Tuija Leino

Pneumococcal carriage in children during their first two years : important role of family exposure

Background. Close family and day-care contacts have been identified as risk factors for pneumococcal (Pnc) carriage. This study addresses the risk of Pnc carriage by infants 2 to 24 months of age in terms of simultaneous carriage of pneumococcus by family members. Methods. Nasopharyngeal swabs were collected from 100 Finnish infants and their family members on 10 scheduled visits (when infant was 2, 3, 4, 5, 6, 9, 12, 15, 18 and 24 months of age). The 7 most common pneumococcal serogroups (4, 6, 9, 14, 18, 19, 23), also represented in the new heptavalent Pnc conjugate vaccine, were analyzed. Marginal logistic regression analyses were performed to assess the relative importance of different predictors for carriage. Results. The carriage of the studied Pnc serogroups increased with age, being highest at the age of 18 months (28%). Among children older than 6 months of age, the strongest predictor of carriage was simultaneous carriage of the same serogroup by another family member (odds ratio, 3.8; 95% confidence interval, 2.1 to 6.9). At the age of 6 months or younger, carriage was rare and was not significantly associated with a family carriage. Conclusions. Young infants (≤6 months old) were largely protected from pneumococcal carriage. After this age family transmission seemed very important despite the small family size. Contrary to some earlier studies communal day care was not associated with an increased risk of Pnc carriage. This could be partly because of the long parental leave in Finland and thus the late age of starting organized day care.

Pneumococcal acute otitis media in relation to pneumococcal nasopharyngeal carriage

Background: Acute otitis media (AOM) is closely associated with viral upper respiratory tract infections, but the most common microbial agent found in the middle ear fluid during AOM is Streptococcus pneumoniae (Pnc). Pnc is also a common colonizer of the nasopharynx, and its prevalence is further increased during the viral infection. The aim of this study was to investigate the interplay between viral infection, pneumococcal acquisition and carriage in the development of Pnc AOM. Methods: Pnc carriage was assessed in a longitudinal study of 329 infants at scheduled visits at 3, 6, 9, 12, 15 and 18 months of age (N = 1715). The clinical outcome of the first episode of respiratory infection (“sick visit,” N = 774) in the following 3-month period was recorded. The occurrence and timing of Pnc AOM in relation to serotype specific carriage at the start of the observation period were assessed. Results: The occurrence, timing and duration of symptoms of the sick visits or the frequency of overall AOM were not associated with preceding pneumococcal carriage. Pnc AOM was in each case associated with concurrent carriage and 3.8 times (95% confidence interval, 1.4–10.0) more often with carriage acquired after the start of the observation period than with carriage already present at the scheduled visit. In all, 79% (55 of 70) of Pnc AOM events were caused by a serotype acquired after the start of the period. Conclusion: The majority of Pnc AOM events develop in association with newly acquired carriage of pneumococcus.

Transmission of Pneumococcal Carriage in Families: A Latent Markov Process Model for Binary Longitudinal Data

Abstract We present a Bayesian data augmentation model to estimate acquisition and clearance rates of carriage of Streptococcus pneumoniae (Pnc) bacteria. The panel observation data comprise 10 measurements of Pnc carriage (carrier/noncarrier of the bacteria) in all members of 97 families with young children over a period of 2 years. Using natural conditional independence assumptions, a transmission model is constructed for the unobserved dependent binary processes of the augmented data. The model explicitly considers carriage transmission within the family and carriage acquisition from the surrounding community. The joint posterior of the model parameters and the augmented data is explored by Markov chain Monte Carlo sampling. The analysis shows that in young children the rate of acquiring carriage of three common Pnc serotypes increases with age. In children less than 2 years old, the duration of carriage is longer than in older family members. Asymptomatic Pnc carriage is found highly transmittable between members of the same family. In young children, the estimated rate of acquiring carriage from a family member carrying Pnc is more than 20-fold to that from acquiring it from the community.

Modelling the impact of varicella vaccination on varicella and zoster.

It has been suggested that the incidence of herpes zoster may increase due to lack of natural boosting under large-scale vaccination with the varicella vaccine. To study the possibility and magnitude of such negative consequences of mass vaccination, we built a mathematical model of varicella and zoster epidemiology in the Finnish population. The model was based on serological data on varicella infection, case-notification data on zoster, and new knowledge about close contacts relevant to transmission of infection. According to the analysis, a childhood programme against varicella will increase the incidence of zoster by one to more than two thirds in the next 50 years. This will be due to increase in case numbers in the 35 years age groups. However, high vaccine coverage and a two-dose programme will be very effective in stopping varicella transmission in the population.

Long-term persistence of immunity after immunisation with Haemophilus influenzae type b conjugate vaccine.

Although Haemophilus influenzae type b (Hib) conjugate vaccines, after licensure in 1987, are now recommended for world-wide use, the duration of protective immunity afforded by them is not known. We therefore assessed the immunogenity at 9-10 years of age in 37 children who had received the first Hib conjugate, PRP-D, in infancy (the Hib-conjugate group) and were now given a dose of Hib polysaccharide (PS) as a test vaccine. The anti-Hib PS antibodies (Hib-ab) were measured before and after this test vaccination, and the values compared to those in 37 control children who had not previously received any Hib vaccine and in 13 children who had received Hib PS vaccine in infancy (the Hib-PS group). Prior to the test vaccination, the Hib-ab concentrations in the Hib-conjugate group were 3.6-fold higher than in the control group. After the test vaccination, the Hib-conjugate group had higher total Hib-ab concentrations, higher proportion of IgG and higher avidity of Hib-ab than the control or the Hib-PS group, suggesting persisting immunological memory in a Hib-c group. A mathematical model, including memory, predicted accurately the Hib-ab concentrations, which are maintained through anamnestic responses to intervening stimuli (Hib or cross-reacting bacteria).

Outbreaks of Streptococcus pneumoniae carriage in day care cohorts in Finland – implications for elimination of transmission

BackgroundDay care centre (DCC) attendees play a central role in maintaining the circulation of Streptococcus pneumoniae (pneumococcus) in the population. Exposure within families and within DCCs are the main risk factors for colonisation with pneumococcal serotypes in DCC attendees.MethodsTransmission of serotype specific carriage was analysed with a continuous time event history model, based on longitudinal data from day care attendees and their family members. Rates of acquisition, conditional on exposure, were estimated in a Bayesian framework utilising latent processes of carriage. To ensure a correct level of exposure, non-participating day care attendees and their family members were included in the analysis. Posterior predictive simulations were used to quantify transmission patterns within day care cohorts, to estimate the basic reproduction number for pneumococcal carriage in a population of day care cohorts, and to assess the critical vaccine efficacy against carriage to eliminate pneumococcal transmission.ResultsThe model, validated by posterior predictive sampling, was successful in capturing the strong temporal clustering of pneumococcal serotypes in the day care cohorts. In average 2.7 new outbreaks of pneumococcal carriage initiate in a day care cohort each month. While 39% of outbreaks were of size one, the mean outbreak size was 7.6 individuals and the mean length of an outbreak was 2.8 months. The role of families in creating and maintaining transmission was minimal, as only 10% of acquisitions in day care attendees were from family members. Considering a population of day care cohorts, a child-to-child basic reproduction number was estimated as 1.4 and the critical vaccine efficacy against acquisition of carriage as 0.3.ConclusionPneumococcal transmission occurs in serotype specific outbreaks of carriage, driven by within-day-care transmission and between-serotype competition. An amplifying effect of the day care cohorts enhances the spread of pneumococcal serotypes within the population. The effect of vaccination, in addition to reducing susceptibility to pneumococcal carriage in the vaccinated, induces a herd effect, thus creating a counter-effect to the amplifying effect of the cohort. Consequently, the critical vaccine efficacy against carriage, required for elimination of transmission, is relatively low. Use of pneumococcal conjugate vaccines is expected to induce a notable herd protection against pneumococcal disease.

High tetanus and diphtheria antitoxin concentrations in Finnish adults―Time for new booster recommendations?

The tetanus and diphtheria vaccination programme in Finland has been running for 50 years. After primary doses, tetanus boosters have been offered to men in military service and decennial boosters recommended for all through the adult life. For 30 years a diphtheria booster was only offered to men in the military service. Not until 1989 diphtheria-tetanus (dT) and diphtheria (d) booster vaccines for adolescence and adults were introduced. In this study serum samples of 990 subjects from 30 years of age, participating in a population survey in 2000-2001, were used to assess the tetanus and diphtheria antitoxin concentrations. More than 70% of the adults up to 50 years of age were fully protected (antitoxin concentrations >0.1 IU mL) against tetanus and diphtheria. Of these adults more that 76% had antitoxin concentrations >1 IU/mL against tetanus, indicating long-term protection but also an increased risk for hyperimmunisation. A comparison of this study and two immunogenicity studies conducted in Finland in 1987-1988 and 1995-1996 shows the impact of an active decennial dT adult booster programme in a country with a high primary tetanus and diphtheria vaccination coverage in infants since the 1950s. Recommendations for limited decennial boosters by increase the time interval between dT boosters up to 20 years as suggested by this study and also studies performed, e.g., in Denmark and Portugal should be considered. Finnish adults born before 1930 should, however, still be vaccinated with decennial boosters, especially against tetanus.

Clustering of serotypes in a longitudinal study of Streptococcus pneumoniae carriage in three day care centres.

BackgroundStreptococcus pneumoniae (pneumococcus) causes a wide range of clinical manifestations that together constitute a major burden of disease worldwide. The main route of pneumococcal transmission is through asymptomatic colonisation of the nasopharynx. Studies of transmission are currently of general interest because of the impact of the new conjugate-polysaccharide vaccines on nasopharyngeal colonisation (carriage). Here we report the first longitudinal study of pneumococcal carriage that records serotype specific exposure to pneumococci simultaneously within the two most important mixing groups, families and day care facilities.MethodsWe followed attendees (N = 59) with their family members (N = 117) and the employees (N = 37) in three Finnish day care centres for 9 months with monthly sampling of nasopharyngeal carriage. Pneumococci were cultured, identified and serotyped by standard methods.ResultsChildren in day care constitute a core group of pneumococcal carriage: of the 36 acquisitions of carriage with documented exposure to homologous pneumococci, the attendee had been exposed in her/his day care centre in 35 cases and in the family in 9 cases. Day care children introduce pneumococci to the family: 66% of acquisitions of a new serotype in a family were associated with simultaneous or previous carriage of the same type in the child attending day care. Consequently, pneumococcal transmission was found to take place as micro-epidemics driven by the day care centres. Each of the three day care centres was dominated by a serotype of its own, accounting for 100% of the isolates of that serotype among all samples from the day care attendees.ConclusionThe transmission of pneumococci is more intense within than across clusters defined by day care facilities. The ensuing micro-epidemic behaviour enhances pneumococcal transmission.

First year experience of rotavirus immunisation programme in Finland.

INTRODUCTION This study aimed to estimate the impact of rotavirus (RV) immunisation programme on the total hospital treated acute gastroenteritis (AGE) burden, as well as, on severe RV disease burden in Finland during the first year after immunisation programme introduction. Such studies can also be considered as a vaccine-probe-study, where unspecific disease burden prevented by immunisation is assumed to be caused by the agent the vaccine is targeted against. METHODS The RV related outcome definitions were based on data registered in the National Hospital Discharge Register coded using ICD 10 codes. Incidences of hospitalised and hospital outpatient cases of AGE and RVGE were compared prior (1999-2005) and after (2010) the start of the programme among children under 5 years of age. ICD 10 codes utilised were A00-A09, R11 and K52. RESULTS The reductions in disease burden, when the post-introduction year was compared to pre-vaccine era, were 80.3% (95% CI 74.5-84.7) in hospital inpatient RVGE among toddlers less than 1 year of age and 53.9% (95% CI 49.8-57.7) when the total inpatient AGE burden was considered in the same age group. For the corresponding hospital outpatient cases the reductions were 78.8% (95% CI 48.4-91.3) and 12.5% (7.1-17.7). The overall vaccine impact against confirmed RVGE in age cohorts eligible for vaccination before the RV season 2010 was 97% (95% CI 90.7-99.0). If the total reductions, both in diagnosed RVGE, as well as in cases without definite microbial diagnosis, were expected to be RVGE, population based estimates for the total disease burden can be obtained: for inpatient RVGE in children less than 1 year of age the estimate is 10.5/1000 pyrs, while the diagnosed specific incidence was less than half of that, 4.9/1000 pyrs. DISCUSSION During the first post-vaccination year 2010, RV immunisation programme clearly managed to control the severe, hospital treated, forms of RVGE. The total disease burden is a more valuable end point than mere diagnosed cases as laboratory confirmation practises change after vaccine introduction. Our study is limited by the very short post-introduction follow up.

Modelling transmission, immunity and disease of Haemophilus influenzae type b in a structured population

An individual-based stochastic simulation model was constructed to study the epidemiology of Haemophilus influenzae type b (Hib) transmission, immunity and invasive disease. Embedded in a demographic model, the transmission model of Hib carriage employs the most important social mixing patterns with three types of contact sites (family, day-care group, and school class). The model includes immunity against invasive Hib disease, initiated and boosted by Hib carriage and cross-reactive bacterial encounters. The model reproduces the observed age patterns in Hib carriage and disease in Finland before large-scale use of the Hib conjugate vaccines. The model was used to investigate characteristics of Hib transmission. The analysis emphasizes transmission between children and adults in families while pointing out the importance of pre-school and school-aged children in maintaining Hib circulation. Carriage in these age groups is thus identified as being essential to target for sustained effects of interventions by vaccination.