Tobacco use continues to be the leading cause of preventable illness and death in the United States. Remarkably, more than nine million preschool-aged children are exposed to secondhand smoke, resulting in increased rates of morbidity and mortality. Even more disturbing is that tobacco use is highest among people with the lowest levels of income and education. Thus, reaching these populations is a challenge facing tobacco control programs. This report describes an innovative pilot project implementing a systems change model that involves multiple stakeholders in integrating evidence-based cessation strategies into federal Head Start programs, which serve low-income adults and their children. The Tobacco Cessation Initiative was developed through a partnership between the American Legacy Foundation, the Mailman School of Public Health at Columbia University, and the Louisiana State University Health Sciences Center School of Public Health. The partnership developed guidelines to fit into the overall mission of Head Start by enabling participating sites to incorporate tobacco cessation identification and referral protocols into their existing infrastructures. This program allowed Head Start sites to incorporate, into their existing family services, protocols for user identification and referral; build partnerships with groups supporting tobacco cessation; link families to cessation services; and educate families about risks associated with exposure to secondhand smoke. Applying system strategies in non-clinical settings such as Head Start offers a way to improve the health and quality of life of preschool children at the highest risk for exposure to secondhand smoke. Although the prevalence of tobacco use is decreasing, one of five adults in the U.S. still smokes, and cigarette smoking continues to be the leading cause of preventable illness and death . The higLow SES and tobacco is an issue for children as well as adults, for 26.2 % of children live in households where someone smokes. Moreover, in households below the poverty line, the percentage is 36.9 % . Nearly Although smokers with lower levels of education generally have less knowledge about the negative health effects associated with smoking, many are interested in quitting . EvidencThis paper describes the development of the HS Tobacco Cessation Initiative, a program promoted by The American Legacy Foundation (Legacy), to incorporate into existing services, protocols to engage families in discussions about tobacco use, to identify tobacco users in households, to build partnerships with groups providing cessation services, and to educate families about risks associated with exposure to SHS.This study was approved by the Institutional Review Board of Louisiana State University Health Sciences Center (LSUHSC). The concept for engaging HS sites in tobacco cessation developed from a partnership between Legacy and the Mailman School of Public Health (MSPH) at Columbia University. Free to Grow (FTG), a community-based initiative of the MSPH, provided entry to 15 HS sites. Of these, 4 agreed to participate in the formative phase of the Initiative.Once the four pilot sites were selected, Legacy and MSPH entered into collaboration with the Behavioral and Community Health Sciences Program of the LSUHSC School of Public Health. The experience of this group in initiating systems change in organizations serving high-risk populations was integral to the development of Initiative guidelines, which were designed to enable participating sites to incorporate cessation identification and referral protocols into their existing infrastructures , 8. ThisFigure There were three phases to this project: formative pilot, program implementation, and site expansion. The Initiative started in 2004 with a 15-month formative phase supported by Legacy. Four HS sites participated in this phase; these sites are described below. Program development continued in 2006 with an implementation program in Pierce County, Washington, and, in 2007, with a more extensive effort in King County, Washington. The goal of this process was to integrate tobacco control strategies into existing HS infrastructure and protocols and to identify strategies for statewide implementation. Since all HS children and their families receive a screening for needs assessment, adding tobacco use and SHS exposure to HS forms provided a framework for including tobacco control in existing protocols.The formative pilot (Phase I) was designed to determine the feasibility of applying, in an HS setting, strategies to integrate, into existing practices, identification and treatment of tobacco use as recommended by the U.S. Public Health Service (USPHS)  and engaDuring Phase I, a series of surveys was administered to determine the extent to which the four sites focus on addressing tobacco issues with their HS families. HS directors completed a modified Baseline Facility Survey (BFS) used in the public hospital system in Louisiana . The dirThe results indicated that directors of the pilot sites recognized the need to change the priority given to addressing tobacco use among HS families; could identify system and resource barriers to tobacco cessation education, training, and outreach; could recommend mechanisms to identify tobacco users; and could educate staff about tobacco cessation and outreach Table .Table 1OIn October 2004, 15 people, representing the four sites, attended a 2-day training session. Legacy provided information about nicotine addiction, evidence-based cessation resources, and the principles and practice of Brief Tobacco Intervention (BTI) , which iThe participants were then able to (a) identify common opportunities and challenges to incorporating tobacco cessation activities into HS environments; (b) draft an implementation plan for cessation activities for presentation to their site directors; (c) identify target populations for inclusion in the cessation models; and (d) perform a preliminary survey of community cessation resources.Personnel at each of the four pilot sites developed cessation models that reflected their community context and partnerships with local agencies addressing tobacco issues. Elements associated with program options varied in complexity, intensity, and staff involvement. There were 5 different options for implementation of cessation-related activities Table . Option The MEO site consisted of 15 centers with 70 staff members serving 298 families. Two HS and eight staff members of partner organizations were trained to provide cessation services. Of the 66 HS households identified as having at least one smoker, 14 individuals accepted a referral, and five of these made a connection with the cessation resource. Tobacco education and cessation information were provided to 300 adults.The CAP served 1262 families, all of whom were queried about household smokers and interest in cessation. All households with smokers (n = 325) received smoking cessation educational information and referral information. Of these, 45 indicated an interest in attending smoking cessation groups; 7 participated in one or more sessions; and 15 reported a contact with the state quit-line.UMHS developed a cessation resource guide and informed their staff members about cessation resources in the community. They added cessation education for families to their regular caseload. Parents in selected centers were shown a 5-min video on SHS. In conjunction with completing a questionnaire, 2350 persons who were enrolled in the Women, Infants and Children program received tobacco education. Of the 478 families enrolled in HS centers, 45 had at least one smoker in the household; seven accepted referral to cessation services; and 4 connected with the referral resource.Marathon County Child Development Agency used a similar approach, informing 50 staff members about community resources and about referring HS families to community-based cessation providers. In HS households, 146 smokers were identified. Of these, 22 were interested in quitting soon; 28 wanted to quit in the next 30–60 days; 16 wanted to quit within the next year; and 80 were not interested in quitting.Phase I formative pilot provided data on the feasibility of using systems change strategies to integrate the identification and treatment of tobacco use recommended in the USPHS 2000 clinical practice guideline in an HS setting. It identified common points of access, existing practices, and personnel most likely to engage families about tobacco use. These activities identified useful strategies that provided a framework for the next phase of the project, program implementation.The Phase II, Program Implementation, was conducted in Pierce County, Washington, at seven HS sites. All HS families were educated about the health risks associated with exposure to SHS, and households with tobacco users were assisted with obtaining cessation services. Strategies, identified in Phase I, included staff training, systems change, and the establishment of new partnerships. Staff training, conducted by regional and national personnel, included tobacco education classes, introductions to BTI and MI, discussion of local and state cessation resources, and alteration of HS forms to identify tobacco users. The family assessment allowed discovery of families with tobacco users. Forms were modified to include questions on tobacco use among family members, household rules restricting tobacco use, and children’s exposure to SHS.Phase II, the timing and processes for integrating tobacco cessation programming into HS facilities were refined. For tobacco programming to occur in tandem with the HS calendar, staff training and system changes were accomplished in the year prior to program initiation. Changing HS forms improved identification of tobacco users and prompted discussions about tobacco use. One finding in this phase was that, in HS, the months of October through February, during which time new and returning students are enrolled and registered, offered the best opportunity to complete training, change forms, and develop new partners.In Phase III to include Public Health—Seattle & King County (PHSKC) in Seattle, Washington, and 12 HS sites, which included 219 staff members and the capacity for 1,294 child enrollees. This phase focused on expanding the reach of the Initiative and understanding the level of technical assistance and stakeholder involvement needed for implementation. The majority of these sites were served by an agency that also served the Phase II sites in King County and had been exposed to form changes through this agency before Phase III began. Baseline assessment of new sites was accomplished by interviews with the site directors or their designee between January and March, 2008. For follow-up, the assessment was re-administered one year later. As in Pierce County, the HS staff in King County received training regarding problems associated with use of tobacco, BTI, MI, and local cessation resources. PHSKC also made small reimbursement-based grants of $2,500 available to sites each of 2 years. Sites mainly used funds for materials and food for family activities. Representatives from nine of the sites attended a two-day group training prior to initiation of the effort in December. At all facilities, on-site training was conducted by PHSKC educators in June, 2008. Training ranged from 2 to 6 h. One site received an introductory training on tobacco issues, while all others had training on BTI. Five sites also had MI training on-site. Receptiveness to and attitudes about tobacco intervention were assessed before and after training. Participating in the training sessions were 101 staff members (52 %); representatives from six of the twelve sites completed both pre- and post-training assessments. Assessment of attitudes about SHS exposure and tobacco interventions before and after training indicated that staff entered training believing that counseling families about SHS exposure and tobacco cessation was important. Prior to training, however, few were confident in their skills for treating tobacco use; after training, there was a fourfold increase in staff confidence.In 2007, the Initiative was expanded to additional sites as During Phase III, home visits, site-based support, educational groups, and meetings with parents provided opportunities to engage parents about tobacco use. At baseline, both resource and system barriers to addressing tobacco use were identified. These included lack of knowledge and education, competing priorities for resources and time, and the lack of a system for screening and utilizing information on smoking status. Ten sites participated in a 12-month follow up and reported increases in staff training to conduct brief interventions for tobacco use (from 1 to 10 sites), delivery of tobacco interventions , systems to document tobacco use and smoke exposure (from 7 to 9), and use of data regarding family tobacco use and SHS exposure to provide resources (from 6 to 10). Nine sites reported working with 109 families to address tobacco use and exposure to SHS, and one site introduced a written plan for addressing tobacco use and SHS exposure. Competing priorities and lack of systems persisted as barriers at follow-up, but lack of knowledge did not.The HS Tobacco Cessation Initiative was grounded in a systems-change approach designed to increase the capacity of HS centers in addressing high rates of tobacco use among low SES families and the exposure of children to SHS. Strategies included adding questions about tobacco use to HS standard forms; enhancing protocols to assess tobacco use; helping administration and staff understand why tobacco control should be a priority; and training staff in how to engage family members in discussions about tobacco use, SHS exposure risks, and cessation, and to make appropriate referrals to cessation support groups . ProtocoIn Phase I, three steps were identified as essential for implementation of cessation support within the HS structure: (1) training to increase staff knowledge of the effects of tobacco use and skill building in the use of MI and BTI; (2) establishing relationships with local and state tobacco cessation providers; and (3) revising HS protocols to identify, engage, and refer family members who use tobacco to appropriate cessation services.Phase II confirmed the following: (1) County health departments will support HS and provide resources to engage families about tobacco use and SHS exposure and provide technical assistance to ensure implementation of newly acquired skills, such as MI and BTI. (2) Existing assessment protocols and family support practices within HS programs provide a point of access for identifying tobacco users. Embedding tobacco questions in the HS forms allows discussions about tobacco use and permits staff to explore readiness to make a quit attempt and willingness to ban or restrict household tobacco use. (3) Modifying forms and program practices should begin 6–9 months prior to the start of a school year and should include input from governing entities and site personnel.In Phase III, resource and system barriers to addressing tobacco use were a key focus, and staff training was identified as an essential component of the Initiative. Follow-up assessment found changes in practices to deliver tobacco interventions, including systematic changes in documentation.Previous studies indicate that after participation in an MI counseling session, parents smoked fewer cigarettes and household nicotine levels decreased , 14. In The systems changes observed in this project required the support of administrators and others responsible for shaping programmatic focus and for building staff support and capacity. Program directors participated in discussions about the importance of addressing tobacco use among HS families, training staff to engage families about tobacco use, and including tobacco assessment and engagement as a component of staff supervision. Each was considered a catalyst for adoption of the Initiative, and for improving the acceptability of engaging families about tobacco use as a part of the commitment to the well-being of the enrolled children. Implementation of the Initiative required formation of relationships between HS staff and local health departments, cessation providers, state health departments, and state quit-line providers. As such, system changes will be more likely achieved when the National Office of Head Start adopts performance standards that specifically address tobacco use and SHS exposure.Limitations: while aspects of systems change could be directly observed , changes in practice  were measured by report of site directors or designees. Direct measurement of these changes and the extent to which they are sustained is warranted.To achieve widespread changes in HS staff and family behaviors, implementation must focus building a sustainable delivery model that includes training personnel to interact with the priority population and expanding strategically across HS sites . Applyin


Many features of this outbreak reinforce the benefit of continued investment in global health security. The variety of factors that contributed to the initial undetected spread of Ebola virus disease in West Africa during 2013–2016 and the difficulty controlling the outbreak once the etiology was identified highlight priorities for disease prevention, detection, and response. These factors include occurrence in a region recovering from civil instability and lacking experience with Ebola response; inadequate surveillance, recognition of suspected cases, and Ebola diagnosis; mobile populations and extensive urban transmission; and the community’s insufficient general understanding about the disease. The magnitude of the outbreak was not attributable to a substantial change of the virus. Continued efforts during the outbreak and in preparation for future outbreak response should involve identifying the reservoir, improving in-country detection and response capacity, conducting survivor studies and supporting survivors, engaging in culturally appropriate public education and risk communication, building productive interagency relationships, and continuing support for basic research. Ebolavirus (family Filoviridae). Ebolaviruses now include EBOV, Sudan virus, Reston virus, Taï Forest virus and Bundibugyo virus. The other genus in the family Filoviridae is Marburgvirus, consisting of Marburg virus and Ravn virus , both of which are associated with severe disease (Marburg virus disease [MVD]) in humans  in Zaire (currently Democratic Republic of Congo) and Sudan (currently Republic of South Sudan)  and domestic transmission  were reported for the first time in several countries  or duiker bushmeat ; the West African outbreak was the first to include multiple reintroductions to urban areas (such as Conakry) from human cases and extensive urban transmission. Porous borders and high population mobility within each country and into neighboring countries exacerbated widespread dissemination of disease from urban and rural transmission  as a reservoir for MBGV, and MBGV spillover events from bats to humans have been documented , and viral RNA detection was localized to the injection site , hammer-headed bat (Hypsignathus monstrosus), Franquet's epauletted fruit bat (Epomops franqueti), straw-colored fruit bat (Eidolon helvum), and Angolan free-tailed bat (Mops condylurus)   and popudylurus)  includinCurbing disease spread requires rapid identification of the initial human case or cluster after a spillover event to permit patient isolation and timely contact tracing. The payoff for investment in surveillance systems and diagnostic capacity to rapidly identify and respond to outbreaks is illustrated by efforts in Uganda and Democratic Republic of Congo, where the past several EVD and MVD outbreaks were quickly identified and restricted to a few cases. Effective contact tracing to interrupt disease transmission is personnel intensive and requires rapid organization and deployment after notification of suspected cases. In all EVD outbreaks to date, most transmission events involve close-contact human-to-human transmission. Because resources are often limited, case investigations should thoroughly rule out known sources of EBOV transmission before investigating speculated or new  sources that have never been reported to be associated with disease in previous filovirus outbreaks. Accomplishing the aforementioned recommendations requires increased awareness at the community clinic level, improved quality of central laboratories and capacity for specimen transport , and more epidemiologists throughout the region. Finally, laboratorians and epidemiologists must work closely with well-trained clinical and infection control personnel to effectively identify and isolate infectious persons . If appropriate diagnostic samples are not collected, cases might be missed at critical points in the response. Blood is the most sensitive diagnostic specimen early in EVD; oral swabbing, although less invasive, does not offer adequate sensitivity until late in the course of disease, but it is a sensitive and appropriate modality for testing postmortem specimens . Sexual1 [42,43 ). This o2,43 [44 ), semen 4 [17,45 ), and ce7,45 [46 ) of pati47 [48,49 [Although understanding putative disease transmission from convalescent patients is essential to prevent EVD, clinicians and public health professionals also must investigate and address disease sequelae and social stigma associated with EVD in affected populations. Convalescent EVD patients reported arthralgia and myalgia more significantly than control patients during the 1995 Kikwit outbreak (47 ). EVD su7 [48,49 ).50 [In addition to medical burdens associated with recovery, survivors are concurrently dealing with considerable psychological issues of fear, denial, and shame. In severe instances, the social stigma associated with disease can be profound, resulting in abandonment by family and friends (reference 50 ).51,52 [52 [52–54 [54 [The response to an EVD outbreak requires rapid, effective, widespread public education. In addition to increased potential for transmission, a lack of public education and knowledge can contribute to panic, anxiety, and psychosocial trauma; fear and distrust of treatment units and responders, sometimes to the point of violence; and isolation, stigmatization, and community ostracism of survivors and family members of patients . Despit1,52 [52 ). To be 2 [52–54 ). Risky 2–54 [54 ).55 [56 [57,58 [Risk communication can prevent or greatly reduce transmission. EBOV transmission occurs through close contact with symptomatic EVD patients. Familial and social networks play a major role in transmission, particularly through caregivers’ contact with infectious fluids from ill persons at home and in healthcare facilities and through contact with deceased persons during funeral rites. Viral transmission is relatively inefficient compared with other highly infectious agents (reference 55 ). An exc55 [56 ): person6 [57,58 ), situatOverall outbreak prevention and response will benefit greatly from continuing efforts to develop relationships with nongovernment organizations operating in the region and encouragement of constructive reform of national and international response agencies. We believe the very large and complex nature of the outbreak made communication within and among agencies exceptionally difficult during the outbreak. Frequently, well-intended centralized decision-making did not translate into appropriate application in the field. During the outbreak, partnering among agencies evolved in an effort to improve communication and the outcome of collaborative efforts, but further improvements are possible. Delegating roles among agencies in accordance with their strengths and abilities to acquire the necessary resources for epidemiologic investigations, diagnostics, clinical care, media relations, public education, and logistics might improve efficiency.Pathogenesis studies and development of diagnostic tests, therapeutic drugs, and vaccines are the foundation of the public heath response. The international scientific community must continue to prioritize research on EBOV and viral pathogens that have yet to manifest into large outbreaks but have the fundamental characteristics to do so: viruses causing high rates of illness and death that are capable of person-to-person transmission and lack therapeutic drugs, vaccines, and other interventions . The development and study of new tools toward the end of an outbreak is more likely to be hampered by a lack of patients, as we observed with the EBOV vaccine trials and new diagnostic test evaluations. Thus, future vital research projects should be poised to deploy at the start of new outbreaks, which will require prioritization and substantial regulatory forethought and preparation. However, research projects should not detract from outbreak response. The benefits of research investigations and fundamental response efforts must be balanced appropriately. In response to the outbreak, EBOV researchers worked together in a remarkable effort to advance research and address questions from the field in real time. Interagency collaborations and the open communication of data should continue after the outbreak to develop vaccines and therapeutic drugs and to address key questions on EBOV and other high-consequence, high-containment hemorrhagic fever viruses.The large size and long duration of the West Africa EVD outbreak and the resulting enormous national and international response efforts yielded many lessons for improved prevention and control efforts for emerging viral diseases. Although the current outbreak comes to a close and other health crises emerge in the news headlines, we must not forget that many features of this tragic outbreak strongly reinforce the benefit of continued investment in global health security efforts.Technical Appendix. Additional references.


Interventions to reduce the burden of disease and mortality in sub-Saharan Africa increasingly recognize the important role that drug retailers play in delivering basic healthcare services. In Nigeria, owner-operated drug retail outlets, known as patent and proprietary medicine vendors (PPMVs), are a main source of medicines for acute conditions, but their practices are not well understood. Greater understanding of the role of PPMVs and the quality of care they provide is needed in order to inform ongoing national health initiatives that aim to incorporate PPMVs as a delivery mechanism.This paper reviews and synthesizes the existing published and grey literature on the characteristics, knowledge and practices of PPMVs in Nigeria. We searched published and grey literature using a number of electronic databases, supplemented with website searches of relevant international agencies. We included all studies providing outcome data on PPMVs in Nigeria, including non-experimental studies, and assessed the rigor of each study using the WHO-Johns Hopkins Rigor scale. We used narrative synthesis to evaluate the findings.We identified 50 articles for inclusion. These studies provided data on a wide range of PPMV outcomes: training; health knowledge; health practices, including drug stocking and dispensing, client interaction, and referral; compliance with regulatory guidelines; and the effects of interventions targeting PPMVs. In general, PPMVs have low health knowledge and poor health treatment practices. However, the literature focuses largely on services for adult malaria, and little is known about other health areas or services for children.This review highlights several concerns with the quality of the private drug retail sector in Nigeria, as well as gaps in the existing evidence base. Future research should adopt a more holistic view of the services provided by PPMV shops, and evaluate intervention strategies that may improve the services provided in this sector. The private sector delivers a substantial portion of healthcare services in many low- and middle-income countries . Across In Nigeria, owner-operated drug retail outlets, or patent and proprietary medicine vendors (PPMVs), are a main source of medicine for acute conditions . NationaPPMVs are defined as “a person without formal training in pharmacy who sells orthodox pharmaceutical products on a retail basis for profit” . They wePPMV licensure does not require formal training in medicine or pharmacy . Rather,Given their numbers, market share, and presence in rural communities, PPMVs represent an important opportunity for improving the delivery of primary healthcare commodities and services. There is growing interest among policymakers and program implementers in Nigeria to further engage PPMVs in primary health care delivery, as evidenced by a number of recent national health initiatives and regulatory changes that explicitly address PPMVs. For example, in 2005, the Essential Medicines list that outlines the drugs PPMVs are permitted to dispense was amended to allow PPMVs to sell artemisinin-based combination therapies (ACTs)  after thThe Government of Nigeria has similarly committed to adding pediatric zinc and co-packaged zinc and oral rehydration salts (ORS) to PPMVs’ list of approved medications as part of the national Essential Medicines Scale-Up Plan. The Plan also includes implementation of continuous education for PPMVs to improve care for common childhood illness . PPMVs hAcross many countries in sub-Saharan Africa, privately owned drug shops, akin to Nigeria’s PPMVs, have increasingly been recognized as important providers of health commodities. Two recent reviews were completed on the characteristics and practices of specialized drug shops and related interventions in sub-Saharan Africa ,31. ThesIn this article, we comprehensively review the evidence on the characteristics, knowledge and practices of PPMVs in Nigeria in order to assess the strength of the existing evidence base, synthesize what is known about this sector of providers, and identify the remaining gaps in knowledge where evidence is weak or does not exist. The results of the review are used to determine priority areas for research and evaluation that are needed to inform effective PPMV intervention design in Nigeria and highlight opportunities for strengthening PPMV practice within the current regulatory context in the country.We searched the published literature using the following electronic databases: PubMed, Social Science Citation Index, Science Citation Index, and Global Health. Grey literature was identified through web searches (Google Scholar) and searches of relevant international agencies, including the United States Agency for International Development, the UK Department for International Development, World Health Organization, and World Bank. Additional literature was identified through searching the reference lists of included articles. Our search included a combination of terms on “Nigeria” and “drug” or “medicine,” and “retailers,” “dealers,” “shops,” “stores,” “detailers,” “sellers,” “vendors,” “outlets,” “dispensers,” or “dispensaries.”We included all articles that presented outcome data on PPMVs. We excluded articles on other types of drug retailers, such as pharmacists and itinerant drug hawkers, which are governed by different policy and regulatory statutes than PPMVs. Due to the limited scholarship on this topic, we included all qualitative and quantitative studies regardless of design, and included studies on any outcome within the PPMV sector. We included only articles published in 2000 or after; changes to the scope of practice and monitoring guidelines that affect the role of PPMVs within Nigeria’s health system make studies published after this date of greater relevance to programmatic and policy initiatives on PPMV practice.Two authors independently screened all titles and abstracts to identify articles for inclusion. Discrepancies in determination of eligibility were decided through consultation with a third author. In order to meet the eligibility criteria, articles had to (1) report at least one PPMV-level outcome, and (2) be published in 2000 or after.We included all PPMV-level outcomes in the review; outcomes were coded during the data extraction process based on the data reported in the literature. In order to facilitate synthesis of the literature, we grouped related outcomes into categories during the analysis stage. Our results are thus presented five categories: PPMV characteristics, shop quality, knowledge, practice, and compliance. PPMV characteristics included PPMVs’ qualifications and training, the services offered by the shop, drugs stocked and drug prices. Shop quality included the quality of storage facilities and drugs stocked, as well as adherence to general pharmacological guidelines. Knowledge was broadly defined, and included PPMV knowledge of any health area as defined by the study in which the outcome was reported. Given the heterogeneity in how knowledge was measured across studies it was not possible to use a standard definition. Practice included all outcomes related to PPMVs’ dealings with their customers, namely dispensing, client interaction and referral. Finally, we defined compliance as related to the national regulatory requirements and legal scope of practice for PPMVs in Nigeria, including licensing, commodities sold, and services offered. Due to the diversity of outcomes, and variation in definitions of each outcome across the reviewed studies, meta-analysis was not possible. We followed the systematic review guidelines in the Cochrane Handbook for Systematic Reviews of Interventions, including for defining and conducting the search, screening and selecting articles, and extracting data for analysis . No protEach study was assessed for methodological rigor and bias using the 9-point rigor scale for non-randomized studies developed by the WHO-Johns Hopkins Synthesizing Intervention Effectiveness Project . This scOf the 226 articles identified through the database and website searches, we screened 117 for review and assessed 51 for eligibility. Articles were excluded during these two stages if they did not include PPMV-specific outcomes. Three additional articles were identified through references. A total of 50 articles were included in the review ; of thesThe existing literature on PPMVs is focused largely in Nigeria’s southern geopolitical regions, with few studies conducted in northern regions , Table 1The majority of studies relied on cross-sectional surveys n = 38, . Only siStudies evaluating the characteristics of PPMVs and their shops included various outcomes on the educational background and training of PPMVs, and the services and medicines offered at their shops. These studies highlight the wide range of health areas across which PPMVs provide services.Qualifications and training. Twenty-seven studies reported on PPMVs’ level of education and/or source of training  are more commonly stocked than emergency contraceptives, female condoms and birth control pills ,63. AnotAll of the evidence on drug prices at PPMVs comes from the malaria literature. These studies showed that prices for anti-malarials at PPMVs are lower than at all other sources except for public sector facilities –39,57,66Nine studies addressed the quality of PPMV shops . The eviAssessments of the equipment and drug storage facilities at PPMVs ,38,68, fKnowledge was the most widely reported outcome in this literature; 28 articles reported on PPMV knowledge of malaria, child health, family planning, tuberculosis (TB) or pharmacological standards . PPMV knMalaria knowledge. The majority of studies (n = 19) addressing PPMV knowledge focused exclusively on malaria Click here for additional data file.


On 6 February 2013, an 8.0 magnitude earthquake generated a tsunami that struck the Santa Cruz Islands, Solomon Islands, killing 10 people and displacing over 4700.A post-disaster assessment of the risk of epidemic disease transmission recommended the implementation of an early warning alert and response network (EWARN) to rapidly detect, assess and respond to potential outbreaks in the aftermath of the tsunami.Almost 40% of the Santa Cruz Islands’ population were displaced by the disaster, and living in cramped temporary camps with poor or absent sanitation facilities and insufficient access to clean water. There was no early warning disease surveillance system.By 25 February, an EWARN was operational in five health facilities that served 90% of the displaced population. Eight priority diseases or syndromes were reported weekly; unexpected health events were reported immediately. Between 25 February and 19 May, 1177 target diseases or syndrome cases were reported. Seven alerts were investigated. No sustained transmission or epidemics were identified. Reporting compliance was 85%. The EWARN was then transitioned to the routine four-syndrome early warning disease surveillance system.It was necessary to conduct a detailed assessment to evaluate the risk and potential impact of serious infectious disease outbreaks, to assess whether and how enhanced early warning disease surveillance should be implemented. Local capacities and available resources should be considered in planning EWARN implementation. An EWARN can be an opportunity to establish or strengthen early warning disease surveillance capabilities. On 6 February 2013, an 8.0 magnitude earthquake generated a three-metre tsunami that struck the remote Santa Cruz Islands –Despite debate over the magnitude of epidemic risk in the post-disaster setting,Given the potential for enhanced disease transmission, the Solomon Islands Ministry of Health and Medical Services requested assistance from the World Health Organization (WHO) to assess and, as necessary, mitigate post-disaster epidemic risk. On 19 and 20 February 2013, a joint, on-site Ministry of Health and Medical Services and WHO assessment identified multiple post-disaster conditions that increased the risk of an epidemic, and recommended implementation of a post-disaster EWARN. We describe here the implementation, monitoring and results of the Santa Cruz Islands post-disaster EWARN, and key lessons learnt.The post-disaster risk assessment identified several factors that increased the risk of epidemic disease transmission. These included limited access to clean water, poor sanitation, high population density in displaced camps, living in bush, scrub and muddy environments, and increased exposure to disease vectors.Senior provincial medical and public health staff worked closely with a WHO epidemiologist to develop an EWARN strategy and implementation plan. The objective was to establish a simple and streamlined surveillance network to assure timely identification of and response to potentially serious disease epidemics. A chaotic post-disaster setting and substantially reduced resources precluded comprehensive disease monitoring. Given the local context and limitations, simplicity was considered essential for successful implementation and operation of the EWARN.Criteria for EWARN site selection included proximity to displaced people and catchment population, and communication capabilities, including mobile phone network, long-wave radio or road connection to the EWARN coordination centre based at the provincial hospital. Five health facilities were selected: the provincial hospital, three health centres and one nursing station, all of which had reliable communication capabilities. The estimated EWARN catchment population was 8000 people, and it included 90% of the 4700 who had been displaced.Eight target diseases and syndromes were selected based on severity , transmission potential (epidemic or possible epidemic capacity) and relevance to the post-disaster setting (present or likely present), as described in the post-disaster risk assessment.An alert was defined as “an increase in number of cases of a specific disease or syndrome beyond what was expected for that reporting site, based on trends in weekly target diseases and standardized thresholds.”Between 21 and 24 February 2013, a joint Ministry of Health and Medical Services and WHO team implemented the EWARN. A senior public health nurse was identified as the EWARN coordinator, responsible for data collection, alert verification, monitoring and response coordination. Two-hour trainings for all Ministry of Health and Medical Services staff involved in the EWARN were conducted at each of the five EWARN sites to review the target diseases and syndromes, case definitions, criteria for unexpected events, data collection forms, reporting procedures and timelines. A local outbreak response team – comprising nursing, health promotion, logistics, and environmental health staff – was established. Also, a half-day training was conducted on EWARN alert verification, and on how to perform investigations and implement rapid control measures. Challenges to EWARN implementation were largely transportation-related; that is, they were related to difficulties in accessing the rural health facilities due to a shortage of available vehicles, competing priorities in the post-disaster phase or a lack of the fuel for the outboard motors needed to visit the northern and eastern villages and health facilities that are remote and accessible only by sea. These challenges were resolved by the provincial nursing director, the most senior Ministry of Health and Medical Services staff on the Santa Cruz Islands, who had the authority to identify and release the necessary resources.Cases that met the case definition for a target disease or syndrome were stratified by age , and recorded on a tally sheet and line list. Surveillance data were communicated weekly via the EWARN coordinator to the Ministry of Health and Medical Services National Surveillance Unit in the capital Honiara, which analysed data and monitored for (and assured verification of) any alert. Any unusual or unexpected event was immediately reported to the EWARN coordinator.Between 25 February and 19 May 2013 (after 12 weeks of EWARN operations), a total of 1177 target diseases or syndrome cases were registered from a total of 5323 estimated consultations. Influenza-like illness was most commonly reported  followed by watery diarrhoea , malaria , acute fever and rash , prolonged fever , suspected dengue , suspected scrub typhus  and bloody diarrhoea ; the remainder of the consultations  were for other causes.Seven alerts were generated, verified and, as necessary, investigated: watery diarrhoea , bloody diarrhoea , acute fever and rash , prolonged fever , suspected dengue  and influenza-like illness . No unusual or expected events were reported through the event-based surveillance. Alerts were verified by asking the relevant health-care providers to confirm the data and provide additional information on clinical features, disease severity, and whether the number of new cases was increasing or decreasing. Verified alerts with evidence of ongoing transmission were investigated by the EWARN outbreak response team. The dengue-like illness alert was a reporting error. Of the six verified alerts, four events were isolated and the rate of new cases returned to baseline without intervention. The two remaining alerts required the investigation team to be dispatched and control measures implemented. None of the alerts progressed to sustained transmission; therefore, no laboratory samples were collected by the investigation teams. Fifty-one weekly reports were received  within 24 hours of the weekly reporting deadline. The remaining nine reports (15%) were not received.We implemented an EWARN that included indicator and event-based surveillance components two weeks after an earthquake and tsunami, despite limited human, medical, laboratory and logistical capacities; a remote setting; and a challenging post-disaster context. Several alerts were reported and investigated, but none led to sustained transmission. In May 2013, a repeated risk assessment found a decreased risk of epidemic transmission. On 20 May, the EWARN was transitioned to a four-syndrome early warning disease surveillance system that aligns with the Solomon Islands and Pacific Syndromic Surveillance Systems.One limitation of the EWARN was an absence of baseline surveillance data to establish alert thresholds . Another limitation was that site-selection criteria may have introduced an unintended bias that systematically recruited sites at higher or lower risk of outbreaks. For example, sites and communities with reliable communication may have better water and sanitation infrastructure that would in turn systematically decrease the risk of enteric disease outbreak in those communities. Also, the EWARN did not capture all affected populations, and localized outbreaks may have been missed.–Certain post-disaster features  increase the risk of an epidemic.Given the substantial human, material and financial resources mobilized in a disaster response, it is important to link post-disaster activities to long-term development goals. EWARN systems, as one element of a disaster response, are well suited to building or strengthening sustainable early warning disease surveillance and response, and thereby help countries meet their International Health Regulation obligations to achieve and maintain essential surveillance and response capacity.We learnt several lessons that will be useful when considering post-disaster early warning disease surveillance . First, Box 1A detailed assessment to evaluate the risk and potential impact of serious infectious disease outbreaks is necessary to assess whether and how enhanced early warning disease surveillance should be implemented.Local capacities and available resources should be considered in planning EWARN implementation.An EWARN can be an opportunity to establish or strengthen early warning disease surveillance capabilities.EWARN, early warning alert and response network.


Island biogeography has greatly contributed to our understanding of the processes determining species' distributions. Previous research has focused on the effects of island geography  and current climate as drivers of island species richness and endemism. Here, we evaluate the potential additional effects of historical climate on breeding land bird richness and endemism in Wallacea and the West Indies. Furthermore, on the basis of species distributions, we identify island biogeographical network roles and examine their association with geography, current and historical climate, and bird richness/endemism. We found that island geography, especially island area but also isolation and elevation, largely explained the variation in island species richness and endemism. Current and historical climate only added marginally to our understanding of the distribution of species on islands, and this was idiosyncratic to each archipelago. In the West Indies, endemic richness was slightly reduced on islands with historically unstable climates; weak support for the opposite was found in Wallacea. In both archipelagos, large islands with many endemics and situated far from other large islands had high importance for the linkage within modules, indicating that these islands potentially act as speciation pumps and source islands for surrounding smaller islands within the module and, thus, define the biogeographical modules. Large islands situated far from the mainland and/or with a high number of nonendemics acted as links between modules. Additionally, in Wallacea, but not in the West Indies, climatically unstable islands tended to interlink biogeographical modules. The weak and idiosyncratic effect of historical climate on island richness, endemism, and network roles indicates that historical climate had little effects on extinction-immigration dynamics. This is in contrast to the strong effect of historical climate observed on the mainland, possibly because surrounding oceans buffer against strong climate oscillations and because geography is a strong determinant of island richness, endemism and network roles. Island biogeography has long fascinated biologists and contributed much to our understanding of the processes that determine species diversity  evaluate whether geography adequately determines the distribution of species on islands or, alternatively, current climate and Quaternary climate-change has left detectable imprints on bird species distributions within equatorial island systems. Specifically, we test the hypothesis that endemic species are found particularly on islands having experienced the least historical climate-change; and (2) assess whether island geography, current climate, historical climate-change or species distribution patterns best explain an island's role in determining biogeographical modules, that is, avian subregions within each archipelago. Specifically, we aim at evaluating the hypothesis that islands responsible for defining biogeographical modules are rich in endemic species, whereas those islands acting as stepping stones between faunal subregions/modules are rich in nonendemics, as proposed by Carstensen et al. . By comphttp://www.worldbirdnames.org/), and for the West Indies, we followed the taxonomy of the American Ornithologists' Union checklist (http://checklist.aou.org/). Compared to the datasets used in Carstensen et al.  and nonbreeding migratory species whose distribution patterns are likely to be determined by factors other than island features  to presumably increasing focus on historical or evolutionary time-scales . In total, our datasets comprised 119 islands and 513 native breeding land birds in Wallacea and 57 islands and 243 native breeding land birds in the West Indies  reflects how well an island is connected within its own module relative to other islands in its module. It is calculated as:Based on species distributions, for each archipelago, we constructed an island-bird presence/absence matrix and used a network approach to detect biogeographical modules and island roles  reflects how an island within a module is connected with respect to other modules, and is defined as:where ki is the number of links of i; and kit is the number of links from i to nodes in module t (including i's own module). When calculating the local topological linkage for each island, only the number of links to the other islands was considered, excluding links of birds to islands , maximum elevation (m), and distance to nearest source mainland (km). For Wallacea, we used Australia, New Guinea, and Borneo as potential extra-Wallacean colonization “mainland” sources   4.0  Table. We repoOf the 513 breeding land bird species in our Wallacea dataset, 300 (58%) are endemics of the region and 213 (42%) are nonendemics that also breed outside of Wallacea. Of the 243 breeding species in West Indies, 176 (72%) are endemics and 67 (28%) nonendemics. Hence, Wallacea has considerably higher bird species richness, but proportionally smaller amount of endemics than the West Indies  than in Wallacea  better than nonendemic richness (72–81%) and endemic richness (69–74%). In the West Indies, high temperature anomaly diminished total species richness and richness of endemics, whereas in Wallacea high temperature anomaly diminished the richness of nonendemics while high temperature and precipitation anomalies increased the richness of endemics. In both archipelagos, the effects of climate anomaly were marginal (0–7%), current climate effects stronger (0–47%) but island geography almost explained as much as the total variation explained (58–82%). In both Wallacea and the West Indies, island area was the single most important variable, increasing the richness of both nonendemics and regional endemics , and the West Indies had six modules , then east to the Banda sea and south around Timor, causing constantly high humidity in flanking mountains, while other parts of the region had variable and more seasonal climates (Hall et al. Alternatively, Quaternary climate-change may have caused endemics in Wallacea and the West Indies to occupy less suitable climate niches – depressing their abundances – and contracted their geographic range within islands, but without causing a significant number of local extinctions. Hence, there may be an undetected extinction debt of endemics, as has also been proposed for high mountain endemic plants in the Alps (Dullinger et al. The influence of island area, elevation and isolation on species richness, and endemism patterns in Wallacea and the West Indies largely corroborate previous island biogeography studies. In both archipelagos, the observed strong positive effect of island area on total species richness and richness of both nonendemics and endemics – as well as the importance of topography for endemics in the West Indies – may be attributable to an array of mechanisms, including greater resources/energy, habitat and climate diversity, topographic heterogeneity, higher potential for speciation, and lower extinction rates on large and mountainous islands (MacArthur and Wilson in situ speciation (Lohman et al. As in a global island biogeographical study on plant species richness (Weigelt and Kreft l, correlated strongly with richness of endemics, whereas regional topological linkage, r, associated best with richness of nonendemics, as hypothesized by Carstensen et al. (l islands were large islands situated far from other large islands, indicating that high l islands potentially act as speciation pumps and source islands for surrounding smaller islands, defining biogeographical modules, that is, avian subregions consisting of many local “module” endemics (Carstensen et al. r islands were in both archipelagos situated distantly from the mainland and were in Wallacea characterized by unstable climates; they may be sink islands acting as stepping stones for widespread and good dispersing nonendemic species whose breeding range extends across biogeographical module borders (Carstensen et al. In both Wallacea and the West Indies, island biogeographical network roles related strongly to species richness/endemism and to island geography. As for species richness and endemism patterns, current and historical climate played only a relatively minor role idiosyncratic to each archipelago. In both archipelagos, local topological linkage, n et al. . MoreoveWe conclude that island area, elevation, and isolation are the most important factors explaining bird distributions on islands, having strong effects on patterns of species richness, endemism and island network roles. Quaternary climate-change, on the other hand, only influences island network roles and the distribution of island endemics to a small degree, at least within archipelagos surrounded by thermally stable tropical seas. However, we cannot rule out that island endemics due to poor ability to cross water currently occupy unsuitable climate niches, that is, island endemics may have experienced declining populations and there may even be an extinction debt of island endemics. Still, taken together with some other results also showing a weak effect of historical climate change on island communities (Kissling et al.


Cumulating data suggest that small noncoding-RNAs such as microRNAs (miRNAs) can be utilized as potential biomarkers for the diagnosis and prognosis of a variety of diseases such as cancer, neurological disorders, cardiovascular disease and Type-II diabetes, etc. MiRNAs can be utilized not only for monitoring of treatments but also for patient stratifications. The Tenth Annual miRNA as Biomarkers and Diagnostics conference, 2014, organized in Boston, MA, was primarily focused on recent advancements in the field of miRNA in the early detection of disease, monitoring tumor growth/progression and its potential for precision medicine. This article summarizes findings presented in the miRNA biomarker as cancer diagnostics session. The overarching projections from this and other sessions were that miRNAs are now well established as regulators of tumorigenesis and can be utilized not only as potential biomarkers for the diagnosis and prognosis of a disease but also are useful in patient stratifications and treatment response. The data presented at the microRNA (miRNA) biomarker as cancer diagnostics session clearly suggested that miRNA profiling has been useful in identifying predictive miRNA signatures associated with tumor growth/progression of various cancer types such as pancreatic cancer, colorectal cancer, osteosarcoma as well as clear cell renal cell carcinoma. Changes of specific miRNAs can be detected in tissues utilizing a slide-based staining assay and from circulating tumor cells from the blood sample as well as in the urine, presenting a noninvasive way to detect miRNAs. Furthermore, detection of exosomic miRNAs in the tumor microenvironment may provide better tools for development of new personalized treatments for cancer patients. Moreover, detection of miRNA‒polymorphisms and miRNA variants may help further improve diagnosis, treatment and prognosis in patients and has profound implications in the fields of pharmacogenomics and precision medicine.miRNA biomarker as cancer diagnostics.Small noncoding-RNAs such as microRNAs (miRNAs) are emerging as prominent disease associated biomarkers and can be utilized not only for patient stratifications but also for monitoring of treatments (i.e. for diagnosis and prognosis). To discuss this, The Tenth Annual microRNA as Biomarkers and Diagnostics conference , organized in Boston, MA, USA brought over 100 representatives from academia, government, clinical laboratories and industry and comprised of 20 presentations (101). The conference broadly covered topics in the area of 1) miRNA biomarkers in drug development; 2) miRNA biomarkers as cancer diagnostics; and 3) miRNA as disease biomarkers (101). This article summarizes the session regarding Prasun J. Mishra, Ph.D.,  opened the session by describing the need for predictive biomarkers in cancer progression/prognosis and why miRNAs are promising candidates in predicting drug response. MiRNAs are small non-coding RNAs, about 21–25 nucleotides in length, that are emerging as a new class of biomarkers. The cancer research field has been at the forefront of advancing miRNA biomarker field for over a decade now. This has been made possible, not only due to the availability of the tumor tissue samples in the clinic, but also recent advancements in the field of miRNA detection and sequencing. MiRNAs are now well established as regulators of tumorigenesis. In cancer, miRNA expression variations are evident across different stages of cancer progression . An incrThe importance and the uniqueness of this session were also emphasized. This particular session was designed to cover recent advancements in the miRNA as biomarker and cancer diagnostics field. The speakers discussed utility of non-coding RNA variants to precision medicine (Prasun Mishra) as well as role of miRNA in tumor microenvironment (Muller Fabbri). The session also highlighted utility of miRNAs profiling in monitoring tumor growth/progression of pancreatic cancer (Lorenzo Sempere), colorectal cancer (Jingfang Ju), circulating osteosarcoma cells (Benjamin Ory) and clear cell renal cell carcinoma (Huiqing Wu) and its utility as a biomarker for precision medicine.Prasun J. Mishra  described recent advances in the field of miRNA polymorphisms and their implications to precision medicine. Recent advancements in microRNA field suggest that genetic variation or polymorphisms present in the miRNA pathway are associated with the prognosis/progression of diseases and drug responses and are emerging as powerful tools to study biology of diseases -6. MicroMuller Fabbri  described role of exosomic miRNA in tumor microenvironment and it’s implication to precision medicine. Cancer is a genetic disease and an increasing evidence indicates that not only cancer cells but also surrounding cells, forming the so-called “tumor microenvironment”, play a key role in cancer biology . MiRNAs Lorenzo F. Sempere  described a slide based miRNA diagnostics tool for pancreatic cancer. MiRNA diagnostics is an emerging area of prognostic and predictive indicators in cancer medicine. Dr. Sempere presented his study focused on the role of miRNAs in initiation and progression of pancreatic cancer . Recent Jingfang Ju  described recent developments in the area of miRNAs as biomarkers in colorectal cancer. 5-Fluorouracil based chemotherapy (e.g. FOLFOX) is the standard chemotherapeutic regimen for treating advanced stage colorectal cancer. Chemoresistance is the major reason for the failure of treating advanced colorectal cancer . MiRNA bBenjamin Ory  described a miRNA profiling method  of circuHuiqing Wu  described a miRNA signature to predict clear cell renal carcinoma. Using frozen tissue cohorts, microarray technology and risk score method, Dr. Wu’s group identified a 4-miRNA signature associated with clear cell renal cell carcinoma (ccRCC) metastasis and prognosis ,21. The The overarching projections from this and other sessions were that miRNAs are now well established as regulators of tumorigenesis and can be utilized not only as potential biomarkers for the diagnosis and prognosis of a disease but also are useful in patient stratifications and treatment response . The datmiRNA: microRNA; UTR: Untranslated region; miRSNP/mir-polymorphism: A SNP or polymorphism that results in loss of a miRNA function; ccRCC: Clear cell renal cell carcinoma; FFPE: Formalin-fixed paraffin-embedded; RT-PCR: Real time PCR; CTCs: Circulating tumor cells; FOLFOX: A chemotherapy regimen to treat colorectal cancer, it includes FOL– Folinic acid (leucovorin), F – Fluorouracil (5-FU) and OX – Oxaliplatin (Eloxatin); TLR8: Toll-like receptor 8; IL-6: Interleukin-6; TNF-alpha: Tumor necrosis factor alpha; DHFR: Dihydrofolate reductase; MTX: Methotrexate.The authors declare that they have no competing interests.Dr. Mishra is a scientist at National Cancer Institute (NCI), National Institutes of Health (NIH). Prior to NCI, he worked at Rutgers Cancer Institute of New Jersey, Robert Wood Johnson Medical School, Rutgers University, for seven years, where his research focus was to identify novel mechanisms of drug resistance, identify mechanism of actions of new drugs, and design novel drugs/combinations to facilitate anticancer drug development. He received his Ph.D. from Rutgers University in Cellular and Molecular Pharmacology with university’s highest honors. In 2008 Dr. Mishra joined the US Department of Health and Human Services, NCI, NIH, where his research focus has primarily been to identify and exploit “druggable” early genetic events, driving cancer progression, using integrated genomics and high-throughput screening, to design a more effective anticancer therapy. His discoveries have led to the development of new and viable strategies of prevention, diagnosis and treatment of cancer patients in the clinic.


Triatoma dimidiata, a widespread vector of Chagas disease that cannot be eliminated. The key to maintaining the risk of transmission of Trypanosoma cruzi at lowest levels is to sustain surveillance throughout endemic areas. Guatemala, El Salvador, and Honduras integrated community-based vector surveillance into local health systems. Community participation was effective in detection of the vector, but some health services had difficulty sustaining their response to reports of vectors from the population. To date, no research has investigated how best to maintain and reinforce health service responsiveness, especially in resource-limited settings.Central American countries face a major challenge in the control of We reviewed surveillance and response records of 12 health centers in Guatemala, El Salvador, and Honduras from 2008 to 2012 and analyzed the data in relation to the volume of reports of vector infestation, local geography, demography, human resources, managerial approach, and results of interviews with health workers. Health service responsiveness was defined as the percentage of households that reported vector infestation for which the local health service provided indoor residual spraying of insecticide or educational advice. Eight potential determinants of responsiveness were evaluated by linear and mixed-effects multi-linear regression. Health service responsiveness  was significantly associated with quarterly monitoring by departmental health offices. Other potential determinants of responsiveness were not found to be significant, partly because of short- and long-term strategies, such as temporary adjustments in manpower and redistribution of tasks among local participants in the effort.Consistent monitoring within the local health system contributes to sustainability of health service responsiveness in community-based vector surveillance of Chagas disease. Even with limited resources, countries can improve health service responsiveness with thoughtful strategies and management practices in the local health systems. Rhodnius prolixus has been almost eliminated, Triatoma dimidiata, which cannot be eliminated, continues to threaten the population in vast areas. To maintain the risk of transmission of Trypanosoma cruzi at lowest levels despite limited resources, Guatemala, El Salvador, and Honduras integrated community-based vector surveillance into local health systems. One challenge to sustaining surveillance is to ensure continuous responsiveness to reports of household infestation from the community. Our research in 12 study areas in the three countries over a five-year period investigated eight potential determinants of health service responsiveness, including volume of vector notifications, local geography, demography, manpower, and managerial approach. We found that consistent (quarterly) monitoring by departmental personnel within the local health services was associated with high response rates. Results of interviews added additional insight.Elimination of domiciliated vectors led to a decreased prevalence of Chagas disease in parts of Latin America. In Central America, where the domiciliated vector  Rhodnius prolixus is almost eliminated, but Triatoma dimidiata remains widespread in the region despite greatly reduced rates of household infestation . Hea. Hea9]. T. dimidiata . In El Salvador all infested households were eligible for spraying, although national guidelines allowed educational advice instead of spraying. Insecticide spraying was carried out principally by vector control technicians in Guatemala, by vector control technicians, health promoters, environmental sanitation inspectors, or trained community personnel in El Salvador, and by trained community personnel in Honduras. The responsible individuals applied pyrethroid insecticide (deltamethrin 5% wp) using a manual pump sprayer (Hudson X-pert) and spraying techniques as employed in the attack phase. Guidelines mandated a response to bug reports within seven days in El Salvador and within one month in Guatemala and Honduras. However, the time to response often exceeded one month because of lack of immediately available sprayers, transportation, or insecticide, and when there were dengue outbreaks.The three countries responded to bug notifications either by insecticide spraying or educational advice, according to different criteria. In Guatemala and Honduras, households were sprayed if infested with nymph(s) or high densities of Departmental technicians monitored community-based surveillance by periodic visits (quarterly on average) to the health centers to review the registry, check spraying equipment, participate in monthly meetings with community health volunteers, and exchange information with the local health personnel. During these visits, they would also supervise and review activities of insecticide spraying and its effects.We defined a health service’s response rate as the percentage of the number of households sprayed or visited for advice by the local health services divided by the number of households infested with Chagas disease vectors as reported by the community. The annual response rate was calculated for each study area between 2008 and 2012, so that a total of 60 response rates (12 areas x 5 years) potentially were available for analysis. If the response occurred during the year following notification, it was considered as an action of the year of notification. A household with consecutive notifications of vector infestation was counted as a single infested household until the health service responded, regardless of interval length between notification and response.Taking in account factors that might influence demand, supply, and work process in community-based vector surveillance, we selected for analysis the following eight variables as potential determinants of health service responsiveness: number of infested households as reported by the community; distance from health centers to departmental capitals; number of operational technicians per 1,000 households; numbers of community volunteers and sprayers per 1,000 households; interval between receipt of vector reports from the community and response by health services, i.e. <3 months, 3–12 months or >12 months; degree of decentralization of response to vector reports, i.e. by health center or departmental office; presence of consistent monitoring by departmental technicians; and presence of technical assistance by JICA.We collected data on surveillance activities, local demography, geography, and human resources during visits to the departmental health offices and health centers during 2013. We interviewed personnel responsible for Chagas disease vector surveillance in each facility to identify any perceived factors or circumstances that might have influenced responsiveness during the five year period.We conducted multivariable linear regression to assess the relationship between the response rate and potential determinants. We further analyzed the data using mixed-effects multi-linear regression, clustering the yearly response rates by health center, to account for differences between and within the health centers. All statistical analyses were conducted using STATA version 12 software.The results of interviews at the 12 health centers and corresponding departmental health offices were analyzed to explain differences in the response rates. We also analyzed the roles of participants  within the five essential functions of community-based surveillance  9] to i to i9] tT. dimidiata infestation in the 12 study areas between 2008 and 2012. Of these, the Ministry of Health responded to 2,041 households  whereas the correlation of assistance from JICA was weak and negative (r = -0.13).Of the eight variables analyzed, two were found by linear regression and mixed-effects multi-linear regression to be significantly associated with health service responsiveness: consistent monitoring by departmental technicians and technical assistance by JICA . In bothHealth centers in Dolores, Honduras and Comapa, Guatemala reported large numbers of infested households in 2009 and 2012, following campaigns in schools to promote bug searches as explained during interviews with health center staff .Response rates followed four general patterns over the 5-year period: 1) nearly 100% response for most of the period, 2) nearly 100% for years 1 to 3 but then falling, 3) fluctuating moderately (between 50% and 100%), and 4) fluctuating substantially (between 0% and 100%) but with a tendency towards improvement.r = 0.71, p<0.01) and assistance from JICA  were seen as in earlier models  monitoring by departmental health offices was a significant determinant of health service responsiveness in community-based vector surveillance of Chagas disease in Guatemala, El Salvador, and Honduras. Perhaps surprisingly, response rates were significantly higher among health centers without presence of technical assistance by the donor (JICA). However, this finding can be explained by the presence of JICA at early stages of planning and implementation of the surveillance program at each study area, during which time response rates were low or fluctuated but subsequently improved. Three-year bilateral projects to establish community-based vector surveillance began in 2008 in El Salvador and Honduras and in 2009 in Guatemala.Health service responsiveness was independent of the volume of bug reports from the community, distance between health centers and departmental offices, numbers of operational technicians in the local health service and community workers, intervals between vector report and institutional response, and degree of decentralization of response.Interviews with health center staff demonstrated the effectiveness of regular monitoring on responsiveness and a decline in response rates following the departure of departmental supervisors in two health centers. This finding confirms previous research on primary health care services in low-resource settings, which showed that work performance was not motivated by written guidelines but by monitoring . BecauseInterviews also shed light into the lack of association between the other potential determinants and health service responsiveness. Although greater numbers of vector reports, for example following campaigns at school, increased the workload of local health services, response rates did not decline because manpower was augmented to meet the demand and tasks were reassigned among local stakeholders. Departmental technicians temporarily increased response capacity by mobilizing operational staff from other districts (as often occurs in reaction to dengue outbreaks) and by organizing extensive spraying operations with health center staff and community sprayers from different villages in the jurisdiction. Stakeholder analysis showed that surveillance tasks normally carried out by health specialists were simplified by the National Chagas Program and shifted to less specialized personnel through training, as we and others have reported previously , 16, 17.Managerial responsibility for response at the departmental office rather than the health center did not appear to affect the response rate. Although the departmental response approach was more vertical and less integrated into primary health care services, interviews showed that both departmental health offices and health centers with high responsiveness were able to find solutions for difficult situations. For instance, departmental vector teams assigned a data collection technician to health centers, concentrated response efforts in time and space, and travelled by motorcycles to reduce transportation costs. A physician and a nurse at one health center posted a large map of the jurisdiction on a billboard in the waiting room and used thumbtacks to represent the number of households reporting vectors in each village and removed them following the appropriate response. Such strategies reinforced the management capacity of the local health services.Longer intervals between receipt of vector reports and health service response did not lead to either higher response rates because of greater efficiency from economies of scale, or to lower response rates due to increased demands to deal with greater number of bug notifications. However, longer intervals are worrisome because of extended time of exposure of the population to the vector and thus greater risk of transmission of infection. Another potential negative impact is that the community may become reluctant to participate in bug notification if the interval is perceived as too long.While portraying the reality of vector surveillance in Guatemala, El Salvador, and Honduras, this observational study has important limitations. The sensitivity of the analysis may have been affected by the limited number of infested households in certain areas and during specific years, and by lack of data at the individual household level, which would have detected repeatedly infested and responded households. Our resources were insufficient to measure outcomes such as household vector infestation rates and incidence and prevalence of Chagas disease. These data would enable analysis of the consequences of not achieving 100% response rate; the effect of spraying vs. educational advice; and the impact of variable quality of responses by specialized vs. lay workers. We were unable to conduct cost analyses that would allow us to compare the effectiveness of the different styles and approaches to integrated surveillance, which varied substantially among the 12 study areas [The greatest challenges to control of Chagas disease in Central America are non-eliminable, widespread vectors and underfunded and irregularly decentralized health systems. Although the disease has been targeted for elimination , a more T. dimidiata, the roles of continued spraying of infested houses and alternative interventions must be determined. In our study, 33.5% of responses to infested households was by insecticide spraying in Guatemala, versus 95.8% in El Salvador and 84.0% in Honduras. This partly reflects periodic scarcity of insecticides in the Guatemalan Ministry of Health, but also a deliberate shift towards house improvement. Multiple cycles of insecticide spraying are effective in reducing household infestation [In the control of non-eliminable vectors, such as estation , but areestation  can be mestation , 23. Theestation , 23. AlsThis research found that consistent monitoring at the departmental level of the Ministry of Health makes a significant difference in health service responsiveness in community-based vector surveillance of Chagas disease. Other potential factors, such as the number of infested households, numbers of health personnel and community workers, distance from departmental health offices to health centers, and degree of decentralization of response seemed to have limited impact on health service responsiveness. Challenges related to these factors were met largely because of managerial efforts of the local health services in implementing short-term and long-term strategies. Basic management practices such as monitoring and supervision combined with thoughtful strategies can improve health service responsiveness in resource-limited settings.S1 Table(XLSX)Click here for additional data file.S2 Table(XLSX)Click here for additional data file.


Patients, clinicians, researchers and payers are seeking to understand the value of using genomic information  to inform clinical decision-making. However, challenges exist to widespread clinical implementation of genomic medicine, a prerequisite for developing evidence of its real-world utility.www.ignite-genomics.org) Network, comprised of six projects and a coordinating center, was established in 2013 to support the development, investigation and dissemination of genomic medicine practice models that seamlessly integrate genomic data into the electronic health record and that deploy tools for point of care decision making. IGNITE site projects are aligned in their purpose of testing these models, but individual projects vary in scope and design, including exploring genetic markers for disease risk prediction and prevention, developing tools for using family history data, incorporating pharmacogenomic data into clinical care, refining disease diagnosis using sequence-based mutation discovery, and creating novel educational approaches.To address these challenges, the National Institutes of Health-funded IGNITE (Implementing GeNomics In pracTicE; This paper describes the IGNITE Network and member projects, including network structure, collaborative initiatives, clinical decision support strategies, methods for return of genomic test results, and educational initiatives for patients and providers. Clinical and outcomes data from individual sites and network-wide projects are anticipated to begin being published over the next few years.The IGNITE Network is an innovative series of projects and pilot demonstrations aiming to enhance translation of validated actionable genomic information into clinical settings and develop and use measures of outcome in response to genome-based clinical interventions using a pragmatic framework to provide early data and proofs of concept on the utility of these interventions. Through these efforts and collaboration with other stakeholders, IGNITE is poised to have a significant impact on the acceleration of genomic information into medical practice. Challenges to clinical implementation of genomic medicine have been identified at multiple levels including limited availability of evidence for clinical utility; ‘genomic unfamiliarity’ of providers, patients and families; limited access to advanced genetic testing and ambiguity of result interpretation; lack of reimbursement for genetic testing; and the need for real-time, point-of-care integration of test results with the electronic health record (EHR) and clinical decision support (CDS) tools.  OvercomiThe goals of the IGNITE network are to 1) expand and link existing genomic medicine implementation efforts; 2) develop new collaborative projects and methods for genomic medicine implementation in diverse settings and populations; 3) contribute to the evidence base of outcomes following the use of genomic information for clinical care; and 4) define, share and disseminate the best practices of genomic medicine implementation, diffusion and sustainability in diverse settings. Each site participating in the NIH-funded IGNITE Network is developing and testing a clinical model for implementing genomic information  into patient care with incorporation of the genomic information into the EHR and measures of outcomes in response to a genomic medicine intervention. In addition, sites are developing novel patient and provider educational models; testing CDS strategies to support clinical use of genomic data; utilizing novel dissemination and sustainability methods; and collecting data on factors influencing adoption of genomic medicine. All IGNITE projects are also examining implementation across a broad range of practice environments, including academic and non-academic settings as well as among diverse socio-economic and demographic patient populations.The IGNITE Network consists of six member projects and a Coordinating Center which along with NHGRI program staff comprise the governing Network Steering Committee Fig. . Each ofFamily health history (FHH) assessments have clearly been shown to identify persons at higher risk for common chronic disease, enabling preemptive and preventive steps, including lifestyle changes, health screenings, testing and early treatment as appropriate . More rehttps://precisionmedicine.duke.edu). The GMM is a novel flexible and adaptable model, with three components, designed to overcome barriers in the implementation of personalized medicine: 1) education of physicians and patients; 2) a health IT-based FHH platform, MeTree™, that collects FHH directly from patients on the front end and generates individualized risk-stratified evidence-based preventive care recommendations for physicians (as well as a pedigree and patient-oriented recommendations) on the back end, and 3) CDS to effectively interpret FHH information and carry out recommendations.This project utilizes a Genomic Medicine Model (GMM) developed in the context of the MeTree™ FHH pilot led by Duke University  develop an optimal strategy for implementing MeTree into routine clinical practice in diverse settings; 2) demonstrate the effectiveness of MeTree in increasing uptake of risk-stratified evidence-based prevention guidelines; 3) create a standardized family health history storage database that can integrate with electronic medical records for bi-directional communication of family and personal history data and risk assessment results, and 4) disseminate guidelines for a FHH intervention in diverse practice settings.The outcome measures for this project include patient, provider and system effects in the following domains: emotional ; behavioral ; biological ; clinical ; and financial . In addition, implementation measures include model reach, effectiveness, adoption, implementation integrity, implementation exposure and maintenance and sustainability of the intervention.APOL1 locus on chromosome 22 have a major effect on and explain most of the excess risk for hypertension associated CKD and its progression to ESRD in African ancestry populations. Hypertension-associated CKD in African Ancestry populations has emerged as a highly relevant and well-suited opportunity for a ‘prototype’ genomic medicine demonstration project for common chronic illnesses managed in primary care settings.Chronic kidney disease (CKD) is commonly associated with hypertension (28 %) and affects 26 million American adults. Most cases of hypertension are managed by primary care providers. African ancestry populations with hypertension (HTN) have 2- to 3-fold higher risk of developing CKD, and a 5-fold increased risk to progress to end stage renal disease (ESRD) when compared with whites. HTN is a risk factor for progression of CKD and for increased cardiovascular disease (CVD) risk with CKD. Thus targeting blood pressure control as a modifiable risk factor may both reduce CVD in people with CKD and reduce progression of CKD to end stage disease. Recent discoveries demonstrate that testable alleles of the APOL1 genetic testing and return of results will be offered at the beginning or at the end of a 1-year evaluation period, respectively. The intervention group will be stratified naturally by APOL1-positive (increased genetic risk) and APOL1-negative (population-average genetic risk) genetic test results. Patients will be informed about their genetic risk status and its implications for their healthcare by trained study coordinators. Their providers will receive CDS stratified by APOL1-positive or -negative results in form of best practice alerts displayed at the beginning of encounters with enrolled patients. In addition to clinical follow-up data available through EHR data mining, standardized research data will be collected through clinical testing and questionnaires administered by study coordinators at 3 and 12-month follow-up visits.The GUARDD study is designed to generate essential insights for sustainable adoption and large-scale dissemination of genomic medicine in diverse clinical settings providing care for common adult-onset diseases in general, and for underserved African Ancestry populations with large excess burden of non-diabetic kidney diseases specifically. Investigators are using community-engaged approaches to enroll 2050 patients of African Ancestry at primary care facilities of the Mount Sinai Health System and of the Institute for Family Health, a network of community health centers with 13 sites in New York City. Patients must be 18–70 years of age, a patient at a participating care site, self-report African American/Black race and have a history of hypertension with no history of diabetes or kidney disease. Eligible patients will be randomized to an intervention or a control group in a seven-to-one ratio where APOL1-positive (estimated N ~ 250) and APOL1-negative (estimated N ~ 1550) intervention groups and the control group without intervention (estimated N ~ 250). Primary outcome measures include 1) change in systolic blood pressure and 2) utilization of blood and urine tests to assess kidney function in the APOL1-positive group compared with APOL1-negative group and control group at 3 and 12 months. Secondary endpoints will include comprehensive provider- and patient-oriented survey outcomes and process measures.Primary outcome measures will be compared among three arms of the GUARDD study, including Genomic-based interventions such as pharmacogenomic testing have the potential to improve patient outcomes and reduce health care system costs. This could occur by reduction of adverse drug reactions and their associated medical costs, through the improvement of drug efficacy for expensive health care conditions, or by the targeting of effective, but expensive therapies to those most likely to benefit. Measurement of such costs is challenging, and not possible without an informatics infrastructure capable of measuring both financial costs and clinical outcomes. As a result, the business case for implementation of genomic and pharmacogenomics testing in large health care systems has not been persuasive.Indiana University School of Medicine and the Indiana University Institute for Personalized Medicine in collaboration with the Eskenazi Health System are conducting a study to evaluate the economic and clinical outcomes associated with embedding a pharmacogenomics program in a system that serves as a health care safety-net in Indianapolis, Indiana. The INGenious project is a prospective, randomized, trial enrolling a total of 6000 patients, with 2000 patients assigned to a pharmacogenetic testing arm and 4000 to a control arm who will be followed, but not tested. A pharmacogenetic test, involving 51 SNPs in 16 genes will be carried out at the beginning of the study in patients in the testing arm upon prompting by an index medication: one of 24 selected as being supported by validated guidelines. This study is randomized between an intervention arm and one that receives no intervention in order that a genotyped group can be compared with one in which undisturbed, routine clinical care is carried out in patients taking the same drugs. Both arms will be followed for one year.The specific aims of the INGENIOUS project include: 1) testing whether Clinical Laboratory Improvements Amendment (CLIA)-certified genotyping that is targeted at 24 widely used drugs is associated with significant reductions in hospital and outpatient economic costs incurred over 1 year; and 2) determining whether pharmacogenetic testing is associated with significant improvements in clinical outcomes over 1 year.The INGENIOUS project is comparing the following outcomes between the two study arms: a) hospital and outpatient economic costs incurred over 1 year; and b) clinical outcomes over 1 year. Cost data are being obtained from patients randomized to either arm of the trial. The categories of inpatient and outpatient charges collected include medication, pharmacy, facility, laboratory test, treatment, professional and others. Clinical outcomes data being collected from the Eskenazi informatics system include the number of admissions, the number of emergency department visits, the number of clinic visits and returns to clinic. In addition, data are being collected on adverse drug reaction diagnostic codes and changes in drug regimens (according to prescribing patterns and the Medication Possession Ratio (MPR) of index medications).There is substantial evidence that both efficacious and adverse responses of many drugs are significantly influenced by genetic variability. There are numerous examples of clinically actionable variants in pharmacogenetics and 10 % of all drugs contain pharmacogenetic information in their FDA-approved product label . Nonethehttp://personalizedmedicine.ufhealth.org/) is a multidisciplinary clinical initiative to implement genomic medicine, with the program built around the long-term perspective that large amounts of genomic data are likely to be available on patients in the future. While the long-term goal of the PMP is to include disease risk prediction and defining disease prognosis, the initial focus is on implementing pharmacogenetics to guide drug decisions in clinical practice.  Network and the CSER  program), IGNITE will also provide synergies to improve the application of genomics to health care [http://www.nih.gov/precisionmedicine/), IGNITE can play a strategic role in assisting this effort to deliver on its goal to impact populations and eventually population health .The IGNITE Network is poised to have a significant impact on the acceleration of genomic information into medical practice. The seven participating organizations include significant expertise in translational research and also have important linkages to health care delivery systems, and patient and advocacy groups. In the short term, each of the projects is defining novel implementation strategies that will eventually inform the broader clinical community on how to bring genomic tools into clinical workflows and health care. Specifically, IGNITE will provide the standardized methods for implementation as well as the common measures to assess the impact of implementation at the patient, provider and health system level . The network will also communicate the results to a broad stakeholder community including regulators, payers and patient and community groups. Because IGNITE projects involve diverse settings, it will be possible to identify specific modifications needed to bring these innovative tools to underserved populations and a variety of practice venues serving diverse populations. Through affiliate members, IGNITE aspires to broaden the range and repertoire of genomic interventions and implementation strategies. Through its interactions with other NHGRI networks that are working with genomic tools and health care information and EHRs   research