Predictors of hepatotoxicity among patients treated with antituberculous medication.

INTRODUCTION: Hepatotoxicity in patients diagnosed with active tuberculosis (TB) is the commonest adverse effect of therapy. We sought to analyse trends in liver function in patients diagnosed with active TB and to determine predictors of hepatotoxicity. METHODS: We studied 275 patients with active TB treated at the Mercy University Hospital (Cork, Ireland) from 2009 to 2014 A retrospective review was undertaken of all patients' laboratory data and patient correspondence to determine predictors of hepatotoxicity. RESULTS: A total of 170 (62%) male and 105 (38%) female patients with active TB with a mean age of 44 years were studied. In total 15 patients (6%) required their medication to be stopped or altered as a consequence of hepatotoxicity. There was a significant difference in age between patients with hepatotoxicity (52.95 years) and those that didn't develop hepatotoxicity (41.33 years) ( P ≤ 0.01). Irish born patients were more likely to develop hepatotoxicity ( P = 0.025). There was no significant association between hepatotoxicity, illicit drug use ( P = 0.211), smoking ( P = 0.95), cavitatory disease ( P = 0.191), site of disease ( p = 0.224), alcohol use ( P = 0.088) or history of alcohol excess ( p = 0.736). Among patients with TB, peak AST values did not occur within the first 2 weeks as widely thought but later (week 10). CONCLUSION: Our study shows hepatotoxicity as a consequence of antituberculous therapy is common. Hepatotoxicity was more common in older patients and Irish born patients, and resulted in drug interruptions and treatment changes. Given the late peak in AST values at week 10 in patients treated with antituberculous therapy, the authors advocate that liver function tests should be monitored regularly throughout the course of treatment.

Reference dosimetry in magnetic fields: formalism and ionization chamber correction factors.

PURPOSE: Magnetic resonance imaging-guided radiotherapy (MRIgRT) provides superior soft-tissue contrast and real-time imaging compared with standard image-guided RT, which uses x-ray based imaging. Several groups are developing integrated MRIgRT machines. Reference dosimetry with these new machines requires accounting for the effects of the magnetic field on the response of the ionization chambers used for dose calibration. Here, the authors propose a formalism for reference dosimetry with integrated MRIgRT devices. The authors also examined the suitability of the TPR10 (20) and %dd(10)x beam quality specifiers in the presence of magnetic fields and calculated detector correction factors to account for the effects of the magnetic field for a range of detectors. METHODS: The authors used full-head and point-source Monte Carlo models of an MR-linac along with detailed detector models of an Exradin A19, an NE2571, and several PTW Farmer chambers to calculate magnetic field correction factors for six commercial ionization chambers in three chamber configurations. Calculations of ionization chamber response (performed with geant4) were validated with specialized Fano cavity tests. %dd(10)x values, TPR10 (20) values, and Spencer-Attix water-to-air restricted stopping power ratios were also calculated. The results were further validated against measurements made with a preclinical functioning MR-linac. RESULTS: The TPR10 (20) was found to be insensitive to the presence of the magnetic field, whereas the relative change in %dd(10)x was 2.4% when a transverse 1.5 T field was applied. The parameters chosen for the ionization chamber calculations passed the Fano cavity test to within ∼0.1%. Magnetic field correction factors varied in magnitude with detector orientation with the smallest corrections found when the chamber was parallel to the magnetic field. CONCLUSIONS: Reference dosimetry can be performed with integrated MRIgRT devices by using magnetic field correction factors, but care must be taken with the choice of beam quality specifier and chamber orientation. The uncertainties achievable under this formalism should be similar to those of conventional formalisms, although this must be further quantified.

Small field detector correction factors kQclin,Qmsr (fclin,fmsr) for silicon-diode and diamond detectors with circular 6 MV fields derived using both empirical and numerical methods.

PURPOSE: The use of radiotherapy fields smaller than 3 cm in diameter has resulted in the need for accurate detector correction factors for small field dosimetry. However, published factors do not always agree and errors introduced by biased reference detectors, inaccurate Monte Carlo models, or experimental errors can be difficult to distinguish. The aim of this study was to provide a robust set of detector-correction factors for a range of detectors using numerical, empirical, and semiempirical techniques under the same conditions and to examine the consistency of these factors between techniques. METHODS: Empirical detector correction factors were derived based on small field output factor measurements for circular field sizes from 3.1 to 0.3 cm in diameter performed with a 6 MV beam. A PTW 60019 microDiamond detector was used as the reference dosimeter. Numerical detector correction factors for the same fields were derived based on calculations from a geant4 Monte Carlo model of the detectors and the Linac treatment head. Semiempirical detector correction factors were derived from the empirical output factors and the numerical dose-to-water calculations. RESULTS: The PTW 60019 microDiamond was found to over-respond at small field sizes resulting in a bias in the empirical detector correction factors. The over-response was similar in magnitude to that of the unshielded diode. Good agreement was generally found between semiempirical and numerical detector correction factors except for the PTW 60016 Diode P, where the numerical values showed a greater over-response than the semiempirical values by a factor of 3.7% for a 1.1 cm diameter field and higher for smaller fields. CONCLUSIONS: Detector correction factors based solely on empirical measurement or numerical calculation are subject to potential bias. A semiempirical approach, combining both empirical and numerical data, provided the most reliable results.

Performance of diagnostic tests for bovine tuberculosis in North American furbearers and implications for surveillance.

Risks of bovine tuberculosis (bTB) transmission from free-ranging wildlife to livestock remain a concern in the United States, in both known endemic areas and where spillover from recently-infected livestock herds occurs. Federal agriculture officials in the United States (US) have recommended surveillance of non-cervid furbearers to determine whether free-ranging wildlife in the vicinity of cattle herd breakdowns are bTB infected, yet the efficacy of common diagnostic tests in these species is largely unknown. We calculated the sensitivity, specificity, predictive values and positive likelihood ratios for bTB infection in carcasses of sixteen species of furbearers tested via: (i) the presence of gross lesions compatible with bTB; (ii) histopathology consistent with bTB; and (iii) the presence of acid-fast bacilli (AFB) on histopathology. The gold standard comparison test was mycobacterial culture of cranial ± visceral lymph nodes pooled for each animal. Forty-two animals distributed across six species cultured bTB positive from among 1522 furbearers tested over thirteen years. The sensitivity of all three tests was poor (10%, 22% and 24% for gross lesions, AFB and histopathology, respectively), while specificities (all ≥ 99%) and negative predictive values (all ≥ 97%) were high. Positive predictive values varied widely (31-75%). Likelihood ratios for culture positivity given a positive test result showed AFB on histopathology to be the most reliable test, and gross lesions the least, though confidence intervals were wide and overlapping. While non-cervid furbearers may prove useful in North American bTB surveillance, wildlife managers should be aware of factors that may abate their utility and complicate interpretation of surveillance.

Distribution of eastern equine encephalomyelitis viral protein and nucleic acid within central nervous tissue lesions in white-tailed deer (Odocoileus virginianus).

An outbreak of eastern equine encephalomyelitis (EEE) occurred in Michigan free-ranging white-tailed deer (Odocoileus virginianus) during late summer and fall of 2005. Brain tissue from 7 deer with EEE, as confirmed by reverse transcriptase polymerase chain reaction, was studied. Detailed microscopic examination, indirect immunohistochemistry (IHC), and in situ hybridization (ISH) were used to characterize the lesions and distribution of the EEE virus within the brain. The main lesion in all 7 deer was a polioencephalomyelitis with leptomeningitis, which was more prominent within the cerebral cortex, thalamus, hypothalamus, and brainstem. In 3 deer, multifocal microhemorrhages surrounded smaller vessels with or without perivascular cuffing, although vasculitis was not observed. Neuronal necrosis, associated with perineuronal satellitosis and neutrophilic neuronophagia, was most prominent in the thalamus and the brainstem. Positive IHC labeling was mainly observed in the perikaryon, axons, and dendrites of necrotic and intact neurons and, to a much lesser degree, in glial cells, a few neutrophils in the thalamus and the brainstem, and occasionally the cerebral cortex of the 7 deer. There was minimal IHC-based labeling in the cerebellum and hippocampus. ISH labeling was exclusively observed in the cytoplasm of neurons, with a distribution similar to IHC-positive neurons. Neurons positive by IHC and ISH were most prominent in the thalamus and brainstem. The neuropathology of EEE in deer is compared with other species. Based on our findings, EEE has to be considered a differential diagnosis for neurologic disease and meningoencephalitis in white-tailed deer.

First isolation and outbreak of OXA-48-producing Klebsiella pneumoniae in an Irish hospital, March to June 2011.

Five OXA-48-producing Klebsiella pneumoniae were detected in a tertiary referral hospital in Ireland between March and June 2011. They were found in the clinical isolates of five cases that were inpatients on general surgical wards. None of the cases had received healthcare at a facility outside of Ireland in the previous 12 months. This is the first report of OXA-48-producing K. pneumoniae in Ireland.

Lymphovascular space involvement in early stage well-differentiated endometrial cancer is associated with increased mortality.

OBJECTIVE: To study the relationship between lymphovascular space involvement (LVSI) in stage 1a or 1b well-differentiated endometrial cancer and survival. DESIGN: Retrospective study consisting of a search of an oncology database to identify women with endometrial cancer between January 1990 and December 2004. SETTING: Tertiary referral centre, Dublin, Ireland. SAMPLE: Women who had well-differentiated stage 1a or 1b endometrial cancer. METHODS: During the period 1990-2004, 226 patients with endometrial cancer were treated in the National Maternity Hospital, Dublin. We looked at all patients who had well-differentiated endometrioid adenocarcinoma of the endometrium with invasion of <50% thickness of the myometrium. Forty-one patients fulfilled these inclusion criteria. The presence or absence of LSVI was determined by review of haematoxylin and eosin sections. Patients were followed for 5 years or till death if earlier. Mortality was calculated. Statistical analysis was performed using Fisher's exact test. An odds ratio and 95% confidence interval was calculated using fixed effect Mantel-Haenszel model. MAIN OUTCOME MEASURES: Death from recurrence of endometrial cancer. RESULTS: Of the 41 patients, five (12%) were found to have (LVSI). Of the five patients with LVSI, three (60%) patients died of recurrence. All patients with recurrence died of disease and none of the patients without LVSI died (0 of 36). Overall, the survival rate was 92.7%. The presence of LVSI was a highly significant predictor of recurrence (P < 0.001). CONCLUSION: In patients with early stage well-differentiated adenocarcinoma of the endometrium, the presence of LVSI is associated with a high risk of death.

Milk leptin in sows and blood leptin and growth of their offspring.

Twenty-one mixed-parity (average 2.4 +/- 0.49) crossbred sows and their offspring were used to determine whether sow milk leptin at farrowing was related to neonatal serum leptin and pig growth to weaning. During farrowing, pigs were randomly allotted to suckling (n = 99) or delayed suckling (n = 89) groups, with delayed suckling pigs placed in a group pen apart from the dam before suckling. Both groups had access to heat lamps. Colostrum samples were collected no more than 2 h after farrowing the first pig. Blood samples were collected from all pigs approximately 2 h after farrowing was complete; pigs were then ear notched and returned to their dams. Pig BW was recorded at 1.2 +/- 0.04 d of age and again at weaning. Milk and blood serum were collected after centrifugation; leptin concentrations were estimated using RIA. Leptin was detected in colostral milk, as expected, and averaged 46.0 +/- 1.1 ng/mL. Pig serum leptin (P < 0.02) was greater in suckling pigs than in delayed suckling pigs, averaging 0.69 +/- 0.08 and 0.54 +/- 0.07 ng/mL, respectively. Although male pigs were heavier (P < 0.01) at birth than female pigs (1,507 +/- 52 vs. 1,381 +/- 43 g), ADG to weaning and weaning weights were similar for both sexes, averaging 229 +/- 14 g and 5,829 +/- 323 g, respectively, for all pigs; serum leptin concentrations were not affected by sex of the pig. Milk serum leptin was not associated with litter size, parity, pig birth weight, ADG to weaning, or weaning weight. Suckling status did not influence ADG to weaning or weaning weight of pigs; neonatal pig serum leptin was not related to birth weight, weaning weight, or ADG to weaning. These results indicate that leptin is not directly related to early neonatal growth in the pig; however, more in-depth studies are needed to determine possible indirect or long-term effects of early leptin exposure.

Animal-side serologic assay for rapid detection of Mycobacterium bovis infection in multiple species of free-ranging wildlife.

Numerous species of mammals are susceptible to Mycobacterium bovis, the causative agent of bovine tuberculosis (TB). Several wildlife hosts have emerged as reservoirs of M. bovis infection for domestic livestock in different countries. In the present study, blood samples were collected from Eurasian badgers (n=1532), white-tailed deer (n=463), brushtail possums (n=129), and wild boar (n=177) for evaluation of antibody responses to M. bovis infection by a lateral-flow rapid test (RT) and multiantigen print immunoassay (MAPIA). Magnitude of the antibody responses and antigen recognition patterns varied among the animals as determined by MAPIA; however, MPB83 was the most commonly recognized antigen for each host studied. Other seroreactive antigens included ESAT-6, CFP10, and MPB70. The agreement of the RT with culture results varied from 74% for possums to 81% for badgers to 90% for wild boar to 97% for white-tailed deer. Small numbers of wild boar and deer exposed to M. avium infection or paratuberculosis, respectively, did not cross-react in the RT, supporting the high specificity of the assay. In deer, whole blood samples reacted similarly to corresponding serum specimens (97% concordance), demonstrating the potential for field application. As previously demonstrated for badgers and deer, antibody responses to M. bovis infection in wild boar were positively associated with advanced disease. Together, these findings suggest that a rapid TB assay such as the RT may provide a useful screening tool for certain wildlife species that may be implicated in the maintenance and transmission of M. bovis infection to domestic livestock.

A study of helminth parasites in culled cows from Ireland.

The objective of this study was to determine the prevalence and intensity of gastrointestinal nematode, lungworm and liver fluke infection in culled cows in Ireland. Abomasa, colorectal contents and livers were collected from 30 to 68 culled beef and dairy cows during autumn 2002 and summer 2003, respectively. Ostertagia ostertagi were found in the abomasa of only three (10%) cows sampled in autumn and in 38 (57%) cows examined in summer. The majority of positive animals had low burdens of O. ostertagi but a few individuals in the group sampled during the summer had a moderate infection (5000-10,000 adult worms). A proportion of the cows in the summer group were also co-infected with small numbers of Trichostrongylus axei. Cooperia oncophora predominated in the recoveries from the larval cultures although O. ostertagi were also recovered. The overall prevalence of Dictyocaulus viviparus was 14%, based on larval identification in faecal samples. Liver fluke, or varying degrees of pathology attributable to Fasciola hepatica, were present in 65% of the livers. The results of this study extend those of previous workers, which were largely limited to dairy cows alone and which focussed on gastrointestinal nematodes and did not include simultaneous infections with lungworm and liver fluke. It was concluded, from the level of polyparasitism evident in this study, that adult cattle should be considered in preventative approaches to bovine helminthosis.

Mycobacterium bovis (bovine TB) exposure as a recreational risk for hunters: results of a Michigan Hunter Survey, 2001.

SETTING: Tuberculosis caused by Mycobacterium bovis (bovine TB) is endemic in the white-tailed deer population of north-eastern Michigan. Hunters may be exposed to M. bovis via cutaneous inoculation while field dressing deer or by ingestion of undercooked venison. Michigan hunters have received inconsistent messages about their risk of acquiring tuberculosis from recreational exposure to deer. The most common health advice offered has been to wear gloves while field dressing deer and to cook venison products thoroughly. OBJECTIVE: Data were collected to quantify these self-protective activities and to characterize hunters practicing these activities. DESIGN: In 2001, we surveyed 1833 hunters who had successfully harvested deer in or near Michigan's bovine TB endemic area in 2000. RESULTS: The survey response rate was 78%. Most hunters (89%) reported field dressing deer, 43% of whom wore gloves. Most hunters (95%) reported eating venison, 55% of whom reported their venison was always cooked thoroughly. Several hunter characteristics, including older age, female sex, higher awareness level, and area of residence, were significantly associated with the practice of these self-protective activities. CONCLUSION: The survey results suggest that hunters should receive consistent advice encouraging glove use while field dressing deer and the thorough cooking of venison products before consumption.

Tuberculosis in free-ranging wildlife: detection, diagnosis and management.

Mycobacterium bovis is emerging as an important pathogen of free-ranging wildlife in which it is a potential source of infection for domestic animals and a threat to valuable wildlife species. This review examines the procedures for the detection, diagnosis and management of M. bovis in wildlife populations. The ante-mortem detection of M. bovis infection in wildlife is difficult, due to the common occurrence of subclinical infections and the deficiencies of the currently available diagnostic tests. Serological tests are insensitive, while tests measuring cell-mediated immune responses show promise, but have not been sufficiently developed for routine use in most species. The diagnosis of M. bovis in free-ranging wildlife relies on post-mortem examination supported by histopathology and microbiology. A feature of M. bovis infections is the variation in the appearance and distribution of lesions in the different host species. Bacterial culture remains the gold standard for diagnosis of tuberculosis, while histopathology is limited by the frequent inability to distinguish lesions caused by M. bovis from those produced by other mycobacterial species. Deoxyribonucleic acid (DNA) fingerprinting and advanced typing techniques are increasingly being used to unravel the epidemiology of mycobacterial infections, including tuberculosis in free-ranging wildlife. An understanding of the epidemiology is essential if procedures are to be developed for the management of tuberculosis in wildlife. Few management options are currently available, especially for protected wildlife. Vaccination is the subject of much research, but further developments are required before it can be used to control tuberculosis in any animals, let alone in free-ranging wildlife.

Unilateral vs. bilateral ultrasound in the monitoring of cerebral microemboli.

We used bilateral transcranial Doppler to monitor the number of microembolic events (ME) in the left and right middle cerebral arteries of 29 patients during cardiac surgery that required extracorporeal circulation. Based on a previously published study, we hypothesized that the commonly used method of doubling unilateral ME counts to obtain an estimated bihemispheric load would result in significant errors of estimation. In our sample, estimated bihemispheric counts were inaccurate by an average of 18% (range 0--80%). Despite this large range of error, calculation of Cronbach's alpha revealed that actual error due to unreliability (4%) was small relative to the large variation in ME counts across subjects in this patient series. These findings suggest that unilateral monitoring is sufficient when the goal is to characterize a given subject's ME load within the context of the other subjects in the sample. However, when precise ME counts are required, bilateral monitoring is essential.

Tuberculous lesions in free-ranging white-tailed deer in Michigan.

Descriptions of the anatomical distribution of Mycobacterium bovis gross lesions in large samples of white-tailed deer (Odocoileus virginianus) are lacking in the scientific literature. This report describes the distribution of gross lesions in the 58 white-tailed deer that cultured positive for M. bovis among the 19,500 submitted for tuberculosis testing in Michigan (USA) in 1999. For the vast majority (19,348) of those tested, only the head was submitted; for others, only extracranial tissues (33) or both the head and extracranial tissues (119) were available. Among those deer that cultured positive, cranial gross lesions were noted most frequently in the medial retropharyngeal lymph nodes, although solitary, unilateral parotid lymph node lesions also were found. Extracranial lesions occurred most commonly in the thorax. The distribution of lesions largely agreed with the few existing case reports of the M. bovis in white-tailed deer, although gross lesions were also found in sites apparently not previously reported in this species (liver, spleen, rumen, mammary gland). Some practical issues that may assist future surveillance and public education efforts are also discussed.

Spatial and temporal comparison of selected cancers in dogs and humans, Michigan, USA, 1964-1994.

Our aim was to investigate the geographic and time distributions of some biologically similar neoplasms in dogs and humans living in Michigan, USA, between 1964 and 1994. Our objective was to describe and compare the patterns of cancer in the two species while assessing the strength and dependence of those patterns. In this retrospective, registry-based study, histologically confirmed incident human and canine cancer cases were mapped, and second-order (K function) spatial analysis and one-dimensional nearest neighbor temporal analysis were performed on residence addresses and dates of hospital discharge/diagnosis. Included in the study were all 528 incident cases of canine lymphosarcoma, mammary adenocarcinoma, melanoma and spindle-cell sarcomas diagnosed at a veterinary teaching hospital between 1964 and 1994 having residence addresses in Ingham, Oakland, and Wayne Counties; and a stratified random sample of 913 incident human cases of comparable cancers diagnosed during the same time period from the same counties. Results suggest that processes determining spatial aggregation of cases in dogs and humans were not independent of each other, did not act uniformly over different geographic areas, operated at spatial scales <2000 m regardless of species, and tend to act upon dogs more strongly at shorter distances than on humans. Little evidence of interspecies concurrence of temporal clustering was found.

Subsequent pulmonary embolism: risk after a negative helical CT pulmonary angiogram--prospective comparison with scintigraphy.

PURPOSE: To determine whether a helical computed tomographic (CT) scan that is negative for pulmonary embolism (PE) is a sufficiently reliable criterion to safely withhold anticoagulation therapy. MATERIALS AND METHODS: Patients with negative helical CT scans were prospectively compared with patients with negative or low-probability scintigrams. In a 460-bed university hospital and clinic, 1,015 adult patients underwent either scintigraphy or helical CT for possible PE for 25 months. Five hundred forty-eight patients who had negative images and were not receiving anticoagulation therapy were prospectively followed up for 3 months for clinical, new imaging, death certificate, or autopsy evidence of subsequent PE. Ninety-seven patients were lost to follow-up. RESULTS: Subsequent PE was found in two (1.0%) of 198 patients with negative CT scans, none of 188 patients with negative ventilation-perfusion (V-P) scans, and five (3.1%) of 162 patients with low-probability V-P scans (not statistically significant). Patients in the helical CT group were hospitalized more often, had more severe disease, had more substantial PE risk factors, and had a higher death rate. No deaths were attributed to PE in either group. CONCLUSION: The frequency of clinical diagnoses of PE after a negative CT scan was low and similar to that after a negative or low-probability V-P scan. Helical CT is a reliable imaging tool for excluding clinically important PE.

Spatial and temporal distribution of selected canine cancers in Michigan, USA, 1964-1994.

Although rates are commonly used to compare regional disease occurrence, rate-independent methods might also be useful in circumstances where geographic occurrence of a disease is known, but calculation of disease rates is not feasible. This is frequently the case for diseases in companion animals, where accurate enumeration of populations-at-risk is often arduous. This study had two objectives: to demonstrate a rate-independent method for investigating disease aggregation in companion animals; and, to assess the spatial and temporal clustering of canine cases of four cancers that are biologically similar in dogs and humans. Geographic information systems and point-pattern analysis were used to assess the spatial and temporal clustering of incident cases of four types of canine cancer in three counties in Michigan between 1964 and 1994, and to generate hypotheses concerning disease aggregation. Significant (P < or = 0.01) spatial clustering was found that varied by county and cancer type. No definitive temporal patterns could be deduced from a temporal analysis of the cases of canine cancer in this study. These results demonstrate distance-based methods for assessing clustering of disease, and suggest that processes determining the aggregation of canine cancer cases do not act in a spatially uniform manner.

Treatment and prophylaxis of psoroptic mange (sheep scab) using an ivermectin intraruminal controlled-release bolus for sheep.

In an experiment to determine the therapeutic efficacy of an ivermectin intraruminal controlled-release (CR) bolus, 14 mixed breed sheep of one lot were infested with Psoroptes ovis and subsequently divided into two groups of seven. In one of these groups each sheep received one ivermectin CR bolus appropriate to its weight, the other group remained as an untreated control. All mites were eliminated from the group receiving the bolus while the control group remained infested, the disease progressed, and all but one sheep required treatment for psoroptic mange before the end of the experimental period. A second lot of 14 sheep, free from P. ovis, were divided equally into two groups to determine the prophylactic efficacy of the ivermectin CR bolus. In one group, each sheep was given an ivermectin CR bolus according to body weight and the sheep in the other group received no medication and served as untreated controls. Twenty-one days later two sheep infested with psoroptic mange were introduced into each of the groups. These donor sheep were removed 10 days later. The group treated with the ivermectin CR bolus remained mange-free and did not harbour any mites. All of the sheep in the control group developed psoroptic mange and required treatment to control the infestation at the end of the experimental period. Sheep that received the ivermectin CR bolus had greater mean weight gains than the control groups in these experiments. The ivermectin CR bolus releases a minimum dose of 20 microg ivermectin kg/day for 100 days: this prolonged activity should prove a valuable asset for the treatment and control of psoroptic mange in sheep.

Treatment of psoroptic mange with reference to epidemiology and history.

Treatment methods in the last century involved the use of substances such as sulphur, mercury, hellebore, arsenic, nicotine and others, applied in various ways. The advent of dips in 1843 signalled an advance. However, the biology of the mite, Psoroptes ovis, the epidemiology of sheep scab and the lack of persistence of the acaricides necessitated repeated laborious treatments to ensure success. In 1947 this changed with the use of organo chlorines (OCs) which had up to 3 months residual activity. The use of OCs led to the eradication of psoroptic mange of sheep in USA. Organo phosphates (OPs) were introduced in the late fifties and synthetic pyrethroids (SPs) in the early seventies. In 1985, due to sheep tissue residues, lindane (OC) was withdrawn from the market and this greatly reduced the capacity for effective sheep scab control. Before the arrival of the endectocidal avermectin, ivermectin in 1978 and its successful use as an acaricide in 1992, control of psoroptic mange was limited to plunge dipping. In 1994 moxidectin, a milbemycin, was found to be effective and to have the added benefit of at least 4 weeks persistent activity. Another avermectin doramectin was shown, in 1995, to successfully treat scab and recently an ivermectin bolus has been introduced which has a 100 days' activity and is fully therapeutic and prophylactic. Strict attention to detail in the use of injectable products is essential in order to achieve satisfactory results. Work is progressing on the use insect growth regulators (IGRs) and also on naturally occurring substances such as linalool, neem and lavender oil. At the CVRL Dublin, promising results have been achieved with neem and some IGRs. Other areas of interest are allemones, synergists, microclimate manipulation, sheep breed resistance and vaccines. Successful control depends on epidemiological knowledge, accurate diagnostic techniques, intimate knowledge of the mite's life cycle, its behaviour on and off the host, its macro and molecular biology, the nature of the pathogenesis of the disease, sheep husbandry practices, nutritional and environmental factors; also farmer awareness and attitudes. The variable responses of sheep to the mite, the unpredictable incubation period, course, manifestations and outcome make this an intriguing and perplexing disease. Ways to overcome these problems and to achieve possible eradication are discussed.