HHS and USDA Amend Rules for Select Agents and Toxins

On October 5, 2012, the Animal and Plant Health Inspection Service (APHIS) of the US Department of Agriculture (USDA) and the Department of Health and Human Services (HHS) published a Final Rule on Possession, Use, and Transfer of Select Agents and Toxins.^1,2 In accordance with authorizing legislation, the rules introduce a number of changes following the biennial review of the select agent and toxin regulations, including adding new viruses to the select agent list while removing others. The rules also reorganize the select agent and toxins list, providing new regulations for Tier 1 agents and toxins—a special subset of agents and toxins classified as a greater risk in the event of an intentional release. The final rules ultimately aim to protect human, animal, and plant health and safety by reducing the likelihood of an accidental or intentional release of these agents. ¹

Following the evaluation of the previous list of select agents and toxins, 3 new viruses have been added to the HHS list based on scientific data related to their significant public health risk. ¹ They are SARS-CoV and Lujo and Chapare viruses. ¹

A larger group of viruses and toxins has been removed from the select agent and toxin list and will be excluded in compliance with part 73 of the rule:

• Cercopithecine herpesvirus 1 (herpes B virus)

One of the larger changes in the HHS list is the tiering of the agents and toxins. The category Tier 1 agents and toxins contains a subset of agents and toxins that present the greatest risk of deliberate misuse with the most significant potential for mass casualties or devastating effects to economy, critical infrastructure, or public confidence. ¹ The HHS list consists of the following:

• Ebola virus

This list of Tier 1 agents also includes the following HHS/USDA overlap agents and toxins:

• Bacillus anthracis

The USDA rule removes the following plant protection and quarantine (PPQ), veterinary services (VS), and HHS/USDA overlap select agents and toxins from the list:

Plant Protection and Quarantine

• Any subspecies of Ralstonia solanacearum except race 3, biovar 2

Veterinary Services

• Any low pathogenic strains of avian influenza virus

HHS/USDA Overlap

• Venezuelan equine encephalitis virus (subtypes ID and IE) ²

In addition to the HHS/USDA overlap agents listed as Tier 1 agents above, only 2 pathogens regulated by USDA will be categorized as Tier 1 agents. These are:

• Foot-and-mouth disease virus

The final rules require that institutions—research and diagnostic facilities; federal, state, and university laboratories; and private commercial and nonprofit enterprises—containing these Tier 1 agents and toxins adhere to more stringent precautions and security measures. Physical security standards include pre-access assessments and registration of the possession, use, and transfer of the select agents and toxins.^1,2 Institutions also must establish an auxiliary power mechanism and have no fewer than 3 physical security barriers for agent holding areas.

All personnel being considered to receive access to these materials would have to undergo an advanced investigation and will experience more frequent federal background probes: from once every 5 years to once every 36 months. ³ Furthermore, the rule requires workers to check any select agent holdings following transit, after any recruitment or termination of a key manager, and after the disappearance of any assets overseen by a specific person. ³

All affected institutions must comply with several of the standards put forth in the final rules by December 4, 2012, while the rest of the changes are effective April 3, 2013. In many cases, entities affected by the newly designated Tier 1 select agents and toxins already employ some or all of the required measures, but some entities may experience additional operational costs. The published rules provide estimates for these additional costs.

The final rules are intended (1) to create a means of ensuring enhanced oversight in the transfer, storage, and use of select agents and toxins; (2) to define the security procedures and suitability assessments for pre-access and continual monitoring of individuals with access to Tier 1 select agents and toxins; and (3) to ensure that entities in possession of such agents and toxins develop and implement effective means of biosafety, information security, and physical security.^1,2 Overall, the final rules aim to reduce the likelihood of the accidental or intentional release of a select agent or toxin and avoid the costs associated with such a release.

In addition to publishing these changes, HHS has also solicited comment on the possible addition of Highly Pathogenic Avian Influenza H5N1 Viruses Containing the Hemagglutinin from the Goose/Guangdong/1/96 lineage to the HHS select agent list. In a request for information and comment, HHS seeks to determine whether influenza viruses of this lineage pose a potential threat to public health and safety. The request for comment is partially based on the fact that all highly pathogenic human H5N1 cases to date are derived from this lineage and that the hemagglutinin molecule enables the virus to infect a host cell. HHS also seeks comment on whether other non-H5N1 influenza strains containing the same Goose/Guangdong/1/96 lineage would pose a threat and whether these strains should be regulated as Tier 1 select agents, as well as particular precautions and safety measures that should be used when working with these strains. ⁴

Kate Gilles

CDC Releases State-by-State Preparedness Report for 2012

On September 20, 2012, the US Centers for Disease Control and Prevention (CDC) released Public Health Preparedness: 2012 State-By-State Report on Laboratory, Emergency Operations Coordination, and Emergency Public Information and Warning Capabilities. ¹ The report describes the status of preparedness activities in the states, localities, and territories that participate in the Public Health Emergency Preparedness (PHEP) cooperative agreement that the CDC administers. Initiated in 2001, PHEP funding is a major source of federal support for public health preparedness. For the 2012 fiscal year, the total available PHEP funding was $619 million. ¹

In order to better organize and track the range of preparedness activities that are supported by PHEP funding, CDC has identified 15 public health preparedness capabilities.¹ They are:

• Public health laboratory capacity

In this report, CDC describes the current status of 3 capabilities: public health laboratory capacity, emergency operations coordination, and emergency public information and warning. The report focuses on those 3 capabilities because of the availability of relevant data. As data on the remaining preparedness capabilities become available, they will be included in future editions of the report.

Discovery of Novel Coronavirus Raises Alarm

On September 22, the United Kingdom reported to the World Health Organization (WHO) a case of acute respiratory syndrome caused by a novel human coronavirus. The patient, a previously healthy 49-year-old male, was transferred from an intensive care unit in Qatar to the UK on September 11, approximately 1 week after developing symptoms. ¹ The patient had visited Saudi Arabia before becoming sick. The UK Health Protection Agency (HPA) identified a novel coronavirus after conducting laboratory testing and reported the case to the WHO in accordance with the International Health Regulations. ²

The discovery of this novel pathogen prompted an aggressive investigation by leading health authorities to identify additional cases, to find the source of the outbreak, and to determine the risk of widespread outbreaks or a global pandemic. The WHO issued an alert and established a preliminary case definition, ³ while scientists at Erasmus University Medical Center sequenced the pathogen and developed 2 diagnostic assays to confirm other infections. ⁴ The speed and intensity of the investigation can be attributed to a heightened awareness of coronaviruses following the outbreak of SARS in 2003. ⁵ The WHO quickly stated publicly that the virus was not SARS and not SARS-like, despite the common genus of virus, and it did not recommend any travel restrictions. ³

The sequence of the virus that caused infection of the Qatari man was compared to a similar infection in a 60-year-old Saudi national who died after experiencing severe pneumonia and renal failure in June 2012. The sequences had a 99.5% match. Additional public health investigations revealed no additional cases and no person-to-person transmission among known contacts of the 2 infected individuals. ⁶

Soon after the novel virus was reported to the WHO, teams of disease experts, many of whom were part of the public health response to SARS in 2003, traveled to Saudi Arabia to try to identify the source of the new coronavirus. ⁷ On October 17, a group of scientists representing the hospital in Saudi Arabia that treated the first patient and Erasmus Medical Center in Rotterdam, the Netherlands, published a detailed case report and molecular and genetic analyses in the New England Journal of Medicine. They also hypothesized that the source of the virus was a species of bats that are found in Saudi Arabia and were found to carry the identified species of coronavirus. ⁸

On November 4, the deputy minister of health of Saudi Arabia announced via ProMED that a third case of human infection caused by this novel human coronavirus had been identified and reported to the WHO. ⁹ As of November 5, details regarding this third case have yet to be described, but no link to the previous cases is suspected. ¹⁰ Although the threat of widespread outbreaks caused by this new virus appears to be low, the emergence of the new virus reinforces the heightened awareness of coronaviruses as pathogens that can cause severe human disease. The ongoing public health and scientific investigations will be important to follow in the coming months.

Kunal J. Rambhia

Outbreaks of H3N2v Influenza Among People and Swine at Agricultural Fairs

In July 2012, the US Centers for Disease Control and Prevention (CDC) began receiving reports of novel H3N2 infections. ¹ By late October, the total number of such infections was 306 people and spanned 10 states. There were 16 hospitalizations and 1 death reported from the virus (Table 1). ² More than 90% of these cases occurred after prolonged exposure to pigs, mostly in agriculture fair settings. ³

This novel H3N2 variant (H3N2v) was first detected in pigs in 2010, and human cases were first identified between August and December 2011; more widespread cases were reported in 2012. ⁴ Different from the seasonal H3N2 virus that commonly circulates among humans, H3N2v is a variant swine influenza virus (ie, a nonhuman virus that normally circulates among pigs but has infected humans). ⁵ The virus is usually transmitted to humans through infected droplets produced when an infected pig coughs or sneezes. ⁴ H3N2v infections are not distinguished clinically from seasonal flu infections and other flulike illnesses; symptoms include fever and respiratory symptoms, such as cough and runny nose, and possibly other symptoms, such as body aches, nausea, vomiting, and diarrhea. ⁴

CDC issued an advisory for fairgoers on preventing flu transmission between pigs and people, but it did not recommend that states cancel pig exhibitions. ⁶ However, a recently published study in Emerging Infectious Diseases indicates that infected animals commonly appear clinically normal, making it difficult to identify infected pigs and prevent them from being publicly exhibited. ⁷ The CDC advisory also recommended that people at high risk for flu complications (eg, children younger than 5 years, pregnant women, and people with particular long-term health conditions) avoid swine barns at fairs. ⁸

Although the vast majority of H3N2v cases identified since July occurred after prolonged swine exposure and no ongoing human-to-human transmission has been identified, the emergence of H3N2v is particularly concerning because the virus contains the matrix gene of the 2009 H1N1 virus, suggesting it has the potential to become more easily transmissible in humans than other swine influenza viruses. ⁴ And although the severity of illnesses associated with H3N2v virus has been similar to seasonal flu virus infections, influenza viruses are known to change, and it is possible that the H3N2v virus could evolve to spread more easily from person to person. ⁴

The vast majority of infected individuals have been younger than age 18, and the median age of infection is 7 years old. Research suggests that children and middle-aged adults have little or no immunity to H3N2v influenza, but approximately half of adolescents and young adults have some degree of immunity. ⁹ The seasonal flu vaccines used over the past 2 years do not improve immune response to H3N2v. A specific vaccine would be required to protect the population in the event H3N2v were to become more widespread. CDC has prepared a candidate H3N2v vaccine, and clinical trials are expected this fall. ⁹

Ryan Morhard

Large Outbreak of West Nile Virus Disease in US

As of October 16, 2012, a total of 4,531 cases of West Nile virus (WNV) disease have been reported to the US Centers for Disease Control and Prevention (CDC). Deaths from the disease have reached 183. Additionally, 2,293 of reported cases were classified as having neuroinvasive disease, such as meningitis or encephalitis. ¹ The number of reported cases so far makes this outbreak of WNV the second largest experienced in the US. The largest occurred in 2003, when a total of 9,862 cases and 264 deaths from WNV were reported. ² However, CDC officials have noted that reported cases for the current outbreak are lower than in 2003 because of an artifact in case reporting, and they have stated that the current outbreak is the most serious in US history. ³

WNV is a mosquitoborne virus that can also infect birds and other animals. About 80% of humans infected with WNV have no symptoms, while up to 20% have mild symptoms such as fever, headache, body aches, nausea, vomiting, and sometimes swollen lymph glands or rash. However, for about 1 person in every 150 infected, serious illness will develop, particularly in older individuals. Those with severe disease may develop encephalitis and experience symptoms such as high fever, headache, neck stiffness, stupor, disorientation, coma, tremors, convulsions, muscle weakness, vision loss, numbness, and paralysis. Some neurological effects may be permanent. ⁴

Historically, WNV was considered to be a disease of Africa, Central Asia, the Middle East, and the Mediterranean, with occasional cases in Europe. But in late August 1999, the disease was discovered in a cluster of patients with viral encephalitis in Queens, NY. Although it is not known for certain when and from where the disease was introduced, the epidemiologic evidence suggests that the virus was first introduced during the spring or early summer of that year, perhaps from Tel Aviv, which was experiencing an epidemic at that time. ⁵ Since the virus was introduced, it has spread westward year by year, and by 2002 it had reached the west coast. ⁶

The 2012 outbreak has affected all of the lower 48 states, but some states have reported a greater disease burden than others. Over 30% of cases were reported from Texas alone, while nearly 70% of cases were reported from just 8 states: Texas, California, Louisiana, Mississippi, Illinois, South Dakota, Michigan, and Oklahoma. ¹ One possible explanation for the larger number of cases this year is an increased mosquito population caused by weather conditions that led to stagnant water pools ideal for mosquito breeding.^7,8

The outbreak has also exposed laboratory testing limits, as the laboratory system was stressed by shortages of diagnostic test kits and staff. Laboratories were forced to hire temporary staff and have laboratory staff work extended shifts, including weekends and holidays. Because there is no specific treatment for WNV, there is little impact from delays in testing, but laboratory system limits could pose a problem in other disease outbreaks. ⁹

Tara Kirk Sell