Etiology of diarrheal hospitalizations following rotavirus vaccine implementation and association of enteric pathogens with malnutrition among under-five children in India.

Malnourished children are at higher risk of mortality and morbidity following diarrheal illness and certain enteropathogens have been associated with malnutrition in children. Very few studies have comprehensively looked at the etiology of diarrhea in malnourished children and most have used conventional diagnostic methods with suboptimal sensitivity. We used a highly sensitive molecular approach against a broad range of pathogens causing diarrhea and examined their association with malnutrition. In addition, we looked at the pathogen diversity of pediatric diarrhea, three years after the nationwide rotavirus vaccine introduction to understand the evolving landscape of pathogens, which is crucial for planning strategies to further reduce the diarrhea burden. Clinical details and diarrheal stool samples were collected from hospitalized children aged < 5 years from three sentinel sites in India for a period of one year. The samples were tested by qPCR for 16 established causes of diarrhea using TaqMan Array Cards. A total of 772 children were enrolled, from whom 482 (62.4%) stool specimens were tested. No specific pathogen was associated with diarrhea among children with acute or chronic malnutrition compared to those with better nutritional status. Overall, adenovirus was the leading pathogen (attributable fraction (AF) 16.9%; 95% CI 14.1 to 19.2) followed by rotavirus (AF 12.6%; 95% CI 11.8 to 13.1) and Shigella (AF 10.9%; 95% CI 8.4 to 16.4). The majority of diarrhea requiring hospitalization in children aged < 2 years could be attributed to viruses, while Shigella was the most common pathogen among children aged > 2 years. These data on the prevalence and epidemiology of enteropathogens identified potential pathogens for public health interventions.

Rotavirus genotypes in children under five years hospitalized with diarrhea in low and middle-income countries: Results from the WHO-coordinated Global Rotavirus Surveillance Network.

Rotavirus is the most common pathogen causing pediatric diarrhea and an important cause of morbidity and mortality in low- and middle-income countries. Previous evidence suggests that the introduction of rotavirus vaccines in national immunization schedules resulted in dramatic declines in disease burden but may also be changing the rotavirus genetic landscape and driving the emergence of new genotypes. We report genotype data of more than 16,000 rotavirus isolates from 40 countries participating in the Global Rotavirus Surveillance Network. Data from a convenience sample of children under five years of age hospitalized with acute watery diarrhea who tested positive for rotavirus were included. Country results were weighted by their estimated rotavirus disease burden to estimate regional genotype distributions. Globally, the most frequent genotypes identified after weighting were G1P[8] (31%), G1P[6] (8%) and G3P[8] (8%). Genotypes varied across WHO Regions and between countries that had and had not introduced rotavirus vaccine. G1P[8] was less frequent among African (36 vs 20%) and European (33 vs 8%) countries that had introduced rotavirus vaccines as compared to countries that had not introduced. Our results describe differences in the distribution of the most common rotavirus genotypes in children with diarrhea in low- and middle-income countries. G1P[8] was less frequent in countries that had introduced the rotavirus vaccine while different strains are emerging or re-emerging in different regions.

Progress Toward Measles Elimination - Worldwide, 2000-2022.

Measles is a highly contagious, vaccine-preventable disease that requires high population immunity for transmission to be interrupted. All six World Health Organization regions have committed to eliminating measles; however, no region has achieved and sustained measles elimination. This report describes measles elimination progress during 2000-2022. During 2000-2019, estimated coverage worldwide with the first dose of measles-containing vaccine (MCV) increased from 72% to 86%, then declined to 81% in 2021 during the COVID-19 pandemic, representing the lowest coverage since 2008. In 2022, first-dose MCV coverage increased to 83%. Only one half (72) of 144 countries reporting measles cases achieved the measles surveillance indicator target of two or more discarded cases per 100,000 population in 2022. During 2021-2022, estimated measles cases increased 18%, from 7,802,000 to 9,232,300, and the number of countries experiencing large or disruptive outbreaks increased from 22 to 37. Estimated measles deaths increased 43% during 2021-2022, from 95,000 to 136,200. Nonetheless, an estimated 57 million measles deaths were averted by vaccination during 2000-2022. In 2022, measles vaccination coverage and global surveillance showed some recovery from the COVID-19 pandemic setbacks; however, coverage declined in low-income countries, and globally, years of suboptimal immunization coverage left millions of children unprotected. Urgent reversal of coverage setbacks experienced during the COVID-19 pandemic can be accomplished by renewing efforts to vaccinate all children with 2 MCV doses and strengthening surveillance, thereby preventing outbreaks and accelerating progress toward measles elimination.

Progress Toward Measles Elimination - African Region, 2017-2021.

Worldwide, measles remains a major cause of disease and death; the highest incidence is in the World Health Organization African Region (AFR). In 2011, the 46 AFR member states established a goal of regional measles elimination by 2020; this report describes progress during 2017-2021. Regional coverage with a first dose of measles-containing vaccine (MCV) decreased from 70% in 2017 to 68% in 2021, and the number of countries with ≥95% coverage decreased from six (13%) to two (4%). The number of countries providing a second MCV dose increased from 27 (57%) to 38 (81%), and second-dose coverage increased from 25% to 41%. Approximately 341 million persons were vaccinated in supplementary immunization activities, and an estimated 4.5 million deaths were averted by vaccination. However, the number of countries meeting measles surveillance performance indicators declined from 26 (62%) to nine (22%). Measles incidence increased from 69.2 per 1 million population in 2017 to 81.9 in 2021. The number of estimated annual measles cases and deaths increased 22% and 8%, respectively. By December 2021, no country in AFR had received verification of measles elimination. To achieve a renewed regional goal of measles elimination in at least 80% of countries by 2030, intensified efforts are needed to recover and surpass levels of surveillance performance and coverage with 2 MCV doses achieved before the COVID-19 pandemic.

Risk Factors for Mortality Among Children Younger Than Age 5 Years With Severe Diarrhea in Low- and Middle-income Countries: Findings From the World Health Organization-coordinated Global Rotavirus and Pediatric Diarrhea Surveillance Networks.

BACKGROUND: Diarrhea is the second leading cause of death in children younger than 5 years of age globally. The burden of diarrheal mortality is concentrated in low-resource settings. Little is known about the risk factors for childhood death from diarrheal disease in low- and middle-income countries. METHODS: Data from the World Health Organization (WHO)-coordinated Global Rotavirus and Pediatric Diarrhea Surveillance Networks, which are composed of active, sentinel, hospital-based surveillance sites, were analyzed to assess mortality in children <5 years of age who were hospitalized with diarrhea between 2008 and 2018. Case fatality risks were calculated, and multivariable logistic regression was performed to identify risk factors for mortality. RESULTS: This analysis comprises 234 781 cases, including 1219 deaths, across 57 countries. The overall case fatality risk was found to be 0.5%. Risk factors for death in the multivariable analysis included younger age (for <6 months compared with older ages, odds ratio [OR] = 3.54; 95% confidence interval [CI], 2.81-4.50), female sex (OR = 1.18; 95% CI, 1.06-1.81), presenting with persistent diarrhea (OR = 1.91; 95% CI, 1.01-3.25), no vomiting (OR = 1.13; 95% CI, .98-1.30), severe dehydration (OR = 3.79; 95% CI, 3.01-4.83), and being negative for rotavirus on an enzyme-linked immunosorbent assay test (OR = 2.29; 95% CI, 1.92-2.74). Cases from the African Region had the highest odds of death compared with other WHO regions (OR = 130.62 comparing the African Region with the European Region; 95% CI, 55.72-422.73), whereas cases from the European Region had the lowest odds of death. CONCLUSIONS: Our findings support known risk factors for childhood diarrheal mortality and highlight the need for interventions to address dehydration and rotavirus-negative diarrheal infections.

Progress Toward Regional Measles Elimination - Worldwide, 2000-2021.

All six World Health Organization (WHO) regions have committed to eliminating measles.* The Immunization Agenda 2021-2030 (IA2030)† aims to achieve the regional targets as a core indicator of impact and positions measles as the tracer of a health system's ability to deliver essential childhood vaccines. IA2030 highlights the importance of ensuring rigorous measles surveillance systems to document immunity gaps and achieve 95% coverage with 2 timely doses of measles-containing vaccine (MCV) among children. This report describes progress toward measles elimination during 2000-2021 and updates a previous report (1). During 2000-2021, estimated global coverage with a first MCV dose (MCV1) increased from 72% to a peak of 86% in 2019, but decreased during the COVID-19 pandemic to 83% in 2020 and to 81% in 2021, the lowest MCV1 coverage recorded since 2008. All countries conducted measles surveillance, but only 47 (35%) of 135 countries reporting discarded cases§ achieved the sensitivity indicator target of two or more discarded cases per 100,000 population in 2021, indicating surveillance system underperformance in certain countries. Annual reported measles incidence decreased 88% during 2000-2016, from 145 to 18 cases per 1 million population, then rebounded to 120 in 2019 during a global resurgence (2), before declining to 21 in 2020 and to 17 in 2021. Large and disruptive outbreaks were reported in 22 countries. During 2000-2021, the annual number of estimated measles deaths decreased 83%, from 761,000 to 128,000; an estimated 56 million measles deaths were averted by vaccination. To regain progress and achieve regional measles elimination targets during and after the COVID-19 pandemic, accelerating targeted efforts is necessary to reach all children with 2 MCV doses while implementing robust surveillance and identifying and closing immunity gaps to prevent cases and outbreaks.

Progress Toward Measles Elimination - South-East Asia Region, 2003-2020.

In 2013, member states of the World Health Organization (WHO) South-East Asia Region* (SEAR) adopted the goal of measles elimination and rubella and congenital rubella syndrome control† by 2020 (1). In 2014, to provide impetus toward achieving this goal, the Regional Director declared measles elimination and rubella control one of the Regional Flagship Priorities. In 2019, SEAR member states declared a revised goal of eliminating both measles and rubella§ by 2023 (2). The recommended strategies to achieve elimination include 1) achieving and maintaining ≥95% coverage with 2 doses of measles- and rubella-containing vaccine in every district through routine or supplementary immunization activities¶ (SIAs); 2) developing and sustaining a sensitive and timely case-based surveillance system that meets recommended performance indicators**; 3) developing and maintaining an accredited laboratory network; 4) achieving timely identification, investigation, and response to measles outbreaks; and 5) collaborating with other public health initiatives to achieve the preceding four strategies. This report updates a previous report and describes progress toward measles elimination in SEAR during 2003-2020 (3). In 2002, coverage with the first dose of a measles-containing vaccine in routine immunization (MCV1) was 70%, and only three countries in SEAR had added a second routine dose of measles-containing vaccine in routine immunization (MCV2). During 2003-2020, all countries introduced MCV2, and estimated coverage with MCV1 increased 35%, from 65% to 88%, and coverage with MCV2 increased 1,233% from 6% to 80%. Approximately 938 million persons were vaccinated in SIAs. Annual reported measles incidence declined by 92%, from 57.0 to 4.8 cases per 1 million population, and estimated deaths decreased by 97%; an estimated 9.3 million deaths were averted by measles vaccination. By 2020, five countries were verified as having achieved measles elimination. To achieve measles elimination in the region by 2023, additional efforts are urgently needed to strengthen routine immunization services and improve measles-containing vaccine (MCV) coverage, conduct periodic high-quality SIAs, and strengthen measles case-based surveillance and laboratory capacity.

Progress Toward Rubella and Congenital Rubella Syndrome Control and Elimination - Worldwide, 2012-2020.

Rubella virus is a leading cause of vaccine-preventable birth defects and can cause epidemics. Although rubella virus infection usually produces a mild febrile rash illness in children and adults, infection during pregnancy, especially during the first trimester, can result in miscarriage, fetal death, stillbirth, or an infant born with a constellation of birth defects known as congenital rubella syndrome (CRS). A single dose of rubella-containing vaccine (RCV) can provide lifelong protection against rubella (1). The Global Vaccine Action Plan 2011-2020 (GVAP) included a target to achieve elimination of rubella in at least five of the six World Health Organization (WHO) regions* by 2020 (2), and WHO recommends capitalizing on the accelerated measles elimination activities as an opportunity to introduce RCV (1). This report updates a previous report (3) and summarizes global progress toward control and elimination of rubella and CRS from 2012, when accelerated rubella control activities were initiated, through 2020. Among 194 WHO Member States, the number with RCV in their immunization schedules has increased from 132 (68%) in 2012 to 173 (89%) in 2020; 70% of the world's infants were vaccinated against rubella in 2020. Reported rubella cases declined by 48%, from 94,277 in 2012 to 49,136 in 2019, and decreased further to 10,194 in 2020. Rubella elimination has been verified in 93 (48%) of 194 countries including the entire Region of the Americas (AMR). To increase the equity of protection and make further progress to eliminate rubella, it is important that the 21 countries that have not yet done so should introduce RCV. Likewise, countries that have introduced RCV can achieve and maintain rubella elimination with high vaccination coverage and surveillance for rubella and CRS. Four of six WHO regions have established rubella elimination goals; the two WHO regions that have not yet established an elimination goal (the African [AFR] and Eastern Mediterranean [EMR] regions) have expressed a commitment to rubella elimination and should consider establishing a goal.

Aetiology and incidence of diarrhoea requiring hospitalisation in children under 5 years of age in 28 low-income and middle-income countries: findings from the Global Pediatric Diarrhea Surveillance network.

INTRODUCTION: Diarrhoea remains a leading cause of child morbidity and mortality. Systematically collected and analysed data on the aetiology of hospitalised diarrhoea in low-income and middle-income countries are needed to prioritise interventions. METHODS: We established the Global Pediatric Diarrhea Surveillance network, in which children under 5 years hospitalised with diarrhoea were enrolled at 33 sentinel surveillance hospitals in 28 low-income and middle-income countries. Randomly selected stool specimens were tested by quantitative PCR for 16 causes of diarrhoea. We estimated pathogen-specific attributable burdens of diarrhoeal hospitalisations and deaths. We incorporated country-level incidence to estimate the number of pathogen-specific deaths on a global scale. RESULTS: During 2017-2018, 29 502 diarrhoea hospitalisations were enrolled, of which 5465 were randomly selected and tested. Rotavirus was the leading cause of diarrhoea requiring hospitalisation (attributable fraction (AF) 33.3%; 95% CI 27.7 to 40.3), followed by Shigella (9.7%; 95% CI 7.7 to 11.6), norovirus (6.5%; 95% CI 5.4 to 7.6) and adenovirus 40/41 (5.5%; 95% CI 4.4 to 6.7). Rotavirus was the leading cause of hospitalised diarrhoea in all regions except the Americas, where the leading aetiologies were Shigella (19.2%; 95% CI 11.4 to 28.1) and norovirus (22.2%; 95% CI 17.5 to 27.9) in Central and South America, respectively. The proportion of hospitalisations attributable to rotavirus was approximately 50% lower in sites that had introduced rotavirus vaccine (AF 20.8%; 95% CI 18.0 to 24.1) compared with sites that had not (42.1%; 95% CI 33.2 to 53.4). Globally, we estimated 208 009 annual rotavirus-attributable deaths (95% CI 169 561 to 259 216), 62 853 Shigella-attributable deaths (95% CI 48 656 to 78 805), 36 922 adenovirus 40/41-attributable deaths (95% CI 28 469 to 46 672) and 35 914 norovirus-attributable deaths (95% CI 27 258 to 46 516). CONCLUSIONS: Despite the substantial impact of rotavirus vaccine introduction, rotavirus remained the leading cause of paediatric diarrhoea hospitalisations. Improving the efficacy and coverage of rotavirus vaccination and prioritising interventions against Shigella, norovirus and adenovirus could further reduce diarrhoea morbidity and mortality.

Progress Toward Regional Measles Elimination - Worldwide, 2000-2020.

In 2012, the World Health Assembly endorsed the Global Vaccine Action Plan,* with the objective of eliminating measles† in five of the six World Health Organization (WHO) regions by 2020 (1). The Immunization Agenda 2021-2030 (IA2030)§ uses measles incidence as an indicator of the strength of immunization systems. The Measles-Rubella Strategic Framework 2021-2030¶ and the Measles Outbreaks Strategic Response Plan 2021-2023** are aligned with the IA2030 and highlight robust measles surveillance systems to document immunity gaps, identify root causes of undervaccination, and develop locally tailored solutions to ensure administration of 2 doses of measles-containing vaccine (MCV) to all children. This report describes progress toward World Health Assembly milestones and measles elimination objectives during 2000-2020 and updates a previous report (2). During 2000-2010, estimated MCV first dose (MCV1) coverage increased globally from 72% to 84%, peaked at 86% in 2019, but declined to 84% in 2020 during the COVID-19 pandemic. All countries conducted measles surveillance, although fewer than one third achieved the sensitivity indicator target of ≥2 discarded†† cases per 100,000 population in 2020. Annual reported measles incidence decreased 88% during 2000-2016, from 145 to 18 cases per 1 million population, rebounded to 120 in 2019, before falling to 22 in 2020. During 2000-2020, the annual number of estimated measles deaths decreased 94%, from 1,072,800 to 60,700, averting an estimated 31.7 million measles deaths. To achieve regional measles elimination targets, enhanced efforts are needed to reach all children with 2 MCV doses, implement robust surveillance, and identify and close immunity gaps.

The Global Landscape of Pediatric Bacterial Meningitis Data Reported to the World Health Organization-Coordinated Invasive Bacterial Vaccine-Preventable Disease Surveillance Network, 2014-2019.

BACKGROUND: The World Health Organization (WHO) coordinates the Global Invasive Bacterial Vaccine-Preventable Diseases (IB-VPD) Surveillance Network to support vaccine introduction decisions and use. The network was established to strengthen surveillance and laboratory confirmation of meningitis caused by Streptococcus pneumoniae, Haemophilus influenzae, and Neisseria meningitidis. METHODS: Sentinel hospitals report cases of children <5 years of age hospitalized for suspected meningitis. Laboratories report confirmatory testing results and strain characterization tested by polymerase chain reaction. In 2019, the network included 123 laboratories that follow validated, standardized testing and reporting strategies. RESULTS: From 2014 through 2019, >137 000 suspected meningitis cases were reported by 58 participating countries, with 44.6% (n = 61 386) reported from countries in the WHO African Region. More than half (56.6%, n = 77 873) were among children <1 year of age, and 4.0% (n = 4010) died among those with reported disease outcome. Among suspected meningitis cases, 8.6% (n = 11 798) were classified as probable bacterial meningitis. One of 3 bacterial pathogens was identified in 30.3% (n = 3576) of these cases, namely S. pneumoniae (n = 2177 [60.9%]), H. influenzae (n = 633 [17.7%]), and N. meningitidis (n = 766 [21.4%]). Among confirmed bacterial meningitis cases with outcome reported, 11.0% died; case fatality ratio varied by pathogen (S. pneumoniae, 12.2%; H. influenzae, 6.1%; N. meningitidis, 11.0%). Among the 277 children who died with confirmed bacterial meningitis, 189 (68.2%) had confirmed S. pneumoniae. The proportion of pneumococcal cases with pneumococcal conjugate vaccine (PCV) serotypes decreased as the number of countries implementing PCV increased, from 77.8% (n = 273) to 47.5% (n = 248). Of 397 H. influenzae specimens serotyped, 49.1% (n = 195) were type b. Predominant N. meningitidis serogroups varied by region. CONCLUSIONS: This multitier, global surveillance network has supported countries in detecting and serotyping the 3 principal invasive bacterial pathogens that cause pediatric meningitis. Streptococcus pneumoniae was the most common bacterial pathogen detected globally despite the growing number of countries that have nationally introduced PCV. The large proportions of deaths due to S. pneumoniae reflect the high proportion of meningitis cases caused by this pathogen. This global network demonstrated a strong correlation between PCV introduction status and reduction in the proportion of pneumococcal meningitis infections caused by vaccine serotypes. Maintaining case-based, active surveillance with laboratory confirmation for prioritized vaccine-preventable diseases remains a critical component of the global agenda in public health.The World Health Organization (WHO)-coordinated Invasive Bacterial Vaccine-Preventable Disease (IB-VPD) Surveillance Network reported data from 2014 to 2019, contributing to the estimates of the disease burden and serotypes of pediatric meningitis caused by Streptococcus pneumoniae, Haemophilus influenzae and Neisseria meningitidis.

The epidemiology of rubella, 2007-18: an ecological analysis of surveillance data.

BACKGROUND: As of 2018, the rubella vaccine had been incorporated into the national immunisation schedule of 168 countries, representing 87% of the world's population. Countries have used different strategies to reduce the burden of congenital rubella syndrome (CRS), such as vaccinating only females. Given the different strategies, and that 26 countries still had not introduced the vaccine, we analysed global rubella surveillance data to understand rubella epidemiology and the effect of vaccination. METHODS: In this ecological analysis, we evaluated surveillance data on rubella cases that had been reported to WHO from 2007 to 2018, by age, vaccination history, and onset year. Cases were classified as either being vaccine eligible or ineligible on the basis of the country's vaccination strategy and the birth year of the person. We required all cases be confirmed by laboratory testing or that they were epidemiologically linked, and we excluded cases defined only by clinical symptoms. Incidence per million people was calculated by use of World Population Prospects data. FINDINGS: Between Jan 1, 2007, and Dec 31, 2018, from data reported to WHO as of Jan 3, 2020, there were 139 486 reported rubella cases, of which 15 613 (11%) were vaccine eligible. Annual incidence ranged from 13·9 cases per million in 2007 to 1·7 cases per million in 2018. In all years, absolute and proportional global incidence were higher among vaccine ineligible cohorts than eligible cohorts. In vaccine ineligible cohorts, 87 666 (74%) of 118 308 cases were in children younger than 15 years, compared with 8423 (54%) of 15 613 cases in vaccine eligible cohorts. Vaccine ineligible women of reproductive age (WRA) had a higher incidence than vaccine eligible WRA, except in 2011-12. INTERPRETATION: Vaccination has been successful in decreasing the burden of rubella, regardless of the strategy used. WRA remain at risk, but the risk is higher in those countries that have yet to introduce the vaccine. These countries should introduce the rubella-containing vaccine as soon as possible, to eliminate rubella, and to prevent the morbidity and mortality associated with CRS. FUNDING: None.

The Changing Global Epidemiology of Measles, 2013-2018.

BACKGROUND: Measles incidence and mortality rates have significantly decreased since vaccine introduction. Despite this progress, however, there has been a global resurgence of measles. To understand the current global epidemiology, we analyzed measles surveillance data. METHODS: We analyzed data on measles cases from 2013-2018 reported to the World Health Organization. Univariate analysis was undertaken based on age, vaccination history, onset year, World Health Organization region, and World Bank income status for the country where the case was reported, and a surrogate indicator of the historical strength of the country's immunization program. Annual incidence and a 2013-2018 mean country incidence per million were calculated. RESULTS: From 2013 through 2018, there were 899 800 reported measles cases, of which 57% occurred unvaccinated or undervaccinated persons, with an unknown vaccination history in another 30%. Lower-middle-income countries accounted for 66% of cases, 23% occurred in persons ≥15 years of age. In countries with stronger historical vaccination programs and higher country income, case patients had higher median ages. CONCLUSIONS: Although most measles case patients are <15 years of age, an age shift is seen in countries with a higher income or a stronger historical vaccination program. Countries must strengthen immunization programs to achieve high vaccination coverage; some must undertake strategies to reach persons ≥15 years of age and close immunity gaps.

Global impact of rotavirus vaccine introduction on rotavirus hospitalisations among children under 5 years of age, 2008-16: findings from the Global Rotavirus Surveillance Network.

BACKGROUND: Rotavirus vaccine use in national immunisation programmes has led to declines in hospital admissions for rotavirus gastroenteritis among children; however, the global impact of rotavirus vaccine introduction has not been described using primary data. We describe the impact of rotavirus vaccine introduction on admissions for acute rotavirus gastroenteritis in primarily low-income and middle-income countries, using 9 years of data from the WHO-coordinated Global Rotavirus Surveillance Network (GRSN). METHODS: Between Jan 1, 2008, and Dec 31, 2016, children younger than 5 years of age who were admitted to hospital with acute gastroenteritis were prospectively enrolled in GRSN sites. We included sites that enrolled children and collected stool specimens monthly and tested at least 100 specimens annually in the impact analysis, with a separate analysis taking into account site continuity. We compared proportions of acute gastroenteritis cases positive for rotavirus in the pre-vaccine and post-vaccine periods and calculated mean proportion changes for WHO regions, with 95% CIs; these findings were then compared with interrupted time series analyses. We did further sensitivity analyses to account for rotavirus vaccination coverage levels and sites that collected specimens for at least 11 months per year and tested at least 80 specimens per year. We also analysed the age distribution of rotavirus-positive cases before and after vaccine introduction. FINDINGS: 403 140 children younger than 5 years of age admitted to hospital with acute gastroenteritis from 349 sites in 82 countries were enrolled over the study period, of whom 132 736 (32·9%) were positive for rotavirus. We included 305 789 children from 198 sites in 69 countries in the impact analysis. In countries that had not introduced rotavirus vaccine in their national immunisation programmes, rotavirus was detected in 38·0% (95% CI 4·8-73·4) of admissions for acute gastroenteritis annually whereas in those that have introduced the vaccine, rotavirus was detected in 23·0% (0·7-57·7) of admissions for acute gastroenteritis, showing a 39·6% (35·4-43·8) relative decline following introduction. Interrupted time series analyses confirmed these findings. Reductions by WHO regions ranged from 26·4% (15·0-37·8) in the Eastern Mediterranean Region to 55·2% (43·0-67·4) in the European Region and were sustained in nine countries (contributing up to 31 sites) for 6-10 years. The age distribution of children with rotavirus gastroenteritis shifted towards older children after rotavirus vaccine introduction. INTERPRETATION: A significant and sustained reduction in the proportion of hospital admissions for acute gastroenteritis due to rotavirus was seen among children younger than 5 years in GRSN sites following rotavirus vaccine introduction. These findings highlight the need to incorporate rotavirus vaccines into immunisation programmes in countries that have not yet introduced them and underline the importance of high-quality surveillance. FUNDING: The GRSN receives funding from Gavi, the Vaccine Alliance and the US Centers for Disease Control and Prevention. No specific funding was provided for this Article.

Software Tools to Facilitate Systematic Review Used for Cancer Hazard Identification.

Objective and systematic methods to search, review, and synthesize published studies are a fundamental aspect of carcinogen hazard classification. Systematic review is a historical strength of the International Agency for Research on Cancer (IARC) Monographs Program and the United States National Toxicology Program (NTP) Office of the Report on Carcinogens (RoC). Both organizations are tasked with evaluating peer-reviewed, published evidence to determine whether specific substances, exposure scenarios, or mixtures pose a cancer hazard to humans. This evidence synthesis is based on objective, transparent, published methods that call for extracting and interpreting data in a systematic manner from multiple domains, including a) human exposure, b) epidemiological evidence, c) evidence from experimental animals, and d) mechanistic evidence. The process involves multiple collaborators and requires an extensive literature search, review, and synthesis of the evidence. Several online tools have been implemented to facilitate these collaborative systematic review processes. Specifically, Health Assessment Workplace Collaborative (HAWC) and Table Builder are custom solutions designed to record and share the results of the systematic literature search, data extraction, and analyses. In addition, a content management system for web-based project management and document submission has been adopted to enable access to submitted drafts simultaneously by multiple co-authors and to facilitate their peer review and revision. These advancements in cancer hazard classification have applicability in multiple systematic review efforts. https://doi.org/10.1289/EHP4224.

Cancer patterns, trends, and transitions in Peru: a regional perspective.

Peru, like several other South American countries, is experiencing remarkable population growth, ageing, and urbanisation, which has given rise to profound changes in its epidemiological profile. Prostate and breast cancer are the most frequent cancers in men and women, respectively, in Lima and Arequipa, the two areas with population-based cancer registries. However, infection-associated cancers (cervix and stomach) are also common, and rank highest in the national cancer mortality profile. Although a foundation of surveillance informs cancer-control initiatives in Peru, improvements in the vital statistics system, and the quality and use of incidence data for the planning and assessment of cancer prevention and control actions, are needed. Existing population-based cancer registries in Lima and Arequipa, and linkages to the established national mandatory cancer reporting system, are crucial for the collection of high-quality data on national cancer incidence. The delivery of effective cancer prevention and control measures requires sustained investment in the collection of high-quality data capable of informing policies and driving research programmes.

Bladder Cancer Incidence and Mortality: A Global Overview and Recent Trends.

CONTEXT: Bladder cancer has become a common cancer globally, with an estimated 430 000 new cases diagnosed in 2012. OBJECTIVE: We examine the most recent global bladder cancer incidence and mortality patterns and trends, the current understanding of the aetiology of the disease, and specific issues that may influence the registration and reporting of bladder cancer. EVIDENCE ACQUISITION: Global bladder cancer incidence and mortality statistics are based on data from the International Agency for Research on Cancer and the World Health Organisation (Cancer Incidence in Five Continents, GLOBOCAN, and the World Health Organisation Mortality). EVIDENCE SYNTHESIS: Bladder cancer ranks as the ninth most frequently-diagnosed cancer worldwide, with the highest incidence rates observed in men in Southern and Western Europe, North America, as well in certain countries in Northern Africa or Western Asia. Incidence rates are consistently lower in women than men, although sex differences varied greatly between countries. Diverging incidence trends were also observed by sex in many countries, with stabilising or declining rates in men but some increasing trends seen for women. Bladder cancer ranks 13th in terms of deaths ranks, with mortality rates decreasing particularly in the most developed countries; the exceptions are countries undergoing rapid economic transition, including in Central and South America, some central, southern, and eastern European countries, and the Baltic countries. CONCLUSIONS: The observed patterns and trends of bladder cancer incidence worldwide appear to reflect the prevalence of tobacco smoking, although infection with Schistosoma haematobium and other risk factors are major causes in selected populations. Differences in coding and registration practices need to be considered when comparing bladder cancer statistics geographically or over time. PATIENT SUMMARY: The main risk factor for bladder cancer is tobacco smoking. The observed patterns and trends of bladder cancer incidence worldwide appear to reflect the prevalence of tobacco smoking.

Cancer patterns and trends in Central and South America.

RATIONALE AND OBJECTIVE: Cancer burden is increasing in Central and South America (CSA). We describe the current burden of cancer in CSA. METHODS: We obtained regional and national-level cancer incidence data from 48 population-based registries (13 countries) and nation-wide cancer mortality data from the WHO (18 countries). We estimated world population age-standardized incidence and mortality rates per 100,000 person-years. RESULTS: The leading cancers diagnosed were prostate, lung, breast, cervix, colorectal, and stomach, which were also the primary causes of cancer mortality. Countries of high/very high human development index (HDI) in the region experienced a high burden of prostate and breast cancer while medium HDI countries had a high burden of stomach and cervical cancers. Between countries, incidence and mortality from all cancers combined varied by 2-3-fold. French Guyana, Brazil, Uruguay, and Argentina had the highest incidence of all cancers while Uruguay, Cuba, Argentina, and Chile had the highest mortality. Incidence of colorectum, prostate and thyroid cancers increased in Argentina, Brazil, Chile and Costa Rica from 1997 to 2008, while lung, stomach and cervical cancers decreased. CONCLUSION: CSA carries a double-burden of cancer, with elevated rates of infection- and lifestyle-related cancers. Encountered variation in cancer rates between countries may reflect differences in registration practices, healthcare access, and public awareness. Resource-dependent interventions to prevent, early diagnose, and treat cancer remain an urgent priority. There is an overwhelming need to improve the quality and coverage of cancer registration to guide and evaluate future cancer control policies and programs.

An assessment of GLOBOCAN methods for deriving national estimates of cancer incidence.

OBJECTIVE: To assess the validity of the GLOBOCAN methods for deriving national estimates of cancer incidence. METHODS: We obtained incidence and mortality data from Norway by region, year of diagnosis, cancer site, sex and 5-year age group for the period 1983-2012 from the NORDCAN database. Estimates for the year 2010 were derived using nine different methods from GLOBOCAN. These included the projection of national historical rates, the use of regional proxies and the combination of national mortality data with mortality to incidence ratios or relative survival proportions. We then compared the national estimates with recorded cancer incidence data. FINDINGS: Differences between the estimates derived using different methods varied by cancer site and sex. Methods based on projections performed better where major changes in recent trends were absent. Methods based on mortality data performed less well for cancers associated with small numbers of deaths and for cancers detectable by screening. In countries with longstanding cancer registries of high quality, regional-based, or trends-based incidence estimates perform reasonably well in comparison with recorded incidence. CONCLUSION: Although the performance of the GLOBOCAN methods varies by cancer site and sex in this study, the results emphasize a need for more high-quality population-based cancer registries - either regional or, where practical and feasible, national registries - to describe cancer patterns and trends for planning cancer control priorities.