Modeling of host genetics and resistance to infectious diseases: understanding and controlling nematode infections

This paper considers approaches to modeling the dynamics of infectious disease and the application of such models to nematode parasite infections in ruminants. Particularly, these models are developed to account for host genetics and may be used to assess the effects of using genetics to control nematode infections. Three main issues are critically examined: the infection transmission cycle from pasture to host to pasture, the expected genetic relationships between resistance and performance, and the risks of parasite evolution in response to genetic changes in the host. To obtain answers that are realistic and of practical use, the modeling approaches require a solid grounding in biology. This biology is formalized and described using mathematical techniques, with the models parameterized using experimental or field data. Transmission dynamics have been quantified by modeling and are backed by strong experimental data. Selection for resistance will be successful in reducing egg output, pasture larval contamination and hence subsequent larval challenge. Modeling frameworks have been developed to predict genetic relationships between resistance to infectious disease and performance in general, and genetic correlations predicted for nematode resistance are close to mean published values. These predicted correlations strengthen as the larval challenge increases and the dietary (protein) adequacy decreases, however modeling challenges remain. Lastly, although convincing experimental data is not yet available, arguments based on modeling suggest that the risks of parasite evolution in response to genetic changes in the host should be less than the risks arising from other control strategies, such as anthelmintics. Thus, modeling techniques predict that selective breeding for resistance should be an effective and sustainable complementary control measure.     

Is AZT/3TC therapy effective against FIV infection or immunopathogenesis?

In vitro and in vivo prophylactic and therapeutic efficacy of AZT/3TC treatment was evaluated against feline immunodeficiency virus (FIV) infection. In vitro studies utilized FIV-infected peripheral blood mononuclear cells (PBMCs) or FIV-infected T-cell lines treated with AZT (azidothymidine) alone, 3TC alone, or AZT/3TC combination and tested for anti-FIV activity and drug toxicity. AZT/3TC combination had additive to synergistic anti-FIV activities in primary PBMC but not in chronically infected cell lines. In vivo studies consisted of four treatment groups (n=15) of SPF cats receiving AZT/3TC combination (5-75 mg/kg/drug PO BID for 8 or 11 weeks) and one control group (n=9) receiving oral placebo. Group I (n=6, 150 mg/kg/drug/day) was treated starting 3 days pre-FIV inoculation, whereas Group II (n=3, 150 mg/kg/drug/day) and Group III (n=3, 100 mg/kg/drug/day) treatments were simultaneous with FIV inoculation. Group IV treatment (n=3, 100 mg/kg/drug/day) was initiated 2 weeks post-FIV inoculation. All cats were monitored for drug toxicity and FIV infection. Eighty-three percent of cats in Group I and 33% of cats in Groups II and III were completely protected from FIV infection. A significant delay in infection and antibody seroconversion was observed in all unprotected cats from Groups I, II and III. Group IV cats had only a slight delay in FIV antibody seroconversion. Adverse drug reactions (anemia and neutropenia) were observed at high doses (100-150 mg/kg/drug/day) were reversible upon lowering the dose (20 mg/kg/drug/day). In contrast, AZT/3TC treatment had no anti-FIV activity in chronically infected cats. Furthermore, severe clinical symptoms caused by adverse drug reactions were observed in some of these cats. Overall, AZT/3TC treatment is effective for prophylaxis but not for therapeutic use in chronically FIV-infected cats.     

When to neuter dogs and cats: a survey of New York state veterinarians' practices and beliefs

Practicing veterinarians in small-animal or mixed-animal practice in New York state were surveyed about their beliefs and practices regarding the age at which dogs and cats should be neutered and their attitudes toward early neutering (at 4 months of age or younger). The majority of veterinarians routinely recommended neutering for all client animals (70.6%) and supported the routine neutering of shelter animals before adoption (90.3%). More veterinarians in this study reported at least one perceived benefit (91.3%) for early neutering than reported at least one perceived risk (84.4%). Veterinarians with experience neutering early were less likely to believe that the procedure was associated with one or more risks.     

A new form of raabeia-type actinosporean (Myxozoa) from the oligochaete Uncinais uncinata

In a study of the oligochaete fauna and their actinosporean parasites in three lakes in Algonquin Park, Canada, a novel form of raabeia-type actinosporean was observed in a single specimen of Uncinais uncinata (?ersted) (Naididae). This form differs from those previously described in its small size, and by having caudal processes that gradually widen and terminate with a single prominent branch.     

Molecular epidemiology of feline bordetellosis in two animal shelters in California,USA

"Kennel cough" in dogs in animal shelters is readily transmissible, reduces adoption rates, and commonly leads to the euthanasia of affected dogs. In cats, tracheobronchitis, conjunctivitis, and pneumonia have been associated with Bordetella bronchiseptica infection-but most cases of upper-respiratory infection (URI) probably are caused by herpesvirus and calicivirus, and many B. bronchiseptica culture-positive cats are clinically normal. Our prospective observational study was undertaken to document the contribution of B. bronchiseptica to disease in cats and dogs from two animal shelters undergoing outbreaks of canine kennel cough, to evaluate whether cross-species transmission might have occurred, and to determine if the presence of infected cats represented a risk to dogs. Clinically defined cases of kennel cough in dogs and URI in cats were investigated in two shelters by calculating clinical-disease incidence, alveolar-lavage cytological examination, bacterial and viral cultures, antibiotic-susceptibility testing, and molecular fingerprinting by pulsed-field gel electrophoresis.In a 40-cat and 40-dog "no-kill" shelter, the prevalences of culture positivity were 47% for B. bronchiseptica and 36% for calicivirus at the same time as two resident dogs demonstrated clinical cough. When no dogs had kennel cough 3 months later, 10% of cats were B. bronchiseptica-culture-positive and 63% calicivirus positive. In a large traditional shelter, the incidence of kennel cough in dogs increased over 12 weeks to a maximum of 19 cases/week/120 dogs, during which time the culture prevalence was 23% for B. bronchiseptica in dogs and 47% in cats. Three to 6 months before the kennel-cough epidemic, no dogs or cats were B. bronchiseptica positive. Very little genetic variability was detected in isolates from these shelters; all isolates except one corresponded to a single strain type which was identical to the pattern in a vaccine used in these shelters. Isolates from other cats, a horse, a llama, and a sea otter were genetically distinct from the shelter isolates. There was widespread resistance to cephalosporins and ampicillin, but low or no resistance to amoxicillin/clavulanate, trimethoprim-sulfamethoxazole, tetracycline, and enrofloxacin. Greater percent resistance was observed in the traditional shelter than in the no-kill shelter and feline isolates were more likely to be resistant than canine isolates.     

Polymerase chain reaction detection of Mycobacterium tuberculosis complex and Mycobacterium avium organisms in formalin-fixed tissues from culture-negative ruminants

In the US eradication program for bovine tuberculosis, a definitive diagnosis depends on the isolation of Mycobacterium bovis. However, in some cases bacterial culture is unsuccessful, even though the tissue is considered suspicious by histopathology because granulomatous lesions and acid-fast organisms are present. The purpose of this study was to determine if polymerase chain reaction (PCR) tests on formalin-fixed tissue would successfully identify the organisms observed in suspect lesions from culture-negative animals. Diagnostic laboratory records were used to select paraffin blocks of tissue from 102 ruminants that had suspect microscopic lesions but no bacterial isolation. Sections from these blocks were examined with PCR primers for IS6110 to detect Mycobacterium tuberculosis complex infection, or with 16S ribosomal RNA and IS900 primers for detection of Mycobacterium avium. The PCR tests successfully identified a mycobacterial infection in 58 of 102 tissues, including 41 M. tuberculosis complex and 17 M. avium (11 subspecies paratuberculosis). These results demonstrate that PCR testing of formalin-fixed tissue, in combination with bacterial culture, may increase the effectiveness of laboratory diagnostic efforts to detect and identify the most common mycobacterial diseases of ruminants.     

Dose selection of selamectin for efficacy against adult fleas (Ctenocephalides felis felis) on dogs and cats

Selamectin, a novel avermectin, was evaluated in two controlled studies (one in Beagles, one in domestic shorthaired cats) to determine an appropriate topical dose for efficacy against adult Ctenocephalides felis felis (C. felis) fleas on dogs and cats for 1 month. For each study, animals were allocated randomly to four treatments. One treatment consisted of the inert formulation ingredients (vehicle) administered as a negative control, and the other three treatments consisted of a single topical dosage of 3, 6, or 9mgkg(-1) of selamectin. In each study, selamectin was administered as a topical dose applied to the skin in a single spot at the base of the neck in front of the scapulae. Dogs and cats were infested with 100 viable unfed C. felis (50 males and 50 females) on days 4, 11, 18, and 27. Seventy-two hours (+/-2h) after each infestation, on days 7, 14, 21, and 30, a comb count to determine the number of viable fleas present on each animal was performed. Efficacy of selamectin on day 30 was used to select an appropriate dose. For dogs and cats, percentage reductions in geometric mean flea comb counts for the three selamectin treatments ranged from 94. 6 to 100% on days 7, 14, and 21, compared with the negative-control treatment. On day 30, reductions in flea comb counts were 81.5, 94.7, and 90.8% for dogs, and 79.8, 98.0, and 96.2% for cats treated with selamectin at 3, 6, or 9mgkg(-1), respectively. For day 30 flea comb counts for dogs and cats, analysis of variance showed that the three selamectin treatments resulted in significantly (P< or =0.05) lower counts than did the negative-control treatment. For dogs and cats, geometric mean flea counts for selamectin administered at a dosage of 3mgkg(-1) were significantly (P< or =0.05) higher than those for the 6 and 9mgkg(-1) treatment dosages combined. There were no significant differences in flea counts between the 6 and 9mgkg(-1) treatments. This analysis was confirmed by linear-plateau modeling. Thus, the optimal dose of selamectin for efficacy against adult fleas for both dogs and cats, as estimated by the turning point (plateau) in the dose response curve, was 6mgkg(-1).     

Cytochrome P-based resistance mechanism and pyrethroid resistance in the field Anopheles albimanus resistance management trial

The relative rates of cytochrome P⁴⁵⁰ selection in southern Mexican Anopheles albimanus populations were investigated during a 3 years indoor residual house spraying intervention with a pyrethroid (PYR) or DDT, a mosaic of organophosphate (OP)-PYR, and the annual rotation of OP-PYR-carbamate (CARB). This insecticide resistance mechanism, initially evenly spread in the mosquito population, correlated with PYR resistance during the second treated year, when cytochrome P⁴⁵⁰ contents increased in most villages of the PYR, rotation and mosaic schemes. However, by the third year, mean cytochrome P⁴⁵⁰ contents declined to susceptible levels in mosquitoes of the rotation and one mosaic group but not in the PYR-treated villages. In DDT-treated villages, a continuous decrement of cytochrome P⁴⁵⁰ levels occurred since the first treatment year, and susceptible levels were observed at the end of the intervention. Most correlations of cytochrome P⁴⁵⁰ levels and PYR resistance were lost during the third year, indicating that another mechanism evolved in resistant mosquito populations.