Development and Promotion of a National Website to Improve Dissemination of Information Related to the Prevention of Mother-to-Child HIV Transmission (PMTCT) in Tanzania.

Websites that address national public health issues provide an important mechanism to improve health education and services in resource limited countries. This article describes the development, promotion and initial evaluation of a national website to increase access to information and resources about prevention of mother-to-child transmission of HIV (PMTCT) among healthcare workers and PMTCT stakeholders in Tanzania. A participatory approach, involving the Tanzania Ministry of Health and Social Welfare (MOHSW) and key PMTCT stakeholders, was used to develop and manage the online PMTCT National Resource Center (NRC), http://pmtct.or.tz/ . The website was created with a content management system software system that does not require advanced computer skills and facilitates content updates and site management. The PMTCT NRC hosts related regularly updated PMTCT-related news, resources and publications. Website implementation, access and performance were evaluated over two years using Google Analytics data about visits, page views, downloads, bounce rates and location of visitors, supplemented by anecdotal feedback. Following its launch in July 2013, the PMTCT NRC website received a total of 28,400 visits, with 66,463 page views, over 2 years; 30 % of visits were from returning visitors. During year 1, visits increased by 80 % from the first to second 6 month period and then declined slightly (9-11 %) but remained stable in Year 2. Monthly visits spiked by about 70 % during October 2013 and January 2014 in response to the release and promotion of revised national PMTCT guidelines and training manuals. The majority of visitors came from primarily urban areas in Tanzania (50 %) and from other African countries (16 %). By year 2, over one-third of visitors used mobile devices to access the site. The successfully implemented PMTCT NRC website provides centralized, easily accessed information designed to address the needs of clinicians, educators and program partners in Tanzania. Ongoing involvement of the MOHSW and key stakeholders are essential ensure the website's growth, effectiveness and sustainability. Additional efforts are needed to expand use of the PMTCT NRC throughout the country. Future evaluations should examine the role of the website in supporting implementation of national PMTCT guidelines and services in Tanzania

Glucocortiocoid Treatment of MCMV Infected Newborn Mice Attenuates CNS Inflammation and Limits Deficits in Cerebellar Development

Infection of the developing fetus with human cytomegalovirus (HCMV) is a major cause of central nervous system disease in infants and children; however, mechanism(s) of disease associated with this intrauterine infection remain poorly understood. Utilizing a mouse model of HCMV infection of the developing CNS, we have shown that peripheral inoculation of newborn mice with murine CMV (MCMV) results in CNS infection and developmental abnormalities that recapitulate key features of the human infection. In this model, animals exhibit decreased granule neuron precursor cell (GNPC) proliferation and altered morphogenesis of the cerebellar cortex. Deficits in cerebellar cortical development are symmetric and global even though infection of the CNS results in a non-necrotizing encephalitis characterized by widely scattered foci of virus-infected cells with mononuclear cell infiltrates. These findings suggested that inflammation induced by MCMV infection could underlie deficits in CNS development. We investigated the contribution of host inflammatory responses to abnormal cerebellar development by modulating inflammatory responses in infected mice with glucocorticoids. Treatment of infected animals with glucocorticoids decreased activation of CNS mononuclear cells and expression of inflammatory cytokines (TNF-α, IFN-β and IFNγ) in the CNS while minimally impacting CNS virus replication. Glucocorticoid treatment also limited morphogenic abnormalities and normalized the expression of developmentally regulated genes within the cerebellum. Importantly, GNPC proliferation deficits were normalized in MCMV infected mice following glucocorticoid treatment. Our findings argue that host inflammatory responses to MCMV infection contribute to deficits in CNS development in MCMV infected mice and suggest that similar mechanisms of disease could be responsible for the abnormal CNS development in human infants infected in-utero with HCMV

Calcium and increased vascular reactivity in hypertension.

Enhanced vascular reactivity in hypertension has been associated with a number of changes in cellular calcium handling. These studies examined potential-operated calcium channel function in hypertension and possible mechanisms that may underlie enhanced vascular sensitivity to catecholamines in this disorder. Contractile responses to the potential-operated calcium channel agonist, Bay K 8644, were markedly increased in thoracic aortic strips from coarctation-hypertensive rats as compared to those from normotensive sham rats. This effect was related to elevated arterial pressure since it was not seen in abdominal aortae from hypertensive rats, a vessel that is protected from increased pressure. The role of pressure per se was supported by findings of increased sensitivity to Bay K 8644 in abdominal aortae from 2 kidney 1 clip hypertensive rats. In this comparable model of hypertension, the abdominal aorta is exposed to elevated blood pressure. To evaluate channel function within the microvasculature, intracellular calcium concentration (Ca\sp{2+}) \sb{\rm i} was measured in rat pancreatic arterioles (15-35 $\mu$m diameter) using microspectrofluorimetry of fura-2. In these vessels, KCl-induced increases in (Ca\sp{2+}) \sb{\rm i} were inhibited by nifedipine, consistent with activation of potential-operated calcium channels. Bay K 8644 evoked an increase in (Ca\sp{2+}) \sb{\rm i} in approximately 25% of arterioles tested from both genetically hypertensive and normotensive control rats. Neither basal (Ca\sp{2+}) \sb{\rm i} nor the change in (Ca\sp{2+}) \sb{\rm i} produced by Bay K 8644 differed between the two strains. However, since arterioles of this size are distal to the major resistance vessels, they may be protected from pressure-induced damage seen in larger arteries. Mechanisms that may account for enhanced vascular sensitivity to norepinephrine in mesenteric arteries from DOCA hypertensive rats were also examined. Agonist affinity and the calcium sensitivity of the contractile elements were not altered in these vessels, but norepinephrine-stimulated \sp{45}Ca\sp{2+} was increased, implicating a change in post receptor signal transduction involving calcium release from intracellular stores. In conclusion, these studies suggest that pressure-induced changes in potential-operated calcium channel function and augmented mobilization of intracellular calcium stores contribute to enhanced vascular reactivity in hypertension.Ph.D.Animal PhysiologyBiological SciencesHealth and Environmental SciencesNursingUniversity of Michigan, Horace H. Rackham School of Graduate Studieshttp://deepblue.lib.umich.edu/bitstream/2027.42/128908/2/9227012.pd

Preconception and Contraceptive Care for Women Living with HIV

Women living with HIV have fertility desires and intentions that are similar to those of uninfected women, and with advances in treatment most women can realistically plan to have and raise children to adulthood. Although HIV may have adverse effects on fertility, recent studies suggest that antiretroviral therapy may increase or restore fertility. Data indicate the increasing numbers of women living with HIV who are becoming pregnant, and that many pregnancies are unintended and contraception is underutilized, reflecting an unmet need for preconception care (PCC). In addition to the PCC appropriate for all women of reproductive age, women living with HIV require comprehensive, specialized care that addresses their unique needs. The goals of PCC for women living with HIV are to prevent unintended pregnancy, optimize maternal health prior to pregnancy, improve maternal and fetal outcomes in pregnancy, prevent perinatal HIV transmission, and prevent HIV transmission to an HIV-uninfected sexual partner when trying to conceive. This paper discusses the rationale for preconception counseling and care in the setting of HIV and reviews current literature relevant to the content and considerations in providing PCC for women living with HIV, with a primary focus on well-resourced settings

Negative life events: risk to health-related quality of life in children and youth with HIV infection

Children and youth with perinatally acquired HIV infection are living longer because of improved drug therapies, but they may be at risk for poor health-related quality of life (HRQOL) outcomes because of nondisease factors. Families affected by HIV disease are more likely to experience major negative life events (NLEs). The effects of NLEs, shown to impact HRQOL in children with other chronic illnesses, have not been evaluated in children with HIV infection. The primary objective of this study was to determine if NLEs occurring in the previous 12 months were associated with increased risk for poorer outcomes in three measures of HRQOL (health perception, behavior problems, and symptom distress) in a cohort of children and youth with HIV infection. The authors conducted a cross-sectional analysis of data determined in 1999 from 1,018 children and youth 5 to 21 years of age enrolled in a longitudinal follow-up study. Multivariate logistic regressions estimated the odds for worse HRQOL outcomes. Children and youth with one or more NLEs had significantly lower health perceptions, more behavior problems, and greater symptom distress than children with no reported NLEs. The occurrence of NLEs may present a significant nondisease risk for diminished HRQOL among children and youth challenged by HIV disease. Nursing efforts to support these younger patients and their families sustaining major family disruption caused by NLEs may improve overall health outcomes in this vulnerable population

Medication Adherence in Children and Adolescents with HIV Infection: Associations with Behavioral Impairment

The impact of behavioral functioning on medication adherence in children with perinatally acquired HIV infection is not well-explored, but has important implications for intervention. This report addresses the relationship between behavioral functioning and child self-report or caregiver report of medication adherence among children and adolescents enrolled in Pediatric AIDS Clinical Trials Group Protocol 219C (conducted 2000–2007). A total of 1134 participants, aged 3–17 years, received a behavioral evaluation and adherence assessment. Complete adherence was defined as taking 100% of prescribed antiretroviral medications during three days preceding the study visit. Multivariable logistic regression models were used to evaluate associations between adherence and behavioral functioning, adjusting for potential confounders, including demographic, psychosocial, and health factors. Children demonstrated higher than expected rates of behavioral impairment (≈7% expected with T > 65) in the areas of conduct problems (14%, z = 7.0, p < 0.001), learning problems (22%, z = 12.2, p < 0.001), somatic complaints (22%, z = 12.6, p < 0.001), impulsivity-hyperactivity (20%, z = 11.1, p < 0.001), and hyperactivity (19%, z = 10.6, p < 0.001). Children with behavioral impairment in one or more areas had significantly increased odds of nonadherence [adjusted odds ratio (aOR) = 1.49, p = 0.04]. The odds of nonadherence were significantly higher for those with conduct problems and general hyperactivity (aOR = 2.03, p = 0.005 and aOR = 1.68, p = 0.02, respectively). Psychosocial and health factors, such as recent stressful life events and higher HIV RNA levels, were also associated with nonadherence. Knowledge of behavioral, health, and social influences affecting the child and family should guide the development of appropriate, evidence-based interventions for medication adherence