Mobility and the spread of human immunodeficiency virus into rural areas of West Africa.

BACKGROUND: In eastern and southern Africa, the human immunodeficiency virus (HIV) epidemic appeared first in urban centres and then spread to rural areas. Its overall prevalence is lower in West Africa, with the highest levels still found in cities. Rural areas are also threatened, however, because of the population's high mobility. We conducted a study in three different communities with contrasting infection levels to understand the epidemiology of HIV infection in rural West Africa. METHOD: A comparative cross-sectional study using a standardized questionnaire and biological tests was conducted among samples in two rural communities of Senegal (Niakhar and Bandafassi, 866 and 952 adults, respectively) and a rural community of Guinea-Bissau (Caio, 1416 adults). We compared the distribution of population characteristics and analysed risk factors for HIV infection in Caio at the individual level. RESULTS: The level of HIV infection was very low in Niakhar (0.3%) and Bandafassi (0.0%), but 10.5% of the adults in Caio were infected, mostly with HIV type 2 (HIV-2). Mobility was very prevalent in all sites. Short-term mobility was found to be a risk factor for HIV infection among men in Caio (adjusted odds ratio (aOR) = 2.06; 95% CI: 1.06-3.99). Women from Caio who reported casual sex in a city during the past 12 months were much more likely to be infected with HIV (aOR = 5.61 95% CI: 1.56-20.15). Short-term mobility was associated with risk behaviours at all sites. CONCLUSIONS: Mobility appears to be a key factor for HIV spread in rural areas of West Africa, because population movement enables the virus to disseminate and also because of the particularly risky behaviours of those who are mobile. More prevention efforts should be directed at migrants from rural areas who travel to cities with substantial levels of HIV infection.

Increased prevalence of retrovirus infections among older women in Africa.

Recent studies of HIV-2 have suggested an increased incidence and prevalence among women older than 45 y compared with younger women. We therefore examined whether this phenomenon applied generally to all 3 major retroviruses, HIV-1, HIV-2 and HTLV-I, among women in Africa. We conducted a MedLine search from 1987 to 1997, using the keywords Africa and HIV-1, HIV-2 or HTLV, respectively. Community studies, national surveys and studies on professional cohorts were selected. Age groups > 45/50 y were compared with the age group with the lowest female/male prevalence ratio between 20 and 44 y of age. Thirty-one studies had sufficient data to be included. The female/male odds ratio (OR) for seropositivity was calculated for the old and the young age groups, respectively, providing the ratio of odds ratios: OR (old)/OR (young). Summary ratios for studies of all 3 retroviruses were estimated. In general we found a higher female/male prevalence ratio in the age group over 45/50 y than in the younger age group. For HIV-1 the odds ratio was 1.82 times [95% confidence interval (CI) 1.19-2.79] higher in the old age group than in the young group. For HIV-2 it was 1.97 [95% CI 0.95-4.08], and for HTLV-I it was 2.02 [95% CI 0.99-4.14] times higher. For all 3 viruses combined, the ratio was 1.88 [95% CI 1.36-2.61]. The few incidence studies of HIV-1 and HIV-2 indicated a similar tendency. Since differential mortality is unlikely to explain the pattern, the increase in the HIV-1, HIV-2 and HTLV-I female/male prevalence ratio suggests that older women may have increased exposure or susceptibility to all 3 retrovirus infections.

Inhibition of human and duck hepatitis B virus by 2',3'-dideoxy-3'-fluoroguanosine in vitro.

The fluorinated guanosine analog 2',3'-dideoxy-3'-fluoroguanosine (FLG) has been shown to have an effect on duck hepatitis B virus (DHBV) in vivo and in vitro. In this study the inhibitory effect of FLG on DHBV and human hepatitis B virus (HBV) was evaluated in vitro. Cell lines transfected either with DHBV or HBV DNA and primary duck hepatocyte cell cultures were used. Virus production was analysed by PCR and a quantitative PCR was established for DHBV for determination of the inhibitory concentrations of the drug. 50% inhibition was achieved with an FLG concentration of 0.2 microg/ml (0.7 microM) and 90% inhibition was observed with an FLG concentration of 1.0 microg/ml (3.7 microM) using the DHBV transfected cell line. FLG showed an effect on DHBV production in primary duck hepatocyte cell cultures at concentrations down to 0.1 microg/ml (0.4 microM). However, the DHBV production returned to pre-treatment levels within a few days after cessation of treatment. HBV production in transfected cell lines was also inhibited by FLG. Both DHBV and HBV DNA-polymerases were inhibited by FLG triphosphate and 50% inhibition was observed at a concentration of 0.05 microg/ml (0.1 microM) for DHBV and 0.03 microg/ml (0.05 microM) for HBV. FLG is an efficient inhibitor of DHBV replication both in vivo and in vitro and of HBV in vitro which makes it a good candidate for treatment of HBV infections. However, it does not completely eliminate the virus since a relapse in virus production was observed when treatment was withdrawn. Therefore it would be interesting to evaluate FLG in combination with other types of anti-HBV drugs.

Pharmacological analysis of acute morphine dependence in infant rats: close molecular relationship of head-shaking precipitated by opiate antagonists and cholinergic neurotransmission.

The influence of drugs affecting different neurotransmitter systems on an acute abstinence head-shaking (AHS) model induced by nalorphine or naloxone was studied in 9-day-old rat pups pretreated (3 h before) with morphine (10 mg/kg, i.p.). One hour after the injection of nalorphine (10 mg/ kg, i.p.) AHS was stopped by a second dose of morphine (10 mg/kg, i.p.) and reinitiated 1 h later by a higher dose of nalorphine (20 mg/kg, i.p.). In other groups AHS was blocked by spiroperidol (0.1 mg/kg, i.p.), clonidine (0.01 mg/kg, i.p.) or scopolamine (50 mg/kg, i.p.). In these groups a second injection of nalorphine did not reinitiate AHS. In dose-effect curve experiments the AHS induced by naloxone or nalorphine was significantly reduced by previous injections of scopolamine, spiroperidol, metergoline or phentolamine in the corresponding groups. Scopolamine was the only antagonist which displaced the AHS dose-effect curves to the right without affecting the maximal response. Since no common receptors exist for a direct competitive interaction between opiate antagonists and scopolamine, these experiments suggest that a direct molecular relationship exists between the tissue concentration of nalorphine (or naloxone) and the endogenous ACh release during abstinence. Thus, the AHS model in 9-day-old rats clearly differentiates specific from non-specific blockade of the abstinence syndrome, and confirms a distinct or primary role of cholinergic neurotransmission in morphine abstinence.

Two inbred rat sublines that differ in spontaneous yawning behavior also differ in their responses to cholinergic and dopaminergic drugs.

This work compares the sensitivities of high-yawning (HY) and low-yawning (LY) sublines of Sprague-Dawley rats to dopaminergic and cholinergic yawning-inducing drugs. HY animals are significantly more sensitive to apomorphine and (-)3PPP than LY animals. Physostigmine is a less effective yawning-inducer in HY than in LY rats. With pilocarpine no differences were detected between both sublines in regard to its yawning-inducing activity. Since yawning behavior is subject to dopaminergic (inhibitory) and cholinergic (excitatory) influences, it is suggested that the genetic differences between these sublines affect the dopaminergic pathways that normally regulate yawning frequency.

The taiep rat: a myelin mutant with an associated oligodendrocyte microtubular defect.

This report describes a new inherited disorder of myelination in the rat, named taiep, in which failure of normal myelination of the CNS and subsequent demyelination result in a progressive neurological disturbance. At two months of age, myelin is present throughout the spinal cord, but is immature in the fasciculus gracilis and corticospinal tracts despite the presence of abundant oligodendrocytes. By 12 months, myelin has largely been lost in these spinal cord tracts and also in more rostral parts of the CNS, such as the cerebellum and optic nerves. Other funiculi of the spinal cord show a more diffuse lack of myelin. Oligodendrocytes develop a unique cellular abnormality, most obviously in older rats, which is characterized by the accumulation of microtubules throughout their cytoplasm. As the mutant rats age, there is a continued protracted breakdown of myelin throughout the CNS, with evidence suggesting either persistent hypomyelination or attempts at remyelination of affected axons. It is proposed that the microtubular defect in oligodendrocytes results in a disruption of the normal myelination process in certain areas of the CNS of this mutant, and eventually leads to failure of maintenance of the myelin sheath.

Age-dependent changes in serotonergic modulation of yawning in the rat.

Serotonin (5-HT) effects on physostigmine (PHY)-induced yawning were studied in LY Sprague-Dawley rats by injecting Lu 10 171 (citalopram), a specific 5-HT uptake blocker, and two antagonists--methiothepine and ritanserin--which differ slightly in the selectivity of their actions on different 5-HT receptor subtypes. Infant and young rats show significant increases in PHY-induced yawning when preinjected with citalopram (5-10 mg/kg). Two-month-old animals show this effect only with 10 mg/kg. With adult animals (3-5 months old), the effect is the opposite: Yawning decreases. The facilitory effect in infant and young rats was counteracted by methiothepine but not by ritanserin, suggesting that it is mediated through 5-HT1A or 5-HT1B receptor subtypes. The inhibitory effect of citalopram in adult rats was unmodified by the two antagonists used, leaving open the possibility that it is mediated by 5-HT3 receptors.

Sleep and EEG disturbances in a rat neurological mutant (taiep) with immobility episodes: a model of narcolepsy-cataplexy.

The electroencephalographic sleep patterns recorded during short periods of time (3 h) of a neurological mutant rat (taiep) were studied. This rat exhibits, among other signs, immobility episodes that are similar to those observed in narcolepsy-cataplexy. We describe findings of long term (6 months) electroencephalographic studies done in 9 mutant and 5 control rats. The mutant rats present electroencephalographic and behavioral disorders consisting of: (a) bursts of cortical waxing and waning waves occurring during the drowsy state; in some animals this activity represents up to 25% of the total drowsiness time; (b) shortened sleep time; (c) fragmented paradoxical sleep; (d) immobility episodes when the animals are subjected to an emotional excitement; and (e) electrographic activity of paradoxical sleep without atonia during the immobility episodes. These findings show that the taiep mutant shows several aspects of narcolepsy-cataplexy and it may represent an experimental model for the study of this pathology.

Food anticipatory yawning rhythm in the rat.

The effect of feeding schedules on the daily rhythm in spontaneous yawning activity was studied in high yawning (HY) Sprague-Dawley rats. If the animals are fed ad libitum and changed from a standard 12-12 light-dark (LD) illumination regime to constant light (LL), the normal predark circadian peak in yawning disappears, to be replaced, after 3 weeks, by two or more ultradian smaller peaks in yawning frequency. Restriction of food availability to 2-2:30 regular hours of the day, in rats under LL conditions, leads to the appearance of a significant preprandial (food anticipatory) peak in yawning. A similar eating-fasting daily cycle of 2-22 h in rats under LD conditions determines the disappearance of the pre-dark peak in yawning activity, and a significant shift in higher yawning frequency towards the couple of hours preceding food availability. This result suggests that restricted feeding is more potent than the LD transition in the entrainment of the daily rhythm in yawning activity.

Genotypic dependency of spontaneous yawning frequency in the rat.

By inbreeding we have obtained two sublines of Sprague-Dawley rats which differ significantly in spontaneous mean yawning frequency (MYF). In generation F21 of the high-yawning (HY) subline MYF was 21.5 yawns/h (y/h) in males and 1.95 y/h in females, at the age of 2 months. In the low-yawning (LY) subline, in generation F16 the MYF was 0.9 y/h in males and only 0.5 y/h in females. During the first 15 days there are no differences in yawning frequency between HY and LY rats. Thereafter yawning increases with age, more steeply in the HY subline. The results of reciprocal crosses between both sublines indicate that the LY character is partially dominant over the HY one.

GABAergic modulation of yawning behavior.

The hypothetical modulation by GABAergic neurons of yawning behavior in the rat was explored with GABA-active drugs. Gamma-acetylenic-GABA, a specific inhibitor of GABA-T, increases yawning frequency when injected at a dose of 7 mg/kg. Baclofen, a GABAB agonist (3 mg/kg), inhibits yawning completely; GABA antagonists, bicuculline and picrotoxin, at subconvulsant doses, also decrease yawning. All drugs were injected intraperitoneally with the exception of apomorphine, which was injected subcutaneously. It is suggested that GABAB receptors play a role in yawning behavior by modulating ACh release, and that GABAA receptors may modify yawning frequency by modulating inhibitory influences on ACh neurons.

Sprague Dawley rat mutant with tremor, ataxia, tonic immobility episodes, epilepsy and paralysis.

A spontaneous neurological mutation was detected in a colony of Sprague Dawley rats. The animals developed a progressive neurological syndrome characterized by tremor (which appeared at the age of 1 month), ataxia (at 4 months), immobility episodes (after 5-6 months), audiogenic seizures and hindlimb paralysis (after 10 months). Cross breeding experiments indicate that this is an autosomal recessive mutation, which we have named taiep subline.

Association of spontaneous and dopaminergic-induced yawning and penile erections in the rat.

In a Sprague-Dawley-derived line of rats, selectively bred to establish a high incidence of spontaneous yawning behavior, the simultaneous and systematic monitoring of yawning and penile erections, during observation periods of one hour, demonstrates a linear correlation between these two behavioral patterns. Dose-effect curves of yawning and penile erections elicited by apomorphine and bromocriptine, and their inhibition by metoclopramide are quite similar. These results strongly suggest that yawning and penile erection are subject to some common regulating and modulating mechanisms, one of which seems to involve dopaminergic pathways.

Circadian variation of yawning behavior.

Circadian variation of spontaneous yawning is demonstrated in a line of Sprague-Dawley rats, genetically selected for high frequency of this motor pattern. Yawning is highest in late light and early dark hours, both under natural and artificial illumination. The hypothetical neurotransmitters underlying this physiological rhythm in yawning are discussed.