Vaccine cold chain in general practices: A prospective study in 75 refrigerators (Keep Cool study)

Autoři: Anika Thielmann aff001;  Marie-Therese Puth aff002;  Christine Kersting aff001;  Johannes Porz aff002;  Birgitta Weltermann aff001
Působiště autorů: Institute for General Practice, University of Duisburg-Essen, University Hospital Essen, Essen, Germany aff001;  Institute of General Practice and Family Medicine, University of Bonn, Bonn, Germany aff002;  Department of Medical Biometry, Informatics and Epidemiology, Faculty of Medicine, University of Bonn, Bonn, Germany aff003
Vyšlo v časopise: PLoS ONE 14(11)
Kategorie: Research Article
doi: 10.1371/journal.pone.0224972



Protecting vaccines from freeze damage is considered one of the most poorly addressed problems in vaccine management. Freezing may impair the potency especially of adsorbed vaccines. The Keep Cool study aims at ensuring optimal vaccine storage conditions in general practices. This publication analyses the baseline data using standardised temperature recordings.


This prospective study in German general practices analysed 7-day temperature recordings of refrigerators used for vaccine storage. Temperatures were recorded continuously using a standardised data logger with an accuracy of ±0.4 °C. The prevalence rates of refrigerators within the target range (2 to 8 °C) and of those reaching critically low temperatures (≤0 °C) were calculated. In addition, the cumulative time and the duration of single episodes beyond the target range were computed. To assess for structural deficits, the prevalence of refrigerators with a cycling of >5 °C was determined. Generalised linear mixed models were applied to analyse correlating factors between the dependent variables ‘within temperature range’ and ‘reaching critically low temperatures’ with practice characteristics.


The study included 64 of 168 practices (38.1% response rate) with 75 refrigerators. The prevalence of refrigerators with temperatures within the target range was 32.0% (n = 24), and 14.7% (n = 11) reached critically low temperatures <0 °C. 44.0% of refrigerators (n = 33) showed temperatures >8 °C and 28.0% (n = 21) <2 °C. Of the 168 hours recorded per refrigerator, the average cumulative time >8 °C was 49 hours, <2 °C 75 hours and ≤0 °C 74 hours. The longest consecutive period of critically low temperatures was 168 hours (mean: 39±53). The prevalence of refrigerators with a cycling range of >5 °C was 29.3%.


Given the importance of immunisation, the results of our study call for action, as two-thirds of the refrigerators exhibited cold chain breaches and 15% reached critically low temperatures threatening vaccine potency.

Klíčová slova:

Hepatitis B – Pediatrics – Physicians – Preventive medicine – Vaccines – Temperature analysis – Thermometers – Yellow fever


1. World Health Organization, Unicef. Global Immunization Data; 2013. Accessed 17 January 2014.

2. World Health Organization. Temperature sensitivity of vaccines. Department of Immunization, Vaccines and Biologicals, World Health Organization. 2006: 1–62.

3. Paul-Ehrlich-Institut. Ausflückungen in Adsorbatimpfstoffen. Bulletin zur Arzneimittelsicherheit—Informationen aus BfArM und PEI; 2012: 12–16.

4. McColloster P, Vallbona C. Graphic-output temperature data loggers for monitoring vaccine refrigeration: implications for pertussis. Am J Public Health. 2011; 101: 46–47. doi: 10.2105/AJPH.2009.179853 21088272

5. Lerman SJ, Gold E. Measles in children previously vaccinated against measles. JAMA. 1971; 216: 1311–1314. 4102807

6. Onoja AL, Adu FD, Tomori O. Evaluation of measles vaccination programme conducted in two separate health centres. Vaccine. 1992; 10: 49–52. doi: 10.1016/0264-410x(92)90419-k 1539460

7. Boros CA, Hanlon M, Gold MS, Roberton DM. Storage at− 3 C for 24 h alters the immunogenicity of pertussis vaccines. Vaccine. 2001; 19: 3537–3542. doi: 10.1016/s0264-410x(01)00063-9 11348721

8. McIntyre RC, Preblud SR, Polloi A, Korean M. Measles and measles vaccine efficacy in a remote island population. Bull World Health Organ. 1982; 60: 767. 6983927

9. Salisbury D, Ramsay M, Noakes K. Immunisation against infectious disease. 3rd ed. London: TSO; 2006.

10. World Health Organization. Aide mémoire for prevention of freeze damage to vaccines. WHO/IVB/07.09. Geneva; 2007.

11. Chojnacky M, Miller W, Ripple D, Strouse G. Thermal Analysis of Refrigeration Systems Used for Vaccine Storage (NISTIR 7656); 2009.

12. Chojnacky M, Miller W, Strouse G. Thermal Analysis of Refrigeration Systems Used for Vaccine Storage (NISTIR 7753). Report on Pharmaceutical Grade Refrigerator and Household Refrigerator/Freezer; 2010.

13. Center for Disease Control. National Center for Immunization and Respiratory Diseases. Vaccine Storage & Handling Toolkit: Centers for Disease Control and Prevention; 2018.

14. Hanson CM, George AM, Sawadogo A, Schreiber B. Is freezing in the vaccine cold chain an ongoing issue? A literature review. Vaccine. 2017; 35: 2127–2133. doi: 10.1016/j.vaccine.2016.09.070 28364920

15. Thielmann A, Sikora M, Schnell U, Gesenhues S, Weltermann B. Impfkühlschrank-und Impfstoffmanagement in Hausarztpraxen: Eine repräsentative, Web-basierte Umfrage unter Hausärzten (Keep Cool I). Das Gesundheitswesen. 2015; 38: 1–6.

16. Weltermann BM, Markic M, Thielmann A, Gesenhues S, Hermann M. Vaccination Management and Vaccination Errors: A Representative Online-Survey among Primary Care Physicians. PloS one. 2014; 9: e105119. doi: 10.1371/journal.pone.0105119 25118779

17. Thielmann A, Viehmann A, Weltermann BM. Effectiveness of a web-based education program to improve vaccine storage conditions in primary care (Keep Cool): study protocol for a randomized controlled trial. Trials. 2015; 16. doi: 10.1186/s13063-015-0824-9 26169675

18. Thielmann A, Puth M-T, Weltermann B. Visual inspection of vaccine storage conditions in general practices:. A cross-sectional study of 75 vaccine refrigerators (Keep Cool study). PloS one: in Revision.

19. Gazmararian JA, Oster NV, Green DC, Schuessler L, Howell K, Davis J, et al. Vaccine storage practices in primary care physician offices: assessment and intervention. Am J Prev Med. 2002; 23: 246–253. doi: 10.1016/s0749-3797(02)00512-3 12406478

20. Bell KN, Hogue C, Manning C, Kendal AP. Risk factors for improper vaccine storage and handling in private provider offices. Pediatrics. 2001; 107: e100. doi: 10.1542/peds.107.6.e100 11389298

21. Page SL, Earnest A, Birden H, Deaker R, Clark C. Improving vaccination cold chain in the general practice setting. Aust Fam Physician. 2008; 37: 892. 19002316

22. Gold MS, Martin L, Nayda CL, Kempe. Electronic temperature monitoring and feedback to correct adverse vaccine storage in general practice. MJA. 1999; 171: 83–84. 10474583

23. Lewis PR, Reimer RF, Dixon AJ. Evaluating the efficacy of vaccine storage in the general practice setting. Aust N Z J Public Health. 2001; 25: 547–550. doi: 10.1111/j.1467-842x.2001.tb00322.x 11824993

24. Australian Government. National vaccine storage guidelines. Strive for 5. 2nd ed. Canberra: Dept. of Health and Ageing; 2013.

25. Matthias DM, Robertson J, Garrison MM, Newland S, Nelson C. Freezing temperatures in the vaccine cold chain: a systematic literature review. Vaccine. 2007; 25: 3980–3986. doi: 10.1016/j.vaccine.2007.02.052 17382434

26. Davaalkham D, Ojima T, Wiersma S, Lkhagvasuren T, Nymadawa P, Uehara R, et al. Administration of hepatitis B vaccine in winter as a significant predictor of the poor effectiveness of vaccination in rural Mongolia: evidence from a nationwide survey. J Epidemiol Community Health. 2007; 61: 578–584. doi: 10.1136/jech.2006.051375 17568048

27. Lee S, Lim H-S, Kim O, Nam J, Kim Y, Woo H, et al. Vaccine Storage Practices and the Effects of Education in Some Private Medical Institutions. J Prev Med Public Health. 2012; 45: 78–89. doi: 10.3961/jpmph.2012.45.2.78 22509448

28. Viehmann A, Thielmann A, Gesenhues S, Weltermann BM. Repräsentieren akademische Hausarztpraxen die hausärztliche Regelversorgung. Eine methodische Annäherung. Do Academic Family Practices Reflect Routine Primary Care? A Methodological Approach. Z Allg Med. 2014; 90: 354–359.

Článek vyšel v časopise


2019 Číslo 11