Creating a National Specimen Referral System in Guinea: Lessons From Initial Development and Implementation.

In the wake of the 2014-2016, West Africa Ebola virus disease (EVD) outbreak, the Government of Guinea recognized an opportunity to strengthen its national laboratory system, incorporating capacity and investments developed during the response. The Ministry of Health (MOH) identified creation of a holistic, safe, secure, and timely national specimen referral system as a priority for improved detection and confirmation of priority diseases, in line with national Integrated Disease Surveillance and Response guidelines. The project consisted of two parts, each led by different implementing partners working collaboratively together and with the Ministry of Health: the development and approval of a national specimen referral policy, and pilot implementation of a specimen referral system, modeled on the policy, in three prefectures. This paper describes the successful execution of the project, highlighting the opportunities and challenges of building sustainable health systems capacity during and after public health emergencies, and provides lessons learned for strengthening national capabilities for surveillance and disease diagnosis.

Funding Public Health Emergency Preparedness in the United States.

The historical precedents that support state and local leadership in preparedness for and response to disasters are in many ways at odds with the technical demands of preparedness and response for incidents affecting public health. New and revised laws and regulations, executive orders, policies, strategies, and plans developed in response to biological threats since 2001 address the role of the federal government in the response to public health emergencies. However, financial mechanisms for disaster response-especially those that wait for gubernatorial request before federal assistance can be provided-do not align with the need to prevent the spread of infectious agents or efficiently reduce the impact on public health. We review key US policies and funding mechanisms relevant to public health emergencies and clarify how policies, regulations, and resources affect coordinated responses.

Mapping of Networks to Detect Priority Zoonoses in Jordan.

Early detection of emerging disease events is a priority focus area for cooperative bioengagement programs. Communication and coordination among national disease surveillance and response networks are essential for timely detection and control of a public health event. Although systematic information sharing between the human and animal health sectors can help stakeholders detect and respond to zoonotic diseases rapidly, resource constraints, and other barriers often prevent efficient cross-sector reporting. The purpose of this research project was to map the laboratory and surveillance networks currently in place for detecting and reporting priority zoonotic diseases in Jordan in order to identify the nodes of communication, coordination, and decision-making where health and veterinary sectors intersect, and to identify priorities and gaps that limit information sharing for action. We selected three zoonotic diseases as case studies: highly pathogenic avian influenza (HPAI) H5N1, rabies, and brucellosis. Through meetings with government agencies and health officials, and desk research, we mapped each system from the index case through response - including both surveillance and laboratory networks, highlighting both areas of strength and those that would benefit from capacity-building resources. Our major findings indicate informal communication exists across sectors; in the event of emergence of one of the priority zoonoses studied, there is effective coordination across the Ministry of Health and Ministry of Agriculture. However, routine formal coordination is lacking. Overall, there is a strong desire and commitment for multi-sectoral coordination in detection and response to zoonoses across public health and veterinary sectors. Our analysis indicates that the networks developed in response to HPAI can and should be leveraged to develop a comprehensive laboratory and surveillance One Health network.

Implementation of the International Health Regulations (2005) Through Cooperative Bioengagement.

Cooperative bioengagement efforts, as practiced by U.S. government-funded entities, such as the Defense Threat Reduction Agency's Cooperative Biological Engagement Program, the State Department's Biosecurity Engagement Program, and parallel programs in other countries, exist at the nexus between public health and security. These programs have an explicit emphasis on developing projects that address the priorities of the partner country as well as the donor. While the objectives of cooperative bioengagement programs focus on reducing the potential for accidental or intentional misuse and/or release of dangerous biological agents, many partner countries are interested in bioengagement as a means to improve basic public health capacities. This article examines the extent to which cooperative bioengagement projects address public health capacity building under the revised International Health Regulations and alignment with the Global Health Security Agenda action packages.

Global health security agenda and the international health regulations: moving forward.

The launch of the Global Health Security Agenda (GHSA) in February 2014 capped over a decade of global efforts to develop new approaches to emerging and reemerging infectious diseases-part of the growing recognition that disease events, whether natural, accidental, or intentional, threaten not just public health, but national, regional, and global security interests. In 2005, the United States, along with other Member States of the World Health Organization (WHO), adopted the revised International Health Regulations [IHR (2005)]. The IHR (2005) conferred new responsibilities on WHO and the global health community to coordinate resources for capacity building and emergency response, and on the now-196 States Parties to develop the core capacities required to detect, assess, report, and respond to potential public health emergencies of international concern. Both GHSA and the IHR aim to elevate political attention and encourage participation, coordination, and collaboration by multiple stakeholders, while leveraging previously existing commitments and multilateral efforts. GHSA and the IHR (2005) are platforms for action; how efforts under each will complement each other remains unclear. Mechanisms that measure progress under these 2 overlapping frameworks will aid in focusing resources and in sustaining political momentum for IHR implementation after 2016.

IDSR as a platform for implementing IHR in African countries.

Of the 46 countries in the World Health Organization (WHO) African region (AFRO), 43 are implementing Integrated Disease Surveillance and Response (IDSR) guidelines to improve their abilities to detect, confirm, and respond to high-priority communicable and noncommunicable diseases. IDSR provides a framework for strengthening the surveillance, response, and laboratory core capacities required by the revised International Health Regulations [IHR (2005)]. In turn, IHR obligations can serve as a driving force to sustain national commitments to IDSR strategies. The ability to report potential public health events of international concern according to IHR (2005) relies on early warning systems founded in national surveillance capacities. Public health events reported through IDSR to the WHO Emergency Management System in Africa illustrate the growing capacities in African countries to detect, assess, and report infectious and noninfectious threats to public health. The IHR (2005) provide an opportunity to continue strengthening national IDSR systems so they can characterize outbreaks and respond to public health events in the region.

Costing framework for International Health Regulations (2005).

The revised International Health Regulations (IHR [2005]) conferred new responsibilities on member states of the World Health Organization, requiring them to develop core capacities to detect, assess, report, and respond to public health emergencies. Many countries have not yet developed these capacities, and poor understanding of the associated costs have created a barrier to effectively marshaling assistance. To help national and international decision makers understand the inputs and associated costs of implementing the IHR (2005), we developed an IHR implementation strategy to serve as a framework for making preliminary estimates of fixed and operating costs associated with developing and sustaining IHR core capacities across an entire public health system. This tool lays the groundwork for modeling the costs of strengthening public health systems from the central to the peripheral level of an integrated health system, a key step in helping national health authorities define necessary actions and investments required for IHR compliance.

Defining health diplomacy: changing demands in the era of globalization.

CONTEXT: Accelerated globalization has produced obvious changes in diplomatic purposes and practices. Health issues have become increasingly preeminent in the evolving global diplomacy agenda. More leaders in academia and policy are thinking about how to structure and utilize diplomacy in pursuit of global health goals. METHODS: In this article, we describe the context, practice, and components of global health diplomacy, as applied operationally. We examine the foundations of various approaches to global health diplomacy, along with their implications for the policies shaping the international public health and foreign policy environments. Based on these observations, we propose a taxonomy for the subdiscipline. FINDINGS: Expanding demands on global health diplomacy require a delicate combination of technical expertise, legal knowledge, and diplomatic skills that have not been systematically cultivated among either foreign service or global health professionals. Nonetheless, high expectations that global health initiatives will achieve development and diplomatic goals beyond the immediate technical objectives may be thwarted by this gap. CONCLUSIONS: The deepening links between health and foreign policy require both the diplomatic and global health communities to reexamine the skills, comprehension, and resources necessary to achieve their mutual objectives.

Incidence of pneumococcal bacteremia requiring hospitalization in rural Thailand.

BACKGROUND: Population-based estimates of the incidence of invasive pneumococcal disease are unavailable for Thailand and other countries in Southeast Asia. We estimated the incidence of pneumococcal bacteremia cases requiring hospitalization in rural Thailand. METHODS: Blood cultures were performed on samples from hospitalized patients in 2 rural provinces where active, population-based surveillance of community-acquired pneumonia is conducted. Blood cultures were performed at clinician discretion and were encouraged for all patients with suspected pneumonia and all children aged <5 years with suspected sepsis. Pneumococcal antigen testing was performed on positive blood culture specimens that failed to grow organisms on subculture. RESULTS: From May 2005 through June 2007, 23,853 blood culture specimens were collected overall, and 7319 were collected from children aged <5 years, which represented 66% and 47% of target patients, respectively. A total of 72 culture-confirmed pneumococcal bacteremia cases requiring hospitalization were identified. An additional 44 patients had media from positive blood cultures that yielded no growth on subculture but that had positive results of pneumococcal antigen testing. Of the 116 confirmed cases of bacteremia, 27 (23%) occurred in children aged <5 years; of these, 9 (33%) were confirmed by antigen testing only. The incidence of pneumococcal bacteremia cases requiring hospitalization among children aged <5 years had a range of 10.6-28.9 cases per 100,000 persons (incidence range if cases detected by antigen are excluded, 7.5-14.0 cases per 100,000 persons). CONCLUSIONS: Invasive pneumococcal disease is more common than was previously suspected in Thailand, even on the basis of estimates limited to hospitalized cases of bacteremia. These estimates, which are close to estimates of the incidence of hospitalized cases of pneumococcal bacteremia in the United States before introduction of pneumococcal conjugate vaccine, provide important data to guide public health care policy and to inform discussions about vaccine introduction in Thailand and the rest of Southeast Asia.

Factors associated with diagnostic evaluation for tuberculosis among adults hospitalized for clinical pneumonia in Thailand.

OBJECTIVE: Thailand is one of 22 countries designated by the World Health Organization as "high burden" with regard to tuberculosis. Preventing nosocomial tuberculosis transmission remains an important, unmet need. We investigated the adequacy of current practices to evaluate hospitalized patients for tuberculosis, which is critical in preventing delayed diagnosis and nosocomial tuberculosis transmission. METHODS: Thailand conducts active, population-based surveillance for pneumonia in 2 rural provinces. Case report forms are completed for all persons who are hospitalized and meet a case definition of having clinical pneumonia. We analyzed how frequently patients had an adequate diagnostic evaluation for infectious pulmonary tuberculosis, in accordance with national guidelines. We conducted multivariate analyses to determine patient and health-system factors associated with an inadequate diagnostic evaluation for tuberculosis and with tuberculosis disease. RESULTS: Of 8,853 cases of clinical pneumonia between September 2003 and March 2006, 73% were in patients not adequately evaluated for tuberculosis. Acid-fast bacilli (AFB)-positive tuberculosis was diagnosed in 188 cases, which was 2% of all pneumonia cases and 12% of pneumonia cases in patients adequately evaluated for tuberculosis. Diagnostic evaluations for tuberculosis were less commonly performed among those who were younger than 25 years of age, were female, and lacked cough, sputum production, hemoptysis, and dyspnea. Among patients adequately evaluated, a clinical syndrome of no cough, no hemoptysis, and normal chest radiography findings had a 95% negative predictive value. CONCLUSIONS: The prevalence of AFB-positive, pulmonary tuberculosis was high among adults hospitalized with clinical pneumonia in Thailand. Most patients were not adequately evaluated for tuberculosis. Efforts are needed to improve identification and diagnosis of infectious tuberculosis cases in hospitalized patients.

Treatment with anti-LFA-1 delays the CD8+ cytotoxic-T-lymphocyte response and viral clearance in mice with primary respiratory syncytial virus infection.

Cytotoxic T lymphocytes (CTLs) play an important role in the immune response against respiratory syncytial virus (RSV) infection. The cell surface molecule lymphocyte function-associated antigen 1 (LFA-1) is an important contributor to CTL activation, CTL-mediated direct cell lysis, and lymphocyte migration. In an attempt to determine the role of LFA-1 during RSV infection, we treated BALB/c mice with monoclonal antibodies to LFA-1 at days -1, +1, and +4 relative to primary RSV infection. Anti-LFA-1 treatment during primary RSV infection led to reduced illness and delayed clearance of virus-infected cells. CTLs from RSV-infected mice that were treated with anti-LFA-1 exhibited diminished cytolytic activity and reduced gamma interferon production. In addition, studies with BrdU (5-bromo-2'-deoxyuridine)- and CFSE [5-(and 6)-carboxyfluorescein diacetate succinimidyl ester]-labeled lymphocytes showed that anti-LFA-1 treatment led to delayed proliferation during RSV infection. These results indicate that LFA-1 plays a critical role in the initiation of the immune response to RSV infection by facilitating CTL activation. These results may prove useful in the development of new therapies to combat RSV infection or other inflammatory diseases.

Construction and characterization of recombinant vaccinia viruses co-expressing a respiratory syncytial virus protein and a cytokine.

Recombinant vaccinia viruses are well-characterized tools that can be used to define novel approaches to vaccine formulation and delivery. While vector co-expression of immune mediators has enormous potential for optimizing the composition of vaccine-induced immune responses, the impact on antigen expression and vector antigenicity must also be considered. Co-expression of IL-4 increased vaccinia virus vector titres, while IFN-gamma co-expression reduced vaccinia virus replication in BALB/c mice and in C57BL/6 mice infected with some recombinant viruses. Protection against respiratory syncytial virus (RSV) challenge was similar in mice immunized with vaccinia virus expressing RSV G glycoprotein and IFN-gamma, even though the replication efficiency of the vector was diminished. These data demonstrate the ability of vector-expressed cytokine to influence the virulence of the vector and to direct the development of selected immune responses. This suggests that the co-expression of cytokines and other immunomodulators has the potential to improve the safety of vaccine vectors while improving the immunogenicity of vaccine antigens.