Precision symptom phenotyping identifies early clinical and proteomic predictors of distinct COVID-19 sequelae.

BACKGROUND: Post-COVID conditions (PCC) are difficult to characterize, diagnose, predict, and treat due to overlapping symptoms and poorly understood pathology. Identifying inflammatory profiles may improve clinical prognostication and trial endpoints. METHODS: 1,988 SARS-CoV-2 positive U.S. Military Health System beneficiaries with quantitative post-COVID symptom scores were included in this analysis. Among participants who reported moderate-to-severe symptoms on surveys collected 6-months post-SARS-CoV-2 infection, principal component analysis (PCA) followed by K-means clustering identified distinct clusters of symptoms. RESULTS: Three symptom-based clusters were identified: a sensory cluster (loss of smell and/or taste), a fatigue/difficulty thinking cluster, and a difficulty breathing/exercise intolerance cluster. Individuals within the sensory cluster were all outpatients during their initial COVID-19 presentation. The difficulty breathing cluster had a higher likelihood of obesity and COVID-19 hospitalization compared to those with no/mild symptoms at 6-months post-infection. Multinomial regression linked early post-infection D-dimer and IL-1RA elevation to fatigue/difficulty thinking, and elevated ICAM-1 concentrations to sensory symptoms. CONCLUSIONS: We identified three distinct symptom-based PCC phenotypes with specific clinical risk factors and early post-infection inflammatory predictors. With further validation and characterization, this framework may allow more precise classification of PCC cases and potentially improve the diagnosis, prognostication, and treatment of PCC.

Understanding "Hybrid Immunity": Comparison and Predictors of Humoral Immune Responses to Severe Acute Respiratory Syndrome Coronavirus 2 Infection (SARS-CoV-2) and Coronavirus Disease 2019 (COVID-19) Vaccines.

BACKGROUND: Comparison of humoral responses in severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccinees, those with SARS-CoV-2 infection, or combinations of vaccine/ infection ("hybrid immunity") may clarify predictors of vaccine immunogenicity. METHODS: We studied 2660 US Military Health System beneficiaries with a history of SARS-CoV-2 infection-alone (n = 705), vaccination-alone (n = 932), vaccine-after-infection (n = 869), and vaccine-breakthrough-infection (n = 154). Peak anti-spike-immunoglobulin G (IgG) responses through 183 days were compared, with adjustment for vaccine product, demography, and comorbidities. We excluded those with evidence of clinical or subclinical SARS-CoV-2 reinfection from all groups. RESULTS: Multivariable regression results indicated that vaccine-after-infection anti-spike-IgG responses were higher than infection-alone (P < .01), regardless of prior infection severity. An increased time between infection and vaccination was associated with greater post-vaccination IgG response (P < .01). Vaccination-alone elicited a greater IgG response but more rapid waning of IgG (P < .01) compared with infection-alone (P < .01). BNT162b2 and mRNA-1273 vaccine-receipt was associated with greater IgG responses compared with JNJ-78436735 vaccine-receipt (P < .01), regardless of infection history. Those with vaccine-after-infection or vaccine-breakthrough-infection had a more durable anti-spike-IgG response compared to infection-alone (P < .01). CONCLUSIONS: Vaccine-receipt elicited higher anti-spike-IgG responses than infection-alone, although IgG levels waned faster in those vaccinated (compared to infection-alone). Vaccine-after-infection elicits a greater humoral response compared with vaccine or infection alone; and the timing, but not disease severity, of prior infection predicted these post-vaccination IgG responses. While differences between groups were small in magnitude, these results offer insights into vaccine immunogenicity variations that may help inform vaccination timing strategies.

The pregnancy factor: the prevalence of depression among women living with HIV enrolled in the African Cohort Study (AFRICOS) by pregnancy status.

Among Sub-Saharan African women living with HIV (WLWH), pregnancy creates unique stressors that may cause depression. We describe the prevalence of depression among WLWH enrolled in the African Cohort Study (AFRICOS) by pregnancy status and describe factors associated with depression. WLWH < 45 years of age underwent six-monthly visits with depression diagnosed using the Center for Epidemiological Studies-Depression scale. Visits were categorized as "pregnant;" "postpartum" (the first visit made after the last pregnancy visit), and "non-pregnant." The prevalence of depression was calculated for each visit type and compared using prevalence odds ratios (POR) with 95% confidence intervals (CI). Logistic regression with generalized estimating equations was used to evaluate sociodemographic factors associated with depression. From January 2013 to March 1, 2020, 1333 WLWH were enrolled, and 214 had pregnancies during follow-up. As compared to the prevalence of depression during "non-pregnant" visits (9.1%), depression was less common at "pregnant" (6.3%; POR = 0.68 [CI: 0.42, 1.09]) and "postpartum" (3.4%; POR = 0.36 [CI: 0.17, 0.76]) visits. When controlling for other factors, the visit category was not independently associated with depression. Visit number, study site, employment status, and food security were independently associated with decreased odds of depression. We observed a lower prevalence of depression during pregnancy and the postpartum period than has been previously described among WLWH during similar time points. We observed protective factors against depression which highlight the impact that holistic and consistent health care at HIV-centered clinics may have on the well-being of WLWH in AFRICOS.

Self-resolving superficial primary cutaneous mucormycosis in a 7-week-old infant.

A 7-week-old girl, born at 30 weeks' gestational age, presented to clinic for evaluation of a crop of vesicular lesions that were noted after removal of a bandage that had been in place for 4 days. A punch biopsy of the lesion revealed fungal elements that were later identified as Rhizopus spp. The lesion began to self-resolve, and no further treatment was needed, with full resolution of the lesion by 1 month after presentation. Clinicians should be aware of the variable presentations of mucormycosis and consider fungal infection in the differential diagnosis when evaluating vulnerable patients with skin eruptions.

Seasonality and Climatic Factors Associated With Human Rhinovirus/Enterovirus Nasopharyngeal Sample Positivity on Oahu, Hawai'i, 2016-2019.

INTRODUCTION: Globally, human rhinoviruses/enteroviruses (HRVs/ENTs), indistinguishable on many widely available molecular platforms, are among the leading causes of the common cold. Geographic and climatic factors impact the peak activity of these viruses. In temperate climates, the peak activity of HRV occurs during autumn and spring whereas that of ENT occurs during autumn and summer. Both viruses are thought to peak during the rainy season in tropical climates like Hawai'i; however, data remain limited. We describe HRV/ENT seasonality and evaluate the climatic factors associated with peak activity among respiratory viral samples processed on Oahu, Hawai'i. MATERIALS AND METHODS: We conducted a retrospective analysis of all respiratory specimens submitted to Tripler Army Medical Center for multiplex polymerase chain reaction testing between May 2016 and May 2019. Among HRV/ENT-positive samples, we recorded the month and year of positivity. Summative monthly positive detection was calculated with peak months above the mean. Associations between temperature, precipitation levels, relative humidity, and wind speed by week and the number of positive samples for HRV/ENT were evaluated using Poisson regression. This analysis was conducted via IRB exempt protocol number 19R18. RESULTS: During our study period, there were 7,143 nasopharyngeal respiratory samples sent for multiplex polymerase chain reaction testing, with 1,572 positive for HRV/ENT (22%). Nineteen percent of respiratory samples positive for HRV/ENT were additionally positive for one or more respiratory pathogens. The majority of HRV/ENT-positive samples arose from children < 5 years of age (n = 959, 61%). Peak months were February, March, May, August, November, and December. After controlling for lagged count and year, average wind speed was the only climatic factor significantly associated with HRV/ENT sample positivity. CONCLUSIONS: The peak monthly activity of HRV/ENT was similar to temperate climates with the exception of peak activity in February. Unlike other tropical climates, lower wind speed was associated with increased weekly HRV/ENT positivity and should be further explored as a transmission factor. Our study contributes to understanding the annual variability of HRV/ENT activity in tropical environments, which can inform clinician expectations regarding respiratory viral symptomatology in this region.

SARS-CoV-2 variant replacement constrains vaccine-specific viral diversification.

Coronavirus disease 2019 (COVID-19) vaccine breakthrough infections have been important for all circulating severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variant periods, but the contribution of vaccine-specific SARS-CoV-2 viral diversification to vaccine failure remains unclear. This study analyzed 595 SARS-CoV-2 sequences collected from the Military Health System beneficiaries between December 2020 and April 2022 to investigate the impact of vaccination on viral diversity. By comparing sequences based on the vaccination status of the participant, we found limited evidence indicating that vaccination was associated with increased viral diversity in the SARS-CoV-2 spike, and we show little to no evidence of a substantial sieve effect within major variants; rather, we show that rapid variant replacement constrained intragenotype COVID-19 vaccine strain immune escape. These data suggest that, during past and perhaps future periods of rapid SARS-CoV-2 variant replacement, vaccine-mediated effects were subsumed with other drivers of viral diversity due to the massive scale of infections and vaccinations that occurred in a short time frame. However, our results also highlight some limitations of using sieve analysis methods outside of placebo-controlled clinical trials.

SARS-CoV-2 infection is associated with self-reported post-acute neuropsychological symptoms within six months of follow-up.

BACKGROUND: Chronic neuropsychological sequelae following SARS-CoV-2 infection, including depression, anxiety, fatigue, and general cognitive difficulties, are a major public health concern. Given the potential impact of long-term neuropsychological impairment, it is important to characterize the frequency and predictors of this post-infection phenotype. METHODS: The Epidemiology, Immunology, and Clinical Characteristics of Emerging Infectious Diseases with Pandemic Potential (EPICC) study is a longitudinal study assessing the impact of SARS-CoV-2 infection in U.S. Military Healthcare System (MHS) beneficiaries, i.e. those eligible for care in the MHS including active duty servicemembers, dependents, and retirees. Four broad areas of neuropsychological symptoms were assessed cross-sectionally among subjects 1-6 months post-infection/enrollment, including: depression (Patient Health Questionnaire-9), anxiety (General Anxiety Disorder-7), fatigue (PROMIS® Fatigue 7a), and cognitive function (PROMIS® Cognitive Function 8a and PROMIS® Cognitive Function abilities 8a). Multivariable Poisson regression models compared participants with and without SARS-CoV-2 infection history on these measures, adjusting for sex, ethnicity, active-duty status, age, and months post-first positive or enrollment of questionnaire completion (MPFP/E); models for fatigue and cognitive function were also adjusted for depression and anxiety scores. RESULTS: The study population included 2383 participants who completed all five instruments within six MPFP/E, of whom 687 (28.8%) had at least one positive SARS-CoV-2 test. Compared to those who had never tested positive for SARS-CoV-2, the positive group was more likely to meet instrument-based criteria for depression (15.4% vs 10.3%, p<0.001), fatigue (20.1% vs 8.0%, p<0.001), impaired cognitive function (15.7% vs 8.6%, p<0.001), and impaired cognitive function abilities (24.3% vs 16.3%, p<0.001). In multivariable models, SARS-CoV-2 positive participants, assessed at an average of 2.7 months after infection, had increased risk of moderate to severe depression (RR: 1.44, 95% CI 1.12-1.84), fatigue (RR: 2.07, 95% CI 1.62-2.65), impaired cognitive function (RR: 1.64, 95% CI 1.27-2.11), and impaired cognitive function abilities (RR: 1.41, 95% CI 1.15-1.71); MPFP/E was not significant. CONCLUSIONS: Participants with a history of SARS-CoV-2 infection were up to twice as likely to report cognitive impairment and fatigue as the group without prior SARS-CoV-2 infection. These findings underscore the continued importance of preventing SARS-CoV-2 infection and while time since infection/enrollment was not significant through 6 months of follow-up, this highlights the need for additional research into the long-term impacts of COVID-19 to mitigate and reverse these neuropsychological outcomes.

Evaluation of Racial Disparities in Suspected Child Abuse among Insured Children with Head Injury.

Previous studies demonstrate racial disparities in child abuse evaluations even after controlling for health insurance coverage. We conducted a cross-sectional study using the Military Health System Data Repository (MDR) of Military Health System (MHS) beneficiaries born between fiscal years 2016 and 2018 to evaluate racial disparities and other factors in the suspicion of child abuse. We observed beneficiaries for 2.5 years after birth and assessed the incidence of head injury using diagnostic codes. Among children with head injury codes, we performed a multivariable logistic regression analysis to measure the association between race and the concurrent use of the diagnostic code for suspected child abuse (SCA) or for the performance of a skeletal survey. There were 195,893 infants included and 45,269 (23.1%) underwent evaluations for head injury. Less than one percent (n = 424) concurrently had the diagnostic code for SCA or a skeletal survey performed within 2 weeks of the head injury evaluation. When controlling for other factors, race was not associated with SCA. Higher military rank was independently associated with decreased odds of SCA. Racial disparities in SCA may be mitigated in the MHS, and further evaluation is needed. Military rank could be a factor in SCA disparities and warrants further study.

A Case of Reactivated Acute Hepatitis in a 12-month-old Infant With Multiviral Infection, Including SARS-CoV-2 and Adenovirus.

Adenovirus hepatitis is of global concern due to its increasing incidence and poorly understood pathogenesis. Historically, adenovirus has contributed to the development of severe hepatitis in immunocompromised patients. The clinical course and management of such infections in previously healthy children remains elusive. We present a case of severe acute hepatitis in a previously healthy 12-month-old infant with a history of SARS-CoV-2 infection followed by multiviral infection including adenovirus. Additional evaluation revealed acute hepatitis without evidence of acute liver failure except for mild coagulopathy. She demonstrated clinical improvement with supportive therapy but later experienced reactivated hepatitis in the setting of a third new viral infection thereby warranting a second hospitalization. A liver biopsy was obtained due to concern for an underlying immunologic or metabolic etiology of her prolonged hepatitis. Our case provides insight into the medical management and clinical course of a previously healthy child with a history of SARS-CoV-2 and adenovirus infections leading to reactivated acute hepatitis.

Comparing the Clinical Courses of Children With Human Rhinovirus/Enterovirus to Children With Other Respiratory Viruses in the Outpatient Setting.

BACKGROUND: While infections caused by rhinoviruses and enteroviruses are common among children, the entirety of their clinical impact remains elusive. We compared the clinical outcomes of children with rhinovirus/enterovirus infections to other common respiratory viruses in outpatient settings. METHODS: We conducted a retrospective analysis of nasopharyngeal samples singly positive for human rhinovirus/enterovirus (HRV/ENT), influenza A/B (FLU) or respiratory syncytial virus (RSV) from patients ≤17 years submitted for clinical testing via multiplex polymerase chain reaction between 2016 and 2019. We evaluated the following outpatient outcomes: days of respiratory symptoms before testing; visits for respiratory symptoms; receipt of a breathing treatment; receipt of antibiotics and hospital admission. Statistical analyses were conducted controlling for age and comorbid conditions. RESULTS: There were 1355 positive samples included in this analysis (HRV/ENT: n = 743, FLU: n = 303 and RSV: n = 309). Compared to HRV/ENT, children with FLU had 28% fewer days of respiratory symptoms (ß: -0.32; 95% confidence interval: -0.46 to -0.18; P < 0.001), fewer visits for respiratory symptoms, and significantly decreased odds of receiving a breathing treatment or antibiotics, and admission to the hospital. Children with RSV had a similar number of days of respiratory symptoms, outpatient visits and odds of hospital admission, but significantly increased odds of receiving a breathing treatment and antibiotics compared to those with HRV/ENT. CONCLUSION: Clinicians should have a high level of vigilance when managing children with positive respiratory viral testing for HRV/ENT given the potential for clinical outcomes similar to and, in some instances, worse than known highly pathogenic viruses.

A machine learning approach identifies distinct early-symptom cluster phenotypes which correlate with hospitalization, failure to return to activities, and prolonged COVID-19 symptoms.

BACKGROUND: Accurate COVID-19 prognosis is a critical aspect of acute and long-term clinical management. We identified discrete clusters of early stage-symptoms which may delineate groups with distinct disease severity phenotypes, including risk of developing long-term symptoms and associated inflammatory profiles. METHODS: 1,273 SARS-CoV-2 positive U.S. Military Health System beneficiaries with quantitative symptom scores (FLU-PRO Plus) were included in this analysis. We employed machine-learning approaches to identify symptom clusters and compared risk of hospitalization, long-term symptoms, as well as peak CRP and IL-6 concentrations. RESULTS: We identified three distinct clusters of participants based on their FLU-PRO Plus symptoms: cluster 1 ("Nasal cluster") is highly correlated with reporting runny/stuffy nose and sneezing, cluster 2 ("Sensory cluster") is highly correlated with loss of smell or taste, and cluster 3 ("Respiratory/Systemic cluster") is highly correlated with the respiratory (cough, trouble breathing, among others) and systemic (body aches, chills, among others) domain symptoms. Participants in the Respiratory/Systemic cluster were twice as likely as those in the Nasal cluster to have been hospitalized, and 1.5 times as likely to report that they had not returned-to-activities, which remained significant after controlling for confounding covariates (P < 0.01). Respiratory/Systemic and Sensory clusters were more likely to have symptoms at six-months post-symptom-onset (P = 0.03). We observed higher peak CRP and IL-6 in the Respiratory/Systemic cluster (P < 0.01). CONCLUSIONS: We identified early symptom profiles potentially associated with hospitalization, return-to-activities, long-term symptoms, and inflammatory profiles. These findings may assist in patient prognosis, including prediction of long COVID risk.

Decreased Self-reported Physical Fitness Following SARS-CoV-2 Infection and the Impact of Vaccine Boosters in a Cohort Study.

Background: The long-term effects of coronavirus disease 2019 (COVID-19) on physical fitness are unclear, and the impact of vaccination on that relationship is uncertain. Methods: We compared survey responses in a 1-year study of US military service members with (n = 1923) and without (n = 1591) a history of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. We fit Poisson regression models to estimate the association between history of SARS-CoV-2 infection and fitness impairment, adjusting for time since infection, demographics, and baseline health. Results: The participants in this analysis were primarily young adults aged 18-39 years (75%), and 71.5% were male. Participants with a history of SARS-CoV-2 infection were more likely to report difficulty exercising (38.7% vs 18.4%; P < .01), difficulty performing daily activities (30.4% vs 12.7%; P < .01), and decreased fitness test (FT) scores (42.7% vs 26.2%; P < .01) than those without a history of infection. SARS-CoV-2-infected participants were at higher risk of these outcomes after adjusting for other factors (unvaccinated: exercising: adjusted risk ratio [aRR], 3.99; 95% CI, 3.36-4.73; activities: aRR, 5.02; 95% CI, 4.09-6.16; FT affected: aRR, 2.55; 95% CI, 2.19-2.98). Among SARS-CoV-2-positive participants, full vaccination before infection was associated with a lower risk of post-COVID-19 fitness impairment (fully vaccinated: exercise: aRR, 0.81; 95% CI, 0.70-0.95; activities: aRR, 0.76; 95% CI, 0.64-0.91; FT: aRR, 0.87; 95% CI, 0.76-1.00; boosted: exercise: aRR, 0.62; 95% CI, 0.51-0.74; activities: aRR, 0.52; 95% CI, 0.41-0.65; FT: aRR, 0.59; 95% CI, 0.49-0.70). Conclusions: In this study of generally young, healthy military service members, SARS-CoV-2 infection was associated with lower self-reported fitness and exercise capacity; vaccination and boosting were associated with lower risk of self-reported fitness loss.

Respiratory Viral Pathogens Among U.S. Military Personnel at a Medical Treatment Facility in Hawaii From 2014 to 2019.

INTRODUCTION: Acute respiratory diseases account for a substantial number of outpatient visits and hospitalizations among U.S. military personnel, significantly affecting mission readiness and military operations. We conducted a retrospective analysis of respiratory viral pathogen (RVP) samples collected from U.S. military personnel stationed in Hawaii and tested at Tripler Army Medical Center from January 2014 to May 2019 in order to describe the etiology, distribution, and seasonality of RVP exposure in a military population. MATERIALS AND METHODS: Samples were analyzed by viral culture or multiplex PCR. Distribution of respiratory viruses over time was analyzed as well as subject demographic and encounter data. Presenting signs and symptoms were evaluated with each RVP. RESULTS: A total of 2,576 military personnel were tested, of which 726 (28.2%) were positive for one or more RVP. Among positive tests, the three most common viral pathogens detected were influenza A (43.0%), rhinovirus (24.5%), and parainfluenza (7.6%). Symptoms were generally mild and most frequently included cough, fever, and body aches. CONCLUSION: Our study evaluated respiratory virus prevalence, seasonality, and association with clinical symptoms for military personnel in an urban tropical setting in Oahu, HI, over a 5-year period. We show that viral prevalence and seasonality in Hawaii are distinct from those of the CONUS. Results contribute to the broader understanding of seasonality, clinical manifestation, and demographics of RVP among active duty military personnel stationed in Hawaii.

COVID-19 Patient-Reported Symptoms Using FLU-PRO Plus in a Cohort Study: Associations With Infecting Genotype, Vaccine History, and Return to Health.

Background: Patient-reported outcomes of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection are an important measure of the full burden of coronavirus disease (COVID). Here, we examine how (1) infecting genotype and COVID-19 vaccination correlate with inFLUenza Patient-Reported Outcome (FLU-PRO) Plus score, including by symptom domains, and (2) FLU-PRO Plus scores predict return to usual activities and health. Methods: The epidemiology, immunology, and clinical characteristics of pandemic infectious diseases (EPICC) study was implemented to describe the short- and long-term consequences of SARS-CoV-2 infection in a longitudinal, observational cohort. Multivariable linear regression models were run with FLU-PRO Plus scores as the outcome variable, and multivariable Cox proportional hazards models evaluated effects of FLU-PRO Plus scores on return to usual health or activities. Results: Among the 764 participants included in this analysis, 63% were 18-44 years old, 40% were female, and 51% were White. Being fully vaccinated was associated with lower total scores (ß = -0.39; 95% CI, -0.57 to -0.21). The Delta variant was associated with higher total scores (ß = 0.25; 95% CI, 0.05 to 0.45). Participants with higher FLU-PRO Plus scores were less likely to report returning to usual health and activities (health: hazard ratio [HR], 0.46; 95% CI, 0.37 to 0.57; activities: HR, 0.56; 95% CI, 0.47 to 0.67). Fully vaccinated participants were more likely to report returning to usual activities (HR, 1.24; 95% CI, 1.04 to 1.48). Conclusions: Full SARS-CoV-2 vaccination is associated with decreased severity of patient-reported symptoms across multiple domains, which in turn is likely to be associated with earlier return to usual activities. In addition, infection with the Delta variant was associated with higher FLU-PRO Plus scores than previous variants, even after controlling for vaccination status.

Antigenic cartography of well-characterized human sera shows SARS-CoV-2 neutralization differences based on infection and vaccination history.

The rapid emergence of SARS-CoV-2 variants challenges vaccination strategies. Here, we collected 201 serum samples from persons with a single infection or multiple vaccine exposures, or both. We measured their neutralization titers against 15 natural variants and 7 variants with engineered spike mutations and analyzed antigenic diversity. Antigenic maps of primary infection sera showed that Omicron sublineages BA.2, BA.4/BA.5, and BA.2.12.1 are distinct from BA.1 and more similar to Beta/Gamma/Mu variants. Three mRNA COVID-19 vaccinations increased neutralization of BA.1 more than BA.4/BA.5 or BA.2.12.1. BA.1 post-vaccination infection elicited higher neutralization titers to all variants than three vaccinations alone, although with less neutralization to BA.2.12.1 and BA.4/BA.5. Those with BA.1 infection after two or three vaccinations had similar neutralization titer magnitude and antigenic recognition. Accounting for antigenic differences among variants when interpreting neutralization titers can aid the understanding of complex patterns in humoral immunity that informs the selection of future COVID-19 vaccine strains.

The prevalence of M. tuberculosis among acid fast bacilli cultures from military health system and veterans affairs beneficiaries in Hawaii and the Pacific Islands from 2002 to 2019.

The prevalence of tuberculosis among military health system (MHS) and Veterans Affairs (VA) beneficiaries in Hawaii and the Pacific Islands has not been previously reported. Our analysis evaluates the prevalence of M. tuberculosis (MTB) among acid fast bacilli culture(s) (AFB) tested at Tripler Army Medical Center (TAMC) on Oahu, HI and describes demographic factors associated with positive samples. We analyzed 9,768 AFBs from 4,129 individuals with AFB specimens processed at TAMC from January 2002 to November 2019: of those who were tested 3,178 were MHS beneficiaries and 951 were VA beneficiaries. There were a total of 40 individuals with MTB-positive cultures over the period of study: 31 MHS beneficiaries and 9 VA beneficiaries. Of the MTB-positive specimens, 93% were from pulmonary samples while the remainder were from lymph node aspirates (5%) and peritoneal samples (2%). Cumulative incidence rates of MTB-isolation were 1.8 per 100,000 MHS beneficiaries and 1.2 per 100,000 VA beneficiaries, both of which were lower than reported incidence rates in Hawaii, the U.S.-affiliated Pacific Islands and the United States for the study period. MHS beneficiaries of Asian-Pacific Islander race or ethnicity had nearly 20 times higher odds of positive AFB than white MHS beneficiaries (OR = 19.56, 95% CI 5.52, 69.29, p = < 0.001). This study demonstrated a higher odds of MTB-positivity associated with Asian-Pacific Islander race or ethnicity and low incidence rates of TB among MHS and VA beneficiaries in Hawaii and the Pacific Islands when compared with the civilian population.

Respiratory Viral Pathogens in Children Evaluated at Military Treatment Facilities in Oahu, Hawaii From 2014 to 2018: Seasonality and Climatic Factors.

Five-year retrospective analysis of respiratory viruses in children less than 18 years old at Tripler Army Medical Center and outlying clinics in Oahu. Respiratory syncytial virus and influenza A showed pronounced seasonality with peaks from September to December and December to March, respectively. Results provide a better understanding of the timing of viral preventive strategies in Oahu.

Seizing opportunities for intervention: Changing HIV-related knowledge among men who have sex with men and transgender women attending trusted community centers in Nigeria.

BACKGROUND: Knowledge of HIV risk factors and reduction strategies is essential for prevention in key populations such as men who have sex with men (MSM) and transgender women (TGW). We evaluated factors associated with HIV-related knowledge among MSM and TGW and the impact of engagement in care at trusted community health centers in Nigeria. METHODS: The TRUST/RV368 cohort recruited MSM and TGW in Lagos and Abuja, Nigeria via respondent driven sampling. During study visits every three months, participants underwent structured interviews to collect behavioral data, received HIV education, and were provided free condoms and condom compatible lubricants. Five HIV-related knowledge questions were asked at enrollment and repeated after 9 and 15 months. The mean number of correct responses was calculated for each visit with 95% confidence intervals (CIs). Multivariable Poisson regression was used to calculate adjusted risk ratios and CIs for factors associated with answering more knowledge questions correctly. RESULTS: From March 2013 to April 2018, 2122 persons assigned male sex at birth were enrolled, including 234 TGW (11.2%). The mean number of correct responses at enrollment was 2.36 (95% CI: 2.31-2.41) and increased to 2.95 (95% CI: 2.86-3.04) and 3.06 (95% CI: 2.97-3.16) after 9 and 15 months in the study, respectively. Among 534 participants who completed all three HIV-related knowledge assessments, mean number of correct responses rose from 2.70 (95% CI: 2.60-2.80) to 3.02 (95% CI: 2.93-3.13) and then 3.06 (95% CI: 2.96-3.16). Factors associated with increased overall HIV-related knowledge included longer duration of study participation, HIV seropositivity, higher education level, and more frequent internet use. CONCLUSIONS: There was suboptimal HIV-related knowledge among Nigerian MSM and TGW at that improved modestly with engagement in care. These data demonstrate unmet HIV education needs among Nigerian MSM and TGW and provide insights into modalities that could be used to address these needs.

The Impact of Vaccine Refusal on Physician Office Visits During the Subsequent 12 Months.

We hypothesized that families who are nonadherent to the routine vaccination schedule (RVS) present less frequently for physician visits. We conducted a retrospective chart review to compare the number of visits made over the subsequent 12-month period by families that refused the RVS versus those who were adherent. Subjects were aged 0 to 4 years, enrolled to Keller Army Hospital, and had a diagnosis indicating the RVS was refused. Age-matched controls, who were adherent to the RVS, were randomly chosen for each case. Subjects made significantly more total visits than CASES: 7 (interquartile range [IQR] = 1-20) versus 6 (IQR = 2-17), p = 0.0049. When each visit type was compared independently, there was no significant difference in the number of acute (p = 0.494) or emergency department (p = 0.077) visits between groups. However, subjects who refused to follow the RVS made significantly fewer routine care visits during the 1-year follow-up period compared to those that adhered to the RVS (p < 0.001).