Chiamydia trachomatis and pneumonia in infants: report of two cases J.A. EMBIL, MD, PH D, FRCP[C]; R.L. OZERE, MD, FRCP[C]; S.W. MACDONALD, B SC, M Sc In two cases of pneumonia associated with Chiamydia trachomatis in infants the symptoms began in the second week of life and the illness was severest at 4 weeks of age. Both infants were afebrile. One had a history of conjunctivitis. Both presented with a characteristic staccato cough and tachypnea but little evidence of peripheral airway obstruction. Chest roentgenograms showed interstitial and alveolar pulmonary infiltration in hyperexpanded lungs. The serum 1gM concentrations were markedly elevated. C. trachomatis was cultured from specimens from both infants and one mother, and titres of antibody to the organism were substantially elevated in one infant and one mother. Dans deux observations de pneumonie associee a Chiamydia trachomatis chez des nouveau-nes les symptOmes ont debute au cours de Ia deuxieme semaine de vie et l'acme de Ia maladie se situalt A l'ige de 4 semaines. Les enfants 6taient tous deux apyretiques. L'un deux avait des ant6cedents de conjonctivite. Les petits malades presentaient, l'un et l'autre, une toux seche repetee caracteristique avec tachypnee mais sans signe net d'obstruction des voies respiratoires peripheriques. Les roentgenographies du thorax montraient une infiltration pulmonaire interstitielle et alveolaire avec surdistension des poumons. On a pu observer une augmentation marquee des taux d'lgM seriques. C. trachomatis fut cultive A partir de prelevements recueillis chez les deux enfants et l'une des meres; une 6l6vation consid6rable des titres d'anticorps A l'organisme a et6 notee chez un enfant et une mAre.

Neonatal inclusion blennorrhea has been known for many years in Canada. Its diagnosis has been based on the demonstration of intracytoplasmic inclusion bodies in Giemsastained preparations of cells obtained from conjunctival scrapings. The introduction of cell culture techniques has also allowed the isolation and identification of C. trachomatis from other sources and secretions.3 In 1975

Schachter and colleagues4 observed that this organism was a probable cause of lower respiratory tract infection or pneumonitis in an infant born to a woman in whom chlamydial infection of the cervix was detected during pregnancy. This observation has since been confirmed by others..7 We report two cases illustrating the clinical and laboratory features of chlamydial pneumonitis, which is probably a much more common disease than is currently recognized. Since some of the clinical features may be confused with those of pertussis in the very young, it is important to distinguish between the conditions so that appropriate treatment can be instituted. Case reports

Case 1 A 4-week-old boy was admitted to

hospital with a 2-week history of cough and episodes of rapid breathing. During the week preceding admission the cough, which was associated with an increased respiratory rate, occurred in paroxysms of increasing frequency with a repetitive staccato pattern and at times interfered with feeding. There was no

Chiamydia trachomatis acquired during an infant's passage through an infected birth canal causes inclusion associated post-tussive laryngospasm conjunctivitis or inclusion blennorrhea. Cervical infection with this orReproduced on the cover of this ganism has been shown to occur issue of the Journal is a Nomarski in 5.0% to 12.7% of pregnant interference contrast photomicrowomen 1,2 graph of a Chiamydia trachomatis From the departments of microbiology and pediatrics, Daihousie University, Izaak Walton Killam Hospital for Children, Halifax Reprint requests to: Dr. JA. Embil, Infectious diseases research unit, Izaak Walton Killam Hospital for Children, Halifax, NS B3J 3G6

inclusion body in irradiated BHK-21 cells stained with iodine; the final magnification is X 1300. The photomicrography was performed by F. Stefani of Dalhousie University's photographic unit.

or vomiting. The baby remained afebrile. The infant was the first born to a 17-year-old woman. During the last trimester of her pregnancy she had experienced vaginal discharge, and loss of amniotic fluid had been noted

24 hours before she was admitted to hospital in labour. The infant weighed 3250 g at birth and his neonatal course was uneventful; he was discharged with his mother 5 days after birth. At the time of admission the infant had moderate respiratory distress and was abnormally pale but not cyanotic; his respiratory rate ranged from 40 to 80/mm and there was moderate subcostal and suprasternal indrawing during inspiration. His nutritional status was satisfactory. Harsh breath sounds and diffuse fine inspiratory rales throughout both lungs were noted on auscultation. The pulse rate was 120 beats/mm, no heart murmurs were audible and the liver and spleen were not enlarged. The initial hemoglobin concentration was 16.5 g/dL and the total leukocyte count was 16.5 x 10'/L, with 42% neutrophils, 12% monocytes and 46% lymphocytes. Analysis of arterial blood gases showed a pH of 7.28, a carbon dioxide tension (PCO2) of 77 mm Hg and an oxygen tension (Po2) (capillary) of 66 mm Hg. A chest roentgenogram (Fig. 1) showed a bilateral pulmonary infiltrate that was most dense in the central third of both lungs although fine linear nodular densities extended to all pulmonary segments. There was no hilar adenopathy or evidence of pleural effusion. The lungs appeared to be hyperexpanded. The heart and the mediastinal contours looked normal. The appearance was thought to be consistent with that of diffuse pneumonia involving mainly the in-

terstitium but also the alveolar portions of the lungs. An electrocardio-

gram was normal. Serum immunoglobulin concentrations were as follows: IgG 1200, 1gM 510 and IgA 23 mg/dL. The 1gM

CMA JOURNAL/NOVEMBER 18, 1978/VOL. 119 1199

value was markedly elevated compared with the mean for this age group, 44 mg/dL.8 The rubella hemagglutination-inhibiting titre was 1:128 and the cold agglutinin titre was 1:4. No bacteria, including Bordetella pertussis, were cultured from the blood or nasopharyngeal aspirates, and investigation of blood, urine and throat swabs ruled out infection with Toxoplasma gondii, rubella virus, cytomegalovirus, Herpesvirus hominis, adenovirus, respiratory syncytial virus, coxsackievirus type B or Mycoplasma pneumoniae. For culture of C. trachomatis, specimens were collected in sucrosephosphate buffer, 0.2 mol/L (2SP) and frozen at - 700C. Thawed specimens were processed with the use of irradiated BHK-21 cells according to the micro cell culture method of McComb and Puzniak,9 except that coverslips were stained with iodine. The observation of characteristic FIG. 1-Case 1: bilateral pneumonia, with interstitial and alveolar infiltrates, in iodine-staining cytoplasmic inclusions 4-week-old boy at time of admission to hospital. in the cells confirmed the presence of C. trachomatis. Throat swabs from the infant and a cervical swab from the mother also yielded C. trachomatis, with six and four inclusions respectively per 5-mm coverslip on the first passage. The infant was treated initially with oxygen, antibiotics (gentamicin and ampicillin) and physiotherapy. During the first week the infant had severe paroxysms of coughing and episodes of rapid breathing, with respiratory rates of up to 1 20/mm, lasting several minutes; however, there was no difficulty with feeding. After review of the history, results of initial investigations and chest roentgenograms, the antimicrobial therapy was changed to oral administration of trimethoprim-sulfamethoxazole, 1.25 mL bid for 14 days. Although the response to therapy was not striking, the baby's condition improved gradually. The cough diminished, the respiratory rate gradually fell to normal and a chest roentgenogram made 16 days after admission showed considerable resolution of the pneumonia (Fig. 2), although clearing was not complete at the time of discharge. At this time auscultation of the chest revealed no rales or rhonchi. Throughout the 3 weeks of hospitalization the baby remained afebrile. FIG. 2-Case 1: resolution of pneumonic infiltrates almost complete 16 days At home the baby's condition con- after admission. 1200 CMA JOURNAL/NOVEMBER 18, 1978/VOL. 119

tinued to improve. A chest roentgenogram made 1 week after discharge showed residual interstitial infiltrate in the right lower lung although the chest sounded clear on auscultation. The cough was less severe and less frequent. Fever, cough and wheezing developed when the baby was 9 months old. A chest roentgenogram showed increased vascularity in the upper lobes of the lungs and hyperinflation, suggestive of chronic lung disease. The baby responded promptly to therapy with ampicillin and orally administered bronchodilators. Specimens for chlamydial cultures were not collected during this illness. Sweat electrolyte concentrations were normal. When the baby was 14 months of age a chest roentgenogram was normal and C. trachomatis could not be cultured. Case 2 A 4-week-old boy was admitted to hospital with a similar history of harsh cough occurring in paroxysms of increasing severity and frequency during the previous week. There was

no associated feeding difficulty, la- over the posterior lung fields during ryngospasm or cyanosis during the inspiration. The cardiovascular findepisodes. The cough was first noted ings were within normal limits and at 1 week of age but was not severe there was no enlargement of the liver until the week before admission, or the spleen. The hemoglobin conwhen the mother noted that the in- centration was 13.6 g/dL and the fant was breathing rapidly. total leukocyte count was 15.3 x The baby was born to a 20-year- 109/L, with 36% neutrophils, 6% old woman, gravida 1, para 1, who eosinophils, 17% monocytes and had experienced vaginal discharge 41 % lymphocytes. The platelet count during the last trimester of pregnan- in a peripheral blood smear was norcy. The membranes had ruptured mal. Analysis of arterial blood gases normally at the time of delivery. The showed a pH of 7.34, a Pco2 of 46 infant's birth weight was 3600 g. mm Hg and a Po2 (capillary) of 56 During the neonatal period he had mm Hg. The serum sodium concenmild bilateral conjunctivitis; cultures tration was 140 mmol/L and the sewere not done and treatment was rum potassium concentration 5.3 not given. mmol/L. At the time of admission the inA chest roentgenogram (Fig. 3) showed evidence of extensive bilafant's pulse rate was 130 beats/mm and his rectal temperature was teral pulmonary infiltration that was 37.2 0C. He had moderate respiratory most prominent in the left lower lobe distress, with a respiratory rate of and involved both the interstitium 60/mm and suprasternal and sub- and the alveolar portions of the lung. costal retraction during inspiration. There was no evidence of hilar adeThere were frequent paroxysms of nopathy or pleural effusion. coughing. His skin colour was norSerum immunoglobulin concentramal. There was mild bilateral con- tions were as follows: IgG 900, 1gM junctivitis without exudate. Ausculta- 300 and IgA 50 mg/dL. The sweat tion of the chest revealed harsh chloride concentration was 9 and 8 breath sounds and diffuse fine rales mmol/L on two occasions. No pathogenic bacteria were cultured from blood, urine or pharyngeal secretions, and cytomegalovirus, H. hominis, adenovirus, respiratory syncytial virus, respiratory syncytial virus, coxsackievirus type B and M. pneumoniae were not cultured from a nasopharyngeal aspirate. Specimens for culture of C. trachomatis were collected and processed as described for case 1. The nasopharyngeal aspirate and the throat swab yielded C. tra.. chomatis, with 42 and 20 inclusions respectively per 5-mm coverslip on the first passage. Three serum samples from the infant, taken at the time of admission and 14 and 24 days later, and one from the mother were submitted to the Harvard School of Public Health, Boston, for serologic testing for C. trachomatis. The serum was tested against a suspension of 5% pooled yolk-sac cultures of Chiamydia (14 serotypes, A to K, L-1, L-2 and L-3) using a microimmunofluorescence technique. Reciprocal antibody titres to C. trachomatis were 320 in all samples from the infant and 160 in that from the mother; both titres were considered significantly elevFIG. 3-Case 2: bilateral pneumonia in 4-week-old boy at time of admission to ated. hospitaL The baby was given intravenously CMA JOURNAL/NOVEMBER 18, 1978/VOL. 119 1201

sulfisoxazole, 150 mg/kg of body weight for 14 days. Improvement was gradual. After 8 days rales were no longer audible during auscultation of the chest and the respiratory rate was normal (40/mm). The cough was less severe and no longer paroxysmal. A chest roentgenogram showed considerable resolution of the pneumonia, with a slight residual increase in interstitial markings. The infant was discharged after 2 weeks of hospitalization. Ten days later the cough was further reduced and a chest roentgenogram appeared normal. Chest auscultation revealed normal breath sounds. Discussion Recent studies in which C. trachomatis has been isolated when cells in culture were modified by irradiation or treatment with antimetabolites to make them more permissive to growth of the organism have shown that cervical infection with C. trachomatis occurs in 5.0% to 12.7%.'. of pregnant women. It has been suggested that 40% to 50% of infants born to infected women may acquire C. trachomatis infection of the conjunctiva at birth.2 The incidence of this infection has been seriously underestimated in the past because in many cases the conjunctivitis is selflimiting and not severe, and because until recently the techniques for establishing the presence of the infection were complex and time-consuming. An association between respiratory tract infection or pneumonia and C. trachomatis has recently been recognized4-7 in infants born to infected women. Beem and Saxon5 reported that infants with chlamydial pneumonia typically manifest major symptoms at 6 weeks of age, but the paroxysms of closely spaced staccato coughs, which gradually increase in frequency and severity, may begin in the second or third week of life. There is little evidence of terminal inspiratory laryngospasm. The severe feeding difficulties and choking spells often associated with infantile pertussis are less frequent in chlamydial pneumonia; this suggests a point of clinical distinction. The infants also have tachypnea without evidence of peripheral airway obstruction. Auscultation of the chest usually discloses fine inspiratory rales; these are rare

in infantile pertussis. Despite these severe symptoms, which are often associated with pronounced roentgenographic changes, the infants remain afebrile and show little evidence of systemic reaction. Approximately 50% of infants with chlamydial pneumonia have a history of conjunctivitis that would be proven by culture to be chlamydial. Since conjunctivitis is frequently unapparent the incidence of infection with C. trachomatis is difficult to determine. Although the course of chlamydial pneumonia varies, preliminary indications are that eventual recovery without apparent late lung sequelae is the rule.5 Chest roentgenograms of persons with chlamydial pneumonia usually show both interstitial and patchy alveolar infiltrates diffusely distributed through the lungs, which appear hyperexpanded. Pleural reaction has rarely been reported.5 The total leukocyte count and differential analysis of the blood smear provide little help in diagnosis, although some patients may show moderate eosinophilia.7 IgG and 1gM concentrations are frequently elevated and, particularly with 1gM, may be considerably above the range of normal values for the age group.5'7 The frequency of lower respiratory tract infection or pneumonia in infants born to women with chlamydial infection of the cervix is not known. Prospective studies of culture-positive versus culture-negative pregnant women will be necessary to determine the frequency of conjunctival and respiratory tract infection in their children. In the last trimester of pregnancy the mothers of both our patients had experienced abnormal or excessive vaginal discharge. C. trachomatis was cultured from the cervical swab obtained from one mother (that in case 1). Both mothers were young and unmarried; a previous study1 has suggested a higher frequency of C. trachomatis infection in infants born to such women in lower socioeconomic groups. Both infants had maximal symptoms suggesting pneumonia at 4 weeks of age, although signs of respiratory tract infection (cough of gradually increasing severity and frequency) had begun during the second week of life. Infantile pertussis was initially considered in the differential

1202 CMA JOURNAL/NOVEMBER 18, 1978/VOL. 119

diagnosis, but not all the clinical features were typical of this condition and there was no family history suggesting contact with persons possibly having pertussis. Signs of systemic reaction were absent. One infant had mild bilateral conjunctivitis during the neonatal period that was still present at the time of admission to hospital at age 4 weeks, but cultures were not done and treatment of the conjunctivitis was not undertaken. Chest roentgenograms showed a combination of interstitial and alveolar pulmonary infiltration in hyperexpanded lungs. Although these findings are not specifically diagnostic of pulmonary chlamydial infection, the age of the infants, coupled with the historical and clinical circumstances, suggested that the pneumonia might be chlamydial. In addition, the serum 1gM concentration was markedly elevated in both infants; this elevation, though not specific for the diagnosis of chlamydial pneumonia, is frequently associated with the infection. On the basis of present clinical experience the optimal antimicrobial therapy and the effectiveness of treatment are still under review. It is obvious that larger clinical trials with various antimicrobials are necessary. The complete clinical spectrum of respiratory tract infection due to C. trachomatis in the very young is still unknown. In the two babies we have described, the severity of illness was sufficient, in our opinion, to require an attempt at specific antimicrobial therapy. Drugs currently available for the treatment of C. trachomatis infections include erythromycin, tetracycline and the sulfonamides.2 Systemic use of tetracyclines should be avoided in infants and children. However, both erythromycin and sulfisoxazole therapy have been reported to favourably influence the course of chlamydial pneumonia. Oral treatment with sulfisoxazole, 150 mg/kg of body weight daily, or erythromycin ethyl succinate, 50 mg/kg of body weight daily, for 2 to 3 weeks has been recommended.10 In cases of pneumonia in infants, specimens submitted for culture of C. trachornatis should include eye and throat swabs, nasopharyngeal aspirates and a cervical swab from the mother. Our limited experience sup-


ports the statement of Harrison and ary, for their cooperation; and Irene colleagues7 that a nasopharyngeal Stephens for technical assistance. This study was supported by grant aspirate is a better specimen for C. trachomatis culture than a throat 9730-213-007 from Health and Welfare swab, since the former provided 42 Canada. inclusions per coverslip and the latter References provided 20. 1. CHANDLER JW, ALEXANDER ER, PHEIFThere was no association with FER TA, et al: Ophthalmia neocytomegalovirus in either of our natorum associated with maternal cases. Cultures of urine, throat swabs chiamydial infections. Trans Am Acad and nasopharyngeal aspirates for cyOph:halmol Otolaryngol 83: 302, 1977 tomegalovirus maintained for 40 days 2. SCHACHTER J: Chlamydial infections (third of three parts). N Engi J Med were negative. 540, 1978 Chlamydiae, which are obligate 3. 298: GORDON FB, QUAN AL: Isolation of intracellular parasites, are true pathothe trachoma agent in cell culture. gens; they do not exist merely on Proc Soc Exp Bid Med 118: 354, 1965 cell surfaces or mucus membranes. Latent or subclinical infection may 4. SCHACHTER J, LUM L, GOODING CA, et al: Pneumonitis following inclusion indicate low levels of reproduction as blennorrhea. J Pediatr 87: 779, 1975 a result of partial suppression by host S. BEEM MO, SAXON EM: Respiratorydefence mechanisms. tract colonization and a distinctive pneumonia syndrome in infants inThe high rates of isolation of and fected with Chiamydia trachomatis. high titres of antibody to C. trachoN Engi J Med 296: 306, 1977 matis reported for infants with this 6. FROMMELL GT, BRUHN FW, type of pneumonia suggest that SCHWARTZMAN JD: Isolation of chlamydiae are etiologically assoChiamydia trachomatis from infant ciated with this disease.44 The clinlung tissue. Ibid, p 1150 ical presentation of the two infants 7. HARRIsoN HR, ENGLISH MG, LEE CK, et al: Chiamydia trachomatis infant we have described in combination pneumonitis: comparison with matched with the isolation of C. trachomatis controls and other infant pneumonitis. from specimens from both and the N Engi J Med 298: 702, 1978 serologic findings in case 2 lend 8. ALLANSMITH M, MCCLELLAN BH, further support to this theory. BUTTERWORTH M, et al: The development of immunoglobulin levels in We thank Deborah Semine, Harvard man. J Pediatr 72: 276, 1968 School of Public Health, Boston, for 9. MCCOMB DE, PUZNIAK CI: Micro performing the microimmunofluorescell culture method for isolation of cence tests; Dr. E.B. Grantmyre, deChiamydia trachomatis. Appi Micropartment of radiology, Izaak Walton biol 28: 727, 1974 Killam Hospital for Children; Dr. J.F. 10. HAMMERSCHLAG MR: Chiamydial Filbee, N.S. Kulkarni and staff, departpneumonia in infants. N Engi J Med 298: 1083, 1978 ment of radiotherapy, Halifax Infirm-


Action: Ibuprofen has demonstrated anti-inflammatory, analgesic, and antipyretic activity in special animal studies designed to specifically demonstrate these effects. Ibuprofen has no demonstrable glucocorticoid effect. Ibuprofen has been found to be less likely to cause gastro-intestinal bleeding in doses usually used than is acetylsalicylic acid. Clinical trials in man have shown the clinical activity of a dose of 1200-1800 mg of ibuprofen daily to be similar to that of 3600 mg of acetylsalicylic acid daily. Indications and Clinical Uses: Ibuprofen is indicated for the treatment of osteoarthritis and rheumatoid arthritis. Contraindications: Ibuprofen should not be used during pregnancy or in paediatric patients because its safety under these conditions has not been established. Ibuprofen should not be used in patients with a history of acetylsalicylic acidinduced bronchospasm. Precautions: Ibuprofen should be used with caution in patients with a history of gastrointestinal ulceration. Ibuprofen has been reported to be associated with toxic amblyopia. Therefore, precautions should be taken to ensure that patients on ibuprofen therapy report to their physicians for full ophthalmological examination if they experience any visual difficulty. Medication should be discontinued if there is any evidence of toxic amblyopia. Adverse Reactions: The following adverse reactions have been noted in patients treated .,ith buprof en. Gasfroinfesfinal: Nausea, vomiting, diarrhoea, constipation, dyspepsia, epigastric pain and guaiac positive stools have been noted. A few cases of gastric or duodenal ulceration, including some complicated by bleeding or perforation have occurred. Cenfra/ Nervous Sysfem: Dizziness, light-headedness, headache, anxiety, mental confusion and depression were noted in some patients treated with ibuprofen. Ophthalmological: Blurred vision was noted in some patients and rarely a sensation of moving lights was observed following administration of ibuprofen. In addition there are three published cases of toxic amblyopia assoc;ated with the use of ibuprofen. Although a definite cause and effect relationship was not established, the attending physicians considered them to be drugrelated. The condition was characterised by reduced visual acuity and difficulty in colour discrimination. Defects (usually centrocaecal) were observed on visual field examination. Symptoms were reversible on discontinuation of treatment. Skin: Maculopapular rashes and generalised pruritus have been reported with ibuprofen therapy. Occasional cases of oedema have also been reported. Laborafory Tesfs: Sporadic abnormalities of liver function tests have occurred in patients on ibuprofen therapy (SGOT, serum bilirubin and alkaline phosphatase) but no definite trend was seen indicating toxicity. Similar abnormalities of white blood count and blood urea determinations were noted. A slight fall in haemoglobin and haematocrit has been noted in some patients.

Symptoms and Treatment ot Overdosage: One

Retrospect: Foreword 1927 The Editorial Board in the past, and more strongly than ever in the coming year, desires that the Journal should represent the professional spirit of service, rather than that it should be regarded as in any way a financial venture, it is the desire of the Board that the Journal should be carried on in the spirit which should inspire all medical work; the desire to do things because they are worth while in themselves. To contribute to a medical journal is a terror to some, a labour to most, a pleasure to few, and of direct personal gain to none. The work of

editing the Journal is difficult because it can offer little financial return to its contributors, and must ask the majority of them to assist as a duty to their profession, to their university and to their country. Medical writing, however, in addition to its being a service is a powerful aid in self-education; self-education in that rarely thought of sense in which the object is attained by one's own mental efforts. Medical writing demands clear thinking and exact expression, and the use of words which will convey the precise meaning desired. It is seldom that clear expression can be secured without effort Can Med Assoc J 17: 2, 1929

case of overdosage has been reported. A oneyear-old child ingested 1200 mg ibuprofen and suffered no ill effects other than being drowsy the next day. Blood levels of ibuprofen reached 711 mcg/ml, which is considerably above the 90 mcg/ml previously recorded as the highest level seen in adults after a single oral dose of 800 mg. The SGPT level, nine days post-ingestion, was 72. No specific antidote is known. Standard measures to stop further absorption and maintain urine output should be implemented at once. The drug is excreted rapidly and excretion is almost complete in six hours. Dosage and Administration: To obtain rapid response at the start of treatment, particolarly when transferring from other anti-inflammatory therapy, Motrin should be given at a dose of 1200 mg per day in four divided doses. Depending on the therapeutic response, the dose may be adjusted downward or upward keeping the tour-times-a-day dosage schedule. The daily dose should not exceed 2400 mg. Maintenance therspy, once maximum response is obtained, will range from 800 to 1200 mg per day. Due to lack of clinical experience, ibuprofen is not indicated for use in children under 12 years of age. Supplied: 200 mg yellow coated tablets, 300 mg white coated tablets and 400 mg orange coated tablets in bottles of 100 and 1000. Product monograph available on request.




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Chlamydia trachomatis and pneumonia in infants: report of two cases.

Chiamydia trachomatis and pneumonia in infants: report of two cases J.A. EMBIL, MD, PH D, FRCP[C]; R.L. OZERE, MD, FRCP[C]; S.W. MACDONALD, B SC, M Sc...
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