The transmission dynamics of Middle East Respiratory Syndrome Coronavirus in dromedary camels: implications for vaccination

Middle East Respiratory Syndrome Coronavirus (MERS-CoV) causes severe disease in humans – with a reported case fatality ratio of 35% – and is capable of causing explosive nosocomial outbreaks. Sporadic outbreaks in the Arabian Peninsula are driven by recurring zoonotic spillover from dromedary camels (Camelus dromedarius), leading to demand for a dromedary vaccine to avert human cases. With two vaccine candidates shown to reduce viral shedding, there is an urgent need to assess the potential impact of dromedary vaccination. This is hindered, however, by poor understanding of the transmission of MERS-CoV in dromedaries and a lack of mathematical models of transmission dynamics. In this thesis, I use mathematical models to better characterise the dynamics of MERS-CoV in dromedary populations and to simulate the potential impact of vaccination. In Chapter 2, published measures of MERS-CoV infection prevalence and seroprevalence in dromedaries are systematically reviewed. In Chapter 3, age-stratified seroprevalence data from dromedary populations across Africa, the Middle East and South Asia are used to fit catalytic models of seroconversion, producing estimates of transmissibility and the rate of waning of maternally acquired antibodies. In Chapter 4, a stochastic, age-structured, dynamic transmission model of MERS-CoV in dromedaries is developed. The model is used to estimate key, epidemiological quantities including R0 and the critical community size, that give an insight into how controllable MERS-CoV is in different dromedary populations. Seasonal calving is also explored as a potential driver of peaks of infection. Finally, in Chapter 5, the dynamic model is extended to simulate vaccination under different efficacy scenarios. The potential impact of vaccination on transmission in dromedaries is evaluated, as well as the optimal age for vaccination. Alongside empirical studies, insights from dynamic models such as those developed in this thesis could contribute to informing an effective response to the zoonotic transmission of MERS-CoV.Open Acces

Environmental Aspects of Zoonotic Diseases

Environmental Aspects of Zoonotic Diseases provides a definitive description, commentary and research needs of environmental aspects related to zoonotic diseases. There are many interrelated connections between the environment and zoonotic diseases such as: water, soil, air and agriculture. The book presents investigations of these connections, with specific reference to environmental processes such as: deforestation, floods, draughts, irrigation practices, soil transfer and their impact on bacterial, viral, fungal, and parasitological spread. Environmental aspects such as climate (tropical, sub-tropical, temperate, arid and semi-arid), developed and undeveloped countries, animal traffic animal border crossing, commercial animal trade, transportation, as well geography and weather on zoonosis, are also discussed and relevant scientific data is condensed and organized in order to give a better picture of interrelationship between the environment and current spread of zoonotic diseases

Zoonoses (Project 1): Wildlife/domestic livestock interactions

The objective of this study was to synthesise the best available scientific knowledge about zoonotic disease transmission through livestock and wildlife interaction (direct or indirect), with emphasis on risk factors, drivers and trajectories of transmission, as well as promising interventions for controlling important zoonoses, based on managing the interaction between domestic livestock and wildlife. A multi-disciplinary team from the International Livestock Research Institute, Kenya, and the Royal Veterinary College, United Kingdom, with expertise in zoonoses, epidemiology, socio-economics, and wildlife, undertook the review. A database of important zoonoses was compiled and used to develop a list of priority zoonoses with a livestock-wildlife interface for developing countries. Spatial relationships between important zoonoses and land use and human population density were explored. A systematic review was carried out focussing on: disease transmission routes, risk factors for disease transmission, drivers of wildlife-livestock interactions, pathogens of wildlife capable of recombining with organisms in livestock, wildlife species that are potential sources of zoonotic pathogens, production and socio-economic factors influencing the risk of transmission, and risk management and control interventions

Emerging infectious diseases

Emerging Infectious Diseases is providing access to these abstracts on behalf of the ICEID 2008 program committee, which performed peer review. Emerging Infectious Diseases has not edited or proofread these materials and is not responsible for inaccuracies or omissions. All information is subject to change.Comments and corrections should be brought to the attention of the authors.Slide Sessions -- Foodborne & waterborne diseases I -- Influenza I -- Surveillance: International -- Zoonotic & animal diseases I -- Methicillin-resistant stapylococcal infections -- Vectorborne diseases -- Foodborne & waterborne diseases II -- Influenza II -- Surveillance: Domestic -- Zoonotic & animal diseases II -- Noscomial infections -- Respiratory diseases -- Health communications -- Blood, organ, & tissue safety -- Tropical diseases -- New rapid diagnostics -- Mobile populations & infectious diseases -- Vaccine-preventable diseases -- Tuberculosis -- Sexually transmitted diseases -- -- Poster Abstracts -- Vaccines & vaccine-preventable diseases -- Antimicrobial resistance -- Climate changes -- Foodborne & waterborne infections -- Health communication -- Infectious causes of chronic diseases -- Influenza -- New or rapid diagnostics -- Nosocomial infections -- Outbreak investigation: Lab & epi response -- Sexually transmitted diseases -- Surveillance: International & new strategies -- Travelers' health & disease importation -- Tropical infections & parasitic diseases -- Vector-borne diseases -- Women, gender, sexual minorities & infectious diseases -- Zoonotic & animal diseases -- Vaccines & vaccine-preventable diseases -- Antimicrobial resistance -- Emerging aspects of HIV -- Foodborne & waterborne infections -- Health communication -- Molecular epidemiology -- Outbreak investigation: Lab & epi response -- Poverty & infectious diseases -- Surveillance: International & new strategies -- Tropical infections & parasitic diseases -- Vector-borne diseases -- Zoonotic & animal diseases -- Vaccines & vaccine-preventable diseases -- Antimicrobial resistance -- Blood, organ, & other tissue safety -- Foodborne & waterborne infections -- Host & microbial genetics -- Influenza -- Molecular epidemiology -- New or rapid diagnostics -- Outbreak investigation: Lab & epi response -- Prevention effectiveness, cost effectiveness, & cost studies -- Surveillance: International & new strategies -- Vector-borne diseases -- Zoonotic & animal diseases -- Vaccines & vaccine-preventable diseases -- Antimicrobial resistance -- Bioterrorism preparedness -- Emerging opportunistic infections -- Foodborne & waterborne infections -- Healthcare worker safety -- Influenza -- Laboratory proficiency testing/quality assurance -- Modeling -- Nosocomial infections -- Outbreak investigation: Lab & epi response -- Vector-borne diseases -- Viral hepatitis -- Zoonotic & animal diseases -- Vaccines & vaccine-preventable diseases -- Antimicrobial resistance -- Emerging opportunistic infections -- Foodborne & waterborne infections -- Influenza -- New or rapid diagnostics -- Nosocomial infections -- Outbreak investigation: Lab & epi response -- Social determinants of infectious disease disparities -- Surveillance: International & new strategies -- Tuberculosis -- Vector-borne diseases -- Zoonotic & animal diseases -- -- Additional Poster Abstracts.Abstracts published in advance of the conference

Development and characterisation of recombinant LSDV-vectored dual vaccines against bovine leukaemia virus and lumpy skin disease virus

Bovine leukaemia virus (BLV) and lumpy skin disease virus (LSDV) are endemic to Africa and cause significant economic losses to the beef and dairy industries. Vaccines are the most cost-effective and efficient way to prevent infection and outbreaks. Currently, there is no commercially available vaccine against BLV. In contrast, there are several live attenuated vaccines against LSDV. A recombinant LSDV which could protect cattle against both LSDV and BLV would be of great benefit to the African continent. This Master’s degree project involved three objectives. Firstly, the genetic variabilities and phylogenetic relationships of eight South African BLV isolates with other BLV strains from different geographical regions worldwide with known genotypes were determined. The BLV full-length envelope (env) and gag genes were successfully sequenced from total DNA extracted from the blood of BLV-infected cattle from a single herd. The analyses indicated that the seven of the South African isolates characterised in this study belonged to genotype 4 and the eighth to genotype 1. Furthermore, amino acid substitutions in the BLV Env and Gag sequences unique to the South African isolates were identified. Secondly, the activity of five selected poxvirus promoters in cells infected with LSDV was assessed by the detection of transient expression of an enhanced green fluorescent protein (eGFP) reporter gene driven by the poxvirus promoters. The promoters tested were a modified early fowlpox virus promoter (pmFP), an early-late promoter of a 7.5 kilodalton polypeptide gene of vaccinia virus (VACV) (p7.5), a synthetic early-late promoter of VACV (pS), a modified early-late promoter of the H5 gene of VACV (pmH5) and a synthetic early-late optimised promoter of VACV (pLEO). The results showed that all the poxvirus promoters were functional in the LSDV-infected cells and the eGFP expression was stable over the 72-hour study period. Lastly, two LSDV-vectored dual vaccines containing BLV immunogen(s) were developed and characterised. The first recombinant LSDV-vectored vaccine contained the BLV Env and Gag immunogens and the second recombinant LSDV-vectored vaccine contained the BLV Env immunogen alone. The presence of the BLV env gene in the recombinant LSDV vaccine was confirmed by polymerase chain reaction (PCR) and the BLV env sequence was confirmed by Sanger sequencing. Furthermore, BLV Env and Gag protein expression were confirmed by immunofluorescent staining and Western blotting, respectively. Future work will involve further purification of the recombinant viruses, confirmation of the production of BLV Gag virus-like particles and the preparation of high titre stocks of the vaccines to test in cattle

Emerg Infect Dis

PMC4550154611

Ecology and evolution of shrew-borne orthohantaviruses in Finland

More than 60% of human emerging infectious diseases (EIDs) are zoonotic. Zoonoses are infectious diseases of animals (usually vertebrates) that can be transmitted to humans. Hantaviruses are emerging zoonotic pathogens that belong to the genus Orthohantavirus and family Hantaviridae in order Bunyavirales. Hantaviruses pose a serious threat to human health because their infection causes two highly fatal diseases: haemorrhagic fever with renal syndrome (HFRS) and hantavirus cardiopulmonary syndrome (HCPS). Rodents have been regarded as the main reservoir and evolutionary scene of hantaviruses. In the last three decades, our knowledge of hantaviruses has broadened significantly. In contrast to the initial assumption that hantaviruses are mainly carried by rodents, many novel hantaviruses have been detected in shrews, moles and bats during the last few years. These findings raise a number of significant questions about the evolutionary history of hantaviruses, their host association and adaptation, the role and frequency of spillover infections and host-switch events, and most importantly, their pathogenicity.   In Finland, Puumala virus (PUUV) has been regarded as the only rodent-borne hantavirus present in the country. To search for novel hantaviruses other than PUUV, various novel hantaviruses were molecularly identified in different species of Soricomorpha ("shrew-form"). Genetic analyses revealed that four soricomorph-borne hantaviruses circulate in Finland, including Boginia virus (BOGV) in Neomys fodiens and Asikkala virus (ASIV) in Sorex minutus. Common shrews (Sorex araneus) harboured two different hantaviruses: Seewis virus (SWSV) and an Altai-like virus, showing the first evidence of co-existence of two distinct hantavirus species circulating simultaneously in one host species population. This host sharing of two divergent hantaviruses in the European common shrews contradicts hantavirus-host specificity, further implying the complexity of hantavirus evolution.   After screening hundreds of S. araneus from all of Finland, we obtained a large data set of new SWSV sequences that enabled phylogeographic analyses of SWSV. The results demonstrated that this shrew-borne hantavirus is similar to rodent-borne hantaviruses, and the post-glacial spread of SWSV into Finland mirrors that of the host, S. araneus: these shrews colonized Finland from the east after the last ice age (12,000–8,000 years ago) and then subsequently spread along emerging land bridges towards the west or north.   Most new hantaviruses discovered in soricomorph and bat hosts instead of rodents have raised questions as to whether any of them will emerge as human pathogens. Therefore, to predict human exposure risk, novel laboratory techniques for molecular and serological hantavirus detection were developed. No evidence of SWSV infection was found among a panel of 486 patient serum samples; however, we demonstrated a cross-reaction of anti-PUUV serum with shrew-borne hantavirus nucleocapsid (N) protein.   This thesis focused on the diversity, host maintenance and cross-species transmission dynamics of soricomorph-borne hantaviruses. The study presented innovative methods to investigate this pertinent topic at the interface of wildlife diseases and human health. The results provided new insights about the ecology, evolutionary origins and phylogeography, and most importantly, the potential pathogenicity of soricomorph-borne hantaviruses. This knowledge in combination with future studies will hopefully lead to a better understanding of host-parasite relationships.Mer än 60 % av alla infektionssjukdomar som drabbar människor är s.k. zoonoser. En viktig zoonos som kan ge blödarfeber är de som orsakas av Hantavirus. Olika typer av Hantavirus orsakar hos människor allt från lätt feber till mycket allvarlig blödarfeber som kan ha dödlig utgång. Hantavirus bärs huvudsakligen av gnagare, varför gnagare har betraktas som den huvudsakliga s.k. reservoaren för Hantavirus. Under de tre senaste decennierna har dock kunskapen kring Hantavirus ökat kraftigt. Idag anses inte längre Hantavirus bäras enbart av gnagare, utan Hantavirus har även hittats i näbbmöss, mullvadar, fladdermöss och till och med insekter. Dessa fynd föranleder flertalet frågor beträffande Hantavirusens evolutionära historia, deras förhållande och anpassningar till sina värddjur, betydelsen av sporadisk smittöverföring till andra djurarter, förändringar i värdart och framförallt ur ett medicinskt perspektiv deras förmåga att framkalla sjukdom. I Finland har historiskt sett Puumulavirus (PUUV) betraktas som den enda typ av gnagarburet-Hantavirus som funnits i landet. I människor orsakar PUUV en mildare form av blödarfeber som kallas för sorkfeber. I sökandet efter nya Hantavirus skilda från PUUV i Finland provtogs olika insektsätare som bl.a. näbbmöss och mullvadar. Genetisk analys visade att fyra olika insektsätarburna Hantavirus cirkulerar i Finland. Bland dessa återfinns Boginiavirus (BOGV) i vattennäbbmus och Askikkalavirus (ASIV) i dvärgnäbbmus. I vanlig näbbmus återfanns två olika Hantavirus (Seewisvirus, SWSV, och ett Altai-likt virus), vilket var det första fyndet av två olika Hantavirus som samexisterar i en och samma värdartspopulation. Samexistensen av två olika Hantavirus i vanlig näbbmus är kontradiktorisk mot den tidigare för Hantavirus så karaktäristiska värdartsspecificiteten, vilket påvisar komplexiteten i evolutionen av Hantavirus. Vanlig näbbmus som fanns bära på SWSV är vida spridd i euroasien med en utbredning från centrala Sibirien till västra Europa. Fältprovtagning av hundratals vanlig näbbmus från hela Finland och isolering av SWSV från dessa möjliggjorde fylogenetisk analys av finska SWSV. Resultaten visade att detta insektsätarassocierade Hantavirus liknar de gnagarburna Hantavirusen. Introduktionen och spridningen av SWSV i Finland efter den senaste istiden återspeglar dess värd, den vanliga näbbmusens kolonialisering av Finland. Näbbmössen kolonialiserade Finland från öster för ca 8-12 tusen år sedan och spred sig därefter mot väst-nordväst. Upptäckten av Hantavirus bland insektsätare, så som näbbmöss och fladdermöss, har väckt frågan huruvida något av dessa virus kan orsaka sjukdom hos människor likt deras gnagarburna släktingar. För att utvärdera risken av SWSV-smitta till människor upprättades nya diagnostiska metoder för SWSV-diagnostik. Inga tecken av SWSV-infektion hittades bland 486 testade patientblodprov. Däremot observerades en korsreaktivitet mellan α-PUUV antikroppar och nukleokapsidproteinet hos Hantavirus isolerat från näbbmöss. Denna doktorsavhandling fokuserade på mångfalden, bibehållandet av virus hos värddjuret och spridning mellan olika värdarter av Hantavirus isolerade från olika insektsätare. Under arbetes gång har innovativa metoder använts för att studera detta viktiga ämne i gränslandet mellan vilddjurssjukdomar och människors hälsa. Denna doktorsavhandling tillsammans med framtida studier kommer förhoppningsvis att leda till en ökad förståelse av relationen mellan värddjur och de virus de bär på

Haemostasis and Virus infections

__Abstract__ Het ontstaan van een bloeding of trombose gedurende of kort volgend op een infectie is een van de meest prominente oorzaken van morbiditeit en sterfte ten gevolge van infectieziekten. Hoewel aanzienlijke vooruitgang is geboekt in het ontrafelen van ziekte mechanismen in bijvoorbeeld bloedvergiftiging (sepsis) en chronische virus infecties (HIV, hepatitis B,C), is de kennis over de mechanismen die verantwoordelijk zijn voor het ontstaan van bloedingen en/ of trombose ten tijde van virale infecties zeer beperkt. In dit proefschrift hebben wij enerzijds verspreiding en diagnostiek van virale bloedende koortsen bestudeerd. Anderzijds onderzochten wij de interactie tussen virale infecties en de stollingscascade. Samengevat heeft het onderzoek beschreven in dit proefschrift bijgedragen aan de kennis van virale infecties en interactie met daarachterliggende mechanismen van trombose en bloedi ng. Uit het epidemiologische onderzoek bleek dat een hantavirus infectie, met als mogelijk gevolg een bloedende koorts, een diagnose is die in ieder geval in Nederland en Suriname nog al eens over het hoofd wordt gezien gebaseerd op de resultaten van de Hanta-Hunting studie. Wat betreft de ziekte mechanisme stud ies lijken op het eerste gezicht zowel virussen die bloedingen veroorzaken als virussen die juist verstopping van een bloedvat kunnen veroorzaken een vergelijkbaar effect te hebben op de bloedstolling, namelijk activatie van de stolling. Factoren die bepalend zijn of een virus infectie leidt tot trombose of bloeding zullen gezocht moeten worden in zeer subtiele verschillen. Hierin lijkt dat zowel de hevigheid van de respons op infectie als het orgaan dat is aangedaan van groot belang kan zijn. Het proefschrift eindigt met een tweetal hoofdstukken gericht op het voorkomen van de infecties behandeld in de eerdere delen. Wij toonden een sterke associatie aan tussen selenium concentratie in gewassen en de incidentie van hant avirus infecties in China. Op basis van vervolg studies in patiënten en experimenten gebruik makende van een endotheelcel model suggereren wij dat de variaties in selenium concentratie zeer waarschijnlijk effect hebben op de verspreiders van hantavirus infecties in Ch ina, ratten en bosmuizen. Of en hoe uiteindelijk selenium suppletie het aantal hantavirus infecties kan doen dalen, zal moeten worden uitgewezen in vervolg studies. de effectiviteit en veiligheid zien van preventie door middel van vaccinatie met een gemodificeerd pokkenvirus (MVA). Op het oppervlakte van dit ongevaarlijke virus is een belangrijk oppervlakte eiwit van het zeer gevaarlijke vogelgriepvirus tot expressie gebracht. Het gebruik van vector als vaccinatie biedt een veelbelovend perspectief voor bescherming tegen vele andere virussen, zoals bijvoorbeeld hantavirussen