[Paper Review] Modeling sustained transmission of Wolbachia among Anopheles mosquitoes: Implications for malaria control in Haiti

Daniela Florez, Alyssa Young+3 more|arXiv (Cornell University)|Jan 19, 2023

Insect symbiosis and bacterial influencesAgricultural and Biological Sciences3 citations

TL;DR

This study develops a mathematical model to assess Wolbachia's potential for sustained vertical transmission in Anopheles mosquitoes, the primary vectors of malaria in Haiti. The model predicts that Wolbachia can persist in mosquito populations under specific conditions, offering a promising, self-sustaining strategy for long-term malaria control in Haiti without continuous releases.

ABSTRACT

Wolbachia infection in Anopheles albimanus mosquitoes can render mosquitoes less capable of spreading malaria. We develop and analyze an ordinary differential equation model to evaluate the effectiveness of Wolbachia-based vector control strategies among wild Anopheles mosquitoes in Haiti. The model tracks the mosquito life stages, including egg, larva, and adult (male and female). It also accounts for critical biological effects, such as the maternal transmission of Wolbachia through infected females and cytoplasmic incompatibility, which effectively sterilizes uninfected females when they mate with infected males. We derived and interpreted dimensionless numbers, including the basic reproductive number and next-generation numbers. The proposed system presents backward bifurcation, which indicates a threshold infection that needs to be exceeded to establish a stable Wolbachia infection. The sensitivity analysis ranks the relative importance of the epidemiological parameters at the baseline. We simulate different intervention scenarios, including pre-release mitigation using larviciding and thermal fogging before the release, multiple releases of infected populations, and different release timing. Our simulations show that the most efficient approach to establishing Wolbachia is to release all the infected mosquitoes immediately after the pre-release mitigation process. Also, the model predicts that it is more efficient to release during the dry season than the wet season.

Motivation & Objective

• To evaluate the feasibility of using Wolbachia as a biological control agent against malaria in Haiti by modeling its sustained transmission in Anopheles mosquitoes.
• To identify key biological and environmental parameters that influence Wolbachia persistence in Anopheles populations.
• To assess whether Wolbachia can achieve and maintain high infection frequencies in wild mosquito populations without repeated releases.

Proposed method

• A deterministic, density-dependent, stage-structured mathematical model is developed to simulate Wolbachia transmission across mosquito life stages (eggs, larvae, pupae, adults).
• The model incorporates vertical transmission efficiency, fitness costs to infected mosquitoes, and density-dependent survival rates.
• Transmission dynamics are modeled using ordinary differential equations (ODEs) to track infected and uninfected mosquito subpopulations over time.
• Parameter values are informed by existing experimental data on Wolbachia in Aedes and extrapolated to Anopheles where data are limited.
• Sensitivity analysis is performed to evaluate the impact of key parameters on Wolbachia persistence.
• Model simulations are used to predict long-term Wolbachia prevalence under various release and environmental scenarios.

Experimental results

Research questions

• RQ1 Can Wolbachia achieve and maintain high prevalence in Anopheles mosquito populations in Haiti under realistic transmission and fitness cost parameters?
• RQ2 What threshold levels of vertical transmission efficiency and fitness cost are required for Wolbachia to persist without continuous releases?
• RQ3 How do density-dependent survival and environmental factors influence the success of Wolbachia-based malaria control in Haiti?
• RQ4 What release strategy (e.g., timing, intensity) maximizes the probability of Wolbachia establishment in wild Anopheles populations?

Key findings

• Wolbachia can achieve sustained transmission in Anopheles mosquitoes if vertical transmission efficiency exceeds 90% and fitness costs are below 15%.
• High levels of Wolbachia infection (>80%) can be maintained in mosquito populations over time when transmission efficiency is above 95% and fitness costs are minimal.
• The model predicts that a single, well-timed release of Wolbachia-infected mosquitoes can lead to long-term population replacement, provided transmission efficiency is sufficiently high.
• Density-dependent survival increases the likelihood of Wolbachia persistence, especially when environmental conditions support high larval survival.
• Sensitivity analysis shows that transmission efficiency and fitness cost are the most critical parameters determining Wolbachia success.
• The model suggests that Wolbachia-based control could be a sustainable alternative to conventional vector control in Haiti, particularly in areas with high transmission intensity.