Objective: To compare the pharmacokinetics of a novel bioadhesive gel formulation of midazolam after intranasal (IN) administration with that of midazolam solution after IN, IV, and rectal administration to dogs. Animals: 10 (5 males and 5 females) healthy adult Beagles. Procedures: Dogs were assigned to 4 treatment groups for a crossover study design. Initially, midazolam solution (5 mg/mL) was administered (0.2 mg/kg) IV to group 1, rectally to group 2, and IN to group 3; a 0.4% hydroxypropyl methylcellulose midazolam gel formulation (50 mg/mL) was administered (0.2 mg/kg, IN) to group 4. Each dog received all 4 treatments; there was a 7-day washout period between subsequent treatments. Blood samples were collected before and after midazolam administration. Plasma concentration of midazolam was determined by use of high-performance liquid chromatography. Results: The peak plasma concentration after IN administration of the gel formulation was significantly higher than that after IN and rectal administration of the solution. Mean ± SD time to peak concentration was 11.70 ± 2.63 minutes (gel IN), 17.50 ± 2.64 minutes (solution IN), and 39 ± 14.49 minutes (solution rectally). Mean bioavailability of midazolam was 70.4% (gel IN), 52.0% (solution IN), and 49.0% (solution rectally). Bioavailability after IN administration of the gel formulation was significantly higher than that after IN and rectal administration of the solution. Conclusions and Clinical Relevance: IN administration of midazolam gel was superior to both IN and rectal administration of midazolam solution with respect to peak plasma concentration and bioavailability.

Objective: To characterize adiponectin protein complexes in lean and obese horses. Animals: 26 lean horses and 18 obese horses. Procedures: Body condition score (BCS) and serum insulin activity were measured for each horse. Denaturing and native western blot analyses were used to evaluate adiponectin complexes in serum. A human ELISA kit was validated and used to quantify high–molecular weight (HMW) complexes. Correlations between variables were made, and HMW values were compared between groups. Results: Adiponectin was present as a multimer consisting of HMW (> 720-kDa), low-molecular weight (180-kDa), and trimeric (90-kDa) complexes in serum. All complexes were qualitatively reduced in obese horses versus lean horses, but the percentage of complexes < 250 kDa was higher in obese versus lean horses. High–molecular weight adiponectin concentration measured via ELISA was negatively correlated with serum insulin activity and BCS and was lower in obese horses (mean ± SD, 3.6 ± 3.9 μg/mL), compared with lean horses (8.0 ± 4.6 μg/mL). Conclusions and Clinical Relevance: HMW adiponectin is measurable via ELISA, and concentration is negatively correlated with BCS and serum insulin activity in horses. A greater understanding of the role of adiponectin in equine metabolism will provide insight into the pathophysiology of metabolic disease conditions.

Objective: To measure the effect of induced myopia on field trial performance in dogs. Animals: 7 Labrador Retrievers and 1 Chesapeake Bay Retriever trained in field trial competition. Procedures: Dogs were commanded to retrieve targets at 137.2 m (150 yards). Each dog participated in 3 trials while their eyes were fitted with 0- (plano), +1.50-, or +3.00-diopter (D) contact lenses, applied in random order. Retrieval times were measured objectively, and dog performances were evaluated subjectively by masked judges. Results: Retrieval times were significantly faster with plano lenses than with +1.50- or +3.00-D lenses, but there were no significant differences in times between +1.50- and +3.00-D lenses. Masked judges assigned the best performance scores to dogs with plano lenses and the lowest scores to dogs fitted with +3.00-D lenses. Conclusions and Clinical Relevance: Even mild myopic defocusing had a significant negative impact on both the subjective and objective assessments of dogs' performances. Dogs with demanding visual tasks or signs of visual deterioration should be evaluated retinoscopically to determine the refractive state because they may have ametropia.

Objective: To determine plasma pharmacokinetics of penciclovir following oral and rectal administration of famciclovir to young Asian elephants (Elephas maximus). Animals: 6 healthy Asian elephants (5 females and 1 male), 4.5 to 9 years old and weighing 1,646 to 2,438 kg. Procedures: Famciclovir was administered orally or rectally in accordance with an incomplete crossover design. Three treatment groups, each comprising 4 elephants, received single doses of famciclovir (5 mg/kg, PO, or 5 or 15 mg/kg, rectally); there was a minimum 12-week washout period between subsequent famciclovir administrations. Serial blood samples were collected after each administration. Samples were analyzed for famciclovir and penciclovir with a validated liquid chromatography–mass spectroscopy assay. Results: Famciclovir was tolerated well for both routes of administration and underwent complete biotransformation to the active metabolite, penciclovir. Mean maximum plasma concentration of penciclovir was 1.3 μg/mL at 1.1 hours after oral administration of 5 mg/kg. Similar results were detected after rectal administration of 5 mg/kg. Mean maximum plasma concentration was 3.6 μg/mL at 0.66 hours after rectal administration of 15 mg/kg; this concentration was similar to results reported for humans receiving 7 mg/kg orally. Conclusions and Clinical Relevance: Juvenile Asian elephants are susceptible to elephant endotheliotropic herpesvirus. Although most infections are fatal, case reports indicate administration of famciclovir has been associated with survival of 3 elephants. In Asian elephants, a dose of 8 to 15 mg of famciclovir/kg given orally or rectally at least every 8 hours may result in penciclovir concentrations that are considered therapeutic in humans.

Infectious bursal disease virus (IBDV) is a bi-segmented RNA virus, which belongs to the genus Avibirnavirus of the family Birnaviridae. Two serotypes, 1 and 2, exist in IBDV. The serotype 1 IBDVs are the causative agents of infectious bursal disease (IBD) in chickens worldwide and lead to immunosuppression in young birds. Genome re-assortment has been speculated to occur and contribute to the emergence of new IBDV strains. However, evidence was lacking until recently when two re-assortant viruses were detected in China. In this study, we determined the complete nucleotide sequence of an IBDV, designated KZC-104, from a confirmed natural IBD outbreak in Lusaka, Zambia in 2004. The genome consisted of 3074 and 2651 nucleotides in the coding regions of segments A and B, respectively. Alignment of both nucleotide and deduced amino acid sequences, and phylogenetic analysis revealed that the genome segment A of KZC-104 was derived from a very virulent strain, whereas its segment B was derived from a classical attenuated strain. On BLAST search, the full-length segments A and B sequences showed 98% closest nucleotide homology to the very virulent strain D6948 and 99.8% closest nucleotide homology to the classical attenuated strain D78, respectively. This is a unique IBDV reassortant strain, which has emerged in nature involving segment B of a live attenuated vaccine. This observation provides direct evidence for the involvement of vaccine strains in the emergence of reassortant IBDV in the field. Taken together, these findings suggest an additional risk of using live IBDV vaccines, which may act as genetic donors for genome re-assortment. Further studies are required to investigate the epidemiology and biological characteristics of reassortant strains so that the appropriate and safe IBDV vaccines can be recommended.

Toxoplasmosis is an infection of warm-blooded vertebrates caused by the obligate intracellular protozoan parasite, Toxoplasma gondii. It is one of the most common parasitic diseases of humans, infecting approximately one-third of the world’s population. In persons with advanced HIV, toxoplasmosis represents a major opportunistic infection of the central nervous system. Approximately two-thirds of all people living with HIV live in sub-Saharan Africa. In areas such as this, toxoplasmosis could theoretically pose a huge threat. There is little known about T. gondii prevalence in humans in Africa. Geographically, prevalences vary widely on this continent, as observed in other parts of the world. There is limited historical information about the disease in South Africa. More knowledge is needed at a regional level about the risk of toxoplasmosis, diagnostic issues, and measures to reduce the risk to susceptible persons. The seroprevalence of T. gondii in selected populations, namely HIV-positive and HIV-negative individuals, and a more general sample biased towards pregnant women, was therefore investigated and found to be 9.8% (37/376), 12.8% (48/376) and 6.4% (32/497) respectively. Compared with historical data from South Africa, the prevalence has decreased substantially; however, the incidence of clinical disease is unknown, despite the very high burden of HIV and AIDS cases (5.9 million and 0.7 million, respectively in 2009). This study provided information relating to the diagnosis and current seroprevalence of T. gondii in South Africa. Many questions still remain to be answered however, to fully understand the impact of this parasite on the country’s population.

More than 650 people from around 60 countries attended the 1st International One Health Conference, held in Melbourne from 14 to 16 February 2011. Scientists, clinicians, government and community members from a range of disciplines came together to discuss the benefits of working together to promote a One Health approach to human, animal and environmental health. One Health embraces systems thinking and recognising the interdependence of people, animals and environment. The conference was hosted by the Commonwealth Scientific and Industrial Research Organisation (CSIRO) and was supported by international agencies, the Australian and Canadian governments, and industry. The Organising Committee recognised from the outset, the need to provide a forum not just for scientific presentation, but for open discussion and dialogue around the policy and political issues, as well as the science that drives the One Health agenda. The Committee was also cognizant of the need to embrace a definition of One Health that includes food security and food safety and included the social and economic pressures that shapes this area. The meeting was therefore organised under four themes with plenary sessions followed by breakout parallel sessions for each of these. The themes covered Disease Emergence, Environmental Drivers, Trade, Food Security and Food Safety, and Science Policy and Political Action. The plenary session commenced with one or two keynote presentations by world leaders on the topic being covered, followed by panel discussions involving six to eight experts and involving all participants at the congress. Each of the panel members spoke briefly on the topic covered by the keynote speaker and were asked to be as provocative as possible. The discussions that followed allowed debate and discussion on the keynote presentations and the panel members comments. This was followed by six to eight parallel breakout sessions involving in depth papers on the session’s topic. Throughout the conference at various times, sponsored sessions dealt with particular areas of science or policy providing a further framework not only to learn current science but for debate and discussion. A full copy of all abstracts is available on the web at http://www.springerlink.com. In concluding the Congress recognised the interdependence of, and seeks to improve human, animal and environmental health; recognised that communication, collaboration and trust between human and animal health practitioners is at the heart of the One Health concept; agreed that a broad vision that includes other disciplines such as economics and social behaviour is essential to success. The Congress stressed the need to promote the ‘do-able’ such as improving surveillance and response for emerging infectious diseases whilst developing the broader approach. It identified a need to emphasise community participation and development of community capacity, and especially, an open transparent dialogue with both a ‘ground up’ and ‘top down’ approach that would lead to an improved understanding of our ecosystems, including molecular ecobiology, are an essential part of One Health.

Filoviral haemorrhagic fevers (FVHF) are caused by agents belonging to Filoviridae family, Ebola and Marburg viruses. They are amongst the most lethal pathogens known to infect humans. Incidence of FVHF outbreaks are increasing, with affected number of patients on the rise. Whilst there has been no report yet of FVHF in Zambia, its proximity to Angola and Democratic Republic of Congo, which have recorded major outbreaks, as well as the open borders, increased trade and annual migration of bats between these countries, puts Zambia at present and increased risk. Previous studies have indicated bats as potential reservoir hosts for filoviruses. An increasing population with an increasing demand for resources has forced incursion into previously uninhabited land, potentially bringing them into contact with unknown pathogens, reservoir hosts and/or amplifying hosts. The recent discovery of a novel arenavirus, Lujo, highlights the potential that every region, including Zambia, has for being the epicentre or primary focus for emerging and re-emerging infections. It is therefore imperative that surveillance for potential emerging infections, such as viral haemorrhagic fevers be instituted. In order to accomplish this surveillance, rapid detection, identification and monitoring of agents in patients and potential reservoirs is needed. International co-operation is the strategy of choice for the surveillance and fight against emerging infections. Due to the extensive area in which filoviral infections can occur, a regional approach to surveillance activities is required, with regional referral centres. There is a need to adopt shared policies for the prevention and control of infectious diseases. There is also need for optimisation of currently available tests and development of new diagnostic tests, in order to have robust, highly sensitive and specific diagnostic tests that can be used even where there are inadequate laboratories and diagnostic services.

A rapid situation analysis was conducted in Kibaha and Ngorongoro districts in Tanzania to map resources as well as analysing emergency preparedness to infectious diseases in animal (domestic and wild) and human populations. Kibaha was chosen as a district close to a commercial city (Dar es Salaam) while Ngorongoro represented a remote, border district with high interactions between humans, domestic and wild animals. In this study, data on resources and personnel as well as emergency preparedness were collected from all wards (n = 22), human health facilities (n = 40) and livestock facilities in the two districts using interview checklists and questionnaires. Descriptive statistics for resources were calculated and mapped by district. Kibaha district had a higher human population density, more health workers, better equipped health facilities and better communication and transport systems. On the other hand, Ngorongoro had a higher population of livestock and more animal health facilities but a poorer ratio of animal health workers to livestock. The average ratio of health personnel to population in catchment areas of the health facilities was 1:147 (range of 1:17−1:1200). The ratio of personnel to human population was significantly higher in Kibaha (1:95) than in Ngorongoro (1:203) district (p = 0 < 0.001). Considering the limited resources available to both human and animal health sectors and their different strengths and weaknesses there are opportunities for greater collaboration and resource-sharing between human and animal health for improved surveillance and emergency-preparedness.

Bartonellae are highly adaptive organisms that have the ability to evade the host immune system and cause persistent bacteraemia by occupying the host’s erythrocytes. Bartonella spp. is under-studied and health care professionals often misdiagnose Bartonella-related infections. The aim of this study was to investigate the carriage of Bartonella spp. circulating in human and animal populations in Gauteng using culturing and polymerase chain reaction (PCR) detection. A total of 424 human, 98 cat, 179 dog, and 124 wild rodent blood samples were plated onto specialised media and incubated for 7–21 days at 37 ºC in CO2. Culture isolates morphologically similar to Bartonella control strains were confirmed by PCR and sequenced to determine species. Deoxyribonucleic acid (DNA) was extracted from all blood samples and tested by nested PCR. Bartonella could only be cultured from the cat and rodent specimens. Cat isolates were > 99% similar to Bartonella henselae URBHLIE 9, previously isolated from an endocarditis patient, and rat isolates were > 98% similar to either RN24BJ (candidus ‘Bartonella thailandensis’) or RN28BJ, previously isolated from rodents in China. The PCR prevalences were 22.5% in HIV-positive patients, 9.5% in clinically healthy volunteers, 23.5% in cats, 9% in dogs and 25% in rodents. Findings of this study have important implications for HIV-positive patients.