Winnipeg
WHOOPING cough is an almost universal infectious disease, with its greatest infectivity in pre-school and school children. While some protection has been afforded against it by vaccination, treatment of the active disease has not progressed as has treatment of other infectious diseases such as scarlet fever and diphtheria. Madsen 1 reports that, of 1,842 vaccinated children, about 25 per cent escaped infection, while of 446 non-vaccinated children less than 2 per cent escaped. This decided improvement warrants the use of vaccines, but still leaves the infected child confronted with some weeks of unpleasantness and a not inconsiderable mortality rate. According to Tice, 2 in the registration area of the United States there were 7,518 deaths in 1934. In the years 1932-34 there were 45,755 cases of whooping cough reported to the Dominion Bureau of Vital Statistics, with 1,982 deaths. Of the fatal cases over 50 per cent occur in the first year of life. The non-fatal cases undergo a most disagreeable experience and lose considerable time from studies, in the case of the schoolchild. The disease is characterized by spasmodic coughing and vomiting, and this spasmodic or paroxysmal stage persists for weeks. How this paroxysmal stage originates, and why it should be so prolonged, has always intrigued investigators, and various hypotheses have been put forward. Among them is one suggested by Brown, 3 that a neurotropic toxin elaborated by the bacillus in the early catarrhal stage affects the vagus and respiratory centres and possibly the sensory nerve-endings in the upper respiratory mucosa. Fixation of this toxin in nervous tissue would explain the comparative failure of vaccines or convalescent serum to influence the course of the disease unless given in the incubation period or early in the catarrhal stage. Both exo- and endotoxins have been obtained from the Bordet-Gengou bacillus.
Ascorbic acid has been investigated by several workers from the standpoint of its detoxicating action. Grootton and Beszonoff 4 record the results of mixing diphtheria toxin and ascorbic acid, incubating very briefly, and injecting the mixture into guinea-pigs. Unneutralized ascorbic acid completely destroyed the toxic action, but this effect was one of pH and not a specific effect. Ascorbic acid neutralized with soda and mixed with the toxin so altered its potency that, of four guinea-pigs receiving 4 M.L.D. of toxin each, one survived and the others died respectively on the 4th, 6th, and 9th day. Controls injected with 4 M.L.D. each of unaltered toxin all died on the 2nd day. These workers, in the same paper, tested the actual bactericidal action of ascorbic acid against various bacteria by adding varying amounts of the acid to the culture medium, bringing the mixture to a pH of 7.0, and inoculating with such organisms as staphylococcus, streptococcus, gonococcus, typhosus, Bordet-Gengou, etc. With 0.5 per cent ascorbic acid mixtures only the gonococcus and Bordet-Gengou bacillus were inhibited, as compared with controls. The gonococcus grew readily in a 0.2 per cent mixture. In a percentage of 0.008, ascorbic acid inhibited the growth of the Bordet-Gengou bacillus. Glacial acetic acid added to the culture medium in corresponding amounts, and then neutralized, failed to affect the growth of this bacillus.
Woringer and Sala 5 reported 4 cases of whooping cough complicated by scurvy occurring among a series of infants treated in their clinic. No scurvy appeared among the other children, although all were on exactly the same dietary regimen. They suggest that vitamin C is an essential part of the body’s defence against the Bordet-Gengou bacillus, and that excessive demands made in the presence of such an infection may so deplete the vitamin stores of the tissues as to lead to the clinical condition of scurvy.
Gander and Niederberger 6 and Hochwald 7 report the use of ascorbic acid in the treatment of pneumonias. Pneumonia cases showed consistently a deficit in vitamin C. Administration of the vitamin produced an effect comparable with that of specific serum. The pulse and temperature subsided by crisis when the avitaminosis was completely relieved, as shown by beginning urinary excretion of the ascorbic acid. When small doses of ascorbic acid were given, the saturation point for the vitamin was reached slowly, and no clinical improvement was shown until this point was reached.
Various investigators 8, 9, 10 have shown that the tissues of normal children and young animals contain more vitamin C than those of normal older subjects, and that the saturation point, as judged by beginning urinary excretion, is attained in young subjects only by much larger doses than relative weights would indicate. This suggests a greater need of vitamin C by young animals, and so a greater storage of it in the presence of an ample supply.
From this evidence, ascorbic acid seemed to have possibilities in the treatment of whooping cough, and one of us (B.M.U.) has been using it in practice for the last two months or so. To date, we can report 9 cases, and 1 from another practitioner.* In each case, diagnosis was made from a history of contact with known cases together with personal observation of the typical cough, vomiting and nocturnal paroxysms. Cough plates or serological tests were not used in this preliminary investigation. Condensed case reports follow.
*Case 4. We are indebted to Dr. C. H. A. Walton for details of this case.
The short series of cases presented is too small to draw any statistical conclusions, but one fact stands out. Ascorbic acid has a definite effect in shortening the period of paroxysms from a matter of weeks to a matter of days. We have not checked by cough plates or otherwise in this preliminary work to see whether the infectivity subsides simultaneously with the spasmodic symptoms, but are continuing with a larger series of cases in which these and other tests will be employed.
|
Case |
Age |
Sez |
Contact |
Duration of |
Treatment |
Results |
|
|
1 |
6 |
M |
School |
6 weeks—typical |
150 mg. per day |
7 days—cough reduced
markedly 10 days—cough disappeared |
|
|
2 |
1½ |
M |
Unknown |
3 weeks—typical |
inhalations sinapisms expectorants |
}3 days |
No effect 7 days—temperature normal, cough reduced 14 days—cough disappeared |
| 175 mg. daily—11 dys | |||||||
|
3 |
12 |
M |
School |
10 days—typical |
200 mg. daily |
6 days—cough reduced 13 days—only occasional night coughs 15 days—all cough absent |
|
|
4 |
6 |
F |
School |
over 4 weeks— |
200 mg. daily |
3 days—cough less, no
vomiting 7 days—occasional cough |
|
|
5 |
2½ |
M |
Known case |
2 weeks—typical |
250 mg. daily |
5 days—cough disappeared | |
|
6 |
7 |
M |
School |
2 weeks—typical |
375 mg. daily |
4 days—cough less 9 days—night cough only 11 days—all cough absent |
|
|
7 |
22 |
Maid |
4dys., paroxysmal |
500 mg.
daily—3 days 125 mg. daily. |
4 days—cough less, no
vomiting 6 days—coughed only once in 2 days 11 days—cough absent |
||
|
8 |
4 |
M |
Known case |
10 days—typical |
500 mg.
daily—4 days 250 mg. daily—4 days |
5 days—cough disappeared | |
|
9 |
6½ |
F |
School |
2 weeks—typical |
500 mg.
daily—4 days 250 mg. daily—5 days |
4 days—cough reduced 7 days—coughed once in 24 hours 9 days—cough disappeared |
|
|
10 |
4½ |
F |
Sister (Case 9) |
1 week—typical |
500 mg.
daily—4 days 250 mg. daily—5 days |
Same as for Case 9 | |
The dosages used have been empirical with a tendency to use larger doses early in the disease as our experience of its effects progressed. The acid is available at reasonable prices, and the danger of overdosage seems negligible. Animals have received 2,000 times their estimated requirements without any deleterious effects. Any excess is excreted by the kidneys.
The ascorbic acid used by us was the Hoffmann-LaRoche product sold under the trade name of “Redoxon”. Grootton and Beszonoff 4 have shown that the product is identical chemically, physically and biologically with the original product prepared by Szent-Györgi.
From The Canadian Medical Association Journal, Volume 37, August 1937, Number 2, pp. 134-136
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