The risk of infection in patients with multiple sclerosis treated with disease-modifying therapies: A Delphi consensus statement.

The risk of infection associated with immunomodulatory or immunosuppressive disease-modifying drugs (DMDs) in patients with multiple sclerosis (MS) has been increasingly addressed in recent scientific literature. A modified Delphi consensus process was conducted to develop clinically relevant, evidence-based recommendations to assist physicians with decision-making in relation to the risks of a wide range of infections associated with different DMDs in patients with MS. The current consensus statements, developed by a panel of experts (neurologists, infectious disease specialists, a gynaecologist and a neuroradiologist), address the risk of iatrogenic infections (opportunistic infections, including herpes and cryptococcal infections, candidiasis and listeria; progressive multifocal leukoencephalopathy; human papillomavirus and urinary tract infections; respiratory tract infections and tuberculosis; hepatitis and gastrointestinal infections) in patients with MS treated with different DMDs, as well as prevention strategies and surveillance strategies for the early identification of infections. In the discussion, more recent data emerged in the literature were taken into consideration. Recommended risk reduction and management strategies for infections include screening at diagnosis and before starting a new DMD, prophylaxis where appropriate, monitoring and early diagnosis.

Vaccinations in patients with multiple sclerosis: A Delphi consensus statement.

BACKGROUND: Patients with multiple sclerosis (MS) are at increased risk of infection. Vaccination can mitigate these risks but only if safe and effective in MS patients, including those taking disease-modifying drugs. METHODS: A modified Delphi consensus process (October 2017-June 2018) was used to develop clinically relevant recommendations for making decisions about vaccinations in patients with MS. A series of statements and recommendations regarding the efficacy, safety and timing of vaccine administration in patients with MS were generated in April 2018 by a panel of experts based on a review of the published literature performed in October 2017. RESULTS: Recommendations include the need for an 'infectious diseases card' of each patient's infectious and immunisation history at diagnosis in order to exclude and eventually treat latent infections. We suggest the implementation of the locally recommended vaccinations, if possible at MS diagnosis, otherwise with vaccination timing tailored to the planned/current MS treatment, and yearly administration of the seasonal influenza vaccine regardless of the treatment received. CONCLUSION: Patients with MS should be vaccinated with careful consideration of risks and benefits. However, there is an urgent need for more research into vaccinations in patients with MS to guide evidence-based decision making.

High performance of a new PCR-based urine assay for HPV-DNA detection and genotyping.

Human papillomavirus (HPV) testing has been proposed as a means of replacing or supporting conventional cervical screening (Pap test). However, both methods require the collection of cervical samples. Urine sample is easier and more acceptable to collect and could be helpful in facilitating cervical cancer screening. The aim of this study was to evaluate the sensitivity and specificity of urine testing compared to conventional cervical smear testing using a PCR-based method with a new, designed specifically primer set. Paired cervical and first voided urine samples collected from 107 women infected with HIV were subjected to HPV-DNA detection and genotyping using a PCR-based assay and a restriction fragment length polymorphism method. Sensitivity, specificity, Positive Predictive Value (PPV), and Negative Predictive Value (NPV) were calculated using the McNemar's test for differences. Concordance between tests was assessed using the Cohen's unweighted Kappa (k). HPV DNA was detected in 64.5% (95% CI: 55.1-73.1%) of both cytobrush and urine samples. High concordance rates of HPV-DNA detection (k = 0.96; 95% CI: 0.90-1.0) and of high risk-clade and low-risk genotyping in paired samples (k = 0.80; 95% CI: 0.67-0.92 and k = 0.74; 95% CI: 0.60-0.88, respectively) were observed. HPV-DNA detection in urine versus cervix testing revealed a sensitivity of 98.6% (95% CI: 93.1-99.9%) and a specificity of 97.4% (95% CI: 87.7-99.9%), with a very high NPV (97.4%; 95% CI: 87.7-99.9%). The PCR-based assay utilized in this study proved highly sensitive and specific for HPV-DNA detection and genotyping in urine samples. These data suggest that a urine-based assay would be a suitable and effective tool for epidemiological surveillance and, most of all, screening programs.

High-risk HPV positivity is a long-term risk factor for recurrence after cervical excision procedure in women living with HIV.

OBJECTIVE: To evaluate the risk factors for recurrence of high-grade disease after cervical excision in women living with HIV (WLWH), with a specific interest in the role of high-risk (HR-) HPV positivity. METHODS: Multicentric retrospective study conducted on WLWH who underwent cervical excision between January 1987 and June 2017 in six Italian institutions. The rate of high-grade recurrence was determined. Risk factors for recurrence and HR-HPV positivity were determined with the Log-rank test and Cox proportional hazards regression models. RESULTS: A total of 271 WLWH were included in the final analysis. A high-grade recurrence was found in 58 (21.4%) patients. Age 41 years or more at inclusion and HR-HPV positivity during follow up were independently associated with a higher risk of disease recurrence with relative risks of 4.15 (95% confidence interval [CI] 2.01-8.58, P < 0.001) and 5.18 (95% CI 2.12-12.67, P < 0.01), respectively. Age 41 years or more (relative risk 1.75, 95% CI 1.01-3.04, P = 0.047) resulted as a risk factor for HR-HPV positivity during follow up. CONCLUSION: HR-HPV positivity is a risk factor for recurrence after cervical excision in WLWH. Women older than 41 years may benefit from a long-term yearly follow up. Future studies regarding HPV vaccination after treatment in WLWH may be useful, considering the protective role of the higher probability of HPV negativity in vaccinated women.

Combined surgery and cidofovir is an effective treatment for genital warts in HIV-infected patients.

OBJECTIVE: To evaluate the efficacy of surgical-cidofovir (SCT), surgical (ST) and cidofovir (CT) treatment of genital warts in HIV-infected patients. DESIGN: Open randomized prospective pilot study. SETTING: Outpatients attending the sexually transmitted disease service of the II Dept of Infectious Diseases, L Sacco Hospital, Milan-Italy. PATIENTS: Consenting HIV-positive patients with anal-genital warts recruited from January 2000 to March 2001. INTERVENTIONS: Three treatment arms: surgical excision by electrocautery, topical 1% cidofovir-gel (5 days per week, maximum 6 weeks) and electrocautery-cidofovir treatment with 1% cidofovir-gel applied within 1 month of surgical treatment (5 days per week for 2 weeks). MAIN OUTCOME MEASURES: Rate of wart clearance and time and rate of relapses within a 6-month follow-up period. RESULTS: Complete response was achieved in 93.1% of 29 patients treated by ST, 76.2% of 26 treated by CT and in 100% of 19 patients treated by SCT (P = 0.0033). The relapse rate in 49 patients followed-up was 73.68% in ST, 35.29% in CT and 27.27% in SCT patients (P = 0.018). Median time to relapses in ST patients was 66 days (Kaplan-Meyer, P = 0.0012). Human papillomavirus DNA was cleared in 52.63% of 19 patients evaluated. The rate of clearance of high risk and low risk genotypes was 0% and 57.14% 25% and 50% 100% and 71.42% in ST, CT and SCT patients, respectively. CONCLUSIONS: A combination of surgical and medical treatment was most effective in clearing lesions completely and in reducing the relapse rate. Human papillomavirus DNA clearance can be attributed to the antiviral effect of cidofovir and could explain the low relapse rate observed. Larger studies are required to determine the most appropriate medical treatment for viral eradication after surgery.