INFECTIONS
Influenzavirus A 2 Infections Presenting with Febrile Convulsions and Gastrointestinal Symptoms in Young Children
D. A. Price, R. J. Postlethwaite, M.
Longson
We present the clinical features of Influenzavirus A 2 infection in 75 young children admitted to a children’s hospital. The most common presenting features were febrile convulsions, vomiting, coughing, diarrhea, and anorexia. At any age, the illness may present with respiratory tract symptoms and signs but in young babies gastrointestinal symptoms are often the presenting complaint. Children aged one to three years often present with febrile convulsions. Only in older children does the adult pattern begin to emerge. Evidence is put forward to suggest that encephalitis in association with influenza can be due to direct invasion of the central nervous system by the virus.
HE
CLINICAL FEATURES of influenza in adults and older children have been well recorded, 1-4 but those in preschool children have received less published attention. Parrott, et al.,5 in their 1962 descriptions of Influenzavirus A2 and B infections in hospitalized children under the age of six years concentrated on the respiratory tract com-
plications and did not mention other features. More recently, it has been pointed out that Influenzavirus A2 infections give rise to febrile convulsions. We here describe a much wider range From the
of clinical phenomena, including
Department
of Child Health and Booth
Hall, Children’s Hospital, Blackley, Manchester 2AA, England.
M9
gastrointestinal symptoms
in
hospitalized
young children.
Epidemiologic Background An outbreak of Influenzavirus A2 infection expected in Great Britain in the winter of
was
1971-72.~ The first isolations were reported the end of November 1971. By December 1971 and January 1972, outbreaks were reported from widely scattered areas of the country.8 Overall, the 1971-72 outbreak of at
influenza was widespread but mild, with most of the cases being reported between December 1971 and March 1972.9 The outbreak in our community commenced in early December 1971 and continued to the end of Febru-
361
Downloaded from cpj.sagepub.com at Bobst Library, New York University on May 23, 2015
TABLE 1. Evidence
of Infection
Erythrocyte sedimentation by a micro-Westergren
mens.
estimated
41 cases. Chest x-rays children.
were
rates were
method in obtained with 34
Results
Virologic Findings
During the period of the outbreak, 800 specimens were examined virologically. Of these, 198 (24.8%) yielded positive isolates. Of 507 throat swabs examined, viruses were isolated from 159 (31.2%); 72 (45.9%) of these isolates were Influenzavirus ~~..~ and 34 (21.4%)
respiratory syncytial
were
ary 1972. No further that.
cases were seen
after
Diagnostic Studies Virologic Methods Throat swabs, urine, and feces, collected into transport media within 24 hours of admission of suspected cases, were inoculated into rhesus monkey kidney H.Ep.2, and human embryo fibroblast cell cultures. In positive isolations, typical cytopathic effects normally appeared in monkey kidney cultures within 72 hours and the identity of the agent was confirmed by hemadsorptioninhibition with type specific Influenzavirus A2 anti-serum, Batch No. 169.D (kindly provided by Dr. C. M. P. Bradstreet, Standards Laboratory, London). Particular care was taken to minimize crosscontamination within the laboratory. Infection of the cell cultures with contaminant simian virus was excluded by appropriate controls. Serologic tests were not undertaken.
Bacteriologic Methods Throat swabs, urine, and feces
were cultured for bacterial pathogens, using standard techniques, in all children presenting with an acute illness. With those presenting with gastrointestinal symptoms, feces were cultured on at least three occasions for bacterial
Echovirus,
one
polio virus,
three adenovirus,
recovered. In these 75, virus was isolated from throat swabs in 69, throat swabs and urine in two, throat swab and feces in one, urine in one, feces in one, and from brain tissue in life and postmortem lung tissue in one.
Bacteriologic Findings All 75 children had throat swabs, urine, and feces cultures for pathogenic bacteria. Thirtyfive children had pathogenic bacteria isolated from throat swabs. There were 20 isolations of Hemophilus parainfluenzae, l1 of Hemophilus influenzae, four of Staphylococcus atreus, four of Pneumococcus, two of Coliforms, one of Beta Hemolytic Streptococcus and one of Proteus d~uigrzris. Twenty-three children had evidences of a lower respiratory tract infection (Table 1). The recovery rate of pathogenic bacteria from throat swabs (11 out of 23, i. e.9 47.8%) did not significantly exceed the overall recovery rate in the series (35 out of 75, i.e,,
46.7%).
Other Investigations
Other
Total and differential white cell counts estimated routinely from capillary speci-
was
and five Coxsackie viruses. No other viruses were isolated from the 75 children from whom Influenzavirus A2 was
pathogens.
were
virus. Virus
isolated from four (4.8%) of 83 urine specimens examined: three of these isolates were Influenzavirus .t~~ and one was mumps virus. Of the feces, 124 specimens were examined virologically. There were 13 (10.5%) isolations; of these, two were Influenzavirus A2, one
Investigations
Eleven children had an absolute leukoand one a leukopenia (assuming a
cytosis
362
Downloaded from cpj.sagepub.com at Bobst Library, New York University on May 23, 2015
range of fi,0®(~-15,t~0Ufmm~). Twenty-eight had a relative neutrophilia and four a relative neutropenia. Of the 41 erythrocyte sedimentation rates estimated, 24 were below 10 mm/hour; six were from 10 to 19; and only 11 from 20 to 28. Of those over 20, nine seemed to have secondary bacterial infections.
TABLE 2.
normal
Presenting Complaints
Clinical Features The presenting complaints are shown in Table 2 and the symptoms and signs in Figures 1 and 2.
Duration of Illness
Ages The ages of the 75 positive cases ranged from 14 days to 14 years but only four children were over five years (two aged eight, one aged nine, and one aged 14). The range from zero to five years is shown in Figure 3. The ages from one month to 11 months are further broken down in Figure 4. Sex
There were 49 males and 26 females, giving male to female ratio of 1.88: 1. Up to the age of six months, the ratio was 3.5:1. a
FIG. 1.
* Rhinorrhea, excessive crying, and irritability presented in two, and epistaxis, constipation, abdominal pain, and a confusional state in one.
By adding the duration of preceding sympthat of hospital stay, some indication of the total length of illness is found. The range was two to 50 days with an average of 9.2 days. The median value was 8 days. The most frequent hospital stay was ten days. toms to
Fever
The highest temperature recorded for each child is represented in Figure 5. Fifteen children had a biphasic temperature pattern. In only four did the fever last over 72 hours, and all four had secondary bacterial infection.
Symptoms.
363
Downloaded from cpj.sagepub.com at Bobst Library, New York University on May 23, 2015
FIG. 2.
Febrile Convulsions
Twenty-six children (34.7%), 14 males and 12 females, aged ten months to five years had febrile convulsions. Of those children aged one to three years inclusively, 24 out of 35, i.e., 68.6%, had febrile convulsions (Fig. 3). Ten of the 26 had previous febrile convulsions or a family history of febrile convulsions. Twenty-six had inflamed fauces. Seventeen had been ill for less than 24 hours. Seven children had vomiting, four had diarrhea, and two had a rash accompanied by generalized lymphadenopathy. As Figure 5 illustrates, the mean temperature in the children with febrile convulsions was higher than in those with other presentations. Virus was isolated from the urine of two of these children. Other Convulsions ,
Two children (a severely dehydrated and a boy with hydrocephalus) had
baby con-
Signs. vulsions unrelated cussed later. Gastrointestinal
to
fever,
as
will be dis-
Symptoms
Fifteen children (20%) had diarrhea and and two others had diarrhea alone. One child had a longstanding diarrhea not attributed to this acute illness (he presented with a febrile fit). No fecal pathogenic bacteria were isolated from any of these cases. The diarrhea lasted from one to nine days, with an average of Eve days. The stools were more frequent than normal and described as yellow or green, watery, and offensive. One child had been given antibiotics before the onset of the diarrhea, and two had had an attack of gastroenteritis in the past. One child had a second-
vomiting
ary pneumonia. Gastrointestinal symptoms assumed the greatest importance in the younger patients.. As can be seen from Figure 4, 50 per cent (9 out of 18) of patients aged six months or
364
Downloaded from cpj.sagepub.com at Bobst Library, New York University on May 23, 2015
’
less had diarrhea and vomiting to a marked extent, and 72.2 per cent (13 out of 18) had anorexia and vomiting and/or diarrhea. Only five babies (37.8%) had respiratory symptoms alone. Three babies were moderately dehydrated but were treated with oral fluids. Two others were severely dehydrated and required intravenous fluids. One of these, a baby of two weeks, presented with severe hypernatremic dehydration. After careful rehydration he began to convulse and required anticonvulsant drugs. His neurologic development has since been abnormal. FIG. 3.
Lower
Age
range 0-5 years.
Respiratory Tract Signs Otitis Media
’
The diagnosis of pneumonia was made when clinical signs of consolidation were present and confirmed by chest x-ray (Table 2). One child had a viral bronchopneumonia as observed at postmortem. Those classed as &dquo;bronchitis&dquo; had coarse rhonchi and crepitations but no localizing signs. Those with marked high pitched expiratory rhonchi and fine crepitations were classed as having asthmatic attacks if they were known asthmatics and were helped by bronchodilators, or otherwise as having bronchiolitis.
FIG. 4.
Age
Thirty-three
children had inflamed
ear
drums, 16 bilaterally and 17 unilaterally. On the basis of a neutrophilia, ten were thought to have a secondary bacterial infection; of these, two had bilateral signs and eight had unilateral signs.
Mortatity One death occurred in a three-year-old boy who had congenital hydrocephalus with a
long-standing Pudenz-Heyer valve
in situ. He
range 0--11 months.
365
Downloaded from cpj.sagepub.com at Bobst Library, New York University on May 23, 2015
found. 1,2 In
school-age children, the illness is similar, though epistaxis, vomiting, and ab-
dominal
pain, and occasionally generalized lymphadenopathy or a rash, may be present.l°~°4 Our experience confirms that Influenza-
FiG. 5.
Temperature -highest
recorded in
hospital.
presented with anorexia, vomiting, rhinora cough, a fever of 38 C, and reddened fauces and ear drums. The valve appeared to
rhea,
be blocked and he became unconscious, fitted and had a cardiopulmonary arrest. He was resuscitated and ventilated artificially. Ventricular taps demonstrated a markedly in-
creased pressure.
Operative decompression
some tissue was asthe from right temporal lobe. He pirated died about 48 hours after onset. Influenzavirus A2 was grown from the aspirated brain substance and at postmortem from the lungs. At postmortem, the brain was in a state of advanced softening and necrosis. Histology revealed marked edema and swelling of glial cells but no perivascular cuffing. The lungs were hemorrhagic and edematous with thrombosis of small vessels, findings deemed consistent with influenzal virus pneumonia. The trachea and posterior epiglottis showed sloughing and small was
unsuccessful, but
hemorrhages. Discussion Influenza in the adult is typically a pyrexial illness with headache, malaise, a dry couth, and nasal obstruction or rhinorrhea, dizzi-
ocular symptoms, insomnia, a sore throat, and sweating. Suffusion and watering of the eyes, nasal obstruction with discharge, pharyngitis and chest signs are commonly ness,
virus A2 can be a potent cause of febrile convulsions .6 Febrile convulsions occurred in onethird of all of our cases, and in two thirds of the children aged one and two years. These children tended to have a short preceding illness with signs of an upper respiratory tract infection. The mean temperature on admission of those with febrile convulsions was significantly higher than the general group; this conflicts with the experience of other investigators.’ It is noteworthy that two of the children with febrile convulsions excreted the virus in the urine, indicating dissemination of the virus and lending some support to the concept that a viremia is important in the pathogenesis of febrile convulsions.
Diarrhea and vomiting were thought to be unusual in one account of influenza from general practiced1 These symptoms rarely 2 occur in adults with influenza One extended study of Influenzavirus ~4,y infection in childrens makes no mention of gastrointestinal symptoms, although this study seems to have been limited to children presenting with febrile convulsions and respiratory tract infections. In our series, in contrast, 17 children (22.7%) had diarrhea and 15 of these had both diarrhea and vomiting. The diarrhea lasted for five days on average. As might be expected, babies aged up to six months were particularly liable to develop these symptoms and may present with severe dehydration and require intravenous fluids. Three of the other children had alternative explanations for the diarrhea (one had had an antibiotic, another had a secondary bacterial pneumonia, and the third a long-standing diarrhea. It is of interest to speculate whether or not this diarrhea represents gastrointestinal invasion by the virus or whether it is a &dquo;parenteral&dquo; effect. Virus was isolated from the feces of only one of these children but the essential role of the Myxovirus lipid
366
Downloaded from cpj.sagepub.com at Bobst Library, New York University on May 23, 2015
in infectivity makes the isolation of the virus from fecal material improbable.
envelope Lower
respiratory tract complications are prominent in hospital practice than in general practice, owing to the selection of more seriously ill patients. In a study from general practice,~1 these complications occurred in 3 per cent of the patients, and middle ear infections in only 1 per cent. We more
found 23 of 75 children
(30.7%) with lower
respiratory tract signs, and ten children (13.3%) with a secondary bacterial otitis media. Serious neurologic complications were few. The baby who had hypernatremic dehydration and convulsions has had some delay in
neurologic development subsequently. There have been descriptions of encephalitis, both fatal and nonfatal, associated with influenza, 10-13 and Oseasohn, et al. 14 have reported four children who died with clinical evidence of influenza and encephalitis. The relationship between the viral illness and the encephalitis has, however, been conjectural. 12 In our fatal case, the postmortem findings closely resemble others previously described .14 Because we isolated Influenzavirus A2 from both
postmortem lung tissue and antemortem brain tissue in our one fatal case, this suggests that the encephalitis in this child was due to direct invasion of the brain substance by the
I
.
virus. It has been suggested that children with congenital malformations are particularly susceptible to Influenzavirus A2 inflection.6 In our series, six children (8%) with known atopic tendencies presented with wheezing attacks. There were a further six children (8%) with congenital malformations or chronic disease, The illness was not generally more severe in this group though our one death did occur in a child with congenital hydrocephalus. The significance of these figures is obscured by the degree of selection in any hospital population. Perhaps of more importance is that, contrary to the experience of others,’ our series did not include a single child with cystic fibrosis even though these
children were nursed on the same wards as those with Influenzavirus A2 infection. All our children with cystic fibrosis had been vaccinated against influenza. It is, therefore, important to define more clearly any other risk groups so that they too can be similarly
protected. Acknowledgments We wish to thank Professor A. Holzel for his advice and criticism of this paper, Dr. B. Marsden for his help, Mr. Stokes and his staff at the North Manchester Regional Virus Laboratory for technical assistance, and the nursing staff for their cooperation. We are grateful to Dr. J. Keen, Dr. B. Wolman, and Mr. H. Maslowski for permission to study the patients in their care.
References Influenza A (Asian) 1957, clinical and features in a general practice. Br. Med. J. 1: 259, 1958. 2. Stuart Harris, C. M.: Twenty years of influenza epidemics. Am. Rev. Resp. Dis. 83: Part II, 54, 1961. 3. Sanders, D. Y., Carroll, N. B., Jeffreys, L. U., Vick, S. S.: Outbreak of influenza A 2 (Hong Kong strain) in a children’s home. South. Med. J. 63: 1.
Fry, J.:
epidemiological
4.
414, 1970. Podesin, R. L., and Felton, W. L.: The clinical picture
of Far East Influenza occurring at the Fourth National Boy Scout Jamboree; report of 616 cases. N. Engl. J. Med. 258: 778, 1958. 5. Parrott, R. M., Kim, H. W., Vargosko, A. J., and Charnock, R. M.: Serious respiratory tract illness as a result of Asian influenza and influenza B infections in children. J. Pediatr. 61: 205, 1962. 6. Brocklebank, J. T., Court, S. D. M., McQuillin, J., Gardner, P. S.: Influenza A infection in children. Lancet II: 497, 1972. 7. Epidemiology, influenza prospects. Br. Med. J.
4: 59, 1971. influenza. Br. Med. J. 1: 259, 1972. influenza and sickness absence. Br. Med. J. 2: 663, 1972. 10. Dubowitz, V.: Influenzal encephalitis. Lancet 1: 8. 9.
Epidemiology, Epidemiology, 140, 1958.
11.
12.
Dunbar, J. M., Jamieson, W. M., Langlands, J. H. M., and Smith, G. H.: Encephalitis and influenza. Br. Med. J. 1: 913, 1958. Flewett, T. H., Hoult, J. G.: Influenzal encephalopathy and postinfluenzal encephalitis. Lancet II: 11, 1958.
13.
McConkey, B., Daws,
R. A.:
Neurological
disorders
associated with Asian influenza. Lancet II: 15, 1958. 14. Oseasohn, R., Andelson, L., Kaji, M.: Clinicopathologic study of 33 fatal cases of Asian influenza. N.
Engl. J.
Med. 260: 509, 1959.
367
Downloaded from cpj.sagepub.com at Bobst Library, New York University on May 23, 2015
Influenzavirus A 2 Infections Presenting with Febrile Convulsions and Gastrointestinal Symptoms in Young Children
D. A. Price, R. J. Postlethwaite, M.
Longson
We present the clinical features of Influenzavirus A 2 infection in 75 young children admitted to a children’s hospital. The most common presenting features were febrile convulsions, vomiting, coughing, diarrhea, and anorexia. At any age, the illness may present with respiratory tract symptoms and signs but in young babies gastrointestinal symptoms are often the presenting complaint. Children aged one to three years often present with febrile convulsions. Only in older children does the adult pattern begin to emerge. Evidence is put forward to suggest that encephalitis in association with influenza can be due to direct invasion of the central nervous system by the virus.
HE
CLINICAL FEATURES of influenza in adults and older children have been well recorded, 1-4 but those in preschool children have received less published attention. Parrott, et al.,5 in their 1962 descriptions of Influenzavirus A2 and B infections in hospitalized children under the age of six years concentrated on the respiratory tract com-
plications and did not mention other features. More recently, it has been pointed out that Influenzavirus A2 infections give rise to febrile convulsions. We here describe a much wider range From the
of clinical phenomena, including
Department
of Child Health and Booth
Hall, Children’s Hospital, Blackley, Manchester 2AA, England.
M9
gastrointestinal symptoms
in
hospitalized
young children.
Epidemiologic Background An outbreak of Influenzavirus A2 infection expected in Great Britain in the winter of
was
1971-72.~ The first isolations were reported the end of November 1971. By December 1971 and January 1972, outbreaks were reported from widely scattered areas of the country.8 Overall, the 1971-72 outbreak of at
influenza was widespread but mild, with most of the cases being reported between December 1971 and March 1972.9 The outbreak in our community commenced in early December 1971 and continued to the end of Febru-
361
Downloaded from cpj.sagepub.com at Bobst Library, New York University on May 23, 2015
TABLE 1. Evidence
of Infection
Erythrocyte sedimentation by a micro-Westergren
mens.
estimated
41 cases. Chest x-rays children.
were
rates were
method in obtained with 34
Results
Virologic Findings
During the period of the outbreak, 800 specimens were examined virologically. Of these, 198 (24.8%) yielded positive isolates. Of 507 throat swabs examined, viruses were isolated from 159 (31.2%); 72 (45.9%) of these isolates were Influenzavirus ~~..~ and 34 (21.4%)
respiratory syncytial
were
ary 1972. No further that.
cases were seen
after
Diagnostic Studies Virologic Methods Throat swabs, urine, and feces, collected into transport media within 24 hours of admission of suspected cases, were inoculated into rhesus monkey kidney H.Ep.2, and human embryo fibroblast cell cultures. In positive isolations, typical cytopathic effects normally appeared in monkey kidney cultures within 72 hours and the identity of the agent was confirmed by hemadsorptioninhibition with type specific Influenzavirus A2 anti-serum, Batch No. 169.D (kindly provided by Dr. C. M. P. Bradstreet, Standards Laboratory, London). Particular care was taken to minimize crosscontamination within the laboratory. Infection of the cell cultures with contaminant simian virus was excluded by appropriate controls. Serologic tests were not undertaken.
Bacteriologic Methods Throat swabs, urine, and feces
were cultured for bacterial pathogens, using standard techniques, in all children presenting with an acute illness. With those presenting with gastrointestinal symptoms, feces were cultured on at least three occasions for bacterial
Echovirus,
one
polio virus,
three adenovirus,
recovered. In these 75, virus was isolated from throat swabs in 69, throat swabs and urine in two, throat swab and feces in one, urine in one, feces in one, and from brain tissue in life and postmortem lung tissue in one.
Bacteriologic Findings All 75 children had throat swabs, urine, and feces cultures for pathogenic bacteria. Thirtyfive children had pathogenic bacteria isolated from throat swabs. There were 20 isolations of Hemophilus parainfluenzae, l1 of Hemophilus influenzae, four of Staphylococcus atreus, four of Pneumococcus, two of Coliforms, one of Beta Hemolytic Streptococcus and one of Proteus d~uigrzris. Twenty-three children had evidences of a lower respiratory tract infection (Table 1). The recovery rate of pathogenic bacteria from throat swabs (11 out of 23, i. e.9 47.8%) did not significantly exceed the overall recovery rate in the series (35 out of 75, i.e,,
46.7%).
Other Investigations
Other
Total and differential white cell counts estimated routinely from capillary speci-
was
and five Coxsackie viruses. No other viruses were isolated from the 75 children from whom Influenzavirus A2 was
pathogens.
were
virus. Virus
isolated from four (4.8%) of 83 urine specimens examined: three of these isolates were Influenzavirus .t~~ and one was mumps virus. Of the feces, 124 specimens were examined virologically. There were 13 (10.5%) isolations; of these, two were Influenzavirus A2, one
Investigations
Eleven children had an absolute leukoand one a leukopenia (assuming a
cytosis
362
Downloaded from cpj.sagepub.com at Bobst Library, New York University on May 23, 2015
range of fi,0®(~-15,t~0Ufmm~). Twenty-eight had a relative neutrophilia and four a relative neutropenia. Of the 41 erythrocyte sedimentation rates estimated, 24 were below 10 mm/hour; six were from 10 to 19; and only 11 from 20 to 28. Of those over 20, nine seemed to have secondary bacterial infections.
TABLE 2.
normal
Presenting Complaints
Clinical Features The presenting complaints are shown in Table 2 and the symptoms and signs in Figures 1 and 2.
Duration of Illness
Ages The ages of the 75 positive cases ranged from 14 days to 14 years but only four children were over five years (two aged eight, one aged nine, and one aged 14). The range from zero to five years is shown in Figure 3. The ages from one month to 11 months are further broken down in Figure 4. Sex
There were 49 males and 26 females, giving male to female ratio of 1.88: 1. Up to the age of six months, the ratio was 3.5:1. a
FIG. 1.
* Rhinorrhea, excessive crying, and irritability presented in two, and epistaxis, constipation, abdominal pain, and a confusional state in one.
By adding the duration of preceding sympthat of hospital stay, some indication of the total length of illness is found. The range was two to 50 days with an average of 9.2 days. The median value was 8 days. The most frequent hospital stay was ten days. toms to
Fever
The highest temperature recorded for each child is represented in Figure 5. Fifteen children had a biphasic temperature pattern. In only four did the fever last over 72 hours, and all four had secondary bacterial infection.
Symptoms.
363
Downloaded from cpj.sagepub.com at Bobst Library, New York University on May 23, 2015
FIG. 2.
Febrile Convulsions
Twenty-six children (34.7%), 14 males and 12 females, aged ten months to five years had febrile convulsions. Of those children aged one to three years inclusively, 24 out of 35, i.e., 68.6%, had febrile convulsions (Fig. 3). Ten of the 26 had previous febrile convulsions or a family history of febrile convulsions. Twenty-six had inflamed fauces. Seventeen had been ill for less than 24 hours. Seven children had vomiting, four had diarrhea, and two had a rash accompanied by generalized lymphadenopathy. As Figure 5 illustrates, the mean temperature in the children with febrile convulsions was higher than in those with other presentations. Virus was isolated from the urine of two of these children. Other Convulsions ,
Two children (a severely dehydrated and a boy with hydrocephalus) had
baby con-
Signs. vulsions unrelated cussed later. Gastrointestinal
to
fever,
as
will be dis-
Symptoms
Fifteen children (20%) had diarrhea and and two others had diarrhea alone. One child had a longstanding diarrhea not attributed to this acute illness (he presented with a febrile fit). No fecal pathogenic bacteria were isolated from any of these cases. The diarrhea lasted from one to nine days, with an average of Eve days. The stools were more frequent than normal and described as yellow or green, watery, and offensive. One child had been given antibiotics before the onset of the diarrhea, and two had had an attack of gastroenteritis in the past. One child had a second-
vomiting
ary pneumonia. Gastrointestinal symptoms assumed the greatest importance in the younger patients.. As can be seen from Figure 4, 50 per cent (9 out of 18) of patients aged six months or
364
Downloaded from cpj.sagepub.com at Bobst Library, New York University on May 23, 2015
’
less had diarrhea and vomiting to a marked extent, and 72.2 per cent (13 out of 18) had anorexia and vomiting and/or diarrhea. Only five babies (37.8%) had respiratory symptoms alone. Three babies were moderately dehydrated but were treated with oral fluids. Two others were severely dehydrated and required intravenous fluids. One of these, a baby of two weeks, presented with severe hypernatremic dehydration. After careful rehydration he began to convulse and required anticonvulsant drugs. His neurologic development has since been abnormal. FIG. 3.
Lower
Age
range 0-5 years.
Respiratory Tract Signs Otitis Media
’
The diagnosis of pneumonia was made when clinical signs of consolidation were present and confirmed by chest x-ray (Table 2). One child had a viral bronchopneumonia as observed at postmortem. Those classed as &dquo;bronchitis&dquo; had coarse rhonchi and crepitations but no localizing signs. Those with marked high pitched expiratory rhonchi and fine crepitations were classed as having asthmatic attacks if they were known asthmatics and were helped by bronchodilators, or otherwise as having bronchiolitis.
FIG. 4.
Age
Thirty-three
children had inflamed
ear
drums, 16 bilaterally and 17 unilaterally. On the basis of a neutrophilia, ten were thought to have a secondary bacterial infection; of these, two had bilateral signs and eight had unilateral signs.
Mortatity One death occurred in a three-year-old boy who had congenital hydrocephalus with a
long-standing Pudenz-Heyer valve
in situ. He
range 0--11 months.
365
Downloaded from cpj.sagepub.com at Bobst Library, New York University on May 23, 2015
found. 1,2 In
school-age children, the illness is similar, though epistaxis, vomiting, and ab-
dominal
pain, and occasionally generalized lymphadenopathy or a rash, may be present.l°~°4 Our experience confirms that Influenza-
FiG. 5.
Temperature -highest
recorded in
hospital.
presented with anorexia, vomiting, rhinora cough, a fever of 38 C, and reddened fauces and ear drums. The valve appeared to
rhea,
be blocked and he became unconscious, fitted and had a cardiopulmonary arrest. He was resuscitated and ventilated artificially. Ventricular taps demonstrated a markedly in-
creased pressure.
Operative decompression
some tissue was asthe from right temporal lobe. He pirated died about 48 hours after onset. Influenzavirus A2 was grown from the aspirated brain substance and at postmortem from the lungs. At postmortem, the brain was in a state of advanced softening and necrosis. Histology revealed marked edema and swelling of glial cells but no perivascular cuffing. The lungs were hemorrhagic and edematous with thrombosis of small vessels, findings deemed consistent with influenzal virus pneumonia. The trachea and posterior epiglottis showed sloughing and small was
unsuccessful, but
hemorrhages. Discussion Influenza in the adult is typically a pyrexial illness with headache, malaise, a dry couth, and nasal obstruction or rhinorrhea, dizzi-
ocular symptoms, insomnia, a sore throat, and sweating. Suffusion and watering of the eyes, nasal obstruction with discharge, pharyngitis and chest signs are commonly ness,
virus A2 can be a potent cause of febrile convulsions .6 Febrile convulsions occurred in onethird of all of our cases, and in two thirds of the children aged one and two years. These children tended to have a short preceding illness with signs of an upper respiratory tract infection. The mean temperature on admission of those with febrile convulsions was significantly higher than the general group; this conflicts with the experience of other investigators.’ It is noteworthy that two of the children with febrile convulsions excreted the virus in the urine, indicating dissemination of the virus and lending some support to the concept that a viremia is important in the pathogenesis of febrile convulsions.
Diarrhea and vomiting were thought to be unusual in one account of influenza from general practiced1 These symptoms rarely 2 occur in adults with influenza One extended study of Influenzavirus ~4,y infection in childrens makes no mention of gastrointestinal symptoms, although this study seems to have been limited to children presenting with febrile convulsions and respiratory tract infections. In our series, in contrast, 17 children (22.7%) had diarrhea and 15 of these had both diarrhea and vomiting. The diarrhea lasted for five days on average. As might be expected, babies aged up to six months were particularly liable to develop these symptoms and may present with severe dehydration and require intravenous fluids. Three of the other children had alternative explanations for the diarrhea (one had had an antibiotic, another had a secondary bacterial pneumonia, and the third a long-standing diarrhea. It is of interest to speculate whether or not this diarrhea represents gastrointestinal invasion by the virus or whether it is a &dquo;parenteral&dquo; effect. Virus was isolated from the feces of only one of these children but the essential role of the Myxovirus lipid
366
Downloaded from cpj.sagepub.com at Bobst Library, New York University on May 23, 2015
in infectivity makes the isolation of the virus from fecal material improbable.
envelope Lower
respiratory tract complications are prominent in hospital practice than in general practice, owing to the selection of more seriously ill patients. In a study from general practice,~1 these complications occurred in 3 per cent of the patients, and middle ear infections in only 1 per cent. We more
found 23 of 75 children
(30.7%) with lower
respiratory tract signs, and ten children (13.3%) with a secondary bacterial otitis media. Serious neurologic complications were few. The baby who had hypernatremic dehydration and convulsions has had some delay in
neurologic development subsequently. There have been descriptions of encephalitis, both fatal and nonfatal, associated with influenza, 10-13 and Oseasohn, et al. 14 have reported four children who died with clinical evidence of influenza and encephalitis. The relationship between the viral illness and the encephalitis has, however, been conjectural. 12 In our fatal case, the postmortem findings closely resemble others previously described .14 Because we isolated Influenzavirus A2 from both
postmortem lung tissue and antemortem brain tissue in our one fatal case, this suggests that the encephalitis in this child was due to direct invasion of the brain substance by the
I
.
virus. It has been suggested that children with congenital malformations are particularly susceptible to Influenzavirus A2 inflection.6 In our series, six children (8%) with known atopic tendencies presented with wheezing attacks. There were a further six children (8%) with congenital malformations or chronic disease, The illness was not generally more severe in this group though our one death did occur in a child with congenital hydrocephalus. The significance of these figures is obscured by the degree of selection in any hospital population. Perhaps of more importance is that, contrary to the experience of others,’ our series did not include a single child with cystic fibrosis even though these
children were nursed on the same wards as those with Influenzavirus A2 infection. All our children with cystic fibrosis had been vaccinated against influenza. It is, therefore, important to define more clearly any other risk groups so that they too can be similarly
protected. Acknowledgments We wish to thank Professor A. Holzel for his advice and criticism of this paper, Dr. B. Marsden for his help, Mr. Stokes and his staff at the North Manchester Regional Virus Laboratory for technical assistance, and the nursing staff for their cooperation. We are grateful to Dr. J. Keen, Dr. B. Wolman, and Mr. H. Maslowski for permission to study the patients in their care.
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