key: cord-020267-0axms5fp
authors: nan
title: RIBAVIRIN AND RESPIRATORY SYNCYTIAL VIRUS
date: 1986-02-15
journal: Lancet
DOI: 10.1016/s0140-6736(86)92323-8
sha: 
doc_id: 20267
cord_uid: 0axms5fp

nan

experience in population medicine; management of the preventive health programme and information system described will require further training and a substantial time commitment. Stocking1O argues that in the absence of extra resources it may be preferable for general practitioners to relinquish some patient contact for a role as "central manager and referral agency" within the practice. Clearly there is considerable scope for substituting less expensive (and in some instances more appropriate) manpower resources for many tasks currently undertaken by general practitioners."

None of the obstacles is insurmountable, and some should be addressed for other reasons. However, ploughing money into FPCs to create the sort of management structure and proficiency that already exists in (often coterminous) health authorities would appear to be both exceptionally wasteful and extremely unlikely in the present economic climate. Reintegration of FPCs and health authorities would be the sensible option, not only to provide a viable management structure for general practice but also to secure the advantages of planned community health care which a closer relation between general practice and community medicine would allow. '2 Even if a new contract was established linking remuneration to performance monitored by FPCs or district health authorities, would it lead to an improvement in the quality of care? Preventive medicine lends itself to objective external assessment-it is possible to measure immunisation rates and screening coverage, for example, with the benefit of a computerised population register-and better care should follow. It is also probable that external audit of accessibility would be a major advance, especially in deprived urban areas.

Nevertheless, external audit of disease management is not without difficulty. Lessons can be learned from the experience of recertification and peer review organisations in the USA.13 At best, external audit can monitor minimum standards, but the highest standards of care must ultimately depend on fostering enthusiasm and stimulating participation in continuing education and research in general practice. And good general practice demands qualities such as kindness and understanding which are not encompassed by performance indicators. The peer review procedure envisaged by the RCGP'4 appears to hold out the best chance of attaining this wider vision of quality of care, and would complement a more formal line of accountability.

On balance, it seems likely that the people of Newcastle will benefit if their general practitioners are contractually required to provide services to agreed 10 standards of minimum performance, especially if the organisation to which the practitioners are accountable is not only equipped with teeth but also is capable of making a rational decision about whom to bite. But if we must wait for the end of the tripartite structure in order to achieve this, then perhaps "waiting for Greenot" is a more apposite description of where we stand.

RIBAVIRIN is an investigational synthetic triazole nucleoside of value in the treatment of Lassa feverl and certain viral respiratory infections. First synthesised in 1972, it possesses an unusually broad spectrum of antiviral activity, inhibiting under laboratory conditions a wide variety of RNA and DNA viruses, including among respiratory viruses influenza types A and B, parainfluenza types 1, 2, and 3, respiratory syncytial virus (RSV), and possibly coronavirus.

Its antiviral effect is expressed at various points in the replicative cycle but generally involves alterations of nucleotide pools and interference with the guanylation step required for 5' capping of viral messenger RNA.2 2 Ribavirin has low cellular toxicity and is well tolerated by human beings, the primary adverse effects being haematological with raised unconjugated bilirubin levels in 25% of subjects on 1 g orally per day and an occasional drop in haemoglobin on 4 g daily. These effects are rapidly reversible and may be related to the accumulation of drug or metabolites in red blood cells. Ribavirin is embryotoxic and teratogenic in laboratory animals, though not in baboons.

In temperate climates, RSV is the most frequent cause of acute lower respiratory tract disease in infants and young children. In Britain RSV accounts for yearly hospitaladmission rates of 12 -5 to 24' 5 per 1000 among infants aged 1-3 months;3 and in North Carolina it is responsible for 24-50% of all admissions for pneumonia in children under 5 years of age.4 In hospital roughly 14% of RSV-infected infants require intensive care and 5% need assisted ventilation.s Although the mortality from RSV infection is generally low, it is especially high in infants with underlying congenital heart disease (37%, rising to 73% with concomitant pulmonary hypertension),5 and in the immunocompromised (23%),6 and is almost certainly raised in infants with bronchopulmonary dysplasia and cystic fibrosis. Outbreaks among the elderly in nursing homes have also been associated with serious illness and a case fatality rate as high as 53°7o has been reported. 7 The efficacy of aerosolised ribavirin in RSV-infected infants has been examined mostly in double-blind trials involving normal children and those with underlying disease. In normal infants with illness for several days, therapy over many -hours improved cough, rales, retractions, bronchiolitis, lethargy, overall severity scores, and arterial oxygen saturation by the second to fourth day.8-1O Similarly RSV-infected infants with bronchopulmonary dysplasia and/or congenital heart disease improved more rapidly on ribavirin than on placebo and here benefit was most noticeable within the first 24 h of treatment and the improvements in arterial pO2 were substantia1.11,12 In these studies, there were no fatalities among 30 ribavirin-treated infants with bronchopulmonary dysplasia and/or congenital heart disease or others requiring prolonged assisted ventilation, suggesting life-saving effects. A bonus of ribavirin is its effect against other important respiratory viruses. Striking improvements were noted in 2 infants treated with ribavirin aerosol for parainfluenza virus type 3 infection complicating severe combined immunodeficiency disease13,14-a combination often causing respiratory failure and death. Moreover, ribavirin aerosol therapy, when started within the first 24 h of symptoms, reduces fever and symptoms from influenza type A (H1N1) and type B in young adults, 11,16 but here the improvements are modest and insufficient to justify treatment in otherwise healthy subjects. The published work thus indicates the feasibility of broad-spectrum antiviral chemotherapy for three or possibly four potentially serious and often clinically indistinguishable repiratory pathogens. It is also noteworthy that resistance to ribavirin developed in none of the RSV strains isolated during treatment, and conceivably the modest reductions in viral shedding found in most investigations may lessen the incidence of nosocomially acquired infection. Delivery of ribavirin via an infant oxygen hood, oxygen tent, inhalation tubing of a respirator, or face mask has the advantage of providing high drug concentrations at the site of viral replication and reduces the likelihood of systemic reactions. Indeed no toxic or adverse effects of aerosol therapy were observed among any of 135 infants or adults studied, many receiving an estimated 0' 82 mg/kg per hourl 6 for periods of 100 h over 5 days.

Few otherwise healthy adults will feel that the accelerated clinical improvement is worth the inconvenience of many hours' confinement for this therapy, however safe. Rather it should be considered for infants with bronchiolitis or pneumonia, and for high-risk patients with underlying cardiopulmonary disorders or immunodeficiency with probable RSV or influenza, and possibly parainfluenza infection. In high-risk patients early treatment seems indicated before onset of life-threatening disease or confirmation of the diagnosis by laboratory means. In Britain, the drug is available on a named patient basis only. 

IT is understandable that the idea of treating urinary incontinence by transferring it to another site should have been slow to gain acceptance, particularly when major surgery is involved. Yet urologists, when faced with intractable cases of urethral leakage, have been making judicious use of uretero-ileo-cutaneous diversion for many years, fortified by the increasing safety of this operation and the improvement of collecting devices. The great majority of cases are women for whom no effective urinal is available.

Uncontrollable reflex detrusor activity due to vesicourethral neuropathy (especially in multiple sclerosis) is the commonest indication, followed by female stress incontinence persisting after multiple local operations. Few surgeons deal with enough cases to make a convincing series and publications devoted to the subject are rare. In one report which appeared nine years ago, urinary diversion had been performed in 12 cases of multiple sclerosis (9 female)1 with very favourable results. It was concluded that urinary diversion should be considered much earlier in the treatment of incontinence in multiple sclerosis and not kept as a last resort.

In a new report Malone and co-workers2 again put urinary diversion in incontinence in a favourable light, stressing the great improvement in the patient's social acceptability that may be achieved. Of the 13 patients 8 had uninhibited detrusor contractions associated with paraplegia (traumatic in 2 and due to multiple sclerosis in 6). In another case of multiple sclerosis an indwelling catheter had produced a patulous urethra. The remaining 4 patients were obstetric cases in all of whom several local operations for stress incontinence had failed. There was no operative mortality and complications such as wound and chest infection and paralytic ileus were limited to the patients with multiple sclerosis. In only one case of this disease was any deterioration of neurological status noted postoperatively. Before the operation 8 of the patients had been unable to lead a reasonable social life, afterwards only 4; the remaining 4.were inhibited more by fear of the stoma leaking or appearing conspicuous than by episodes of appliance failure. In fact, 11 patients had either no leaks or only occasional leakage in the three months before interviews. 2 patients had troublesome dermatitis around the stoma and in 2 there was stomal ulceration with bleeding, but no one regretted having had the operation. The most common complication was pyocystis (in 4 patients) which was relieved by vaginal vesicostomy performed with the aid of a Payr's crushing clamp.3 Malone et al suggest that prophylactic use of this operation should be considered especially in elderly or infirm patients. They also stress the importance of a stomatherapy service for all the patients, and of specialised nursing care and physiotherapy for those with multiple sclerosis. The importance of longterm follow-up is emphasised, for early detection of urolithiasis as well as stomal or uretero-ileal stenosis.

In the future fewer diversions may be required, thanks to advances in artificial sphincters and techniques of bladder denervation. Particularly promising in women with multiple sclerosis is the injection of phenol into the vesical plexus bilaterally through the vagina and perineum. In one series of

Lassa fever. Effective therapy with ribavirin

Mechanisms of action of ribavirin

Report to the Medical Council Subcommittee on respiratory syncytial virus vaccines Respiratory syncytial virus infection: admissions to hospital in industrial, urban, and rural areas

Pneumonia: an eleven-year study in a pediatric practice

Respiratory syncytial viral infection in infants with congenital heart disease

Respiratory syncytial virus in immunocompromised children

Communicable Disease Surveillance Centre. Respiratory syncytial virus infection in the elderly 1976-82