine response was evident, but with little pathology indicating meningoencephalitis. These data suggest that RVFV pathogenesis in mice is associated with a loss of liver function due to liver necrosis and hepatitis yet the long-term course of disease for those that might survive the initial hepatitis is neurologic in nature which is supported by observations of human disease and the BALB/c mouse model

Tissue Tropism and Target Cells of NSs-Deleted Rift Valley Fever Virus in Live Immunodeficient Mice

Rift Valley fever, caused by a member of the Bunyaviridae family, has spread during recent years to most sub-Saharan African countries, in Egypt and in the Arabian peninsula. The virus can be transmitted by insect vectors or by direct contacts with infectious tissues. The analysis of virus replication and dissemination in laboratory animals has been hampered by the need to euthanize sufficient numbers of animals and to assay appropriate organs at various time points after infection to evaluate the viral replication. By following the bioluminescence and fluorescence of Rift Valley fever viruses expressing light reporters, we were able to track the real-time dissemination of the viruses in live immunodeficient mice. We showed that the first infected organs were the thymus, spleen and liver, but the liver rapidly became the main location of viral replication. Phagocytes also appeared as important targets, and their systemic depletion by use of clodronate liposomes decreased the number of viruses in the blood, delayed the viral dissemination and prolonged the survival of the infected mice

Planetary Rings

Planetary rings are the only nearby astrophysical disks, and the only disks that have been investigated by spacecraft. Although there are significant differences between rings and other disks, chiefly the large planet/ring mass ratio that greatly enhances the flatness of rings (aspect ratios as small as 1e-7), understanding of disks in general can be enhanced by understanding the dynamical processes observed at close-range and in real-time in planetary rings. We review the known ring systems of the four giant planets, as well as the prospects for ring systems yet to be discovered. We then review planetary rings by type. The main rings of Saturn comprise our system's only dense broad disk and host many phenomena of general application to disks including spiral waves, gap formation, self-gravity wakes, viscous overstability and normal modes, impact clouds, and orbital evolution of embedded moons. Dense narrow rings are the primary natural laboratory for understanding shepherding and self-stability. Narrow dusty rings, likely generated by embedded source bodies, are surprisingly found to sport azimuthally-confined arcs. Finally, every known ring system includes a substantial component of diffuse dusty rings. Planetary rings have shown themselves to be useful as detectors of planetary processes around them, including the planetary magnetic field and interplanetary impactors as well as the gravity of nearby perturbing moons. Experimental rings science has made great progress in recent decades, especially numerical simulations of self-gravity wakes and other processes but also laboratory investigations of coefficient of restitution and spectroscopic ground truth. The age of self-sustained ring systems is a matter of debate; formation scenarios are most plausible in the context of the early solar system, while signs of youthfulness indicate at least that rings have never been static phenomena.Comment: 82 pages, 34 figures. Final revision of general review to be published in "Planets, Stars and Stellar Systems", P. Kalas and L. French (eds.), Springer (http://refworks.springer.com/sss