Systemic Scedosporium prolificans infection in an 11-month-old Border collie with cobalamin deficiency secondary to selective cobalamin malabsorption (canine Imerslund-Gräsbeck syndrome).

An 11-month-old Border collie presented collapsed and continued to deteriorate rapidly despite supportive treatment. The dog had a history of failure to thrive and recurring respiratory infection. Laboratory abnormalities included neutrophilic leucocytosis, Heinz body anaemia, hyperammonaemia, hyperbilirubinaemia, proteinuria and hypocobalaminaemia. Post-mortem examination revealed multi-focal necrosis within the heart, kidneys, pancreas, liver, meninges and cerebral cortex. Fungal hyphae in lesions were identified as Scedosporium prolificans following culture. Subsequent genotyping confirmed that the dog carried the CUBN:c.8392delC mutation in a homozygous state, verifying hereditary cobalamin deficiency (a.k.a. Imerslund-Gräsbeck syndrome). Cobalamin deficiency may have been a predisposing factor for the development of systemic fungal infection in this dog.

New and emerging pathogens in canine infectious respiratory disease.

Canine infectious respiratory disease is a common, worldwide disease syndrome of multifactorial etiology. This review presents a summary of 6 viruses (canine respiratory coronavirus, canine pneumovirus, canine influenza virus, pantropic canine coronavirus, canine bocavirus, and canine hepacivirus) and 2 bacteria (Streptococcus zooepidemicus and Mycoplasma cynos) that have been associated with respiratory disease in dogs. For some pathogens a causal role is clear, whereas for others, ongoing research aims to uncover their pathogenesis and contribution to this complex syndrome. Etiology, clinical disease, pathogenesis, and epidemiology are described for each pathogen, with an emphasis on recent discoveries or novel findings.

Investigation into the causes of canine infectious respiratory disease: antibody responses to canine respiratory coronavirus and canine herpesvirus in two kennelled dog populations.

Two training centres for working dogs were monitored for one year to determine the presence of viruses and viral antibodies and their association with canine infectious respiratory disease (CIRD). Tonsillar swabs and serum were obtained from dogs on entry into the kennels and in regular intervals thereafter. Additional samples were collected during outbreaks of CIRD. The swabs were examined by virus culture and PCR for canine parainfluenza virus, canine adenovirus, canine herpesvirus (CHV) and canine respiratory coronavirus (CRCoV). Furthermore the prevalence of antibodies to CHV and CRCoV was determined. During this study CIRD was reported mainly in one of the two kennels investigated. In that kennel antibody responses to CRCoV indicated a seasonal occurrence of the virus, which coincided with two outbreaks of respiratory disease. CHV antibody responses were detected throughout the year. In the other kennel, which reported few cases of CIRD a high prevalence of antibodies to CRCoV was detected on entry but only sporadic seroconversions to CRCoV or CHV. By PCR three dogs were found positive for CRCoV in one kennel whereas all PCR tests for other viruses were negative for both kennels. Virus culture failed to detect any viruses in either kennel.

Adeno-associated virus seropositivity and HPV-induced cervical cancer in Spain and Colombia.

Extensive experimental and limited epidemiologic data suggest that adeno-associated viruses (AAV) can have antioncogenic activity and may be protective factors for the development of cervical cancer. To examine the association between AAV-2 IgG antibodies and cervical neoplasia in Spain and Colombia, we tested for AAV-2 antibodies using an ELISA assay for 109 women with invasive cervical cancer, 100 population-based controls age-matched to the invasive cases, 77 women with carcinoma in situ (CIN III) and 100 clinic-based controls age-matched to the CIN III cases. Human papillomavirus (HPV) DNA was detected in cervical exfoliated cells by polymerase chain reaction using HPV-L1 and GP5+/6+ consensus primers. The prevalence of AAV-2 antibody titers >100 was significantly lower in invasive cervical cancer cases than control participants. When comparing women with invasive cancer with controls or with CIN III cases, a pattern of decreasing cervical cancer risk with increasing AAV-2 titers was observed. Elevated AAV antibody titers (>100) were inversely associated with invasive cervical cancer (OR 0.3; 95% CI 0.1-0.7), although results were not statistically significant after controlling for HPV (OR 0.4; 95% CI 0.1-1.6). In contrast, AAV-2 antibodies were not significantly associated with the risk of CIN III (OR 1.4; 95% CI 0.3-6.8). These results provide supportive evidence that AAV infection may be a protective factor for the development of invasive cervical cancer. Alternatively, the lower AAV-2 seroprevalence in invasive cervical cancer cases may be due to an immunosuppressive effect of cervical cancer on AAV antibody response. To investigate whether a direct viral interaction is occurring, future studies should aim to resolve at what frequency AAV is found in the genital tract and to clarify further whether AAV may infect the same HPV-positive cells in the cervix.

DNA of adeno-associated virus (AAV) in testicular tissue and in abnormal semen samples.

BACKGROUND: Human genital tissues, including spermatozoa, have been found to be frequently infected with the helper-virus dependent parvovirus, adeno-associated virus (AAV). METHODS: To assess the role of AAV infection in disorders of the male reproductive system, semen samples from 95 men (including 73 men attending a fertility programme) and testicular samples from patients with azoospermia (n = 38) or prostate cancer (n = 8) were analysed using polymerase chain reaction for the presence of AAV DNA. Semen quality was assessed according to World Health Organization guidelines and the grade of atrophy of testicular biopsies was determined histomorphologically. RESULTS: AAV DNA was detected in 38% (28/73) of ejaculates from men with abnormal semen analyses (oligoasthenozoospermia or asthenozoospermia) and in 4.6% of normal semen samples (1/22, P = 0.003). DNA from AAV helper-viruses (human papillomaviruses, cytomegalovirus) was detected at similar frequencies in normal and abnormal semen samples. In testes, AAV DNA was detected in 10 out of 38 biopsies from infertile men (26%), and in 2 out of 8 orchidectomy samples. CONCLUSION: The data show an increased incidence of AAV infection with abnormal semen analysis. Detection of AAV DNA in the testes might point to a role for AAV infection in male infertility, possibly by interfering with spermatozoa development.

Detection of adeno-associated virus in human semen: does viral infection play a role in the pathogenesis of male infertility?

OBJECTIVE: To evaluate the occurrence of adeno-associated virus (AAV) DNA and/or human papillomavirus (HPV) DNA in the semen of infertile men as a possible factor in the pathogenesis of male infertility. DESIGN: Descriptive pilot study. SETTING: University-based diagnostic and research laboratory. PATIENT(S): Semen specimens were collected from 30 men with diagnosed infertility and from 8 control subjects. INTERVENTION(S): Diagnostic spermiograms were made and the semen specimens were separated into seminal fluid, nonspermatozoal cells, and spermatozoa using a Ficoll gradient technique. MAIN OUTCOME MEASURE(S): The presence of AAV and HPV DNA in the different fractions of the ejaculates from the infertile men and the control subjects was detected by polymerase chain reaction. Semen quality was analyzed according to World Health Organization guidelines. RESULT(S): Adeno-associated virus DNA was detected in 30% (9/30) of the ejaculates from the infertile men. No AAV DNA was found in the ejaculates from the 8 control subjects. In 8 of 9 samples, AAV DNA could be found only in the spermatozoal fraction of the specimen. Seven of 9 semen specimens that contained viral DNA also demonstrated oligoasthenozoospermia. Both AAV and HPV DNA was found in the spermatozoal fraction of 3 of 30 specimens. CONCLUSION(S): The data demonstrate for the first time the occurrence of AAV infection in human semen. Sperm motility seems to be affected by the presence of AAV.

Update on the prevalence of serum antibodies (IgG and IgM) to adeno-associated virus (AAV).

In view of presumed non-pathogenicity, tumor suppressive properties, and site-specific integration of the viral genome the human parvovirus, adeno-associated virus (AAV) has gained great interest as a gene transduction vector. Data on the seroprevalence of antibodies to AAV vary between reports, probably due to the different serological methods used. In order to understand better the immune response to AAV during natural infection, sera from different age groups and various geographical regions were compared for AAV antibodies using an ELISA. The data show that the prevalence of antibodies to AAV is similar in Europe (Germany, France, and Switzerland), Brazil, and Japan, indicating worldwide infection. It was confirmed that infection takes place during childhood. However, declining seropositivity thereafter and a second increase of seropositivity after 30 years of age suggests reinfection or reactivation of latent virus in particular as the prevalence of IgM antibodies in adults is relatively high. Furthermore, pregnant women were found to be significantly more frequently seropositive than non-pregnant controls, hinting at a reactivation of persistent AAV (up to 80% of women carry AAV in genital tissue) in specific hormonal conditions, e.g., pregnancy. Cross-reaction of serum antibodies with the different AAV types (defined by complement fixation) was observed by ELISA and neutralization tests confirming earlier results. The results suggest an unstable AAV antibody response allowing lifelong reinfection or reactivation of persisting virus possibly due to partial immunotolerance after an infection in utero, at delivery or during early infancy.