The incidence and severity of virus infections in a children's respiratory intensive care unit during an influenza A epidemic were studied. Infections caused by the Port Chalmers strain of influenza A or by an adenovirus were associated with severe, often fatal, pneumonia, whereas infections caused by respiratory syncytial virus or cytomegalovirus carried a good prognosis

Du T. Naude, W.

Keen, G.A.

Kipps, A.

Klein, M.

English

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14 December 1974 S.A. MEDICAL JOURNAL 2543Virus Infections in Children in a RespiratoryIntensive Care Unit during an Influenza EpidemicW. DU T. NAUDE, M. KLEIN, G. A. KEEN, A. KIPPSSUMMARYThe incidence and severity of virus infections in a children'srespiratory intensive care unit during an influenza Aepidemic were studied. Infections caused by the PortChalmers strain of influenza A or by an adenovirus wereassociated with severe, often fatal, pneumonia, whereasinfections caused by respiratory syncytial virus or cyto-megalovirus carried a good prognosis.S. Air. Med. l., 48, 2543 (1974).A short circumscribed outbreak of influenza A caused bythe Port Chalrners strain (the so-called Kiwi 'flu) occurredin the general population of Cape Town during the mid-winter months of 1974. During this period, there was astriking increase in the number of children admitted to therespiratory intensive care unit (R-ICU) with severe bron-chopulmonary disease. This was unexpected, since others'"have found that influenza epidemics do not generally in-crease the rates of serious respiratory illness in children.This study was undertaken to analyse the events in theR-ICU which caused a marked increase in admissionduring the epidemic period lasting from the last week ofJune to the end of July 1974.PATIENTS AND METHODSThe investigations were done on children admitted to a 6-bedded R-ICU for non-White patients in the Red CrossWar Memorial Children's Hospital. Because of the limitedaccommodation, only those patients in severe respiratoryfailure, based on the following blood gas criteria, wereadmitted: p.CO, above 60 mrnHg, or p.O, below 150mrnHg in FIO, 1,0. The diagnosis in each case was esta-blished on the usual clinical and radiographic criteria.Pneumonia and bronchiolitis were the predominant ex-pressions of pulmonary infection. The 4 Black and 19Coloured children were from the lower socio-economicstrata of the community, evidenced by their generally lowbody weight for age.Laboratory InvestigationsNasopharyngeal secretions were collected within 24hours of admission and sent with a minimum of delay tothe laboratory for microbiological study. Tracheal aspirateswere obtained from those patients with endotracheal tubesneeding assisted ventilation. As a rule, only one specimenwas obtained from each patient for virological investiga-tion. Paired sera were not routinely collected.Virus isolations were achieved by standard methods,using human fibroblasts for cytomegalovirus, HeLa cellsfor adenovirus and respiratory syncytial virus, and primaryvervet monkey cells for herpesvirus, para-influenza virus,and influenza virus in which viral presence was recognisedby cytopathic effect or by haemadsorption. The influenzavirus strains were also isolated in embryonated eggs.Viruses were identified by the appropriate neutralisation,haemadsorption inhibition or haemagglutination inhibitiontests. This series of investigations did not include culturefor Mycoplasma pneumoniae.The Influenza EpidemicThe first isolations of A/Port Chalmers influenza viruswere made from two specimens received in the laboratoryon 26 June, one from an adult and one from a patient inthe R-ICU. Isolations of this virus continued throughoutthe next 5 weeks, up to the end of July. There were nofurther isolations of influenza A virus from patients in theR-ICU and the epidemic in the general public graduallysubsided.RESULTSAdmissionsCoinciding almost exactly with an outbreak of influenzaA virus in the general community, there was a dramaticincrease in the number of non-White patients requiringadmission to hospital for severe respiratory disease, butthere was no similar increase among the White patients(Table I).TABLE I. TOTAL HOSPITAL ADMISSIONS FOR RESPIRATORYDISEASE-MRc Virus Research Unit and Department of Paediatrics andChild Health, University of Cape TownW. DU T. NAUD:f:, M.SC., M.MED. (PATH.), M.D.M. KLEIN, M.B. CH.B., F.C.P. (S.A.)G. A. KEEN, B.SC., M.B. CH.B., M.MED. (PATH.)A. KIPPS, M.D., F.R.C.PATH.Date received: 13 November 1974.PatientsWhiteNon-WhiteMay14209June13219July10263Aug.6139Sept.15157--2544 S.-A. MEDIESE TYDSKRIF14 Desember 1974Virus IsolationsSpecific Viral IllnessesHerpes simplex virus was cultured from 4 patients, adeno-virus from 2, cytomegalovirus from 4 and para-influenzavirus (type 3) was isolated only once.Two viruses were isolated from the aspirates of 3 Chil-dren: an adenovirus with an influenza virus in one, aherpes simplex virus with an adenovirus in another, and arespiratory syncytial virus with a cytomegalovirus in thethird.The virus isolations during each week of the epidemicperiod are shown in Fig. I and are contrasted with thefioures for routine virus isolations from this unit in pre-vious and subsequent months. Viruses were isolated from59% of the nasopharyngeal and tracheal aspirates examinedand just over one half of them were influenza or respira-tory syncytial virus.Influenza virus was isolated from 8 patients, of whom 4were under I year of age. One of these was 3 weeks oldand the other 3 months. Six of the 8 patients presented withpneumonia, one had laryngotracheobronchitis requiring anartificial airway, and in one, influenza complicated iieverebilateral bronchiectasis. Three patients died. Two wereseverely malnourished with weights less than 70~'" of thatexpected for age, and the third had a dual infection withan adenovirus. Postmortem examination was possible ononly one patient and the histological features were highlysuggestive of an adenovirus bronchiolitis in addition toan influenzal pneumonia, but an adenovirus was not cul-tured during life or at autopsy.The 8 patients, from whom respiratory syncytial viruswas cultured, varied in age from 10 days to 16 weeks andstayed in hospital for periods of 5 - 10 days. All werenormally developed for age. In 6 of these patients, theclinical diagnosis was bronchiolitis and in 2, viral pneu-monia. A 4-week old male with pneumonia died, and atautopsy the lymphoid tissues were found to be almosttotally depleted of T -cells.Herpes simplex virus was grown from 4 children. Twopresented with laryngotracheobronchitis llld recovered.The other 2 died. One with kwashiorkur had miliarytuberculos;s and a viral type pneumonia confirmed histo-logically. The other had clinical features compatible witha disseminated herpesvirus infection and had a concurrentadenovirus infection.Cytomegalovirus was isolated from 3 aspirates frompatients aged between 23 days and 9 weeks. Two presentedwith bronchiolitis and the third with pneumonia. Allrecovered and were discharged from hospital after 7 - 28days. .Both patients from whom an adenovirus was cultureddied. In each instance the virus was present in the naso-pharyngeal secretions with another virus; in one patientwith an influenza virus and in the other with a herpessimplex virus. In addition, one other patient had evidenceof a combined influenzal and adenovirus infection atautopsy (vide supra).Para-influenza virus was grown from a year-old femalechild with a relentlessly progressive pneumonia, who diedafter 18 d'ays.(j)f-Zwf-<!n..cBAMONT HSIIIIIL -25------50JISOLATIONSJ,- ,- - - -,, IIIr---- J,IIAVIRUS4321321~ooz(/)Zo.-<~o(/)Bacteriological CultureFig. 1. Weekly virus isolations between April and August1974 from children in the respiratory intensive care unit.A = isolations of respiratory syncytial virus; B = isola-tions of A/Port Chalmers influenza virus; C = totalisolations, Each bar represents one week. Broken line =total monthly R-ICU admissions.During the month of July 1974, the number of non-White patients with acute respiratory failure admitted tothe R-ICU was almost double the average monthly intake(Fig. I). Admission returned to normal levels in Augustand September.Surprisingly few significant bacterial pathogens wereisolated from the respiratory specimens, possibly owing tothe use of antibiotic therapy before admission to the ward.Only 5 species were isolated from 5 patients: Pneumococ-cus, Haemophilus influenzae, Pseudomonas, Salmonellaand Mycobacterium tuberculosis.'From the 44 nasopharyngeal" or tracheal aspirates sub-mitted for examination, 26 virus- strains were grown from23 patients. Three children had simultane~us infectionswith two viruses.Influenza A/Port Chalrners virus was isolated from 8patients and' respiratory syncytial virus "from "8'2ithers,14 December 1974 S.A. MEDICAL JOURNAL 2545-Ten of the 23 patients from whom viruses were isolateddied.DISCUSSIONOur attempts to explain the sudden increase in the admis-sions to the non-White R-ICU were largely success-ful. During the 5-week period under study, there were infact two epidemics, one caused by the A/Port Chalmersstrain of influenza virus and the other by respiratorysyncytial virus. While the influenza outbreak in July waslater than usual (March in 1973 and April - May in 1970),the epidemic of respiratory syncytial virus infectionsoccurred as expected in July, as it had done with peakincidences in July 1972 and July 1973. Such a fortuitouscoincidence of epidemics of these two viruses has beenrecorded by others,'·4 who also showed that cross-infectionsby influenza and respiratory syncytial viruses were com-mon in children's wards. The fact that the viruses wereisolated from 'specimens taken within 24 hours of admis-sion suggests that the virus infections in our patients wereacquired outside the hospital.It was interesting that a para-influenza virus was isolatedonly once during this period, despite the fact that it wasisolated several times in May from children in this ward.This may be due to some form of interference,' possiblyrelated to interferon. Viruses vary in their capacity toinduce interferon production and in their sensitivity toits inhibitory action. All the dual infections were causedby viruses (cytomegalovirus, herpesvirus, adenovirus) whichhave been considered to be relatively resistant to the anti-viral effect· of interferon; whereas the para-influenzaviruses ~re relatively sensitive. This may in part explainthe persistence of cytomegalovirus, herpesvirus and adeno-vi~es~ an~ the eX~lusion of para-influenza viruses duringt~IS epidemiC. The Isolation on 3 occasions of cytomegalo-Virus from these aspirates has raised the question of theirp~rticipatio~ in. the pathogenesis of lower respiratory tractdisease. This virus may be present in the saliva of 9% ofinfants and children under the age of 4 years in the UKand it may affect the lung.' It is known to cause pulmonarylesions in immunologically compromised adults andchildren, and may well do so in malnourished childrensince these often have depressed cellular immunemechanisms.'A~enoviruses are commonly present in the upperrespuatory tract of healthy children but may cause severe5lung damage in susceptible children, such as those understudy in this investigation. Both of the patients fromwhom an adenovirus was isolated died and it may havebeen a contributory cause of death in a third patient withinfluenza.. The ages of the children with respiratory syncytial virusmfection are similar to those described by others, but 4 ofthe 8 patients with influenza were under I year of age and2 died. This is contrary to the commonly expressed viewthat influenzallower respiratory tract disease rarely occursbelow J year of age.Serious pulmonary disease of viral origin seldom occursin t?e a?sence of some additional factor which impairs thepatients responses. The outstanding contributory factorsamong our patients seem to be their low socio-economicand poor nutritional status. The importance of these fac-t~rs. was. brought into focus by the complete absence of aslml1ar lllcrease in respiratory illnesses amon" the Whitechildren (Table I) during the epidemic. The ~ortality ofthese pulmonary viral infections was high in the under-privileged children in this study, with 10 of the 23 withproved viral infections dying. The long-term consequencesfor the survivors of these serious bronchopulmonary ill-nesses are not yet known, but it is likely that they lead toan appreciable incidence of respiratory disability in child-hood and adult life:There are as yet no prophylactic vaccines against mostof these viral respiratory tract infections and early in-fluenza immunisation is not widely practised. The dis-c~epancy between the incidences of serious pulmonarydisease between the low and higher socio-economic groups(Table I) implies that this group of diseases could begreatly reduced by raising the living standards of the non-White patients. Health authorities should pursue this "oalwith vigour. '='REFERENCES1. Foy. H. M .• Cooney, M. K., Maletsky. A. J. and Grayston. J. T.(1973): Amer. J. Epidemiol.. 97. 80.2. Grist, N. R .. Ross. C. A. and Stott. E. J. (1967): Br.t. Med. 1.. I. 456.3. Gardner. P. S.• Court. S. D. M., Brocklebank, J. T.. Downham.M. A. P. S. and Weightman. D. (1973): Ibid., 2, 571.4. Weightman, D., Downham, M. A. P. S. and Gardner. P. S. (19H):J. Hyg. Camb., 73. 53. .5. Glezen, P..W. and Denny, F. W. (1973): New Engl. J. Med., 288, 498.6. Baron, S. In FlInter, N. B., ed. (1973): Interferons and Interferon In-ducers, chap!. 3, p. 35. Amsterdam: North Holland Publishing7. Stem, H. (1968): Brit. Med. J., 1, 665. .8. Smythe. P. M., Schonland, M., Brereton-Stiles, G. G .• Coovadia H.M., Grace, H. J., Leomng, W. E. K., Mafoyane, A., Parent, M: A.and Vos, G. H. (1971): Lancet. 2. 9399. Colley, J. R. T., Douglas, J. W. B. and Reid. D. D. (1973): Brit.Med. J., 3, 195. .

Virus Infections in Children in a Respiratory Intensive Care Unit during an Influenza Epidemic

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Virus Infections in Children in a Respiratory Intensive Care Unit during an Influenza Epidemic

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