Ecology and conservation biology of avian malaria.

Avian malaria is a worldwide mosquito-borne disease caused by Plasmodium parasites. These parasites occur in many avian species but primarily affect passerine birds that have not evolved with the parasite. Host pathogenicity, fitness, and population impacts are poorly understood. In contrast to continental species, introduced avian malaria poses a substantial threat to naive birds on Hawaii, the Galapagos, and other archipelagoes. In Hawaii, transmission is maintained by susceptible native birds, competence and abundance of mosquitoes, and a disease reservoir of chronically infected native birds. Although vector habitat and avian communities determine the geographic distribution of disease, climate drives transmission patterns ranging from continuous high infection in warm lowland forests, seasonal infection in midelevation forests, and disease-free refugia in cool high-elevation forests. Global warming is expected to increase the occurrence, distribution, and intensity of avian malaria across this elevational gradient and threaten high-elevation refugia, which is the key to survival of many susceptible Hawaiian birds. Increased temperatures may have already increased global avian malaria prevalence and contributed to an emergence of disease in New Zealand.

Incidence of poxvirus-like lesions in two estuarine dolphin populations in Australia: links to flood events.

We report on the incidence of poxvirus-like lesions assessed by photographic identification in two estuarine populations of bottlenose dolphins (Tursiops aduncus) in Australia over a 3-year period. Poxvirus infections of odontocetes are characterized by pinhole or ring-like skin lesions that appear as solitary or coalesced circular gray blemishes. Environmental and physiological stressors are believed to contribute to their manifestation (Van Bressem et al., 2009b). A total of 187 boat-based surveys were completed from October 2003 to September 2006 in the Clarence River (CR) and Richmond River (RR) estuaries, with 720 dolphins sighted. Forty-six individuals, including calves, were identified in the CR and 23 in the RR. We investigated the temporal relationship between four flood events that occurred in the region during the study period and the occurrence of poxvirus-like skin lesions. Dolphin poxvirus-like lesions were not observed in these populations prior to 2004. Following flood events in 2004, 2005 and 2006, a total of 10 new cases were observed, 6 in the CR and 4 in the RR. Our data suggest that the occurrence of dolphin poxvirus-like lesions may be an indicator for climatic events such as flooding. Long-term follow-up of these estuarine populations is required to further clarify the factors leading to 'outbreaks' of poxvirus infections.

Use of a targeted oncolytic poxvirus, JX-594, in patients with refractory primary or metastatic liver cancer: a phase I trial.

BACKGROUND: JX-594 is a targeted oncolytic poxvirus designed to selectively replicate in and destroy cancer cells with cell-cycle abnormalities and epidermal growth factor receptor (EGFR)-ras pathway activation. Direct oncolysis plus granulocyte-macrophage colony-stimulating factor (GM-CSF) expression also stimulates shutdown of tumour vasculature and antitumoral immunity. We aimed to assess intratumoral injection of JX-594 in patients with refractory primary or metastatic liver cancer. METHODS: Between Jan 4, 2006, and July 4, 2007, 14 patients with histologically confirmed refractory primary or metastatic liver tumours (up to 10.9 cm total diameter) that were amenable to image-guided intratumoral injections were enrolled into this non-comparative, open-label, phase I dose-escalation trial (standard 3x3 design; two to six patients for each dose with 12-18 estimated total patients). Patients received one of four doses of intratumoral JX-594 (10(8) plaque-forming units [pfu], 3x10(8) pfu, 10(9) pfu, or 3x10(9) pfu) every 3 weeks at Dong-A University Hospital (Busan, South Korea). Patients were monitored after treatment for at least 48 h in hospital and for at least 4 weeks as out-patients. Adverse event-monitoring according to the National Cancer Institute Common Toxicity Criteria (version 3) and standard laboratory toxicity grading for haematology, liver and renal function, coagulation studies, serum chemistry, and urinalysis were done. The primary aims were to ascertain the maximum-tolerated dose (MTD) and safety of JX-594 treatment. Data were also collected on pharmacokinetics, pharmacodynamics, and efficacy. Analysis was per protocol. This study is registered with ClinicalTrials.gov, number NCT00629759. FINDINGS: Of 22 patients with liver tumours who were assessed for eligibility, eight patients did not meet inclusion criteria. Therefore, 14 patients, including those with hepatocellular, colorectal, melanoma, and lung cancer, were enrolled. Patients were heavily pretreated (5.6 previous treatments, SD 2.8, range 2.0-12.0) and had large tumours (7.0 cm diameter, SD 2.7, range 1.8-10.9). Patients received a mean of 3.4 (SD 2.2, range 1.0-8.0) cycles of JX-594. All patients were evaluable for toxicity. All patients experienced grade I-III flu-like symptoms, and four had transient grade I-III dose-related thrombocytopenia. Grade III hyperbilirubinaemia was dose-limiting in both patients at the highest dose; the MTD was therefore 1x10(9) pfu. JX-594 replication-dependent dissemination in blood was shown, with resultant infection of non-injected tumour sites. GM-CSF expression resulted in grade I-III increases in neutrophil counts in four of six patients at the MTD. Tumour responses were shown in injected and non-injected tumours. Ten patients were radiographically evaluable for objective responses; non-evaluable patients had contraindications to contrast medium (n=2) or no post-treatment scans (n=2). According to Response Evaluation Criteria in Solid Tumors (RECIST), three patients had partial response, six had stable disease, and one had progressive disease. INTERPRETATION: Intratumoral injection of JX-594 into primary or metastatic liver tumours was generally well-tolerated. Direct hyperbilirubinaemia was the dose-limiting toxicity. Safety was acceptable in the context of JX-594 replication, GM-CSF expression, systemic dissemination, and JX-594 had anti-tumoral effects against several refractory carcinomas. Phase II trials are now underway.

Buffalopox: an emerging and re-emerging zoonosis.

Outbreaks of buffalopox or pox-like infections affecting buffaloes, cows and humans have been recorded in many parts of the world. Since the first outbreak in India, a large number of epidemics have occurred. Unlike in the previous years, generalized forms of the disease are now rare; however, there are severe local forms of the disease affecting the udder and teats, leading to mastitis thereby undermining the productivity of milk animals. The causative agent buffalopox virus (BPXV) is a member of the Orthopoxvirus, and is closely related to Vaccinia virus (VACV), the type-species of the genus. Earlier studies with restriction fragment length polymorphism and recent investigations involving sequencing of the genes that are essential in viral pathogenesis have shown that BPXV is phylogenetically very closely related to VACV and may be considered as a clade of the latter. The review discusses the epidemiology, novel diagnostic methods for the disease, and molecular biology of the virus, and infers genetic relationships of BPXV with other members of the genus.

Avipoxvirus infection in peregrine falcons (Falco peregrinus) from a reintroduction programme in Germany.

Poxvirus infections are common in domestic birds in Germany, but they are rare in birds of prey. Only species of falconidae imported from Arabian or Asian countries have so far tested positive for poxvirus, and, among these, only raptors kept for falconry. As part of a reintroduction programme in the northern county of Mecklenburg-Western Pomerania, which is adjacent to the Baltic Sea, 21 young peregrine falcons were released into the wild; six of them died and one was examined postmortem, its tissues being examined by light and electron microscopy. In addition, an ELISA for fowlpox, pigeonpox and canarypox was applied. No virus could be isolated and propagation in culture failed, but virus particles were detected by electron microscopy in lesions from its skin and tongue.

Viral infections in atopic dermatitis: pathogenic aspects and clinical management.

A number of different widespread and disseminated viral infections can occur in patients with atopic dermatitis. Eczema molluscatum is troublesome but not dangerous. Although eczema vaccinatum is rare, it is life-threatening and of increased concern as smallpox vaccinations are reintroduced as a response to possible bioterrorism. There is little information on the course of smallpox itself in atopic dermatitis. Eczema herpeticum is the most common member of this group; recent advances in understanding its pathogenesis might contribute to a more successful management of this serious complication.

Evolución inusual de un nódulo de los ordeñadores en un trasplantado renal / Unusual evolution of milker's nodule in a kidney trasplant recipient

Un varón de 47 años desarrolló a los 7 meses de un segundo trasplante renal un nódulo de los ordeñadores que tardó 6 meses en involucionar espontáneamente en lugar de las 4 a 6 semanas habituales (AU)

[Milker's nodules]. / Malkerknuder.

Milker's nodule is a parapox virus infection seen mostly on the hands of dairy farmers. We saw 15 cases over a period of two years in the County of North Jutland. Clinically, milker's nodule goes through a papular, a nodular and a crusted stage. Most patients were seen when the infection was in the nodular stage, an often painful condition requiring treatment. Three patients developed an erythema multiformelike secondary eruption. Lesions from nine patients were removed for histological examination. The histology of all lesions was consistent with milker's nodule. In three of seven patients parapox virus was demonstrated by electron microscopy. Treatment was commonly curettage followed by cauterization.

Receptors for gamma-interferon encoded by poxviruses: implications for the unknown origin of vaccinia virus.

Poxviruses encode soluble interferon-gamma receptors (IFN-gamma Rs) that inhibit IFN-gamma activity and play a major role in virus pathogenesis. In contrast to the highly species specific cellular homologues, the vaccinia IFN-gamma R has novel broad species specificity. This has implications for the unknown origin and natural host(s) of vaccinia virus, the vaccine used for smallpox eradication.

Animal poxviruses transmitted from cat to man: current event with lethal end.

We report about the infection of an 18-year-old man with an orthopox virus (OPV) which was transmitted by a cat. The infectious route from cat to man could be proved by epidemiological, virological and serological methods. The corresponding techniques are described. The patient had not been vaccinated against smallpox and was intensively immunosuppressed by medication on account of a severe endogeneous eczema combined with an allergic asthma bronchiale. A cyclic poxvirus disease developed with a generalised, partly confluent pox virus exanthema disseminated over the body. The clinical symptoms were similar to a "variola pustulosa haemorrhagica". The young man died of a lung embolism in the course of the intensive medical therapy. The haemorrhagic character of the pox virus pustules with central necrosis (pox navel) could be reproduced in the rabbit skin and on chorioallantois membranes. The pox virus isolated from the patient could be differentiated from variola, vaccinia and monkeypox virus. It is a member of the group of "cowpox-like viruses". The environmental importance of these OPVs is discussed.

Wallace P. Rowe lecture. Poxviruses of laboratory animals.

Currently the subfamily Chordopoxvirinae, the poxviruses of vertebrates, is subdivided into eight genera, containing some 20-30 species; an inexact figure because the birdpox viruses have not yet been properly investigated taxonomically. I have discussed seven species belonging to three genera, all of which have caused infection and usually disease in mammals commonly used in the laboratory. The list could have been extended had I included chickens and swine as laboratory animals, for that would have meant that I would have spoken about the birdpox viruses and swinepox virus as well. However, I think I have said enough to remind you of the importance of this family of viruses to those of you concerned with laboratory animal medicine. I believe that Wally Rowe would have been interested, for every case I have described presents problems in the ecology of viruses, and like my mentor Macfarlane Burnet, Wally approached virology from an ecological point of view, whether he was thinking about the DNA provirus of retroviruses and the host chromosome, the pathogenesis of disease, or the spread of viruses in animal populations, all topics to which he made major contributions.

Mousepox in inbred mice innately resistant or susceptible to lethal infection with ectromelia virus. II. Pathogenesis.

The pathogenesis of mousepox due to infection with ectromelia virus strain NIH-79 was characterized in genetically susceptible (BALB/cAnNCr) and genetically resistant (C57BL/6NCr) mice. BALB/c mice inoculated subcutaneous (s.c.) or intranasally (i.n.) had high mortality. Most mice died within 7 days from severe necrosis of the spleen and liver. Necrotic foci in livers of BALB/c mice that survived beyond 7 days often were accompanied by mononuclear cell infiltrates and by hyperplasia of lymphoid tissues. C57BL/6 mice inoculated by either route remained asymptomatic and necrotic lesions were mild or absent, whereas focal non-suppurative hepatitis and lymphoid hyperplasia were prominent. Infectious virus and viral antigen were distributed widely in tissues of BALB/c mice, but had limited distribution in C57BL/6 mice. Both mouse strains had infection of the respiratory tract, genital tract, oral tissues and bone marrow, and BALB/c mice also had infection of the intestines. Both strains also developed serum antibody to vaccinia virus antigen after infection. The results show that ectromelia virus occurs in tissues conducive to mouse to mouse transmission and that the severity and character of mousepox lesions correlate directly with resistance and susceptibility to infection. They also support the concept that cellular immunity contributes to survival from infection.

Pathogenesis of buffalo-pox virus in buffalo calves.

Pathogenesis of buffalo-pox virus (BP4 strain) in buffalo calves following intradermal inoculation revealed bimodal thermal reaction. The prominent symptoms were lacrimation, mucoprulent nasal discharge and diarrhoea. The typical pook lesions produced in the skin were passed through reseolar, papular, vesicular, pustular and desquamative stages of infection followed with a second rash, between day 6-8 on the lips, tongue, neck, perinium region and around the nostrils and eyes. After the eclipse phase of 10 hours, the concentration of the virus started increasing logarithmically. Thereafter, the virus was subsequently detected in the regional lymphnode, blood stream and central organs viz., lung, liver & spleen on 2nd, 4th and 5th day, respectively. In blood stream the virus was found to be associated with white blood cells. Secondary viremia was again on day 6 post-inoculation. Gross and microscopic changes were observed in these organs. The presence of virus along with pathologic changes were also detected in stomach and intestine. The disease ran a course of 13 to 15 days.

Studies on pathogenesis of buffalo pox virus in rabbits: quantitative assay of virus in different organs.

The buffalo pox virus was found to multiply in the skin, the primary site of inoculation with an eclipse phase of 12 hr. The virus was then detected in the skin after 15 hr followed by its appearance in regional lymph nodes 36 hr postinoculation. Primary viremia was detected 48 hr postinoculation, followed by detection of virus in the lungs, liver, and spleen. The virus multiplied in the lungs on day 4 and in the liver and spleen on day 5 postinoculation and its release led to secondary viremia. In a follow-up from day 7 to 14 postinoculation, the virus was detected in the kidneys, stomach, intestines, and gonads.