Diversity and characterization of HIV-1 subtypes in the United States, 2008-2016.

PURPOSE: This article describes subtype diversity among diagnosed HIV-1 infections in the United States during 2008-2016 by demographic or risk group and over time. METHODS: HIV-1 polymerase sequences reported to the National HIV Surveillance System for persons in 17 U.S. states with HIV infection diagnosed during 2008-2016 were subtyped using COMET, an automated subtyping tool, and National HIV Surveillance System demographic data were analyzed. RESULTS: Subtype B was identified in 93.6% of 121,793 reported sequences. The most common non-B subtypes and circulating recombinant forms (CRFs) were C, CRF02_AG, A, CRF01_AE, and G. Elevated percentages of non-B subtypes or CRFs were found in persons who were female, aged less than 13 years at diagnosis, Asian, or had transmission attributable to heterosexual contact (females only) or perinatal exposure. Foreign-born persons had a higher percentage of non-B subtypes. The prevalence of non-B subtypes and CRFs increased from 5.0% in 2008 to 8.5% in 2016; among specific subtypes and CRFs, subtype G and CRF01_AE increased. CONCLUSIONS: Subtype B remains the predominant strain in the United States. Non-B subtypes and CRFs were not widespread, but diversity and numbers increased from 2008 through 2016, which could have consequences for clinical management, diagnostic testing, and vaccine development.

Stability of diluted smallpox vaccine under simulated clinical conditions.

CONTEXT: During a mass smallpox immunization campaign, vaccine may be exposed to ambient temperatures for extended periods of time. OBJECTIVE: To determine the viability of undiluted and 5x diluted DryVax smallpox vaccine after cycling vaccine in and out of refrigeration for 2 weeks, as might occur during an immunization campaign. DESIGN: Two vials of Dryvax vaccine were reconstituted as per manufacturer's instructions (1x) and two vials were reconstituted using 5x the recommended diluent (5x). Every 12h over 2 weeks, vials were cycled between refrigeration and room temperature (1x-RT, 5x-RT) or ice bath (1x-cold, 5x-cold). Each vial was sampled in triplicate at time of reconstitution and thereafter at 24 or 48 h intervals. MAIN OUTCOME MEASURES: Viability measured by viral plaque forming units per ml (pfu/ml). RESULTS: All four vaccine vials showed a decline in virus titer over the 2-week period but remained well above 10(7)pfu/ml. Compared with titers on the day of reconstitution (day 0), titers at the end of the study (day 14) had declined by 0.4--0.6l og in all vials (Table 1). Linear regression analysis suggested that decay in viral titer occurred more rapidly in vials exposed to room temperature compared with vials kept on ice and in vaccine diluted 1x compared with vaccine diluted 5x. CONCLUSIONS: After 2 weeks, viability was greater than 10(7)pfu/ml, the titer suggested by Frey et al. as necessary to ensure successful vaccination in more than 97% of vaccinees. When removed from refrigeration, keeping the vaccine on ice lowers the decline in titer.

Human monkeypox infection: a family cluster in the midwestern United States.

BACKGROUND: The outbreak of monkeypox in the Midwestern United States during June 2003 marks the first documented human infection in the Western Hemisphere. Consistent with those in outbreaks in Africa, most cases in this outbreak were associated with febrile rash illness. We describe a cluster of monkeypox in a family with a spectrum of clinical illness, including encephalitis, and outline the laboratory confirmation of monkeypox. METHODS: Standardized patient information was collected by questionnaire and medical chart review; all cases described were laboratory confirmed. Laboratory methods included nucleic acid detection, viral culture, serologic testing, histopathologic evaluation, and immunohistochemical testing. RESULTS: Of 3 family members with monkeypox, 2 had rash illness only, and 1 required hospitalization for severe encephalitis. The family member with the mildest clinical course had previously received smallpox vaccination. Diagnostic testing by both polymerase chain reaction and culture revealed infectious monkeypox virus in skin lesions of all 3 patients; 2 patients had orthopoxvirus detected by immunohistochemistry in skin lesions. The patient with encephalitis had orthopoxvirus-reactive immunoglobulin M (IgM) in cerebrospinal fluid. All patients had detectable IgM responses to orthopoxvirus antigens. CONCLUSIONS: These 3 patients illustrate a spectrum of clinical illness with monkeypox despite a common source of exposure; manifestation and severity of illness may be affected by age and prior smallpox vaccination. We report that monkeypox, in addition to causing febrile rash illness, causes severe neurologic infection, and we discuss the use of novel laboratory tests for its diagnosis.