Development of Onchocerca volvulus in humanized NSG mice and detection of parasite biomarkers in urine and serum

Patton, John B.; Bennuru, Sasisekhar; Eberhard, Mark L.; Hess, Jessica A.; Torigian, April; Lustigman, Sara; Nutman, Thomas B.; Abraham, David

https://doi.org/10.1371/journal.pntd.0006977.g001 Humanized NSG (HuNSG) mice: NSG mice that had received a human CD34 + stem cell transfer, (4) BLT: NSG mice that had been engrafted with human fetal liver derived CD34 + stem cells and engrafted with fetal thymus and liver tissues. After 4, 8 or 12-weeks, animals were necropsied and worms were recovered and measured. Solid colored bar is the geometric mean of the lengths of larvae recovered. Solid black line is the geometric mean of the length of L3 recovered from black flies and dotted line is the 95 th confidence interval. � Asterisk represents statistical difference, p value � 0.05, in length of larvae recovered from mice. Complete statistical analyses for all groups are included on S2 BLT mice humanized with fetal thymus, liver and CD34 + stem cells, which display an enhanced repertoire of the developing human cells [58] , were infected with 100 O. volvulus L3 and then necropsied at 4-and 8-weeks post infection. At 4-weeks post infection BLT mice had an established infection rate of 77% with a GM of 4.8 (range 2-10) worms/mouse. At 8-weeks post infection BLT mice had an established infection rate of 60% with a GM of 2.3 (range 2-3) worms/mouse (Fig 1D) . Growth of the parasites was equivalent to that seen in the NSG mice and the other humanized models with the maximum length reaching 1,080 μm at 4-weeks (Min: 391 μm, GM: 623 μm) and 1,448 μm at 8-weeks (Min: 730 μm, GM: 949 μm) (Fig 2) . The overall growth was significant between the L3 and worms 4-weeks post infection (p<0.0001) and between worms recovered at the 4-and 8-week time points (p<0.0001).