Stable HEV IgG seroprevalence in Belgium between 2006 and 2014.

Recent European studies suggest an emergence of hepatitis E virus (HEV) infection. We evaluated trends in birth cohort-specific HEV seroprevalence and regional differences in Belgium. HEV IgG seroprevalence was analysed on national serum banks (1579 and 2087 samples for 2006 and 2014, respectively. Hepatitis E virus antigen was tested on positive samples. Observed data were modelled using a generalized additive model with a complementary log-log link. No significant differences between birth cohorts or sexes were found. Modelling identified the individual's age and province as relevant factors. The probability of HEV seropositivity increases significantly with age. An estimated total of 434 819 (yearly rate of 54,352) (sero-)infections were found between 2006 and 2014. Overall, HEV IgG seroprevalences were 4.1% (64/1579, 95% CI 3.1-5.1) and 5.8% (121/2087, CI 4.8-6.9) in 2006 and 2014, respectively. Observed HEV antigen seroprevalence was 0.027% (1/3666) for the entire cohort. These results show stable HEV IgG seroprevalence in Belgium.

Sample size calculation for estimating key epidemiological parameters using serological data and mathematical modelling.

BACKGROUND: Our work was motivated by the need to, given serum availability and/or financial resources, decide on which samples to test in a serum bank for different pathogens. Simulation-based sample size calculations were performed to determine the age-based sampling structures and optimal allocation of a given number of samples for testing across various age groups best suited to estimate key epidemiological parameters (e.g., seroprevalence or force of infection) with acceptable precision levels in a cross-sectional seroprevalence survey. METHODS: Statistical and mathematical models and three age-based sampling structures (survey-based structure, population-based structure, uniform structure) were used. Our calculations are based on Belgian serological survey data collected in 2001-2003 where testing was done, amongst others, for the presence of Immunoglobulin G antibodies against measles, mumps, and rubella, for which a national mass immunisation programme was introduced in 1985 in Belgium, and against varicella-zoster virus and parvovirus B19 for which the endemic equilibrium assumption is tenable in Belgium. RESULTS: The optimal age-based sampling structure to use in the sampling of a serological survey as well as the optimal allocation distribution varied depending on the epidemiological parameter of interest for a given infection and between infections. CONCLUSIONS: When estimating epidemiological parameters with acceptable levels of precision within the context of a single cross-sectional serological survey, attention should be given to the age-based sampling structure. Simulation-based sample size calculations in combination with mathematical modelling can be utilised for choosing the optimal allocation of a given number of samples over various age groups.

Follow-up of serotype distribution and antimicrobial susceptibility of Streptococcus pneumoniae in child carriage after a PCV13-to-PCV10 vaccine switch in Belgium.

BACKGROUND: A three year pneumococcal carriage study was set up in Belgium when the vaccination programme switched from a 13-valent (PCV13) to a 10-valent (PCV10) vaccine. We compared the first follow-up period (October 2016 - June 2017, year 2, Y2) for nasopharyngeal carriage, serotype distribution and antimicrobial susceptibility of S. pneumoniae with the baseline (January-July 2016, year 1, Y1). MATERIALS/METHODS: A single nasopharyngeal swab was taken in children (6-30 months), either attending one of the 112 day-care centres (DCCs), or visiting one of the 21 physicians for an acute otitis media (AOM). S. pneumoniae were cultured, screened for antimicrobial susceptibility, and serotyped. RESULTS: In Y2, 1218 samples were collected. The majority of the Y2-children (>85%) was vaccinated appropriately for their age. Children in Y2 received either PCV13 only (DCC: 23.5%; AOM: 24.6%), PCV10 only (DCC: 29.8%; AOM: 37.7%), or a mix of both vaccines (DCC: 31.9%; AOM: 25.4%). Pneumococcal carriage rates were high (Y2, DCC: 68.2%; AOM: 64.8%). Among carriers, prevalence of PCV13 serotypes was low (Y2 vs Y1, DCC: 3.5% vs 5.4%; AOM: 7.6% vs 7.7%). Although prevalence of PCV13-non-PCV10 serotypes did not increase significantly compared to Y1 (Y2 vs Y1, DCC: 1.6% vs 0.9%; Y2 vs Y1, AOM: 5.1% vs 0.0%), the proportion of serotypes 3, 6A, 19A among PCV13 serotype carriers in DCC was significantly higher in Y2 (46.2% vs Y1: 16.0%, p-value = 0.034). Serotypes 23B and 15B were the predominant non-vaccine serotypes (Y2). Among detected strains, non-susceptibility to at least one of five antibiotics tested (penicillin, tetracycline, erythromycin, levofloxacin, cotrimoxazole) was comparable to Y1 (Y2 vs Y1, DCC: 41.3% vs 42.4%; AOM: 49.4% vs 48.1%). CONCLUSION: After completion of the PCV13-to-PCV10 vaccine switch in Belgium, the proportion of PCV13-non-PCV10 serotypes (mainly 19A) significantly increased among PCV13 serotype carriers in DCC, stressing the need for strengthened surveillance as the PCV10-vaccinated population grows.

Coverage of recommended vaccines during pregnancy in Flanders, Belgium. Fairly good but can we do better?

BACKGROUND: In Flanders, Belgium, pertussis vaccination is recommended since 2013 and available free-of-charge in every pregnancy between 24 and 32 weeks of gestation. Influenza vaccination is recommended for more than 10 years with a co-payment system in the second or third trimester of pregnancy, when pregnancy coincides with the influenza season. This study aims to estimate the coverage of pertussis and influenza vaccination during pregnancy in 2016 and to determine predictors for missing vaccination. METHODS: Postpartum women were visited at home for a vaccination coverage survey using an Expanded Program on Immunization (EPI)-based two-stage cluster sampling design. Predictors for missed vaccination were identified using a multiple logistic regression model. RESULTS: Among 481 participating women, 69.3% were vaccinated against pertussis and 47.2% were vaccinated against influenza. Moreover, 65.3% of pertussis vaccine recipients and 96.9% of influenza vaccine recipients were vaccinated within the recommended gestational window. Surprisingly, among women who were completely informed (i.e. on disease-associated risks, maternal vaccination costs and recommendations), still 12.4% were unvaccinated against pertussis and 23.9% against influenza. In the final models, the only common predictor of missing maternal pertussis and influenza vaccination was multiparity. Significant predictors of maternal pertussis vaccination were family income (less likely if unknown or low (< €3000) than if moderate (€3001-€4000)) and hospital of delivery (less likely if >800 annual deliveries than <800). Significant predictors of maternal influenza vaccination, though with less straight-forward associations, were maternal ethnicity and educational level, involvement of a gynaecologist in pregnancy follow-up, and characteristics of the hospital of delivery. CONCLUSION: In Flanders, more than two-third of pregnant women receives pertussis vaccination but less than half of them receives the influenza vaccine. Further improvement for both maternal vaccination programs can be achieved by targeting the underserved populations and diminishing vaccination hurdles.

Nasopharyngeal s. pneumoniae carriage and density in Belgian infants after 9 years of pneumococcal conjugate vaccine programme.

BACKGROUND: In Belgium, the infant pneumococcal conjugate vaccine (PCV) programme changed from PCV7 (2007-2011) to PCV13 (2011-2015) and to PCV10 (2015-2016). A 3-year nasopharyngeal carriage study was initiated during the programme switch in 2016. Main objective of the year 1 assessment was to obtain a baseline measurement of pneumococcal carriage prevalence, carriage density, serotype distribution and antibiotic resistance. MATERIALS/METHODS: Two infant populations aged 6-30 months and without use of antibiotics in the seven days prior to sampling were approached: (1) attending one of 85 randomly selected day-care centres (DCC); (2) presenting with AOM at study-trained general practitioners and paediatricians. Demographic and clinical characteristics were documented and a single nasopharyngeal swab was taken. S. pneumoniae were cultured, screened for antibiotic resistance and serotyped, and quantitative Taqman real-time PCR (qRT-PCR) targeting LytA was performed. RESULTS: Culture-based (DCC: 462/760; 60.8% - AOM: 27/39; 69.2%) and LytA-based (DCC: 603/753; 80.1% - AOM: 32/39; 82.1%) carriage prevalence was high. Average pneumococcal DNA load in LytA-positive day-care samples was 6.5 × 106 copies/µl (95%CI = 3.9-9.2 × 106, median = 3.5 × 105); DNA load was positively associated with signs of common cold and negatively with previous antibiotic use. Culture-based frequency of 13 pneumococcal vaccine (PCV) serotypes was 5.4% in DCC and 7.7% in AOM, with 19F and 14 being most frequent, and frequencies below 0.5% for serotypes 3, 6A, 19A in both populations. Predominant non-PCV serotypes were 23B and 23A in day-care and 11A in infants with AOM. In day-care, resistance to penicillin was rare (<0.5%) and absent against levofloxacin; 32.7% and 16.9% isolates were cotrimoxazole- and erythromycin-resistant respectively. CONCLUSION: Four years after PCV13 introduction in the vaccination programme, PCV13 serotype carriage was rare in infants throughout Belgium and penicillin resistance was rare. Continued surveillance in the context of a PCV programme switch is necessary.

Mathematical models used to inform study design or surveillance systems in infectious diseases: a systematic review.

BACKGROUND: Mathematical models offer the possibility to investigate the infectious disease dynamics over time and may help in informing design of studies. A systematic review was performed in order to determine to what extent mathematical models have been incorporated into the process of planning studies and hence inform study design for infectious diseases transmitted between humans and/or animals. METHODS: We searched Ovid Medline and two trial registry platforms (Cochrane, WHO) using search terms related to infection, mathematical model, and study design from the earliest dates to October 2016. Eligible publications and registered trials included mathematical models (compartmental, individual-based, or Markov) which were described and used to inform the design of infectious disease studies. We extracted information about the investigated infection, population, model characteristics, and study design. RESULTS: We identified 28 unique publications but no registered trials. Focusing on compartmental and individual-based models we found 12 observational/surveillance studies and 11 clinical trials. Infections studied were equally animal and human infectious diseases for the observational/surveillance studies, while all but one between humans for clinical trials. The mathematical models were used to inform, amongst other things, the required sample size (n = 16), the statistical power (n = 9), the frequency at which samples should be taken (n = 6), and from whom (n = 6). CONCLUSIONS: Despite the fact that mathematical models have been advocated to be used at the planning stage of studies or surveillance systems, they are used scarcely. With only one exception, the publications described theoretical studies, hence, not being utilised in real studies.

Combined interventions to reduce HIV incidence in KwaZulu-Natal: a modelling study.

BACKGROUND: Combined prevention interventions, including early antiretroviral therapy initiation, may substantially reduce HIV incidence in hyperendemic settings. Our aim was to assess the potential short-term impact of combined interventions on HIV spreading in the adult population of Mbongolwane and Eshowe (KwaZulu-Natal, South Africa) using sex- and age-specific scenarios, and age-targeted interventions. METHODS: A mathematical model was used with data on adults (15-59 years) from the Mbongolwane and Eshowe HIV Impact in Population Survey to compare the effects of various interventions on the HIV incidence rate. These interventions included increase in antiretroviral therapy (ART) coverage with extended eligibility criteria, increase in voluntary medical male circumcision (VMMC), and implementation of pre-exposure prophylaxis (PrEP) among women. RESULTS: With no additional interventions to the ones in place at the time of the survey (ART at CD4 < 350 and VMMC), incidence will decrease by 24% compared to the baseline rate. The implementation of "ART at CD4<500" or "ART for all" would reduce further the incidence rate by additional 8% and 15% respectively by 4 years and 20% and 34% by 10 years. Impacts would be higher with age-targeted scenarios than without. CONCLUSIONS: In Mbongolwane and Eshowe, implementation of the new South African guidelines, recommending ART initiation regardless of CD4 count, would accelerate incidence reduction. In this setting, combining these guidelines, VMMC, and PrEP among young women could be an effective strategy in reducing the incidence to low levels.

Estimating HIV Incidence Using a Cross-Sectional Survey: Comparison of Three Approaches in a Hyperendemic Setting, Ndhiwa Subcounty, Kenya, 2012.

OBJECTIVES: Estimating HIV incidence is critical for identifying groups at risk for HIV infection, planning and targeting interventions, and evaluating these interventions over time. The use of reliable estimation methods for HIV incidence is thus of high importance. The aim of this study was to compare methods for estimating HIV incidence in a population-based cross-sectional survey. DESIGN/METHODS: The incidence estimation methods evaluated included assay-derived methods, a testing history-derived method, and a probability-based method applied to data from the Ndhiwa HIV Impact in Population Survey (NHIPS). Incidence rates by sex and age and cumulative incidence as a function of age were presented. RESULTS: HIV incidence ranged from 1.38 [95% confidence interval (CI) 0.67-2.09] to 3.30 [95% CI 2.78-3.82] per 100 person-years overall; 0.59 [95% CI 0.00-1.34] to 2.89 [95% CI 0.86-6.45] in men; and 1.62 [95% CI 0.16-6.04] to 4.03 [95% CI 3.30-4.77] per 100 person-years in women. Women had higher incidence rates than men for all methods. Incidence rates were highest among women aged 15-24 and 25-34 years and highest among men aged 25-34 years. CONCLUSION: Comparison of different methods showed variations in incidence estimates, but they were in agreement to identify most-at-risk groups. The use and comparison of several distinct approaches for estimating incidence are important to provide the best-supported estimate of HIV incidence in the population.

Potential impact of multiple interventions on HIV incidence in a hyperendemic region in Western Kenya: a modelling study.

BACKGROUND: Multiple prevention interventions, including early antiretroviral therapy initiation, may reduce HIV incidence in hyperendemic settings. Our aim was to predict the short-term impact of various single and combined interventions on HIV spreading in the adult population of Ndhiwa subcounty (Nyanza Province, Kenya). METHODS: A mathematical model was used with data on adults (15-59 years) from the Ndhiwa HIV Impact in Population Survey to compare the impacts on HIV prevalence, HIV incidence rate, and population viral load suppression of various interventions. These interventions included: improving the cascade of care (use of three guidelines), increasing voluntary medical male circumcision (VMMC), and implementing pre-exposure prophylaxis (PrEP) use among HIV-uninfected women. RESULTS: After four years, improving separately the cascade of care under the WHO 2013 guidelines and under the treat-all strategy would reduce the overall HIV incidence rate by 46 and 58 %, respectively, vs. the baseline rate, and by 35 and 49 %, respectively, vs. the implementation of the current Kenyan guidelines. With conservative and optimistic scenarios, VMMC and PrEP would reduce the HIV incidence rate by 15-25 % and 22-28 % vs. the baseline, respectively. Combining the WHO 2013 guidelines with VMMC would reduce the HIV incidence rate by 35-56 % and combining the treat-all strategy with VMMC would reduce it by 49-65 %. Combining the WHO 2013 guidelines, VMMC, and PrEP would reduce the HIV incidence rate by 46-67 %. CONCLUSIONS: The impacts of the WHO 2013 guidelines and the treat-all strategy were relatively close; their implementation is desirable to reduce HIV spread. Combining several strategies is promising in adult populations of hyperendemic areas but requires regular, reliable, and costly monitoring.

Estimation and Short-Term Prediction of the Course of the HIV Epidemic Using Demographic and Health Survey Methodology-Like Data.

BACKGROUND: Mathematical models have played important roles in the understanding of epidemics and in the study of the impacts of various behavioral or medical measures. However, modeling accurately the future spread of an epidemic requires context-specific parameters that are difficult to estimate because of lack of data. Our objective is to propose a methodology to estimate context-specific parameters using Demographic and Health Survey (DHS)-like data that can be used in mathematical modeling of short-term HIV spreading. METHODS AND FINDINGS: The model splits the population according to sex, age, HIV status, and antiretroviral treatment status. To estimate context-specific parameters, we used individuals' histories included in DHS-like data and a statistical analysis that used decomposition of the Poisson likelihood. To predict the course of the HIV epidemic, sex- and age-specific differential equations were used. This approach was applied to recent data from Kenya. The approach allowed the estimation of several key epidemiological parameters. Women had a higher infection rate than men and the highest infection rate in the youngest age groups (15-24 and 25-34 years) whereas men had the highest infection rate in age group 25-34 years. The immunosuppression rates were similar between age groups. The treatment rate was the highest in age group 35-59 years in both sexes. The results showed that, within the 15-24 year age group, increasing male circumcision coverage and antiretroviral therapy coverage at CD4 ≤ 350/mm3 over the current 70% could have short-term impacts. CONCLUSIONS: The study succeeded in estimating the model parameters using DHS-like data rather than literature data. The analysis provides a framework for using the same data for estimation and prediction, which can improve the validity of context-specific predictions and help designing HIV prevention campaigns.

Injury incidence rates of cyclists compared to pedestrians, car occupants and powered two-wheeler riders, using a medical registry and mobility data, Rhône County, France.

PURPOSE: In France, the bicycle's modal share is stabilizing after a decline; in some of France's major cities, it has even increased since the 1990s. It is hence relevant to improve the knowledge of the injury risk associated with cycling, compared with other means of transport such as car, walking and powered two-wheeler (PTW) riding. METHODS: The injury incidence rates were estimated by the ratio between accident data and mobility (exposure) data. Two accident data sources were used: police data and hospital-based data (outpatients and inpatients) from the Rhône road trauma Registry. This provides four injury categories: all-injury, hospitalization, serious-injury and fatal-injury. Exposure data were estimated from a regional household travel survey (RTS), using three measures of mobility: number of trips, distance traveled and time spent traveling. The survey was carried out from November 2005 to April 2006, on weekdays, outside school and public holidays; this seasonality was corrected using the 2007-2008 national household travel survey (NTS) that covered an entire year. Only information involving accidents and trips in, and residents of, the Rhône County (1.6 million inhabitants, including the city Lyon) were included in our study. Trends of injury rates were also evaluated in Greater Lyon, using previous travel surveys. RESULTS: The PTW riders had the highest all-injury, hospitalization, serious-injury and fatal-injury rates, followed by cyclists, and lastly by pedestrians and car occupants. The rates between men and women seemed similar among pedestrians and among car occupants. For car occupants, pedestrians and cyclists, the age group 18-25 years had higher all-injury rate compared with the age group 25-65 years. On the contrary, the age group≥65 years seemed to have higher hospitalization and serious-injury rates, compared with the age group 25-65 years. For cyclists, the injury rates seemed higher in non-dense areas than in dense areas. Between 1996-1997 and 2005-2006 and with regards to time spent traveling, the all-injury, serious-injury and fatal-injury rates seemed to have decreased for car occupants and cyclists. CONCLUSION: The higher risk for PTW riders is confirmed and quantified; it is very high. Decrease in injury rates seems more marked for cyclists; this may indicate the "safety in numbers" effect. Countermeasures for improving road safety could be implemented, especially for vulnerable road user types. However, they will not be sufficient to fill in the gap between the much higher risk for PTW riders and that of car occupants. Exposure-based injury rates can be a tool for monitoring and evaluating the effectiveness of policies and programs, and for comparisons between countries.

Impaired bone microarchitecture at the distal radius in older men with low muscle mass and grip strength: the STRAMBO study.

The aim was to study the association between bone microarchitecture and muscle mass and strength in older men. Volumetric bone mineral density (vBMD) and bone microarchitecture were assessed in 810 men aged ≥60 years at the distal radius by high-resolution peripheral computed tomography (HR-pQCT). Areal bone mineral density (aBMD) and appendicular muscle mass (ASM) were assessed by dual-energy X-ray absorptiometry (DXA). Relative ASM of the upper limbs (RASM-u.l.) was calculated as ASM of the upper limbs/(height)(2). Grip strength was measured by dynanometry. In multivariable models, men in the lowest RASM-u.l. quartile had lower cross-sectional area (CSA), cortical area (Ct.Ar), cortical thickness (Ct.Th), and trabecular area (Tb.Ar) at distal radius compared with men in the highest quartile. The trends remained significant after adjustment for grip strength. Men in the lowest quartile of the normalized grip strength (grip strength/[height](2)) had lower aBMD, total vBMD, Ct.Ar, Ct.Th, Tb.vBMD, and Tb.N, and higher Tb.Sp and Tb.Sp.SD. The associations for Ct.Ar, total vBMD, Ct.Th, Tb.vBMD, and Tb.Sp remained significant after adjustment for RASM-u.l. In the models including RASM-u.l. and normalized grip strength, CSA and Tb.Ar were associated with RASM-u.l. but not with the strength. Lower Ct.Th, Tb.vBMD, and Tb.N were associated with lower grip strength but not with RASM-u.l. Lower Ct.Ar was associated with lower grip strength and with lower RASM-u.l. In conclusion, in older men, low RASM-u.l. and low grip strength are associated with poor cortical and trabecular microarchitecture partly independently of each other, after adjustment for confounders.