What is known about modified insects for disease prevention?: a systematic review

The modification and release of insects to suppress or replace natural insect vectors constitutes a promising tool for vector control and disease prevention, facing the unprecedented global emergence of vector-borne diseases. Little is known regarding these innovative modification strategies and available evidence is not standardized turning it difficult to reflect on their actual efficacy and eventual effects. This work conducted a systematic review, gathering and analyzing research articles from PubMed and Biblioteca Virtual em Saúde databases whose results directly report efficacy and effects of the use of modified insects for disease prevention until 2016. Within more than 1500 publications that were screened a total of 349 where analyzed. A total of 12/3.4% reported field-based evidence, and 41/11.7% covered modification stretagies’ efficacy after insects’ release, their epidemiology impact or its long-term efficacy. Examples of successful results were the replacement of natural field populations by wolbachia-infected mosquitoes in 5 weeks, and the elimination of a population in laboratory cages after transgenic mosquitoes release over 10–20 weeks. Variability in the effective results were described (90/25.7%) questioning its reproducibility in different settings. We also found 38/10.9% publications reporting reversal outcomes, such as an increase of vector population after release. Ecological effects such as horizontal transfer events to non-target species (54/15.5%), and wolbachia -induced worsening pathogenesis on mammal filarial diseases (10/2.9%) were also reported. Present work revealed promising outcomes of both suppressing and replacing approaches. However, it also revealed a need of field-based evidence mainly regarding epidemiologic and long-term impact of insect modification strategies. It pointed out some eventual irreversible and important effects that must not be ignored when considering open-field releases, and that may constitute constraints to generate the missing field evidence. Moreover, the level of variability of existing evidence suggests the need of local/specific evidence in each setting of an eventual release. Author summary Innovative strategies are needed to arrest the unprecedented increase of vector-borne disease incidence, distribution and severity. Several modification techniques are being tried all over the world. However this is still an emergent topic with scarce available information and of complex understanding. Present work is the unique structured review regarding the use of modified insects for vector-borne disease prevention, bringing neutral and robust evidence that will contribute with critical insights regarding these approaches. Here we explored more than 1200 publications and analyzed 349 publications on this subject, describing the actual efficacy and reported effects of several modification strategies. More than 30 categories were reported such as, the type of modification, the year of the publication, the species were results were tested, the type of study, and also type of Efficacy Outcome (from modification to long-term) and/or the type of Effects Outcome (from physiologic to ecologic effects). Analysis revealed promising outcomes regarding vector-control and disease prevention. However insects’ modification strategies still lack field-based evidence mainly regarding epidemiological and long-term efficacy. Eventual reversal outcomes on disease transmission, or irreversible biological effects (including horizontal transfer to non-target species or worsening pathogenesis in particular diseases in mammals), were also described. These effects need to be explored, dispelled or resolved before field trials occur in human residential areas. Some of these questions could only have a robust answer if these strategies would be implemented, needing to take the risk to observe reversal outcomes and/or irreversible effects. These findings reflect the big dilemma that is under the use of modified insects to prevent vector-borne diseases. Findings could support health authorities in decision-making and regulatory committees during advisory processes, by evaluating the pros/cons of each modifying technique for a particular setting. Moreover they could also summarize what is crucial to inform to communities if planning open field releases in residential areas.