Naja nigricincta nigricincta venom, a murine model. Evaluation of skeletal and cardio-myonecrosis, kidney injury and inflammatory response along with neutralisation efficacy by the SAIMR/SAVP - And EchiTAb-Plus-ICP polyvalent antivenoms.

African spitting cobra, Naja nigricincta nigricincta (Zebra snake), envenomation is an important cause of snakebite morbidity and mortality in Namibia. The snake is endemic to central and northern Namibia as well as southern Angola. The venom is mainly cytotoxic, resulting in aggressive dermo-necrosis and often accompanied by severe systemic complications. No specific antivenom exists. Rhabdomyolysis, systemic inflammatory response, haemostatic abnormalities, infective necrotising fasciitis as well as acute kidney failure have been documented. Based on murine models, this study assessed SAVP/SAIMR - and EchiTAb-Plus-ICP polyvalent antivenom neutralisation as well as subdermal necrosis. Additional muscle, cardiac, kidney and lung histology, creatine kinase measurements and post-mortems were performed. An intravenous median lethal dose (LD50) of Naja nigricincta nigricincta venom was determined at 18.4 (CI: 16.3; 20.52) µg and a subdermal lethal dose at 15.3(CI: 12.96; 17.74)µg. The SAIMR/SAVP polyvalent antivenom median effective dose (ED50) was 1.2 ml antivenom/1 mg venom equating to a potency (WHO) of 1 ml antivenom neutralising 0.63 mg venom and approximately 240 ml (24 vials) needed for initial treatment. The ED50 of the EchiTAb-Plus-ICP was 1 ml antivenom/1 mg venom and a potency of 65 mg venom/ml antivenom (3.3 x LD50), estimating 230 ml (23 vials) for treatment. Histology and serology (creatine kinase) evidenced venom induced skeletal myotoxicity, which was not prevented by the antivenoms tested. Cardiac myonecrosis, an inflammatory response, direct venom kidney tubular necrosis and cardio-pulmonary failure were documented.

THE IMPACT OF SUPPLEMENTARY FEEDING OF PIG CARCASSES ON PLASMA VITAMIN E CONCENTRATIONS IN CAPTIVE CAPE VULTURES (GYPS COPROTHERES).

With vulture population numbers on the decline globally, many countries resort to supplementary feeding to maintain colony health. Despite what is perceived as adequate feeding in South Africa, colonies are still characterized by poor breeding success. One reason could be that supplementary sites fail to meet micronutrient needs of birds. With results from zoological gardens indicating that some carcasses are low in their vitamin E concentrations, vitamin deficiencies may be an underlying problem. For this study it was determined if the feeding of whole pig carcasses, a common food item, could have a negative effect on plasma vitamin E concentrations in a captive colony. Plasma vitamin E concentrations were 7.38 ± 2.92 and 4.51 ± 1.24 after feeding whole pig carcasses (n = 14). Behaviorally, the birds also avoided the viscera and fat when feeding. Reasons for their low vitamin E concentrations could have resulted from the birds consuming only the pork meat, which is known to be low in vitamin E, or from natural peroxidation because of the high fat content of the carcasses. The study thus highlights the need for further research to ascertain the impact of feeding pig carcasses on wild vultures feeding routinely at supplementary feeding sites and also for considerations towards vitamin E supplementation.

Prevalence of colistin resistance and antibacterial resistance in commensal Escherichia coli from chickens: An assessment of the impact of regulatory intervention in South Africa.

BACKGROUND: Antimicrobial resistance (AMR) is a global health problem largely due to the overuse of antimicrobials. In recognition of this, the World Health Assembly in 2015 agreed on a global action plan to tackle AMR. Following the global emergence of the mcr-1-associated colistin resistance gene in the livestock industry in 2016, several countries including South Africa restricted the veterinary use of colistin as the gene threatens the clinical utility of the drug. This study is a follow-up to the restriction in place in order to evaluate the impact of such policy adoption. OBJECTIVE: To assess the prevalence of antibacterial resistance (ABR), and the mcr-1 colistin resistance gene in broiler chicken over a 2-year period, as a follow-up to the veterinary ban on colistin use in South Africa. METHODS: A total of 520 swab samples were obtained during 2019 (March-April) and 2020 (February-March), from healthy broiler chicken carcasses (n = 20) and chicken droppings in transport crates (n = 20) at various poultry abattoirs (N = 7) in the Gauteng province of South Africa. Escherichia coli organisms were isolated and subjected to a panel of 24 antibacterials using the MicroScan machine. Screening for mcr-1 colistin resistance gene was undertaken using PCR. RESULT: Four hundred and thirty-eight (438) E. coli strains were recovered and none demonstrated phenotypic resistance towards colistin, amikacin, carbapenems, tigecycline and piperacillin/tazobactam. The mcr-1 gene was not detected in any of the isolates tested. Resistances to the aminoglycosides (0%-9.8%) and fluoroquinolones (0%-18.9%) were generally low. Resistances to ampicillin (32%-39.3%) and trimethoprim/sulphamethoxazole (30.6%-3.6%) were fairly high. A significant (p < 0.05) increase in cephalosporins and cephamycin resistance was noted in the year 2020 (February-March) when compared with the year 2019 (March-April). CONCLUSION: The absence of mcr-1 gene and colistin resistance suggests that mitigation strategies adopted were effective and clearly demonstrated the significance of regulatory interventions in reducing resistance to critical drugs. Despite the drawback in regulatory framework such as free farmers access to antimicrobials OTC and a dual registration system in place, there is a general decline in the prevalence of ABR when the present data are compared with the last national veterinary surveillance on AMR (SANVAD 2007). To further drive resistance down, mitigation strategies should focus on strengthening regulatory framework, the withdrawal of OTC dispensing of antimicrobials, capping volumes of antimicrobials, banning growth promoters and investing on routine surveillance/monitoring of AMR and antimicrobial consumption.

A premature stop codon in the CYP2C19 gene may explain the unexpected sensitivity of vultures to diclofenac toxicity.

The unintended environmental exposure of vultures to diclofenac has resulted in the deaths of millions of old-world vultures on the Asian subcontinent. While toxicity has been since associated with a long half-life of elimination and zero order metabolism, the actual constraint in biotransformation is yet to be clarified. For this study we evaluated if the evident zero order metabolism could be due to defects in the CYP2C9/2C19 enzyme system. For this, using whole genome sequencing and de-novo transcriptome alignment, the vulture CYP2C19 open reading frame was identified through Splign analysis. The result sequence analysis revealed the presence of a premature stop codon on intron 7 of the identified open reading frame. Even if the stop codon was not present, amino acid residue analysis tended to suggest that the enzyme would be lower in activity than the equivalent human enzyme, with differences present at sites 105, 286 and 289. The defect was also conserved across the eight non-related vultures tested. From these results, we conclude that the sensitivity of the old-world vultures to diclofenac is due to the non-expression of a viable CYP2C19 enzyme system. This is not too dissimilar to the effects seen in certain people with a similar defective enzyme.

Sub-lethal impacts of lead poisoning on blood biochemistry, immune function and delta-aminolevulinic acid dehydratase (δ-ALAD) activity in Cape (Gyps coprotheres) and white-backed (G. africanus) Vulture chicks.

Although the prevalence of lead poisoning in southern Africa's Gyps vultures is now well-established, its finer physiological effects on these endangered species remain poorly characterised. We evaluated the sub-lethal impact of acute lead exposure on Cape and White-backed Vulture chicks from two breeding colonies in South Africa, by analysing its possible effects on key blood biochemistry parameters, immune function, packed cell volume and δ-aminolevulinic acid dehydratase (δ-ALAD) activity. All 37 White-backed Vulture nestlings sampled displayed elevated lead levels (>10 µg/dL), and seven had blood [Pb] >100 µg/dL. Eight of 28 Cape Vulture nestlings sampled had blood [Pb] exceeding background exposure, with one showing blood [Pb] >100 µg/dL. Delta-aminolevulinic acid dehydratase (δ-ALAD) activity was significantly and negatively related to blood [Pb] in nestlings from both species, with 50% inhibition of the enzyme predicted to occur at blood [Pb] = 52.8 µg/dL (White-backed Vulture) and 18.8 µg/dL (Cape Vulture). Although no significant relationship was found between % packed cell volume (PCV) and blood [Pb], the relatively lower mean PCV of 32.9% in White-backed Vulture chicks, combined with normal serum protein values, is likely indicative of depression or haemolytic anaemia. The leukogram was consistent in both species, although the presence of immature heterophils suggested an inflammatory response in White-backed Vulture chicks with blood [Pb] >100 µg/dL. Values for cholesterol, triglycerides, total serum protein, albumin, globulin, albumin/globulin ratio, alanine aminotransferase (ALT) and gamma-glutamyl transferase (GGT) were consistent with values previously reported. Calcium and phosphorus concentrations suggested no adverse effects on bone metabolism. A significant decrease in urea: uric acid (U:UA) ratio at blood [Pb] >100 µg/dL in White-backed Vulture chicks, brought about by a decrease in urea production, raises the possibility of hepatic abnormality. These results suggest that δ-ALAD activity may serve as a sensitive biomarker of lead toxicity in both species, while highlighting the need to better understand the significant variability in sensitivity that is observed, even between closely related members of the same genus.

A Technical Report on the Potential Effects of Heat Stress on Antioxidant Enzymes Activities, Performance and Small Intestinal Morphology in Broiler Chickens Administered Probiotic and Ascorbic Acid during the Hot Summer Season.

Oxidative stress negatively affects the welfare of broiler chickens leading to poor productivity and even death. This study examined the negative effect of heat stress on antioxidant enzyme activities, small intestinal morphology and performance in broiler chickens administered probiotic and ascorbic acid during the hot summer season, under otherwise controlled conditions. The study made use of 56 broiler chickens; which were divided into control; probiotic (1 g/kg); ascorbic acid (200 mg/kg) and probiotic + ascorbic acid (1 g/kg and 200 mg/kg, respectively). All administrations were given via feed from D1 to D35 of this study. Superoxide dismutase, glutathione peroxidase and catalase activities were highly significant (p < 0.0001) in the treatment groups compared to the control. Performance indicators (water intake and body weight gain) were significantly higher (p < 0.05) in the probiotic and probiotic + ascorbic acid group. The height of duodenal, jejunal and ileal villi, and goblet cell counts of broiler chickens were significantly different in the treatment groups. In conclusion, the study showed that heat stress negatively affects the levels of endogenous antioxidant enzymes, performance and the morphology of small intestinal epithelium, while the antioxidants were efficacious in ameliorating these adverse effects.

Experimental safety testing confirms that the NSAID nimesulide is toxic to Gyps vultures in India.

Population declines of Gyps vultures throughout South Asia were caused by unintentional poisoning by the NSAID diclofenac, which was subsequently banned. However, other vulture-toxic NSAIDs are available, including nimesulide, which, in experiments carried out in South Africa, was shown to be toxic to Gyps vultures. We report on safety-testing of nimesulide carried out on Himalayan Griffons G. himalayensis. We gave two vultures a dose of nimesulide by oral gavage at the maximum level of exposure, with two controls dosed with benzyl alcohol. In the two tested birds, plasma nimesulide concentrations peaked after six hours, while serum uric acid concentrations increased steadily up until 24 h post-treatment, after which both birds died, displaying severe visceral gout. The control birds showed no adverse clinical or biochemical signs. We confirm that nimesulide is toxic to Gyps vultures. Veterinary use of nimesulide should be banned in all Gyps vulture range countries in the region.

Veterinary pharmaceuticals and declining Cape Griffon Vulture (Gyps coprotheres) numbers: A potential threat to developing embryos.

Cape Vultures (Gyps coprotheres) are a vulnerable Old-World Vulture species in southern Africa. Of the numerous threats to their survival, malicious and accidental poisonings remain a major concern. Despite the dangers of poisonings little is however known about the more insidious effects of toxins on egg survival, despite the species known to have a long generational length. For this study, an extensive literature review focusing on veterinary pharmaceuticals was undertaken. Literature for vultures was scarce, with most studies focusing on the domestic chicken. Using information for domestic chickens, the risk was characterised from likely vulture exposure to production animal carcasses with residues of said drugs. From this various antibiotics, medetomidine and albendazole were identified with embryotoxic or teratogenic effects. We suggest that these drugs be tested to elucidate their dose-response relationship and/or mitigation measures to minimise vulture exposure.

Do Pathogenic Escherichia coli Isolated from Gallus gallus in South Africa Carry Co-Resistance Toward Colistin and Carbapenem Antimicrobials?

Colistin and carbapenems are critically important antimicrobials often used as a last resort to manage multidrug-resistant bacterial infections in humans. With limited alternatives, resistance to these antimicrobials is of concern as organisms could potentially spread horizontally rendering treatments ineffective. The aim of this study was to investigate co-resistance to colistin and carbapenems among Escherichia coli isolated from poultry in South Africa. Forty-six E. coli strains obtained from clinical cases of breeder and broiler chickens were used. In addition to other antibiotics, all the isolates were tested against colistin and carbapenems using broth microdilution. Multiplex polymerase chain reactions were used to investigate the presence of colistin (mcr-1 to 5) and carbapenem (blaOXA-48, blaNDM-1, and blaVIM) resistance genes. Isolates exhibiting colistin resistance (>2 µg/mL) underwent a whole-genome sequencing analysis. Resistance to colistin (10.9%) and cefepime (6.5%) was noted with all colistin-resistant strains harboring the mcr-1 gene. None of the E. coli isolates were resistant to carbapenems nor carried the other resistant genes (mcr-2 to 5, blaOXA-48, blaNDM-1, and blaVIM). The mcr-1-positive strains belonged to sequence types ST117 and ST156 and carried virulence genes ompA, aslA, fdeC, fimH, iroN, iutA, tsh, pic, ast A and set 1A/1B. In conclusion, clinical E. coli strains from chickens in this study possessed mobile resistance genes for colistin and several other clinically relevant antimicrobials but not carbapenems. Additionally, they belonged to sequence types in addition to carrying virulence factors often associated with human extraintestinal pathogenic E. coli infections. Thus, the potential risk of transmitting these strains to humans cannot be underestimated especially if sick birds are dispatched into the thriving poorly regulated Cornish hen industry. The need for routine veterinary surveillance and monitoring of antimicrobial resistance, antimicrobial use and the importance of strengthening regulations guiding the informal poultry sector remains important.

Identifying the origin of lead poisoning in white-backed vulture (Gyps africanus) chicks at an important South African breeding colony: a stable lead isotope approach.

Elevated lead levels in scavenging raptors can originate from a variety of environmental and anthropogenic sources, including soil, water, mining activities and legacy lead from leaded fuel, but has mostly been attributed to fragments of lead-based ammunition embedded in the tissues of carcasses. To identify the origins of lead in the tissues of white-backed vulture (Gyps africanus) chicks at Dronfield Nature Reserve, South Africa, we used MC-ICP-MS to compare the isotopic composition of lead in blood samples to those of soil in the chicks' immediate environment, different mining activities in South Africa and lead ammunition commonly used in hunting and game management practices. The isotopic ratios in vulture blood samples ranged widely (207Pb/206Pb: 0.827-0.911), but fell within those measured for ammunition (0.761-0.938). Dronfield water can be excluded as a significant source, as the lead concentration for water was below detection limits. Uranium, coal, atmospheric Pb, legacy Pb from fuel and Pb mining can also be excluded as significant sources, based on the limited overlap with Pb isotopic ratios measured in vulture blood. Whereas 55% of chicks we sampled displayed isotopic ratios consistent with Dronfield soil, the low local Pb concentration and the low extractable Pb levels in South African soil in general, imply that soil Pb is unlikely the major source of Pb in WBV chicks, especially in birds with elevated blood Pb levels, i.e. > 20 µg/dL. Our results, when considered in the context of vulture feeding ecology and low Pb levels in non-scavenging birds in South Africa, imply the major source of elevated Pb levels in WBV chicks to be fragments of lead-based ammunition embedded in the carrion fed to them by their parents.

Do Pharmaceuticals in the Environment Pose a Risk to Wildlife?

The vast majority of knowledge related to the question "To what extent do pharmaceuticals in the environment pose a risk to wildlife?" stems from the Asian vulture crisis (>99% decline of some species of Old World vultures on the Indian subcontinent related to the veterinary use of the nonsteroidal anti-inflammatory drug [NSAID] diclofenac). The hazard of diclofenac and other NSAIDs (carprofen, flunixin, ketoprofen, nimesulide, phenylbutazone) to vultures and other avian species has since been demonstrated; indeed, only meloxicam and tolfenamic acid have been found to be vulture-safe. Since diclofenac was approved for veterinary use in Spain and Italy in 2013 (home to ~95% of vultures in Europe), the risk of NSAIDs to vultures in these countries has become one of the principal concerns related to pharmaceuticals and wildlife. Many of the other bodies of work on pharmaceutical exposure, hazard and risk to wildlife also relate to adverse effects in birds (e.g., poisoning of scavenging birds in North America and Europe from animal carcasses containing pentobarbital, secondary and even tertiary poisoning of birds exposed to pesticides used in veterinary medicine as cattle dips, migratory birds as a vector for the transfer of antimicrobial and antifungal resistance). Although there is some research related to endocrine disruption in reptiles and potential exposure of aerial insectivores, there remain numerous knowledge gaps for risk posed by pharmaceuticals to amphibians, reptiles, and mammals. Developing noninvasive sampling techniques and new approach methodologies (e.g., genomic, in vitro, in silico, in ovo) is important if we are to bridge the current knowledge gaps without extensive vertebrate testing. Environ Toxicol Chem 2023;00:1-16. © 2022 The Authors. Environmental Toxicology and Chemistry published by Wiley Periodicals LLC on behalf of SETAC. This article has been contributed to by U.S. Government employees and their work is in the public domain in the USA.

Metabolism of aceclofenac to diclofenac in the domestic water buffalo Bubalus bubalis confirms it as a threat to Critically Endangered Gyps vultures in South Asia.

Vulture declines in South Asia were caused by accidental poisoning by the veterinary non-steroidal anti-inflammatory drug (NSAID) diclofenac. Although veterinary use of diclofenac has been banned, other vulture-toxic NSAIDs are legally available, including aceclofenac, which has been shown to metabolise into diclofenac in domestic cattle. We gave nine domestic water buffalo the recommended dose of aceclofenac (2 mg kg-1 body weight), collected blood at intervals up to 48 h, and carried out a pharmacokinetic analysis of aceclofenac and its metabolite diclofenac in plasma. Aceclofenac was rapidly converted to diclofenac, and was barely detectable in plasma at any sampling time. Diclofenac was present within 20 min, and peaked 4-8 h after dosing. Aceclofenac is a prodrug of diclofenac, and behaves similarly in domestic water buffalo as it did in domestic cattle, posing the same risk to vultures. We recommend an immediate ban on the veterinary use of aceclofenac across vulture-range countries.

Effect of cytochrome P450 inhibition on toxicity of diclofenac in chickens: Unravelling toxicity in Gyps vultures.

Diclofenac was responsible for the decimation of Gyps vulture species on the Indian subcontinent during the 1980s and 1990s. Gyps vultures are extremely sensitive (the lethal dose 50 [LD50] ~ 0.1 mg/kg - 0.2 mg/kg), with toxicity appearing to be linked to metabolic deficiency, demonstrated by the long T1/2 (~12 h - 17 h). This is in striking comparison to the domestic chicken (Gallus gallus domesticus), in which the LD50 is ~10 mg/kg and the T1/2 is ~1 h. The phase 1 cytochrome P450 (CYP) 2C subfamily has been cited as a possible reason for metabolic deficiency. The aim of this study was to determine if CYP2C9 homolog pharmacogenomic differences amongst avian species is driving diclofenac toxicity in Gyps vultures. We exposed each of 10 CYP-inhibited test group chickens to a unique dose of diclofenac (as per the Organisation for Economic Co-operation and Development [OECD] toxicity testing guidelines) and compared the toxicity and pharmacokinetic results to control group birds that received no CYP inhibitor. Although no differences were noted in the LD50 values for each group (11.92 mg/kg in the CYP-inhibited test group and 11.58 mg/kg in the control group), the pharmacokinetic profile of the test group was suggestive of partial inhibition of CYP metabolism. Evaluation of the metabolite peaks produced also suggested partial metabolic inhibition in test group birds, as they produced lower amounts of metabolites for one of the three peaks demonstrated and had higher diclofenac exposure. This pilot study supports the hypothesis that CYP metabolism is varied amongst bird species and may explain the higher resilience to diclofenac in the chicken versus vultures.

The non-steroidal anti-inflammatory drug nimesulide kills Gyps vultures at concentrations found in the muscle of treated cattle.

Throughout South Asia, cattle are regularly treated with non-steroidal anti-inflammatory drugs (NSAIDs) and their carcasses are left for scavengers to consume. Residues of the NSAID diclofenac in cattle carcasses caused widespread mortality and catastrophic population declines in three species of Gyps vulture during the 1990s and 2000s. Diclofenac is now banned, but other NSAIDs are used in its place. Different lines of evidence, including safety testing in Gyps vultures, have shown that some of these other NSAIDs are toxic, or probably toxic, to vultures. The NSAID nimesulide is widely available and commonly used, and has been found in dead vultures with signs of renal failure (i.e. visceral gout) and without the presence of diclofenac and/or other vulture-toxic NSAIDs. Nimesulide is therefore probably toxic to vultures. Here, we report safety testing of nimesulide in Gyps vultures. In a controlled toxicity experiment, we gave two vultures the maximum likely exposure (MLE) of nimesulide calculated from initial pharmacokinetic and residue experiments in cattle. Two other control birds were given an oral dose of water. Both vultures dosed with nimesulide died within 30 h, after showing outward signs of toxicity and increases in biochemical indicators of renal failure. Post-mortem examinations found extensive visceral gout in both vultures. Both control vultures survived without biochemical indicators of renal failure. With this evidence, we call for an immediate and comprehensive ban of nimesulide throughout South Asia to ensure the survival of the region's Critically Endangered vultures. More generally, testing the impacts of drugs on non-target species should be the responsibility of the pharmaceutical industry, before their veterinary use is licensed.

Antimicrobial resistance and mcr-1 gene in Escherichia coli isolated from poultry samples submitted to a bacteriology laboratory in South Africa.

BACKGROUND AND AIM: Antimicrobial resistance (AMR) and recently mobilized colistin resistance (mcr-1) associated colistin resistance among Escherichia coli isolates have been attributed to the overuse of antimicrobials in livestock production. E. coli remains an important pathogen, often associated with mortality and low carcass weight in poultry medicine; therefore, the need to use antimicrobials is common. The study aimed to determine the AMR profile and presence of mcr-1 and mcr-2 genes in avian pathogenic E. coli from poultry samples tested at a bacteriology laboratory for routine diagnosis. This is a first step in understanding the effectiveness of mitigation strategies. MATERIALS AND METHODS: Fifty E. coli strains were assessed for resistance against ten antimicrobial drugs using broth microdilution. All isolates with a colistin minimum inhibitory concentration (MIC) of 2 µg/mL were analyzed for the presence of mcr-1 and mcr-2 genes by employing the polymerase chain reaction. For each isolate, the following farm information was obtained: farm location, type of farm, and on-farm use of colistin. RESULTS: Sixty-eight percent of the strains were resistant to at least one antimicrobial; 44% were multiple drug-resistant (MDR). Most E. coli isolates were resistant to doxycycline (44%), trimethoprim-sulfamethoxazole (38%), ampicillin (32%), and enrofloxacin (32%). None of the E. coli strains was resistant to colistin sulfate (MIC90 of 2 µg/mL). Only one E. coli isolate held the mcr-1 gene; none carried the mcr-2 gene. CONCLUSION: Resistance among E. coli isolates in this study was fairly high. Resistance to commonly used antimicrobials was observed, such as doxycycline, trimethoprim-sulfamethoxazole, and enrofloxacin. Only a single E. coli strain carried the mcr-1 gene, suggesting that mcr-1 and mcr-2 genes are common among isolates in this study. The prevalence of AMR, however, suggests that farmers must implement standard biosecurity measures to reduce E. coli burden, and antimicrobial use to prolong the efficacy life span of some of these drugs.

The spread and antimicrobial resistance of Staphylococcus aureus in South African dairy herds - A review.

Staphylococcus aureus is internationally recognised as a principal agent of mastitis and the foremost reason for economic loss in the dairy industry. The limited data available on organism-specific antibiotic resistance surveillance in dairy cattle have stimulated the need for such a review article. The objective of this study was to review relevant literature on antimicrobial resistance of mastitis-causing staphylococci isolated from dairy cows in South Africa compared to other countries. Factors relating to the incidence of mastitis and treatment strategies in terms of the One Health concept and food security were included. The Web of Science (all databases) and relevant websites were used, and articles not written in English were excluded. The incidence of mastitis varied between South Africa and other countries. Antimicrobial resistance patterns caused by S. aureus also varied in regions within Southern Africa and those of other countries although some similarities were shown. Antimicrobial resistance differed between S. aureus bacteria that were maltose positive and negative (an emerging pathogen). The results highlighted the importance of the availability of organism-specific surveillance data of the incidence of mastitis and antibiotic resistance for specific countries and within similar climatic conditions. Accurate knowledge about whether a specific pathogen is resistant to an antibiotic within a certain climate, country, area or farm should reduce the incidence of unnecessary or incorrect treatment with antibiotics. This should enable dairy farmers to deal with these organisms in a more effective manner. Therefore such research should be ongoing.

Diclofenac toxicity in susceptible bird species results from a combination of reduced glomerular filtration and plasma flow with subsequent renal tubular necrosis.

Diclofenac caused the death of millions of vultures on the Asian subcontinent. Other non-steroidal anti-inflammatory drugs (NSAIDs) have since also been shown to be toxic to vultures with the exception of meloxicam. For this study, we evaluated the effect of diclofenac on renal uric acid transport and glomerulus filtration in an acute toxicity model. In a two-phase study with the same birds, healthy chickens (a validated model species) were treated intravenously with para-amino hippuric acid (PAH) and iohexol (IOH) in combination in phase 1. In phase 2, the same PAH and IOH combination was then combined with diclofenac (10 mg/kg). In both phases, blood and faeces were sequentially collected. In phase 1, the birds showed no signs of ill health. Moreover, PAH, IOH and uric acid clearance was rapid. In phase 2, two chickens showed early signs of hyperuricemia 8 hours after exposure and died approximately 24h later. Necropsy showed classic signs of renal damage and gout. Diclofenac had a rapid plasma half-life of elimination of less than 2 hours indicating that toxicity was likely due to an irreversible destruction of a physiological process. All the birds in phase 2 had decreased uric acid, PAH and IOH clearance in comparison to phase 1. The decrease in PAH clearance was variable between the birds (average of 71%) but was near 98% reduced in the two birds that died. It is concluded that diclofenac alters both renal perfusion and renal plasma flow, with death associated with tubular secretion being reduced to negligible functionality for a prolonged period. This would support previous in vitro findings of early cell death from ROS accumulation. However, further evaluation is needed to elucidate this final step.

Corrigendum: Investigation of the acaricidal activity of the acetone and ethanol extracts of 12 South African plants against the adult ticks of Rhipicephalus turanicus.

No abstract available.

Corrigendum: Acaricidal activity of the aqueous and hydroethanolic extracts of 15 South African plants against Rhipicephalus turanicus and their toxicity on human liver and kidney cells.

No abstract available.

COVID-19 disaster management plans for two laboratory animal facilities in South Africa.

Policies and guidelines are available for acute disasters such as earthquakes, fire and floods, however, little is available on how laboratory animal facilities should mitigate subacute disasters like the COVID-19 pandemic that imposed major restrictions on the free movement of people. As such, laboratory animal facilities had to find plausible mitigating measures to safeguard the welfare of animals in their care, to prevent animal suffering if staff could not reach the animals, albeit with limited time. The simplest approach was to stop active experiments and halt animal breeding, or to euthanize all animals. Challenges with such methods included the ethical debate regarding euthanasia of animals at the start of a pandemic and the need to perform a harm-benefit analysis while drafting the disaster plans, termination of studies at advanced stages with information loss or killing of genetically modified strains that would be difficult to replace.Two research animal facilities in South Africa addressed these challenges by implementing several changes such as allowing only essential studies to continue, maintaining small breeding colonies for essential strains, and providing staff with private transport for travelling to and from work to avoid public transport and risk of exposure to SARS-CoV-2. Engineering changes included redesigning working areas to cater for social distancing.The mitigating measures put in place by the two laboratory animal facilities were successful in ensuring the continued welfare of animals during the COVID-19 lockdown restrictions. These measures can be adopted in future pandemics that lead to restricted movement of staff.Plans de gestion en cas de catastrophes telles que le COVID-19 pour deux installations d'animaux de laboratoire en Afrique du Sud.