Quantifying and mapping the burden of human and animal rabies in Iraq.

Rabies was first reported in ancient Iraqi civilizations, yet it remains a poorly quantified and important public health threat in the region. Efforts to control rabies in Iraq including dog population control, and vaccination of livestock and dogs, have increased since 2010. Officially reported data on human rabies, dog bites, and animal rabies cases between 2012 and 2017 are analysed here to assess the effect of existing control efforts, to inform future strategies, and to highlight gaps in surveillance and reporting.

Isolation, antigenicity and immunogenicity of Lleida bat lyssavirus.

The lyssaviruses are an important group of viruses that cause a fatal encephalitis termed rabies. The prototypic lyssavirus, rabies virus, is predicted to cause more than 60 000 human fatalities annually. The burden of disease for the other lyssaviruses is undefined.

Rabies.

Rabies is a life-threatening neglected tropical disease: tens of thousands of cases are reported annually in endemic countries (mainly in Africa and Asia), although the actual numbers are most likely underestimated. Rabies is a zoonotic disease that is caused by infection with viruses of the Lyssavirus genus, which are transmitted via the saliva of an infected animal. Dogs are the most important reservoir for rabies viruses, and dog bites account for >99% of human cases.

Current status of rabies and prospects for elimination.

Rabies is one of the most deadly infectious diseases, with a case-fatality rate approaching 100%. The disease is established on all continents apart from Antarctica; most cases are reported in Africa and Asia, with thousands of deaths recorded annually. However, the estimated annual figure of almost 60,000 human rabies fatalities is probably an underestimate.

Emerging technologies for the detection of rabies virus: challenges and hopes in the 21st century.

The diagnosis of rabies is routinely based on clinical and epidemiological information, especially when exposures are reported in rabies-endemic countries. Diagnostic tests using conventional assays that appear to be negative, even when undertaken late in the disease and despite the clinical diagnosis, have a tendency, at times, to be unreliable. These tests are rarely optimal and entirely dependent on the nature and quality of the sample supplied.

Experimental infection of serotine bats (Eptesicus serotinus) with European bat lyssavirus type 1a.

The serotine bat (Eptesicus serotinus) accounts for the vast majority of bat rabies cases in Europe and is considered the main reservoir for European bat lyssavirus type 1 (EBLV-1, genotype 5). However, so far the disease has not been investigated in its native host under experimental conditions. To assess viral virulence, dissemination and probable means of transmission, captive bats were infected experimentally with an EBLV-1a virus isolated from a naturally infected conspecific from Germany.

Experimental study of European bat lyssavirus type-2 infection in Daubenton's bats (Myotis daubentonii).

European bat lyssavirus type 2 (EBLV-2) can be transmitted from Daubenton's bats to humans and cause rabies. EBLV-2 has been repeatedly isolated from Daubenton's bats in the UK but appears to be present at a low level within the native bat population. This has prompted us to investigate the disease in its natural host under experimental conditions, to assess its virulence, dissemination and likely means of transmission between insectivorous bats.

Investigating antibody neutralization of lyssaviruses using lentiviral pseudotypes: a cross-species comparison.

Cross-neutralization between rabies virus (RABV) and two European bat lyssaviruses (EBLV-1 and -2) was analysed using lentiviral pseudotypes as antigen vectors. Glycoprotein (G-protein) cDNA from RABV challenge virus standard-11 (CVS-11) and EBLV-1 and -2 were cloned and co-expressed with human immunodeficiency virus (HIV) or murine leukemia virus (MLV) gag-pol and packageable green fluorescent protein (GFP) or luciferase reporter genes in human cells. The harvested lentiviral (HIV) vector infected over 40% of baby hamster kidney (BHK) target cells, providing high-titre pseudotype stocks.

The application of genetic markers for EBLV surveillance in European bat species.

The United Kingdom has performed passive surveillance for European bat lyssaviruses (EBLVs) since 1987, and species-targeted surveillance since 2003. One critical component of these studies is the accurate identification of bats either submitted for testing or sampled in the field. Identification is dependent on numerous morphological characteristics.

Up-regulation of chemokine gene transcripts and T-cell infiltration into the central nervous system and dorsal root ganglia are characteristics of experimental European bat lyssavirus type 2 infection of mice.

European bat lyssaviruses (EBLV) types 1 and 2 are closely related to classical rabies virus (RABV), and are capable of causing rabies in terrestrial mammals, including humans. The authors have investigated the murine host innate immune response in the brain, salivary gland, spinal cord, and blood, following peripheral inoculation with EBLV-2. In the brain, increases in Toll-like receptor-3 (TLR-3) transcript preceded overt disease, with a range of inflammatory gene transcripts increasing during the clinical stage of infection.

Phylogenetic comparison of rabies viruses from disease outbreaks on the Svalbard Islands.

Periodic wildlife rabies epizootics occur in Arctic regions. The original sources of these outbreaks are rarely identified. In 1980, a wildlife epizootic of rabies occurred on the previously rabies-free Svalbard Islands, Norway.

Susceptibility of sheep to European bat lyssavirus type-1 and -2 infection: a clinical pathogenesis study.

European bat lyssaviruses (EBLVs) have been known to cross the species barrier from their native bat host to other terrestrial mammals. In this study, we have confirmed EBLV-1 and EBLV-2 susceptibility in sheep (Ovis ammon) following intracranial and peripheral (intramuscular) inoculation. Notably, mild clinical disease was observed in those exposed to virus via the intramuscular route.

Comparative analysis of the full genome sequence of European bat lyssavirus type 1 and type 2 with other lyssaviruses and evidence for a conserved transcription termination and polyadenylation motif in the G-L 3' non-translated region.

We report the first full-length genomic sequences for European bat lyssavirus type-1 (EBLV-1) and type-2 (EBLV-2). The EBLV-1 genomic sequence was derived from a virus isolated from a serotine bat in Hamburg, Germany, in 1968 and the EBLV-2 sequence was derived from a virus isolate from a human case of rabies that occurred in Scotland in 2002. A long-distance PCR strategy was used to amplify the open reading frames (ORFs), followed by standard and modified RACE (rapid amplification of cDNA ends) techniques to amplify the 3' and 5' ends.

Ability of rabies vaccine strains to elicit cross-neutralising antibodies.

Two European Bat Lyssaviruses (EBLV-1 and EBLV-2) have been identified (n > 750 cases) in European bat species. In addition, EBLVs have been detected as "spillover" cases in three humans, one stone marten and four sheep. A further concern is the interaction of companion animals with infected bats and the possibility of subsequent lyssavirus infection.

Occupational lyssavirus risks and post-vaccination monitoring.

In the UK, rabies pre-exposure vaccination involves a 3-dose course (DO, 7 & 28) and reinforcing doses at a 2-3 year intervals. This booster schedule had been implemented following scientific evidence indicating that a reduction in the previous regime interval of 3-5 years was warranted. The regime changes were particularly relevant to high risk groups that may encounter rabies virus.

Molecular epidemiology of rabies viruses in Europe.

Several different strains of classical rabies virus co-circulate in Europe. In order to investigate the roles of the host species and topography on the molecular epidemiology of these viruses, a 400 bp region of the nucleoprotein gene was sequenced and compared with more than 500 European virus isolates. Viruses from 21 European countries were represented including some unique panels of archived isolates from the former Republic of Yugoslavia, Estonia, the Czech Republic, Poland and Austria.

European bat lyssaviruses: Distribution, prevalence and implications for conservation.

Worldwide, there are more than 1100 species of the Order Chiroptera, 45 of which are present in Europe, and 16 in the UK. Bats are reservoirs of, or can be infected by, several viral diseases, including rabies virus strains (in the Lyssavirus genus). Within this genus are bat variants that have been recorded in Europe; European bat lyssavirus 1 (EBLV-1), European bat lyssavirus 2 (EBLV-2) and, four currently unclassified isolates.

Airborne transmission of lyssaviruses.

In 2002, a Scottish bat conservationist developed a rabies-like disease and subsequently died. This was caused by infection with European bat lyssavirus 2 (EBLV-2), a virus closely related to Rabies virus (RABV). The source of this infection and the means of transmission have not yet been confirmed.

Wildlife rabies in Western Turkey: the spread of rabies through the western provinces of Turkey.

The incidence of rabies has decreased in Turkey during recent years. However, an increasing number of rabies cases have been reported in the Aegean (western) region of Turkey. The virus appears to have maintained a foothold in the urban areas of the province of Izmir with only three cases per year being reported during the mid-1990s.

A molecular epidemiological study of rabies epizootics in kudu (Tragelaphus strepsiceros) in Namibia.

Background: A panel of 37 rabies virus isolates were collected and studied, originating mainly from the northern and central regions of Namibia, between 1980 and 2003.

Results: These virus isolates demonstrated a high degree of genetic similarity with respect to a 400 bp region of the nucleoprotein gene, with the virus isolates originating from kudu antelope (n = 10) sharing 97.2-100% similarity with jackal isolates, and 97-100% similarity with those isolated from domestic dogs.

Molecular epidemiological study of Arctic rabies virus isolates from Greenland and comparison with isolates from throughout the Arctic and Baltic regions.

We report a molecular epidemiological study of rabies in Arctic countries by comparing a panel of novel Greenland isolates to a larger cohort of viral sequences from both Arctic and Baltic regions. Rabies virus isolates originating from wildlife (Arctic/red foxes, raccoon-dogs and reindeer), from domestic animals (dogs/cats) and from two human cases were investigated. The resulting 400 bp N-gene sequences were compared with isolates representing neighbouring Arctic or Baltic countries from North America, the former Soviet Union and Europe.

Detection and strain differentiation of European bat lyssaviruses using in situ hybridisation.

A protocol suitable for the detection of rabies virus and the related European bat lyssaviruses type 1 and 2 is described. In situ hybridisation, employing digoxigenin labelled riboprobes was used for the detection of lyssavirus RNA in mouse-infected brain tissue. The principal advantage of this technique, compared to routine methods used for histopathology, is that this method is robust, highly sensitive, and specific for assessing the presence of RNA in different tissues.