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The U.S. territory of American Samoa has experienced recent outbreaks of illnesses caused by viruses transmitted by Aedes species mosquitoes, including dengue, chikungunya, and Zika virus. In November 2016, a traveler from the Solomon Islands tested positive for infection with dengue virus type 2 (DENV-2). Additional dengue cases were identified in the subsequent weeks through passive and active surveillance. Suspected dengue cases were tested locally with a dengue rapid diagnostic test (RDT) for DENV nonstructural protein 1 (NS1). Specimens from RDT-positive cases and patients meeting the dengue case definition were tested by real-time reverse transcription-polymerase chain reaction (real-time RT-PCR) at Hawaii State Laboratories. During November 2016-October 2018, a total of 3,240 patients were tested for evidence of DENV infection (118 by RDT-NS1 alone, 1,089 by real-time RT-PCR alone, and 2,033 by both methods), 1,081 (33.4%) of whom tested positive for dengue (19.5 per 1,000 population). All 941 real-time RT-PCR-positive specimens were positive for DENV-2. The monthly number of laboratory-confirmed cases peaked at 120 during December 2017. Among laboratory-confirmed dengue cases, 380 (35.2%) patients were hospitalized; one patient, who was transferred to American Samoa for care late in his illness, died. The public health response to this outbreak included disposal of solid waste to remove mosquito breeding sites, indoor residual spraying of pesticides in schools, reinforcement of dengue patient management education, and public education on mosquito avoidance and seeking medical care for symptoms of dengue.

•Blinded clinical field trial.•Anti-Leishmania vaccine as immunotherapy significantly reduced clinical progression.•Vaccine decreased mortality in Leishmania infantum-infected, healthy, dogs. Better tools are necessary to eliminate visceral leishmaniasis (VL). Modeling studies for regional Leishmania elimination indicate that an effective vaccine is a critical tool. Dogs are the reservoir host of L. infantum in Brazil and the Mediterranean basin, and therefore are an important target for public health interventions as well as a relevant disease model for human VL. No vaccine has been efficacious as an immunotherapy to prevent progression of already diagnostically positive individuals to symptomatic leishmaniasis. We performed a double-blinded, block-randomized, placebo-controlled, vaccine immunotherapy trial testing the efficacy of a recombinant Leishmania A2 protein, saponin-adjuvanted, vaccine, LeishTec®, in owned hunting dogs infected with L. infantum. The primary outcome was reduction of clinical progression, with reduction of mortality as a secondary outcome. Vaccination as an immunotherapy reduced the risk of progression to clinically overt leishmaniasis by 25% in asymptomatic dogs (RR: 1.33 95% C.I. 1.009–1.786 p-value: 0.0450). Receiving vaccine vs. placebo reduced all-cause mortality in younger asymptomatic dogs by 70% (RR: 3.19 95% C.I.: 1.185–8.502 p-value = 0.0245). Vaccination of infected-healthy animals with an anti-Leishmania vaccine significantly reduced clinical progression and decreased all-cause mortality. Use of vaccination in infected-healthy dogs can be a tool for Leishmania control.

On December 7, 2022, the Texas Department of State Health Services (DSHS) Public Health Region 6/5 South (PHR 6/5S) and DSHS Consumer Protection Division were notified by Galveston County Health District of 10 consumer complaints of illness after consumption of raw (nine complaints) and smoked (one) oysters at local restaurants during November 27–December 4. [...]norovirus outbreaks are primarily detected when persons report illness or health care providers report a suspected outbreak. Abbreviations: DSHS = Texas Department of State Health Services; FL DOH = Florida Department of Health; GCHD = Galveston County Health District; GI = gastrointestinal; NSSP = National Shellfish Sanitation Program; PHR 6/5S = Public Health Region 6/5 South; TX 1 = Texas Oyster Harvest Area 1.

Difficulty understanding speech in the presence of noise is a common complaint of middle-aged and older adults with and without hearing loss. There is an incomplete picture of what contributes to difficulties understanding speech-in-noise in adults who have normal audiograms. As humans we listen binaurally, so declines in binaural processing may contribute to speech-in-noise difficulties. We examined the effects of age on the upper frequency limit of interaural phase difference (IPD) detection and IPD detection at fixed frequencies. We also examined a speech-in-noise measure of spatial separation across young and middle-aged, normal-hearing individuals. Participants were young (n=12) and middle-aged (n=8) adults with normal and symmetrical hearing from 250-8000 Hz. Two interaural phase difference tasks were undertaken. The first assessed interaural phase difference discrimination across frequencies and the second assessed interaural phase difference discrimination at fixed frequencies (500, 750, 1000, 1125 Hz). In addition, the speech-in-noise measure of benefit from spatial separation was assessed by having subjects complete the words-in-noise test with speech and noise at 0° and again with speech at 0° and noise at 90°. The young group had significantly higher (better) upper frequency limits for interaural phase difference discrimination. There was no statistically significant difference between the IPD discrimination at fixed frequencies for the young and middle-aged group, contrary to what was hypothesized. The young group also did not have a greater benefit from spatial separation compared to the middle-aged group. The outcomes from this study add to a growing body of literature suggesting a decline in the upper frequency limit of IPD discrimination with advancing age. This negative effect of aging begins in middle-aged, normal-hearing listeners. The results from this study also suggest that factors other than age and IPD discrimination affect spatial processing in middle-aged adults with clinically normal audiograms. Knowing what contributes to difficulty understanding speech-in-noise will aid in counseling patients and will improve approaches to aural rehabilitation.

American Samoa has experienced multiple outbreaks of mosquitoborne viral disease in recent years, including chikun...gunya in 2014, dengue in 2015, and Zika in 2016. During November 2016-October 2018, 1,081 laboratory-confirmed dengue cases were identified, with only dengue virus type 2 detected. The epidemic peaked in December 2017, after which, case counts slowly decreased. Sustainable, effective interventions are still needed to control dengue, as is continued emphasis on clinical management to reduce mortality. Persons residing in or traveling to areas with risk for dengue should use insect repellent, wear long sleeves and pants, and stay in residences with screens on doors and windows.

The gut microbiota is increasingly recognized as an important regulator of host immunity and brain health. The aging process yields dramatic alterations in the microbiota, which is linked to poorer health and frailty in elderly populations. However, there is limited evidence for a mechanistic role of the gut microbiota in brain health and neuroimmunity during aging processes. Therefore, we conducted fecal microbiota transplantation from either young (3-4 months) or old (19-20 months) donor mice into aged recipient mice (19-20 months). Transplant of a microbiota from young donors reversed aging-associated differences in peripheral and brain immunity, as well as the hippocampal metabolome and transcriptome of aging recipient mice. Finally, the young donor-derived microbiota attenuated selective age-associated impairments in cognitive behavior when transplanted into an aged host. Our results reveal that the microbiome may be a suitable therapeutic target to promote healthy aging.

BackgroundThe cumulative economic burden of rare diseases surpasses that of common conditions, yet patterns of healthcare resource utilization (HRU) across rare diseases remain poorly characterized. This study leverages multimodal data collected during clinical care and through surveys to provide an in-depth evaluation of HRU across the disease journey of individuals with rare genetic diseases. Individuals with a confirmed diagnosis of Kleefstra syndrome (KS; n = 40) or SLC6A1 epileptic encephalopathy (SLC6A1; n = 30) were recruited. Structured and unstructured data were abstracted from participants’ medical records. Encounters per person-year of follow-up were calculated and compared pre- and post-diagnosis. Parents/guardians completed surveys assessing the impact of the participant’s diagnosis on their care.ResultsRecords were available for a median of 6.4 years of follow-up from 268 unique healthcare facilities (median per patient = 4.5 facilities). Numbers of healthcare encounters were not significantly different 1 year pre- and post-diagnosis for either condition; however, the proportion of specialty encounters pre- and post-diagnosis varied significantly. Genetics encounters decreased for both conditions post-diagnosis. Cardiology, sleep medicine, and radiology encounters increased in KS post-diagnosis; conversely, audiology encounters decreased in KS post-diagnosis, and radiology encounters decreased in SLC6A1 post-diagnosis. Among specialty encounter types assessed, general practitioner (e.g. primary care, including pediatrics) encounters were the most common type for KS participants and the second-most common for SLC6A1 participants (after neurology encounters) both 1 year pre- and post-diagnosis. The number of both echocardiograms and electrocardiograms (ECG) significantly increased in KS 1 year post-diagnosis. 68% of survey respondents indicated that the participant’s care changed post-diagnosis.ConclusionsThough there was no significant difference in the number of encounters pre- and post-diagnosis, significant changes in types of HRU suggest that diagnosis leads to more appropriate care and treatment. Advocacy organizations, researchers, drug developers, payors, and policymakers should consider the value of an early diagnosis to improve long-term outcomes and quality of life for patients and invest in measures that will shorten the time to diagnosis accordingly.

Environmental factors, including westernised diets and alterations to the gut microbiota, are considered risk factors for inflammatory bowel diseases (IBD). The mechanisms underpinning diet-microbiota-host interactions are poorly understood in IBD. We present evidence that feeding a lard-based high-fat (HF) diet can protect mice from developing DSS-induced acute and chronic colitis and colitis-associated cancer (CAC) by significantly reducing tumour burden/incidence, immune cell infiltration, cytokine profile, and cell proliferation. We show that HF protection was associated with increased gut microbial diversity and a significant reduction in Proteobacteria and an increase in Firmicutes and Clostridium cluster XIVa abundance. Microbial functionality was modulated in terms of signalling fatty acids and bile acids (BA). Faecal secondary BAs were significantly induced to include moieties that can activate the vitamin D receptor (VDR), a nuclear receptor richly represented in the intestine and colon. Indeed, colonic VDR downstream target genes were upregulated in HF-fed mice and in combinatorial lipid-BAs-treated intestinal HT29 epithelial cells. Collectively, our data indicate that HF diet protects against colitis and CAC risk through gut microbiota and BA metabolites modulating vitamin D targeting pathways. Our data highlights the complex relationship between dietary fat-induced alterations of microbiota-host interactions in IBD/CAC pathophysiology.