Biomechanical strength of triceps tendon repairs: systematic review and meta-regression analysis of human cadaveric studies.

PURPOSE: It is unclear which triceps tendon repair constructs and techniques produce the strongest biomechanical performance while minimizing the risk of gap formation and repair failure. We aimed to determine associations of construct and technique variables with the biomechanical strength of triceps tendon repairs. PubMed, Embase, Cochrane Library, Web of Science, Scopus, and ClinicalTrials.gov were systematically searched for peer-reviewed studies on biomechanical strength of triceps tendon repairs in human cadavers. 6 articles met the search criteria. Meta-regression was performed on the pooled dataset (123 specimens). Outcomes of interest included gap formation, failure mode, and ultimate failure load. Covariates were fixation type; number of implants; and number of sutures. Stratification by covariates was performed. We found no association between fixation type and ultimate failure load; however, suture anchor fixation was associated with less gap formation compared with transosseous direct repair (ß = - 1.1; 95% confidence interval [CI]:- 2.2, - 0.04). A greater number of implants was associated with smaller gap formation (ß = - 0.77; 95% CI: - 1.3, - 0.28) while a greater number of sutures was associated with higher ultimate failure load ( ß= 3; 95% CI: 21, 125). In human cadaveric models, the number of sutures used in triceps tendon repairs may be more important than the fixation type or number of implants for overall strength. If using a transosseous direct repair approach to repair triceps tendon tears, surgeons may choose to use more sutures in their repair in order to balance the risk of larger gap formation when compared to indirect repair techniques. LEVEL OF EVIDENCE: Level III.

The zoonotic flaviviruses of southern, south-eastern and eastern Asia, and Australasia: the potential for emergent viruses.

The genus Flaviviridae comprises about 70 members, of which about 30 are found in southern, south-eastern and eastern Asia and Australasia. These include major pathogens such as Japanese encephalitis (JE), West Nile (WN), Murray Valley encephalitis (MVE), tick-borne encephalitis, Kyasanur Forest disease virus, and the dengue viruses. Other members are known to be associated with mild febrile disease in humans, or with no known disease. In addition, novel flaviviruses continue to be discovered, as demonstrated recently by New Mapoon virus in Australia, Sitiawan virus in Malaysia, and ThCAr virus in Thailand. About 19 of these viruses are mosquito-borne, six are tick-borne, and four have no known vector and represent isolates from rodents or bats. Evidence from phylogenetic studies suggest that JE, MVE and Alfuy viruses probably emerged in the Malaya-Indonesian region from an African progenitor virus, possibly a virus related to Usutu virus. WN virus, however, is believed to have emerged in Africa, and then dispersed through avian migration. Evidence suggests that there are at least seven genetic lineages of WN virus, of which lineage 1b spread to Australasia as Kunjin virus, lineages 1a and 5 spread to India, and lineage 6 spread to Malaysia. Indeed, flaviviruses have a propensity to spread and emerge in new geographic areas, and they represent a potential source for new disease emergence. Many of the factors associated with disease emergence are present in the region, such as changes in land use and deforestation, increasing population movement, urbanization, and increasing trade. Furthermore, because of their ecology and dependence on climate, there is a strong likelihood that global warming may significantly increase the potential for disease emergence and/or spread.

Salmonella infections in Antarctic fauna and island populations of wildlife exposed to human activities in coastal areas of Australia.

Salmonella infections in Antarctic wildlife were first reported in 1970 and in a search for evidence linking isolations with exposure to human activities, a comparison was made of serovars reported from marine fauna in the Antarctic region from 1982-2004 with those from marine mammals in the Northern hemisphere. This revealed that 10 (83%) Salmonella enterica serovars isolated from Antarctic penguins and seals were classifiable in high-frequency (HF) quotients for serovars prevalent in humans and domesticated animals. In Australia, 16 (90%) HF serovars were isolated from marine birds and mammals compared with 12 (86%) HF serovars reported from marine mammals in the Northern hemisphere. In Western Australia, HF serovars from marine species were also recorded in humans, livestock, mussels, effluents and island populations of wildlife in urban coastal areas. Low-frequency S. enterica serovars were rarely detected in humans and not detected in seagulls or marine species. The isolation of S. Enteritidis phage type 4 (PT4), PT8 and PT23 strains from Adélie penguins and a diversity of HF serovars reported from marine fauna in the Antarctic region and coastal areas of Australia, signal the possibility of transient serovars and endemic Salmonella strains recycling back to humans from southern latitudes in marine foodstuffs and feed ingredients.

Does antiviral therapy have a role in the control of Japanese encephalitis?

Approximately 2 billion people live in countries where Japanese encephalitis (JE) presents a significant risk to humans and animals, particularly in China and India, with at least 700 million potentially susceptible children. The combined effects of climate change, altered bird migratory patterns, increasing movement of humans, animals and goods, increasing deforestation and development of irrigation projects will inevitably lead to further geographic dispersal of the virus and an enhanced threat. Although most human infections are mild or asymptomatic, some 50% of patients who develop encephalitis suffer permanent neurologic defects, and 25% die. Vaccines have reduced the incidence of JE in some countries. No specific antiviral therapy is currently available. Interferon alpha-2a was tested in a double-blind placebo-controlled trial on children with Japanese encephalitis, but with negative results. There is thus a real need for antivirals that can reduce the toll of death and neurological sequelae resulting from infection with JE virus. Here we briefly review the epidemiological problems presented by this virus, the present state of drug development and the contributory role that antiviral therapy might play in developing future control strategies for JE.

Introduction: conceptualizing and partitioning the emergence process of zoonotic viruses from wildlife to humans.

This introduction provides a telegraphic overview of the processes of zoonotic viral emergence, the intricacies of host-virus interactions, and the distinct role of biological transitions and modifying factors. The process of emergence is conceptualized as two transition stages which are common and required for all disease emergence, (1) human contact with the infectious agent and (2) cross-species transmission of the agent, and two transition stages which are not required for emergence and appear unavailable to many zoonotic pathogens, (3) sustained human-to-human transmission and (4) genetic adaptation to the human host. The latter two transitions are presumably prerequisites for the pandemic emergence of a pathogen. The themes introduced herein are amplified and explored in detail by the contributors to this volume. Each author explores the mechanisms and unique circumstances by which evolution, biology, history, and current context have contrived to drive the emergence of different zoonotic agents by a series of related events; although recognizable similarities exist among the events leading to emergence the details and circumstances are never repetitive.

Henipaviruses: emerging paramyxoviruses associated with fruit bats.

Two related, novel, zoonotic paramyxoviruses have been described recently. Hendra virus was first reported in horses and thence humans in Australia in 1994; Nipah virus was first reported in pigs and thence humans in Malaysia in 1998. Human cases of Nipah virus infection, apparently unassociated with infection in livestock, have been reported in Bangladesh since 2001. Species of fruit bats (genus Pteropus) have been identified as natural hosts of both agents. Anthropogenic changes (habitat loss, hunting) that have impacted the population dynamics of Pteropus species across much of their range are hypothesised to have facilitated emergence. Current strategies for the management of henipaviruses are directed at minimising contact with the natural hosts, monitoring identified intermediate hosts, improving biosecurity on farms, and better disease recognition and diagnosis. Investigation of the emergence and ecology of henipaviruses warrants a broad, cross-disciplinary ecosystem health approach that recognises the critical linkages between human activity, ecological change, and livestock and human health.

Climatic, high tide and vector variables and the transmission of Ross River virus.

This report assesses the impact of the variability in environmental and vector factors on the transmission of Ross River virus (RRV) in Brisbane, Australia. Poisson time series regression analyses were conducted using monthly data on the counts of RRV cases, climate variables (Southern Oscillation Index and rainfall), high tides and mosquito density for the period of 1998-2001. The results indicate that increases in the high tide (relative risk (RR): 1.65; 95% confidence interval (CI): 1.20-2.26), rainfall (RR: 1.45; 95% CI: 1.21-1.73), mosquito density (RR: 1.17; 95% CI: 1.09-1.27), the density of Culex annulirostris (RR: 1.25; 95% CI: 1.13-1.37) and the density of Ochlerotatus vigilax (RR: 2.39; 95% CI: 2.30-2.48), each at a lag of 1 month, were statistically significantly associated with the rise of monthly RRV incidence. The results of the present study might facilitate the development of early warning systems for reducing the incidence of this wide-spread disease in Australia and other Pacific island nations.

Flavivirus isolations from mosquitoes collected from Saibai Island in the Torres Strait, Australia, during an incursion of Japanese encephalitis virus.

Adult mosquitoes (Diptera: Culicidae) were collected in January and February 2000 from Saibai Island in the Torres Strait of northern Australia, and processed for arbovirus isolation during a period of Japanese encephalitis (JE) virus activity on nearby Badu Island. A total of 84 210 mosquitoes were processed for virus isolation, yielding six flavivirus isolates. Viruses obtained were single isolates of JE and Kokobera (KOK) and four of Kunjin (KUN). All virus isolates were from members of the Culex sitiens Weidemann subgroup, which comprised 53.1% of mosquitoes processed. Nucleotide sequencing and phylogenetic analysis of the pre-membrane region of the genome of JE isolate TS5313 indicated that it was closely related to other isolates from a sentinel pig and a pool of Cx. gelidus Theobald from Badu Island during the same period. Also molecular analyses of part of the envelope gene of KUN virus isolates showed that they were closely related to other KUN virus strains from Cape York Peninsula. The results indicate that flaviviruses are dynamic in the area, and suggest patterns of movement south from New Guinea and north from the Australian mainland.

Emerging encephalitogenic viruses: lyssaviruses and henipaviruses transmitted by frugivorous bats.

Three newly recognized encephalitogenic zoonotic viruses spread from fruit bats of the genus Pteropus (order Chiroptera, suborder Megachiroptera) have been recognised over the past decade. These are: Hendra virus, formerly named equine morbillivirus, which was responsible for an outbreak of disease in horses and humans in Brisbane, Australia, in 1994; Australian bat lyssavirus, the cause of a severe acute encephalitis, in 1996; and Nipah virus, the cause of a major outbreak of encephalitis and pulmonary disease in domestic pigs and people in peninsula Malaysia in 1999. Hendra and Nipah viruses have been shown to be the first two members of a new genus, Henipavirus, in the family Paramyxoviridae, subfamily Paramyxovirinae, whereas Australian bat lyssavirus is closely related antigenically to classical rabies virus in the genus Lyssavirus, family Rhabdoviridae, although it can be distinguished on genetic grounds. Hendra and Nipah viruses have neurological and pneumonic tropisms. The first humans and equids with Hendra virus infections died from acute respiratory disease, whereas the second human patient died from an encephalitis. With Nipah virus, the predominant clinical syndrome in humans was encephalitic rather than respiratory, whereas in pigs, the infection was characterised by acute fever with respiratory involvement with or without neurological signs. Two human infections with Australian bat lyssavirus have been reported, the clinical signs of which were consistent with classical rabies infection and included a diffuse, non-suppurative encephalitis. Many important questions remain to be answered regarding modes of transmission, pathogenesis, and geographic range of these viruses.

Virus spread, tissue inflammation and antiviral response in brains of flavivirus susceptible and resistant mice acutely infected with Murray Valley encephalitis virus.

Inborn resistance to flaviviruses, conferred by a single chromosome 5 locus Flv, is a genetic trait operative in wild mice and a few strains of laboratory mice. In this study we have used in situ hybridisation to trace the spread of flavivirus genomic RNA within the brains of flavivirus susceptible C3H/HeJARC and congenic resistant C3H.PRI- Flv(r) mice following infection with Murray Valley encephalitis virus (MVE) in parallel to studying a brain histopathology and induction of cellular genes involved in antiviral response. We find that in contrast to a high viral RNA content in brains of susceptible mice, viral RNA was markedly reduced in the cortex, olfactory bulb, thalamus and hypothalamus of resistant mice. Trace amounts of viral RNA were detected in the medulla oblongata while it was completely absent from the hippocampus, pons and cerebellum of resistant mice at different time points post infection. The low virus titres within brains of resistant mice coincided with a very mild inflammation, low counts of infiltrating inflammatory cells, and lower IFN I/II and TNFalpha gene induction than in susceptible mice. Furthermore, transcripts of several genes belonging to a 2',5'-oligoadenylate synthetase ( OAS) family, implicated in IFN I-inducible OAS/RNase L antiviral pathway, showed similar brain tissue induction in both strains of mice suggesting only minor contribution of this pathway to the resistance phenotype.

Mosquito host-feeding patterns and implications for Japanese encephalitis virus transmission in northern Australia and Papua New Guinea.

Japanese encephalitis (JE) virus spread to northern Australia during the 1990s, transmitted by Culex annulirostris Skuse and other mosquitoes (Diptera: Culicidae). To determine the relative importance of various hosts for potential vectors of JE virus, we investigated the host-feeding patterns of mosquitoes in northern Australia and Western Province of Papua New Guinea, with particular attention to pigs, Sus scrofa L. - the main amplifying host of JE virus in South-east Asia. Mosquitoes were collected by CDC light traps baited with dry ice and 1-octen-3-ol, run 16.00-08.00 hours, mostly set away from human habitations, if possible in places frequented by feral pigs. Bloodmeals of 2569 mosquitoes, representing 15 species, were identified by gel diffusion assay. All species had fed mostly on mammals: only <10% of bloodmeals were from birds. The predominant species was Cx. annulirostris (88%), with relatively few (4.4%) bloodmeals obtained from humans. From all 12 locations sampled, the mean proportion of Cx. annulirostris fed on pigs (9.1%) was considerably lower than fed on other animals (90.9%). Highest rates of pig-fed mosquitoes (>30%) were trapped where domestic pigs were kept close to human habitation. From seven of eight locations on the Australian mainland, the majority of Cx. annulirostris had obtained their bloodmeals from marsupials, probably the Agile wallaby Macropus agilis (Gould). Overall proportions of mosquito bloodmeals identified as marsupial were 60% from the Gulf Plains region of Australia, 78% from the Cape York Peninsula and 64% from the Daru area of Papua New Guinea. Thus, despite the abundance of feral pigs in northern Australia, our findings suggest that marsupials divert host-seeking Cx. annulirostris away from pigs. As marsupials are poor JE virus hosts, the prevalence of marsupials may impede the establishment of JE virus in Australia.

Antibody-dependent enhancement of Murray Valley encephalitis virus virulence in mice.

Enhancement of flavivirus infection in vitro in the presence of subneutralizing concentrations of homologous or heterologous antiserum has been well described. However, the importance of this phenomenon in the enhancement of flavivirus infection in vivo has not been established. In order to study antibody-mediated enhancement of flavivirus infection in vivo, we investigated the effect of passive immunization of mice with Japanese encephalitis virus (JE) antiserum on the outcome of infection with Murray Valley encephalitis virus (MVE). We show that prior treatment of mice with subneutralizing concentrations of heterologous JE antiserum resulted in an increase in viraemia titres and in mortality following challenge with wild-type MVE. Our findings support the hypothesis that subneutralizing concentrations of antibody may enhance flavivirus infection and virulence in vivo. These findings are of potential importance for the design of JE vaccination programs in geographic areas in which MVE co-circulates. Should subneutralizing concentrations of antibody remain in the population following JE vaccination, it is possible that enhanced disease may be observed during MVE epidemics.

Collection of wind-borne haematophagous insects in the Torres Strait, Australia.

Circumstantial evidence has implicated wind-borne mosquitoes (Diptera: Culicidae) in the introduction of Japanese encephalitis (JE) virus into Australia from the New Guinea mainland. A study was initiated on Saibai Island in the northern Torres Strait, during January and February 2000, to identify the potential source of insects collected in aerial (kytoon) and surface-level traps. Wind speed and direction were recorded to determine wind profiles during insect sampling. Northerly winds capable of carrying insects from New Guinea to Saibai Island were only present on three out of 18 nights sampled. Only three male mosquitoes, comprising two Verrallina funerea (Theobald) and one Ochlerotatus vigilax (Skuse), were collected in aerial samples, and were most likely of local origin. Culicoides midges were also collected in aerial nets and included gravid/parous C. bundyensis Lee and Reye, and one parous C. histrio Johannsen. Highest densities of arthropods (up to 1562/million m3) were on 30 January 2000 when NW winds, sustained for six hours, probably introduced midges from the New Guinea mainland. Adult mosquitoes (including three female Ve. funerea and a single female Ficalbia) and Culicoides (including two gravid C. bundyensis and one parous C. cordiger Macfie) were also collected in 2 m high mast nets during northerly surface winds. Although the results do not provide evidence that wind-blown mosquitoes introduced JE from New Guinea into Australia, they do not preclude that strong N winds associated with low pressure systems SW of the Torres Strait could have done so. However, results suggest that Culicoides were more likely than mosquitoes to reach high altitude and travel long distances during the light N winds experienced during the study.

Managing emerging diseases borne by fruit bats (flying foxes), with particular reference to henipaviruses and Australian bat lyssavirus.

Since 1994, a number of novel viruses have been described from bats in Australia and Malaysia, particularly from fruit bats belonging to the genus Pteropus (flying foxes), and it is probable that related viruses will be found in other countries across the geographical range of other members of the genus. These viruses include Hendra and Nipah viruses, members of a new genus, Henipaviruses, within the family Paramyxoviridae; Menangle and Tioman viruses, new members of the Rubulavirus genus within the Paramyxoviridae; and Australian bat lyssavirus (ABLV), a member of the Lyssavirus genus in the family Rhabdoviridae. All but Tioman virus are known to be associated with human and/or livestock diseases. The isolation, disease associations and biological properties of the viruses are described, and are used as the basis for developing management strategies for disease prevention or control. These strategies are directed largely at disease minimization through good farm management practices, reducing the potential for exposure to flying foxes, and better disease recognition and diagnosis, and for ABLV specifically, the use of rabies vaccine for pre- and post-exposure prophylaxis. Finally, an intriguing and long-term strategy is that of wildlife immunization through plant-derived vaccination.

Vector competence of Australian mosquitoes (Diptera: Culicidae) for Japanese encephalitis virus.

Australian mosquitoes were evaluated for their ability to become infected with and transmit a Torres Strait strain of Japanese encephalitis virus. Mosquitoes, which were obtained from either laboratory colonies and collected using Centers for Disease Control and Prevention light traps baited with CO2 and octenol or reared from larvae, were infected by feeding on a blood/sucrose solution containing 10(4.5 +/- 0.1) porcine stable-equine kidney (PS-EK) tissue culture infectious dose50/mosquito of the TS3306 virus strain. After 14 d, infection and transmission rates of 100% and 81%, respectively, were obtained for a southeast Queensland strain of Culex annulirostris Skuse, and 93% and 61%, respectively, for a far north Queensland strain. After 13 or more days, infection and transmission rates of > 90% and > or = 50%, respectively, were obtained for southeast Queensland strains of Culex sitiens Wiedemann and Culex quinquefasciatus Say, and a far north Queensland strain of Culex gelidus Theobald. Although infection rates were > 55%, only 17% of Ochlerotatus vigilax (Skuse) and no Cx. quinquefasciatus, collected from far north Queensland, transmitted virus. North Queensland strains of Aedes aegypti L., Ochlerotatus kochi (Dönitz), and Verrallina funerea (Theobald) were relatively refractory to infection. Vertical transmission was not detected among 673 F1 progeny of Oc. vigilax. Results of the current vector competence study, coupled with high field isolation rates, host feeding patterns and widespread distribution, confirm the status of Cx. annulirostris as the major vector of Japanese encephalitis virus in northern Australia. The relative roles of other species in potential Japanese encephalitis virus transmission cycles in northern Australia are discussed.

Isolation of arboviruses from mosquitoes (Diptera: Culicidae) collected from the Gulf Plains region of northwest Queensland, Australia.

As part of investigations into Japanese encephalitis (JE) virus and related flaviviruses in northern Australia, 153,529 mosquitoes were collected and processed for virus isolation from the Gulf Plains region of northwest Queensland. Collections from within 30 km of each of the townships of Croydon, Normanton and Karumba yielded 3,087 (2.0%), 66,009 (43.0%), and 84,433 (55.0%) mosquitoes, respectively, from which 16 viruses were isolated. Four isolates of Murray Valley encephalitis (MVE), two of Kunjin (KUN), three of Ross River (RR), and one of Sindbis (SIN) viruses were obtained from Culex sitiens subgroup mosquitoes. Molecular identification of the mosquito species composition of these virus positive pools revealed that most isolates were from pools containing mainly Culex annulirostris Skuse and low numbers of Culex palpalis (Taylor). Only three pools, one each of MVE, KUN, and RR, were from mosquitoes identified exclusively as Cx. annulirostris. Other viruses isolated include one Edge Hill virus from Ochlerotatus normanensis (Taylor), an isolate of SIN from Anopheles meraukensis Venhuis, two isolates of RR from Anopheles amictus Edwards, and single isolates of RR from Anopheles bancroftii Giles andAedes lineatopennis (Ludlow). The isolate of RR from Ae. lineatopennis was the first reported from this species. The public health implications of these isolations in the Gulf Plains region are discussed briefly.