The PRECISE (PREgnancy Care Integrating translational Science, Everywhere) Network's first protocol: deep phenotyping in three sub-Saharan African countries

BACKGROUND: The PRECISE (PREgnancy Care Integrating translational Science, Everywhere) Network is a new and broadly-based group of research scientists and health advocates based in the UK, Africa and North America. METHODS: This paper describes the protocol that underpins the clinical research activity of the Network, so that the investigators, and broader global health community, can have access to 'deep phenotyping' (social determinants of health, demographic and clinical parameters, placental biology and agnostic discovery biology) of women as they advance through pregnancy to the end of the puerperium, whether those pregnancies have normal outcomes or are complicated by one/more of the placental disorders of pregnancy (pregnancy hypertension, fetal growth restriction and stillbirth). Our clinical sites are in The Gambia (Farafenni), Kenya (Kilifi County), and Mozambique (Maputo Province). In each country, 50 non-pregnant women of reproductive age will be recruited each month for 1 year, to provide a final national sample size of 600; these women will provide culturally-, ethnically-, seasonally- and spatially-relevant control data with which to compare women with normal and complicated pregnancies. Between the three countries we will recruit ≈10,000 unselected pregnant women over 2 years. An estimated 1500 women will experience one/more placental complications over the same epoch. Importantly, as we will have accurate gestational age dating using the TraCer device, we will be able to discriminate between fetal growth restriction and preterm birth. Recruitment and follow-up will be primarily facility-based and will include women booking for antenatal care, subsequent visits in the third trimester, at time-of-disease, when relevant, during/immediately after birth and 6 weeks after birth. CONCLUSIONS: To accelerate progress towards the women's and children's health-relevant Sustainable Development Goals, we need to understand how a variety of social, chronic disease, biomarker and pregnancy-specific determinants health interact to result in either a resilient or a compromised pregnancy for either mother or fetus/newborn, or both. This protocol has been designed to create such a depth of understanding. We are seeking funding to maintain the cohort to better understand the implications of pregnancy complications for both maternal and child health

The cost‐effectiveness of prophylaxis strategies for individuals with advanced HIV starting treatment in Africa

Introduction Many HIV‐positive individuals in Africa have advanced disease when initiating antiretroviral therapy (ART) so have high risks of opportunistic infections and death. The REALITY trial found that an enhanced‐prophylaxis package including fluconazole reduced mortality by 27% in individuals starting ART with CD4 <100 cells/mm3. We investigated the cost‐effectiveness of this enhanced‐prophylaxis package versus other strategies, including using cryptococcal antigen (CrAg) testing, in individuals with CD4 <200 cells/mm3 or <100 cells/mm3 at ART initiation and all individuals regardless of CD4 count. Methods The REALITY trial enrolled from June 2013 to April 2015. A decision‐analytic model was developed to estimate the cost‐effectiveness of six management strategies in individuals initiating ART in the REALITY trial countries. Strategies included standard‐prophylaxis, enhanced‐prophylaxis, standard‐prophylaxis with fluconazole; and three CrAg testing strategies, the first stratifying individuals to enhanced‐prophylaxis (CrAg‐positive) or standard‐prophylaxis (CrAg‐negative), the second to enhanced‐prophylaxis (CrAg‐positive) or enhanced‐prophylaxis without fluconazole (CrAg‐negative) and the third to standard‐prophylaxis with fluconazole (CrAg‐positive) or without fluconazole (CrAg‐negative). The model estimated costs, life‐years and quality‐adjusted life‐years (QALY) over 48 weeks using three competing mortality risks: cryptococcal meningitis; tuberculosis, serious bacterial infection or other known cause; and unknown cause. Results Enhanced‐prophylaxis was cost‐effective at cost‐effectiveness thresholds of US$300 and US$500 per QALY with an incremental cost‐effectiveness ratio (ICER) of US$157 per QALY in the CD4 <200 cells/mm3 population providing enhanced‐prophylaxis components are sourced at lowest available prices. The ICER reduced in more severely immunosuppressed individuals (US$113 per QALY in the CD4 <100 cells/mm3 population) and increased in all individuals regardless of CD4 count (US$722 per QALY). Results were sensitive to prices of the enhanced‐prophylaxis components. Enhanced‐prophylaxis was more effective and less costly than all CrAg testing strategies as enhanced‐prophylaxis still conveyed health gains in CrAg‐negative patients and savings from targeting prophylaxis based on CrAg status did not compensate for costs of CrAg testing. CrAg testing strategies did not become cost‐effective unless the price of CrAg testing fell below US$2.30. Conclusions The REALITY enhanced‐prophylaxis package in individuals with advanced HIV starting ART reduces morbidity and mortality, is practical to administer and is cost‐effective. Efforts should continue to ensure that components are accessed at lowest available prices

Late Presentation With HIV in Africa: Phenotypes, Risk, and Risk Stratification in the REALITY Trial.

This article has been accepted for publication in Clinical Infectious Diseases Published by Oxford University PressBackground: Severely immunocompromised human immunodeficiency virus (HIV)-infected individuals have high mortality shortly after starting antiretroviral therapy (ART). We investigated predictors of early mortality and "late presenter" phenotypes. Methods: The Reduction of EArly MortaLITY (REALITY) trial enrolled ART-naive adults and children ≥5 years of age with CD4 counts .1). Results: Among 1711 included participants, 203 (12%) died. Mortality was independently higher with older age; lower CD4 count, albumin, hemoglobin, and grip strength; presence of World Health Organization stage 3/4 weight loss, fever, or vomiting; and problems with mobility or self-care at baseline (all P < .04). Receiving enhanced antimicrobial prophylaxis independently reduced mortality (P = .02). Of five late-presenter phenotypes, Group 1 (n = 355) had highest mortality (25%; median CD4 count, 28 cells/µL), with high symptom burden, weight loss, poor mobility, and low albumin and hemoglobin. Group 2 (n = 394; 11% mortality; 43 cells/µL) also had weight loss, with high white cell, platelet, and neutrophil counts suggesting underlying inflammation/infection. Group 3 (n = 218; 10% mortality) had low CD4 counts (27 cells/µL), but low symptom burden and maintained fat mass. The remaining groups had 4%-6% mortality. Conclusions: Clinical and laboratory features identified groups with highest mortality following ART initiation. A screening tool could identify patients with low CD4 counts for prioritizing same-day ART initiation, enhanced prophylaxis, and intensive follow-up. Clinical Trials Registration: ISRCTN43622374.REALITY was funded by the Joint Global Health Trials Scheme (JGHTS) of the UK Department for International Development, the Wellcome Trust, and Medical Research Council (MRC) (grant number G1100693). Additional funding support was provided by the PENTA Foundation and core support to the MRC Clinical Trials Unit at University College London (grant numbers MC_UU_12023/23 and MC_UU_12023/26). Cipla Ltd, Gilead Sciences, ViiV Healthcare/GlaxoSmithKline, and Merck Sharp & Dohme donated drugs for REALITY, and ready-to-use supplementary food was purchased from Valid International. A. J. P. is funded by the Wellcome Trust (grant number 108065/Z/15/Z). J. A. B. is funded by the JGHTS (grant number MR/M007367/1). The Malawi-Liverpool–Wellcome Trust Clinical Research Programme, University of Malawi College of Medicine (grant number 101113/Z/13/Z) and the Kenya Medical Research Institute (KEMRI)/Wellcome Trust Research Programme, Kilifi (grant number 203077/Z/16/Z) are supported by strategic awards from the Wellcome Trust, United Kingdom. Permission to publish was granted by the Director of KEMRI. This supplement was supported by funds from the Bill & Melinda Gates Foundation

The global impact of non-communicable diseases on macro-economic productivity: a systematic review

© 2015, The Author(s). Non-communicable diseases (NCDs) have large economic impact at multiple levels. To systematically review the literature investigating the economic impact of NCDs [including coronary heart disease (CHD), stroke, type 2 diabetes mellitus (DM), cancer (lung, colon, cervical and breast), chronic obstructive pulmonary disease (COPD) and chronic kidney disease (CKD)] on macro-economic productivity. Systematic search, up to November 6th 2014, of medical databases (Medline, Embase and Google Scholar) without language restrictions. To identify additional publications, we searched the reference lists of retrieved studies and contacted authors in the field. Randomized controlled trials, cohort, case–control, cross-sectional, ecological studies and modelling studies carried out in adults (>18 years old) were included. Two independent reviewers performed all abstract and full text selection. Disagreements were resolved through consensus or consulting a third reviewer. Two independent reviewers extracted data using a predesigned data collection form. Main outcome measure was the impact of the selected NCDs on productivity, measured in DALYs, productivity costs, and labor market participation, including unemployment, return to work and sick leave. From 4542 references, 126 studies met the inclusion criteria, many of which focused on the impact of more than one NCD on productivity. Breast cancer was the most common (n = 45), followed by stroke (n = 31), COPD (n = 24), colon cancer (n = 24), DM (n = 22), lung cancer (n = 16), CVD (n = 15), cervical cancer (n = 7) and CKD (n = 2). Four studies were from the WHO African Region, 52 from the European Region, 53 from the Region of the Americas and 16 from the Western Pacific Region, one from the Eastern Mediterranean Region and none from South East Asia. We found large regional differences in DALYs attributable to NCDs but especially for cervical and lung cancer. Productivity losses in the USA ranged from 88 million US dollars (USD) for COPD to 20.9 billion USD for colon cancer. CHD costs the Australian economy 13.2 billion USD per year. People with DM, COPD and survivors of breast and especially lung cancer are at a higher risk of reduced labor market participation. Overall NCDs generate a large impact on macro-economic productivity in most WHO regions irrespective of continent and income. The absolute global impact in terms of dollars and DALYs remains an elusive challenge due to the wide heterogeneity in the included studies as well as limited information from low- and middle-income countries.WHO; Nestle´ Nutrition (Nestec Ltd.); Metagenics Inc.; and AX

Seroprevalence of anti-SARS-CoV-2 IgG antibodies in Kenyan blood donors

The spread of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in Africa is poorly described. The first case of SARS-CoV-2 in Kenya was reported on 12 March 2020, and an overwhelming number of cases and deaths were expected, but by 31 July 2020, there were only 20,636 cases and 341 deaths. However, the extent of SARS-CoV-2 exposure in the community remains unknown. We determined the prevalence of anti–SARS-CoV-2 immunoglobulin G among blood donors in Kenya in April–June 2020. Crude seroprevalence was 5.6% (174 of 3098). Population-weighted, test-performance-adjusted national seroprevalence was 4.3% (95% confidence interval, 2.9 to 5.8%) and was highest in urban counties Mombasa (8.0%), Nairobi (7.3%), and Kisumu (5.5%). SARS-CoV-2 exposure is more extensive than indicated by case-based surveillance, and these results will help guide the pandemic response in Kenya and across Africa

Seroprevalence of antibodies to SARS-CoV-2 among health care workers in Kenya

Background Few studies have assessed the seroprevalence of antibodies against SARS-CoV-2 among Health Care Workers (HCWs) in Africa. We report findings from a survey among HCWs in three counties in Kenya. Methods We recruited 684 HCWs from Kilifi (rural), Busia (rural) and Nairobi (urban) counties. The serosurvey was conducted between 30th July 2020 and 4th December 2020. We tested for IgG antibodies to SARS-CoV-2 spike protein using ELISA. Assay sensitivity and specificity were 93% (95% CI 88-96%) and 99% (95% CI 98-99.5%), respectively. We adjusted prevalence estimates using Bayesian modeling to account for assay performance. Results Crude overall seroprevalence was 19.7% (135/684). After adjustment for assay performance seroprevalence was 20.8% (95% CrI 17.5-24.4%). Seroprevalence varied significantly (p<0.001) by site: 43.8% (CrI 35.8-52.2%) in Nairobi, 12.6% (CrI 8.8-17.1%) in Busia and 11.5% (CrI 7.2-17.6%) in Kilifi. In a multivariable model controlling for age, sex and site, professional cadre was not associated with differences in seroprevalence. Conclusion These initial data demonstrate a high seroprevalence of antibodies to SARS-CoV-2 among HCWs in Kenya. There was significant variation in seroprevalence by region, but not by cadre

Raltegravir-intensified initial antiretroviral therapy in advanced HIV disease in Africa: A randomised controlled trial

Background In sub-Saharan Africa, individuals infected with HIV who are severely immunocompromised have high mortality (about 10%) shortly after starting antiretroviral therapy (ART). This group also has the greatest risk of morbidity and mortality associated with immune reconstitution inflammatory syndrome (IRIS), a paradoxical response to successful ART. Integrase inhibitors lead to significantly more rapid declines in HIV viral load (VL) than all other ART classes. We hypothesised that intensifying standard triple-drug ART with the integrase inhibitor, raltegravir, would reduce HIV VL faster and hence reduce early mortality, although this strategy could also risk more IRIS events. Methods and findings In a 2×2×2 factorial open-label parallel-group trial, treatment-naive adults, adolescents, and children >5 years old infected with HIV, with cluster of differentiation 4 (CD4) 0.7) and despite significantly greater VL suppression with raltegravir-intensified ART at 4 weeks (343/836 [41.0%] versus 113/841 [13.4%] with standard ART, p < 0.001) and 12 weeks (567/789 [71.9%] versus 415/803 [51.7%] with standard ART, p < 0.001). Through 48 weeks, there was no evidence of differences in mortality (aHR = 0.98 [95% CI 0.76–1.28], p = 0.91); in serious (aHR = 0.99 [0.81–1.21], p = 0.88), grade-4 (aHR = 0.88 [0.71–1.09], p = 0.29), or ART-modifying (aHR = 0.90 [0.63–1.27], p = 0.54) adverse events (the latter occurring in 59 [6.5%] participants with raltegravir-intensified ART versus 66 [7.3%] with standard ART); in events judged compatible with IRIS (occurring in 89 [9.9%] participants with raltegravir-intensified ART versus 86 [9.5%] with standard ART, p = 0.79) or in hospitalisations (aHR = 0.94 [95% CI 0.76–1.17], p = 0.59). At 12 weeks, one and two raltegravir-intensified participants had predicted intermediate-level and high-level raltegravir resistance, respectively. At 48 weeks, the nucleoside reverse transcriptase inhibitor (NRTI) mutation K219E/Q (p = 0.004) and the non-nucleoside reverse transcriptase inhibitor (NNRTI) mutations K101E/P (p = 0.03) and P225H (p = 0.007) were less common in virus from participants with raltegravir-intensified ART, with weak evidence of less intermediate- or high-level resistance to tenofovir (p = 0.06), abacavir (p = 0.08), and rilpivirine (p = 0.07). Limitations of the study include limited clinical, radiological, and/or microbiological information for some participants, reflecting available services at the centres, and lack of baseline genotypes. Conclusions Although 12 weeks of raltegravir intensification was well tolerated and reduced HIV viraemia significantly faster than standard triple-drug ART during the time of greatest risk for early death, this strategy did not reduce mortality or clinical events in this group and is not warranted. There was no excess of IRIS-compatible events, suggesting that integrase inhibitors can be used safely as part of standard triple-drug first-line therapy in severely immunocompromised individuals. Trial registration ClinicalTrials.gov NCT01825031

Agricultural Information Worldwide, vol. 6, 2014

Agricultural Information Worldwide, Volume 6, 2014In this issue: FROM THE EDITOR’S DESK / Jim Morris-Knower (3); Conference Reflections / Antoinette Paris Greider (4). ARTICLES: Keynote Address: The State of Information Literacy Policy: A Global Priority / Sharon Weiner (5); Framing of Climate Change News in Four National Daily Newspapers in Southern Nigeria / Agwu Ekwe Agwu, Chiebonam Justina Amu (11); Access and Use of Information Communication Technologies by Women Staff of Public Extension Service in the North Central Zone of Nigeria / Agwu Ekwe Agwu, Elizabeth Ene Ogbonnah (18); Providing User Preferred Information Resources for a New Faculty of Agriculture, Nnamdi Azikiwe Univeristy, Awka, Nigeria / Chinwe V. Anunobi, Andrew U. Ogbonna (25); Diffusion of Scientific Knowledge in Agriculture: The Case for Africa / Shimelis Assefa, Daniel Gelaw Alemneh, Abebe Rorissa (34); The Use of Social Media in Agricultural Research Workflows in Ghana and Kenya / Justin Chisenga, Richard Kedemi, Joel Sam (48); Towards Mobile Agricultural Information Services in Zimbabwean Libraries: Challenges and Opportunities for Small Sacle Farmers in Utilizing ICTs for Sustainable Food Production / Collence Takaingenhamo Chisita, Thembani Malapela (58); Agriculture and Natural Resource Scientists' Biodiversity Information Needs: Barriers and Facilitators to Use and Access in the U.S. Southeast / Miriam L.E. Steiner Davis, Carol Tenopir, Suzie Allard (66); French Agricultural Research Institute Paves the Way to Open Access: Feedback from CIRAD / Marie-Claude Deboin, Cécile Fovet-Rabot (77); Exploring Relevance of Agro Input Dealers in Disseminating and Communicating of Soil Fertility Management Knowledge: The Case of Siaya and Trans Nzoia Counties, Kenya / T. B. Etyang, J. J. Okello, S. Zingore, P. F. Okoth, F. S. Mairura, A. Mureithi, B. S. Waswa (82); Plantwise Knowledge Bank: Building Sustainable Data and Information Processes to Support Plant Clinics in Kenya / Cambria Finegold, MaryLucy Oronje, Margo C. Leach, Teresia Karanja, Florence Chege, Shaun L.A. Hobbs (96); Innovation in Extension Services for Improved Farmer Access to Agricultural Information in Uganda / Patrick Kasangaki (102); Managing a Web Portal Adapting to New Technologies / Soonho Kim, Kathryn Pace Kincheloe, Yuan Gao, Valdete Berisha (107); Library Outreach to University Farm Staff / Emily MacKenzie, Natalie Waters (114); Enhancing Access to Research in Institutional Repositiories through API / Ryan Miller, Indira Yerramareddy (118); Building Capacity of Smallholder Farmers in Agribusiness and Entrepreneurship Skills in Northern Uganda / Basil Mugonola, Callistus Baliddawa (122); The Data Landscpe of the Coral Triangle / Jeanette Norris (127); Agricultural Information Access Among Smallholder Farmers: Comparative Assessment of Peri-Urban and Rural Settings in Kenya / Dorine Odongo (133); From Local to Global: Launching the New Rangelands West Portals and Database / Jeanne L. Pfander, Barbara S. Hutchinson, Valeria Pesce, Matt Rahr (138); Seed Village Programme: An Innovative Approach for Small Farmers / Dheeraj Singh, M. K. Chaudhary, M. L. Meena, M. M. Roy (143); Transformation of Indian Agricultural Libraries in a Digital and Collaborative Era: A Case Study / Neena Singh, Anil Chikate (147); Collaboration for Impact / Indira Yerramareddy, Luz Marina Alvaré, Katarlah Taylor (157