Effects of paracetamol use on the immune response after hepatitis B vaccination

Paracetamol (Acetaminophen) is an over the counter medicine and considered safe
when used according to the
instruction leaflet. The 'consultatiebureau' advices to use paracetamol as a
remedy for pain and fever after vaccination in
small children. Individuals who have experienced fever or pain after
vaccination are advised to use paracetamol
prior to further vaccinations. Recently published results indicates a negative
influence on vaccination response (lower
antibody titers) in infants that were prophylactically administered paracetamol
prior to vaccination to prevent fever. A lower vaccination response could
result in lower effectivity of vaccination. This effect has not been shown in
adults to date. Also, it is not known if there is an important role for timing
of paracetamol - prophylactic or therapeutic use - in this effect on
vaccination response. It is important to gain insight into the effects of
paracetamol use during vaccination. Health organisations should have enough
information to offer a good advice about the use of paracetamol
during vaccination procedures.

Phase 1: Investigate a possible suppressing effect of prophylactic paracetamol
use in adults on the response of the hepatitis B vaccination.
Phase 2: Study the association between timing of the use of paracetamol during
hepatitis B vaccination and the development of the immune response in adults.

Two-phase study. In phase 1 we will investigate if prophylactic use of
paracetamol has an effect on the immune response of adults after a hepatitis B
vaccination. In phase 2 we will investigate if there is a difference between
prophylactic and therapeutic use of paracetamol on the vaccination response.
The first month of phase 1 and 2 of the study is interventional, after that it
will turn into an observational study.
It is important to realize that we only start with phase 2 of this study if we
find any effects of paracetamol on the immune response after vaccination in
phase 1.

Phase 1: There is one intervention and one control group. The intervention
group have to take paracertamol for 24 hours (1000 mg / 8h) starting directly
after the vaccination. The control group takes no paracetamol. Every
participant will take paracetamol according to the intervention or control
group during the first and second hepatitis B vaccinations.

Phase 2: There are two invervention groups that have to take paracertamol for
24 hours (1000 mg / 8h). Timing of the
paracetamol use is different: group 1 will take paracetamol at the time of
vaccination (prophylactic use) and group 2 starts
taking paracetamol 6 hours after vaccination (therapeutic use 1). Every
participant will take paracetamol according to one of the three groups during
the first and second hepatitis B vaccinations.

Participants who take paracetamol prophylactically or therapeutically will
probably suffer less from side effects of
vaccination, such as fever and pain. Participation to this study will
significantly contribute to the scientific knowledge,
resulting in a better advice of health organizations about the use of
paracetamol during vaccination procedures.
There is a possibility that some participants could have a reduced antibody
titer at the end of the study. The antibody
concentration of every participant will be determined and evaluated, like is
routinely done after hepatitis B vaccination. An
extra booster vaccination will be offered if the antibody concentration is too
low for protection against hepatitis B. This is
the normal policy and is not different for students that participate in this
study and those that do not.
The study population exists of young health care students that are routinely
vaccinated against hepatitis B. In the
vaccination protocol a blood sample is routinely taken 1 month after the third
vaccination and for this study we will draw 21
mL. of extra blood. An extra blood sample (7 ml.) will be taken specifically
for this study prior to the third vaccination.
Antibody titers (prior to and 1 month after the third vaccination) and
functionality of lymphocyte subpopulations (1 month after the third
vaccination) will be determined in the blood.