Abstract: We included five trials involving 1350 participants in the original review. The updated review identified no new trials. The evidence from two small trials (one trial including infants and one including adolescents) was insufficient to allow any definitive statements to be made about the effects of the needles evaluated in the trials on vaccine immunogenicity and reactogenicity. The remaining three trials (1135 participants) contributed data to comparisons between 25 G 25 mm, 23 G 25 mm, and 25 G 16 mm needles. These trials included infants predominantly aged from two to six months undergoing intramuscular vaccination in the anterolateral thigh using the World Health Organization (WHO) injection technique (skin stretched flat, needle inserted at a 90° angle and up to the needle hub in healthy infants). The vaccines administered were combination vaccines containing diphtheria, tetanus, and whole-cell pertussis antigens (DTwP). In some trials, the vaccines also contained Haemophilus influenzae type b (DTwP-Hib) and hepatitis B (DTwP-Hib-Hep B) antigen components. Primary outcomes Incidence of vaccine-preventable diseases: No trials reported this outcome. Procedural pain and crying: Using a wider gauge 23 G 25 mm needle may slightly reduce procedural pain (low-quality evidence) and probably leads to a slight reduction in the duration of crying time immediately after vaccination (moderate-quality evidence) compared with a narrower gauge 25 G 25 mm needle (one trial, 320 participants). The effects are probably not large enough to be clinically relevant. Secondary outcomes Immune response: There is probably little or no difference in immune response, defined in terms of the proportion of seroprotected infants, between use of 25 G 25 mm, 23 G 25 mm, or 25 G 16 mm needles to administer a series of three doses of a DTwP-Hib vaccine at ages two, three, and four months (moderate-quality evidence, one trial, numbers of participants in analyses range from 309 to 402. The immune response to the pertussis antigen was not measured). Severe and non-severe local reactions: 25 mm needles (either 25 G or 23 G) probably lead to fewer severe and non-severe local reactions after DTwP-Hib vaccination compared with 25 G 16 mm needles (moderate-quality evidence, one trial, 447 to 458 participants in analyses). We estimate that one fewer infant will experience a severe local reaction (extensive redness and swelling) after the first vaccine dose for every 25 infants vaccinated with the longer rather than the shorter needle (number needed to treat for an additional beneficial outcome (NNTB) with a 25 G 25 mm needle: 25 (95% confidence interval (CI) 15 to 100); NNTB with a 23 G 25 mm needle: 25 (95% CI 17 to 100)). We estimate that one fewer infant will experience a non-severe local reaction (any redness, swelling, tenderness, or hardness (composite outcome)) at 24 hours after the first vaccine dose for every 5 or 6 infants vaccinated with a 25 mm rather than a 16 mm needle (NNTB with a 25 G 25 mm needle: 5 (95% CI 4 to 10); NNTB with a 23 G 25 mm needle: 6 (95% CI 4 to 13)). The results are similar after the second and third vaccine doses. Using a narrow gauge 25 G 25 mm needle may produce a small reduction in the incidence of local reactions after each dose of a DTwP vaccine compared with a wider gauge 23 G 25 mm needle, but the effect estimates are imprecise (low-quality evidence, two trials, 100 to 459 participants in analyses). Systemic reactions: The comparative effects of 23 G 25 mm, 25 G 25 mm, and 25 G 16 mm needles on the incidence of postvaccination fever and other systemic events such as drowsiness, loss of appetite, and vomiting are uncertain due to the very low quality of the evidence. Using 25 mm needles (either 23 G or 25 G) for intramuscular vaccination procedures in the anterolateral thigh of infants using the WHO injection technique probably reduces the occurrence of local reactions while achieving a comparable immune response to 25 G 16 mm needles. These findings are applicable to healthy infants aged two to six months receiving combination DTwP vaccines with a reactogenic whole-cell pertussis antigen component. These vaccines are predominantly used in low- and middle-income countries. The applicability of the findings to vaccines with acellular pertussis components and other vaccines with different reactogenicity profiles is uncertain.

Plain-language summary: We included five studies involving 1350 people. We rated the quality of the evidence from studies as very low, low, moderate, or high. Very low-quality evidence means that we are very uncertain about the results. High-quality evidence means that we are very confident in the results. There were problems with the design of some studies, and data were insufficient to answer some parts of our review question. The quality of the evidence from two studies was too low to allow us to draw any conclusions about the effects of the needles compared in the studies. However, there was sufficient evidence from the remaining three studies to allow us to reach conclusions. The three studies that allowed us to reach conclusions involved 1135 healthy infants aged mostly between two and six months. The infants were vaccinated in the thigh with either 25 G 25 mm (narrow, long needles), 23 G 25 mm (wide, long needles), or 25 G 16 mm needles (narrow, short needles). The needles were inserted at right angles (90° angle) into the skin and pushed down into the muscle of the thigh. The vaccines injected were combination vaccines designed to protect against several diseases including diphtheria (D), tetanus (T), whooping cough (pertussis), and Haemophilus influenzae type b disease (Hib). The vaccines all contained whole-cell pertussis (wP) vaccine antigens. These vaccines are commonly used in low- and middle-income countries but not in high-income countries. Our review findings are therefore most relevant to low- and middle-income countries. We found moderate-quality evidence that infants vaccinated in the thigh with 25 mm needles probably have fewer severe reactions (extensive redness and swelling in the thigh) after DTwP-Hib vaccination than infants vaccinated with 16 mm needles. We also found that the longer needles probably lead to fewer non-severe reactions such as mild swelling, tenderness, and redness after vaccination. The immune response to the vaccine is probably similar with the long and the short needles. We found low-quality evidence that the wide, long needle may slightly reduce the pain of the vaccination procedure compared with the narrow, long needle. We found moderate-quality evidence that the wide, long needle probably slightly reduces the duration of crying immediately following vaccination compared with the narrow, long needle. The differences in pain and crying between use of the wide and narrow needles are probably too small to be of any practical importance. We found low-quality evidence that infants vaccinated with the narrow, long needle may have slightly fewer non-severe reactions than infants vaccinated with the wide, long needle. We do not know if needle size has an effect on fever or other reactions that sometimes occur after vaccination including drowsiness, loss of appetite, and vomiting due to the very low quality of the evidence. The evidence in our review is current to October 2017.