Pediatr Infect Dis J, 1991;10:42-70891-3668/91/$03.00/0Copyright @ 1991 by Williams & Wilkins

Vol. 10, No.1Printed in U.S.A.

IAN M. FORGIE, BSC, KEVIN P. O'NEILL, MRCP, NELLIE LLOYD-EVANS, MSC,

MAIJA LEINONEN, PHD, HARRY CAMPBELL, MRCP, HILTON C. WHITTLE, FRCP AND

BRIAN M. GREENWOOD, FRCP

Seventy-four children ages 1 to 9 years hos-pitalized because of severe pneumonia were in-vestigated using blood cultures, lung aspirates,nasopharyngeal aspirates, serology and antigendetection procedures. A bacterial infection wasidentified in 57 (77%), a viral infection was seenin 25 (34%) and 18 (24%) had mixed viral-bacterial infections. The bacterial pathogensmost frequently identified were Streptococcuspneumoniae and Haemophilus influenzae foundin 61 and 15% of patients, respectively. Theviral pathogen most frequently recovered wasrespiratory syncytial virus (12%). Evidence ofChlamydia pneumoniae strain TWAR and My-coplasmapneumoniae infection was found in 12and 4% of cases, respectively. Overall a poten-tial pathogen was identified in 60 (81 %) chil-dren, with evidence of polymicrobial infectionin 30 cases (40.5%). The study provides infor-mation 0]1 the relative role of different infec-tious agents in the etiology of severe pneumoniain children in a developing country.

occur in developing countries. In The Gambia, one ofthe smallest, poorest and most densely populatedcountries in Africa, respiratory infections are the com-monest cause of death in children surviving the neo-natal period4 and pneumonia is a main reason forpediatric admission to the Medical Research Council(MRC) Hospital, Fajara.

Knowledge of the etiology of pneumonia in childrenin developing countries is essential before rationalcontrol programs can be implemented. Although vi-ruses are the major cause of acute lower respiratorytract infections (ALRI) in children in industrializedcountries5,6 there is strong evidence that bacterialinfections are responsible for the severity and highmortality associated with pneumonia in children indeveloping countries.6, 7 However, conclusive evidence

for the bacterial etiology of pneumonia in young chil-dren is difficult to obtain because few patients canproduce sputum and the specimen is usually contam-inated by oropharyngeal organisms. Blood culturesare positive in only 10 to 30% of children with bacte-rial pneumonia.8 Lung aspiration is a more sensitivetechnique, being positive in approximately 50 to 70%of cases, but is suitable only for patients with localizedconsolidation who can be kept under close observa-tion. An earlier study9 done in The Gambia demon-strated that, as in other developing countries, Strep-tococcus pneumoniae and Haemophilus influenzae arethe most common bacterial causes of severe pneu-monia. Infection by these bacteria was identified in 53and 20%, respectively, of hospitalized patients withlobar pneumonia. However, neither virologic investi-gations nor serologic investigations were performed inthat study. Thus the main objectives of the presentstudy have been to investigate the role of antigen andantibody tests in the diagnosis of bacterial infectionin Gambian children with pneumonia, to elucidate therole of various nonbacterial agents in the etiology ofpneumonia in these children and to investigate the

INTRODUCTION

Acute respiratory infections can be ranked alongsidediarrhea and malnutrition as the major causes ofserious illness and death in children in developingcountries.1 Of the 15 million children younger than 5years that are estimated to die annually approximately4 million die of pneumonia.2.3 Most of these deaths

Accepted for publication Aug. 23, 1990.From the Medical Research Council Laboratories, Fajara, Banjul,

The Gambia (IMF, KPO, HC, HCW, BMG); Gambia Government/MRC Joint Research Unit, Fajara, The Gambia (NL); and NationalPublic Health Institute, Helsinki, Finland (ML).

Key Words: Acute respiratory infections, pneumonia, children,Streptococcus pneumoniae, Haemophilus influenzae, respiratory syn-cytial virus, Chlamydia pneumoniae.

Address for reprints: Dr. K. P. O'Neill, Department of ChildHealth, Ninewells Hospital, Dundee, United Kingdom.

42

Vol. 10, No. ., January, 1991 43THE PEDIATRIC INFECTIOUS DISEASE JOURNAL

relationship between bacterial and nonbacterial infec-tions. We know of only four previous studies in whichviral cultures and serology together with lung aspira-tion or blood culture have been done on the samechildren in a developing country .10-13 In one study thevirus culture techniques were inadequate11 whereasanother was performed in a population with readyaccess to antibiotics!2 In this paper we report ourfindings in children ages 1 to 9 years; findings ininfants with ALRI are reported in the accompanyingpaper.14

immunoelectrophoresis and type-specific latex testsfor the 10 commonest types of S. pneumoniae isolatedin the Gambia as reported previously .16

Antibodies to pneumococcal pneumolysin, to H. in-fluenzae and to Moraxella catarrhalis were measuredusing enzyme-linked immunoassays as described pre-viously in 59 paired sera.17.18 The diagnostic criteriafor bacterial antibody assays were identical to thosedescribed previously.14

Virology. The methodology used has been de-scribed in detail in the previous paper.14 A 3-fold riseor greater in enzyme-linked immunoassay antibodytiter to respiratory syncytial virus (RSV) was acceptedas evidence of recent RSV infection.

Antibodies to Chlamydia pneumoniae and Chlamy-dia trachomatis were assayed by Dr. Pekka Saikku,Department of Virology, University of Helsinki, Fin-land, with the use of microimmunofluorescence asdescribed previously .19

Other investigations. Differential and total WBCcounts were performed by standard methods and C-reactive protein concentrations were measured inacute phase sera by immunoturbidometry using aCobas Mira@ automatic analyzer (Roche Diagnostica,Basel, Switzerland).

RESULTS

Cases. Seventy-four children with severe ALRIwere investigated during the 22-month study period.Forty-six children were male and 28 were female.Sixty-four cases were between 1 and 4 years of ageand 10 cases were between 5 and 9 years of age. Ofthe 70 patients who had a chest radiograph taken 68(97.1%) had radiologic changes consistent with ALRIand 49 (70%) had lobar pneumonia. Fourteen (18.9%)were unable to drink and 4 (5.1%) were cyanosed.Thus, according to the World Health Organizationclassification of acute lower respiratory infections, 58(78.3% ) children had severe pneumonia and 16(21.6% ) had very severe pneumonia. The main clinicalfeatures found in children in each age group are sum-marized in Table 1. Forty-three cases were investi-gated during 12 dry season months and 31 during 10wet season months. Two patients died.

Bacterial infections. Blood culture was per-formed on all patients and lung aspiration on 29patients. Evidence of bacterial infection was found in57 (77%) children. Pneumococcal pneumonia was di-agnos~d in 45 (60.8%) patients (Table 2): S. pneumo-niae was c~ltured from 17 patients (7 from lung aspi-rates, 7 by blood culture and in 3 cases from bothspecimens) .A further 28 children had indirect evi -

dence of pneumococcal infection either by antigendetection in body fluids (20 children) and/or by serol-ogy (18 patients). Four had sterile lung aspirates whichwere positive for pneumococcal antigen and in 6 other

p A TIENTS AND METHODS

Patients and samples. Children between the agesof 1 and 9 years who presented to the MRC hospital,Fajara, with a clinical diagnosis of ALR1 betweenAugust, 1986, and May, 1988, and who had obviouschest indrawing were investigated. This physical signwas selected because it has been recommended by theWorld Health Organization as being helpful for pri-mary health care workers to discriminate betweenmoderate and severe disease.15 All children were ex-amined by the study clinician and signs includingrespiratory rate, cyanosis, nasal flaring, pulse, tem-perature and auscultatory findings were recorded.Most children came from the periurban area surround-ing the MRC Laboratories as described in Paper 1!4

A chest roentgenogram was taken on admission andurine and a nasopharyngeal aspirate (NPA) were col-lected. Abnormal radiologic findings were recorded bythe project clinician according to prearranged codingcriteria and without knowledge of the patients' iden-tity. Provided parental permission was granted lungaspirates were obtained from children with obviousradiologic evidence of consolidation. Twenty-ninelung aspirations were done without complications.Venous blood was collected from all patients for cul-ture, hemoglobin estimation, differential white bloodcell (WBC) count, C-reactive protein (CRP) concen-tration and a blood film was prepared and examinedfor malaria parasites. Serum was taken at the time ofthe acute infection and approximately 2 weeks laterfor serologic studies. Patients were normally treatedwith oral trimethopril:1l-sulfamethoxazole or oralchloramphenicol. Parenteral benzylpenicillin or chlor-amphenicol were given in more severe cases. Therapywas occasionally altered in the light of microbiologicfindings.

Bacteriology. Culture of blood and lung aspiratespecimens for bacteria was performed as describedpreviously .16 Specimens of urine and serum were proc-essed and tested for pneumococcal and H. influenzaepolysaccharide antigen with the use of commerciallatex agglutination tests (Bactigen@; Wampole Labo-ratories, Cranbury, NJ; Slidex meningite-kit@; Bio-merieux, Charbonnieres-les-Bains, France), counter

Vol. 10, No.1, January, 199144 THE PEDIATRIC INFECTIOUS DISEASE JOURNAL

TABLE I. Clinical characteristics of 74 childrenhospitalized with severe pneumonia by age group

7434:!: 26

46:2838.6:!: 0.94148:!: 2261:!: 1274 (100)55 (74)14 (18;9)

4 (5.4)31 (42)32 (43)30 (41)

3 (4)10 (14)

7068 (97.1)49 (70.0)9.5:!: 2.4

21.1 :!: 9.7lOO:!: 80

with Ho influenzae (Table 2). The bacterium was cul-tured from one patient and one patient had Ho influ-enzae type b antigen detected in the urine by latexagglutination. A further nine children were found tohave rising antibody titers to this organism.

Fifteen other patients had a bacterial infection.Staphylococcus aureus was cultured from the lungaspirate of 3 patients and from the blood of 1 patient.Moraxella catarrhalis infection was demonstrated byserology in 7 patients and Salmonella typhi (1) andviridans streptococci (3) were isolated from the bloodof the 4 remaining patients (Table 2).

Six children had recently received antibiotics at thetime of admission. A bacterial diagnosis was made infive of these patients, two of which were made byblood culture.

Viral infections. Sixty-seven patients were inves-tigated for viral infection (90.5%). A respiratory virusinfection was identified in 21 (31.3%). All diagnoseswere made by isolation from NPAs or by serology. Noviruses were isolated from any of the 28 lung aspiratesthat were cultured. RSV was the commonest viralagent identified (Table 2). The virus was isolated from4 patients, 2 of whom also had serologic evidence of

Total no. (%)Age (months)Sex (M:F)Temperature rc)Pulse rateRespiratory rateIndrawingFlaringInability to drinkCyanosisBronchial breathingCrepitationsDiminished air entryWheezeNormal breath soundsChest radiograph

SatisfactoryAbnormalLobal consolidation

HemoglobinWBC (xlO3 cells/mm3)CRP (mg/liter)

T ABLE 2. Etiologic diagnoses established among 74children hospitalized with severe pneumonia by age group

5-9YearsPathogen 1-4 Years All Ages

n= 64

48 (75r39 (60.9)10 (15.6)

4 (6.25)4 (6.25)2 (3.1)

n=58

23 (39.6)8 (13.8)3 (5.1)2 (3.4)6 (10.3)2 (3.4)5 (8.6)

8 (12.5)2 (3.1)

51 (79.7)

n= 10 n= 74

9 (90)6 (60)1 (10)3 (30)02 (20)

n=9

57 (77.0)45 {60.8)11 (14.8)

7 (9.4)4 (5.4)4 (5.4)

n=67

Any bacterium

Streptococcus pneumoniae

Haemophilus influenzaeMoraxello catarrhalis

Staphylococcus aureus

Other ba<:teria

---

) ANTIGEN DETECTION(.-33)

2 (22)

1 (11)

0

0

1 (10)

0

0

25932725

93

60

Any virusRSVInfluenza BParainfluenzaAdenovirusRhinovil1JsOther virus

Other agen1;sChlamydia pneumoniaeMycoplasma pneumoniae

Any pathogen

"'--/;NEUMOL YSINSEROLOGY(.-25)

FIG. 1. Venn diagram showing interrelationships of differentmethods used to diagnose pneumococcal infection in children hos-pitalized with severe ALRI. Paired sera for measuring antibodies topneumococcal pneumolysin were not available from 15 patients.

1 (11)

1 (11)

9 (100)

.Numbers in parentheses. percent.

10~ RAINS .""""","'"" RAINS

A

~

"~ tj-

E

~ 4-

Cases with evidence of

Aug Oct Dec Feb Apr Jun Aug Oct Dec Feb Apr1986 1987 1988

MONTHS

FIG. 2. Seasonal distribution of children hospitalized with severeALRI together with the number of patients who had evidence of

pneumococcal infection.

children antigen was demonstrated in acute serum orurine by counterimmunoelectrophoresis. The remain-ing 18 children were diagnoses by detection of antigenin urine by a serotype specific latex test (8) or bydemonstrating a rise in antibody to pneumolysin (7)or both (3). Figure 1 shows how the various methodsused to diagnose pneumococcal infection compared inthe 45 patients with presumed pneumococcal disease.Note that paired sera for assay of antibodies to pneu-mococcal pneumolysin were not available from 7 pa-tients who evidence of pneumococcal infection byanother technique (including 5 culture-positive pa-tients). The number of cases with evidence of S.pneumoniae infections identified by month of study isshown in Figure 2.

Eleven (14.8%) children had evidence of infection

(37.3)(12.1)(4.1)(2.7)(9.4)(2.7)(6.7)

(12.1){4.1)(81.1)

Vol. 10, No.1, January, 1991 THE PEDIATRIC INFECTIOUS DISEASE JOURNAL 45

virus infection, 10 (22%) had evidence of M. pneu-moniae or C. pneumoniae infection and 5 (11) hadevidence of infection by other bacteria.

Other laboratory investigations. The CRP con-centration in acute phase serum samples was meas-ured in 60 of the children hospitalized with severeALRI. The mean :t SD was 100 :t 80 mg/liter. Thirty-one children had a CRP concentration in excess of100 mg/liter (51.6%). WBC counts were performed onblood specimens from 56 children (76%). The mean :tSD WBC was 21.1 :t 9.8 with 41 (73% ) children havinga WBC count above 15 X 103/mm3.

Clinical features and etiology. Because only 3patients had evidence of a viral infection alone it wasnot possible to compare clinical signs in patients withviral infections and in those with bacterial infections.No significant differences were found in clinical signs,mean CRP concentration or WBC count between thegroup of 27 children who had evidence of infection bya single bacterium and the group of 30 children inwhom 2 or more potentially pathogenic agents wereidentified.

infection by RSV (paired sera were not available forthe other 2 patients from whom RSV was isolated). Afurther 5 patients had only serologic evidence of RSVinfection. Other respiratory viruses identified wereadenoviruses (7 cases), influenza B (3 cases), parain-fluenza (2 cases) and rhinoviruses (2 cases). In addi-tion herpE~s simplex w~s recovered from 4 cases andan enterovirus from 1 case. Overall a viral infection,other than cytomegalovirus (CMV), was identified in25 patients (37.3%). CMV was recovered from 14 cases(20.9%).

Serologic evidence of C. pneumoniae infection wasfound in 9 patients of whom 8 also had evidence ofconcurrent pneumococcal infection. Eight of the 9 C.pneumoniae infections were in children ages 1 to 4years of age, the remaining case being in an 8-year-old child I:Table 2). Three children, ages 1, 2 and 7years, had a rising antibody titer to Mycoplasma pneu-moniae by complement fixation test.

Multiple infections. One or more pathogens wereidentified in 60 patients (81%). In only 3 cases (4.5%)was a virus the only infectious agent identified. Twoof these cases were infected with RSV and one withadenovirus. In contrast 32 children had evidence ofbacterial infection alone (43%) of whom 5 had evi-dence of infection by more than one bacterium. Evi-dence of pneumococcal infection alone was found in19 (25.6%) cases, H. influenzae alone in 3 (4%) casesand Staph. aureus alone in 2 (2.7% ) cases.

Multiple infections were found in 30 (40.5%) pa-tients (including the 5 dual bacterial infections re-ported above). Figure 3 is a Venn diagram showinghow infections with different types of infectious agentinterrelated. Eighteen cases had evidence of infectionby 2 organisms, 9 with 3 organisms, 2 with 4 organismsand 1 with 5 organisms. Eighteen cases were mixedviral-bacterial infections (27.2%). All 11 patients inwhom C. pneumoniae or M. pneUmoniae infection wasdiagnosed had evidence of concurrent infection bybacteria; 4 patients in addition had evidence of viralinfection.

Of the 45 patients with evidence of pneumococcalinfection 15 (33%) also had evidence of a respiratory

,\BACTERIAVn=57!

MYCOPLASMA(n .11)

32

FIG. 3. Venn diagram showing interrelationships of bacterial,respiratory viral and chlamydial/mycoplasmal infections in childrenhospitalized with severe ALRl.

DISCUSSION

The high proportion of bacterial infections found inthis group of patients is in agreement with previousstudies of children in developing countries hospital-ized because of severe pneumonia.10-13, 20 We have also

confirmed that So pneumoniae is the most importantagent of pneumonia in these children. Although theinsensitivity of blood culture in detecting bacterialinfection in cases of pneumonia is well recognizedB itis clear that many bacterial infections remain unde-tected, even when more reliable and sensitive methodssuch as lung aspiration are used. Shann7 has previ-ously commented on the occurrence of false-negativesusing lung aspirates. Although 45 (61%) of the pa-tients we studied were demonstrated to have evidenceof pneumococcal infection, So pneumoniae was cul-tured from only 17 patients (23% ) .While it is acceptedthat indirect methods of diagnosis cannot give ascertain a diagnosis as bacterial isolation and that somecaution is required in accepting these figures, it islikely that the prevalence of pneumococcal pneumoniain The Gambia is considerably higher than is demon-strable by conventional bacteriology .

The incidence of lobar pneumonia has been ob-served to vary with the season in West Africa.21MacFarlane et al.22 have reported that, at least inadults, cases of lobar pneumonia occur most fre-quently in the dry season and speculated that thismay be because nasopharyngeal defenses are de-pressed because of drying. In this study we found thehighest incidence of pneumococcal pneumonia inMarch of each year, which is the mid-dry season inThe Gambia when absolute humidity is low.

H. influenzae infection was dialZnosed by culture or

Vol. 10, No.1, January, 1991THE PEDIATRIC INFECTIOUS DISEASE JOURNAL46

If

IJ

antigen detection in only 2 patients, a lower propor-tion than found in a parallel study14 of 90 infants lessthan 12 months of age, in whom 3 positive diagnoseswere made by culture and 4 by antigen detection. Thisfinding is in keeping with previous observations onthe pattenl of H. influenzae meningitis in TheGambia23 which have shown that 84% of cases of thisinfection occur during the first year of life. MoreoverH. influenzae was cultured from the blood or lungaspirate of 6 of 19 children less than 12 months of agewho were investigated at the beginning of this studybut who were not eligible for inclusion in the finalanalysis. The interpretation of the 9 serologic diag-noses of H. influenzae infection in children 1 to 9 yearsold is difficult as none was substantiated by eitherculture or antigen detection. However, no antibodyresponse to H. influenzae was found in paired serafrom 40 Gambian children with malaria.

Viral infections were, as expected, much less com-mon than bacterial infections in the group of patientsstudied, 70% of whom had radiologic evidence of con-solidation. This again contrasts with the findings ininfants in whom a viral infection, particularly RSV,was found in a high proportion of cases!4 The overallvirus isolation rate is similar to that of previous stud-ies in developing countries which performed lung as-pirates and viral cultures or serology on children (ap-proximately 30%).10-13 No virus was isolated from anyof 29 lung aspirates cultured despite the use of iden-tical culture conditions for NP A and lung aspiratespecimens. It is possible although unlikely that thesterile saline into which the lung aspirate was collectedwas insufficient to maintain viable viruses for theshort period before inoculation of the specimen intoviral transport medium. Shann et al.13 isolated 5 vi-ruses from 62 lung aspirates (8%) by drawing thespecimen into tissue culture medium.

CMV was isolated from the NPA of 14 patients(20.9%). Respiratory tract excretion of CMV in younghealthy children is well-recognized24 and has beenfound to be common in young Gambian children.25Although the virus has been implicated as a cause ofpneumonit;is in neonates26 and the immunocompro-mised it is unlikely that CMV alone was responsiblefor pneumonia in any of the patients in our study. Allpatients who were excreting CMV also had evidenceof infection by another agent and it is likely that CMVexcretion was either coincidental with or a conse-quence of the patient's condition rather than thecause.

C. pneumoniae is a recently described chlamydialspecies which has been associated with pneumonia inyoung adults, military recruits and those with chronicdiseases,19,27 as well as Filipino children with ALRI.28In the present study all 9 children with serologicevidence of recent C. pneumoniae infection had addi-tional evidence of infection by other pathogens. This

would suggest that by itself C. pneumoniae is not animportant cause of severe pneumonia in Gambianchildren but may contribute to the severity of thedisease in patients with concurrent infection. In con-trast in the study of Filipino children with ALRI, theorganism was often the only potential pathogen iden-tified.28

No evidence of C. trachomatis infection was foundin any of the 40 paired serum specimens tested bymicroimmunofluorescence nor was the organism iso-lated from any of the NP A and lung aspirate speci -

mens cultured.Only three patients had evidence of M. pneumoniae

and all had evidence of concurrent infection with otherpathogens. M. pneumoniae is reported to be one of thecommonest causes of mild pneumonia in school agedchildren in the United States.29 The low number ofdiagnoses in this study may reflect the high proportionof children younger than 3 years of age (70% ) and theseverity of illness investigated. Alternatively the studymay have been performed during a period when theprevalence of M. pneumoniae infection was low.

Infection by a potential pathogen was identified in81% of the children ages 1 to 9 years that wereinvestigated. Evidence of infection by more than onepathogen was found in 40.5%. Other investigatorshave also found mixed infections in a high proportionof hospitalized children with severe ALRI. Paisley etal.3° in a study of 102 hospitalized children youngerthan 5 years in Denver found multiple infections in33 (32%). Hietala et al.31 found serological evidence ofbacterial in 19 (37%) of 51 pediatric patients withdocumented viral infection and proposed that mixedinfections are more common than previously reported.Nichol and Cherry32 have suggested that the severityof respiratory illness may be related to infection bymultiple agents and more recently Pio et al.6 have alsocommented that the significance of multiple infectionsin the pathogenesis of severe disease may have beenunderestimated. However, Turner et al.,33 in a studyof pediatric outpatients in Northern California, foundthat concurrent viral and bacterial infection was notassociated with unusually severe disease. In the pres-ent study of hospitalized children with severe ALRImultiple infection was not found to be associated withmore severe disease as defined by an increase in meanrespiratory or heart rate, mean temperature, meanCRP concentration or WBC count, or the presence oflobar pneumonia. However, because all the patientsstudied were already severely ill marked changes inthese parameters might not be expected.

The mortality in this study was low (2.5%). One ofthe children who died was culture-positive for S. pneu-moniae and had serologic evidence of infection by RSVand C. pneumoniae. No pathogen was identified in theother child. Both children were 23 months old. TheMRC hospital is well provided for with clinicians,

47Vol. 10, No.1, January, 1991 THE PEDIATRIC ~NFECTIOUS DISEASE JOURNAL

tract infections in children in Cali, Columbia. Pediatrics1976;57:123-30.

13. Shann F, Gratten M, Germer S, Linnemann V, Hazlett D,Payne R. Aetiology of pneumonia in children in Goroka Hos-pital, Papua New Guinea. Lancet 1984;2:537-41.

14. Forgie IM, O'Neill KP, Lloyd-Evans N, et al. The etiology ofacute lower respiratory tract infections in Gambian children: I.Acute lower respiratory infection in infants presenting at thehospital. Pediatr Infect Dis J 1991;10:33-41.

15. World Health Organization. Case management of acute respi-ratory infections in children in developing countries. Report ofa working group meeting. WHO (1985), Document No. WHO/RSD/85.15 Rev 1.

16. O'Neill KP, Lloyd-Evans N, Campbell H, Forgie IM, SaballyS, Greenwood BM. A latex agglutination test for the diagnosisof pneumococcal pneumonia in children. Br Med J

1989;298:1061-4.17. Jalonen E, Paton JC, Koskela M, Kerrtula Y, Leinonen M.

Measurement of antibody responses to pneumolysin: a prom-ising method for the aetiological diagnosis of pneumococcalpneumonia. J Infect 1989;19:127-34.

18. Kerrtula Y, Leinonen M, Koskela M, Makela PH. The aetiologyof pneumonia: application of bacterial serology and basic labo-ratory methods. J Infect 1987;14:21-30.

19. Kleemola M, Saikku P, Visakorpi R, Wang SP, Grayston JT.Epidemics of pneumonia caused by TW AR, a new Chlamydiaorganism, in military trainees in Finland. J Infect Dis

1988;157:230-6.20. Silverman M., Stratton D, Diallo A, Egler LJ. Diagnosis of

acute bacterial pneumonia in Nigerian children. Arch Dis Child

1977;52:925-31.21. Warrell DA. Respiratory tract infections in the tropics. Prac-

titioner 1975;215:740-6.22. MacFarlane JT, Adegboye DS, Warrell MJ. Mycoplasmapneu-

moniae and the aetiology of lobar pneumonia in northern Ni-geria. Thorax 1979;34:713-9.

23. Bijlmer H. Haemophilus influenzae meningitis in The Gambia.J Infect Dis (in press).

24. Peckham CS, Johnson C, Ades A, Pearl K, Chin KS. Earlyacquisition of cytomegalovirus infection. Arch Dis Child

1987;62:780-5.25. Bello CSS. Cytomegalovirus infection in The Gambia. Thesis

submitted to Ahmadu Bello University, Nigeria, 1984:224 pp.26. Stagno S, Brasfield DM, Brown MB, et al. Infant pneumonitis

associated with cytomegalovirus, Chlamydia, Pneumocystis andUreaplasma: a prospective study. Pediatrics 1981;68:322-9.

27. Grayston JT, Diwan VK, Cooney M, Wang S-P. Community-and hospital-acquired pneumonia associated with ChlamydiaTWAR infection demonstrated serologically. Arch Intern Med1989;149:169-73.

28. Saikku P, Ruutu P, Leinonen M, Panelius J, Tupasi TE,Grayston JT. Acute lower-respiratory-tract infection associatedwith Chlamydia TW AR antibody in Filipino children. J InfectDis 1988;158:1095-7.

29. Denny FW, Clyde W A. Acute lower respiratory tract infectionsin nonhospitalized children. J Pediatr 1986;108:635-46.

30. Paisley JW, Lauer BA, McIntosh K, Glode MP, Schachter J,Rumack C.Pathogens associated with acute lower respiratorytract infection in young children. Pediatric Infect Dis J

1984;3:14-9.31. Hietala J, Uhari M, Tuokko H, Leinonen M. Mixed bacterial

and viral infections are common in children. Pediatr Infect DisJ 1989;8:683-6c

32. Nichol KP, Cherry JD. Bacterial-viral interrelationships inrespiratory tract infections in children. N Engl J Med1967;277:667-72.

33: Turner RE, Lande AE, Chase P, Hilton N, Weinberg D. Pneu-monia in pediatric outpatients: cause and clinical manifesta-tions. J Pediatr 1987;111:194-200.

nursing staff, drugs and equipment, and referrals come

mostly from the nearby periurban area. These factors

possibly account for the low mortality observed corn"

pared with other studies in developing countries but

suggest that ALRI of childhood is a rewarding disease

to treat.Although some uncertainty must remain about the

validity of diagnostic methods other than culture our

findings strongly suggest that the pneumococcus is

the dominant cause of pneumonia in Gambian chil-

dren ages 1 to 9 years who present to the hospital. H.

influenzae and RSV were found much less frequently

than in a group of infants who were studied concur-

rently. Thus programs for the management of acute

respiratory infections in Gambian children must in-

clude an antibiotic which will be rapidly effective

against the pneumococcus. Our results highlight once

again the urgent need for a pneumococcal vaccine that

is effective when given to young children.

ACKNOWLEDGMENTSWe thank Haddy Sillah, Mariama Sanneh and Raili Kalliokoski

for technical assistance; Chris Grummitt for measuring CRP con-centrations; Jo Armstrong for statistical advice and Musu Bojangand Lamin Manneh for their excellent field work.

REFERENCES1. Denny FW, Loda FA. Acute respiratory infections are the

leading cause of death in children in developing countries. AmJ Trop Med Hyg 1986;35:1-2.

2. Leowski J. Mortality from acute respiratory infections in chil-dren under 5 years of age: global estimates. World Health Stat

Q 1986;39:138-44.3. Gwatkin DR. How many die? A set of demographic estimates

of the annual number of infant and child deaths in the world.Am J Publ Health 1980;70:1286-9.

4. Greenwood BM, Greenwood AM, Bradley AK, Tulloch S, HayesR, Oldfield FSJ. Deaths in infancy and early childhood in awell-vaccinated, rural, West African population. Ann TropPaediatr 1987;7:91-9.

5. Murphy TF, Henderson FW, Clyde WA, Collier AM, DennyFW. Pneumonia: an eleven-year study in a pediatric practice.Am J E;pidemiolI981;113:12-21.

6. Pio A, Leowski J, Ten Dam HG. The magnitude of the problemof acute respiratory infections. In: Douglas RM, Kirby-EatonE, eds. Proceedings of an international workshop on acuterespiratory infections, Sydney, August, 1984. Adelaide, Aus-tralia: University of Adelaide, 1985:3-16.

7. Shann F. Etiology of severe pneumonia in children in develop-ing countries. Pediatr Infect Dis J 1986;5:247-51.

8. Anonymous. Pneumonia in childhood. [Editorial] Lancet

1988;1:741-3.9. Wall RA, Corrah PT, Mabey DCW, Greenwood BM. The

etiology of lobar pneumonia in The Gambia. Bull WHO1986;64:553-8.

10. Hughes JR, Sinha DP, Cooper MR, Shah KV, Bose SK. Lungtap in childhood: bacteria, viruses and mycoplasmas in acutelower respiratory tract infections. Pediatrics 1969;44:477-85.

11. Mimica I, Donoso E, Howard JE, Ledermann G W .Lung punc-ture in the etiological diagnosis of pneumonia. Am J Dis Child1971;122:278-82.

12. Escobar JA, Dover AS, Duenos A, et al. Etiology of respiratory