A carotenoid-deficient mutant in Pantoea sp. YR343, a bacteria isolated from the Rhizosphere of Populus deltoides, is defective in root colonization

The complex interactions between plants and their microbiome can have a profound effect on the health and productivity of the plant host. A better understanding of the microbial mechanisms that promote plant health and stress tolerance will enable strategies for improving the productivity of economically important plants. Pantoea sp. YR343 is a motile, rod-shaped bacterium isolated from the roots of Populus deltoides that possesses the ability to solubilize phosphate and produce the phytohormone indole-3-acetic acid (IAA). Pantoea sp. YR343 readily colonizes plant roots and does not appear to be pathogenic when applied to the leaves or roots of selected plant hosts. To better understand the molecular mechanisms involved in plant association and rhizosphere survival by Pantoea sp. YR343, we constructed a mutant in which the crtB gene encoding phytoene synthase was deleted. Phytoene synthase is responsible for converting geranylgeranyl pyrophosphate to phytoene, an important precursor to the production of carotenoids. As predicted, the ΔcrtB mutant is defective in carotenoid production, and shows increased sensitivity to oxidative stress. Moreover, we find that the ΔcrtB mutant is impaired in biofilm formation and production of IAA. Finally we demonstrate that the ΔcrtB mutant shows reduced colonization of plant roots. Taken together, these data suggest that carotenoids are important for plant association and/or rhizosphere survival in Pantoea sp. YR343.Work at the University of Notre Dame was supported by DOE grant SC0006642 (RM) and by a subcontract from Oak Ridge National Laboratory (SP).http://www.frontiersin.orgam2016Microbiology and Plant Patholog

Casting a Wide Net: HIV Drug Resistance Monitoring in Pre-Exposure Prophylaxis Seroconverters in the Global Evaluation of Microbicide Sensitivity Project.

BACKGROUND: Evidence of HIV drug resistance (HIVDR) in individuals using oral pre-exposure prophylaxis (PrEP) who acquire HIV is limited to clinical trials and case studies. More data are needed to understand the risk of HIVDR with oral PrEP during PrEP rollout. Mechanisms to collect these data vary, and are dependent on cost, scale of PrEP distribution, and in-country infrastructure for the identification, collection, and testing of samples from PrEP seroconverters. METHODS: The Global Evaluation of Microbicide Sensitivity (GEMS) project, in collaboration with country stakeholders, initiated HIVDR monitoring among new HIV seroconverters with prior PrEP use in Eswatini, Kenya, South Africa, and Zimbabwe. Standalone protocols were developed to assess HIVDR among a national sample of PrEP users. In addition, HIVDR testing was incorporated into existing demonstration projects for key populations. LESSONS LEARNED: Countries are supportive of conducting a time-limited evaluation of HIVDR during the early stages of PrEP rollout. As PrEP rollout expands, the need for long-term HIVDR monitoring with PrEP will need to be balanced with maintaining national HIV drug resistance surveillance for pretreatment and acquired drug resistance. Laboratory capacity is a common obstacle to setting up a monitoring system. CONCLUSIONS: Establishing HIV resistance monitoring within PrEP programs is feasible. Approaches to drug resistance monitoring may evolve as the PrEP programs mature and expand. The methods and implementation support offered by GEMS assisted countries in developing methods to monitor for drug resistance that best fit their PrEP program needs and resources

Variation in Effectiveness of HIV Assisted Partner Services by Region, Rural Location and Gender in Kenya: A Cluster Randomized Trial

Thesis (Master's)--University of Washington, 2016-08Introduction Assisted partner services (aPS), a strategy to test and link to care the sexual partners of HIV infected persons, is effective in finding new HIV cases. This study assessed whether the effectiveness of aPS differs by region, rural location and gender in a cluster-randomized controlled trial in Kenya. Methods Eighteen HIV testing sites were randomized to provide immediate aPS or aPS delayed for 6 weeks. Generalized estimating equations with a Poisson link, robust standard errors and exchangeable correlation structure were used to assess whether the effectiveness of receiving immediate aPS in getting a sexual partner tested, newly diagnosed with HIV, and linked to care was modified by region (Nairobi/Central vs. Nyanza), testing location (urban vs. rural/peri-urban),and gender. Results We enrolled 1119 index clients and 1286 partners between August 2013 and June 2015.The effectiveness of aPS in getting a sexual partner tested for HIV was modified by region (p=0.001), location (p=0.018), and gender (p=0.061).Comparing the immediate and the delayed arm, partner testing increased 7 fold in Nyanza compared to a 3 fold increase in Nairobi (Incidence Rate Ratio (IRR) 7.2; 95% Confidence Interval (CI) 5.4, 9.6 vs IRR 3.4 95%CI 2.3, 4.8), a 7-fold increase in rural/peri-urban sites compared to a 4-fold increase in urban sites (IRR 6.6; 95%CI 4.5, 9.6 vs. IRR 3.54 95%CI 2.5, 5.0), and a 6-fold increase among female index clients compared to a 4-fold increase among male index clients (IRR 5.8 95%CI 4.2, 7.9 vs IRR 3.7; 95% CI 2.4, 5.8)). In addition, there was a 9-fold increase in newly diagnosing a partner with HIV among female index clients compared to a 3-fold increase among male index clients (IRR 9.1; 95% CI 4.0, 20.9 vs IRR 3.2 95% CI 1.7, 6.0). Conclusions While aPS was effective among the overall study population in Kenya, the size of the effect differed by region, location, and gender. These differences can help to guide the target populations and geographies for aPS as it is rolled out in Kenya. Attribution of support: This abstract was made possible through grants from the US National Institutes of Health (NIH), R01 A1099974-04 and the Fogarty International Center (FIC) D43 TW009580

Cardiovascular Disease among HIV-positive and HIV-negative Kenyan Adults

Thesis (Ph.D.)--University of Washington, 2020Over half of the people living with HIV (PLHIV) reside in Eastern and Southern Africa where cardiovascular related mortality has continued to increase in the past decade. Data from high income countries estimates that PLHIV have shown an estimated 2-fold increased risk of cardiovascular disease (CVD) compared to HIV-negative individuals. This may be the result of traditional risk factors, including smoking, hypertension, unhealthy diets and lack of physical activity. It may also be as result of inflammation due to HIV or the use of antiretroviral therapy (ART) that has been associated with dyslipidemia, insulin resistance, and glucose intolerance, which frequently manifest as metabolic syndrome (MetS), a significant predictor of CVD. Despite increasing concerns of elevated risk of CVD among PLHIV, there is limited data on CVD risk factors, metabolic syndrome, the role of inflammation and the cost of CVD screening in sub-Saharan Africa (SSA). Data comparing people living with and without HIV infection are especially limited. To fill the knowledge gap, we conducted a study that compares cardiovascular risk among HIV-positive and HIV-negative Kenyan adults in Western Kenya. This dissertation compares the burden of cardiovascular disease risk factors among HIV-positive and HIV negative adults, examines the relationship between inflammation and these risk factors, and determines the cost of introducing CVD screening in health settings in Kenya. The first aim was to determine the prevalence and predictors of MetS and its individual components (hypertension, diabetes, elevated triglycerides, low HDL cholesterol, and abdominal obesity) and to compare risk profiles using the atherosclerotic CVD (ASCVD) risk score among 300 HIV-positive and 300 HIV-negative Kenyan adults in Western Kenya. We hypothesized that HIV-positive adults would have a higher prevalence of MetS and a higher ASCVD risk profile compared to HIV-negative individuals. The second aim was to compare immune activation and inflammatory markers that have been associated with increased CVD risk among HIV-positive and HIV-negative Kenyan adults in Western Kenya. We hypothesized that inflammatory markers, including interleukin-1 beta (IL-1β), interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-α), and high-sensitivity C-reactive protein (hsCRP) would be higher among HIV-positive individuals when compared to HIV-negative individuals. The third aim was to estimate the incremental costs of integrating cardiovascular disease screening into on-going outpatient and HIV services in Kisumu County Hospital in Kenya. In the first aim, we conducted a cross-sectional study among adults ≥30 years of age with and without HIV infection seeking care at Kisumu County Hospital. Participants completed a health questionnaire and vital signs, anthropomorphic measurements, and blood for fasting blood glucose and lipids were obtained. MetS was defined using 2009 Consensus Criteria and the 10-year Atherosclerotic CVD (ASCVD) risk score was calculated using the Pooled Cohort Equation as outlined in the 2019 American College of Cardiology (ACC) / American Heart Association (AHA) Guideline on the Primary Prevention of Cardiovascular Disease. MetS prevalence was high in both HIV-positive and HIV-negative adults in western Kenya (1 in 20 and 1 in 10, respectively). Importantly, PLHIV were less likely to have MetS and had lower ASCVD risk scores than HIV-negative participants. In the second aim, using a multiplex immunoassay, we measured IL-1β, IL-6, TNF-α, and hsCRP concentrations among the same participants. We found higher levels of inflammatory markers (IL-1β, IL-6, TNF-α, and hsCRP) among PLHIV compared to HIV-negative participants. The majority of PLHIV were virally suppressed and higher concentrations among PLHIV persisted even after adjusting for traditional risk CVD factors, including dyslipidemia, obesity, diabetes and smoking. In the third aim, using a societal perspective, we conducted a micro costing study using time-in-motion measurements and semi-structured questionnaires to assess the direct medical costs, direct non-medical costs and indirect costs of CVD screening. The incremental cost of CVD screening for diabetes, hypertension and dyslipidemia was estimated at $35 per person and this was reduced by 40$21 if we adopted a high-risk screening scenario. Laboratory supplies were the main cost driver, accounting for 74% of this cost. Together these findings emphasize the need for CVD risk assessment among people living with and without HIV infection and the importance of further longitudinal studies to determine those risk factors that are most predictive of CVD events. We found CVD screening to be feasible, but the cost could be further reduced through global negotiations for more affordable laboratory testing options. We anticipate that this dissertation work will inform future studies of CVD among PLHIV and in pushing forward the policy initiatives on CVD screening in countries of sub-Saharan Africa

Patient-reported outcomes for diabetes and hypertension care in low- and middle-income countries: A scoping review.

IntroductionPatient-reported outcome measures (PROMs) assess patients' perspectives on their health status, providing opportunities to improve the quality of care. While PROMs are increasingly used in high-income settings, limited data are available on PROMs use for diabetes and hypertension in low-and middle-income countries (LMICs). This scoping review aimed to determine how PROMs are employed for diabetes and hypertension care in LMICs.MethodsWe searched PubMed, EMBASE, and ClinicalTrials.gov for English-language studies published between August 2009 and August 2019 that measured at least one PROM related to diabetes or hypertension in LMICs. Full texts of included studies were examined to assess study characteristics, target population, outcome focus, PROMs used, and methods for data collection and reporting.ResultsSixty-eight studies met the inclusion criteria and reported on PROMs for people diagnosed with hypertension and/or diabetes and receiving care in health facilities. Thirty-nine (57%) reported on upper-middle-income countries, 19 (28%) reported on lower-middle-income countries, 4 (6%) reported on low-income countries, and 6 (9%) were multi-country. Most focused on diabetes (60/68, 88%), while 4 studies focused on hypertension and 4 focused on diabetes/hypertension comorbidity. Outcomes of interest varied; most common were glycemic or blood pressure control (38), health literacy and treatment adherence (27), and acute complications (22). Collectively the studies deployed 55 unique tools to measure patient outcomes. Most common were the Morisky Medication Adherence Scale (7) and EuroQoL-5D-3L (7).ConclusionPROMs are deployed in LMICs around the world, with greatest reported use in LMICs with an upper-middle-income classification. Diabetes PROMs were more widely deployed in LMICs than hypertension PROMs, suggesting an opportunity to adapt PROMs for hypertension. Future research focusing on standardization and simplification could improve future comparability and adaptability across LMIC contexts. Incorporation into national health information systems would best establish PROMs as a means to reveal the effectiveness of person-centered diabetes and hypertension care

Patient-reported outcomes for diabetes and hypertension care in low- and middle-income countries: A scoping review

Introduction Patient-reported outcome measures (PROMs) assess patients’ perspectives on their health status, providing opportunities to improve the quality of care. While PROMs are increasingly used in high-income settings, limited data are available on PROMs use for diabetes and hypertension in low-and middle-income countries (LMICs). This scoping review aimed to determine how PROMs are employed for diabetes and hypertension care in LMICs. Methods We searched PubMed, EMBASE, and ClinicalTrials.gov for English-language studies published between August 2009 and August 2019 that measured at least one PROM related to diabetes or hypertension in LMICs. Full texts of included studies were examined to assess study characteristics, target population, outcome focus, PROMs used, and methods for data collection and reporting. Results Sixty-eight studies met the inclusion criteria and reported on PROMs for people diagnosed with hypertension and/or diabetes and receiving care in health facilities. Thirty-nine (57%) reported on upper-middle-income countries, 19 (28%) reported on lower-middle-income countries, 4 (6%) reported on low-income countries, and 6 (9%) were multi-country. Most focused on diabetes (60/68, 88%), while 4 studies focused on hypertension and 4 focused on diabetes/hypertension comorbidity. Outcomes of interest varied; most common were glycemic or blood pressure control (38), health literacy and treatment adherence (27), and acute complications (22). Collectively the studies deployed 55 unique tools to measure patient outcomes. Most common were the Morisky Medication Adherence Scale (7) and EuroQoL-5D-3L (7). Conclusion PROMs are deployed in LMICs around the world, with greatest reported use in LMICs with an upper-middle-income classification. Diabetes PROMs were more widely deployed in LMICs than hypertension PROMs, suggesting an opportunity to adapt PROMs for hypertension. Future research focusing on standardization and simplification could improve future comparability and adaptability across LMIC contexts. Incorporation into national health information systems would best establish PROMs as a means to reveal the effectiveness of person-centered diabetes and hypertension care. </jats:sec

Tackling syndemics by integrating infectious and noncommunicable diseases in health systems of low- and middle-income countries: A narrative systematic review.

The co-occurrence of infectious diseases (ID) and non-communicable diseases (NCD) is widespread, presenting health service delivery challenges especially in low-and middle-income countries (LMICs). Integrated health care is a possible solution but may require a paradigm shift to be successfully implemented. This literature review identifies integrated care examples among selected ID and NCD dyads. We searched PubMed, PsycINFO, Cochrane Library, CINAHL, Web of Science, EMBASE, Global Health Database, and selected clinical trials registries. Eligible studies were published between 2010 and December 2022, available in English, and report health service delivery programs or policies for the selected disease dyads in LMICs. We identified 111 studies that met the inclusion criteria, including 56 on tuberculosis and diabetes integration, 46 on health system adaptations to treat COVID-19 and cardiometabolic diseases, and 9 on COVID-19, diabetes, and tuberculosis screening. Prior to the COVID-19 pandemic, most studies on diabetes-tuberculosis integration focused on clinical service delivery screening. By far the most reported health system outcomes across all studies related to health service delivery (n = 72), and 19 addressed health workforce. Outcomes related to health information systems (n = 5), leadership and governance (n = 3), health financing (n = 2), and essential medicines (n = 4)) were sparse. Telemedicine service delivery was the most common adaptation described in studies on COVID-19 and either cardiometabolic diseases or diabetes and tuberculosis. ID-NCD integration is being explored by health systems to deal with increasingly complex health needs, including comorbidities. High excess mortality from COVID-19 associated with NCD-related comorbidity prompted calls for more integrated ID-NCD surveillance and solutions. Evidence of clinical integration of health service delivery and workforce has grown-especially for HIV and NCDs-but other health system building blocks, particularly access to essential medicines, health financing, and leadership and governance, remain in disease silos