Lessons Learned from CDC's Global COVID-19 Early Warning and Response Surveillance System.

Early warning and response surveillance (EWARS) systems were widely used during the early COVID-19 response. Evaluating the effectiveness of EWARS systems is critical to ensuring global health security. We describe the Centers for Disease Control and Prevention (CDC) global COVID-19 EWARS (CDC EWARS) system and the resources CDC used to gather, manage, and analyze publicly available data during the prepandemic period. We evaluated data quality and validity by measuring reporting completeness and compared these with data from Johns Hopkins University, the European Centre for Disease Prevention and Control, and indicator-based data from the World Health Organization. CDC EWARS was integral in guiding CDC's early COVID-19 response but was labor-intensive and became less informative as case-level data decreased and the pandemic evolved. However, CDC EWARS data were similar to those reported by other organizations, confirming the validity of each system and suggesting collaboration could improve EWARS systems during future pandemics.

Yellow Fever Outbreak - Kongo Central Province, Democratic Republic of the Congo, August 2016.

On April 23, 2016, the Democratic Republic of the Congo's (DRC's) Ministry of Health declared a yellow fever outbreak. As of May 24, 2016, approximately 90% of suspected yellow fever cases (n = 459) and deaths (45) were reported in a single province, Kongo Central Province, that borders Angola, where a large yellow fever outbreak had begun in December 2015. Two yellow fever mass vaccination campaigns were conducted in Kongo Central Province during May 25-June 7, 2016 and August 17-28, 2016. In June 2016, the DRC Ministry of Health requested assistance from CDC to control the outbreak. As of August 18, 2016, a total of 410 suspected yellow fever cases and 42 deaths were reported in Kongo Central Province. Thirty seven of the 393 specimens tested in the laboratory were confirmed as positive for yellow fever virus (local outbreak threshold is one laboratory-confirmed case of yellow fever). Although not well-documented for this outbreak, malaria, viral hepatitis, and typhoid fever are common differential diagnoses among suspected yellow fever cases in this region. Other possible diagnoses include Zika, West Nile, or dengue viruses; however, no laboratory-confirmed cases of these viruses were reported. Thirty five of the 37 cases of yellow fever were imported from Angola. Two-thirds of confirmed cases occurred in persons who crossed the DRC-Angola border at one market city on the DRC side, where ≤40,000 travelers cross the border each week on market day. Strategies to improve coordination between health surveillance and cross-border trade activities at land borders and to enhance laboratory and case-based surveillance and health border screening capacity are needed to prevent and control future yellow fever outbreaks.

Rapid Laboratory Identification of Neisseria meningitidis Serogroup C as the Cause of an Outbreak - Liberia, 2017.

On April 25, 2017, a cluster of unexplained illness and deaths among persons who had attended a funeral during April 21-22 was reported in Sinoe County, Liberia (1). Using a broad initial case definition, 31 cases were identified, including 13 (42%) deaths. Twenty-seven cases were from Sinoe County (1), and two cases each were from Grand Bassa and Monsterrado counties, respectively. On May 5, 2017, initial multipathogen testing of specimens from four fatal cases using the Taqman Array Card (TAC) assay identified Neisseria meningitidis in all specimens. Subsequent testing using direct real-time polymerase chain reaction (PCR) confirmed N. meningitidis in 14 (58%) of 24 patients with available specimens and identified N. meningitidis serogroup C (NmC) in 13 (54%) patients. N. meningitidis was detected in specimens from 11 of the 13 patients who died; no specimens were available from the other two fatal cases. On May 16, 2017, the National Public Health Institute of Liberia and the Ministry of Health of Liberia issued a press release confirming serogroup C meningococcal disease as the cause of this outbreak in Liberia.

Assessment of public health events through International Health Regulations, United States, 2007-2011.

Under the current International Health Regulations, 194 states parties are obligated to report potential public health emergencies of international concern to the World Health Organization (WHO) within 72 hours of becoming aware of an event. During July 2007-December 2011, WHO assessed and posted on a secure web portal 222 events from 105 states parties, including 24 events from the United States. Twelve US events involved human influenza caused by a new virus subtype, including the first report of influenza A(H1N1)pdm09 virus, which constitutes the only public health emergency of international concern determined by the WHO director-general to date. Additional US events involved 5 Salmonella spp. outbreaks, botulism, Escherichia coli O157:H7 infections, Guillain-Barré syndrome, contaminated heparin, Lassa fever, an oil spill, and typhoid fever. Rapid information exchange among WHO and member states facilitated by the International Health Regulations leads to better situation awareness of emerging threats and enables a more coordinated and transparent global response.

International Health Regulations--what gets measured gets done.

The global spread of severe acute respiratory syndrome highlighted the need to detect and control disease outbreaks at their source, as envisioned by the 2005 revised International Health Regulations (IHR). June 2012 marked the initial deadline by which all 194 World Health Organization (WHO) member states agreed to have IHR core capacities fully implemented for limiting the spread of public health emergencies of international concern. Many countries fell short of these implementation goals and requested a 2-year extension. The degree to which achieving IHR compliance will result in global health security is not clear, but what is clear is that progress against the threat of epidemic disease requires a focused approach that can be monitored and measured efficiently. We developed concrete goals and metrics for 4 of the 8 core capacities with other US government partners in consultation with WHO and national collaborators worldwide. The intent is to offer an example of an approach to implementing and monitoring IHR for consideration or adaptation by countries that complements other frameworks and goals of IHR. Without concrete metrics, IHR may waste its considerable promise as an instrument for global health security against public health emergencies.

U.S. Government engagement in support of global disease surveillance.

Global cooperation is essential for coordinated planning and response to public health emergencies, as well as for building sufficient capacity around the world to detect, assess and respond to health events. The United States is committed to, and actively engaged in, supporting disease surveillance capacity building around the world. We recognize that there are many agencies involved in this effort, which can become confusing to partner countries and other public health entities. This paper aims to describe the agencies and offices working directly on global disease surveillance capacity building in order to clarify the United States Government interagency efforts in this space.

What We Are Watching-Top Global Infectious Disease Threats, 2013-2016: An Update from CDC's Global Disease Detection Operations Center.

To better track public health events in areas where the public health system is unable or unwilling to report the event to appropriate public health authorities, agencies can conduct event-based surveillance, which is defined as the organized collection, monitoring, assessment, and interpretation of unstructured information regarding public health events that may represent an acute risk to public health. The US Centers for Disease Control and Prevention's (CDC's) Global Disease Detection Operations Center (GDDOC) was created in 2007 to serve as CDC's platform dedicated to conducting worldwide event-based surveillance, which is now highlighted as part of the "detect" element of the Global Health Security Agenda (GHSA). The GHSA works toward making the world more safe and secure from disease threats through building capacity to better "Prevent, Detect, and Respond" to those threats. The GDDOC monitors approximately 30 to 40 public health events each day. In this article, we describe the top threats to public health monitored during 2012 to 2016: avian influenza, cholera, Ebola virus disease, and the vector-borne diseases yellow fever, chikungunya virus, and Zika virus, with updates to the previously described threats from Middle East respiratory syndrome-coronavirus (MERS-CoV) and poliomyelitis.

United States Notifications of Travelers from Ebola-Affected Countries.

The International Health Regulations (IHR), an international law under the auspices of the World Health Organization (WHO), mandates that countries notify other countries of "travelers under public health observation." Between November 10, 2014, and July 12, 2015, the US Centers for Disease Control and Prevention (CDC) made 2,374 notifications to the National IHR Focal Points in 114 foreign countries of travelers who were monitored by US health departments because they had been to an Ebola-affected country in West Africa. Given that countries have preidentified focal points as points of contacts for sharing of public health information, notifications could be made by CDC to a trusted public health recipient in another country within 24 hours of receipt of the traveler's information from a US health department. The majority of US health departments used this process, offered by CDC, to notify other countries of travelers intending to leave the United States while being monitored in their jurisdiction.

Early Identification and Prevention of the Spread of Ebola in High-Risk African Countries.

In the late summer of 2014, it became apparent that improved preparedness was needed for Ebola virus disease (Ebola) in at-risk countries surrounding the three highly affected West African countries (Guinea, Sierra Leone, and Liberia). The World Health Organization (WHO) identified 14 nearby African countries as high priority to receive technical assistance for Ebola preparedness; two additional African countries were identified at high risk for Ebola introduction because of travel and trade connections. To enhance the capacity of these countries to rapidly detect and contain Ebola, CDC established the High-Risk Countries Team (HRCT) to work with ministries of health, CDC country offices, WHO, and other international organizations. From August 2014 until the team was deactivated in May 2015, a total of 128 team members supported 15 countries in Ebola response and preparedness. In four instances during 2014, Ebola was introduced from a heavily affected country to a previously unaffected country, and CDC rapidly deployed personnel to help contain Ebola. The first introduction, in Nigeria, resulted in 20 cases and was contained within three generations of transmission; the second and third introductions, in Senegal and Mali, respectively, resulted in no further transmission; the fourth, also in Mali, resulted in seven cases and was contained within two generations of transmission. Preparedness activities included training, developing guidelines, assessing Ebola preparedness, facilitating Emergency Operations Center establishment in seven countries, and developing a standardized protocol for contact tracing. CDC's Field Epidemiology Training Program Branch also partnered with the HRCT to provide surveillance training to 188 field epidemiologists in Côte d'Ivoire, Guinea-Bissau, Mali, and Senegal to support Ebola preparedness. Imported cases of Ebola were successfully contained, and all 15 priority countries now have a stronger capacity to rapidly detect and contain Ebola.The activities summarized in this report would not have been possible without collaboration with many U.S and international partners (http://www.cdc.gov/vhf/ebola/outbreaks/2014-west-africa/partners.html).

Isolation of west nile and sindbis viruses from mosquitoes collected in the Nile Valley of Egypt during an outbreak of Rift Valley fever.

As part of an evaluation of potential vectors of arboviruses during a Rift Valley fever (RVF) outbreak in the Nile Valley of Egypt in August 1993, we collected mosquitoes in villages with known RVF viral activity. Mosquitoes were sorted to species, pooled, and processed for virus isolation both by intracerebral inoculation into suckling mice and by inoculation into cell culture. A total of 33 virus isolates was made from 36,024 mosquitoes. Viruses were initially identified by indirect fluorescent antibody testing and consisted of 30 flaviviruses (all members of the Japanese encephalitis complex, most probably West Nile [WN] virus) and three alphaviruses (all members of western equine encephalitis complex, most probably Sindbis). The identity of selected viruses was confirmed by reverse transcriptase-polymerase chain reaction and sequencing. Culex antennatus (Becker) and Culex perexiguus Theobald accounted for five (17%) and 23 (77%) of the WN virus isolations, respectively. Despite isolation of viruses from 32 pools of mosquitoes (both WN and Sindbis viruses were isolated from a single pool), RVF virus was not isolated from these mosquitoes, even though most of them are known competent vectors collected during an ongoing RVF outbreak. Thus, it should be remembered, that even during a known arbovirus outbreak, other arboviruses may still be circulating and causing disease.

The global outbreak alert and response network.

The Global Outbreak Alert and Response Network (GOARN) was established in 2000 as a network of technical institutions, research institutes, universities, international health organisations and technical networks willing to contribute and participate in internationally coordinated responses to infectious disease outbreaks. It reflected a recognition of the need to strengthen and coordinate rapid mobilisation of experts in responding to international outbreaks and to overcome the sometimes chaotic and fragmented operations characterising previous responses. The network partners agreed that the World Health Organization would coordinate the network and provide a secretariat, which would also function as the operational support team. The network has evolved to comprise 153 institutions/technical partners and 37 additional networks, the latter encompassing a further 355 members and has been directly involved in 137 missions to 79 countries, territories or areas. Future challenges will include supporting countries to achieve the capacity to detect and respond to outbreaks of international concern, as required by the International Health Regulations (2005). GOARN's increasing regional focus and expanding geographic composition will be central to meeting these challenges. The paper summarises some of network's achievements over the past 13 years and presents some of the future challenges.

What we are watching--five top global infectious disease threats, 2012: a perspective from CDC's Global Disease Detection Operations Center.

Disease outbreaks of international public health importance continue to occur regularly; detecting and tracking significant new public health threats in countries that cannot or might not report such events to the global health community is a challenge. The Centers for Disease Control and Prevention's (CDC) Global Disease Detection (GDD) Operations Center, established in early 2007, monitors infectious and non-infectious public health events to identify new or unexplained global public health threats and better position CDC to respond, if public health assistance is requested or required. At any one time, the GDD Operations Center actively monitors approximately 30-40 such public health threats; here we provide our perspective on five of the top global infectious disease threats that we were watching in 2012: 1 avian influenza A (H5N1), 2 cholera, 3 wild poliovirus, 4 enterovirus-71, and 5 extensively drug-resistant tuberculosis11†Current address: Division of Integrated Biosurveillance, Armed Forces Health Surveillance Center, US Department of Defense, Silver Spring, MD, USA.

Assessing the continuum of event-based biosurveillance through an operational lens.

This research follows the Updated Guidelines for Evaluating Public Health Surveillance Systems, Recommendations from the Guidelines Working Group, published by the Centers for Disease Control and Prevention nearly a decade ago. Since then, models have been developed and complex systems have evolved with a breadth of disparate data to detect or forecast chemical, biological, and radiological events that have a significant impact on the One Health landscape. How the attributes identified in 2001 relate to the new range of event-based biosurveillance technologies is unclear. This article frames the continuum of event-based biosurveillance systems (that fuse media reports from the internet), models (ie, computational that forecast disease occurrence), and constructs (ie, descriptive analytical reports) through an operational lens (ie, aspects and attributes associated with operational considerations in the development, testing, and validation of the event-based biosurveillance methods and models and their use in an operational environment). A workshop was held in 2010 to scientifically identify, develop, and vet a set of attributes for event-based biosurveillance. Subject matter experts were invited from 7 federal government agencies and 6 different academic institutions pursuing research in biosurveillance event detection. We describe 8 attribute families for the characterization of event-based biosurveillance: event, readiness, operational aspects, geographic coverage, population coverage, input data, output, and cost. Ultimately, the analyses provide a framework from which the broad scope, complexity, and relevant issues germane to event-based biosurveillance useful in an operational environment can be characterized.

An outbreak of Rift Valley fever in Northeastern Kenya, 1997-98.

In December 1997, 170 hemorrhagic fever-associated deaths were reported in Garissa District, Kenya. Laboratory testing identified evidence of acute Rift Valley fever virus (RVFV). Of the 171 persons enrolled in a cross-sectional study, 31(18%) were anti-RVFV immunoglobulin (Ig) M positive. An age-adjusted IgM antibody prevalence of 14% was estimated for the district. We estimate approximately 27,500 infections occurred in Garissa District, making this the largest recorded outbreak of RVFV in East Africa. In multivariable analysis, contact with sheep body fluids and sheltering livestock in one s home were significantly associated with infection. Direct contact with animals, particularly contact with sheep body fluids, was the most important modifiable risk factor for RVFV infection. Public education during epizootics may reduce human illness and deaths associated with future outbreaks.