Journal of Infection (1992 ) 24, 31-36
Virus infections of the respiratory tract in HIV-infected children R. A. Hague,*~ S. E. B u r n s , t F. D. H a r g r e a v e s , t J. Y. Q. M o k * a n d P . L. Yap:[:
* Infectious Diseases Unit, City Hospital, Edinburgh, ~fRegional Virus Laboratory, City Hospital, Edinburgh and Edinburgh and South East Scotland Blood Transfusion Service, Edinburgh, Scotland, U.K. Accepted for publication I August 1991 Summary In order to determine whether the rates of respiratory viral infection and the severity of respiratory symptoms in HIV-infected children were higher than those in noninfected children, nose and throat swabs for viral isolation were taken at 3-month intervals during the first 2 years of life from 5o children born to HIV-infected women. Similar samples were obtained during the first year of life from 19 control children born to HIV seronegative mothers. Of the 5o children, five proved to be HIV-infected while 45 were presumed to be uninfected. HIV-infected children had significantly more respiratory symptoms and a higher proportion of samples from which viruses were isolated than the non-HIV-infected children. Also, more infected episodes required admission to hospital in the HIV-infected group. There was no such difference between the non-HIV-infected and the control children. Three HIVinfected children received intravenous immunoglobulin therapy. Among these the proportion of positive samples for viral isolation was greater before than after treatment began. These results suggest that HIV-infected children are more susceptible to recurrent viral infection and that passive immunotherapy may be of benefit to such children.
Introduction T h e susceptibility o f H I V - i n f e c t e d children to respiratory infections caused by bacteria and o t h e r o p p o r t u n i s t i c organisms is w e l l - r e c o r d e d , 1-3 b u t the natural h i s t o r y o f respiratory infections due to viruses in such children has received little attention. W e t h e r e f o r e u n d e r t o o k a prospective study o f H I V infected children in o r d e r to d e t e r m i n e w h e t h e r the rates of respiratory viral isolation and the severity o f r e s p i r a t o r y s y m p t o m s in H I V - i n f e c t e d were h i g h e r t h a n in n o n - H I V - i n f e c t e d children using as controls children f r o m the same s o c i o - e c o n o m i c group.
Patients and methods All the children were a m o n g those participating in the E d i n b u r g h H I V Perinatal T r a n s m i s s i o n Study. 4'5 Fifty children b o r n to H I V seropositive m o t h e r s below the age o f 2 years were studied prospectively. Five (group A) Address correspondence to : Dr R. A. Hague, Department of Paediatrics, Royal Victoria Infirmary, Newcastle upon Tyne NEI 4LP, U.K. oi63-4453/92/oioo3I +06 $03.00/0
© 1992 The British Society for the Study of Infection
32
R. A. H A G U E
ET AL.
proved to be infected with H I V . ~ One died at 4 months, the remaining four being aged 33-71 months. T h r e e of these children were treated with intravenous immunoglobulin (IV IgG), 2oo m g / k g every 3 weeks as previously described. 7 Another group of 45 children (group B) were considered not to be infected with H I V since they were clinically well and repeatedly H I V antibody and antigen negative. As an additional control group, I9 children whose fathers were H I V seropositive b u t whose mothers were H I V seronegative were also investigated for a period of I year (group C), thereafter declining further participation. All children in the study were seen at 3 m o n t h l y intervals and s y m p t o m s suggestive of respiratory infection since the previous visit were recorded. Children were examined for signs of respiratory infection. N o s e and throat swabs were taken and placed together in viral transport medium. O n e set of swabs was taken at each visit b u t results of specimens taken during admission to hospital were not included in this study. Results were analysed b y means of the X2 test for statistical significance. Virological methods N o s e and throat swabs taken from each child were c o m b i n e d in a single vial of viral transport m e d i u m containing antibiotics to suppress bacterial growth as well as fetal calf serum to stabilise the virus. T h e samples were transported to the laboratory within 2 h. I f any delay was anticipated, swabs in transport m e d i u m were stored at 4 °C before transport. In the laboratory, cells collected on the swabs were r e s u s p e n d e d in a small volume of transport m e d i u m before they were inoculated into cultures of primary b a b o o n kidney, h u m a n epithelial cells (HEp2) and h u m a n fibroblasts ( M R C 5 ) . T h e inoculated cells were incubated at 36 °C and examined twice weekly for evidence of a cytopathic effect. F u r t h e r confirmatory tests were made on cells affected. Influenza, parainfluenza, respiratory syncytial (RS), measles, and herpes simplex viruses were confirmed b y means of monoclonal or polyclonal antibodies in a fluorescent antibody test. s Adenovirus, Coxsackie and Echo viruses were identified by neutralisation tests. 9 Rhinovirus was identified by acid stability testing. Cytomegalovirus ( C M V ) was identified b y its characteristic cytopathic effect on M R C 5 cells. Results A total of 3oi samples was collected over a period of 24 months. Results are summarised in T a b l e I. Although a few opportunities for sampling were missed, these did not differ b e t w e e n groups. G r o u p A had significantly more respiratory infections and m o r e samples positive for viral isolation than group B. Over the first year, however, groups B and C did not differ significantly (Table II). T h e viruses isolated are listed in T a b l e III. T h e r e was no significant difference among the three groups in the proportion of positive virus isolations associated with symptoms. S y m p t o m s usually accompanied infections with influenza A, parainfluenza, R S and adenovirus infections, whereas isolation of C M V or Coxsackie virus was more often asymptomatic. Six of the IO proven
Virus infections in HIV-infected children
33
Table I Episodes of respiratory infection and virus isolation in HIV-infected
and non-infected children in the first 2 years of life Group
A
N u m b e r of p a t i e n t s N u m b e r of samples Age r a n g e (mean, m e d i a n ) N u m b e r of m i s s e d s a m p l i n g opportunities (%) N u m b e r of s y m p t o m a t i c episodes of r e s p i r a t o r y infection N u m b e r o f positive virus isolations
B
5 30 3 - 2 4 (14"5, 15) 4/34 (II'8)
P*
45 220 N,N, N.S.
3 - 2 4 (I4"O, I 5 ) 2 2 / 2 4 2 (9"1)
14
41
Virus infections of the respiratory tract in HIV-infected children R. A. Hague,*~ S. E. B u r n s , t F. D. H a r g r e a v e s , t J. Y. Q. M o k * a n d P . L. Yap:[:
* Infectious Diseases Unit, City Hospital, Edinburgh, ~fRegional Virus Laboratory, City Hospital, Edinburgh and Edinburgh and South East Scotland Blood Transfusion Service, Edinburgh, Scotland, U.K. Accepted for publication I August 1991 Summary In order to determine whether the rates of respiratory viral infection and the severity of respiratory symptoms in HIV-infected children were higher than those in noninfected children, nose and throat swabs for viral isolation were taken at 3-month intervals during the first 2 years of life from 5o children born to HIV-infected women. Similar samples were obtained during the first year of life from 19 control children born to HIV seronegative mothers. Of the 5o children, five proved to be HIV-infected while 45 were presumed to be uninfected. HIV-infected children had significantly more respiratory symptoms and a higher proportion of samples from which viruses were isolated than the non-HIV-infected children. Also, more infected episodes required admission to hospital in the HIV-infected group. There was no such difference between the non-HIV-infected and the control children. Three HIVinfected children received intravenous immunoglobulin therapy. Among these the proportion of positive samples for viral isolation was greater before than after treatment began. These results suggest that HIV-infected children are more susceptible to recurrent viral infection and that passive immunotherapy may be of benefit to such children.
Introduction T h e susceptibility o f H I V - i n f e c t e d children to respiratory infections caused by bacteria and o t h e r o p p o r t u n i s t i c organisms is w e l l - r e c o r d e d , 1-3 b u t the natural h i s t o r y o f respiratory infections due to viruses in such children has received little attention. W e t h e r e f o r e u n d e r t o o k a prospective study o f H I V infected children in o r d e r to d e t e r m i n e w h e t h e r the rates of respiratory viral isolation and the severity o f r e s p i r a t o r y s y m p t o m s in H I V - i n f e c t e d were h i g h e r t h a n in n o n - H I V - i n f e c t e d children using as controls children f r o m the same s o c i o - e c o n o m i c group.
Patients and methods All the children were a m o n g those participating in the E d i n b u r g h H I V Perinatal T r a n s m i s s i o n Study. 4'5 Fifty children b o r n to H I V seropositive m o t h e r s below the age o f 2 years were studied prospectively. Five (group A) Address correspondence to : Dr R. A. Hague, Department of Paediatrics, Royal Victoria Infirmary, Newcastle upon Tyne NEI 4LP, U.K. oi63-4453/92/oioo3I +06 $03.00/0
© 1992 The British Society for the Study of Infection
32
R. A. H A G U E
ET AL.
proved to be infected with H I V . ~ One died at 4 months, the remaining four being aged 33-71 months. T h r e e of these children were treated with intravenous immunoglobulin (IV IgG), 2oo m g / k g every 3 weeks as previously described. 7 Another group of 45 children (group B) were considered not to be infected with H I V since they were clinically well and repeatedly H I V antibody and antigen negative. As an additional control group, I9 children whose fathers were H I V seropositive b u t whose mothers were H I V seronegative were also investigated for a period of I year (group C), thereafter declining further participation. All children in the study were seen at 3 m o n t h l y intervals and s y m p t o m s suggestive of respiratory infection since the previous visit were recorded. Children were examined for signs of respiratory infection. N o s e and throat swabs were taken and placed together in viral transport medium. O n e set of swabs was taken at each visit b u t results of specimens taken during admission to hospital were not included in this study. Results were analysed b y means of the X2 test for statistical significance. Virological methods N o s e and throat swabs taken from each child were c o m b i n e d in a single vial of viral transport m e d i u m containing antibiotics to suppress bacterial growth as well as fetal calf serum to stabilise the virus. T h e samples were transported to the laboratory within 2 h. I f any delay was anticipated, swabs in transport m e d i u m were stored at 4 °C before transport. In the laboratory, cells collected on the swabs were r e s u s p e n d e d in a small volume of transport m e d i u m before they were inoculated into cultures of primary b a b o o n kidney, h u m a n epithelial cells (HEp2) and h u m a n fibroblasts ( M R C 5 ) . T h e inoculated cells were incubated at 36 °C and examined twice weekly for evidence of a cytopathic effect. F u r t h e r confirmatory tests were made on cells affected. Influenza, parainfluenza, respiratory syncytial (RS), measles, and herpes simplex viruses were confirmed b y means of monoclonal or polyclonal antibodies in a fluorescent antibody test. s Adenovirus, Coxsackie and Echo viruses were identified by neutralisation tests. 9 Rhinovirus was identified by acid stability testing. Cytomegalovirus ( C M V ) was identified b y its characteristic cytopathic effect on M R C 5 cells. Results A total of 3oi samples was collected over a period of 24 months. Results are summarised in T a b l e I. Although a few opportunities for sampling were missed, these did not differ b e t w e e n groups. G r o u p A had significantly more respiratory infections and m o r e samples positive for viral isolation than group B. Over the first year, however, groups B and C did not differ significantly (Table II). T h e viruses isolated are listed in T a b l e III. T h e r e was no significant difference among the three groups in the proportion of positive virus isolations associated with symptoms. S y m p t o m s usually accompanied infections with influenza A, parainfluenza, R S and adenovirus infections, whereas isolation of C M V or Coxsackie virus was more often asymptomatic. Six of the IO proven
Virus infections in HIV-infected children
33
Table I Episodes of respiratory infection and virus isolation in HIV-infected
and non-infected children in the first 2 years of life Group
A
N u m b e r of p a t i e n t s N u m b e r of samples Age r a n g e (mean, m e d i a n ) N u m b e r of m i s s e d s a m p l i n g opportunities (%) N u m b e r of s y m p t o m a t i c episodes of r e s p i r a t o r y infection N u m b e r o f positive virus isolations
B
5 30 3 - 2 4 (14"5, 15) 4/34 (II'8)
P*
45 220 N,N, N.S.
3 - 2 4 (I4"O, I 5 ) 2 2 / 2 4 2 (9"1)
14
41
