Olivier le Polain de Waroux

Age-Dependent Prevalence of Nasopharyngeal Carriage of Streptococcus pneumoniae before Conjugate Vaccine Introduction: A Prediction Model Based on a Meta-Analysis.

Introduction Data on the prevalence of nasopharyngeal carriage of S.pneumoniae in all age groups are important to help predict the impact of introducing pneumococcal conjugate vaccines (PCV) into routine infant immunization, given the important indirect effect of the vaccine. Yet most carriage studies are limited to children under five years of age. We here explore the association between carriage prevalence and serotype distribution in children aged ≥5 years and in adults compared to children. Methods We conducted a systematic review of studies providing carriage estimates across age groups in healthy populations not previously exposed to PCV, using MEDLINE and Embase. We used Bayesian linear meta-regression models to predict the overall carriage prevalence as well as the prevalence and distribution of vaccine and nonvaccine type (VT and NVT) serotypes in older age groups as a function of that in <5 y olds. Results Twenty-nine studies compromising of 20,391 individuals were included in the analysis. In all studies nasopharyngeal carriage decreased with increasing age. We found a strong positive linear association between the carriage prevalence in pre-school childen (<5 y) and both that in school aged children (5–17 y olds) and in adults. The proportion of VT serotypes isolated from carriers was consistently lower in older age groups and on average about 73% that of children <5 y among 5–17 y olds and adults respectively. We provide a prediction model to infer the carriage prevalence and serotype distribution in 5–17 y olds and adults as a function of that in children <5 years of age. Conclusion Such predictions are helpful for assessing the potential population-wide effects of vaccination programmes, e.g. via transmission models, and thus assist in the design of future pneumococcal conjugate vaccination strategies.

Timeliness and completeness of vaccination and risk factors for low and late vaccine uptake in young children living in rural southern Tanzania

BACKGROUND We studied coverage and timeliness of vaccination and risk factors for low and delayed vaccine uptake in children aged <2 years in rural Tanzania. METHODS We used data from a cluster survey conducted in 2004, which included 1403 children. Risk factors were analysed by log-binomial regression adjusted for the clustering. The analysis was restricted to BCG, first and third dose of Diphtheria-Tetanus-Pertussis vaccines (DTP-1 and DTP-3) and first dose of measles-containing vaccine (MCV-1). RESULTS Coverage for BCG, DTP-1, DTP-3 and MCV-1 was 94%, 96%, 90% and 86%, respectively. Delayed vaccination (>1 month after the recommended age) occurred in 398/1205 (33%) children for BCG, 404/1189 (34%) for DTP-1, 683/990 (69%) for DTP-3 and 296/643 (46%) for MCV-1. Coverage was lower for all vaccines except DTP-1 in children living ≥5 km from a healthcare facility. Delayed uptake was associated with poverty. Low and delayed MCV-1 vaccination was associated with low maternal education. Delayed BCG vaccination was associated with ethnicity and rainy season. CONCLUSION Despite reasonably high vaccination coverage, we observed substantial vaccination delays, particularly for DTP-3 and MCV-1. We found specific factors associated with low and/or delayed vaccine uptake. These findings can help to improve strategies to reach children who remain inadequately protected.

Clinical Impact of MALDI-TOF MS Identification and Rapid Susceptibility Testing on Adequate Antimicrobial Treatment in Sepsis with Positive Blood Cultures

Shortening the turn-around time (TAT) of positive blood culture (BC) identification (ID) and susceptibility results is essential to optimize antimicrobial treatment in patients with sepsis. We aimed to evaluate the impact on antimicrobial prescription of a modified workflow of positive BCs providing ID and partial susceptibility results for Enterobacteriaceae (EB), Pseudomonas aeruginosa and Staphylococcus aureus on the day of BC positivity detection. This study was divided into a pre-intervention period (P0) with a standard BC workflow followed by 2 intervention periods (P1, P2) with an identical modified workflow. ID was performed with MALDI-TOF MS from blood, on early or on overnight subcultures. According to ID results, rapid phenotypic assays were realized to detect third generation cephalosporin resistant EB/P. aeruginosa or methicillin resistant S. aureus. Results were transmitted to the antimicrobial stewardship team for patient’s treatment revision. Times to ID, to susceptibility results and to optimal antimicrobial treatment (OAT) were compared across the three study periods. Overall, 134, 112 and 154 positive BC episodes in P0, P1 and P2 respectively were included in the analysis. Mean time to ID (28.3 hours in P0) was reduced by 65.3% in P1 (10.2 hours) and 61.8% in P2 (10.8 hours). Mean time to complete susceptibility results was reduced by 27.5% in P1 and 27% in P2, with results obtained after 32.4 and 32.6 hours compared to 44.7 hours in P0. Rapid tests allowed partial susceptibility results to be obtained after a mean time of 11.8 hours in P1 and 11.7 hours in P2. Mean time to OAT was decreased to 21.6 hours in P1 and to 17.9 hours in P2 compared to 36.1 hours in P0. Reducing TAT of positive BC with MALDI-TOF MS ID and rapid susceptibility testing accelerated prescription of targeted antimicrobial treatment thereby potentially improving the patients’ clinical outcome.

The serotype distribution among healthy carriers before vaccination is essential for predicting the impact of pneumococcal conjugate vaccine on invasive disease.

Pneumococcal conjugate vaccines (PCVs) have substantially reduced morbidity and mortality of pneumococcal disease. The impact of the 7-valent PCV on all-serotype invasive pneumococcal disease (IPD) among children was reported to vary between high-income countries. We investigate the ability to predict this heterogeneity from pre-vaccination data. We propose a parsimonious model that predicts the impact of PCVs from the odds of vaccine serotype (VT) among carriers and IPD cases in the pre-PCV period, assuming that VT are eliminated in a mature PCV programme, that full serotype replacement occurs in carriage and that invasiveness of the NVT group is unchanged. We test model performance against the reported impact of PCV7 on childhood IPD in high-income countries from a recent meta-analysis. The odds of pre-PCV7 VT IPD, PCV schedule, PCV coverage and whether a catch up campaign was used for introduction was gathered from the same analysis. We conducted a literature review and meta-analysis to obtain the odds of pre-PCV7 VT carriage in the respective settings. The model predicted the reported impact on childhood IPD of mature PCV programmes; the ratio of predicted and observed incidence risk ratios was close to 1 in all settings. In the high income settings studied differences in schedule, coverage, and catch up campaigns were not associated with the observed heterogeneity in impact of PCV7 on childhood all-serotype IPD. The pre-PCV7 proportion of VT IPD alone also had limited predictive value. The pre-PCV7 proportion of VT carriage and IPD are the main determinants for the impact of PCV7 on childhood IPD and can be combined in a simple model to provide predictions of the vaccine preventable burden of IPD.

Identifying human encounters that shape the transmission of Streptococcus pneumoniae and other acute respiratory infections

Highlights • Individual risk of pneumococcal carriage and of acute respiratory symptoms increases with the number of close contacts.• More frequent contact with young children increases the risk of pneumococcal carriage in adults.• The risk of nasopharyngeal carriage did not increase with the frequency of short casual contacts, irrespective of age.

Carriage prevalence and serotype distribution of Streptococcus pneumoniae prior to 10-valent pneumococcal vaccine introduction: A population-based cross-sectional study in South Western Uganda, 2014.

Background Information on Streptococcus pneumoniae nasopharyngeal (NP) carriage before the pneumococcal conjugate vaccine (PCV) introduction is essential to monitor impact. The 10-valent PCV (PCV10) was officially introduced throughout Ugandan national childhood immunization programs in 2013 and rolled-out countrywide during 2014. We aimed to measure the age-specific Streptococcus pneumoniae carriage and serotype distribution across all population age groups in the pre-PCV10 era in South Western Uganda. Methods We conducted a two-stage cluster, age-stratified, cross-sectional community-based study in Sheema North sub-district between January and March 2014. One NP swab was collected and analyzed for each participant in accordance with World Health Organization guidelines. Results NP carriage of any pneumococcal serotype was higher among children <2 years old (77%; n = 387) than among participants aged ≥15 years (8.5%; n = 325) (chi2 p < 0.001). Results Of the 623 positive cultures, we identified 49 serotypes among 610 (97.9%) isolates; thirteen (2.1%) isolates were non-typeable. Among <2 years old, serotypes 6A, 6B, 14, 15B, 19F and 23F accounted for half of all carriers. Carriage prevalence with PCV10 serotypes was 29.4% among individuals aged <2 years (n = 387), 23.4% in children aged 2–4 years (n = 217), 11.4% in 5–14 years (n = 417), and 0.4% among individuals ≥15 years of age (n = 325). The proportion of carried pneumococci serotypes contained in PCV10 was 38.1% (n = 291), 32.8% (n = 154), 29.4% (n = 156), and 4.4% (n = 22) among carriers aged <2 years, 2–4 years, 5–14 years and ≥15 years, respectively. Discussion In Sheema district, the proportion of PCV10 serotypes was low (<40%), across all age groups, especially among individuals aged 15 years or older (<5%). PCV10 introduction is likely to impact transmission among children and to older individuals, but less likely to substantially modify pneumococcal NP ecology among individuals aged 15 years or older.

Prevalence of and Risks for Internal Contamination among Hospital Staff Caring for a Patient Contaminated with a Fatal Dose of Polonium-210

BACKGROUND Alexander Litvinenko died on November 23, 2006, from acute radiation sickness syndrome caused by ingestion of polonium-210 (²¹⁰Po). OBJECTIVE The objective was to assess the prevalence of and risk factors for internal contamination with ²¹⁰Po in healthcare workers (HCWs) caring for the contaminated patient. SETTING Hospital. PARTICIPANTS HCWs who had direct contact with the patient. METHODS We interviewed 43 HCWs and enquired about their activities and use of personal protective equipment (PPE). Internal contamination was defined as urinary ²¹⁰Po excretion above 20 mBq within 24 hours. We obtained risk ratios (RRs) for internal contamination using Poisson regression. RESULTS Thirty-seven HCWs (86%) responded, and 8 (22%) showed evidence of internal contamination, all at very low levels that were unlikely to cause adverse health outcomes. Daily care of the patient (washing and toileting the patient) was the main risk factor (RR, 3.6 [95% confidence interval (CI), 1.1-11.6]). In contrast, planned invasive procedures were not associated with a higher risk. There was some evidence of a higher risk associated with handling blood samples (RR, 3.5 [95% CI, 0.8-15.6]) and changing urine bags and/or collecting urine samples (RR, 2.7 [95% CI, 0.8-9.5]). There was also some evidence that those who reported not always using standard PPE were at higher risk than were others (RR, 2.5 [95% CI, 0.8-8.1]). CONCLUSIONS The sensitive quantitative measurement enabled us to identify factors associated with contamination, which by analogy to other conditions with similar transmission mechanisms may help improve protection and preparedness in staff dealing with an ill patient who experiences an unknown illness.

Predicting The Impact Of Pneumococcal Conjugate Vaccine Programme Options In Vietnam: A Dynamic Transmission Model

Background Catch-up campaigns (CCs) at the introduction of the pneumococcal conjugate vaccines (PCVs) may accelerate the impact of PCVs. However, limited vaccine supplies may delay vaccine introduction if additional doses are needed for such campaigns. We studied the relative impact of introducing PCV13 with and without catch-up campaign, and the implications of potential introduction delays. Methods We used a dynamic transmission model applied to the population of Nha Trang in Sout central Vietnam. Four strategies were considered: routine vaccination (RV) only, and RV alongside catch-up campaigns among <1y olds (CC1), <2y olds (CC2) and <5y olds (CC5). The model was parameterised with local data on human social contact rates, and was fitted to local carriage data. Post-PCV predictions were based on best estimates of parameters governing post-PCV dynamics, including serotype competition, vaccine efficacy and duration of protection. Results Our model predicts elimination of vaccine-type (VT) carriage across all age groups within 10 years of introduction in all scenarios with near-complete replacement by non-VT. Most of the benefit of CCs is predicted to occur within the first 3 years after introduction, with the highest impact in the first year, when IPD incidence is predicted to be 11% (95%CrI 9 – 14%) lower than RV with CC1, 25% (21 – 30 %) lower with CC2 and 38% (32 – 46%) lower with CC5. However, CCs would only prevent more cases of IPD insofar such campaigns do not delay introduction by more than 31 (95%CrI 30 – 32) weeks with CC1, 58 (53 – 63) weeks with CC2 and 89 (78 – 101) weeks for CC5. Conclusion CCs are predicted to offer a substantial additional reduction in pneumococcal disease burden over RV alone, if their implementation does not result in much introduction delay. Those findings are important to help guide vaccine introduction in countries that have not yet introduced PCV, particularly in Asia.

Social mixing in Fiji: Who-eats-with-whom contact patterns and the implications of age and ethnic heterogeneity for disease dynamics in the Pacific Islands

Empirical data on contact patterns can inform dynamic models of infectious disease transmission. Such information has not been widely reported from Pacific islands, nor strongly multi-ethnic settings, and few attempts have been made to quantify contact patterns relevant for the spread of gastrointestinal infections. As part of enteric fever investigations, we conducted a cross-sectional survey of the general public in Fiji, finding that within the 9,650 mealtime contacts reported by 1,814 participants, there was strong like-with-like mixing by age and ethnicity, with higher contact rates amongst iTaukei than non-iTaukei Fijians. Extra-domiciliary lunchtime contacts follow these mixing patterns, indicating the overall data do not simply reflect household structures. Inter-ethnic mixing was most common amongst school-age children. Serological responses indicative of recent Salmonella Typhi infection were found to be associated, after adjusting for age, with increased contact rates between meal-sharing iTaukei, with no association observed for other contact groups. Animal ownership and travel within the geographical division were common. These are novel data that identify ethnicity as an important social mixing variable, and use retrospective mealtime contacts as a socially acceptable metric of relevance to enteric, contact and respiratory diseases that can be collected in a single visit to participants. Application of these data to other island settings will enable communicable disease models to incorporate locally relevant mixing patterns in parameterisation.

Predicting the impact of pneumococcal conjugate vaccine programme options in Vietnam

ABSTRACT Although catch-up campaigns (CCs) at the introduction of pneumococcal conjugate vaccines (PCVs) may accelerate their impact, supply constraints may limit their benefit if the need for additional PCV doses results in introduction delay. We studied the impact of PCV13 introduction with and without CC in Nha Trang, Vietnam – a country that has not yet introduced PCV – through a dynamic transmission model. We modelled the impact on carriage and invasive pneumococcal disease (IPD) of routine vaccination (RV) only and that of RV with CCs targeting <1y olds (CC1), <2y olds (CC2) and <5y olds (CC5). The model was fitted to nasopharyngeal carriage data, and post-PCV predictions were based on best estimates of parameters governing post-PCV dynamics. With RV only, elimination in carriage of vaccine-type (VT) serotypes is predicted to occur across all age groups within 10 years after introduction, with near-complete replacement by non-VT. Most of the benefit of CCs is predicted to occur within the first 3 years with the highest impact at one year, when IPD incidence is predicted to be 11% (95%CrI 9 – 14%) lower than RV with CC1, 25% (21 – 30 %) lower with CC2 and 38% (32 – 46%) lower with CC5. However, CCs would only prevent more cases of IPD insofar as such campaigns do not delay introduction by more than about 6, 12 and 18 months for CC1, CC2 and CC5. Those findings are important to help guide vaccine introduction in countries that have not yet introduced PCV, particularly in Asia.