Prospective study to evaluate incidence and indicators for early detection of ethambutol toxicity

AimsTo evaluate incidence of toxic optic neuropathy in patients receiving ethambutol (EMB) for 6 months and to identify its early indicators.MethodsWe included 50 patients on anti-tubercular therapy (ATT) including EMB (HRE regimen) based on total body weight for 6 months. Best-corrected visual acuity (ETDRS), colour vision (Ishihara pseudo-isochromatic plates), contrast sensitivity (Pelli-Robson chart), Humphrey visual field analysis (HVF 30-2 SITA FAST), pattern visual evoked response (VER) and spectral-domain optical coherence tomography (SDOCT) for ganglion cell inner plexiform layer (GCIPL) and retinal nerve fibre layer (RNFL) analysis were assessed at baseline and at 2, 4 and 6 months after starting ATT.ResultsMean age of the patients was 36.5±14.7 years with male:female ratio of 2.5:1. Mean daily dosage of EMB was 17.5±1.3 mg/kg/day. No significant change was observed in visual acuity, contrast sensitivity, color vision and mean or pattern SD on HVF at 6 months. Significant increase in VER latency of >2 SD (>125 ms) was observed in 46% eyes on follow-up indicating subclinical toxicity. Significant loss of mean RNFL (from 100.79±16.05 μm to 89.96±13.79 μm) and GCIPL thickness (from 83.1±5.60 μm to 79.85±6.45 μm) was observed at 6 months (p=0.001 for both). Patients with subclinical toxicity had significantly greater damage in temporal RNFL quadrant, supero-nasal and infero-nasal GCIPL sectors compared with others.ConclusionThe incidence of clinical EMB optic neuropathy was <2%, though subclinical damage in the form of increase in VER latency, and decrease in RNFL and GCIPL on OCT was seen in 46% eyes.

Prevalence of mimosine and DHP toxicity in cattle grazing Leucaena leucocephala pastures in Queensland, Australia

A postal survey of the level of awareness of leucaena toxicity and an on-farm study of the toxicity status of Queensland cattle herds grazing leucaena were conducted to investigate the prevalence of mimosine and dihydroxypyridine (DHP) toxicity in Queensland. In total, 195 of 356 graziers surveyed responded to the postal survey. Sixty-three percent had inoculated their cattle with in vitro Synergistes jonesii inoculum (produced in an anaerobic fermenter) and 30% of these had inoculated more than once. The remainder used inappropriate procedures. Many graziers (43%) had occasionally observed toxicity symptoms of hair loss and poor animal growth rates. In the on-farm study, the toxicity status of 385 animals in 44 individually managed herds on 36 properties was determined by urine analysis of mimosine and DHP concentrations. No animals were experiencing mimosine toxicity, based on low concentrations of this compound found in the urine. Using the criterion that average herd urine concentrations of DHP >100 μg/mL was indicative of subclinical toxicity, 48% of herds were exposed to subclinical toxicity due to dominant 3,4-DHP (21%) or dominant 2,3-DHP (27%) toxicity; many of these herds had been inoculated with S. jonesii and were thought to be protected. The finding that 27% of herds were excreting high concentrations of 2,3-DHP was unexpected. Statistical analysis of herd-management data revealed that the method used by graziers to inoculate their herds was significantly (P < 0.05) but weakly linked to herd protection status. It was concluded that subclinical 3,4-DHP and 2,3-DHP toxicity remains a problem in Queensland and is likely to be limiting animal production in a significant number of cattle grazing leucaena-grass pastures.

Incidence of subclinical toxicity in goats and dairy cows consuming leucaena (Leucaena leucocephala) in Thailand

A survey of the leucaena toxicity status in four major goat-producing provinces of Thailand where leucaena is fed as the principal dietary component was conducted. Three adjacent dairy farms in one province where leucaena silage was being fed were also sampled. Urine samples were collected from 63 animals on six goat farms and from 32 cows on three dairy farms. Samples were acidified, cleaned and analysed by high performance liquid chromatography for 3,4-DHP and 2,3-DHP concentrations, using a modified procedure developed at the University of Queensland. Total DHP concentrations varied from 375 to 3357 μg/mL on goat farms, and from 142 to 182 μg/mL on dairy farms. These concentrations are indicative of subclinical toxicity that might cause reduced feed intake and productivity. The impact of high DHP on productivity needs to be further studied because leucaena is a readily available source of high-protein forage for ruminant industries in Thailand.

Selenium concentration in the blood of ruminants grazing in northern New South Wales. 4. Relationship with tissue concentrations and wool production of Merino sheep

Relationships between selenium (Se) concentrations in blood and tissues, and between Se in blood or plasma and wool production were examined in fine-wool Merino ewes. Flock 1 contained 136 ewes, none of which were mated, and flock 2 contained 93 ewes which reared a lamb to weaning and 27 ewes which failed to lamb. Both flocks grazed Se deficient pastures, and were supplemented with varying quantities of sodium selenate given by mouth as aqueous solutions at 14-day intervals. Ewes in flock 1 were allocated to 17 and in flock 2 to 7 supplementation treatments, the range being from 0 to 8 mg Se/l4 days in both flocks. Wool production was measured before treatments were imposed, and for 2 years for flock 1 and 1 year for flock 2 after treatments were imposed. Samples of blood and plasma were taken at 3-monthly intervals from all sheep during the period of supplementation, and samples of liver, kidney and diaphragm were taken at the end of the experiment from sheep in flock 1; all samples were analysed for Se. Relationships between Se concentrations in blood, plasma or tissues and the quantity of supplementary Se given approached an asymptote at higher levels of supplementation, indicating that absorption or ultilization of Se were impaired at these levels; there was no evidence of clinical or subclinical toxicity. The asymptote was reduced in ewes which reared a lamb. Wool production generally increased when small quantities of supplementary Se were given, but there was no further response at higher levels, the greatest response of approximately 10% was observed in ewes which reared a lamb to weaning. Relationships between wool production, and blood, plasma and tissue Se concentrations were derived using a bent stick model which predicted that ewes would respond to supplementary Se when blood Se concentration was <O.022 to <0.076 8g Se/mL in the different groups; the higher values were observed in ewes rearing a lamb to weaning. The corresponding range in plasma was <0.014 to <0.044 8g Se/mL. It is suggested that Se concentrations <0.070 and <0.040 8g Se/mL in blood and plasma respectively indicate breeding ewes may respond to supplementation and could be used as guidelines for extension purposes; corresponding values for non-breeding sheep were <0.040 and <0.020 8g Se/mL respectively.

WEIGHT CHANGES IN CATTLE ON DRY RANGE IN RELATION TO CHEMICAL TREATMENTS FOR FLY CONTROL

The weight gains of yearling calves were analysed in a field experiment primarily designed to compare the distribution of flies among animals in two large herds, one unprotected and the other treated regularly for the control of biting flies. The treated animals received three applications of Co-Ral as a 0.5% wettable-powder suspension at 3-week intervals. Weight gains in the treated herd were lower by 6.5% of body weight as compared with the control herd. Weight gains increased in the treated herd after DDT was substituted for Co-Ral in the fly-control operation. The reduction in weight gains in the treated herd was attributed to subclinical toxicity of the organophosphate pesticide during repeated treatments.