Population Attributable Risk of Wheeze in 2-<6-Year-old Children, Following a Respiratory Syncytial Virus Lower Respiratory Tract Infection in The First 2 Years of Life.

BACKGROUND: There is limited evidence regarding the proportion of wheeze in young children attributable to respiratory syncytial virus lower respiratory tract infections (RSV-LRTI) occurring early in life. This cohort study prospectively determined the population attributable risk (PAR) and risk percent (PAR%) of wheeze in 2-<6-year-old children previously surveilled in a primary study for RSV-LRTI from birth to their second birthday (RSV-LRTI<2Y). METHODS: From 2013 to 2021, 2-year-old children from 8 countries were enrolled in this extension study (NCT01995175) and were followed through quarterly surveillance contacts until their sixth birthday for the occurrence of parent-reported wheeze, medically-attended wheeze or recurrent wheeze episodes (≥4 episodes/year). PAR% was calculated as PAR divided by the cumulative incidence of wheeze in all participants. RESULTS: Of 1395 children included in the analyses, 126 had documented RSV-LRTI<2Y. Cumulative incidences were higher for reported (38.1% vs. 13.6%), medically-attended (30.2% vs. 11.8%) and recurrent wheeze outcomes (4.0% vs. 0.6%) in participants with RSV-LRTI<2Y than those without RSV-LRTI<2Y. The PARs for all episodes of reported, medically-attended and recurrent wheeze were 22.2, 16.6 and 3.1 per 1000 children, corresponding to PAR% of 14.1%, 12.3% and 35.9%. In univariate analyses, all 3 wheeze outcomes were strongly associated with RSV-LRTI<2Y (all global P < 0.01). Multivariable modeling for medically-attended wheeze showed a strong association with RSV-LRTI after adjustment for covariates (global P < 0.0001). CONCLUSIONS: A substantial amount of wheeze from the second to sixth birthday is potentially attributable to RSV-LRTI<2Y. Prevention of RSV-LRTI<2Y could potentially reduce wheezing episodes in 2-<6-year-old children.

Enhancing Pharmacovigilance in Côte d'Ivoire: Impact of GSK's Training and Mentoring Pilot Project in the Abidjan Region.

INTRODUCTION: Pharmacovigilance (PV) in sub-Saharan Africa relies on passive surveillance but underreporting of adverse events (AEs) by health care professionals (HCPs) is a major challenge. A PV enhancement project was implemented to address this in Côte d'Ivoire. OBJECTIVE: To improve safety surveillance of medicines through PV training and mentoring of HCPs in selected health care facilities (HCFs). METHODS: This collaborative project between national PV stakeholders, GSK, and PATH was implemented from September 2018 to February 2020 in Abidjan region, Côte d'Ivoire. Trained PV focal points provided training and regular mentoring of HCPs. Key performance indicator (KPI) categories for AE reporting were the volume of AE reports, efficiency of report transmission and data entry, quality of reports, and quality of the central (Vigilance Unit) response to AE reports. RESULTS: Overall, 1427 HCPs at 91 HCFs were trained. In the 8 months before implementation, 33 AE reports were received versus 85 after 3 months and 361 after 18 months of implementation (71 [83.5%] and 278 [77.0%], respectively, from Abidjan). The KPIs with the highest proportions were: AE reports received centrally (100%), complete AE reports (69.0%), AE reports entered into the local PV database within 48 h (99.6%), and AE reports entered into the global database, VigiBase (86.7%). Report notification within 72 h, causality assessment, and serious AE reporting had proportions below 20%; feedback to reporters was provided for only 0.4% of reports. CONCLUSION: Regular PV trainings and mentoring improved AE reporting in Côte d'Ivoire but further enhancement is required to improve passive safety surveillance.

Medicines and vaccines should be safe and effective for use in the general population. Health care professionals therefore have the responsibility to continuously monitor medicinal products and report any unwanted medical occurrence (adverse event). Training and mentoring of health care professionals can improve adverse event reporting. In Côte d'Ivoire, a training and mentoring project was implemented by GSK, PATH (a non-governmental organisation), and the Ministry of Health, with the objective of increasing adverse event reporting. Over the period of 18 months, 1427 health care professionals from 91 health care facilities in the Abidjan region received training and mentoring. Between January and August 2018, before the project began, 33 adverse event reports were submitted at the central level (to the country's Vigilance Unit), with 11 (33.3%) from the Abidjan region. From September to December 2018, the first three months of project implementation, 85 reports were received, with 71 (83.5%) coming from the Abidjan region. This number increased to 361 by the end of the 18-month project, with 278 (77.0%) coming from the Abidjan region. Training of health care professionals therefore improved adverse event reporting, mainly from the Abidjan region but also nationwide. Assessments of the efficiency of adverse event reporting and the quality of adverse events reports received by the Vigilance Unit showed promising results, although there was room for improvement. Lessons learned from this project can flexibly serve the needs of other countries with less functional systems for reporting adverse events associated with medicinal products.

Estimated public health impact of human rotavirus vaccine (HRV) and pneumococcal polysaccharide protein D-conjugate vaccine (PHiD-CV) on child morbidity and mortality in Gavi-supported countries.

Vaccine impact models against rotavirus disease (RD) and pneumococcal disease (PD) in low- and middle-income countries assume vaccine coverage based on other vaccines. We propose to assess the impact on severe disease cases and deaths avoided based on vaccine doses delivered by one manufacturer to Gavi-supported countries. From the number of human rotavirus vaccine (HRV) and pneumococcal polysaccharide protein D-conjugate vaccine (PHiD-CV) doses delivered, we estimated the averted burden of disease 1) in a specific year and 2) for all children vaccinated during the study period followed-up until 5 years (y) of age. Uncertainty of the estimated impact was assessed in a probabilistic sensitivity analysis using Monte-Carlo simulations to provide 95% confidence intervals. From 2009 to 2019, approximately 143 million children received HRV in 57 Gavi-supported countries, avoiding an estimated 18.7 million severe RD cases and 153,000, deaths. From 2011 to 2019, approximately 146 million children received PHiD-CV in 36 countries, avoiding an estimated 5.0 million severe PD cases and 587,000 deaths. The number of severe cases and deaths averted for all children vaccinated during the study period until 5 years of age were about 23.2 million and 190,000, respectively, for HRV, and 6.6 million and 749,000, respectively, for PHiD-CV. Models based on doses delivered help to assess the impact of vaccination, plan vaccination programs and understand public health benefits. In 2019, HRV and PHiD-CV doses delivered over a 5-y period may have, on average, averted nine severe disease cases every minute and one child death every 4 min.

What is the context?The WHO added the pneumococcal conjugate vaccine and the rotavirus vaccine in the recommended vaccination schedule of all countries in 2007 and 2009, respectively.Previous studies estimated the public health benefit of these vaccines by approximating the number of children who received them.What is new?We used an alternative approach to estimate the benefit based on actual number of doses of the vaccines, human rotavirus vaccine (HRV; Rotarix) and pneumococcal polysaccharide protein D-conjugate vaccine (PHiD-CV; Synflorix) delivered to each country considered.The study analyzed data from children under 5 years of age in 60 Gavi-supported countries by identifying the number of vaccine doses delivered, estimating the number of children fully covered, applying the country-specific disease epidemiology, estimating the number of severe disease cases and deaths avoided.From 2009 to 2019, approximately 143 million children were vaccinated with HRV avoiding an estimated 18.7 million severe rotavirus disease cases and 153,000 deaths.From 2011 to 2019, about 146 million children were vaccinated with pneumococcal vaccine avoiding an estimated 5.0 million severe pneumococcal disease cases and 587,000 deaths.What is the impact? The benefit of HRV and PHiD-CV in Gavi-supported countries is often estimated based on assumptions of vaccine coverage rates.A modeling approach based on doses delivered by the vaccine manufacturer can provide an additional view on the potential vaccine benefits and improve planning, contribution, and sustainability of the immunization programs at a country level.In 2019, HRV and PHiD-CV together averted nine cases of severe disease each minute and one child death every 4 minutes.

Unveiling the contributions of immunization for progressing towards Universal Health Coverage.

The aim of the United Nations' Sustainable Development Goal (SDG)3 is to ensure healthy lives and promote well-being for all, at all ages; including reducing maternal and child mortality, combating communicable and non-communicable diseases, and achieving Universal Health Coverage (UHC). UHC aims to provide everyone with equal access to quality essential and comprehensive healthcare services including preventions, interventions, and treatments, without exposing them to financial hardship. Making progress toward UHC requires significant investment in technical and financial resources and countries are pursuing the implementation of cost-saving measures within health systems to help them achieve UHC. Whilst many countries are far from attaining UHC, all countries, particularly low- and middle-income countries, can take steps toward achieving UHC. This paper discusses key data showing how immunization is a fundamental, cost-effective tool for reducing morbidity and mortality associated with infectious disease in all populations, creating more productive communities, reducing treatment costs, and consequently, facilitating social and economic advancement. Immunization is key to advancing toward UHC by relieving the burden that diseases place on the healthcare services, freeing essential resources to use elsewhere within the healthcare system. Immunization is an essential, readily available strategy that countries can deploy to achieve UHC and the SDG3 agenda.

Impact of COVID-19 pandemic on routine immunization.

The current COVID-19 global pandemic continues to impact healthcare services beyond those directly related to the management of SARS-CoV-2 transmission and disease. We reviewed the published literature to assess the pandemic impact on existing global immunization activities and how the impact may be addressed. Widespread global disruption in routine childhood immunization has impacted a majority of regions and countries, especially in the initial pandemic phases. While data indicate subsequent recovery in immunization rates, a substantial number of vulnerable people remain unvaccinated. The downstream impact may be even greater in resource-limited settings and economically poorer populations, and consequently there are growing concerns around the resurgence of vaccine-preventable diseases, particularly measles. Guidance on how to address immunization deficits are available and continue to evolve, emphasizing the importance of maintaining and restoring routine immunization and necessary mass vaccination campaigns during and after pandemics. In this, collaboration between a broad range of stakeholders (governments, industry, healthcare decision-makers and frontline healthcare professionals) and clear communication and engagement with the public can help achieve these goals.Key messagesThe COVID-19 pandemic has a substantial impact on essential immunization activities.Disruption to mass vaccination campaigns increase risk of VPD resurgence.Catch-up campaigns are necessary to limit existing shortfalls in vaccine uptake.Guidance to mitigate these effects continues to evolve.

Rotavirus vaccines performance: dynamic interdependence of host, pathogen and environment.

INTRODUCTION: As of January 2021, rotavirus vaccination programs have been implemented in 109 countries and their use has resulted in a positive impact on rotavirus-related diarrheal hospitalizations and mortality in children below 5 years of age. Despite these successes, several countries in Africa and Asia where disease burden is high have not yet implemented rotavirus vaccination at all or at a scale sufficient enough to demonstrate impact. This could be, among other reasons, due to poor vaccine coverage and the modest levels of efficacy and effectiveness of the vaccines in these resource-limited settings. AREAS COVERED: We review various factors related to the human host (malnutrition, maternally derived antibodies and breastfeeding, genetic factors, blood group, and co-administration with oral polio vaccine), rotavirus pathogen (force of infection, strain diversity and coinfections), and the environment (related to the human microbiome) which reflect complex and interconnected processes leading to diminished vaccine performance in resource-limited settings. EXPERT OPINION: Addressing the limiting factors for vaccine efficacy is needed but likely to take a long time to be resolved. An immediate solution is to increase the immunization coverage to higher values generating an overall effect of adequate proportion of protected population to reduce the prevalence of rotavirus disease.

PLAIN LANGUAGE SUMMARYWhat is the context?Rotavirus is contagious and causes severe diarrhea in children below 5 years of age. It caused 128,500 deaths and 258 million episodes of diarrhea in 2016.Vaccines protecting children from rotavirus are given orally and have been implemented in 109 countries and used for more than a decade. They considerably decreased the number of hospitalizations and deaths.Several Asian and African countries experience rotavirus infections in large numbers and lag behind in implementing rotavirus vaccination programs.In these countries, rotavirus vaccines only prevent a smaller percentage of severe cases. The reasons for this reduction in vaccination impact are not widely known.What is new?We reviewed the literature to identify the reasons that could explain the differences in vaccination impact worldwide.Factors that might influence the impact of vaccination include Infected children (malnutrition, breastfeeding, blood group, and co-administration with oral polio vaccine);Circulating virus(es) (force of infection, number of new strains, and coinfections with other pathogens) Environment: human microbiome (microorganisms at the surface and in the body; that could be altered by diet, method of childbirth, or hygiene).Why is this important?In summary, rotavirus vaccination has reduced rotavirus-associated hospitalizations and deaths; however, more research is needed to understand the factors influencing the impact of vaccination in order to optimize them. (see Figure 1 ­ Graphical PLS).

Measles, mumps, rubella prevention: how can we do better?

INTRODUCTION: Measles, mumps, and rubella incidence decreased drastically following vaccination programs' implementation. However, measles and mumps' resurgence was recently reported, outbreaks still occur, and challenges remain to control these diseases. AREAS COVERED: This qualitative narrative review provides an objective appraisal of the literature regarding current challenges in controlling measles, mumps, rubella infections, and interventions to address them. EXPERT OPINION: While vaccines against measles, mumps, and rubella (including trivalent vaccines) are widely used and effective, challenges to control these diseases are mainly related to insufficient immunization coverage and changing vaccination needs owing to new global environment (e.g. traveling, migration, population density). By understanding disease transmission peculiarities by setting, initiatives are needed to optimize vaccination policies and increase vaccination coverage, which was further negatively impacted by COVID-19 pandemic. Also, awareness of the potential severity of infections and the role of vaccines should increase. Reminder systems, vaccination of disadvantaged, high-risk and difficult-to-reach populations, accessibility of vaccination, healthcare infrastructure, and vaccination services management should improve. Outbreak preparedness should be strengthened, including implementation of high-quality surveillance systems to monitor epidemiology. While the main focus should be on these public health initiatives to increase vaccination coverage, slightly more benefits could come from evolution of current vaccines.

PLAIN LANGUAGE SUMMARYWhat is the context?Measles, mumps, and rubella are highly contagious diseases associated with significant medical and societal burden. Effective vaccines against these diseases are available, and the implementation of vaccination programs drastically reduced disease incidence globally. However, reports of measles and mumps outbreaks in the last few years highlight remaining challenges to eliminate these diseases.What does the review highlight?We conducted a literature review to identify challenges associated with controlling measles, mumps, and rubella infections, and interventions needed to address them. We identified 11 challenges mainly related to low immunization coverage and vaccine characteristics. Societal challenges could be addressed by increasing awareness of disease severity and vaccines impact, targeting high-risk, unvaccinated, and under-vaccinated populations, improving vaccination access, setting up clear outbreak preparedness plans, and implementing country-specific vaccination policies. System weaknesses could be addressed through improving vaccination services and health infrastructure, implementing high-quality surveillance, patient invite, and reminder systems, ensuring vaccine implementation and long-term supply. Interventions related to vaccine characteristic challenges could include adaptation of vaccination schedules (shorter interval between doses, administration of a third dose) and development of vaccines against emerging strains.What is the take-home message?Policymakers should support the following strategies to increase vaccination coverage and reach elimination of measles, mumps, and rubella: strengthening health systems and vaccination access; raising awareness of disease severity and vaccination impact; limiting disease propagation owing to global changing environment and population dynamics (traveling, migration); improving surveillance systems to rapidly address the immunity gaps against disease resurgence.

Long-Term Persistence of Antibody Response with Two Doses of Inactivated Hepatitis A Vaccine in Children.

INTRODUCTION: Hepatitis A virus infection is more severe in adults than children. Although vaccination can protect adults, current childhood programs cover a large population more successfully. Childhood vaccination is, therefore, a solution to protecting adults if it induces lasting immunity. Fifteen-year protection has been demonstrated in children, but longer-term data are only available for adults. We aimed to predict long term persistence of antibody in children beyond 15 years and assess if immunological mechanisms triggered by vaccination support longer-term protection. METHODS: Long-term clinical studies using hepatitis A (HAV) or A/B vaccines (HAB) containing 720 or 1440 Enzyme-linked immunosorbent assay Units (EU) of hepatitis A virus antigen were identified. Duration of persistence of antibodies and possible protection was determined by descriptively comparing antibody geometric mean concentration (GMC) kinetics, as well as GMC (95% confidence interval) at 15 years post-vaccination across studies. Immunological mechanism studies describing hepatitis A vaccination were identified. RESULTS: One study in children 12-15 years (2-dose HAB 720) and four in adults (2-dose HAV 1440 and 3-dose HAB 720) showed comparable GMC kinetics and per year rates of change up to 15 years. At 15 years, the GMC in children [414.7 mEU/ml (336.9; 510.5)] was in the same range as in adults [range 282.6 (217.6; 367.0) to 550.1 (416.0; 727.4)]. Based on these data, mathematical model predictions from adult studies (showing > 85% protected at 50 years) were deemed likely to also apply to children. Studies identified, both humoral and cell-mediated responses are induced following vaccination. CONCLUSION: Based on comparable antibody data in adults and children up to 15 years, similar longer-term antibody persistence is expected in children with 2-dose inactivated hepatitis A 720 containing vaccine at least up to 50 years. Accordingly, improving routine childhood hepatitis A vaccination coverage could protect against more severe disease in adulthood. Fig. 1 Plain language summary TRIAL REGISTRATION: ClinicalTrials.gov identifiers, NCT00875485, NCT01000324, NCT01037114, NCT00289757, NCT00291876.

Vaccine confidence: the keys to restoring trust.

During the 20th century, the discovery of modern vaccines and ensuing mass vaccination dramatically decreased the incidence of many infectious diseases and in some cases eliminated them. Despite this, we are now witnessing a decrease in vaccine confidence that threatens to reverse the progress made. Considering the different extents of low vaccine confidence in different countries of the world, both developed and developing, we aim to contribute to the discussion of the reasons for this, and to propose some viable scientific solutions to build or help restore vaccine confidence worldwide.

Strengthening national health research systems in the WHO African Region - progress towards universal health coverage.

BACKGROUND: Health challenges and health systems set-ups differ, warranting contextualised healthcare interventions to move towards universal health coverage. As such, there is emphasis on generation of contextualized evidence to solve local challenges. However, weak research capacity and inadequate resources remain an impendiment to quality research in the African region. WHO African Region (WHO AFR) facilitated the adoption of a regional strategy for strengthening national health research systems (NHRS) in 2015. We assessed the progress in strengthening NHRS among the 47 member states of the WHO AFR. METHODS: We employed a cross sectional survey design using a semi structured questionnaire. All the 47member states of WHO AFR were surveyed. We assessed performance against indicators of the regional research strategy, explored facilitating factors and barriers to strengthening NHRS. Using the research barometer, which is a metric developed for the WHO AFR we assessed the strength of NHRS of member states. Data were analysed in Excel Software to calculate barometer scores for NHRS function and sub-function. Thematic content was employed in analysing the qualitative data. Data for 2014 were compared to 2018 to assess progress. RESULTS: WHO AFR member states have made significant progress in strengthening their NHRS. Some of the indicators have either attained or exceeded the 2025 targets. The average regional barometer score improved from 43% in 2014 to 61% in 2018. Significant improvements were registered in the governance of research for health (R4H); developing and sustaining research resources and producing and using research. Financing R4H improved only modestly. Among the constraints are the lengthy ethical clearance processes, weak research coordination mechanisms, weak enforcement of research laws and regulation, inadequate research infrastructure, limited resource mobilisation skills and donor dependence. CONCLUSION: There has been significant improvement in the NHRS of member states of the WHO AFRO since the last assessment in 2014. Improvement across the different objectives of the regional research strategy is however varied which compromises overall performance. The survey highlighted the areas with slow improvement that require a concerted effort. Furthermore, the study provides an opportunity for countries to share best practice in areas of excellence.

Immunogenicity of pneumococcal conjugate vaccine formulations containing pneumococcal proteins, and immunogenicity and reactogenicity of co-administered routine vaccines - A phase II, randomised, observer-blind study in Gambian infants.

BACKGROUND: Two conserved pneumococcal proteins, pneumolysin toxoid (dPly) and pneumococcal histidine triad protein D (PhtD), combined with 10 polysaccharide conjugates from the pneumococcal non-typeable Haemophilus influenzae protein D-conjugate vaccine (PHiD-CV) in two investigational pneumococcal vaccine (PHiD-CV/dPly/PhtD) formulations were immunogenic and well-tolerated when administered to Gambian children. Here, we report immunogenicity of the polysaccharide conjugates, and immunogenicity and reactogenicity of co-administered routine vaccines. METHODS: In this phase II, controlled, observer-blind, single-centre study, healthy infants aged 8-10 weeks were randomised (1:1:1:1:1:1) to six groups. Four groups received 3+0 schedule (2-3-4 months [M]) of PHiD-CV/dPly/PhtD (10 or 30 µg of each protein), PHiD-CV, or 13-valent pneumococcal conjugate vaccine; and two groups received 2+1 schedule (2-4-9 M) of PHiD-CV/dPly/PhtD (30 µg of each protein) or PHiD-CV. All infants received diphtheria-tetanus-whole cell pertussis-hepatitis B-Haemophilus influenzae type b (DTPw-HBV/Hib) and oral trivalent polio vaccines (OPV) at 2-3-4 M, and measles, yellow fever, and OPV vaccines at 9 M. We evaluated immune responses at 2-5-9-12 M; and reactogenicity 0-3 days post-vaccination. RESULTS: 1200 infants were enrolled between June 2011 and May 2012; 1152 completed the study. 1 M post-primary vaccination, for each PHiD-CV serotype except 6B and 23F, ≥97.4% (3+0 schedule) and ≥96.4% (2+1 schedule) of infants had antibody concentrations ≥0.2 µg/mL. Immune responses were comparable between groups within the same vaccination schedules. Observed antibody geometric mean concentrations (GMCs) increased by 1 M post-primary vaccination compared to pre-vaccination. In the following months, GMCs and opsonophagocytic activity titres waned, with an increase post-booster for the 2+1 schedule. Immune responses to protein D and, DTPw-HBV/Hib, OPV, measles, and yellow fever vaccines were not altered by co-administration with pneumococcal proteins. Reactogenicity of co-administered vaccines was comparable between groups and did not raise concerns. CONCLUSION: Immune responses to the 10 PHiD-CV polysaccharide conjugates and co-administered vaccines were not altered by addition of dPly and PhtD. ClinicalTrials.gov identifier NCT01262872.

Transformation of World Health Organization's management practice and workforce to fit the priorities of African countries.

INTRODUCTION: The WHO Regional Office for Africa developed an evidence-based tool, called the Dalberg tool to guide the functional review and restructuring of the workforce and management of the country offices to better fit the health priorities of Member States. METHODS: The Dalberg tool was used in conjunction with a series of consultations and dialogues to review twenty-two countries have undergone the functional review. Results: the "core functions" in WHO country offices (WCOs) were identified. These are health coordination, strengthening of health systems, generation of evidence and strategic information management, and preparedness against health emergencies. RESULTS: In order to standardize country office functions, categorization of countries was undertaken, based on specific criteria, such as health system performance towards Universal Health Coverage (UHC), health emergencies, burden of communicable and non-communicable diseases, subnational presence and national population size. CONCLUSION: Following the functional review, the staff is now better aligned with country and organizational priorities. For example, the functional review has taken into consideration: (i) the ongoing polio transition planning; (ii) the implementation of the WHO emergency programme in countries; (iii) the investment case for strengthening routine immunization in Africa; and (iv) regional flagship programmes, such as adolescent health and UHC. The delivery of the core functions above will require the hiring of additional capacities and expertise in most country offices if deemed fit-for-purpose.

Proceedings of the first African Health Forum: effective partnerships and intersectoral collaborations are critical for attainment of Universal Health Coverage in Africa.

BACKGROUND: Universal Health Coverage (UHC)is central to the health Sustainable Development Goals(SDG). Working towards UHC is a powerful mechanism for achieving the right to health and promoting human development which is a priority area of focus for the World Health Organization WHO. As a result, the WHO Regional Office for Africa convened the first-ever Africa Health Forum, co- hosted by the government of Rwanda in Kigali in June 2017 with the theme "Putting People First: The Road to Universal Health Coverage in Africa". The Forum aimed to strengthen and forge new partnerships, align priorities and galvanize commitment to advance the health agenda in Africa in order to attain UHC and the SDGs. This paper reports the proceedings and conclusions of the forum. METHODS: The forum was attended by over 800 participants. It employed moderated panel and public discussions, and side events with political leaders, policy makers and technicians from ministries of health and finance, United Nations agencies, the private sector, the academia, philanthropic foundations, youth, women and non-governmental organizations drawn from within and outside the Region. CONCLUSIONS: The commitment to achieve UHC was a collective expression of the belief that all people should have access to the health services they need without risk of financial hardship. The attainment of UHC will require a significant paradigm shift, including development of new partnerships especially public-private partnerships in selected areas with limited government resources, intersectoral collaboration to engage in interventions that affect health but are outside the purview of the ministries in charge of health and identification of public health issues where knowledge gaps exist as research priorities. The deliberations of the Forum culminated into a "Call-to-Action" - Putting People First: The Road to Universal Health Coverage in Africa, which pledged a renewed determination for Member States, in partnership with the private Sector, WHO, other UN Agencies and partners to support the attainment of the SDGs and UHC. There was agreement that immediate action was required to implement the call-to-action, and that the African Regional Office of WHO should develop a plan to rapidly operationalize the outcomes of the meeting.

Four-Gene Pan-African Blood Signature Predicts Progression to Tuberculosis.

Rationale: Contacts of patients with tuberculosis (TB) constitute an important target population for preventive measures because they are at high risk of infection with Mycobacterium tuberculosis and progression to disease.Objectives: We investigated biosignatures with predictive ability for incident TB.Methods: In a case-control study nested within the Grand Challenges 6-74 longitudinal HIV-negative African cohort of exposed household contacts, we employed RNA sequencing, PCR, and the pair ratio algorithm in a training/test set approach. Overall, 79 progressors who developed TB between 3 and 24 months after diagnosis of index case and 328 matched nonprogressors who remained healthy during 24 months of follow-up were investigated.Measurements and Main Results: A four-transcript signature derived from samples in a South African and Gambian training set predicted progression up to two years before onset of disease in blinded test set samples from South Africa, the Gambia, and Ethiopia with little population-associated variability, and it was also validated in an external cohort of South African adolescents with latent M. tuberculosis infection. By contrast, published diagnostic or prognostic TB signatures were predicted in samples from some but not all three countries, indicating site-specific variability. Post hoc meta-analysis identified a single gene pair, C1QC/TRAV27 (complement C1q C-chain / T-cell receptor-α variable gene 27) that would consistently predict TB progression in household contacts from multiple African sites but not in infected adolescents without known recent exposure events.Conclusions: Collectively, we developed a simple whole blood-based PCR test to predict TB in recently exposed household contacts from diverse African populations. This test has potential for implementation in national TB contact investigation programs.

Strengthening the Acute Flaccid Paralysis (AFP) Surveillance Component of the Polio Eradication Initiative through Short Message Service (SMS) Reminders; Experience from Sokoto State, Nigeria 2014.

Eradication of poliomyelitis remains a public health priority due to the paralytic effects of the virus on children and impact on global health system. However, existing gaps in surveillance can hinder eradication. Improved timeliness of identification and reporting of acute flaccid paralysis (AFP) cases with further confirmation of Wild Poliovirus (WPV) in stool samples, can help Nigeria achieve the performance indicators of non-polio AFP rate of ≥ 2/100,000 population aged < 15 years and ≥80% stool sample collection adequacy. To ascertain the awareness of AFP case definition and detection by health care workers and to evaluate the impact of SMS-based reporting on the AFP surveillance system the study was conducted from November 2013 to July 2014. In Sokoto state, 112 health facilities (focal sites) were operational and participated in this study. All AFP focal points for the 112 facilities were included in the study. In addition to AFP focal points, two clinicians per facility where possible, were included in the study. The study focused exclusively on reports from focal sites. The methodology was a one group pretest-posttest design conducted in 3 phases. 1) Pre-intervention Knowledge, Attitude and Practices (KAP) survey, 2) SMS implementation and 3) Post-intervention KAP. Results were analysed using the independent sample t-test to assess the increase in knowledge, attitudes, or practice scores pre- and post- training. The study showed improved knowledge gap of health care workers on AFP surveillance between pre and post intervention. It shows that this approach of improved surveillance will be effective in countries in hard to reach, access compromised or countries/place without sufficient surveillance staff.

Kinetics of antibodies against pneumococcal proteins and their relationship to nasopharyngeal carriage in the first two months of life.

INTRODUCTION: The currently used Streptococcus pneumoniae vaccines have had a significant impact on the pneumococcal diseases caused by the serotypes they cover. Their limitations have stimulated a search for alternate vaccines that will cover all serotypes, be affordable and effective in young children. Pneumococcal protein antigens are potential vaccine candidates that may meet some of the shortfalls of the current vaccines. Thus, this study aimed to determine the relationship between antibodies against pneumococcal protein antigens and nasopharyngeal carriage in infants. METHODS: One hundred and twenty mother-infant pairs were enrolled into the study. They had nasopharyngeal swabs(NPS) taken at birth and every two weeks for the first eight weeks after delivery, and blood samples were obtained at birth and every four weeks for the first eight weeks after delivery. Nasopharyngeal carriage of S. pneumoniae was determined from the NPS and antibodies against the pneumococcal proteins CbpA, PspA and rPly were measured in the blood samples. RESULTS: The S. pneumoniae carriage rate in infants increased to that of mothers by eight weeks of age. The odds of carriage in infants was 6.2 times (95% CI: 2.0-18.9) higher when their mothers were also carriers. Bacterial density in infants was lower at birth compared to their mothers (p = 0.004), but increased with age and became higher than that of their mothers at weeks 4 (p = 0.009), 6 (p = 0.002) and 8 (p<0.0001). At birth, the infants' antibodies against CbpA, and rPly pneumococcal protein antigens were similar, but that of PspA was lower (p<0.0001), compared to their mothers. Higher antibody concentrations to CbpA [OR (95% CI): 0.49 (0.26-0.92, p = 0.03)], but not PspA and rPly, were associated with protection against carriage in the infants. CONCLUSION: Naturally induced antibodies against the three pneumococcal protein antigens were transferred from mother to child. The proportion of infants with nasopharyngeal carriage and the bacterial density of S. pneumoniae increased with age within the first eight weeks of life. Higher concentrations of antibodies against CbpA, but not PspA and rPly, were associated with reduced risk of nasopharyngeal carriage of S. pneumoniae in infants.

A population-based national estimate of the prevalence and risk factors associated with hypertension in Rwanda: implications for prevention and control.

BACKGROUND: Hypertension is a leading cause of cardiovascular diseases and a growing public health problem in many developed and developing countries. However, population-based data to inform policy development are scarce in Rwanda. This nationally representative study aimed to determine population-based estimates of the prevalence and risk factors associated with hypertension in Rwanda. METHODS: We conducted secondary epidemiological analysis of data collected from a cross-sectional population-based study to assess the risk factors for NCDs using the WHO STEPwise approach to Surveillance of non-communicable diseases (STEPS). Adjusted odds ratios at 95% confidence interval were used to establish association between hypertension, socio-demographic characteristics and health risk behaviors. RESULTS: Of the 7116 study participants, 62.8% were females and 38.2% were males. The mean age of study participants was 35.3 years (SD 12.5). The overall prevalence of hypertension was 15.3% (16.4% for males and 14.4% for females). Twenty two percent of hypertensive participants were previously diagnosed. A logistic regression model revealed that age (AOR: 8.02, 95% CI: 5.63-11.42, p < 0.001), living in semi-urban area (AOR: 1.30, 95% CI: 1.01-1.67, p = 0.040) alcohol consumption (AOR: 1.24, 95% CI: 1.05-1.44, p = 0.009) and, raised BMI (AOR: 3.93, 95% CI: 2.54-6.08, p < 0.001) were significantly associated with hypertension. The risk of having hypertension was 2 times higher among obese respondents (AOR: 3.93, 95% CI: 2.54-6.08, p-value < 0.001) compared to those with normal BMI (AOR: 1.74, 95% CI: 1.30-2.32, p-value < 0.001). Females (AOR: 0.75, 95% CI: 0.63-0.88, p < 0.001) and students (AOR: 0.45, 95% CI: 0.25-0.80, p = 0.007) were less likely to be hypertensive. CONCLUSION: The findings of this study indicate that the prevalence of hypertension is high in Rwanda, suggesting the need for prevention and control interventions aimed at decreasing the incidence taking into consideration the risk factors documented in this and other similar studies.

Mycobacterium tuberculosis Infection in Close Childhood Contacts of Adults with Pulmonary Tuberculosis is Increased by Secondhand Exposure to Tobacco.

Tobacco use is a major risk factor for tuberculosis (TB). Secondhand smoke (SHS) is also a risk factor for TB and to a lesser extent, Mycobacterium tuberculosis infection without disease. We investigated the added risk of M. tuberculosis infection due to SHS exposure in childhood contacts of TB cases in The Gambia. Participants were childhood household contacts aged ≤ 14 years of newly diagnosed pulmonary TB (PTB) cases. The intensity of exposure to the case was categorized according to whether contacts slept in the same room, same house, or a different house as the case. Contacts were tested with an enzyme-linked immunospot interferon gamma release assay. In multivariate regression models, M. tuberculosis infection was associated with increasing exposure to a case (odds ratios [OR]: 3.9, 95% confidence interval [CI]: 2.11-71.4, P < 0.001]) and with male gender (OR: 1.5 [95% CI: 1.12-2.11], P = 0.008). Tobacco use caused a 3-fold increase in the odds of M. tuberculosis infection in children who slept closest to a case who smoked within the same home compared with a nonsmoking case (OR: 8.0 [95% CI: 2.74-23.29] versus 2.4 [95% CI: 1.17-4.92], P < 0.001). SHS exposure as an effect modifier appears to greatly increase the risk of M. tuberculosis infection in children exposed to PTB cases. Smoking cessation campaigns may be important for reducing transmission of M. tuberculosis to children within households.

Efficacy of a novel, protein-based pneumococcal vaccine against nasopharyngeal carriage of Streptococcus pneumoniae in infants: A phase 2, randomized, controlled, observer-blind study.

BACKGROUND: Conserved pneumococcal proteins are potential candidates for inclusion in vaccines against pneumococcal diseases. In the first part of a two-part study, an investigational vaccine (PHiD-CV/dPly/PhtD-30) containing 10 pneumococcal serotype-specific polysaccharide conjugates (10VT) combined with pneumolysin toxoid and pneumococcal histidine triad protein D (30µg each) was well tolerated by Gambian children. Part two, presented here, assessed the efficacy of two PHiD-CV/dPly/PhtD formulations against pneumococcal nasopharyngeal carriage (NPC) prevalence in infants. METHODS: In this phase 2, randomized, controlled, observer-blind trial, healthy infants aged 8-10weeks, recruited from a peri-urban health center, were randomized (1:1:1:1:1:1) into six groups. Four groups received PHiD-CV/dPly/PhtD (10 or 30µg of each protein), PHiD-CV, or 13-valent pneumococcal conjugate vaccine at ages 2-3-4months (3+0 infant schedule) and two groups PHiD-CV/dPly/PhtD-30 or PHiD-CV at 2-4-9months (2+1 infant schedule). The primary objective was impact on non-10VT NPC at ages 5-9-12months. Secondary objectives included confirmatory analysis of protein dose superiority and safety/reactogenicity. Impact on pneumococcal NPC acquisition, bacterial load, and ply and phtD gene sequencing were explored. RESULTS: 1200 infants were enrolled between June 2011 and May 2012. Prevalences of pneumococcal (60-67%) and non-10VT (55-61%) NPC were high at baseline. Across all post-vaccination time points, efficacy of PHiD-CV/dPly/PhtD-10 and PHiD-CV/dPly/PhtD-30 against non-10VT NPC (3+0 schedule) was 1.1% (95% CI -21.5, 19.5) and 2.1% (-20.3, 20.3), respectively; efficacy of PHiD-CV/dPly/PhtD-30 (2+1 schedule) was 0.5% (-22.1, 18.9) versus PHiD-CV. No differences were observed in pneumococcal NPC acquisition, clearance, or bacterial load. Both protein-based vaccines elicited immune responses to pneumococcal proteins. CONCLUSIONS: In this high carriage prevalence setting, inclusion of pneumococcal proteins in the PHiD-CV/dPly/PhtD investigational vaccine had no impact on pneumococcal NPC in infants, regardless of protein dose or schedule. Future evaluations will assess its impact against pneumococcal disease endpoints. FUNDING: PATH, GlaxoSmithKline Biologicals SA. ClinicalTrials.gov identifier NCT01262872.

Polio eradication in the African Region on course despite public health emergencies.

The World Health Organization, African Region is heading toward eradication of the three types of wild polio virus, from the Region. Cases of wild poliovirus (WPV) types 2 and 3 (WPV2 and WPV3) were last reported in 1998 and 2012, respectively, and WPV1 reported in Nigeria since July 2014 has been the last in the entire Region. This scenario in Nigeria, the only endemic country, marks a remarkable progress. This significant progress is as a result of commitment of key partners in providing the much needed resources, better implementation of strategies, accountability, and innovative approaches. This is taking place in the face of public emergencies and challenges, which overburden health systems of countries and threaten sustainability of health programmes. Outbreak of Ebola and other diseases, insecurity, civil strife and political instability led to displacement of populations and severely affected health service delivery. The goal of eradication is now within reach more than ever before and countries of the region should not relent in their efforts on polio eradication. WHO and partners will redouble their efforts and introduce better approaches to sustain the current momentum and to complete the job. The carefully planned withdrawal of oral polio vaccine type II (OPV2) with an earlier introduction of one dose of inactivated poliovirus vaccine (IPV), in routine immunization, will boost immunity of populations and stop cVDPVs. Environmental surveillance for polio viruses will supplement surveillance for AFP and improve sensitivity of detection of polio viruses.