COVID-19 Incidence and Death Rates Among Unvaccinated and Fully Vaccinated Adults with and Without Booster Doses During Periods of Delta and Omicron Variant Emergence - 25 U.S. Jurisdictions, April 4-December 25, 2021.

Previous reports of COVID-19 case, hospitalization, and death rates by vaccination status† indicate that vaccine protection against infection, as well as serious COVID-19 illness for some groups, declined with the emergence of the B.1.617.2 (Delta) variant of SARS-CoV-2, the virus that causes COVID-19, and waning of vaccine-induced immunity (1-4). During August-November 2021, CDC recommended§ additional primary COVID-19 vaccine doses among immunocompromised persons and booster doses among persons aged ≥18 years (5). The SARS-CoV-2 B.1.1.529 (Omicron) variant emerged in the United States during December 2021 (6) and by December 25 accounted for 72% of sequenced lineages (7). To assess the impact of full vaccination with additional and booster doses (booster doses),¶ case and death rates and incidence rate ratios (IRRs) were estimated among unvaccinated and fully vaccinated adults by receipt of booster doses during pre-Delta (April-May 2021), Delta emergence (June 2021), Delta predominance (July-November 2021), and Omicron emergence (December 2021) periods in the United States. During 2021, averaged weekly, age-standardized case IRRs among unvaccinated persons compared with fully vaccinated persons decreased from 13.9 pre-Delta to 8.7 as Delta emerged, and to 5.1 during the period of Delta predominance. During October-November, unvaccinated persons had 13.9 and 53.2 times the risks for infection and COVID-19-associated death, respectively, compared with fully vaccinated persons who received booster doses, and 4.0 and 12.7 times the risks compared with fully vaccinated persons without booster doses. When the Omicron variant emerged during December 2021, case IRRs decreased to 4.9 for fully vaccinated persons with booster doses and 2.8 for those without booster doses, relative to October-November 2021. The highest impact of booster doses against infection and death compared with full vaccination without booster doses was recorded among persons aged 50-64 and ≥65 years. Eligible persons should stay up to date with COVID-19 vaccinations.

Detection of Tickborne Relapsing Fever Spirochete, Austin, Texas, USA.

In March 2017, a patient became febrile within 4 days after visiting a rustic conference center in Austin, Texas, USA, where Austin Public Health suspected an outbreak of tickborne relapsing fever a month earlier. Evaluation of a patient blood smear and molecular diagnostic assays identified Borrelia turicatae as the causative agent. We could not gain access to the property to collect ticks. Thus, we focused efforts at a nearby public park, <1 mile from the suspected exposure site. We trapped Ornithodoros turicata ticks from 2 locations in the park, and laboratory evaluation resulted in cultivation of 3 B. turicatae isolates. Multilocus sequencing of 3 chromosomal loci (flaB, rrs, and gyrB) indicated that the isolates were identical to those of B. turicatae 91E135 (a tick isolate) and BTE5EL (a human isolate). We identified the endemicity of O. turicata ticks and likely emergence of B. turicatae in this city.

Evaluating the risk of tick-borne relapsing fever among occupational cavers-Austin, TX, 2017.

Tick-borne relapsing fever (TBRF) is a potentially serious spirochetal infection caused by certain species of Borrelia and acquired through the bite of Ornithodoros ticks. In 2017, Austin Public Health, Austin, TX, identified five cases of febrile illness among employees who worked in caves. A cross-sectional serosurvey and interview were conducted for 44 employees at eight organizations that conduct cave-related work. Antibodies against TBRF-causing Borrelia were detected in the serum of five participants, four of whom reported recent illness. Seropositive employees entered significantly more caves (Median 25 [SD: 15] versus Median 4 [SD: 16], p = 0.04) than seronegative employees. Six caves were entered more frequently by seropositive employees posing a potentially high risk. Several of these caves were in public use areas and were opened for tours. Education of area healthcare providers about TBRF and prevention recommendations for cavers and the public are advised.

Effects of coincident 5-HT1A receptor stimulation and NMDA receptor antagonism on L-DOPA-induced dyskinesia and rotational behaviors in the hemi-parkinsonian rat.

RATIONALE: Serotonin 1A receptor (5-HT1AR) agonists reduce L-DOPA-induced dyskinesia and enhance motor function in experimental and clinical investigations of Parkinson's disease (PD). While the mechanism(s) by which these effects occur are unclear, recent research suggests that modulation of glutamate neurotransmission contributes. OBJECTIVE: To further delineate the relationship between 5-HT1A receptors and glutamate, the current study examined the effects of the 5-HT1AR agonist, +/-8-OH-DPAT and the N-methyl-D-aspartic acid receptor (NMDAR) antagonist, MK-801, on L-DOPA-induced motor behavior. MATERIALS AND METHODS: Unilateral 6-hydroxydopamine lesioned male Sprague-Dawley rats were rendered dyskinetic with 1 week of daily L-DOPA (12 mg/kg, i.p.) + benserazide (15 mg/kg, i.p.). On test days, one group of rats received pretreatments of: +/-8-OH-DPAT (0, 0.03, 0.1, 0.3 mg/kg, i.p.) or MK-801 (0, 0.03, 0.1, 0.3 mg/kg, i.p.). A second group was administered combined +/-8-OH-DPAT (0, 0.03 or 0.1 mg/kg, i.p.) + MK-801 (0, 0.1 mg/kg, i.p.). Pretreatments were followed by L-DOPA administration, after which, abnormal involuntary movements (AIMs) and rotations were monitored. To investigate effects on motor performance, subthreshold doses of +/-8-OH-DPAT (0.03 mg/kg, i.p.) + MK-801 (0.1 mg/kg, i.p.) were administered to L-DOPA-naïve hemiparkinsonian rats before the forepaw adjusting steps test. RESULTS: Individually, both +/-8-OH-DPAT and MK-801 dose-dependently decreased L-DOPA-induced AIMs without affecting rotations. Combined subthreshold doses of +/-8-OH-DPAT+MK-801 reduced L-DOPA-induced AIMs and potently enhanced contralateral rotations without altering L-DOPA-induced motor improvements. CONCLUSIONS: The current results indicate a functional interaction between 5-HT1AR and NMDAR that may improve pharmacological treatment of PD patients.

Effects of noradrenergic denervation on L-DOPA-induced dyskinesia and its treatment by α- and ß-adrenergic receptor antagonists in hemiparkinsonian rats.

While L-3,4-dihydroxyphenylalanine (L-DOPA) remains the standard treatment for Parkinson's disease (PD), long-term efficacy is often compromised by L-DOPA-induced dyskinesia (LID). Recent research suggests that targeting the noradrenergic (NE) system may provide relief from both PD and LID, however, most PD patients exhibit NE loss which may modify response to such strategies. Therefore this investigation aimed to characterize the development and expression of LID and the anti-dyskinetic potential of the α2- and ß-adrenergic receptor antagonists idazoxan and propranolol, respectively, in rats receiving 6-OHDA lesions with (DA lesion) or without desipramaine protection (DA+NE lesion). Male Sprague-Dawley rats (N=110) received unilateral 6-hydroxydopamine lesions. Fifty-three rats received desipramine to protect NE neurons (DA lesion) and 57 received no desipramine reducing striatal and hippocampal NE content 64% and 86% respectively. In experiment 1, the development and expression of L-DOPA-induced abnormal involuntary movements (AIMs) and rotations were examined. L-DOPA efficacy using the forepaw adjusting steps (FAS) test was also assessed in DA- and DA+NE-lesioned rats. In experiment 2, DA- and DA+NE-lesioned rats received pre-treatments of idazoxan or propranolol followed by L-DOPA after which the effects of these adrenergic compounds were observed. Results demonstrated that moderate NE loss reduced the development and expression of AIMs and rotations but not L-DOPA efficacy while anti-dyskinetic efficacy of α2- and ß-adrenergic receptor blockade was maintained. These findings suggest that the NE system modulates LID and support the continued investigation of adrenergic compounds for the improved treatment of PD.

Serotonin 1B receptor stimulation reduces D1 receptor agonist-induced dyskinesia.

Dopamine replacement therapy for the treatment of Parkinson's disease leads to deleterious abnormal involuntary movements (AIMs), known as L-3,4-dihydroxyphenylalanine (L-DOPA)-induced dyskinesia, which parallels enhanced striatal dopamine D1 receptor-mediated signaling. Recent evidence suggests stimulation of striatal serotonin (5-HT) 1B receptors may reduce D1-mediated signaling. Given this potential antidyskinetic mechanism, male hemiparkinsonian Sprague-Dawley rats received treatments of D1 receptor agonist, SKF81297, (0.8 mg/kg) or L-DOPA (12 mg/kg, subcutaneous injection). Dyskinetic movements were rated using the AIMs scale. Rats were then administered vehicle (100% dimethyl sulfoxide) or the 5-HT1B receptor agonist, CP94253, (1.5 or 3.0 mg/kg, subcutaneous injection), followed by SKF81297 or L-DOPA and rated for AIMs. Results indicate that CP94253 mitigates both L-DOPA and D1 receptor agonist-induced dyskinesia. These findings suggest that 5-HT1B receptor stimulation directly diminishes D1 receptor-mediated dyskinesia, implicating an important target for the treatment of L-DOPA-induced dyskinesia.