title: Sequential modelling of the effects of mass drug treatments on anopheline-mediated lymphatic filariasis infection in Papua New Guinea.
abstract: BACKGROUND
  Lymphatic filariasis (LF) has been targeted by the WHO for global eradication leading to the implementation of large scale intervention programs based on annual mass drug administrations (MDA) worldwide. Recent work has indicated that locality-specific bio-ecological complexities affecting parasite transmission may complicate the prediction of LF extinction endpoints, casting uncertainty on the achievement of this initiative. One source of difficulty is the limited quantity and quality of data used to parameterize models of parasite transmission, implying the important need to update initially-derived parameter values. Sequential analysis of longitudinal data following annual MDAs will also be important to gaining new understanding of the persistence dynamics of LF. Here, we apply a Bayesian statistical-dynamical modelling framework that enables assimilation of information in human infection data recorded from communities in Papua New Guinea that underwent annual MDAs, into our previously developed model of parasite transmission, in order to examine these questions in LF ecology and control.
  
  
  RESULTS
  Biological parameters underlying transmission obtained by fitting the model to longitudinal data remained stable throughout the study period. This enabled us to reliably reconstruct the observed baseline data in each community. Endpoint estimates also showed little variation. However, the updating procedure showed a shift towards higher and less variable values for worm kill but not for any other drug-related parameters. An intriguing finding is that the stability in key biological parameters could be disrupted by a significant reduction in the vector biting rate prevailing in a locality.
  
  
  CONCLUSIONS
  Temporal invariance of biological parameters in the face of intervention perturbations indicates a robust adaptation of LF transmission to local ecological conditions. The results imply that understanding the mechanisms that underlie locally adapted transmission dynamics will be integral to identifying points of system fragility, and thus countermeasures to reliably facilitate LF extinction both locally and globally.
authors.affiliation: Department of Biological Sciences, University of Notre Dame, Notre Dame, Indiana, United States of America. bsingh1@nd.edu
authors.forename: Brajendra K
authors.initials: BK
authors.lastname: Singh
authors.forename: Moses J
authors.initials: MJ
authors.lastname: Bockarie
authors.forename: Manoj
authors.initials: M
authors.lastname: Gambhir
authors.forename: Peter M
authors.initials: PM
authors.lastname: Siba
authors.forename: Daniel J
authors.initials: DJ
authors.lastname: Tisch
authors.forename: James
authors.initials: J
authors.lastname: Kazura
authors.forename: Edwin
authors.initials: E
authors.lastname: Michael
mesh_terms: D017677:Age Distribution; D000818:Animals; D000852:Anopheles / Q000502:physiology*; D001499:Bayes Theorem; D016002:Discriminant Analysis; D004605:Elephantiasis, Filarial / Q000188:drug therapy* / Q000453:epidemiology / Q000469:parasitology*; D006306:Health Surveys; D006801:Humans; D008954:Models, Biological; D010219:Papua New Guinea / Q000453:epidemiology; D015995:Prevalence; D014958:Wuchereria bancrofti / Q000502:physiology