Endemic cryptosporidiosis and exposure to municipal tap water in persons with acquired immunodeficiency syndrome (AIDS): A case-control study

BACKGROUND: In persons with acquired immunodeficiency syndrome (AIDS), Cryptosporidium parvum causes a prolonged, severe diarrheal illness to which there is no effective treatment, and the risk of developing cryptosporidiosis from drinking tap water in non-outbreak settings remains uncertain. To test the hypothesis that drinking tap water was associated with developing cryptosporidiosis, we conducted a matched case-control study among persons with AIDS in San Francisco. METHODS: Among patients reported to the San Francisco AIDS Registry from May 1996 through September 1998, we compared patients who developed cryptosporidiosis to those who did not. Cases were individually matched to controls based on age, sex, race/ethnicity, CD4(+ )T lymphocyte count, date of CD4(+ )count, and date of case diagnosis. Population attributable fractions (PAFs) were calculated. RESULTS: The study consisted of 49 cases and 99 matched controls. In the multivariable analysis with adjustments for confounders, tap water consumption inside and outside the home at the highest exposure categories was associated with the occurrence of cryptosporidiosis (inside the home: odds ratio (OR), 6.76; 95% CI 1.37–33.5, and outside the home: OR 3.16; 95% CI 1.23–8.13). The PAF was 85%; that is, the proportion of cases of cryptosporidiosis in San Francisco AIDS patients attributable to tap water consumption could have been as high as 85%. CONCLUSIONS: Although the results from this observational study cannot be considered definitive, until there is more data, we recommend persons with AIDS, especially those with compromised immune systems, consider avoiding tap water

Exploiting evolutionary steering to induce collateral drug sensitivity in cancer

Drug resistance mediated by clonal evolution is arguably the biggest problem in cancer therapy today. However, evolving resistance to one drug may come at a cost of decreased fecundity or increased sensitivity to another drug. These evolutionary trade-offs can be exploited using 'evolutionary steering' to control the tumour population and delay resistance. However, recapitulating cancer evolutionary dynamics experimentally remains challenging. Here, we present an approach for evolutionary steering based on a combination of single-cell barcoding, large populations of 108-109 cells grown without re-plating, longitudinal non-destructive monitoring of cancer clones, and mathematical modelling of tumour evolution. We demonstrate evolutionary steering in a lung cancer model, showing that it shifts the clonal composition of the tumour in our favour, leading to collateral sensitivity and proliferative costs. Genomic profiling revealed some of the mechanisms that drive evolved sensitivity. This approach allows modelling evolutionary steering strategies that can potentially control treatment resistance

Transcutaneous immunization as preventative and therapeutic regimens to protect against experimental otitis media due to nontypeable Haemophilus influenzae

We have developed three nontypeable Haemophilus influenzae (NTHI) adhesin-derived immunogens that are significantly efficacious against experimental otitis media (OM) due to NTHI when delivered parenterally. We now expanded our preventative immunization strategies to include transcutaneous immunization (TCI) as a less invasive, but potentially equally efficacious, regimen to prevent OM due to NTHI. Additionally, we examined the potential of TCI as a therapeutic immunization regimen to resolve ongoing experimental OM. Preventative immunization with NTHI outer membrane protein (OMP) P5- and type IV pilus-targeted immunogens, delivered with the adjuvant LT(R192G-L211A), induced significantly earlier clearance of NTHI from the nasopharynges and middle ears of challenged chinchillas compared with receipt of immunogen or adjuvant alone. Moreover, therapeutic immunization resulted in significant resolution of established NTHI biofilms from the middle ear space of animals compared with controls. These data advocate TCI with the adhesin-directed immunogens as an efficacious regimen for prevention and resolution of experimental NTHI-induced OM

Trends and connections across the Antarctic cryosphere

Satellite observations have transformed our understanding of the Antarctic cryosphere. The continent holds the vast majority of Earth’s fresh water, and blankets swathes of the Southern Hemisphere in ice. Reductions in the thickness and extent of floating ice shelves have disturbed inland ice, triggering retreat, acceleration and drawdown of marine-terminating glaciers. The waxing and waning of Antarctic sea ice is one of Earth’s greatest seasonal habitat changes, and although the maximum extent of the sea ice has increased modestly since the 1970s, inter-annual variability is high, and there is evidence of longer-term decline in its extent