A retrospective assessment of the completeness and timeliness of meningococcal disease notifications in the Republic of Ireland over a 16-year period, 1999-2015.

OBJECTIVES: To assess how invasive meningococcal disease (IMD) records held by the Irish Meningitis & Sepsis Reference Laboratory (IMSRL) compare to records of IMD notifications reported on the national integrated electronic Computerised Infectious Disease Reporting (CIDR) system. STUDY DESIGN: We assessed the completeness, data quality and timeliness of IMD notifications and reference laboratory records for the period between 01 July 1999 and 30 June 2015 by identifying discrepant and/or missing data items in a matched case data set and by measuring the timeliness of case reporting. METHODS: We matched anonymised cases notified to CIDR to records based at the IMSRL using birth, reporting and onset dates with gender and laboratory parameters of meningococcal strain characteristics and method of confirmation. Completeness, data quality and the timeliness of notifications were assessed by a stratified sensitivity-based technique and by calculating the average difference between IMSRL and CIDR reporting dates. RESULTS: CIDR recorded a total of 3163 notifications, of which 2759 (87.2%) were matched to IMSRL records. Completeness of IMD case classification as confirmed was estimated to be >99%. Examining the levels of discrepant or missing data in both matched CIDR and IMSRL records as a measure of data quality, recording of demographic items and meningococcal group showed least differences, recording of laboratory case confirmation method and meningococcal strain characteristics were less well recorded, with detail on clinical presentation/diagnosis least well recorded. Overall average annual difference between CIDR and IMSRL recording dates was 3.2 days (95% confidence interval 2.6-3.8). CONCLUSIONS: A high quality of IMD surveillance in Ireland was demonstrated, but scope for improvements in timeliness and capture of enhanced surveillance data regarding date of onset and strain-specific characteristics were identified.

Immunosurveillance of naturally occurring feline leukemia.

When compared to their housemates that subsequently developed leukemia, cats that remained healthy had five-to tenfold higher (geometric mean) humoral antibody titers to the feline oncornavirus-associated cell membrane antigen. This is compatible with the application of the immunosurveillance hypothesis to the natural development of leukemia in an outbred mammalian species.

Lack of evidence of pregnancy-induced alloantibodies in dogs.

BACKGROUND: It is controversial whether or not pregnant bitches become sensitized to red blood cell (RBC) antigens. HYPOTHESIS: Bitches do not develop alloantibodies to RBC antigens during gestation and can be used safely as blood donors. ANIMALS: The study group included 35 healthy female dogs with a prior history of 1 (n = 12), 2 (n = 14), or >or= 3 (n = 9) pregnancies. The control group consisted of 15 healthy female dogs without any history of pregnancy. METHODS: All dogs were blood typed for dog erythrocyte antigens (DEA) 1.1, 1.2, 3, 4, 5, and 7 using ethylenediaminetetraacetic acid blood samples and polyclonal antisera. Antibody screening was performed with serum and canine RBC panels of known blood type. An autocontrol and direct antiglobulin test were performed to rule out the presence of autoantibodies. RESULTS: The only alloantibodies identified were those against DEA 7 and the prevalence of anti-DEA 7 alloantibodies was similar in dogs with known history of pregnancy (11.4%) and in the control group (13.3%). CONCLUSIONS AND CLINICAL IMPORTANCE: These results confirm previous studies and clinical transfusion medicine experience. Naturally occurring anti-DEA 7 alloantibodies have been reported but their clinical relevance has not been shown. Pregnancy does not appear to sensitize dogs to RBC antigens. Consequently, dogs with prior history of pregnancy can be used safely as blood donors. Conversely, no additional pretransfusion compatibility studies would be required should these dogs themselves need to be transfused.

Efficacy and toxicosis of VELCAP-C treatment of lymphoma in cats.

BACKGROUND: Lymphoma is the most common malignancy affecting cats. A protocol employing vincristine, l-asparaginase, cyclophosphamide, doxorubicin, and prednisone (VELCAP-S) is effective and well tolerated in dogs with lymphoma. A 24-week variation of this protocol (VELCAP-C) was developed for treatment of cats. HYPOTHESIS: That VELCAP-C will result in survival times for cats with lymphoma that are similar to those obtained when cats are treated with a protocol that includes fewer chemotherapy agents. ANIMALS: Sixty-one cats with lymphoma. METHODS: Retrospective study. Outcomes evaluated were response to VELCAP-C therapy, toxicosis, and survival time. The effect of signalment, staging, CBC, and serum chemistry profile and dosage on these outcomes was examined. RESULTS: Six cats (10%) completed the protocol with a median survival of 1189 days. Forty-three percent (23 of 61) of the cats achieved complete response (CR) with a median survival time of 62 days. Cats that required a dose reduction of any drug during induction were more likely to achieve CR. Weight loss and hepatomegaly at diagnosis were negatively associated with response to treatment. Increased lactate dehydrogenase (LDH) serum activity at the time of initial treatment correlated with decreased survival times. CONCLUSIONS AND CLINICAL IMPORTANCE: This multi agent protocol did not provide improved survival over historical data using protocols with fewer agents. Serum LDH activity levels might provide useful prognostic information for cats with lymphoma.

Mushroom-derived maitake PETfraction as single agent for the treatment of lymphoma in dogs.

BACKGROUND: Maitake PETfraction is a standardized essence extracted from the mushroom Maitake (Grifola frondosa) that has antitumor activity in tumor-bearing mice. In addition, PETfraction induces apoptosis in human prostate and bladder cancer cells and suppresses the proliferation in vitro of several canine tumor cell lines, such as lymphoma (Cl-1), mammary gland (CF33), and connective tissue (CF21). HYPOTHESIS: Maitake PETfraction is effective as a single agent in dogs with lymphoma. ANIMALS: Fifteen dogs with confirmed intermediate or high-grade lymphoma were enrolled into this prospective, noncontrolled, clinical trial. Inclusion criteria were an expected survival time of at least 2 weeks and no major organ dysfunction. METHODS: Maitake PETfraction was administered at a dose of 3 drops/kg/day divided into 2 doses given 1 hour before feeding. Dogs were evaluated by physical examination with tumor measurement, body weight, CBC, and chemistry profile before treatment and after 2, 4, 8, and 12 weeks. At each visit, owners completed a questionnaire addressing overall quality of life, appetite, and any adverse effects noted. RESULTS: A decrease in lymph node size of greater than 50% (objective response) was not seen in any of the dogs. Thirteen dogs developed progressive disease before the 4th week. The median treatment duration was 27 days (range, 9-228). PETfraction was well accepted, and minimal adverse effects were observed. Two dogs developed hyphema. It was not known if this was related to progressive lymphoma or was an adverse effect of treatment. CONCLUSIONS: No objective responses were observed to administration of Maitake PETfraction, and the drug was well tolerated in these dogs.

Orthovoltage radiation and weekly low dose of doxorubicin for the treatment of incompletely excised soft-tissue sarcomas in 39 dogs.

The efficacy and toxicity of orthovoltage radiation therapy and concurrent low doses of doxorubicin for the treatment of incompletely excised soft-tissue sarcomas in 39 dogs was investigated retrospectively. The 39 dogs had 40 soft-tissue sarcomas and received 51 Gy orthovoltage radiation in 17 daily 3 Gy fractions; they also received 10 mg/m(2) doxorubicin once a week administered intravenously one hour before the dose of radiation. The median follow-up time was 910 days. The tumours recurred locally in seven of the dogs, in five of them within the radiation field; the median time to their recurrence was 213 days (range 63 to 555 days). Six of the dogs developed a distant metastasis after a median time of 276 days (range eight to 826 days). The one-year and two- to four-year tumour control rates were 84 per cent and 81 per cent, respectively, and the one-, two- and three- to four-year survival rates were 85 per cent, 79 per cent and 72 per cent, respectively. Tumours with a mitotic rate of more than 9 per 10 high-power fields were significantly more likely to recur, and the dogs with such tumours survived for significantly shorter periods.

Feline oncornavirus-associated cell membrane antigen. III. Antibody titers in cats from leukemia cluster households.

Serum samples from 182 healthy cats residing in environments known to have a natural exposure to feline leukemia virus (FeLV) were examined for the presence of antibody to the feline oncornavirus-associated cell membrane antigen. The number included 138 cats from leukemia-"cluster" households. Such cats previously showed greatly increased frequencies of FeLV infection, as determined by the virus group-specific antigen (gasa) in peripheral blood leukocytes and platelets. The geometric mean antibody titer for all 182 cats with known exposure to FeLV was 4.69, more than four times higher than the mean titer for healthy pet cats from the same geographic areas but with no known FeLV exposure. About 92 percent of the cats in exposure environments were positive for FeLV gsa or feline oncornavirus-associated cell membrane antigen (FOCMA) antibody, and gsa-positive cats had lower FOCMA antibody geometric mean titers than gsa-negative cats. In the exposure environments, no differences were seen for cats of different sexes, but a higher geometric mean antibody titer was observed for cats 5 years and over when compared to younger groups. These results prove that previous reports of increased incidences of leukemia in cluster households were not due to chance alone, but rather to increased infection rates of cats in the FeLV environment. Also, they suggest that horizontal transmission of FeLV is highly efficient under crowded conditions, and that most cats naturally exposed to virus elicit an active immune response.

Feline oncornavirus-associated cell membrane antigen. IV. Antibody titers in cats with naturally occurring leukemia, lymphoma, and other diseases.

Cats with naturally occurring leukemia and lymphoma had low or negative humoral antibody titers to the feline oncornavirus-associated cell membrane antigen (FOCMA). Geographic differences were seen in the relative frequencies of various forms of lymphoproliferative neoplasms. Lymphatic leukemia and thymic lymphoma were most common in Boston, whereas alimentary lymphoma was most frequent in Glasgow. No significant differences were found in geometric mean FOCMA antibody titers for the various forms of leukemia-lymphoma or for feline leukemia virus (FeLV)-positive as compared to FeLV-negative cats. Approximately 70% of 76 Boston cats with nonregenerative anemias were FeLV gs antigen (gsa) positive; this was similar to the percentage with leukemia-lymphoma from the same population that was positive. Fifty-five to 62% of the Boston cats with other infectious diseases, such as peritonitis and septicemia, were gsa positive. We postulate that this is due to a predisposition to infectious diseases by the immunosuppressive action of FeLV. Young cats from the Boston population that developed lymphoma, infectious peritonitis, and certain other diseases were more likely to be FeLV gsa positive than older cats with the same diseases.

Feline oncornavirus-associated cell membrane antigen. II. Antibody titers in healthy cats from household and laboratory colony environments.

Antibody titers to the feline oncornavirusassociated cell membrane antigen (FOCMA) were determined for 447 healthy cats from laboratory colony and household environments. Only 2.7 percent of 221 cats from colony environments were antibody positive as compared to 50.4 percent of 256 cats from household environments. Incidence of FOCMA antibody and geometric mean antibody titer for pet cats from New York City representing single cat apartment habitats were substantially lower than values for unscreened cats from the Boston, Glasgow, and Detroit suburban environments. Geometric mean antibody titer for young adults in the Boston population was significantly higher than titers for kittens or aged cats. This may be due to greater mobility resulting in increased exposure to other cats. In contrast to the high frequency of FOCMA antibody positivity in pet-cat populations, less than 2 percent of the same groups were positive for virus group-specific antigen in peripheral blood leukocytes and platelets. This was interpreted as an indication that many more cats became infected with feline leukemia virus under natural conditions that the number developing persistent virus infection and/or clinical leukemia.

Comparison of virus-positive and virus-negative cases of feline leukemia and lymphoma.

One hundred eighty-four cases of feline leukemia and lymphoma diagnosed in Boston from 1972 through 1976 were investigated. Fifty-eight % of these cases were lymphoma, and 42% were leukemia. Sixty-seven % of the cats had positive fluorescent antibody tests for circulating feline leukemia virus. The rest (33%) were virus negative. Clinically and epidemiologically, the virus-positive and virus-negative cases were remarkably similar except for their age at diagnosis. Virus-negative cats tended to be older (mean age at diagnosis, 4.9 years) as compared to virus-positive cats (3.5 years). For 22 cases of leukemia and lymphoma diagnosed after the age of 8 years, 15 were virus negative. The minimum mean induction period (time from first positive virus test to diagnosis of cancer) for 19 cats that were virus positive and healthy at their first test was 16.7 months (range, 2 to 41 months).

Immune response to leukemia virus and tumor-associated antigens in cats.

Cats represent an unusually valuable model for studying the role of the immune response to leukemia, lymphoma, and other mesodermal neoplasms. The agents that cause spontaneous feline leukemias, lymphomas, and fibrosarcomas, the feline leukemia and sarcoma viruses, are well characterized. A specific tumor cell membrane antigen, designated the feline oncornavirus-associated cell membrane antigen (FOCMA) has also been described. Feline leukemia and feline sarcoma viruses are antigenically indistinguishable, and FOCMA is common for both. Both laboratory-induced and spontaneous feline leukemias, lymphomas, and fibrosarcomas are available for study. A clear correlation has been shown between the resistance of cats to development of lethal tumors following inoculation of feline sarcoma virus and the presence of high humoral antibody titers to FOCMA. The geometric mean antibody titer to FOCMA for cats that resisted growth of fibrosarcomas was more than 20-fold higher than the mean for cats that succumbed to lethally progressing tumors. Cats with induced or spontaneous leukemia or lymphoma also have either no detectable FOCMA antibody or very low levels. Conversely, some cats resist development of leukemia or lymphoma following natural exposure to feline leukemia virus in leukemia cluster households, and these cats have high FOCMA antibody titers. These results support the concept of a natural immunosurveillance mechanism against leukemia or lymphoma development in an outbred mammalian species.

Biology of feline leukemia virus in the natural environment.

The feline leukemia virus (FeLV) was discovered in 1964 in a cluster of cats with lymphosarcoma. The observed clustering of cases of feline lymphosarcoma suggested that FeLV was an infectious agent for cats. The development of a simple immunofluorescent test for FeLV permitted a seroepidemiological study to be undertaken on the distribution of the virus in cats living in their natural environment. Over 2000 cats were tested, and the results showed conclusively that FeLV is an infectious agent for cats. This finding has now been independently confirmed using three different test procedures. After the infectious nature of FeLV was discovered, a simple FeLV test and removal program was devised to control the spread of the virus in the natural environment. The spread of FeLV was controlled in 45 households by removing the FeLV-infected cats, while in 25 households, where the infected cats were left in contact with the uninfected cats, 12% of the uninfected cats became infected. The ultimate control of FeLV awaits the development of an effective FeLV vaccine, which now seems feasible since we have already experimentally immunized some cats with attenuated FeLV. Although FeLV is infectious for cats there is no evidence that FeLV can infect humans.

Photodynamic therapy of naturally occurring tumors in animals using a novel benzophenothiazine photosensitizer.

5-Ethylamino-9-diethylaminobenzo[a]phenothiazinium chloride (EtNBS) is a novel photodynamic therapy (PDT) photosensitizer with efficacy against experimental murine tumors. In this preliminary study, dogs and cats with naturally occurring tumors were treated with EtNBS-PDT to determine safety and efficacy. Fifteen treatments were performed on 13 animals (9 treatments in 8 cats and 6 treatments in 5 dogs), generally using 400 J of 652 nm light. Two feline sublingual squamous cell carcinomas (SCCs) responded briefly (minor response). Six feline facial SCCs were treated, resulting in two partial responses and four long-term complete responses (CR). Two canine intraoral SCCs were treated; one responded minimally for 2 weeks (minor response), and one achieved long-term CR. One canine cutaneous mast cell tumor achieved CR, and one canine ocular mast cell tumor responded briefly. One canine ocular melanoma did not respond to treatment. Systemic reactions included nausea associated with photosensitizer injection in two cats and two dogs, elevated body temperatures during treatment in two dogs, elevated body temperature 2 days after PDT in one cat, and inappetance for 2 weeks in one cat. A peripheral neuropathy of undetermined cause occurred in one cat 2 weeks after PDT and resolved without treatment. Local reaction was well tolerated in 13 of 15 treatments. All animals were exposed to normal daylight after less than 5 days (mean, 3.5 days) without residual photosensitization. EtNBS-PDT is safe for dogs and cats and has activity against selected naturally occurring tumors, with an overall objective response rate (partial response + CR) of 61.5%.

Feline immunodeficiency virus and feline leukemia virus infections and their relationships to lymphoid malignancies in cats: a retrospective study (1968-1988).

Sera from 353 cats with naturally occurring feline leukemia virus (FeLV) infection were collected in Boston, Los Angeles, New York City, and Seattle between 1968 and 1988. These sera were retrospectively assayed by enzyme-linked immunosorbent assay for antibodies to feline immunodeficiency virus (FIV). Fifty-one (14.4%) of the FeLV-positive sera had antibodies to FIV, indicating dual oncovirus and lentivirus infections. FIV infections were confirmed by Western blot analysis, antibodies against the 15 and 27 kDa proteins being used as definitive markers. FIV infection was diagnosed in one cat sampled in 1968 and in eight other cats sampled before 1975 in New York City. Illnesses exhibited by coinfected cats were similar to those of cats infected with FeLV only. Two unrelated cats with multicentric fibrosarcomas were found to be simultaneously infected with FIV, FeLV, and feline sarcoma virus. FIV was less contagious than FeLV in 73 cats residing in an exposure household between 1977 and 1980 as determined by evaluation of sera collected sequentially. In this household, 15 resident cats became FeLV infected whereas no cats contracted FIV infection. Comparison of serologic results from 53 cats with leukemia/lymphoma and matched controls confirmed a strong correlation between FeLV viremia and leukemia/lymphoma. A significant correlation between FIV infection and lymphoproliferative malignancies was also found independent of FeLV infection.

Epidemiologic association between virus-negative feline leukemia and the horizontally transmitted feline leukemia virus.

About two-thirds of the natural cases of feline leukemia-lymphoma are assumed to be caused by the feline leukemia virus (FeLV) because they occur in cats, which harbor this agent, and FeLV will induce the disease under laboratory conditions. Epidemiological evidence is presented which associates cases of naturally occurring 'virus negative' feline leukemia with exposure to FeLV.

Models of hospital drug policy in the UK.

OBJECTIVES: Pharmacists in UK National Health Service (NHS) hospitals have a long tradition of involvement in the development of drug policy. This paper describes various approaches that have been employed in the development and implementation of drug policy in hospitals and examines the evidence for their effectiveness and acceptability in the context of a changing health service. METHODS: A series of focused interviews was conducted with a range of staff, including doctors, nurses, pharmacists and managers at eight hospitals. Interview sites were selected on the basis of a national survey of clinical pharmacy roles and were broadly representative of UK NHS hospitals. Interview data were analysed using constant comparison and analytic induction. RESULTS: Three models used in the development of drug policy were identified: a 'traditional' model, in which a drug and therapeutics committee establishes a hospital-wide formulary which is implemented by pharmacists; a 'combined' model, in which there is much more emphasis on tailoring policies and feedback to specialties or clinical directorates; and a 'medical control' model, in which prescribing decisions are made by individual doctors without reference to explicit policies and with little active pharmacy involvement. Pharmacy involvement was seen as vital to the development of effective policies but hospital-specific factors influenced the choice of model at particular sites. CONCLUSIONS: Hospitals may be moving towards the 'combined' model which could have advantages in the current internal market within the NHS. However, evaluations of the various approaches to drug policy should help inform this decision.

Treatment of immune-mediated hemolytic anemia in dogs with cyclophosphamide.

A review of 60 cases of immune-mediated hemolytic anemia (IMHA) in the dog was performed in order to characterize the disease and to identify potential prognostic indicators. Dogs ranged in age from 1 to 13 years, with a mean age of 6.5 years. The 2 most commonly affected breeds were Cocker Spaniels and Labrador Retrievers. Fifty-two of the 60 dogs tested (87%) were autoagglutination positive and spherocytes were present in 45 (75%). Forty-one (89%) of 46 patients tested positive for the presence of immunoglobulin on the red blood cell surface (Coombs assay). The most common clinical signs at presentation were lethargy, weakness, pale mucous membranes, icterus, hemoglobinuria, and anorexia. PCV less than 25% was present in 59 (98%) dogs. At the time of presentation, 35 dogs (58%) had a nonregenerative anemia, whereas 25 patients (42%) had a regenerative response. Thrombocytopenia was seen in 41 (68%) dogs. Nine of 34 dogs (26%) had a prolonged prothrombin time, 19 of 34 (56%) had a prolonged activated partial thromboplastin clotting time, and 12 of 34 (35%) had abnormal fibrinogen concentrations. All dogs received prednisone at immunosuppressive doses (2.2-4.4 mg/kg PO as a single or divided dose every 24 hours) and cyclophosphamide as primary therapy. Forty-one dogs (63%) received cyclophosphamide at 50 mg/m2 q24h for 4 days, whereas 9 dogs (15%) received an initial high dose (200 mg/m2) followed by 3 days of a lower dose (50 mg/m2 q24h). No statistical difference in survival times was found for either protocol. Thirteen dogs were treated with azathioprine in addition to cyclophosphamide and prednisone. The median survival time of dogs that received all 3 drugs was 370 days as compared to 9 days for those dogs that were treated with cyclophosphamide and prednisone alone. Thirty-one (52%) dogs died from the disease, 13 (22%) dogs were alive, and 15 (25%) dogs were lost to follow-up. The median length of survival for all dogs was 21 days. Eight dogs that were discharged from the hospital suffered a relapse (PCV < 25%).

Cytosine arabinoside as a single agent for the induction of remission in canine lymphoma.

Cytosine arabinoside (AraC) was administered as a continuous IV infusion to 15 dogs with malignant lymphoma at a dose of 300 mg/m2/d for 2 consecutive days. Dogs were re-examined 7 d after treatment for response to therapy and for hematologic toxicity. Regardless of response, all dogs were started on combination chemotherapy at this time. Other toxicities were reported by owners. No dog responded objectively to Ara-C treatment, although 1 dog with circulating lymphoblasts had partial regression of lymphadenopathy but persistent blastemia. Thrombocytopenia (platelet count < 200,000/microL) 7 days posttreatment was the most commonly encountered hematologic toxicity, occurring in 10 of 14 dogs. Three of these 10 dogs were also mildly neutropenic (neutrophil counts of 2000 to 3000 cell/microL). Nonhematologic toxicity occurred in 8 of 15 dogs and was principally gastrointestinal in nature and mild in severity. Cytosine arabinoside at a dose of 300 mg/m2/day was not considered an active drug for the induction of remission in dogs with lymphoma.

Lupus-type "anticoagulant" in a dog with hemolysis and thrombosis.

A circulating anticoagulant was detected in a 2-year-old Chesapeake Bay Retriever with hemolytic anemia, nephrotic syndrome, thrombocytopenia, polyarthropathy, and pulmonary thromboembolism. A persistent prolongation of the activated partial thromboplastin time (aPTT) was detected, and it did not correct with repeated administration of fresh frozen plasma. The aPTT was still prolonged, with a 1:1 mixture of patient's plasma and normal dog plasma in vitro, suggesting the presence of a circulating inhibitor. Results of assays to characterize the inhibitor were compatible with those described for the lupus anticoagulant in human patients with systemic lupus erythematosus. Paradoxically, patients having the lupus anticoagulant are at increased risk for thrombosis. Pulmonary thromboembolism has been described as a frequent complication of immune-mediated hemolytic anemia in the dog, and the presence of a circulating anticoagulant should be considered as a potential mechanism.

Evaluation of a multidrug chemotherapy protocol (ACOPA II) in dogs with lymphoma.

A chemotherapeutic protocol using cyclophosphamide, vincristine, prednisone, doxorubicin, and L-asparaginase (ACOPA II) was evaluated in dogs with lymphoma. The response rate for 68 dogs treated with ACOPA II (complete remission [CR] 65%, partial remission [PR] 10%) was lower than that for 41 dogs treated with a related protocol previously evaluated (ACOPA I; CR 76%, PR 12%). Initial treatment with doxorubicin and prednisone did not decrease the prevalence or severity of toxicity during induction. The mortality during induction was 22%. The median duration of CR for dogs treated with ACOPA II was 9 months, with 40% still in remission at 1 year and 21% at 2 years. The rate of CR was lower for dogs with signs of illness at presentation (substage b) and for dogs weighing less than 15 kg. Age was negatively correlated with survival time and duration of remission. Dogs with immunoblastic lymphoma had a more favorable prognosis than did those with lymphoblastic lymphoma. Survival times were also longer for dogs in substage a at presentation. Seven dogs in which treatment was discontinued while in remission had comparable remission duration to that achieved by dogs receiving long-term maintenance chemotherapy.