Elisabetta Pandolfi

Close Encounters in a Pediatric Ward: Measuring Face-to-Face Proximity and Mixing Patterns with Wearable Sensors

Background Nosocomial infections place a substantial burden on health care systems and represent one of the major issues in current public health, requiring notable efforts for its prevention. Understanding the dynamics of infection transmission in a hospital setting is essential for tailoring interventions and predicting the spread among individuals. Mathematical models need to be informed with accurate data on contacts among individuals. Methods and Findings We used wearable active Radio-Frequency Identification Devices (RFID) to detect face-to-face contacts among individuals with a spatial resolution of about 1.5 meters, and a time resolution of 20 seconds. The study was conducted in a general pediatrics hospital ward, during a one-week period, and included 119 participants, with 51 health care workers, 37 patients, and 31 caregivers. Nearly 16,000 contacts were recorded during the study period, with a median of approximately 20 contacts per participants per day. Overall, 25% of the contacts involved a ward assistant, 23% a nurse, 22% a patient, 22% a caregiver, and 8% a physician. The majority of contacts were of brief duration, but long and frequent contacts especially between patients and caregivers were also found. In the setting under study, caregivers do not represent a significant potential for infection spread to a large number of individuals, as their interactions mainly involve the corresponding patient. Nurses would deserve priority in prevention strategies due to their central role in the potential propagation paths of infections. Conclusions Our study shows the feasibility of accurate and reproducible measures of the pattern of contacts in a hospital setting. The obtained results are particularly useful for the study of the spread of respiratory infections, for monitoring critical patterns, and for setting up tailored prevention strategies. Proximity-sensing technology should be considered as a valuable tool for measuring such patterns and evaluating nosocomial prevention strategies in specific settings.

Immunization coverage and timeliness of vaccination in Italian children with chronic diseases

Since children with chronic diseases represent a primary target for immunization strategies, it is important that their immunization coverage and timeliness of vaccines is optimal. We performed a study to measure immunization coverage and timeliness of vaccines in children with type 1 diabetes, HIV infection, Down syndrome, cystic fibrosis, and neurological diseases. A total of 275 children aged 6 months-18 years were included in the study. Coverage for diphtheria-tetanus-pertussis (DTP), polio (Pol), and hepatitis B (HBV) vaccines approximated 85% at 24 months, while measles-mumps-rubella (MMR) coverage was 62%. Immunization coverage for seasonal influenza was 59%. The analysis of timeliness revealed that there was heterogeneity among children with different chronic diseases. A proportional hazard model showed that children with HIV infection had the longest time to complete three doses of DTP, Pol, and HBV, and those with neurological diseases received the first dose of MMR later than the other categories. Causes of missing or delayed vaccination mostly included a concurrent acute disease. Children with chronic diseases should be strictly monitored for routine and recommended vaccinations, and health care providers and families should be properly informed to avoid false contraindications.

Switched memory B cells maintain specific memory independently of serum antibodies: the hepatitis B example.

The immunogenicity of a vaccine is conventionally measured through the level of serum Abs early after immunization, but to ensure protection specific Abs should be maintained long after primary vaccination. For hepatitis B, protective levels often decline over time, but breakthrough infections do not seem to occur. The aim of this study was to demonstrate whether, after hepatitis B vaccination, B‐cell memory persists even when serum Abs decline. We compared the frequency of anti‐hepatitis‐specific memory B cells that remain in the blood of 99 children five years after priming with Infanrix®‐hexa (GlaxoSmithKline) (n=34) or with Hexavac® (Sanofi Pasteur MSD) (n=65). These two vaccines differ in their ability to generate protective levels of IgG. Children with serum Abs under the protective level, <10 mIU/mL, received a booster dose of hepatitis B vaccine, and memory B cells and serum Abs were measured 2 wk later. We found that specific memory B cells had a similar frequency in all children independently of primary vaccine. Booster injection resulted in the increase of memory B cell frequencies (from 11.3 in 106 cells to 28.2 in 106 cells, p<0.01) and serum Abs (geometric mean concentration, GMC from 2.9 to 284 mIU/mL), demonstrating that circulating memory B cells effectively respond to Ag challenge even when specific Abs fall under the protective threshold.

Influenza-Like Illness Surveillance on Twitter through Automated Learning of Naïve Language

Twitter has the potential to be a timely and cost-effective source of data for syndromic surveillance. When speaking of an illness, Twitter users often report a combination of symptoms, rather than a suspected or final diagnosis, using naïve, everyday language. We developed a minimally trained algorithm that exploits the abundance of health-related web pages to identify all jargon expressions related to a specific technical term. We then translated an influenza case definition into a Boolean query, each symptom being described by a technical term and all related jargon expressions, as identified by the algorithm. Subsequently, we monitored all tweets that reported a combination of symptoms satisfying the case definition query. In order to geolocalize messages, we defined 3 localization strategies based on codes associated with each tweet. We found a high correlation coefficient between the trend of our influenza-positive tweets and ILI trends identified by US traditional surveillance systems.

Hepatitis B specific T cell immunity induced by primary vaccination persists independently of the protective serum antibody level

In 2005, in accordance with recommendations made by the European Medicines Agency, the Italian Drug Agency ordered withdrawal of the hexavalent Hexavac(®) vaccine (Sanofi Pasteur MSD) from the market. Concerns had been raised about the low immunogenicity of the hepatitis B virus component of the vaccine, assessed by measurement of serum antibody levels, and its potential consequences on long-term protection against hepatitis B infection. We evaluated memory T cell response to establish whether there are differences in the protective mechanisms among children who had received either Hexavac(®) or Infanrix-hexa(®) (GlaxoSmithKline) as their primary vaccination. Immunological memory was determined by measuring the ability of T cells to proliferate and secrete IFNγ by ELISA and intracellular cytokines (IFNγ and IL-2) when cultured with hepatitis B surface antigen (HBsAg). The different memory subsets of T cells were also measured. The results indicate that, although they generate different serum antibody levels, both vaccines are efficient in generating T recall responses in vitro five years after the primary vaccination. The less immunogenic Hexavac(®) vaccine induces a strong T antigen response, as indicated by increased blast proliferation and the enhanced presence of memory subsets after HBsAg recall stimulation. These findings suggest that cellular immune response should be considered alongside serological markers as a surrogate of protection.

Attitudes towards HPV immunization of Italian mothers of adolescent girls and potential role of health professionals in the immunization program.

We assessed the knowledge of Italian mothers of adolescent girls about HPV and HPV vaccination, their willingness to immunize their daughters, and their perception of the role of different medical specialists in the HPV immunization strategy by a telephone interview. Fifty-four percent of the 807 interviewed mothers reported to have ever heard about HPV, and 84% of them were willing to immunize their daughters. Pediatricians most frequently provided information on HPV vaccine (31%), and were perceived as the preferred immunization providers (77%). Acceptance of HPV immunization was high and was not associated with knowledge of HPV.

Epidemiology of pertussis in italy: Disease trends over the last century

We reviewed the epidemiology of pertussis in Italy over the last 125 years to identify disease trends and factors that could have influenced these trends. We described mortality rates (1888-2012), case fatality rates (1925-2012), cumulative incidence rates (1925-2013) and age-specific incidence rates (1974-2013). We compared data from routine surveillance with data from a paediatric sentinel surveillance system to estimate under-notification. Pertussis mortality decreased from 42.5 per 100,000 population in 1890 to no reported pertussis-related death after 2002. Incidence decreased from 86.3 per 100,000 in 1927 to 1 per 100,000 after 2008. Vaccine coverage increased from 32.8% in 1993 to about 96% after 2006. As for under-notification, mean sentinel/routine surveillance incidence ratio increased with age (from 1.8 in <1 year-olds to 12.9 in 10-14 year-olds). Pertussis mortality decreased before the introduction of immunisation. Incidence has decreased only after the introduction of pertussis vaccine and in particular after the achievement of a high immunisation coverage with acellular vaccines. Routine surveillance does not show an increase in cumulative incidence nor in ≥ 15 year-olds as reported by other countries. Underrecognition because of atypical presentation and the infrequent use of laboratory tests may be responsible for under-notification, and therefore affect incidence reports and management of immunisation programmes.

The effect of physician’s recommendation on seasonal influenza immunization in children with chronic diseases

BackgroundDespite recommendations by Health Authorities, influenza immunization coverage remains low in children with chronic diseases. Different medical providers involved in the management of children with chronic conditions may affect the pattern of influenza vaccine recommendations and coverage. The likelihood of vaccination by type of provider in children with chronic conditions is poorly understood. Therefore, the objectives of this study were to analyze the pattern and the effect of recommendations for seasonal influenza immunization provided by different physician profiles to families of children with chronic diseases and to measure the frequency of immunization in the study population.MethodsWe recruited children with chronic diseases aged 6 months–18 years who subsequently presented to specialty clinics for routine follow-up visits, during spring 2009, in three Italian Regions Families of children with chronic diseases were interviewed during routine visits at reference centers through a face-to-face interview. We analyzed the following immunization predictors: having received a recommendation toward influenza immunization by a health provider; child’s sex and age; mothers and fathers’ age; parental education and employment; underlying child’s disease; number of contacts with health providers in the previous year. Influenza immunization coverage was calculated as the proportion of children who received at least one dose of seasonal influenza vaccine in the previous season. We calculated prevalence ratios and we used a generalized linear model with Poisson family, log link and robust error variance to assess the effect of socio-demographic variables, underlying diseases, and recommendations provided by physicians on influenza immunization.ResultsWe enrolled 275 families of children with chronic diseases. Overall influenza coverage was 57.5%, with a low of 25% in children with neurological diseases and a high of 91.2% in those with cystic fibrosis. While 10.6% of children who did not receive any recommendation toward influenza immunization were immunized, among those who received a recommendation 87.5-94.7% did, depending on the health professional providing the recommendation. Receiving a recommendation by any provider is a strong predictor of immunization (PR = 8.5 95% CI 4.6;15.6) Most children received an immunization recommendation by a specialty (25.8%) or a family pediatrician (23.3%) and were immunized by a family pediatrician (58.7%) or a community vaccinator (55.2%).ConclusionsReceiving a specific recommendation by a physician is a strong determinant of being immunized against seasonal influenza in children with chronic diseases independently of other factors. Heterogeneity exists among children with different chronic diseases regarding influenza recommendation despite international guidelines. Increasing the frequency of appropriate recommendations toward influenza immunization by physicians is a single powerful intervention that may increase coverage in children with chronic conditions.

Humoral and B-cell memory responses in children five years after pertussis acellular vaccine priming

The resurgence of pertussis suggests the need for greater efforts in understanding the long-lasting protective responses induced by vaccination. In this paper we dissect the persistence of humoral and B-cell memory responses induced by primary vaccination with two different acellular pertussis (aP) vaccines, hexavalent Hexavac(®) vaccine (Hexavac) (Sanofi Pasteur MSD) and Infanrix hexa(®) (Infanrix) (GlaxoSmithKline Biologicals). We evaluated the specific immune responses in the two groups of children, 5 years after primary vaccination by measuring the persistence of IgG and antibody secreting cells (ASC) specific for vaccine antigens. Part of the enrolled children received only primary vaccination, while others had the pre-school boost dose. A similar level of antigen-specific IgG and ASC was found in Infanrix and Hexavac vaccinated children. The mean IgG levels were significantly higher in children that received the pre-school boost as compared with children that did not receive the boost dose. A longer persistence after the pre-school boost of IgG-Pertussis Toxin (PT) and IgG-pertactin levels was observed in Infanrix primed children, but it was not statistically significant. More than 80% of children presented a positive ASC B memory response. Around 50% of children still presented protective IgG-PT levels which are reduced to 36% in no-boosted children. The pre-school booster dose restores the percentage of protected children above 50%. In conclusion our data underline the importance of giving a booster dose 5 years after primary vaccination and suggest the need for a new vaccine able to induce a long lasting protective response.

Women participating in a web-based preconception study have a high prevalence of risk factors for adverse pregnancy outcomes

BackgroundAdverse pregnancy outcomes (APOs) can be increased by preconception risk factors and lifestyles.We measured the prevalence of preconception risk factors for APOs in a population of Italian women of childbearing age enrolled in a web-based study.MethodsParticipants were enrolled through a web platform (http://www.mammainforma.it). After enrollment, participants filled in a questionnaire regarding socio-demographic characteristics, clinical data and preconception risk factors for adverse pregnancy outcomes. Through logistic regression, we explored how the prevalence of risk factors was affected by age, education level, employment, parity, physician’s recommendation and knowledge of the specific risk factor.ResultsWe enrolled a total of 728 women. Sixty-two percent had a University degree, 84% were employed and 77% were planning their first pregnancy.Nearly 70% drank alcohol in any quantity; 16% were smokers; 6% was underweight; 21.4% was overweight; 51.6% did not assume folic acid; 22% was susceptible to rubella, 44.5% to hepatitis b and 13.2% to varicella.According to the multivariate analysis, compared to women who already had at least one pregnancy, nulliparous women had a higher BMI [OR 1.60 (CI 1.02;2.48)] and were less likely to be susceptible to rubella [OR 0.33 (CI 0.20;0.58)] and to be consuming alcohol [OR 0.47 (CI 0.31;0.70)] or cigarettes [OR 0.48 (CI 0.26;0.90)].Appropriate knowledge was associated with a correct behavior regarding smoking, drinking alcohol and folic acid supplementation.ConclusionsThis study shows that the prevalence of risk factors for APOs in our population is high.Interventions aimed at reducing risk factors for APOs are needed and, to this purpose, a web intervention may represent a feasible tool to integrate tailored information and to inform preconception counseling targeting a specific group of women planning a pregnancy who are engaged on the web.