Quarantine for pandemic influenza control at the borders of small island nations

Abstract

Background: Although border quarantine is included in many influenza pandemic plans, detailed guidelines have yet to be formulated, including considerations for the optimal quarantine length. Motivated by the situation of small island nations, which will probably experience the introduction of pandemic influenza via just one airport, we examined the potential effectiveness of quarantine as a border control measure.

Methods: Analysing the detailed epidemiologic characteristics of influenza, the effectiveness of quarantine at the borders of islands was modelled as the relative reduction of the risk of releasing infectious individuals into the community, explicitly accounting for the presence of asymptomatic infected individuals. The potential benefit of adding the use of rapid diagnostic testing to the quarantine process was also considered.

Results: We predict that 95% and 99% effectiveness in preventing the release of infectious individuals into the community could be achieved with quarantine periods of longer than 4.7 and 8.6 days, respectively. If rapid diagnostic testing is combined with quarantine, the lengths of quarantine to achieve 95% and 99% effectiveness could be shortened to 2.6 and 5.7 days, respectively. Sensitivity analysis revealed that quarantine alone for 8.7 days or quarantine for 5.7 days combined with using rapid diagnostic testing could prevent secondary transmissions caused by the released infectious individuals for a plausible range of prevalence at the source country (up to 10%) and for a modest number of incoming travellers (up to 8000 individuals).

Conclusion: Quarantine at the borders of island nations could contribute substantially to preventing the arrival of pandemic influenza (or at least delaying the arrival date). For small island nations we recommend consideration of quarantine alone for 9 days or quarantine for 6 days combined with using rapid diagnostic testing (if available).

Figure 1

Performance of quarantine combined with rapid diagnostic testing. r₁(t) is the probability of releasing infectious individuals following the quarantine of length t days. S_e = sensitivity of the rapid diagnostic test; S_p = specificity of the rapid diagnostic test; p = prevalence at the source community. Among infected individuals, those testing negative after quarantine of length t (i.e., p(1-S_e)r₁(t)) are released into the community. Among uninfected individuals, those testing negative (i.e., (1-p)S_p) are released.

Figure 2

Probability density functions of the incubation period and generation time of influenza. Gamma distribution was employed to model the incubation period (i.e., the time from infection to onset), whereas lognormal distribution was fitted to the generation time (i.e., the time from infection of a primary case to infection of a secondary case by the primary case). The mean and variance of the incubation period and generation time are estimated as 1.43 days and 0.48 days² and 2.92 days and 5.57 days², respectively. For the original data see: [22] and [26].

Figure 3

Effectiveness of quarantine with and without use of rapid diagnostic testing as a function of time since infection (i.e., time since arrival). Different effectiveness measures of quarantine are comparatively shown. The dashed line represents the effectiveness of quarantine, measured as the relative reduction of the risk of releasing "symptomatic infected" individuals (regardless of infectiousness) based on the incubation period alone. The two continuous lines measure the effectiveness as the relative reduction of the risk of releasing "infectious individuals" into the community, based on the incubation period, generation time and probability of symptomatic disease, with (thin) and without (thick) use of rapid diagnostic testing. The sensitivity of the rapid diagnostic test was assumed to be 69.0% (based on current test performance for seasonal influenza A [34]).

Figure 4

Sensitivity of the number of infectious cases released into the community (after quarantine) to the different lengths of quarantine and prevalence levels at the source. A. Quarantine alone. B. Quarantine combined with rapid diagnostic testing. Sensitivity of the number of released infectious cases into the community (after quarantine) is examined for different lengths of quarantine (2.8, 4.8, 5.7 and 8.7 days) and prevalence levels at the source (1%, 5% and 10%). Each dot represents median estimate of 100 simulation runs. The whiskers extend out to 5th and 95th percentiles of the simulations.

Figure 5

Sensitivity of the number of secondary transmissions caused by released infectious individuals to the different lengths of quarantine and prevalence levels at the source. A. Quarantine alone. B. Quarantine combined with rapid diagnostic testing. Sensitivity of the number of secondary transmissions caused by released infectious individuals is examined for different lengths of quarantine (2.8, 4.8, 5.7 and 8.7 days) and prevalence levels at the source (1%, 5% and 10%). Each dot represents median estimate of 100 simulation runs. The whiskers extend out to 5th and 95th percentiles of the simulations.

Figure 6

Diagnostic performance of quarantine with use of rapid diagnostic testing. A. Positive predictive values (PPV) and B. Negative predictive values (NPV) of quarantine combined with rapid diagnostic testing as functions of the length of quarantine and prevalence at the source. For the quarantine of 3 days or longer, PPV is less sensitive to the length of quarantine and depends almost only on the prevalence. NPV is sensitive to both the length of quarantine and prevalence at the source, achieving extremely high estimates to correctly release true negative individuals into the community.

Figure 7

Sensitivity of the effectiveness of quarantine to uncertain epidemiologic variables. A & B. Effectiveness of quarantine as a function of the ratio of the cumulative generation time among asymptomatic to symptomatic cases. Sensitivity of the point estimates of the effectiveness with baseline values of 95% and 99% are examined in A and B, respectively. C. Sensitivity of the effectiveness of quarantine in the presence of rapid diagnostic testing to the diagnostic sensitivity among asymptomatic infected individuals. D. Effectiveness of quarantine with imperfect efficacy of case detection of symptomatic cases.