Bacterial nasopharyngeal carriage following infant immunization with pneumococcal conjugate vaccines according to a 2+1 schedule in children in South Africa: an exploratory analysis of two clinical trials

Figures & data

Figure 1. Study designs

PCV7, 7-valent pneumococcal conjugate vaccine; PHiD-CV, pneumococcal non-typeable Haemophilus influenzae protein D conjugate vaccine; DTaP-IPV//Hib, diphtheria toxoid-tetanus toxoid-acellular pertussis-trivalent inactivated polio vaccine and H. influenzae type b conjugate vaccine; HBV, hepatitis B vaccine; HRV, human rotavirus vaccine; OPV, oral poliovirus vaccine; DTPw-HBV/Hib, diphtheria-tetanus-whole cell pertussis-hepatitis B vaccine combined with lyophilized H. influenzae type b tetanus conjugate vaccine; PCV, pneumococcal conjugate vaccine; M, months of age; W, weeks of age. Pipette depicts oral vaccination; syringe depicts intramuscular vaccination.

Table 1. Age at each study visit (total vaccinated cohort)

	PCV7 trial N = 250		PHiD-CV trial N = 100
Visit	n	Mean age (SD), weeks		n	Mean age (SD), weeks
6 weeks (primary dose 1)	249	6.3 (0.33)		100	6.4 (0.41)
4 months (post-primary dose 2)	236	20.4 (1.4)		98	18.8 (0.82)
9–10 months (booster dose)	228	39.9 (0.68)		98	40.4 (1.4)
10–11 months	227	41.1 (0.74)		98	44.9 (1.4)
12–13 months	220	52.6 (0.67)		97	52.4 (0.27)
15–18 months	215	70.1 (3.9)		97	65.6 (0.82)
16–19 months	214	71.6 (4.4)		97	70.0 (0.81)
24–27 months	203	105.1 (1.5)		97	104.7 (0.57)

PCV7, 7-valent pneumococcal conjugate vaccine; PHiD-CV, pneumococcal non-typeable Haemophilus influenzae protein D conjugate vaccine; N, number of children who received at least one vaccine dose; n, number of children with swab sample available and cultured at the respective visit and previous visit(s); SD, standard deviation.

Figure 2. Colonization rates with Streptococcus pneumoniae at each visit in children who received PCV7 or PHiD-CV according to a 2 + 1 vaccination schedule (total vaccinated cohort)

PCV7, 7-valent pneumococcal conjugate vaccine; PHiD-CV, pneumococcal non-typeable Haemophilus influenzae protein D conjugate vaccine; any Spn, any S. pneumoniae serotypes; 7VT, S. pneumoniae serotypes included in PCV7; W, weeks of age; M, months of age; N, number of children with available results at the considered visit.

The error bars indicate 95% confidence intervals.

Table 2. Cumulative acquisition of Streptococcus pneumoniae serotypes (any, 7VT, non-7VT serotypes, [1, 5, 7F], 6B, 9V, 14, 19F, 23F, vaccine-related 6A and 19A serotypes) in children who received PCV7 or PHiD-CV according to a 2 + 1 vaccination schedule (total vaccinated cohort)

	PCV7 trial				PHiD-CV trial
Age at visit	N	n	%	95% CI*	N	n	%	95% CI*
Any S. pneumoniae serotype
4 months	236	129	54.7	48.1, 61.1	98	56	57.1	46.7, 67.1
9–10 months	228	179	78.5	72.6, 83.7	98	76	77.6	68.0, 85.4
10–11 months	227	191	84.1	78.7, 88.6	98	82	83.7	74.8, 90.4
12–13 months	220	196	89.1	84.2, 92.9	97	90	92.8	85.7, 97.0
15–18 months	215	204	94.9	91.0, 97.4	97	93	95.9	89.8, 98.9
16–19 months	214	205	95.8	92.2, 98.1	97	94	96.9	91.2, 99.4
24–27 months	203	195	96.1	92.4, 98.3	97	96	99.0	94.4, 100
Any of S. pneumoniae 7VT
4 months	236	41	17.4	12.8, 22.8	98	24	24.5	16.4, 34.2
9–10 months	228	72	31.6	25.6, 38.0	98	36	36.7	27.2, 47.1
10–11 months	227	82	36.1	29.9, 42.7	98	40	40.8	31.0, 51.2
12–13 months	220	87	39.6	33.0, 46.3	97	47	48.5	38.2, 58.8
15–18 months	215	100	46.5	39.7, 53.4	97	53	54.6	44.2, 64.8
16–19 months	214	102	47.7	40.8, 54.6	97	54	55.7	45.2, 65.8
24–27 months	203	109	53.7	46.6, 60.7	97	61	62.9	52.5, 72.5
Any of S. pneumoniae non-7VT
4 months	236	90	38.1	31.9, 44.7	98	33	33.7	24.4, 43.9
9–10 months	228	138	60.5	53.9, 66.9	98	60	61.2	50.8, 70.9
10–11 months	227	155	68.3	61.8, 74.2	98	66	67.3	57.1, 76.5
12–13 months	220	167	75.9	69.7, 81.4	97	74	76.3	66.6, 84.3
15–18 months	215	179	83.3	77.6, 88.0	97	82	84.5	75.8, 91.1
16–19 months	214	182	85.0	79.6, 89.5	97	84	86.6	78.2, 92.7
24–27 months	203	183	90.1	85.2, 93.9	97	86	88.7	80.6, 94.2
Any of S. pneumoniae serotypes 1, 5, 7F
4 months	236	1	0.4	0.0, 2.3	98	2	2.0	0.3, 7.2
9–10 months	228	1	0.4	0.0, 2.4	98	3	3.1	0.6, 8.7
10–11 months	227	1	0.4	0.0, 2.4	98	3	3.1	0.6, 8.7
12–13 months	220	2	0.9	0.1, 3.2	97	3	3.1	0.6, 8.8
15–18 months	215	3	1.4	0.3, 4.0	97	3	3.1	0.6, 8.8
16–19 months	214	4	1.9	0.5, 4.7	97	3	3.1	0.6, 8.8
24–27 months	203	3	1.5	0.3, 4.3	97	3	3.1	0.6, 8.8
S. pneumoniae serotype 6B
4 months	236	9	3.8	1.8, 7.1	98	2	2.0	0.3, 7.2
9–10 months	228	14	6.1	3.4, 10.1	98	5	5.1	1.7, 11.5
10–11 months	227	14	6.2	3.4, 10.1	98	7	7.1	2.9, 14.2
12–13 months	220	15	6.8	3.9, 11.0	97	10	10.3	5.1, 18.1
15–18 months	215	19	8.8	5.4, 13.5	97	11	11.3	5.8, 19.4
16–19 months	214	18	8.4	5.1, 13.0	97	13	13.4	7.3, 21.8
24–27 months	203	18	8.9	5.3, 13.7	97	14	14.4	8.1, 23.0
S. pneumoniae serotype 9V
4 months	236	4	1.7	0.5, 4.3	98	3	3.1	0.6, 8.7
9–10 months	228	4	1.8	0.5, 4.4	98	3	3.1	0.6, 8.7
10–11 months	227	4	1.8	0.5, 4.5	98	3	3.1	0.6, 8.7
12–13 months	220	4	1.8	0.5, 4.6	97	4	4.1	1.1, 10.2
15–18 months	215	4	1.9	0.5, 4.7	97	5	5.2	1.7, 11.6
16–19 months	214	4	1.9	0.5, 4.7	97	5	5.2	1.7, 11.6
24–27 months	203	5	2.5	0.8, 5.7	97	6	6.2	2.3, 13.0
S. pneumoniae serotype 14
4 months	236	3	1.3	0.3, 3.7	98	3	3.1	0.6, 8.7
9–10 months	228	7	3.1	1.2, 6.2	98	4	4.1	1.1, 10.1
10–11 months	227	9	4.0	1.8, 7.4	98	4	4.1	1.1, 10.1
12–13 months	220	9	4.1	1.9, 7.6	97	5	5.2	1.7, 11.6
15–18 months	215	11	5.1	2.6, 9.0	97	8	8.3	3.6, 15.6
16–19 months	214	13	6.1	3.3, 10.2	97	8	8.3	3.6, 15.6
24–27 months	203	15	7.4	4.2, 11.9	97	10	10.3	5.1, 18.1
S. pneumoniae serotype 19F
4 months	236	12	5.1	2.7, 8.7	98	5	5.1	1.7, 11.5
9–10 months	228	20	8.8	5.4, 13.2	98	11	11.2	5.7, 19.2
10–11 months	227	22	9.7	6.2, 14.3	98	13	13.3	7.3, 21.6
12–13 months	220	31	14.1	9.8, 19.4	97	13	13.4	7.3, 21.8
15–18 months	215	41	19.1	14.0, 25.0	97	16	16.5	9.7, 25.4
16–19 months	214	44	20.6	15.4, 26.6	97	19	19.6	12.2, 28.9
24–27 months	203	52	25.6	19.8, 32.2	97	25	25.8	17.4, 35.7
S. pneumoniae serotype 23F
4 months	236	12	5.1	2.7, 8.7	98	9	9.2	4.3, 16.7
9–10 months	228	31	13.6	9.4, 18.7	98	11	11.2	5.7, 19.2
10–11 months	227	38	16.7	12.1, 22.2	98	11	11.2	5.7, 19.2
12–13 months	220	37	16.8	12.1, 22.4	97	14	14.4	8.1, 23.0
15–18 months	215	40	18.6	13.6, 24.5	97	16	16.5	9.7, 25.4
16–19 months	214	40	18.7	13.7, 24.6	97	17	17.5	10.6, 26.6
24–27 months	203	44	21.7	16.2, 28.0	97	22	22.7	14.8, 21.3
S. pneumoniae serotype 6A
4 months	236	15	6.4	3.6, 10.3	98	0	0.0	-
9–10 months	228	28	12.3	8.3, 17.3	98	5	5.1	1.7, 11.5
10–11 months	227	31	13.7	9.5, 18.8	98	5	5.1	1.7, 11.5
12–13 months	220	32	14.6	10.2, 19.9	97	12	12.4	6.6, 20.6
15–18 months	215	39	18.1	13.2, 24.0	97	15	15.5	8.9, 24.2
16–19 months	214	40	18.7	13.7, 24.6	97	15	15.5	8.9, 24.2
24–27 months	203	47	23.2	17.5, 29.6	97	19	19.6	12.2, 28.9
S. pneumoniae serotype 19A
4 months	236	7	3.0	1.2, 6.0	98	3	3.1	0.6, 8.7
9–10 months	228	21	9.2	5.8, 13.7	98	5	5.1	1.7, 11.5
10–11 months	227	23	10.1	6.5, 14.8	98	6	6.1	2.3, 12.9
12–13 months	220	26	11.8	7.9, 16.8	97	6	6.2	2.3, 13.0
15–18 months	215	33	15.4	10.8, 20.9	97	11	11.3	5.8, 19.4
16–19 months	214	35	16.4	11.7, 22.0	97	15	15.5	8.9, 24.2
24–27 months	203	47	23.2	17.5, 29.6	97	21	21.7	13.9, 31.2

PCV7, 7-valent pneumococcal conjugate vaccine; PHiD-CV, pneumococcal non-typeable Haemophilus influenzae protein D conjugate vaccine; N, number of children with swabs cultured at the considered visit and previous visit(s); n/%, cumulative number/percentage of children with acquisition associated to the specified serotype(s) at the considered visit; CI, confidence interval; 7VT, S. pneumoniae serotypes included in PCV7; non-7VT, S. pneumoniae serotypes not included in PCV7.

Data are presented for individual serotypes for which >5 cumulative cases were recorded up to the last visit in either PCV7 or PHiD-CV recipients.

*Potential similarities (or differences) between groups were assessed based on the overlap of the 95% CIs.

Figure 3. Kaplan-Meier estimates of the percentages of children who received PCV7 or PHiD-CV according to a 2 + 1 vaccination schedule and were never found colonized with Streptococcus pneumoniae (total vaccinated cohort)

PCV7, 7-valent pneumococcal conjugate vaccine; PHiD-CV, pneumococcal non-typeable Haemophilus influenzae protein D conjugate vaccine; 7VT, S. pneumoniae serotypes included in PCV7; non-7VT, S. pneumoniae serotypes not included in PCV7.

Figure 4. Kaplan-Meier estimates of the percentages children who received PCV7 or PHiD-CV according to a 2 + 1 vaccination schedule and were never found colonized with Haemophilus influenzae or Staphylococcus aureus (total vaccinated cohort)

PCV7, 7-valent pneumococcal conjugate vaccine; PHiD-CV, pneumococcal non-typeable H. influenzae protein D conjugate vaccine.

Figure 5. Plain language summary

Data availability statement

Anonymized individual participant data and study documents from PHiD-CV study (NCT00829010) can be requested for further research from www.clinicalstudydatarequest.com.

For the PCV7 study, data are available upon request to Wits Health Consortium and after they have signed a material transfer agreement.