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A CHRISTMAS APPEAL
1399
CORRESPONDENCE A CHRISTMAS APPEAL
of THE LANCET as the time for the increases SiR,—My anxiety distribution of our Christmas gifts draws near. I am indebted to many of your readers who have responded to the appeal which was made in October, but I fear that the amount subscribed to date falls far short of the sum which is needed if we are to give the much valued Christmas gift of 30s. to all our regular -
To the Editor
of variations in the incubation
period, since it will be at least, by differences in length of illness before death occurs. We think, however, that some part of the skewness is almost certainly due to variations in incubation time. For one thing, it is very unusual for a mouse to show any signs of determined, in part
-
beneficiaries. Christmas Day to all of
us is a very special day ; it brings back memories of happy days in the past, and all have the wish to make each Christmas Day a happy day in our own home life. I have intense sympathy for so many of our beneficiaries living in loneliness, some in one bedsitting-room, at a rental of 10s. a week, without relatives and without friends, and who can look only to the Fund as the society which " never forgets them " on Christmas Day. I ask everyone who reads this last appeal not to pass it by but to send a donation, however small or large, without delay to the hon. treasurer, Royal Medical Benevolent Fund, 11, Chandos-street, Cavendish-square, London, W.l, so that we may be in a position to give the 30s. Christmas gift to those who have so little of their own and who are befriended I am, Sir, yours faithfully, by the Fund. THOS. BARLOW, President. BARLOW, President. Nov. 30th.
INCUBATION PERIOD OF TYPHOID
To the Editor
of
THE LANCET
to the epidemic of typhoid at or milk-borne epidemics of and to waterCroydon, enteric infection in general, two questions arise in which useful analogies are, perhaps, afforded by experimental observations on mice infected with
SiR,-In relation
Bact.
typhi-murium (Bact. aertrycke).
In human epidemics in which a large number of persons are exposed to the risk of infection from polluted water or milk during a few consecutive days, and the risk is then removed by appropriate measures, it is not uncommonly assumed that, apart from contact infections, cases should cease to occur within If twenty-one days were allowed some fixed period. as the maximal probable incubation period, and seven days were added to this to allow for the definite diagnosis of a suspected case, it might be supposed that no primary case would be notified later than twenty-eight days after the initial risk had been
removed. Our experience with mice leads us to suspect that this assumption is ill-founded. In certain experiments that we have performed, we have records of 440 normal susceptible mice that were given by mouth doses of living Bact. typhi-muriam varying from 100 million to 500 million bacilli. Each mouse was thereafter housed in a separate cage, with strict precautions to avoid all cross-infection. During the subsequent twenty-eight days 300 of these mice died of mouse-typhoid. The mortality in relation to time is shown in the accompanying Figure. It will be noted that the majority of deaths occurred between the seventh and fourteenth days, with a modal frequency on the tenth and eleventh days. But the curve of mortality is markedly skew, with a pronounced extension to the right, and some mice were still dying of the disease twenty-five days or more after infection. It would not be just to regard the form of the mortality curve as an accurate reflexion
one or two days before its death. emphasise below, we have ample evidence that a high proportion of the mice that survive in apparent health for twenty-eight days are still harbouring the causative organism in their
illness for For
more
another,
than
as we
tissues. Additional evidence, pointing in the same direction, is afforded by the findings obtained in another experiment. In this experiment several hundred mice were submitted, for various periods, to the risk of contact infection in a herd in which mouse-typhoid was epidemic, and were then removed and kept in isolation in separate cages for sixty days. This longer period of observation enabled us to note that a small number of mice died of mouse-typhoid after being removed from all risk of infection for periods of thirty to forty-six days, and after remaining in apparent health for almost the whole of this period. It seems to us probable that the average incubation time, and the average time between infection and death in those that die, are expressions of a modal reaction between a particular parasite and a particular host, and that this mode may be rather widely departed from in a proportion of cases, probably in relation to the size of the infecting dose received, or to variations in the natural resistance of individual hosts, or to many other factors. We have little doubt, so far as the mouse is concerned, that the skewness of the mortality curve is in part due to the fact that many mice develop an infection which displays no clinical symptoms, and which may remain
long periods, and eventually disappear unless it is activated by some secondary Whether a mouse that dies thirty or more
latent for
altogether,
factor. after infection does so because it has been days " incubating " the disease for an unusually long period, or because a latent infection has become active and lethal, it is impossible to say. The point of interest is that, when any large number of animals are infected synchronously, or within a short period of time, sickness and deaths will continue to occur for a period considerably in excess of that indicated as likely by the modal course of events. It seems to us probable that the same may be true of typhoid in man and that, apart altogether from contact infections,
CORRESPONDENCE A CHRISTMAS APPEAL
of THE LANCET as the time for the increases SiR,—My anxiety distribution of our Christmas gifts draws near. I am indebted to many of your readers who have responded to the appeal which was made in October, but I fear that the amount subscribed to date falls far short of the sum which is needed if we are to give the much valued Christmas gift of 30s. to all our regular -
To the Editor
of variations in the incubation
period, since it will be at least, by differences in length of illness before death occurs. We think, however, that some part of the skewness is almost certainly due to variations in incubation time. For one thing, it is very unusual for a mouse to show any signs of determined, in part
-
beneficiaries. Christmas Day to all of
us is a very special day ; it brings back memories of happy days in the past, and all have the wish to make each Christmas Day a happy day in our own home life. I have intense sympathy for so many of our beneficiaries living in loneliness, some in one bedsitting-room, at a rental of 10s. a week, without relatives and without friends, and who can look only to the Fund as the society which " never forgets them " on Christmas Day. I ask everyone who reads this last appeal not to pass it by but to send a donation, however small or large, without delay to the hon. treasurer, Royal Medical Benevolent Fund, 11, Chandos-street, Cavendish-square, London, W.l, so that we may be in a position to give the 30s. Christmas gift to those who have so little of their own and who are befriended I am, Sir, yours faithfully, by the Fund. THOS. BARLOW, President. BARLOW, President. Nov. 30th.
INCUBATION PERIOD OF TYPHOID
To the Editor
of
THE LANCET
to the epidemic of typhoid at or milk-borne epidemics of and to waterCroydon, enteric infection in general, two questions arise in which useful analogies are, perhaps, afforded by experimental observations on mice infected with
SiR,-In relation
Bact.
typhi-murium (Bact. aertrycke).
In human epidemics in which a large number of persons are exposed to the risk of infection from polluted water or milk during a few consecutive days, and the risk is then removed by appropriate measures, it is not uncommonly assumed that, apart from contact infections, cases should cease to occur within If twenty-one days were allowed some fixed period. as the maximal probable incubation period, and seven days were added to this to allow for the definite diagnosis of a suspected case, it might be supposed that no primary case would be notified later than twenty-eight days after the initial risk had been
removed. Our experience with mice leads us to suspect that this assumption is ill-founded. In certain experiments that we have performed, we have records of 440 normal susceptible mice that were given by mouth doses of living Bact. typhi-muriam varying from 100 million to 500 million bacilli. Each mouse was thereafter housed in a separate cage, with strict precautions to avoid all cross-infection. During the subsequent twenty-eight days 300 of these mice died of mouse-typhoid. The mortality in relation to time is shown in the accompanying Figure. It will be noted that the majority of deaths occurred between the seventh and fourteenth days, with a modal frequency on the tenth and eleventh days. But the curve of mortality is markedly skew, with a pronounced extension to the right, and some mice were still dying of the disease twenty-five days or more after infection. It would not be just to regard the form of the mortality curve as an accurate reflexion
one or two days before its death. emphasise below, we have ample evidence that a high proportion of the mice that survive in apparent health for twenty-eight days are still harbouring the causative organism in their
illness for For
more
another,
than
as we
tissues. Additional evidence, pointing in the same direction, is afforded by the findings obtained in another experiment. In this experiment several hundred mice were submitted, for various periods, to the risk of contact infection in a herd in which mouse-typhoid was epidemic, and were then removed and kept in isolation in separate cages for sixty days. This longer period of observation enabled us to note that a small number of mice died of mouse-typhoid after being removed from all risk of infection for periods of thirty to forty-six days, and after remaining in apparent health for almost the whole of this period. It seems to us probable that the average incubation time, and the average time between infection and death in those that die, are expressions of a modal reaction between a particular parasite and a particular host, and that this mode may be rather widely departed from in a proportion of cases, probably in relation to the size of the infecting dose received, or to variations in the natural resistance of individual hosts, or to many other factors. We have little doubt, so far as the mouse is concerned, that the skewness of the mortality curve is in part due to the fact that many mice develop an infection which displays no clinical symptoms, and which may remain
long periods, and eventually disappear unless it is activated by some secondary Whether a mouse that dies thirty or more
latent for
altogether,
factor. after infection does so because it has been days " incubating " the disease for an unusually long period, or because a latent infection has become active and lethal, it is impossible to say. The point of interest is that, when any large number of animals are infected synchronously, or within a short period of time, sickness and deaths will continue to occur for a period considerably in excess of that indicated as likely by the modal course of events. It seems to us probable that the same may be true of typhoid in man and that, apart altogether from contact infections,