Asymptomatic carriage of malaria parasites is common in high transmission intensity areas and confounds clinical case definitions for research studies. This is important for investigations that aim to identify immune correlates of protection from clinical malaria. The proportion of fevers attributable to malaria parasites is widely used to define different thresholds of parasite density associated with febrile episodes. We investigated whether varying intensity of malaria transmission had a significant impact on parasite density thresholds. We used the same dataset to explore an alternative statistical approach using the probability of developing fevers as a choice over threshold cut-offs as the former has been reported to increase predictive power.
Data from children monitored longitudinally between 2005 and 2017 from Junju and Chonyi in Kilifi, Kenya were analysed. We compare the performance of Bayesian-latent class and logistic power models in estimating malaria attributable fractions and probabilities of having fever given a parasite density with changing malaria transmission intensity. Zero-inflated beta regressions were used to assess the impact of using probabilities to evaluate anti-merozoite antibodies as correlates of protection compared with multilevel binary regression.
Malaria transmission intensity declined from over 49% to 5% between 2006 and 2017 respectively. During this period, malaria attributable fraction varied between 27%-59% using logistic regression compared to 10%-36% using the Bayesian latent class approach. Both models estimated similar patterns of fevers attributable to malaria with changing transmission intensities. The former performed well in estimating the probabilities of having fever, while the latter was efficient in determining the parasite density threshold. However, compared to the logistic power model, the Bayesian algorithm yielded lower estimates for both attributable fractions and probabilities of fever. In modelling the association of merozoite antibodies and clinical malaria, both approaches resulted in comparable estimates, but the utilization of probabilities had a better statistical fit.
Malaria attributable fractions varied with an overall decline in the malaria transmission intensity in this setting but did not significantly impact the outcomes of analyses aimed at identifying immune correlates of protection. These data confirm the statistical advantage of using probabilities over binary data.