Journal of Infection (I 992) z5, 31 I-315
CASE REPORTS Influenza B virus infection associated with non-bacterial septic shock-like illness D. G. J a i m o v i c h , * A. K u m a r , C. L. S h a b i n o a n d R. F o r m o l i
Department of Pediatrics and Human Development, Divisions of Critical Care and Infectious Diseases, Bronson Methodist Hospital, Michigan State University College of Human Medicine, East Lansing, Nil, U.S.A. Accepted for publication 24 February r992 Summary We report the details of four children aged between 6 months and 5"5 years who had underlying chronic disease and who developed life-threatening illness in association with influenza virus B infection. Influenza has received relatively little attention, yet its morbidity and mortality in children can be considerable. This report emphasises the need to vaccinate the population groups at high risk, such as children with cardiovascular disorders, chronic bronchopulmonary, metabolic and renal disease and chronic neurological disorders.
Introduction M a n y agents capable of causing respiratory infection in children have been identified; influenza has received relatively little attention. Yet the morbidity and mortality of this disease in children can be considerable, particularly during periods of epidemic spread or in those with chronic and debilitating illnesses. 1'~ T h e spectrum of clinical manifestations resulting from influenza virus infections is broad. T h e majority result in self-limiting illnesses such as bronchitis, rhinopharyngitis, croup and bronchopneumonia. Rarely is the illness complicated by life-threatening complications such as Reye's syndrome, toxic shock syndrome or respiratory failure. D u r i n g the m o n t h s between N o v e m b e r r988 and February I989, 26 culture proven cases of influenza B were admitted to our institution. We report four of these patients who had chronic a n d / o r debilitating illnesses, and who presented with a clinical state of septic shock. N o n e of these patients had associated Staphylococcus aureus infection. We defined septic shock as a clinical syndrome consisting of circulatory dysfunction with tissue hypoperfusion leading to a deteriorating clinical state. We based the diagnosis on acquired clinical data such as fever or hypothermia, tachycardia, tachypnoea and organ system dysfunction as manifested by altered mentation, hypoxaemia or oliguria. T o our knowledge the association of shock and influenza B, * Address correspondence to: Dr D. G. Jaimovich, University of Illinois, Department of Pediatrics M / C 856, Division of Critical Care, P.O. Box 6998, Chicago, IL 60680, U.S.A. oi63-4453/92/o6o3II +05 $08.00/0 14
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without a concomitant or secondary bacterial infection, has not been reported in the paediatric literature. Case reports
Case I
R.S. was a 21-month-old white female with a history of prematurity and bronchopulmonary dysplasia. She also had a seizure disorder and chronic otitis media. On this final admission the patient presented with malaise, rising temperature to 39"6 °C and increasing respiratory rate with a non-productive cough. On admission, chest X-ray showed bilateral diffuse infiltrates superimposed on chronic pulmonary markings. Nasopharyngeal swabs were obtained for viral studies. On the third hospital day, the patient was transferred to the Paediatric Intensive Care Unit because of hypoperfusion, fever and tachypnoea. At that time her temperature was 4o'5 °C, heart rate I86/min, respiration 56/min and blood pressure 6o m m H g systolic. She required aggressive fluid and vasopressor resuscitation and mechanical ventilation. Chest X-ray showed extensive bilateral alveolar infiltrates consistent with non-cardiogenic pulmonary oedema (adult respiratory distress syndrome). T h e WBC count was 5.I × IO9/1 with 7I % segmented leucocytes, 4 % band forms, 22 % lymphocytes, and 3 % monocytes. Blood, urine, CSF and tracheal aspirate were negative for bacterial culture. Antimicrobial therapy included a third-generation cephalosporin and gentamicin. Six days after admission the patient's nasopharyngeal cultures grew influenza B virus. She then developed D - I - C and hypotension, and became refractory to maximal ventilatory and inotropic support. She died 20 days after admission. Case z
V. S. is a 5"5-year-old white male, resident in a nursing home, with a history of severe anoxic ischaemic encephalopathy and seizure disorder secondary to near drowning. T h e patient had a tracheostomy for airway protection and control of secretions. Several days before admission he developed fever to 4o °C, increased coughing, viscous tracheal secretions and tachypnoea. On admission chest X-ray revealed a right upper lobe infiltrate and scattered interstitial infiltrates. Blood, urine and CSF cultures were negative for bacteria, fungi, legionella and mycobacteria. Tracheal aspirate grew influenza B virus, Proteus mirabilis and Pseudomonas aeruginosa. These bacteria were presumed to be as a result of colonisation since previous scout cultures grew the same organisms. Physical examination revealed an obese obtunded child, the latter thought to be secondary to the anoxic injury. He was in moderate respiratory distress, with a respiratory rate of 4o-5o/min , throughout the lung fields were rhonchi, rales and expiratory wheezes. T h e heart rate was I78/min and blood pressure 90/65 mmHg. T h e WBC was I8"3 x Io9/1 with 85% segmented neutrophils, 6 % band forms, 7 ~o lymphocytes, and 2 % monocytes. Therapy included ticarcillin, tobramycin and mechanical ventilation. T h e patient continued to have pyrexias to 4o °C during the first 2 weeks of hospitalisation but he then gradually improved and was weaned off ventilatory support. On day 45 he was transferred back to the nursing home.
Influenza B septic shock
313
Case 3
D . S . is a 6-month-old black male with multiple medical problems including deletion of the long arm of chromosome no. 2, D a n d y - W a l k e r cyst, hydrocephalus, and failure to thrive. T h e patient had been irritable, with febrile episodes and a mild cough 5 days before admission. He presented to the hospital with respiratory distress and apnoea associated with cyanosis. He was intubated, mechanically ventilated, and given fluid resuscitation. Physical examination revealed a sleepy but irritable child with a rectal temperature of 4o °C, pulse of I8O beats/min, respiratory rate of 6 o / m i n (before intubation), a blood pressure of 72 m m H g by palpation, and weight of 4"95 kg (less than 5th percentile). Scattered rhonchi and wheezing with subcostal and intercostal retraction were noted. T h e W B C count was I9"7 x IO"/1 with I8 % segmented neutrophils, 4 1 % band forms, 39 % lymphocytes, 1% monocytes and 1% metamyelocytes. Bacterial cultures of C S F , blood, and urine were negative. Nasopharyngeal swabs were obtained for viral culture. A chest X-ray showed right middle and upper lobe atelectasis. T h e patient was empirically treated with nafciUin and a third-generation cephalosporin. On day 9 of hospitalisation, influenza B virus culture from the nasopharyngeal swab was reported. Antibiotics were then discontinued. T h e patient required a tracheostomy because of repeated extubation failures. He was discharged h o m e requiring supplemental oxygen and daily nebulised bronchodilator therapy from which he was weaned during the next 45 days. Case 4 R . H . was an I 8 - m o n t h - o l d white female, with multiple medical problems including cerebral palsy, psychomotor retardation, microcephaly and failure to thrive. She had a I weeks' history of respiratory symptoms and mild fever. She presented in severe respiratory distress and was intubated and mechanically ventilated u p o n admission. She also required massive fluid resuscitation and inotropic support. Fresh frozen plasma, packed red blood cells and platelet transfusions were administered to treat coagulopathy. Physical examination revealed a small, emaciated child with agonal respirations (before intubation), a rectal temperature of 31.6 °C, and pulse of 85/rain. T h e blood pressure was not palpable. T h e patient's skin colour was dusky and capillary refill exceeded 4 s. T h e W B C count was 12"5 X lO9/1 with 18% segmented neutrophils, 68 % band forms and 14 % lymphocytes. Bacterial cultures of blood, tracheal aspirate and urine were negative as were bacterial antigen tests on urine. L u m b a r puncture was deferred due to the patient's coagulopathy. T r e a t m e n t was started empirically with a third-generation cephalosporin and nafcillin. Nasopharyngeal swab cultures identified influenza B virus. T h e patient continued to deteriorate, had a cardiorespiratory arrest and died 12 h after admission. An autopsy was not authorised by the family. Discussion
Influenza B virus causes illnesses similar to influenza A infection, but the severity is usually less and duration shorter. In the four patients reported here, 14-2
3~4
D. G. JAIMOVICH ET AL.
however, influenza B virus infection resulted in a life-threatening illness. Lifethreatening complications caused by Staphylococcus aureus toxic shock syndrome following influenza or influenza-like illness are well recognized) '~ None of the four patients presented here had evidence of bacterial tracheitis or other S. aureus infection. Recovery of bacteria from tracheal aspirate or airway culture has very little, if any, correlation with the role of the bacteria in the aetiology of the respiratory illness. However, influenza B virus was recovered from respiratory tract cultures of our four patients. Illness due to influenza B virus is generally associated with more prominent nasal and eye complaints and relatively few systemic findings, unlike the disease reported here. Leukopenia (less than 4"5 x i09/1 WBCs) has been noted in about 2 5 ~/o cases. T h e differential cell count is of no diagnostic value since approximately one third of patients have normal values, a third have relative lymphopenia; and a further third relative neutropenia. Our patients, overall, showed a significant increase in immature band forms, Marked leucocytosis has been observed frequently in infants with influenza virus infection. 5 Review of the paediatric literature reveals that influenza A virus infections are more commonly recognised than those caused by influenza B virus, yet Reye's Syndrome may occur after influenza B 6 and, less commonly, after influenza A. 7 Other host characteristics considered to influence the clinical expression of influenza infection include pre-existing chronic pulmonary, cardiac, and neuromuscular disease. T h e basis for this doctrine however, derives almost exclusively from pathological and epidemiological analysis of influenza infections in adult patients. 8,9 In children with chronic illness however, the available data are surprisingly meagre. T h e four cases reported in our study had a pre-existing debilitating disease. A number of studies have been carried out on asthmatic children but with conflicting results. 1°-1~ In view of this we feel that the manifestations and severity of influenza infection in other paediatric 'high risk' categories deserve further study. None of the patients reported here had received influenza vaccine. We emphasise that child population groups at high risk should be vaccinated and this will include children with cardiovascular disorders, chronic bronchopulmonary, metabolic and renal disease and chronic neurological disorders. TM Current and future influenza vaccines deserve wider use, and special attention should be focused on a subset of patients with chronic disease who are at highest risk of developing life-threatening influenza virus infection. References
I. Glezen WP. Serious morbidity and mortality associated with influenza epidemics. Epidemiol Rev 1982; 4: 25-44. 2. Parrott RH, Vargosko AJ, Chanock RM. Serious respiratory tract illness as a result of Asian influenza and influenza B infections in children. J Pediatr I962; 6I : 2o5-213. 3. MacDonald KL, Osterholm MT, Hedberg et al. Toxic shock syndrome. J A M A I987; z57: IO53-IO58. 4. Dan BB. Toxic shock syndrome: back to the future, ffAA4A I987; 257: lO94-1o95. 5. Hall CB, Douglas RG. Nosocomial influenzainfection as a cause of intercurrent fevers in infants. Pediatrics 1975; 55 : 673-677. 6. CoreyL, Rubin RJ, Hattwick MA, Noble GR, CassidyE. A nationwideoutbreak of Reye's Syndrome. Its epidemiologicrelationship to influenza B. Am J Med 1976; 6x : 615-625.
Influenza B septic shock
315
7. Ruben F L , Michaels RH. Reye's Syndrome with associated influenza A and B virus infection. JAMA r975; z34: 4IO-4IZ. 8. Eickhoff T C , Sherman IL, Serfling RE. Observations on excess mortality associated with epidemic influenza. JAMA r96I ; I76: 776-782. 9. Hers JF, Mosurel N, Mulder J. Bacteriology and histo-pathology of the respiratory tract and lungs in fatal Asian influenza. Lancet 1958; ii: I r 4 r - r I43. to. McIntosh K, Ellis EF, Hoffman LS, Lybass T G , Eller JJ, Fulginiti VA. T h e association of viral and bacterial respiratory infections with exacerbations of wheezing in young asthmatic children. J Pediatr I974; 8z: 578-590. I I. Minor TE, Dick EC, Baker JW, Ouellette JJ, Cohen M, Reed CE. Rhinovirus and influenza type A infections as precipitants of asthma. Am Rev Respir Dis I976; 1,3: I49-I53. I2. Minor TE, Dick EC, De Meo A N , Ouellette JJ, Cohen M, Reed CE. Virus as precipitants of asthmatic attacks in children. J A M A I974; zz7: 292-298. I3. Centers for Disease Control. Recommendation of the Public Health Service Advisory Committee on Immunization Practices. Influenza vaccine. Morbid Mortal Weekly Report I984; 33 : 253-266.
CASE REPORTS Influenza B virus infection associated with non-bacterial septic shock-like illness D. G. J a i m o v i c h , * A. K u m a r , C. L. S h a b i n o a n d R. F o r m o l i
Department of Pediatrics and Human Development, Divisions of Critical Care and Infectious Diseases, Bronson Methodist Hospital, Michigan State University College of Human Medicine, East Lansing, Nil, U.S.A. Accepted for publication 24 February r992 Summary We report the details of four children aged between 6 months and 5"5 years who had underlying chronic disease and who developed life-threatening illness in association with influenza virus B infection. Influenza has received relatively little attention, yet its morbidity and mortality in children can be considerable. This report emphasises the need to vaccinate the population groups at high risk, such as children with cardiovascular disorders, chronic bronchopulmonary, metabolic and renal disease and chronic neurological disorders.
Introduction M a n y agents capable of causing respiratory infection in children have been identified; influenza has received relatively little attention. Yet the morbidity and mortality of this disease in children can be considerable, particularly during periods of epidemic spread or in those with chronic and debilitating illnesses. 1'~ T h e spectrum of clinical manifestations resulting from influenza virus infections is broad. T h e majority result in self-limiting illnesses such as bronchitis, rhinopharyngitis, croup and bronchopneumonia. Rarely is the illness complicated by life-threatening complications such as Reye's syndrome, toxic shock syndrome or respiratory failure. D u r i n g the m o n t h s between N o v e m b e r r988 and February I989, 26 culture proven cases of influenza B were admitted to our institution. We report four of these patients who had chronic a n d / o r debilitating illnesses, and who presented with a clinical state of septic shock. N o n e of these patients had associated Staphylococcus aureus infection. We defined septic shock as a clinical syndrome consisting of circulatory dysfunction with tissue hypoperfusion leading to a deteriorating clinical state. We based the diagnosis on acquired clinical data such as fever or hypothermia, tachycardia, tachypnoea and organ system dysfunction as manifested by altered mentation, hypoxaemia or oliguria. T o our knowledge the association of shock and influenza B, * Address correspondence to: Dr D. G. Jaimovich, University of Illinois, Department of Pediatrics M / C 856, Division of Critical Care, P.O. Box 6998, Chicago, IL 60680, U.S.A. oi63-4453/92/o6o3II +05 $08.00/0 14
© I992 The British Society for the Study of Infection j IN 25
312
D . G . JAIMOVICH E T A L .
without a concomitant or secondary bacterial infection, has not been reported in the paediatric literature. Case reports
Case I
R.S. was a 21-month-old white female with a history of prematurity and bronchopulmonary dysplasia. She also had a seizure disorder and chronic otitis media. On this final admission the patient presented with malaise, rising temperature to 39"6 °C and increasing respiratory rate with a non-productive cough. On admission, chest X-ray showed bilateral diffuse infiltrates superimposed on chronic pulmonary markings. Nasopharyngeal swabs were obtained for viral studies. On the third hospital day, the patient was transferred to the Paediatric Intensive Care Unit because of hypoperfusion, fever and tachypnoea. At that time her temperature was 4o'5 °C, heart rate I86/min, respiration 56/min and blood pressure 6o m m H g systolic. She required aggressive fluid and vasopressor resuscitation and mechanical ventilation. Chest X-ray showed extensive bilateral alveolar infiltrates consistent with non-cardiogenic pulmonary oedema (adult respiratory distress syndrome). T h e WBC count was 5.I × IO9/1 with 7I % segmented leucocytes, 4 % band forms, 22 % lymphocytes, and 3 % monocytes. Blood, urine, CSF and tracheal aspirate were negative for bacterial culture. Antimicrobial therapy included a third-generation cephalosporin and gentamicin. Six days after admission the patient's nasopharyngeal cultures grew influenza B virus. She then developed D - I - C and hypotension, and became refractory to maximal ventilatory and inotropic support. She died 20 days after admission. Case z
V. S. is a 5"5-year-old white male, resident in a nursing home, with a history of severe anoxic ischaemic encephalopathy and seizure disorder secondary to near drowning. T h e patient had a tracheostomy for airway protection and control of secretions. Several days before admission he developed fever to 4o °C, increased coughing, viscous tracheal secretions and tachypnoea. On admission chest X-ray revealed a right upper lobe infiltrate and scattered interstitial infiltrates. Blood, urine and CSF cultures were negative for bacteria, fungi, legionella and mycobacteria. Tracheal aspirate grew influenza B virus, Proteus mirabilis and Pseudomonas aeruginosa. These bacteria were presumed to be as a result of colonisation since previous scout cultures grew the same organisms. Physical examination revealed an obese obtunded child, the latter thought to be secondary to the anoxic injury. He was in moderate respiratory distress, with a respiratory rate of 4o-5o/min , throughout the lung fields were rhonchi, rales and expiratory wheezes. T h e heart rate was I78/min and blood pressure 90/65 mmHg. T h e WBC was I8"3 x Io9/1 with 85% segmented neutrophils, 6 % band forms, 7 ~o lymphocytes, and 2 % monocytes. Therapy included ticarcillin, tobramycin and mechanical ventilation. T h e patient continued to have pyrexias to 4o °C during the first 2 weeks of hospitalisation but he then gradually improved and was weaned off ventilatory support. On day 45 he was transferred back to the nursing home.
Influenza B septic shock
313
Case 3
D . S . is a 6-month-old black male with multiple medical problems including deletion of the long arm of chromosome no. 2, D a n d y - W a l k e r cyst, hydrocephalus, and failure to thrive. T h e patient had been irritable, with febrile episodes and a mild cough 5 days before admission. He presented to the hospital with respiratory distress and apnoea associated with cyanosis. He was intubated, mechanically ventilated, and given fluid resuscitation. Physical examination revealed a sleepy but irritable child with a rectal temperature of 4o °C, pulse of I8O beats/min, respiratory rate of 6 o / m i n (before intubation), a blood pressure of 72 m m H g by palpation, and weight of 4"95 kg (less than 5th percentile). Scattered rhonchi and wheezing with subcostal and intercostal retraction were noted. T h e W B C count was I9"7 x IO"/1 with I8 % segmented neutrophils, 4 1 % band forms, 39 % lymphocytes, 1% monocytes and 1% metamyelocytes. Bacterial cultures of C S F , blood, and urine were negative. Nasopharyngeal swabs were obtained for viral culture. A chest X-ray showed right middle and upper lobe atelectasis. T h e patient was empirically treated with nafciUin and a third-generation cephalosporin. On day 9 of hospitalisation, influenza B virus culture from the nasopharyngeal swab was reported. Antibiotics were then discontinued. T h e patient required a tracheostomy because of repeated extubation failures. He was discharged h o m e requiring supplemental oxygen and daily nebulised bronchodilator therapy from which he was weaned during the next 45 days. Case 4 R . H . was an I 8 - m o n t h - o l d white female, with multiple medical problems including cerebral palsy, psychomotor retardation, microcephaly and failure to thrive. She had a I weeks' history of respiratory symptoms and mild fever. She presented in severe respiratory distress and was intubated and mechanically ventilated u p o n admission. She also required massive fluid resuscitation and inotropic support. Fresh frozen plasma, packed red blood cells and platelet transfusions were administered to treat coagulopathy. Physical examination revealed a small, emaciated child with agonal respirations (before intubation), a rectal temperature of 31.6 °C, and pulse of 85/rain. T h e blood pressure was not palpable. T h e patient's skin colour was dusky and capillary refill exceeded 4 s. T h e W B C count was 12"5 X lO9/1 with 18% segmented neutrophils, 68 % band forms and 14 % lymphocytes. Bacterial cultures of blood, tracheal aspirate and urine were negative as were bacterial antigen tests on urine. L u m b a r puncture was deferred due to the patient's coagulopathy. T r e a t m e n t was started empirically with a third-generation cephalosporin and nafcillin. Nasopharyngeal swab cultures identified influenza B virus. T h e patient continued to deteriorate, had a cardiorespiratory arrest and died 12 h after admission. An autopsy was not authorised by the family. Discussion
Influenza B virus causes illnesses similar to influenza A infection, but the severity is usually less and duration shorter. In the four patients reported here, 14-2
3~4
D. G. JAIMOVICH ET AL.
however, influenza B virus infection resulted in a life-threatening illness. Lifethreatening complications caused by Staphylococcus aureus toxic shock syndrome following influenza or influenza-like illness are well recognized) '~ None of the four patients presented here had evidence of bacterial tracheitis or other S. aureus infection. Recovery of bacteria from tracheal aspirate or airway culture has very little, if any, correlation with the role of the bacteria in the aetiology of the respiratory illness. However, influenza B virus was recovered from respiratory tract cultures of our four patients. Illness due to influenza B virus is generally associated with more prominent nasal and eye complaints and relatively few systemic findings, unlike the disease reported here. Leukopenia (less than 4"5 x i09/1 WBCs) has been noted in about 2 5 ~/o cases. T h e differential cell count is of no diagnostic value since approximately one third of patients have normal values, a third have relative lymphopenia; and a further third relative neutropenia. Our patients, overall, showed a significant increase in immature band forms, Marked leucocytosis has been observed frequently in infants with influenza virus infection. 5 Review of the paediatric literature reveals that influenza A virus infections are more commonly recognised than those caused by influenza B virus, yet Reye's Syndrome may occur after influenza B 6 and, less commonly, after influenza A. 7 Other host characteristics considered to influence the clinical expression of influenza infection include pre-existing chronic pulmonary, cardiac, and neuromuscular disease. T h e basis for this doctrine however, derives almost exclusively from pathological and epidemiological analysis of influenza infections in adult patients. 8,9 In children with chronic illness however, the available data are surprisingly meagre. T h e four cases reported in our study had a pre-existing debilitating disease. A number of studies have been carried out on asthmatic children but with conflicting results. 1°-1~ In view of this we feel that the manifestations and severity of influenza infection in other paediatric 'high risk' categories deserve further study. None of the patients reported here had received influenza vaccine. We emphasise that child population groups at high risk should be vaccinated and this will include children with cardiovascular disorders, chronic bronchopulmonary, metabolic and renal disease and chronic neurological disorders. TM Current and future influenza vaccines deserve wider use, and special attention should be focused on a subset of patients with chronic disease who are at highest risk of developing life-threatening influenza virus infection. References
I. Glezen WP. Serious morbidity and mortality associated with influenza epidemics. Epidemiol Rev 1982; 4: 25-44. 2. Parrott RH, Vargosko AJ, Chanock RM. Serious respiratory tract illness as a result of Asian influenza and influenza B infections in children. J Pediatr I962; 6I : 2o5-213. 3. MacDonald KL, Osterholm MT, Hedberg et al. Toxic shock syndrome. J A M A I987; z57: IO53-IO58. 4. Dan BB. Toxic shock syndrome: back to the future, ffAA4A I987; 257: lO94-1o95. 5. Hall CB, Douglas RG. Nosocomial influenzainfection as a cause of intercurrent fevers in infants. Pediatrics 1975; 55 : 673-677. 6. CoreyL, Rubin RJ, Hattwick MA, Noble GR, CassidyE. A nationwideoutbreak of Reye's Syndrome. Its epidemiologicrelationship to influenza B. Am J Med 1976; 6x : 615-625.
Influenza B septic shock
315
7. Ruben F L , Michaels RH. Reye's Syndrome with associated influenza A and B virus infection. JAMA r975; z34: 4IO-4IZ. 8. Eickhoff T C , Sherman IL, Serfling RE. Observations on excess mortality associated with epidemic influenza. JAMA r96I ; I76: 776-782. 9. Hers JF, Mosurel N, Mulder J. Bacteriology and histo-pathology of the respiratory tract and lungs in fatal Asian influenza. Lancet 1958; ii: I r 4 r - r I43. to. McIntosh K, Ellis EF, Hoffman LS, Lybass T G , Eller JJ, Fulginiti VA. T h e association of viral and bacterial respiratory infections with exacerbations of wheezing in young asthmatic children. J Pediatr I974; 8z: 578-590. I I. Minor TE, Dick EC, Baker JW, Ouellette JJ, Cohen M, Reed CE. Rhinovirus and influenza type A infections as precipitants of asthma. Am Rev Respir Dis I976; 1,3: I49-I53. I2. Minor TE, Dick EC, De Meo A N , Ouellette JJ, Cohen M, Reed CE. Virus as precipitants of asthmatic attacks in children. J A M A I974; zz7: 292-298. I3. Centers for Disease Control. Recommendation of the Public Health Service Advisory Committee on Immunization Practices. Influenza vaccine. Morbid Mortal Weekly Report I984; 33 : 253-266.
