The unprecedented 2014–2016 West Africa Ebola epidemic devastated Guinea, Liberia, and Sierra Leone, 3 of the world’s poorest nations (13). These countries accounted for >99% of reported cases (28,652) and deaths (11,325) from Ebola virus infections (6). Ending the epidemic required enormous efforts from affected countries and collaborations with international partners, including CDC (6). CDC supported >3,500 staff deployments, engaging in epidemiologic fieldwork, laboratory testing, risk-reduction communications, improvements in infection control, and research on risk factors for transmission, viral persistence, and an Ebola vaccine (Table 1).

In December 2014, the US Congress authorized $1.2 billion in emergency funding for CDC to end the Ebola epidemic and accelerate GHSA implementation in partnering countries (Figure 1) (14). In early 2015, these funds made it possible for CDC to augment its response with new CDC country offices in Guinea, Liberia, and Sierra Leone, which enhanced response activities to end the epidemic. These countries are now implementing GHSA to build national resilience and preparedness capability (Table 1; Figure 1). Key examples of this work’s impact are the efficient identification and control of the past 7 Ebola virus clusters (17) during 2015–2016 and the rapid response to a cluster of deaths from Neisseria meningitidis infection in Liberia in 2017 (18). These countries are demonstrating that they are now better prepared to prevent, detect, and respond to serious disease threats (Table 2).

The 2014–2016 West Africa Ebola epidemic was the largest emergency response in CDC’s history (6). The identification, training, and deployments of >3,500 CDC staff taxed agency human resource systems and challenged response continuity in the early months. To ensure sustained readiness for the next health emergency, CDC now trains and rosters a Global Rapid Response Team of >400 experts with a broad range of technical and language skills, poised to deploy on short notice and remain in the field for up to 6 months (Table 1).

During September 2015–June 2017, these responders were mobilized >420 times and contributed >14,000 cumulative person-days to emergency response in the field, in Atlanta’s Emergency Operations Center (EOC), or both (Table 1). During this period, the Global Rapid Response Team responded to 13 emergencies in 25 countries, including Zika virus in the Americas (217 mobilizations, 9,494 person-days, 15 countries and territories, and EOC); yellow fever in Angola and the Democratic Republic of the Congo (20 mobilizations and 1,097 person-days); Hurricane Matthew in Haiti (59 mobilizations and 1,235 person-days); and, most recently, Ebola virus in the Democratic Republic of the Congo.

Humanitarian crises resulting from natural disasters (e.g., earthquakes, tsunamis, floods, and droughts); armed conflict; or civil strife routinely lead to large-scale population displacements. Whether migrating outside their countries as refugees or internally displaced in their homelands, disrupted populations routinely experience increased illness and death from respiratory and diarrheal pathogens associated with overcrowding; disrupted health services (e.g., childhood immunizations, treatment for HIV and tuberculosis); and lost access to food, clean water, and sanitation (19,20). For >50 years, CDC has provided technical support to WHO, United Nations agency partners, and others to define the public health aspects of such complex humanitarian emergencies and establish disease surveillance and interventions to mitigate the health consequences of displacement (21–24).

The number of persons affected by complex emergencies has increased over the past decade. In 2016 alone, >125 million persons needed humanitarian assistance (25). During 2007–2016, CDC responded to >20 crises that each affected >10,000 people, each with a crude mortality rate of >1/10,000 persons/day (e.g., the 2010 earthquake in Haiti, the Horn of Africa drought and famine of 2011–2014, and the Syrian crisis since 2012). During 2011–2016, CDC deployed staff for >380 missions in >40 countries to apply public health principles and epidemiologic science to mitigate the health impacts of complex emergencies (Table 1). For the crisis in Syria, CDC deployed staff who worked with nongovernmental organizations and the United Nations Children’s Fund to establish and train staff to conduct surveillance, measles vaccination campaigns, and nutritional surveys. In response to the 2011–2012 Horn of Africa famine, CDC worked with partners to implement morbidity and mortality surveillance systems in 3 countries (Table 1).

The terrorist attacks of September 11, 2001, intentional use of anthrax spores as a biologic agent during that same year, and increasing numbers of outbreaks and complex humanitarian responses prompted CDC to develop a US-based public health emergency management (PHEM) program (26). CDC initially implemented its incident management system (IMS) and activated its EOC in response to SARS outbreaks in 2002–2003. During 2001–2016, CDC has responded to 62 public health emergency events; on 244 other occasions, components of PHEM were used to support responses not requiring full EOC activation. In 2009, the PHEM program began assisting MOHs with strengthening their emergency preparedness through IMS trainings, EOCs, and emergency response plan development.

In 2013, in response to increasing global requests for more sustained emergency management training out of CDC’s EOC, CDC established its PHEM Fellowship Program. Also in 2013, CDC received accreditation from the Emergency Management Accreditation Program (27). CDC is now a recognized world leader in PHEM, providing technical assistance to GHSA and other countries (Figure 1).

CDC established the Global Disease Detection Operations Center (GDDOC) in early 2007 to identify and monitor health threats to the American public and global community. Using event-based surveillance for early alerting and situation awareness, a team of analysts routinely monitor numerous information sources (e.g., Internet, traditional and social media) for disease events using keywords in >50 languages, and validate accuracy with MOHs, WHO, Food and Agricultural Organization of the United Nations, World Organisation for Animal Health, and other partners. GDDOC monitors 30–40 public health threats daily, tracking situations that could develop into public health emergencies of international concern (28). During 2007–2016, GDDOC conducted event-based surveillance and disseminated information on >1,500 outbreaks occurring in >190 countries (Table 1).

GDDOC outbreak response support has included staff deployments and the provision of personal protective equipment, laboratory diagnostic test equipment, reagents, and supplies. GDDOC deploys CDC staff directly to the host country and through the WHO-hosted Global Outbreak Alert and Response Network. Emergency funding from the US Congress in 2014 for Ebola and GHSA made it possible to dramatically augment bilateral and Global Outbreak Alert and Response Network deployments for the West Africa Ebola epidemic. During 2016–2017, GHSA support substantively enhanced GDDOC’s capacity to conduct event-based surveillance.

Following the 2002–2003 SARS outbreak, in 2004, the US Congress authorized funding for CDC to establish a regional Global Disease Detection (GDD) Program. Currently, CDC works with MOHs in 10 countries (Table 1; Figure 2) to host GDD Centers in a network supporting >90 countries. GDD Centers develop public health capacity by conducting epidemiology-, informatics-, and laboratory-based activities and scientific research. GDD Centers characterize public health threats through surveillance, applied research, and pathogen detection and discovery. During 2006–2016, GDD Centers conducted surveillance for key infectious diseases and syndromes; established >380 new diagnostic tests in national or local laboratories in 59 countries; assisted in the discovery and/or detection of 79 strains or pathogens new to the world, country, or region, responded to 2,051 requests for disease outbreak assistance; and trained 115,566 professionals at the national and regional level on public health topics (Table 1). Increasingly, GDD Centers are leading applied research and surveillance efforts to identify the most effective and efficient capacity-building activities that ensure health security.

With growing recognition that infectious disease outbreaks can become pandemics, resulting in considerable loss of life and economic cost, GHSA was launched in February 2014 by 29 countries, WHO, the Food and Agricultural Organization of the United Nations, and the World Organisation for Animal Health to rapidly identify and mitigate infectious disease threats at their source (15). Now, >60 nations are GHSA member countries (Figure 1). The group of 7 industrialized democracies (G7), South Korea, Canada, Nordic countries, and a growing list of private partners have pledged financial support for GHSA implementation in up to 76 countries (Figure 1).

In 2015, the US government committed to accelerating GHSA implementation with 31 countries and the Caribbean Community, an organization of 15 island nations (Figure 1). The United States is investing >$1 billion to advance GHSA’s prevent, detect, and respond framework against infectious disease threats through implementation of 11 measurable action packages (Table 2) (14–16). In 17 Phase I countries, 14 Phase II countries, and the Caribbean Community (Figure 1; Table 1), CDC supports country capacity assessments, 5-year roadmaps, and annual GHSA implementation plan development. In addition, in Phase I countries, CDC provides financial support for implementation of these action packages; substantial progress was achieved in the first year (16). To reduce the risk of emergent zoonotic infections, 13 countries have expanded surveillance systems in humans, wildlife, and animals to foster prevention (Table 1). Ten countries have expanded surveillance systems to include more vaccine-preventable diseases (VPDs), which should strengthen national vaccine delivery systems, including the capacity for emergency vaccination to mitigate an outbreak. For example, community-level monitoring can accelerate targeted immunization, halving the number of vaccine-preventable meningococcal disease cases in West Africa outbreaks (29,30).

To enable disease detection and response efforts, a strong national reference laboratory system requires a tiered laboratory network, including capable central reference laboratories linked to regional and peripheral laboratories with appropriate testing capacities at each level; systems for timely and safe transport of samples and return of results; and procedures that assess and ensure quality. GHSA resources have supported enhanced training for laboratory technicians in 17 Phase I countries, and 16 countries have detected dangerous pathogens using new equipment (Table 1). All 17 Phase I countries have established or expanded the training of field-based epidemiologists, thereby greatly enhancing the number of staff that can detect and effectively respond to health threats at the subjurisdictional level.

A national IMS with coordination of response through EOCs is essential for mitigating public health threats. Sixteen Phase I countries have established or strengthened their national EOCs to manage and monitor health events in real time; of these, 11 have activated their EOCs for simulated and/or real emergency responses.

With so few countries meeting their IHR 2005 commitments through 2014, a validated monitoring program to measure and facilitate progress toward compliance was needed. With CDC support, external and independent GHSA assessments were piloted throughout 2015 in 6 countries to establish a baseline for targeting implementation (Table 1; Figure 3). In February 2016, WHO, working with CDC and GHSA partner countries, adopted the Joint External Evaluation (JEE) tool to harmonize independent monitoring for both GHSA targets and IHR 2005 compliance efforts across all 19 IHR core preparedness capacities (31). JEEs are designed to establish a baseline measurement for a country’s capacity, inform national policy setting, target resources, track progress, and highlight priority areas for improvement.

By mid-July 2017, 52 JEE country assessments were complete, and 27 JEE reports were publicly posted. An additional 25 countries are scheduled for a JEE through 2018 (Table 1; Figure 3).

A well-trained and retained public health workforce is a cornerstone for achieving IHR compliance. CDC is helping develop a global workforce through the FETP-Advanced, modeled after CDC’s 2-year Epidemic Intelligence Service (11). Since FETP’s inception outside North America in 1980, CDC has supported FETPs-Advanced in 65 countries and graduated >3,900 advanced field epidemiologists (Table 1; Figure 2); of these graduates, up to 80% continue to serve in public health programs in their home countries (12). In GHSA Phase I countries, >1,600 persons have completed FETP training. In 2001, CDC started an FETP-Intermediate of 6–9 months’ duration to address district-level public health surveillance and outbreak response gaps in 13 countries. Through 2016, >700 disease detectives had completed intermediate training. During 2005–2016, FETP-Advanced graduates conducted >3,300 outbreak investigations (Table 1). In response to the West Africa Ebola epidemic, FETP prioritized the expansion of FETP-Frontline programs, providing a 3-month training for district surveillance officers to improve local disease detection and response. During 2014–2016, CDC supported 24 new FETP-Frontline programs, mentoring >1,860 participants (Table 1).

Since the 1980s, CDC has supported influenza surveillance and laboratory capacity globally. As of June 2017, CDC supports influenza activities in 79 countries, assisting MOHs and other laboratory partners in the Global Influenza Surveillance and Response Network in the early detection of potential pandemic threats and provides the world with access to new influenza strains to enable the development of effective seasonal influenza vaccines and vaccines against novel influenza strains that have pandemic potential (e.g., the H7N9 avian strain currently circulating in China) (32). With GHSA support, the online International Reagent Resource portal (https://www.internationalreagentresource.org/) has provided reagents to national influenza laboratories and other respiratory disease laboratories worldwide.

CDC has supported global laboratory networks for polio, measles, and rubella for several decades, providing diagnostic testing, technical support, training, and reference laboratory services. Since 2001, CDC has worked with MOHs, WHO, and the Meningitis Vaccine Project, funded by the Bill and Melinda Gates Foundation, to develop and administer meningococcal vaccines to millions of persons living in the Africa meningitis belt and leads the MenAfriNet Consortium to enhance surveillance to monitor the effectiveness of vaccines and emergence of new meningococcal strains (33).

GHSA supports MOHs to conduct surveillance for severe respiratory diseases and other illness clusters. To support this effort, laboratories are provided with test kits and reagents, packaging and shipping protocols, and training in advanced molecular testing methods, allowing detection of multiple pathogens simultaneously.

Most known, new, or emerging infectious disease threats are zoonotic in origin (34,35). Zoonoses are responsible for an estimated >2 billion human illnesses and 2 million human deaths annually (36). Under GHSA, many countries are undertaking efforts to identify and prioritize zoonotic diseases of greatest national concern through a One Health approach (i.e., linking human, environmental, and animal health) (37). This approach helps a country focus limited resources for surveillance, laboratory capacity building, outbreak response, and prevention and control efforts and helps to enhance communication, collaboration, and engagement across critical sectors of government. With technical assistance from experts on zoonotic and emerging infectious diseases, many countries have initiated surveillance to establish etiologies of acute febrile illness. These efforts have begun to increase countries’ capacity to collect sterile specimens; prepare, store, and ship specimens; and collect and report data to clinicians and surveillance systems. Acute febrile illness surveillance has contributed to countries’ understanding of etiologies and pathogen-specific disease burden and can inform clinical algorithms and care and treatment of patients with acute febrile illness. GHSA implementation has demonstrated that enhancing disease-specific capacity improves national public health capacity building overall. Coordinated efforts between cholera experts and emergency management to prevent, detect, and respond to cholera in Cameroon have led to increasing timeliness of EOC activation for other outbreaks. Preventing zoonotic or emerging infectious diseases is one of the critical tenets of GHSA. CDC infection, prevention, and control experts are supporting efforts to build infection control and antimicrobial drug resistance capacity in 10 GHSA Phase I countries. During the West Africa Ebola epidemic, widespread gaps in infection, prevention, and control systems and resources led to outbreak amplification (38). Today, these national policies and practice guidelines are in the Ebola-affected countries to help support sustainability of these efforts.

Country capacity to conduct high-quality VPD surveillance is critical to increase coverage to prevent, detect, and respond to VPD outbreaks. CDC has supported global laboratory networks for polio, measles, and rubella for several decades, providing diagnostic testing, technical support, training, and reference laboratory services. An effective multidisciplinary workforce, including epidemiologists, laboratorians, and data managers, is needed to collect, analyze, and report VPD surveillance data that are accurate, timely, and useful for decision making.

Since 1998, CDC has provided technical and financial support to develop VPD surveillance capacity in low- and middle-income countries through the Stop Transmission of Polio (STOP) program of the Global Polio Eradication Initiative (39). Through July 2017, a total of 2,010 STOP volunteers have been trained in surveillance principles to detect and respond to polio and other VPDs. These volunteers have deployed in 48 teams for 3–6-month assignments to 77 countries (Table 1) (39). STOP volunteers have played a crucial role in enhancing country capacity to respond to outbreaks of other priority infectious diseases, contributing to CDC’s global health protection platform. CDC also has supported 4 countries at high risk for polio to build their own national STOP programs (Table 1) (40–42). VPD surveillance also helps build countries’ public health systems. For example, in Nigeria in 2014, the polio EOC quickly converted to respond to Ebola (43).

National governments are responsible for keeping their citizens healthy and addressing public health challenges. To that end, many countries have established national public health institutes (NPHIs) to carry out essential public health functions, including outbreak detection and response (44,45), and facilitate progress toward IHR 2005 compliance. CDC is the US government’s NPHI and is 1 of >100 members representing 88 countries in the International Association of National Public Health Institutes (IANPHI) (Table 1). With IANPHI, CDC directly supports >20 IANPHI countries in establishing or strengthening their own NPHIs (Figure 2) through developing strategic plans aligned with public health priorities, determining necessary policy changes, creating sustainability plans, and providing technical assistance (Table 1).

Outbreaks, regional epidemics, and pandemics are costly (46–50). During February–July 2003, SARS spread across 4 continents, infected 8,100 persons, killed 774 persons, and cost the global economy $40 billion (46). In the first year of the 2009 influenza H1N1 pandemic, >575,400 persons succumbed worldwide (47). A severe influenza pandemic could cost as much as 4.9% of the world’s gross domestic product (48). In 2015, the West Africa Ebola epidemic cost Guinea, Liberia, and Sierra Leone about $2.2 billion (49).

Because of the recognized need to achieve IHR 2005 compliance worldwide to ensure health security, increasing number of countries that have made GHSA commitments, and early progress achieved with GHSA implementation, the world is becoming better prepared to respond to threats. CDC is helping advance health security through its global health protection platform. More work is needed and momentum in GHSA implementation needs to be sustained so Americans and citizens around the world will have enhanced protection from newly emerging infectious diseases and other health threats.