In vivo emergence of high-level resistance during treatment reveals the first identified mechanism of amphotericin B resistance in Candida auris.

OBJECTIVE: Candida auris has emerged as a health-care-associated and multidrug-resistant fungal pathogen of great clinical concern. As many as 50% of C. auris clinical isolates are reported to be resistant to amphotericin B, but no mechanisms contributing to this resistance have been identified. Here we describe a clinical case in which high-level amphotericin B resistance was acquired in vivo during therapy and undertake molecular and genetic studies to identify and characterize the genetic determinant of resistance. METHODS: Whole-genome sequencing was performed on four C. auris isolates obtained from a single patient case. Cas9-mediated genetic manipulations were then used to generate mutant strains harbouring mutations of interest, and these strains were subsequently subjected to amphotericin B susceptibility testing and comprehensive sterol profiling. RESULTS: A novel mutation in the C. auris sterol-methyltransferase gene ERG6 was found to be associated with amphotericin B resistance, and this mutation alone conferred a >32-fold increase in amphotericin B resistance. Comprehensive sterol profiling revealed an abrogation of ergosterol biosynthesis and a corresponding accumulation of cholesta-type sterols in isolates and strains harbouring the clinically derived ERG6 mutation. CONCLUSIONS: Together these findings definitively demonstrate mutations in C. auris ERG6 as the first identified mechanism of clinical amphotericin B resistance in C. auris and represent a significant step forward in the understanding of antifungal resistance in this emerging public health threat.

Mutations in TAC1B: a Novel Genetic Determinant of Clinical Fluconazole Resistance in Candida auris.

Candida auris has emerged as a multidrug-resistant pathogen of great clinical concern. Approximately 90% of clinical C. auris isolates are resistant to fluconazole, the most commonly prescribed antifungal agent, and yet it remains unknown what mechanisms underpin this fluconazole resistance. To identify novel mechanisms contributing to fluconazole resistance in C. auris, fluconazole-susceptible C. auris clinical isolate AR0387 was passaged in media supplemented with fluconazole to generate derivative strains which had acquired increased fluconazole resistance in vitro Comparative analyses of comprehensive sterol profiles, [3H]fluconazole uptake, sequencing of C. auris genes homologous to genes known to contribute to fluconazole resistance in other species of Candida, and relative expression levels of C. aurisERG11, CDR1, and MDR1 were performed. All fluconazole-evolved derivative strains were found to have acquired mutations in the zinc-cluster transcription factor-encoding gene TAC1B and to show a corresponding increase in CDR1 expression relative to the parental clinical isolate, AR0387. Mutations in TAC1B were also identified in a set of 304 globally distributed C. auris clinical isolates representing each of the four major clades. Introduction of the most common mutation found among fluconazole-resistant clinical isolates of C. auris into fluconazole-susceptible isolate AR0387 was confirmed to increase fluconazole resistance by 8-fold, and the correction of the same mutation in a fluconazole-resistant isolate, AR0390, decreased fluconazole MIC by 16-fold. Taken together, these data demonstrate that C. auris can rapidly acquire resistance to fluconazole in vitro and that mutations in TAC1B significantly contribute to clinical fluconazole resistance.IMPORTANCECandida auris is an emerging multidrug-resistant pathogen of global concern, known to be responsible for outbreaks on six continents and to be commonly resistant to antifungals. While the vast majority of clinical C. auris isolates are highly resistant to fluconazole, an essential part of the available antifungal arsenal, very little is known about the mechanisms contributing to resistance. In this work, we show that mutations in the transcription factor TAC1B significantly contribute to clinical fluconazole resistance. These studies demonstrated that mutations in TAC1B can arise rapidly in vitro upon exposure to fluconazole and that a multitude of resistance-associated TAC1B mutations are present among the majority of fluconazole-resistant C. auris isolates from a global collection and appear specific to a subset of lineages or clades. Thus, identification of this novel genetic determinant of resistance significantly adds to the understanding of clinical antifungal resistance in C. auris.

An Azole-Tolerant Endosomal Trafficking Mutant of Candida albicans Is Susceptible to Azole Treatment in a Mouse Model of Vaginal Candidiasis.

We recently reported that a Candida albicans endosomal trafficking mutant continues to grow after treatment with the azole antifungals. Herein, we report that the vps21Δ/Δ mutant does not have a survival advantage over wild-type isolates after fluconazole treatment in a mouse model of vaginal candidiasis. Furthermore, loss of VPS21 does not synergize with established mechanisms of azole resistance, such as overexpression of efflux pumps or of Erg11p, the target enzyme of the azoles. In summary, although loss of VPS21 function enhances C. albicans survival after azole treatment in vitro, it does not seem to affect azole susceptibility in vivo.

Antifungal adjuvants: Preserving and extending the antifungal arsenal.

As the rates of systemic fungal infections continue to rise and antifungal drug resistance becomes more prevalent, there is an urgent need for new therapeutic options. This issue is exacerbated by the limited number of systemic antifungal drug classes. However, the discovery, development, and approval of novel antifungals is an extensive process that often takes decades. For this reason, there is growing interest and research into the possibility of combining existing therapies with various adjuvants that either enhance activity or overcome existing mechanisms of resistance. Reports of antifungal adjuvants range from plant extracts to repurposed compounds, to synthetic peptides. This approach would potentially prolong the utility of currently approved antifungals and mitigate the ongoing development of resistance.

Chronic treatment with a tryptophan-rich protein hydrolysate improves emotional processing, mental energy levels and reaction time in middle-aged women.

Common pharmacological treatments of mood disorders aim to modulate serotonergic neurotransmission and enhance serotonin levels in the brain. Brain serotonin levels are dependent on the availability of its food-derived precursor essential amino acid tryptophan (Trp). We tested the hypothesis that delivery of Trp via food may serve as an alternative treatment, and examined the effects of a Trp-rich, bioavailable dietary supplement from egg protein hydrolysate on cognitive and emotional functions, mood state, and sleep quality. In a randomised, placebo-controlled, parallel trial, fifty-nine mentally and physically healthy women aged 45-65 years received placebo (n 30) or the supplement (n 29) (both as 0.5 g twice per d) for 19 d. Emotional processing was significantly changed by supplementation, exhibiting a shift in bias away from negative stimuli. The results for the Affective Go/No-Go Task exhibited a slowing of responses to negative words, suggesting reduced attention to negative emotional stimuli. The results for the Facial Emotional Expression Rating Task also supported a shift away from attention to negative emotions and a bias towards happiness. An increase in arousal-like symptoms, labelled 'high energy', shorter reaction times and a slight benefit to sustained attention were observed in the treated subjects. Finally, when the supplement was taken 60-90 min before bedtime, a feeling of happiness before going to bed was consistently reported. In summary, daily consumption of a low-dose supplement containing bioavailable Trp may have beneficial effects on emotional and cognitive functions.

Contribution of clinically derived mutations in ERG11 to azole resistance in Candida albicans.

In Candida albicans, the ERG11 gene encodes lanosterol demethylase, the target of the azole antifungals. Mutations in ERG11 that result in an amino acid substitution alter the abilities of the azoles to bind to and inhibit Erg11, resulting in resistance. Although ERG11 mutations have been observed in clinical isolates, the specific contributions of individual ERG11 mutations to azole resistance in C. albicans have not been widely explored. We sequenced ERG11 in 63 fluconazole (FLC)-resistant clinical isolates. Fifty-five isolates carried at least one mutation in ERG11, and we observed 26 distinct positions in which amino acid substitutions occurred. We mapped the 26 distinct variant positions in these alleles to four regions in the predicted structure for Erg11, including its predicted catalytic site, extended fungus-specific external loop, proximal surface, and proximal surface-to-heme region. In total, 31 distinct ERG11 alleles were recovered, with 10 ERG11 alleles containing a single amino acid substitution. We then characterized 19 distinct ERG11 alleles by introducing them into the wild-type azole-susceptible C. albicans SC5314 strain and testing them for susceptibilities to FLC, itraconazole (ITC), and voriconazole (VRC). The strains that were homozygous for the single amino acid substitutions Y132F, K143R, F145L, S405F, D446E, G448E, F449V, G450E, and G464S had a ≥ 4-fold increase in FLC MIC. The strains that were homozygous for several double amino acid substitutions had decreased azole susceptibilities beyond those conferred by any single amino acid substitution. These findings indicate that mutations in ERG11 are prevalent among azole-resistant clinical isolates and that most mutations result in appreciable changes in FLC and VRC susceptibilities.

An international survey of nutritional practices in low- and middle-income countries: a report from the International Society of Pediatric Oncology (SIOP) PODC Nutrition Working Group.

BACKGROUND/OBJECTIVES: Optimal nutritional status is important in children with cancer, as it can influence clinical outcomes. To improve the nutritional health of children and adolescents receiving treatment for cancer residing in low income and middle-income countries (LMIC), we investigated nutrition practices among these nations' institutions providing treatment for childhood cancer. SUBJECT/METHODS: A cross-sectional survey of nutrition practice was administered to staff members at institutions providing treatment for children with cancer between 2011 and 2012. Countries classified as low income and middle income were divided by geographical region. Final analysis was performed with 96 surveys, which included 27 institutions from Asia, 27 institutions from Latin America and Caribbean, 27 institutions from Africa and 15 institutions from Europe. RESULTS: The study found that 55% of institutions had a dietician available on their service. Access to dieticians, lack of nutrition resources and lack of nutrition education of staff were the main barriers to providing nutrition care in LMIC. Half of the institutions performed nutritional assessment at diagnosis, and the methods used varied widely. Twenty-nine percent of all institutions used complementary and alternate therapies within their clinical practice, and 35% of institutions reported that nutrition education was provided to patients and families. CONCLUSIONS: Priority areas for improving the nutritional management in LMIC include the following: (1) improved nutrition education and assessment tools for doctors and nurses; (2) increased availability of nutrition education resources for families and patients; and (3) identification of the role of complementary and alternative therapies in closing gaps in symptom management in these institutions.

Effects of acute treatment with a tryptophan-rich protein hydrolysate on plasma amino acids, mood and emotional functioning in older women.

RATIONALE: Effective functioning of the neurotransmitter serotonin is important for optimal cognitive and emotional function. Dietary supplements able to increase availability to the brain of the precursor amino acid, tryptophan (TRP), and thereby enhance serotonin synthesis, can have measurable impact on these psychological processes. OBJECTIVES: This study involves a randomised controlled trial of a TRP-rich egg-white protein hydrolysate (DSM Nutritional Products Ltd., Switzerland) on plasma amino acids, cognition, mood and emotional processing in older women. METHODS: Following a baseline test day without treatment, 60 healthy women aged 45-65 years received drinks containing either 2 or 4 g of TRP-rich protein hydrolysate product or 3.11 g casein hydrolysate as a control. One hour later, they undertook a 2-h battery of cognitive and emotional tests. RESULTS: The TRP-rich protein hydrolysate produced the expected dose-dependent increase in the ratio of plasma TRP to competing large neutral amino acids. TRP-rich protein hydrolysate (2 g only) prevented both the decline in wellbeing and increase in fatigue seen over the test session in the control group. This treatment dose resulted in a significant shift in emotional processing towards positive words and reduced negative bias in assessing negative facial expressions. Effects on cognition were small and not statistically reliable and are not reported here. However, there was no evidence for any adverse effects. CONCLUSIONS: Consumption of a low dose of TRP-rich protein hydrolysate may have beneficial effects on emotional function that could promote feelings of wellbeing, possibly conferring resistance to deterioration in mood in healthy subjects or depressive episodes.

A comparison of the effect of mindfulness and relaxation on responses to acute experimental pain.

BACKGROUND: This study aimed to investigate the efficacy of mindfulness training in comparison with relaxation training on pain, threshold and tolerance during the cold pressor task. METHODS: Undergraduate psychology students (n = 140) were randomly assigned to receive reassuring or threatening information about the cold pressor. Participants were then re-randomized to receive mindfulness or a control intervention: relaxation training. RESULTS: Analyses confirmed that the threat manipulation was effective in increasing worry, fear of harm and expectations of pain, and reducing coping efficacy. Interaction effects revealed that mindfulness was effective in increasing curiosity and reducing decentring under conditions of high threat but not low threat. Other interactions on cognitive variables (attentional bias to pain and self-focus) confirmed that mindfulness and relaxation appeared to exert influences under different conditions (i.e. mindfulness: high threat; and relaxation: low threat). Despite these cognitive effects being discerned under different conditions, there were no differences between mindfulness and relaxation on pain, tolerance or threshold in either threat group. CONCLUSIONS: These results show that a single, brief session of mindfulness based on body scanning is not sufficient to change the way in which individuals approach an experimental pain task in comparison with relaxation, which has previously been shown to be ineffective.

Review and meta-analysis of the short-term effects of a vegetable oil emulsion on food intake.

Several short-term studies have investigated the effects of a vegetable oil emulsion on subsequent food intake, although findings have been inconsistent. This work aimed to review all studies, and investigate differences in study outcomes based on methodology. All known studies were identified. Data were abstracted from published studies (n = 7). Details of unpublished studies were gained from investigators/sponsors (n = 5), or were unavailable for reasons of confidentiality (n = 4). Available data were combined using meta-analyses. A combined appetite suppressant effect of the emulsion compared with control was found for test meal intake at approximately 4, 12 and 36 h post-treatment: smallest combined mean difference (random effects model) = 0.53 MJ (95% confidence interval 0.20, 0.86), P < 0.01. However, considerable heterogeneity (variability) between study results was also found (smallest I(2) = 94%, P < 0.01), questioning the predictive validity of the above findings. Meta-regression suggested this heterogeneity to be related to differences in the processed nature of the product, treatment dose and in particular year of study (smallest B = 0.54, 95% confidence interval 0.06, 1.03, P = 0.04), although again heterogeneity was found. The only consistent finding was a lack of effect on food intake 4 h post-preload in studies conducted after 2003. These results suggest a small but inconsistent appetite suppressant effect of the vegetable oil emulsion. However, due to the large heterogeneity, no definitive conclusions can be drawn.

Supplementation with a low-moderate dose of n-3 long-chain PUFA has no short-term effect on bone resorption in human adults.

Previous research suggests that n-3 PUFA may play a role in bone health. The present analysis aimed to investigate the impact of n-3 PUFA supplementation on bone resorption in adult men and women. Serum samples from 113 mild-moderately depressed individuals (twenty-six males and eighty-seven females, aged 18-67 years) randomised to receive 1·48 g EPA+DHA/d (n 53) or placebo (n 60) for 12 weeks as part of a large recent randomised controlled trial were assayed for n-3 PUFA status and a bone resorption marker, C-terminal cross-linking telopeptide of type 1 collagen (ß-CTX). Regression analyses revealed that n-3 PUFA status following supplementation was associated with randomisation (placebo/n-3 PUFA) (B = 3·25, 95 % CI 2·60, 3·91, P < 0·01). However, ß-CTX status following supplementation was not associated with randomisation (B = - 0·01, 95 % CI - 0·03, 0·04). Change in ß-CTX status was also not associated with change in n-3 PUFA status (B = - 0·002, 95 % CI - 0·01, 0·01). These findings provide no evidence for an association between n-3 PUFA supplementation (1·48 g EPA+DHA/d) for 12 weeks and bone resorption in humans assessed by ß-CTX, and suggest that n-3 PUFA supplementation may be unlikely to be of benefit in preventing bone loss.

A comparison of the effect of attention training and relaxation on responses to pain.

This study aimed to investigate the efficacy of an attention training technique (ATT) on pain ratings, threshold and tolerance during the cold pressor task. One hundred and three undergraduate students were randomly assigned to receive either threat-alleviating or threat-inducing information about the task. Participants were then re-randomized to receive either ATT or progressive muscle relaxation (PMR). Hence, the present study had a 2 (threat expectancy: high vs. low)x2 (training: ATT vs. PMR) design. Analyses confirmed that the threat manipulation was effective in increasing the harm associated with the task. ATT resulted in a relative reduction in hypervigilance to sensory pain words compared to PMR. ATT was also associated with a lower degree of focus on internal sensations, but not mindfulness or difficulty disengaging from pain words. Results showed that, relative to relaxation training, those receiving ATT reported pain less quickly than those receiving relaxation, although there were no differences between the training groups for tolerance or pain ratings. These results show that ATT changes the cognitive processes of internal/external focus and hypervigilance towards sensory pain words, but not difficulty disengaging or mindfulness. Although ATT changed threshold, the fact that neither pain ratings nor tolerance was affected suggests that a single, brief session of ATT may not be sufficient to affect broader change. Nonetheless, this study shows that ATT can change cognitive processes thought to be associated with heightened perception of pain and that this changes how quickly pain is registered and is therefore worthy of further investigation.

Flexible sigmoidoscopy and whole colonic imaging in the diagnosis of cancer in patients with colorectal symptoms.

BACKGROUND: The aim was to identify the patients with colorectal symptoms most likely to benefit from whole colonic imaging (WCI) to diagnose colorectal cancer and those for whom flexible sigmoidoscopy (FS) may be initially sufficient. METHODS: This prospective observational study (16 years) included 16 433 newly referred patients with symptoms or signs of colorectal cancer. RESULTS: Colorectal cancer was diagnosed in 946 patients (diagnostic yield 5.8 per cent), 815 (86.2 per cent) in the rectum or sigmoid (distal) and 131 (13.8 per cent) in the proximal colon. Some 15 829 patients (96.3 per cent) presented with symptoms alone (without iron deficiency anaemia or abdominal mass). Of 787 cancers in these patients, 750 (95.3 per cent) were distal. The prevalence of proximal cancer above and below the age of 60 years was 0.4 per cent (33 of 8249) and 0.1 per cent (four of 7580) respectively. Of 16 256 patients having FS, 5665 (34.8 per cent) had WCI. Of the other 10 591, five subsequently presented with proximal cancers. FS missed ten (1.3 per cent) of 796 cancers. CONCLUSION: Patients with iron deficiency anaemia or a mass require WCI. However, in patients with symptoms alone, FS detects 95 per cent of cancers, and the diagnostic yield of WCI after FS is very low. Alternative management strategies need to be developed to avoid unnecessary investigations in this low-risk group.

No clear evidence of an association between plasma concentrations of n-3 long-chain polyunsaturated fatty acids and depressed mood in a non-clinical population.

Previous research suggests that low n-3 long-chain polyunsaturated fatty acid (n-3PUFA) status is associated with higher levels of depression in clinical populations. This analysis aimed to investigate the relationship between depressed mood and n-3PUFA status in a non-clinical population. The analysis was conducted on data collected as part of a large randomized controlled trial investigating the impact of n-3PUFA supplementation on depressed mood in a community-based population. On entry into the trial, data on depressed mood were collected using the Depression, Anxiety and Stress Scales (DASS) and the Beck Depression Inventory (BDI). Plasma concentrations of various n-3PUFAs and n-6 long-chain polyunsaturated fatty acids (n-6PUFAs) were obtained from fasting venous blood samples, and various demographics were also measured. Using regression, there was no evidence of an association between either measure of depressed mood and any of the measures of n-3PUFA status or of n-6PUFA:n-3PUFA ratios. Clear associations were also not found when demographic factors were included in the analyses. These findings suggest that n-3PUFAs may not have a role in the aetiology of minor depression. This is also consistent with the results of other studies that have not demonstrated an association between depressed mood and n-3PUFA status in non-clinical populations and epidemiological studies that have not demonstrated an association between depressed mood and n-3PUFA intake in these populations.

Judgement of the quality of bowel preparation at screening flexible sigmoidoscopy is associated with variability in adenoma detection rates.

BACKGROUND AND STUDY AIMS: Adenoma detection rates (ADRs) at screening flexible sigmoidoscopy are known to vary between endoscopists. Variability in the technique used and in the quality of bowel preparation may explain this. The aim of this study was to establish whether there is a relationship between the grading of bowel preparation and the ADR. MATERIALS AND METHODS: The relationship between the ADR and assessment of bowel preparation was examined using the full United Kingdom Flexible Sigmoidoscopy Screening Trial data set (n = 38 601). The consistency of the bowel preparation classification was then investigated by six experienced endoscopists (video scorers), who examined 260 flexible sigmoidoscopy cases - 20 from each of the 13 trial endoscopists. RESULTS: Overall, the ADR was significantly higher in flexible sigmoidoscopy examinations with excellent or good bowel preparation ( P = 0.02). However, endoscopists with a higher ADR coded a smaller proportion of their examinations as having excellent/good preparation ( P = 0.002). Video scorers agreed with the trial endoscopists' definition of bowel preparation in 48.9 % of the readings, but they scored the quality of preparation as poorer than the trial endoscopists in 36.4 % and 40.6 %, respectively, in the intermediate-performance group (10 % < ADR < 14 %) and lower-performance group (ADR or =14 %). There was a significant linear trend between the proportion scored as having poor bowel preparation and the ADR ( P < 0.001), varying from 2.7 % in the higher-performance ADR group to 13.4 % in the lower-performance group. CONCLUSIONS: Endoscopists with a higher ADR are more likely to be critical of the quality of bowel preparation. Training in judgement processes such as non-acceptance of suboptimal bowel preparation is required in order to ensure universally high standards in screening procedures.

Genome-wide expression profiling reveals genes associated with amphotericin B and fluconazole resistance in experimentally induced antifungal resistant isolates of Candida albicans.

OBJECTIVES: The aim of this study was to identify changes in the gene expression profile of Candida albicans associated with the acquisition of experimentally induced resistance to amphotericin B and fluconazole. METHODS: C. albicans SC5314 was passed in increasing concentrations of amphotericin B to generate isolate SC5314-AR. Susceptibility testing by Etest revealed SC5314-AR to be highly resistant to both amphotericin B and fluconazole. The gene expression profile of SC5314-AR was compared with that of SC5314 using DNA microarray analysis. Sterol composition was determined for both strains. RESULTS: Upon examination of MICs of antifungal compounds, it was found that SC5314-AR was resistant to both amphotericin B and fluconazole. By microarray analysis a total of 134 genes were found to be differentially expressed, that is up-regulated or down-regulated by at least 50%, in SC5314-AR. In addition to the cell stress genes DDR48 and RTA2, the ergosterol biosynthesis genes ERG5, ERG6 and ERG25 were up-regulated. Several histone genes, protein synthesis genes and energy generation genes were down-regulated. Sterol analysis revealed the prevalence of sterol intermediates eburicol and lanosterol in SC5314-AR, whereas ergosterol was the predominant sterol in SC5314. CONCLUSION: Along with changes in expression of these ergosterol biosynthesis genes was the accumulation of sterol intermediates in the resistant strain, which would account for the decreased affinity of amphotericin B for membrane sterols and a decreased requirement for lanosterol demethylase activity in membrane sterol production. Furthermore, other genes are implicated as having a potential role in the polyene and azole antifungal resistant phenotype.

Identification of genes differentially expressed in association with reduced azole susceptibility in Saccharomyces cerevisiae.

OBJECTIVE: An isolate of S. cerevisiae with reduced susceptibility to fluconazole and itraconazole was developed in the laboratory and used to identify genes that are differentially expressed in association with this phenotype. METHODS: S. cerevisiae strain ATCC 9763 was passaged in increasing concentrations of itraconazole. Itraconazole and fluconazole MICs for the initial isolate (9763S) were 2 and 16 mg/L and for the final isolate (9763I) were 16 and > or =64 mg/L, respectively. Duplicate sets of total RNA from 9763S and 9763I were isolated and hybridized to Affymetrix S98 yeast arrays. To validate results, six differentially expressed genes were further examined by RT-PCR. RESULTS: Of the nearly 6400 open reading frames represented on the array, a total of 116 genes (1.8%) were found to be differentially expressed. Cell wall maintenance genes TIR4 and CCW12, sterol metabolism gene UPC2, small molecule transport genes AUS1 and YHK8, and stress response gene CUP1-1 were expressed at a level at least 2.5-fold higher than the expression level found in 9763S. Eleven energy generation genes, ionic homeostasis genes FRE1, FRE2 and FRE4, and sterol metabolism genes ERG8 and ERG13 were expressed at least 2.5-fold lower than the expression level found in 9763S. CONCLUSIONS: Several genes found to be differentially expressed in this study have been shown previously to be differentially expressed in the fungal response to azole treatment. In addition, the potential role of AUS1 and/or YHK8 as mediators of drug efflux is intriguing and warrants further study.

Sustainable veterinary medicine for the new era.

Sustainability aims to harmonise life on Earth without compromising the essential natural resources that should be the birthright of future generations. 'Sustainable medicine' (SM) is just one component of the wide range of possible sustainable approaches to peaceful co-existence. Sustainable medicine envisions an uncomplicated system of maintaining the health of people and animals, both now and for many years to come. This type of medicine is based on ancient wisdom, knowledge and healing arts, combined with the advantages and technical achievements of modern science and other areas of medicine; it is an integrated approach to preventive, safe and affordable healing. The term sustainable medicine also implies that the main therapeutic materials used in the course of practising this type of medicine can be replaced or replenished with minimal environmental damage after harvesting. The aim of sustainable medicine is to maintain the balance of nature, allowing an estimated 7 to 100 million species of life forms to co-exist and reproduce, and to sustain the long-term future of this planet. The world is in the midst of an environmental crisis: anthropogenic environmental damage in the last century was greater than in any previous century. One of the major concerns is the misuse of medicines, and the resulting immune depletion in people and animals. Many traditional medical systems have taught that appropriate adaptation by, and of, an effective defence system is the key to health and survival. This is only possible if priority is given to a preventive rather than a curative approach to health care; the very same approach that is advocated by proponents of SM: an approach based on proper diagnosis and the use of personalised, tailor-made medicine. The authors propose SM (the combination of the advantages of modern, traditional and complementary medical systems) as the best approach to providing better health care services for people and animals. The article presents a brief history of traditional medicines and outlines strategies for developing SM. The authors highlight some important factors in the development of SM in animal health care and attempt to encourage veterinarians to adopt a sustainable approach to treating animals.