Marta Luisa Ciofi degli Atti

Mitigation Measures for Pandemic Influenza in Italy: An Individual Based Model Considering Different Scenarios

Background Individual-based models can provide the most reliable estimates of the spread of infectious diseases. In the present study, we evaluated the diffusion of pandemic influenza in Italy and the impact of various control measures, coupling a global SEIR model for importation of cases with an individual based model (IBM) describing the Italian epidemic. Methodology/Principal Findings We co-located the Italian population (57 million inhabitants) to households, schools and workplaces and we assigned travel destinations to match the 2001 census data. We considered different R0 values (1.4; 1.7; 2), evaluating the impact of control measures (vaccination, antiviral prophylaxis -AVP-, international air travel restrictions and increased social distancing). The administration of two vaccine doses was considered, assuming that first dose would be administered 1-6 months after the first world case, and different values for vaccine effectiveness (VE). With no interventions, importation would occur 37–77 days after the first world case. Air travel restrictions would delay the importation of the pandemic by 7–37 days. With an R0 of 1.4 or 1.7, the use of combined measures would reduce clinical attack rates (AR) from 21–31% to 0.3–4%. Assuming an R0 of 2, the AR would decrease from 38% to 8%, yet only if vaccination were started within 2 months of the first world case, in combination with a 90% reduction in international air traffic, closure of schools/workplaces for 4 weeks and AVP of household and school/work close contacts of clinical cases. Varying VE would not substantially affect the results. Conclusions This IBM, which is based on country-specific demographic data, could be suitable for the real-time evaluation of measures to be undertaken in the event of the emergence of a new pandemic influenza virus. All preventive measures considered should be implemented to mitigate the pandemic.

Diagnosis and management of pertussis

PERTUSSIS IS INCREASING IN FREQUENCY among children too young to be vaccinated and among adolescents and adults. This increase is due mainly to waning immunity among vaccinated individuals, who become susceptible during adolescence and adulthood and maintain the circulation of Bordetella pertussis. Infants are at highest risk of severe illness requiring hospital admission, complications and death. The clinical presentation in adolescents, adults and vaccinated individuals may be atypical, with paroxysmal cough of short duration or simply a persistent cough. Culture and polymerase chain reaction may be used to identify B. pertussis infection, but their sensitivity is high only in the early phase of the disease. Serologic tests are not standardized for the diagnosis of pertussis, and their clinical application is limited. Erythromycin is still considered in some countries to be the “gold standard” for therapy and prophylaxis; however, azithromycin and clarithromycin seem equally efficacious and are associated with fewer side effects.

Persistence of protection through 33 months of age provided by immunization in infancy with two three-component acellular pertussis vaccines

A large, randomized, placebo-controlled clinical trial in Italy on two three-component pertussis vaccines, given as DTaP in infancy, one manufactured by SmithKline and Beecham (SB) and one by Chiron Biocine (CB), found each vaccine to be 84% efficacious through the average age of 24 months. The cohort of children enrolled in the trial was followed with unmodified case ascertainment procedures for nine additional calendar months, during which partial unblinding occurred, for the unvaccinated randomized group. For the DTaP groups, the specific vaccine assignment remained double-blinded throughout the entire additional observation period. Pertussis was defined as paroxysmal cough lasting at least 21 days and confirmed by culture or serology. In the additional 9 months the observed absolute efficacy was 78% (95% CI, 62-87%) for SB DTaP vaccine and 89% (95% CI, 79-94%) for CB DTaP. The relative risk of developing pertussis in SB DTaP recipients compared to CB DTaP vaccinees was 1.99 (95% CI, 1.13-3.51). By combining observations from the initial and additional follow-up periods, the overall observed vaccine efficacy through an average age of 33 months of SB DTaP was 80% and of CB DTaP, 85%.

Outbreak of Paralytic Poliomyelitis in Albania, 1996: High Attack Rate Among Adults and Apparent Interruption of Transmission Following Nationwide Mass Vaccination

After >10 years without detection of any cases of wild virus-associated poliomyelitis, a large outbreak of poliomyelitis occurred in Albania in 1996. A total of 138 paralytic cases occurred, of which 16 (12%) were fatal. The outbreak was due to wild poliovirus type 1, isolated from 69 cases. An attack rate of 10 per 100,000 population was observed among adults aged 19-25 years who were born during a time of declining wild poliovirus circulation and had been vaccinated with two doses of monovalent oral poliovirus vaccines (OPVs) that may have been exposed to ambient temperatures for prolonged periods. Control of the epidemic was achieved by two rounds of mass vaccination with trivalent oral poliovirus vaccine targeted to persons aged 0-50 years. This outbreak underscores the ongoing threat of importation of wild poliovirus into European countries, the importance of delivering potent vaccine through an adequate cold chain, and the effectiveness of national OPV mass vaccination campaigns for outbreak control.

Clinical, social and relational determinants of paediatric ambulatory drug prescriptions due to respiratory tract infections in Italy

ObjectivesCollecting information on patterns of drug prescriptions and on factors influencing prescribing decisions is fundamental for supporting the rational use of drugs. This study was aimed at investigating patterns of drug prescription in paediatric outpatients and at evaluating determinants of prescriptions for respiratory tract infections (RTIs).MethodsWe conducted a national cross-sectional survey involving primary care paediatricians and parents. Diagnoses and prescriptions made at each consultation were described. Poisson regression models were used to analyse determinants of drug and antibiotic prescriptions for visits due to RTIs.ResultsA total of 4,302 physician and parent questionnaires were analysed. These corresponded to 2,151 visits, 792 of which were due to RTIs. Drugs were prescribed in 83.4% of RTI visits, while antibiotics were prescribed in 40.4%. According to paediatricians’ perceptions, 84.2% of parents of children with a RTI expected to receive a drug prescription. Paediatricians’ perception of parental expectations was the strongest determinant for prescription of drugs and specifically of antibiotics [adjusted relative risk (RR): 1.7 and 3.6, respectively; P < 0.001]. However, in 77.1% of RTI visits, paediatricians judged themselves as not being influenced at all by parents’ expectations in their decision to prescribe.ConclusionsThis study underscores that relational factors, in particular perceived parental expectations, are one of the leading factors of drug prescriptions in paediatric ambulatory care settings, reinforcing the opinion that communication between physicians and parents can affect prescription patterns.

Description of two measles outbreaks in the Lazio Region, Italy (2006-2007). Importance of pockets of low vaccine coverage in sustaining the infection

BackgroundDespite the launch of the national plan for measles elimination, in Italy, immunization coverage remains suboptimal and outbreaks continue to occur. Two measles outbreaks, occurred in Lazio region during 2006-2007, were investigated to identify sources of infection, transmission routes, and assess operational implications for elimination of the disease.MethodsData were obtained from several sources, the routine infectious diseases surveillance system, field epidemiological investigations, and molecular genotyping of virus by the national reference laboratory.ResultsOverall 449 cases were reported, sustained by two different stereotypes overlapping for few months. Serotype D4 was likely imported from Romania by a Roma/Sinti family and subsequently spread to the rest of the population. Serotype B3 was responsible for the second outbreak which started in a secondary school. Pockets of low vaccine coverage individuals (Roma/Sinti communities, high school students) facilitated the reintroduction of serotypes not endemic in Italy and facilitated the measles infection to spread.ConclusionsCommunities with low vaccine coverage represent a more serious public health threat than do sporadic susceptible individuals. The successful elimination of measles will require additional efforts to immunize low vaccine coverage population groups, including hard-to-reach individuals, adolescents, and young adults. An enhanced surveillance systems, which includes viral genotyping to document chains of transmission, is an essential tool for evaluating strategy to control and eliminate measles

The epidemiology of Varicella Zoster Virus infection in Italy

BackgroundThe epidemiological importance of varicella and zoster and the availability of an efficacious and safe vaccine have led to an important international debate regarding the suitability of mass vaccination. The objective of the study was to describe the epidemiology of varicella and zoster in Italy and to determine whether there have been changes with respect to observations provided by an analogous study conducted 8 years ago, in order to define the most appropriate vaccination strategy.MethodsA number of data sources were evaluated, a cross-sectional population-based seroprevalence study was conducted on samples collected in 2004, and the results were compared with data obtained in 1996.ResultsThe data from active and passive surveillance systems confirm that varicella is a widespread infectious disease which mainly affects children. VZV seroprevalence did not substantially differ from that found in the previous study. The sero-epidemiological profile in Italy is different from that in other European countries. In particular, the percentage of susceptible adolescents is at least nearly twice as high as in other European countries and in the age group 20–39 yrs, approximately 9% of individuals are susceptible to VZV.ConclusionThe results of this study can contribute to evaluating the options for varicella vaccination. It is possible that in a few years, in all Italian Regions, there will exist the conditions necessary for implementing a mass vaccination campaign and that the large-scale availability of MMRV tetravalent vaccines will facilitate mass vaccination.

A cohort study to evaluate persistence of hepatitis B immunogenicity after administration of hexavalent vaccines

BackgroundIn 2001, two hexavalent vaccines were licensed in Italy (Hexavac®, Infanrix Hexa®), and since 2002 were extensively used for primary immunization in the first year of life (at 3, 5, 11/12 months of age). In 2005, the market authorization of Hexavac® was precautionary suspended by EMEA, because of doubts on long-term protection against hepatitis B virus. The objectives of this study were to evaluate the persistence of antibodies to anti-HBs, in children in the third year of life, and to investigate the response to a booster dose of hepatitis B vaccine.MethodsParticipant children were enrolled concomitantly with the offering of anti-polio booster dose, in the third year of life. Anti-HBs titers were determined on capillary blood samples. A booster dose of hepatitis B vaccine was administered to children with anti-HBs titers < 10 mIU/ml, with the monovalent precursor product of the previously received hexavalent vaccine. HBsAb titers were tested again one month after the booster.ResultsSera from 113 children previously vaccinated with Hexavac®, and from 124 vaccinated with Infanrix Hexa® were tested for anti-HBs. Titers were ≥ 10 mIU/ml in 69% and 96% (p < 0,0001) respectively. The proportion of children with titers ≥ 100 mIU/ml did also significantly differ among groups (27% and 78%; p < 0,0001).Post-booster, 93% of children achieved titers ≥ 10 mIU/ml, with no significant difference by vaccine group.DiscussionFifteen months after third dose administration, a significant difference in anti-HBs titers was noted in the two vaccine groups considered. Monovalent hepatitis B vaccine administration in 3-year old children induced a proper booster response, confirming that immunologic memory persists in children with anti-HBs titers < 10 mIU/ml. However, long-term persistence of HBV protection after hexavalent vaccines administration should be further evaluated over time.

Invasive Type e Haemophilus influenzae Disease in Italy

We describe the first reported cases of invasive type e Haemophilus influenzae disease in Italy. All five cases occurred in adults. The isolates were susceptible to ampicillin and eight other antimicrobial agents. Molecular analysis showed two distinct type e strains circulating in Italy, both containing a single copy of the capsulation locus.

Presence of Multiple Copies of the Capsulation b Locus in Invasive Haemophilus influenzae Type b (Hib) Strains Isolated from Children with Hib Conjugate Vaccine Failure

Most invasive Haemophilus influenzae type b strains possess a duplication of the capsulation locus. Further amplification resulting in as many as 5 copies has been described. To verify whether amplification is involved in vaccine failure, the number of copies of the locus was determined by Southern blotting in 90 strains from children with true vaccine failure (TVF) between 1993 and 1999 and in 139 strains from unvaccinated children (50 collected between 1993 and 1999 and 89 collected between 1991 and 1992, before routine immunization was introduced). A significantly greater proportion of strains from TVFs contained multiple copies, compared with strains from control children (24% vs. 10%; P = .0379), which suggests that amplification of the capb locus may be a contributory factor in vaccine failure. The presence of multiple-copy strains was associated with disease other than meningitis.