Texas professionals are employing a one health approach to protect the United States against biosecurity threats.

Texas is a geographically large state with large human and livestock populations, many farms, a long coastal region, and extreme fluctuations in weather. During the last 15 years, the state of Texas has frequently suffered disasters or catastrophes causing extensive morbidity and economic loss. These disasters often have complicated consequences requiring multi-faceted responses. Recently, an interdisciplinary network of professionals from multiple academic institutions has emerged to collaborate in protecting Texas and the USA using a One Health approach. These experts are training the next generation of scientists in biopreparedness; increasing understanding of pathogens that cause repetitive harm; developing new therapeutics and vaccines against them; and developing novel surveillance approaches so that emerging pathogens will be detected early and thwarted before they can cause disastrous human and economic losses. These academic One Health partnerships strengthen our ability to protect human and animal health against future catastrophes that may impact the diverse ecoregions of Texas and the world.

Suicide clusters among young Kenyan men.

Suicide is a leading cause of global mortality. Suicide clusters have recently been identified among peer networks in high-income countries. This study investigates dynamics of suicide clustering within social networks of young Kenya men (n = 532; 18-34 years). We found a strong, statistically significant association between reported number of friends who previously attempted suicide and present suicide ideation (odds ratio = 1.9; 95% confidence interval (1.42, 2.54); p < 0.001). This association was mediated by lower collective self-esteem (23% of total effect). Meaning in life further mediated the association between collective self-esteem and suicide ideation. Survivors of peer suicide should be evaluated for suicide risk.

Neglect, Sexual Abuse, and Witnessing Intimate Partner Violence During Childhood Predicts Later Life Violent Attitudes Against Children Among Kenyan Women: Evidence of Intergenerational Risk Transmission From Cross-Sectional Data.

Violence against children, including corporal punishment, remains a global concern. Understanding sources of support for corporal punishment within cultures, and the potential for intergenerational transmission of child maltreatment, is essential for policy-development and community engagement to protect children. In this study, we use data from a cross-section of women in Meru County, Kenya (n = 1,974) to profile attitudes toward violence against children using the Velicer Attitudes Towards Violence-Child subscale. We find reported histories of sexual abuse, emotional and physical neglect, and witnessing interpersonal violence during childhood predict more violent attitudes toward children in adulthood. The pathway between these forms of child maltreatment and violent attitudes is significantly mediated by family function, perceived stress, and attitudes toward violence against women. Interventions to prevent sexual abuse, intimate partner violence, and promote attachments between parents and children may benefit future generations in this population. Furthermore, secondary prevention of the effects of these childhood adversities may require development of social support, improving family function and challenging violent attitudes against women.

Elimination of intravascular thrombi prevents early mortality and reduces gliosis in hyper-inflammatory experimental cerebral malaria.

BACKGROUND: Cerebral malaria (CM) is the most lethal outcome of Plasmodium infection. There are clear correlations between expression of inflammatory cytokines, severe coagulopathies, and mortality in human CM. However, the mechanisms intertwining the coagulation and inflammation pathways, and their roles in CM, are only beginning to be understood. In mice with T cells deficient in the regulatory cytokine IL-10 (IL-10 KO), infection with Plasmodium chabaudi leads to a hyper-inflammatory response and lethal outcome that can be prevented by anti-TNF treatment. However, inflammatory T cells are adherent within the vasculature and not present in the brain parenchyma, suggesting a novel form of cerebral inflammation. We have previously documented behavioral dysfunction and microglial activation in infected IL-10 KO animals suggestive of neurological involvement driven by inflammation. In order to understand the relationship of intravascular inflammation to parenchymal dysfunction, we studied the congestion of vessels with leukocytes and fibrin(ogen) and the relationship of glial cell activation to congested vessels in the brains of P. chabaudi-infected IL-10 KO mice. METHODS: Using immunofluorescence microscopy, we describe severe thrombotic congestion in these animals. We stained for immune cell surface markers (CD45, CD11b, CD4), fibrin(ogen), microglia (Iba-1), and astrocytes (GFAP) in the brain at the peak of behavioral symptoms. Finally, we investigated the roles of inflammatory cytokine tumor necrosis factor (TNF) and coagulation on the pathology observed using neutralizing antibodies and low-molecular weight heparin to inhibit both inflammation and coagulation, respectively. RESULTS: Many blood vessels in the brain were congested with thrombi containing adherent leukocytes, including CD4 T cells and monocytes. Despite containment of the pathogen and leukocytes within the vasculature, activated microglia and astrocytes were prevalent in the parenchyma, particularly clustered near vessels with thrombi. Neutralization of TNF, or the coagulation cascade, significantly reduced both thrombus formation and gliosis in P. chabaudi-infected IL-10 KO mice. CONCLUSIONS: These findings support the contribution of cytokines, coagulation, and leukocytes within the brain vasculature to neuropathology in malaria infection. Strikingly, localization of inflammatory leukocytes within intravascular clots suggests a mechanism for interaction between the two cascades by which cytokines drive local inflammation without considerable cellular infiltration into the brain parenchyma.

How do Kenyan orphan girls experience less meaningful lives and how much does it matter for 'health'?

BACKGROUND: Currently, 2.5 million orphaned children are living in Kenya and 56 million orphaned children are living across sub-Saharan Africa. No empirical research has investigated meaningfulness of life among this population, and few studies provide perspectives on the life-course consequences of losing a parent during childhood. METHODS: In this study, we assess life meaningfulness in cross section of Kenyan women (n = 1974) in a semi-rural area of the country (Meru County) collected during June 2015. We used two sets of mediation analyses to assess (1) whether meaningfulness of life was lower among women who reported a parental death during their childhood, and how this association was mediated by social support, family functioning, school completion and HIV+ status of household, and (2) the extent to which lower subjective overall health among women who experienced orphanhood during childhood was mediated by less meaningfulness of life. RESULTS: Women who experienced a parental death during childhood reported significantly less meaningful lives as adults. Lower social support and family functioning explained approximately 40% of the disparity. Women who experienced a parental death during childhood also had significantly worse subjective overall health, 18% of which was explained by lower meaningfulness of life. CONCLUSIONS: Further study on life meaningfulness and family capital in the context of the orphan crisis in sub-Saharan Africa is warranted, and required to promote equity across the lifespan. Policy efforts to support orphans and vulnerable children should target strengthening support networks and family functioning to optimize self-reported health outcomes.

Adverse Childhood Experiences Predict Alcohol Consumption Patterns Among Kenyan Mothers.

OBJECTIVE: We analyze whether adverse childhood experiences predict weekly alcohol consumption patterns of Kenyan mothers and their partners. METHOD: Randomly selected respondents (n = 1,976) were asked about adverse childhood experiences and alcohol consumption patterns for themselves and their partners. Fixed effect models were used to determine odds of reporting weekly alcohol consumption and the number of beverages typically consumed, controlling for wealth, age, education, and partner alcohol consumption. RESULTS: Cumulative adverse childhood experiences predicted higher odds of weekly alcohol consumption of the respondent and her partner. Childhood exposure to physical abuse, emotional neglect, and mental illness in the household significantly increased odds of weekly alcohol consumption by the respondent. More drinks consumed per typical session were higher among respondents with more cumulative adversities. Physical and emotional abuse significantly predicted number of drinks typically consumed by the respondent. CONCLUSIONS: To our knowledge, this is the first study to explore and find associations between adverse childhood experiences and alcohol consumption in Kenya. Consistent with high-income settings, exposure to childhood adversities predicted greater alcohol consumption among Kenyan women.

Childhood exposure to emotional abuse and later life stress among Kenyan women: a mediation analysis of cross-sectional data.

BACKGROUND AND OBJECTIVE: We explore whether perceived stress among Kenyan mothers is predicted by childhood exposure to emotional abuse - both witnessed among parents and experienced directly. Further, we explore whether this association is mediated by social support, family functioning and polygynous marriage. DESIGN: We used cross-sectional data from a systematic random sample (n = 1974) of mothers in semi-rural Kenya. METHODS: Data were collected using validated scales and trained interviewers. Analyses were conducted using bootstrapped structural equation models and fixed-effects linear regression models, controlling for age and household wealth. RESULTS: Reported experience of emotional abuse - both directly experienced and observed among household adults - was high in the present population (72.5% and 69%, respectively). Perceived stress among women was significantly higher if they were exposed to more emotional abuse during childhood (p < .001). Lower social support, worse family functioning and higher rates of polygynous marriage mediated pathways between emotional abuse exposure during childhood and adult perceived stress. CONCLUSION: Future research should investigate whether social integration, identity formation and self-esteem underlie observed dynamics in sub-Saharan Africa. Efforts to promote social integration and support should target children currently experiencing emotional abuse, and may include child-targeted high quality television programing and adult-targeted media and celebrity campaigns.

Testing and testing positive: childhood adversities and later life HIV status among Kenyan women and their partners.

Background: Adverse childhood experiences are a critical feature of lifelong health. No research assesses whether childhood adversities predict HIV-testing behaviors, and little research analyzes childhood adversities and later life HIV status in sub-Saharan Africa. Methods: We use regression models with cross-sectional data from a representative sample (n = 1974) to analyze whether adverse childhood experiences, separately or as cumulative exposures, predict reports of later life HIV testing and testing HIV+ among semi-rural Kenyan women and their partners. Results: No significant correlation was observed between thirteen cumulative childhood adversities and reporting prior HIV testing for respondent or partner. Separately, childhood sexual abuse and emotional neglect predicted lower odds of reporting having previously been tested for HIV. Witnessing household violence during one's childhood predicted significantly higher odds of reporting HIV+. Sexual abuse predicted higher odds of reporting a partner tested HIV+. Conclusions: Preventing sexual abuse and household violence may improve HIV testing and test outcomes among Kenyan women. More research is required to understand pathways between adverse childhood experiences and partner selection within Kenya and sub-Saharan Africa, and data presented here suggest understanding pathways may help improve HIV outcomes.

Why do Kenyan children live on the streets? Evidence from a cross-section of semi-rural maternal caregivers.

Globally, study of factors contributing to the street-migration of the tens of millions of street-involved children focus almost exclusively on children's perspectives. In this study, we assess household and maternal factors associated with street-migration of children through self-report of 1974 randomly selected women in semi-rural Kenya. Contributing new perspectives on this global phenomenon, data show a statistically significant association between increased maternal childhood adversities and street-migration of children (p<0.001). Higher household wealth (p<0.01) and maternal education (p<0.05) were associated with lower odds of street-migration of children. Social support, reporting HIV+, school enrollment of biologically-related children, overall health, reported alcohol use, and functional literacy significantly mediated these pathways. Protecting children from street-migration in the next generation requires reducing childhood adversities in the present generation.

Child-street migration among HIV-affected families in Kenya: a mediation analysis from cross-sectional data.

Within Kenya, an estimated quarter of a million children live on the streets, and 1.8 million children are orphaned. In this study, we analyze how HIV contributes to the phenomenon of child-street migration. We interviewed a random community sample of caregiving women (n = 1974) in Meru County, Kenya, using a structured questionnaire in summer 2015. Items included reported HIV prevalence of respondent and her partner, social support, overall health, school enrollment of biologically related children and whether the respondent has a child currently living on the streets. Controlling for alcohol use, education, wealth, age and household size, we found a positive-graded association between the number of partners living with HIV and the probability that a child lives on the street. There was little difference in the odds of a child living on the street between maternally affected and paternally affected households. Lower maternal social support, overall health and school enrollment of biologically related children mediated 14% of the association between HIV-affected households and reporting child-street migration. Street-migration of children is strongly associated with household HIV, but the small percentage of mediated effect presents a greater need to focus on interactions between household and community factors in the context of HIV. Programs and policies responding to these findings will involve targeting parents and children in HIV-affected households, and coordinate care between clinical providers, social service providers and schools.

Improved water and household water purification practices among orphans and vulnerable children in a multi-sectoral empowerment program in Eastern province, Kenya.

Water quality is an important determinant of diarrheal illnesses, especially affecting children in sub-Saharan Africa. Orphans and vulnerable children (OVC) in sub-Saharan Africa are at increased risk of poor quality drinking water, and therefore of diarrheal illness. The present study assesses primary drinking water source and typical household water purification among OVC households involved in a multi-sectoral empowerment program in semi-rural Kenya. Findings show water purification practices, but not water source, significantly increase with more time in the program. Other factors associated with safer water include household income, orphan type, food consumption and security, school completion, psychological resilience, engaging in sexual intercourse with more than one partner in the past 12 months, and previous year's financial status. Incorporating water quality improvements in a community-based empowerment program such as the one described may be one method of improving water quality and decreasing diarrheal illnesses among OVCs in sub-Saharan Africa.

Exploring Pathways Between HIV+ Status and Excellent Overall Health Among Kenyan Women: Family Functioning, Meaningfulness of Life, Seroconcordance, Social Support and Considering the Need for Integrated Care.

As people living with HIV/AIDS (PLWHA) live longer, and HIV incidence declines, health systems are transitioning from vertical-only care delivery to horizontal integration with social and other services. This is essential to responding to the chronic nature of the disease, and health systems must respond to full-breadth of socio-economic conditions facing PLWHA. We use excellent self-rated health as a referent, and assess the role of non-biomedical conditions in mediating HIV+ status and excellent overall health among a large community sample of Kenyan women. After controlling for age and wealth, we found significant mediation by social support, partner HIV status, meaningfulness of life, family functioning, food sufficiency, and monthly income. If the goal of health systems is to help all people attain the highest level of health, integrating vertical HIV services with socio-economic support and empowerment may be required. Further investigation of the relative contribution of social support, family functioning, food and financial sufficiency should be conducted longitudinally, ideally in collaboration with HIV clinical services.

Self-Efficacy Mediates the Association between Partner Trust and Condom Usage among Females but not Males in a Kenyan Cohort of Orphan and Vulnerable Youth.

Continuing gains against incidence of HIV and other unwanted consequences of unprotected sex requires deeper understanding of characteristics of condom usage among sexually active youth. The present study assesses whether partner trust predicts condom usage, and whether potential associations were mediated by general self-efficacy, among a cohort of sexually active adolescents in Meru County, Kenya. We also sought to discover associations between socio-economic status, psychological resilience and partner trust to increase understanding of trust towards one's intercourse partner. Mediation analyses, stratified by gender, reveal that condom usage is predicted by self-efficacy and partner trust among females but not males. Higher psychological resilience predicts lower partner trust among both genders. Partner trust was lower among female respondents who were not literate, but did not significantly vary by literacy among males. Reported previous monthly earnings were not significantly associated with partner trust among males or females. The present findings support further study on partner trust, and its association with protective sex behaviors. Further, interventions targeting condom usage among females may benefit from actions to increase awareness of partner sexual behavior and increasing self-efficacy.

Factors associated with general self-efficacy and resilience among youth heads of households in Kenya.

This study assesses resilience and general self-efficacy among Kenyan orphans and vulnerable children (n = 1060) active in a community-based program combining economic household strengthening with psychosocial support. Quantile regression analyses modeled associations between the 25th, 50th, and 75th percentiles of resilience and general self-efficacy and multiple covariates. Program participation positively predicted increased general self-efficacy at all levels. Program participation predicted increased resilience at the 25th percentile but decreased resilience at the 75th percentile. Other significant predictors included economic, educational, sexual behavior and other demographic factors. This study suggests support for an integrated approach to economic and psychosocial empowerment.

Sexual Behavior Among Young Carers in the Context of a Kenyan Empowerment Program Combining Cash-Transfer, Psychosocial Support, and Entrepreneurship.

This study examined associations between sexual initiation, unprotected sex, and having multiple sex partners in the past year with participation in a three-year empowerment program targeting orphan and vulnerable children (OVC). The Kenya-based program combines community-conditioned cash transfer, psychosocial empowerment, health education, and microenterprise development. Program participants (n = 1,060) were interviewed in a cross-sectional design. Analyses used gender-stratified hierarchical logit models to assess program participation and other potential predictors. Significant predictors of increased female sexual activity included less program exposure, higher age, younger age at most recent parental death, fewer years of schooling, higher food consumption, higher psychological resilience, and lower general self-efficacy. Significant predictors of increased male sexual activity included more program exposure, higher age, better food consumption, not having a living father, and literacy. Findings support a nuanced view of current cash transfer programs, where female sexual activity may be reduced through improved financial status but male sexual activity may increase. Targeting of OVC sexual risk behaviors would likely benefit from being tailored according to associations found in this study. Data suggest involving fathers in sexual education, targeting women who lost a parent at a younger age, and providing social support for female OVC may decrease risk of human immunodeficiency virus (HIV) transmission.

How can we improve healthcare access and general self-rated health among orphans and vulnerable children? Findings from a Kenyan cross-sectional study.

OBJECTIVES: This study analyzes healthcare access and general self-rated health (GSRH) among orphan and vulnerable child (OVC) households enrolled in an empowerment program in Eastern Province, Kenya. Analyses investigate whether reported monthly income mediates the association between program participation and medical security. Predictors of GSRH are also investigated. METHODS: Cross-sectional survey data on families (n = 707) participating in a multisectoral empowerment program were collected in June 2012. Regression methods were used to investigate study aims. RESULTS: Monthly income mediated 14.3 % of the total effect of program participation on healthcare accessibility. Program participation was not significantly associated with higher GSRH. CONCLUSIONS: Increased reported monthly income predicted improved healthcare access, but only explained a portion of improved healthcare access in the study population. Partnerships between community-based empowerment programs and clinical providers might successfully target multiple outcomes among OVC, including improved healthcare access, though further research on potential synergies is required. GSRH was associated with increased access to food, medical care, literacy, safe drinking water and household income. Further research on GSRH among OVC should target measurement validity, potential sources of disparity in GSRH between OVC and non-OVC, and targets for improving GSRH among OVC.

Mycobacterium tuberculosis-specific CD8+ T cell recall in convalescing TB subjects with HIV co-infection.

Memory T cell populations recover following phase I chemotherapy for tuberculosis (TB) and augment the effectiveness of antibiotics during the continuation phase of treatment. For those with human immunodeficiency virus (HIV), the CD8(+)T cells may have an especially important role in host defense to Mycobacterium tuberculosis (M.tb) as CD4(+)T cell function and/or numbers decline. Here we performed a preliminary study to investigate the impact of HIV infection status on CD8(+)T cell effector function during the convalescent TB period. Peripheral blood samples from convalescent HIV(+) and HIV(-) TB subjects were used to determine CD4(+)T cell count and monitor antigen-specific CD8(+) T cell activation of effector function (lymphoproliferation, IFN-γ, granulysin) in response to M.tb antigen. Our preliminary results suggest that HIV co-infection is associated with moderate suppression of the M.tb-specific memory CD8(+)T cell compartment in many subjects convalescent for TB. Interestingly, highly activated CD8(+)T cells were observed in recall experiments using peripheral blood from several HIV+ subjects that had low (<200 cells/mm(3)) CD4(+)T cell counts. Further investigation may provide important information for development of novel approaches to target M.tb-specific CD8(+)T cell memory to protect against TB in HIV-endemic regions.

Time to virological failure with atazanavir/ritonavir and lopinavir/ritonavir, with or without an H2-receptor blocker, not significantly different in HIV observational database study.

A retrospective electronic database study was conducted to determine any differences in time to virological failure and percent of virological failure among HIV-infected patients concurrently receiving H2-blockers versus patients not receiving these agents while receiving atazanavir (ATV)/ritonavir (r) or lopinavir (LPV)/r-containing antiretroviral treatment regimens. Data were culled from October 2003 (when ATV became commercially available) through February 2006. Virological failure was defined as (1) two plasma HIV-1 RNA levels >400 copies/mL after at least one HIV-1 RNA level below the level of detection or (2) failure to achieve an HIV-1 RNA <400 copies/mL within 24 weeks. Data from 267 ATV/r-treated patients who met the case definition were compared with data from 670 LPV/r-treated patients. Approximately 10% of the ATV/r group received concurrent H2-blockers when compared with 20% of the LPV/r group. Multivariate analysis showed no statistically significant differences regarding time to virological failure between or among the four subgroups, adjusting for differences in baseline characteristics (P = 0.79, log-rank test). At 750 days following treatment initiation, the proportion of patients not experiencing virological failure was 56% in the ATV/r-blocker subgroup, 48% in the ATV/r-alone subgroup, 45% in the LPV/r-alone subgroup and 42% in the LPV/r-blocker subgroup.

A randomized, prospective study of phenotype susceptibility testing versus standard of care to manage antiretroviral therapy: CCTG 575.

OBJECTIVE: To assess phenotype susceptibility testing (PHENO) with standard of care (SOC) to improve antiretroviral therapy. DESIGN: A prospective, multicenter study of 238 patients taking a stable antiretroviral regimen for > 6 months, with one or two protease inhibitors (PI) and entry HIV RNA > 400 copies/ml. METHOD: Patients were randomized to receive or not receive PHENO results for selecting antiretroviral regimens. Primary outcome was HIV RNA measures. RESULTS: At baseline, median CD4 cell count was 277 x 10 cells/l and HIV RNA was 10 000 copies/ml; 76% had not taken a non-nucleoside reverse transcriptase inhibitor drug (NNRTI). There were significant differences between the groups in selection of baseline nucleoside reverse transcriptase inhibitor (NRTI). At month 6, reduction in HIV RNA was 0.71 and 0.69 log10 copies/ml for PHENO and SOC, respectively; the proportion with < 400 copies/ml (48%) was the same for both groups. No differences were seen at month 12. In a subgroup with resistance to four or more PI, 50% of the PHENO versus 17% of the SOC had HIV RNA < 400 copies/ml at month 6 (P = 0.02). The number of NNRTI and PI, but not NRTI, in the regimen that were active by phenotype at baseline was a strong independent predictor of viral suppression (P < 0.006). Use of alternative NRTI sensitivity cut-offs improved their predictive value. CONCLUSIONS: Although virological outcome was similar in both groups, the potential benefit of PHENO was seen in patients with more resistant virus. Lack of appropriate cut-offs may have partially accounted for the lack of benefit from PHENO and demonstrated the need to identify clinically relevant sensitivity cut-off points.