Investigating the impact of poverty on colonization and infection with drug-resistant organisms in humans: a systematic review

Background Poverty increases the risk of contracting infectious diseases and therefore exposure to antibiotics. Yet there is lacking evidence on the relationship between income and non-income dimensions of poverty and antimicrobial resistance. Investigating such relationship would strengthen antimicrobial stewardship interventions. Methods A systematic review was conducted following Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. PubMed, Ovid, MEDLINE, EMBASE, Scopus, CINAHL, PsychINFO, EBSCO, HMIC, and Web of Science databases were searched in October 2016. Prospective and retrospective studies reporting on income or non-income dimensions of poverty and their influence on colonisation or infection with antimicrobial-resistant organisms were retrieved. Study quality was assessed with the Integrated quality criteria for review of multiple study designs (ICROMS) tool. Results Nineteen articles were reviewed. Crowding and homelessness were associated with antimicrobial resistance in community and hospital patients. In high-income countries, low income was associated with Streptococcus pneumoniae and Acinetobacter baumannii resistance and a seven-fold higher infection rate. In low-income countries the findings on this relation were contradictory. Lack of education was linked to resistant S. pneumoniae and Escherichia coli. Two papers explored the relation between water and sanitation and antimicrobial resistance in low-income settings. Conclusions Despite methodological limitations, the results suggest that addressing social determinants of poverty worldwide remains a crucial yet neglected step towards preventing antimicrobial resistance

Importance of Ethnicity, CYP2B6 and ABCB1 Genotype for Efavirenz Pharmacokinetics and Treatment Outcomes: A Parallel-group Prospective Cohort Study in two sub-Saharan Africa Populations.

We evaluated the importance of ethnicity and pharmacogenetic variations in determining efavirenz pharmacokinetics, auto-induction and immunological outcomes in two African populations. ART naïve HIV patients from Ethiopia (n = 285) and Tanzania (n = 209) were prospectively enrolled in parallel to start efavirenz based HAART. CD4+ cell counts were determined at baseline, 12, 24 and 48 weeks. Plasma and intracellular efavirenz and 8-hydroxyefvairenz concentrations were determined at week 4 and 16. Genotyping for common functional CYP2B6, CYP3A5, ABCB1, UGT2B7 and SLCO1B1 variant alleles were done. Patient country, CYP2B6*6 and ABCB1 c.4036A>G (rs3842A>G) genotype were significant predictors of plasma and intracellular efavirenz concentration. CYP2B6*6 and ABCB1 c.4036A>G (rs3842) genotype were significantly associated with higher plasma efavirenz concentration and their allele frequencies were significantly higher in Tanzanians than Ethiopians. Tanzanians displayed significantly higher efavirenz plasma concentration at week 4 (p<0.0002) and week 16 (p = 0.006) compared to Ethiopians. Efavirenz plasma concentrations remained significantly higher in Tanzanians even after controlling for the effect of CYP2B6*6 and ABCB1 c.4036A>G genotype. Within country analyses indicated a significant decrease in the mean plasma efavirenz concentration by week 16 compared to week 4 in Tanzanians (p = 0.006), whereas no significant differences in plasma concentration over time was observed in Ethiopians (p = 0.84). Intracellular efavirenz concentration and patient country were significant predictors of CD4 gain during HAART. We report substantial differences in efavirenz pharmacokinetics, extent of auto-induction and immunologic recovery between Ethiopian and Tanzanian HIV patients, partly but not solely, due to pharmacogenetic variations. The observed inter-ethnic variations in efavirenz plasma exposure may possibly result in varying clinical treatment outcome or adverse event profiles between populations

3,6-dimethoxyxanthone from 2,2’,4,4’- tetrahydroxy-benzophenone via Microwave-Assisted Annulation

Xanthones are tricyclic aromatic compounds that have multiple pharmacological uses due to their anti-tumor, antioxidant, anti-inflammatory, anti-bacterial, and potentially chemopreventive properties. The target of this research was to optimize a two-step synthesis of 3,6-dimethoxyxanthone (3) from 2,2’,4,4’-tetrahydroxy-benzophenone (1) via microwave-assisted (200 °C, 30-40 min., 150 W) sodium acetate-catalyzed annulation. The product, 3,6-dihydroxyxanthone (2), was then methylated to (3) using dimethyl sulfate (DMS) and sodium carbonate in acetone at reflux. The product yields were 93% (\u3e99% purity) for (2) and 94% (\u3e99% purity) for (3). Characterization was accomplished using 1H NMR, FTIR, melting point, TLC, HPLC, and GCMS. The product (3) was made available for additional screening and research, such as synthesizing dyes like fluorescein and its derivatives

Market Access, Intensification and Productivity of Common Bean in Ethopia: A microeconomic analysis

This work analyses on-farm adjustments in land allocation and intensification in a commercial crop following the increases in market demand in a developing economy. Drawing from the survey conducted among common bean producers in Ethiopia in 2008, a two stage econometric method was used to investigate the contribution of market access and other micro-level factors in facilitating crop intensification and productivity. Ethiopia is the leading commercial producer and exporter of common bean in Africa but also one of the countries in Africa with high levels of soil nutrient depletion. Understanding factors that influence input use and productivity is critical for food security and agricultural sustainability in the country. Based on farm survey data, it was shown that most farmers had expanded their area under common bean but the use of fertilizer and improved varieties was still low. Increase in the intensity of fertilizer and seed use produces an increase in yield and so is market access. Market access has intensification as well as specialization effects on common bean yield. Access to credit, extension and household wealth are other factors that facilitate common bean intensification while risk increasing factors constrain it

Tuberculous lesions not detected by routine abattoir inspection: the experience of the Hossana municipal abattoir, southern Ethiopia

Summary The efficacy of the meat inspection procedures implemented for the detection of tuberculous cattle was evaluated by testing for bovine tuberculosis in 751 animals. The study involved routine inspection at slaughter, collection of tissues for detailed examination in the laboratory, and bacteriological investigation to identify Mycobacterium bovis. Of the 751 carcasses examined, 34 (4.5%) were found to have tuberculous lesions. Routine abattoir inspection detected only 29.4% of the carcasses with visible lesions. Eighty-four percent of the tuberculous lesions were found in the lungs and thoracic lymph nodes, 11.5% in the lymph nodes of the head, and the remaining 4.5% in the mesenteric and other lymph nodes of the carcasses. In addition, M. bovis was isolated from a carcass that presented no gross tuberculosis lesions. The low sensitivity of routine abattoir inspection demonstrates that existing necropsy procedures should be improved

Posterior lamellar versus bilamellar tarsal rotation surgery for trachomatous trichiasis: Long-term outcomes from a randomised controlled trial.

BACKGROUND: We re-examined the participants of a clinical trial four years after enrolment to identify which of the two most commonly used eyelid surgery procedures to treat the blinding stage of trachoma (trachomatous trichiasis, TT), the posterior Lamellar Tarsal Rotation (PLTR) and Billamelar Tarsal Rotation (BLTR), gives better results in the long-term. METHODS: A randomised, controlled, single masked clinical trial was done in Ethiopia. At baseline, adults (aged >18 years with upper lid unoperated TT were recruited from a community-based screening. Participants were randomly assigned (1:1), to either BLTR or PLTR surgery, stratified by surgeon. At 4 years an independent assessor masked to allocation examined the trial participants' eyes using the same procedures as for the baseline and earlier follow-ups. The primary outcome was the proportion of individuals who had recurrence (postoperative TT, PTT) at the 4-year examination, or a history of repeat surgery in the 4-year period. The intervention effect was estimated by logistic regression, controlled for surgeon as a fixed effect in the model. The trial is registered with the Pan African Clinical Trials Registry (number PACTR201401000743135). FINDINGS: 1000 participants with TT were enrolled, randomly assigned, and treated (501 in the BLTR group and 499 in the PLTR group) between Feb 13, 2014, and May 31, 2014. At year 4, 943 (94.3%) participants were re-examined (471, PLTR; 472, BLTR) and included in the primary outcome analysis. PTT had developed in 169/943 (17•9%) study eyes, among which 129 (76•3%) had minor trichiasis (≤5 lashes touching the eye). PTT was significantly more frequent at 4-year in the BLTR arm (105/472 [22•2%]) than the PLTR arm (64/471 [13•6%]), adjusted OR 1•82 (95% CI, 1•29-2•56); p = 0•0006, with 8•6% (95%CI 3•8-13•5) risk difference. INTERPRETATION: The PLTR surgical procedure had superior long-term outcomes to the BLTR with significantly lower risk of PTT supporting the current WHO guideline that the PLTR should be the procedure of choice for training new surgeons in the programmatic management of TT

Antimicrobial Use, Residues, Resistance and Governance in the Food and Agriculture Sectors, Tanzania

All infections are potentially curable as long as the etiological agents are susceptible to antimicrobials. The increased rate at which antimicrobials are becoming ineffective is a global health risk of increasing concern that threatens withdrawal of beneficial antimicrobials for disease control. The increased demand for food of animal origin, in particular eggs, meat and milk has led to intensification and commercial production systems where excessive use and misuse of antimicrobials may prevail. Antimicrobials, handled and used by farmers and animal attendants with no formal education, may be predisposed to incorrect dosages, misuse, incorrect applications and non-adherence to withdrawal periods. This study was conducted to assess the regulatory roles and governance of antimicrobials, establish the pattern and extent of their use, evaluate the antimicrobial residues and resistance in the food animals and crop agriculture value chains, and relate these findings to existing strategies in place for combating the emergence of antimicrobial resistance in Tanzania. A multimethod approach (desk review, field study and interviews) was used. Relevant establishments were also visited. High levels of resistance to penicillin G, chloramphenicol, streptomycin and oxytetracycline have been reported, especially for Actinobacter pyogenes, Staphylococcus hyicus, Staphylococcus intermedius and Staphylococcus aureus from dairy cattle with mastitis and in humans. Similar trends were found in poultry where eggs and meat are contaminated with Escherichia coli strains resistant to amoxicillin + clavulanate, sulphamethoxazole and neomycin. An increasing trend of emerging multidrug resistant E. coli, Klebsiella pneumoniae, Staphylococcus aureus and Salmonella was also found in food animals. An increase in methicillin resistant Staphlococcus aureus (MRSA) and extended-spectrum beta-lactamase (ESBL) in the livestock sector in Tanzania have been reported. The pathogens isolated in animals were resistant to ampicillin, augmentin, gentamicin, co-trimoxazole, tetracycline, amoxicillin, streptomycin, nalidixic acid, azithromycin, chloramphenicol, tylosin, erythromycin, cefuroxime, norfloxacin and ciprofloxacin. An increased usage of antimicrobials for prophylaxis, and therapeutics against pathogens and for growth promotion in livestock, aquaculture and crop production were observed. A One Health strategic approach is advocated to combat antimicrobial resistance (AMR) in the food and agriculture sectors in Tanzania. Practical recommendations include (a) legislation review and implementation" (b) antimicrobial use (AMU), AMR and antimicrobial residue (AR) awareness and advocacy among stakeholders along the value chain" (c) strengthening of surveillance and monitoring programs for AMU, AMR and AR" (d) enhanced development and use of rapid and innovative diagnostic tests and the promotion of biosecurity principles" and (e) good husbandry practices. The utilization of this information to improve public health policies and reduce the burden of AMR will be beneficial

Effect of repeated epilation for minor trachomatous trichiasis on lash burden, phenotype and surgical management willingness: A cohort study.

BACKGROUND: WHO endorsed the use of epilation as an alternative treatment to surgery for the management of both minor unoperated TT (UTT) and postoperative TT (PTT). However, some trachoma control programmes hesitated to implement epilation citing concerns that it would hamper TT surgical acceptance and result in larger numbers of and stiffer trichiatic eyelashes than the original TT lashes. We investigated the burden and phenotypes of post-epilation trichiatic eyelashes, and willingness to accept surgical management separately in unoperated and postoperative TT cases. METHODOLOGY/PRINCIPAL FINDINGS: We recruited cases with minor (≤5 eyelashes from the upper eyelid touching the eye or evidence of epilation in <1/3rd of the upper eyelid) UTT (170) and PTT (169) from community-based screenings in Amhara Region, Ethiopia. Participants eyes were examined and data on present and future willingness to accept surgical management collected at baseline and every month for 6-months. Eyelashes touching the eye were counted and their phenotypes documented. Participants were trained on how to epilate. Epilation was done by the participants at home and by the examiner during follow-ups when requested by the participant. Follow-up rates were ≥97%. There was evidence of a significant reduction in the burden of trichiatic eyelashes in unoperated (mean difference = -0.90 [-1.11- -0.69]; RR = 0.50 [95% CI, 0.40-0.62]; p<0.0001), and postoperative (mean difference = -1.16 [-1.36- -0.95]; RR = 0.38 [95% CI, 0.31-0.48]; p<0.0001) cases 6-month after frequent epilation. Post-epilation trichiatic eyelashes at 6-months had higher odds of being thin (40.2% vs 55.8%, OR = 1.88 [95% CI, 1.21-2.93]; p = 0.0048), weak (39.8% vs 70.8%, OR = 3.68 [95%CI,2.30-5.88]; p<0.0001), and half-length (30.9% vs 43.3%, OR = 1.71 [1.09-2.68]; p = 0.020) than the pre-epilation trichiatic eyelashes in unoperated cases. There was a significant increase in the proportion of weak trichiatic eyelashes (OR = 1.99 [95% CI, 1.03-3.83; p = 0.039) in postoperative cases. In all 6 follow-up time points, 120/164 (73.2%) of unoperated and 134/163 (82.2%) of postoperative cases indicated that they would accept surgery if their trichiasis progressed. CONCLUSIONS/SIGNIFICANCE: In this study setting, frequent epilation neither hampers surgical acceptance nor results in more damaging trichiatic eyelashes than the pre-epilation lashes; and can be used as an alternative to the programmatic management of minor unoperated and postoperative TT cases

Breeding schemes: what are they, how to formalize them, and how to improve them?

Open Access Journal; Published online: 21 Jan 2022Formalized breeding schemes are a key component of breeding program design and a gateway to conducting plant breeding as a quantitative process. Unfortunately, breeding schemes are rarely defined, expressed in a quantifiable format, or stored in a database. Furthermore, the continuous review and improvement of breeding schemes is not routinely conducted in many breeding programs. Given the rapid development of novel breeding methodologies, it is important to adopt a philosophy of continuous improvement regarding breeding scheme design. Here, we discuss terms and definitions that are relevant to formalizing breeding pipelines, market segments and breeding schemes, and we present a software tool, Breeding Pipeline Manager, that can be used to formalize and continuously improve breeding schemes. In addition, we detail the use of continuous improvement methods and tools such as genetic simulation through a case study in the International Institute of Tropical Agriculture (IITA) Cassava east-Africa pipeline. We successfully deploy these tools and methods to optimize the program size as well as allocation of resources to the number of parents used, number of crosses made, and number of progeny produced. We propose a structured approach to improve breeding schemes which will help to sustain the rates of response to selection and help to deliver better products to farmers and consumers

Human milk immune factors, maternal nutritional status, and infant sex: The INSPIRE study

Breastfeeding is an energetically costly and intense form of human parental investment, providing sole-source nutrition in early infancy and bioactive components, including immune factors. Given the energetic cost of lactation, milk factors may be subject to tradeoffs, and variation in concentrations have been explored utilizing the Trivers-Willard hypothesis. As human milk immune factors are critical to developing immune system and protect infants against pathogens, we tested whether concentrations of milk immune factors (IgA, IgM, IgG, EGF, TGFβ2, and IL-10) vary in response to infant sex and maternal condition (proxied by maternal diet diversity [DD] and body mass index [BMI]) as posited in the Trivers-Willard hypothesis and consider the application of the hypothesis to milk composition.This study is supported with funds from the National Science Foundation's INSPIRE Track 1 Grant: What is Normal Milk? Sociocultural, Evolutionary, Environmental, and Microbial Aspects of Human Milk Composition (Award #1344288), National Institutes of Health NICHD R01 HD092297 and the US Department of Agriculture National Institute of Food and Agriculture, Hatch project IDA01643 and in-kind donations from Medela. We sincerely thank the Washington State University Health Equity Center for their support. Additionally, we thank Andrew Doel (Medical Research Council Unit, The Gambia) for field supervision and logistics planning and Alansan Sey for questionnaire administration and taking anthropometric measurements in The Gambia; Jane Odei (University of Ghana) for supervising field data collection in Ghana; Haile Belachew (Hawassa University), and Birhanu Sintayehu for planning and logistics and the administration and staff at Adare Hospital in Hawassa for assistance with logistics in Ethiopia; Catherine O. Sarange (Egerton University) for field supervision and logistics planning and Milka W. Churuge and Minne M. Gachau for recruiting, questionnaire administration, and taking anthropometric measurements in Kenya; Gisella Barbagelatta (Instituto de Investigación Nutricional) for field supervision and logistics planning, Patricia Calderon (Instituto de Investigación Nutricional) for recruiting, questionnaire administration, and taking anthropometric measurements, and Roxana Barrutia (Instituto de Investigación Nutricional) for the management and shipping of samples in Peru; Leónides Fernández, Cristina García-Carral and Irene Espinosa (Complutense University of Madrid) for technical assistance and expertise, and M. Ángeles Checa (Zaragoza, Spain), Katalina Legarra (Guernica, Spain), and Julia Mínguez (Huesca, Spain) for participation in the collection of samples in Spain; Kirsti Kaski and Maije Sjöstrand (both Helsingborg Hospital) for participation in the collection of samples, questionnaire administration, and anthropometric measurements in Sweden; Renee Bridge and Kara Sunderland (both University of California, San Diego); Janae Carrothers and Shelby Hix (Washington State University) for logistics planning, recruiting, questionnaire administration, sample collection, and taking anthropometric measurements in California and Washington; Glenn Miller (Washington State University) for his expertise and critical logistic help that were needed for shipping samples and supplies worldwide.Peer reviewe