[Serological study carried out in Cambodia during a tetanus vaccination in adults]

In 1997, the Ministry of Health tested the feasibility and serological activity of a two-dose vaccine at one year interval within a catch-up tetanus immunization programme in a rural population. In the district of Angkor Thom in the Siem Reap province (15,000 inhabitants), a team of nurses and administrative clerks travelling by motorcycle, conducted between February 1998 and February 1999 an EPI and tetanus immunization of the whole population gathered in meeting points. In 132 childbearing age female volunteers, 49 following a two-dose schedule at one year interval, and 70 following a WHO three-dose schedule, with two doses at one month interval and a booster dose one year later tetanus antibodies have been measured before vaccination, one year after the first dose or the two first doses, and six months after the second or third dose of vaccine. 129 male volunteers of the same age were also recruited in the serological study following only the two-dose schedule. The titration was done first with monoantigen ELISA, then with mouse seroneutralisation, the reference method for measuring tetanus seroprotection. Only 148 (57%) volunteers completely attended the serological study Compared to seroneutralisation, sensitivity for seroprotection with ELISA was 89% (CI95%: 85%-94%) and specificity 84% (CI95%: 81%-89%). The coverage of the general population vaccinated with two doses, in both sexes and in all age-groups, increased on average from 5% to 70%. The three-dose schedule gave significantly more protection than the two-dose schedule in women tested with seroneutralisation. On a first sample in those with no protective antibodies and testifying they had not been vaccinated before, 51% of these volunteers after one dose and 93% after two doses acquired protective antibodies. On first sample, 52% of female volunteers had protective antibodies in seroneutralisation, against 11.7% in men. 14% of subjects tested in ELISA and 6.8% tested in seroneutralisation showed in a second sample a decrease in titres, although they had received a tetanus vaccine. For unprotected volunteers on first sample and testifying they had not been vaccinated before, neither age nor past chronic cutaneous lesions or cows living around their houses, two possible sources of contact with CI. tetani, increased significantly seroconversion. Only female volunteers were significantly more seroconverting (81%) compared to men of same age (51%) (RR: 1.60, CI95%: I. 17-2.18) suggesting a memory bias in women supposed to be vaccinated by EPI. 30% of volunteers in ELISA and 14% in seroneutralisation showed spontaneous protecting antibodies in the first sample without having any document or memory of a past tetanus vaccination. Tested by seroneutralisation, no relation was to be found for having spontaneous antibodies with past chronic cutaneous lesions and cows living around their houses. Only the eldest (35-45 y.o.) female volunteers showed significantly more spontaneous antibodies (RR: 3.83, CIs%: 1.74-8.2) than men in the same age-group. A memory bias may be found also in this female age-group. Good serological response should encourage implementation of a catch-up tetanus vaccination in this country considering the large number of unprotected adults, mainly male adults. Due to problems with notification and recalling past vaccinations, only a prospective study in an unimmunized large cohort, studying all possible factors of tetanus toxin neutralisation, could confirm the existence and cause of spontaneous antibodies. Excluding vaccination in at-risk population for such a study would be however ethically unacceptable.