Chlamydial persistence is a reversible state generated during conditions deleterious to growth. In persistence, Chlamydia trachomatis remains viable but atypical, with an enlarged, aberrant form and quiescent metabolism. It favours chronic chlamydiosis, leading to serious sequelae. Although the mechanism of persistence formation is still unknown, more reliable molecular approaches tend to confirm that its occurs in vivo, even lasting 3 years. One approach consists of identifying unprocessed rRNA found only in viable Chlamydia, when infection is not apparent. Another approach, referring to the fact that immunity is type-specific, consists of showing by genotyping that multiple recurrences are due to the same genovar. At the molecular level, persistence is characterized by increased expression of ct755, one of the three heat shock protein (hsp60)-coding genes. In addition, chromosomal replication occurs continuously, and cell division is blocked possibly due to the repression of genes such as ftsW and amiA. At the immunological level, persistence reveals the failure of host-defence mechanisms because of reduced or suppressed pro-inflammatory or cytotoxic responses.

Although the number of known HIV-infected students in Madagascar increased significantly between 1989 and 1995, very little is known about student behaviour with regard to AIDS. The study objectives were: to describe Malagasy students' sexual behaviour and condom use; to document students' perceptions about condoms; and to study the relationships between students' socio-demographic characteristics, their perceptions about condoms, and their condom use. The survey used a cross-sectional design and was conducted at the Antananarivo's university campus sites. Anonymous questionnaires were self-administered to 320 randomly selected students.Descriptive statistics and 95% confidence intervals were calculated. Logistic regressions were performed to identify the predictors of condom use. Participants' average age was 24 years. Approximately 80% of the participants reported sexual experiences, and the average age at sexual debut was 19 years. Only 5.7% reported consistent condom use. Common reasons for non-use were steady relationships (75.6%), the perception that condoms were useful only during ovulation periods (8.7%), and the decrease of pleasure (6.4%). The predictors of condom use were male gender, and the perception that condoms were useful during ovulation periods.Risky sexual behaviours with regard to AIDS were prevalent in this community. An HIV prevention programme is recommended. Keywords: Sexual behaviour, condoms, HIV, students, Madagascar. RésuméBien que le nombre connu des étudiants malgaches infectés par le VIH ait largement augmenté entre 1989 et 1995, l'information sur le comportement des étudiants par rapport au SIDA est très limitée. Les objectifs de cette étude furent: 1) décrire le comportement sexuel des étudiants malgaches et l'utilisation du préservatif, 2) documenter les perceptions des étudiants envers les préservatifs, 3) examiner dans quelle mesure l'utilisation du préservatif par les étudiants varie en fonction de leurs caractéristiques sociodémographiques et leurs perceptions envers les préservatifs. Cette étude a été menée dans les sites du campus universitaire d' Antananarivo en utilisant un devis transversal. Un questionnaire anonyme a été auto-administré à 320 étudiants sélectionnés au hasard. Des statistiques descriptives et intervalles de confiance à 95% ont été calculés. La régression logistique a été utilisée pour identifier les déterminants de l'utilisation du préservatif. La moyenne d'âge des participants était de 24 ans. Environ 80% des répondants ont signalé avoir eu des rapports sexuels et l'âge moyen de premiers rapports était de 19 ans. Seulement 5,7% ont rapporté l'utilisation systématique du préservatif. Les raisons de non utilisation furent les suivantes : être dans une relation stable (75,6%), la perception que le préservatif est uniquement utile durant la période d' ovulation (8,7%) et la réduction du plaisir (6,4%). Le genre masculin et l'argument d' ovulation ont été identifiés comme prédicteurs d'utilisation de préservatifs. Les comportements sexuels à risque...

1 To test the feasibility of administering antibiotics by subcutaneous infusion to the elderly, we compared the pharmacokinetics of tobramycin (single dose of 80 mg) given by hypodermoclysis (HDC) with the kinetics of the antibiotic injected intravenously (i.v.) in 10 young (<50 years old) and 10 elderly (>65 years old) healthy volunteers. Similar studies were performed with ampicillin (single dose of 1 g) in 12 young and 10 older healthy volunteers. 2 Compared with the i.v. route, HDC delayed the time to reach the maximal plasma concentration (t max ) of tobramycin in young volunteers: 32±6 (s.d.) min vs 88±46, P<0.005, and older volunteers: 27±4 min vs 89±15, P<0.005. Administration of the antibiotics by HDC was well tolerated. The plasma concentration of tobramycin 30 min after the end of infusion (C 60 ) was lower (P<0.05) following HDC than after the i.v. route in both young, 2.2±0.7 vs 3.5±0.8 mg ml−1, and elderly subjects, 2.2±0.8 vs 3.8±0.9. mg ml−1. 3 The area under the curve (AUC) of tobramycin given by HDC was slightly smaller than when given i.v., i.e. in young subjects: 740±225 (s.d.) vs 893±223 mg ml−1 min, NS, and in the elderly: 980±228 vs 1056±315 mg ml−1 min, NS. 4 When ampicillin was administered by HDC, the t max was also delayed in young volunteers: 45±18 vs 23±6 min, and in the elderly: 49±18 vs 27±4 min, P<0.005, the AUC was greater by HDC than i.v. in the young volunteers: 4527±1658 mg ml−1 min vs 3810±1033 mg ml−1 min and in the elderly: 6795±2094 mg ml−1 min vs 4217±1518 mg ml−1 min, and the C 60 was higher by HDC in the young: 27±7 vs 24±9 mg ml−1, and in the elderly: 32±9 vs 23±11 mg ml−1, P<0.05. 5 In conclusion, HDC delays the entry of the antibiotic into the systemic circulation, but did not affect the amount available. HDC was well tolerated and could become an adequate method for antibiotic administration to the elderly.

Correspondence to: Dr M. Ravaoarinoro, Département de microbiologie médicale et infectiologie, section de microbiologie clinique, CHUM-Hôtel-Dieu, 3840 rue St-Urbain, Porte 5-206, Montréal, QC H2W 1T8, Canada. E-mail: madeleine.ravaoarinoro.chum@ssss.gouv.qc.ca AbstractChlamydia trachomatis, an intracellular obligate bacterium, remains responsible for a large spectrum of disorders that can progress to chronic diseases, resulting in severe sequelae, such as tubal infertility and blindness. These sequelae may be due to deleterious immune responses induced by repeated or persistent infections. By initiating and regulating inflammation as well as immune responses, pro-inflammatory cytokines secreted by local infected epithelial and immune cells, such as monocytes, may play an essential role in immunity and in the immunopathogenesis of chlamydial diseases. In this study, we mimicked the in vivo interaction between epithelial cells and monocytes by co-culturing epithelial-like HeLa cells with monocyte-like THP-1 cells. Pro-inflammatory cytokines [interleukin-b (IL-1b), IL-6, IL-8, IL-10, IL-12p70 and tumour necrosis factora (TNF-a)] were measured by multiplexed cytometric bead array assay over a period of 18 days. We observed that pro-inflammatory cytokine secretion was augmented after C. trachomatis infection in HeLa and THP-1 cells. However, this heightened secretion was subsequently reduced. When infected HeLa cells were co-cultured with THP-1 cells, IL-6 and IL-8 secretion was sustained, IL-1b expression followed a bell-shaped curve and IL-10, IL-12p70 and TNF-a synthesis was downregulated. IL-6 and IL-8 may be involved in the immunopathogenesis of chronic chlamydial infections. We also observed that throughout C. trachomatis persistence induced by doxycycline (Dox) treatment, IL-1b, IL-6, IL-8 and TNF-a expression was reduced, whereas the synthesis of IL-10 and IL12p70 remained unchanged but not sustained. Thus, during chlamydial persistence infection evoked by treatment with Dox, none of the tested cytokines showed sustained expression.

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Amikacin, netilmicin and tobramycin were incorporated into either anionic or cationic liposomes prepared by sonication. The influence of lipid constituents (charges) on encapsulation efficiency was determined after lysis of vesicles by 0.2% (v/v) Triton X-100. The in-vitro activities of the liposomal aminoglycosides were evaluated against Pseudomonas aeruginosa by agar dilution and compared with free antibiotics. Normal human pooled sera, incubated at 37 degrees C, were supplemented with anionic or cationic liposomes containing known fixed concentrations of amikacin, netilmicin or tobramycin. At various time intervals (0-48 h), samples were taken and antibiotic concentrations determined by the enzyme multiplied immunoassay technique (EMIT). The encapsulation efficiency of cationic liposomes (amikacin 17.1 +/- 1.55%, netilmicin: 5.63 +/- 1.13%, tobramycin 6.7 +/- 0.5%) was approximately 30% higher than that of anionic liposomes (amikacin 12.3 +/- 0.95%, netilmicin 4.0 +/- 0.06%, tobramycin 5.13 +/- 0.18%). Anionic and cationic liposomes in human serum still retained 79.13 +/- 4.04% and 82.71 +/- 2.6% of amikacin, 50.67 +/- 1.8% and 38.6 +/- 0.8% of netilmicin, and 89.09 +/- 1.0% and 88.93 +/- 0.4% of tobramycin, respectively, after 48 h of incubation at 37 degrees C under 5% CO2. The MICs of amikacin (2, 16 and 2 mg/L), netilmicin (2, 1 and 4 mg/L) and tobramycin (1, 2 and 4 mg/L) in free, anionic or cationic liposomal formulations, respectively, were relatively comparable except for anionic liposomal amikacin for which the MIC was increased eight-fold. Empty cationic or anionic liposomes had no effect on bacterial growth. Cationic liposomes containing aminoglycosides should be evaluated further for the treatment of pseudomonal infection.

Tetracycline and doxycycline were encapsulated in cationic, anionic and neutral liposomes. The amounts of antibiotic encapsulated, the stability of each preparation at 4 degrees C for 4 weeks, and the kinetics of the release of entrapped drug into human sera were assessed by high-performance liquid chromatography. The toxicities of the liposome preparations on human erythrocytes and HeLa 229 cells were evaluated in vitro. The results showed that doxycycline was entrapped more efficiently than tetracycline, and that doxycycline-entrapped liposomes were more stable at 4 degrees C and in human sera, and less cytotoxic than tetracycline-entrapped liposomes.

The rates at which free, cationic and anionic liposomal forms of amikacin, netilmicin and tobramycin kill Pseudomonas aeruginosa were studied in vitro. Control inocula with no antibiotic yielded 6.76, 9.53 and 9.74 log CFU/ml at 0, 6 and 24 h, respectively. Empty anionic or cationic liposomes had no effect on bacterial growth. The killing rates of free antibiotics against the bacterial strain were not enhanced by the addition of either empty anionic or cationic liposomes. After 6 and 24 h of exposure at 1, 2 and 4 times the minimum inhibitory concentrations, free amikacin, netilmicin and tobramycin demonstrated a more rapid bactericidal effect than encapsulated anionic or cationic liposomes. The killing rates of liposomal aminoglycosides were lower than those of free aminoglycosides at identical concentrations, suggesting that only fractions of the encapsulated drugs were released from liposomes.