The potential of targeted antibody prophylaxis in SARS outbreak control: a mathematic analysis

Abstract

Background: Severe acute respiratory syndrome (SARS) coronavirus-like viruses continue to circulate in animal reservoirs. If new mutants of SARS coronavirus do initiate another epidemic, administration of prophylactic antibodies to risk groups may supplement the stringent isolation procedures that contained the first SARS outbreak.

Method: We developed a mathematical model to investigate the effects of hospital admission and targeted antibody prophylaxis on the reproduction number R, defined as the number of secondary cases generated by an index case, during different SARS outbreak scenarios.

Results: Assuming a basic reproduction number R(0)=3, admission of patients to hospital within 4.3 days of symptom onset is necessary to achieve outbreak control without the need to further reduce community-based transmission. Control may be enhanced by providing pre-exposure prophylaxis to contacts of hospitalized patients, and through contact tracing and provision of post-exposure prophylaxis. Antibody prophylaxis may also be employed to reduce R below one and thereby restrict outbreak size and duration.

Conclusions: Patient isolation alone can be sufficient to control SARS outbreaks provided that the time from onset to admission is short. Antibody prophylaxis as supplemental measure generally allows for containment of higher R(0) values and restricts both the size and duration of an outbreak.

Figure 1

Schema of the flow of individuals between epidemiological compartments. Members of the susceptible population (compartment S) may become infected after contact with an infectious person. Infected persons first enter an asymptomatic phase. Because there is no evidence of pre-symptomatic transmission of SARS, we assume that infectivity begins with the onset of clinical symptoms. Hence, the exposed population (compartment E) is composed of non-infectious, asymptomatically infected individuals whereas the infectious population (compartment I) is composed of symptomatically infected individuals, some of which have been diagnosed with SARS and are admitted to hospital (superscript H). As death from SARS takes place on a similar timescale as recovery, we consider a composite endpoint of persons who have either died or recovered from SARS (compartment R).

Figure 2

The reproduction number R, the number of secondary cases produced by an index case, in relation to the time from onset of disease to hospital admission and the rate of hospital transmission relative to community-based transmission. (a) and (b) are based on a basic reproduction number R₀=3 which corresponds to a mean admission interval of 7.4 days and a relative rate of hospital transmission c=0.20 (see Table 1). The dotted line in (a) refers to the condition for containment $R<1$. In (b), the dotted line refers to the baseline value of c=0.20. (c) shows how the condition for containment depends on the basic reproduction number, with the dotted line referring to the baseline value R₀=3.

Figure 3

Critical vaccination coverage for containment of SARS transmission as a function of the basic reproduction number R₀ and the time from onset of disease to hospital admission. In (a) and (b), it is assumed that hospital-based transmission is effectively blocked, i.e. c=0. The duration of contact tracing for post-exposure prophylaxis is set at r=1 day in (a) and at r=3 days in (b). In (c), the duration of contact tracing is set at r=1 day, but hospital-based transmission is assumed to continue at 5% of the rate of community-based transmission, i.e. c=0.05.

Figure 4

Scatter plots of outbreak size versus duration in 1000 stochastic model runs for simulated outbreaks with n=10 initial cases. In (a), general control measures are chosen such that R=0.87. Supplemental measures may yield R=0.56 (b), R=0.44 (c) or R=0.20 (d), thus restricting both outbreak size and duration. Outbreak size is the cumulative number of persons infected, including the n=10 initial cases. Outbreak duration is the time until the last patient is discharged from hospital. The shaded area demarcates the 95th percentiles of outbreak size and duration.