Baseline Asymptomatic Malaria Infection and Immunogenicity of Recombinant Vesicular Stomatitis Virus-Zaire Ebola Virus Envelope Glycoprotein.

BACKGROUND: The effect of malaria infection on the immunogenicity of the recombinant vesicular stomatitis virus-Zaire Ebola virus envelope glycoprotein (GP) vaccine (rVSVΔG-ZEBOV-GP) (ERVEBO) is unknown. METHODS: The Sierra Leone Trial to Introduce a Vaccine Against Ebola (STRIVE) vaccinated 7998 asymptomatic adults with rVSVΔG-ZEBOV-GP during the 2014-2016 Ebola epidemic. In STRIVE's immunogenicity substudy, participants provided blood samples at baseline and at 1, 6, and 9-12 months. Anti-GP binding and neutralizing antibodies were measured using validated assays. Baseline samples were tested for malaria parasites by polymerase chain reaction. RESULTS: Overall, 506 participants enrolled in the immunogenicity substudy and had ≥1 postvaccination antibody titer. Of 499 participants with a result, baseline malaria parasitemia was detected in 73 (14.6%). All GP enzyme-linked immunosorbent assay (ELISA) and plaque reduction neutralization test (PRNT) geometric mean titers (GMTs) at 1, 6, and 9-12 months were above baseline, and 94.1% of participants showed seroresponse by GP-ELISA (≥2-fold rise and ≥200 ELISA units/mL), while 81.5% showed seroresponse by PRNT (≥4-fold rise) at ≥1 postvaccination assessment. In participants with baseline malaria parasitemia, the PRNT seroresponse proportion was lower, while PRNT GMTs and GP-ELISA seroresponse and GMTs showed a trend toward lower responses at 6 and 9-12 months. CONCLUSION: Asymptomatic adults with or without malaria parasitemia had robust immune responses to rVSVΔG-ZEBOV-GP, persisting for 9-12 months. Responses in those with malaria parasitemia were somewhat lower.

Implementing an Ebola Vaccine Study - Sierra Leone.

In October 2014, the College of Medicine and Allied Health Sciences of the University of Sierra Leone, the Sierra Leone Ministry of Health and Sanitation, and CDC joined the global effort to accelerate assessment and availability of candidate Ebola vaccines and began planning for the Sierra Leone Trial to Introduce a Vaccine against Ebola (STRIVE). STRIVE was an individually randomized controlled phase II/III trial to evaluate efficacy, immunogenicity, and safety of the recombinant vesicular stomatitis virus Ebola vaccine (rVSV-ZEBOV). The study population was health care and frontline workers in select chiefdoms of the five most affected districts in Sierra Leone. Participants were randomized to receive a single intramuscular dose of rVSV-ZEBOV at enrollment or to receive a single intramuscular dose 18-24 weeks after enrollment. All participants were followed up monthly until 6 months after vaccination. Two substudies separately assessed detailed reactogenicity over 1 month and immunogenicity over 12 months. During the 5 months before the trial, STRIVE and partners built a research platform in Sierra Leone comprising participant follow-up sites, cold chain, reliable power supply, and vaccination clinics and hired and trained at least 350 national staff. Wide-ranging community outreach, informational sessions, and messaging were conducted before and during the trial to ensure full communication to the population of the study area regarding procedures and current knowledge about the trial vaccine. During April 9-August 15, 2015, STRIVE enrolled 8,673 participants, of whom 453 and 539 were also enrolled in the safety and immunogenicity substudies, respectively. As of April 28, 2016, no Ebola cases and no vaccine-related serious adverse events, which by regulatory definition include death, life-threatening illness, hospitalization or prolongation of hospitalization, or permanent disability, were reported in the study population. Although STRIVE will not produce an estimate of vaccine efficacy because of low case frequency as the epidemic was controlled, data on safety and immunogenicity will support decisions on licensure of rVSV-ZEBOV.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).

Cultivation of an Adaptive Domestic Network for Surveillance and Evaluation of Emerging Infections.

Accomplishments of this program have provided numerous dividends and might benefit areas outside infectious diseases.

Effect of Culture-Independent Diagnostic Tests on Future Emerging Infections Program Surveillance.

The Centers for Disease Control and Prevention Emerging Infections Program (EIP) network conducts population-based surveillance for pathogens of public health importance. Central to obtaining estimates of disease burden and tracking microbiological characteristics of these infections is accurate laboratory detection of pathogens. The use of culture-independent diagnostic tests (CIDTs) in clinical settings presents both opportunities and challenges to EIP surveillance. Because CIDTs offer better sensitivity than culture and are relatively easy to perform, their use could potentially improve estimates of disease burden. However, changes in clinical testing practices, use of tests with different sensitivities and specificities, and changes to case definitions make it challenging to monitor trends. Isolates are still needed for performing strain typing, antimicrobial resistance testing, and identifying other molecular characteristics of organisms. In this article, we outline current and future EIP activities to address issues associated with adoption of CIDTs, which may apply to other public health surveillance.

Update on progress in electronic reporting of laboratory results to public health agencies - United States, 2014.

Since 2010, CDC has provided resources from the Prevention and Public Health Fund of the Affordable Care Act to 57 state, local, and territorial health departments through the Epidemiology and Laboratory Capacity for Infectious Diseases cooperative agreement to assist with implementation of electronic laboratory reporting (ELR)* from clinical and public health laboratories to public health agencies. To update information from a previous report about the progress in implementing ELR in the United States, CDC examined regular communications between the agency and the 57 health departments during 2012-2014. The results indicated that, as of July 2014, 67% of the approximately 20 million laboratory reports received annually for notifiable conditions were received electronically, compared with 62% in July 2013. These electronic reports were received by 55 of the 57 jurisdictions and came from 3,269 (up from nearly 2,900 in July 2013) of approximately 10,600 reporting laboratories. The proportion of laboratory reports received electronically varied by jurisdiction. In 2014, compared with 2013, the number of jurisdictions receiving >75% of laboratory reports electronically was higher (21 versus 14), and the number of jurisdictions receiving <25% of reports electronically was lower (seven versus nine). National implementation of ELR continues to increase and appears it might reach 80% of total laboratory report volume by 2016.

Telephone triage service data for detection of influenza-like illness.

BACKGROUND: Surveillance for influenza and influenza-like illness (ILI) is important for guiding public health prevention programs to mitigate the morbidity and mortality caused by influenza, including pandemic influenza. Nontraditional sources of data for influenza and ILI surveillance are of interest to public health authorities if their validity can be established. METHODS/PRINCIPAL FINDINGS: National telephone triage call data were collected through automated means for purposes of syndromic surveillance. For the 17 states with at least 500,000 inhabitants eligible to use the telephone triage services, call volume for respiratory syndrome was compared to CDC weekly number of influenza isolates and percentage of visits to sentinel providers for ILI. The degree to which the call data were correlated with either CDC viral isolates or sentinel provider percentage ILI data was highly variable among states. CONCLUSIONS: Telephone triage data in the U.S. are patchy in coverage and therefore not a reliable source of ILI surveillance data on a national scale. However, in states displaying a higher correlation between the call data and the CDC data, call data may be useful as an adjunct to state-level surveillance data, for example at times when sentinel surveillance is not in operation or in areas where sentinel provider coverage is considered insufficient. Sufficient population coverage, a specific ILI syndrome definition, and the use of a threshold of percentage of calls that are for ILI would likely improve the utility of such data for ILI surveillance purposes.

Decision instrument for the isolation of pneumonia patients with suspected pulmonary tuberculosis admitted through US emergency departments.

STUDY OBJECTIVE: Many patients with pneumonia are admitted to respiratory isolation for possible tuberculosis (TB), but most do not have active TB. We created a decision instrument to predict which pneumonia patients do not need admission to a TB isolation bed. METHODS: The design was a prospective case series conducted in 11 university-affiliated, urban, US emergency departments (EDs) (EMERGEncy ID NET). Participants were patients admitted to the hospital through the ED with a diagnosis of pneumonia or suspected TB. The main outcome measure was derivation and validation of a sensitive decision instrument to identify patients not having TB (and not requiring isolation) according to clinical data and chest radiographs. RESULTS: Of 5,079 pneumonia patients, 224 (4.4%) had pulmonary TB according to sputum cultures or tissue staining. The instrument derived to predict which patients did not have pulmonary TB included no TB history or previous positive tuberculin skin test result, nonimmigrant, not homeless, not recently incarcerated, no recent weight loss, and no apical infiltrate or cavitary lesion on plain chest radiograph. When tested on the validation subgroup, the decision instrument exhibited a negative predictive value of 99.7% (95% confidence interval [CI] 99.1% to 99.9%), and a sensitivity of 96.4% (95% CI 91.1% to 99.0%). CONCLUSION: A decision instrument can accurately predict which patients with pneumonia do not require admission to TB isolation rooms.

Disease surveillance and the academic, clinical, and public health communities.

The Emerging Infections Programs (EIPs), a population-based network involving 10 state health departments and the Centers for Disease Control and Prevention, complement and support local, regional, and national surveillance and research efforts. EIPs depend on collaboration between public health agencies and clinical and academic institutions to perform active, population-based surveillance for infectious diseases; conduct applied epidemiologic and laboratory research; implement and evaluate pilot prevention and intervention projects; and provide capacity for flexible public health response. Recent EIP work has included monitoring the impact of a new conjugate vaccine on the epidemiology of invasive pneumococcal disease, providing the evidence base used to derive new recommendations to prevent neonatal group B streptococcal disease, measuring the impact of foodborne diseases in the United States, and developing a systematic, integrated laboratory and epidemiologic method for syndrome-based surveillance.

Infectious disease hospitalizations among American Indian and Alaska native infants.

OBJECTIVE: To describe the burden and trends in hospitalizations associated with infectious diseases among American Indian and Alaska Native (AI/AN) infants. METHODS: First-listed infectious disease hospitalizations and hospitalization rates among AI/AN infants and infants in the general US population from 1988-1999 were analyzed by using Indian Health Service/tribal hospital discharge data and the National Hospital Discharge Survey data, respectively. RESULTS: Infectious disease hospitalizations accounted for 53% of all AI/AN infant hospitalizations and approximately 43% of all US infant hospitalizations during 1988-1999. The annual hospitalization rate for infectious diseases among AI/AN infants declined from 27,486 per 100,000 infants in 1988 to 14,178 per 100,000 infants in 1999. However, the rates for AI/AN infants within the Alaska, Southwest, and Northern Plains regions remained higher than that for the general US infant population at the end of the study period. Lower respiratory tract infection hospitalizations accounted for almost 75% of AI/AN infant infectious disease hospitalizations, and the lower respiratory tract infection hospitalization rate for AI/AN infants was twice that for US infants. CONCLUSIONS: Although infectious disease hospitalization rates for AI/AN infants have declined, AI/AN infants continue to have a higher infectious disease burden than the general US infant population.

Investigation of bioterrorism-related anthrax, United States, 2001: epidemiologic findings.

In October 2001, the first inhalational anthrax case in the United States since 1976 was identified in a media company worker in Florida. A national investigation was initiated to identify additional cases and determine possible exposures to Bacillus anthracis. Surveillance was enhanced through health-care facilities, laboratories, and other means to identify cases, which were defined as clinically compatible illness with laboratory-confirmed B. anthracis infection. From October 4 to November 20, 2001, 22 cases of anthrax (11 inhalational, 11 cutaneous) were identified; 5 of the inhalational cases were fatal. Twenty (91%) case-patients were either mail handlers or were exposed to worksites where contaminated mail was processed or received. B. anthracis isolates from four powder-containing envelopes, 17 specimens from patients, and 106 environmental samples were indistinguishable by molecular subtyping. Illness and death occurred not only at targeted worksites, but also along the path of mail and in other settings. Continued vigilance for cases is needed among health-care providers and members of the public health and law enforcement communities.

Epidemiologic investigations of bioterrorism-related anthrax, New Jersey, 2001.

At least four Bacillus anthracis-containing envelopes destined for New York City and Washington, D.C. were processed at the Trenton Processing and Distribution Center (PDC) on September 18 and October 9, 2001. When cutaneous anthrax was confirmed in a Trenton postal worker, the PDC was closed. Four cutaneous and two inhalational anthrax cases were identified. Five patients were hospitalized; none died. Four were PDC employees; the others handled or received mail processed there. Onset dates occurred in two clusters following envelope processing at the PDC. The attack rate among the 170 employees present when the B. anthracis-containing letters were sorted on October 9 was 1.2%. Of 137 PDC environmental samples, 57 (42%) were positive. Five (10%) of 50 local post offices each yielded one positive sample. Cutaneous or inhalational anthrax developed in four postal employees at a facility where B. anthracis-containing letters were processed. Cross-contaminated mail or equipment was the likely source of infection in two other case-patients with cutaneous anthrax.

Surveillance for anthrax cases associated with contaminated letters, New Jersey, Delaware, and Pennsylvania, 2001.

In October 2001, two inhalational anthrax and four cutaneous anthrax cases, resulting from the processing of Bacillus anthracis-containing envelopes at a New Jersey mail facility, were identified. Subsequently, we initiated stimulated passive hospital-based and enhanced passive surveillance for anthrax-compatible syndromes. From October 24 to December 17, 2001, hospitals reported 240,160 visits and 7,109 intensive-care unit admissions in the surveillance area (population 6.7 million persons). Following a change of reporting criteria on November 8, the average of possible inhalational anthrax reports decreased 83% from 18 to 3 per day; the proportion of reports requiring follow-up increased from 37% (105/286) to 41% (47/116). Clinical follow-up was conducted on 214 of 464 possible inhalational anthrax patients and 98 possible cutaneous anthrax patients; 49 had additional laboratory testing. No additional cases were identified. To verify the limited scope of the outbreak, surveillance was essential, though labor-intensive. The flexibility of the system allowed interim evaluation, thus improving surveillance efficiency.

Neurocysticercosis in radiographically imaged seizure patients in U.S. emergency departments.

Neurocysticercosis appears to be on the rise in the United States, based on immigration patterns and published cases series, including reports of domestic acquisition. We used a collaborative network of U.S. emergency departments to characterize the epidemiology of neurocysticercosis in seizure patients. Data were collected prospectively at 11 university-affiliated, geographically diverse, urban U.S. emergency departments from July 1996 to September 1998. Patients with a seizure who underwent neuroimaging were included. Of the 1,801 patients enrolled in the study, 38 (2.1%) had seizures attributable to neurocysticercosis. The disease was detected in 9 of the 11 sites and was associated with Hispanic ethnicity, immigrant status, and exposure to areas where neurocysticercosis is endemic. This disease appears to be widely distributed and highly prevalent in certain populations (e.g., Hispanic patients) and areas (e.g., Southwest).

Update on Emerging Infections From the Centers for Disease Control and Prevention.

[Cheney P: Fatal human plague-Arizona and Colorado, 1996. Ann Emerg Med March 1998;31:410-411.].

Comparison of Three Selective Enrichment Methods for the Isolation of Listeria monocytogenes from Naturally Contaminated Foods.

Three selective enrichment procedures-the U.S. Food and Drug Administration (FDA) method, the U.S. Department of Agriculture (USDA) method, and the Netherlands Government Food Inspection Service (NGFIS) method-were compared for isolating Listeria monocytogenes from contaminated foods. The foods were obtained from the refrigerators of patients with culture-proven listeriosis who were identified through multistate active surveillance in a U.S. population of 19 million. The study was designed to identify foods that may be important in transmission of L. monocytogenes in sporadic cases of human listeriosis. Of 899 foods analyzed by all three methods, 121 were positive for L. monocytogenes by at least one method. The three enrichment methods detected L. monocytogenes in 65% (FDA), 74% (USDA), and 74% (NGFIS) of the foods shown to contain L. monocytogenes . The differences among the three methods were not statistically significant. However, the recovery of L. monocytogenes by a combination of any two methods (USDA-FDA 88%, USDA-NGFIS 91%, FDA-NGFIS 87%) was significantly better than that by one method alone (p < 0.02). The differences among the combinations of methods were not statistically significant. These results suggest that at least two enrichment methods must be used in combination to recover L. monocytogenes from contaminated foods with a success rate near 90%. Correlations were observed between negative results and low (<0.3 CFU/g) level of L. monocytogenes contamination for the USDA (p << 0.001) and NGFIS (p << 0.001) methods. A similar but somewhat weaker association was observed for the FDA method (p < 0.06).