Annals of Tropical Paediatrics International Child Health
ISSN: 0272-4936 (Print) 1465-3281 (Online) Journal homepage: http://www.tandfonline.com/loi/ypch19
Effect of pneumococcal vaccine on morbidity from acute lower respiratory tract infections in Papua New Guinean children D. Lehmann, T. F. de C. Marshall, I. D. Riley & M. P. Alpers To cite this article: D. Lehmann, T. F. de C. Marshall, I. D. Riley & M. P. Alpers (1991) Effect of pneumococcal vaccine on morbidity from acute lower respiratory tract infections in Papua New Guinean children, Annals of Tropical Paediatrics, 11:3, 247-257, DOI: 10.1080/02724936.1991.11747510 To link to this article: http://dx.doi.org/10.1080/02724936.1991.11747510
Published online: 13 Jul 2016.
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Citing articles: 16 View citing articles
Full Terms & Conditions of access and use can be found at http://www.tandfonline.com/action/journalInformation?journalCode=ypch19 Download by: [Australian Catholic University]
Date: 24 August 2017, At: 23:36
Annals of Tropical Paediatrics (1991) 11, 247-257
Effect of pneumococcal vaccine on morbidity from acute lower respiratory tract infections in Papua New Guinean children
Downloaded by [Australian Catholic University] at 23:36 24 August 2017
D. LEHMANN, T. F. de C. MARSHALL*, I. D. RILEY** & M. P. ALPERS Papua New Guinea Institute of Medical Research, Goroka, Papua New Guinea, *Department of Epidemiology & Population Sciences, London School of Hygiene and Tropical Medicine, and** Tropical Health Program, Faculty of Medicine, University of Queensland, Brisbane, Australia (Received 9 January 1991)
Summary The effect of a 14-valent pneumococcal polysaccharide vaccine on morbidity from acute lower respiratory tract infection (ALRI) was determined in a randomized double-blind controlled trial in children under the age of 5 years living in the Papua New Guinea highlands. The vaccine did not protect against mild ALRI. Vaccine efficacy in the study as a whole was 28% for moderate/ severe ALRI, which was not statistically significant though consistent with the significant effect on mortality. Children entered the trial in five separate cohorts 4 months apart. The incidence of disease and vaccine efficacy varied between cohorts and with age. There was no vaccine effect in the first cohort, which had a much higher proportion of older children. The effect was greatest and statistically significant among those groups encountering an epidemic of moderate and severe ALRI at a young age. It was therefore in children at the most vulnerable age in times of greatest incidence of disease that the vaccine had its most potent effect. It is postulated that the efficacy of pneumococcal vaccine is dependent on the predominant invading serotypes in the period after vaccination, the age at which children develop immunocompetence to specific vaccine serotypes, and the levels of naturally acquired specific immunity already present in children at the time of vaccination, and that for all of these conditions there will be a cohort effect.
Introduction Three trials of pneumococcal capsular polysaccharide vaccine against acute lower respiratory tract infections (ALRI) in children under the age of 5 years have now been carried out in the Papua New Guinea (PNG) highlands. 1•2 We have named these Tari 1, Tari 2, and Asaro. 2 The vaccine has been shown to protect against death from acute
lower respiratory tract infection with an efficacy of 50% in children vaccinated under 2 years of age. 2 The firsttrial in Tari, Southern Highlands Province (Tari 1) showed protective efficacy against morbidity from ALRI of 37% in children aged 17 months or more. 1 This paper describes the effect of the vaccine on ALRI morbidity in a subset of the children who participated in the second Tari trial (Tari 2).
Methods Reprint requests to: Dr D. Lehmann, Papua New Guinea Institute of Medical Research, P.O. Box 60, Goroka, Papua New Guinea.
The methods and background to the Tari 2 trial have already been described. 2 The
Downloaded by [Australian Catholic University] at 23:36 24 August 2017
248
D. Lehmann et al.
trial was double-blind and fully randomized by individual. Participants received either vaccine, Pneumovax (Merck, Sharp and Dohme) containing 14 capsular serotypes of pneumococcus (1, 2, 3, 4, 6A, 7F, 8, 9N, 12F, 14, 18C, 19F, 23F and 25, Danish nomenclature), or saline placebo. In an initial immunization round in October and November 1981, a cross-section of children aged 6-59 months were vaccinated. It was intended that children would then enter the trial continuously at 6 months of age. However, this was impracticable in view of the scattered distribution of the population and therefore four further vaccination rounds were carried out during which all unvaccinated children of 4 months of age and older were included. Each of the five rounds thus provided a cohort of children. Children aged less than 18 months at the time of their first immunization were offered a booster 1 year later. Morbidity surveillance was carried out independently of the vaccine trial by 12 lay reporters between October 1981 and November 1983. Approximately 2000 children under 10 years of age (half the total number of children under regular demographic surveillance by the Tari Research Unit) were monitored for episodes of illness fortnightly in an area which formed a band across the Tari Basin and which was within relatively easy access for regular supervision. By interviewing the guardian and examining the child, it was possible to report any illness occurring in the preceding fortnight. In addition, six primary health care workers and a staff member working in the Tari Major Health Centre reported details of the episodes of illness in trial participants who sought treatment. Children who were not seen on two consecutive visits of the reporter were reported absent and only re-entered the study population if they were later present for two consecutive visits. The two periods of reporters' annual leave at Christmas were excluded entirely from the period at risk.
A classification of symptom complexes for lay reporting, developed for populationbased studies in PNG, was used during the trial, and severity of ALRI was defined as follows:
mild ALRI: cough with either fever or breathlessness; moderate ALRI: as for mild but also with chest indrawing; severe ALRI: as for moderate but also with difficulty in feeding or cyanosis or heart failure, defined according to the PNG standard treatment schedule. 3 Episodes of ALRI recorded either as a sole event or in conjunction with another illness (e.g. diarrhoea, measles) were considered in this study. All illness reports were checked and final diagnoses were allocated regularly throughout the study by one of the authors (DL). Where ALRI was determined as the underlying cause of death, the episode was included as one of severe ALRI. Incidence rates of ALRI (number of episodes divided by the period at risk) were calculated overall and for specified age ranges of risk or periods after vaccination. The periods were calculated by adding the days present in the surveillance area for each child, excluding periods of absence as defined above, while the child was within the specified age range or the specified period after vaccination. The numbers of episodes were similarly totalled and rates of incidence expressed as episodes per year of risk over all eligible children. Risk was assumed to start 15 days after the first vaccination or placebo. For the relatively few children who received a second dose, risk was 'restarted' 15 days after the second dose. Estimates of vaccine efficacy (VE) were calculated as percentages from VE= 1-[(rate in vaccine group)/ (rate in placebo group)] Statistical tests between groups of children were taken from regression analysis with episodes per child as the dependent variable. Terms for age of vaccination and admission
249
Pneumococcal vaccine effect in pneumonia
TABLE I. Number of children entering the trial by age in months at first vaccination, admission cohort number and date on which placebo (P) or vaccine (V) was given
Admission Time of cohort vaccination
Downloaded by [Australian Catholic University] at 23:36 24 August 2017
2 3 4 5 Total
Oct-Nov81 Feb-Apr82 July 82 Oct82 Feb-Mar83
p
V
p
V
Age at vaccination (months) 12-17 18-23 24-35 p p p V V V
0 19 10 23 11
0 16 12 11 10
26 44 22 28 24
32 31 20 20 21
38 14 4 10 8
33 14 8 3 8
42 15 2 2 5
46
14 3 4
82 30 4 6 6
104 28 5 4 2
168 43 2 13 8
161 33 4 6 8
356 165 82 62
376 136 52 48 50
63
49
144
124
74
66
66
68
128
143
234
212
709
662
6-11
ISSN: 0272-4936 (Print) 1465-3281 (Online) Journal homepage: http://www.tandfonline.com/loi/ypch19
Effect of pneumococcal vaccine on morbidity from acute lower respiratory tract infections in Papua New Guinean children D. Lehmann, T. F. de C. Marshall, I. D. Riley & M. P. Alpers To cite this article: D. Lehmann, T. F. de C. Marshall, I. D. Riley & M. P. Alpers (1991) Effect of pneumococcal vaccine on morbidity from acute lower respiratory tract infections in Papua New Guinean children, Annals of Tropical Paediatrics, 11:3, 247-257, DOI: 10.1080/02724936.1991.11747510 To link to this article: http://dx.doi.org/10.1080/02724936.1991.11747510
Published online: 13 Jul 2016.
Submit your article to this journal
View related articles
Citing articles: 16 View citing articles
Full Terms & Conditions of access and use can be found at http://www.tandfonline.com/action/journalInformation?journalCode=ypch19 Download by: [Australian Catholic University]
Date: 24 August 2017, At: 23:36
Annals of Tropical Paediatrics (1991) 11, 247-257
Effect of pneumococcal vaccine on morbidity from acute lower respiratory tract infections in Papua New Guinean children
Downloaded by [Australian Catholic University] at 23:36 24 August 2017
D. LEHMANN, T. F. de C. MARSHALL*, I. D. RILEY** & M. P. ALPERS Papua New Guinea Institute of Medical Research, Goroka, Papua New Guinea, *Department of Epidemiology & Population Sciences, London School of Hygiene and Tropical Medicine, and** Tropical Health Program, Faculty of Medicine, University of Queensland, Brisbane, Australia (Received 9 January 1991)
Summary The effect of a 14-valent pneumococcal polysaccharide vaccine on morbidity from acute lower respiratory tract infection (ALRI) was determined in a randomized double-blind controlled trial in children under the age of 5 years living in the Papua New Guinea highlands. The vaccine did not protect against mild ALRI. Vaccine efficacy in the study as a whole was 28% for moderate/ severe ALRI, which was not statistically significant though consistent with the significant effect on mortality. Children entered the trial in five separate cohorts 4 months apart. The incidence of disease and vaccine efficacy varied between cohorts and with age. There was no vaccine effect in the first cohort, which had a much higher proportion of older children. The effect was greatest and statistically significant among those groups encountering an epidemic of moderate and severe ALRI at a young age. It was therefore in children at the most vulnerable age in times of greatest incidence of disease that the vaccine had its most potent effect. It is postulated that the efficacy of pneumococcal vaccine is dependent on the predominant invading serotypes in the period after vaccination, the age at which children develop immunocompetence to specific vaccine serotypes, and the levels of naturally acquired specific immunity already present in children at the time of vaccination, and that for all of these conditions there will be a cohort effect.
Introduction Three trials of pneumococcal capsular polysaccharide vaccine against acute lower respiratory tract infections (ALRI) in children under the age of 5 years have now been carried out in the Papua New Guinea (PNG) highlands. 1•2 We have named these Tari 1, Tari 2, and Asaro. 2 The vaccine has been shown to protect against death from acute
lower respiratory tract infection with an efficacy of 50% in children vaccinated under 2 years of age. 2 The firsttrial in Tari, Southern Highlands Province (Tari 1) showed protective efficacy against morbidity from ALRI of 37% in children aged 17 months or more. 1 This paper describes the effect of the vaccine on ALRI morbidity in a subset of the children who participated in the second Tari trial (Tari 2).
Methods Reprint requests to: Dr D. Lehmann, Papua New Guinea Institute of Medical Research, P.O. Box 60, Goroka, Papua New Guinea.
The methods and background to the Tari 2 trial have already been described. 2 The
Downloaded by [Australian Catholic University] at 23:36 24 August 2017
248
D. Lehmann et al.
trial was double-blind and fully randomized by individual. Participants received either vaccine, Pneumovax (Merck, Sharp and Dohme) containing 14 capsular serotypes of pneumococcus (1, 2, 3, 4, 6A, 7F, 8, 9N, 12F, 14, 18C, 19F, 23F and 25, Danish nomenclature), or saline placebo. In an initial immunization round in October and November 1981, a cross-section of children aged 6-59 months were vaccinated. It was intended that children would then enter the trial continuously at 6 months of age. However, this was impracticable in view of the scattered distribution of the population and therefore four further vaccination rounds were carried out during which all unvaccinated children of 4 months of age and older were included. Each of the five rounds thus provided a cohort of children. Children aged less than 18 months at the time of their first immunization were offered a booster 1 year later. Morbidity surveillance was carried out independently of the vaccine trial by 12 lay reporters between October 1981 and November 1983. Approximately 2000 children under 10 years of age (half the total number of children under regular demographic surveillance by the Tari Research Unit) were monitored for episodes of illness fortnightly in an area which formed a band across the Tari Basin and which was within relatively easy access for regular supervision. By interviewing the guardian and examining the child, it was possible to report any illness occurring in the preceding fortnight. In addition, six primary health care workers and a staff member working in the Tari Major Health Centre reported details of the episodes of illness in trial participants who sought treatment. Children who were not seen on two consecutive visits of the reporter were reported absent and only re-entered the study population if they were later present for two consecutive visits. The two periods of reporters' annual leave at Christmas were excluded entirely from the period at risk.
A classification of symptom complexes for lay reporting, developed for populationbased studies in PNG, was used during the trial, and severity of ALRI was defined as follows:
mild ALRI: cough with either fever or breathlessness; moderate ALRI: as for mild but also with chest indrawing; severe ALRI: as for moderate but also with difficulty in feeding or cyanosis or heart failure, defined according to the PNG standard treatment schedule. 3 Episodes of ALRI recorded either as a sole event or in conjunction with another illness (e.g. diarrhoea, measles) were considered in this study. All illness reports were checked and final diagnoses were allocated regularly throughout the study by one of the authors (DL). Where ALRI was determined as the underlying cause of death, the episode was included as one of severe ALRI. Incidence rates of ALRI (number of episodes divided by the period at risk) were calculated overall and for specified age ranges of risk or periods after vaccination. The periods were calculated by adding the days present in the surveillance area for each child, excluding periods of absence as defined above, while the child was within the specified age range or the specified period after vaccination. The numbers of episodes were similarly totalled and rates of incidence expressed as episodes per year of risk over all eligible children. Risk was assumed to start 15 days after the first vaccination or placebo. For the relatively few children who received a second dose, risk was 'restarted' 15 days after the second dose. Estimates of vaccine efficacy (VE) were calculated as percentages from VE= 1-[(rate in vaccine group)/ (rate in placebo group)] Statistical tests between groups of children were taken from regression analysis with episodes per child as the dependent variable. Terms for age of vaccination and admission
249
Pneumococcal vaccine effect in pneumonia
TABLE I. Number of children entering the trial by age in months at first vaccination, admission cohort number and date on which placebo (P) or vaccine (V) was given
Admission Time of cohort vaccination
Downloaded by [Australian Catholic University] at 23:36 24 August 2017
2 3 4 5 Total
Oct-Nov81 Feb-Apr82 July 82 Oct82 Feb-Mar83
p
V
p
V
Age at vaccination (months) 12-17 18-23 24-35 p p p V V V
0 19 10 23 11
0 16 12 11 10
26 44 22 28 24
32 31 20 20 21
38 14 4 10 8
33 14 8 3 8
42 15 2 2 5
46
14 3 4
82 30 4 6 6
104 28 5 4 2
168 43 2 13 8
161 33 4 6 8
356 165 82 62
376 136 52 48 50
63
49
144
124
74
66
66
68
128
143
234
212
709
662
6-11
