An Observational Cohort Comparison of Facilitators of Retention in Care and Adherence to Anti-Eetroviral Therapy at an HIV Treatment Center in Kenya

BACKGROUND: Most HIV treatment programs in resource-limited settings utilize multiple facilitators of adherence and retention in care but there is little data on the efficacy of these methods. We performed an observational cohort analysis of a treatment program in Kenya to assess which program components promote adherence and retention in HIV care in East Africa. METHODS: Patients initiating ART at A.I.C. Kijabe Hospital were prospectively enrolled in an observational study. Kijabe has an intensive program to promote adherence and retention in care during the first 6 months of ART that incorporates the following facilitators: home visits by community health workers, community based support groups, pharmacy counseling, and unannounced pill counts by clinicians. The primary endpoint was time to treatment failure, defined as a detectable HIV-1 viral load; discontinuation of ART; death; or loss to follow-up. Time to treatment failure for each facilitator was calculated using Kaplan-Meier analysis. The relative effects of the facilitators were determined by the Cox Proportional Hazards Model. RESULTS: 301 patients were enrolled. Time to treatment failure was longer in patients participating in support groups (448 days vs. 337 days, P<0.001), pharmacy counseling (480 days vs. 386 days, P = 0.002), pill counts (482 days vs. 189 days, P<0.001) and home visits (485 days vs. 426 days, P = 0.024). Better adherence was seen with support groups (89% vs. 82%, P = 0.05) and pill counts (89% vs. 75%, P = 0.02). Multivariate analysis using the Cox Model found significant reductions in risk of treatment failure associated with pill counts (HR = 0.19, P<0.001) and support groups (HR = 0.43, P = 0.003). CONCLUSION: Unannounced pill counts by the clinician and community based support groups were associated with better long term treatment success and with better adherence

Informal Urban Settlements and Cholera Risk in Dar es Salaam, Tanzania

In 2008, for the first time in human history, more than half of the world's population was living in urban areas, and this proportion is expected to increase. As a result of poor economic opportunities and an increasing shortage of affordable housing, much of the spatial growth in many of the world's fastest growing cities is a result of the expansion of informal settlements where residents live without security of tenure and with limited access to basic infrastructure. Although inadequate water and sanitation facilities, crowding, and other poor living conditions can have a significant impact on the spread of infectious diseases, analyses relating these diseases to ongoing global urbanization, especially at the neighborhood and household level in informal settlements, have been infrequent. To begin to address this deficiency, we analyzed urban environmental data and the burden of cholera in Dar es Salaam, Tanzania. We found that cholera incidence was most closely associated with informal housing, population density, and the income level of informal residents. Our analysis suggests that the current growth of many cities in developing countries and expansion of informal settlements will be associated with increased risks to human health, including cholera and other infectious diseases, and underscores the importance of urban planning, resource allocation, and infrastructure placement and management, as the rapidly progressive trend of global urbanization proceeds

Consumer–brand identification revisited: An integrative framework of brand identification, customer satisfaction, and price image and their role for brand loyalty and word of mouth

Consumer–brand identification has received considerable attraction among scholars and practitioners in recent years. We contribute to previous research by proposing an integrative model that includes consumer–brand identification, customer satisfaction, and price image to investigate the interrelationships among these constructs as well as their effects on brand loyalty and positive word of mouth. To provide general results, we empirically test the model using a sample of 1443 respondents from a representative consumer panel and 10 service/product brands. The results demonstrate that identification, satisfaction, and price image significantly influence both loyalty and word of mouth. Moreover, we find significant interrelationships among the constructs: Identification positively influences both satisfaction and price image, which also increases satisfaction. By disclosing the relative importance of three separate ways of gaining and retaining customers, this study helps managers more appropriately choose the right mix of branding, pricing, and relationship marketing. From an academic point of view, our research is the first to explicitly examine the effects of the concept of identification for price management and to integrate variables from the fields of branding, relationship marketing, and behavioral pricing, which have separately been identified as particularly important determinants of marketing outcomes

The effect of parental rearing conditions on offspring life history in Anopheles stephensi

Background The environmental conditions experienced by parents are increasingly recognized to impact the success of offspring. Little is known on the presence of such parental effects in Anopheles. If present, parental effects could influence mosquito breeding programmes, some malaria control measures and have epidemiological and evolutionary consequences. Methods The presence of parental effects on offspring emergence time, size, survival, blood meal size and fecundity in laboratory reared An. stephensi were tested. Results Parental rearing conditions did not influence the time taken for offspring to emerge, or their size or survival as adults. However, parental effects were influential in determining the fecundity of daughters. Counter-intuitively, daughters of parents reared in low food conditions produced larger egg clutches than daughters of parents reared in high food conditions. Offspring reared in low food conditions took larger blood meals if their parents had also experienced a low food environment. Conclusion So far as we are aware, this is the first evidence of parental effects on progeny in Anophele

The Neglected Tropical Diseases of Latin America and the Caribbean: A Review of Disease Burden and Distribution and a Roadmap for Control and Elimination

The neglected tropical diseases (NTDs) represent some of the most common infections of the poorest people living in the Latin American and Caribbean region (LAC). Because they primarily afflict the disenfranchised poor as well as selected indigenous populations and people of African descent, the NTDs in LAC are largely forgotten diseases even though their collective disease burden may exceed better known conditions such as of HIV/AIDS, tuberculosis, or malaria. Based on their prevalence and healthy life years lost from disability, hookworm infection, other soil-transmitted helminth infections, and Chagas disease are the most important NTDs in LAC, followed by dengue, schistosomiasis, leishmaniasis, trachoma, leprosy, and lymphatic filariasis. On the other hand, for some important NTDs, such as leptospirosis and cysticercosis, complete disease burden estimates are not available. The NTDs in LAC geographically concentrate in 11 different sub-regions, each with a distinctive human and environmental ecology. In the coming years, schistosomiasis could be eliminated in the Caribbean and transmission of lymphatic filariasis and onchocerciasis could be eliminated in Latin America. However, the highest disease burden NTDs, such as Chagas disease, soil-transmitted helminth infections, and hookworm and schistosomiasis co-infections, may first require scale-up of existing resources or the development of new control tools in order to achieve control or elimination. Ultimately, the roadmap for the control and elimination of the more widespread NTDs will require an inter-sectoral approach that bridges public health, social services, and environmental interventions

Lipoglycans Contribute to Innate Immune Detection of Mycobacteria

Innate immune recognition is based on the detection, by pattern recognition receptors (PRRs), of molecular structures that are unique to microorganisms. Lipoglycans are macromolecules specific to the cell envelope of mycobacteria and related genera. They have been described to be ligands, as purified molecules, of several PRRs, including the C-type lectins Mannose Receptor and DC-SIGN, as well as TLR2. However, whether they are really sensed by these receptors in the context of a bacterium infection remains unclear. To address this question, we used the model organism Mycobacterium smegmatis to generate mutants altered for the production of lipoglycans. Since their biosynthesis cannot be fully abrogated, we manipulated the biosynthesis pathway of GDP-Mannose to obtain some strains with either augmented (∼1.7 fold) or reduced (∼2 fold) production of lipoglycans. Interestingly, infection experiments demonstrated a direct correlation between the amount of lipoglycans in the bacterial cell envelope on one hand and the magnitude of innate immune signaling in TLR2 reporter cells, monocyte/macrophage THP-1 cell line and human dendritic cells, as revealed by NF-κB activation and IL-8 production, on the other hand. These data establish that lipoglycans are bona fide Microbe-Associated Molecular Patterns contributing to innate immune detection of mycobacteria, via TLR2 among other PRRs

Patient Retention and Adherence to Antiretrovirals in a Large Antiretroviral Therapy Program in Nigeria: A Longitudinal Analysis for Risk Factors

Substantial resources and patient commitment are required to successfully scale-up antiretroviral therapy (ART) and provide appropriate HIV management in resource-limited settings. We used pharmacy refill records to evaluate risk factors for loss to follow-up (LTFU) and non-adherence to ART in a large treatment cohort in Nigeria.We reviewed clinic records of adult patients initiating ART between March 2005 and July 2006 at five health facilities. Patients were classified as LTFU if they did not return >60 days from their expected visit. Pharmacy refill rates were calculated and used to assess non-adherence. We identified risk factors associated with LTFU and non-adherence using Cox and Generalized Estimating Equation (GEE) regressions, respectively. Of 5,760 patients initiating ART, 26% were LTFU. Female gender (p < 0.001), post-secondary education (p = 0.03), and initiating treatment with zidovudine-containing (p = 0.004) or tenofovir-containing (p = 0.05) regimens were associated with decreased risk of LTFU, while patients with only primary education (p = 0.02) and those with baseline CD4 counts (cell/ml(3)) >350 and <100 were at a higher risk of LTFU compared to patients with baseline CD4 counts of 100-200. The adjusted GEE analysis showed that patients aged <35 years (p = 0.005), who traveled for >2 hours to the clinic (p = 0.03), had total ART duration of >6 months (p<0.001), and CD4 counts >200 at ART initiation were at a higher risk of non-adherence. Patients who disclosed their HIV status to spouse/family (p = 0.01) and were treated with tenofovir-containing regimens (p < or = 0.001) were more likely to be adherent.These findings formed the basis for implementing multiple pre-treatment visit preparation that promote disclosure and active community outreaching to support retention and adherence. Expansion of treatment access points of care to communities to diminish travel time may have a positive impact on adherence

Evidence for the Contribution of the Hemozoin Synthesis Pathway of the Murine Plasmodium yoelii to the Resistance to Artemisinin-Related Drugs

Plasmodium falciparum malaria is a major global health problem, causing approximately 780,000 deaths each year. In response to the spreading of P. falciparum drug resistance, WHO recommended in 2001 to use artemisinin derivatives in combination with a partner drug (called ACT) as first-line treatment for uncomplicated falciparum malaria, and most malaria-endemic countries have since changed their treatment policies accordingly. Currently, ACT are often the last treatments that can effectively and rapidly cure P. falciparum infections permitting to significantly decrease the mortality and the morbidity due to malaria. However, alarming signs of emerging resistance to artemisinin derivatives along the Thai-Cambodian border are of major concern. Through long-term in vivo pressures, we have been able to select a murine malaria model resistant to artemisinins. We demonstrated that the resistance of Plasmodium to artemisinin-based compounds depends on alterations of heme metabolism and on a loss of hemozoin formation linked to the down-expression of the recently identified Heme Detoxification Protein (HDP). These artemisinins resistant strains could be able to detoxify the free heme by an alternative catabolism pathway involving glutathione (GSH)-mediation. Finally, we confirmed that artemisinins act also like quinolines against Plasmodium via hemozoin production inhibition. The work proposed here described the mechanism of action of this class of molecules and the resistance to artemisinins of this model. These results should help both to reinforce the artemisinins activity and avoid emergence and spread of endoperoxides resistance by focusing in adequate drug partners design. Such considerations appear crucial in the current context of early artemisinin resistance in Asia

A Research Agenda for Helminth Diseases of Humans: Social Ecology, Environmental Determinants, and Health Systems

In this paper, the Disease Reference Group on Helminth Infections (DRG4), established in 2009 by the Special Programme for Research and Training in Tropical Diseases (TDR), with the mandate to review helminthiases research and identify research priorities and gaps, focuses on the environmental, social, behavioural, and political determinants of human helminth infections and outlines a research and development agenda for the socioeconomic and health systems research required for the development of sustainable control programmes. Using Stockols' social-ecological approach, we describe the role of various social (poverty, policy, stigma, culture, and migration) and environmental determinants (the home environment, water resources development, and climate change) in the perpetuation of helminthic diseases, as well as their impact as contextual factors on health promotion interventions through both the regular and community-based health systems. We examine these interactions in regard to community participation, intersectoral collaboration, gender, and possibilities for upscaling helminthic disease control and elimination programmes within the context of integrated and interdisciplinary approaches. The research agenda summarises major gaps that need to be addressed