Missed doses during vaccinations- Are they a concern?

Most countries ensure that their population is protected by having national programs of vaccine delivery and strong recommendations. I am not of the autism school, so I support such programs. However  I thought of writing this blog due to doctor’s reactions to missed vaccine doses.

Post maternity leave, when most working women rejoin duties ,  upto two doses of primary vaccines have mostly been   administered. However, once on duty, due to exigencies of work,  the remaining doses could be delayed. The doctor’s reaction often is, how can you miss the schedule, risk to the baby , do it as soon as possible blah blah , making the poor mother feel guilty, tense, anxious, leading to hot debates and arguments within the family. Is a missed /delayed dose worth the anxiety? Let us see what science says. Let us also look at various recommended schedules and some clinical studies

Principle of vaccination

Initial doses prime the subject as body  recognises a foreign/potentially pathogenic antigen. Initial defence is launched, basal levels of antibodies are generated and a memory is created. Subsequent/Booster dose is like a reinfection. Memory cells are activated, a massive response generated and antibody levels grow exponentially. Hence most vaccines are administered as a multiple dose schedule. All recommendations also mention a catch up schedule where the first does itself is started late in life. But we are discussing missed doses.

Schedules

Let us first look at the Hib, DPT vaccine schedule. IAP recommends 6,10, 14 weeks and booster at 18-24 months. USA recommends 2,4,6 months, UK 2,3,4 months, and South and West Australia 6 weeks,4 months and 6 months. The timing of booster also differs amongst countries.

Let us now look at hepatitis B. IAP recommends  0, 6 wks and 6 mths,  South Africa and Nigeria  0,6,10,14 wks, UK 0,1,2,12 mths, USA 0, 1-2 mths, 6-18 mths, Australia South and West 0, 6 wks, 4 mths , 6 mths. It is obvious that while all countries are concerned about vertical transmission at birth the rest depends on endemicity and national burden of the disease.

In practice all these regimens are equally effective. There are numerous studies using different schedules all giving excellent seroconversion.  The more the gap between doses better was the seroconversion. Obviously the schedule is not important.

Dose of antigens

Surprisingly even if the amount of antigen used for immunization is reduced, it results in adequate seroconversion, as has been seen in case of hepatitis B. In case of rabies vaccine the intradermal route uses one fifth the dose of the intramuscular route and yet provides effective protection. So amount injected is also not an issue

In fact there is no uniform scheme of vaccination worldwide. Schemes are devised based on disease burden in the country and convenience and scientific validation of  using various vaccines simultaneously.

A change in schedule means multiple large long term studies involving millions.  Hence change to a better schemes cannot be frequently propogated due to regulatory and commercial compulsions

To conclude

• It is important to complete as much immunisation as possible in the 1^st six months, and the whole course by 2  years
• But delay of a dose, or even missing a dose should not be of grave concern because
  • Various dose regimens give equal protection
  • Vaccines with lesser amount of antigenic material or in smaller doses also provide protection
  • Later the subsequent dose better the protection

References

• IAP schedule of immunisation
• Australian national immunisation schedule2015
• US catchup schedule2015
• WHO immunisation table positionpaper2015
• UK immunisation schedule
• Vaccine Schedules for South Africa for 2015
• Agladioglu SY et al , Infection (2011) 39:489–490
• Campagne G et al , J. Trop. Med. Hyg., 59(5), 1998, pp. 837–842
• Heath PT et al, Arch Dis Child 2002;86:396–399
• Phadke MA et al, Indian Paediatrics 1997. 34:779
• Espinoza et al. BMC Infectious Diseases 2010, 10:297
• Hadida A et al. Tropical Medicine and International Health 1998. 3:95-99
• Lee H et al. J Korean Med Sci 2010; 25: 90-6
• Marshal H et al International Journal of Infectious Diseases (2010) 14, e41—e49

 – Dr Vishwas Sovani , January 2018