Randomized trial of sulfamethoxazole + trimethoprim versus procaine penicillin for the outpatient treatment of childhood pneumonia in Zimbabwe.

Randomized trial of sulfamethoxazole + trimethoprim versus procaine penicillin for the outpatient treatment of childhood pneumonia in Zimbabwe D.J. Keeley,1 F.K. Nkrumah,2 & C. Kapuyanyika3 Reported are the results of a randomized trial of sulfamethoxazole + trimethoprim versus procaine penicillin for the outpatient treatment of pneumonia in 614 children aged 3 months to 12 years at primary health care clinics in Chitungwiza, a large town near Harare, Zimbabwe. Diagnosis and treatment were carried out by nurses, without medical supervision. The presence of lower respiratory tract infection that required antibiotics was diagnosed on the basis of a recent history of a cough and the presence of a respiratory rate of greater than 50 per minute. Patients were followed up by a research nurse with minimal drop-out losses. Referred children were examined and assessed by a doctor at the Chitungwiza General Hospital. Of the study children, 65 (11%) were referred to hospital, but only 8 (1.3%) had pneumonia that required a change in the treatment (5 in the sulfamethoxazole + trimethoprim group and 3 in the procaine penicillin group). There were no significant differences in outcome between the two treatment groups. One child, who had evidence of infection with human immunodeficiency virus (HIV), died. Sulfamethoxazole+ trimethoprim and procaine penicillin were highly and equally effective for the outpatient treatment of children who had been clinically diagnosed to have pneumonia by primary health care workers. Introduction Acute respiratory infections (ARI) are estimated to be responsible for over a third of all deaths of children under 5 years of age in developing countries (1). As a result, a worldwide campaign has been initiated by WHO to reduce child morbidity and mortality from such infections (2). In Zimbabwe, a national ART control programme was initiated in April 1987; the training materials that were distributed outline the criteria for case recognition and management by primary health care workers and closely follow WHO recommendations. Both the WHO and the Zimbabwe ARI programmes recommend sulfameth- oxazole + trimethoprim (co-trimoxazole) or procaine penicillin as alternative therapies for children with ARI who require antibiotic treatment as outpatients.8 ' Consultant Paediatrician, Chitungwiza General Hospital, Zim- babwe. Requests for reprints should be addressed to this author at 4 Witley Road, London N19 5SQ, England. 2 Professor of Paediatrics and Child Health, Godfrey Huggins School of Medicine, Harare, Zimbabwe. 3 Research Nurse, Chitungwiza General Hospital, Zimbabwe. Case management of acute respiratory infections in developing countries. Report of a Working Group Meeting, Geneva, 3-6 April 1964. Unpublished document WHO/RSD/85.15 Rev. 2. Reprint No. S061 We studied the effectiveness of this management policy in two busy urban municipal primary health care clinics in Zimbabwe, and in a randomized trial compared the outcome oftreatment using sulfamethox- azole + trimethoprim with that using procaine peni- cillin. Patients and methods The study was carried out in Chitungwiza (estimated population, 350 000), a town situated 15 km south of Harare, the capital. Children under 5 years of age made up 19% of the population at the most recent census in 1982. The town consists largely of small brick or breeze-block houses, most of which have electricity, water, and mains sanitation, although there is a great deal of overcrowding. The population is entirely African. Some employment is provided by local industry but the town functions mainly as a high density dormitory suburb for people who work or are seeking work in Harare. Chitungwiza is served by four municipal primary health care clinics and one 250-bed general hospital that opened in 1984. The study was carried out at the two busiest clinics (Seke North and Zen- geza). During the period of the study neither clinic had a doctor and diagnosis and treatment were carried out entirely by nursing staff. Bulletin of the World Health Organization, 68 (2): 185-192 (1990) ( World Health Organization 1990 165 D.J. Keeley et al. The study was conducted between mid-Novem- ber 1987 and mid-March 1988. Before starting, staff at both clinics were carefully instructed in the case management guidelines for children with ARI.b Chil- dren aged 3 months to 12 years who presented at the clinics and were diagnosed to have pneumonia that could be treated on an outpatient basis were entered into the study. Following ARI programme guidelines, the diagnosis was based primarily on a recent history of a cough and a respiratory rate of over 50 per minute. In the Zimbabwe programme, immediate referral to hospital is recommended if, in addition, a child has chest indrawing without wheeze, is unable to drink, is malnourished, or aged under 3 months. Children who required immediate referral to hospital were excluded from the study. Also, children not resident in Chitungwiza or whose mothers indicated that they were unlikely to remain in the town for the following 2 weeks were excluded in order to minimize follow-up losses. All children entered into the study were seen at the two neighbourhood primary health care clinics; the likelihood that any of them might have received prior treatment with antibiotics from another source was very remote. After the decision to treat with antibiotics had been made, allocation to the treatment modality was made by drawing the next in a numbered sequence of sealed envelopes. The enclosed proforma specified which drug to use according to a computer-generated randomization sequence. The patient's name, address, age, weight, and sex were recorded as well as the axillary temperature and the presence or absence of a respiratory rate of greater than 50 per minute and chest indrawing. The mothers of children entered into the study were encouraged to return to the clinic daily for 5 days, irrespective of whether sulfamethoxazole + trimethoprim or procaine penicillin had been pre- scribed, and then to come back 1 week after comple- tion of treatment (12 days after entry) for a follow-up visit. To improve compliance, it was explained that no further charges would be made for the duration of treatment and that the child would be seen each day with the minimum of waiting. At each visit a record of attendance, temperature, respiratory rate and general condition was made on the child's proforma. Clinic staff were instructed to refer to hospital any child who did not show a satisfactory response to treatment; in particular, any child who developed chest indrawing, inability to drink, or for whom a respiratory rate of greater than 50 per minute persis- ted for more than 48 hours after starting treatment. An approximate check on compliance with sulfa- bSee footnote a, p. 185. methoxazole + trimethoprim was made by examining drug containers. The dosages used are shown in Table 1. Each clinic was visited daily 5 days a week by the research nurse, who checked on the progress of the study and on patient compliance. Any child who failed to present for treatment with procaine peni- cillin was visited at home within 2 days to encourage continued attendance. Sulfamethoxazole + trimetho- prim defaulters were visited at home on or about the fifth day to check on their response and compliance with the treatment. Children who failed to attend for a final follow-up were visited on or soon after the date of the missed appointment. At the nurse's home visits, an account from a mother that her child was well together with a normal respiratory rate were taken as evidence of satisfactory response to the treatment. Temperatures were not measured at these visits. Any child who was judged by the clinic staff not to be making a satisfactory response to treatment- according to the above-mentioned criteria-was referred to hospital. At the hospital, the doctor who assessed the child recorded basic clinical details, chest X-ray findings, together with details of the case management and progress made. The treatment for pneumonia was recorded as a failure if the child presented to the hospital between day 2 and day 14 from the start of therapy with a cough, respiratory rate of over 50 per minute, and radiological signs of pneumonia. Bronchiolitis was diagnosed for infants with a first episode of wheezing, and asthma for children with wheezing and a history of similar episodes. To ensure that treatment failures were not missed, an alphabetical index of the patients who had been entered in the study was cross-checked against Table 1: Dosages of procalne penicillin and sulfamethox- azole+trlmethoprim used In the study Age group Dosage", Procaine penicillinb < 12 months 0.5 1-3 years 1.0 3-5 years 1.5 5-12 years 2.0 Sulfamethoxazole + trimethoprimc <6 months 2.5 6 months-2 years 5.0 2-5 years 7.5 5-12 years 10 Dosages shown for procaine penicillin are ml (once daily) and for sulfamethoxazole + trimethoprim, ml (twice daily). b 1 ml contained 300 mg procaine penicillin. c 5 ml contained 240 mg sulfamethoxazole+trimethoprim. 186 WHO Bulletin OMS. Vol 68 1990. Treatment of childhood pneumonia: sulfamethoxazole+ trimethoprim versus procalne penicillin all admissions during the study period to the paediatric ward at Chitungwiza General Hospital, all admissions to the paediatric wards at Harare Central Hospital of children who had Chitungwiza addresses, and all deaths of children recorded at the mortuaries of both hospitals. Differences between the treatment groups were tested for significance by the x2 test (for proportions) and Student's t-test (for means). Results A total of 617 children were entered in the study. Three were later excluded from the analysis-two because of first-day referral after entry (one in the sulfamethoxazole + trimethoprim group, diagnosed to have asthma, and one in the procaine penicillin group, diagnosed to have pneumonia)-and one aged under 3 months. Of the remaining 614 children, 303 were treated with sulfamethoxazole + trimethoprim and 311 with procaine penicillin. All but one of the children entered in the study were accounted for at follow-up on or after the twelfth day from the start of treatment. The clinic records were checked regularly by the research nurse to identify children with a diagnosis of pneumonia or chest infection who had not been entered in the study. During the study period the records indicated that 120 children were referred directly to hospital, 21 were not entered because they resided outside or were imminently about to depart from Chitungwiza, while only four apparently eligible children had not been entered. Four children were entered into the study on two separate occasions. One, a 10-year old, was not referred to hospital either time. The other three were referred and were found to have wheezing with normal chest X-rays. All were re-entered over 6 weeks after their date of first entry. Of the 303 children in the sulfamethoxazole+ trimethoprim group, 237 (78%) attended the clinic daily for the full 5 days; 43 of these children required a home visit on day 5 and 73 on day 12. No failure to comply with taking the medication was detected, but much reliance in this regard had to be placed on the mothers' accounts. Of the 311 children in the procaine penicillin group, 299 (96%) received the 5-day treatment. Of the latter children, 16 defaulted but returned to complete their course of five injections after a home visit, with a period of treatment interruption of up to 3 days. There were no treatment failures among these 16 children. Four children defaulted, however, after 1-3 days and received no further treatment-all were well on follow-up. The eight remaining patients were referred to hospital before treatment was completed. Five patients required a home visit on day 5 and 74 on day 12. There were no significant differences between the children in the two treatment groups with respect to their age and sex distributions, nutritional status, or clinical condition on admission to the study (Table 2). Fig. 1 shows the age distribution of the two groups and illustrates the marked preponderance of children under 2 years of age in both study groups. Table 3 shows data on the treatment outcome and follow-up for the two groups. There was no significant difference between the groups in terms of the number of patients referred to hospital or the number classified as pneumonia treatment failures. Four children were still unwell at the last contact: three in the sulfamethoxazole+trimethoprim group (two with asthma, who had normal chest X-rays, and one who failed to thrive) and one in the procaine penicillin group (diagnosed in the outpatient depart- ment to have bronchiolitis with a normal chest X-ray, but was not seen for follow-up). In 8% of both Table 2: Comparison of various characteristics of children In the two treatment groups Sulfamethoxazole + trimethoprim Procaine penicillin (n=303) (n=311) Significance Sex ratio (male/female) 1.02 1.10 NS" Mean % of 50th centile weight for age 98.3 (12.8)b 95.3 (13.1) NS n=287 n=291 % aged 3-12 months 49 43 NS % aged 1-5 years 47 51 NS % aged 5-12 years 4 6 NS Mean number of days' coughing at entry 3.4 (2.0); range 1-21 3.6 (2.4); range 1-28 NS % afebrile 22 21 NS % febrile (37-38°C) 27 23 NS % febrile (>38°C) 51 56 NS % with recession at entry 2 3 NS NS=not significant. Figures in parentheses are standard deviations. WHO Bulletin OMS. Vol 68 1990. 187 Fig. trel z grc rep wit nui D.J. Keeley et al. . 1. Plot of the age distribution of children In the two hospital or visited at home at least 7 days after itment groups. referral or discharge from hospital, with the single 160. exception noted above. -* Sulfamethoxazole + trlmethoprim Table 4 shows the diagnoses made for the 65 140 Procaine w.iclinn children who were referred to hospital during the 120. course of the study. Of the 35 children who received 100. sulfamethoxazole+ trimethoprim, 18 were seen in the first 5 days after entry into the study. The corres- 80 ponding proportion for the procaine penicillin group 60 was 8 out of 30. All referrals made from the start of 40. '\the study until 2 weeks after the last patient wasrecruited are shown. Of the 44 referrals that were 20 diagnosed to have cough caused by a condition other - than pneumonia, 28 had chest radiographs that were 0 2 4 6 8 10 12 either normal (25) or exhibited only hyperinflation Ag. (yearn) (3). Of the two late referrals with a cough and dyspnoea, one was treated at referral with procaine)ups the presumption of cure was based on a penicillin but insufficient information was recorded ort by relatives or, in a few cases, neighbours, to allow a diagnosis. The other, originally treated thout the child having been seen by the research with sulfamethoxazole+trimethoprim, had received rse. All referred children were reviewed at the procaine penicillin for 5 days prior to referral, Table 3: Data on the outcome and follow-up of children In the two treatment groups Sulfamethoxazole+ trimethoprim Procaine penicillin (n= 303) (n=311) Significance No. referred to hospital 35 (12)' 30 (10) NSb No. admitted to hospital 12 (4.0) 5 (1.6) P=0.04 (one-tailed) No. diagnosed to have pneumonia with treatment failure 5 (1.6) 3 (0.96) NS No. who died 1c 0 No. who completed initial treatment without referral and were well at final follow-up 268 (88) 281 (90) NS No. of children seen well at final follow-up 275 (92) 285 (92) NS No. of children reported well at final follow-up 24 (8) 25 (8) NS No. still unwell at last contact 3 1 NS ' Figures in parentheses are percentages. b NS=not significant. Seropositive for human immunodeficiency virus (HIV). Table- 4: Distribution of the diagnoses for children referred to hospital during the study Sulfamethoxazole + trimethoprim Procaine penicillin (n= 303) (n= 311) Significance Pneumonia with treatment failure 5 3 NS' Pneumonia-no change of treatment 3 2 NS Bronchiolitis 5 7 Asthma 9 5 Chronic cough 2 5 Upper respiratory tract infection 6 5 Gastroenteritis 2 1 Urticaria 1 0 Late referral with cough and dyspnoea 2 0 Failed to attend hospital 0 2 Total 35 30 NS a NS=not significant. 188 WHO Bulletin OMS. Vol 68 1990. Treatment of childhood pneumonia: sulfamethoxazole+trimethoprim versus procalne penicillin had a chest X-ray that indicated consolidation, and patients who were classified as pneumonia treatment was successfully treated as an outpatient with sulfa- failures. methoxazole + trimethoprim. Clinical details of the eight patients for whom a Table 5 provides a summary of the diagnoses diagnosis of failed treatment for pneumonia was made for referred patients who were admitted to made are shown in Table 6. Four of the eight (three hospital, including those for seven of the eight who received sulfamethoxazole+trimethoprim and Table 5: Summary of the reasons why referred children were admitted to hospital Sulfamethoxazole + trimethoprim Procaine penicillin (n= 303) (n=311) Pneumonia/failed treatment 4 3 Pneumonia/treatment continued 2 1 Bronchiolitis 2 0 Asthma 3 0 Urticaria 1 0 Upper respiratory tract infection 0 1 (croup) Total 12 5 Table 6: Summary of the clinical details for the eight children who were classified as pneumonia treatment failures % of the 50th Treatment group, centile weight Day of sex"/age (months) for age referral Clinical details Sulfamethoxazole + trimethoprim: F/4 102 2 Temperature, 40 °C, RRb > 50, recessing. Liver and spleen enlarged. Chest X-ray: lobar pneumonia with effusion. Treated with intravenous cloxacillin and chloramphenicol. Little improvement. Taken home against advice. Died the same day. HIV positivec M/27 105 2 Temperature, 38 °C, RR > 50, recessing. Chest X-ray: bilateral basalshadowing. Treated with benzyl penicillin. Home on procaine penicillin. Well on follow-up F/8 88 3 Temperature, 39 °C, RR > 50, recessing. Chest X-ray: right lower zone shadowing. Treated with benzyl penicillin. Home after 5 days. Well on follow-up F/14 98 2 Temperature, 37.5 °C, RR >50, recessing. Chest X-ray: right lower zone shadowing. Referred on second day because of vomiting. Treated with benzyl penicillin. Home after 5 days. Well on follow-up M/9 85 10 Temperature, 37.2 °C, RR not recorded. Alar flare and right-sided crepitations. Chest X-ray: right lower zone shadowing. Treated with procaine penicillin as an outpatient. Well on follow-up F/8 85 12 Temperature, 37 °C, RR > 50, no recession. Chest X-ray: right midzone shadowing. Admitted and treated with sulfamethoxazole+trimethoprim. Home after 2 days. Well on follow-up Procaine penicillin: F/9 102 2 Temperature, 39°C, RR > 50, recessing. Chest X-ray: right midzone shadowing. Impetigo. Treated with benzyl penicillin and cloxacillin for 5 days. Well on follow-up M/8 104 3 Temperature, 39 °C, RR > 50, recessing. Chest X-ray: bilateral patchy midzone shadowing. Treated with benzyl penicillin for 3 days, then home on procaine penicillin. Well on follow-up 'F=female; M=male. b RR=respiration rate. C HIV=human immunodeficiency virus. WHO Bulletin OMS. Vol 68 1990. 189 D.J. Keeley et al. one, procaine penicillin) were admitted on the second day of treatment. Altogether, 65 of the children entered in the study were referred to hospital. Only eight were diagnosed to have pneumonia that failed to respond to initial treatment (five in the sulfamethoxa- zole + trimethoprim group and three in the procaine penicillin) and all but one of these were admitted to hospital; the other was treated as an outpatient. Only one child in the study died, a 4-month-old in the sulfamethoxazole + trimethoprim group who had anaemia and hepatosplenomegaly in addition to clinical and radiological signs of pneumonia. An enzyme-linked immunosorbent assay (ELISA) for antibodies to human immunodeficiency virus (HIV) was strongly positive for this child and her mother. The only adverse reaction detected during the study was for a child who developed urticaria on the fifth day of treatment with sulfamethoxazole + trimethoprim. This child was admitted and treated with antihistamines and the rash settled uneventfully. Vomiting proved to be a problem only for one child who received sulfamethoxazole + trimethoprim: this child was referred to hospital on the second day and was admitted as a treatment failure and given benzyl penicillin (see Table 6). Discussion The rationale for the protocols recommended by WHO for the management of ARI in children in developing countries has been discussed in detail elsewhere.c Studies in the USA and Papua New Guinea have shown tachypnoea to be the best clin- ical predictor of pneumonia in children (3,4). A respiratory rate greater than 50 per minute is there- fore advocated as the indication for administering antibiotics to a child with ARI. Lung aspirate studies of children with pneumonia in a number of develop- ing countries have consistently indicated that Strep- tococcus pneumoniae and Haemophilus influenzae are the most common pathogens (5-7). Daily intramuscular injection of procaine peni- cillin achieves blood levels of the drug that are effective against S. pneumoniae and most strains of H. influenzae (8). Both these microorganisms are also highly sensitive to sulfamethoxazole + trimethoprim, which is in addition active against Staphylococcus aureus, Chiamydia spp., and Pneumocystis carinii-all of which may be important causes of pneumonia in developing countries (7, 9). c Respiratory infections in children: management at small hos- pitals. Background notes and a manual for doctors. Unpublished document WHO/RSD/86.26. Each drug poses problems of compliance. Intra- muscular injections are reliable, but long journey distances to clinics and waiting times, and the cost of repeat attendances may prove important disincen- tives to completion of treatment. Treatment with sulfamethoxazole + trimethoprim does not require repeated attendance at the clinic but careful instruc- tions have to be given, and reliance has to be placed on the parent to administer the drug correctly. Based on data obtained from the Government Central Stores in Zimbabwe, the current cost of a 5-day treatment of a 2-year-old child with sulfameth- oxazole + trimethoprim syrup (50 ml) is US$ 0.36; that of procaine penicillin (5 ml) is US$ 0.16, while five syringes and needles cost a further US$ 0.16. Treatment with procaine penicillin is more time- consuming for nursing staff. The study compared the reliability of these two therapies for childhood pneumonia that had been diagnosed and judged suitable for outpatient treat- ment by nurses in primary health care clinics. Excluded from the study, therefore, were children who were seriously ill at presentation (as evidenced, for example, by chest indrawing or inability to drink), those suffering from obvious malnutrition, and infants aged under 3 months. The relatively good nutritional status of the study children (mean, 97% of the 50th centile for weight for age; 6.5% below 80% of the 50th centile) is partly explained by this design aspect and cannot be taken to be indicative of the overall nutritional status of the community in which the study was carried out. The high reliability of outpatient treatment for pneumonia that we found might not be reproduced in situations, where, for example, more malnourished children have to be treated as outpatients. The only difference of note in the outcome of the two treatment groups was the higher rate of admissions (4.0% versus 1.6%) for the sulfamethoxazole + trimethoprim group, which mainly arose because there were two admissions of children with bronchiolitis and three with asthma in this group. All five of these children had chest radiographs that showed no evidence of pneumonia. The study was conducted over a 4-month period. It is possible that there may be a seasonal variation in the prevalence of different respiratory pathogens, which might in turn have affected our results. We do not have any reliable information as to the existence or not of such a seasonal variation in Zimbabwe. No formal check was made on the accuracy of the nurses' clinical findings or on the reliability of their diagnoses. Some of the children entered in the study may have been suffering from other conditions such as bronchiolitis and asthma-although meeting the prescribed criteria for acute lower respiratory 190 WHO Bulletin OMS. Vol 68 1990. Treatment of childhood pneumonia: sulfamethoxazole+trimethoprim versus procalne penicillin infection that required treatment with antibiotics. We do not know the proportion of children who were entered in the study with nonbacterial infections whose course would have been unaffected by any antibiotic given. However, if only 25% of the study children actually had bacterial pneumonia this would still correspond to a treatment failure rate of only 5%. Despite these reservations, therefore, our results suggest that both sulfamethoxazole + trimethoprim and procaine penicillin are highly reliable treatments for childhood pneumonia, with no significant dif- ference in their reliability. Furthermore, the study showed that a high degree of compliance with either treatment can be achieved if attention is given to minimizing the cost and time disincentives. A study in the Gambia that compared the use of sulfamethoxazole+trimethoprim with that of a single injection of fortified procaine penicillin followed by oral ampicillin in the (mainly outpatient) treatment of children with pneumonia also reported that the two regimens gave a high and equal success rate (10). Sulfamethoxazole+ trimethoprim can be given to patients who cannot easily be brought to clinics for daily injections. In circumstances where the sup- ply of disposable needles or of adequate sterilization equipment is problematic it may, however, be appropriate to rely wholly on sulfamethoxazole + trimethoprim for the primary treatment of pneumonia. This may be of particular relevance in areas of high HIV seropositivity. Our findings strongly support the guidelines for the outpatient case management of pneumonia in children advocated by the WHO Control of Acute Respiratory Infections unit. Furthermore, the results suggest that paramedical workers can reliably recog- nize and effectively manage cases of childhood pneumonia at primary health care clinics, par- ticularly if they are backed up by efficient and depen- dable referral facilities. The major challenge in case management of ARI at the primary health care level in our context may be to reduce the undoubted over- use of antibiotics without producing a concomitant rise in the current low rate of failure to treat pneumonia successfully. In view of the apparent reliability of the recom- mended treatment, much emphasis needs to be placed in ARI control programmes on educational and health care policy interventions designed to ensure that children, especially infants, are brought early for treatment. Studies should be carried out to determine the reasons for delays in seeking treatment in order to design such interventions effectively. Improved ARI case management must be com- plemented by optimal access to health care facilities and by the provision of health education at the community level if it is to achieve its maximum impact. This implies that ARI control programmes, like other primary health care interventions, should be integrated into a comprehensive primary health care system. R6sum6 Zimbabwe: Essal randomis6 de I'assoclatlon sulfam6thoxazole + trlm6thoprlme et de la p6niciline procaine pour le traltement des pneumopathles Infantiles Les resultats d'un essai randomis6 portant sur le traitement ambulatoire, soit par I'association sul- famethoxazole+trimethoprime, soit par la peni- cilline procaine, de 614 enfants ag6s de 3 mois a 12 ans et atteints de pneumopathie, sont rapportes ici. L'etude a ete effectuee dans deux dispensaires de soins de sant6 primaires de Chitungwiza, une grande ville situee pres d'Harare, au Zimbabwe, de novembre 1987 a mars 1988. Le diagnostic a et pose par le personnel infirmer, qui a egalement institue le traitement sans supervision medicale directe. Avant le debut de cette etude, le personnel de ces dispensaires avait recu des directives precises concernant la prise en charge des enfants atteints d'infections respiratoires aigues (IRA). Le diagnostic d'infection des voies respiratoires inferieures necessitant un traitement par les anti- biotiques reposait sur des antecedents recents de toux et sur 1'existence d'une fr6quence respiratoire superieure a 50 par minute. Les enfants envoyes directement a i'hopital n'ont pas fait partie de cette etude. Les sujets ont M6 vus quotidiennement pendant les 5 jours du traitement, puis reexamines une semaine apres la fin du traitement. Ceux qui ne se sont pas present6s a la derni6re visite ont et6 examines a leur domicile par une infirmiere, et peu d'entre eux ont ete perdus de vue. Les enfants envoyes a i'h6pital en cours de traitement ont et examines par un medecin' de i'h6pital general de Chitungwiza, qui a etabli pour eux un bilan. On a considere qu'il y avait echec therapeutique si 1'enfant entrait a l'h6pital entre le deuxieme et le quatorzieme jour apr6s le debut du traitement avec de la toux, une frequence respira- toire superieure a 50 par minute et des signes radiologiques de pneumopathie. Sur les 614 en- fants inclus dans l'etude, 65 (11%) ont ete par la suite envoy's i I'h6pital, mais 8 d'entre eux seule- ment (1, 3%) presentaient une pneumopathie neces- sitant une modification du traitement (5 dans le groupe sulfamethoxazole+trimethoprime et 3 dans le groupe penicilline procaine). On n'a observe aucune difference significative concernant WHO Bulletin OMS. Vol 68 19901 191 D.J. Keeley et al. les r6sultats des deux traitements. Un enfant est decede, avec des signes d'infection par le virus de l'immunodeficience humaine (VIH). Les deux m6di- caments ont et6 aussi efficaces l'un que l'autre pour le traitement ambulatoire des enfants chez qui les agents de soins de sante primaires avaient diagnostique une pneumopathie. Le traitement par le sulfamethoxazole+trimethoprime peut etre retenu en toute confiance; celui a la penicilline procaine semble aussi efficace, mais prend plus de temps aux agents de soins de sante et neces- site de disposer de reserves de materiel sterile. Dans certains cas, il peut donc etre plus approprie d'avoir uniquement recours au sulfametho- xazole+trimethoprime pour le traitement de fond des pneumopathies de l'enfant. Les r6sultats de cette etude confirment net- tement le bien-fonde des directives relatives a la prise en charge en ambulatoire des pneumo- pathies de l'enfant preconisees par le service OMS de Lutte contre les Infections respiratoires aigues. Etant donne la fiabilite apparente du traitement recommande, il faudra mettre l'accent, dans les programmes de lutte contre les IRA, sur les interventions en matiere de politique de soins de sante ayant pour but de faire en sorte que les enfants, et en particulier les nourrissons, soient amenes au dispensaire le plus tot possible pour 4tre traites. Si l'on veut qu'elle ait un impact maximal, I'amelioration de la prise en charge des cas d'infection respiratoire aigue doit donc s'accompagner d'un acces plus aise aux installa- tions de soins de sante et d'efforts d'education sanitaire au niveau communautaire. Acknowledgements This study was supported by the Research Fund of the University Department of Paediatrics and Child Health, Godfrey Huggins School of Medicine, University of Zim- babwe, Harare, Zimbabwe. We thank Dr M. Simoye, Medical Officer of Health, Chitungwiza, for permission to conduct the study, and Matron Choguya and her staff for their enthusiastic cooperation. Finally, we are grateful to Dr M. Bassett for advice on the statistical analysis of the data, and the Secretary for Health for permission to publish the findings. References 1. Plo, A. et al. The magnitude of the problem of acute respiratory infections. In: Douglas R.M. & Kirby- Eaton, E., ed. Acute Respiratory Infections in Child- hood: Proceedings of the International Workshop, Sydney, August 1984. Adelaide, University of Adelaide, 1985, pp. 3-16. 2. A programme for controlling acute respiratory infec- tions in children: Memorandum from a WHO meeting. Bulletin of the World Health Organization, 62: 47-58 (1984). 3. Leventhal, J.M. Clinical predictors of pneumonia as a guide to ordering chest roentgenograms. Clinical pediatrics, 21: 730-734 (1982). 4. Shann, F. et al. Acute lower respiratory tract infec- tions in children: possible criteria for selection of patients for antibiotic therapy and hospital admission. Bulletin of the World Health Organization, 62: 749-753 (1984). 5. Escobar, J. et al. Etiology of respiratory tract infec- tion in children in Cali, Colombia. Pediatrics, 57:123- 130 (1976). 6. Silverman, M. et al. Diagnosis of acute bacterial pneumonia in Nigerian children: value of needle aspiration of lung and of countercurrent immunoelec- trophoresis. Archives of disease in childhood, 52: 925-931 (1977). 7. Shann, F. et al. The aetiology of pneumonia in chil- dren in Goroka Hospital, Papua New Guinea. Lancet 2: 537-541 (1984). 8. Shann, F. et al. Serum levels of penicillin in PNG children. In: Proceedings of the 18th Annual Sym- posium of the Medical Society of Papua New Guinea. Port Moresby, 1982. 9. Shann, F. et al. Pneumonia associated with pneumocystis, respiratory syncytial virus, chlamydia, mycoplasma, and cytomegalovirus in children in Papua New Guinea. British medical journal, 292: 314-317 (1986). 10. Campbell, H. et al. Trial of co-trimoxazole versus procaine penicillin with ampicillin in treatment of community-acquired pneumonia in young Gambian children. Lancet, 2: 1182-1184 (1988). 192 WHO Bulletin OMS. Vol 68 1990.