Disseminated M. avium complex infection in the Swiss HIV Cohort Study: declining incidence, improved prognosis and discontinuation of maintenance therapy.

Introduction of potent antiretroviral combination therapy (ART) has reduced overall morbidity and mortality amongst HIV-infected adults. Some prophylactic regimes against opportunistic infections can be discontinued in patients under successful ART. (1) The influence of the availability of ART on incidence and mortality of disseminated M. avium Complex infection (MAC). (2) The safety of discontinuation of maintenance therapy against MAC in patients on ART. The Swiss HIV-Cohort Study, a prospective multicentre study of HIV-infected adults. Patients with a nadir CD4 count below 50 cells/mm3 were considered at risk for MAC and contributed to total follow-up time for calculating the incidence. Survival analysis was performed by using Kaplan Meier and Cox proportional hazards methods. Safety of discontinuation of maintenance therapy was evaluated by review of the medical notes. 398 patients were diagnosed with MAC from 1990 to 1999. 350 had a previous CD4 count below 50 cells/mm3. A total of 3208 patients had a nadir CD4 count of less than 50 cells/mm3 during the study period and contributed to a total follow-up of 6004 person-years. The incidence over the whole study period was 5.8 events per 100 person-years. In the time period of available ART the incidence of MAC was significantly reduced (1.4 versus 8.8 events per 100 person-years, p < 0.001). Being diagnosed after 1995 was the most powerful predictor of better survival (adjusted hazard ratio for death: 0.27; p < 0.001). None of 24 patients discontinuing maintenance therapy while on ART experienced recurrence of MAC during a total follow-up of 56.6 person-years (upper 95% confidence limit 5.3 per 100 person-years). Introducing ART has markedly reduced the risk of MAC for HIV-infected individuals with a history of very low CD4 counts. Survival after diagnosis of MAC has improved after ART became available. In patients responding to ART, discontinuation of maintenance therapy against M. avium may be safe.

Genetic and phenotypic population divergence on a microgeographic scale in brown trout.

Salmonid populations of many rivers are rapidly declining. One possible explanation is that habitat fragmentation increases genetic drift and reduces the populations' potential to adapt to changing environmental conditions. We measured the genetic and eco-morphological diversity of brown trout (Salmo trutta) in a Swiss stream system, using multivariate statistics and Bayesian clustering. We found large genetic and phenotypic variation within only 40 km of stream length. Eighty-eight percent of all pairwise F(ST) comparisons and 50% of the population comparisons in body shape were significant. High success rates of population assignment tests confirmed the distinctiveness of populations in both genotype and phenotype. Spatial analysis revealed that divergence increased with waterway distance, the number of weirs, and stretches of poor habitat between sampling locations, but effects of isolation-by-distance and habitat fragmentation could not be fully disentangled. Stocking intensity varied between streams but did not appear to erode genetic diversity within populations. A lack of association between phenotypic and genetic divergence points to a role of local adaptation or phenotypically plastic responses to habitat heterogeneity. Indeed, body shape could be largely explained by topographic stream slope, and variation in overall phenotype matched the flow regimes of the respective habitats.

Persistent unequal sex ratio in a population of grayling (salmonidae) and possible role of temperature increase.

In some fishes, water chemistry or temperature affects sex determination or creates sex-specific selection pressures. The resulting population sex ratios are hard to predict from laboratory studies if the environmental triggers interact with other factors, whereas in field studies, singular observations of unusual sex ratios may be particularly prone to selective reporting. Long-term monitoring largely avoids these problems. We studied a population of grayling (Thymallus thymallus) in Lake Thun, Switzerland, that has been monitored since 1948. Samples of spawning fish have been caught about 3 times/week around spawning season, and water temperature at the spawning site has been continuously recorded since 1970. We used scale samples collected in different years to determine the average age of spawners (for life-stage specific analyses) and to identify the cohort born in 2003 (an extraordinarily warm year). Recent tissue samples were genotyped on microsatellite markers to test for genetic bottlenecks in the past and to estimate the genetically effective population size (N(e) ). Operational sex ratios changed from approximately 65% males before 1993 to approximately 85% males from 1993 to 2011. Sex ratios correlated with the water temperatures the fish experienced in their first year of life. Sex ratios were best explained by the average temperature juvenile fish experienced during their first summer. Grayling abundance is declining, but we found no evidence of a strong genetic bottleneck that would explain the apparent lack of evolutionary response to the unequal sex ratio. Results of other studies show no evidence of endocrine disruptors in the study area. Our findings suggest temperature affects population sex ratio and thereby contributes to population decline. Persistencia de Proporción de Sexos Desigual en una Población de Tímalos (Salmonidae) y el Posible Papel del Incremento de la Temperatura.