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3 JUSTIFICACIÓN

5.3 Análisis de amenaza de la zona de estudio

The burden of leptospirosis was estimated in terms of DALYs.

Disability-Adjusted Life Years (DALYs)

DALYs is a measure of years of healthy life lost due to disease estimated by adding years of life lost (YLL) and years lost due to disability (YLD).

DALY s=Y LL+Y LD (4.1)

The first argument in Formula 4.1 (YLL) takes into account mortality due to leptospirosis, which is extremely low in New Zealand and therefore ignored. The second argument in DALYs estimation (Formula 4.1) is YLD. It quantifies to what extent a person is disabled during illness and it is calculated using Formula 4.2, where I represents the number of incident cases; DW the disability weight, indicating how ill or disable a person is during illness; and D the duration of illness.

Y LD=I×DW ×D (4.2)

Annual incidence of leptospirosis

Estimates of the association between Leptospira sero-status and influenza-like illness were obtained from three studies targeting occupational groups at risk of

leptospirosis in New Zealand. The first investigation focused on abattoir work- ers that were blood sampled twice with an adjusted interval of one year to as- sess sero-conversion to Leptospira serovars Hardjo-bovis and Pomona and the as- sociated incidence of influenza-like illness (Dreyfus et al. 2015b). The other two investigations addressed the sero-prevalence of Hardjo-bovis, Pomona, Leptospira bogpetersenii serovars Ballum (Ballum) and Tarassovi (Tarassovi), and Leptospira interrogans serovar Copenhageni (Copenhageni) among veterinarians (Sanhueza et al. 2015) and farmers of beef cattle, sheep, and deer (Chapter 2). In both studies, participants were asked to recall influenza-like illness episodes in the 18 months prior to sampling.

The population attributable risk (PAR) is a measure of association that indicates the incidence risk of disease in the population over a specified time period that can be attributed to exposure. It is calculated as the incidence in the total population minus the incidence in the non-exposed group. PAR was approximated from these three studies as the risk of influenza-like illness associated with Leptospira sero- positivity. A Bayesian model was used to estimate PAR and its 95% probability intervals (Pirikahu et al. 2016). The estimated PARs of farmers and veterinarians were adjusted to a one-year incidence by a factor of 2/3 since the participants had been questioned about influenza-like illness for an 18 months period.

The population of abattoir workers (n=16,224), people farming dairy or beef cattle, sheep, and/or deer (n=70,461) and veterinarians (n=1,989) in New Zealand were obtained from the 2013 census according to the Australian and New Zealand Standard Classification of Occupations (ANZSCO) (Anonymous 2013). The number of farmers at risk of leptospirosis was reduced using estimates of vaccine coverage in each livestock species (see Cost of vaccination for details) and mean vaccine effi- cacy of 82% (Chapter 5). The number of farmers was multiplied by one minus the proportion of farms that vaccinate against leptospirosis and the PAR to obtain the expected number of farmers having influenza-like illness attributed toLeptospira in- fection each year. Prevalence data were not available for dairy cattle workers. Thus, to estimate leptospirosis incidence, the specific PAR for farmers of beef cattle, sheep and/or deer was applied to this occupational group.

The PAR for groups not at risk of occupational leptospirosis, i.e. without oc- cupational contact with animals, could not be approximated from available data as

4.3. MATERIALS AND METHODS 111 equivalent studies had not been done for such groups, so public surveillance data were used. During the last 14 years, on average 18.1% of notified cases were peo- ple in low occupational risk groups (ESR 2002-2015). The number of leptospirosis cases in abattoir workers, farmers and veterinarians was assumed to reflect 81.9% of the cases in the population. Hence, the number of cases in occupational groups not at risk of leptospirosis was calculated as the expected number of cases in high risk occupational groups multiplied by the ratio 18.1/81.9. The total New Zealand working population used in the simulation was 3,670,750 people (Anonymous 2016).

Based on data of Dreyfus et al. (2015b), a proportion of 0.136 (95% CI 0.048– 0.333) of incident cases was assumed to develop a severe illness and the remaining 0.864 a mild influenza-like illness. Uncertainty was added by fitting a Beta distribu- tion with mode of 0.136 and upper 95% CI as 95% upper boundary. The number of mild infections was the difference between the total number of cases and the number of severe cases. It was also assumed that 30.2% (95% CI 24.2–36.2) of the severe cases would experience post-acute sequelae of disease (Goris et al. 2013). For this, a Beta distribution of mode 0.302 and 95% upper boundary of 0.362 was used.

Duration of illness and disability weights

An acute episode of severe illness was observed to last for 16 days (Goris et al. 2013). To simulate this value, a Poisson distribution with a mean of 16 days was used. For the duration of mild illness, a Poisson distribution with a mean of four days was used. This value was approximated from the 4.4 days off-work that abat- toir workers spent due to influenza-like illness (Dreyfus et al. 2015b).

The duration of persistent complaints, observed in The Netherlands by Goris et al. (2013), was used to simulate the duration of post-acute sequelae. For this, a Geo- metric distribution with a probability parameter of 0.065 was used in the stochastic simulation.

The 95% confidence intervals for disability weights for leptospirosis were taken from values observed for infectious diseases after an acute severe illness (0.139– 0.298), acute moderate illness (0.033–0.081) and post-acute sequelae (0.170–0.355) (Salomon et al. 2012). Uniform distributions were fitted to simulate these values

using lower and upper boundaries as minimum and maximum values.