TREATMENT OF NEUROCYSTICERCOSIS: IS PRAZIQUANTEL THE NEW HOPE?

262

Points of View TREATMENT OF NEUROCYSTICERCOSIS: IS PRAZIQUANTEL THE NEW HOPE? M. MOODLEY

A. MOOSA

Department of Paediatrics and Child Health, Faculty of Medicine, University of Natal, PO Box 17039, Congella 4013, South Africa

CYSTICERCOSIS, the commonest parasitic infection of the system, is endemic in central and south south-east America, Asia, India, the Caribbean, and southern African It has also been more frequently diagnosed in the USA, partly because of increased immigration from Mexico and also because of increased detection by computerised tomography (CT).’ Neurocysticercosis causes various neurological symptoms: in South African children, epilepsy, with or without focal signs, is the commonest presentation, followed by a syndrome of raised intracranial pressure and central

nervous

meningoencephalitis.23 Hydrocephalus, a frequent presentation in adults, is less common in children.2Until the present decade, treatment of this potentially handicapping infection was largely limited to treatment of the complications: anticonvulsants for seizure control, corticosteroids for raised intracranial pressure secondary to cerebral oedema, ventriculoperitoneal shunts for relief of hydrocephalus, and surgical removal of large cysts.1’s In 1978, the antitrematode drug, praziquantel, was shown to be highly effective against experimental cysticercosis. It has been hailed as the "new hope" for cysticercosis since its first use in man in 1980. Most of the early studies seemed to indicate a favourable response to praziquantel, but none had objective criteria for evaluation. 7,9 The first "objective" study on the value of praziquantel in cerebral cysticercosis was reported by Sotelo et at They documented the disappearance or reduction in size of viable cerebral cysts on CT brain scans in 26 clinically stable adult patients, 3 months after treatment with praziquantel. This was hailed as a major advance," but the study was flawed. Firstly, they treated a highly selected group of patients with an uncommon form of cerebral cysticercosis (macroscopic intraparenchymal cysts shown by CT scan). Patients in whom contrast CT scans showed cysts with surrounding oedema or inflammation were excluded, because the authors had "observed that in some patients the cyst is spontaneously replaced by inflammatory tissue within a few months".’ Secondly, the control groups were retrospectively selected. Two control groups were studied: 12 patients (Group A) had previous studies with a mean (SD) follow-up of 6-4 months (1-5) before the praziquantel trial. Group B consisted of 5 patients chosen from the CT scan archives with a mean follow up of 15 months (38); both groups of patients all had initial CT scans with no radiological follow-up, so the natural history of the disease was not known at the time of selection for the trial when new CT scans were obtained. A prospective therapeutic study by Van Dellen and McKeown"’ of 66 patients with active neurocysticercosis showed a 98 % improvement by 1 year on sequential CT scans. Improvement was assessed as complete if all CT scan features (eg, number of active lesions, extent and severity of oedema, and evidence of raised intracranial pressure) had resolved 12 months after

praziquantel therapy. The major drawback in this otherwise carefully documented study is the absence of concurrent controls. The advent of praziquantel as a "major advance" in the treatment of cerebral cysticercosis has encouraged many clinicians to use this drug. However, the conclusion that praziquantel is a highly effective therapy has been challenged because of the lack of a double-blind controlled trial and descriptions of spontaneous clinical and CT scan improvement in certain types of cerebral cysticercosis.2,3,12-14 In a series of 61 children with cerebral cysticercosis from South Africa, 43% had epilepsy, 34% had raised intracranial pressure, and 13% had meningoencephalitis.1 None were treated with praziquantel, yet their disease was satisfactorily controlled. Miller et al 12 showed spontaneous resolution of cysticercosis cysts in CT scans of 3 patients from the United States, 16 to 39 months after their first scans. They wrote that "these cases are typical in most respects of our large population of patients with cysticercosis", and "we have observed other cysts that resolve spontaneously and do not necessarily calcify" .12 Mitchell and Crawford14 describe 52 children or young adults with intraparenchymal cerebral cysticercosis who were observed for 2 to 72 months. 42 had acute inflamed lesions, with or without co-existing chronic calcification; 10 patients had only calcified active lesions. Single lesions were seen in 39, and multiple in 13. 51 patients had seizures which were treated satisfactorily with anticonvulsants. None of these patients were given praziquantel but "all active lesions resolved completely or with punctate calcification in 2 to 9 months according to CT scan findings". 14 In our experience, intraparenchymal cerebral cysticercosis is usually a self-limiting disease which only requires supportive treatment (eg, steroids for raised intracranial pressure, anticonvulsants for seizures, and rarely surgical intervention for relief of hydrocephalus and removal of large cysts). Furthermore, treatment of cerebral cysticercosis with praziquantel is not without side-effects: exacerbation of symptoms has been recorded in more than 90% of cases according to Ciferrils and in 92% of Sotelo’s patients. Many investigators have been reluctant to undertake double-blind controlled trials because of the "striking benefits" described in previous reports, and claim that it would be unethical to withhold a "proven remedy" for neurocysticercosis.11 However, reports of spontaneous improvement in clinical signs and CT scan appearances in some cases of neurocysticercosis point strongly to the need for such a trial. Correspondence should be addressed to A.

M.

REFERENCES 1. Sotelo J, Escobedo F, Rodriguez-Carbajal J, Torres B, Rubio-Donnadieu F. Therapy

2.

3. 4. 5.

6. 7.

of parenchymal brain cysticercosis with praziquantel. N Engl J Med 1984; 310: 1001-07. Thomson AJ, De Villers JC, Moosa A, Van Dellen JR. Cerebral cysticercosis in children in South Africa. Ann Trop Pediatr 1984; 4: 67-77. Dawood AA, Moosa A. Cerebral cysticercosis in children. J Trop Pediatr 1984, 30: 136-39. Earnest MP, Barth Reller L, Filley CM, Grek AJ. Neurocysticercosis in the United States: 35 cases and a review. Rev Infect Dis 1987; 9: 961-79. De Ghetaldi LD, Norman RM, Douville AW. Cerebral cysticercosis treated biphasically with dexamethasone and praziquantel Ann Intern Med 1983; 99: 179-81. Thomas H, Connert R. The efficacy of praziquantel against experimental cysticercosis and hydatidosis. Z Parasitend 1978; 55: 165-79. Bell DR Cysticercosis a new hope. Br Med J 1984; 289: 857-58.

263

CLINICAL FREEDOM: TWO LESSONS FOR THE UK FROM US EXPERIENCE WITH PRIVATISATION OF HEALTH CARE LYNN ETHEREDGE

PHILIP R. LEE

Policy Studies, School of Medicine, San Francisco, California, USA

Institute for Health

Kingdom (UK), politicians and policy analysts seem increasingly eager to apply lessons from the United States (US) to the National Health Service (NHS). It is clear that the Thatcher Government strongly favours increased marketplace competition and privatisation of IN the United

health services. There has been support for increased competition,1 for creation of internal markets within the NHS,2,3 and for managed care.4 There has been a rapid increase in US-style employer-provided health insurance benefits. There has been a substantial increase in the number of proprietary hospitals outside the NHS, and in the contracting of hospital services through competitive bidding.s There has been a transformation of regional and district management within the NHS, with a system of general management replacing consensus management.6 And, since the liberalisation of consultant contracts in 1980, the number of consultants engaging in private practice has increased substantially, as has their income from private

practice.’7 These developments reflect an ideology that has strongly influenced health care policies in the US, particularly during the almost eight years of the Reagan administration. Yet there are growing concerns, among physicians and others in the US, about the impact of the policies on medical care costs, on the commercialisation of medicine, and on physician autonomy.8-12 As a result of these new marketoriented policies, physicians in the US are now the most litigated-against, second-guessed, and paperwork-laden physicians in western industrialised democracies. Physicians’ day-to-day clinical decisionmaking-com-

today

monly referred to as clinical freedom-is increasingly subject to review and approval by "case managers" working for employers, insurance carriers, and government financed and regulated professional review organisations. Malpractice suits and administrative costs are multiplying. The growing adversarial relationship with private and public payers and loss of physician autonomy are closely related to the growing view that medical care should be treated like any other private business. The long-term consequences of these trends for the medical profession and medical

care

in the US

are

very serious: will medicine

8 Vasconcelos D, Cruz Segura H, Gomez HM, Alanis GN Selective indications for the use of praziquantel in the treatment of brain cysticercosis. J Neurol Neurosurg Psychiatry 1987, 50: 383-88. 9 Betero D, Castano S. Treatment of cysticercosis w ith praziquantel in Colombia Am J Trop Med Hyg 1982; 31: 811-21 10 Nash TE, Neva FA. Recent advances in the diagnosis and treatment of cerebral cysticercosis N Engl J Med 1984; 311: 1492-95 11. Van Dellen JR, McKeown CP Praziquantel in active cerebral cysticercosis. JNeurosurg 1988; 22: 92-96. 12 Miller B, Grinnell V, Goldberg MA, Heiner D. Spontaneous radiographic disappearance of cerebral cysticercosis: three cases. Neurology 1983; 33: 1377-79 13 Handler LC, Mervis B. Cerebral cysticercosis with reference to the natural history of parenchymal lesions. Am J Neuroradiol 1983, 4: 709-12 14. Mitchell WG, Crawford TO. Intraparenchymal cerebral cysticercosis in children Diagnosis and treatment. Pediatrics 1988; 82: 76-82 15 Ciferri F Praziquantel for cysticercosis of the brain parenchyma N Engl J Med 1984, 311: 733

profession, or will it become influenced by large purchasers and the ethics of increasingly the marketplace? What will be the effect on the clinical freedom of physicians and on the quality of medical care? What would be the consequences for the UK of adopting a more competitive model for the NHS and expanding the role of private health insurance and private practice? Of a growing commercial influence? The dangers to the NHS of following the mixed public-private model of the US have been pointed out by others. There is a risk that a US-style approach could result in the overuse of technology services at the expense of primary care and in a two-class system of care.13,14 If the Government succeeds in diminishing, or perhaps even eliminating, the NHS, British physicians may suffer the same fate that awaits their American colleagues.15 A recent review of private health care in Britain detailed current developments in the UK and defined many of the critical issues of privatisation facing the NHS.7 We believe that the dangers to the medical profession of a growing private sector in the UK have not been sufficiently appreciated by physicians. We address here two major dilemmas that have arisen from an increasing emphasis on the marketplace, competition, and commercialisation in medical care in the US: first, diminishing physician autonomy and clinical freedom; and second, the leaping administrative costs and burdens, including those in the physician’s office. continue

as an autonomous

DIMINISHING PHYSICIAN AUTONOMY

The Role

of Lawyers, Courts, and Regulatory Agencies The issue of malpractice is a growing concern in the US and the medical profession is sinking in public esteem. When public regard for the medical profession is low, physicians are more likely to be the target of malpractice suits. The number of suits has lately been increasing substantially: studies by the American Medical Association show that the rate of malpractice suits against private practice physicians more than tripled in the first five years of this decade. 37% of US physicians have had a medical malpractice suit against them in their career, and more than ten malpractice claims per hundred physicians were filed in 1985. For some specialities, such as obstetrics and orthopaedic surgery, these rates are much higher.16 These developments have resulted in a rapid increase in the cost of malpractice insurance premiums. Professional liability premiums for private practice physicians in the US increased by 22% annually from 1982 to 1986. By 1986, annual premiums were an average of$12 800 per physician; premiums for obstetrician/gynaecologists were more than double this amount ($29 300) and were even higher for orthopaedic surgeons ($35 200). In some areas, orthopaedic surgeons and obstetrician/gynaecologists pay annual premiums of nearly$100 000. Because of these trends, defensive medicine-ie, more laboratory tests, more patient investigations, more consultations, and more follow-up visits to guard against malpractice suits-is now a consideration in clinical practice for private physicians. In one study, the costs of defensive medicine were more than 3-5 times the cost of malpractice insurance premiums and accounted for almost 15% of the total US expenditures for physicians’ services.18 The courts, in their interpretation of antitrust laws, also have had a role in substituting the competitive process of the market for professional self-regulation. The concept of