Application of Freedom From Infection Analysis to Nigerian Cross-Sectional Lymphatic Filariasis Survey Data Restricted; Files Only

Noland, Gregory (Summer 2018)

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Lymphatic filariasis (LF), or “elephantiasis”, is a mosquito-transmitted parasitic disease affecting 67.9 million people in 73 countries. Infection leads to lymphatic dysfunction that results in swelling of limbs (lymphedema) and genitals (male hydrocele), and painful recurrent inflammation.  The World Health Organization (WHO) targets “elimination of LF as a public health problem” through 1) mass drug administration (MDA) to interrupt parasite transmission and 2) morbidity management and disability prevention (MMDP) to care for those already affected by LF.  WHO guidelines currently exist for validation of LF elimination as a public health problem through a series of transmission assessment surveys (TAS) with a critical threshold of 2% (1% in areas where LF is transmitted by Aedes mosquitoes)—the levels below which transmission is presumed unsustainable.  WHO also recently indicated that countries may request verification of elimination of LF transmission (elimination sensu stricto), but acknowledged that specific requirements for such verification have not yet been agreed.  This study assessed Freedom From Infection (FFI) analysis to fill this gap.  FFI employs probability theory to estimate the probability that disease prevalence in a population is below a pre-determined threshold. This novel application of FFI was conducted using data from a series of cross-sectional LF antigen surveys in eight districts of Plateau and Nasarawa states, Nigeria encompassing 31,714 individuals tested over an eleven-year period (2007—2017) through school-based TAS surveys of children aged 6—7 years old and community-based cluster surveys of individuals > 2 years.  Results indicate a high probability (>0.90) at all examined thresholds (2%, 1%, 0.1%, 1 case) that areas with lower baseline LF transmission (<20% antigenemia) were free from LF infection by 2007, five to six years after the start of MDA, while high FFI probability (>0.99) was observed between 2012—2015, around 11—13 years after the start of MDA, for three areas of higher baseline transmission.  These results correspond well with cross-sectional survey conclusions.  In summary, initial application of FFI analysis to LF shows good concordance with cross-sectional survey data, thereby offering a tool, that with refinement, could serve as a viable analytic framework to verify elimination of LF transmission.

Table of Contents

Chapter I: Background   1

Biology 2

Pathology          4

Diagnostics        5

Global LF Elimination Program 6

LF Survey Designs         8

Disease Control Definitions        10

Chapter II: Manuscript   13

Introduction      16

Methods             18

Survey area        18

Survey Designs 20

Ethical approval and consent procedures 23

Descriptive statistics       23

Freedom from Infection Analysis             24

Results  24

Descriptive Results of Cross Sectional Surveys   24

Freedom From Infection Analysis            26

Discussion         27

Tables   31

Figures 35

Chapter III:  Summary, Public Health Implications, Possible Future Directions            39

Summary           40

Public Health Implications          40

Possible Future Directions          42

References         44

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