A Refined Guinea Pig Model of Foot-and-Mouth Disease Virus Infection for Assessing the Efficacy of Antiviral Compounds.

An antiviral containment strategy for foot-and-mouth disease (FMD) outbreaks could support or replace current contingency plans in case of an outbreak in Europe and could spare many healthy animals from being pre-emptively culled. Recently, substantial progress has been made towards the development of small molecule drugs that inhibit FMD virus (FMDV) replication in vitro. For the initial in vivo evaluation of antiviral lead molecules, a refined FMDV-infection model in guinea pigs (GP) is herewith described. This GP model was validated by demonstrating the antiviral effect of T-1105 (an influenza virus inhibitor with reported activity against FMDV). Sixteen animals were orally administered with T-1105 twice daily (400 mg/kg/day) for five consecutive days and inoculated intraplantarly with 100 GPID50 of the GP-adapted FMDV strain O1 Manisa 1 h after the first administration. The efficacy of T-1105 was compared with that of prophylactic vaccination with a highly potent double-oil emulsion-inactivated O1 Manisa vaccine. Ten animals received a single, full (2 ml) cattle vaccine dose and were inoculated 3 weeks later. Fourteen T-1105-treated and all vaccinated GP were completely protected from generalization of vesicular lesions. At 2 dpi, viral RNA was detected in serum of 9/16 T-1105-treated and of 6/10 vaccinated animals. At 4 dpi, viral RNA was detected in serum, organs and oral swabs of half of the T-1105-treated animals and only in the serum of 1/10 of the vaccinated animals. Mean viral RNA levels in serum and organs of T-1105-treated and vaccinated animals were reduced compared to untreated controls (P < 0.01). T-1105 conferred a substantial clinical and virological protection against infection with O1 Manisa, similar to the protection afforded by vaccination. These results validate the suitability of the enhanced GP model for the purpose of initial evaluation of inhibitors of FMDV replication and illustrate the potential of selective inhibitors of viral replication to control FMD outbreaks.

Proof of concept for the inhibition of foot-and-mouth disease virus replication by the anti-viral drug 2'-C-methylcytidine in severe combined immunodeficient mice.

Recent European contingency plans envisage emergency vaccination as an animal-friendly control strategy for foot-and-mouth disease (FMD). Anti-viral drugs may be used as an alternative or complementary measure. We here demonstrate that the nucleoside analogue 2'-C-methylcytidine (2'CMC) protects severe combined immunodeficient (SCID) mice against lethal FMD virus infection. In brief, SCID mice were inoculated with serotype A FMD virus and treated for five consecutive days with 2'CMC. All 15 treated mice remained healthy until the end of the study at 14 days post-infection (dpi). At that time, viral RNA was no longer detected in 13 of 15 treated mice. All eight untreated mice suffered from an acute generalized disease and were euthanized for ethical reasons on average at 4 dpi. These results illustrate the potential of small molecules to control FMD.

Evaluation of routine ultrasound examination for the prenatal diagnosis of malformation.

In 1986, a retrospective survey was undertaken in the southern part of the province of Hainaut, Belgium, in order to measure the frequency of ultrasound examinations during pregnancy and to evaluate the effectiveness of the routine practice of echography screening for the detection of congenital malformations in an unselected population. The reference populations comprised 8316 pregnancies covered by the EUROCAT Registry of Hainaut. In 1986, 190 congenital malformations cases were registered. For each of the 190 cases, one control ending in the birth of a non-malformed infant was retrospectively selected. The analysis showed that an average of four ultrasound examinations were performed during pregnancy. When all malformations are considered, the sensitivity of the screening is 14% (27/190). Sensitivity of detection varied from 100% for gross malformations such as anencephaly to 0% for defects of a minor size such as facial clefts. In these 27 cases, obstetrical interventions following prenatal diagnosis were termination of pregnancy in 14 cases and induction of labor in 3 cases. Antenatal care was planned in 8 cases, 5 of which had early surgical repair. In the control group, a malformation was suspected in 3 of the 144 pregnancies (specificity of detection, 98%).