Academic journal article Bulletin of the World Health Organization

Performance and Potency of Tetanus Toxoid: Implications for Eliminating Neonatal Tetanus

Academic journal article Bulletin of the World Health Organization

Performance and Potency of Tetanus Toxoid: Implications for Eliminating Neonatal Tetanus

Article excerpt


In 1989 the World Health Assembly adopted a resolution calling for the global elimination of neonatal tetanus (NT) as a public health problem by 1995.(a) In this respect, one of the key strategies identified by WHO is the achievement and maintenance, among women of childbearing age in high-risk areas, of high coverage levels for at least two doses of tetanus toxoid (TT).(b) Studies have demonstrated that two doses of properly spaced TT protect the offspring of female recipients against NT (1-3). To be maximally effective, the first two doses of TT (TT1 and TT2) should be given at intervals of at least 4 weeks, with the ideal interval between TT2 and birth being at least 4 weeks (4,5)(c) In addition, the interval between TT1 and TT2 and that between TT2 and the delivery of the child are critical to ensuring good immunogenicity (6). The proportion of women whose titres reach a protective level becomes greater with increasing intervals between TT1 and TT2 and between TT2 and birth. WHO estimates that in 1994, a total of 46% of pregnant women had received two doses of TT (7).(d)

To eliminate NT globally. not only must TT coverage levels be raised but the vaccine must be safe and potent. There have been reports of NT occurring in infants born to women who had received at least two doses of TT (8,9), causing some workers to question its potency (8,10). However. as with any vaccine. some seroconversion failures arc to be expected. even when it is administered at the appropriate intervals. Thus, case reports of NT among infants horn to vaccinated women do not necessarily imply that TT is not effective. Nevertheless. monitoring case reports of NT and the vaccination status of the mothers concerned is important since this provides information about the field performance of TT. Therefore. reports of NT cases in infants born to vaccinated women (i.e. potential TT failures) must be evaluated to determine whether the observed number of failures is greater than expected and whether the doses were properly spaced. If either of these is found to be the case. further evaluation of TT production and effectiveness would be warranted.

Field epidemiological studies in Bangladesh and in selected areas of Pakistan have demonstrated that the effectiveness(e) of two doses of TT in preventing NT was [is less than] 50% (11,12) In Bangladesh, subsequent inspection of production facilities revealed multiple deficiencies in TT production, and locally produced TT was determined to be subpotent by two WHO reference laboratories (11). In Pakistan, UNICEF-supplied TT collected from the field in 1992 in selected areas and nationally produced TT (used for the army but not in the national Expanded Programme on Immunization (EPI)) were tested for potency. The potency of the UNICEF-supplied TT collected from the field several years after the observations on TT field effectiveness was borderline, although the potency of the vaccine at release had been adequate, and the potency of the nationally produced TT was subpotent.(f)

In this article we review two aspects of monitoring the performance of TT: published reports of NT cases from a review of the literature that included information on the vaccination status of the mothers of infants who developed NT; and currently available information on the quality of TT manufactured in countries where NT cases still occur.

Sources of data

Data on vaccination coverage, reported disease incidence, and NT estimated deaths were obtained from the EPI Information System, Global Programme for Vaccines and Immunizations, WHO, Geneva.(d) Information on TT production procedures, quality. and potency were obtained through the Task Force on Situation Analysis (TFSA) of the Children's Vaccine Initiative. The TFSA has identified as high priority for production assessments, vaccine-producing countries that also report NT cases. Manufacturers in 10 of these countries (Bangladesh, Brazil, Egypt, India, Indonesia, Islamic Republic of Iran, Mexico. …

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