Parasite infections cause a staggering burden of disease worldwide, especially in children. Intestinal parasite infections lead to chronic anemia and malnutrition, causing physical and cognitive stunting. The ScreenChip technology has been adapted for parasitic nematodes, specifically A. ceylanicum and A. suum host-stage larvae (1).
These infections can be treated by anthelmintic drugs, but resistance to anthelmintic (anti-worm) drugs is a growing problem worldwide, especially in veterinary medicine. Limitations of current anthelmintic drugs include increasing drug resistance and a limited spectrum of activity across parasite species. New anthelmintic treatments are urgently needed, yet the current drug development pipeline is inadequate.
Introducing the ScreenChip System: a platform to study parasitology and drug resistance
The ScreenChip System can be used with parasitic nematodes for anthelmintic drug development and studies of drug resistance:
- Obtain a direct readout of the electrical activity of muscles and neurons, which is ideal for screens seeking compounds that disrupt electrical signaling (Fig. 1).
- Obtain data from a range of parasitic species of humans and animals including host-stage hookworm.
- Potential anthelmintics can be tested on the parasitic species targeted for killing (Fig. 2).
- Quantitative analysis of the effects of applied compounds can suggest testable hypotheses regarding compounds’ modes of action, molecular mechanisms of resistance, or other properties (Fig. 3).
- Obtain rapid (within minutes) detection of anthelmintic drug resistance (Fig. 4).
An EPG recording from a host-stage hookworm larva
Fig. 1. (A) A. ceylanicum larva (stage L4, from hamster) positioned in a microfluidic recording channel. (B) EPG recording from same. Modified from (1).
Obtain data from a range of parasitic species of humans and animals and see the effects of anthelmintic drugs
Fig. 2. Inhibition of neuromuscular activity after switching from control medium to 1 µM ivermectin (IVM) in (A) A. ceylanicum L4 (from hamster), (B) A. suum L3 (from swine), or (C) aqueous extract of Momordica chirantia (MCE) in A. ceylanicum L4 (2).
Obtain quantitative data from H. contortus, the barber pole worm, a common livestock parasite
Fig. 3. EPG recording from H. contortus L4, activated in vitro from infective L3 (5).
Detection of drug resistance:
Resistance to anthelmintic drugs is a growing problem worldwide, especially in veterinary medicine. ScreenChip recordings provide a sensitive method for detecting and quantifying resistance.
Observe and quantify drug resistance using a sensitive read-out of neuromuscular function.
Fig. 4. Demonstration of anthelmintic drug resistance in C. elegans. (A) In a wild type C. elegans (day 1 adult), EPG activity was unaffected by switching (grey bar) from control medium to control medium (M9 buffer with serotonin). (B) Switching to 3 µM IVM caused rapid cessation of pumping in a wild type worm. (C) C. elegans strain DA1316, bearing 3 mutations in the Glu-gated Cl channel to which IVM binds, were dramatically less susceptible to inhibition by 3 µM IVM than wild type worms (4).
(1) Weeks JC, W.M. Roberts, K.J. Robinson, M. Keaney, J.J. Vermeire, J.F. Urban Jr., S.R. Lockery, J.M. Hawdon (2016) Microfluidic platform for electrophysiological recordings from host-stage hookworm and Ascaris suum larvae: A new tool for anthelmintic research, International Journal for Parasitology: Drugs and Drug Resistance, 6:314-328. DOI: 10.1016/j.ijpddr.2016.08.001.
(2) Wolpert BJ, Beauvoir MG, Wells EF, Hawdon JM (2008) Plant vermicides of Haitian Vodou show in vitro activity against larval hookworm. J Parasitol. 2008 Oct;94(5):1155-60. doi: 10.1645/GE-1446.1; Weeks JC, Robinson KJ, Roberts WM and Hawdon JM, unpublished data.
(3) Weeks JC, Robinson KJ, Roberts WM, R. Storey and Wolstenholme AJ, unpublished data.
(4) Weeks JC, Robinson KJ, Lockery SR and Roberts WM, unpublished data.