Risk Factors for Early Childhood Infection of Human Herpesvirus-8 in Zambian Children: The Role of Early Childhood Feeding Practices

Background—Human herpesvirus-8 (HHV-8) infection in early childhood is common throughout sub-Saharan Africa with prevalence increasing throughout childhood. Specific routes of transmission have not been clearly delineated, though HHV-8 is present in high concentrations in saliva. Methods—To understand the horizontal transmission of HHV-8 within households to children we enrolled for cross-sectional analysis, 251 households including 254 children, age two and under, in Lusaka, Zambia. For all children, plasma was screened for HHV-8 and HIV-1 and health and behavioral questionnaires were completed. Multi-level logistic regression analysis was conducted to assess independent factors for HHV-8 infection in children. Results—Risk factors for HHV-8 infection included increasing number of HHV-8 positive household members [OR 2.5 (95% CI: 1.9, 3.3) P \u3c 0.01] and having a primary caregiver who tested the temperature of food with their tongue prior to feeding the child [OR 2.4 (95% CI: 1.93, 3.30) P =0.01]. Breastfeeding was protective against infection with HHV-8 for children [OR 0.3 (95% CI: 0.16, 0.72) P \u3c0.01]. Conclusions—These results indicate that exposure to HHV-8 in the household increases risk for early childhood infection with specific feeding behaviors likely playing a role in transmission. Impact—Interventions to protect children from infection should emphasize the possibility of infection through sharing of foods

The Zambia Children\u27s KS-HHV8 Study: Rationale, Study Design, and Study Methods

The epidemic of human immunodeficiency virus in Zambia has led to a dramatic rise in the incidence of human herpesvirus-8 (HHV-8)–associated Kaposi\u27s sarcoma in both adults and children. However, there is a paucity of knowledge about the routes of HHV-8 transmission to young children. The Zambia Children\u27s KS-HHV8 Study, a large, prospective cohort study in Lusaka, Zambia, was launched in 2004 to investigate the role of household members as a source of HHV-8 infection in young children and social behaviors that may modify the risk of HHV-8 acquisition. This cohort is distinct from other epidemiologic studies designed to investigate HHV-8 incidence and transmission because it recruited and followed complete households in the urban central African context. Between July 2004 and March 2007, 1,600 households were screened; 368 households comprising 464 children and 1,335 caregivers and household members were enrolled. Follow-up of this population continued for 48 months postrecruitment, affording a unique opportunity to study horizontal transmission of HHV-8 and understand the routes and sources of transmission to young children in Zambia. The authors describe the study rationale, design, execution, and characteristics of this cohort, which provides critical data on the epidemiology and transmission of HHV-8 to young children in Zambia

Physician perceptions of primary prevention: qualitative base for the conceptual shaping of a practice intervention tool

BACKGROUND: A practice intervention must have its basis in an understanding of the physician and practice to secure its benefit and relevancy. We used a formative process to characterize primary care physician attitudes, needs, and practice obstacles regarding primary prevention. The characterization will provide the conceptual framework for the development of a practice tool to facilitate routine delivery of primary preventive care. METHODS: A focus group of primary care physician Opinion Leaders was audio-taped, transcribed, and qualitatively analyzed to identify emergent themes that described physicians' perceptions of prevention in daily practice. RESULTS: The conceptual worth of primary prevention, including behavioral counseling, was high, but its practice was significantly countered by the predominant clinical emphasis on and rewards for secondary care. In addition, lack of health behavior training, perceived low self-efficacy, and patient resistance to change were key deterrents to primary prevention delivery. Also, the preventive focus in primary care is not on cancer, but on predominant chronic nonmalignant conditions. CONCLUSIONS: The success of the future practice tool will be largely dependent on its ability to "fit" primary prevention into the clinical culture of diagnoses and treatment sustained by physicians, patients, and payers. The tool's message output must be formatted to facilitate physician delivery of patient-tailored behavioral counseling in an accurate, confident, and efficacious manner. Also, the tool's health behavior messages should be behavior-specific, not disease-specific, to draw on shared risk behaviors of numerous diseases and increase the likelihood of perceived salience and utility of the tool in primary care

Effects of antiplatelet therapy on stroke risk by brain imaging features of intracerebral haemorrhage and cerebral small vessel diseases: subgroup analyses of the RESTART randomised, open-label trial

Background Findings from the RESTART trial suggest that starting antiplatelet therapy might reduce the risk of recurrent symptomatic intracerebral haemorrhage compared with avoiding antiplatelet therapy. Brain imaging features of intracerebral haemorrhage and cerebral small vessel diseases (such as cerebral microbleeds) are associated with greater risks of recurrent intracerebral haemorrhage. We did subgroup analyses of the RESTART trial to explore whether these brain imaging features modify the effects of antiplatelet therapy

Practice Inquiry: Clinical Uncertainty as a Focus for Small-Group Learning and Practice Improvement

PROBLEM: Many primary care physicians in nonacademic settings lack a collegial forum for engaging the clinical uncertainties inherent in their work. PROGRAM DESCRIPTION: “Practice Inquiry” is proposed as a set of small-group, practice-based learning and improvement (PBLI) methods designed to help clinicians better manage case-based clinical uncertainty. Clinicians meet regularly at their offices/clinics to present dilemma cases, share clinical experience, review evidence for blending with experience, and draw implications for practice improvement. From 2001 through 2005, Practice Inquiry was introduced to sites in the San Francisco Bay Area as a demonstration effort. Meeting rosters, case logs, a feedback survey, and meeting field notes documented implementation and provided data for a formative, qualitative evaluation. PROGRAM EVALUATION: Of the 30 sites approached, 14 held introductory meetings. As of summer 2006, 98 clinicians in 11 sites continue to hold regularly scheduled group meetings. Of the 118 patient cases presented in the seven oldest groups, clinician–patient relationship and treatment dilemmas were most common. Clinician feedback and meeting transcript data provided insights into how busy practitioners shared cases, developed trust, and learned new knowledge/skills for moving forward with patients. DISCUSSION: Ongoing clinician involvement suggests that Practice Inquiry is a feasible, acceptable, and potentially useful set of PBLI methods. Two of the Practice Inquiry’s group learning tasks received comparatively less focus: integrating research evidence with clinical experience and tracking dilemma case outcomes. Future work should focus on reducing the methodological limitations of a demonstration effort and examining factors affecting clinician participation. Set-aside work time for clinicians, or other equally potent incentives, will be necessary for the further elaboration of these PBLI methods aimed at managing uncertainty

Profiling of Differentially Expressed Genes Using Suppression Subtractive Hybridization in an Equine Model of Chronic Asthma

Background :\ud Gene expression analyses are used to investigate signaling pathways involved in diseases. In asthma, they have been primarily derived from the analysis of bronchial biopsies harvested from mild to moderate asthmatic subjects and controls. Due to ethical considerations, there is currently limited information on the transcriptome profile of the peripheral lung tissues in asthma.\ud \ud Objective :\ud To identify genes contributing to chronic inflammation and remodeling in the peripheral lung tissue of horses with heaves, a naturally occurring asthma-like condition.\ud \ud Methods :\ud Eleven adult horses (6 heaves-affected and 5 controls) were studied while horses with heaves were in clinical remission (Pasture), and during disease exacerbation induced by a 30-day natural antigen challenge during stabling (Challenge). Large peripheral lung biopsies were obtained by thoracoscopy at both time points. Using suppression subtractive hybridization (SSH), lung cDNAs of controls (Pasture and Challenge) and asymptomatic heaves-affected horses (Pasture) were subtracted from cDNAs of horses with heaves in clinical exacerbation (Challenge). The differential expression of selected genes of interest was confirmed using quantitative PCR assay.\ud \ud Results :\ud Horses with heaves, but not controls, developed airway obstruction when challenged. Nine hundred and fifty cDNA clones isolated from the subtracted library were screened by dot blot array and 224 of those showing the most marked expression differences were sequenced. The gene expression pattern was confirmed by quantitative PCR in 15 of 22 selected genes. Novel genes and genes with an already defined function in asthma were identified in the subtracted cDNA library. Genes of particular interest associated with asthmatic airway inflammation and remodeling included those related to PPP3CB/NFAT, RhoA, and LTB4/GPR44 signaling pathways.\ud \ud Conclusions :\ud Pathways representing new possible targets for anti-inflammatory and anti-remodeling therapies for asthma were identified. The findings of genes previously associated with asthma validate this equine model for gene expression studies

THE EPIDEMIOLOGY OF HUMAN HERPESVIRUS-8: TRANSMISSION OF INFECTION TO CHILDREN IN ZAMBIAN HOUSEHOLDS

Human Herpes virus-8 (HHV-8) is the known etiologic agent for several malignant pathologies, including Kaposi’s sarcoma (KS), the most common tumor in children in sub-Saharan Africa. Saliva is implicated as the culprit of transmission; however there is a paucity of information regarding transmission to young children. In this study, we investigated the hypothesis that household behaviors exposing the susceptible child to saliva increase the risk of transmission of HHV-8 to that child. To test our hypothesis a large prospective cohort study in Lusaka, Zambia, enrolling 464 young children and their households, was followed for 48 months. Socio-demographics, health histories, feeding and child-rearing behaviors were assessed. At enrollment, 75 HHV-8 positive children were analyzed for existing risk factors contributing to HHV-8 seropositivity. Analysis for independent variables found that for each additional HHV-8 positive household member, there was 2.5 greater odds for the child to be HHV-8 positive (P \u3c 0.01). Of the household saliva sharing risk behaviors, a primary caregiver testing temperature of food prior to feeding to a child posed a 2.4 greater odds (P = 0.01). A child having been breastfed offered a decreased risk (OR 0.3, P \u3c 0.01). Of the enrolled children, 270 children were available for longitudinal analysis. Of these, 137 children seroconverted to become HHV-8 positive, an incidence of 29.94 per 100 child-years. Most significant independent behavioral risk factors for HHV-8 seroconversion included increased risk with current breastfeeding (HR 2.1, P = 0.002), increased risk with use of pacifier (HR 9.0, P = 0.01), and greater risk with household members blowing on food prior to sharing with child (HR 2.8, P = 0.05). Other studies in this report include development of an HHV-8 serodiagnostic assay. Taken together, this report describes the epidemiology of HHV-8 transmission to a susceptible child within households, and the association with saliva sharing behaviors. Our results support the need for increased public awareness and education regarding risks of viral transmission with child-rearing behaviors that expose the child to saliva. Advisor: Charles Woo

Prevalence of human herpesvirus 8 (HHV8) and hepatitis C virus (HCV) in a rural community with high risk for blood borne infections in central China

Former illegal blood donation in the past decade has caused HIV outbreaks in some rural areas in China. Other HIV associated virus infections, such as human herpesvirus 8 (HHV8) in such areas are still not well defined. In order to explore HHV8 and HCV seroprevalence and potential risk factors in such areas, a cross-sectional study with 305 HIV positive and 315 HIV negative subjects recruited from a rural county in Shanxi province was conducted, where illegal blood collection was reported. Interview questionnaires and serum testing were carried out with these participants. HCV and HHV8 seroprevalence were found to be higher in HIV positive than negative group (76.4% vs. 2.5%; 15.4% vs. 4.8% respectively), while the difference in HBV seroprevalence was not significant. Co-infection with HCV and HHV8 was also more prevalent in the HIV positive group. HIV status (odds ratio [OR], 2.71; 95% confidence interval [CI], 1.16–6.30) and HBV status (OR, 2.56; 95%CI: 1.14–5.75) were independently associated with HHV8 infection. HIV status (OR, 23.03; 95%CI: 9.95–53.27) and blood/plasma selling history (OR, 14.57; 95%CI: 7.49–28.23) were strongly associated with HCV infection. These findings demonstrate that both HHV8 and HCV infections are prevalent in this community. HIV infection is an important risk factor for both HHV8 and HCV infection. HBV infection is associated with HHV8 infection but not with HCV infection. It is possible that HHV8 and HBV, but not HCV, may have similar mode of transmission in this population

Risk Factors for Early Childhood Infection of Human Herpesvirus-8 in Zambian Children: The Role of Early Childhood Feeding Practices

Background—Human herpesvirus-8 (HHV-8) infection in early childhood is common throughout sub-Saharan Africa with prevalence increasing throughout childhood. Specific routes of transmission have not been clearly delineated, though HHV-8 is present in high concentrations in saliva. Methods—To understand the horizontal transmission of HHV-8 within households to children we enrolled for cross-sectional analysis, 251 households including 254 children, age two and under, in Lusaka, Zambia. For all children, plasma was screened for HHV-8 and HIV-1 and health and behavioral questionnaires were completed. Multi-level logistic regression analysis was conducted to assess independent factors for HHV-8 infection in children. Results—Risk factors for HHV-8 infection included increasing number of HHV-8 positive household members [OR 2.5 (95% CI: 1.9, 3.3) P \u3c 0.01] and having a primary caregiver who tested the temperature of food with their tongue prior to feeding the child [OR 2.4 (95% CI: 1.93, 3.30) P =0.01]. Breastfeeding was protective against infection with HHV-8 for children [OR 0.3 (95% CI: 0.16, 0.72) P \u3c0.01]. Conclusions—These results indicate that exposure to HHV-8 in the household increases risk for early childhood infection with specific feeding behaviors likely playing a role in transmission. Impact—Interventions to protect children from infection should emphasize the possibility of infection through sharing of foods