Detecting infection hotspots: Modeling the surveillance challenge for elimination of lymphatic filariasis

Background: During the past 20 years, enormous efforts have been expended globally to eliminate lymphatic filariasis (LF) through mass drug administration (MDA). However, small endemic foci (microfoci) of LF may threaten the presumed inevitable decline of infections after MDA cessation. We conducted microsimulation modeling to assess the ability of different types of surveillance to identify microfoci in these settings. Methods: Five or ten microfoci of radius 1, 2, or 3 km with infection marker prevalence (intensity) of 3, 6, or 10 times background prevalence were placed in spatial simulations, run in R Version 3.2. Diagnostic tests included microfilaremia, immunochromatographic test (ICT), and Wb123 ELISA. Population size was fixed at 360,000 in a 60 x 60 km area; demographics were based on literature for Sub-Saharan African populations. Background ICT prevalence in 6–7 year olds was anchored at 1.0%, and the prevalence in the remaining population was adjusted by age. Adults≥18 years, women aged 15–40 years (WCBA), children aged 6–7 years, or children≤5 years were sampled. Cluster (CS), simple random sampling (SRS), and TAS-like sampling were simulated, with follow-up testing of the nearest 20, 100, or 500 persons around each infection-marker-positive person. A threshold number of positive persons in follow-up testing indicated a suspected microfocus. Suspected microfoci identified during surveillance and actual microfoci in the simulation were compared to obtain a predictive value positive (PVP). Each parameter set was referred to as a protocol. Protocols were scored by efficiency, defined as the most microfoci identified, the fewest persons requiring primary and follow-up testing, and the highest PVP. Negative binomial regression was used to estimate aggregate effects of different variables on efficiency metrics. Results: All variables were significantly associated with efficiency metrics. Additional follow-up tests beyond 20 did not greatly increase the number of microfoci detected, but significantly negatively impacted efficiency. Of 3,402 protocols evaluated, 384 (11.3%) identified all five microfoci (PVP 3.4–100.0%) and required testing 0.73–35.6% of the population. All used SRS and 378 (98.4%) only identified all five microfoci if they were 2–3 km diameter or high-intensity (6x or 10x); 374 (97.4%) required ICT or Wb123 testing to identify all five microfoci, and 281 (73.0%) required sampling adults or WCBA. The most efficient CS protocols identified two (40%) microfoci. After limiting to protocols with 1-km radius microfoci of 3x intensity (n = 378), eight identified all five microfoci; all used SRS and ICT and required testing 31.2–33.3% of the population. The most efficient CS and TAS-like protocols as well as those using microfilaremia testing identified only one (20%) microfocus when they were limited to 1-km radius and 3x intensity. Conclusion: In this model, SRS, ICT, and sampling of adults maximized microfocus detection efficiency. Follow-up sampling of more persons did not necessarily increase protocol efficiency. Current approaches towards surveillance, including TAS, may not detect small, low-intensity LF microfoci that could remain after cessation of MDA. The model provides many surveillance protocols that can be selected for optimal outcomes. Author summary: Accurately tracking the success of elimination programs becomes increasingly difficult as elimination nears. For some diseases, such as lymphatic filariasis, this is compounded by the absence of symptoms during the infectious period as well as the natural and unevenly-distributed presence of small residual foci of infection (microfoci). Microfoci, when they are present, pose a threat to long-term elimination because they may lead to recrudescence, but it is unclear which surveillance approaches provide sufficient confidence to confirm their absence on a large scale. While we do not know the concentration of infections in a microfocus that would lead to certain recrudescence, we can quantitate the ability of different surveillance approaches to detect microfoci of different size and concentration. The model presented in this paper can be used to inform late-stage elimination program surveillance strategies for infections that include, but are not limited to, lymphatic filariasis.