4. Adverse effects.
| Study ID | No. of participants | PCV type | Redness | Swelling | Pain/tenderness | Fever | Serious adverse events |
| Black 2000/Fireman 2003 | 37,868 | CRM197‐PCV7 | Depending on timing of dose, redness occurred in around 10% to 14% of children receiving CRM197‐PCV7 versus 5% to 9% of children receiving MenC vaccination. More severe redness (> 3 cm) occurred in 0% to 0.6% of children receiving CRM197‐PCV7, and did not differ significantly between CRM197‐PCV7 and MenC groups. |
Depending on timing of dose, swelling occurred in around 10% to 12% of children receiving CRM197‐PCV7 versus 3% to 8% of children receiving MenC vaccination. More severe swelling (> 3 cm) occurred in 0.1% to 0.6% of children receiving CRM197‐PCV7, and did not differ significantly between CRM197‐PCV7 and MenC groups. |
Depending on timing of dose, tenderness was reported in 15% to 23% of children receiving CRM197‐PCV7, and did not differ significantly between CRM197‐PCV7 and MenC groups. | Depending on timing of dose, fever > 38 °C occurred in around 15% to 24% of children receiving CRM197‐PCV7 versus 9% to 17% of children receiving MenC vaccination. Fever (> 39 °C) occurred in 0.9% to 2.5% of children receiving CRM197‐PCV7, and did not differ significantly between CRM197‐PCV7 and MenC groups. |
No severe adverse events related to vaccination resulting in hospitalisation, emergency, or clinic visits were reported. |
| Dagan 2001 | 264 | CRM197‐PCV9 | Depending on timing of dose, redness occurred in 5% to 6% of children receiving CRM197‐PCV9 versus 0% to 5% of children receiving MenC vaccination. | Depending on timing of dose, swelling occurred in 7% to 12% of children receiving CRM197‐PCV9 versus 0% to 5% of children receiving MenC vaccination. | Depending on timing of dose, tenderness was reported in 25% to 38% of children receiving CRM197‐PCV9 versus 0% to 8% of children receiving MenC vaccination. | Depending on timing of dose, fever > 38 °C occurred in around 15% to 44% of children receiving CRM197‐PCV9 versus 8% to 25% of children receiving MenC vaccination. Fever (> 39.5 °C) occurred in only 1 child receiving CRM197‐PCV9 versus 3 children receiving MenC vaccination. |
Not reported |
| Eskola 2001/Palmu 2009 | 1662 | CRM197‐PCV7 | Depending on timing of dose, redness occurred in 14% to 20% of children receiving CRM197‐PCV7 versus 9% to 16% of children receiving hepatitis vaccines. More severe redness (> 2.5 cm) occurred in 0% to 0.9% of children receiving CRM197‐PCV7, and did not differ significantly between CRM197‐PCV7 and hepatitis vaccine groups. |
Depending on timing of dose, swelling occurred in 5% to 6% of children receiving CRM197‐PCV7 versus 2% to 6% of children receiving hepatitis vaccines. More severe swelling (> 2.5 cm) occurred in 0.5% to 1.3% of children receiving CRM197‐PCV7, and did not differ significantly between CRM197‐PCV7 and hepatitis vaccine groups. |
Depending on timing of dose, pain was reported in 3% to 8% of children receiving CRM197‐PCV7 versus 2% to 3% of children receiving hepatitis vaccines. | Fever (> 39 °C) occurred in 0.4% to 2.0% of children receiving CRM197‐PCV7 versus 0.2% to 1.7% of children receiving hepatitis vaccines. | No significant differences between vaccine groups were observed for unexpected events (6 versus 4 events). 1 child in the CRM197‐PCV7 group died from bowel obstruction, necrosis, and shock at the age of 8 months (85 days after administration of third dose), but death was assessed as unrelated to study vaccine (autopsy revealed mesenteric defects with volvulus and other congenital abnormalities). |
| Jansen 2008 | 579 | CRM197‐PCV7/TIV | ‐ | ‐ | ‐ | ‐ | Quote: “In general, the vaccinations were well‐tolerated, and no immediate or severe adverse events were recorded.” |
| Kilpi 2003 | 1666 | OMPC‐PCV7 | OMPC‐PCV7 caused local reactions within 3 days of each dose more often than the hepB vaccine (data not shown). | OMPC‐PCV7 caused local reactions within 3 days of each dose more often than the hepB vaccine (data not shown). | Not reported | Not reported | There were no statistically significant differences in the occurrence of any diagnosis among individuals who experienced serious adverse events between the 2 vaccine groups. 1 child in the OMPC‐PCV7 group died from volvulus due to bowel obstruction. Death was assessed as unrelated to study vaccine. |
| Prymula 2006 | 4968 | PHiD‐CV11 | Not reported | Not reported | Not reported | Not reported | The percentages of infants with unsolicited symptoms that were judged to be causally related to vaccination were similar in the PHiD‐CV11 and hepA groups (2.5% versus 3.0%). 14 serious adverse events were judged to be causally related to vaccination: 8 occurred in children receiving PHiD‐CV11 vaccination (7 after co‐administration with Infanrix hexa and 1 after PHiD‐CV11 booster) versus 6 in children receiving hepatitis A control vaccine (7 after co‐administration with Infanrix hexa and 1 after hepatitis A booster with Infanrix hexa). All events, apart from 1 case of epilepsy in the hepatitis A group, resolved without sequelae. 4 children died during the study, 1 in the PHiD‐CV11 group (8 months after third dose, diagnosis of epilepsy was made; 25 months after the third dose the child had grand mal epilepsy and died from suffocation). None of the deaths were regarded by the investigators as related to the study vaccine. |
| Tregnaghi 2014/Sáez‐Llorens 2017 | 23,821 | PHiD‐CV10 | Not reported | Not reported | Not reported | Not reported | Serious adverse events did not differ significantly between PHiD‐CV10 and hepatitis control vaccines (21.5% versus 22.6%). Only 1 event (in the control group) was judged to be causally related to vaccination by the investigator, and it resolved without sequelae. 19 children died in the PHiD‐CV10 group (0.16%) versus 26 in the control group (0.22%). None of the deaths were considered by the investigator to be causally related to vaccination. |
| Veenhoven 2003 | 383 | CRM197‐PCV7 | Not reported | Not reported | Not reported | Not reported | No serious adverse events were noted after administration of CRM197‐PCV7 or hepatitis control vaccines. |
| Vesikari 2016 | 6178 | PHiD‐CV10 | Not reported | Not reported | Not reported | Not reported | Serious adverse events considered by the investigator to be causally related to vaccination were reported in 4 infants in the PHiD‐CV10 group (all in 3 + 1 group: sepsis with non‐specified aetiology in 1 infant, pyrexia in 1 infant, convulsion in 2 infants) and in 2 infants in hepB group (petit mal epilepsy in 1 infant and pyrexia in 1 infant). 1 fatal serious adverse event (sudden infant death, not considered to be vaccination related) was reported in the PHiD‐CV10 (2 + 1) group. |
CRM197‐PCV7: 7‐valent pneumococcal conjugate vaccine conjugated to carrier protein CRM197 CRM197‐PCV7/TIV: trivalent influenza vaccine plus 7‐valent pneumococcal conjugate vaccine conjugated to carrier protein CRM197 CRM197‐PCV9: 9‐valent pneumococcal conjugate vaccine conjugated to carrier protein CRM197 hepA: hepatitis A hepB: hepatitis B MenC: meningococcus type C OMPC‐PCV7: 7‐valent pneumococcal conjugate vaccine conjugated to the outer membrane protein complex of Neisseria meningitidis serogroup B PHiD‐CV10: 10‐valent pneumococcal conjugate vaccine conjugated to protein D (surface lipoprotein of non‐typeable Haemophilus influenzae) PHiD‐CV11: 11‐valent pneumococcal conjugate vaccine conjugated to protein D (surface lipoprotein of non‐typeable Haemophilus influenzae) TIV: trivalent influenza vaccine