Human Infectious Disease

We use epidemiological and evolutionary models to address questions in human vector-borne disease.

Dengue

Numerous studies have shown that the majority of DENV infections are inapparent and that the ratio of inapparent to symptomatic infections (I/S) fluctuates substantially year-to-year.  However, the mechanisms explaining these large fluctuations are not well understood. We used a mechanistic model to test the hypothesis that in dengue-endemic areas, frequent boosting (i.e., exposures to DENV that do not lead to extensive viremia and result in a <4-fold rise in antibody titers) of the immune response can be protective against symptomatic disease and this can explain fluctuating I/S ratios.

  • Alexander L. W., R. Ben-Shachar, L. C. Katzelnick, G. Kuan, A. Balmaseda, E. Harris & M. Boots (2021). Boosting can explain patterns of fluctuations of ratios of inapparent to symptomatic dengue virus infections. Proceedings of the National Academy of Sciences 118 (14) e2013941118.

The four serotypes of dengue show a characteristic out of phase pattern in Bangkok, while the phylogenetic analysis of the data shows evidence of an immune interaction between the serotypes. We used models to show that partial cross-immunity was sufficient to cause the out of phase dynamics providing evidence for cross-immunity between dengue serotypes.

  • Adams, B., E. C. Holmes, C. Zhang, M. P. Mammen Jr, S. Nimmannitya, S. Kalayanarooj and M. Boots (2006). Cross-protective immunity can account for the alternating epidemic pattern of dengue virus serotypes circulating in Bangkok. Proceedings of the National Academy of Science. 103, 14234-14239.

We had previously shown that the large difference between the dengue serotypes could be explained by antibody-dependent enhancement on death.

  • Kawaguchi, I., A. Sasaki & M. Boots (2003). Antibody-dependent enhancement explains coexistence in dengue serotypes. Proceedings of the Royal Society, Series B 270, 2241-2247.

Further models look at the role of mosquito transmission of dengue.

Malaria

We have also looked at the dynamics of Malaria in northern Thailand.

  • Childs, D.Z, Cattadori I, Wannapa Suwonkerd & Somsak Prajakwong, Boots, M (2006). Long-term patterns of Malaria incidence in Northern Thailand. Transactions of the Royal Society of Tropical Medicine and Hygiene, 100 (7): 623-631.

And built a dynamical seasonally forced model of malaria that looks at reasons for the contrasting epidemic dynamics of malaria in Thailand and Kenya.

  • Childs, D.Z. & M. Boots (2010). Seasonal Forcing, Immunity and the Dynamics of Malaria.  Journal of the Royal Society Interface, 7, 309-319.

Work on mosquitoes has looked at host fidelity in Japanese encephalitis vectors and more applied entomology on Aedes.

  • Mwandawiro, C.S., M. Boots, N. Tuno, Y. Tsuda & M. Takagi (2000). Host choice in Japanese Encephalitus vectors in Northern Thailand. Transactions of the Royal Society of Tropical Medicine and Hygiene, 94, 238-242.