Surveillance of influenza-like illness in France. The example of the 1995/1996 epidemic.

STUDY OBJECTIVES: To discover if continuous computerised collection of morbidity data through a medical practice based sentinel network can be used to monitor influenza-like illness (ILI) epidemics. To obtain rough estimates of influenza vaccine effectiveness. DESIGN: Continuous passive surveillance of ILI through a computerised network of voluntary sentinel general practitioners (SGPs) in France (Sentinelle system). SETTING: Five hundred SGPs practices. PARTICIPANTS: Since 1984, SGPs updated a database with information on eight communicable diseases including ILI, via videotext terminals. Each ILI case is defined by the association of a sudden fever of 39 degrees C or above, respiratory symptoms, and myalgias. An ILI epidemic is detected when the national weekly incidence rate exceeds a seasonal threshold for two successive weeks. MAIN RESULTS: An ILI epidemic was reported from November 1995 to January 1996. In total, 13,951 individual cases were reported by SGPs during the epidemic period. The size of the epidemic (number of patients consulting a GP) was estimated to be 2,370,000 subjects. Maps of the epidemic showed that all regions have reported a high level ILI activity. The attack rate was the highest in school age children (13.5/100) and decreased as the age rose. Nearly 6% of the reported ILI cases among adults and elderly were vaccinated. The flu vaccine effectiveness against ILI was estimated to be 66% (95% CI 73%, 92%), ranging between 83% (95% CI 73%, 92%) among the subjects aged 15 to 24 years old to 16% (95% CI -12%, 44%) among the subjects aged 75 years or older. CONCLUSIONS: The Sentinelle system demonstrated adequate sensitivity and timeliness regarding ILI epidemic. Moreover, results of the monitoring were made available on the internet to increase the dissemination of information. Also, estimates of influenza vaccine effectiveness have been easily obtained. Altogether, they represent key points for the control of crisis situation such as ILI epidemics or pandemics.

Antidepressant treatment in helpless rats: effect on the electrophysiological activity of raphe dorsalis serotonergic neurons.

Chronic treatment with antidepressants renders serotonergic neuronal firing less sensitive to the inhibitory effect of serotonin (5-HT) reuptake blockers in the rat, and this has been considered as a major correlate of the therapeutic action of these drugs. We investigated whether the same mechanisms could be evidenced in an experimental model of depression, the learned helplessness paradigm. Rats rendered helpless by a single session of inescapable electrical footshocks exhibit, for several days, depression-like behavioural deficits which can be reversed by sub-chronic, but not acute, treatment with antidepressants. Recording of serotonergic neurons in the dorsal raphe nucleus revealed that, under baseline conditions, the spontaneous firing was similar in helpless rats and in non-helpless controls. However, neurons in the former group exhibited an enhanced sensitivity to the inhibitory action of the 5-HT reuptake blocker, citalopram (ED50 = 0.18 +/- 0.02 mg/kg IV in helpless rats versus 0.27 +/- 0.03 mg/kg IV in controls, P < 0.05). Treatment with zimeldine during 3 consecutive days induced in both helpless and control rats, a decrease in the inhibitory response of serotonergic neurons to the citalopram challenge, which resulted in a normalization of the neuronal reactivity in the helpless group (ED50 = 0.31 +/- 0.03 mg/kg IV). Since this adaptive phenomenon parallels the behavioural improvement induced by the repeated administration of zimeldine and other antidepressants in helpless rats, it might be considered as a crucial event in the mechanism of therapeutic action of these drugs.

Failure of CCK receptor ligands to modify anxiety-related behavioural suppression in an operant conflict paradigm in rats.

The effects of cholecystokinin (CCK) receptor ligands were studied in the rat safety signal withdrawal conflict procedure, an operant paradigm sensitive to both anxiolytic and anxiogenic compounds. In this procedure, behavioural suppression of lever pressing for food was induced by the withdrawal of a conditioned signal for safety without the usual presentation of a conditioned signal for danger. The compounds tested were selective CCK-B antagonists [CI-988 (0.01-1 mg/kg SC), L-365,260 (0.004-2 mg/kg IP) and LY 262,691 (0.001-1 mg/kg SC)], CCK-B agonists [CCK-4 (0.01-1 mg/kg SC) and BC 264 (0.004-1 mg/kg IP)] and CCK-A antagonists [devazepide (0.001-1 mg/kg SC) and lorglumide (0.01-1 mg/kg SC)]. None of these drugs induced the expected behavioural effects, i.e. an anxiolytic-like release of the behavioural suppression with CCK-B and, possibly, CCK-A antagonists and/or a further reduction of lever pressing with CCK-B agonists, indicative of an anxiogenic-like potential. In contrast, the established anxiolytic lorazepam (0.06-0.25 mg/kg IP), as well as diazepam (2 mg/kg IP) and buspirone (0.25 mg/kg SC) used as positive control drugs, released the suppression of pressing for food during the period associated with the safety signal withdrawal, whereas picrotoxin (1 mg/kg IP), used as an anxiogenic control, further reduced responding during this conflict period. The present results contrast with a series of published data suggesting the involvement of CCK processes in anxiety-related behaviour in rodent models such as the elevated plus-maze or the light:dark two compartment test, and in panic disorders in humans.(ABSTRACT TRUNCATED AT 250 WORDS)

Effects of 5-HT1A receptor ligands on a safety signal withdrawal procedure of conflict in the rat.

The present study evaluated in the rat the ability of various 5-HT1A receptor agonists to exert an "anxiolytic-like" release of the suppression of lever pressing for food induced by the withdrawal of a conditioned signal for safety without presentation of a conditioned signal for punishment. During the period associated with the safety signal withdrawal (Saf.CS-/Pun.CS-), control rats exhibited a typical pattern of responding with an initial strong blockade of responding that lessened over the period as presses were rewarded and shocks omitted. The 5-HT1A receptor partial agonists buspirone (0.125-0.5 mg/kg) and 8-(2-[2,3-dihydro-1,4-benzodioxin-2-yl- methylamino]ethyl)-8-azaspiro[4,5]decane-7,9-dione methyl sulfonate (MDL 73005EF; 0.5-2 mg/kg) and the full agonist (+)-4-[N-(5-methoxy-chroman-3-yl)-N-propylamino]-butyl-8- azaspiro[4,5]decane-7,9-dione (S 20499; 0.125-1 mg/kg) produced a robust and dose-related release of pressing during the Saf.CS-/Pun.CS- period. This effect was less marked with ipsapirone (0.125-1 mg/kg). Conversely, 8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT; 0.06-0.25 mg/kg), a full agonist, was completely inactive and did not prevent MDL 73005EF (1-2 mg/kg) or diazepam (0.125 mg/kg) from releasing the suppressed behavior. The specific 5-HT1A antagonist (+)-N-tert-butyl-3-4-(2-methoxyphenyl)piperazin-1-yl-2-phenylpr opa namide [(+)-WAY 100135; 0.25-8 mg/kg] and the beta-adrenoceptor/5-HT1A antagonist (-)-tertatolol (2-8 mg/kg) did not modify the behavioral blockade, nor did (+)-WAY 100135 (2-4 mg/kg) reduce the ability of buspirone (0.25 mg/kg) to enhance responding during the Saf.CS-/Pun.CS- period.(ABSTRACT TRUNCATED AT 250 WORDS)

Safety signal withdrawal: a behavioural paradigm sensitive to both "anxiolytic" and "anxiogenic" drugs under identical experimental conditions.

A new method involving the blockade of operant behaviour induced by the withdrawal of a conditioned signal for safety without presentation of a punishment signal has been developed for studying drugs with anxiolytic or anxiogenic properties. For this purpose, rats were trained under two alternating components of a multiple schedule of reinforcement FR8 (food)/FR1 (food) + RR 50% (shocks randomly delivered with 50 +/- 15% of the presses). The nonpunished and punished periods were signalled by one cue light above the right lever (safety signal) or the left lever (punishment signal), respectively. On the test session (safety signal withdrawal), the safety signal was turned off at the end of the first nonpunished period, but the punishment signal was not presented (every press was food rewarded and no shocks were delivered). During this period (4 min), rats exhibited a strong blockade of responding that lessened over time. This suppression seemed not to be caused by intervening events such as novelty, temporal conditioning, schedule of food delivery or ambiguity of the signal presented. The behavioural blockade induced by withdrawal of the safety signal was reduced by benzodiazepines: diazepam (0.5-4 mg/kg), chlordiazepoxide (4-8 mg/kg), nitrazepam (0.25-2 mg/kg), alprazolam (0.25-1 mg/kg), and partial agonists at benzodiazepine receptors: bretazenil (0.125-8 mg/kg) and ZK 91296 (32-64 mg/kg). Various 5-HT-related drugs also lessened the behavioural blockade:pCPA (3 x 150 mg/kg) and the 5-HT1A receptor agonists, buspirone (0.25-2 mg/kg), gepirone (0.25-1 mg/kg) but not 8-OH-DPAT. Compounds that may cause anxiety in humans further enhanced the blockade of lever pressing induced by the safety signal withdrawal at doses that did not modify baseline responding: d-amphetamine (0.125-0.5 mg/kg), caffeine (16 mg/kg) and picrotoxin (1 mg/kg). FG 7142 (8 mg/kg) and CGS 8216 (2-8 mg/kg) decreased responding during both components of the session. Therefore, the present paradigm seems sensitive to both "anxiolytic" and "anxiogenic" effects of drugs under identical procedural conditions.

Effects of neuroleptic drugs, clonidine and lithium on the expression of conditioned behavioral excitation in rats.

Rats with a history of daily (21 days) amphetamine (2.5 mg/kg) treatment showed enhanced activity when under placebo in their amphetamine-associated environment. We found that this conditioned effect was reduced by haloperidol (0.06; 0.125; 0.25 mg/kg), pimozide (0.25; 0.5 mg/kg) and sulpiride (8; 16; 32 mg/kg) but only at doses similar to or, in the case of pimozide, higher than those required to antagonize the unconditioned stimulant effects of amphetamine (2.5 mg/kg). Conversely, we observed that clonidine (7; 15; 30; 60 micrograms/kg) or lithium regimen (between days 15 and 21) leading to lithium plasma levels of 1.3 +/- 0.1 mEq/l, abolished amphetamine-conditioned hyperactivity but did not affect the unconditioned stimulation of amphetamine or locomotor activity in control rats. Moreover, we found that hyperactivity induced by the daily anticipation of food delivery shared identical pharmacological sensitivity with the behavioural excitation produced by a conditioning history with amphetamine. In light of the antimanic properties of lithium and clonidine and the ability of this latter drug to reduce noradrenergic transmission, our findings raise the possibility that incentive activity may model noradrenergic-dependent aspects of mania.