Interim results of an ecological experiment — Conjugate vaccination against the pneumococcus and serotype replacement

Figures & data

Table 1. Young Children: Most Prominent IPD-Causing NVT in Countries that have Introduced PCV13-CRM into their Infant Immunization Program

						Serotypes comprising at least 5% of all pediatric NVT (Rank)
Country and reference	Year(s) included	Total # of Isolates	Disease	NVT as % of all Isolates	Age Group	S1	S2	S3	S4	S5	S6	S7	S8	S9	S10	S11	Serotypes <5% but with statistically significant increase	# serogroups needed for 50% NVT coverage
US^30	2012–13	177	IPD	86%	<5	22F	33F	38	35B	19A	15B	15C	3	23B	12F
						13	11	10	9		8	8	7	6	5			5
UK^24	2013-14	260	IPD	81%	<5	24F^*	22F	33F	15A	8	12F
						13	10	9	8	7	7							6
France^23	2012	201	IPD	80%	<2	24F^* ^*	12F^* ^*	15B	15A	19A	22F
						26	13	10	8		7							4
US^28	2011-13	67	mening	78%	<19	19A	35B	22F	33F	15C	10	23A	23B	15A	6C	3
							12	10	10	8	8	8	6	6	6	6		6
Israel^66	2012–13	155	IPD	73%	<5	12F	19A	15B/C	33F	3
						36		10	7	7								3
France^90	2011-12	154	mening	71%	<15	12F^* ^*	19A	24F^* ^*	22F	10A	15A	15B	33F	6C
						20		14	9	9	7	5	5	5				4
Canada^91	2012	244	IPD	68%	<5	19A	22F^*	3	23B^*	15C	38	11A	15B				38^*
							15	14	7	7	6	5	5					6
Argentina^92	2014	104	IPD	66%	<2	24	12F	19A	23B	16F	15B	3	9N
						17	13		9	7	6	6	6					5
Japan^93	2014	96	IPD	64%	<5	19A	15A	24F	15B	10A	15C	22F	23A
							26	16	13	11	10	10	5					3
Belgium^89	2013	176	IPD	64%	<5	12F	24F	19A	33F	10A
						19	12		11	>6								>5
South Africa^26	2012	369	IPD	58%	<2	8	19A	15B	12F
						17		11	7									>6
Australia^94	2012	155	IPD	55%	<5	19A	22F	3	33F	35B	15C	23B	10A	15B	6C
							13	13	10	9	9	9	5	5	5			5
US^85	2011	119	IPD	55%	<18	19A	33F	11	3	6C	15B	23A	10	12	15C
							12	9	8	8	6	6	5	5	5			7
Spain^95	2011–12	79	IPD	51%	<15	3	19A	22F	11A	15B	12F	25A
(Madrid)						15		10	8	8	5	5						6
Taiwan^86	2014–15	105	IPD	50%	<5	19A	15 non-B	15B	23A
							53	11	9									1
US^96	2013	118	AOM	83%	<13	19A	35B	3	23B	15A	21	15B	15C	16	31
							12	12	9	7	6	6	6	6	5			6
Israel^97	2012–13	80	AOM	82%	<2	15B/C	19A	16F	35B	3
						10		9	9	7								>5
France^98	2011	152	AOM	54%	<17	19A	3	15A^* ^*	35B	23A^* ^*	11A
							16	12	12	7	6							5

Footnote: Only studies with at least 50 isolates, and only serotypes that represent at least 5% of all NVT. ^* = associated with statistically significant increase; ^{* *} = highlighted as noteworthy increase, but no statistics provided

Table 2. Young Children: Most Prominent Non-Vaccine Types (NVT) Causing IPD in Countries that Introduced PHiD-CV-10 into the Infant Immunization Program

Country and reference	Year(s) included	Total # of Isolates	Disease	NVT as % of all Isolates	Age Group	Serotypes comprising at least 5% of all pediatric NVT (Rank)												Serotypes <5% but with statistically significant increase	# serogroups needed for 50% NVT coverage
						S1	S2	S3	S4	S5	S6	S7	S8	S9	S10	S11	S12
Countries that used PHiD-CV-10
Netherlands^22	2011–14	57	IPD	74%	3-38 mo	10A	19A	33F	15C	22F	8	12F
						38		14	10	7	5	5							2
Canada^33	2012	66	IPD	65%	<5	19A	3	10A	38	23A	11A	15A	22F	15C	33F	9N
(Quebec)							14	14	12	9	7	7	7	5	5	5			5
Brazil^99	2012	110	IPD	54%	<2	3	19A	11A	22F	6C	12F	20	24F
						22		10	8	5	5	5	5						5
New Zealand^21	2013–14	89	IPD	46%	<5	19A	3	6C	8	11A	33F	9N	10A	15B	22F	23B	35
							29	12	10	7	7	5	5	5	5	5	5		3
Chile^99	2012	90	IPD	46%	<2	19A	3	12F	24F	22F	33F	6C	11A	15B	15C	38
							15	15	12	10	10	5	5	5	5	5			4
Finland^100	2013–14	60	IPD	45%	<5	19A	3	22F	15B	23A
							37	15	11	7									2
Colombia^101	2014	91	IPD	40%	<5	19A	3	11A	16F	15B	8	15C
							22	14	8	8	8	6							4
Countries that used both PHiD-CV-10 and PCV13-CRM
Germany^32	2013–14	165	IPD	84%	<16	24F	3	15C	10A	12F	38	33F	19A	15B				34^*
						11	9	8	8	6	6	6		5					7
Germany^27	2010–12	194	mening	76%	<16	10A	19A	23B*	12F	15C	3	22F	35B
						9		9	8	7	7	5	5						7
Mexico^99	2012	60	IPD	28%	<2	19A	23B	35B	6C	10A	15B
							24	18	12	12	12								3

Footnote: Only studies with at least 50 isolates, and only serotypes that represent at least 5% of all NVT. ^* = associated with statistically significant increase

Table 3. Older Children and Adults: Most Prominent Non-Vaccine Types (NVT) Causing IPD in Countries that Introduced PCV13-CRM into the Infant Immunization Program

Country and reference	Year(s) included	Total # of Isolates	Age Group	NVT as % of all Isolates	Serotypes comprising at least 5% of all older children/adult NVT (Rank)										Serotypes <5% but with statistically significant increase	# serogroups needed for 50% NVT coverage
					S1	S2	S3	S4	S5	S6	S7	S8	S9	S10
US^30	2012-13	>710	>65	>84%	22F	3	6C	23A	35B	19A	11A	16F
					25	23	15	11	10		9	8				3
UK^24	2013-14	2036	>65	80%	8^*	22F	3	15A^*	12F^*	19A	24F^*	33F			10A^*
					14	12	9	8	7		5	5				5
Uruguay^99	2012	76	>60	78%	3	12F	22F	8
					27	24	12	8								2
Canada^91	2012	937	>65	70%	22F^*	19A	3	15A	23A^*	6C	10A				23B^*
					19		14	8	8	7	5					5
Ireland^102	2014	261	>5	70%	22F	15A^* ^*	3	8^* ^*	19A	10A^* ^*	33F
					12	11	11	11		6	5					4
Taiwan^86	2014-15	323	>65	>67%	3	15 non-B	19A	23A
					25	15		5								>3
Australia^94	2012	524	>65	67%	19A	3	6C	22F	15A	11A
						19	17	13	8	7						4
Spain^103	2012	284	all ages	65%	3	19A	22F^*	8	6C
(Galicia)					25		10	8	7							4
Spain^104	2012-14	206	> 20	64%	3	19A	11A	22F^*	23A	23B	6C	15B	35B
(Mallorca)					18		17	9	6	6	5	5	5			4
Argentina^92	2014	71	>60	63%	3	8	24	9N	6C	12F
					20	11	11	9	7	7						4
Norway^29	2012	607	>5	62%	22F^* ^*	19A	3	23B^* ^*	6C	8					15A^* ^*
					23		13	7	6	6						5
Spain^87	2010-13	180	> 5	62%	3	19A	6C^*†	23A/23B	22F	8	9N	15A^* ^†
(Navarra)					29		11	10	9	8	5	5				3
UK^105	2012-13	927	> 2	62%	19A	8^*	3	22F	15A^*	12F	33F^*	31	23A^*	6C	10A^*, 23B^*, 24F^*,38^*
(Oxford)						18	14	12	7	7	6	5	5	5		4
Switzerland^88	2012	703	>16	55%	3^*	19A	22^*	8	9 not 9V	15^*					6C^*
					28		12	11	7	5						3
South Africa^26	2012	1262	25-44	48%	19A	12F	8	3	9N	16F	13	22F
						19	10	9	6	6	5	5				5

Footnote: Only studies with at least 50 isolates, and only serotypes that represent at least 5% of all NVT. ^* = associated with statistically significant increase; ^{* *} = highlighted as noteworthy increase, but no statistics provided; † = significant in >65 y only

Table 4. Older Children and Adults: Most Prominent Non-Vaccine Types (NVT) Causing IPD in Countries that Introduced PHiD-CV-10 into the Infant Immunization Program

Country and reference	Year(s) included	Total # of Isolates	Age Group	NVT as % of all Isolates	Serotypes comprising at least 5% of all older child/adult NVT (Rank)										Serotypes <5% but with statistically significant increase	# serogroups needed for 50% NVT coverage
					S1	S2	S3	S4	S5	S6	S7	S8	S9	S10
Countries that used PHiD-CV-10
Canada^33	2012	271	> 5	64%	3	19A	22F	15A	9N	33F	6C	11A	12F
(Quebec)					17		14	8	7	6	5	5	5			4
Brazil^99	2012	230	>60	63%	3	12F	20	19A	8	25A	6C
					17	13	7		6	6	5					6
Colombia^101	2014	263	>14	60%	19A	3	23A	11A	15A	16F	22F	6C
						13	9	8	8	6	6	5				6
Finland^100	2014	355	>65	57%	3	22F	19A	15B	9N
					30	21		5	5							2
New Zealand^21	2014	416	>5	57%	19A	22F	3	6C	8	9N	16	35	11A
						16	14	9	8	6	6	6	5			5
Chile^99	2012	194	>60	55%	3	19A	11A	22F	12F	38	8	10A	15B
					28		8	7	6	5	5	5	5			5
Brazil^106	2011-12	125	all ages	44%	3	12F	8	11A	19A	20
					18	15	15	11		9						4
Countries that used both PCV13-CRM and PHiD-CV-10
Germany^32	2013-14	2062	>15	79%	3	12F^*	22F^*	19A	8^*	9N^*	24F^*	10A^*	15A^*	23B^*	6C^*, 12A^*, 16F^* 35B^*
					19	11	10		7	6	5	5	5	5		5
Germany^27	2010-13	444	>15	71%	23B^*	3	19A	12F	22F	23A	11A	10A
(meningitis)					13	13		8	8	6	5	5				6

Footnote: Only studies with at least 50 isolates, and only serotypes that represent at least 5% of all NVT. ^* = associated with statistically significant increase

Figure 1. Most prominent NVT causing IPD in young children or older adults in countries that have introduced higher-valent PCVs. Y-axis: % each serotype represented of all NVT in that study. Upper panel (young children) includes the 18 data sets from combined Tables 1 and 2 comprising age ranges <2 years, 3-38 months, or <5 years. Lower panel (older adults) includes the 10 data sets from combined Tables 3 and 4 comprising age ranges >60 years or >65 years. Within each serotype grouping, the bars from left to right are in the same order as the studies in the combined tables, i.e., the left-most bar values represents the study with the highest proportion of NVT/all types, and the right-most the lowest. To accommodate as much information from the table as possible, for graphical purposes several serotyping assumptions were made. Panel A: Israel⁶⁶: 15B/C=>15B; US⁸⁷: 10=>10A; 11=> 11A; 12=>12F; Taiwan⁸⁸:15 non-B=>15A. Panel B: Spain⁸⁹: 23A/B=> 23A; NZ²¹: 16=>16F; Switzerland⁹⁰: 22=>22F; 9 non 9V=> 9N; 15=>15A; Taiwan⁸⁸: 15 non-B=>15A. For graphical reasons, the Taiwan young children 15A and older children/adults serotype 3 values are only depicted up to 40%, and it was assumed that the number of 10A isolates from Belgium,⁹¹ listed as >6, was 6. Note that a missing bar doesn't necessarily mean zero, just <5% of NVT isolates. NVT was defined as all serotypes except 1,4,5,6A,6B,7F,9V,14,18C,19A,19F,23F.

Figure 2. Most prominent NVT causing IPD in young children in countries that have introduced PCV13-CRM or PHiD-CV-10. Y axis: % each serotype represented of all NVT in that study. Upper panel (PCV13-CRM) includes the 11 data sets from Table 1, and lower panel (PHiD-CV-10) includes the 7 data sets from Table 2, which comprise age ranges <2 years, 3–38 months, or <5 years, and which used only PCV13-CRM or PHiD-CV-10. Values for each serotype represent % of all NVT IPD in each data set. Same bar ordering and serotype assumptions were made as in legend to Figure 1.

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