- Email: [email protected]
SULPHONAMIDES IN MALARIA
1147
they dismiss, favouring a " hereditary predisposition ". Here, we feel, they are taking a step backwards by invoking a diagnosis like the old " gastric neuroses "-which in the end all turned out to be organic-and the illnesses of these children may eventually be similarly explained. One possible cause may be temporary intolerance for certain factors in the diet. Holzel et al. first described lactase deficiency which was congenital and familial, and this condition is specifically excluded from Davidson and Wasserman’s group. On the other hand, evidence seems to be emerging that there can be a temporary loss of enzyme activity, usually the aftermath of gastroenteritis, which resolves spontaneously in a matter of months. That would fit in well with the onset after birth and the spontaneous " disappearance of the irritable colon". Meanwhile, it is well to recognise this type of case, but its xtiology might be better regarded as so far unexplained. Psediatric enzymologists are unravelling this situation, and further advances in our understanding of causes and choice of treatment will come before long.
SULPHONAMIDES IN MALARIA
INTEREST is
growing in the use of sulphonamide drugs adjunctive treatment for malaria, particuresistant Plasmodium falciparum. They are larly against considered to be competitive inhibitors of generally acid p-aminobenzoic (P.A.B.A.), which can be shown to antagonise the action of sulphadiazine against plasmodium in animals.3 4 The potentiating effect of sulphadiazine on the activity of pyrimethamine in human P. falciparum malaria was demonstrated by Hurly5 and confirmed by other workers.6-8The mechanism of this potentiation is obscure, but it may be that the P.A.B.A. inhibitors such as sulphadiazine interfere with the synthesis of folic acid from P.A.B.A. or other precursors, while pyrimethamine, like chlorguanide and chlorproguanil, interferes with the synthesis of folinic acid.4 9 as
alternative
or
syndrome,13 and the potential hazards of other long-acting sulphonamide drugs 14 may well apply to this particular compound. The emergence of drug-resistant malaria is a big health problem in most tropical areas, and although resistance is usually specific for particular drugs 4 or groups of drugs, multiresistant strains also appear. On the evidence so far the therapeutic advantages of this convenient form of combined treatment in chloroquineresistant cases outweigh the possible risks of toxic effects. Although, as Harinasuta et al. point out, its injudicious use may extend drug resistance, it must be welcomed as a distinct advance in malaria control.
THE PUBLIC-HEALTH SERVICE
DOCTORS in the
public-health service have been, and remain, underpaid: a departmental officer receives an initial salary of E1515, rising by eight annual increments to E2130. Last June the staff side of committee C of the Medical Whitley Council submitted a claim, based on increases awarded by the Review Body to other doctors in the National Health Service, on behalf of doctors in the public-health service. The employers’ side has always insisted on offering the staff side the same increases - as comparable grades of other (non-medical) localauthority employees, without regard to Review Body awards; a claim on behalf of one such group (whose negotiating machinery is entirely separate from the Medical Whitley Council) has been referred to the National Board for Prices and Incomes, whose report is expected later this year, and the employers’ side of the Medical Whitley Council has refused to make an offer until the Board’s decision is known. Meanwhile the Mallaby Committee on Local Authority Staffing has reported a critical situation in the recruitment of public-health
Professor Harinasuta and others now record on p. 1117 their experience with a long-acting sulphonamide, sulphormethoxine, in chloroquine-resistant malaria in Thailand. A single dose alone cured 11 out of 18 patients, and a smaller dose combined with a single dose of pyrimethamine cured 11 out of 15 patients. A combination of sulphormethoxine and chloroquine cured 11out of 13 patients. These findings agree with those of other investigators,’ 10 -12 and the sum of evidence suggests that the most effective regimen is 1000 mg. of sulphormethoxine combined with 50 mg. of pyrimethamine in a single dose. Moreover, whereas the response to the sulphonamide alone is slow, the therapeutic effect of the combination is
doctors. The British Medical Guild (which is the British Medical Association in its trade-union hat) has now recommended doctors not to apply for public-health appointments, and the British Medical Journal (which is the journal of the Association) is to refuse advertisements of public-health posts, until an acceptable offer of an increase has been made. The Lancet, unlike the B.M.J., will continue at present to accept advertisements for the public-health service. Withholding advertisements can only aggravate a critical situation " and thus make conditions harder both for the public and for an already understaffed service. The employers’ side seems to have been-to say the leastdilatory, but this hardly justifies a declaration of war. No agreement has been broken; the employers’ side is not bound by the Review Body’s findings. The truth is that
rapid. Although
public-health doctors, now grossly underpaid, were already somewhat underpaid when the staff side first gave
Harinasuta et al. found no clinical or laboraevidence of drug toxicity in their patients, sulphortory methoxine has been implicated in cases of Stevens-Johnson 2. Holzel, A., Schwarz, V., Sutcliffe, K. W. Lancet, 1959, i, 1126. 3. Bishop, A. Biol. Rev. 1959, 34, 445. 4. Thompson, P. E. in Annual Review of Pharmacology (edited by H. W. Elliott); vol. VII, p. 82. Palo Alto, U.S.A., 1967. 5. Hurly, M. G. D. Trans. R. Soc. trop. Med. Hyg. 1959, 53, 412. 6. McGregor, I. A., Williams, K., Goodwin, L. G. Br. med. J. 1963, ii, 728. 7. Laing, A. B. G. ibid. 1964, ii, 1439. 8. Laing, A. B. G. ibid. 1965, i, 905. 9. Rollo, I. M. Br. J. Pharmac. Chemother. 1955, 10, 208. 10. Laing, A. B. G. Bull. Wld Hlth Org. 1966, 34, 308. 11. Chin, W., Contacos, P. G., Coatney, G. R., King, H. K. Am. J. trop. Med. Hyg. 1966, 15, 823. 12. Bartelloni, P. J., Sheehy, T. W., Tigertt, W. D. J. Am. med. Ass. 1967,
199, 173.
"
notice of its claim in November, 1965; and the present unsatisfactory situation is the unhappy outcome of past failure to secure a reasonable level of remuneration in the service. The Association, we believe, is right to seek to relate pay of doctors in the public-health service to that of doctors elsewhere in the N.H.S.; and it can reasonably expect more support in this endeavour than it has hitherto received from a hospital-minded Ministry of Health. But the negativisitic attitude reflected in the Association’s latest action is unlikely to promote this
change. 13. 14.
Meyler, L. Side Effects of Drugs; vol. v, p. 272. Amsterdam, 1966. Lancet, Jan. 21, 1967, p. 150.
they dismiss, favouring a " hereditary predisposition ". Here, we feel, they are taking a step backwards by invoking a diagnosis like the old " gastric neuroses "-which in the end all turned out to be organic-and the illnesses of these children may eventually be similarly explained. One possible cause may be temporary intolerance for certain factors in the diet. Holzel et al. first described lactase deficiency which was congenital and familial, and this condition is specifically excluded from Davidson and Wasserman’s group. On the other hand, evidence seems to be emerging that there can be a temporary loss of enzyme activity, usually the aftermath of gastroenteritis, which resolves spontaneously in a matter of months. That would fit in well with the onset after birth and the spontaneous " disappearance of the irritable colon". Meanwhile, it is well to recognise this type of case, but its xtiology might be better regarded as so far unexplained. Psediatric enzymologists are unravelling this situation, and further advances in our understanding of causes and choice of treatment will come before long.
SULPHONAMIDES IN MALARIA
INTEREST is
growing in the use of sulphonamide drugs adjunctive treatment for malaria, particuresistant Plasmodium falciparum. They are larly against considered to be competitive inhibitors of generally acid p-aminobenzoic (P.A.B.A.), which can be shown to antagonise the action of sulphadiazine against plasmodium in animals.3 4 The potentiating effect of sulphadiazine on the activity of pyrimethamine in human P. falciparum malaria was demonstrated by Hurly5 and confirmed by other workers.6-8The mechanism of this potentiation is obscure, but it may be that the P.A.B.A. inhibitors such as sulphadiazine interfere with the synthesis of folic acid from P.A.B.A. or other precursors, while pyrimethamine, like chlorguanide and chlorproguanil, interferes with the synthesis of folinic acid.4 9 as
alternative
or
syndrome,13 and the potential hazards of other long-acting sulphonamide drugs 14 may well apply to this particular compound. The emergence of drug-resistant malaria is a big health problem in most tropical areas, and although resistance is usually specific for particular drugs 4 or groups of drugs, multiresistant strains also appear. On the evidence so far the therapeutic advantages of this convenient form of combined treatment in chloroquineresistant cases outweigh the possible risks of toxic effects. Although, as Harinasuta et al. point out, its injudicious use may extend drug resistance, it must be welcomed as a distinct advance in malaria control.
THE PUBLIC-HEALTH SERVICE
DOCTORS in the
public-health service have been, and remain, underpaid: a departmental officer receives an initial salary of E1515, rising by eight annual increments to E2130. Last June the staff side of committee C of the Medical Whitley Council submitted a claim, based on increases awarded by the Review Body to other doctors in the National Health Service, on behalf of doctors in the public-health service. The employers’ side has always insisted on offering the staff side the same increases - as comparable grades of other (non-medical) localauthority employees, without regard to Review Body awards; a claim on behalf of one such group (whose negotiating machinery is entirely separate from the Medical Whitley Council) has been referred to the National Board for Prices and Incomes, whose report is expected later this year, and the employers’ side of the Medical Whitley Council has refused to make an offer until the Board’s decision is known. Meanwhile the Mallaby Committee on Local Authority Staffing has reported a critical situation in the recruitment of public-health
Professor Harinasuta and others now record on p. 1117 their experience with a long-acting sulphonamide, sulphormethoxine, in chloroquine-resistant malaria in Thailand. A single dose alone cured 11 out of 18 patients, and a smaller dose combined with a single dose of pyrimethamine cured 11 out of 15 patients. A combination of sulphormethoxine and chloroquine cured 11out of 13 patients. These findings agree with those of other investigators,’ 10 -12 and the sum of evidence suggests that the most effective regimen is 1000 mg. of sulphormethoxine combined with 50 mg. of pyrimethamine in a single dose. Moreover, whereas the response to the sulphonamide alone is slow, the therapeutic effect of the combination is
doctors. The British Medical Guild (which is the British Medical Association in its trade-union hat) has now recommended doctors not to apply for public-health appointments, and the British Medical Journal (which is the journal of the Association) is to refuse advertisements of public-health posts, until an acceptable offer of an increase has been made. The Lancet, unlike the B.M.J., will continue at present to accept advertisements for the public-health service. Withholding advertisements can only aggravate a critical situation " and thus make conditions harder both for the public and for an already understaffed service. The employers’ side seems to have been-to say the leastdilatory, but this hardly justifies a declaration of war. No agreement has been broken; the employers’ side is not bound by the Review Body’s findings. The truth is that
rapid. Although
public-health doctors, now grossly underpaid, were already somewhat underpaid when the staff side first gave
Harinasuta et al. found no clinical or laboraevidence of drug toxicity in their patients, sulphortory methoxine has been implicated in cases of Stevens-Johnson 2. Holzel, A., Schwarz, V., Sutcliffe, K. W. Lancet, 1959, i, 1126. 3. Bishop, A. Biol. Rev. 1959, 34, 445. 4. Thompson, P. E. in Annual Review of Pharmacology (edited by H. W. Elliott); vol. VII, p. 82. Palo Alto, U.S.A., 1967. 5. Hurly, M. G. D. Trans. R. Soc. trop. Med. Hyg. 1959, 53, 412. 6. McGregor, I. A., Williams, K., Goodwin, L. G. Br. med. J. 1963, ii, 728. 7. Laing, A. B. G. ibid. 1964, ii, 1439. 8. Laing, A. B. G. ibid. 1965, i, 905. 9. Rollo, I. M. Br. J. Pharmac. Chemother. 1955, 10, 208. 10. Laing, A. B. G. Bull. Wld Hlth Org. 1966, 34, 308. 11. Chin, W., Contacos, P. G., Coatney, G. R., King, H. K. Am. J. trop. Med. Hyg. 1966, 15, 823. 12. Bartelloni, P. J., Sheehy, T. W., Tigertt, W. D. J. Am. med. Ass. 1967,
199, 173.
"
notice of its claim in November, 1965; and the present unsatisfactory situation is the unhappy outcome of past failure to secure a reasonable level of remuneration in the service. The Association, we believe, is right to seek to relate pay of doctors in the public-health service to that of doctors elsewhere in the N.H.S.; and it can reasonably expect more support in this endeavour than it has hitherto received from a hospital-minded Ministry of Health. But the negativisitic attitude reflected in the Association’s latest action is unlikely to promote this
change. 13. 14.
Meyler, L. Side Effects of Drugs; vol. v, p. 272. Amsterdam, 1966. Lancet, Jan. 21, 1967, p. 150.