Impact of COVID-19 on Adolescent HIV Prevention and Treatment Research in the AHISA Network.

Members of the Adolescent HIV Prevention and Treatment Implementation Science Alliance (AHISA) network conduct research aiming to close gaps between what is known to be impactful across the HIV prevention and treatment cascade, and services delivered to optimize outcomes for adolescents/young adults (AYA) in high HIV-prevalence settings. The COVID-19 pandemic introduced new challenges which threaten to exacerbate care and access disparities. We report results of a survey among AHISA teams with active AYA HIV research programs in African countries to determine how the pandemic has impacted their efforts. Results highlighted the detrimental impact of the pandemic on research efforts and the expanded need for implementation research to help provide evidence-based, context-specific pandemic recovery support. Key lessons learned included the viability of remote service delivery strategies and other innovations, the need for adaptive systems that respond to evolving contextual needs, and the need for organized documentation plans, within empathic and flexible environments.

Impact of COVID-19 on Adolescent HIV Prevention and Treatment Services in the AHISA Network.

We investigated perceived impacts of COVID-19 on the delivery of adolescent HIV treatment and prevention services in sub-Saharan Africa (SSA) by administering a survey to members of the Adolescent HIV Prevention and Treatment Implementation Science Alliance (AHISA) from February to April 2021. We organized COVID-19 impacts, as perceived by AHISA teams, under three themes: service interruptions, service adjustments, and perceived individual-level health impacts. AHISA teams commonly reported interruptions to prevention programs, diagnostic testing, and access to antiretroviral therapy (ART). Common service adjustments included decentralization of ART refills, expanded multi-month ART distribution, and digital technology use. Perceived individual-level impacts included social isolation, loss to follow-up, food insecurity, poverty, and increases in adolescent pregnancies and sexually transmitted infections. The need for collaboration among stakeholders were commonly cited as lessons learned by AHISA teams. Survey findings highlight the need for implementation science research to evaluate the effects of pandemic-related HIV service adaptations in SSA.

Genetic Variation and Sensory Perception of a Pediatric Formulation of Ibuprofen: Can a Medicine Taste Too Good for Some?

There is wide variation in how individuals perceive the chemosensory attributes of liquid formulations of ibuprofen, encompassing both adults and children. To understand personal variation in the taste and chemesthesis properties of this medicine, and how to measure it, our first scientific strategy centered on utilizing trained adult panelists, due to the complex and time-consuming psychophysical tasks needed at this initial stage. We conducted a double-blind cohort study in which panelists underwent whole-genome-wide genotyping and psychophysically evaluated an over-the-counter pediatric medicine containing ibuprofen. Associations between sensory phenotypes and genetic variation near/within irritant and taste receptor genes were determined. Panelists who experienced the urge to cough or throat sensations found the medicine less palatable and sweet, and more irritating. Perceptions varied with genetic ancestry; panelists of African genetic ancestry had fewer chemesthetic sensations, rating the medicine sweeter, less irritating, and more palatable than did those of European genetic ancestry. We discovered a novel association between TRPA1 rs11988795 and tingling sensations, independent of ancestry. We also determined for the first time that just tasting the medicine allowed predictions of perceptions after swallowing, simplifying future psychophysical studies on diverse populations of different age groups needed to understand genetic, cultural-dietary, and epigenetic factors that influence individual perceptions of palatability and, in turn, adherence and the risk of accidental ingestion.

Youth perspectives of working with near peer youth lay counsellors: The Safe Haven Pilot.

Youth living with HIV (YLWH) have higher rates of common mental disorders (CMDs) when compared with HIV-negative youth. We adapted the Friendship Bench to create a problem solving-based counselling intervention in Botswana delivered by near peer youth lay counsellors for YLWH called Safe Haven. In August 2020, and from June to August 2021, we conducted 22 semistructured interviews with youth aged 13-25 years with mild-to-moderate symptoms of CMDs. Two independent coders carried out an inductive thematic analysis of the transcribed interviews with discrepancies discussed to consensus. Safe Haven was seen as largely acceptable among the youth. Youth felt Safe Haven was a place where they had freedom of expression and could receive practical advice from well-trained and approachable counsellors. Trained youth lay peer counsellors show promise to meet the mental health needs of mild and moderately symptomatic youth, where mental health professionals are in short supply.

Symptoms of depression, anxiety, and thoughts of suicide/self-injury in adolescents and young adults living with HIV in Botswana.

Globally, mental health problems have been reported to be more common in youth living with HIV (YLWH) than in the general population, but routine mental health screening is rarely done in high-volume HIV clinics. In 2019, YLWH in a large HIV clinic in Botswana were screened using the Generalized Anxiety Scale-7 (GAD-7) and Patient Health Questionnaire-9 (PHQ-9) in a pilot standard-of-care screening programme. Two-way ANOVA was used to describe the effects of age group (12-<16, 16-<20 and 20-25 years old) and sex on GAD-7 and PHQ-9 scores. Chi-square statistics were used to compare characteristics of YLWH with and without potential suicidality/self-harm symptoms based on question 9 in the PHQ-9. Among 1 469 YLWH, 33.1%, 44.3% and 15.0% had anxiety, depression and potential suicidality/self-harm symptoms respectively. YLWH of 20-25 years old and 16-<20 years old had higher GAD-7 scores compared to 12-<16-year-olds (p = 0.014 and p = <0.001 respectively). Female YLWH of 20-25 years old had higher PHQ-9 scores compared to 12-<16-year-olds (p = 0.002). There were no other sex-age dynamics that were statistically significant. Female YLWH endorsed more thoughts of suicidality/self-harm than males (17% versus 13%, p = 0.03 respectively). Given the proportion of YLWH with mental health symptoms, Botswana should enhance investments in mental health services for YLWH, especially for young female adults who bear a disproportionate burden.

Predictive Validity of a Computerized Battery for Identifying Neurocognitive Impairments Among Children Living with HIV in Botswana.

Children living with HIV (HIV+) experience increased risk of neurocognitive deficits, but standardized cognitive testing is limited in low-resource, high-prevalence settings. The Penn Computerized Neurocognitive Battery (PennCNB) was adapted for use in Botswana. This study evaluated the criterion validity of a locally adapted version of the PennCNB among a cohort of HIV+ individuals aged 10-17 years in Botswana. Participants completed the PennCNB and a comprehensive professional consensus assessment consisting of pencil-and-paper psychological assessments, clinical interview, and review of academic performance. Seventy-two participants were classified as cases (i.e., with cognitive impairment; N = 48) or controls (i.e., without cognitive impairment; N = 24). Sensitivity, specificity, positive predictive value, negative predictive value, and the area under receiver operating characteristic curves were calculated. Discrimination was acceptable, and prediction improved as the threshold for PennCNB impairment was less conservative. This research contributes to the validation of the PennCNB for use among children affected by HIV in Botswana.

Medical stakeholder perspectives on implementing a computerized battery to identify neurocognitive impairments among youth in Botswana.

HIV infection and in utero exposure, common in Sub-Saharan Africa, are associated with pediatric neurocognitive impairment. Cognitive screening can identify impairments, but it is rarely used in this setting. The Penn Computerized Neurocognitive Battery (PennCNB), an evidence-based cognitive screening tool, was adapted for use in Botswana. To facilitate future implementation, 20 semi-structured interviews were conducted to elicit key stakeholders' perspectives on factors likely to be related to successful uptake of the PennCNB in clinical settings. An integrated analytic approach combining constructs from the Consolidated Framework for Implementation Research and modified grounded theory was used. Results underscore the need for cognitive screening in Botswana and the acceptability of the PennCNB. Implementation barriers include limited time and resources, whereas facilitators include standard procedures for introducing new tools into medical settings and for training implementers. Recommended implementation strategies include integrating screening into the existing workflow, implementing the tool in the medical and educational sectors, and targeting selection of children for assessment. This research addresses the research-to-practice gap by engaging in pre-implementation inquiry and designing for implementation. Results will inform the development of strategies to maximize the likelihood of successful implementation of the PennCNB to identify neurocognitive impairment in children in this high-need setting.

Reasons for discordance between antiretroviral adherence measures in adolescents.

Adolescents with suboptimal medication taking may deceive caregivers about non-adherence. We conducted a 5-year longitudinal study of adolescents monitored simultaneously with both easily manipulated (e.g., self-report) and hard to manipulate (e.g., microelectronic data) strategies. Adolescents with repeatedly high adherence on the former and low adherence on the latter were invited along with their parental figures ("parents") to participate. We conducted focus groups and semi-structured interviews, separately for adolescents and parents, to elucidate drivers of discordant measures. Forty-seven adolescents and 26 parents participated in focus groups and 4 adolescents were interviewed. Adolescents described hiding pills, discarding pills, and lying. Their motivations included fear of disappointing those who care about them, desire to avoid admonishment by parents and clinic staff, and desire to avoid remedial adherence counseling. Both adolescents and parents considered negative feedback for prior poor adherence to be key motivation to hide current poor adherence from clinic staff. Providing positive feedback for truth-telling, rather than for "evidence" of excellent adherence, might help adolescent patients and their parents to develop stronger treatment alliances with each other and with clinic staff. Such alliances would allow adherence interventions to be better targeted and more fruitful in increasing adherence.

Building a Community Based Mental Health Program for Adolescents in Botswana: Stakeholder Feedback.

BACKGROUND: When planning interventions for adolescents, adult interventions should not be used 'as is' in youth settings. Stakeholder engagement can help understand the overall adolescent mental health ecosystem and adapt existing evidence-based interventions for the youth. OBJECTIVE: To understand the overall mental health needs of adolescents in Botswana and the necessary adaptations required for an adolescent lay counselor based intervention in the country. METHODS: We used the theory of change model and the nominal group technique in five stakeholder meetings. Meetings were held to discuss the mental health needs of youth in Botswana and identify priorities for a lay counsellor based intervention modelled after the Friendship Bench intervention, an existing mental health intervention for adults. RESULTS: The root causes of mental health problems among Botswana's youth identified by stakeholders included limited mental health knowledge among the youth and the community, family problems, poor communication, low self-esteem, the rapid growth of technology, and biological/genetic predisposition. Structurally barriers included: mental illness-related stigma, lack of psychosocial support, incomplete follow up for health services, cultural beliefs about mental illness, and fragmented mental health services. The stakeholders envisage a program that could empower adolescents and youth counselors to address mental health concerns for a healthier community. The group identified and prioritized several key elements of an effective lay counselor intervention. CONCLUSIONS: A diverse group of community stakeholders can illustrate critical mental health needs and elements that countries could use to adapt and contextualize a lay counsellor based mental health intervention for new populations such as the youth.

Psychological Reactance is a Novel Risk Factor for Adolescent Antiretroviral Treatment Failure.

Psychological reactance is an aversive response to perceived threats against personal agency. For adolescents receiving HIV treatment in Botswana, we utilized a two-question, medication-specific reactance tool to assess whether: (1) verbal reminders to take medicines made adolescents want to avoid taking them, and, (2) whether adolescents felt anger when reminded to take medicines. Reactant adolescents had 2.05-fold (95% CI 1.23, 3.41) greater odds of treatment failure than non-reactant adolescents (p = 0.03). Adjusted risk of treatment failure was 14% (95% CI 3%, 28%) greater for each point elevation in reactance score (p = 0.016). Autonomy over medication-taking did not modify the association between reactance and treatment failure. Psychological reactance may be a useful interventional target for improving adolescent adherence.

Interventions for Children with Neurocognitive Impairments in Resource-Limited Settings: A Systematic Review.

Many children and adolescents around the world suffer from neurocognitive deficits due to chronic disorders, such as Human Immunodeficiency Virus (HIV) and malaria. Resource-limited settings exacerbate the risk of negative cognitive outcomes due to high prevalence of associated disorders, poverty, and limited access to interventions. Current literature does not provide consensus regarding the efficacy of interventions to support children with cognitive impairments in low-resource settings. This research aimed to identify and evaluate interventions for youth with neurocognitive deficits in resource-limited settings. A systematic review of peer-reviewed literature was conducted within five databases (PubMed, Web of Science, CINAHL, PsycInfo, and WHO Index Medicus). Cognitive impairment was broadly defined to be inclusive of aspects of intellectual and cognitive functioning (e.g., working memory, attention, executive function). The income status of the country or countries in which each study was located was determined according to World Bank Income Status. Studies conducted in countries classified as low- or middle-income were included. Since low-resource areas exist within high-income countries, the resource availability within study settings in high-income countries was systematically evaluated for inclusion. The search yielded 19 articles that met all inclusion criteria. Interventions included strategies involving caregiver training, computerized and non-computerized cognitive training, physical activity, and nutritional supplementation. Interventions were administered in medical facilities, educational facilities, or the home. The majority of the interventions targeted the domains of memory and attention. Overall, the efficacy of interventions was inconsistent. Further, results indicated that the relationship between cognitive improvement and intervention types was not consistent across cognitive domains. However, when evaluating studies on an individual basis, some strategies demonstrated clinically- and statistically-significant improvement in cognitive function among specific groups of children. The low article yield highlights that few researchers have evaluated pediatric cognitive support interventions in low-resource contexts. This review suggests support strategies that should be considered for future studies as neurocognitive screening capacity improves in resource-limited settings.

Pharmacy Refill Data are Poor Predictors of Virologic Treatment Outcomes in Adolescents with HIV in Botswana.

In adults living with HIV, pharmacy refill data are good predictors of virologic failure (VF). The utility of pharmacy refill data for predicting VF in adolescents has not been reported. We evaluated data from 291 adolescents on antiretroviral therapy. The main outcome measure was VF, defined as two consecutive HIV viral load measurements ≥ 400 copies/mL during 24-months of follow-up. Pharmacy refill non-adherence was defined as two consecutive refill adherence measurements < 95% during the same period. Fifty-three (18%) adolescents experienced VF. One hundred twenty-eight (44%) adolescents had refill non-adherence. Refill non-adherence had poor discriminative ability for indicating VF (receiver operating characteristic AUC = 0.60). Sensitivity and specificity for predicting VF was poor (60% (95% CI 46-74%) and 60% (95% CI 53-66%), respectively). The lack of a viable surrogate for VF in adolescents highlights the urgent need for more access to virologic testing and novel methods of monitoring adolescent treatment adherence.

A standardized low-cost peer role-playing training intervention improves medical student competency in communicating bad news to patients in Botswana.

OBJECTIVE: The purpose of this study was to demonstrate effectiveness of an educational training workshop using role-playing to teach medical students in Botswana to deliver bad news. METHOD: A 3-hour small group workshop for University of Botswana medical students rotating at the Princess Marina Hospital in Gaborone was developed. The curriculum included an overview of communication basics and introduction of the validated (SPIKES) protocol for breaking bad news. Education strategies included didactic lecture, handouts, role-playing cases, and open forum discussion. Pre- and posttraining surveys assessed prior exposure and approach to breaking bad news using multiple-choice questions and perception of skill about breaking bad news using a 5-point Likert scale. An objective structured clinical examination (OSCE) with a standardized breaking bad news skills assessment was conducted; scores compared two medical student classes before and after the workshop was implemented.ResultForty-two medical students attended the workshop and 83% (35/42) completed the survey. Medical students reported exposure to delivering bad news on average 6.9 (SD = 13.7) times monthly, with 71% (25/35) having delivered bad news themselves without supervision. Self-perceived skill and confidence increased from 23% (8/35) to 86% (30/35) of those who reported feeling "good" or "very good" with their ability to break bad news after the workshop. Feedback after the workshop demonstrated that 100% found the SPIKES approach helpful and planned to use it in clinical practice, found role-playing helpful, and requested more sessions. Competency for delivering bad news increased from a mean score of 14/25 (56%, SD = 3.3) at baseline to 18/25 (72%, SD = 3.6) after the workshop (p = 0.0002).Significance of resultsThis workshop was effective in increasing medical student skill and confidence in delivering bad news. Standardized role-playing communication workshops integrated into medical school curricula could be a low-cost, effective, and easily implementable strategy to improve communication skills of doctors.

Distinctive barriers to antiretroviral therapy adherence among non-adherent adolescents living with HIV in Botswana.

Levels of adherence to HIV treatment are lower among adolescents compared with older and younger individuals receiving similar therapies. We purposely sampled the most and least adherent adolescents from a 300-adolescent longitudinal HIV treatment adherence study in Gaborone, Botswana. Multiple objective and subjective measures of adherence were available and study participants were selected based on sustained patterns of either excellent or poor adherence over a one-year period. Focus group discussions (FGD) and in-depth interviews (IDI) were conducted with the adolescents and a subset of their caregivers with the goal of revealing barriers and facilitators of adherence. Focus groups were segregated by adherence classification of the participants. Following coding of transcripts, matrices were developed based on participants' adherence classifications in order to clarify differences in themes generated by individuals with different adherence characteristics. 47 adolescents and 25 adults were included. The non-adherent adolescents were older than the adherent adolescents (median age 18 years (IQR 16-19) vs. 14 years (IQR 12-15 years)), with median time on treatment near 10 years in both groups. Interference with daily activities, concerns about stigma and discrimination, side effects, denial of HIV status, and food insecurity arose as challenges to adherence among both those who were consistently adherent and those who were poorly-adherent to their medications. Low outcome expectancy, treatment fatigue, mental health and substance use problems, and mismatches between desired and received social support were discussed only among poorly adherent adolescents and their caregivers. Challenges raised only among adolescents and caregivers in the non-adherent groups are hypothesis-generating, identifying areas that may have a greater contribution to poor outcomes than challenges faced by both adherent and non-adherent adolescents. The contribution of these factors to poor outcomes should be explored in future studies.

Prevalence and predictors of alcohol and drug use among secondary school students in Botswana: a cross-sectional study.

BACKGROUND: Alcohol and illicit drug use has been recognized as a growing problem among adolescents in Botswana. Little is known about factors affecting alcohol and drug use among Botswana's secondary school students. To aid the design and implementation of effective public health interventions, we sought to determine the prevalence of alcohol and drug use in secondary school students in urban and peri-urban areas of Botswana, and to evaluate risk and protective factors for substance use. METHODS: We performed a 72-item cross-sectional survey of students in 17 public secondary schools in Gaborone, Lobatse, Molepolole and Mochudi, Botswana. The World Health Organization's (WHO) Alcohol Use Disorder Identification Test (AUDIT) was used to define hazardous drinking behavior. Using Jessor's Problem Behavior Theory (PBT) as our conceptual framework, we culturally-adapted items from previously validated tools to measure risk and protective factors for alcohol and drug use. Between-group differences of risk and protective factors were compared using univariate binomial and multinomial-ordinal logit analysis. Relative risks of alcohol and drug use by demographic, high risks and low protections were calculated. Multivariate ordinal-multinomial cumulative logit analysis, multivariate nominal-multinomial logit analysis, and binominal logit analysis were used to build models illustrating the relationship between risk and protective factors and student alcohol and illicit drug use. Clustered data was adjusted for in all analyses using Generalized Estimating Equations (GEE) methods. RESULTS: Of the 1936 students surveyed, 816 (42.1%) reported alcohol use, and 434 (22.4%) met criteria for hazardous alcohol use. Illicit drug use was reported by 324 students (16.7%), with motokwane (marijuana) being the most commonly used drug. Risk factors more strongly associated with alcohol and drug use were reported alcohol availability, individual and social vulnerability factors, and poor peer modeling. Individual and social controls protections appear to mitigate risk of student alcohol and drug use. CONCLUSIONS: Alcohol and illicit drug use is prevalent among secondary school students in Botswana. Our data suggest that interventions that reduce the availability of alcohol and drugs and that build greater support networks for adolescents may be most helpful in decreasing alcohol and drug use among secondary school students in Botswana.

Patterns of HIV Treatment Adherence do not Differ Between Male and Female Adolescents in Botswana.

We hypothesized that longer and more frequent dosing gaps among boys in Botswana taking antiretroviral therapy (ART) for human immunodeficiency virus (HIV) infection compared to girls could account for previously seen gender-specific differences in outcomes. We monitored 154 male and 134 female adolescents for 2 years with medication event monitoring systems (MEMS). Median adherence was 95.6 % for males and 95.7 % for females (p = 0.40). There were no significant gender differences in the number of ≥7 day (p = 0.55) and ≥14 day (p = 0.48) dosing gaps. The median maximal gap was 7.7 days for males and 8.0 days for females (p = 0.47). These findings are not consistent with clinically meaningful gender differences in adherence.

Prediction of HIV Virologic Failure Among Adolescents Using the Pediatric Symptom Checklist.

Psychosocial dysfunction is a risk factor for treatment non-adherence among children and adolescents. A previous study showed that high scores on the Pediatric Symptom Checklist (PSC) were associated with a history of HIV virologic failure. We assessed whether high scores on the PSC could predict virologic failure in HIV-infected youth. Caregivers of 234 adolescents between the ages of 10 and 16 years were asked to complete a PSC at baseline. Elevated PSC scores were associated with virologic failure in the subsequent 6 months. PSC scores may help guide resource utilization when viral load monitoring is limited.

Factors associated with self-reported adherence among adolescents on antiretroviral therapy in Zimbabwe.

Nonadherence to medication is the key obstacle to human immunodeficiency virus (HIV) treatment success. The group at highest risk of nonadherence is adolescents, but relatively little is known about risk factors for and protective factors against poor adherence in this age group. We undertook a cross-sectional study of 262 HIV-infected adolescents aged 10-19 years on antiretroviral therapy at two clinics in Harare, Zimbabwe, to investigate personal and system-level factors associated with optimal self-reported adherence. Suboptimal adherence was common with only 101 (39%) reporting "excellent" adherence. Having the guardian present at each clinical encounter, comfort with asking questions to the health provider and participating in group sessions led by a professional facilitator were all significantly associated with excellent adherence (p < 0.05). Strengthening the parent-child dyad and professional-led groups as strategies to improve adherence should be evaluated.

The adherence-outcome relationship is not altered by diary-driven adjustments of microelectronic monitor data.

PURPOSE: The purpose of this study was to determine whether diary-driven adjustment of Medication Event Monitoring System (MEMS) data based on Supporting Information strengthens the relationship between measured antiretroviral medication adherence and plasma HIV viral load (VL). METHODS: HIV+ adolescents on antiretroviral treatment were monitored with MEMS for 30 days preceding a VL measurement. The primary outcome was VL ≥ 400 copies/mL. Handwritten diaries were used to comprehensively record deviations from recommended use (bottle opened but dose not taken or bottle not opened and dose taken). Data were adjusted ("cleaned") based on diary events. Data were "capped" at the prescribed number of doses/day. Receiver operator characteristic analysis compared the relationships between (i) raw MEMS data, (ii) diary-cleaned, (iii) capped, or (iv) cleaned and capped MEMS data and VL. RESULTS: Over 30 days preceding VL measurements, 273 adolescents had 465 diary events. Capping resulted in fewer patients classified as 95% adherent (65.2%) compared with raw data (71.4%), p < 0.001. Adherence was highly associated with VL (OR 1.05, p < 0.001). The area under the receiver operating characteristic curve for continuous adherence compared with VL was 0.89 (95%CI: 0.82-0.95). Neither diary-cleaning, capping, nor cleaning and capping MEMS data significantly altered the association between adherence and VL (p = 0.14, 0.40, and 0.19, respectively). CONCLUSION: Medication Event Monitoring System data-cleaning based on diary entries did not affect the adherence-VL relationship.

Etiologies of Mild and Moderate Diarrheal Illness among Children in Consuelo, Dominican Republic.

Since the rotavirus vaccine was included in the Dominican Republic's national immunization schedule in 2012, the microbiologic etiologies of acute gastroenteritis have not been described. This study aimed to determine the contribution of rotavirus as an etiology of acute gastroenteritis over a 12-month period in children under 5 years of age in both an inpatient and an outpatient setting in Consuelo, Dominican Republic. All children who were seen at Niños Primeros en Salud clinic or admitted to Hospital Municipal Dr. Angel Ponce Pinedo for acute gastroenteritis during January 2021-April 2022 were enrolled in the study. Stools were evaluated for rotavirus, enteric parasites, and pathogenic bacteria. Pathogen detection was compared between outpatients and inpatients and on the basis of child's vaccination status. From 181 children enrolled, 170 stool samples were collected, 28 (16.5%) from inpatients and 142 (83.5%) from outpatients. Rotavirus was the most commonly detected pathogen and was proportionately more common among hospitalized children, with nine (32.1%) cases among hospitalized children and 16 (11.3%) among outpatient children. (Pearson χ2 = 8.1, P = 0.004). Among patients with a positive rotavirus result, vaccination rate was lower among moderate (hospitalized) (three of six; 50%) compared with mild (outpatient) diarrhea patients (12 of 15; 80%). Giardia lamblia (10%) was the next most prevalent pathogen detected in both inpatients and outpatients using standard laboratory measures. Despite the availability of rotavirus vaccination, rotavirus remains a common cause of gastrointestinal illness among children under 5 years of age in our cohort. Incomplete vaccination status was associated with hospitalization for gastrointestinal illness.