Estimates of the basic reproduction number for rubella using seroprevalence data and indicator-based approaches.

The basic reproduction number (R0) of an infection determines the impact of its control. For many endemic infections, R0 is often estimated from appropriate country-specific seroprevalence data. Studies sometimes pool estimates from the same region for settings lacking seroprevalence data, but the reliability of this approach is unclear. Plausibly, indicator-based approaches could predict R0 for such settings. We calculated R0 for rubella for 98 settings and correlated its value against 66 demographic, economic, education, housing and health-related indicators. We also trained a random forest regression algorithm using these indicators as the input and R0 as the output. We used the mean-square error to compare the performances of the random forest, simple linear regression and a regional averaging method in predicting R0 using 4-fold cross validation. R0 was <5, 5-10 and >10 for 81, 14 and 3 settings respectively, with no apparent regional differences and in the limited available data, it was usually lower for rural than urban areas. R0 was most correlated with educational attainment, and household indicators for the Pearson and Spearman correlation coefficients respectively and with poverty-related indicators followed by the crude death rate considering the Maximum Information Coefficient, although the correlation for each was relatively weak (Pearson correlation coefficient: 0.4, 95%CI: (0.24,0.48) for educational attainment). A random forest did not perform better in predicting R0 than simple linear regression, depending on the subsets of training indicators and studies, and neither out-performed a regional averaging approach. R0 for rubella is typically low and using indicators to estimate its value is not straightforward. A regional averaging approach may provide as reliable an estimate of R0 for settings lacking seroprevalence data as one based on indicators. The findings may be relevant for other infections and studies estimating the disease burden and the impact of interventions for settings lacking seroprevalence data.

Estimating the health impact of vaccination against ten pathogens in 98 low-income and middle-income countries from 2000 to 2030: a modelling study.

BACKGROUND: The past two decades have seen expansion of childhood vaccination programmes in low-income and middle-income countries (LMICs). We quantify the health impact of these programmes by estimating the deaths and disability-adjusted life-years (DALYs) averted by vaccination against ten pathogens in 98 LMICs between 2000 and 2030. METHODS: 16 independent research groups provided model-based disease burden estimates under a range of vaccination coverage scenarios for ten pathogens: hepatitis B virus, Haemophilus influenzae type B, human papillomavirus, Japanese encephalitis, measles, Neisseria meningitidis serogroup A, Streptococcus pneumoniae, rotavirus, rubella, and yellow fever. Using standardised demographic data and vaccine coverage, the impact of vaccination programmes was determined by comparing model estimates from a no-vaccination counterfactual scenario with those from a reported and projected vaccination scenario. We present deaths and DALYs averted between 2000 and 2030 by calendar year and by annual birth cohort. FINDINGS: We estimate that vaccination of the ten selected pathogens will have averted 69 million (95% credible interval 52-88) deaths between 2000 and 2030, of which 37 million (30-48) were averted between 2000 and 2019. From 2000 to 2019, this represents a 45% (36-58) reduction in deaths compared with the counterfactual scenario of no vaccination. Most of this impact is concentrated in a reduction in mortality among children younger than 5 years (57% reduction [52-66]), most notably from measles. Over the lifetime of birth cohorts born between 2000 and 2030, we predict that 120 million (93-150) deaths will be averted by vaccination, of which 58 million (39-76) are due to measles vaccination and 38 million (25-52) are due to hepatitis B vaccination. We estimate that increases in vaccine coverage and introductions of additional vaccines will result in a 72% (59-81) reduction in lifetime mortality in the 2019 birth cohort. INTERPRETATION: Increases in vaccine coverage and the introduction of new vaccines into LMICs have had a major impact in reducing mortality. These public health gains are predicted to increase in coming decades if progress in increasing coverage is sustained. FUNDING: Gavi, the Vaccine Alliance and the Bill & Melinda Gates Foundation.

Vaccine equity in low and middle income countries: a systematic review and meta-analysis.

BACKGROUND: Evidence to date has shown that inequality in health, and vaccination coverage in particular, can have ramifications to wider society. However, whilst individual studies have sought to characterise these heterogeneities in immunisation coverage at national level, few have taken a broad and quantitative view of the contributing factors to heterogeneity in immunisation coverage and impact, i.e. the number of cases, deaths, and disability-adjusted life years averted. This systematic review aims to highlight these geographic, demographic, and sociodemographic characteristics through a qualitative and quantitative approach, vital to prioritise and optimise vaccination policies. METHODS: A systematic review of two databases (PubMed and Web of Science) was undertaken using search terms and keywords to identify studies examining factors on immunisation inequality and heterogeneity in vaccination coverage. Inclusion criteria were applied independently by two researchers. Studies including data on key characteristics of interest were further analysed through a meta-analysis to produce a pooled estimate of the risk ratio using a random effects model for that characteristic. RESULTS: One hundred and eight studies were included in this review. We found that inequalities in wealth, education, and geographic access can affect vaccine impact and vaccination dropout. We estimated those living in rural areas were not significantly different in terms of full vaccination status compared to urban areas but noted considerable heterogeneity between countries. We found that females were 3% (95%CI[1%, 5%]) less likely to be fully vaccinated than males. Additionally, we estimated that children whose mothers had no formal education were 28% (95%CI[18%,47%]) less likely to be fully vaccinated than those whose mother had primary level, or above, education. Finally, we found that individuals in the poorest wealth quintile were 27% (95%CI [16%,37%]) less likely to be fully vaccinated than those in the richest. CONCLUSIONS: We found a nuanced picture of inequality in vaccination coverage and access with wealth disparity dominating, and likely driving, other disparities. This review highlights the complex landscape of inequity and further need to design vaccination strategies targeting missed subgroups to improve and recover vaccination coverage following the COVID-19 pandemic. TRIAL REGISTRATION: Prospero, CRD42021261927.

Should NICE reconsider the 2016 UK guidelines on TB contact tracing? A cost-effectiveness analysis of contact investigations in London.

BACKGROUND: In January 2016, clinical TB guidance in the UK changed to no longer recommend screening contacts of non-pulmonary, non-laryngeal (ETB) index cases. However, no new evidence was cited for this change, and there is evidence that screening these contacts may be worthwhile. The objective of this study was to estimate the cost-effectiveness of screening contacts of adult ETB cases and adult pulmonary or laryngeal TB (PTB) cases in London, UK. METHODS: We carried out a cross-sectional analysis of data collected on TB index cases and contacts in the London TB register and an economic evaluation using a static model describing contact tracing outcomes. Incremental cost-effectiveness ratios (ICERs) were calculated using no screening as the baseline comparator. All adult TB cases (≥15 years old) in London from 2012 to 2015, and their contacts, were eligible (2465/5084 PTB and 2559/6090 ETB index cases were included). RESULTS: Assuming each contact with PTB infects one person/month, the ICER of screening contacts of ETB cases was £78 000/quality-adjusted life-years (QALY) (95% CI 39 000 to 140 000), and screening contacts of PTB cases was £30 000/QALY (95% CI 18 000 to 50 000). The ICER of screening contacts of ETB cases was £30 000/QALY if each contact with PTB infects 3.4 people/month. Limitations of this study include the use of self-reported symptomatic periods and lack of knowledge about onward transmission from PTB contacts. CONCLUSIONS: Screening contacts of ETB cases in London was almost certainly not cost-effective at any conventional willingness-to-pay threshold in England, supporting recent changes to National Institute for Health and Care Excellence national guidelines.

Mycobacterium tuberculosis transmission in an ethnically-diverse high incidence region in England, 2007-11.

BACKGROUND: Transmission patterns in high tuberculosis incidence areas in England are poorly understood but need elucidating to focus contact tracing. We study transmission within and between age, ethnic and immigrant groups using molecular data from the high incidence West Midlands region. METHODS: Isolates from culture-confirmed tuberculosis cases during 2007-2011 were typed using 24-locus Mycobacterial Interspersed Repetitive Unit-Variable Number Tandem Repeats (MIRU-VNTR). We estimated the proportion of disease attributable to recent transmission, calculated the proportion of isolates matching those from the two preceding years ("retrospectively clustered"), and identified risk factors for retrospective clustering using multivariate analyses. We calculated the ratio (RCR) between the observed and expected proportion clustered retrospectively within or between age, ethnic and immigrant groups. RESULTS: Of the 2159 available genotypes (79% of culture-confirmed cases), 34% were attributed to recent transmission. The percentage retrospectively clustered decreased from 50 to 24% for 0-14 and ≥ 65 year olds respectively (p = 0.01) and was significantly lower for immigrants than the UK-born. Higher than expected clustering occurred within 15-24 year olds (RCR: 1.4 (95% CI: 1.1-1.8)), several ethnic groups, and between UK-born or long-term immigrants with the UK-born (RCR: 1.8 (95% CI: 1.1-2.4) and 1.6 (95% CI: 1.2-1.9) respectively). CONCLUSIONS: This study is the first to consider "who clusters with whom" in a high incidence area in England, laying the foundation for future whole-genome sequencing work. The higher than expected clustering seen here suggests that preferential mixing between some age, ethnic and immigrant groups occurs; prioritising contact tracing to groups with which cases are most likely to cluster retrospectively could improve TB control.

An evaluation of tuberculosis contact investigations against national standards.

BACKGROUND: Contact tracing is a key element in England's 2015 collaborative TB strategy, although proposed indicators of successful contact tracing remain undescribed. METHODS: We conducted descriptive and multivariable analyses of contact tracing of TB cases in London between 1 July 2012 and 31 December 2015 using cohort review data from London's TB Register, identifying characteristics associated with improved indicators and yield. RESULTS: Of the pulmonary TB cases notified, 60% (2716/4561) had sufficient information for inclusion. Of these, 91% (2481/2716) had at least 1 contact (median: 4/case (IQR: 2-6)) identified, with 86% (10 251/11 981) of these contacts evaluated. 4.1% (177/4328), 1.3% (45/3421) and 0.70% (51/7264) of evaluated contacts of pulmonary smear-positive, pulmonary smear-negative and non-pulmonary cases, respectively, had active disease. Cases who were former prisoners or male were less likely to have at least one contact identified than those never imprisoned or female, respectively. Cases diagnosed at clinics with more directly observed therapy or social workers were more likely to have one or more contacts identified. Contacts screened at a different clinic to their index case or of male index cases were less likely to be evaluated than those screened at the same clinic or of women, respectively; yield of active disease was similar by sex. 10% (490/4850) of evaluated child contacts had latent TB infection. CONCLUSIONS: These are the first London-wide estimates of TB contact tracing indicators which are important for monitoring the strategy's success and informing risk assessment of index cases. Understanding why differences in indicators occur between groups could improve contact tracing outcomes.

Simulations for designing and interpreting intervention trials in infectious diseases.

BACKGROUND: Interventions in infectious diseases can have both direct effects on individuals who receive the intervention as well as indirect effects in the population. In addition, intervention combinations can have complex interactions at the population level, which are often difficult to adequately assess with standard study designs and analytical methods. DISCUSSION: Herein, we urge the adoption of a new paradigm for the design and interpretation of intervention trials in infectious diseases, particularly with regard to emerging infectious diseases, one that more accurately reflects the dynamics of the transmission process. In an increasingly complex world, simulations can explicitly represent transmission dynamics, which are critical for proper trial design and interpretation. Certain ethical aspects of a trial can also be quantified using simulations. Further, after a trial has been conducted, simulations can be used to explore the possible explanations for the observed effects. CONCLUSION: Much is to be gained through a multidisciplinary approach that builds collaborations among experts in infectious disease dynamics, epidemiology, statistical science, economics, simulation methods, and the conduct of clinical trials.

The Relationship Between School Holidays and Transmission of Influenza in England and Wales.

School closure is often considered as an influenza control measure, but its effects on transmission are poorly understood. We used 2 approaches to estimate how school holidays affect the contact parameter (the per capita rate of contact sufficient for infection transmission) for influenza using primary care data from England and Wales (1967-2000). Firstly, we fitted an age-structured susceptible-infectious-recovered model to each year's data to estimate the proportional change in the contact parameter during school holidays as compared with termtime. Secondly, we calculated the percentage difference in the contact parameter between holidays and termtime from weekly values of the contact parameter, estimated directly from simple mass-action models. Estimates were combined using random-effects meta-analysis, where appropriate. From fitting to the data, the difference in the contact parameter among children aged 5-14 years during holidays as compared with termtime ranged from a 36% reduction to a 17% increase; estimates were too heterogeneous for meta-analysis. Based on the simple mass-action model, the contact parameter was 17% (95% confidence interval: 10, 25) lower during holidays than during termtime. Results were robust to the assumed proportions of infections that were reported and individuals who were susceptible when the influenza season started. We conclude that school closure may reduce transmission during influenza outbreaks.

Age- and Sex-Specific Social Contact Patterns and Incidence of Mycobacterium tuberculosis Infection.

We aimed to model the incidence of infection with Mycobacterium tuberculosis among adults using data on infection incidence in children, disease prevalence in adults, and social contact patterns. We conducted a cross-sectional face-to-face survey of adults in 2011, enumerating "close" (shared conversation) and "casual" (shared indoor space) social contacts in 16 Zambian communities and 8 South African communities. We modeled the incidence of M. tuberculosis infection in all age groups using these contact patterns, as well as the observed incidence of M. tuberculosis infection in children and the prevalence of tuberculosis disease in adults. A total of 3,528 adults participated in the study. The reported rates of close and casual contact were 4.9 per adult per day (95% confidence interval: 4.6, 5.2) and 10.4 per adult per day (95% confidence interval: 9.3, 11.6), respectively. Rates of close contact were higher for adults in larger households and rural areas. There was preferential mixing of close contacts within age groups and within sexes. The estimated incidence of M. tuberculosis infection in adults was 1.5-6 times higher (2.5%-10% per year) than that in children. More than 50% of infections in men, women, and children were estimated to be due to contact with adult men. We conclude that estimates of infection incidence based on surveys in children might underestimate incidence in adults. Most infections may be due to contact with adult men. Treatment and control of tuberculosis in men is critical to protecting men, women, and children from tuberculosis.

The timing of tuberculosis after isoniazid preventive therapy among gold miners in South Africa: a prospective cohort study.

BACKGROUND: The durability of isoniazid preventive therapy (IPT) in preventing tuberculosis (TB) is limited in high-prevalence settings. The underlying mechanism (reactivation of persistent latent TB or reinfection) is not known. We aimed to investigate the timing of TB incidence during and after IPT and associated risk factors in a very high TB and HIV-prevalence setting, and to compare the observed rate with a modelled estimate of TB incidence rate after IPT due to reinfection. METHODS: In a post-hoc analysis of a cluster-randomized trial of community-wide IPT among South African gold miners, all intervention arm participants that were dispensed IPT for at least one of the intended 9 months were included. An incident TB case was defined as any participant with a positive sputum smear or culture, or with a clinical TB diagnosis assigned by a senior study clinician. Crude TB incidence rates were calculated during and after IPT, overall and by follow-up time. HIV status was not available. Multivariable Cox regression was used to analyse risk factors by follow-up time after IPT. Estimates from a published mathematical model of trial data were used to calculate the average reinfection TB incidence in the first year after IPT. RESULTS: Among 18,520 participants (96% male, mean age 41 years, median follow-up 2.1 years), 708 developed TB. The TB incidence rate during the intended IPT period was 1.3/100 person-years (pyrs; 95% confidence interval (CI), 1.0-1.6) and afterwards 2.3/100 pyrs (95% CI, 1.9-2.7). TB incidence increased within 6 months followed by a stable rate over time. There was no evidence for changing risk factors for TB disease over time after miners stopped IPT. The average TB incidence rate attributable to reinfection in the first year was estimated at 1.3/100 pyrs, compared to an observed rate of 2.2/100 pyrs (95% CI, 1.8-2.7). CONCLUSIONS: The durability of protection by IPT was lost within 6-12 months in this setting with a high HIV prevalence and a high annual risk of M. tuberculosis infection. The observed rate was higher than the modelled rate, suggesting that reactivation of persistent latent infection played a role in the rapid return to baseline TB incidence.

Tuberculosis control in South African gold mines: mathematical modeling of a trial of community-wide isoniazid preventive therapy.

A recent major cluster randomized trial of screening, active disease treatment, and mass isoniazid preventive therapy for 9 months during 2006-2011 among South African gold miners showed reduced individual-level tuberculosis incidence but no detectable population-level impact. We fitted a dynamic mathematical model to trial data and explored 1) factors contributing to the lack of population-level impact, 2) the best-achievable impact if all implementation characteristics were increased to the highest level achieved during the trial ("optimized intervention"), and 3) how tuberculosis might be better controlled with additional interventions (improving diagnostics, reducing treatment delay, providing isoniazid preventive therapy continuously to human immunodeficiency virus-positive people, or scaling up antiretroviral treatment coverage) individually and in combination. We found the following: 1) The model suggests that a small proportion of latent infections among human immunodeficiency virus-positive people were cured, which could have been a key factor explaining the lack of detectable population-level impact. 2) The optimized implementation increased impact by only 10%. 3) Implementing additional interventions individually and in combination led to up to 30% and 75% reductions, respectively, in tuberculosis incidence after 10 years. Tuberculosis control requires a combination prevention approach, including health systems strengthening to minimize treatment delay, improving diagnostics, increased antiretroviral treatment coverage, and effective preventive treatment regimens.

Prospective evaluation of a complex public health intervention: lessons from an initial and follow-up cross-sectional survey of the tuberculosis strain typing service in England.

BACKGROUND: The national tuberculosis strain typing service (TB-STS) was introduced in England in 2010. The TB-STS involves MIRU-VNTR typing of isolates from all TB patients for the prospective identification, reporting and investigation of TB strain typing clusters. As part of a mixed-method evaluation, we report on a repeated cross-sectional survey to illustrate the challenges surrounding the evaluation of a complex national public health intervention. METHODS: An online initial and follow-up questionnaire survey assessed the knowledge, attitudes and practices of public health staff, physicians and nurses working in TB control in November 2010 and March 2012. It included questions on the implementation, experience and uptake of the TB-STS. Participants that responded to both surveys were included in the analysis. RESULTS: 248 participants responded to the initial survey and 137 of these responded to the follow-up survey (56% retention). Knowledge: A significant increase in knowledge was observed, including a rise in the proportion of respondents who had received training (28.6% to 67.9%, p = 0.003), and the self-rated knowledge of how to use strain typing had improved ('no knowledge' decreased from 43.2% to 27.4%). Attitudes: The majority of respondents found strain typing useful; the proportion that reported strain typing to be useful was similar across the two surveys (95.7% to 94.7%, p = 0.67). Practices: There were significant increases between the initial and follow-up surveys in the number of respondents who reported using strain typing (57.0% to 80.5%, p < 0.001) and the proportion of time health protection staff spent on investigating TB (2.74% to 7.08%, p = 0.04). CONCLUSIONS: Evaluation of a complex public health intervention is challenging. In this example, the immediate national roll-out of the TB-STS meant that a controlled survey design was not possible. This study informs the future development of the TB-STS by identifying the need for training to reach wider professional groups, and argues for its continuation based on service users' perception that it is useful. By highlighting the importance of a well-defined sampling frame, collecting baseline information, and including all stakeholders, it provides lessons for the implementation of similar services in other countries and future evaluations of public health interventions.

Age-specific prevalence of IgG against measles/rubella and the impact of routine and supplementary immunization activities: A multistage random cluster sampling study with mathematical modelling.

BACKGROUND: Vietnam continues to have measles and rubella outbreaks following supplementary immunization activities (SIA) and routine immunization despite both having high reported coverage. To evaluate immunization activities, age-specific immunity against measles and rubella, and the number of averted Congenital Rubella Syndrome (CRS) cases, must be estimated. METHODS: Dried blood spots were collected from 2091 randomly selected individuals aged 1-39 years. Measles and rubella virus-specific immunoglobulin G (IgG) were measured by enzyme immunoassay. Results were considered positive at ≥120 mIU/mL for measles and ≥10 IU/mL for rubella. The number of CRS cases averted by immunization since 2014 were estimated using mathematical modelling. RESULTS: Overall IgG seroprevalence was 99.7% (95%CI: 99.2-99.9) for measles and 83.6% (95%CI: 79.3-87.1) for rubella. Rubella IgG seroprevalence was higher among age groups targeted in the SIA than in non-targeted young adults (95.4% [95%CI: 92.9-97.0] vs 72.4% [95%CI: 63.1-80.1]; P < 0.001). The estimated number of CRS cases averted in 2019 by immunization activities since 2014 ranged from 126 (95%CI: 0-460) to 883 (95%CI: 0-2271) depending on the assumed postvaccination reduction in the force of infection. CONCLUSIONS: The results suggest the SIA was effective, while young adults born before 1998 who remain unprotected for rubella require further vaccination.

Estimating the health effects of COVID-19-related immunisation disruptions in 112 countries during 2020-30: a modelling study.

BACKGROUND: There have been declines in global immunisation coverage due to the COVID-19 pandemic. Recovery has begun but is geographically variable. This disruption has led to under-immunised cohorts and interrupted progress in reducing vaccine-preventable disease burden. There have, so far, been few studies of the effects of coverage disruption on vaccine effects. We aimed to quantify the effects of vaccine-coverage disruption on routine and campaign immunisation services, identify cohorts and regions that could particularly benefit from catch-up activities, and establish if losses in effect could be recovered. METHODS: For this modelling study, we used modelling groups from the Vaccine Impact Modelling Consortium from 112 low-income and middle-income countries to estimate vaccine effect for 14 pathogens. One set of modelling estimates used vaccine-coverage data from 1937 to 2021 for a subset of vaccine-preventable, outbreak-prone or priority diseases (ie, measles, rubella, hepatitis B, human papillomavirus [HPV], meningitis A, and yellow fever) to examine mitigation measures, hereafter referred to as recovery runs. The second set of estimates were conducted with vaccine-coverage data from 1937 to 2020, used to calculate effect ratios (ie, the burden averted per dose) for all 14 included vaccines and diseases, hereafter referred to as full runs. Both runs were modelled from Jan 1, 2000, to Dec 31, 2100. Countries were included if they were in the Gavi, the Vaccine Alliance portfolio; had notable burden; or had notable strategic vaccination activities. These countries represented the majority of global vaccine-preventable disease burden. Vaccine coverage was informed by historical estimates from WHO-UNICEF Estimates of National Immunization Coverage and the immunisation repository of WHO for data up to and including 2021. From 2022 onwards, we estimated coverage on the basis of guidance about campaign frequency, non-linear assumptions about the recovery of routine immunisation to pre-disruption magnitude, and 2030 endpoints informed by the WHO Immunization Agenda 2030 aims and expert consultation. We examined three main scenarios: no disruption, baseline recovery, and baseline recovery and catch-up. FINDINGS: We estimated that disruption to measles, rubella, HPV, hepatitis B, meningitis A, and yellow fever vaccination could lead to 49 119 additional deaths (95% credible interval [CrI] 17 248-134 941) during calendar years 2020-30, largely due to measles. For years of vaccination 2020-30 for all 14 pathogens, disruption could lead to a 2·66% (95% CrI 2·52-2·81) reduction in long-term effect from 37 378 194 deaths averted (34 450 249-40 241 202) to 36 410 559 deaths averted (33 515 397-39 241 799). We estimated that catch-up activities could avert 78·9% (40·4-151·4) of excess deaths between calendar years 2023 and 2030 (ie, 18 900 [7037-60 223] of 25 356 [9859-75 073]). INTERPRETATION: Our results highlight the importance of the timing of catch-up activities, considering estimated burden to improve vaccine coverage in affected cohorts. We estimated that mitigation measures for measles and yellow fever were particularly effective at reducing excess burden in the short term. Additionally, the high long-term effect of HPV vaccine as an important cervical-cancer prevention tool warrants continued immunisation efforts after disruption. FUNDING: The Vaccine Impact Modelling Consortium, funded by Gavi, the Vaccine Alliance and the Bill & Melinda Gates Foundation. TRANSLATIONS: For the Arabic, Chinese, French, Portguese and Spanish translations of the abstract see Supplementary Materials section.

Estimates of the global burden of Congenital Rubella Syndrome, 1996-2019.

OBJECTIVES: Many countries introduced rubella-containing vaccination (RCV) after 2011, following changes in recommended World Health Organization (WHO) vaccination strategies and external support. We evaluated the impact of these introductions. METHODS: We estimated the country-specific, region-specific, and global Congenital Rubella Syndrome (CRS) incidence during 1996-2019 using mathematical modeling, including routine and campaign vaccination coverage and seroprevalence data. RESULTS: In 2019, WHO African and Eastern Mediterranean regions had the highest estimated CRS incidence (64 [95% confidence intervals (CI): 24-123] and 27 [95% CI: 4-67] per 100,000 live births respectively), where nearly half of births occur in countries that have introduced RCV. Other regions, where >95% of births occurred in countries that had introduced RCV, had a low estimated CRS incidence (<1 [95% CI: <1 to 8] and <1 [95% CI: <1 to 12] per 100,000 live births in South-East Asia [SEAR] and the Western Pacific [WPR] respectively, and similarly in Europe and the Americas). The estimated number of CRS births globally declined by approximately two-thirds during 2010-2019, from 100,000 (95% CI: 54,000-166,000) to 32,000 (95% CI: 13,000-60,000), representing a 73% reduction since 1996, largely following RCV introductions in WPR and SEAR, where the greatest reductions occurred. CONCLUSIONS: Further reductions can occur by introducing RCV in remaining countries and maintaining high RCV coverage.

Comparison of population-based measles-rubella immunoglobulin G antibody prevalence between 2014 and 2019 in Lao People's Democratic Republic: Impacts of the national immunization program.

OBJECTIVES: We evaluated the effectiveness of the Lao People's Democratic Republic's measles-rubella immunization program using the seroprevalence from two cross-sectional surveys. METHODS: The nationwide surveys occurred in 2014 and 2019 using a multistage cluster sampling, both requiring samples from 2184 individuals from 52 randomly selected villages. Immunoglobulin G titers, measured using enzyme-linked immunosorbent assay, were considered positive at ≥120 mIU/ml (measles) and ≥10 IU/ml (rubella). We calculated the vaccination-related reduction in the force of rubella infection and the number of congenital rubella syndrome cases averted in 2019. RESULTS: We collected 2135 (women: 55.2%, mean age: 23.2 years) and 2001 (52.7%, 23.1 years) samples in 2014 and 2019, respectively. During 2014-2019, immunoglobulin G prevalence increased from 83.9% (95% confidence interval [CI]: 83.8-84.0) to 98.3% (97.7-98.8) for measles and from 75.4% (75.3-75.5) to 87.8% (86.4-89.2) for rubella. The most plausible reduction in the average force of rubella infection was 100% (95% CI: 28-100) since vaccination started, averting 78 (95% CI: 42-128) congenital rubella syndrome cases in 2019. CONCLUSION: This is the first population-based study for measles and rubella at two different time points in developing countries. Measles and rubella seroprevalence increased significantly during 2014-2019, greatly exceeding the immunity thresholds for their elimination.

Feasibility of measles and rubella vaccination programmes for disease elimination: a modelling study.

BACKGROUND: Marked reductions in the incidence of measles and rubella have been observed since the widespread use of the measles and rubella vaccines. Although no global goal for measles eradication has been established, all six WHO regions have set measles elimination targets. However, a gap remains between current control levels and elimination targets, as shown by large measles outbreaks between 2017 and 2019. We aimed to model the potential for measles and rubella elimination globally to inform a WHO report to the 73rd World Health Assembly on the feasibility of measles and rubella eradication. METHODS: In this study, we modelled the probability of measles and rubella elimination between 2020 and 2100 under different vaccination scenarios in 93 countries of interest. We evaluated measles and rubella burden and elimination across two national transmission models each (Dynamic Measles Immunisation Calculation Engine [DynaMICE], Pennsylvania State University [PSU], Johns Hopkins University, and Public Health England models), and one subnational measles transmission model (Institute for Disease Modeling model). The vaccination scenarios included a so-called business as usual approach, which continues present vaccination coverage, and an intensified investment approach, which increases coverage into the future. The annual numbers of infections projected by each model, country, and vaccination scenario were used to explore if, when, and for how long the infections would be below a threshold for elimination. FINDINGS: The intensified investment scenario led to large reductions in measles and rubella incidence and burden. Rubella elimination is likely to be achievable in all countries and measles elimination is likely in some countries, but not all. The PSU and DynaMICE national measles models estimated that by 2050, the probability of elimination would exceed 75% in 14 (16%) and 36 (39%) of 93 modelled countries, respectively. The subnational model of measles transmission highlighted inequity in routine coverage as a likely driver of the continuance of endemic measles transmission in a subset of countries. INTERPRETATION: To reach regional elimination goals, it will be necessary to innovate vaccination strategies and technologies that increase spatial equity of routine vaccination, in addition to investing in existing surveillance and outbreak response programmes. FUNDING: WHO, Gavi, the Vaccine Alliance, US Centers for Disease Control and Prevention, and the Bill & Melinda Gates Foundation.

School closures and student contact patterns.

To determine how school closure for pandemic (H1N1) 2009 affected students' contact patterns, we conducted a retrospective questionnaire survey at a UK school 2 weeks after the school reopened. School closure was associated with a 65% reduction in the mean total number of contacts for each student.

Transmission dynamics and control measures of COVID-19 outbreak in China: a modelling study.

COVID-19 is reported to have been brought under control in China. To understand the COVID-19 outbreak in China and provide potential lessons for other parts of the world, in this study we apply a mathematical model with multiple datasets to estimate the transmissibility of the SARS-CoV-2 virus and the severity of the illness associated with the infection, and how both were affected by unprecedented control measures. Our analyses show that before 19th January 2020, 3.5% (95% CI 1.7-8.3%) of  infected people were detected; this percentage increased to 36.6% (95% CI 26.1-55.4%) thereafter. The basic reproduction number (R0) was 2.33 (95% CI 1.96-3.69) before 8th February 2020; then the effective reproduction number dropped to 0.04(95% CI 0.01-0.10). This estimation also indicates that control measures taken since 23rd January 2020 affected the transmissibility about 2 weeks after they were introduced. The confirmed case fatality rate is estimated at 9.6% (95% CI 8.1-11.4%) before 15 February 2020, and then it reduced to 0.7% (95% CI 0.4-1.0%). This shows that SARS-CoV-2 virus is highly transmissible but may be less severe than SARS-CoV-1 and MERS-CoV. We found that at the early stage, the majority of R0 comes from undetected infectious people. This implies that successful control in China was achieved through reducing the contact rates among people in the general population and increasing the rate of detection and quarantine of the infectious cases.