Estimating the health effects of COVID-19-related immunisation disruptions in 112 countries during 2020-30: a modelling study.

BACKGROUND: There have been declines in global immunisation coverage due to the COVID-19 pandemic. Recovery has begun but is geographically variable. This disruption has led to under-immunised cohorts and interrupted progress in reducing vaccine-preventable disease burden. There have, so far, been few studies of the effects of coverage disruption on vaccine effects. We aimed to quantify the effects of vaccine-coverage disruption on routine and campaign immunisation services, identify cohorts and regions that could particularly benefit from catch-up activities, and establish if losses in effect could be recovered. METHODS: For this modelling study, we used modelling groups from the Vaccine Impact Modelling Consortium from 112 low-income and middle-income countries to estimate vaccine effect for 14 pathogens. One set of modelling estimates used vaccine-coverage data from 1937 to 2021 for a subset of vaccine-preventable, outbreak-prone or priority diseases (ie, measles, rubella, hepatitis B, human papillomavirus [HPV], meningitis A, and yellow fever) to examine mitigation measures, hereafter referred to as recovery runs. The second set of estimates were conducted with vaccine-coverage data from 1937 to 2020, used to calculate effect ratios (ie, the burden averted per dose) for all 14 included vaccines and diseases, hereafter referred to as full runs. Both runs were modelled from Jan 1, 2000, to Dec 31, 2100. Countries were included if they were in the Gavi, the Vaccine Alliance portfolio; had notable burden; or had notable strategic vaccination activities. These countries represented the majority of global vaccine-preventable disease burden. Vaccine coverage was informed by historical estimates from WHO-UNICEF Estimates of National Immunization Coverage and the immunisation repository of WHO for data up to and including 2021. From 2022 onwards, we estimated coverage on the basis of guidance about campaign frequency, non-linear assumptions about the recovery of routine immunisation to pre-disruption magnitude, and 2030 endpoints informed by the WHO Immunization Agenda 2030 aims and expert consultation. We examined three main scenarios: no disruption, baseline recovery, and baseline recovery and catch-up. FINDINGS: We estimated that disruption to measles, rubella, HPV, hepatitis B, meningitis A, and yellow fever vaccination could lead to 49 119 additional deaths (95% credible interval [CrI] 17 248-134 941) during calendar years 2020-30, largely due to measles. For years of vaccination 2020-30 for all 14 pathogens, disruption could lead to a 2·66% (95% CrI 2·52-2·81) reduction in long-term effect from 37 378 194 deaths averted (34 450 249-40 241 202) to 36 410 559 deaths averted (33 515 397-39 241 799). We estimated that catch-up activities could avert 78·9% (40·4-151·4) of excess deaths between calendar years 2023 and 2030 (ie, 18 900 [7037-60 223] of 25 356 [9859-75 073]). INTERPRETATION: Our results highlight the importance of the timing of catch-up activities, considering estimated burden to improve vaccine coverage in affected cohorts. We estimated that mitigation measures for measles and yellow fever were particularly effective at reducing excess burden in the short term. Additionally, the high long-term effect of HPV vaccine as an important cervical-cancer prevention tool warrants continued immunisation efforts after disruption. FUNDING: The Vaccine Impact Modelling Consortium, funded by Gavi, the Vaccine Alliance and the Bill & Melinda Gates Foundation. TRANSLATIONS: For the Arabic, Chinese, French, Portguese and Spanish translations of the abstract see Supplementary Materials section.

Geographic clustering of travel-acquired infections in Ontario, Canada, 2008-2020.

As the frequency of international travel increases, more individuals are at risk of travel-acquired infections (TAIs). In this ecological study of over 170,000 unique tests from Public Health Ontario's laboratory, we reviewed all laboratory-reported cases of malaria, dengue, chikungunya, and enteric fever in Ontario, Canada between 2008-2020 to identify high-resolution geographical clusters for potential targeted pre-travel prevention. Smoothed standardized incidence ratios (SIRs) and 95% posterior credible intervals (CIs) were estimated using a spatial Bayesian hierarchical model. High- and low-incidence areas were described using data from the 2016 Census based on the home forward sortation area of patients testing positive. A second model was used to estimate the association between drivetime to the nearest travel clinic and incidence of TAI within high-incidence areas. There were 6,114 microbiologically confirmed TAIs across Ontario over the study period. There was spatial clustering of TAIs (Moran's I = 0.59, p<0.0001). Compared to low-incidence areas, high-incidence areas had higher proportions of immigrants (p<0.0001), were lower income (p = 0.0027), had higher levels of university education (p<0.0001), and less knowledge of English/French languages (p<0.0001). In the high-incidence Greater Toronto Area (GTA), each minute increase in drive time to the closest travel clinic was associated with a 3% reduction in TAI incidence (95% CI 1-6%). While urban neighbourhoods in the GTA had the highest burden of TAIs, geographic proximity to a travel clinic in the GTA was not associated with an area-level incidence reduction in TAI. This suggests other barriers to seeking and adhering to pre-travel advice.

Comparison of model predictions of typhoid conjugate vaccine public health impact and cost-effectiveness.

Models are useful to inform policy decisions on typhoid conjugate vaccine (TCV) deployment in endemic settings. However, methodological choices can influence model-predicted outcomes. To provide robust estimates for the potential public health impact of TCVs that account for structural model differences, we compared four dynamic and one static mathematical model of typhoid transmission and vaccine impact. All models were fitted to a common dataset of age-specific typhoid fever cases in Kolkata, India. We evaluated three TCV strategies: no vaccination, routine vaccination at 9 months of age, and routine vaccination at 9 months with a one-time catch-up campaign (ages 9 months to 15 years). The primary outcome was the predicted percent reduction in symptomatic typhoid cases over 10 years after vaccine introduction. For three models with economic analyses (Models A-C), we also compared the incremental cost-effectiveness ratios (ICERs), calculated as the incremental cost (US$) per disability-adjusted life-year (DALY) averted. Routine vaccination was predicted to reduce symptomatic cases by 10-46 % over a 10-year time horizon under an optimistic scenario (95 % initial vaccine efficacy and 19-year mean duration of protection), and by 2-16 % under a pessimistic scenario (82 % initial efficacy and 6-year mean protection). Adding a catch-up campaign predicted a reduction in incidence of 36-90 % and 6-35 % in the optimistic and pessimistic scenarios, respectively. Vaccine impact was predicted to decrease as the relative contribution of chronic carriers to transmission increased. Models A-C all predicted routine vaccination with or without a catch-up campaign to be cost-effective compared to no vaccination, with ICERs varying from $95-789 per DALY averted; two models predicted the ICER of routine vaccination alone to be greater than with the addition of catch-up campaign. Despite differences in model-predicted vaccine impact and cost-effectiveness, routine vaccination plus a catch-up campaign is likely to be impactful and cost-effective in high incidence settings such as Kolkata.

The utility of a maximum entropy species distribution model for Ixodes scapularis in predicting the public health risk of Lyme disease in Ontario, Canada.

Lyme disease is an emerging public health threat in Ontario, Canada due to ongoing range expansion of the tick vector, Ixodes scapularis. Tick density is an important predictor of human Lyme disease risk and is typically measured using active tick surveillance via drag sampling, which is time and resource-intensive. New cost-effective tools are needed to augment current surveillance activities. Our objective was to evaluate the ability of a maximum entropy (Maxent) species distribution model to predict I. scapularis density in three regions of Ontario - Ottawa, Kingston, and southern Ontario - in order to determine its utility in predicting the public health risk of Lyme disease. Ticks were collected via drag sampling at 60 sites across the three regions. Model-predicted habitat suitability was calculated from a previously constructed Maxent model as the mean predicted habitat suitability within a 1-km radius of each site. Spearman's correlation coefficient was used to quantify the continuous relationship between model-predicted habitat suitability and tick density, and negative binomial regression was used to quantify the relationship between tick density and model-predicated habitat suitability. Spearman's correlation coefficients for the full study area, Kingston region, and Ottawa region were 0.517, 0.707, and 0.537, respectively, indicating a moderate positive relationship and ability of the model to predict tick density. Regression analysis further demonstrated a significant positive association between tick density and model-predicted habitat suitability (p< 0.001). Using a dichotomized measure of model-predicted habitat suitability, the incidence rate ratio - the ratio of ticks per m2 in sites predicted to have a 'suitable' habitat compared to those predicted to have 'not suitable' habitat - was 33.95, indicating that tick density was significantly higher at sites situated in areas with predicted suitable habitat. Given that tick density is an important component of Lyme disease risk, the ability to predict high tick density locations using the Maxent model may make it a cost-effective tool for identifying geographic areas that pose elevated public health risk of Lyme disease.

Clinical Considerations for Routine Auditory and Vestibular Monitoring in Patients With Cystic Fibrosis.

Purpose Specific classes of antibiotics, such as aminoglycosides, have well-established adverse events producing permanent hearing loss, tinnitus, and balance and/or vestibular problems (i.e., ototoxicity). Although these antibiotics are frequently used to treat pseudomonas and other bacterial infections in patients with cystic fibrosis (CF), there are no formalized recommendations describing approaches to implementation of guideline adherent ototoxicity monitoring as part of CF clinical care. Method This consensus statement was developed by the International Ototoxicity Management Working Group (IOMG) Ad Hoc Committee on Aminoglycoside Antibiotics to address the clinical need for ototoxicity management in CF patients treated with known ototoxic medications. These clinical protocol considerations were created using consensus opinion from a community of international experts and available evidence specific to patients with CF, as well as published national and international guidelines on ototoxicity monitoring. Results The IOMG advocates four clinical recommendations for implementing routine and guideline adherent ototoxicity management in patients with CF. These are (a) including questions about hearing, tinnitus, and balance/vestibular problems as part of the routine CF case history for all patients; (b) utilizing timely point-of-care measures; (c) establishing a baseline and conducting posttreatment evaluations for each course of intravenous ototoxic drug treatment; and (d) repeating annual hearing and vestibular evaluations for all patients with a history of ototoxic antibiotic exposure. Conclusion Increased efforts for implementation of an ototoxicity management program in the CF care team model will improve identification of ototoxicity signs and symptoms, allow for timely therapeutic follow-up, and provide the clinician and patient an opportunity to make an informed decision about potential treatment modifications to minimize adverse events. Supplemental Material https://doi.org/10.23641/asha.16624366.

The Supine Superior Semicircular Canal Dehiscence Test.

Purpose The purpose of this clinical focus article is to describe a new method for assessment of superior semicircular canal dehiscence by laying the patient supine during Valsalva-induced nystagmus testing. Method The traditional Valsalva-induced nystagmus test is described, followed by a new method for assessment of superior semicircular dehiscence conducted by laying the patient supine during testing. A case study is presented to illustrate this new testing technique known as the Supine Superior Semicircular Canal Dehiscence Test. Results It is hypothesized that during Valsalva-induced nystagmus testing performed in the upright, seated position, the dura mater could potentially seal the superior semicircular canal fistula, thereby concealing a defect in the bony labyrinth and yielding a false-negative test. To circumvent this, the patient should be placed in the supine position during Valsalva-induced nystagmus testing in order to prevent the dura mater from inadvertently sealing itself against the petrous portion of the temporal bone. The Supine Superior Semicircular Canal Dehiscence Test may reveal the defect in the bony labyrinth and improve the sensitivity of the Valsalva-induced nystagmus test. Conclusions The Supine Superior Semicircular Canal Dehiscence Test may be more sensitive for identifying superior semicircular canal dehiscence in patients with traditional symptoms and a negative Valsalva-induced nystagmus test in the seated position. While a case study is presented to illustrate the potential benefits of including the Supine Superior Semicircular Canal Dehiscence Test in the battery of diagnostic tests, further research is needed in larger samples.

A multi-year assessment of blacklegged tick (Ixodes scapularis) population establishment and Lyme disease risk areas in Ottawa, Canada, 2017-2019.

Canadians face an emerging threat of Lyme disease due to the northward expansion of the tick vector, Ixodes scapularis. We evaluated the degree of I. scapularis population establishment and Borrelia burgdorferi occurrence in the city of Ottawa, Ontario, Canada from 2017-2019 using active surveillance at 28 sites. We used a field indicator tool developed by Clow et al. to determine the risk of I. scapularis establishment for each tick cohort at each site using the results of drag sampling. Based on results obtained with the field indicator tool, we assigned each site an ecological classification describing the pattern of tick colonization over two successive cohorts (cohort 1 was comprised of ticks collected in fall 2017 and spring 2018, and cohort 2 was collected in fall 2018 and spring 2019). Total annual site-specific I. scapularis density ranged from 0 to 16.3 ticks per person-hour. Sites with the highest density were located within the Greenbelt zone, in the suburban/rural areas in the western portion of the city of Ottawa, and along the Ottawa River; the lowest densities occurred at sites in the suburban/urban core. B. burgdorferi infection rates exhibited a similar spatial distribution pattern. Of the 23 sites for which data for two tick cohorts were available, 11 sites were classified as "high-stable", 4 were classified as "emerging", 2 were classified as "low-stable", and 6 were classified as "non-zero". B. burgdorferi-infected ticks were found at all high-stable sites, and at one emerging site. These findings suggest that high-stable sites pose a risk of Lyme disease exposure to the community as they have reproducing tick populations with consistent levels of B. burgdorferi infection. Continued surveillance for I. scapularis, B. burgdorferi, and range expansion of other tick species and emerging tick-borne pathogens is important to identify areas posing a high risk for human exposure to tick-borne pathogens in the face of ongoing climate change and urban expansion.

The effects of repeated low-level blast exposure on hearing in marines.

BACKGROUND: The study evaluates a group of Military Service Members specialized in blast explosive training called "Breachers" who are routinely exposed to multiple low-level blasts while teaching breaching at the U.S. Marine Corps in Quantico Virginia. The objective of this study was to determine if there are any acute or long-term auditory changes due to repeated low-level blast exposures used in training. The performance of the instructor group "Breachers" was compared to a control group, "Engineers". METHODS: A total of 11 Breachers and four engineers were evaluated in the study. The participants received comprehensive auditory tests, including pure-tone testing, speech-in-noise (SIN) measures, and central auditory behavioral and objective tests using early and late (P300) auditory evoked potentials over a period of 17 months. They also received shorter assessments immediately following the blast-exposure onsite at Quantico. RESULTS: No acute or longitudinal effects were identified. However, there were some interesting baseline effects found in both groups. Contrary to the expected, the onsite hearing thresholds and distortion product otoacoustic emissions were slightly better at a few frequencies immediately after blast-exposure than measurements obtained with the same equipment weeks to months after each blast-exposure. CONCLUSIONS: To date, the current study is the most comprehensive study that evaluates the long-term effects of blast-exposure on hearing. Despite extensive testing to assess changes, the findings of this study suggest that the levels of current exposures used in this military training environment do not seem to have an obvious deleterious effect on hearing.

North Pole Marathon Laboratory Lessons and Field Success.

BACKGROUND: This case study documents the training, laboratory preparation, and in-race performance data from Great Britain's top finisher in the 13(th) edition of the UVU North Pole Marathon. CASE REPORT: We report data from a preparatory laboratory test in simulated cold conditions (-15°C) with and without wind chill during high- and low-intensity expected 'race pace' running. These tests examined the adequacy of the selected clothing assembly and provided recommendations for the race. The tests established that there was no risk of hypothermia, as the clothing assembly provided too much insulation; terminal rectal temperature was 39.25°C. Skin temperature (Tsk) data revealed no impending risk of frostbite; nadir Tsk was 20.2°C at the hamstring. Oxygen consumption data revealed the self-selected high intensity was potentially not sustainable based on estimates of substrate utilization. We recommended: 1) a maximum running speed; 2) some of the clothing base layers could be removed pre-race; 3) vents and/or zips could be used to offload or retain heat; and 4) an even pacing profile should be adopted. DISCUSSION: The participant completed the race in 6:55:24 (h:mm:ss) in temperatures of -41°C. GPS data revealed a positive pacing template (i.e., marginally quicker in the first half). Neither hypothermia nor frostbite occurred. Peak pace from the laboratory tests was not consistently exceeded. Marathon performance can be undertaken in one of the world's most inhospitable environments when careful consideration is given to clothing insulation and exercise intensity by planning for the dynamic thermal changes that may occur as the race ensues.

The Vestibular Effects of Repeated Low-Level Blasts.

The objective of this study was to use a prospective cohort of United States Marine Corps (USMC) instructors to identify any acute or long-term vestibular dysfunction following repeated blast exposures during explosive breaching training. They were assessed in clinic and on location during training at the USMC Methods of Entry School, Quantico, VA. Subjects received comprehensive baseline vestibular assessments and these were repeated in order to identify longitudinal changes. They also received shorter assessments immediately following blast exposure in order to identify acute findings. The main outcome measures were the Neurobehavioral Symptom Inventory, vestibular Visual Analog Scale (VAS) of subjective vestibular function, videonystagmography (VNG), vestibular evoked myogenic potentials (VEMP), rotary chair (including the unilateral centrifugation test), computerized dynamic posturography, and computerized dynamic visual acuity. A total of 11 breachers and 4 engineers were followed for up to 17 months. No acute effects or longitudinal deteriorations were identified, but there were some interesting baseline group differences. Upbeat positional nystagmus was common, and correlated (p<0.005) with a history of mild traumatic brain injury (mTBI). Several instructors had abnormally short low-frequency phase leads on rotary chair testing. This study evaluated breaching instructors over a longer test period than any other study, and the results suggest that this population appears to be safe from a vestibular standpoint at the current exposure levels. Upbeat positional nystagmus correlated with a history of mTBI in this population, and this has not been described elsewhere. The data trends also suggest that this nystagmus could be an acute blast effect. However, the reasons for the abnormally short phase leads seen in rotary chair testing are unclear at this time. Further investigation seems warranted.

"Float first and kick for your life": Psychophysiological basis for safety behaviour on accidental short-term cold water immersion.

INTRODUCTION: Accidental cold-water immersion (CWI) evokes the life threatening cold shock response (CSR) which increases the risk of drowning. Consequently, the safety behaviour selected is critical in determining survival; the present advice is to 'float first' and remain stationary (i.e. rest). We examined whether leg only exercise (i.e., treading water; 'CWI-Kick') immediately on CWI could reduce the symptoms of the CSR, offset the reduction in cerebral blood flow that is known to occur and reduce the CSR's symptoms of breathlessness. We also examined whether perceptual responses instinctive to accidental CWI were exacerbated by this alternative behaviour. We contrasted CWI-Kick to a 'CWI-Rest' condition and a thermoneutral control (35°C); 'TN-Rest'. METHOD: Seventeen participants were tested (9 males, 8 females). All immersions were standardised; water temperature in cold conditions (i.e., 12°C) was matched ±/0.5°C within participant. Middle cerebral artery blood flow velocity (MCAv) and cardiorespiratory responses were measured along with thermal perception (sensation and comfort) and dyspnoea. Data were analysed using repeated measures ANOVA (alpha level of 0.05). RESULTS: MCAv was significantly reduced in CWI-Rest (-6 (9)%; 1st minute of immersion) but was offset by leg only exercise immediately on cold water entry; CWI-Kick MCAv was never different to TN-Rest (-3 (16)% cf. 5 (4)%). All CWI cardiorespiratory and perceptual responses were different to TN-Rest but were not exacerbated by leg only exercise. DISCUSSION: Treading water may aid survival by offsetting the reduction in brain blood flow velocity without changing the instinctive behavioural response (i.e. perceptions). "Float first - and kick for your life" would be a suitable amendment to the water safety advice.

Evidence of central and peripheral vestibular pathology in blast-related traumatic brain injury.

OBJECTIVE: To prospectively assay the vestibular and oculomotor systems of blast-exposed service members with traumatic brain injury (TBI). STUDY DESIGN: Prospective, nonblinded, nonrandomized descriptive study. SETTING: Tertiary care facility (Department of Defense Medical Center). PATIENTS: Twenty-four service members recovering from blast-related TBI sustained in Iraq or Afghanistan. INTERVENTIONS: Focused history and physical, videonystagmography (VNG), rotational chair, cervical vestibular-evoked myogenic potentials, computerized dynamic posturography, and self-report measures. RESULTS: Vestibular testing confirms a greater incidence of vestibular and oculomotor dysfunction in symptomatic (vestibular-like dizziness) personnel with blast-related TBI relative to asymptomatic group members. VNG in the symptomatic group revealed abnormal nystagmus or oculomotor findings in 6 of 12 subjects tested. Similarly, rotational chair testing in this group revealed evidence of both peripheral (4/12) and central (2/12) vestibular pathology. By contrast, the asymptomatic group revealed less vestibular impairment with 1 of 10 rotational chair abnormalities. The asymptomatic group was further characterized by fewer aberrant nystagmus findings (4/12 abnormal VNGs). Computerized dynamic posturography testing revealed no significant differences between groups. Self-report measures demonstrated differences between groups. CONCLUSION: Vestibular function testing confirms a greater incidence of peripheral vestibular hypofunction in dizzy service members with blast-related TBI relative to those who are asymptomatic. Additionally, oculomotor abnormalities and/or nystagmus consistent with central involvement were present in 10 of the 24 study participants tested. The precise cause of these findings remains unknown.

Transforming superior canal dehiscence to chronic subjective dizziness: from SCD to CSD.

Patients presenting with chronic dizziness and no identifiable vestibular impairments have been described as having "extravestibular" symptoms, or "psychogenic dizziness." In 2005, Staab and Ruckenstein described a syndrome they referred to as "chronic subjective dizziness" (CSD), which characterized this concept more clearly. According to Staab and Ruckenstein (2003), the primary physical symptoms of CSD are continual nonvertiginous dizziness or subjective imbalance that persists for 3 mo or longer. Patients suffering from CSD often describe their dizziness as a rocking or swaying when sitting or standing. This case study describes a 41-yr-old female who originally presented with complaints of noise-induced vertigo. The patient's history, imaging studies, and balance function examinations led to the diagnosis of a right-sided superior canal dehiscence (SCD). After surgical repair of the dehiscence, the quantitative electrophysiological tests returned to normal. However, the patient's scores on measures of anxiety, depression, and self-perceived dizziness handicap increased significantly postoperatively. This case illustrates the transformation of a peripheral end-organ impairment (i.e., SCD) into a psychiatric condition (i.e., CSD).

Characterizing self-reported dizziness and otovestibular impairment among blast-injured traumatic amputees: a pilot study.

The incidence of vestibular and audiologic injury related to blast injury remains underreported. The primary objective of this study was to document self-reported otovestibular impairment in blast-injured amputees. Secondary objectives include a description of the Walter Reed Army Medical Center Blast Injury Questionnaire and other aspects of the audiology service and amputee physical therapy section standards of care for blast injury management. A case study illustrates the application of these standards of care. Thirty-three patients were evaluated by audiologists and physical therapists using the Walter Reed Army Medical Center Blast Injury Questionnaire, followed by audiologic and vestibular screening; 24% of patients reported symptoms of vertigo or oscillopsia following blast trauma, and 51% reported subjective hearing loss. The case study subject reported an increase in function after vestibular rehabilitation therapy. Thorough screening by audiologists and physical therapists can facilitate appropriate diagnosis and management for blast-injured patients.