The Safety of PsA-TT in Pregnancy: An Assessment Performed Within the Navrongo Health and Demographic Surveillance Site in Ghana.

BACKGROUND: Group A meningococcal disease occurs in large epidemics within the meningitis belt of Africa that includes northern Ghana. Major epidemics in the meningitis belt have infection rates ranging from 100 to 800 per 100 000 population. In 2012, a group A meningococcal conjugate vaccine, PsA-TT (MenAfriVac), was introduced into the region in large campaigns. METHODS: We report here on the safety of this vaccine when used in pregnant women in the Navrongo region of Ghana. RESULTS: Rates of events in 1730 immunized pregnant women and their infants were compared to the rates of the same events in pregnant women who did not receive the vaccine during the campaign and also to women who were pregnant in the prior year. CONCLUSIONS: We found no evidence of any safety concerns when this vaccine was administered during pregnancy.

Lessons Learned From Enhancing Vaccine Pharmacovigilance Activities During PsA-TT Introduction in African Countries, 2010-2013.

BACKGROUND: The rollout of the group A meningococcal vaccine, PsA-TT, in Africa's meningitis belt countries represented the first introduction of a vaccine specifically designed for this part of the world. During the first year alone, the number of people who received the vaccine through mass vaccination campaigns was several hundredfold higher than that of subjects who participated in the closely monitored clinical trials. Implementation of a system to identify rare but potentially serious vaccine reactions was therefore a high priority in the design and implementation of those campaigns. METHODS: National authorities and their technical partners set up effective vaccine pharmacovigilance systems, including conducting active surveillance projects. RESULTS: Implementation of national expert advisory groups to review serious adverse events following immunization in all countries and active monitoring of conditions of interest in 3 early-adopter countries did not identify particular concerns with the safety profile of PsA-TT, which had already provided tremendous public health benefits. CONCLUSIONS: Lessons learned from this experience will help to improve preparations for future vaccine introductions in resource-poor settings and capitalize on such efforts to advance vaccine safety systems in the future.

Active Surveillance for Adverse Events After a Mass Vaccination Campaign With a Group A Meningococcal Conjugate Vaccine (PsA-TT) in Mali.

BACKGROUND: The monovalent meningococcal A conjugate vaccine (PsA-TT, MenAfriVac) was developed for use in the "meningitis belt" of sub-Saharan Africa. Mali was 1 of 3 countries selected for early introduction. As this is a new vaccine, postlicensure surveillance is particularly important to identify and characterize possible safety issues. METHODS: The national vaccination campaign was phased from September 2010 to November 2011. We conducted postlicensure safety surveillance for PsA-TT in 40 government clinics from southern Mali serving approximately 400 000 people 1-29 years of age. We conducted analyses with individual-level data and population-level data, and we calculated rates of adverse events using the conditional exact test, a modified vaccine cohort risk interval method, and a modified self-controlled case series method for each outcome of interest, including 18 prespecified adverse events and 18 syndromic categories. RESULTS: An increased rate of clinic visits for fever within 3 days after vaccination was found using multiple methods for all age groups. Although other signals were found with some methods, complete assessment of all other prespecified outcomes and syndromic categories did not reveal that PsA-TT was consistently associated with any other health problem. CONCLUSIONS: No new safety concerns were identified in this study. These results are consistent with prelicensure data and other studies indicating that PsA-TT is safe. The approach presented could serve as a model for future active postlicensure vaccine safety monitoring associated with large-scale immunization campaigns in low-income countries.

A single dose multi-ingredient pre-workout supplement enhances upper body resistance exercise performance.

Introduction: Multi-ingredient pre-workout supplements (MIPS) are commonly used by individuals looking to enhance exercise performance and augment adaptations to training. However, the efficacy of commercially available MIPS is largely dependent on the ingredient profile, and new formulations should be investigated to determine their effectiveness. Therefore, the purpose of this study was to examine the effects of a commercially available MIPS product on performance during an upper body resistance exercise protocol. Methods: Twenty resistance-trained participants (10 men, 10 women) volunteered to complete this double-blind, placebo-controlled, crossover study consisting of 3 visits. Visit 1 consisted of body composition, 1-repetition maximum (1RM) testing, and familiarization. Visits 2 and 3 consisted of supplementation with either MIPS or placebo (PLA) 1 h prior to completion of an upper body resistance exercise workout during which power output, repetitions completed, rating of perceived exertion (RPE), and perceived recovery were recorded. Assessments of reaction time, isometric mid-thigh pull, and perceived levels of focus, energy, fatigue, and "muscle pump" were also completed before supplementation, 1 h after supplementation, and immediately after exercise. Results: Statistical analysis revealed significant main effects of trial for reaction time (p < 0.001) and bench press peak power (p = 0.026) indicating better performance during the MIPS trial. Furthermore, total number of repetitions completed significantly increased (p = 0.003) during the MIPS (96.90 ± 21.31 repetitions) trial compared to PLA (89.50 ± 18.37 repetitions). Additionally, overall session RPE was significantly lower (p = 0.002) during the MIPS (7.6 ± 1.2) trial compared to PLA (8.3 ± 0.9). Discussion: These findings suggest that acute supplementation with this MIPS improved upper body resistance exercise performance while reducing participant RPE. Further research should investigate the efficacy of chronic supplementation with this MIPS as the acute response provided an ergogenic benefit.

Current status and future directions of post-marketing vaccine safety monitoring with focus on USA and Europe.

Vaccine safety research is a key component of public health programs. Regulatory agencies need to be able to make informed decisions. Public health authorities need to respond to vaccine concerns before they turn into large scale scares reducing vaccine uptake and derailing immunization programs. Several post-licensure vaccine safety monitoring systems have been established in the USA and Europe, and methods such as rapid cycle analysis have been developed for real-time detection and analysis of safety issues. Accurate and reliable vaccine product testing and monitoring requires high quality data of populations of 100 million and above depending on the frequency of the event, vaccine coverage, and the time pressure during which data need to be generated. This requires post-licensure safety studies utilizing large linked population based databases of exposure and outcomes. Harmonized methods for development and linkage of these databases across countries need to be further developed, validated and implemented. Concerted action between the US and Europe could move vaccine safety monitoring to today's level of requirements globally and should be pursued.

Vaccine safety issues at the turn of the 21st century.

Global gains in vaccination coverage during the early 21st century have been threatened by the emergence of antivaccination groups that have questioned the effectiveness of vaccines to generate public distrust of vaccines and immunisation programmes. This manuscript summarises six key topics that have been at the centre of global discussions on vaccine safety during the early 21st century: thiomersal in multi-dose non-live vaccines, aluminium adjuvants used with several non-live vaccines, autism and auto-immune conditions as possible consequences of vaccination, a risk of immune overload with increasing numbers of vaccinations, and detrimental non-specific effects (NSEs) of vaccination. For each topic, we describe the hypothesis behind the public concern, the evidence reviewed by the WHO's Global Advisory Committee for Vaccine Safety (GACVS) during 1999-2019, and any significant new data that has emerged since GACVS conclusions were made. Although the scientific evidence on these issues overwhelmingly supports the safety of vaccines, communication messages to caregivers and providers need to condense and convey scientific information in an appropriate way to address concerns contributing to vaccine distrust. In addition, there is need for further studies specifically designed to address both positive and negative NSE of vaccination. The role of GACVS will be increasingly important in evaluating the evidence and engaging the global community in promoting and assuring the safety of vaccines in the decades to come as we move into an era in which we use new vaccination platforms, antigens and formulations.

Evolving pharmacovigilance requirements with novel vaccines and vaccine components.

This paper explores the pipeline of new and upcoming vaccines as it relates to monitoring their safety. Compared with most currently available vaccines, that are constituted of live attenuated organisms or inactive products, future vaccines will also be based on new technologies. Several products that include such technologies are either already licensed or at an advanced stage of clinical development. Those include viral vectors, genetically attenuated live organisms, nucleic acid vaccines, novel adjuvants, increased number of antigens present in a single vaccine, novel mode of vaccine administration and thermostabilisation. The Global Advisory Committee on Vaccine Safety (GACVS) monitors novel vaccines, from the time they become available for large scale use. GACVS maintains their safety profile as evidence emerges from post-licensure surveillance and observational studies. Vaccines and vaccine formulations produced with novel technologies will have different safety profiles that will require adapting pharmacovigilance approaches. For example, GACVS now considers viral vector templates developed on the model proposed by Brighton Collaboration. The characteristics of those novel products will also have implications for the risk management plans (RMPs). Questions related to the duration of active monitoring for genetic material, presence of adventitious agents more easily detected with enhanced biological screening, or physiological mechanisms of novel adjuvants are all considerations that will belong to the preparation of RMPs. In addition to assessing those novel products and advising experts, GACVS will also consider how to more broadly communicate about risk assessment, so vaccine users can also benefit from the committee's advice.

Novel vaccine safety issues and areas that would benefit from further research.

Vaccine licensure requires a very high safety standard and vaccines routinely used are very safe. Vaccine safety monitoring prelicensure and postlicensure enables continual assessment to ensure the benefits outweigh the risks and, when safety problems arise, they are quickly identified, characterised and further problems prevented when possible. We review five vaccine safety case studies: (1) dengue vaccine and enhanced dengue disease, (2) pandemic influenza vaccine and narcolepsy, (3) rotavirus vaccine and intussusception, (4) human papillomavirus vaccine and postural orthostatic tachycardia syndrome and complex regional pain syndrome, and (5) RTS,S/adjuvant system 01 malaria vaccine and meningitis, cerebral malaria, female mortality and rebound severe malaria. These case studies were selected because they are recent and varied in the vaccine safety challenges they elucidate. Bringing these case studies together, we develop lessons learned that can be useful for addressing some of the potential safety issues that will inevitably arise with new vaccines.

Importance of background rates of disease in assessment of vaccine safety during mass immunisation with pandemic H1N1 influenza vaccines.

Because of the advent of a new influenza A H1N1 strain, many countries have begun mass immunisation programmes. Awareness of the background rates of possible adverse events will be a crucial part of assessment of possible vaccine safety concerns and will help to separate legitimate safety concerns from events that are temporally associated with but not caused by vaccination. We identified background rates of selected medical events for several countries. Rates of disease events varied by age, sex, method of ascertainment, and geography. Highly visible health conditions, such as Guillain-Barré syndrome, spontaneous abortion, or even death, will occur in coincident temporal association with novel influenza vaccination. On the basis of the reviewed data, if a cohort of 10 million individuals was vaccinated in the UK, 21.5 cases of Guillain-Barré syndrome and 5.75 cases of sudden death would be expected to occur within 6 weeks of vaccination as coincident background cases. In female vaccinees in the USA, 86.3 cases of optic neuritis per 10 million population would be expected within 6 weeks of vaccination. 397 per 1 million vaccinated pregnant women would be predicted to have a spontaneous abortion within 1 day of vaccination.

Global landscape analysis of no-fault compensation programmes for vaccine injuries: A review and survey of implementing countries.

To update the landscape analysis of vaccine injuries no-fault compensation programmes, we conducted a scoping review and a survey of World Health Organization Member States. We describe the characteristics of existing no-fault compensation systems during 2018 based on six common programme elements. No-fault compensation systems for vaccine injuries have been developed in a few high-income countries for more than 50 years. Twenty-five jurisdictions were identified with no-fault compensation programmes, of which two were recently implemented in a low- and a lower-middle-income country. The no-fault compensation programmes in most jurisdictions are implemented at the central or federal government level and are government funded. Eligibility criteria for vaccine injury compensation vary considerably across the evaluated programmes. Notably, most programmes cover injuries arising from vaccines that are registered in the country and are recommended by authorities for routine use in children, pregnant women, adults (e.g. influenza vaccines) and for special indications. A claim process is initiated once the injured party or their legal representative files for compensation with a special administrative body in most programmes. All no-fault compensation programmes reviewed require standard of proof showing a causal association between vaccination and injury. Once a final decision has been reached, claimants are compensated with either: lump-sums; amounts calculated based on medical care costs and expenses, loss of earnings or earning capacity; or monetary compensation calculated based on pain and suffering, emotional distress, permanent impairment or loss of function; or combination of those. In most jurisdictions, vaccine injury claimants have the right to seek damages either through civil litigation or from a compensation scheme but not both simultaneously. Data from this report provide an empirical basis on which global guidance for implementing such schemes could be developed.

A Prospective Cohort Study on the Safety of Infant Pentavalent (DTwP-HBV-Hib) and Oral Polio Vaccines in Two South Indian Districts.

BACKGROUND: Safety of pentavalent (DTwP-HBV-Hib) vaccine has been a public concern in India and other countries. This study attempted to document the association of serious adverse events following immunization (AEFI, including hospitalizations and deaths of all causes) with the 3 doses of pentavalent and oral poliovirus (OPV) vaccines. METHODS: A cohort of 30,688 infants in 2 south Indian districts were enrolled and followed-up between October 2014 and May 2016, following their first vaccination with DTwP-HBV-Hib and OPV at public health facilities. During weekly follow-ups, by telephone or home visits, the serious AEFIs (hospitalizations and deaths) occurring any time after each vaccination until 4 weeks after third dose were documented. The incidence risk ratios (IRRs) of serious AEFIs in the first (days 0-6) and fourth weeks (days 21-27) after the vaccine doses were compared using the poisson regression analysis. RESULTS: Of the 30,688 infants enrolled, 30,208 received their third doses of vaccines. During the 4-week periods following each vaccination, there were 365 hospitalizations and 17 deaths. Adjusted incidence risk ratio of 3 doses combined for post-vaccination serious AEFIs during the first week compared with fourth week was 0.8 [95% confidence interval: 0.6-1.0]. CONCLUSIONS: There was no increased risk of a serious AEFIs during the first week after any of the 3 doses of pentavalent and OPV vaccination compared with the fourth week. In the absence of any temporal clustering, mortality and hospitalization rates observed in vaccinated infants probably reflects the natural occurrence of such events.

An approach for preparing and responding to adverse events following immunization reported after hepatitis B vaccine birth dose administration.

The success of immunization programs in lowering the incidence of vaccine preventable diseases (VPDs) has led to increased public attention on potential health risks associated with vaccines. As a result, a scientifically rigorous response to investigating reported adverse events following immunization (AEFI) and effective risk communications strategies are critical to ensure public confidence in immunization. Globally, an estimated 257 million people have chronic hepatitis B virus (HBV) infection, which causes more than 686,000 premature deaths from liver cancer and cirrhosis. Hepatitis B vaccination is the most effective way to prevent mother-to-child transmission of HBV infection, especially when a timely birth dose is given within 24 h of birth. However, an infant's risk of dying is highest in the neonatal period, and thus, administering HepB-BD within 24 h of birth overlaps with the most fragile period in an infant's life. A working group formed in July 2016 following the publication of the case reports of the effects on vaccination coverage of media reports of infant deaths after HepB-BD administration in China and Vietnam. The goal of the working group was to create a framework and describe best practices for preparing for and responding to AEFI reported after HepB-BD administration, using existing resources. The framework includes six steps, including three preparation steps and three response steps. This document is written for national and regional immunization program staff. Prior to using the framework for preparation and response to AEFIs reported after HepB-BD administration, staff members should be familiar with how AEFI are detected, reported, and investigated in the country. The document might also be of interest to national regulatory staff members who monitor vaccine safety within the country.

Immunization stress-related response - Redefining immunization anxiety-related reaction as an adverse event following immunization.

The Council for the International Organizations of Medical Sciences (CIOMS) and WHO working group on pharmacovigilance defines five cause specific AEFI which includes an immunization anxiety-related reaction. Historically this term has been used to describe a range of symptoms and signs that may arise after immunization that are related to "anxiety" about the immunization. However, the term "anxiety" does not adequately capture all the elements of this cause specific AEFI. In 2015, the Global Advisory Committee for Vaccine Safety convened an expert working group with the purpose of redefining, preventing and managing this particular AEFI. The term "Immunization Stress-Related Response" is proposed to replace the former terminology. We present a manual that redefines this AEFI and present a framework for prevention, diagnosis and management in both an individual and also when such events occur as clusters and affect multiple individuals. Since such mass events can result in cessation of immunization programmes and/or a loss of public confidence, a communication response is essential.

The use of web analytics combined with other data streams for tailoring online vaccine safety information at global level: The Vaccine Safety Net's web analytics project.

The Vaccine Safety Net's Web Analytics Project (VSN-WAP) was launched in October 2017 to monitor the behavior of users visiting websites belonging to the VSN, a global network of websites providing science-based information on vaccine safety. Participating websites could provide web metrics in two ways: through a Google Analytics (GA) script, which automatically forwarded metrics to a central account and through manual input (MI) of a reduced subset of metrics (Sessions, Page Views, New Users, Bounce Rate, Views/Session and Average Session Duration), which were pooled with the metrics obtained through GA. Additional metrics were obtained from websites providing data through Google Analytics (Country, Age, Sex, Device). We report results from February 2018 to March 2019. In March 2019, 32 websites were participating in the project (21 through GA, 11 through MI). From February 2018 to March 2019 we recorded 22,471,535 sessions, with 38,307,349 page views. Sessions, New Users and Page views progressively increased, Views/Session, Bounce Rate and Average Session Duration remained stable. Most users were female (68%) and belonged to the 25-34 age range (37%), followed by 35-44 (22%) and 18-24 (19%). Fifty-four percent of users connected from a mobile device, 42% from a desktop and 4% from a tablet. Digital media monitoring techniques can provide insights on the characteristics of users with a specific interest in vaccines. These data can be exploited to improve the performance of websites providing information on vaccines to the general public.

The science of vaccine safety: Summary of meeting at Wellcome Trust.

Vaccines are everywhere hugely successful but are also under attack. The reason for the latter is the perception by some people that vaccines are unsafe. However that may be, vaccine safety, life any other scientific subject, must be constantly studied. It was from this point of view that a meeting was organized at the Wellcome Trust in London in May 2019 to assess some aspects of vaccine safety as subjects for scientific study. The objective of the meeting was to assess what is known beyond reasonable doubt and conversely what areas need additional studies. Although the meeting could not cover all aspects of vaccine safety science, many of the most important issues were addressed by a group of about 30 experts to determine what is already known and what additional studies are merited to assess the safety of the vaccines currently in use. The meeting began with reviews of the current situation in different parts of the world, followed by reviews of specific controversial areas, including the incidence of certain conditions after vaccination and the safety of certain vaccine components. Lastly, information about the human papillomavirus vaccine was considered because its safety has been particularly challenged by vaccine opponents. The following is a summary of the meeting findings. In addition to this summary, the meeting organizers will explore opportunities to perform studies that would enlarge knowledge of vaccine safety.

Economic and immunisation safety surveillance characteristics of countries implementing no-fault compensation programmes for vaccine injuries.

Improvements in vaccine safety surveillance and investigative capacity lead to identification of rare reactions attributable to vaccination. As a result, the issue of fair compensation for those who experience vaccine injuries is gaining growing attention. Although vaccine injury compensation programmes (VICP) have been developed in a few countries for more than 50 years, no global policy guidance to guide vaccine injury compensation in all countries wishing to adopt such compensation schemes is currently available. To update the landscape analysis of no-fault compensation programmes and characterize VICP implementing countries, we conducted a survey of all 194 Member States from the World Health Organization and received feedback from 151. This analysis describes the economic and vaccine safety surveillance characteristics of Member States implementing VICPs. This analysis describes the characteristics of 25 Member States implementing a compensation programmes. Characteristics examined include economic, vaccination and safety surveillance indicators. Twenty of the 25 Member States (80%) with compensation programmes are categorized as high-income countries, 20/25 (80%) met the Global Vaccine Action Plan (GVAP) safety indicator of reporting at least ten annual reports of adverse events following immunization per 100,000 population, 21/25 (84%) met the GVAP coverage indicator by achieving greater than 90% third dose of Diphtheria, Tetanus and Pertussis vaccine (DTP3) and 17/25 (68%) assessed vaccine hesitancy in 2017. All Member States with VICP have a national immunization technical advisory group. This study identified growing interest in the implementation of no-fault compensation programs beyond high-income countries. Global policies guiding compensation should be developed for countries regardless of the maturity of their immunization programmes. RESEARCH IN CONTEXT: As a result of improved vaccine safety surveillance, World Health Organization (WHO) Member States are facing situations where known untoward serious vaccine reactions are documented, including in low- and middle-income settings. This has led to increased interest for the development of national no-fault compensation policies for vaccine injuries. As of 2010, compensation schemes for vaccine related injuries had been identified and characterized in 19 out of 194 WHO member states. All these programmes were in the industrialized world with none in low- and middle-income countries. Previous reviews have described the characteristics of the existing programmes based on the six common elements identified by Evans in 1999 with less emphasis on characteristics from countries implementing these no-fault compensation programmes. This manuscript aimed to identify predictors of countries implementing no-fault compensation programmes for vaccine injuries and update the inventory of existing programmes as part of a more comprehensive global landscape evaluation of existing programmes. This information will be useful for country self-evaluation and future compensation policy formulation as discussion to develop policies guiding the implementation of vaccine injury compensation continues to gain growing attention.

Haemophilus influenzae type b conjugate vaccine is highly effective in the Ugandan routine immunization program: a case-control study.

OBJECTIVE: To study the effectiveness of the Haemophilus influenzae type b (Hib) vaccination program in Uganda. METHODS: Case-control study of Hib vaccine effectiveness against Hib meningitis. Cases were children hospitalized with Hib meningitis confirmed by culture and/or latex agglutination. Cases were identified retrospectively from July 2002 to July 2004, and prospectively from July 2004 to July 2005. Each case-patient was matched by age to three neighbourhood and three hospital controls; all children were eligible to receive Hib vaccine through the routine schedule. Vaccine effectiveness was evaluated by conditional logistic regression, controlling for confounding variables. RESULTS: We enrolled 41 cases; their median age was 6 months. Only six (15%) cases, all HIV-negative, had received >/=2 doses of Hib vaccine, compared with 64% of neighbourhood controls and 70% of hospital controls. Controlling for maternal education, the only variable which remained in the multivariable model, vaccine effectiveness for two or three doses vs. no dose was 99% [95% confidence intervals (CI) 92-100%] and 96% (95% CI 80-100%) when cases were compared with neighbourhood and hospital controls, respectively. CONCLUSION: In Uganda, Hib vaccine was highly effective in the context of the routine immunization schedule. Sustained routine use of Hib vaccine will contribute to the prevention of childhood morbidity and mortality.

Use of a new global indicator for vaccine safety surveillance and trends in adverse events following immunization reporting 2000-2015.

Reporting of adverse events following immunization (AEFI) is a key component for functional vaccine safety monitoring system. The aim of our study is to document trends in the AEFI reporting ratio globally and across the six World Health Organization (WHO) regions. We describe the number of AEFI reports communicated each year through the World Health Organization/United Nations Children's Fund Joint Reporting Form on Immunization from 2000 to 2015. The AEFI reporting ratios (annual AEFI reports per 100,000 surviving infants) were calculated to identify WHO countries (n = 191 in 2000 and n = 194 by 2015) that met a minimal reporting ratio of 10, a target set by the Global Vaccine Action Plan for vaccine safety monitoring as a proxy measure for a functional AEFI reporting system. The number of countries reporting any AEFI fluctuated over time but with progress from 32 (17%) in 2000 to 124 (64%) in 2015. In 2015, the global average AEFI reporting ratio was 549 AEFI reports per 100,000 surviving infants. The number of countries with AEFI reporting ratios greater than 10 increased from 8 (4%) in 2000 to 81 (42%) in 2015. In 2015, 60% of countries in the WHO Region of the Americas reported at least 10 AEFI per 100,000 surviving infants, followed by 55% in European Region, 43% in Eastern Mediterranean Region, 33% in Western Pacific Region, 27% in South-East Asia Region and 21% in African Region. Overall, AEFI reporting has increased over the past sixteen years worldwide, but requires strengthening in a majority of low- and middle- income countries. The AEFI reporting ratio is useful for benchmarking and following trends over time; but does not provide information on the quality of the reporting system and does not guarantee capacity to detect and manage a vaccine safety problem at a national level. Additional efforts are required to ensure and improve data quality, AEFI reporting and surveillance of immunization safety in every country.

Intussusception in Young Children: Protocol for Multisite Hospital Sentinel Surveillance in India.

India has recently introduced a rotavirus vaccine under a universal immunization program. There is limited information on intussusception, an adverse event, following immunization in children from India. We are conducting sentinel surveillance for intussusception in children aged under two years at 19 hospitals. The sentinel sites' selection followed a multistage process. The surveillance combines retrospective surveillance for 69 months and prospective surveillance for 18 months. The suspected intussusception cases shall be reviewed for capturing confirmed cases and detailed data collection and classification according to Brighton Collaboration criteria. Data shall be analysed to describe epidemiology, trends, regional and seasonal variations, clinical profiles, management modalities, and outcomes of intussusception. The combination of prospective and retrospective surveillance shall be informative about the trend of intussusception over the last seven years in India. At four sites where rotavirus vaccines have been introduced, the change in intussusception trends shall be documented. The potential association with rotavirus vaccines and other vaccines shall be assessed using case-control and self-controlled case series methodology. Results are forthcoming. The results shall support the national vaccine safety surveillance effort by providing baseline estimates of intussusception for continued monitoring. The surveillance protocol and site selection processes shall inform similar vaccine-safety surveillance in India and other developing countries.