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One-dose Treatment for Malaria
383
and found
cornual implantation of the placenta of in 60% breech presentations, whereas, in his total series, almost 90% of the placentae were on the anterior or posterior uterine wall. S’J’!
over
certainly accepts it, and he claims that the cornualfundal placenta makes the upper pole of the uterus narrower than the lower pole, and so leads to breech He showed that out of 70 of his cases for which full data were available, the placenta was in the right cornu in 20 and in the left cornu in 50. He suggested that, because of the normal dextrorotation of the uterus, the placenta in the left cornu would interfere to a greater extent with the shape and capacity of the upper pole than the placenta in the right cornu. The effects of dextrorotation and right cornual implantation would thus tend to counteract each other. We publish this week two articles dealing with the Mr. FELL management of breech presentation. examines a series of 107 attempts at external version under anaesthesia at the Middlesex Hospital. He concludes that, though 2 babies were lost, the procedure is justifiable because the mortality due to uncomplicated breech delivery during the same period was 9%. His conelusions and figures are similar to those of PEEL and Cr,AYTON.34 In 4 of his cases attempted version caused some placental separation and in 3 others labour began prematurely, so the foetal-mortality rate might well have been greater. As 48 of the 107 versions were carried out before the 36th week, premature labour could have been a serious matter.
presentation.
During version it is very tempting to use just a little more force in an attempt to succeed ; and it is here that the greatest danger of version under anesthesia lies. Mr. MAIR, in his article on p. 361, opposes the use of anaesthesia for version except in very special circumstances. In general, he favours version without anaesthesia but with careful preparation and adequate premedication. Nearly all the failures will, he thinks, be cases of frank breech presentation, for which, provided the frank breech is engaged and there is no pelvic deformity or serious disproportion, he advocates surgical induction of labour by rupture of the forewaters. His view is that the opposition to induction in breech presentation is largely based on the fear of prolapse of the cord, and that this risk is eliminated when the frank breech is engaged. The induction is performed when the baby’s weight is estimated at 6-7 lb. ;: it is well known that the mortality in breech deliveries is greatest when the babies are either very small or very large. The two difficulties are the correct estimation of weight and the possible failure of the uterus to respond efficiently to the induction-a possibility hich MAIR does not discuss. His results are good 33. Lull, C. B., Kimbrough, R. A. Clinical Obstetrics. Philadelphia, 1953. 34. Peel, J. H., Clayton, S. G. J. Obst. Gynœc., Brit. Emp. 1948,
55, 614.
(only 1 baby was lost in 71 uncomplicated deliveries), but in a larger series a few babies might be lost front
infection and other factors associated with induced labour, unless the obstetrician was prepared to perform caesarean section in every case which failed to to induction. respond promptly V ARTAN 28 29 followed much the same lines as MAIR, who now emphasises them as part of a planned policy. This policy could not be followed in general practice, but NixoN and HICKSON 35 think that all breech presentations, whether in primigravidee or multiparae, should be delivered in hospital. This is sound advice because of the complications that may arise, and because very few practitioners can handle sufficient cases to become or remain proficient in their management. For the unexpected emergency, however, the use of the cross-bed position, the generous episiotomy, and the avoidance of traction remain the principal means
of avoiding
or
overcoming complications.
One-dose Treatment for Malaria THE old idea of a drug powerful enough to cure a disease at a single dose-the dosis magna sterilisansIt has been is becoming almost a commonplace. achieved in malaria, but most of the investigations have been made in patients who presumably have some degree of immunity to the disease. This immunity is a relative affair, better known as " premunition," which depends for its maintenance on continuing infection, and which is often incomplete and therefore compatible with occasional attacks of fever. The point is that in such a patient the results of chemotherapy are likely to be different from, and probably more favourable than, the effects of treatment in non-immune persons. Nevertheless, the prospect of effective treatment of an attack of malaria by a single dose of a drug is very welcome forjust this kind of patient. It means that the dose can be given under supervision, often in the outpatient department, and that the uncertainty of dosage when drugs are given to primitive people for administration at home is avoided. The mother of an African child, who knows nothing of tablets and dosage, can hardly be expected to carry out treatment which needs repetition at stated intervals, but a single dose given at hospital or dispensary is a different matter, if it is effective. There is much evidence that with the newer antimalarial drugs such a dose is effective. Several drugs have been used in this way : ’Camoquin,’ for instance, in a single dose of 400 mg., or two doses of 200 mg., by mouth, reduced pyrexia in an average of 24-8 hours, and eliminated parasites from the blood in 46-6 hours in a trial in India 36 ; and rather similar results were reported from elsewhere in India,37 and in Malaya. 38 In Honduras, HOEKENGA39 gave single doses of 0-4-1-0 g. of camoquin base to 380 patients in an endemic, area of whom half had Plasmodium falciparum and half had P. vivax infection ; few failed to respond. In Bolivia, a dose of 0-8 g. (for adults) cleared the blood in 28 hours.40 These single doses of camoquin were all given by
35. Nixon, W. C. W., Hickson, E. B. A Guide to Obstetrics in General Practice. London, 1953. 36. Khan, N., Suri, R. M., Nair, P. M. Indian med. Gaz. 1951, 37. 38. 39. 40.
86, 293. Ansari, M. Y.
Indian J. med. Sci. 1952, 6, 306. Med. J. Malaya, 1951, 6, 24. Hoekenga, M. T. J. Amer, med. Ass. 1952, 149, 1369. Villarojos, V. M. Amer. J. trop. Med. 1951, 31, 703.
Wallace, R. B.
384 it can be used intravenously, and PAYNE et al. 41 gave 150 mg. of base by this route to 5 patients
mouth, but
with naturally acquired P. vivax malaria, with quick clinical cure. In these trials of single-dose treatment the question at issue is the effect on the immediate attack, and camoquin shows up well ; indeed, VILLAREJOS 40 claims that it can cure P. frxlcipar2cm malaria radically, and even reduce the relapse-rate of P. vivax malaria. Chloroquine also shows this prompt result. In Spanish Guinea, VILA CORO 42 found as much value in a single dose (]"5 g. for adults) as in longer courses, with rapid disappearance of symptoms ; and iri Nigeria JELLIFFE and JELLIFFE 43 gave a single intramuscular dose of 5 mg. of base per kg. bodyweight to African children, who were cured within 2 days. These African infections were predominantly due to P. falciparum, and the same infection in Haiti responded similarly to a single dose of 2 g. (for adults) of hydroxychloroquine.44 Proguanil can also give clinical cure after a single dose, but MACDONALD and RAO 45 bring out a point of importance. They gave 300 mg. to adults and 200 mg. to children, most of whom had some premunition, and most of them were free from pyrexia and parasites in 72 hours. But almost half of them eventually relapsed, even some with P. falciparum, in an area of Ceylon where reinfection was unlikely. They therefore concludethat single-dose treatment should not be given if radical cure is desired. Pyrimethamine (‘ Daraprim ’) is the last-comer, and for patients with some premunition it too has given good single-dose results. ARCHIBALD 46 gave 25 mg. to Lagos school-children, and McGpEGtOR and SMITH 47 gave 0-25-0-5 mg. per kg. to Africans in Gambia. In these trials clinical cure was achieved within 72 hours. Similarly in Tunisia and Indo-China, ScsNEiDER et al. 48 found that a single dose of 50 mg. of base was effective within little more than 2 days. In Kenya Africans, JONES 49 found that 50 mg. was rapidly successful, even in 3 cases of cerebral malaria; but, commenting on this report, MCROBFRT 50 hopes that experiments on the oral administration of pyrimethamine in cerebral malaria in non-immunes or in unconscious Africans will not be contemplated. Indeed, although MOGREGOR and SMITH 47 were able to clear the blood with these minute doses, GOODWIN 51 thinks that the chief value of this drug may be in suppression. It is still too early to say. To sum up, therefore, several drugs will cure an attack of malaria if given in a single dose, and if the patient has some premunition ; but if radical cure is the aim, or if non-immunes are being treated, a single dose is probably not enough. But, even so, this is a remarkably useful quality of these modern drugs ; and, of course, a dose of quinine will clear up many an attack in semi-immune people. 41. Payne, E. H., Villarejos, V. M., Sharp, E. A., Reinertson, J. W., Wille, W. S. Ibid, p. 698. 42. Vila Coro. Z. Tropenmed. u. Parasit. 1951, 3, 158. 43. Jelliffe, D. B., Jelliffe, E. F. B. Trans. R. Soc. trop. Med. Hyg. 1953, 47, 235. 44. Loughlin, E. H., Rice, J. B., Wells, H. S., Rappaport, I., Joseph, A. A., Rene, H. Antibiotics, 1952, 2, 171. 45. Macdonald, O. J. S., Rao, P. V. Ceylon J. med. Sci. 1950, 7, 55. 46. Archibald, H. M. Brit. med. J. 1951, ii. 821. 47. McGregor, I. A., Smith, D. A. Ibid, 1952, i, 730. 48. Schneider, J., Canet, J., Dupoux, R. Bull. Soc. Path. exot. 1952, 45, 33. 49. Jones, S. A. Trans. R. Soc. trop. Med. Hyg. 1952, 46, 564. 50. McRobert, G. R. Trop. Dis. Bull. 1953, 50, 186. 51. Goodwin, L. G. Trans. R. Soc. trop. Med. Hyg. 1952, 46, 485.
Annotations THE FREEDOM OF THE ROAD To step from a car to the sidewalk is to embrace a different constellation of prejudices : to the pedestrianall drivers are possible knaves, to the driver all pedestrians are probable fools ; and the walking motorist distrusts drivers no less passionately than the driving motorist distrusts pedestrians. Nothing could better exemplify the partiality of human judgment. Mr. T. C. Foley,1 secretary of the Pedestrians Association, is aware of this split in our nature, which allows each of us to be both Jekyll and Hyde-or rather, allows each of us to be two aspects of Jekyll, while everybody else is two aspects of Hyde. " We cannot expect," Mr. Foley (in the character of pedestrian) remarks, " to maintain the free use of the highway as it existed before the motorcar age. The practical issue is, however, how much of that freedom are we to give up, and how much incon. venience and delay should we accept in order to reduce the risk of accident to ourselves and to assist the flow of vehicular traffic, in which as drivers, cyclists or passengers we also have an interest." The pedestrian, he points out (and in that character we can all agree with him), is already put to great inconvenience by motor traffic. To take only one example, there was a time when buses stopped immediately outside Underground stations ; today the pressure of traffic prohibits this arrangement, and the pedestrian often has a longish walk from the station to the stop. On a wet day, or when he is carrying a heavy bag, this may cause him to regret the old swift days of the horse buses. Roundabouts, road bridges, traffic lights, and subways set further hazards in his course and compel him to live up to his name ; as Mr. Foley very fairly says, Impressive figures are sometimes quoted estimating the economic loss caused by delays to vehicular traffic, but nothing is said about the economic loss due to delays to pedestrians." Even on country roads the pedestrian is often put to risk and inconvenience because the lack of a footpath obliges him to share the highway with cars and lorries. Yet in the past twenty years accidents to pedestrians have gone down, while those to motorists have gone up; and in our character of motorists, it seems, we are now pressing the Ministry of Transport to introduce legislation to restrict our rights as pedestrians still further. These proposed restrictions Mr. Foley summarises as follows : "
1. It shall be an offence for a pedestrian (a) to fail to conform to the signal of a police officer regulating traffic; and (b) to cross the road at a light-controlled crossing when the lights are against him, or when there is a light warning don’t cross." 2. Experiments should be conducted in certain areas forbidding the public to cross the road within a certain distance of pedestrian crossings (a) where there is a guard rail, and (b) where there is no guard rail. "
There
serious
practical objections, Mr. Foley pedestrians to obey the same rules asking as us motorists. For one thing the policeman has his hands full-and occupied-in directing the traffic. As pedestrians we make use of his signals in choosing when to cross, but we should probably miss many a good opportunity if we had to wait for him to give us a directive ; and it would all add to our delays. Again, a policeman’s signal to traffic at a T-junction often
thinks,
to
are
us
enables us to cross half the road to an island ; most of would find it frustrating to be denied even this half measure of progress without the direct sanction of the law. He also suggests that there is a certain amount of confusion about zebra crossings. We pedestrians believe us
1. The Regulation of Pedestrians. Summer, 1953.
Reprinted from the Pedestrian,
and found
cornual implantation of the placenta of in 60% breech presentations, whereas, in his total series, almost 90% of the placentae were on the anterior or posterior uterine wall. S’J’!
over
certainly accepts it, and he claims that the cornualfundal placenta makes the upper pole of the uterus narrower than the lower pole, and so leads to breech He showed that out of 70 of his cases for which full data were available, the placenta was in the right cornu in 20 and in the left cornu in 50. He suggested that, because of the normal dextrorotation of the uterus, the placenta in the left cornu would interfere to a greater extent with the shape and capacity of the upper pole than the placenta in the right cornu. The effects of dextrorotation and right cornual implantation would thus tend to counteract each other. We publish this week two articles dealing with the Mr. FELL management of breech presentation. examines a series of 107 attempts at external version under anaesthesia at the Middlesex Hospital. He concludes that, though 2 babies were lost, the procedure is justifiable because the mortality due to uncomplicated breech delivery during the same period was 9%. His conelusions and figures are similar to those of PEEL and Cr,AYTON.34 In 4 of his cases attempted version caused some placental separation and in 3 others labour began prematurely, so the foetal-mortality rate might well have been greater. As 48 of the 107 versions were carried out before the 36th week, premature labour could have been a serious matter.
presentation.
During version it is very tempting to use just a little more force in an attempt to succeed ; and it is here that the greatest danger of version under anesthesia lies. Mr. MAIR, in his article on p. 361, opposes the use of anaesthesia for version except in very special circumstances. In general, he favours version without anaesthesia but with careful preparation and adequate premedication. Nearly all the failures will, he thinks, be cases of frank breech presentation, for which, provided the frank breech is engaged and there is no pelvic deformity or serious disproportion, he advocates surgical induction of labour by rupture of the forewaters. His view is that the opposition to induction in breech presentation is largely based on the fear of prolapse of the cord, and that this risk is eliminated when the frank breech is engaged. The induction is performed when the baby’s weight is estimated at 6-7 lb. ;: it is well known that the mortality in breech deliveries is greatest when the babies are either very small or very large. The two difficulties are the correct estimation of weight and the possible failure of the uterus to respond efficiently to the induction-a possibility hich MAIR does not discuss. His results are good 33. Lull, C. B., Kimbrough, R. A. Clinical Obstetrics. Philadelphia, 1953. 34. Peel, J. H., Clayton, S. G. J. Obst. Gynœc., Brit. Emp. 1948,
55, 614.
(only 1 baby was lost in 71 uncomplicated deliveries), but in a larger series a few babies might be lost front
infection and other factors associated with induced labour, unless the obstetrician was prepared to perform caesarean section in every case which failed to to induction. respond promptly V ARTAN 28 29 followed much the same lines as MAIR, who now emphasises them as part of a planned policy. This policy could not be followed in general practice, but NixoN and HICKSON 35 think that all breech presentations, whether in primigravidee or multiparae, should be delivered in hospital. This is sound advice because of the complications that may arise, and because very few practitioners can handle sufficient cases to become or remain proficient in their management. For the unexpected emergency, however, the use of the cross-bed position, the generous episiotomy, and the avoidance of traction remain the principal means
of avoiding
or
overcoming complications.
One-dose Treatment for Malaria THE old idea of a drug powerful enough to cure a disease at a single dose-the dosis magna sterilisansIt has been is becoming almost a commonplace. achieved in malaria, but most of the investigations have been made in patients who presumably have some degree of immunity to the disease. This immunity is a relative affair, better known as " premunition," which depends for its maintenance on continuing infection, and which is often incomplete and therefore compatible with occasional attacks of fever. The point is that in such a patient the results of chemotherapy are likely to be different from, and probably more favourable than, the effects of treatment in non-immune persons. Nevertheless, the prospect of effective treatment of an attack of malaria by a single dose of a drug is very welcome forjust this kind of patient. It means that the dose can be given under supervision, often in the outpatient department, and that the uncertainty of dosage when drugs are given to primitive people for administration at home is avoided. The mother of an African child, who knows nothing of tablets and dosage, can hardly be expected to carry out treatment which needs repetition at stated intervals, but a single dose given at hospital or dispensary is a different matter, if it is effective. There is much evidence that with the newer antimalarial drugs such a dose is effective. Several drugs have been used in this way : ’Camoquin,’ for instance, in a single dose of 400 mg., or two doses of 200 mg., by mouth, reduced pyrexia in an average of 24-8 hours, and eliminated parasites from the blood in 46-6 hours in a trial in India 36 ; and rather similar results were reported from elsewhere in India,37 and in Malaya. 38 In Honduras, HOEKENGA39 gave single doses of 0-4-1-0 g. of camoquin base to 380 patients in an endemic, area of whom half had Plasmodium falciparum and half had P. vivax infection ; few failed to respond. In Bolivia, a dose of 0-8 g. (for adults) cleared the blood in 28 hours.40 These single doses of camoquin were all given by
35. Nixon, W. C. W., Hickson, E. B. A Guide to Obstetrics in General Practice. London, 1953. 36. Khan, N., Suri, R. M., Nair, P. M. Indian med. Gaz. 1951, 37. 38. 39. 40.
86, 293. Ansari, M. Y.
Indian J. med. Sci. 1952, 6, 306. Med. J. Malaya, 1951, 6, 24. Hoekenga, M. T. J. Amer, med. Ass. 1952, 149, 1369. Villarojos, V. M. Amer. J. trop. Med. 1951, 31, 703.
Wallace, R. B.
384 it can be used intravenously, and PAYNE et al. 41 gave 150 mg. of base by this route to 5 patients
mouth, but
with naturally acquired P. vivax malaria, with quick clinical cure. In these trials of single-dose treatment the question at issue is the effect on the immediate attack, and camoquin shows up well ; indeed, VILLAREJOS 40 claims that it can cure P. frxlcipar2cm malaria radically, and even reduce the relapse-rate of P. vivax malaria. Chloroquine also shows this prompt result. In Spanish Guinea, VILA CORO 42 found as much value in a single dose (]"5 g. for adults) as in longer courses, with rapid disappearance of symptoms ; and iri Nigeria JELLIFFE and JELLIFFE 43 gave a single intramuscular dose of 5 mg. of base per kg. bodyweight to African children, who were cured within 2 days. These African infections were predominantly due to P. falciparum, and the same infection in Haiti responded similarly to a single dose of 2 g. (for adults) of hydroxychloroquine.44 Proguanil can also give clinical cure after a single dose, but MACDONALD and RAO 45 bring out a point of importance. They gave 300 mg. to adults and 200 mg. to children, most of whom had some premunition, and most of them were free from pyrexia and parasites in 72 hours. But almost half of them eventually relapsed, even some with P. falciparum, in an area of Ceylon where reinfection was unlikely. They therefore concludethat single-dose treatment should not be given if radical cure is desired. Pyrimethamine (‘ Daraprim ’) is the last-comer, and for patients with some premunition it too has given good single-dose results. ARCHIBALD 46 gave 25 mg. to Lagos school-children, and McGpEGtOR and SMITH 47 gave 0-25-0-5 mg. per kg. to Africans in Gambia. In these trials clinical cure was achieved within 72 hours. Similarly in Tunisia and Indo-China, ScsNEiDER et al. 48 found that a single dose of 50 mg. of base was effective within little more than 2 days. In Kenya Africans, JONES 49 found that 50 mg. was rapidly successful, even in 3 cases of cerebral malaria; but, commenting on this report, MCROBFRT 50 hopes that experiments on the oral administration of pyrimethamine in cerebral malaria in non-immunes or in unconscious Africans will not be contemplated. Indeed, although MOGREGOR and SMITH 47 were able to clear the blood with these minute doses, GOODWIN 51 thinks that the chief value of this drug may be in suppression. It is still too early to say. To sum up, therefore, several drugs will cure an attack of malaria if given in a single dose, and if the patient has some premunition ; but if radical cure is the aim, or if non-immunes are being treated, a single dose is probably not enough. But, even so, this is a remarkably useful quality of these modern drugs ; and, of course, a dose of quinine will clear up many an attack in semi-immune people. 41. Payne, E. H., Villarejos, V. M., Sharp, E. A., Reinertson, J. W., Wille, W. S. Ibid, p. 698. 42. Vila Coro. Z. Tropenmed. u. Parasit. 1951, 3, 158. 43. Jelliffe, D. B., Jelliffe, E. F. B. Trans. R. Soc. trop. Med. Hyg. 1953, 47, 235. 44. Loughlin, E. H., Rice, J. B., Wells, H. S., Rappaport, I., Joseph, A. A., Rene, H. Antibiotics, 1952, 2, 171. 45. Macdonald, O. J. S., Rao, P. V. Ceylon J. med. Sci. 1950, 7, 55. 46. Archibald, H. M. Brit. med. J. 1951, ii. 821. 47. McGregor, I. A., Smith, D. A. Ibid, 1952, i, 730. 48. Schneider, J., Canet, J., Dupoux, R. Bull. Soc. Path. exot. 1952, 45, 33. 49. Jones, S. A. Trans. R. Soc. trop. Med. Hyg. 1952, 46, 564. 50. McRobert, G. R. Trop. Dis. Bull. 1953, 50, 186. 51. Goodwin, L. G. Trans. R. Soc. trop. Med. Hyg. 1952, 46, 485.
Annotations THE FREEDOM OF THE ROAD To step from a car to the sidewalk is to embrace a different constellation of prejudices : to the pedestrianall drivers are possible knaves, to the driver all pedestrians are probable fools ; and the walking motorist distrusts drivers no less passionately than the driving motorist distrusts pedestrians. Nothing could better exemplify the partiality of human judgment. Mr. T. C. Foley,1 secretary of the Pedestrians Association, is aware of this split in our nature, which allows each of us to be both Jekyll and Hyde-or rather, allows each of us to be two aspects of Jekyll, while everybody else is two aspects of Hyde. " We cannot expect," Mr. Foley (in the character of pedestrian) remarks, " to maintain the free use of the highway as it existed before the motorcar age. The practical issue is, however, how much of that freedom are we to give up, and how much incon. venience and delay should we accept in order to reduce the risk of accident to ourselves and to assist the flow of vehicular traffic, in which as drivers, cyclists or passengers we also have an interest." The pedestrian, he points out (and in that character we can all agree with him), is already put to great inconvenience by motor traffic. To take only one example, there was a time when buses stopped immediately outside Underground stations ; today the pressure of traffic prohibits this arrangement, and the pedestrian often has a longish walk from the station to the stop. On a wet day, or when he is carrying a heavy bag, this may cause him to regret the old swift days of the horse buses. Roundabouts, road bridges, traffic lights, and subways set further hazards in his course and compel him to live up to his name ; as Mr. Foley very fairly says, Impressive figures are sometimes quoted estimating the economic loss caused by delays to vehicular traffic, but nothing is said about the economic loss due to delays to pedestrians." Even on country roads the pedestrian is often put to risk and inconvenience because the lack of a footpath obliges him to share the highway with cars and lorries. Yet in the past twenty years accidents to pedestrians have gone down, while those to motorists have gone up; and in our character of motorists, it seems, we are now pressing the Ministry of Transport to introduce legislation to restrict our rights as pedestrians still further. These proposed restrictions Mr. Foley summarises as follows : "
1. It shall be an offence for a pedestrian (a) to fail to conform to the signal of a police officer regulating traffic; and (b) to cross the road at a light-controlled crossing when the lights are against him, or when there is a light warning don’t cross." 2. Experiments should be conducted in certain areas forbidding the public to cross the road within a certain distance of pedestrian crossings (a) where there is a guard rail, and (b) where there is no guard rail. "
There
serious
practical objections, Mr. Foley pedestrians to obey the same rules asking as us motorists. For one thing the policeman has his hands full-and occupied-in directing the traffic. As pedestrians we make use of his signals in choosing when to cross, but we should probably miss many a good opportunity if we had to wait for him to give us a directive ; and it would all add to our delays. Again, a policeman’s signal to traffic at a T-junction often
thinks,
to
are
us
enables us to cross half the road to an island ; most of would find it frustrating to be denied even this half measure of progress without the direct sanction of the law. He also suggests that there is a certain amount of confusion about zebra crossings. We pedestrians believe us
1. The Regulation of Pedestrians. Summer, 1953.
Reprinted from the Pedestrian,