Targeting the human papillomavirus for prevention of cervical cancer

Different types of human papillomavirus (HPV) vary in the extent they cause precursor lesions (CIN) and cancer. There are limited long-term efficacy data on HPV testing in primary screening Among 72 cervical cancers in Mozambique, HPV 16 and 18 were the most frequent HPV types (69% of cases). Comparing 108 cervical cancers cases and 517 matched controls nested within a population-based cohort in Taiwan, HPV 16 seropositivity implied a 6-fold increased cancer risk. In a cohort of 5696 women in Sweden, HPV types 16, 31 and 33 conveyed the highest risks for future high-grade CIN (CIN 2+), attributing to 33.1%, 18.3% and 7.7% of CIN 2+ cases, respectively. In a pooled analysis of seven European longitudinal studies of HPV-based cervical screening, the cumulative incidence rate of CIN grade 3 or worse (CIN 3+) was higher after 3 years among women with normal cytology than among women with a negative HPV test after 6 years. Finally, in a randomized cervical cancer screening trial in Sweden, adding testing for HPV persistence resulted in a 51% (95% CI: 13-102) increase of CIN 2+ at prevalent screening, which was followed by a reduction of 42% (95% CI: 4-76) of CIN 2+ at incident screening. In conclusion, HPV-based cervical cancer screening protects against future CIN 2+, and the long-term protective effect should enable extended screening intervals to 6 years. Albeit HPV 16 is the most important carcinogenic HPV type all over the world, different ?high-risk? HPV types convey distinctly different risks for CIN 2+, which should be considered in design of screening tests and vaccines

Treatment of Herpes Simplex Virus Type 2 Meningitis:A Survey Among Infectious Diseases Specialists in France, Sweden, Australia, and Denmark

BACKGROUND: We aimed to describe attitudes toward treatment of herpes simplex virus type 2 (HSV-2) meningitis and prioritize future trials. METHODS: This was a self-administered online survey of HSV-2 meningitis treatment among infectious diseases (ID) specialists in France, Sweden, Australia, and Denmark. RESULTS: A total of 223 ID specialists (45% female) from France (36%), Denmark (24%), Sweden (21%), and Australia (19%) participated in the survey, primarily from university hospitals (64%). The estimated overall response rate was 11% and ranged from 6% (Australia) to 64% (Denmark). Intravenous (IV) acyclovir followed by oral valacyclovir was the favored treatment in 110 of 179 (61%), whereas monotherapy with either IV acyclovir or oral valacyclovir was used by 35 of 179 (20%) and 34 of 179 (19%), respectively. The median total duration was reported to be 7 days (interquartile range, 7–10 days) regardless of antiviral regimen. Immunocompromise influenced decisions on antiviral treatment in 110 of 189 (58%) of respondents, mainly by prolonged total duration of treatment (36/110 [33%]), prolonged IV administration (31/110 [28%]), and mandatory antiviral treatment (25/110 [23%]). Treatment with acyclovir/valacyclovir versus placebo and comparison of acyclovir versus valacyclovir were assigned the highest prioritization scores for future randomized controlled trials on HSV-2 meningitis. CONCLUSIONS: Perceptions of indications for as well as type and duration of antiviral treatment varied substantially among ID specialists

Human papillomavirus genotypes in cervical cancers in Mozambique.

The distribution of human papillomavirus (HPV) types in cervical cancers is essential for design and evaluation of HPV type-specific vaccines. To follow up on a previous report that HPV types 35 and 58 were the dominant HPV types in cervical neoplasia in Mozambique, the HPV types in a consecutive case series of 74 invasive cervical cancers in Mozambique were determined. The most common worldwide major oncogenic HPV types 16 and 18 were present in 69 % of cervical cancers, suggesting that a vaccine targeting HPV-16 and -18 would have a substantial impact on cervical cancer also in Mozambique

COVID-19 Modeling Outcome versus Reality in Sweden

It has been very difficult to predict the development of the COVID-19 pandemic based on mathematical models for the spread of infectious diseases, and due to major non-pharmacological interventions (NPIs), it is still unclear to what extent the models would have fit reality in a "do nothing" scenario. To shed light on this question, the case of Sweden during the time frame from autumn 2020 to spring 2021 is particularly interesting, since the NPIs were relatively minor and only marginally updated. We found that state of the art models are significantly overestimating the spread, unless we assume that social interactions significantly decrease continuously throughout the time frame, in a way that does not correlate well with Google-mobility data nor updates to the NPIs or public holidays. This leads to the question of whether modern SEIR-type mathematical models are unsuitable for modeling the spread of SARS-CoV-2 in the human population, or whether some particular feature of SARS-CoV-2 dampened the spread. We show that, by assuming a certain level of pre-immunity to SARS-CoV-2, we obtain an almost perfect data-fit, and discuss what factors could cause pre-immunity in the mathematical models. In this scenario, a form of herd-immunity under the given restrictions was reached twice (first against the Wuhan-strain and then against the alpha-strain), and the ultimate decline in cases was due to depletion of susceptibles rather than the vaccination campaign

Prophylactic anticoagulation with low molecular weight heparin in COVID-19: cohort studies in Denmark and Sweden

OBJECTIVES: To evaluate safety and effectiveness of prophylactic anticoagulation with low molecular weight heparin (LMWH) in individuals hospitalised for COVID-19. METHODS: Using healthcare records from the capital region of Denmark (March 2020-February 2021) and Karolinska University Hospital in Sweden (February 2020-September 2021), we conducted an observational cohort study comparing clinical outcomes 30 days after admission among individuals hospitalised for COVID-19 starting prophylactic LMWH during the first 48 hours of hospitalisation with outcomes among those not receiving prophylactic anticoagulation. We used inverse probability weighting to adjust for confounders and bias due to missing information. Risk ratios, risk differences and robust 95% confidence intervals (CI) were estimated using binomial regression. Country-specific risk ratios were pooled using random-effects meta-analysis. RESULTS: We included 1692 and 1868 individuals in the Danish and Swedish cohorts. Of these, 771 (46%) and 1167 (62%) received prophylactic LMWH up to 48 hours after admission. The combined mortality in Denmark and Sweden was 12% (N=432) and the pooled risk ratio was 0.89 (CI 0.61-1.29) comparing individuals who received LMWH to those who did not. The relative risk of ICU admission was 1.12 (CI 0.85-1.48), while we observed no increased risk of bleeding (RR 0.60, 0.14-2.59). The relative risk of venous thromboembolism was 0.68 (CI: 0.33-1.38) in Sweden. Less than 5 VTE events were observed among individuals receiving LMWH in Denmark, preventing a meaningful analysis. CONCLUSION: We found no benefit on mortality with prophylactic LMWH and no increased risk of bleeding among COVID-19 patients receiving prophylactic LMWH

Duration of Treatment for Pseudomonas aeruginosa Bacteremia: a Retrospective Study

Introduction: There is no consensus regarding optimal duration of antibiotic therapy for Pseudomonas aeruginosa bacteremia. We aimed to evaluate the impact of short antibiotic course. Methods: We present a retrospective multicen ter study including patients with P. aeruginosa bacteremia during 2009–2015. We evaluated outcomes of patients treated with short (6–- 10 days) versus long (11–15 days) antibiotic courses. The primary outcome was a composite of 30-day mortality or bacteremia recurrence and/or persistence. Univariate and inverse probability treatment-weighted (IPTW) adjusted multivariate analysis for the primary outcome was performed. To avoid immortal time bias, the landmark method was used. Results: We included 657 patients; 273 received a short antibiotic course and 384 a long course. There was no significant difference in baseline characteristics of patients. The com posite primary outcome occurred in 61/384 patients in the long-treatment group (16%) versus 32/273 in the short-treatment group (12%) (p = 0.131). Mortality accounted for 41/384 (11%) versus 25/273 (9%) of cases, respectively. Length of hospital stay was signif icantly shorter in the short group [median 13 days, interquartile range (IQR) 9–21 days, versus median 15 days, IQR 11–26 days, p = 0.002]. Ten patients in the long group dis continued antibiotic therapy owing to adverse events, compared with none in the short group. On univariate and multivariate analyses, dura tion of therapy was not associated with the primary outcome. Conclusions: In this retrospective study, 6–- 10 days of antibiotic course for P. aeruginosa bacteremia were as effective as longer courses in terms of survival and recurrence. Shorter ther apy was associated with reduced length of stay and less drug discontinuation