Treatment of ocular squamous cell carcinomas in cattle with interleukin-2.

In total, 174 bovine ocular squamous cell carcinomas of varying sizes (20 to 2800 mm(2) in area) were treated daily with peritumoural injections of solvent, or solvent containing 5000 U, 20,000 U, 200,000 U, 500,000 U, 1 million U or 2 million U interleukin-2 (IL-2) for 10 days. The tumours were measured and clinically staged before treatment and at one, three, four, nine and 20 months after treatment. After 20 months, 14 per cent of the tumours treated with the solvent had regressed completely, a significantly smaller proportion than the 55 per cent treated with 5000 U IL-2, 52 per cent treated with 20,000 U IL-2, 58 per cent treated with 200,000 U IL-2, 50 per cent treated with 500,000 U IL-2, 69 per cent of tumours treated with 1 million U IL-2, 52 per cent treated with 2 million U IL-2. The tumours on the third eyelid and limbus were the most responsive.

The epidemiology of rabies in Zimbabwe. 1. Rabies in dogs (Canis familiaris).

The epidemiology of rabies in dogs in Zimbabwe is described using data from 1950, when rabies was re-introduced after a 37-year absence, to 1996. Dogs constituted 45.7% of all laboratory-confirmed rabies cases and were the species most frequently diagnosed with the disease. Slightly more cases were diagnosed from June to November than in other months. From 1950 to the early 1980s, most dog cases were recorded from commercial farming areas, but since the early 1980s most have been recorded from communal (subsistence farming) areas. This change appears to be due to improved surveillance in communal areas and not to any change in the prevalence of rabies. Dog rabies therefore appears to be maintained mainly in communal area dog populations, particularly the large communal area blocks. Urban rabies was not important except in the city of Mutare. Where dog rabies prevalence was high, the disease was cyclic with periods between peak prevalence ranging from 4-7 years. Dog rabies cases were, on the whole, independent of jackal rabies and rabies in other carnivores. There was a significant negative relationship between the annual number of rabies vaccine doses administered nationally to dogs and the annual number of dog rabies cases lagged by one year, indicating that the past levels of immunisation coverage have had a significant effect on the number of rabies cases. However, dog vaccination coverage has clearly not been adequate to prevent the regular occurrence of rabies in dogs.

The epidemiology of rabies in Zimbabwe. 2. Rabies in jackals (Canis adustus and Canis mesomelas).

The epidemiology of rabies in Canis adustus (the side-striped jackal) and Canis mesomelas (the black-backed jackal) in Zimbabwe is described using data collected from 1950-1996. Cases in the two species made up 25.2% of all confirmed cases, second only to domestic dogs. Since the species of jackal cases was not recorded on rabies submission forms, the country was divided into areas according to species dominance and jackal cases were assigned to either C. adustus or C. mesomelas dominant zones or a sympatric zone where the relative status of the species is not known. Jackal rabies in both species is maintained in the commercial farming sector. Jackal rabies in the C. adustus zone occurs as dense epidemics, which begin at a single focus and spread centrifugally. The foci were initiated by rabid dogs, but once initiated the epidemic is maintained by C. adustus independently of other species. The extent of outbreaks in the C. adustus zone was limited by geographical (landuse type and jackal species interface) boundaries. Jackal rabies in C. adustus zones showed two seasonal peaks with the main peak occurring during late summer and the second peak during winter. In the C. mesomelas zone jackal rabies was more sparse but it occurred during most years. C. mesomelas is also able to maintain rabies independently of other species, although the epidemiology of the disease in this species is unclear. Transmission of rabies cycles between the two jackal species zones does not appear to occur as epidemics terminate when crossing the C. adustus and C. mesomelas interface boundaries.

Local low-dose IL-2 therapy.

Interleukin-2 (IL-2) is a powerful drug for treating cancer. However, it is only powerful if it is properly applied. That is, IL-2 should be applied at the tumor site, because at the transition of normal and malignant tissue are the tumor infiltrating cells. These should be activated by IL-2. Local application implies that IL-2 can be used in relatively low doses. It is becoming clear that even a single injection of IL-2 can cure cancer. IL-2 can also enhance the therapeutic effects of irradiation and Cisplatin. Locally applied IL-2 therapy is virtually non-toxic.

Efficacy of SAG-2 oral rabies vaccine in two species of jackal (Canis adustus and Canis mesomelas).

Trials were carried out to test the efficacy of SAG-2 oral rabies vaccine in two species of jackals, namely the side-striped jackal (C. adustus) and the black-backed jackal (C. mesomelas). The first trial tested the efficacy of SAG-2 when given by direct oral administration at doses of 6.5 and 7.5 log10 median tissue culture infectious doses (TCID50). One side-striped jackal which had received the higher dose did not seroconvert and succumbed to challenge, while all other jackals seroconverted and resisted a lethal challenge. The second trial tested the efficacy in side-striped jackals only of the SAG-2 vaccine when given within chicken head baits. A volume of 1.8 ml of vaccine fluid with titers of 7.0 or 8.0 log10 TCID50/ml were placed into blisters which were stapled under the skin of the chicken heads. All jackals (5/5) which received 8.0 log10 TCID50/ml and 3 of 5 which received 7.0 log10 TCID50/ml seroconverted and resisted lethal challenge. A third trial tested the rate of vaccine virus titer loss in chicken head baits placed under field conditions. Titer loss was marked in baits which were not protected from direct sunshine, whereas under vegetation cover approximately log10 TCID50/ml was lost every 3 days. Hence, it was concluded that a bait vaccine virus titer of 8.0 log10 TCID50/ml will be sufficient to immunize wild jackal populations if enough baits can be consumed by jackals within 3 days. This conclusion needs to be tested through the use of oral vaccine in field trials.

Innocuity studies of SAG-2 oral rabies vaccine in various Zimbabwean wild non-target species.

The SAG-2 modified live rabies vaccine was tested for innocuity when administered by the oral route in several potential wild non-target bait-consuming species, as follows: ten chacma baboons (Papio ursinus), six African civets (Civettictis civetta), six slender mongooses (Galerella sanguinea), six honey badgers (Mellivora capensis), six large-spotted genets (Genetta tigrina), 39 multi-mammate mice (Mastomys natalensis), 26 bushveld gerbils (Tatera leucogaster) and six pied crows (Corvus albus). At least 9.0 log10 median tissue culture infectious doses (TCID50), given in a volume of 1 ml, was administered orally to each of the animals, except the rodents which received 8.0 log10 TCID50, given in 0.1 ml. All the animals were observed for not < 90 days for signs of vaccine-induced rabies. Most of the species were also tested for vaccine virus replication in the oral cavity and persistent virus infection in the brain, salivary gland and tonsil. None of the animals died of rabies and no persistent infection was found. Rabies virus which was pathologically and serotypically indistinguishable from the vaccinal strain was isolated from the saliva of one genet 1 day after vaccine administration. From this study it was concluded that SAG-2 rabies vaccine would be safe for use in most situations where oral vaccination campaigns for jackals are required in Zimbabwe.

Phenotype and serotype of Pasteurella multocida isolates from diseases of dogs and cats in Zimbabwe.

A variety of disease manifestations, comprising skin bite wounds, pyothorax, respiratory and genitourinary tract infections, in 202 dogs and cats presented to the University Clinic, were investigated for the presence of Pasteurella multocida. Of these, 25-42% of various cases (69) were found to be infected with P. multocida. P. multocida-associated respiratory tract infections were more common than bite wounds or genitourinary tract infections. The regimen of treatment consisted of those antibiotics, sensitivity to which had been confirmed in vitro. Following detailed characterization of the isolates of P. multocida, in order to assign them to the reclassified taxa of Pasteurella, a preponderance of P. multocida subspecies multocida and septica were recorded. There did not appear to be a correlation between the reclassified taxa and their serotypes. Certain strains of different species or subspecies belonged to a common serotype and vice versa. However, the strains which were serotyped belonged to capsular type A, except for a solitary isolate from a cat which was capsular type D. Type D is known to cause atrophic rhinitis and does not appear to have been isolated either from a dog or a cat. Two strains, one from a dog and another from a cat, were identified as group EF-4 bacteria. This group of organisms has been incriminated in human wounds resulting from dog/cat bites, and has so far not been reported in Africa. Three different species, P. stomatis, P. dagmatis and P. multocida subspecies multocida were simultaneously isolated from a case of chronic bronchitis in a dog. There was no evidence of any relationship between disease manifestation in a host and the isolation of a particular taxon of Pasteurella, except that P. canis and Pasteurella taxon 16 were only isolated from dogs.

Optimal regimes for local IL-2 tumour therapy.

In this report we present studies on optimal regimes for regional IL-2 therapy, focused on dose, schedule and site of injection. Original data obtained in 2 murine tumour models show that all 3 factors are of importance. Anti-tumour responses were most effective when IL-2 was administered regionally 5 to 10 times, at doses ranging from 7,000 to 33,000 IU/day every day or every other day. This resulted in cure rates of more than 40% in mice bearing ascitic tumour that had also disseminated to liver and lungs. The importance of these data is discussed in the light of previous results of our group. These results illustrate that the doses and schedules used in this study are not effective exclusively in these 2 tumour models but may have a more general applicability.

Biochemical and haematological values in abattoir pigs with and without subclinical lesions.

The biochemical and haematological profiles of 379 pigs with or without various gross pathological lesions in an abattoir in Zimbabwe were studied to see whether there were any differences between the levels of haematological and biochemical values, and health status (with and without pathological lesions). On the basis of observable gross pathology, 134 pigs were classified as having one or more subclinical lesions (liver milk spot, pneumonia, pleurisy, pericarditis, abscesses and arthritis). Seventy-six of these were males and 58 females. There were observable sex differences in the mean haematological and biochemical values obtained. Erythrocyte counts showed significant differences in mean values (P < 0.05) among groups of pigs found with various pathological lesions. The biochemical values showed significant group differences for ALP, ALT, AST, and LDH.

Ocular squamous cell carcinoma in Simmental cattle in Zimbabwe.

In Zimbabwe, ocular squamous cell carcinoma (OSCC) was frequently observed in 5 breeding herds of Simmental cattle, a Bos taurus breed originating from Switzerland. In these herds, initial signs of OSCC were already noticeable in cattle about 3 years old. Gradually, OSCC prevalence increased, and 36 to 53% of cattle over 7 years old had 1 or more tumors. More tumors developed in Simmental cattle with periorbital white skin than in cattle with periorbital pigmented skin. Other breeds of cattle (eg, Friesian) also are partly white-faced and live in Zimbabwe in a comparable environment; yet, OSCC prevalence was lower in those breeds.

Therapy of bovine ocular squamous-cell carcinoma with local doses of interleukin-2: 67% complete regressions after 20 months of follow-up.

We have tested the therapeutic potency of peritumorally injected low doses of interleukin-2 (IL-2). Seventy tumours of the bovine ocular squamous-cell carcinoma (BOSCC), 1-3 cm in diameter, were treated with 5000, 20,000 or 200,000 U IL-2 from Eurocetus (Chiron) to find the optimal dose for treatment. Injections were given peritumorally on Monday to Friday on 2 consecutive weeks. The size of the tumours was measured before treatment and 1, 3, 4, 9 and 20 months after treatment. After 9 months complete regression was observed in 89% of the tumours treated with 5000 U IL-2, 80% treated with 20,000 U and 67% treated with 200,000 U. After 20 months, there was complete regression of 35%, 31% and 67% of the tumours respectively. The 9- and 20-month results of the 200,000-U treatment are significantly better than those of the 5000-U and 20,000-U treatments taken together. This protocol may be useful to treat advanced inoperable tumours (e.g. of the nasopharynx or skin) of human patients.

Efficacy of SAD (Berne) rabies vaccine given by the oral route in two species of jackal (Canis mesomelas and Canis adustus).

Eight black-backed jackals (Canis mesomelas) and seven side-striped jackals (Canis adustus) were given SAD (Berne) rabies vaccine by direct oral instillation. Three different vaccine doses were used: 10(6.3), 10(6.8) and 10(7.5) median tissue culture infectious doses. Two additional jackals were given vaccine in chicken heads. One group of jackals was challenged with a lethal dose of jackal-derived rabies virus 1 mo after vaccination and a second group 12 mo after vaccination. All 17 vaccinated jackals developed high and persistent serum neutralizing antibody titers. All challenged jackals resisted a lethal dose of rabies virus, whereas three control jackals given the same challenge succumbed to rabies.

Naturally occurring tetracycline-like fluorescence in sections of femur from jackals in Zimbabwe.

In assessing the potential of the tetracycline compounds as biomarkers in oral rabies vaccination campaigns in jackals in Zimbabwe, the natural prevalence of fluorescent compounds in bone tissue from jackals was investigated. Femur samples were taken from unbaited jackals received for routine rabies diagnosis, and thin undecalcified sections were cut and viewed under an ultraviolet microscope. Of 131 femur samples examined, 49 (37 per cent) had fluorescent markings indistinguishable from those of tetracycline. The result implies that the tetracycline compounds, which are commonly used in rabies baiting campaigns in Europe and North America, cannot be used as biomarkers in jackals in Zimbabwe.

Local bacillus Calmette-Guérin therapy for bovine vulval papilloma and carcinoma.

Thirty cows from a pedigree Friesian dairy herd with bovine vulva papilloma and carcinoma were treated by intralesional injections of live bacillus Calmette-Guérin (BCG). This treatment induced total regression of all of six carcinomas. Whilst, after treatment, limited regression was also observed in advanced papillomas, BCG has little or no effect on the early stages of papillomas. This is the first study of BCG therapy in this type of cancer.

Antitumor effect of locally injected low doses of recombinant human interleukin-2 in bovine vulval papilloma and carcinoma.

In many human clinical trials and in various animal tumor models, the antitumor effect of high doses of systemically applied interleukin-2 (IL-2) is tested. Our studies focused on the effects of low doses of locally injected IL-2. In this paper, the effect of local injection of low doses of IL-2, i.e. a total dose of 25,000-50,000 units, into papillomas or carcinomas of the bovine vulva is described. In 19 out of 23 (83%) cows treated with IL-2 an effect on the tumor load was observed; in three of these animals, complete regression was obtained. In the majority of cases, regression was not restricted to the tumors injected with IL-2.

Phenotypic characterization of Zimbabwean isolates of Pasteurella multocida.

The phenotypic characteristics of 60 Zimbabwean isolates of Pasteurella multocida sensu stricto, from disease syndromes in different host species were studied. A number of representative strains were also serotyped. Consistent results were obtained in the tests for; catalase, oxidase, urease, indole, acid in glucose, inositol, salicin and sucrose. There was no obvious relationship between serotype, host or disease and the pattern of utilization of certain substrates by an isolate. This has been discussed in the context of recent proposals to reclassify Pasteurella and P. multocida on genotypic and phenotypic studies. It is suggested that notwithstanding the relevance of genetic studies in circumscribing P. multocida, the phenotype and disease significance of the taxon should not be ignored. A case of bronchitis in a dog which was simultaneously colonized by three different strains of Pasteurella is described. Also septicaemic pasteurellosis in a Nile crocodile (Crocodylus niloticus) is reported and for the first time prevalence of various serotypes in pasteurellosis of animals in Zimbabwe.

Low doses of interleukin-2 can cure large bovine ocular squamous cell carcinoma.

Four cows bearing large Ocular Squamous Cell Carcinomas (BOSCC) were treated by 10 intratumoral injections (Monday-Friday for 2 consecutive weeks) of 200,000 U Interleukin-2 (Cetus). Tumors regressed in 2 out of 4 cases. This result shows that even large tumors may regress after local IL-2 treatment.

Reproduction in female cattle in a communal farming area of Zimbabwe.

Cattle in a communal farming area of Zimbabwe were identified and examined in the late dry and mid wet season of 1985/86. Ovarian activity rates were 17.9% and 38.6% in the dry and wet season respectively. Pregnancy rates were 16.1% and 24.6% respectively. A major limitation to reproduction was the percentage of anoestrous females. There was no evidence of a seasonal calving pattern. Median body condition score was 2.0 in the dry season and 1.5 in the wet season. Adult females of body condition score 2.5 and above had ovarian activity rates of 41.9% and pregnancy rates of 41.9 per cent. Those with a body condition score below 2.5 had rates of 26.8% and 16.4% respectively. Serum progesterone levels in pregnant animals were positively related to body condition score, with some animals having progesterone levels similar to non-pregnant animals. Metabolic profiles suggested that the major limiting nutrient in both seasons was nitrogen, although other micronutrients might also be involved in low reproductive rates.