Reductions in risk behaviour provide the most consistent explanation for declining HIV-1 prevalence in Uganda.

OBJECTIVE: To monitor the HIV-1 epidemic in Western Uganda and the possible impact of interventions. DESIGN: Results from sentinel surveillance of HIV-1 seroprevalence were compared with cross-sectional serosurvey data and model simulations. METHODS: Age-specific trends in HIV-1 prevalence between 1991 and 1997 amongst antenatal clinic (ANC) attenders in the town of Fort Portal, where a comprehensive AIDS control programme has been implemented since 1991, were analysed. Results were compared with outputs from a mathematical model simulating the HIV-1 epidemic in Uganda. Two scenarios were modelled: one without and one with behaviour change. Sentinel surveillance data were compared with data from a population-based HIV-1 serosurvey at the study site, which was carried out in early 1995. RESULTS: Data from 3271 ANC attenders identified greater education and being single as risk factors for HIV-1 infection. A significant decrease of risk for women with secondary school education over time was observed, whereas the risk for illiterate women remained high. Among women aged 15-19 years (n = 1045) education and marital status-adjusted HIV-1 prevalence declined steadily from 32.2% in 1991 to 10.3% in 1997. For 20-24-year-old women (n = 1010) HIV-1 prevalence increased until 1993 from 19.9% to 31.7% and decreased thereafter (21.7% in 1997). These trends closely follow the prediction of the model simulation assuming behaviour change, and for 1995-1997, confidence intervals of the HIV-1 prevalence estimate exclude the model output for an uninfluenced epidemic. No clear trends of HIV-1 prevalence were found in older women (n = 1216) and comparisons with the model were ambiguous. Sentinel surveillance data at the time of the population survey closely reflected results for the female general population sample for the two younger age-groups (15-19 and 20-24 years). In contrast, pregnant women aged 25-29 years showed significantly lower rates than the population sample (20.8% versus 45.1%). CONCLUSION: HIV-1 prevalence amongst ANC attenders aged 15-24 years can be used to monitor the HIV-1 epidemic in the given setting. Declining trends of HIV-1 prevalence in women aged 15-19 and 20-24 years most likely correspond to a reduced HIV-1 incidence attributable to changes in behaviour. Our data also show that sentinel surveillance data need to be age-stratified to give useful information.

Inhibition of endotoxin-induced macrophage tumor necrosis factor expression by a prostacyclin analogue and its beneficial effect in experimental lipopolysaccharide intoxication.

Tumor necrosis factor (TNF), a protein produced in large quantities by endotoxin-activated macrophages, has been implicated as an important mediator of the lethal effect of endotoxin. A stable prostacyclin analogue (iloprost) was investigated for its ability to interfere with TNF secretion of lipopolysaccharide (LPS)-stimulated macrophages. It could be demonstrated by bioassays that LPS-induced TNF production was suppressed in a dose-dependent manner when macrophages were treated with iloprost at the time of LPS stimulation. Northern blot analysis revealed that iloprost inhibited TNF production at the transcription level. In vivo, endotoxin-induced mortality rates in galactosamine-sensitized mice could be significantly (P less than .05) reduced by iloprost administration. It is assumed that prostacyclin modulates endotoxin-induced and TNF-mediated inflammation in septic shock.

Prevention of murine cerebral malaria by a stable prostacyclin analog.

Iloprost, a synthetic prostacyclin analog, successfully prevents the development of cerebral malaria in mice. Malaria antigen-induced tumor necrosis factor (TNF) production could be inhibited by iloprost in vitro and in vivo. Northern analysis of TNF mRNA revealed that malaria antigen-induced TNF expression was suppressed at the transcription level.

Pentoxifylline prevents murine cerebral malaria.

Pentoxifylline, a widely used methylxanthine, was tested for its capacity to prevent cerebral malaria (CM) in Plasmodium berghei ANKA-infected CBA/Ca mice. Nine of 12 control mice developed neurologic signs and died from CM approximately 2 weeks after infection. All 12 mice treated with daily intraperitoneal pentoxifylline (1 mg) for 10 days after infection did not develop CM. All surviving mice developed high parasitemia and severe anemia and died 2 weeks later without neurologic signs. In pentoxifylline-treated mice, serum tumor necrosis factor (TNF) bioactivity was nondetectable, whereas control mice had high TNF levels on day 6 after infection. These findings were supported by in vitro investigations of malaria antigen-induced TNF synthesis. Northern blot analysis of TNF mRNA from stimulated macrophages showed that pentoxifylline inhibited TNF expression at the transcription level, and TNF bioactivity in supernatants was strongly depressed. These findings make pentoxifylline a potential candidate for study as a supportive agent in human CM.

Interferon-gamma treatment in mice experimentally infected with Trichinella spiralis.

Interferon-tau (IFN-tau) treatment of Trichinella spiralis-infected BALB/c mice was investigated. The therapeutic regimen consisted of daily intraperitoneal injection of 10(4) U murine IFN-tau for 7 days, starting at 2 weeks post-infection. Striated muscle samples (diaphragm, thigh) were collected at 4, 8 and 12 weeks after infection. The muscle larval burden, the degree of encystation and the digestion of T. spiralis larvae were investigated. Furthermore, immunohistochemical studies of the inflammatory cell infiltrate around encysted larvae were performed. The results demonstrated an influence of IFN-tau treatment on the CD4+ and CD8+ subset distribution during the immune response but revealed no difference in the degree of encystation or digestion of encapsulated larvae as compared with control values.