The role of rapid diagnostics in managing Ebola epidemics

Abstract

Ebola emerged in West Africa around December 2013 and swept through Guinea, Sierra Leone and Liberia, giving rise to 27,748 confirmed, probable and suspected cases reported by 29 July 2015. Case diagnoses during the epidemic have relied on polymerase chain reaction-based tests. Owing to limited laboratory capacity and local transport infrastructure, the delays from sample collection to test results being available have often been 2 days or more. Point-of-care rapid diagnostic tests offer the potential to substantially reduce these delays. We review Ebola rapid diagnostic tests approved by the World Health Organization and those currently in development. Such rapid diagnostic tests could allow early triaging of patients, thereby reducing the potential for nosocomial transmission. In addition, despite the lower test accuracy, rapid diagnostic test-based diagnosis may be beneficial in some contexts because of the reduced time spent by uninfected individuals in health-care settings where they may be at increased risk of infection; this also frees up hospital beds. We use mathematical modelling to explore the potential benefits of diagnostic testing strategies involving rapid diagnostic tests alone and in combination with polymerase chain reaction testing. Our analysis indicates that the use of rapid diagnostic tests with sensitivity and specificity comparable with those currently under development always enhances control, whether evaluated at a health-care-unit or population level. If such tests had been available throughout the recent epidemic, we estimate, for Sierra Leone, that their use in combination with confirmatory polymerase chain-reaction testing might have reduced the scale of the epidemic by over a third.

Figure 1

Three Ebola health-care-unit diagnostic testing and patient triage strategies. Patients seeking care are first admitted to a holding area where they wait to be either admitted to a confirmed ward or discharged back to the community. We examine three diagnostic testing strategies. a, Polymerase chain reaction (PCR)-only: patients await their test results in a single holding area. When PCR test results become available, individuals are either sent to a confirmed ward or discharged back to the community. b, Dual strategy (rapid diagnostic test (RDT) and PCR): based on initial RDT results, patients seeking care are kept in separate high- or low-risk wards. When PCR test results become available, individuals are either sent to a confirmed ward or discharged back to the community. c, RDT-only: the RDT result alone determines who is sent to a confirmed ward or discharged back to the community. Patients are either infected (red), uninfected (blue) or exposed within the holding area (infected, but not yet infectious, blue outline and red centre). The RDT is assumed to have a lower sensitivity and may give incorrect classifications (false positives and false negatives), which can result in nosocomial further transmission in the community if true Ebola cases are erroneously discharged.

Figure 2

Case fatality ratio (CFR) of patients seeking care divided by the CFR if those same Ebola and non-Ebola cases had remained in the community. Each row represents a particular stage in the epidemic: from left to right: early (a,b, c), during the peak (d,e,f), shortly after the peak (g,h,i) and once the epidemic is tailing off(j,k,l). Each column reflects a testing strategy, namely polymerase chain reaction (PCR)-only (a,d,g,j), dual strategy (b,e,h,k) and rapid diagnostic test (RDT)-only (c,f,i,l). White horizontal lines show the threshold bed capacity below which demand cannot be met for PCR-only (same threshold as dual strategy) and RDT-only. Solid grey and black lines (left panels, a,d,g,j) indicate, respectively, where the outcomes of PCR-only and RDT-only are equivalent, and where the outcomes of dual (RDT and PCR) testing and RDT-only are equivalent. Those lines delimit parameter space where (1) dual strategy is best followed by PCR-only and then RDT-only, (2) dual strategy is best followed by RDT-only and then PCR-only and (3) RDT-only is best followed by dual strategy and then PCR-only. On the left of the white solid vertical line (specific for the testing the benefit of care is sufficient to decrease the average CFR among patients seeking care (unaware of their disease status, and assuming hospital infection control has not improved over the course of the epidemic). The black arrows on the right y-axis of the RDT-only plots indicate the likely availability of beds at the corresponding stage of the epidemic (Table 2); however, this is likely to have varied between different health-care units.

Figure 3

Relative reproduction number of patients with Ebola who are seeking care for dual strategy and rapid diagnostic test (RDT)-only, compared to polymerase chain reaction (PCR)-only, at the peak of the epidemic (see Table 2 for parameters). For a,b bed capacity is unlimited, whereas for c,d the health-care unit has 200 beds (Table 2). The outcome using a dual (RDT and PCR) strategy is shown in a,c, whereas b,d present the outcome using RDT-only. For the specified parameters and when bed capacity is unlimited, the reproduction number for the PCR-only strategy is 0.53 (0.99 when bed capacity is limited to 200). The PCR-only outcome is independent of the RDT’s sensitivity and specificity. Solid grey and black lines indicate, respectively, where the outcomes of PCR-only and RDT-only are equivalent, and where the outcomes of dual (RDT and PCR) testing and RDT-only are equivalent. Those lines delimit parameter space where (1) dual strategy is best followed by PCR-only and then RDT-only, (2) dual strategy is best followed by RDT-only and then PCR-only and (3) RDT-only is best followed by dual strategy and then PCR-only. The black circle indicates the World Health Organization reported sensitivity and specificity of the ReEBOV RDT (92% and 85%, respectively).

Figure 4

Ebola outbreak in Sierra Leone. a, Observed (grey bars) and expected (coloured lines) weekly incidence of confirmed and probable Ebola cases during the outbreak in Sierra Leone. The red line presents the expected incidence using the polymerase chain reaction (PCR)-only strategy on which the model was calibrated. Other lines present the estimated incidence under counterfactual scenarios: rapid diagnostic test (RDT)-only (blue), dual strategy (green), PCR-only with faster test results delivered within 1 day (purple) or RDT-only with near-perfect sensitivity and specificity of 99% each (orange). b, Bed capacity (grey) and usage (colours) throughout the epidemic in Sierra Leone for the same scenarios as in (a).