Globally, scabies causes substantial morbidity and mortality. In the tropics, scabies promotes opportunistic bacterial infections, leading to cellulitis/necrotizing fasciitis, bacteraemia, renal disease and rheumatic fever / heart disease. With no vaccine or diagnostic tools and limited treatment options, scabies is considered neglected by WHO. Pathobiology is poorly understood, due to an absence of molecular information on mite infestation, bacterial co-infection and the interactions thereof.
Based on epidemiology in scabies-endemic tropical locations1-5, scabies is a key underlying factor of secondary bacterial infections (See Fig 1 below). Our laboratory provided the first experimental evidence indicating that the mite creates a protective microhabitat, thereby facilitating the proliferation of opportunistic pathogens6-9. Very high rates of complicated skin-borne infections with opportunistic pathogens are reported in Indigenous Australians10,11, and the situation is similar in many resource poor settings globally.
Rheumatic fever and rheumatic heart disease are inflammatory diseases that occur after infection with group A streptococcus (GAS). The bacterial infection causes the immune system to start attacking the body, creating an autoimmune disorder. Currently, there is no vaccine to prevent rheumatic fever or rheumatic heart disease. Northern Australia’s Aboriginal population have the highest recorded incidence worldwide. Similarly, very high rates of invasive staphylococcal infection have been reported in adult and paediatric Indigenous populations in Australia.
Novel acaricides are urgently needed, as current drugs often fail because they do not kill mite eggs and/or have short half-lives. Drug resistance is emerging. Another major challenge is the lack of early diagnostic markers for infection. Without reliable, sensitive and simple diagnostic tools, it is difficult to distinguish scabies from numerous skin conditions with similar symptoms. Delayed diagnosis causes rapid transmission in overcrowded living conditions. The central challenge is that mite biology, scabies pathogenesis and the mechanisms underlying the three-way interactions of mites, bacteria and skin immunity are poorly understood but essential to design suitable interventions.
- identify key therapeutic and diagnostic targets, and molecular mechanisms underlying scabies pathogenesis from our comprehensive and integrated scabies multi-omics databases
- leading the international scabies microbiome program to define the impact of scabies on the microbiome of healthy skin and examine the synergy between mites and bacteria
- based on biological knowledge, develop multiple candidate scabicides which, with support from industry partners, will enter pre-clinical and clinical studies
- Gear, R.J., Carter, J.C., Carapetis, J.R., Baird, R. & Davis, J.S. Changes in the clinical and epidemiological features of group A streptococcal bacteraemia in Australia’s Northern Territory. Trop Med Int Health 20, 40-47 (2015).
- McMeniman, E., et al. Skin disease in the first two years of life in Aboriginal children in East Arnhem Land. Australas J Dermatol 52, 270-273 (2011).
- Whitehall, J., Kuzulugil, D., Sheldrick, K. & Wood, A. Burden of paediatric pyoderma and scabies in North West Queensland. J Paediatr Child Health 49, 141-143 (2013).
- McDonald, M., Currie, B.J. & Carapetis, J.R. Acute rheumatic fever: a chink in the chain that links the heart to the throat? Lancet Infect Dis 4, 240-245 (2004).
- Hoy, W.E., et al. Post-streptococcal glomerulonephritis is a strong risk factor for chronic kidney disease in later life. Kidney international 81, 1026-1032 (2012).
- Swe, P.M., Christian, L.D., Lu, H.C., Sriprakash, K.S. & Fischer, K. Complement inhibition by Sarcoptes scabiei protects Streptococcus pyogenes – An in vitro study to unravel the molecular mechanisms behind the poorly understood predilection of S. pyogenes to infect mite-induced skin lesions. PLoS Negl Trop Dis 11, e0005437 (2017).
- Mika, A., et al. Complement inhibitors from scabies mites promote streptococcal growth–a novel mechanism in infected epidermis? PLoS Negl Trop Dis 6, e1563 (2012).
- Bergstrom, F.C., et al. Scabies mite inactivated serine protease paralogs inhibit the human complement system. J Immunol 182, 7809-7817 (2009).
- Swe, P.M. & Fischer, K. A scabies mite serpin interferes with complement-mediated neutrophil functions and promotes staphylococcal growth. PLoS Negl Trop Dis 8, e2928 (2014).
- Carapetis, J.R. & Currie, B.J. Group A streptococcus, pyoderma, and rheumatic fever. Lancet 347, 1271-1272 (1996).
- Marshall, C.S., et al. Acute post-streptococcal glomerulonephritis in the Northern Territory of Australia: a review of 16 years data and comparison with the literature. Am J Trop Med Hyg 85, 703-710 (2011).
Figure 1. Complexity & impact of scabies7.