Influence of SARS-CoV-2 mRNA Vaccine Booster among Cancer Patients on Active Treatment Previously Immunized with Inactivated versus mRNA Vaccines: A Prospective Cohort Study.

Cancer patients on chemotherapy have a lower immune response to SARS-CoV-2 vaccines. Therefore, through a prospective cohort study of patients with solid tumors receiving chemotherapy, we aimed to determine the immunogenicity of an mRNA vaccine booster (BNT162b2) among patients previously immunized with an inactivated (CoronaVac) or homologous (BNT162b2) SARS-CoV-2 vaccine. The primary outcome was the proportion of patients with anti-SARS-CoV-2 neutralizing antibody (NAb) seropositivity at 8-12 weeks post-booster. The secondary end points included IgG antibody (TAb) seropositivity and specific T-cell responses. A total of 109 patients were included. Eighty-four (77%) had heterologous vaccine schedules (two doses of CoronaVac followed by the BNT162b2 booster) and twenty-five had (23%) homologous vaccine schedules (three doses of BNT162b2). IgG antibody positivity for the homologous and heterologous regimen were 100% and 96% (p = 0.338), whereas NAb positivity reached 100% and 92% (p = 0.13), respectively. Absolute NAb positivity and Tab levels were associated with the homologous schedule (with a beta coefficient of 0.26 with p = 0.027 and a geometric mean ratio 1.41 with p = 0.044, respectively). Both the homologous and heterologous vaccine regimens elicited a strong humoral and cellular response after the BNT162b2 booster. The homologous regimen was associated with higher NAb positivity and Tab levels after adjusting for relevant covariates.

Effect of switch trimming on udder and teat hygiene of dairy cows.

The study objective was to determine the effects of trimming the switch of dairy cows on teat-end bacterial counts and udder hygiene scores. Cows (n = 102) were blocked by days in milk, milk production, and parity and then assigned to (a) treatment (trimming of their tail switch using a commercially available trimmer), or (b) control (unaltered tails). Udder hygiene was recorded for cows on Days 0 (initiation of treatment), 32, and 64. A subset of cows (n = 21) was used to assess Streptococci and coliform bacterial populations on teat ends. Samples were collected by swabbing the left front teat end before milking on Days 0, 32, and 64 and were cultured within 24 hr of sampling. The GLIMMIX and PROC Frequency (SAS Version 9.3) were used to analyze data. There were no treatment effects of switch trimming on hygiene scores or bacterial counts. These findings suggest that udder hygiene may not be driven by tail status. Environmental and management factors, such as cleanliness, stall bedding, and stall design, may be more important contributing factors in maintaining udder health.

Genetic variation in CXCR1 haplotypes linked to severity of Streptococcus uberis infection in an experimental challenge model.

Mastitis, an inflammation of the mammary gland, costs the dairy industry billions of dollars in lost revenues annually. The prevalence and costs associated with mastitis has made genetic selection methods a target for research. Previous research has identified amino acid changes at positions 122, 207, 245, 327, and 332 in the IL8 receptor, CXCR1, that result in three dominant amino acid haplotypes: VWHKH, VWHRR, and AWQRR. We hypothesize different haplotype combinations influence a cow's resistance, strength, and duration of response to mastitis. To test this, Holstein dairy cows (n=40) were intramammarily challenged with Streptococcus uberis within 3 d post-calving. All cows developed mastitis based on isolation of S. uberis from the challenged quarter at least twice. All cows with the VWHRR x VWHRR (n=5) and AWQRR x VWHRR (n=6) haplotype combinations required antibiotic therapy due to clinical signs of mastitis and tended (P=0.08) to be different from cows with a VWHRR x VWHKH (n=6) haplotype combination where only 33.3% required antibiotic therapy. Cows with a VWHRR homozygous haplotype combination displayed significantly higher responses to challenge indicated by elevated S. uberis counts (4340±5,521.9CFU/mL; P=0.01), mammary scores (1.1±0.18; P=0.03), milk scores (0.9±0.17; P=0.002), and SCC (1,010,832±489,993cells/mL; P=0.03). Contrastingly, AWQRR x VWHRR cows had significantly lower S. uberis counts (15.3±16.46CFU/mL; P=0.01), mammary scores (0.3±0.16; P=0.03), milk scores (0±0.15; P=0.002), and SCC (239,261±92,264.3cells/mL; P=0.03). Cows of the VWHKH x VWHRR haplotype combination displayed responses to challenge statistically comparable to other haplotype combinations, but appeared to have an earlier peak in SCC in comparison to all other haplotype combinations. Haplotype combination did not influence milk yield (P=0.6). Our results suggest using combinations of the SNPs within the CXCR1 gene gives a better indication of a cow's ability to combat S. uberis mastitis and could resolve prior studies' conflicting results focusing on individual SNP.

Protective effect of anti-SUAM antibodies on Streptococcus uberis mastitis.

In the present study, the effect of anti-recombinant Streptococcus uberis adhesion molecule (SUAM) antibodies against S. uberis intramammary infections (IMI) was evaluated using a passive protection model. Mammary quarters of healthy cows were infused with S. uberis UT888 opsonized with affinity purified anti-rSUAM antibodies or hyperimmune sera. Non-opsonized S. uberis UT888 were used as a control. Mammary quarters infused with opsonized S. uberis showed mild-to undetectable clinical symptoms of mastitis, lower milk bacterial counts, and less infected mammary quarters as compared to mammary quarters infused with non-opsonized S. uberis. These findings suggest that anti-rSUAM antibodies interfered with infection of mammary gland by S. uberis which might be through preventing adherence to and internalization into mammary gland cells, thus facilitating clearance of S. uberis, reducing colonization, and causing less IMI.

Pharmacokinetics of ponazuril after oral administration to healthy llamas (Lama glama).

OBJECTIVE: To determine the pharmacokinetics after oral administration of a single dose of ponazuril to healthy llamas. ANIMALS: 6 healthy adult llamas. PROCEDURES: Ponazuril (20 mg/kg) was administered once orally to 6 llamas (day 0). Blood samples were obtained on days 0, 0.5, 1, 2, 3, 4, 5, 6, 7, 9, 11, 14, 21, 28, 35, 42, and 49. Serum ponazuril concentrations were determined by use of a validated reverse-phase high-performance liquid chromatography assay with UV absorbance detection. Pharmacokinetic parameters were derived by use of a standard noncompartmental pharmacokinetic analysis. RESULTS: Mean ± SD area under the serum concentration-time curve was 7,516 ± 2,750 h•mg/L, maximum serum ponazuril concentration was 23.6 ± 6.0 mg/L, and the elimination half-life was 135.5 ± 16.7 hours. Serum concentration of ponazuril peaked at 84 hours (range, 48 to 120 hours) after administration and gradually decreased but remained detectable for up to 35 days after administration. No adverse effects were observed during the study period. CONCLUSIONS AND CLINICAL RELEVANCE: The rate and extent of absorption following oral administration of a single dose of ponazuril were sufficient to result in potentially effective concentrations, and the drug was tolerated well by llamas. At this dose, ponazuril resulted in serum concentrations that were high enough to be effective against various Apicomplexans on the basis of data for other species. The effective ponazuril concentration that will induce 50% inhibition of parasite growth for Eimeria macusaniensis in camelids is currently unknown.

Surgical site infection in liver transplant recipients: impact of the type of perioperative prophylaxis.

Surgical site infection (SSI) is an important cause of morbidity after orthotopic liver transplantation (OLT). Perioperative antibiotic prophylaxis is one of the main modifiable risk factors. We prospectively investigated the epidemiology, risk factors, and prognosis of SSI in a cohort of 167 OLT. Two different schedules of antibiotic SSI prophylaxis were compared. Fifty-six episodes of SSI were included (0.34 episodes/patient). The SSI incidence among patients who received cefazolin and amoxicillin-clavulanate did not differ. Bacteria caused all episodes. The most common pathogen was Escherichia coli (21.25%), among which 47% were extended-spectrum beta-lactamase producers. The only risk factor for SSI was antibiotic therapy before OLT. Patients with SSI had a longer hospital and intensive care unit stay (P<0.05), but survival did not differ. In conclusion, SSI has a high incidence despite antibiotic perioperative prophylaxis; therefore, an integral perspective of SSI and a multifactorial approach other than antimicrobial prophylaxis are needed to prevent it.

Comparative transmission of multiple herpesviruses and simian virus 40 in a baboon breeding colony.

Little is known about the natural history of herpesviruses indigenous in baboons. Here, we describe the development of ELISAs for five herpesviruses. These assays were used to test more than 950 serum samples collected from approximately 210 infant/juvenile and 130 adult baboons in a captive breeding colony over a period of seven years. Results indicated that baboon cytomegalovirus, lymphocryptovirus, and rhadinovirus are transmitted efficiently within the colony and are acquired at an early age. Baboon alpha-herpesvirus HVP2 and polyomavirus simian virus 40 (SV40) were acquired later and by fewer juveniles than were the other three herpesviruses. More than 60% of baboons acquired HVP2 before reaching sexual maturity, indicating that oral infection of infants and juveniles, rather than sexual transmission between adults, is the predominant mode of transmission for this virus. Antibody to simian varicella virus (SVV) was found in about 40% of baboons. SVV was acquired principally by infants and juveniles; few adults seroconverted despite seronegative adults being in constant contact with infants and juveniles undergoing primary infection. Time of seroconversion was not statistically correlated to specific individual herpesviruses, suggesting that each virus is acquired as an independent infection event rather than multiple viruses being acquired at the same time. Several baboons that were delivered by cesarean section and were housed separate from, but in close proximity to, other baboons remained free of many or all viruses for several years, suggesting that, similar to human herpesviruses, baboon herpesviruses and SV40 are transmitted principally by direct contact.