The Moral Injury Symptoms Scale-Military Version-Short Form: Further Scale Validation in a U.S. Veteran Sample.

This study assessed the Moral Injury Symptoms Scale - Military Version - Short Form's (MISS-M-SF) factor structure and construct validity. Participants included 3650 combat-deployed U.S. veterans who answered all 10 MISS-M-SF items from the sixth wave of The Veterans Metric Initiative (TVMI). EFA results suggested a two-factor solution, based on item wording, fit best. CFA results indicated a bifactor model (one general factor and two method factors, based on item wording) fit best. Further investigation revealed that a one-factor model could be used despite the data's multidimensionality. Item-level analyses revealed four items represented the general factor exceptionally well, potentially simplifying assessment in research and clinical applications. Construct validity was also demonstrated through moderate to high correlations with conceptually related measures.

Neurophysiological patterns associated with blunted emotional face processing and withdrawal tendencies in young children exposed to intimate partner violence.

Studies linking child maltreatment to abnormal neurophysiological responses to emotional stimuli and mental health impairment have not specifically explored these patterns in young children exposed to intimate partner violence (IPV). The present study examined two neurophysiological indicators, resting-state electroencephalography and an emotion event-related potential (ERP) in 21 IPV exposed and 30 nonexposed children ages 4-6 years recruited from the community and domestic violence shelters. Frontal alpha asymmetry (FAA) was assessed while at rest. FAA is often associated with avoidant/withdrawn behavior and increased risk of IPV-related mental health conditions (e.g., depression). Additionally, the late positive potential (LPP) ERP component, reflecting motivated attention, was acquired in the context of an age-appropriate affective oddball paradigm with low probability animal pictures as targets and human facial expressions (angry, happy, neutral) as distracters. Results demonstrated that IPV-exposed children, compared with nonexposed children, exhibited lower left FAA during resting state and reduced LPPs to oddball targets and affective faces relative to neutral faces in the oddball task. Together, these results suggest neural patterns associated with a blunted response to emotional stimuli and withdrawal tendencies, respectively, in young children exposed to IPV. Implications for emotional socialization in this vulnerable population are discussed.

The Family Socialization Interview-Revised (FSI-R): a Comprehensive Assessment of Parental Disciplinary Behaviors.

Elucidating the complex mechanisms by which harsh parenting increases risk of child psychopathology is key to targeted prevention. This requires nuanced methods that capture the varied perceptions and experiences of diverse families. The Family Socialization Interview-Revised (FSI-R), adapted from an interview developed by Dodge et al. (Child Development, 65, 649-665, 1994), is a comprehensive, semi-structured interview for characterizing methods of parental discipline used with young children. The FSI-R coding system systematically rates parenting style, usual discipline techniques, and most intense physical and psychological discipline based on rater judgment across two eras: (1) birth to the previous year, and (2) the previous year to present. The current study examined the psychometric properties of the FSI-R in a diverse, high-risk community sample of 386 mothers and their children, ages 3 to 6 years. Interrater reliability was good to excellent for codes capturing physically and psychologically harsh parenting, and restrictive/punitive parenting styles. Findings supported the FSI-R's convergent and incremental validity. Importantly, the FSI-R demonstrated incremental utility, explaining unique variance in children's externalizing and internalizing symptoms beyond that explained by traditional surveys and observed parenting. The FSI-R appeared particularly promising for capturing risk associated with young children's depressive symptoms, as these were generally not significantly associated with other measures of harsh parenting. Overall, findings support the added value of the FSI-R within a multi-method assessment of disciplinary practices across early child development. Future implications for prevention are discussed.

Attention bias in the developmental unfolding of post-traumatic stress symptoms in young children at risk.

BACKGROUND: Threat-related attention bias relates to anxiety and posttraumatic stress symptoms in adults and adolescents, but few longitudinal studies examine such associations in young children. This study examines prospective relations among attention bias, trauma exposure, and anxiety and trauma symptoms in a sample previously reported to manifest cross-sectional associations between attention bias and observed anxiety at preschool age. METHODS: Young children [mean (MN) = 5.0, ±0.7 years, n = 208] from a community-based sample completed the dot-probe task to assess their attention biases in response to angry faces. At baseline (T1) and at follow-up approximately 9 months later (T2), anxiety and trauma exposure (i.e. violent and noninterpersonal events) and symptoms were assessed by maternal report. RESULTS: Neither attention bias nor baseline or recent trauma exposure predicted later anxiety. In contrast, attention bias toward threat and recent trauma exposure significantly predicted later trauma symptoms. There was evidence of symptom specificity such that attention bias toward threat significantly predicted hyperarousal and dissociation, but not avoidance or re-experiencing symptoms. Finally, moderation analyses indicated that the relationship between attention bias and trauma symptoms may differ according to children's experiences of probable abuse. CONCLUSIONS: Attention profiles and trauma exposure may increase the risk that young children will develop trauma symptoms. Individual differences in these attentional patterns and children's exposure history may impact outcomes among high-risk children with potential implications for intervention.

Examining Patterns of Exposure to Family Violence in Preschool Children: A Latent Class Approach.

Young children can experience violence directly or indirectly in the home, with some children exposed to multiple forms of violence. These polyvictims often experience violence that is severe, chronic, and multifaceted. The current study used latent class analysis to identify and examine the pattern of profiles of exposure to family violence (i.e., violence directed towards the child and between caregivers) among a sample of 474 children ages 3-6 year who were drawn from the Multidimensional Assessment of Preschoolers Study (Wakschlag et al., 2014). The data yielded 3 classes: a polyvictimized class (n = 72; 15.2%) with high probability of exposure to all forms of violence, a harsh parenting class (n = 235; 49.5%), distinguished mainly by child-directed physical discipline in the absence of more severe forms of violence, and a low-exposure class (n = 167; 35.2%). Classes were differentiated by contextual factors, maternal characteristics, and mother-reported and observational indicators of parenting and child functioning with most effect sizes between medium and large. These findings add to emerging evidence linking polyvictimization to impaired caregiving and adverse psychological outcomes for children and offer important insight for prevention and intervention for this vulnerable population.

Management of a Patient With Toxic Epidermal Necrolysis Using Silicone Transfer Foam Dressings and a Secondary Absorbent Dressing.

BACKGROUND: Toxic epidermal necrolysis (TEN) is an exfoliative disorder of the skin usually caused by a drug reaction. The primary goal of wound care for patients with TEN is prevention of further mechanical trauma to the skin, along with management of wound infection. CASE: A 77-year-old woman with TEN was successfully managed with a perforated silver soft contact foam and a superabsorbent outer layer. Topical therapy combined nanoparticle silver for management of wound infection and minimized trauma to the skin as only the outer layer needed to be changed. CONCLUSION: The silicone foam dressing with silver sulfate epithelialization and reduced pain and trauma associated with dressing changes.

Attention bias and anxiety in young children exposed to family violence.

BACKGROUND: Attention bias toward threat is associated with anxiety in older youth and adults and has been linked with violence exposure. Attention bias may moderate the relationship between violence exposure and anxiety in young children. Capitalizing on measurement advances, this study examines these relationships at a younger age than previously possible. METHODS: Young children (mean age 4.7, ±0.8) from a cross-sectional sample oversampled for violence exposure (N = 218) completed the dot-probe task to assess their attention biases. Observed fear/anxiety was characterized with a novel observational paradigm, the Anxiety Dimensional Observation Scale. Mother-reported symptoms were assessed with the Preschool Age Psychiatric Assessment and Trauma Symptom Checklist for Young Children. Violence exposure was characterized with dimensional scores reflecting probability of membership in two classes derived via latent class analysis from the Conflict Tactics Scales: Abuse and Harsh Parenting. RESULTS: Family violence predicted greater child anxiety and trauma symptoms. Attention bias moderated the relationship between violence and anxiety. CONCLUSIONS: Attention bias toward threat may strengthen the effects of family violence on the development of anxiety, with potentially cascading effects across childhood. Such associations maybe most readily detected when using observational measures of childhood anxiety.

Contextual variation in young children's observed disruptive behavior on the DB-DOS: implications for early identification.

BACKGROUND: Contextual variation in child disruptive behavior is well documented but remains poorly understood. We first examine how variation in observed disruptive behavior across interactional contexts is associated with maternal reports of contextual variation in oppositional-defiant behavior and functional impairment. Second, we test whether child inhibitory control explains the magnitude of contextual variation in observed disruptive behavior. METHODS: Participants are 497 young children (mean age = 4 years, 11 months) from a subsample of the MAPS, a sociodemographically diverse pediatric sample, enriched for risk of disruptive behavior. Observed anger modulation and behavioral regulation problems were coded on the Disruptive Behavior Diagnostic Observation Schedule (DB-DOS) during interactions with parent and examiner. Oppositional-defiant behavior, and impairment in relationships, with parents and nonparental adults, were measured with the Preschool Age Psychiatric Assessment (PAPA) interview with the mother. Functional impairment in the home and out-and-about was assessed with the Family Life Impairment Scale (FLIS), and expulsion from child care/school was measured with the baseline survey and FLIS. RESULTS: Observed disruptive behavior on the DB-DOS Parent Context was associated with oppositional-defiant behavior with parents, and with impairment at home and out-and-about. Observed disruptive behavior with the Examiner was associated with oppositional-defiant behavior with both parents and nonparental adults, impairment in relationships with nonparental adults, and child care/school expulsion. Differences in observed disruptive behavior in the Parent versus Examiner Contexts was related to the differences in maternal reports of oppositional-defiant behavior with parents versus nonparental adults. Children with larger decreases in disruptive behavior from Parent to Examiner Context had better inhibitory control and fewer attention-deficit/hyperactivity disorder symptoms. CONCLUSIONS: The DB-DOS showed clinical utility in a community sample for identifying contextual variation that maps onto reported oppositional-defiant behavior and functioning across contexts. Elucidating the implications of contextual variation for early identification and targeted prevention is an important area for future research.

Punishment insensitivity and impaired reinforcement learning in preschoolers.

BACKGROUND: Youth and adults with psychopathic traits display disrupted reinforcement learning. Advances in measurement now enable examination of this association in preschoolers. The current study examines relations between reinforcement learning in preschoolers and parent ratings of reduced responsiveness to socialization, conceptualized as a developmental vulnerability to psychopathic traits. METHODS: One hundred and fifty-seven preschoolers (mean age 4.7 ± 0.8 years) participated in a substudy that was embedded within a larger project. Children completed the 'Stars-in-Jars' task, which involved learning to select rewarded jars and avoid punished jars. Maternal report of responsiveness to socialization was assessed with the Punishment Insensitivity and Low Concern for Others scales of the Multidimensional Assessment of Preschool Disruptive Behavior (MAP-DB). RESULTS: Punishment Insensitivity, but not Low Concern for Others, was significantly associated with reinforcement learning in multivariate models that accounted for age and sex. Specifically, higher Punishment Insensitivity was associated with significantly lower overall performance and more errors on punished trials ('passive avoidance'). CONCLUSIONS: Impairments in reinforcement learning manifest in preschoolers who are high in maternal ratings of Punishment Insensitivity. If replicated, these findings may help to pinpoint the neurodevelopmental antecedents of psychopathic tendencies and suggest novel intervention targets beginning in early childhood.

The differential impact of COVID-19 on the psychological stress of post-9/11 veterans: Gender, race, and ethnicity.

The COVID-19 pandemic has led to economic turndowns, social restrictions, and family life alterations. The stress induced by the public health crisis and its consequences are beginning to be explored. This study examined stress experiences since the pandemic'sonset in work, financial, social, and health domainsamong a large sample of post-9/11, United States military veterans. The sample, who separated from active-duty service or deactivated from active status in a reserve component in 2016, completed an online survey (n = 3180) in 2020. Participants were 70% White non-Hispanic, 81% male, and had an average age of 38 years. Frequencies and descriptive statistics were calculated. Female veterans and veterans of colour reported significantly higher levels of stress across most life domains. The results suggest White, male, post-9/11 veterans may be somewhat protected from COVID-19 stress, but that the pandemic is exacerbatinghealth and social disparities experienced by post-9/11 veterans of colour and female veterans. Supports and comprehensive care, particularly targeted towardsat-risk populations, are likely needed to provide sufficient resources for resiliency during and after the pandemic.

The Moderating and Mediating Role of Responsive Parenting Behavior in Explaining the Link between Intimate Partner Violence and Posttraumatic Stress Symptoms in Young Children.

Responsive parenting serves an influential role in explaining the link between children's exposure to intimate partner violence (IPV) and children's mental health impairment, but how this occurs is not well elucidated. In some cases, researchers examine parenting as a mediator to explain how IPV leads to maladaptive outcomes (i.e., IPV negatively impacts one's capacity for responsive parenting, which in turn impacts children), whereas others examine moderation in which either the absence of responsive parenting exacerbates adverse outcomes or increased responsive parenting buffers risk. Mediation addresses theoretical questions about how or why IPV leads to maladaptive outcomes, whereas moderation addresses who might be most impacted. However, responsive parenting has rarely, if ever, been tested as both a mediator and moderator of the link between IPV and posttraumatic stress symptoms (PTSS) within the same sample. The current study examined the mediating and moderating role of responsive parenting on physical IPV exposure and child PTSS in a longitudinal sample of 391 children ages 3 to 5 years (M = 4.74, SD = 0.89). Self-report measures of physical IPV exposure, parenting practices, and PTSS were completed by mothers. We found that responsive parenting significantly moderated and mediated the association between physical IPV exposure and child PTSS over time. Studies that include tests of both moderation and mediation are critical for advancing mechanistic insight into the role of parenting in the etiology of mental health impairment in children exposed to IPV.

Feasibility and utility of a combined nasogastric-tube-and-string-test device for bacteriologic confirmation of pulmonary tuberculosis in young children.

For microbiological confirmation of pediatric pulmonary tuberculosis (PTB), gastric aspirates (GA) are often operationally unfeasible without hospitalization, and the encapsulated orogastric string test is not easily swallowed in young children. The Combined-NasoGastric-Tube-and-String-Test (CNGTST) enables dual collection of GA and string specimens. In a prospective cohort study in Kenya, we examined its feasibility in children under five with presumptive PTB and compared the bacteriological yield of string to GA. Paired GA and string samples were successfully collected in 95.6 % (281/294) of children. Mycobacterium tuberculosis was isolated from 7.0 % (38/541) of GA and 4.3 % (23/541) of string samples, diagnosing 8.2 % (23/281) of children using GA and 5.3 % (15/281) using string. The CNGTST was feasible in nearly all children. Yield from string was two-thirds that of GA despite a half-hour median dwelling time. In settings where the feasibility of hospitalisation for GA is uncertain, the string component can be used to confirm PTB.

Xpert MTB/RIF Ultra versus mycobacterial growth indicator tube liquid culture for detection of Mycobacterium tuberculosis in symptomatic adults: a diagnostic accuracy study.

BACKGROUND: Xpert MTB/RIF Ultra (Ultra) is an automated molecular test for the detection of Mycobacterium tuberculosis in sputum. We compared the sensitivity of Ultra to that of mycobacterial growth indicator tube (MGIT) liquid culture, considered the most sensitive assay in routine clinical use. METHODS: In this prospective, multicentre, cross-sectional diagnostic accuracy study, we used a non-inferiority design to assess whether the sensitivity of a single Ultra test was non-inferior to that of a single liquid culture for detection of M tuberculosis in sputum. We enrolled adults (age ≥18 years) with pulmonary tuberculosis symptoms in 11 countries and each adult provided three sputum specimens with a minimum volume of 2 mL over 2 days. Ultra was done directly on sputum 1, and Ultra and MGIT liquid culture were done on resuspended pellet from sputum 2. Results of MGIT and solid media cultures done on sputum 3 were considered the reference standard. The pre-defined non-inferiority margin was 5·0%. FINDINGS: Between Feb 18, 2016, and Dec 4, 2019, we enrolled 2906 participants. 2600 (89%) participants were analysed, including 639 (25%) of 2600 who were positive for tuberculosis by the reference standard. Of the 2357 included in the non-inferiority analysis, 877 (37%) were HIV-positive and 984 (42%) were female. Sensitivity of Ultra performed directly on sputum 1 was non-inferior to that of sputum 2 MGIT culture (MGIT 91·1% vs Ultra 91·9%; difference -0·8 percentage points; 95% CI -2·8 to 1·1). Sensitivity of Ultra performed on sputum 2 pellet was also non-inferior to that of sputum 2 MGIT (MGIT 91·1% vs Ultra 91·9%; difference -0·8 percentage points; -2·7 to 1·0). INTERPRETATION: For the detection of M tuberculosis in sputum from adults with respiratory symptoms, there was no difference in sensitivity of a single Ultra test to that of a single MGIT culture. Highly sensitive, rapid molecular approaches for M tuberculosis detection, combined with advances in genotypic methods for drug resistance detection, have potential to replace culture. FUNDING: US National Institute of Allergy and Infectious Diseases.

An algorithm for tuberculosis screening and diagnosis in people with HIV.

BACKGROUND: Tuberculosis screening is recommended for people with human immunodeficiency virus (HIV) infection to facilitate early diagnosis and safe initiation of antiretroviral therapy and isoniazid preventive therapy. No internationally accepted, evidence-based guideline addresses the optimal means of conducting such screening, although screening for chronic cough is common. METHODS: We consecutively enrolled people with HIV infection from eight outpatient clinics in Cambodia, Thailand, and Vietnam. For each patient, three samples of sputum and one each of urine, stool, blood, and lymph-node aspirate (for patients with lymphadenopathy) were obtained for mycobacterial culture. We compared the characteristics of patients who received a diagnosis of tuberculosis (on the basis of having one or more specimens that were culture-positive) with those of patients who did not have tuberculosis to derive an algorithm for screening and diagnosis. RESULTS: Tuberculosis was diagnosed in 267 (15%) of 1748 patients (median CD4+ T-lymphocyte count, 242 per cubic millimeter; interquartile range, 82 to 396). The presence of a cough for 2 or 3 weeks or more during the preceding 4 weeks had a sensitivity of 22 to 33% for detecting tuberculosis. The presence of cough of any duration, fever of any duration, or night sweats lasting 3 or more weeks in the preceding 4 weeks was 93% sensitive and 36% specific for tuberculosis. In the 1199 patients with any of these symptoms, a combination of two negative sputum smears, a normal chest radiograph, and a CD4+ cell count of 350 or more per cubic millimeter helped to rule out a diagnosis of tuberculosis, whereas a positive diagnosis could be made only for the 113 patients (9%) with one or more positive sputum smears; mycobacterial culture was required for most other patients. CONCLUSIONS: In persons with HIV infection, screening for tuberculosis should include asking questions about a combination of symptoms rather than only about chronic cough. It is likely that antiretroviral therapy and isoniazid preventive therapy can be started safely in people whose screening for all three symptoms is negative, whereas diagnosis in most others will require mycobacterial culture.

Clinical validity of a brief measure of early childhood social-emotional/behavioral problems.

OBJECTIVE: To address a pressing need for measures of clinically significant social-emotional/behavioral problems in young children by examining several validity indicators for a brief parent-report questionnaire. METHODS: An ethnically and economically diverse sample of 213 referred and nonreferred 2- and 3-year-olds was studied. The validity of the Brief Infant-Toddler Social-Emotional Assessment (BITSEA) Problem Index and Internalizing and Externalizing scales was evaluated relative to a "gold standard" diagnostic interview, as well as the Child Behavior Checklist (CBCL). RESULTS: The validity of the BITSEA Problem Index relative to Diagnosis (sensitivity = 72.7%-80.8%, specificity = 70.0%-83.3%) and clinical-range CBCL scores (sensitivity = 80.0%-96.2%, specificity = 75.0%-89.9%) was supported in the full sample and within minority/nonminority groups. Additional results supported the validity of the BITSEA Internalizing and Externalizing scales. CONCLUSIONS: Documented validity suggests that the BITSEA may be a valuable tool to aid screening, identification, and assessment efforts targeting early-emergent social-emotional/behavioral problems. Practical implications and generalizability are discussed.

Nontuberculous mycobacterial disease in patients with HIV in Southeast Asia.

RATIONALE: Although nontuberculous mycobacteria (NTM) are widely documented as a cause of illness among HIV-infected people in the developed world, studies describing the prevalence of NTM disease among HIV-infected people in most resource-limited settings are rare. OBJECTIVES: To evaluate the prevalence of mycobacterial disease in HIV-infected patients in Southeast Asia. METHODS: We enrolled people with HIV from three countries in Southeast Asia and collected pulmonary and extrapulmonary specimens to evaluate the prevalence of mycobacterial disease. We adapted American Thoracic Society/Infectious Disease Society of America guidelines to classify patients into NTM pulmonary disease, NTM pulmonary disease suspects, NTM disseminated disease, and no NTM categories. MEASUREMENTS AND MAIN RESULTS: In Cambodia, where solid media alone was used, NTM was rare. Of 1,060 patients enrolled in Thailand and Vietnam, where liquid culture was performed, 124 (12%) had tuberculosis and 218 (21%) had NTM. Of 218 patients with NTM, 66 (30%) were classified as NTM pulmonary disease suspects, 9 (4%) with NTM pulmonary disease, and 10 (5%) with NTM disseminated disease. The prevalence of NTM disease was 2% (19 of 1,060). Of 51 patients receiving antiretroviral therapy (ART), none had NTM disease compared with 19 (2%) of 1,009 not receiving ART. CONCLUSIONS: Although people with HIV frequently have sputum cultures positive for NTM, few meet a strict case definition for NTM disease. Consistent with previous studies, ART was associated with lower odds of having NTM disease. Further studies of NTM in HIV-infected individuals in tuberculosis-endemic countries are needed to develop and validate case definitions.

Bidirectional effects of parental and adolescent symptom change in trauma-focused cognitive behavioral therapy.

OBJECTIVE: The current study examines dynamic, bidirectional associations between parent and adolescent symptom improvement in response to children's therapy for posttraumatic stress disorder (PTSD). METHOD: Data were collected from a racially and ethnically heterogeneous sample of 1,807 adolescents (age 13-18 years old; 69% female) and a parent participating in Trauma-Focused Cognitive Behavioral Therapy (TF-CBT) at a community outpatient behavioral health clinic. Parents self-reported their depressive symptoms and youth self-reported their PTSD and depressive symptoms at the onset of treatment and every three months for up to nine months. Using a bivariate dual change score model (BDCSM) we examine: (a) individual dyad members' change in symptoms and (b) the bidirectional associations between changes in the parent's and youth's symptoms across treatment. RESULTS: Parents' and adolescents' symptoms at the start of treatment were correlated and both parents' and adolescents' symptoms decreased over the course of treatment. Parents' elevated depressive symptoms at each time point contributed to smaller decreases in their children's PTSD and depressive symptoms at the subsequent time point. Adolescents' elevated symptoms at each time point contributed to greater decreases in their parents' symptoms at the subsequent time point. CONCLUSIONS: These findings highlight the impact that parents and children have on each other's response to children's trauma-focused psychotherapy. Notably, parents' depressive symptoms appeared to slow their children's progress in treatment, suggesting that attending to parents' symptoms and providing them with supportive services may be an important adjunct to children's interventions. (PsycInfo Database Record (c) 2023 APA, all rights reserved).

The Effects of Adverse Childhood Experiences and Warfare Exposure on Military Sexual Trauma Among Veterans.

Military sexual trauma (MST) is a pervasive problem; this study examined the relationship of the precursory traumas of adverse childhood experiences (ACEs) and warfare exposure with MST. Post-9/11 veterans were surveyed at 3 months and at 24 to 30 months post-military separation. Female veterans who experienced at least 1 ACE but no warfare exposure were significantly more likely to receive unwanted sexual attention. Veterans (males and females) experiencing three or more ACEs but no warfare exposure were significantly more likely to receive unwanted sexual attention and contact. Experiencing only warfare exposure was not related to unwanted sexual attention or contact for females; however, a significant interaction was found between combined warfare exposure, ACEs, and MST for males and females. Veterans who reported warfare exposure and one to two or three or more ACEs were more likely to report unwanted sexual attention and/or contact. Exploration of individual ACEs revealed a significant relationship between childhood sexual abuse and unwanted sexual contact. For females, witnessing domestic violence predicted unwanted sexual contact. There was also a significant interaction between childhood sexual abuse and warfare exposure. Females who experienced both childhood sexual abuse and warfare exposure were significantly more likely to receive unwanted sexual attention and unwanted sexual contact. Albeit a small sample, males who experienced both were also significantly more likely to receive unwanted sexual attention. The findings reveal that precursory traumatic experiences in childhood and the interaction of ACEs and warfare exposure during military service can increase the likelihood of unwanted sexual attention and contact. This research further substantiates the need for screening efforts. It also demonstrates the importance of practitioners engaging in trauma-informed care principles and practices to address the residual effects of previous experiences during sexual trauma or mental health treatment efforts.

Machine learning to predict bacteriologic confirmation of Mycobacterium tuberculosis in infants and very young children.

Diagnosis of tuberculosis (TB) among young children (<5 years) is challenging due to the paucibacillary nature of clinical disease and clinical similarities to other childhood diseases. We used machine learning to develop accurate prediction models of microbial confirmation with simply defined and easily obtainable clinical, demographic, and radiologic factors. We evaluated eleven supervised machine learning models (using stepwise regression, regularized regression, decision tree, and support vector machine approaches) to predict microbial confirmation in young children (<5 years) using samples from invasive (reference-standard) or noninvasive procedure. Models were trained and tested using data from a large prospective cohort of young children with symptoms suggestive of TB in Kenya. Model performance was evaluated using areas under the receiver operating curve (AUROC) and precision-recall curve (AUPRC), accuracy metrics. (i.e., sensitivity, specificity), F-beta scores, Cohen's Kappa, and Matthew's Correlation Coefficient. Among 262 included children, 29 (11%) were microbially confirmed using any sampling technique. Models were accurate at predicting microbial confirmation in samples obtained from invasive procedures (AUROC range: 0.84-0.90) and from noninvasive procedures (AUROC range: 0.83-0.89). History of household contact with a confirmed case of TB, immunological evidence of TB infection, and a chest x-ray consistent with TB disease were consistently influential across models. Our results suggest machine learning can accurately predict microbial confirmation of M. tuberculosis in young children using simply defined features and increase the bacteriologic yield in diagnostic cohorts. These findings may facilitate clinical decision making and guide clinical research into novel biomarkers of TB disease in young children.

Prevalence and functional profile of SARS-CoV-2 T cells in asymptomatic Kenyan adults.

BackgroundSARS-CoV-2 infection in Africa has been characterized by a less severe disease profile than what has been observed elsewhere, but the profile of SARS-CoV-2-specific adaptive immunity in these mainly asymptomatic patients has not, to our knowledge, been analyzed.MethodsWe collected blood samples from residents of rural Kenya (n = 80), who had not experienced any respiratory symptoms or had contact with individuals with COVID-19 and had not received COVID-19 vaccines. We analyzed spike-specific antibodies and T cells specific for SARS-CoV-2 structural (membrane, nucleocapsid, and spike) and accessory (ORF3a, ORF7, ORF8) proteins. Pre-pandemic blood samples collected in Nairobi (n = 13) and blood samples from mild-to-moderately symptomatic COVID-19 convalescent patients (n = 36) living in the urban environment of Singapore were also studied.ResultsAmong asymptomatic Africans, we detected anti-spike antibodies in 41.0% of the samples and T cell responses against 2 or more SARS-CoV-2 proteins in 82.5% of samples examined. Such a pattern was absent in the pre-pandemic samples. Furthermore, distinct from cellular immunity in European and Asian COVID-19 convalescents, we observed strong T cell immunogenicity against viral accessory proteins (ORF3a, ORF8) but not structural proteins, as well as a higher IL-10/IFN-γ cytokine ratio profile.ConclusionsThe high incidence of T cell responses against different SARS-CoV-2 proteins in seronegative participants suggests that serosurveys underestimate SARS-CoV-2 prevalence in settings where asymptomatic infections prevail. The functional and antigen-specific profile of SARS-CoV-2-specific T cells in African individuals suggests that environmental factors can play a role in the development of protective antiviral immunity.FundingUS Centers for Disease Control and Prevention, Division of Global Health Protection; the Singapore Ministry of Health's National Medical Research Council (COVID19RF3-0060, COVID19RF-001, COVID19RF-008, MOH-StaR17Nov-0001).