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ANNEX 4 Vaccine effectiveness
VACCINE EFFECTIVENESS
(73-74)
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1. Theory
Vaccine effectiveness (VE) refers to vaccine protection achieved in the field within a vaccination programme. This may differ from vaccine efficacy, which refers to protection under ideal conditions.
Vaccine effectiveness can vary unpredictably and should be monitored, particularly when there are outbreaks occurring within a vaccination programme. For human medicine, evaluation of vaccine effectiveness is a key step in the assessment of vaccines after they have been licensed.
Vaccine protection in the field may differ from protection achieved under ideal conditions owing to poor adherence to cold chain and shelf life requirements. In addition, different batches of vaccine may have different potencies, and individual immune responses to vaccination will vary.
Vaccine effectiveness is typically calculated by comparing incidence of disease or infection in vaccinated animals with incidence in unvaccinated animals that were exposed to a similar level of virus using the equation:
VE = (RU –RV)/RU (equation 1)
where RU is the incidence risk or rate in the unvaccinated population, and RV is the incidence in those vaccinated.
The equation can be reformulated as:
VE = 1 – RV/RU (equation 2)
and it is normally given as a percentage.
The data needed to calculate VE are often collected in field studies (27).
Several different designs are possible. One simple design based on investigation of outbreaks is described in detail below. Readers are referred to other texts for details of other designs (8, 27, 33). Many of the methods are not possible in disease-free populations, as they require cases of disease.
2.1 Outbreak selection
– Select a large farm or village that has vaccinated within the last six months but subsequently experienced an outbreak of FMD (several adjacent villages/farms affected by the same outbreak may be assessed in the same investigation).
– VE is investigated as soon as the outbreak has finished (the tail-end of an outbreak may be adequate).
– There must be good records of which animals were vaccinated. Small-holdings may remember details adequately.
– Farmers must be aware of which animals developed
FMD.
– There must be no recent history of exposure to FMD prior to the outbreak (in the previous three years).
– Additional vaccination performed during the outbreak will complicate the investigation.
2.2 Sampling and data collection (templates are included)
– Details of local livestock management, vaccination and
FMD history are gathered (Table 9).
– Households/groups with known FMDV exposure are visited, that is, those with cases or known contact with cases. If there is insufficient time to include all eligible households/groups, a random sample should be selected. Failing that, equal proportions of households/ groups may be systematically selected from different geographic sections of a village or large farm.
– Within households, details of whether an animal was affected by FMD and details of vaccination are then collected for each animal. Animals are blood sampled (this may include only cattle 24 months old). All cattle receive an oral examination for FMD lesions on the hard palate, gums, lips and tongue (extruded) except when impossible or unsafe.
– Oral vesicles and blisters typically appear about four days after infection. They typically heal within ten days, leaving a scar that becomes less visible over time, although foci lacking lingual papillae may be visible for weeks (1). As the appearance of clinical signs is strongly correlated with shedding and transmission, this is a relevant outcome for assessing vaccine protection.
– Cattle under six months of age can be excluded, as they may have maternally derived antibody protection.
– An investigation may take three trained staff approximately eight days with poor handling facilities requiring at least 250 cattle, preferably many more, to be sampled, although a sample size calculation should be performed.
Table 9. Information collected during a retrospective cohort vaccine effectiveness investigation
Holding details:
– Province, district, village and farmer name, type of grazing (none, private, common), herd size, date of first and last FMD case
Animal details: – Animal ear tag number, age, sex, housing group, breed – FMD (i) reported by farmer, (ii) seen on examination, (iii) detected on serology
Vaccination details:
– Date of last vaccination, type and batch number of FMD vaccine received last, number of vaccine doses received in lifetime, time between outbreak and last vaccination, group vaccine coverage at last round of vaccination (calculated from data)
2.3 Analysis
The simplest analysis is to look at incidence (number of cases/number of animals) according to the number of doses of vaccine that animals have received in their lifetime. Consider an animal diseased if FMD was reported by the farmer or detected on examination. Infection status can be assessed by NSP serology if purified vaccines are used.
The effectiveness of the last dose of vaccine may be assessed using equation 1 or 2, preferably making a separate estimate for cattle that have received different numbers of vaccine doses over their lifetime. Where vaccination is rigorously performed, vaccination will be highly correlated with age, and it may not be possible to separate the protective effect of age from that of the vaccine effect. Where unvaccinated cattle of all ages are present, this effect may be controlled for using multivariable regression techniques or Mantel–Haenszel methods. If this is not done, the raw unadjusted VE is likely to be biased and misleading. Other confounders should also be investigated. However, conclusions may still be made about vaccine protection by observing incidence in vaccinated animals and judging whether or not it is unacceptably high, particularly in those animals vaccinated many times.
Strengths: This method is relatively inexpensive, it can be conducted rapidly and it is likely to obtain a result.
Weaknesses: The method relies on farmer recollection and records, and so cross-checking of different sources is recommended. Outbreaks investigated could be isolated cases of vaccine failure and may not reflect typical vaccine performance. Unvaccinated control animals may not always be present.
For more details see Knight-Jones et al. (27).
The past decade has been an exciting period for the control of foot and mouth disease (FMD). The Progressive Control Pathway for FMD (PCP-FMD) was developed to provide a novel stepwise methodology for a cost-effective, risk-management approach to FMD control, and it is now the backbone for the implementation of the FAO-OIE Global Foot and Mouth Disease Control Strategy (2012). The costs of vaccination, one of the most important tools for managing this devastating disease, represent 90% of the total expense of FMD control, so it is essential to plan and evaluate vaccine and vaccination effectiveness to convince decision makers to continue implementing rigorous control measures. These guidelines provide expert advice on how to ensure the success of vaccination programmes. They are designed to guide and assess national or sub-national vaccination programmes at various stages of the PCP-FMD, and will be equally helpful for countries looking to regain FMD-free status following an incursion of FMD, in accordance with the standards in the OIE Terrestrial Animal Health Code. They stress the importance of having up-to-date information on the virus strains circulating in a given area and highlight the importance of effective Veterinary Services in the implementation of FMD control programmes. Given that most readers and users may have a broad background in disease management and may not necessarily be FMD specialists, the contributors have sought to provide a balance of scientific background, methodology and practical examples.
