- Email: [email protected]
Prevention of Leprosy
534
started with twice-weekly increments of 500 mg. daily 15 until side-effects occur or daily dosage of 8 g. is reached. When the optimum dosage for the patient has been established, minor adjustments are usually required either in total dose or in the timing of individual doses. Thus these patients need contin-
uing supervision so long as they are being treated; but usually benefit is so well maintained that they require no encouragement to persevere with treatment.
Prevention of Leprosy IT’s an ill wind ... The appearance of chloroquineresistant falciparum malaria in Vietnam led to intensive research based on a chance observation by ARCHIBALD and Ross 16 that dapsone (diaphenylsul-
fone, diaminodiphenylsulphone) was partially effective in preventing malaria in leprosy patients receiving the drug regularly. Among a series of synthetic sulphone derivatives investigated, acedapsone (4,4’-
diacetyldiaminodiphenyl sulphone, D.A.D.D.s.)
was
found to have certain advantages when parenterally administered as a repository drug for malarial prophylaxis.17 ,18 It has suppressed falciparum infection in man for sixty days. A potentially more promising field now seems to be in the treatment and prevention of leprosy. The wheel has turned full circle. Since multiplication of Mycobacterium leprae in the mouse footpad is suppressed by concentrations of dapsone as low as 0.00001 % administered in the diet,19 there is some justification for the trial in man of a repository drug such as acedapsone, which is slowly degraded in the tissues to compounds with demonstrable antimycobacterial activity, such as dapsone or some sulphone metabolite with one free amino group. In man, a single intramuscular injection of 225 mg. of acedapsone in a benzyl-benzoate/castoroil suspension releases dapsone at the rate of 2-4 mg. a day for seventy-seven days, giving a serum level of about 50 ng. per ml., which is above the minimum inhibitory concentration judged from extrapolation of the findings in mice. In the mouse, acedapsone in a dose of 6 mg. per kg. suppressed bacterial activity almost completely for two months. Several clinical trials of acedapsone in the treatment of leprosy 20 have followed the first report from SHEPARD et a1.p and the article by Dr. SLOAN and his colleagues in an earlier page of this issue confirms the findings of workers in other countries. 15.
Godwin-Austen,
R.
B., Frears, C. C., Bergmann, S. Br. med. J.
1971, i, 267. 16. 17. 18.
Archibald, H. M., Ross, C. M. J. trop. Med. Hyg. 1960, 63, 25. Thompson, P. E. Int. J. Leprosy, 1967, 35, 605. Laing, A. G. B., Pringle, G., Lane, F. C. T. Am. J. trop. Med. Hyg.
19. 20.
Shepard, C. C. Soc. exp. Biol. Med. 1967, 124, 430. Russell, D. A., Shepard, C. C., McRae, D. H., Scott, G. C., Vincin, D. R. Am. J. trop Med. Hyg. 1971, 20, 495. Shepard, C. C., Tolentino, J. G., McRae, D. H. ibid. 1968, 17, 192.
1966, 15, 838.
21.
The main interest of this report concerns what the authors call " the chemoprophylactic efficacy " of the drug in the population studied, and the observation that far fewer new overt leprosy infections were seen (6, against the expected 35) in the three years during which most of the people at risk received acedapsone in the same amounts as those given to patients diagnosed as having active leprosy. Since in the great majority of cases leprosy shows itself, after a silent or latent period, within two to four years, it is presumed that very few additional new cases should arise. As in similar investigations, the results presented by SLOAN et al. might be interpreted as confirming the efficacy of treatment of cases of leprosy (known, unsuspected, and preclinical infections), reducing to zero their capacity to disseminate viable bacilli within a few months of the institution of treatment, rather than as providing protection against challenge by M. leprae in the environment. Any such inquiry is hampered by lack of knowledge of the exact mode of transmission of the bacilli and their successful transepithelial implantation into susceptible subjects. A point of some importance is the possibility that drug-resistant strains of M. leprae may emerge in infected patients in whom the organisms are exposed for long periods to low concentrations of the drug. Trials of dapsone as the chemoprophylactic agent in areas of high leprosy prevalence have produced suggestive but equivocal results in respect of lepromatous leprosy.22-25 An effective and cheap prophylactic agent is urgently needed for leprosy control. In the opinion of some investigators, B.C.G. vaccination holds out real prospects of protection of exposed populations, and the simplicity of its administration and its low cost certainly commend it to field workers. The highly satisfactory protection-rates achieved in Uganda 26 have not been paralleled in Burma 27 or Papua and New Guinea,28 for reasons which are still There has been some suggestion that debated. vaccination with B.C.G. might with advantage be followed by chemoprophylaxis with dapsone in order to afford maximum protection to exposed subjects.29 The real test of any reputed prophylaxis in leprosy is the definite prevention of clinical disease in those exposed to leprosy challenge who are innately incapable of developing cell-mediated immunity. However, any reduction in the incidence of tuberculoid leprosy, with its accompaniment of severe peripheral 22. Lancet, 1966, i, 354. 23. Wardekar, R. V. Lepr. India, 1969, 41, 240. 24. Noordeen, S. K. ibid. p. 247. 25. W.H.O. Expert Committee on Leprosy: Fourth Report. Tech. Rep. Ser. Wld Hlth Org. 1970, no. 459. 26. Brown, J. A. K., Stone, M. M., Sutherland, I. Br. med. J. 1968, i, 24. 27. Bechelli, L. M., Garbajosa, G., Uemura, K., Engler, V., Dominguez, V. Martinez, Paredes, L., Sundaresan, T., Koch, G., Matejka, M. Bull. Wld Hlth Org. 1970, 42, 235. 28. Scott, G. C., Wigley, S. C., Russell, D. A. Int. J. Leprosy, 1966,
34, 139. 29. ibid. 1969,
37,
412.
535
neuropathy, injection of
would be welcome.
An intramuscular
active
antimycobacterial compound days for three years has definite administrative and cost advantages over twice-weekly oral dapsone ingestion for an indefinite period, and also over fortnightly parenteral injections of a 2025 % w/v suspension of dapsone in oil. The acceptability of the regimen used by SLOAN et al. and its applicability to the vast populations exposed to a real and feared risk of leprosy are matters for further controlled investigation. an
every seventy-seven
A Shout of Anger A HEALTH service cannot be good unless the people who work in it know they are getting a fair deal.
in nine separate functional councils,- all considering different claims at random times. They have to operate a system in which computer experts, or work-study practitioners, and any others who can take their labour into the open market-place, are treated far more generously than those, particularly the paramedical workers and technicians, for whom the N.H.S. is in effect a monopoly employer. Nursing administrators struggling to achieve a safe level of staffing know only too well the agency story: a hospital nurse who finds her N.H.S. salary too low joins an agency instead; the hospital then hires her services from the agency for far more than the Whitley rate, and the agency and the nurse split the difference. As a result, traditional hospital loyalties
disintegrate.
This is the story as it comes from an angry Mr. need faith in the for BRINTON and his many supporters. All are disThey system deciding salarythat their and confidence claims will be scales, satisfied, though they may have differing remedies. Some say the system could work well, if applied less thoughtfully discussed in a spirit of genuine negotiation. This was the original aim of Whitleyism, rigidly and more imaginatively: others would prefer a Health Service review body for all professions; or though until now the N.H.S. variety has seemed rather like a steam-age branch railway in Dorset: an unaligned pay research unit; or a unified Health often sometimes Service wages policy; or the creation of broad salary slow, cumbersome, late, missing bands within which local management can operate connections, but getting there in the end. Now the lid has been taken off, and a shoal of letters to The with some degree of freedom. Whatever the reason, and whatever the remedy, there can no longer be any Times, following Mr. HENRY BRINTON’s resignation from the Administrative and Clerical Whitley doubt that the health workers whom the Secretary of reveal that the brand of N.H.S. State hopes to lead into a reconstructed service in Council, Whitleyism is distrusted and resented by people of every pro1974 are a disillusioned and disaffected force, whose fession : indeed, the loss of confidence is so widemorale is beginning to disintegrate. We see a need for an entirely fresh deal, which will spread that sober and dedicated staff are now seriously considering the demo and the strike as the only recognise the essential unity and interdependence of means of getting a fair hearing. all health workers; management and staff must work What has happened to the fair hopes of N.H.S. out together, in genuine face-to-face negotiation, a since 1948 ? The Whitleyism correspondence straightforward system of salary relativities between columns of The Times give the answer with disturbing the various professions, with rewards comparable with those outside the N.H.S. And if health workers clarity. Surprisingly, it turns out that the Management Side has no power: it follows the instructions of are to concentrate on their real task, instead of who never appear at the negotiatTreasury officials perpetually fingering their pay-slips, they must feel have no Individual table. sure that their representatives are negotiating with managers ing hospital conditions can the rates and only apply power: they people who have power to settle, without having to laid down by a Whitley Council whose Management disappear into the darkness for further orders. If Side is a mouthpiece for the Treasury. So staff can national policy requires that the Treasury voice be to a local who management, only complain powerless heard, then Treasury representatives should be at themselves can only complain to a powerless Managethe table to answer the arguments of the other side. ment Side, who themselves can only put up with a Over and above all this, a good National Health bad system or, like Mr. BRINTON, vote with their feet Service ought to be proud to set an example as a good and depart. The heart of the discontent seems to be employer, to be ready itself to initiate improvements not only low salaries, though some of these are disin staff conditions, and to have a care for all its staff, the graceful enough, but knowledge that the Staff Side particularly those in the professions which are small is dealing with a Management Side which cannot of numerically, vital medically, but have little muscle its own volition concede a claim, however well in the political lobbies. Sir KEITH JOSEPH would be wise to heed this justified, without the prior consent of a group of who from the are absentees people remarkably unanimous shout of disapproval. He has permanent have to table. administrators Luckless negotiating already shown a concern for the major reconstruction of the National Health Service in 1974. Unless he implement Whitley decisions which are sometimes tackles this discredited Whitley system now, 1974 of Torquemadan complexity, with overlapping nonsenses flowing from separate jockeying for position may prove too late.
started with twice-weekly increments of 500 mg. daily 15 until side-effects occur or daily dosage of 8 g. is reached. When the optimum dosage for the patient has been established, minor adjustments are usually required either in total dose or in the timing of individual doses. Thus these patients need contin-
uing supervision so long as they are being treated; but usually benefit is so well maintained that they require no encouragement to persevere with treatment.
Prevention of Leprosy IT’s an ill wind ... The appearance of chloroquineresistant falciparum malaria in Vietnam led to intensive research based on a chance observation by ARCHIBALD and Ross 16 that dapsone (diaphenylsul-
fone, diaminodiphenylsulphone) was partially effective in preventing malaria in leprosy patients receiving the drug regularly. Among a series of synthetic sulphone derivatives investigated, acedapsone (4,4’-
diacetyldiaminodiphenyl sulphone, D.A.D.D.s.)
was
found to have certain advantages when parenterally administered as a repository drug for malarial prophylaxis.17 ,18 It has suppressed falciparum infection in man for sixty days. A potentially more promising field now seems to be in the treatment and prevention of leprosy. The wheel has turned full circle. Since multiplication of Mycobacterium leprae in the mouse footpad is suppressed by concentrations of dapsone as low as 0.00001 % administered in the diet,19 there is some justification for the trial in man of a repository drug such as acedapsone, which is slowly degraded in the tissues to compounds with demonstrable antimycobacterial activity, such as dapsone or some sulphone metabolite with one free amino group. In man, a single intramuscular injection of 225 mg. of acedapsone in a benzyl-benzoate/castoroil suspension releases dapsone at the rate of 2-4 mg. a day for seventy-seven days, giving a serum level of about 50 ng. per ml., which is above the minimum inhibitory concentration judged from extrapolation of the findings in mice. In the mouse, acedapsone in a dose of 6 mg. per kg. suppressed bacterial activity almost completely for two months. Several clinical trials of acedapsone in the treatment of leprosy 20 have followed the first report from SHEPARD et a1.p and the article by Dr. SLOAN and his colleagues in an earlier page of this issue confirms the findings of workers in other countries. 15.
Godwin-Austen,
R.
B., Frears, C. C., Bergmann, S. Br. med. J.
1971, i, 267. 16. 17. 18.
Archibald, H. M., Ross, C. M. J. trop. Med. Hyg. 1960, 63, 25. Thompson, P. E. Int. J. Leprosy, 1967, 35, 605. Laing, A. G. B., Pringle, G., Lane, F. C. T. Am. J. trop. Med. Hyg.
19. 20.
Shepard, C. C. Soc. exp. Biol. Med. 1967, 124, 430. Russell, D. A., Shepard, C. C., McRae, D. H., Scott, G. C., Vincin, D. R. Am. J. trop Med. Hyg. 1971, 20, 495. Shepard, C. C., Tolentino, J. G., McRae, D. H. ibid. 1968, 17, 192.
1966, 15, 838.
21.
The main interest of this report concerns what the authors call " the chemoprophylactic efficacy " of the drug in the population studied, and the observation that far fewer new overt leprosy infections were seen (6, against the expected 35) in the three years during which most of the people at risk received acedapsone in the same amounts as those given to patients diagnosed as having active leprosy. Since in the great majority of cases leprosy shows itself, after a silent or latent period, within two to four years, it is presumed that very few additional new cases should arise. As in similar investigations, the results presented by SLOAN et al. might be interpreted as confirming the efficacy of treatment of cases of leprosy (known, unsuspected, and preclinical infections), reducing to zero their capacity to disseminate viable bacilli within a few months of the institution of treatment, rather than as providing protection against challenge by M. leprae in the environment. Any such inquiry is hampered by lack of knowledge of the exact mode of transmission of the bacilli and their successful transepithelial implantation into susceptible subjects. A point of some importance is the possibility that drug-resistant strains of M. leprae may emerge in infected patients in whom the organisms are exposed for long periods to low concentrations of the drug. Trials of dapsone as the chemoprophylactic agent in areas of high leprosy prevalence have produced suggestive but equivocal results in respect of lepromatous leprosy.22-25 An effective and cheap prophylactic agent is urgently needed for leprosy control. In the opinion of some investigators, B.C.G. vaccination holds out real prospects of protection of exposed populations, and the simplicity of its administration and its low cost certainly commend it to field workers. The highly satisfactory protection-rates achieved in Uganda 26 have not been paralleled in Burma 27 or Papua and New Guinea,28 for reasons which are still There has been some suggestion that debated. vaccination with B.C.G. might with advantage be followed by chemoprophylaxis with dapsone in order to afford maximum protection to exposed subjects.29 The real test of any reputed prophylaxis in leprosy is the definite prevention of clinical disease in those exposed to leprosy challenge who are innately incapable of developing cell-mediated immunity. However, any reduction in the incidence of tuberculoid leprosy, with its accompaniment of severe peripheral 22. Lancet, 1966, i, 354. 23. Wardekar, R. V. Lepr. India, 1969, 41, 240. 24. Noordeen, S. K. ibid. p. 247. 25. W.H.O. Expert Committee on Leprosy: Fourth Report. Tech. Rep. Ser. Wld Hlth Org. 1970, no. 459. 26. Brown, J. A. K., Stone, M. M., Sutherland, I. Br. med. J. 1968, i, 24. 27. Bechelli, L. M., Garbajosa, G., Uemura, K., Engler, V., Dominguez, V. Martinez, Paredes, L., Sundaresan, T., Koch, G., Matejka, M. Bull. Wld Hlth Org. 1970, 42, 235. 28. Scott, G. C., Wigley, S. C., Russell, D. A. Int. J. Leprosy, 1966,
34, 139. 29. ibid. 1969,
37,
412.
535
neuropathy, injection of
would be welcome.
An intramuscular
active
antimycobacterial compound days for three years has definite administrative and cost advantages over twice-weekly oral dapsone ingestion for an indefinite period, and also over fortnightly parenteral injections of a 2025 % w/v suspension of dapsone in oil. The acceptability of the regimen used by SLOAN et al. and its applicability to the vast populations exposed to a real and feared risk of leprosy are matters for further controlled investigation. an
every seventy-seven
A Shout of Anger A HEALTH service cannot be good unless the people who work in it know they are getting a fair deal.
in nine separate functional councils,- all considering different claims at random times. They have to operate a system in which computer experts, or work-study practitioners, and any others who can take their labour into the open market-place, are treated far more generously than those, particularly the paramedical workers and technicians, for whom the N.H.S. is in effect a monopoly employer. Nursing administrators struggling to achieve a safe level of staffing know only too well the agency story: a hospital nurse who finds her N.H.S. salary too low joins an agency instead; the hospital then hires her services from the agency for far more than the Whitley rate, and the agency and the nurse split the difference. As a result, traditional hospital loyalties
disintegrate.
This is the story as it comes from an angry Mr. need faith in the for BRINTON and his many supporters. All are disThey system deciding salarythat their and confidence claims will be scales, satisfied, though they may have differing remedies. Some say the system could work well, if applied less thoughtfully discussed in a spirit of genuine negotiation. This was the original aim of Whitleyism, rigidly and more imaginatively: others would prefer a Health Service review body for all professions; or though until now the N.H.S. variety has seemed rather like a steam-age branch railway in Dorset: an unaligned pay research unit; or a unified Health often sometimes Service wages policy; or the creation of broad salary slow, cumbersome, late, missing bands within which local management can operate connections, but getting there in the end. Now the lid has been taken off, and a shoal of letters to The with some degree of freedom. Whatever the reason, and whatever the remedy, there can no longer be any Times, following Mr. HENRY BRINTON’s resignation from the Administrative and Clerical Whitley doubt that the health workers whom the Secretary of reveal that the brand of N.H.S. State hopes to lead into a reconstructed service in Council, Whitleyism is distrusted and resented by people of every pro1974 are a disillusioned and disaffected force, whose fession : indeed, the loss of confidence is so widemorale is beginning to disintegrate. We see a need for an entirely fresh deal, which will spread that sober and dedicated staff are now seriously considering the demo and the strike as the only recognise the essential unity and interdependence of means of getting a fair hearing. all health workers; management and staff must work What has happened to the fair hopes of N.H.S. out together, in genuine face-to-face negotiation, a since 1948 ? The Whitleyism correspondence straightforward system of salary relativities between columns of The Times give the answer with disturbing the various professions, with rewards comparable with those outside the N.H.S. And if health workers clarity. Surprisingly, it turns out that the Management Side has no power: it follows the instructions of are to concentrate on their real task, instead of who never appear at the negotiatTreasury officials perpetually fingering their pay-slips, they must feel have no Individual table. sure that their representatives are negotiating with managers ing hospital conditions can the rates and only apply power: they people who have power to settle, without having to laid down by a Whitley Council whose Management disappear into the darkness for further orders. If Side is a mouthpiece for the Treasury. So staff can national policy requires that the Treasury voice be to a local who management, only complain powerless heard, then Treasury representatives should be at themselves can only complain to a powerless Managethe table to answer the arguments of the other side. ment Side, who themselves can only put up with a Over and above all this, a good National Health bad system or, like Mr. BRINTON, vote with their feet Service ought to be proud to set an example as a good and depart. The heart of the discontent seems to be employer, to be ready itself to initiate improvements not only low salaries, though some of these are disin staff conditions, and to have a care for all its staff, the graceful enough, but knowledge that the Staff Side particularly those in the professions which are small is dealing with a Management Side which cannot of numerically, vital medically, but have little muscle its own volition concede a claim, however well in the political lobbies. Sir KEITH JOSEPH would be wise to heed this justified, without the prior consent of a group of who from the are absentees people remarkably unanimous shout of disapproval. He has permanent have to table. administrators Luckless negotiating already shown a concern for the major reconstruction of the National Health Service in 1974. Unless he implement Whitley decisions which are sometimes tackles this discredited Whitley system now, 1974 of Torquemadan complexity, with overlapping nonsenses flowing from separate jockeying for position may prove too late.