Organophosphate sheep dip: clinical aspects of long-term low-dose exposure

Report of a joint working party of the Royal College of Physicians and Royal College of Psychiatrists

This report, published in November 1998, was commissioned by the Department of Health. The report includes sections on: the toxicology of OPs; evidence given by patients, support groups and doctors on symptoms, diagnosis and management; and an analysis of clinical symptoms. The report makes recommendations on diagnosis, the management of patients, patient facilities and further research. It can be obtained from the Publications Department, Royal College of Physicians of London, 11 St Andrews Place, Regent's Park, London NW1 4LE.

Summary of the report

Preface

The Royal College of Physicians and Royal College of Psychiatrists set -up a working party on organophosphate (OP) sheep dip exposure with a widely drawn membership to hear evidence from sufferers, from those representing them, and from experts in this field, with the following terms of reference:

1. To advise on clinical management of patients with symptoms which may be attributable to chronic OP sheep dip exposure.
2. To review any new clinical evidence and bring it to the attention of the Medical and Scientific Panel of the Veterinary Products Committee and the Advisory Committee on Pesticides.
3. To advise on how to undertake clinical studies recommended by the Medical and Scientific Panel of the Veterinary Products Committee.

Background

Organophosphate pesticides, which are widely used in treating crops and farm animals, exert their toxic effects on insects and mammals mainly by their ability to inhibit cholinesterases. Depending on the degree of exposure, the effects can be widespread involving the central, peripheral and, particularly, the autonomic nervous systems. Acute toxic reactions in human subjects may include dizziness, blurred vision, abdominal symptoms, abnormalities of cardiac and voluntary muscle function and, in severe cases, confusion, convulsions, cardiac rhythm abnormalities and death. An intermediate syndrome may occur,typically at 1-4 days after exposure (characterised by proximal muscle paralysis), and a delayed polyneuropathy at 2-4 weeks (characterised by motor and sensory deficits prin- cipally affecting the legs).

Evidence that long-term low dose exposure - either episodic as in OP sheep dipping by farmers or continuous in professional sheep dippers - causes chronic sequelae is currently the subject of much research. Abnormalities identified in some - but not all - studies include subtle cognitive impairment (eg impaired attention and reaction times), greater psychiatric morbidity and minor sensory changes. How OPs might cause such effects is unknown. These population-based studies suffer from a number of methodological weaknesses such as small numbers, poor response rates, limited or absent information on the extent of acute exposures to different OPs, selection bias and inappropriate or questionable control subjects all of which could affect the outcome of the study, limit its power to reveal an effect and influence the interpretation of the results. Moreover, the biological significance of some of the tests used is not clear. The possibility that a bias exists against publishing negative studies in this field cannot be excluded.

Evidence received concerning symptoms

The working party received oral and written evidence from sufferers who had experienced OP sheep dip associated symptoms, and from OP sheep dip patient support groups. In addition to 'dipper's flu', a wide range of symptoms was described, many of which were severe; for example headache, limb pains, fatiguability, sleep disturbance, poor concentration, mood change and suicidal thoughts. The symptoms were often so distressful that sufferers were forced to stop working with serious consequences for their families.

Analysis of clinical symptoms

The symptoms and the distress are genuine, and can continue for a long time; some individuals seriously contemplate suicide. Studies on OP-exposed populations have shown subtle cognitive changes, suggesting that OPs may underlie some of the symptoms experienced. Other possible explanations for the symptoms are naturally occurring illnesses, for example severe anxiety or depression, which have been intuitively attributed by the sufferer to OP exposure. Exposure to potentially harmful circumstances or to products that differ widely in terms of their physical nature or chemical composition can, nevertheless, result in a relatively similar group of symptoms. To elucidate the role of OPs in these symptoms, further studies will be needed. Meanwhile, the severity of the symptoms, and the consequent disruption to family life and to work, make it essential to provide an adequate level of clinical care for those who experience symptoms following OP sheep dip exposure.

Evidence received concerning diagnosis and management

Existing clinical services do not, in the main, provide satisfactory management for those with symptoms associated with OP sheep dip exposure. In part, this may be because of current uncertainty regarding the cause of the symptom. Although some sufferers were helped by treatment strategies offered by NHS practitioners or by those in the private sector (although in the latter case often expensive), there is currently no objective evidence-based justification for their use.

RECOMMENDATIONS

Patients seeking advice for symptoms associated with OP sheep dip exposure usually turn first to their family doctor, the Health and Safety Executive or clinical centres of the National Poisons Information Service. This initial consultation requires sympathetic handling; the patient's symptoms must be treated seriously. A detailed clinical history and examination are essential. Some basic laboratory tests are useful, and blood acetylcholinesterase levels can be measured if the exposure to OPs is recent. The temptation to over-investigate should be resisted; further investigations should depend on the specialist's assessment of the history and on clinical examination. As many of these patients are found not to have abnormalities on specialised testing, it is important at the outset to discuss expectations and thus avoid later disappointment and frustration.

In the present state of knowledge, an open-minded, eclectic and pragmatic approach to management of OP-related illness is recommended. This can follow principles used in a range of other poorly understood medical disorders; cognitive behaviour therapy has proved relatively effective in such conditions. Management must begin by establishing a therapeutic alliance with the patient and agreeing goals. Specific symptoms, such as depression, fatigue, sleep disorder and suicidal thoughts, should be managed vigorously in the usual way, for example, antidepressants as well as with cognitive behavioural techniques to counteract beliefs and subsequent behaviours which may develop in the aftermath of an acute illness and serve to perpetuate it. Management of OP-related illness presents several challenges in addition to the general lack of knowledge about the causes and mechanisms underlying the condition. These include the media interest surrounding the topic, hostility and suspicion on the part of some sufferers towards the reliability and objectivity of medical opinion or official advice, and above all, ongoing litigation. Preventing a recurrence of symptomatology which might result from re-exposure to OP chemicals is an area which requires careful handling and would particularly benefit from well designed studies.

Existing clinical services for patients with symptoms associated with OP sheep dip exposure are unsatisfactory. The patient's GP should in most cases be responsible for diagnosis and management, but specialist referral may be needed in some cases. Consideration should be given to setting up specialist centres in appropriate areas to complement existing National Poisons Information Services treatment centres.

Two themes for research emerged from the working party's deliberations: (1) epidemiological studies aimed at developing means of quantifying OP sheep dip exposure and relating this to the clinical symptoms; (2) prospective trials to assess treatment efficacy.