Joseph Little

 Performance and potency of tetanus toxoid: implications for eliminating neonatal tetanus
Neonatal tetanus (NT) is a major cause of mortality in developing countries, with over 400,000 deaths estimated to occur annually. WHO has adopted the goal of eliminating NT worldwide, and a major strategy for its prevention is the administration of at least two properly spaced doses of tetanus toxoid (TT) to women of childbearing age in high-risk areas to protect passively their newborns at birth. In certain countries the locally produced TT vaccine has been shown to be subpotent, while other countries have reported NT among infants born to vaccinated women. An extensive review of production and quality control procedures was carried out between 1993 and 1995 in 8 of 22 TT-producing countries that also report NT cases, with a more superficial assessment being carried out in the remaining 14 countries. Only 4 of the 22 countries have a functioning national control authority to monitor TT production and vaccine quality. A total of 80 TT lots from 21 manufacturers in 14 of the 22 NT-reporting countries were tested for potency. Of these, 15 lots from eight manufacturers in seven countries had potency values below WHO requirements. TT potency can also be compromised by improper vaccine handling. To eliminate neonatal tetanus worldwide requires assurance that all doses of TT meet WHO production and quality requirements and that the field effectiveness of TT is monitored through systematic NT case investigations and assessment of coverage.
PIP:
Neonatal tetanus (NT) causes an estimated 400,000 deaths annually in developing countries. One major way to prevent NT is to administer at least two properly spaced doses of tetanus toxoid (TT) to women of childbearing age in high-risk areas in order to passively protect their newborns at birth. However, locally-produced TT vaccine in some countries has been found to be subpotent, while other countries have reported NT among infants born to vaccinated women. An extensive review of production and quality control procedures was conducted between 1993 and 1995 in 8 of 22 TT-producing countries which also report NT cases. A less exhaustive examination was conducted in the other 14 countries. Among the 22 countries which both report NT cases and produce TT, only Brazil, India, Indonesia, and Mexico have fully functioning national control authorities to monitor TT production and vaccine quality. 80 TT lots from 21 manufacturers in 14 of the 22 countries were tested for potency. 15 lots from 8 manufacturers in 7 countries had potency values below World Health Organization (WHO) requirements. TT potency can also be compromised by improper vaccine handling. If NT is going to be eliminated worldwide, all doses of TT must meet WHO production and quality requirements. Moreover, the field effectiveness of TT must be monitored through systematic NT case investigations and the assessment of coverage.

 Effects of freezing on DPT and DPT-IPV vaccines, adsorbed
This paper summarizes evaluation of whether DPT and DPT-IPV from Connaught Laboratories Ltd. are visually altered by freezing in response to concern that some adsorbed DPT products can be visually unchanged, despite loss of potency from freeze damage. Data from 80 vials tested under various conditions suggest that the shake test is ineffective in field conditions. Authors recommend that a temperature-monitoring device be included with vaccines during transport, either a min-max thermometer, temperature logger, or Freeze WatchTM indicators.

 Factors affecting the immunogenicity and potency of tetanus toxoid: implications for the elimination of neonatal and non-neonatal tetanus as public health problems
An estimated 400,000 deaths occur annually from neonatal tetanus (NT). In 1989 WHO adopted the goal of eliminating NT as a public health problem worldwide. To achieve this, and to control non-neonatal tetanus (non-NT), WHO recommends that newborns be passively protected at birth by the antepartum administration of at least two doses of tetanus toxoid (TT) to their mothers and that all children subsequently receive at least three doses of diphtheria-tetanus-pertussis (DTP) vaccine. For this strategy to be effective, the TT used must be immunogenic. Potential factors that may affect TT immunogenicity need to be evaluated if NT is to be eliminated and if non-NT is to be controlled. Although data are conflicting, concurrent malarial infection may decrease the immune response to TT; however, malarial chemoprophylaxis may enhance the immune response. Malnutrition does not appear to affect immunogenicity; nevertheless, one study suggests that vitamin A deficiency is associated with an impaired immune response. Although it has been postulated that placental transfer of tetanus antibody is impaired in African women, a survey of the published literature suggests that this is not the case. Freezing TT has been shown to decrease its potency, but its impact on immunogenicity needs more evaluation.
PIP:
An estimated 400,000 children die annually due to neonatal tetanus (NT). In 1989, the World Health Organization (WHO) adopted the goal of eliminating NT as a public health problem worldwide. To that end, and in order to control non-neonatal tetanus (non-NT), the WHO recommends that newborn infants be passively protected at birth by the antepartum administration of at least 2 doses of tetanus toxoid (TT) to their mothers and that all children subsequently receive at least 3 doses of diphtheria-tetanus-pertussis (DTP) vaccine. However, the TT employed must be immunogenic in order for the strategy to work. Although the data are conflicting, concurrent malarial infection may decrease the immune response to TT, while malarial chemoprophylaxis may enhance immune response. Malnutrition does not appear to affect immunogenicity, although a study suggests that vitamin A deficiency is associated with an impaired immune response. A survey of the published literature suggests that there is no basis for accepting the hypothesis that placental transfer of tetanus antibody is impaired in African women. Finally, freezing TT has been shown to decrease its potency, but its effect upon immunogenicity remains to be determined.

 Assessing the potency and immunogenicity of inactivated poliovirus vaccine after exposure to freezing temperatures
According to manufacturers, inactivated poliovirus vaccines (IPVs) are freeze sensitive and require storage between 2°C and 8°C, whereas oral poliovirus vaccine requires storage at -20 °C. Introducing IPV into ongoing immunization services might result in accidental exposure to freezing temperatures and potential loss of vaccine potency. To better understand the effect of freezing IPVs, samples of single-dose vaccine vials from Statens Serum Institut (VeroPol) and multi-dose vaccine vials from Sanofi Pasteur (IPOL) were exposed to freezing temperatures mimicking what a vaccine vial might encounter in the field. D-antigen content was measured to determine the in vitro potency by ELISA. Immunogenicity testing was conducted for a subset of exposed IPVs using the rat model. Freezing VeroPol had no detectable effect on in vitro potency (D-antigen content) in all exposures tested. Freezing of the IPOL vaccine for 7 days at -20 °C showed statistically significant decreases in D-antigen content by ELISA in poliovirus type 1 (p 

 Using long-range freeze-preventive vaccine carriers in Nepal: A study of equipment performance, acceptability, systems fit, and cost
Preventing vaccine freezing is one of the biggest challenges in vaccine management. Until 2018, vaccine carriers used in the immunization program lacked features to prevent vaccine freezing. Freeze-preventive vaccine carriers (FPVCs) have an engineered liner that buffers vaccines from direct exposure to frozen ice packs. A field evaluation of three FPVCs was conducted in 24 health posts in eastern Nepal. The objective was to evaluate the FPVCs’ performance, acceptability, systems fit, and cost, to inform prequalification and introduction planning. The study was carried out in two phases: in the first phase, FPVCs containing dummy vaccines (labeled “Not for Human Use”) were transported to outreach sessions along with a standard vaccine carrier (SVC); in the second phase, the FPVCs were used for transporting vaccines taken to outreach sessions and used for vaccinating eligible children. The study gathered quantitative and qualitative data from health workers, logbooks, and electronic temperature monitors placed inside and outside the FPVCs. Results indicate the FPVCs successfully prevented temperatures below 0 °C more than 99% of the time—except at one site, where ambient temperatures were below the minimum rated testing temperature specified by the World Health Organization. Internal cool-down times for the FPVCs were highly variable, as were mean kinetic temperatures, possibly driven by the wide range of ambient temperatures and higher-than-expected variations in freezer performance, which, along with the need to transport ice packs to some locations, affected ice-pack temperatures. Almost all health workers requested smaller, lighter-weight FPVCs but appreciated the FPVCs’ ability to prevent vaccines from freezing while avoiding undue heat exposure. FPVCs had benefit-cost ratios greater than 1 and hence good value for money. Results point to the importance of understanding the intended environment of use and the need for smaller, short-range as well as long-range carriers.