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Gibson D.G.,International Vaccine Access Center | Ochieng B.,Centers for Disease Control and Prevention | Kagucia E.W.,International Vaccine Access Center | Were J.,Centers for Disease Control and Prevention | And 5 more authors.
The Lancet Global Health | Year: 2017

Background As mobile phone access continues to expand globally, opportunities exist to leverage these technologies to support demand for immunisation services and improve vaccine coverage. We aimed to assess whether short message service (SMS) reminders and monetary incentives can improve immunisation uptake in Kenya. Methods In this cluster-randomised controlled trial, villages were randomly and evenly allocated to four groups: control, SMS only, SMS plus a 75 Kenya Shilling (KES) incentive, and SMS plus 200 KES (85 KES = USD$1). Caregivers were eligible if they had a child younger than 5 weeks who had not yet received a first dose of pentavalent vaccine. Participants in the intervention groups received SMS reminders before scheduled pentavalent and measles immunisation visits. Participants in incentive groups, additionally, received money if their child was timely immunised (immunisation within 2 weeks of the due date). Caregivers and interviewers were not masked. The proportion of fully immunised children (receiving BCG, three doses of polio vaccine, three doses of pentavalent vaccine, and measles vaccine) by 12 months of age constituted the primary outcome and was analysed with log-binomial regression and General Estimating Equations to account for correlation within clusters. This trial is registered with, number NCT01878435. Findings Between Oct 14, 2013, and Oct 17, 2014, we enrolled 2018 caregivers and their infants from 152 villages into the following four groups: control (n=489), SMS only (n=476), SMS plus 75 KES (n=562), and SMS plus 200 KES (n=491). Overall, 1375 (86%) of 1600 children who were successfully followed up achieved the primary outcome, full immunisation by 12 months of age (296 [82%] of 360 control participants, 332 [86%] of 388 SMS only participants, 383 [86%] of 446 SMS plus 75 KES participants, and 364 [90%] of 406 SMS plus 200 KES participants). Children in the SMS plus 200 KES group were significantly more likely to achieve full immunisation at 12 months of age (relative risk 1·09, 95% CI 1·02–1·16, p=0·014) than children in the control group. Interpretation In a setting with high baseline immunisation coverage levels, SMS reminders coupled with incentives significantly improved immunisation coverage and timeliness. Given that global immunisation coverage levels have stagnated around 85%, the use of incentives might be one option to reach the remaining 15%. Funding Bill & Melinda Gates Foundation. © 2017 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY license

Feikin D.R.,International Vaccine Access Center | Feikin D.R.,Centers for Disease Control and Prevention | Scott J.A.G.,Wellcome Trust Research Programme | Scott J.A.G.,London School of Hygiene and Tropical Medicine | Gessner B.D.,Voltaire
The Lancet | Year: 2014

Vaccine probe studies have emerged in the past 15 years as a useful way to characterise disease. By contrast, traditional studies of vaccines focus on defining the vaccine effectiveness or efficacy. The underlying basis for the vaccine probe approach is that the difference in disease burden between vaccinated and unvaccinated individuals can be ascribed to the vaccine-specific pathogen. Vaccine probe studies can increase understanding of a vaccine's public health value. For instance, even when a vaccine has a seemingly low efficacy, a high baseline disease incidence can lead to a large vaccine-preventable disease burden and thus that population-based vaccine introduction would be justified. So far, vaccines have been used as probes to characterise disease syndromes caused by Haemophilus influenzae type b, pneumococcus, rotavirus, and early infant influenza. However, vaccine probe studies have enormous potential and could be used more widely in epidemiology, for example, to define the vaccine-preventable burden of malaria, typhoid, paediatric influenza, and dengue, and to identify causal interactions between different pathogens.

Johnson H.L.,International Vaccine Access Center | Nonyane B.A.S.,International Vaccine Access Center | Deloria-Knoll M.,International Vaccine Access Center | OBrien K.L.,International Vaccine Access Center
PLoS ONE | Year: 2013

Background:Pneumococcal pneumonia causes significant morbidity and mortality among adults. Given limitations of diagnostic tests for non-bacteremic pneumococcal pneumonia, most studies report the incidence of bacteremic or invasive pneumococcal disease (IPD), and thus, grossly underestimate the pneumococcal pneumonia burden. We aimed to develop a conceptual and quantitative strategy to estimate the non-bacteremic disease burden among adults with community-acquired pneumonia (CAP) using systematic study methods and the availability of a urine antigen assay.Methods and Findings:We performed a systematic literature review of studies providing information on the relative yield of various diagnostic assays (BinaxNOW® S. pneumoniae urine antigen test (UAT) with blood and/or sputum culture) in diagnosing pneumococcal pneumonia. We estimated the proportion of pneumococcal pneumonia that is bacteremic, the proportion of CAP attributable to pneumococcus, and the additional contribution of the Binax UAT beyond conventional diagnostic techniques, using random effects meta-analytic methods and bootstrapping. We included 35 studies in the analysis, predominantly from developed countries. The estimated proportion of pneumococcal pneumonia that is bacteremic was 24.8% (95% CI: 21.3%, 28.9%). The estimated proportion of CAP attributable to pneumococcus was 27.3% (95% CI: 23.9%, 31.1%). The Binax UAT diagnosed an additional 11.4% (95% CI: 9.6, 13.6%) of CAP beyond conventional techniques. We were limited by the fact that not all patients underwent all diagnostic tests and by the sensitivity and specificity of the diagnostic tests themselves. We address these resulting biases and provide a range of plausible values in order to estimate the burden of pneumococcal pneumonia among adults.Conclusions:Estimating the adult burden of pneumococcal disease from bacteremic pneumococcal pneumonia data alone significantly underestimates the true burden of disease in adults. For every case of bacteremic pneumococcal pneumonia, we estimate that there are at least 3 additional cases of non-bacteremic pneumococcal pneumonia.

Levine O.S.,International Vaccine Access Center | Bloom D.E.,Harvard University | Cherian T.,Immunizations | De Quadros C.,Sabin Institute | And 4 more authors.
The Lancet | Year: 2011

Vaccines have already saved many lives and they have the potential to save many more as increasingly elaborate technologies deliver new and effective vaccines against both infectious diseases - for which there are currently no effective licensed vaccines - such as malaria, tuberculosis, and HIV and non-infectious diseases such as hypertension and diabetes. However, these new vaccines are likely to be more complex and expensive than those that have been used so effectively in the past, and they could have a multifaceted effect on the disease that they are designed to prevent, as has already been seen with pneumococcal conjugate vaccines. Deciding which new vaccines a country should invest in requires not only sound advice from international organisations such as WHO but also a well informed national immunisation advisory committee with access to appropriate data for local disease burden. Introduction of vaccines might need modification of immunisation schedules and delivery procedures. Novel methods are needed to finance the increasing number of new vaccines that have the potential to save lives in countries that are too poor to afford them. Here, we discuss some options. © 2011 Elsevier Ltd.

Gessner B.D.,Agence de Medecine Preventive | Feikin D.R.,International Vaccine Access Center | Feikin D.R.,Centers for Disease Control and Prevention
Vaccine | Year: 2014

Traditionally, vaccines have been evaluated in clinical trials that establish vaccine efficacy (VE) against etiology-confirmed disease outcomes, a measure important for licensure. Yet, VE does not reflect a vaccine's public health impact because it does not account for relative disease incidence. An additional measure that more directly establishes a vaccine's public health value is the vaccine preventable disease incidence (VPDI), which is the incidence of disease preventable by vaccine in a given context. We describe how VE and VPDI can vary, sometimes in inverse directions, across disease outcomes and vaccinated populations. We provide examples of how VPDI can be used to reveal the relative public health impact of vaccines in developing countries, which can be masked by focus on VE alone. We recommend that VPDI be incorporated along with VE into the analytic plans of vaccine trials, as well as decisions by funders, ministries of health, and regulatory authorities. © 2014 Elsevier Ltd.

A new report finds some progress in combatting pneumonia and diarrhea among young children in the nations most severely impacted by the two diseases, but they remain responsible for hundreds of thousands of preventable deaths around the world. In 2015, pneumonia and diarrhea together led to one of every four deaths globally that occurred in children under five years old. These two diseases are largely preventable with vaccines and simple and inexpensive treatments. Of the 15 countries profiled in the report -- those with the highest rates of death globally due to the two diseases -- seven have mortality rates of 25 per 1,000 live births or higher due to pneumonia and diarrhea alone. This translates into an estimated 450,000 deaths among children under age five in these countries. The 2016 Pneumonia and Diarrhea Progress Report: Reaching Goals Through Action and Innovation is being issued by the International Vaccine Access Center (IVAC) at the Johns Hopkins Bloomberg School of Public Health today ahead of World Pneumonia Day, which takes place every year on November 12. IVAC began publishing its annual report in 2010 with the goal of highlighting two diseases that would, if more children received vaccinations and/or treatment, lead to fewer deaths. "Pneumonia and diarrhea fly under the radar," says Kate O'Brien, MD, MPH, a professor in the Bloomberg School's Department of International Health and IVAC's executive director. "These illnesses are so common that many people and organizations fail to recognize the need to step up efforts and identify creative solutions to fight them. Although most cases are easily prevented and treated, they often prove deadly when families cannot access basic health services such as vaccines and antibiotic treatment." In the report, IVAC identifies the 15 countries with the greatest number of deaths from pneumonia and diarrhea among children under the age of five in a given year. IVAC then uses a scoring method based on the Global Action Plan for the Prevention of Pneumonia and Diarrhea (GAPPD) developed by the World Health Organization and UNICEF. A country's "GAPPD score" measures the use of interventions that protect against, prevent and treat pneumonia and diarrhea. The higher the score, the more interventions are being used. These interventions include vaccination, exclusive breastfeeding, access to care and use of antibiotics, oral rehydration solution and zinc to treat the illnesses. These measures are known to prevent childhood deaths due to pneumonia and diarrhea and could help achieve the United Nations' Sustainable Development target goal of reducing under-five mortality to at least 25 per 1,000 live births by 2030. Key report findings include: • Overall GAPPD scores in 2016 varied widely from a low of 20 percent (Somalia) to a high of 74 percent (Tanzania), with all 15 focus countries falling below the 86 percent target for the overall GAPPD score. In 2015, the scores varied from 20 percent (Somalia) to 72 percent (Tanzania), virtually unchanged compared to this year's scores. • Twelve countries improved their GAPPD scores since 2015, with Niger making the biggest gain, up 11 points. In 2015, seven countries improved their score. • Only six of the highest-burden countries (Angola, Ethiopia, India, Niger, Sudan and Tanzania) have introduced rotavirus vaccines in their routine immunization program to help prevent a substantial portion of diarrhea deaths and hospitalizations. India introduced rotavirus vaccines in four states in 2015. • Fifteen years after pneumococcal conjugate vaccines' first introduction globally in 2000 (the United States was first to implement the vaccine), five of the highest pneumonia burden countries (India, Indonesia, Chad, China and Somalia) are still not using the vaccine in their routine immunization programs. India recently announced a partial introduction in five states, beginning in 2017. • Antibiotic use to treat pneumonia in the 15 highest-burden countries varies greatly, from seven percent in Ethiopia to 64 percent in Afghanistan. • Rates of exclusive breastfeeding during a child's first six months of life remain low. Currently, 10 of the 15 countries with the most child pneumonia and diarrhea deaths have exclusive breastfeeding rates that still fall short of the 50 percent GAPPD target. There is strong evidence demonstrating that about half of all diarrhea episodes and about a third of respiratory infections could be averted by breastfeeding. The rate of death from all causes in children under the age of five years has been cut by more than half worldwide since 1990, from 91 deaths per 1,000 live births to 43 in 2015. "The report highlights incredible progress in child health since 1990, but cautions against complacency in fighting the two leading killers of children," O'Brien says. "We can do better, we can make better use of the tools in hand and we have great opportunities to create innovations that will save lives." See the report at:

McIntyre P.B.,University of Sydney | O'Brien K.L.,International Vaccine Access Center | Greenwood B.,London School of Hygiene and Tropical Medicine | Van De Beek D.,University of Amsterdam
The Lancet | Year: 2012

Three bacteria-Haemophilus infl uenzae, Streptococcus pneumoniae, and Neisseria meningitidis-account for most acute bacterial meningitis. Measurement of the eff ect of protein-polysaccharide conjugate vaccines is most reliable for H infl uenzae meningitis because one serotype and one age group account for more than 90% of cases and the incidence has been best measured in high-income countries where these vaccines have been used longest. Pneumococcal and meningococcal meningitis are caused by diverse serotypes and have a wide age distribution; measurement of their incidence is complicated by epidemics and scarcity of surveillance, especially in low-income countries. Near elimination of H infl uenzae meningitis has been documented after vaccine introduction. Despite greater than 90% reductions in disease attributable to vaccine serotypes, all-age pneumococcal meningitis has decreased by around 25%, with little data from low-income settings. Near elimination of serogroup C meningococcal meningitis has been documented in several high-income countries, boding well for the eff ect of a new serogroup A meningococcal conjugate vaccine in the African meningitis belt.

Levine O.,International Vaccine Access Center
American Journal of Public Health | Year: 2012

For the influenza pandemic of 2009-2010, countries responded to the direct threat of influenza but may have missed opportunities and strategies to limit secondary pneumococcal infections. Delivering both vaccines together can potentially increase pneumococcal polysaccharide vaccine (PPV23) immunization rates and prevent additional hospitalizations and mortality in the elderly and other highrisk groups. We used PubMed to review the literature on the concomitant use of PPV23 with seasonal influenza vaccines. Eight of 9 clinical studies found that a concomitant program conferred clinical benefits. The 2 studies that compared the cost-effectiveness of different strategies found concomitant immunization to be more cost-effective than either vaccine given alone. Policymakers should consider a stepwise strategy to reduce the burden of secondary pneumococcal infections during seasonal and pandemic influenza outbreaks.

Constenla D.O.,International Vaccine Access Center
Revista Panamericana de Salud Publica/Pan American Journal of Public Health | Year: 2015

Objective. A decision-analytic model was constructed to evaluate the economic impact of post-introduction pneumococcal conjugate vaccine (PCV) programs in Ecuador, Honduras, and Paraguay from the societal perspective. Methods. Hypothetical birth cohorts were followed for a 20-year period in each country. Estimates of disease burden, vaccine effectiveness, and health care costs were derived from primary and secondary data sources. Costs were expressed in 2014 US$. Sensitivity analyses were performed to assess the impact of model input uncertainties. Results. Over the 20 years of vaccine program implementation, the health care costs per case ranged from US$ 764 854 to more than US$ 1 million. Vaccination prevented more than 50% of pneumococcal cases and deaths per country. At a cost of US$ 16 per dose, the cost per disability-adjusted life year (DALY) averted for the 10-valent PCV (PCV10) and the 13-valet PCV (PCV13) ranged from US$ 796 (Honduras) to US$ 1 340 (Ecuador) and from US$ 691 (Honduras) to US$ 1 166 (Ecuador) respectively. At a reduced price (US$ 7 per dose), the cost per DALY averted ranged from US$ 327 (Honduras) to US$ 528 (Ecuador) and from US$ 281 (Honduras) to US$ 456 (Ecuador) for PCV10 and PCV13 respectively. Several model parameters influenced the results of the analysis, including vaccine price, vaccine efficacy, disease incidence, and costs. Conclusions. The economic impact of post-introduction PCV needs to be assessed in a context of uncertainty regarding changing antibiotic resistance, herd and serotype replacement effects, differential vaccine prices, and government budget constraints.

Davis S.M.,International Vaccine Access Center | Deloria-Knoll M.,International Vaccine Access Center | Kassa H.T.,International Vaccine Access Center | O'Brien K.L.,International Vaccine Access Center | O'Brien K.L.,Center for American Indian Health
Vaccine | Year: 2013

Background: Invasive disease due to Streptococcus pneumoniae remains an important worldwide cause of morbidity and mortality, particularly in young children and the elderly. The development and use of pneumococcal conjugate vaccines (PCVs) have had a dramatic impact on rates of vaccine-type invasive pneumococcal disease (IPD) not only in the pediatric population targeted for vaccination but in non-vaccinated age-groups as well. This indirect effect is directly mediated by a reduction of vaccine-type nasopharyngeal carriage and thus transmission by vaccinated children. Current PCV licensing procedures do not take into consideration nasopharyngeal carriage impact, and thus the indirect effect. This review summarizes the evidence for the indirect effect of PCV on vaccine-type disease and its correlation with changes in carriage among unvaccinated populations, to assess the basis for inclusion of carriage in the PCV licensing process. Methods: Randomized controlled trials, surveillance and other observational studies published between 1994 and 2013 were systematically identified from global, regional and review databases and conference abstracts. We included as primary evidence, studies in non-vaccinated groups addressing changes in both vaccine-type IPD and carriage between pre- and post-PCV introduction periods; studies missing one of these four components were included as supporting rather than primary evidence. Results: We identified studies from 14 countries, nearly all developed countries. Vaccine-type IPD and carriage in non-targeted populations consistently decreased after PCV introduction, with the magnitude of decrease growing over time. Where IPD and carriage were observed in the same population, VT-decreases occurred contemporaneously. These relationships held true across age-groups and between indigenous and non-indigenous populations in the US and Australia. Conclusions: Indirect PCV impact on VT-IPD and VT-carriage has been significant. Impact on carriage should be considered for inclusion in the PCV licensure process as a predictor of indirect effects. © 2013.

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