Stopping vaccination

each selected location, a sample size of animals is taken that would detect infection given that if the infection is present within the location, a given proportion of animals would be expected to be infected and at a given level of confidence. For example, it may be decided that if the infection is present, at least 1 percent of locations would be infected and that within an infected location, at least 5 percent of animals would become infected. The level of confidence of detection is often 95 percent at both levels. This design would then be described as being 95/1 at the level of the location and 95/5 within each sampled location.

It is recommended that the exact design and sample size estimation be undertaken by an experienced epidemiologist with training in this type of sample design and that local conditions be well-understood by this person during the design phase.

Sample size tables are easily available, as is software that can generate sample sizes for very large or smaller population sizes; however, their use without taking local conditions into account will often lead to a sample size which is either too large for the available resources or too small for the degree of confidence required. The major factors influencing the size of the sample are the expected prevalence within a herd if it were to be infected and the degree of certainty of detecting an infection if it is present. The expected proportion of herds that would be infected is also important.

Also important are the characteristics of the assay used and, particularly, the sensitivity and specificity of the assay. Ideally, the assay would be both highly sensitive and highly specific in order to avoid false positive and false negative results, but this is not always available, technically possible or within the budget available. In all designs, the sensitivity of the test must be taken into account when selecting the sample size, resulting in an increased size to prevent a herd being identified as negative when it is, in fact, infected.

A more difficult problem is that of false positive results. Virtually no test is 100 percent specific, and given the often large numbers of negative samples that are tested, some false positive results are to be expected. How these animals and herds are dealt with can be politically difficult. They should certainly be revisited and carefully examined for signs of disease. Known susceptible sentinel animals could be introduced. It may be possible to rule out infection through careful analysis of the results or through the use of complementary assays (i.e. enzyme linked immunosorbent assay (ELISA) and virus neutralization).

For all of the above reasons, it is strongly recommended that an experienced epidemiologist be closely involved in the design of the survey and the analysis of the results.

stoPPIng vaccInatIon

The use of vaccination during an outbreak can complicate the move from control to recovery phases. The issue of an exit strategy from vaccination should be considered before it is commenced, as mentioned in the planning stage.

Vaccination may make the demonstration of absence of infection difficult to achieve. Many vaccines are known to prevent disease, and while they decrease shedding and spread of the pathogen, they may not eliminate all infection. In these circumstances, the vaccine may mask infection, so that the demonstration of antibodies will not necessarily be equivalent to a demonstration of freedom from infection.

In some cases, there are assays that can differentiate between infection with field pathogens and response to vaccination, which would allow a DIVA testing regime. These