Strengthening immunization programs through innovative sub-national public-private partnerships in selected provinces in the Democratic Republic of the Congo.

BACKGROUND: Low immunization coverage rates in the Democratic Republic of Congo (DRC) have been reflective of challenges with vaccine access, support and delivery in the country. Motivated by measles and vaccine-derived polio virus (VDPV) outbreaks in 2016-17 and low vaccination rates, the provinces of Haut Lomami and Tanganyika were identified as pilot locations for an innovative approach focused on establishing a consortium of partners supporting local government. This approach was formalized through Memorandums of Understanding (MoUs) between the Bill and Melinda Gates Foundation and Provincial governments in 2018. A third province, Lualaba, established an MoU in 2021. MOU IMPLEMENTATION: These MoUs were 5-year partnerships designed to aid provinces in meeting four key objectives: 80 % immunization coverage, management/elimination of polio/cVDPV outbreaks, improvement of vaccine accessibility, and transfer of immunization service management to provincial leadership. OUTCOMES: During the MoU period, Haut-Lomami saw an increase in full immunization coverage, from 35.7 % (MICS 2018) to 88.9 % (VCS 2021-22), the highest in country. A sharp drop in percentage of zero-dose children was observed in the 3 provinces, confirming improved access to immunization services. Tanganyika saw initial improvement in full immunization coverage, followed by a drop in the VCS 2021-22 due to COVID-19 and healthcare worker strikes. Coverage improved in Tanganyika in the 2023 VCS. The 3 provinces increased their financial contributions to routine immunization and are now the top contributing provinces. While no cVDPV cases were recorded in 2020 and 2021, cVDPV1 and cVDPV2 outbreaks are afflicting the 3 provinces since 2022. CONCLUSIONS: Ultimately, the provincial MoUs were successful in bolstering provincial autonomy and capacity building with the biggest success being a drop in zero-dose children. While not all objectives have been met, the MoU approach served as an innovative program for key aspects of strengthening routine immunization in the DRC.

A Successful National and Multipartner Approach to Increase Immunization Coverage: The Democratic Republic of Congo Mashako Plan 2018-2020.

BACKGROUND: The immunization system in the Democratic Republic of the Congo faces many challenges, including persistent large-scale outbreaks of polio, measles, and yellow fever; a large number of unvaccinated children for all antigens; minimal and delayed funding; and poor use of immunization data at all levels. In response, the Expanded Programme on Immunization within the Ministry of Health (MOH) collaborated with global partners to develop a revitalization strategy for the routine immunization (RI) system called the Mashako Plan. MASHAKO PLAN DESIGN AND DEVELOPMENT: The Mashako Plan aimed to increase full immunization coverage in children aged 12-23 months by 15 percentage points overall in 9 of 26 provinces within 18 months of implementation. In 2018, we conducted a diagnostic review and identified gaps in coordination, service delivery, vaccine availability, real-time monitoring, and evaluation as key areas for intervention to improve the RI system. Five interventions were then implemented in the 9 identified provinces. DISCUSSION: According to the 2020 vaccine coverage survey, full immunization coverage increased to 56.4%, and Penta3/DTP3 increased to 71.1% across the Mashako Plan provinces; the initial objective of the plan was reached and additional improvements in key service delivery indicators had been achieved. Increases in immunization sessions held per month, national stock of pentavalent vaccine, and supervision visits conducted demonstrate that simple, measurable changes at all levels can quickly improve immunization systems. Despite short-term improvements in all indicators tracked, challenges remain in vaccine availability, regular funding of immunization activities, systematic provision of immunization services, and ensuring long-term sustainability. CONCLUSIONS: Strong commitment of MOH staff combined with partner involvement enabled the improvement of the entire system. A simple set of interventions and indicators focused the energy of managers on discrete actions to improve outcomes. Further exploration of the results is necessary to determine the long-term impact and generate all-level engagement for sustainable success in all provinces.

Vaccine-derived poliovirus serotype 2 outbreaks and response in the Democratic Republic of the Congo, 2017-2021.

Vaccine-derived polioviruses (VDPVs) can emerge from Sabin strain poliovirus serotypes 1, 2, and 3 contained in oral poliovirus vaccine (OPV) after prolonged person-to-person transmission where population vaccination immunity against polioviruses is suboptimal. VDPVs can cause paralysis indistinguishable from wild polioviruses and outbreaks when community circulation ensues. VDPV serotype 2 outbreaks (cVDPV2) have been documented in The Democratic Republic of the Congo (DRC) since 2005. The nine cVDPV2 outbreaks detected during 2005-2012 were geographically-limited and resulted in 73 paralysis cases. No outbreaks were detected during 2013-2016. During January 1, 2017-December 31, 2021, 19 cVDPV2 outbreaks were detected in DRC. Seventeen of the 19 (including two first detected in Angola) resulted in 235 paralysis cases notified in 84 health zones in 18 of DRC's 26 provinces; no notified paralysis cases were associated with the remaining two outbreaks. The DRC-KAS-3 cVDPV2 outbreak that circulated during 2019-2021, and resulted in 101 paralysis cases in 10 provinces, was the largest recorded in DRC during the reporting period in terms of numbers of paralysis cases and geographic expanse. The 15 outbreaks occurring during 2017-early 2021 were successfully controlled with numerous supplemental immunization activities (SIAs) using monovalent OPV Sabin-strain serotype 2 (mOPV2); however, suboptimal mOPV2 vaccination coverage appears to have seeded the cVDPV2 emergences detected during semester 2, 2018 through 2021. Use of the novel OPV serotype 2 (nOPV2), designed to have greater genetic stability than mOPV2, should help DRC's efforts in controlling the more recent cVDPV2 outbreaks with a much lower risk of further seeding VDPV2 emergence. Improving nOPV2 SIA coverage should decrease the number of SIAs needed to interrupt transmission. DRC needs the support of polio eradication and Essential Immunization (EI) partners to accelerate the country's ongoing initiatives for EI strengthening, introduction of a second dose of inactivated poliovirus vaccine (IPV) to increase protection against paralysis, and improving nOPV2 SIA coverage.

Outcomes of the Deployment of the Auto-Visual Acute Flaccid Paralysis Detection and Reporting (AVADAR) System for Strengthening Polio Surveillance in Africa From 2017 to 2018: Evaluation Study.

BACKGROUND: As we move toward a polio-free world, the challenge for the polio program is to create an unrelenting focus on smaller areas where the virus is still present, where children are being repeatedly missed, where immunity levels are low, and where surveillance is weak. OBJECTIVE: This article aimed to describe a possible solution to address weak surveillance systems and document the outcomes of the deployment of the Auto-Visual Acute Flaccid Paralysis Detection and Reporting (AVADAR) project. METHODS: This intervention was implemented in 99 targeted high-risk districts with concerns for silent polio circulation from eight countries in Africa between August 1, 2017, and July 31, 2018. A total of 6954 persons (5390 community informants and 1564 health workers) were trained and equipped with a smartphone on which the AVADAR app was configured to allow community informants to send alerts on suspected acute flaccid paralysis (AFP) and allow health worker to use electronic checklists for investigation of such alerts. The AVADAR and Open Data Kit ONA servers were at the center of the entire process. A dashboard system and coordination teams for monitoring and supervision were put in place at all levels. RESULTS: Overall, 96.44% (24,142/25,032) of potential AFP case alerts were investigated by surveillance personnel, yielding 1414 true AFP cases. This number (n=1414) reported through AVADAR was higher than the 238 AFP cases expected during the study period in the AVADAR districts and the 491 true AFP cases reported by the traditional surveillance system. A total of 203 out of the 1414 true AFP cases reported were from special population settings, such as refugee camps and insecure areas. There was an improvement in reporting in silent health areas in all the countries using the AVADAR system. Finally, there were 23,473 reports for other diseases, such as measles, diarrhea, and cerebrospinal meningitis, using the AVADAR platform. CONCLUSIONS: This article demonstrates the added value of AVADAR to rapidly improve surveillance sensitivity. AVADAR is capable of supporting countries to improve surveillance sensitivity within a short interval before and beyond polio-free certification.

Vaccine procurement in the Middle East and North Africa region: Challenges and ways of improving program efficiency and fiscal space.

Improving vaccine procurement performance has been a priority concern of national health authorities in the Middle East and North Africa (MENA) region for years particularly in terms of its role in accessing new vaccines and assuring a steady supply of quality vaccines at affordable prices. This article reviews the vaccine procurement mechanisms in the MENA region; analyzes the factors and drivers affecting demand for and supply of vaccines; discusses the main challenges; and suggests measures which can increase efficiency gains and generate the budgetary room to introduce life-saving vaccines. Based on in-depth analysis of available data and interviews with key informants at the regional and country level, this paper explains why most of the current strategies do not sufficiently recognize the specific characteristics of vaccine markets and best practices in procurement given these markets. The paper suggests potential efficiency gains for governments and global partners from pooling demand and moving from transaction-based purchasing to strategic purchasing in order to strengthen immunization services and introduce more life-saving vaccines.

Immunisation financing and programme performance in the Middle East and North Africa, 2010 to 2017.

Immunisation is a cornerstone to primary health care and is an exceptionally good value. The 14 low-income and middle-income countries in the Middle East and North Africa region make up 88% of the region's population and 92% of its births. Many of these countries have maintained high immunisation coverage even during periods of low or negative economic growth. However, coverage has sharply deteriorated in countries directly impacted by conflict and political unrest. Approximately 1.3 million children were not completely vaccinated in 2017, as measured by third dose of diphtheria-pertussis-tetanus vaccine. Most of the countries have been slow to adopt the newer, more expensive life-saving vaccines mainly because of financial constraints and the socioeconomic context. Apart from the three countries that have had long-standing assistance from Gavi, the Vaccine Alliance, most countries have not benefited appreciably from donor and partner activities in supporting their health sector and in achieving their national and subnational immunisation targets. Looking forward, development partners will have an important role in helping reconstruct health systems in conflict-affected countries. They can also help with generating evidence and strategic advocacy for high-priority and cost-effective services, including immunisation. Governments and ministries of health would ensure important benefits to their populations by investing further in their immunisation programmes. Where possible, the health system can create and expand fiscal space from efficiency gains in harmonising vaccine procurement mechanisms and service integration; broader revenue generation from economic growth; and reallocation of government budgets to health, and from within health, to immunization.

Breaking the inertia in coverage: Mainstreaming under-utilized immunization strategies in the Middle East and North Africa region.

Vaccination coverage rates have stagnated in the past several years in many middle-income countries (MICs), especially in the UNICEF Middle East and North Africa region, with political and economic turmoil as contributing factors. This paper reviews country experiences with three under-utilized strategies aimed at increasing vaccination coverage and reducing disparities between socio-economic and geographic groups in MICs. These strategies include: (1) identifying and accounting for displaced, mobile and neglected populations; (2) assessing and addressing missed opportunities for vaccination, including by expanding immunization into the second year of life and beyond; and (3) engaging effectively with the private/nongovernmental health providers in the coordination, provision and reporting of immunization services. The examples focus primarily on quality data collection, analysis, use and reporting aspects of the strategies. While data are limited, there is evidence from MICs that each of these strategies can have a positive impact on vaccination coverage, especially among marginalized populations.

Efforts to monitor Global progress on individual and community demand for immunization: Development of definitions and indicators for the Global Vaccine Action Plan Strategic Objective 2.

The Second Strategic Objective of the Global Vaccine Action Plan, "individuals and communities understand the value of vaccines and demand immunization as both their right and responsibility", differs from the other five in that it does not focus on supply-side aspects of immunization programs but rather on public demand for vaccines and immunization services. This commentary summarizes the work (literature review, consultations with experts, and with potential users) and findings of the UNICEF/World Health Organization Strategic Objective 2 informal Working Group on Vaccine Demand, which developed a definition for demand and indicators related to Strategic Objective 2. Demand for vaccines and vaccination is a complex concept that is not external to supply systems but rather encompasses the interaction between human behaviors and system structure and dynamics.

Vaccine stockouts around the world: Are essential vaccines always available when needed?

INTRODUCTION: As countries rise to the challenge of implementing the priorities of this "Decade of Vaccine" and their commitments delineated in the Global Vaccine Action Plan (GVAP), many continue to face important challenges of securing a continuous supply of essential vaccine for their national immunization programme. This study provides evidence on the incidence of vaccine stockouts in countries, their root causes and their potential impact on service delivery. METHODS: Vaccine stockout indicators collected from the WHO-UNICEF Joint Reporting Form (JRF) and UNICEF's Vaccine Forecasting Tool were analysed for the years covering the first half of the GVAP (2011 to 2015) and using 2010 as the baseline year. While the JRF collects annual information on national and subnational stockouts by vaccine, the UNICEF Vaccine Forecasting Tool has the advantage of requesting UNICEF procuring countries to report on the reasons underpinning any stockouts. RESULTS: Every year on average, one in every three WHO Member States experiences at least one stockout of at least one vaccine for at least one month. The incidence is most pronounced in Sub-Saharan Africa where 38% of countries in this area of the world report national-level stockouts. The vaccines most affected are DTP containing vaccines (often combined with HepB and Hib) and BCG. They account for respectively 43% and 31% of stockout events reported. While national level vaccine stockouts occur in countries of all income groups, middle income countries are the most affected. In 80% of cases, national level stockouts were due to reasons internal to countries. More specifically, 39% of stockouts were attributable to government funding delays, 23% were caused by delays in the procurement processes, and poor forecasting and stock management at country level accounted for an additional 18%. When a national level stockout of vaccines occurs, there is an 89% chance that a subnational stockout will occur at district level. More concerning is that if a district level stockout occurs, this will lead to an interruption of vaccination services in 96% of cases. DISCUSSION: There continues to be important challenges of ensuring a continuous availability of essential vaccines. The global community, together with countries, urgently need to design effective interventions aimed at reducing the frequency and mitigating the impact of stockouts.

State of inequality in diphtheria-tetanus-pertussis immunisation coverage in low-income and middle-income countries: a multicountry study of household health surveys.

BACKGROUND: Immunisation programmes have made substantial contributions to lowering the burden of disease in children, but there is a growing need to ensure that programmes are equity-oriented. We aimed to provide a detailed update about the state of between-country inequality and within-country economic-related inequality in the delivery of three doses of the combined diphtheria, tetanus toxoid, and pertussis-containing vaccine (DTP3), with a special focus on inequalities in high-priority countries. METHODS: We used data from the latest available Demographic and Health Surveys and Multiple Indicator Cluster Surveys done in 51 low-income and middle-income countries. Data for DTP3 coverage were disaggregated by wealth quintile, and inequality was calculated as difference and ratio measures based on coverage in richest (quintile 5) and poorest (quintile 1) household wealth quintiles. Excess change was calculated for 21 countries with data available at two timepoints spanning a 10 year period. Further analyses were done for six high-priority countries-ie, those with low national immunisation coverage and/or high absolute numbers of unvaccinated children. Significance was determined using 95% CIs. FINDINGS: National DTP3 immunisation coverage across the 51 study countries ranged from 32% in Central African Republic to 98% in Jordan. Within countries, the gap in DTP3 immunisation coverage suggested pro-rich inequality, with a difference of 20 percentage points or more between quintiles 1 and 5 for 20 of 51 countries. In Nigeria, Pakistan, Laos, Cameroon, and Central African Republic, the difference between quintiles 1 and 5 exceeded 40 percentage points. In 15 of 21 study countries, an increase over time in national coverage of DTP3 immunisation was realised alongside faster improvements in the poorest quintile than the richest. For example, in Burkina Faso, Cambodia, Gabon, Mali, and Nepal, the absolute increase in coverage was at least 2·0 percentage points per year, with faster improvement in the poorest quintile. Substantial economic-related inequality in DTP3 immunisation coverage was reported in five high-priority study countries (DR Congo, Ethiopia, Indonesia, Nigeria, and Pakistan), but not Uganda. INTERPRETATION: Overall, within-country inequalities in DTP3 immunisation persist, but seem to have narrowed over the past 10 years. Monitoring economic-related inequalities in immunisation coverage is warranted to reveal where gaps exist and inform appropriate approaches to reach disadvantaged populations. FUNDING: None.

Implementing efficient and sustainable collaboration between National Immunization Technical Advisory Groups: Report on the 3rd International Technical Meeting, Paris, France, 8-9 December 2014.

Many experts on vaccination are convinced that efforts should be made to encourage increased collaboration between National Immunization Technical Advisory Groups on immunization (NITAGs) worldwide. International meetings were held in Berlin, Germany, in 2010 and 2011, to discuss improvement of the methodologies for the development of evidence-based vaccination recommendations, recognizing the need for collaboration and/or sharing of resources in this effort. A third meeting was held in Paris, France, in December 2014, to consider the design of specific practical activities and an organizational structure to enable effective and sustained collaboration. The following conclusions were reached: (i) The proposed collaboration needs a core functional structure and the establishment or strengthening of an international network of NITAGs. (ii) Priority subjects for collaborative work are background information for recommendations, systematic reviews, mathematical models, health economic evaluations and establishment of common frameworks and methodologies for reviewing and grading the evidence. (iii) The programme of collaborative work should begin with participation of a limited number of NITAGs which already have a high level of expertise. The amount of joint work could be increased progressively through practical activities and pragmatic examples. Due to similar priorities and already existing structures, this should be organized at regional or subregional level. For example, in the European Union a project is funded by the European Centre for Disease Prevention and Control (ECDC) with the aim to set up a network for improving data, methodology and resource sharing and thereby supporting NITAGs. Such regional networking activities should be carried out in collaboration with the World Health Organization (WHO). (iv) A global steering committee should be set up to promote international exchange between regional networks and to increase the involvement of less experienced NITAGs. NITAGs already collaborate at the global level via the NITAG Resource Centre, a web-based platform developed by the Health Policy and Institutional Development Unit (WHO Collaborating Centre) of the Agence de Médecine Préventive (AMP-HPID). It would be appropriate to continue facilitating the coordination of this global network through the AMP-HPID NITAG Resource Centre. (v) While sharing work products and experiences, each NITAG would retain responsibility for its own decision-making and country-specific recommendations.

Supporting countries in establishing and strengthening NITAGs: lessons learned from 5 years of the SIVAC initiative.

To empower governments to formulate rational policies without pressure from any group, and to increase the use of evidence-based decision-making to adapt global recommendations on immunization to their local context, the WHO has recommended on multiple occasions that countries should establish National Immunization Technical Advisory Groups (NITAGs). The World Health Assembly (WHA) reinforced those recommendations in 2012 when Member States endorsed the Decade of Vaccines Global Vaccine Action Plan (GVAP). NITAGs are multidisciplinary groups of national experts responsible for providing independent, evidence-informed advice to health authorities on all policy-related issues for all vaccines across all populations. In 2012, according to the WHO-UNICEF Joint Reporting Form, among 57 countries eligible for immunization program financial support from the GAVI Alliance, only 9 reported having a functional NITAG. Since 2008, the Supporting Independent Immunization and Vaccine Advisory Committees (SIVAC) Initiative (at the Agence de Médecine Préventive or AMP) in close collaboration with the WHO and other partners has been working to accelerate and systematize the establishment of NITAGs in low- and middle-income countries. In addition to providing direct support to countries to establish advisory groups, the initiative also supports existing NITAGs to strengthen their capacity in the use of evidence-based processes for decision-making aligned with international standards. After 5 years of implementation and based on lessons learned, we recommend that future efforts should target both expanding new NITAGs and strengthening existing NITAGs in individual countries, along three strategic lines: (i) reinforce NITAG institutional integration to promote sustainability and credibility, (ii) build technical capacity within NITAG secretariats and evaluate NITAG performance, and (iii) increase networking and regional collaborations. These should be done through the development and dissemination of tools and guidelines, and information through a variety of adapted mechanisms.

Indicators to assess National Immunization Technical Advisory Groups (NITAGs).

A National Immunization Technical Advisory Group (NITAG) is an expert advisory committee that provides evidence-based recommendations to the Ministry of Health (MoH) to guide immunization programs and policies. The World Health Organization (WHO), the Initiative for Supporting National Independent Immunization and Vaccine Advisory Committees (SIVAC) at Agence de Médecine Préventive (AMP) and the US Centers for Disease Control and Prevention (US CDC) engaged NITAG stakeholders and technical partners in the development of indicators to assess the effectiveness of NITAGs. A list of 17 process, output and outcome indicators was developed and tested in 14 countries to determine whether they were understandable, feasible to collect, and useful for the countries. Based on the findings, a revised version of the indicators is proposed for self-assessment in the countries, as well as for global monitoring of the NITAGs.

Establishment of a National Immunization Technical Advisory Group in Côte d'Ivoire: process and lessons learned.

In January 2010, Côte d'Ivoire became the first GAVI-eligible country in sub-Saharan Africa to establish a National Immunization Technical Advisory Group (NITAG). The Côte d'Ivoire "National Committee of Independent Experts for Vaccination and Vaccines" (CNEIV-CI) was created to strengthen national capacity for evidence-based policy decisions with regard to immunization and vaccines. The primary reasons for success in Côte d'Ivoire were a strong political will, the availability of sufficient national expertise, a step-by-step country-driven process, and the provision of technical assistance to the Ministry of Health. The challenges included operating within the socio-political crisis, and initial reluctance from some stakeholders due to the potential overlap with other existing committees. The latter rapidly dissolved over the course of numerous meetings held with the SIVAC Initiative to clarify the mandate of a NITAG.

Report on the 1st international workshop on procedures for the development of evidence-based vaccination recommendations, Berlin, Germany, 22-23 November 2010.

In November 2010, experts from European and North-American countries met in Berlin, Germany, to discuss improved methods for the development of evidence-based vaccination recommendations. The objectives of the workshop were to (i) review current procedures and experiences of National Immunization Technical Advisory Groups (NITAGs) in developing a framework for evidence-based vaccination recommendations, (ii) discuss the applicability of methods like Grading of Recommendations Assessment, Development and Evaluation (GRADE), and (iii) to identify opportunities for international collaboration to support NITAGs in the development of vaccination recommendations at country-level. Recognizing that a systematic and transparent approach is necessary to promote the quality and acceptance of vaccination recommendations, various decision making frameworks have been implemented by national and international advisory groups addressing common key aspects of knowledge, such as the burden of disease or characteristics of the vaccine. There are several challenges when grading the quality of evidence of some immunization-specific topics (e.g. population-level effects of vaccination). This does not, however, necessitate development of an entirely new systematic methodology. The participants concluded that (i) GRADE or a modification of this methodology is suitable for the grading of quality of evidence related to vaccine effectiveness and safety, and that (ii) international cooperation would be beneficial to develop common framework methodologies for certain aspects of national immunization recommendation developments in order to avoid duplication of efforts, to build on existing strengths, and to support NITAGs worldwide.

Consultation on interactions between National Regulatory Authorities and National Immunization Technical Advisory Groups.

A consultation during the Developing Country Vaccine Regulators' Network meeting of May 2010 considered the interactions between the National Immunization Technical Advisory Group (NITAG) and the National Regulatory Authority (NRA) in various countries. This meeting was co-hosted by the WHO and the Supporting Independent Immunization and Vaccine Advisory Committees Initiative implemented by the Agence de Médecine Préventive in partnership with the International Vaccine Institute. Representatives from Developing Country Vaccine Regulators' Network and representatives from several additional countries' regulatory authorities met representatives from NITAGs and/or the National Immunization Program from these countries (Brazil, Canada, China, Cuba, France, Indonesia, Iran, South Africa, Thailand, Vietnam and the USA). The objectives of the workshop included a discussion on the issues of NRA-NITAG interaction, the assessment of the advantages of different models of interaction and proposals for an optimal coordination process for market authorization and recommendations for use of vaccines. It was concluded that there is need for increased and more formal interactions between NRAs and NITAGs, a clear framework establishing a formal interaction and early interactions before market authorization. NRA experts being at the same time NITAG ex officio members and vice versa are solutions which can be adopted by countries. The NRA issues the license based on the evidence submitted by the manufacturer. The NITAG makes recommendations based on scientific evidence, public health needs and policy, and consideration of the license conditions. If there is a need to make recommendations that are not covered by the license evidence then there should be interactions between NITAG, NRA and the license holder to encourage the license-holder to submit appropriate evidence, or to ensure that the justification for the off-label recommendation is communicated to the users of the medicine.

Increased risk of contralateral breast cancers among overweight and obese women: a time-dependent association.

Breast cancer (BC) survivors are at increased risk of second cancers. Obesity is commonly recognized as a risk factor of BC in postmenopausal period and a prognosis factor in BC regardless of menopausal status. Our aim was to study whether overweight BC survivors were at increased risk of contralateral BC (CBC). Our population was a large cohort of women followed since a first BC without distant spread and/or synchronous CBC. Body mass index (BMI) was assessed at diagnosis time. Binary codings of BMI were used to oppose overweight and obese patients to the others. Survival analyses were used including Cox models. Assumed hypothesis of proportional hazards was explored using graphical methods, Schoenfeld residuals and time-dependant covariates. In case of non-proportional hazards, survival models were computed over time periods. Over 15,000 patients were included in our study. Incidence of CBC was 8.8 (8.3-9.3)/1000 person-years and increased during follow-up. A significant time-dependent association between overweight and CBC was observed. After 10 years of follow-up, we found a significant increased hazard of CBC among patients with a BMI above 25 kg/m(2): the adjusted hazard ratio was 1.50(1.21-1.86), P = 0.001. After 10 years of follow-up, our study found a poorer prognosis among overweight BC survivors regarding CBC events. While benefits from diet habits and weight control may be expected during the long-term follow-up, they have yet to be established using randomized clinical trials.

The Supporting Independent Immunization and Vaccine Advisory Committees (SIVAC) initiative: a country-driven, multi-partner program to support evidence-based decision making.

Multiple health priorities, limited human resources and logistical capacities, as well as expensive vaccines with limited funds available increase the need for evidence-based decision making in immunization programs. The aim of the Supporting Independent Immunization and Vaccine Advisory Committees (SIVAC) Initiative is to support countries in the establishment or strengthening of National Immunization Technical Advisory Groups (NITAGs) that provide recommendations on immunization policies and programs (e.g., vaccination schedules, improvements of routine immunization coverage, new vaccine introduction, etc.). SIVAC, a program funded by the Bill & Melinda Gates Foundation, is based on a country-driven, step-by-step process that ensures its support is tailored to country needs and emphasizes NITAG sustainability. SIVAC supports countries by reinforcing the capacities of the NITAG scientific and technical secretariat and by providing specific support activities established in consultation with the country and other international partners. Additionally, SIVAC and partners have built an electronic platform, the NITAG Resource Center, that provides information, tools, and briefings to NITAGs and the immunization community.

Is obesity an independent prognosis factor in woman breast cancer?

BACKGROUND: Breast cancer and obesity represent important public health issues in most western countries. A number of studies found a negative prognosis effect of obesity or excess of weight in woman breast cancer. However, to date, this issue remains controversial. The objectives of this study were to confirm the prognosis role of obesity on a large cohort of patients and to investigate a potential independent effect. MATERIALS AND METHODS: We constituted a cohort of 14,709 patients who were recruited and treated at the Curie Institute (Paris) from 1981 to 1999. These patients were followed prospectively for a first unilateral invasive breast cancer without distant metastasis. Obesity was defined by a Body Mass Index (BMI) above 30 kg/m(2) according to the World Health Organization recommendations. RESULTS: Obese patients (8%) presented more extended tumors at diagnosis time suggesting a delayed breast cancer diagnosis. However, obesity appeared as a negative prognosis factor for several events in respectively univariate and multivariate survival analysis: metastasis recurrence (HR = 1.32[1.19-1.48]; HR = 1.12[1.00-1.26]), disease free interval (1.20[1.08-1.32]; 1.10[0.99-1.22]), overall survival (1.43[1.28-1.60]; 1.12[0.99-1.25]) and second primary cancer outcome (1.57[1.19-2.07]; 1.43[1.09-1.89]). Even if obese patients presented more advanced tumors at diagnosis time, multivariate analysis showed that there was a relevant independent effect. Other BMI codings, distinguishing overweight patients or using BMI as a continuous variable, showed a consistent correlation between BMI's value and prognosis effect. Interaction analysis revealed a more important obesity effect in the presence of tumor estrogen receptors and among limited extent tumors. CONCLUSIONS: This survey confirms the prognosis role of obesity on one of the largest cohort by investigating several prognosis events. While independent obesity effect linked to hormonal disorders appeared consistent as obesity's mechanism, we stress that obesity prognosis effect was also related to breast cancer presentation at diagnosis time.