Rapid Diagnostic Testing for Response to the Monkeypox Outbreak - Laboratory Response Network, United States, May 17-June 30, 2022.

As part of public health preparedness for infectious disease threats, CDC collaborates with other U.S. public health officials to ensure that the Laboratory Response Network (LRN) has diagnostic tools to detect Orthopoxviruses, the genus that includes Variola virus, the causative agent of smallpox. LRN is a network of state and local public health, federal, U.S. Department of Defense (DOD), veterinary, food, and environmental testing laboratories. CDC developed, and the Food and Drug Administration (FDA) granted 510(k) clearance* for the Non-variola Orthopoxvirus Real-time PCR Primer and Probe Set (non-variola Orthopoxvirus [NVO] assay), a polymerase chain reaction (PCR) diagnostic test to detect NVO. On May 17, 2022, CDC was contacted by the Massachusetts Department of Public Health (DPH) regarding a suspected case of monkeypox, a disease caused by the Orthopoxvirus Monkeypox virus. Specimens were collected and tested by the Massachusetts DPH public health laboratory with LRN testing capability using the NVO assay. Nationwide, 68 LRN laboratories had capacity to test approximately 8,000 NVO tests per week during June. During May 17-June 30, LRN laboratories tested 2,009 specimens from suspected monkeypox cases. Among those, 730 (36.3%) specimens from 395 patients were positive for NVO. NVO-positive specimens from 159 persons were confirmed by CDC to be monkeypox; final characterization is pending for 236. Prompt identification of persons with infection allowed rapid response to the outbreak, including isolation and treatment of patients, administration of vaccines, and other public health action. To further facilitate access to testing and increase convenience for providers and patients by using existing provider-laboratory relationships, CDC and LRN are supporting five large commercial laboratories with a national footprint (Aegis Science, LabCorp, Mayo Clinic Laboratories, Quest Diagnostics, and Sonic Healthcare) to establish NVO testing capacity of 10,000 specimens per week per laboratory. On July 6, 2022, the first commercial laboratory began accepting specimens for NVO testing based on clinician orders.

CDC Deployments to State, Tribal, Local, and Territorial Health Departments for COVID-19 Emergency Public Health Response - United States, January 21-July 25, 2020.

Coronavirus disease 2019 (COVID-19) is a viral respiratory illness caused by SARS-CoV-2. During January 21-July 25, 2020, in response to official requests for assistance with COVID-19 emergency public health response activities, CDC deployed 208 teams to assist 55 state, tribal, local, and territorial health departments. CDC deployment data were analyzed to summarize activities by deployed CDC teams in assisting state, tribal, local, and territorial health departments to identify and implement measures to contain SARS-CoV-2 transmission (1). Deployed teams assisted with the investigation of transmission in high-risk congregate settings, such as long-term care facilities (53 deployments; 26% of total), food processing facilities (24; 12%), correctional facilities (12; 6%), and settings that provide services to persons experiencing homelessness (10; 5%). Among the 208 deployed teams, 178 (85%) provided assistance to state health departments, 12 (6%) to tribal health departments, 10 (5%) to local health departments, and eight (4%) to territorial health departments. CDC collaborations with health departments have strengthened local capacity and provided outbreak response support. Collaborations focused attention on health equity issues among disproportionately affected populations (e.g., racial and ethnic minority populations, essential frontline workers, and persons experiencing homelessness) and through a place-based focus (e.g., persons living in rural or frontier areas). These collaborations also facilitated enhanced characterization of COVID-19 epidemiology, directly contributing to CDC data-informed guidance, including guidance for serial testing as a containment strategy in high-risk congregate settings, targeted interventions and prevention efforts among workers at food processing facilities, and social distancing.

Detecting Emerging Infectious Diseases: An Overview of the Laboratory Response Network for Biological Threats.

The Laboratory Response Network (LRN) was established in 1999 to ensure an effective laboratory response to high-priority public health threats. The LRN for biological threats (LRN-B) provides a laboratory infrastructure to respond to emerging infectious diseases. Since 2012, the LRN-B has been involved in 3 emerging infectious disease outbreak responses. We evaluated the LRN-B role in these responses and identified areas for improvement. LRN-B laboratories tested 1097 specimens during the 2014 Middle East Respiratory Syndrome Coronavirus outbreak, 180 specimens during the 2014-2015 Ebola outbreak, and 92 686 specimens during the 2016-2017 Zika virus outbreak. During the 2014-2015 Ebola outbreak, the LRN-B uncovered important gaps in biosafety and biosecurity practices. During the 2016-2017 Zika outbreak, the LRN-B identified the data entry bottleneck as a hindrance to timely reporting of results. Addressing areas for improvement may help LRN-B reference laboratories improve the response to future public health emergencies.

Can mentorship improve laboratory quality? A case study from influenza diagnostic laboratories in Southeast Europe.

BACKGROUND: Strengthening the quality of laboratory diagnostics is a key part of building global health capacity. In 2015, the Centers for Disease Control and Prevention (CDC), the Southeast European Center for Surveillance and Control of Infectious Diseases (SECID), WHO European Regional Office (WHO EURO) and American Public Health Laboratories (APHL) collaborated to address laboratory quality training needs in Southeast Europe. Together, they developed a quality assurance (QA) mentorship program for six national laboratories (Laboratories A-E) in five countries utilizing APHL international consultants. The primary goal of the mentorship program was to help laboratories become recognized by WHO as National Influenza Centers (NICs). The program aimed to do this by strengthening influenza laboratory capacity by implementing quality management systems (QMS) action steps. After 1 year, we evaluated participants' progress by the proportion of QMS action steps they had successfully implemented, as well as the value of mentorship as perceived by laboratory mentees, mentors, and primary program stakeholders from SECID and WHO EURO. METHODS: To understand perceived value we used the qualitative method of semi-structured interviews, applying grounded theory to the thematic analysis. RESULTS: Mentees showed clear progress, having completed 32 to 68% [median: 62%] of planned QMS action steps in their laboratories. In regards to the perceived value of the program, we found strong evidence that laboratory mentorship enhances laboratory quality improvement by promoting accountability to QMS implementation, raising awareness of the importance of QMS, and fostering collaborative problem solving. CONCLUSION: In conclusion, we found that significant accomplishments can be achieved when QA programs provide dedicated technical mentorship for QMS implementation. Since the start of the mentoring, Laboratory "B" has achieved NIC recognition by WHO, while two other labs made substantial progress and are scheduled for recognition in 2018. In the future, we recommend that mentorship is more inclusive of laboratory directors, and that programs evaluate the amount of staff time needed for mentorship activities, including lab-based assessments and mentoring.

Mapping of the US Domestic Influenza Virologic Surveillance Landscape.

Influenza virologic surveillance is critical each season for tracking influenza circulation, following trends in antiviral drug resistance, detecting novel influenza infections in humans, and selecting viruses for use in annual seasonal vaccine production. We developed a framework and process map for characterizing the landscape of US influenza virologic surveillance into 5 tiers of influenza testing: outpatient settings (tier 1), inpatient settings and commercial laboratories (tier 2), state public health laboratories (tier 3), National Influenza Reference Center laboratories (tier 4), and Centers for Disease Control and Prevention laboratories (tier 5). During the 2015-16 season, the numbers of influenza tests directly contributing to virologic surveillance were 804,000 in tiers 1 and 2; 78,000 in tier 3; 2,800 in tier 4; and 3,400 in tier 5. With the release of the 2017 US Pandemic Influenza Plan, the proposed framework will support public health officials in modeling, surveillance, and pandemic planning and response.

Measuring influenza laboratory capacity: use of a tool to measure improvements.

BACKGROUND: To collect information, identify training needs, and assist with influenza capacity building voluntary laboratory capacity assessments were conducted using a standardized tool in CDC cooperative agreement countries. To understand the usefulness of comparing results from repeat assessments and to determine if targeted training supported improvements, this paper details comparison of assessment results of conducting 17 repeat laboratory assessments between 2009 and 2013. METHODS: Laboratory assessments were conducted by SMEs in 17 laboratories (16 countries). We reviewed the quantitative assessment results of the laboratories that conducted both an initial and follow up assessment between 2009 to 2013 using repeated measures of Anova, (Mixed procedure of SAS (9.3)). Additionally, we compared the overall summary scores and the assessor recommendations from the two assessments. RESULTS: We were able to document a statistically significant improvement between the first and second assessments both on an aggregate as well as individual indicator score. Within the international capacity tool three of the eight categories recorded statistically significant improvement (equipment, management, and QA/QC), while the other tool categories (molecular, NIC, specimen, safety and virology) showed improvement in scores although not statistically significant. CONCLUSIONS: We found that using a standardized tool and quantitative framework is useful for documenting capacity and performance improvement in identified areas over time. The use of the tool and standard reports with assessor recommendations assisted laboratories with establishing, maintaining, and improving influenza laboratory practices. On-going assessments and the consistent application of the analytic framework over time will continue to aid in building a measurement knowledge base for laboratory capacity.

Comparative analytical evaluation of the respiratory TaqMan Array Card with real-time PCR and commercial multi-pathogen assays.

In this study, a multicenter evaluation of the Life Technologies TaqMan(®) Array Card (TAC) with 21 custom viral and bacterial respiratory assays was performed on the Applied Biosystems ViiA™ 7 Real-Time PCR System. The goal of the study was to demonstrate the analytical performance of this platform when compared to identical individual pathogen specific laboratory developed tests (LDTs) designed at the Centers for Disease Control and Prevention (CDC), equivalent LDTs provided by state public health laboratories, or to three different commercial multi-respiratory panels. CDC and Association of Public Health Laboratories (APHL) LDTs had similar analytical sensitivities for viral pathogens, while several of the bacterial pathogen APHL LDTs demonstrated sensitivities one log higher than the corresponding CDC LDT. When compared to CDC LDTs, TAC assays were generally one to two logs less sensitive depending on the site performing the analysis. Finally, TAC assays were generally more sensitive than their counterparts in three different commercial multi-respiratory panels. TAC technology allows users to spot customized assays and design TAC layout, simplify assay setup, conserve specimen, dramatically reduce contamination potential, and as demonstrated in this study, analyze multiple samples in parallel with good reproducibility between instruments and operators.

Capacity building in national influenza laboratories--use of laboratory assessments to drive progress.

BACKGROUND: Laboratory testing is a fundamental component of influenza surveillance for detecting novel strains with pandemic potential and informing biannual vaccine strain selection. The United States (U.S.) Centers for Disease Control and Prevention (CDC), under the auspices of its WHO Collaborating Center for Influenza, is one of the major public health agencies which provides support globally to build national capacity for influenza surveillance. Our main objective was to determine if laboratory assessments supported capacity building efforts for improved global influenza surveillance. METHODS: In 2010, 35 national influenza laboratories were assessed in 34 countries, using a standardized tool. Post-assessment, each laboratory received a report with a list of recommendations for improvement. Uptake of recommendations were reviewed 3.2 mean years after the initial assessments and categorized as complete, in-progress, no action or no update. This was a retrospective study; follow-up took place through routine project management rather than at a set time-point post-assessment. WHO data on National Influenza Centre (NIC) designation, External Quality Assessment Project (EQAP) participation and FluNet reporting was used to measure laboratory capacity longitudinally and independently of the assessments. All data was further stratified by World Bank country income category. RESULTS: At follow-up, 81% of 614 recommendations were either complete (350) or in-progress (145) for 32 laboratories (91% response rate). The number of countries reporting to FluNet and the number of specimens they reported annually increased between 2005, when they were first funded by CDC, and 2010, the assessment year (p < 0.01). Improvements were also seen in EQAP participation and NIC designation over time and more so for low and lower-middle income countries. CONCLUSIONS: Assessments using a standardized tool have been beneficial to improving laboratory-based influenza surveillance. Specific recommendations helped countries identify and prioritize areas for improvement. Data from assessments helped CDC focus its technical assistance by country and region. Low and lower-middle income countries made greater improvements in their laboratories compared with upper-middle income countries. Future research could include an analysis of annual funding and technical assistance by country. Our approach serves as an example for capacity building for other diseases.

Use of rapid influenza diagnostic tests under field conditions as a screening tool during an outbreak of the 2009 novel influenza virus: practical considerations.

BACKGROUND: Rapid influenza diagnostic tests (RIDTs) are used in various settings as a first-line screen of patient specimens. During the initial outbreak of the 2009 novel influenza A/H1N1 virus, the Nebraska Public Health Laboratory (NPHL) adopted a testing algorithm, attempting to maximize the usefulness of RIDTs. However, it became apparent that a high percentage of the positive specimens received from off-site facilities were negative for influenza viruses by the confirmatory test, the Luminex xTAG Respiratory Viral Panel (RVP) molecular assay. OBJECTIVES: To explore the cause of discrepancies between RIDTs results obtained from on-site facility testing versus confirmatory testing performed at NPHL. STUDY DESIGN: Specimens (n=336) tested with RIDTs at off-site facilities and screened for high-probability of containing H1N1 were sent to the NPHL for confirmatory testing by RVP. RESULTS: Of 336 specimens analyzed, 104 were negative for influenza A or B by both RIDT and RVP; 127 were positive by both tests; 102 were positive by RIDT only; and 3 were positive by RVP only. Using the RVP assay as the gold standard, overall RIDT characteristics in this screened population were: sensitivity=97.7% (95%CI: 92.5, 99.3); specificity=48.1% (95%CI: 40.4, 55.8); positive predictive value=54.3% (95%CI: 47.0, 61.4); and negative predicative value=97.1% (95%CI: 90.6, 99.1). CONCLUSIONS: The results show that the confirmation of RIDT-positive results varied widely by testing site. Possible explanations for the discrepancies in performance characteristics include testing a narrowly defined sample population, test facility characteristics, facility work load, and seasonal timing.

Molecular identification of Mycobacterium chimaera as a cause of infection in a patient with chronic obstructive pulmonary disease.

This report describes a case of Mycobacterium chimaera infection in a patient with a history of chronic obstructive pulmonary disease where the organism was identified by using molecular methods. M. chimaera was identified from fresh lung tissue and from an instrument-negative mycobacterial growth indicator tube broth culture. The utility of using sequence analysis of the internal transcribed spacer region for the rapid identification of a slow-growing nontuberculous Mycobacterium spp. where conventional culture methods were not successful was shown.

An outbreak of avian mycobacteriosis caused by Mycobacterium intracellulare in little blue penguins (Eudyptula minor).

Mycobacterium intracellulare (MIT) was diagnosed postmortem by culture and supporting histopathology in seven birds from a flock of little blue penguins (Eudyptula minor) at the Henry Doorly Zoo (HDZ). These birds represented 20% of the deaths in the population over a 4 yr period. Clinical signs in affected birds included severe respiratory distress characterized by open-mouth breathing with chronic debilitation. On exam, plaques were noted in the larynx, trachea, and soft tissue of the caudal oropharynx. Index cases were identified on necropsy in two birds on loan to another institution in 2003. Following a case confirmed antemortem at the HDZ, a three-drug protocol of rifampin (15 mg/kg p.o. s.i.d.), ethambutol (15 mg/kg p.o. s.i.d.), and clarithromycin (10 mg/kg p.o. s.i.d.) was started on this bird in 2004 and extended to the entire flock in 2005. Gastric wash, fecal samples, and throat plaques were obtained antemortem on five birds within the flock, selected because of the presence of oral plaques, and tested by culture followed by a polymerase chain reaction assay. MIT was detected in gastric washes from four birds and in throat plaques from all five. Three more birds died during treatment. After the seventh bird died, antimicrobial susceptibility testing performed in July 2007 indicated that the MIT was now resistant to most antibiotics tested, including rifampin and ethambutol. The treatment regimen was changed to minocycline (10 mg/kg p.o. b.i.d.) and clarithromycin (10 mg/kg p.o. s.i.d.). Oral plaques were not seen on monthly rechecks of the flock through November 2008. The proposed mechanism of transmission is exposure to wild birds but the source has not been determined. These cases of avian mycobacteriosis caused by MIT are the first known cases reported in little blue penguins.