Modelling the Effects of Seasonality and Socioeconomic Impact on the Transmission of Rift Valley Fever Virus

Rift Valley fever (RVF) is an important mosquito-borne viral zoonosis in Africa and the Middle East that causes human deaths and significant economic losses due to huge incidences of death and abortion among infected livestock. Outbreaks of RVF are sporadic and associated with both seasonal and socioeconomic effects. Here we propose an almost periodic three-patch model to investigate the transmission dynamics of RVF virus (RVFV) among ruminants with spatial movements. Our findings indicate that, in Northeastern Africa, human activities, including those associated with the Eid al Adha feast, along with a combination of climatic factors such as rainfall level and hydrological variations, contribute to the transmission and dispersal of the disease pathogen. Moreover, sporadic outbreaks may occur when the two events occur together: 1) abundant livestock are recruited into areas at risk from RVF due to the demand for the religious festival and 2) abundant numbers of mosquitoes emerge. These two factors have been shown to have impacts on the severity of RVF outbreaks. Our numerical results present the transmission dynamics of the disease pathogen over both short and long periods of time, particularly during the festival time. Further, we investigate the impact on patterns of disease outbreaks in each patch brought by festival- and seasonal-driven factors, such as the number of livestock imported daily, the animal transportation speed from patch to patch, and the death rate induced by ceremonial sacrifices. In addition, our simulations show that when the time for festival preparation starts earlier than usual, the risk of massive disease outbreaks rises, particularly in patch 3 (the place where the religious ceremony will be held).     

A Modeling Approach to Investigate Epizootic Outbreaks and Enzootic Maintenance of Rift Valley Fever Virus

We propose a mathematical model to investigate the transmission dynamics of Rift Valley fever (RVF) virus among ruminants. Our findings indicate that in endemic areas RVF virus maintains at a very low level among ruminants after outbreaks and subsequent outbreaks may occur when new susceptible ruminants are recruited into endemic areas or abundant numbers of mosquitoes emerge when herd immunity decreases. Many factors have been shown to have impacts on the severity of RVF outbreaks; a higher probability of death due to RVF among ruminants, a higher mosquito:ruminant ratio, or a shorter lifespan of animals can amplify the magnitude of the outbreaks; vaccination helps to reduce the magnitude of RVF outbreaks and the loss of animals efficiently, and the maximum vaccination effort (a high vaccination rate and a larger number of vaccinated animals) is recommended before the commencement of an outbreak but can be reduced later during the enzootic.     

Predictive Factors and Risk Mapping for Rift Valley Fever Epidemics in Kenya

Background

To-date, Rift Valley fever (RVF) outbreaks have occurred in 38 of the 69 administrative districts in Kenya. Using surveillance records collected between 1951 and 2007, we determined the risk of exposure and outcome of an RVF outbreak, examined the ecological and climatic factors associated with the outbreaks, and used these data to develop an RVF risk map for Kenya.

Methods

Exposure to RVF was evaluated as the proportion of the total outbreak years that each district was involved in prior epizootics, whereas risk of outcome was assessed as severity of observed disease in humans and animals for each district. A probability-impact weighted score (1 to 9) of the combined exposure and outcome risks was used to classify a district as high (score ≥ 5) or medium (score ≥2 - <5) risk, a classification that was subsequently subjected to expert group analysis for final risk level determination at the division levels (total = 391 divisions). Divisions that never reported RVF disease (score < 2) were classified as low risk. Using data from the 2006/07 RVF outbreak, the predictive risk factors for an RVF outbreak were identified. The predictive probabilities from the model were further used to develop an RVF risk map for Kenya.

Results

The final output was a RVF risk map that classified 101 of 391 divisions (26%) located in 21 districts as high risk, and 100 of 391 divisions (26%) located in 35 districts as medium risk and 190 divisions (48%) as low risk, including all 97 divisions in Nyanza and Western provinces. The risk of RVF was positively associated with Normalized Difference Vegetation Index (NDVI), low altitude below 1000m and high precipitation in areas with solonertz, luvisols and vertisols soil types (p <0.05).

Conclusion

RVF risk map serves as an important tool for developing and deploying prevention and control measures against the disease.     

Rift Valley fever knowledge,mitigation strategies and communication preferences among male and female livestock farmers in Eastern Province,Rwanda

The Government of Rwanda reported an outbreak of Rift Valley fever (RVF) in the Eastern Province in 2018. To respond to the outbreak, vaccination and education campaigns about the disease were carried out. Because RVF cases continue to be detected in Rwanda and the disease impacts livelihoods and health, accurate knowledge and communication are imperative. The objectives of this study were to evaluate knowledge and risk perceptions of RVF transmission among livestock farmers in Nyagatare District, Eastern Province, Rwanda, and to compare RVF knowledge, risk perceptions, and farming practices between male and female livestock farmers. This cross-sectional, quantitative study was conducted in selected sectors of Nyagatare District in the Eastern Province of Rwanda in June 2019. A 34-question survey was used to ask about demographics, livestock ownership, risk perceptions about zoonotic diseases and livestock management, RVF knowledge, preferred communication sources and information sharing strategies, and protective strategies for RVF mitigation while working with livestock. Livestock farmers were interviewed at three milk collection centers, two village meeting points, a farm cooperative meeting, and during door-to-door visits in villages. In total, 123 livestock farmers were interviewed. The survey found that most livestock farmers lacked knowledge about epizootic and zoonotic transmission of RVF, more male livestock farmers were familiar with RVF and risk mitigation strategies, and female livestock farmers are not viewed as reliable sources of information. Additionally, most livestock farmers had not vaccinated their animals against RVF despite past vaccination campaigns. Radio was the most popular communication channel. These findings show that RVF knowledge and information sharing are inadequate among livestock farmers in Eastern Province. Therefore, vaccination and education campaigns may need to be reevaluated within the context of these trends in order to prepare for future RVF outbreaks.     

Fresh fruit and vegetables as vehicles for the transmission of human pathogens

Much research into food‐borne human pathogens has focused on transmission from foods of animal origin. However, recent investigations have identified fruits and vegetables are the source of many disease outbreaks. Now believed to be a much larger contributor to produce‐associated outbreaks than previously reported, norovirus outbreaks are commonly caused by contamination of foods from hands of infected workers. Although infections with Shiga toxin‐producing E. coli O157 have been linked to beef more often than to any other food product, severe outbreaks have been traced to consumption of contaminated radish sprouts and pre‐packaged spinach. Similarly, while infections with Salmonella have mainly been linked to consumption of foods of animal origin, many outbreaks have been traced to contaminated fresh produce. E. coli O157 binds to lettuce leaves by alternative mechanisms involving the filamentous type III secretions system, flagella and the pilus curli. Association of Salmonella with fresh produce appears to be serovar‐specific involving flagella, curli, cellulose, and O antigen capsule. A better understanding of plant, microbiological, environmental, processing and food handling factors that facilitate contamination will allow development of evidence‐based policies, procedures and technologies aimed at reducing the risk of contamination of fresh produce.     

Association of Symptoms and Severity of Rift Valley Fever with Genetic Polymorphisms in Human Innate Immune Pathways

BackgroundMultiple recent outbreaks of Rift Valley Fever (RVF) in Africa, Madagascar, and the Arabian Peninsula have resulted in significant morbidity, mortality, and financial loss due to related livestock epizootics. Presentation of human RVF varies from mild febrile illness to meningoencephalitis, hemorrhagic diathesis, and/or ophthalmitis with residual retinal scarring, but the determinants for severe disease are not understood. The aim of the present study was to identify human genes associated with RVF clinical disease in a high-risk population in Northeastern Province, Kenya.Conclusions/SignificanceOf the 46 SNPs tested, TLR3, TLR7, TLR8, MyD88, TRIF, MAVS, and RIG-I were repeatedly associated with severe symptomatology, suggesting that these genes may have a robust association with RVFV-associated clinical outcomes. Studies of these and related genetic polymorphisms are warranted to advance understanding of RVF pathogenesis.     

Integrated Analysis of Environment,Cattle and Human Serological Data: Risks and Mechanisms of Transmission of Rift Valley Fever in Madagascar

BackgroundRift Valley fever (RVF) is a vector-borne disease affecting ruminants and humans. Madagascar was heavily affected by RVF in 2008–2009, with evidence of a large and heterogeneous spread of the disease. The identification of at-risk environments is essential to optimize the available resources by targeting RVF surveillance in Madagascar. Herein, the objectives of our study were: (i) to identify the environmental factors and areas favorable to RVF transmission to both cattle and human and (ii) to identify human behaviors favoring human infections in Malagasy contexts.Conclusions/SignificanceOur integrated approach analyzing environmental, cattle and human datasets allow us to bring new insight on RVF transmission patterns in Madagascar. The association between cattle seroprevalence, humid environments and high cattle density suggests that concomitant vectorial and direct transmissions are critical to maintain RVF enzootic transmission. Additionally, in the at-risk humid environment of the western, north-western and the eastern-coast areas, suitable to Culex and Anopheles mosquitoes, vectorial transmission probably occurs in both cattle and human. The relative contribution of vectorial or direct transmissions could be further assessed by mathematic modelling.     

Complete genome analysis of 33 ecologically and biologically diverse Rift Valley fever virus strains reveals widespread virus movement and low genetic diversity due to recent common ancestry

Rift Valley fever (RVF) virus is a mosquito-borne RNA virus responsible for large explosive outbreaks of acute febrile disease in humans and livestock in Africa with significant mortality and economic impact. The successful high-throughput generation of the complete genome sequence was achieved for 33 diverse RVF virus strains collected from throughout Africa and Saudi Arabia from 1944 to 2000, including strains differing in pathogenicity in disease models. While several distinct virus genetic lineages were determined, which approximately correlate with geographic origin, multiple exceptions indicative of long-distance virus movement have been found. Virus strains isolated within an epidemic (e.g., Mauritania, 1987, or Egypt, 1977 to 1978) exhibit little diversity, while those in enzootic settings (e.g., 1970s Zimbabwe) can be highly diverse. In addition, the large Saudi Arabian RVF outbreak in 2000 appears to have involved virus introduction from East Africa, based on the close ancestral relationship of a 1998 East African virus. Virus genetic diversity was low (~5%) and primarily involved accumulation of mutations at an average of 2.9 × 10⁻⁴ substitutions/site/year, although some evidence of RNA segment reassortment was found. Bayesian analysis of current RVF virus genetic diversity places the most recent common ancestor of these viruses in the late 1800s, the colonial period in Africa, a time of dramatic changes in agricultural practices and introduction of nonindigenous livestock breeds. In addition to insights into the evolution and ecology of RVF virus, these genomic data also provide a foundation for the design of molecular detection assays and prototype vaccines useful in combating this important disease.     

Rift Valley Fever Risk Map Model and Seroprevalence in Selected Wild Ungulates and Camels from Kenya

Since the first isolation of Rift Valley fever virus (RVFV) in the 1930s, there have been multiple epizootics and epidemics in animals and humans in sub-Saharan Africa. Prospective climate-based models have recently been developed that flag areas at risk of RVFV transmission in endemic regions based on key environmental indicators that precede Rift Valley fever (RVF) epizootics and epidemics. Although the timing and locations of human case data from the 2006–2007 RVF outbreak in Kenya have been compared to risk zones flagged by the model, seroprevalence of RVF antibodies in wildlife has not yet been analyzed in light of temporal and spatial predictions of RVF activity. Primarily wild ungulate serum samples from periods before, during, and after the 2006–2007 RVF epizootic were analyzed for the presence of RVFV IgM and/or IgG antibody. Results show an increase in RVF seropositivity from samples collected in 2007 (31.8%), compared to antibody prevalence observed from 2000–2006 (3.3%). After the epizootic, average RVF seropositivity diminished to 5% in samples collected from 2008–2009. Overlaying maps of modeled RVF risk assessments with sampling locations indicated positive RVF serology in several species of wild ungulate in or near areas flagged as being at risk for RVF. Our results establish the need to continue and expand sero-surveillance of wildlife species Kenya and elsewhere in the Horn of Africa to further calibrate and improve the RVF risk model, and better understand the dynamics of RVFV transmission.     

Combining hydrology and mosquito population models to identify the drivers of rift valley Fever emergence in semi-arid regions of west Africa

Background

Rift Valley fever (RVF) is a vector-borne viral zoonosis of increasing global importance. RVF virus (RVFV) is transmitted either through exposure to infected animals or through bites from different species of infected mosquitoes, mainly of Aedes and Culex genera. These mosquitoes are very sensitive to environmental conditions, which may determine their presence, biology, and abundance. In East Africa, RVF outbreaks are known to be closely associated with heavy rainfall events, unlike in the semi-arid regions of West Africa where the drivers of RVF emergence remain poorly understood. The assumed importance of temporary ponds and rainfall temporal distribution therefore needs to be investigated.

Methodology/Principal Findings

A hydrological model is combined with a mosquito population model to predict the abundance of the two main mosquito species (Aedes vexans and Culex poicilipes) involved in RVFV transmission in Senegal. The study area is an agropastoral zone located in the Ferlo Valley, characterized by a dense network of temporary water ponds which constitute mosquito breeding sites.The hydrological model uses daily rainfall as input to simulate variations of pond surface areas. The mosquito population model is mechanistic, considers both aquatic and adult stages and is driven by pond dynamics. Once validated using hydrological and entomological field data, the model was used to simulate the abundance dynamics of the two mosquito species over a 43-year period (1961–2003). We analysed the predicted dynamics of mosquito populations with regards to the years of main outbreaks. The results showed that the main RVF outbreaks occurred during years with simultaneous high abundances of both species.

Conclusion/Significance

Our study provides for the first time a mechanistic insight on RVFV transmission in West Africa. It highlights the complementary roles of Aedes vexans and Culex poicilipes mosquitoes in virus transmission, and recommends the identification of rainfall patterns favourable for RVFV amplification.     

Knowledge,Attitudes and Practices (KAP) on Rift Valley Fever among Pastoralist Communities of Ijara District,North Eastern Kenya

Outbreaks of Rift Valley fever (RVF), a mosquito-borne viral zoonosis, have previously been associated with unusually heavy rainfall and extensive flooding. The disease is a serious public health problem in Africa and the Middle East, and is a potential global health threat. In Kenya, outbreaks of the disease have disproportionately affected impoverished pastoralist communities. This study sought to assess the knowledge, attitudes and practices (KAP) regarding RVF among the pastoralists of North Eastern Kenya, and to establish the determinants of KAP on RVF. A cross-sectional study involving 392 pastoralists living in Ijara district (Masalani and Ijara wards) was carried out using an interview questionnaire. All respondents interviewed (100%) had heard about RVF disease. They recognized that the disease is dangerous (99%), and had a positive attitude towards vaccination of animals (77%). However, few respondents knew that abortion (11%) and high mortality of young animals (10%) were key signs of RVF in animals. Very few (4%) use any form of protection when handling sick animals to avoid infection. Significant factors associated with knowledge were being in a household with a history of RVF infection (OR = 1.262, 95% CI = 1.099–1.447), having more livestock (OR = 1.285, 95% CI = 1.175–1.404) and the place of residence, Masalani (OR = 0.526, 95% CI = 0.480–0.576). Overall knowledge score on RVF was found to be a significant predictor of good preventive practice of the disease (OR = 1.073, 95% CI = 1.047–1.101). Despite the positive attitude that pastoralist communities have towards the prevention of RVF, there exist gaps in knowledge and good practices on the disease. Therefore there is need for public health education to address these gaps, and to identify and facilitate the removal of barriers to behavioural change related to the prevention of RVF.     

Inter-epidemic Acquisition of Rift Valley Fever Virus in Humans in Tanzania

Background

In East Africa, epidemics of Rift Valley fever (RVF) occur in cycles of 5–15 years following unusually high rainfall. RVF transmission during inter-epidemic periods (IEP) generally passes undetected in absence of surveillance in mammalian hosts and vectors. We studied IEP transmission of RVF and evaluated the demographic, behavioural, occupational and spatial determinants of past RVF infection.

Methodology

Between March and August 2012 we collected blood samples, and administered a risk factor questionnaire among 606 inhabitants of 6 villages in the seasonally inundated Kilombero Valley, Tanzania. ELISA tests were used to detect RVFV IgM and IgG antibodies in serum samples. Risk factors were examined by mixed effects logistic regression.

Findings

RVF virus IgM antibodies, indicating recent RVFV acquisition, were detected in 16 participants, representing 2.6% overall and in 22.5% of inhibition ELISA positives (n = 71). Four of 16 (25.0%) IgM positives and 11/71 (15.5%) of individuals with inhibition ELISA sero-positivity reported they had had no previous contact with host animals. Sero-positivity on inhibition ELISA was 11.7% (95% CI 9.2–14.5) and risk was elevated with age (odds ratio (OR) 1.03 per year; 95% CI 1.01–1.04), among milkers (OR 2.19; 95% CI 1.23–3.91), and individuals eating raw meat (OR 4.17; 95% CI 1.18–14.66). Households keeping livestock had a higher probability of having members with evidence of past infection (OR = 3.04, 95% CI = 1.42–6.48) than those that do not keep livestock.

Conclusion

There is inter-epidemic acquisition of RVFV in Kilombero Valley inhabitants. In the wake of declining malaria incidence, these findings underscore the need for clinicians to consider RVF in the differential diagnosis for febrile illnesses. Several types of direct contact with livestock are important risk factors for past infection with RVFV in this study’s population. However, at least part of RVFV transmission appears to have occurred through bites of infected mosquitoes.     

Modeling the Spatial Spread of Rift Valley Fever in Egypt

Rift Valley fever (RVF) is a severe viral zoonosis in Africa and the Middle East that harms both human health and livestock production. It is believed that RVF in Egypt has been repeatedly introduced by the importation of infected animals from Sudan. In this paper, we propose a three-patch model for the process by which animals enter Egypt from Sudan, are moved up the Nile, and then consumed at population centers. The basic reproduction number for each patch is introduced and then the threshold dynamics of the model are established. We simulate an interesting scenario showing a possible explanation of the observed phenomenon of the geographic spread of RVF in Egypt.     

First External Quality Assessment of Molecular and Serological Detection of Rift Valley Fever in the Western Mediterranean Region

Rift Valley fever (RVF) is a mosquito-borne viral zoonosis which affects humans and a wide range of domestic and wild ruminants. The large spread of RVF in Africa and its potential to emerge beyond its geographic range requires the development of surveillance strategies to promptly detect the disease outbreaks in order to implement efficient control measures, which could prevent the widespread of the virus to humans. The Animal Health Mediterranean Network (REMESA) linking some Northern African countries as Algeria, Egypt, Libya, Mauritania, Morocco, Tunisia with Southern European ones as France, Italy, Portugal and Spain aims at improving the animal health in the Western Mediterranean Region since 2009. In this context, a first assessment of the diagnostic capacities of the laboratories involved in the RVF surveillance was performed. The first proficiency testing (external quality assessment—EQA) for the detection of the viral genome and antibodies of RVF virus (RVFV) was carried out from October 2013 to February 2014. Ten laboratories participated from 6 different countries (4 from North Africa and 2 from Europe). Six laboratories participated in the ring trial for both viral RNA and antibodies detection methods, while four laboratories participated exclusively in the antibodies detection ring trial. For the EQA targeting the viral RNA detection methods 5 out of 6 laboratories reported 100% of correct results. One laboratory misidentified 2 positive samples as negative and 3 positive samples as doubtful indicating a need for corrective actions. For the EQA targeting IgG and IgM antibodies methods 9 out of the 10 laboratories reported 100% of correct results, whilst one laboratory reported all correct results except one false-positive. These two ring trials provide evidence that most of the participating laboratories are capable to detect RVF antibodies and viral RNA thus recognizing RVF infection in affected ruminants with the diagnostic methods currently available.     

Multiple virus lineages sharing recent common ancestry were associated with a Large Rift Valley fever outbreak among livestock in Kenya during 2006-2007

Rift Valley fever (RVF) virus historically has caused widespread and extensive outbreaks of severe human and livestock disease throughout Africa, Madagascar, and the Arabian Peninsula. Following unusually heavy rainfall during the late autumn of 2006, reports of human and animal illness consistent with RVF virus infection emerged across semiarid regions of the Garissa District of northeastern Kenya and southern Somalia. Following initial RVF virus laboratory confirmation, a high-throughput RVF diagnostic facility was established at the Kenyan Central Veterinary Laboratories in Kabete, Kenya, to support the real-time identification of infected livestock and to facilitate outbreak response and control activities. A total of 3,250 specimens from a variety of animal species, including domesticated livestock (cattle, sheep, goats, and camels) and wildlife collected from a total of 55 of 71 Kenyan administrative districts, were tested by molecular and serologic assays. Evidence of RVF infection was found in 9.2% of animals tested and across 23 districts of Kenya, reflecting the large number of affected livestock and the geographic extent of the outbreak. The complete S, M, and/or L genome segment sequence was obtained from a total of 31 RVF virus specimens spanning the entire known outbreak period (December-May) and geographic areas affected by RVF virus activity. Extensive genomic analyses demonstrated the concurrent circulation of multiple virus lineages, gene segment reassortment, and the common ancestry of the 2006/2007 outbreak viruses with those from the 1997-1998 east African RVF outbreak. Evidence of recent increases in genomic diversity and effective population size 2 to 4 years prior to the 2006-2007 outbreak also was found, indicating ongoing RVF virus activity and evolution during the interepizootic/epidemic period. These findings have implications for further studies of basic RVF virus ecology and the design of future surveillance/diagnostic activities, and they highlight the critical need for safe and effective vaccines and antiviral compounds to combat this significant veterinary and public health threat.     

Phylogeography of Rift Valley Fever virus in Africa reveals multiple introductions in Senegal and Mauritania

Rift Valley Fever (RVF) virus (Family Bunyaviridae) is an arthropod-borne RNA virus that infects primarily domestic ruminants and occasionally humans. RVF epizootics are characterized by numerous abortions and mortality among young animals. In humans, the illness is usually characterized by a mild self-limited febrile illness, which could progress to more serious complications. RVF virus is widespread and endemic in many regions of Africa. In Western Africa, several outbreaks have been reported since 1987 when the first major one occurred at the frontier of Senegal and Mauritania. Aiming to evaluate the spreading and molecular epidemiology in these countries, RVFV isolates from 1944 to 2008 obtained from 18 localities in Senegal and Mauritania and 15 other countries were investigated. Our results suggest that a more intense viral activity possibly took place during the last century compared to the recent past and that at least 5 introductions of RVFV took place in Senegal and Mauritania from distant African regions. Moreover, Barkedji in Senegal was possibly a hub associated with the three distinct entries of RVFV in West Africa.     

Changing pattern of hepatocellular carcinoma (HCC) and its risk factors in Egypt: possibilities for prevention

The burden of hepatocellular carcinoma (HCC) has been increasing in Egypt with a doubling in the incidence rate in the past 10 years. This has been attributed to several biological (e.g. hepatitis B and C virus infection) and environmental factors (e.g. aflatoxin, AF). Other factors such as cigarette smoking, occupational exposure to chemicals such as pesticides, and endemic infections in the community, such as schistosomiasis, may have additional roles in the etiology or progression of the disease. Estimates of the burden of cancer caused by these factors provide an opportunity for prevention. Previously, there was strong evidence that hepatitis B virus (HBV) was the major cause of HCC in Egypt, but more recently HCV has become the predominant factor associated with the more recent epidemic of HCC. It has been well documented that Egypt has one of the highest prevalence rates of HCV infection in the world. The natural history of HCV infection and disease progression, however, are influenced by additional factors such as duration of infection, age at infection, sex, co-infection with HBV, the level of HCV viraemia and its genotype. The role of exposure to aflatoxins and development of HCC in Egypt was historically less clear. Nevertheless, recent food sampling surveys and population-based studies indicated that exposure to aflatoxins in Egypt may have been underestimated in the past. Recent results indicated that both local and imported samples were positive for aflatoxin B1 (AFB1, 17.5% and 20%, respectively), with concentrations ranging from 3 to 25 microg/kg. The level of AFB1 was dependent on the area of collection as well as the season of the year. In a population-based study, the level and frequency of aflatoxin M1 (AFM1, a major metabolite of aflatoxin B1 excreted in breast milk) was assessed as a biomarker of maternal exposure. The samples were collected from a selected group of 388 Egyptian lactating mothers during May-September 2003. Non-working status, obesity, high corn oil consumption, and the number of offspring contributed to the variability in occurrence of AFM1 in breast milk. Prevention and intervention approaches directed to risk factors of HCC can play a critical role in its prevention. In the case of HCV infection a prevention programme can be achieved by changing personal behaviors and/or cultural habits which are risk factors for HCV transmission, such as injection with contaminated syringes, blood transfusion, surgical operations, venous catheterization, use of common syringes, dental treatment and circumcision at home. Prevention of exposure to aflatoxins can be achieved either at community (via good agriculture practices) or individual levels (treatment or dietary interventions). In conclusion, due to the alarming increase in the incidence of HCC in Egypt, there is a need to further investigate the contribution of these emerging risk factors to the development of HCC in Egypt. This may enable us to determine the susceptibility to HCC among high-risk groups and to provide these individuals with effective measures for early prevention or intervention.     

Comparison of Human and Animal Surveillance Data for H5N1 Influenza A in Egypt 2006–2011

Background

The majority of emerging infectious diseases are zoonotic (transmissible between animals and humans) in origin, and therefore integrated surveillance of disease events in humans and animals has been recommended to support effective global response to disease emergence. While in the past decade there has been extensive global surveillance for highly pathogenic avian influenza (HPAI) infection in both animals and humans, there have been few attempts to compare these data streams and evaluate the utility of such integration.

Methodology

We compared reports of bird outbreaks of HPAI H5N1 in Egypt for 2006–2011 compiled by the World Organisation for Animal Health (OIE) and the UN Food and Agriculture Organization (FAO) EMPRESi reporting system with confirmed human H5N1 cases reported to the World Health Organization (WHO) for Egypt during the same time period.

Principal Findings

Both human cases and bird outbreaks showed a cyclic pattern for the country as a whole, and there was a statistically significant temporal correlation between the data streams. At the governorate level, the first outbreak in birds in a season usually but not always preceded the first human case, and the time lag between events varied widely, suggesting regional differences in zoonotic risk and/or surveillance effectiveness. In a multivariate risk model, lower temperature, lower urbanization, higher poultry density, and the recent occurrence of a bird outbreak were associated with increased risk of a human case of HPAI in the same governorate, although the positive predictive value of a bird outbreak was low.

Conclusions

Integrating data streams of surveillance for human and animal cases of zoonotic disease holds promise for better prediction of disease risk and identification of environmental and regional factors that can affect risk. Such efforts can also point out gaps in human and animal surveillance systems and generate hypotheses regarding disease transmission.     

Stand‐replacing fires reduce susceptibility of lodgepole pine to mountain pine beetle outbreaks in Colorado

Aim As climate change is increasing the frequency, severity and extent of wildfire and bark beetle outbreaks, it is important to understand how these disturbances interact to affect ecological patterns and processes, including susceptibility to subsequent disturbances. Stand‐replacing fires and outbreaks of mountain pine beetle (MPB), Dendroctonus ponderosae, are both important disturbances in the lodgepole pine, Pinus contorta, forests of the Rocky Mountains. In the current study we investigated how time since the last stand‐replacing fire affects the susceptibility of the stand to MPB outbreaks in these forests. We hypothesized that at a stand‐scale, young post‐fire stands (< c. 100–150 years old) are less susceptible to past and current MPB outbreaks than are older stands. Location Colorado, USA. Methods We used dendroecological methods to reconstruct stand‐origin dates and the history of outbreaks in 23 lodgepole pine stands. Results The relatively narrow range of establishment dates among the oldest trees in most sampled stands suggested that these stands originated after stand‐replacing or partially stand‐replacing fires over the past three centuries. Stands were affected by MPB outbreaks in the 1940s/1950s, 1980s and 2000s/2010s. Susceptibility to outbreaks generally increased with stand age (i.e. time since the last stand‐replacing fire). However, this reduced susceptibility of younger post‐fire stands was most pronounced for the 1940s/1950s outbreak, less so for the 1980s outbreak, and did not hold true for the 2000s/2010s outbreak. Main conclusions Younger stands may not have been less susceptible to the most recent outbreak because: (1) after stands reach a threshold age of > 100–150 years, stand age does not affect susceptibility to outbreaks, or (2) the high intensity of the most recent outbreak reduces the importance of pre‐disturbance conditions for susceptibility to disturbance. If the warm and dry conditions that contribute to MPB outbreaks concurrently increase the frequency and/or extent of severe fires, they may thereby mitigate the otherwise increased landscape‐scale susceptibility to outbreaks. Potential increases in severe fires driven by warm and dry climatic trends may lead to a negative feedback by making lodgepole pine stands less susceptible to future MPB outbreaks.     

Single-dose immunization with virus replicon particles confers rapid robust protection against Rift Valley fever virus challenge

Rift Valley fever virus (RVFV) causes outbreaks of severe disease in people and livestock throughout Africa and the Arabian Peninsula. The potential for RVFV introduction outside the area of endemicity highlights the need for fast-acting, safe, and efficacious vaccines. Here, we demonstrate a robust system for the reverse genetics generation of a RVF virus replicon particle (VRP(RVF)) vaccine candidate. Using a mouse model, we show that VRP(RVF) immunization provides the optimal balance of safety and single-dose robust efficacy. VRP(RVF) can actively synthesize viral RNA and proteins but lacks structural glycoprotein genes, preventing spread within immunized individuals and reducing the risk of vaccine-induced pathogenicity. VRP(RVF) proved to be completely safe following intracranial inoculation of suckling mice, a stringent test of vaccine safety. Single-dose subcutaneous immunization with VRP(RVF), although it is highly attenuated, completely protected mice against a virulent RVFV challenge dose which was 100,000-fold greater than the 50% lethal dose (LD(50)). Robust protection from lethal challenge was observed by 24 h postvaccination, with 100% protection induced in as little as 96 h. We show that a single subcutaneous VRP(RVF) immunization initiated a systemic antiviral state followed by an enhanced adaptive response. These data contrast sharply with the much-reduced survivability and immune responses observed among animals immunized with nonreplicating viral particles, indicating that replication, even if confined to the initially infected cells, contributes substantially to protective efficacy at early and late time points postimmunization. These data demonstrate that replicon vaccines successfully bridge the gap between safety and efficacy and provide insights into the kinetics of antiviral protection from RVFV infection.