Epidemiology and transmission dynamics of Streptococcus pneumoniae in low and lower-middle income settings: implications for vaccination strategies

Disease due to Streptococcus pneumoniae is a major cause of mortality and morbidity globally. Pneumococcal conjugate vaccines (PCVs) are being routinely introduced in immunisation programmes with support from Gavi, the Vaccine alliance, in low-income countries but uncertainty remains around the impact of different PCV introduction strategies in such settings, and in particular catch-up campaigns (CCs), which so far have not been conducted in Gavi-supported countries due to supply constraints. This thesis explored the potential impact on nasopharyngeal carriage and disease of introducing PCV with and without CCs, in Nha Trang, Vietnam, through a dynamic transmission model. Vietnam is yet to introduce PCV vaccination, as are most South-East Asian countries. Additional studies on the vaccine efficacy against carriage (VEC) and its waning, social contact patterns relevant for pneumococcal transmission, and age-specific epidemiology of carriage and serotype distribution were also conducted, the results of which fed directly into the transmission model. A meta-analysis provided the first ever-global estimates of VEC and its waning, by serotype and schedule. A large survey in southwest Uganda, collecting data on both social contact patterns and carriage from the same participants, shed light on which social contacts are important for pneumococcal transmission, showing that the frequency of close contacts, but not casual contacts, increased the colonisation risk, thereby informing the parameterisation of the transmission model. Results from the latter predicted elimination of vaccine type (VT) serotypes with near-complete replacement by non-VT across all age groups, within 10 years of PCV introduction with 90% coverage. The predicted benefit of CCs to expanded age groups was most pronounced in the first three years after PCV introduction, insofar that CCs result in limited introduction delays. This thesis provided important insight into the epidemiology and transmission dynamics of pneumococci, to inform policy in countries that have not yet introduced PCV

The Efficacy and Duration of Protection of Pneumococcal Conjugate Vaccines Against Nasopharyngeal Carriage: A Meta-Regression Model.

BACKGROUND: Pneumococcal conjugate vaccines (PCVs) reduce disease largely through their impact on nasopharyngeal (NP) carriage acquisition of Streptococcus pneumoniae, a precondition for developing any form of pneumococcal disease. We aimed to estimate the vaccine efficacy (VEC) and duration of protection of PCVs against S. pneumoniae carriage acquisition through meta-regression models. METHODS: We identified intervention studies providing NP carriage estimates among vaccinated and unvaccinated children at any time after completion of a full vaccination schedule. We calculated VEC for PCV7 serotypes, grouped as well as individually, and explored cross-protective efficacy against 6A. Efficacy estimates over time were obtained using a Bayesian meta-logistic regression approach, with time since completion of vaccination as a covariate. RESULTS: We used data from 22 carriage surveys (15 independent studies) from 5 to 64 months after the last PCV dose, including 14,298 children. The aggregate VEC for all PCV7 serotypes 6 months after completion of the vaccination schedule was 57% (95% credible interval: 50-65%), varying by serotype from 38% (19F) to 80%. Our model provides evidence of sustained protection of PCVs for several years, with an aggregate VEC of 42% (95% credible interval: 19-54%) at 5 years, although the waning differed between serotypes. We also found evidence of cross-protection against 6A, with a VEC of 39% 6 months after a complete schedule, decreasing to 0 within 5 years postvaccination. CONCLUSION: Our results suggest that PCVs confer reasonable protection against acquisition of pneumococcal carriage of the 7 studied serotypes, for several years after vaccination, albeit with differences across serotypes.<br/

Assessment of left ventricular mass and volumes by three-dimensional echocardiography in patients with or without wall motion abnormalities: comparison against cine magnetic resonance imaging

To evaluate if three-dimensional echocardiography (3-DE) is as accurate and reproducible as cine magnetic resonance imaging (cMR) in estimating left ventricular (LV) parameters in patients with and without wall motion abnormalities (WMA)

Characteristics of human encounters and social mixing patterns relevant to infectious diseases spread by close contact: a survey in Southwest Uganda.

BACKGROUND: Quantification of human interactions relevant to infectious disease transmission through social contact is central to predict disease dynamics, yet data from low-resource settings remain scarce. METHODS: We undertook a social contact survey in rural Uganda, whereby participants were asked to recall details about the frequency, type, and socio-demographic characteristics of any conversational encounter that lasted for ≥5 min (henceforth defined as 'contacts') during the previous day. An estimate of the number of 'casual contacts' (i.e. < 5 min) was also obtained. RESULTS: In total, 566 individuals were included in the study. On average participants reported having routine contact with 7.2 individuals (range 1-25). Children aged 5-14 years had the highest frequency of contacts and the elderly (≥65 years) the fewest (P < 0.001). A strong age-assortative pattern was seen, particularly outside the household and increasingly so for contacts occurring further away from home. Adults aged 25-64 years tended to travel more often and further than others, and males travelled more frequently than females. CONCLUSION: Our study provides detailed information on contact patterns and their spatial characteristics in an African setting. It therefore fills an important knowledge gap that will help more accurately predict transmission dynamics and the impact of control strategies in such areas

Infant contact in day-care centres in Vietnam: A cross-sectional study to understand infant infection risk

Background: Infant contact information (skin-to-skin contact between infants and others) is important to understand Streptococcus pneumoniae transmission patterns. A few studies have investigated infant contact patterns by asking the mother/guardian to record all contacts a child makes in one day. However, this approach does not capture contact behaviour in day-care. Our study describes the frequency and nature of physical contacts of infants in day-care to understand infant infection risk in day-care in Nha Trang, central Vietnam. Methods: This cross-sectional study enrolled infants aged less than 12 months, attending 10 randomly selected day-care centres in Nha Trang. Physical contacts of each infant for one day at the day-care centre were observed and recorded. The mean number of contacts of infants and its factors were assessed using negative binomial regression. Results: In total 14 infants, aged 6 to 11 months, were enrolled, and a total of 96 contacts were observed. The mean number of contacts an infant made in one day was 6.9. Infants who walked independently (age-adjusted rate ratio 1.68, 95% confidence interval 1.06-2.68) and those cared for in a larger group (1.99, 1.42-2.79) had more contacts at day-care. About 50% of infants made contact with at least one person from a commune different from the infant\u27s, and 50% made contact with at least one other infant at day-care. Conclusion: This study found that day-care attendance may be one factor that increases contact rates of infants in Nha Trang and diversifies them in terms of age and geographical spread. In this study, day-care attendance not only increased contact rates beyond those usually experienced by young children cared at home but specifically increased the contact rates with other children and adults from other communes. Day-care may play a key role in the transmission of respiratory pathogens like Streptococcus pneumoniae to infants

Determinants of high residual post-PCV13 pneumococcal vaccine-type carriage in Blantyre, Malawi:a modelling study

Background In November 2011, Malawi introduced the 13-valent pneumococcal conjugate vaccine (PCV13) into the routine infant schedule. Four to 7 years after introduction (2015–2018), rolling prospective nasopharyngeal carriage surveys were performed in the city of Blantyre. Carriage of Streptococcus pneumoniae vaccine serotypes (VT) remained higher than reported in high-income countries, and impact was asymmetric across age groups. Methods A dynamic transmission model was fit to survey data using a Bayesian Markov-chain Monte Carlo approach, to obtain insights into the determinants of post-PCV13 age-specific VT carriage. Results Accumulation of naturally acquired immunity with age and age-specific transmission potential were both key to reproducing the observed data. VT carriage reduction peaked sequentially over time, earlier in younger and later in older age groups. Estimated vaccine efficacy (protection against carriage) was 66.87% (95% CI 50.49–82.26%), similar to previous estimates. Ten-year projected vaccine impact (VT carriage reduction) among 0–9 years old was lower than observed in other settings, at 76.23% (CI 95% 68.02–81.96%), with sensitivity analyses demonstrating this to be mainly driven by a high local force of infection. Conclusions There are both vaccine-related and host-related determinants of post-PCV13 pneumococcal VT transmission in Blantyre with vaccine impact determined by an age-specific, local force of infection. These findings are likely to be generalisable to other Sub-Saharan African countries in which PCV impact on carriage (and therefore herd protection) has been lower than desired, and have implications for the interpretation of post-PCV carriage studies and future vaccination programs.</p

Factors associated with delayed presentation to healthcare facilities for Lassa fever cases, Nigeria 2019: a retrospective cohort study.

BACKGROUND: Large outbreaks of Lassa fever (LF) occur annually in Nigeria. The case fatality rate among hospitalised cases is ~ 20%. The antiviral drug ribavirin along with supportive care and rehydration are the recommended treatments but must be administered early (within 6 days of symptom onset) for optimal results. We aimed to identify factors associated with late presentation of LF cases to a healthcare facility to inform interventions. METHODS: We undertook a retrospective cohort study of all laboratory confirmed LF cases reported in Nigeria from December 2018 to April 2019. We performed descriptive epidemiology and a univariate Cox proportional-hazards regression analysis to investigate the effect of clinical (symptom severity), epidemiological (age, sex, education, occupation, residential State) and exposure (travel, attendance at funeral, exposure to rodents or confirmed case) factors on time to presentation. RESULTS: Of 389 cases, median presentation time was 6 days (IQR 4-10 days), with 53% attending within 6 days. There were no differences in presentation times by sex but differences were noted by age-group; 60+ year-olds had the longest delays while 13-17 year-olds had the shortest. By sex and age, there were differences seen among the younger ages, with 0-4-year-old females presenting earlier than males (4 days and 73% vs. 10 days and 30%). For 5-12 and 13-17 year-olds, males presented sooner than females (males: 5 days, 65% and 3 days, 85% vs. females: 6 days, 50% and 5 days, 61%, respectively). Presentation times differed across occupations 4.5-9 days and 20-60%, transporters (people who drive informal public transport vehicles) had the longest delays. Other data were limited (41-95% missing). However, the Cox regression showed no factors were statistically associated with longer presentation time. CONCLUSIONS: Whilst we observed important differences in presentation delays across factors, our sample size was insufficient to show any statistically significant differences that might exist. However, almost half of cases presented after 6 days of onset, highlighting the need for more accurate and complete surveillance data to determine if there is a systemic or specific cause for delays, so to inform, monitor and evaluate public health strategies and improve outcomes

Social contact patterns and implications for infectious disease transmission: a systematic review and meta-analysis of contact surveys

Background: Transmission of respiratory pathogens such as SARS-CoV-2 depends on patterns of contact and mixing across populations. Understanding this is crucial to predict pathogen spread and the effectiveness of control efforts. Most analyses of contact patterns to date have focussed on high-income settings. Methods: Here, we conduct a systematic review and individual-participant meta-analysis of surveys carried out in low- and middle-income countries and compare patterns of contact in these settings to surveys previously carried out in high-income countries. Using individual-level data from 28,503 participants and 413,069 contacts across 27 surveys we explored how contact characteristics (number, location, duration and whether physical) vary across income settings. Results: Contact rates declined with age in high- and upper-middle-income settings, but not in low-income settings, where adults aged 65+ made similar numbers of contacts as younger individuals and mixed with all age-groups. Across all settings, increasing household size was a key determinant of contact frequency and characteristics, but low-income settings were characterised by the largest, most intergenerational households. A higher proportion of contacts were made at home in low-income settings, and work/school contacts were more frequent in high-income strata. We also observed contrasting effects of gender across income-strata on the frequency, duration and type of contacts individuals made. Conclusions: These differences in contact patterns between settings have material consequences for both spread of respiratory pathogens, as well as the effectiveness of different non-pharmaceutical interventions

Адаптация гидравлической модели водостока к бассейнам рек Дунай и Днестр

Гидравлическая модель водостока адаптирована к бассейну рек Дунай и Днестр. По данным орографии, атмосферных осадках или поверхностном стоке она позволяет рассчитывать объемы, расходы и уровни воды с пространственным разрешением 1 км. В модели возможно использование данные об экосистемах на земной поверхности, типах почвы. По данным наблюдений стока оценены среднемесячные величины расходов рек, которые соответствуют наблюдениям, что позволяет применять модель в дальнейших оценках стока, наносов и т.д.Hydraulic model of water inflow is adapted to the Danube and the Dniester rivers basin. According to the orography, precipitation and surface inflow data it permits to calculate water volumes, discharges and levels with spatial resolution 1 km. It is possible to use the data on ecosystems on the ground surface, types of soil in the model. According to the observations data of the inflow the average monthly values of river discharges corresponding to the observations are estimated. It permits to apply the model in the further estimations of inflow, alluvia e t.c