Acta Nedica Scandinavica. Vol. CXXXV, fusc. 11, 1949.

From the Infectious dbeases Hospital at Ostersund. Sweden. (Head: I. Lundholm M D.)

Prognostic and Pathogenetic Aspects on Some Early Synip- toms in Poliomyelitis.'

BY

I. LUNDHOLM.

(Submitted for publication September 18, 1948.)

The most important part of research into the nature of poliomyelitis naturally devolves upon epidemiologists and experimental bacteriologists. However, a uniformly observed and systemathized clinical material might well aid in elu- cidating some hitherto unsolved questions. The present report is based on a ma- terial comprising 461 cases observed during the 1937-39 epidemic in the District of Jamtland, Sweden.2 The object of our studies was to establish the prognostic importance of some early symptoms and to try to clear up the much debated question concerning the part played by pharyngeal symptoms in the pathogenesis of infantile paralysis.

Pirstly the author will briefly review the extent of our knowledge about polio- myelitis a t the present time. Already in 1911 Pettersson, Kling and Wernstedt demonstrated the presence of polio virus in the pharynx and feces. In 1928 Kling's continued investigations led to his then published theory stating that the virus was spread by water and entered the organism by way of the stomach and in- testines. Later investigations have corroborated the presence of virus in the pha- ynx and intestines, and we now know that virus may be found in the feces 6 to 8 weeks and sometimes longer after the onset of poliomyelitis. A natural con- sequence of this was to look for virus in sewer water where i t was first found by Paul and Trask and somewhat later by Kling et al. Evans calculates that mostly 1 g feces contains an infectious dose of poliomyelitis virus but the concentration may, sometimes, be so high that the infectious dose can be contained in 0.0001 g feces which fact might explain the sporadic presence of virus in sewer water. In a moderate epidemic of poliomyelitis Evans estimates the number of virus car- riers to 1 yo of the population.

~

'Cramdated by Klas Lindskog. The author wishes to express his indebtedness to The State Institute of Human Genetics and its

Chief Professor Gunnar Dahl6erg for the statistical treatment of the material.

SOME EARLY SYMPTOMS IN POLIONYELITIC. 121

In America Melnick, among others, have put the number of virus carrying per- sons in districts served by some virus infected sewer systems a t 50 to 70 per thou- sand. I n these same districts the poliomyelitis morbidity was 0.13 per thousand. Therefore the number of healthy virus carriers outnumbered the number of polio- myelitis patients in a proportion of 500: 1. I n 1944 Kling, Olin and FBhrzus, basing themselves on certain observations and experiments, developed their theory about the transmission of poliomyelitis by drinking water which in a given district has become infected from sewers adjacent to virus polluted water mains. The same authors have also motivated a theory concerning specific mass immu- nisation of urban populations through infected pipe water in locations where a polio epidemic has been rampant. In the year 1938 Jonsson in a thesis inquired critically into the possibilities of proving that poliomyelitis infection is spread through water or personal contact.

The proved presence of virus all the way from the oral cavity and pharynx to the rectum has been termed the extraneural infection. Both as regards pharynx and intestines this infection may run its course with no sign of any symptoms. Sometimes, indeed, the only way to demonstrate i t is to experimentally prove the presence of virus in for instance pharyngeal secretions. In addition to this extraneural infection we then in a few cases have the neuroinfection which, conse- quently, may be thought of as a rare complication. Due to the fact that polio- myelitis infection has exactly the same effect in chimpanzees as in man i t has been possible to reproduce the neuroinfection experimentally. Similarly mice have been used for experimental purposes and in them also there is an extraneural and a neuroinfection. The essential difference between man and mice in this respect is, however, that in man the extraneural infection attacks the oral cavity and pharynx as well. That it may run its course without symptoms in these organs has already been mentioned. It is, on the contrary, surprising to find the statement that this pharyngeal infection in man, judging by observations made up to the present, always should run its course devoid of symptoms and be capable of de- monstration solely through the presence of virus in the pharyngeal secretion. On the contrary, i t appears from the description of the early symptoms of polio- myelitis to be given in the following that the pharyngeal infection is a very in- tricate problem.

At present the mechanics of poliomyelitis infection are not fully understood but a number of important advances have, none the less, been made. We know from the findings of Landsteiner, Levaditi and Pastia in 1911 and other sources that tonsils from patients who have died in poliomyelitis contain virus. During the polio epidemic of 1936-38 Kling, Olin and Gard, studying sections from btersund and other locations, in 4 cases of 32 demonstrated the presence of virus in the mesenteric glands, and in 1 of 2 cases in the cervical glands. The authors leave open the question whether the findings are signs of general infection of the lymphatic system, or if they imply that a station has been found for the virus on its way from the port of entry to the central nervous system.

In a symposium of 1947 dealing with infantile paralysis (unpublished) Gard, basing his assumptions both on the above and other similar experiments and on

122 I. LUNDIIOLM.

the established fact that true poliomyelitis often is preceded by a distinctly sep- arate phase with pharyngeal and intestinal symptoms, develops the theory that the virus is conveyed passively from the intestinal lumen, where i t may be found in enormous quantities during an epidemic, by the lymph to regional lymphatic glands which usually act as a barrier to further progress of the virus. A non-specific infection (of intestine or pharynx) desquamates the sinus endothelium of the lym- phatic glands, exposes the ramifications of the sympathetic nerves, permits virus to gain access to nervous tissue and to spread rapidly to the anterior horn cells of the spinal cord or brain.

Here a short resum6 will be given of the early symptomatology of poliomyelitis and reference is made to table 1 which is based on the investigated Jiimtland cases and also contains some complementary figures from Pranconi's and Jonsson's reports. First, however, i t should be noted that the material comprises two essen- tially different types of the disease, viz. 81 so called abortive cases, which only had meningitis with cellular increase in liquor, and 380 cases who suffered from paresis.

igt- 7.5

12.8 51.3 0

30.0 60.0 26.5 17.5 23.7 46.1

Table 1.

Number of Cases with Various Symptoms in Percent.

Paresii

7.0 9.3

48.4 0.7

25.2 76.7 43.4 34.2 12.0 84.3

S y m p t o m s

Pharyngeal pains.. ..... Tonsillitis ............ Pharyngitis . . . . . . . . . . . Diarrhea .............. Vomiting . . . . . . . . . . . . . Headache . . . . . . . . . . . . . Backache ............. Kcrnig'a symptom. ..... Neckache . . . . . . . . . . . . . Neck stiffness .........

Own material (Men + Women)

Two-attack cases

1st attack

ibor- tive - 35.0 42.a 57.1 2.5

12.5 47.5 12.0 - - -

'aresim

- 35.6 37.5 71.4 5.2

16.4 55.0 20.0 - - -

- ~

2nd attack

_ _ -~

One attack Meningitis

stage

ibor- tive - 15.0 5.0

25.0 0

22.5 72.5 24.3 5.0

15.0 41.5

__

'aresi,

- 13.2 10.1 45.8 2.5

34.1 72.7 37.4 32.7 11.0 72.1

Fanconi Jonsson

Two attacks __

Linor llness

- 27.2

7.4

3.3 12.5 22.5

fenin. gitis

- 52 66

Initial symptoms

ibor- tive

6

3 34 74

- 'aresii - 11

3 44 76

According to the following rules the cases of paresis have been divided into slight, moderate and severe cases. This procedure has been strictly adhered to and, briefly, the groups are: 1) Slight cases from those with traces of paresis in an isolated muscle group to those with slight paresis in several muscle groups, all having in common that the paresis disappeared completely within three weeks. 2) Moderate cases with moderate paresis in one or, mostly, several muscle groups, sometimes in an entire extremity, and which did not heal within 3 weeks. 3) Severe cases with marked paresis in large portions of, as a rule, several muscle groups and not infrequently with total paresis of one or more limbs all of which later have undergone treatment for disablement. This last group also includes all fatal cases.

SOME EARLY SYMPTOMS IN POLIOMYELITIS. 123

Frequency difference between 1st and2nd Abortive cases Paresis cases

attacks

It should be kept in mind that nowadays the most common conception of the early symptoms of poliomyelitis is that firstly there is a catarrhal phase of a few days' duration with symptoms from the pharynx or of infectious nature generally, secondly, in some cases, an interval without symptoms followed by a phase of in- cipient meningitis which heralds the onset of symptoms that with certainty can be ascribed to poliomyelitis virus. I n the entire Jiimtland material one attack was approximately as frequent as two, viz. 56.7 I: 2.3 yo.

The early symptoms could be split up into three separate groups (table 1). The first group comprises both pharyngeal symptoms in the form of anamnestic- ally reported throat pains, objectively observed tonsillitis or pharyngitis and also diarrhea, indicating irritation in the intestinal tract. Obviously the latter symptom is very rare in our material. Pharyngeal symptoms are, on the other hand, all the more common. The second group comprises the triad vomiting, headache and backache. These symptoms are such that they might indicate a general infection of the organism due to a multiplicity of reasons. Headache is, however, much more common in the meningitis phase than in the catarrhal phase, in the second stage of the illness this is especially due to the neuroinfection with concomitant irrita- tion of the central nervous system. The same applies to backache and vomiting. The third group, finally, comprises direct symptoms of the neuroinfection, especi- ally Kernig's sign and neck stiffness when, however, the neckache as such may be of doubtful origin but as it does not occur in the first stage of the 2-stage ill- ness i t may be presumed to be connected with the neuroinfection.

Frequency differ- a ~ ~ ~ ~ $ , ~ ~ ~ r e - ' O n e attack 2nd attack

sis cases I

Table 2. Differences between the Percentages in Table 1 (Own Material).

28.2 f 17.3 23.0 & 17.6 8.8 i: 4.5

21.1 i: 5 .2 23.4 & 5.2

1

i Pharyngeal pains . . . . . . . . Tonsillitis . . . . . . . . . . . . . . Pharyngitis . . . . . . . . . . . . . Vomiting . . . . . . . . . . . . . . . Headache ............... Backache . . . . . . . . . . . . . . .

I I i I I 27.5 f 8.7 30.1 f 19.4

5.8 & 20.3 17.5 f 8.9 12.5 5 11.0 13.6 & 9.3

38.2 i: 8.4

Summing up i t may be said that the frequency of catarrhal symptoms show a decreasing tendency from the first stage t o the second (tables 1 and 2). A significant difference is, however, only to be found in connection with the pharyngeal pains. Reliable information about tonsillitis and pharyngitis is not so frequent in the first stage of the illness and this implies that the frequency will be somewhat uncertain (considerable mean errors). For headache, vomiting and backache the figures naturally show the opposite tendency, i. e. the frequency is greater in the second stage of the illness. Here there is a definite difference in paresis cases re- garding headache and backache which undoubtedly are most common in the second stage of the illness because of the incipient meningitis.

124 I. LUNDHOLM.

~~~ ~ ~~

Cases with Cell content ! Abortive I Paresis Difference

One attack .................. Max. 200 cells per cubio mm 72 yo 52 yo 20 f 8.0 Max. 400 cells per cubio mm 90 yo 74 % 16 f 5.8

Two attacks ................. Max. 400 cells per cubio mm 80 % lgi % 19 f 7.4

Comparing paresis and abortive cases we shall now pass on to examine various symptoms from a prognostic point of view (Table 1). It should be noted that in patients who only have the first phase of the illness there probably is a higher frequency of pharyngitis in paresis than in abortive cases. I n the first stage of a two-phase illness cases resulting in paresis also show higher values for pharyngitis but the mean errors are large and no definite conclusions can be drawn. For other catarrhal symptoms there is no difference between paresis and abortive cases. Therefore i t is unsafe to assume that a severe infection of the pharynx would imply a larger risk of the poliomyelitis infection resulting in paresis than in i t being abortive.

The cases were also grouped with regard to the highest temperature run and thus i t was demonstrated that patients suffering one attack have at temperature of 39.2" & 0.05" while abortive cases had 38.9 O 3 0.11". The difference 0.3 & 0.12 is probable and would seem to indicate that a higher temperature implies a greater risk of paresis. The same tendency is evident in the second stage of a 2-phase illness. Here also the temperature is higher in the meningitis stage of the paresis cases, i. e. those who are prognostically worse. From his observations Fanconi has drawn the same conclusion, and probably they are correct. I n the first phase, on the other hand, no difference in temperature between abortive and paresis cases could be demonstrated in our material. Therefore I have been unable to confirm Fanconi's statement that a high temperature during the first phase in- dicates a better prognosis.

Prognostically, the stiffness of the neck may be put to good use. As is shown in table 1 and 2 the differences are considerable. An absence of neck stiffness in either 1- or 2-phase attacks is more characteristic of abortive than paresis cases. Often meningitis in the abortive form can be diagnosed only by means of hypersensi- tive tests such as Amoss' sign, the so called three-foot phenomenon in which the patient is unable to sit upright without arm support, or Spines' symptom im- plying that the knees cannot be touched with the mouth. There is, moreover, a parallel between the mildness of the meningitis and the lower cell counts in liquor which I shall now discuss (table 3). The cell count in the lumbar fluid has, as a matter of fact, considerable interest from a prognostic point of view. During the polio epidemic described here it has been very common indeed that the patients have come in in an early stage of meningitis and then the problem arose whether the cell count in the lumbar fluid could give any prognostic hints. If we put an upper limit to the number of cells in liquor a t 200, 72 % of the one-phase abortive

, One attack .................. I Two attacks . . . . . . . . . . . . . . . . .

Table 8. Cell Content in Spinal Fluid.

Median 110 70 Median 170 275 105 1

60ME EARLY SYMPTOM8 IN POLIOMYELITIS. 125

cases had a cell count of 200 or less, while only 52 yo of the paresis cases had the same low cell count. Judging by this limit the number of cells in the abortive cases is probably lower. For the difference is alla times the mean error. To see whether this tendency is consistent we chose another limit and other conditions. Still considering only one-phase cases and putting the limit a t 400 cells we get the same result. Of 39 abortive cases 35 or 90 yo had a t most 400 cells; of the paresis cases only 74 % (152 of 206) had this low cell count. The difference 16 f 5.8 % is probable with this limit too. In the second stage of a 2-phase illness 80 yo (32 of 40) abortive cases and 61 yo (94 of 154) paresis cases had a cell count of a t most 400. The difference is 19 f 7.4 % and, as we see, it amounts to more than 21/* times the mean error. Therefore we here too have the same tendency as in the one- phase attacks. As a rule abortive cases show lower cell counts then do paresis cases. Another way of expressing this is to avail ourselves of the so called median, i. e. the number of cells below which half the number of cases fall. For one-phase attacks we have that the paresis median is 180 and the abortive median 110, and in two-phase attacks the median for the paresis cases is 275 and for the abortive cases 170, which thus also reflects the lower cell content in the abortive cases.

Summing up we can say that the lower the number of cells in liquor the more probable i t is that our case will be an abortive one. Some may consider this obvious, something that i t is a waste of time and effort t o investigate. The phenomenon is not, however, consistent, a t any rate in inflammations which simultaneously at- tack brain, spinal cord and meninges, e. g. encephalomyelitis. As far as I can see the lower cell count in abortive cases is well worth taking into account.

We now come to the effect of age on the course of the disease. It is a fairly general observation that in civilized countries the severity of the disease increases in pro- portion to the age of the patient. The individual cases become more serious and the risk for epidemics greater. A sorting according to age a t onset of disease has been carried out but i t cannot be used to estimate the risk of contracting poliomyelitis a t various ages as our figures were not calculated as a percentage of the population in each group, which, as Jihsson first pointed out, is imperative if we wish to make comparisons. In our material 58 % of the cases were less than 15 years old and 41 yo were 15 and up, but this actually says nothing about the risk of getting infected. The severity of the disease in the different groups can, however, be compared by using these tabulations. This has been done in tables 4 a and 4 b. If we consider the group 15 years and up, we find that 44.3 Yo of the paresis cases come within this group, while abortive poliomjelitis is represented in 28.9 % of the cases. The difference is 15.4 & 5.6 yo and, consequently, very nearly significant. Patients over 15 years of age who contract infantile paralysis run a greater risk of getting paresis than younger people. Judging by severity the cases may be divided into 52.9 % slight, 16.5 Yo moderate and 30.6 % severe cases. Here also the age of 15 implied a turning point. Above that age the frequency of slight and severe cases is about the same, whereas below 15 slight cases number 62.3 % and severe cases only 24.2. The difference is 38.1 f 4.5 % and thus very significant (table 4 b). Therefore a paresis case has had a much better chance of taking a benevolent course when the patient was under 15.

9-492281. A c f a med. Scandinno. V o l . CXXXI'.

126 I. LUNDIIOLM.

1 No. of cases

I

Table 4 a.

Distribution on Age Groups in Percent.

% I -

under 15 y’rs 1 15 y’rs and up

Abortive cases ..................... . I 81 ~ i?:; 1 28.9}, 1 100.1) ~

Paresis cases.. ....................... 380 44.3 100.0 , ~

Difference 15.4 & 5.6 %.

Table 4 b .

Distribution in Percent of Paresis Cases of Increasing Severity on the two Age Groups.

Severity -

Slight ................................ Moderate ............................. Severe ................................

Total yo Deaths

Under 15 y’rs

62.3 13.511 24.2 I

~~~

100.0 6.8

15 y’rs and up

39.8 21.1 39.1

100.0 18.6

-. _ _

I Difference between age groupr

22.5 f 5.1 1 7.6 f 4.0 14.9 * 4.7 I - ~

11.8 f 3.5 I

Difference 38.1 f 4.5 %.

Finally, mortality in infantile paralysis was much less frequent in patients be- low 15 than in those who had passed this dividing line; the mortality in the former group being 6.8 % as compared to 18 .6 % in the latter. The difference is 11.8 & 3.5. The mortality is in other words three times greater in patients older than 15 years.

There are many possible explanations of these findings, but the material is an insufficient basis for detailed analysis. The age of 15 implies that puberty is at an end, a definite adjustment in the endocrine system. After that age chances of exposure outside the home are greater, too, and this should be emphasized, the possibilities of overworking the neuromuscular apparatus are far greater. It has been my experience, judging by some observations from the present material, that paresis mostly occurs in muscle groups which somehow or other have been strained one-sidedly. The cases observed are, however, too few to permit of any conclusions being drawn but continued observations of this nature might yield good results.

The ethiology of the prestage of the 2-phase illness which in America has been called >)minor illness)) and by Panconi ninapparent poliomyelitis)), has naturally commanded much interest. Table 1 makes i t clear that pharyngeal infection is very common in the first stage of a 2-phase illness. Like Fanconi, American in- vestigators have interpreted this pharyngeal infection as the first stage of polio- myelitis, i. e. they consider it due to polio virus. Panconi gives the following reasons for his hypothesis: In his material the minor illness is so common that i t amounts to 44.3 %. My material yields figures of the same magnitude, whereas Gottberg,

SOME EARLY SYMPTOMS I N POLIOMYELITIS. 127

Mean.. .......................

for instance, puts the 2-phase attacks a t 28 %. Jonsson’s material from Eskils- tuna, Sweden, did, on the other hand, yield the figure 85 %. In a small hospital epidemic of polio which was closely observed Fanconi found double attacks in 16 cases out of 21. Of course, the figures for the double illness must vary in rela- tion to the possibilities of observation available during the catarrhal stage and patients’ attentiveness to their own symptoms. The reason given for the spe- cificity of the minor illness is that in ))apparent poliomyelitis)) virus has been de- monstrated in the pharynx. By itself this means little, and the same applies to the fact that in individual cases the minor illness has been proved contagious. The presence of virus in the pharynx needs not imply that i t is the cause of the irrita- tion. The relationship between virus and pharyngeal symptoms is however of great importance and will be discussed below. A final argument put forward to support the theory that the catarrhal stage is caused by virus is the 2-phase course with a free interval characterizing several virus infections e. 9. morbilli, myalgia epidemica or parotitis-meningitis where there has been no question of a different ethiology for the first and second phase.

1 , 4.1 & 0.5 , 4.S &-0.3

Table 5. Symptom-free Interval between 1st and 2nd Attack.

Days

1 ........................... 2 ........................... 3 ........................... 4 ........................... 5 ......................... 6 ........................... 7 ........................... 8 ........................... 9 ........................... 10 ........................... 11-13 ....................... 14-21 .......................

Abortive cases

9 3 4 7 5 2 6 - -

2 -

Paresis cases

19 17 28 23 25 14 12 2 1 7 5 -

Several authors, e. g. Pette, von Pfauiidler and Gard, consider the pharyngeal infection to be caused by some aspecific contagious matter and not by polio- myelitis virus. The reasons given are that catarrhal symptoms are absent in ex- perimentally induced poliomyelitis in chimpanzees, that virus is strictly neurotropic, that well known and very characteristic diseases such as morbilli and scarlatina in isolated cases may take the place of the pharyngeal infection as a so called ))door opener)). A last reason for the non-specificity of the minor illness is its mul- tiplicity of manifestations. One of Gard’s contentions is that catarrhal symptoms in the so called minor illness have not been proved and, therefore, he assumes that the minor illness is caused by bacteria which give totally different clinical results and which do the job of breaking down the patient’s resistance. It is clear from this material and that of other investigators that there are catarrhal symp- toms in the first stage of poliomyelitis. Their genetic importance is, however, open to discussion and I shall return to this subject later, but first we shall more

128 I. LUNDIIOLM.

Cases with pharyngeal symptoms of some kind

Cases without pharyngeal 17.2 1 54.8

closely study the interval without symptoms between the first and second phase of infantile paralysis.

Table 5 illustrates the duration of the symptom-free interval. Evidently the variability is considerable. However, the average length is approximately the same whether or not paresis sets in. The interval may, however, be prolonged con- siderably. In 6 cases we have observed a duration of 2 or 3 weeks. A variability of this magnitude has no correspondence in other known virus infections having a 2-phase course.

This brings us to subject of the pathogenetic importance of the pharyngeal symptoms. I would point out that these symptoms were common in a large per- centage of the first stage of the disease but had a tendency to decrease in the men- ingitis stage, but without disappearing altogether.

Grouping the cases with respect to some kind of pharyngeal symptoms (table 6) we find good correspondence for the number of abortive cases, paresis cases of varying severity and fatal cases. Accordingly poliomyelitis has the same ten- dency to manifest itself in paretic or abortive form and shows paresis of approxi- mately the same severity and has the same mortality whether or not there have been incipient pharyngeal symptoms. I n other words it is impossible using this material to prove that the presence of a pharyngeal infection has had any in- fluence on the course of the disease.

14.5 30.7 100.0

Table 6.

Distribution i n Percent by Degree of Severity on the Different Groups with Respect to the Presence of Pharyngeal Symptoms.

I have above mentioned two possibilities regarding the relationship between the pharyngeal infection and infantile paralysis or rather the neuroinfeotion. Strictly speaking we can imagine four possibilities.

1. Pharyngeal symptoms and poliomyelitis are coincidental. 2. The neuroinfection in poliomyelitis furthers the development of pharyngeal

3. The pharyngeal infection is aspecific and opens way for poliomyelitis virus. 4. The pharyngeal symptoms are due to poliomyelitis. Whatever the mechanism, we must take the possibility of faulty diagnosis of the

pharyngeal symptoms into account as this depends on the power of observation and judgement of the clinician. The frequencies given by different authors vary widely. In my material the figures are moderately high. If pharyngeal symptoms

symptoms which in other respects are unconnected with the disease.

SOME EARLY SYMPTOMS IN POLIOMYELITIBi. 129

were purely coincidental their frequency would by no means be so high, therefore a coincidence may be considered out of the question.

Coming to alternative 2, I would point out that virus often has been demon- strated in patients long before the onset of catarrhal symptoms from the pharynx, such symptoms may therefore benefit from the extraneural virus infection. This would seem to be quite in line with the varying intervals from the pharyngeal symptoms to the stage of neuroinfection and also correspond well with the fact that no connection has been found between paresis severity and pharyngeal symptoms.

The third possibility is largely dependent on how the virus actually is trans- mitted from mucous membranes to nervous tissue. If virus were active in this respect and the pharyngeal infection in some cases took the part of oway opener)) this would imply that virus reached the nervous tissue in cases when it could not have got there on its own accord. In such cases i t would be reasonable to expect less malignant paresis than when virus makes its own way. Although i t can not, of course, be absolutely certain that there is parallelism between the ability of virus to reach the nervous system and its malignity, the lack of connection be- tween the severity of the neuroinfection and pharyngeal infection seems to dis- favour this alternative.

The corresponding reasoning applies if Gard’s hypothesis about the passage of virus between mucous membranes and lymphatic glands is correct. He thinks that the virus is passively conveyed with the lymph and cannot multiply until it reaches nervous tissue. This would mean that severe poliomyelitis should ac- company pharyngeal infection, and my material does not support this view.

Similar objections may be raised against the fourth alternative stating that the pharyngeal symptoms are dependent on the virus. Some parallelism could be ex- pected between the severity of the neuroinfection and pharyngeal symptoms, even though one naturally can not say that i t certainly should be so. I n my opin- ion i t seems more important that known virus diseases with a two-phase course and a free interval display a temporally far more constant interval, e. g. morbilli, myalgia epidemica, some leptospiroses, isolated cases of parotitis-meningitis with one or two days’ interval between parotitis and meningitis.

The two clinical findings which may be said to be conclusively proved by my investigation, viz. that there is no parallelism between the severity of the neuro- infection and the presence of pharyngeal symptoms and the existence of a very variable interval between the catarrhal pre-stage and the meningitis stage, both bespeak the possibility (alternative 2) that the so called extraneural poliomyelitis infection, i. e. the presence of virus in pharynx and intestinal tract, has furthered the development of a non-specific pharyngeal infection which per se is unimportant. The proof is not conclusive but the explanation seems to be the most natural one.

Quite another question, which however is of great practical importance, con- cerns the spreading of poliomyelitis from person to person by air-contagion, through contact infection in other words.

If there is virus on a catarrhally inflamed mucous membrane such spreading seems to be possible. As we have mentioned the problem has been thoroughly

130 I. LUNDIIOLM.

analyzed by Jonsson who has developed a new procedure for investigating air-con- tagion - a very difficult task. His studies do not, however, prove that air-contagion plays a decisive r6le in the spreading of poliomyelitis. Studies into the spread- ing of epidemics have, as we know, shown that in school classes where there has been a case of poliomyelitis secondary cases are rare. During epidemics, on the other hand, i t is very common that several members of the same family contract the disease. During the Jiimtland epidemic, for instance, family infections oc- curred in a large number of cases. Such facts lead to the conclusion that spread- ing in a manner analogous to virus infections of the influensa type in any case is of secondary importance. If personal contact matters it must evidently be very close implying that patients have used the same cooking utensils, beds etc. The few investigations dealing with the presence of virus in the pharynx are based on a small number of cases. They corroborate each other in as far as a large per- centage - Howe mentions 43 % - showed the presence of virus in the pharynx during the first three days of illness. But that virus already after four days is very rare in this location. Symptoms of inflammation are, however, more lasting, Nat- urally these circumstances do not exclude the possibility of infection being spread from the pharynx which very well could take place during the first day or two and which, just as well as the theory regarding the spreading of infection by way of the feces, is compatible with the general observation that patients who have reached the paralysis stage seldom cause secondary cases. It should be noted, however, that intimate human contact in any case is a factor in the spreading of poliomyelitis which takes place all the time, but these contacts can not explain the explosive outbreaks in the autumns.

Trask and Paul have demonstrated the presence of virus in flies. Ward, Melnick and Horstman have managed to infect monkeys by means of food which by flies had been polluted with virus in the homes of poliomyelitis patients. Hereby these investigators have arrived a t the conclusion that infection transmitted by flies might be the cause of the seasonal variations in the frequency of poliomyelitis. We have earlier in the foregoing reviewed Kling’s et al. theories concerning the part played by drinking water as an infection carrier.

While on the subject of contact infection I would add that virus from an in- flamed pharyngeal mucous membrane by no means is as contagious as virus from nasal mucous membrane. (Cf. Hamburger’s report on the spreading of hemolytic streptococci from pharynx and nose.) Strangely enough, however, the common cold is very rare indeed as a symptom of poliomyelitis. I n our present material no cold was observed. Likewise we now know through experimental investiga- tions that virus does not occur in the nasal secretion.

Summing up we may say that the possibilities of spreading virus of infantile paralysis probably are many and varied, and that i t would be unsafe to disregard spreading of infection by direct or indircet transmission from the patient’s pharynx during the first days of illness but that the importance of this manner probably is small in comparison to that taking place i.1 other ways through spreading by water or flies of virus from the intestinal tract of man.

FOME EARLY SYMPTOMS I N POLIOMYELITEF. 131

Summary.

During a poliomyelitis epidemic in 1937-39 in the province of Jamtland, Sweden, the author carried out systematic clinical observations on 461 cases of which 81 had meningitis only and the remaining 380 meningitis and paresis. The paresis cases were designated as slight, moderate and severe. Statistical treatment of the material.

The investigation showed that after 15 years of age the risk of contracting a paretic form of poliomyelitis was much greater and that the paresis then very likely would be more severe and that the mortality was three times as great as before the age of 15. Approximately half the number of cases had 2-phase poliomyelitis with a catarrhal pre-stage and a high frequency of pharyngeal symptoms, then a symptom-free interval and finally the meningitis stage. A comparison may be made with the division into stages that has been made in speaking about the extraneural infection with virus present in the pharynx and intestines, and the neural infection with changes in the central nervous system. I n the meningitis stage abortive cases run a smaller temperature, they have less stiffness of the neck and their cell content in liquor is less than that in the paresis cases.

The ethiology of the pharyngeal symptoms in the catarrhal stage has by some authors been considered an aspecific contagion which makes way for the polio- myelitis virus, by others as the virus itself. From his own materials the author €eels justified in making the following statements: 1) The duration of the symptom- free interval is on an average equal in paresis and abortive cases but in both groups its variability is considerable, the interval sometimes being 2-3 weeks. 2) Polio- myelitis has the same tendency to manifest itself abortively and paretically, results in paresis of the same severity and has the same mortality whether or not there have been pharyngeal symptoms in the introductory stage of the disease. These results agree badly with earlier assumptions regarding the relationship between the catarrhal stage and neuroinfection. Instead they lead to a new hypothesis stating that the so called extraneural infection - the presence of virus in pharynx and intestines - aids in the development of an aspecific pharyngeal infection which makes no difference to the course of the poliomyelitis.

Although the spreading of polioinfection by water is well supported bacterio- logically, i t is unsafe to disregard the spreading of infection from the pharynx also in the early stage of certain cases. This is because virus has been demonstrated in the pharynx and catarrhal symptoms are very common.

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132 I. LUNDHOLM.

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