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Molecular epidemiology of Rift Valley fever and its socio-economic impact in selected areas of Tanzania
Abstract
Rift Valley fever (RVF) is a viral notifiable zoonotic disease primarily of domestic ruminants that cause significant socio-economic impacts. Using the 2006-07 outbreak cases, this study aimed to establish the molecular epidemiology of Rift Valley fever virus (RVFV) and its socio-economic impact in selected areas of Tanzania. Data for awareness and socio-economic study were collected in Arusha, Manyara and Morogoro regions using questionnaires, focus group discussions and in-depth interviews with key informants. Molecular epidemiological study used samples that were collected during the outbreaks. Analysis of selected samples was done using RVF Inhibition Enzyme-Linked Immunosorbent Assay (ELISA) and Reverse Transcription Polymerase Chain Reaction (RT-PCR). Results indicate that there was little knowledge on disease (all clinical signs scored <50%) and the difference between the three regions was statistically significant (P=0.00459). Socio-economic impacts of RVF shown by this study included; animal and human deaths, disruption of livestock market chains, inability of pastoralists to achieve their daily demands, inability to obtain protein leading to malnutrition and monetary loss at individual and national level during control of the disease. The proportion of positive serum samples by RVF inhibition ELISA was 39.5% (n=200) and 17.6% (n=108) by RT-PCR. ELISA detected 41 (38.7%), 32 (39.0%) and 6 (50.0%), the RT-PCR detected 11 (0.2%), 7 (0.2%) and 1 (0.1%) positive results in cattle, goats and sheep respectively. These findings have demonstrated low knowledge of community on RVF and the presence of RVF virus in the country. Thus, more education and engagement is needed to the community together with further characterization of the virus from different geographical locations in order to establish the profile of strains circulating in the country and develop more effective and efficient control strategies.
... The results indicate that 8.2% of the goats and sheep tested in this study have encountered RVFV sometime during their life. The latest outbreak in Tanzania with a subsequent vaccination campaign was in 2007, 7 years before this study (15). The seropositive animals younger than 7 years (n 023) did not live during the major outbreak and must have been exposed to virus after this outbreak. ...
... In the interviews with livestock keepers, none of them mentioned RVF as being among the most feared diseases. Chengula (15) pointed out that a majority of the people interviewed in the regions Arusha, Morogoro, and Manyara did not know that RVF was an outbreak disease. There have also been indications that a big part of the population does not know that RVF is a zoonosis (21). ...
Introduction:
Rift Valley fever (RVF) is a zoonosis primarily affecting ruminants, resulting in epidemic abortions, fever, nasal and ocular discharges, haemorrhagic diarrhoea, and a high mortality rate among young animals. Rift Valley fever virus (RVFV) is an arthropod-borne RNA virus occurring in epizootic periods associated with heavy rainfall. The last outbreak of RVF in Tanzania was in 2006-2007, resulting in severe economic losses and impaired food security due to greater number of deaths of livestock. The aim of this study was to investigate the presence of antibodies against RVFV in sheep and goats in two different regions of Tanzania during an inter-epidemic period (IEP). In addition, the perception of important diseases among livestock keepers was assessed.
Material and methods:
A cross-sectional serological survey was conducted in three purposively selected districts in Arusha and Morogoro regions of Tanzania. Serum samples from 354 sheep and goats were analysed in a commercial RVFV competitive ELISA. At the sampling missions, a questionnaire was used to estimate the socio-economic impact of infectious diseases.
Results and discussion:
In total, 8.2% of the analysed samples were seropositive to RVF, and most seropositive animals were younger than 7 years, indicating a continuous circulation of RVFV in the two regions. None of the livestock keepers mentioned RVF as an important livestock disease.
Conclusions:
This study confirms that RVFV is circulating at low levels in small ruminants during IEPs. In spite of recurring RVF outbreaks in Tanzania, livestock keepers seem to have a low awareness of the disease, making them poorly prepared and thus more vulnerable to future RVF outbreaks.
Rift Valley Fever is mosquito-borne viral infection affecting animals and humans. It is an acute viral disease that affects domestic animals such as cattle, buffalo, sheep, goats, and camels and primarily domestic livestock, but can be passed to humans causing fever. Serious complications like jaundice, haemorrhage, renal failure may occur in chronic cases. Spread is by the bite of infected mosquitoes, typically the Aedes or Culex genera. Humans are also readily infected through aerosols from infected animals when humidity is high, or by exposure to infected animal tissues, aborted fetuses, mosquito bites, and laboratory procedures. ELISA test confirms diagnosis along with careful symptomatic observation.
Rift Valley fever (RVF) virus is an arbovirus in the _Bunyaviridae_ family that, from phylogenetic analysis, appears to have first emerged in the mid-19th century and was only identified at the beginning of the 1930s in the Rift Valley region of Kenya. Despite being an arbovirus with a relatively simple but temporally and geographically stable genome, this zoonotic virus has already demonstrated a real capacity for emerging in new territories, as exemplified by the outbreaks in Egypt (1977), Western Africa (1988) and the Arabian Peninsula (2000), or for re-emerging after long periods of silence as observed very recently in Kenya and South Africa. The presence of competent vectors in countries previously free of RVF, the high viral titres in viraemic animals and the global changes in climate, travel and trade all contribute to make this virus a threat that must not be neglected as the consequences of RVF are dramatic, both for human and animal health. In this review, we present the latest advances in RVF virus research. In spite of this renewed interest, aspects of the epidemiology of RVF virus are still not fully understood and safe, effective vaccines are still not freely available for protecting humans and livestock against the dramatic consequences of this virus.
This paper reviews preparedness for containing and controlling emerging and re-emerging diseases drawing lessons from disease events that occurred in animal and human populations in the last five decades (1961-2011). A comprehensive analysis based on retrieval and analysis of grey and published literature as well as reported cases was carried out to document type and trend of occurrence of emerging and re-emerging infectious diseases in different parts of Tanzania. Overall, the majority of diseases reported in the country were viral in nature followed by bacterial diseases. The trend for the occurrence shows a number of new emerging diseases as well as re-occurrence of old diseases in both animal (domestic and wild) and human populations. In humans, the major disease epidemics reported in the last five decades include cholera, influenza A H1N1, plague and rubella. In animals, the major epidemic diseases reported were Contagious Bovine Pleuropneumonia, Contagious Caprine Pleuropneumonia, Peste des petits ruminants and Giraffe Ear and Skin Diseases. Some epidemics have been reported in both human and animal populations including Rift Valley fever and anthrax. The emergence of the ‘fit-for purpose’ approaches and technologies such as the discipline of One Health, use of participatory epidemiology and disease surveillance and mobile technologies offers opportunity for optimal use of limited resources to improve early detection, diagnosis and response to disease events and consequently reduced impact of such diseases in animal and human populations.
In East Africa, Rift Valley fever (RVF) usually occurs as explosive epizootics with prolonged inter-epidemic
periods on the order of 8 to 10 years. The episodic nature of the disease and the rapid evolution of outbreaks create special
challenges for its mitigation and control. Following the events of the 2006 and 2007 RVF outbreak in East Africa,
decision-makers assembled their collective experiences in the form of a risk-based decision support tool to help guide
responses in future emergencies. The premise of the tool is that a series of natural events are indicative of the increasing
risk of an outbreak and that actions should be matched to this evolving risk profile. In this manner, investment in prevention and control can be qualitatively optimized. The decision support tool is a living document written through stakeholder input. This publication captures the current tool as an example of risk-based decision support.
Rift Valley Fever (RVF) is an arthropod borne viral disease affecting livestock (cattle, sheep, goats and camels), wildlife and humans caused by Phlebovirus. The disease occurs in periodic cycles of 4-15 years associated with flooding from unusually high precipitations in many flood-prone habitats. Aedes and Culex spp and other mosquito species are important epidemic vectors. Because of poor living conditions and lack of knowledge on the pathogenesis of RVF, nomadic pastoralists and agro-pastoralists are at high risk of contracting the disease during epidemics. RVF is a professional hazard for health and livestock workers because of poor biosafety measures in routine activities including lack of proper Personal Protective Equipment (PPE). Direct exposure to infected animals can occur during handling and slaughter or through veterinary and obstetric procedures or handling of specimens in laboratory. The episodic nature of the disease creates special challenges for its mitigation and control and many of the epidemics happen when the governments are not prepared and have limited resource to contain the disease at source. Since its first description in 1930s Tanzania has recorded six epidemics, three of which were after independence in 1961. However, the 2007 epidemic was the most notable and wide spread with fatal human cases among pastoralists and agro-pastoralists concurrent with high livestock mortality. Given all the knowledge that exist on the epidemiology of the disease, still the 2006/2007 epidemic occurred when the government of Tanzania was not prepared to contain the disease at source. This paper reviews the epidemiology, reporting and outbreak investigation, public awareness, preparedness plans and policy as well as challenges for its control in Tanzania.
BACKGROUND: In recent years, evidence of Rift Valley fever (RVF) transmission during inter-epidemic periods in parts of Africa has increasingly been reported. The inter-epidemic transmissions generally pass undetected where there is no surveillance in the livestock or human populations. We studied the presence of and the determinants for inter-epidemic RVF transmission in an area experiencing annual flooding in southern Tanzania. METHODOLOGY: A cross-sectional sero-survey was conducted in randomly selected cattle, sheep and goats in the Kilombero river valley from May to August 2011, approximately four years after the 2006/07 RVF outbreak in Tanzania. The exposure status to RVF virus (RVFV) was determined using two commercial ELISA kits, detecting IgM and IgG antibodies in serum. Information about determinants was obtained through structured interviews with herd owners. FINDINGS: An overall seroprevalence of 11.3% (n = 1680) was recorded; 5.5% in animals born after the 2006/07 RVF outbreak and 22.7% in animals present during the outbreak. There was a linear increase in prevalence in the post-epidemic annual cohorts. Nine inhibition-ELISA positive samples were also positive for RVFV IgM antibodies indicating a recent infection. The spatial distribution of seroprevalence exhibited a few hotspots. The sex difference in seroprevalence in animals born after the previous epidemic was not significant (6.1% vs. 4.6% for females and males respectively, p = 0.158) whereas it was significant in animals present during the outbreak (26.0% vs. 7.8% for females and males respectively, p15 km from the flood plain were more likely to have antibodies than those living
A reverse Transcriptase (RT) Polymerase Chain Reaction (RT-PCR) was developed and evaluated for detection of Rift valley fever virus in cell culture and serum samples from acute hemorrhagic fever cases. A pair of primers selected from the Medium (M) RNA gene segment of RVFV was used for RT-PCR amplification. The RT-PCR produced a 342-base pair (bp) from RVF RNAs extracted from smith burn vaccine strain propagated in vero cell culture and sera from infected humans and animals. However, the RT-PCR assay did not amplify the specific 342 bp product from RNAs extracted from closely related hemorrhagic fever viruses including Crimean Congo Hemorrhagic Fever Virus (CCHFV), Dengue virus, total RNA extracted from non infected vero cells. The described RT-PCR provides rapid, sensitive and specific method for detection of RVFV in cell culture and directly in serum samples. The RT-PCR assay should be recommended for inclusion during epidemiological surveys and outbreaks of the disease among humans and susceptible animal populations.
A Rift Valley fever (RVF) epidemic affecting animals on domestic livestock farms was reported in South Africa during January-August 2010. The first cases occurred after heavy rainfall, and the virus subsequently spread countrywide. To determine the possible effect of environmental conditions and vaccination on RVF virus transmissibility, we estimated the effective reproduction number (Re) for the virus over the course of the epidemic by extending the Wallinga and Teunis algorithm with spatial information. Re reached its highest value in mid-February and fell below unity around mid-March, when vaccination coverage was 7.5%-45.7% and vector-suitable environmental conditions were maintained. The epidemic fade-out likely resulted first from the immunization of animals following natural infection or vaccination. The decline in vector-suitable environmental conditions from April onwards and further vaccination helped maintain Re below unity. Increased availability of vaccine use data would enable evaluation of the effect of RVF vaccination campaigns.
A Reverse Transcriptase(RT) polymerase reaction(RT-PCR) based assay was developed and evaluated for detection of rift valley fever virus(RVFV) ribonucleic acid(RNA). A pairs of oligoribonucleotide primers(RVF 1 and RVF2), selected from the small(s) RNA genome segment of RVFV virus, were designed and used as a target for PCR amplification. The primers RVFV1 and RVFV2 resulted in amplification of a primary 490 base pairs(bp) PCR product. The PCR products were amplified from RNAs extracted from RVFV field isolates and vaccine stains, propagated in Vero cell cultures. Amplification products were not detected when the RT-PCR- based assay was applied to RNA from other related hemorrhagic fevers viruses including, Crimean congo Hemorrhagic fever(CCHF); dengue virus; epizootic hemorrhagic disease virus and total nucleic acid extracts from uninfected Vero cells. The described RT-PCR-based assay provides a rapid, sensitive and specific assay for detection of RVFV in cell culture and should be recommended for for inclusion during an outbreak of the disease among humans and susceptible livestock.
Key words: Viral hemorrhagic fevers, RVFV, sRNA, RT-PCR
To estimate the prevalence of hydatidosis, cysticercosis, tuberculosis, leptospirosis, brucellosis and toxoplasmosis in slaughtered bovine stock (aged ±3 years) at Tanga city abattoir, Tanzania.
Prevalence estimation of the five zoonotic diseases was undertaken through an active abattoir and sero-survey was carried out in Tanga city, during the period of January 2002 and March 2004. Serum samples collected from a sub-sample (n=51) of the slaughter stock were serologically screened for antibodies against brucellosis, leptospirosis and toxoplasmosis using Rose Bengal plate test, microscopic agglutination test (for 5 serovars of Leptospira interrogans) and Eiken latex agglutination test, respectively. The same animals were tested for tuberculosis using the single intradermal tuberculin test.
Post mortem examination of 12 444 slaughter cattle (10 790 short horn zebu and 1 654 graded) over a period of twenty two months, showed a prevalence of 1.56% (194) for hydatidosis, 1.49% (185) for cysticercosis and 0.32% (40) for tuberculosis. In all three zoonoses, a statistically significant difference in infection rates was noted between the short horn zebu and graded breeds (P<0.05). The overall seroprevalences of animals with brucellosis, toxoplasmosis and leptospirosis antibodies were found to be 12%, 12% and 51%, respectively. The most common leptospiral antibodies detected were those against antigens of serovars Leptospira hardjo (29%), Leptospira tarassovi (18%), Leptospira bataviae (4%) and Leptospira pomona (0%). With regard to tuberculosis, 10% (n=5) of the animals tested were classified as non-specific reactors or inconclusive.
The study findings suggest that brucellosis, toxoplasmosis and leptospirosis are prevalent in Tanga and provide definitive evidence of slaughtered stock exposure to these zoonotic agents with concurrent public health consequences.
Introduction
Dynamics of most of vector-borne diseases are strongly linked to global and local environmental changes. Landscape changes are indicators of human activities or natural processes that are likely to modify the ecology of the diseases. Here, a landscape approach developed at a local scale is proposed for extracting mosquito favourable biotopes, and for testing ecological parameters when identifying risk areas of Rift Valley fever (RVF) transmission. The study was carried out around Barkedji village, Ferlo region, Senegal.
Methods
In order to test whether pond characteristics may influence the density and the dispersal behaviour of RVF vectors, and thus the spatial variation in RVFV transmission, we used a very high spatial resolution remote sensing image (2.4 m resolution) provided by the Quickbird sensor to produce a detailed land-cover map of the study area. Based on knowledge of vector and disease ecology, seven landscape attributes were defined at the pond level and computed from the land-cover map. Then, the relationships between landscape attributes and RVF serologic incidence rates in small ruminants were analyzed through a beta-binomial regression. Finally, the best statistical model according to the Akaike Information Criterion corrected for small samples (AICC), was used to map areas at risk for RVF.
Results
Among the derived landscape variables, the vegetation density index (VDI) computed within a 500 m buffer around ponds was positively correlated with serologic incidence (p<0.001), suggesting that the risk of RVF transmission was higher in the vicinity of ponds surrounded by a dense vegetation cover. The final risk map of RVF transmission displays a heterogeneous spatial distribution, corroborating previous findings from the same area.
Conclusions
Our results highlight the potential of very high spatial resolution remote sensing data for identifying environmental risk factors and mapping RVF risk areas at a local scale.
Although Rift Valley fever is a disease that, through its wider societal effects, disproportionately affects vulnerable communities with poor resilience to economic and environmental challenge, Rift Valley fever virus has since its discovery in 1931 been neglected by major global donors and disease control programs. We describe recent outbreaks affecting humans and animals and discuss the serious socioeconomic effects on the communities affected and the slow pace of development of new vaccines. We also discuss the mixed global response, which has largely been fueled by the classification of the virus as a potential bioterrorism agent and its potential to migrate beyond its traditional eastern African boundaries. We argue for a refocus of strategy with increased global collaboration and a greater sense of urgency and investment that focuses on an equity-based approach in which funding and research are prioritized by need, inspired by principles of equity and social justice.
Infectious diseases account for nearly 40% of the burden of human mortality and morbidity in low-income countries, of which 7% is attributable to zoonoses and 13% to recently emerging diseases from animals. One of the strategic approaches for effective surveillance, monitoring and control of infectious diseases compromising health in both humans and animals could be through a combination of multiple disciplines. The approach can be achieved through a joint effort from stakeholders comprising health professionals (medical and veterinary), social, economic, agricultural, environmental and other interested parties. With resource scarcity in terms of number of staff, skills and facility in low-income countries, participatory multi- sectoral and multidisciplinary approaches in limiting the burden of zoonotic diseases could be worthwhile. We review challenging issues that may limit the 'One Health' approach for infectious diseases surveillance in Tanzania with a focus on Health Policy and how best the human and animal health systems could be complemented or linked to suit the community in need for disease control under the theme's context.
Africa has the highest burden of infectious diseases in the world and yet the least capacity for its risk management. It has therefore become increasingly important to search for 'fit-for- purpose' approaches to infectious disease surveillance and thereby targeted disease control. The fact that the majority of human infectious diseases are originally of animal origin means we have to consider One Health (OH) approaches which require inter-sectoral collaboration for custom-made infectious disease surveillance in the endemic settings of Africa. A baseline survey was conducted to assess the current status and performance of human and animal health surveillance systems and subsequently a strategy towards OH surveillance system was developed. The strategy focused on assessing the combination of participatory epidemiological approaches and the deployment of mobile technologies to enhance the effectiveness of disease alerts and surveillance at the point of occurrence, which often lies in remote areas. We selected three study sites, namely the Ngorongoro, Kagera River basin and Zambezi River basin ecosystems. We have piloted and introduced the next-generation Android mobile phones running the EpiCollect application developed by Imperial College to aid geo-spatial and clinical data capture and transmission of this data from the field to the remote Information Technology (IT) servers at the research hubs for storage, analysis, feedback and reporting. We expect that the combination of participatory epidemiology and technology will significantly improve OH disease surveillance in southern Africa.
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.
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.
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.
The aim of this study was to determine the activity of the Rift Valley Fever Virus (RVFV) in non-exposed regions in Saudi Arabia following the outbreak that had occurred in the southwestern region of Saudi Arabia in 2000 -2001. An Enzyme-Linked Immunosorbent Assay (ELISA) was used to detect anti-RVFV IgG antibodies among subjects working in abattoirs or adjacent livestock holding yards as a high risk group and healthy blood donors as a control group in seven non-epidemic regions of Saudi Arabia (Jeddah, Makkah, Al-Madina, Riyadh, Taif, Dammam, Yanbou). The serological tests were carried out at the Special Infectious Agents Unit, Biosafety Level 3, King Fahd Medical Research Centre, at King Abdulaziz University, Jeddah. A total of 1256 high-risk subjects (working in abattoirs or adjacent livestock holding yards) and 1216 blood donors were studied. Only 9 of 1256 (0.72%) high risk subjects and 2 of 1260 (0.16%) blood donors were RVFV IgG positive. All nine high risk RVFV-IgG positive subjects were of Bangladeshi nationality, whereas the two positive donors were of Saudi nationality from Dammam city. High risk practice that increases the risk of exposure to RVFV infection at work or at home was also studied. The reason for positive RVFV-IgG in the two supposedly-low risk blood donors was likely an old exposure to the virus in the epidemic regions (Jazan, Tihama of Asir, and Al-Qunfuda) back in 2000 -2001. This could not be confirmed as it was not possible to contact these two donors to inquire about a past history of visiting any of the epidemic regions. The study confirms that the RVF epidemic in Saudi Arabia was confined to the epidemic regions (Jazan, Tihama of Asir, and Al-Qunfuda) with no serological evidence of spread of the infection among human subjects living outside the epicenters. The preventive measures undertaken at the time of the epidemic and thereafter by the concerned parties such as the Ministry of Health, Ministry of Agriculture, and Ministry of Municipality, clearly prevented the spread of RVFV to the rest of Saudi Arabia.
Another important component of arbovirus surveillance is the detection of virus in arthropod vector populations. Traditional methods include trapping vectors such as mosquitoes, ticks, and midges, identifying them to species level and analysing vector pools for known viruses of interest. Virus isolation by inoculating mice, embryonated eggs, or colonized vector species has largely been replaced by in vitro methods (e.g., inoculation of arthropod and vertebrate cell lines), but is still the most effective means for monitoring virus activity for some viruses. However, the enhanced technologies for the specific detection of viral nucleic acid, such as multiplexed real-time PCR protocols, provide more rapid, sensitive, and specific approaches for detecting virus activity in vector populations. Furthermore, the recent application of next-generation sequencing technologies to rapidly analyze nucleic acid of unidentified viral isolates provides a revolutionary approach for the discovery and genetic characterization of new vector-borne viruses.
The Rift Valley fever virus (RVFV) is an arthropod-borne phlebovirus. RVFV mostly causes outbreaks among domestic ruminants with a major economic impact. Human infections are associated with these events, with a fatality rate of 0.5-2%. Since the virus is able to use many mosquito species of temperate climates as vectors, it has a high potential to spread to outside Africa.
We conducted a stratified, cross-sectional sero-prevalence survey in 1228 participants from Mbeya region, southwestern Tanzania. Samples were selected from 17,872 persons who took part in a cohort study in 2007 and 2008. RVFV IgG status was determined by indirect immunofluorescence. Possible risk factors were analyzed using uni- and multi-variable Poisson regression models. We found a unique local maximum of RVFV IgG prevalence of 29.3% in a study site close to Lake Malawi (N = 150). The overall seroprevalence was 5.2%. Seropositivity was significantly associated with higher age, lower socio-economic status, ownership of cattle and decreased with distance to Lake Malawi. A high vegetation density, higher minimum and lower maximum temperatures were found to be associated with RVFV IgG positivity. Altitude of residence, especially on a small scale in the high-prevalence area was strongly correlated (PR 0.87 per meter, 95% CI = 0.80-0.94). Abundant surface water collections are present in the lower areas of the high-prevalence site. RVF has not been diagnosed clinically, nor an outbreak detected in the high-prevalence area.
RVFV is probably circulating endemically in the region. The presence of cattle, dense vegetation and temperate conditions favour mosquito propagation and virus replication in the vector and seem to play major roles in virus transmission and circulation. The environmental risk-factors that we identified could serve to more exactly determine areas at risk for RVFV endemicity.
Studies on Rift Valley Fever Virus (RVFV) infection process and morphogenesis have been hampered due to the biosafety conditions required to handle this virus, making alternative systems such as recombinant virus-like particles, that may facilitate understanding of these processes are highly desirable. In this report we present the expression and characterization of RVFV structural proteins N, Gn and Gc and demonstrate the efficient generation of RVFV virus-like particles (VLPs) using a baculovirus expression system.
A recombinant baculovirus, expressing nucleocapsid (N) protein of RVFV at high level under the control of the polyhedrin promoter was generated. Gel filtration analysis indicated that expressed N protein could form complex multimers. Further, N protein complex when visualized by electron microscopy (EM) exhibited particulate, nucleocapsid like-particles (NLPs). Subsequently, a single recombinant virus was generated that expressed the RVFV glycoproteins (Gn/Gc) together with the N protein using a dual baculovirus vector. Both the Gn and Gc glycoproteins were detected not only in the cytoplasm but also on the cell surface of infected cells. Moreover, expression of the Gn/Gc in insect cells was able to induce cell-cell fusion after a low pH shift indicating the retention of their functional characteristics. In addition, assembly of these three structural proteins into VLPs was identified by purification of cells' supernatant through potassium tartrate-glycerol gradient centrifugation followed by EM analysis. The purified particles exhibited enveloped structures that were similar to the structures of the wild-type RVFV virion particle. In parallel, a second recombinant virus was constructed that expressed only Gc protein together with N protein. This dual recombinant virus also generated VLPs with clear spiky structures, but appeared to be more pleomorphic than the VLPs with both glycoproteins, suggesting that Gc and probably also Gn interacts with N protein complex independent of each other.
Our results suggest that baculovirus expression system has enormous potential to produce large amount of VLPs that may be used both for fundamental and applied research of RVFV.
Rift Valley fever(RVF) virus is an arbovirus in the Bunyaviridae family that, from phylogenetic analysis, appears to have first emerged in the mid-19th century and was only identified at the beginning of the 1930's in the Rift Valley region of Kenya. Despite being an arbovirus with a relatively simple but temporally and geographically stable genome, this zoonotic virus has already demonstrated a real capacity for emerging in new territories, as exemplified by the outbreaks in Egypt (1977), Western Africa (1988) and the Arabian Peninsula (2000), or for re-emerging after long periods of silence as observed very recently in Kenya and South Africa. The presence of competent vectors in countries previously free of RVF, the high viral titres in viraemic animals and the global changes in climate, travel and trade all contribute to make this virus a threat that must not be neglected as the consequences of RVF are dramatic, both for human and animal health. In this review, we present the latest advances in RVF virus research. In spite of this renewed interest, aspects of the epidemiology of RVF virus are still not fully understood and safe, effective vaccines are still not freely available for protecting humans and livestock against the dramatic consequences of this virus.
To capture lessons from the 2007 Rift Valley fever (RVF) outbreak, epidemiological studies were carried out in Kenya and Tanzania. Somali pastoralists proved to be adept at recognizing symptoms of RVF and risk factors such as heavy rainfall and mosquito swarms. Sandik, which means "bloody nose," was used by Somalis to denote disease consistent with RVF. Somalis reported that sandik was previously seen in 1997/98, the period of the last RVF epidemic. Pastoralists communicated valuable epidemiological information for surveillance and early warning systems that was observed before international warnings. The results indicate that an all or none approach to decision making contributed to the delay in response. In the future, a phased approach balancing actions against increasing risk of an outbreak would be more effective. Given the time required to mobilize large vaccine stocks, emergency vaccination did not contribute to the mitigation of explosive outbreaks of RVF.
We analyzed the extent of livestock involvement in the latest Rift Valley fever (RVF) outbreak in Kenya that started in December 2006 and continued until June 2007. When compared with previous RVF outbreaks in the country, the 2006-07 outbreak was the most extensive in cattle, sheep, goats, and camels affecting thousands of animals in 29 of 69 administrative districts across six of the eight provinces. This contrasted with the distribution of approximately 700 human RVF cases in the country, where over 85% of these cases were located in four districts; Garissa and Ijara districts in Northeastern Province, Baringo district in Rift Valley Province, and Kilifi district in Coast Province. Analysis of livestock and human data suggests that livestock infections occur before virus detection in humans, as supported by clustering of human RVF cases around livestock cases in Baringo district. The highest livestock morbidity and mortality rates were recorded in Garissa and Baringo districts, the same districts that recorded a high number of human cases. The districts that reported RVF in livestock for the first time in 2006/07 included Kitui, Tharaka, Meru South, Meru central, Mwingi, Embu, and Mbeere in Eastern Province, Malindi and Taita taveta in Coast Province, Kirinyaga and Murang'a in Central Province, and Baringo and Samburu in Rift Valley Province, indicating that the disease was occurring in new regions in the country.
Historical outbreaks of Rift Valley fever (RVF) since the early 1950s have been associated with cyclical patterns of the El Niño/Southern Oscillation (ENSO) phenomenon, which results in elevated and widespread rainfall over the RVF endemic areas of Africa. Using satellite measurements of global and regional elevated sea surface temperatures, elevated rainfall, and satellite derived-normalized difference vegetation index data, we predicted with lead times of 2-4 months areas where outbreaks of RVF in humans and animals were expected and occurred in the Horn of Africa, Sudan, and Southern Africa at different time periods from September 2006 to March 2008. Predictions were confirmed by entomological field investigations of virus activity and by reported cases of RVF in human and livestock populations. This represents the first series of prospective predictions of RVF outbreaks and provides a baseline for improved early warning, control, response planning, and mitigation into the future.
In January 2007, an outbreak of Rift Valley fever (RVF) was detected among humans in northern Tanzania districts. By the end of the outbreak in June, 2007, 511 suspect RVF cases had been recorded from 10 of the 21 regions of Tanzania, with laboratory confirmation of 186 cases and another 123 probable cases. All confirmed RVF cases were located in the north-central and southern regions of the country, with an eventual fatality rate of 28.2% (N = 144). All suspected cases had fever; 89% had encephalopathy, 10% hemorrhage, and 3% retinopathy. A total of 169 (55%) of the 309 confirmed or probable cases were also positive for malaria as detected by peripheral blood smear. In a cohort of 20 RVF cases with known outcome that were also positive for human immunodeficiency virus, 15 (75%) died. Contact with sick animals and animal products, including blood, meat, and milk, were identified as major risk factors of acquiring RVF.
A large Rift Valley fever (RVF) outbreak occurred in Kenya from December 2006 to March 2007. We conducted a study to define risk factors associated with infection and severe disease. A total of 861 individuals from 424 households were enrolled. Two hundred and two participants (23%) had serologic evidence of acute RVF infection. Of these, 52 (26%) had severe RVF disease characterized by hemorrhagic manifestations or death. Independent risk factors for acute RVF infection were consuming or handling products from sick animals (odds ratio [OR] = 2.53, 95% confidence interval [CI] = 1.78-3.61, population attributable risk percentage [PAR%] = 19%) and being a herds person (OR 1.77, 95% CI = 1.20-2.63, PAR% = 11%). Touching an aborted animal fetus was associated with severe RVF disease (OR = 3.83, 95% CI = 1.68-9.07, PAR% = 14%). Consuming or handling products from sick animals was associated with death (OR = 3.67, 95% CI = 1.07-12.64, PAR% = 47%). Exposures related to animal contact were associated with acute RVF infection, whereas exposures to mosquitoes were not independent risk factors.
The sample size calculation for a prevalence only needs a simple formula. However, there are a number of practical issues in selecting values for the parameters required in the formula. Several practical issues are addressed and appropriate recommendations are given. The paper also suggests the application of a software calculator that checks the normal approximation assumption and incorporates finite population correction in the sample size calculation.
Rift Valley fever virus (RVFV) causes large outbreaks of acute febrile and often fatal illness among humans and domesticated animals in sub-saharan Africa and the Arabian peninsula. RVFV is a member of the family Bunyaviridae, genus Phlebovirus. Like all members of this large virus family, it contains a three-segmented genome of negative/ambisense strand RNA, packaged into viral nucleocapsid protein, and enveloped by a lipid bilayer containing two viral glycoproteins. During the past years, there was an increased interest in RVFV epidemiology, molecular biology, and virulence mechanisms. Here, we will try to provide an overview over the basic features of this significant pathogen, and review the latest developments in this highly active research field.
During 2 successive rainy seasons, January 2008 through May 2008 and November 2008 through March 2009, Rift Valley fever virus (RVFV) caused outbreaks in Madagascar. Human and animal infections were confirmed on the northern and southern coasts and in the central highlands. Analysis of partial sequences from RVFV strains showed that all were similar to the strains circulating in Kenya during 2006-2007. A national cross-sectional serologic survey among slaughterhouse workers at high risk showed that RVFV circulation during the 2008 outbreaks included all of the Malagasy regions and that the virus has circulated in at least 92 of Madagascar's 111 districts. To better predict and respond to RVF outbreaks in Madagascar, further epidemiologic studies are needed, such as RVFV complete genome analysis, ruminant movement mapping, and surveillance implementation.
This article describes the epidemiology, distribution, prevalence, pathogenesis, transmission, clinical signs, differential diagnosis, prevention and control of Rift Valley Fever in domestic animals, wild animals and man.
Rift Valley fever (RVF) virus is an emerging pathogen that is transmitted in many regions of sub-Saharan Africa, parts of Egypt, and the Arabian peninsula. Outbreaks of RVF, like other diseases caused by hemorrhagic fever viruses, typically present in locations with very limited health resources, where initial diagnosis must be based only on history and physical examination. Although general signs and symptoms of human RVF have been documented, a specific clinical syndrome has not been described. In 2007, a Kenyan outbreak of RVF provided opportunity to assess acutely ill RVF patients and better delineate its presentation and clinical course. Our data reveal an identifiable clinical syndrome suggestive of severe RVF, characterized by fever, large-joint arthralgia, and gastrointestinal complaints and later followed by jaundice, right upper-quadrant pain, and delirium, often coinciding with hemorrhagic manifestations. Further characterization of a distinct RVF clinical syndrome will aid earlier detection of RVF outbreaks and should allow more rapid implementation of control.
The authors wish to report that the previously published sequence was erroneous in the region corresponding to nucleotides 6015 to 6606. The correct sequence is 6404 bases long and is accessible in the EMBL database under the same number as previously (no. X56464). The title should now read: Completion of the genome sequence of Rift Valley fever phlebovirus indicates that the L RNA is negative sense and codes for a putative transcriptase-replicase.
Rift Valley fever virus (RVFV) has been cited as a potential biological-weapon threat due to the serious and fatal disease it causes in humans and animals and the fact that this mosquito-borne virus can be lethal in an aerosolized form. Current human and veterinary vaccines against RVFV, however, are outdated, inefficient, and unsafe. We have incorporated the RVFV glycoprotein genes into a nonreplicating complex adenovirus (CAdVax) vector platform to develop a novel RVFV vaccine. Mice vaccinated with the CAdVax-based vaccine produced potent humoral immune responses and were protected against lethal RVFV infection. Additionally, protection was elicited in mice despite preexisting immunity to the adenovirus vector.
Affecting both livestock and humans, Rift Valley Fever is considered as one of the most important viral zoonoses in Africa. However, no licensed vaccines or effective treatments are yet available for human use. Naked DNA vaccines are an interesting approach since the virus is highly infectious and existing attenuated Rift Valley Fever virus vaccine strains display adverse effects in animal trials. In this study, gene-gun immunisations with cDNA encoding structural proteins of the Rift Valley Fever virus were evaluated in mice. The induced immune responses were analysed for the ability to protect mice against virus challenge.
Immunisation with cDNA encoding the nucleocapsid protein induced strong humoral and lymphocyte proliferative immune responses, and virus neutralising antibodies were acquired after vaccination with cDNA encoding the glycoproteins. Even though complete protection was not achieved by genetic immunisation, four out of eight, and five out of eight mice vaccinated with cDNA encoding the nucleocapsid protein or the glycoproteins, respectively, displayed no clinical signs of infection after challenge. In contrast, all fourteen control animals displayed clinical manifestations of Rift Valley Fever after challenge.
The appearance of Rift Valley Fever associated clinical signs were significantly decreased among the DNA vaccinated mice and further adjustment of this strategy may result in full protection against Rift Valley Fever.
This paper reports on the development and validation of a real-time reverse transcription-loop-mediated isothermal amplification
assay (RT-LAMP) targeting the genomic large RNA segment of Rift Valley fever virus (RVFV). The set of six designed RT-LAMP
primers identified strains of RVFV isolated in geographically distinct areas over a period of 50 years; there was no cross-reactivity
with other genetically related and unrelated arboviruses. When testing serial sera and plasma from sheep experimentally infected
with wild-type RVFV, there was 100% agreement between results of the RT-LAMP, a TaqMan-based real-time PCR, and virus isolation.
Similarly, the assay had very high levels of diagnostic sensitivity and specificity when testing various clinical specimens
from humans and animals naturally infected with the virus during recent outbreaks of the disease in Africa. The detection
of specific viral genome targets in positive clinical specimens was achieved in less than 30 min. As a highly accurate, rapid,
and very simple nucleic acid detection format, the RT-LAMP has the potential to be used in less-well-equipped laboratories
in Africa and as a portable device during RVF outbreaks in remote areas, and it can be a valuable tool for the differential
diagnosis of viral hemorrhagic fevers.
The development and validation of a one-step, single-tube, real-time accelerated reverse-transcription loop-mediated isothermal
amplification (RT-LAMP) for the detection of the L RNA segment of Rift Valley fever virus (RVFV) are described. The assay
was performed at a constant temperature (63°C), with a real-time follow-up using a LightCycler and a double-stranded-DNA-intercalating
fluorochrome. The assay is highly sensitive and comparable to real-time RT-PCR, with a detection limit of ∼10 RNA copies per
assay. However, the RT-LAMP assay is much faster than traditional RT-PCR and generates results in <30 min for most diluted
samples. The specificity of the primers was established using other, related arboviruses as well as virus-containing and virus-free
sera. The RT-LAMP assay reported here is thus a valuable tool for the rapid detection of RVFV in field diagnostic laboratories.
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.
Recent disease epidemics and their spread around the world have illustrated the weaknesses of disease surveillance and early warning systems (EWS), both at national and international levels. These diseases continuously threaten the livestock sector on a worldwide basis, some with major public health impact. EWS and accurate forecasting of new outbreaks of epidemic livestock diseases that may also affect wildlife, and the capacity for spread of such diseases to new areas is an essential pre-requisite to their effective containment and control. Because both the geographical and seasonal distribution of many infectious diseases are linked to climate, the possibility of using climaterelated environmental factors as predictive indicators, in association with regular disease surveillance activities, has proven to be relevant when establishing EWS for climate-related diseases. This article reviews the growing importance of using geographical information systems in predictive veterinary epidemiology and its integration into EWS, with a special focus on Rift Valley fever. It shows that, once fully validated in a country or region, this technology appears highly valuable and could play an increasing role in forecasting major epidemics, providing lead time to national veterinary services to take action to mitigate the impact of the disease in a cost-effective manner.
Most outbreaks of Rift Valley fever (RVF) occur in remote locations after floods. To determine environmental risk factors and long-term sequelae of human RVF, we examined rates of previous Rift Valley fever virus (RVFV) exposure by age and location during an interepidemic period in 2006. In a randomized household cluster survey in 2 areas of Ijara District, Kenya, we examined 248 residents of 2 sublocations, Gumarey (village) and Sogan-Godud (town). Overall, the RVFV seropositivity rate was 13% according to immunoglobulin G ELISA; evidence of interepidemic RVFV transmission was detected. Increased seropositivity was found among older persons, those who were male, those who lived in the rural village (Gumarey), and those who had disposed of animal abortus. Rural Gumarey reported more mosquito and animal exposure than Sogan-Godud. Seropositive persons were more likely to have visual impairment and retinal lesions; other physical findings did not differ.
Principles and Practice of Clinical Virology is the bible for all working in the field of clinical virology - from the trainee to the expert because there's always something new to learn! As before, the book provides a detailed account of the diagnosis and treatment of virus infections, with a stronger emphasis on clinical expertise and management. Each chapter deals with a single virus or group or viruses and is written by leading international experts in the field. What's new in this edition Showcases the wealth of new knowledge acquired on virus infections and reflects the discovery of newly recognized emerging infections, the improvement or development of new vaccines, and an increasing repertoire of antiviral agents for treatment. All chapters have been thoroughly revised and there are a number of new contributors, joining the cadre of internationally-recognized experts. Includes a new chapter on vaccinology covering the principles relating to the development and use of vaccines generally, which complements the specific vaccines described in the other chapters. The two chapters on nosocomial infections have been enlarged and will be particularly useful for those having to advise on the management of hospital-acquired infections. Emphasizes the rapid accumulation of new information in such fields as retroviruses, particularly HIV, SARS, hepatitis C and influenza, including avian influenza.
Zoonoses are infections naturally transmitted between vertebrate animals and humans. An exploratory questionnaire-based survey of animal health workers(n=36) and livestock keepers(n=43) was carried out from April 2001 to March 2002 in Tanga and Arusha regions, northern Tanzania, to assess local knowledge, attitudes and public awareness for animal zoonoses. A combination of closed and open-ended questions, focus group discussions and ranking techniques were employed to gather information on perceptions concerning the type of zoonotic diseases prevalent in the study area, level of risk, mode of transmission and methods of preventing disease transmission from animals to humans. The results demonstrated that rabies, tuberculosis and anthrax were considered the three most common zoonotic diseases. Sharing living accommodation with animals, consumption of un-treated livestock products (i.e. milk, meat or eggs) and attending to parturition were perceived as routes of transmission. Knowledge about zoonosis was higher in smallholder dairy (92%; 33/36) than traditional livestock keepers (P<0.05). On the contrary, the perceived risk of contracting a zoonosis was significantly higher in traditional livestock (86%; 6/7) than smallholder dairy keepers (P<0.05). Stratification of the risk of zoonosis by farm location revealed that rural farms (85%; 7/8) were considered significantly at a higher risk when compared to peri or urban located farms (P<0.05). Most of the respondents stated cooking of meat or boiling of milk as a way to prevent transmission. However, there was a significant difference in the perception of the risk posed by contact with potentially infected animals /or animal products with animal health workers having a much higher level of perception compared to livestock keepers. These results suggest that in the Tanga and Arusha, Tanzania, patchy awareness and knowledge of zoonoses, combined with food consumption habits and poor animal husbandry are likely to expose respondents to an increased risk of contracting zoonoses. Public health promotion on education and inter-disciplinary one-health collaboration between vets, public health practitioners and policy makers should result in a more efficient and effective joint approach to the diagnosis and control of zoonoses in Tanzania.
The real-time polymerase chain reaction (RT-PCR), also called quantitative real-time polymerase chain reaction (QRT-PCR) or kinetic polymerase chain reaction (kPCR), is a technique used to simultaneously quantify and amplify a DNA molecule. It is used to determine whether a specific DNA sequence is present in the sample; and if it is present, the number of copies in the sample. It is the real-time version of quantitative polymerase chain reaction (qPCR), itself a modification of polymerase chain reaction (PCR). The procedure of RT-PCR follows the regular PCR procedure, but the DNA is quantified after each round of amplification. Two common methods of quantification are the use of fluorescent dyes that intercalate with double-strand DNA, and modified DNA oligonucleotide probes that fluoresce when hybridized with a complementary DNA. RT-PCR could be combined with reverse transcription polymerase chain reaction to quantify messenger RNA (mRNA) at a particular time for in a particular cell or tissue type. (The Journal of American Science. 2006;2(3):1-15).
Rift Valley fever virus (RVFV), which belongs to the genus Phlebovirus, family Bunyaviridae, is a negative-stranded RNA virus carrying a tripartite RNA genome. RVFV is transmitted by mosquitoes and causes large outbreaks among ruminants and humans in Africa and the Arabian Peninsula. Human patients develop an acute febrile illness, followed by a fatal hemorrhagic fever, encephalitis or ocular diseases, whereas ruminants experience abortions during outbreak. Effective vaccination of both humans and ruminants is the best approach to control Rift Valley fever. This article summarizes the development of inactivated RVFV vaccine, live attenuated vaccine, and other new generation vaccines.
A cross-sectional sero survey of 199 apparently healthy persons from various occupations was carried out in Tanga, Tanzania in November 2004 to investigate exposure to Rift Valley fever (RVF) virus. Sera were tested for the presence of antibodies to RVF virus by the inhibition enzyme-linked immunosorbent assay (ELISA) for detecting immunoglobulin G (IgG). All reactive sera were further tested by the capture ELISA test and specific RVF immunoglobulin M (IgM) assay. Eight (4.0%) tested positive for IgG and none of the samples tested positive for IgM. Among the occupational groups examined, the seroprevalence was 7.3%, 1.5%, and 9.5% in the abattoir workers, livestock keepers, and others categories, respectively. Seropositivity was higher in men (5.3%) than women (1.5 %) and increased markedly in men aged between 20 to 40 years, with no significant differences among the age groups and sexes. The results indicate that a small proportion of people in Tanga municipality were exposed to RVF virus infection prior to 2007 disease outbreak in Tanzania. These findings need to be taken into consideration when future disease control programs are implemented.
A safe laboratory procedure, based on a sandwich ELISA (sAg-ELISA), was developed and evaluated for the detection of nucleocapsid protein (NP) of Rift Valley fever virus (RVFV) in specimens inactivated at 56 degrees C for 1h in the presence of 0.5% Tween-20 (v/v) before testing. Polyclonal capture and detection immune sera were generated respectively in sheep and rabbits immunized with recombinant NP antigen. The assay was highly repeatable and specific; it detected strains of RVFV from the entire distributional range of the disease, isolated over a period of 53 years; no cross-reactivity with genetically related African phleboviruses or other members of the family Bunyaviridae was observed. In specimens spiked with RVFV, including human and animal sera, homogenates of liver and spleen tissues of domestic ruminants, and Anopheles mosquito homogenates, the sAg-ELISA detection limit ranged from log(10)10(2.2) to 10(3.2) TCID(50)/reaction volume. The ELISA detected NP antigen in spiked bovine and sheep liver homogenates up to at least 8 days of incubation at 37 degrees C whereas infectious virus could not be detected at 48h incubation in these adverse conditions. Compared to virus isolation from sera from RVF patients and sheep infected experimentally, the ELISA had 67.7% and 70% sensitivity, and 97.97% and 100% specificity, respectively. The assay was 100% accurate when testing tissues of various organs from mice infected experimentally and buffalo foetuses infected naturally. The assay was able to detect NP antigen in infective culture supernatants 16-24h before cytopathic effects were observed microscopically and as early as 8h after inoculation with 10(5.8) TCID(50)/ml of RVFV. This ability renders the assay for rapid identification of the virus when its primary isolation is attempted in vitro. As a highly specific, safe and simple assay format, the sAg-ELISA represents a valuable diagnostic tool for use in less equipped laboratories in Africa, and for routine differential diagnosis of viral hemorrhagic fevers.