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Updated: Sep 2, 2026
Sand Fly (Phlebotomus papatasi) Embryo Microinjection for CRISPR/Cas9 Mutagenesis
Published on: November 17, 2020
Experimental infection of nonhuman primates with sandfly fever virus
D J McClain1, P L Summers, W D Pratt
1Division of Virology, U.S. Army Medical Research Institute of Infectious Diseases, Fort Detrick, Frederich, Maryland, USA.
Abstract:
Due to the lack of an animal model, previous studies of sandfly fever have relied upon human challenge trials. We examined the infectivity and potential pathogenicity of sandfly fever virus in cynomolgus monkeys (Macaca fascicularis). Three different preparations of sandfly fever virus. Sicilian strain, and a placebo were compared by different routes of administration. The most notable postchallenge clinical event was a decrease in lymphocytes in the intramuscularly challenged monkeys. Plaque-reduction neutralization responses peaked earlier in animals challenged intravenously as compared with those in animals challenged intramuscularly. There was no evidence for neurotropism or meningeal inflammation. Sandfly fever virus was infectious for cynomolgus monkeys, but produced no detectable clinical disease that might serve as a marker for animal modeling studies. On the other hand, the preclinical data provide supportive evidence for safe parenteral administration of a Sicilian strain of sandfly fever virus inoculum to humans as a challenge model for sandfly fever disease.
Insights
Sandfly fever virus infects cynomolgus monkeys but causes no clear disease, limiting its use as an animal model. Preclinical data suggest the Sicilian strain is safe for human challenge studies.
Area of Science:
- Virology
- Infectious Diseases
- Primate Models
Background:
- Sandfly fever studies historically relied on human challenge trials due to the absence of a suitable animal model.
- Investigating alternative models is crucial for understanding sandfly fever virus pathogenesis and developing countermeasures.
Purpose of the Study:
- To evaluate the infectivity and pathogenicity of sandfly fever virus in cynomolgus monkeys (Macaca fascicularis).
- To assess the potential of cynomolgus monkeys as an animal model for sandfly fever.
Main Methods:
- Three preparations of sandfly fever virus (Sicilian strain) and a placebo were administered to cynomolgus monkeys via different routes (intravenous and intramuscular).
- Clinical observations, including lymphocyte counts, and serological responses (plaque-reduction neutralization) were monitored post-challenge.
Main Results:
- Sandfly fever virus was infectious in cynomolgus monkeys, but no significant clinical disease was observed.
- The most notable finding was a transient decrease in lymphocytes in intramuscularly challenged monkeys.
- Intravenous challenge resulted in earlier peak plaque-reduction neutralization responses compared to intramuscular challenge.
- No evidence of neurotropism or meningeal inflammation was detected.
Conclusions:
- Cynomolgus monkeys are susceptible to sandfly fever virus infection, but do not develop a clinically apparent disease, thus not serving as an ideal animal model.
- Preclinical findings support the safety of parenteral administration of the Sicilian strain for use in human challenge models of sandfly fever.
