It is estimated that 190 million individuals are at risk of blindness from trachoma, and that control by mass drug administration (MDA) is reducing this risk in many populations. Programs are monitored using prevalence of follicular trachoma disease (TF) in children. However, as programs progress to low prevalence there are challenges interpreting this indirect measure of infection. PCR and sero-surveillance are being considered as complementary tools to monitor low-level transmission, but there are questions on how they can be most effectively used. We use a previously-published, mathematical model to explore the dynamic relationship between TF and PCR throughout a control program and a sero-catalytic model to evaluate the utility of two cross-sectional sero-surveys for estimating sero-conversion rates. The simulations show that whilst PCR is more sensitive than TF at detecting infection, the probability of detecting at least one positive individual declines during an MDA program more quickly for PCR than for TF (for the same sample size). Towards the end of a program there is a moderate chance of a random sample showing both low PCR prevalence and higher TF prevalence, which may contribute to the lack of correlation observed in epidemiological studies. We also show that conducting two cross-sectional sero-surveys 10 years apart can provide more precise and accurate estimation of epidemiological parameters than a single survey, supporting previous findings that whilst serology holds great promise, multiple cross-sections from the same community are needed to generate the most valuable information about transmission. These results highlight that the quantitative dynamics of infection and disease should be included alongside the many logistical and practical factors to be considered in designing a monitoring and evaluation strategy at the operational research level, in order to help subsequently inform data collection for individual country programs. Whilst our simulations provide some insight, they also highlight that some level of longitudinal, individual-level data on reinfection and disease may be needed to monitor elimination progress.