Abstract

The relative risk of disease transmission caused by the potential release of transgenic vectors, such as through sterile insect technique or gene drive systems, is assessed with comparison with wild-type vectors. The probabilistic risk framework is demonstrated with an assessment of the relative risk of lymphatic filariasis, malaria and o'nyong'nyong arbovirus transmission by mosquito vectors to human hosts given a released transgenic strain of Anopheles coluzzii carrying a dominant sterile male gene construct. Harm is quantified by a logarithmic loss function that depends on the causal risk ratio, which is a quotient of basic reproduction numbers derived from mathematical models of disease transmission. The basic reproduction numbers are predicted to depend on the number of generations in an insectary colony and the number of backcrosses between the transgenic and wild-type lineages. Analogous causal risk ratios for short-term exposure to a single cohort release are also derived. These causal risk ratios were parametrized by probabilistic elicitations, and updated with experimental data for adult vector mortality. For the wild-type, high numbers of insectary generations were predicted to reduce the number of infectious human cases compared with uncolonized wild-type. Transgenic strains were predicted to produce fewer infectious cases compared with the uncolonized wild-type.

Highlights

  • IntroductionGenetic vector control and risk of disease transmission

  • The mortality parameter was believed by experts to substantively depend on infection status for lymphatic filariasis (§3.1) because ingestion of microfilariae can increase mortality of the vector (e.g. [66])

  • For wild-type vectors infected with Wuchereria bancrofti filaria, the mortality rate increased with the number of insectary generations

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Summary

Introduction

Genetic vector control and risk of disease transmission. The relative risk of disease transmission is investigated for the release of a transgenic vector as part of an entomological study. Development pathway that investigates the potential for gene drive technology to suppress malaria 2 vectors and thereby reduce malaria transmission [1]. For gene drive technology applied to vector control of mosquitoes, probabilistic safety assessments should compare the risks of disease transmission by transgenic mosquitoes relative to wild-type mosquitoes of the same genetic background [2,3]. The theoretical framework developed here is broadly applicable and may be used to support general assessments for the relative risk of disease transmission by transgenic and wild-type vectors. The risk approach is demonstrated for transgenic vectors in a genetically engineered sterile insect technique (SIT) entomological study

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