Chikungunya virus, a mosquito-borne alphavirus, causes acute febrile illness with polyarthralgia. Groups at risk for severe disease include neonates, people with underlying medical conditions, and those aged 65 years. Several chikungunya vaccines are in late clinical development with licensure expected in the United States during 2023. We administered a questionnaire to randomly selected households in the U.S. Virgin Islands (USVI) to assess interest in a hypothetical chikungunya vaccine. Estimates were calibrated to age and sex of USVI population, and univariate and multivariable analyses were performed. Of 966 participants, 520 (adjusted 56%, 95% CI = 51-60%) were interested in receiving the vaccine. Of 446 participants not interested in vaccination, 203 (adjusted 47%, 95% CI = 41-52%) cited safety concerns as the reason. Educational efforts addressing vaccine safety concerns and risk factors for severe disease would likely improve vaccine acceptability and uptake among those most at risk.

Diagnostic stewardship means ordering the right tests, for the right patient at the right time to inform optimal clinical care. Diagnostic stewardship is an integral part of antibiotic stewardship efforts to optimize antibiotic use and improve patient outcomes, including reductions in antibiotic resistance, and treatment of sepsis. CDC's Division of Healthcare Quality Promotion (DHQP) hosted a meeting on improving patient safety through diagnostic stewardship with a focus on the use of the laboratory. The meeting identified emerging issues in the field of diagnostic stewardship, raised awareness of these issues among stakeholders, and discussed strategies and interventions to address the issues-all with an emphasis on improved outcomes and patient safety. This white paper summarizes the key takeaways of the meeting including needs for diagnostic stewardship implementation, promising future avenues for diagnostic stewardship implementation, and areas of needed research.

BACKGROUND: West Nile virus (WNV) is the leading cause of arboviral disease in the United States and is associated with significant morbidity and mortality. A previous analysis found that a vaccination program targeting persons aged ≥60 years was more cost effective than universal vaccination, but costs remained high. METHODS: We used a mathematical Markov model to evaluate cost-effectiveness of an age- and incidence-based WNV vaccination program. We grouped states and large counties (≥100,000 persons aged ≥60 years) by median annual WNV incidence rates from 2004 to 2017 for persons aged ≥60 years. We defined WNV incidence thresholds, in increments of 0.5 cases per 100,000 persons ≥60 years. We calculated potential cost per WNV vaccine-prevented case and per quality adjusted life years (QALYs) saved. RESULTS: Vaccinating persons aged ≥60 years in states with an annual incidence of WNV neuroinvasive disease of ≥0.5 per 100,000 resulted in approximately half the cost per health outcome averted compared to vaccinating persons aged ≥60 years in all the contiguous United States. This approach could potentially prevent 37% of all neuroinvasive disease cases and 63% of WNV-related deaths nationally. Employing such a threshold at a county-level further improved cost-effectiveness ratios while preventing 19% and 30% of WNV-related neuroinvasive disease cases and deaths, respectively. CONCLUSIONS: An age- and incidence-based WNV vaccination program could be a more cost-effective strategy than an age-based program while still having a substantial impact on lowering WNV-related morbidity and mortality.

West Nile virus (WNV) and St. Louis encephalitis virus (SLEV) are closely related mosquito-borne flaviviruses that cause clinical disease ranging from febrile illness to encephalitis. The standard for serological diagnosis is immunoglobulin M (IgM) testing followed by confirmatory plaque reduction neutralization test (PRNT) to differentiate the infecting virus. However, the PRNT is time-consuming and requires manipulation of live virus. During concurrent WNV and SLEV outbreaks in Arizona in 2015, we assessed use of a diagnostic algorithm to simplify testing. It incorporated WNV and SLEV ratios based on positive-to-negative (P/N) values derived from the IgM antibody-capture enzyme-linked immunosorbent assay. We compared each sample's ratio-based result with the confirmed WNV or SLEV sample result indicated by PRNT or PCR testing. We analyzed data from 70 patients with 77 serum and cerebrospinal fluid samples, including 53 patients with confirmed WNV infection and 17 patients with confirmed SLEV infection. Both WNV and SLEV ratios had specificity >/=95%, indicating a high likelihood that each ratio was correctly identifying the infecting virus. The SLEV ratio sensitivity of 30% was much lower than the WNV ratio sensitivity of 91%, likely because of higher cross-reactivity of SLEV antibodies and generation of lower P/N values. The standard for serological diagnosis of WNV and SLEV infections remains IgM testing followed by PRNT. However, these results suggest the ratios could potentially be used as part of a diagnostic algorithm in outbreaks to substantially reduce the need for PRNTs.

Laboratory-based surveillance for arboviral diseases is challenging in resource-limited settings. We evaluated the use of filter paper-dried sera for detection of dengue virus (DENV) RNA during an outbreak in American Samoa. Matched liquid and filter paper-dried sera were collected from patients with suspected dengue and shipped to a reference laboratory for diagnostic testing. RNA was extracted from each sample and tested for DENV RNA by real-time reverse transcription-polymerase chain reaction (RT-PCR). Of 18 RT-PCR-positive liquid specimens, 14 matched filter paper-dried specimens were positive for a sensitivity of 78% (95% CI, 55-91%). Of 82 RT-PCR-negative liquid specimens, all filter paper-dried specimens were negative for a specificity of 100% (95% CI, 96-100%). Shipping of filter paper-dried specimens was similarly timely but less expensive than shipping liquid sera. Using filter paper-dried serum or blood can be a cost-effective and sustainable approach to surveillance of dengue and other arboviral diseases in resource-limited settings.

Arthropodborne viruses (arboviruses) are transmitted to humans primarily through the bites of infected mosquitoes or ticks. West Nile virus (WNV) is the leading cause of domestically acquired arboviral disease in the continental United States (1). Other arboviruses, including Jamestown Canyon, La Crosse, Powassan, St. Louis encephalitis, and eastern equine encephalitis viruses, cause sporadic cases of disease and occasional outbreaks. This report summarizes surveillance data reported to CDC from U.S. states in 2017 for nationally notifiable arboviruses. It excludes dengue, chikungunya, and Zika viruses because, in the continental United States, these viruses are acquired primarily through travel. In 2017, 48 states and the District of Columbia (DC) reported 2,291 cases of domestic arboviral disease, including 2,097 (92%) WNV disease cases. Among the WNV disease cases, 1,425 (68%) were classified as neuroinvasive disease (e.g., meningitis, encephalitis, or acute flaccid paralysis), for a national rate of 0.44 cases per 100,000 population. More Jamestown Canyon and Powassan virus disease cases were reported in 2017 than in any previous year. Because arboviral diseases continue to cause serious illness, maintaining surveillance is important to direct and promote prevention activities.

St. Louis encephalitis virus (SLEV), an arthropod-borne flavivirus, can cause disease presentations ranging from mild febrile illness through severe encephalitis. We reviewed U.S. national SLEV surveillance data for 2003 through 2017, including human disease cases and nonhuman infections. Over the 15-year period, 198 counties from 33 states and the District of Columbia reported SLEV activity; 97 (49%) of those counties reported SLEV activity only in nonhuman species. A total of 193 human cases of SLEV disease were reported, including 148 cases of neuroinvasive disease. A median of 10 cases were reported per year. The national average annual incidence of reported neuroinvasive disease cases was 0.03 per million. States with the highest average annual incidence of reported neuroinvasive disease cases were Arkansas, Arizona, and Mississippi. No large outbreaks occurred during the reporting period. The most commonly reported clinical syndromes were encephalitis (N = 116, 60%), febrile illness (N = 35, 18%), and meningitis (N = 25, 13%). Median age of cases was 57 years (range 2-89 years). The case fatality rate was 6% (11/193) and all deaths were among patients aged > 45 years with neuroinvasive disease. Nonhuman surveillance data indicated wider SLEV activity in California, Nevada, and Florida than the human data alone suggested. Prevention depends on community efforts to reduce mosquito populations and personal protective measures to decrease exposure to mosquitoes.