A one health approach to strengthening antimicrobial stewardship in Wakiso District, Uganda

Antimicrobial stewardship (AMS), as one of the global strategies to promote responsible use of antimicrobials to prevent antimicrobial resistance (AMR), remains poor in many low-and middle-income countries (LMICs). We implemented a project aimed at strengthening AMS in Wakiso district, Uganda using a One Health approach. A total of 86 health practitioners (HPs), including animal health workers, and 227 community health workers (CHWs) participated in training workshops, and over 300 pupils from primary schools were sensitized on AMR, AMS, and infection prevention and control (IPC). We further established two multidisciplinary online communities of practice (CoPs) for health professionals and students, with a current membership of 321 and 162, respectively. In addition, a Medicine and Therapeutics Committee (MTC) was set up at Entebbe Regional Referral Hospital. The project evaluation, conducted three months after training, revealed that the majority of the HPs (92.2%) and CHWs (90.3%) reported enhanced practices, including improved hand washing (57.3% and 81.0%, respectively). In addition, 51.5% of the HPs reported a reduction in the quantity of unnecessary antibiotics given per patient. This project demonstrates that AMS interventions using a One Health approach can promote understanding of the prudent use of antimicrobials and improve practices at health facilities and in communities

Factors affecting actualisation of the WHO breastfeeding recommendations in urban poor settings in Kenya

Poor breastfeeding practices are widely documented in Kenya, where only a third of children are exclusively breastfed for 6 months and only 2% in urban poor settings. This study aimed to better understand the factors that contribute to poor breastfeeding practices in two urban slums in Nairobi, Kenya. In-depth interviews (IDIs), focus group discussions (FGDs) and key informant interviews (KIIs) were conducted with women of childbearing age, community health workers, village elders and community leaders and other knowledgeable people in the community. A total of 19 IDIs, 10 FGDs and 11 KIIs were conducted, and were recorded and transcribed verbatim. Data were coded in NVIVO and analysed thematically. We found that there was general awareness regarding optimal breastfeeding practices, but the knowledge was not translated into practice, leading to suboptimal breastfeeding practices. A number of social and structural barriers to optimal breastfeeding were identified: (1) poverty, livelihood and living arrangements; (2) early and single motherhood; (3) poor social and professional support; (4) poor knowledge, myths and misconceptions; (5) HIV; and (6) unintended pregnancies. The most salient of the factors emerged as livelihoods, whereby women have to resume work shortly after delivery and work for long hours, leaving them unable to breastfeed optimally. Women in urban poor settings face an extremely complex situation with regard to breastfeeding due to multiple challenges and risk behaviours often dictated to them by their circumstances. Macro-level policies and interventions that consider the ecological setting are needed

Polarimetric geometric modeling for mm-VLBI observations of black holes

The Event Horizon Telescope (EHT) is a millimeter very long baseline interferometry (VLBI) array that has imaged the apparent shadows of the supermassive black holes M87* and Sagittarius A*. Polarimetric data from these observations contain a wealth of information on the black hole and accretion flow properties. In this work, we develop polarimetric geometric modeling methods for mm-VLBI data, focusing on approaches that fit data products with differing degrees of invariance to broad classes of calibration errors. We establish a fitting procedure using a polarimetric "m-ring" model to approximate the image structure near a black hole. By fitting this model to synthetic EHT data from general relativistic magnetohydrodynamic models, we show that the linear and circular polarization structure can be successfully approximated with relatively few model parameters. We then fit this model to EHT observations of M87* taken in 2017. In total intensity and linear polarization, the m-ring fits are consistent with previous results from imaging methods. In circular polarization, the m-ring fits indicate the presence of event-horizon-scale circular polarization structure, with a persistent dipolar asymmetry and orientation across several days. The same structure was recovered independently of observing band, used data products, and model assumptions. Despite this broad agreement, imaging methods do not produce similarly consistent results. Our circular polarization results, which imposed additional assumptions on the source structure, should thus be interpreted with some caution. Polarimetric geometric modeling provides a useful and powerful method to constrain the properties of horizon-scale polarized emission, particularly for sparse arrays like the EHT

Dysregulation of the haem-haemopexin axis is associated with severe malaria in a case-control study of Ugandan children.

BACKGROUND: Malaria is associated with haemolysis and the release of plasma haem. Plasma haem can cause endothelial injury and organ dysfunction, and is normally scavenged by haemopexin to limit toxicity. It was hypothesized that dysregulation of the haem-haemopexin pathway contributes to severe and fatal malaria infections. METHODS: Plasma levels of haemin (oxidized haem), haemopexin, haptoglobin, and haemoglobin were quantified in a case-control study of Ugandan children with Plasmodium falciparum malaria. Levels at presentation were compared in children with uncomplicated malaria (UM; n = 29), severe malarial anaemia (SMA; n = 27) or cerebral malaria (CM; n = 31), and evaluated for utility in predicting fatal (n = 19) vs non-fatal (n = 39) outcomes in severe disease. A causal role for haemopexin was assessed in a pre-clinical model of experimental cerebral malaria (ECM), following disruption of mouse haemopexin gene (hpx). Analysis was done using Kruskall Wallis tests, Mann-Whitney tests, log-rank tests for survival, and repeated measures ANOVA. RESULTS: In Ugandan children presenting with P. falciparum malaria, haemin levels were higher and haemopexin levels were lower in SMA and CM compared to children with UM (haemin, p \u3c 0.01; haemopexin, p \u3c 0.0001). Among all cases of severe malaria, elevated levels of haemin and cell-free haemoglobin at presentation were associated with subsequent mortality (p \u3c 0.05). Compared to ECM-resistant BALB/c mice, susceptible C57BL/6 mice had lower circulating levels of haemopexin (p \u3c 0.01), and targeted deletion of the haemopexin gene, hpx, resulted in increased mortality compared to their wild type littermates (p \u3c 0.05). CONCLUSIONS: These data indicate that plasma levels of haemin and haemopexin measured at presentation correlate with malaria severity and levels of haemin and cell-free haemoglobin predict outcome in paediatric severe malaria. Mechanistic studies in the ECM model support a causal role for the haem-haemopexin axis in ECM pathobiology

Interaction forces between particles stabilized by a hydrophobically modified inulin surfactant.

Submitted versio

Designed to fail? Revisiting Uganda’s maternal health policies to understand policy design issues underpinning missed targets for reduction of maternal mortality ratio (MMR): 2000-2015

Background: Despite Uganda and other sub-Saharan African countries missing their maternal mortality ratio (MMR) targets for Millennium Development Goal (MDG) 5, limited attention has been paid to policy design in the literature examining the persistence of preventable maternal mortality. This study examined the specific policy interventions designed to reduce maternal deaths in Uganda and identified particular policy design issues that underpinned MDG 5 performance. We suggest a novel prescriptive and analytical (re)conceptualization of policy in terms of its fidelity to ‘3Cs’ (coherence of design, comprehensiveness of coverage and consistency in application) that could have implications for future healthcare programming. Methods: We conducted a retrospective study. Sixteen Ugandan maternal health policy documents and 21 national programme performance reports were examined, and six key informant interviews conducted with national stakeholders managing maternal health programmes during the reference period 2000-2015. We applied the analytical framework of the ‘three delay model’ combined with a broader literature on ‘policy mixing.’ Results: Despite introducing fourteen separate policy instruments over 15 years with the goal of reducing maternal mortality, by the end of the MDG period in 2015, only 87.5% of the interventions for the three delays were covered with a notable lack of coherence and consistency evident among the instruments. The three delays persisted at the frontline with 70% of deaths by 2014 attributed to failures in referral policies while 67% of maternal deaths were due to inadequacies in healthcare facilities and trained personnel in the same period. By 2015, 37.3% of deaths were due to transportation issues. Conclusion: The piecemeal introduction of additional policy instruments frequently distorted existing synergies among policies resulting in persistence of the three delays and missed MDG 5 target. Future policy reforms should address the ‘three delays’ but also ensure fidelity of policy design to coherence, comprehensiveness and consistency

Risk factors of virologic failure and slow response to art among HIV-infected children and adolescents in Nairobi

Background: Antiretroviral therapy (ART) in resource-limited settings is effective when backed up with adequate clinical, immunological, and virologic monitoring. Undetected, virologic failure results in increased HIV-1 drug resistance mutations (DRMs), morbidity and mortality, or the need for costly second-line and third-line ART.Objective: To evaluate the prevalence, patterns, and risk factors of virologic failure and slow response to ART, among children and adolescents in resource-limited settings in Nairobi, Kenya.Design: A Retrospective study.Setting: The 8 Lea Toto Programme (LTP) Clinics in Dagoretti, Dandora, Kangemi, Kariobangi, Kawangware, Kibera, Mukuru, and Zimmerman areas of Nairobi. Subjects: One hundred and forty-six HIV-infected children and adolescents aged 1 month to 19 years of the LTP in Nairobi Kenya. Medical and demographic data including, HIV-1 viral loads, information on adherence to ART, HIV-1 DRMs and other key determinants of virologic failure, collected over a period of 2 years, was used for this study.Results: A threshold of 1,000 HIV RNA copies/ml was used to determine treatment outcome. The virologic failure rates in this cohort were 43.8% after 6 months, 32.2% after 12 months, 28.8% after 18 months, and 24.0% after 24 months of first-line ART. Twelve (8.2%) of 146 children showed a slow response to ART: they initially failed ART at 12 months, but had treatment success after 18 to 24 months. The rates of virologic rebound were 4 (2.7%) after 18 months and 3 (2.1%) after 24 months of ART. Multivariate Cox proportional hazards regression revealed that children with suboptimal adherence to ART were 37 times more likely to experience virologic failure (P = 0.000003).Conclusions: This study showed that ART implementation in resource-limited settings is effective when regular virologic monitoring, adherence counselling, and HIV-DR testing are available. Secondly, adherence to ART is a strong predictor of treatment outcome for children and adolescents in resourcelimited settings. Therefore, methods of optimizing adherence levels should be explored and implemented

Resistance of andean beans and advanced breeding lines to root rots in Uganda

Root rots cause severe yield losses of up to >70% in common bean ( Phaseolus vulgaris L.) in most parts of the world, with devastating effects on the major commercial bean cultivars in East and Central Africa. Increased intensity of droughts and rains, and higher temperatures influence the occurrence and distribution of root rots, resulting in increased epidemics. The causal pathogens tend to occur in a complex, and since most cultivars do not have broad resistance, adverse effects continue to occur. The objective of this study was to evaluate the levels of dual resistance of new breeding lines (BL) developed for root rot resistance, as well as Andean (ADP) genotypes, for resistance to Fusarium (FRR) and Pythium root rots (PRR). Altogether, 316 new BL developed for root rot resistance and 295 ADP bean genotypes were evaluated at Kawanda in Uganda. There were significant differences (P<0.05) among genotypes for both root rots and yield. Thirty and 1.9 percent of the BL and ADP genotypes expressed resistance to both root rots. In addition, more than 80% of ADP genotypes showed susceptibility to both root rots. Yield was generally poor with means of 458 kg ha-1 for ADP, and ranging from 949 to 1075 kg ha-1 for the BL groups. Nonetheless, the 0.3 and 2.4% of the ADP and BL that yielded >2000 kg ha-1 expressed high yield potential, considering that majority of the genotypes yielded below 1000 kg ha-1.Les pourritures des raciness de haricot ( Phaseolus vulgaris L.) causent plus 70% de pertes de rendement allant dans la plupart des r\ue9gions du monde, avec des effets d\ue9vastateurs sur les principaux cultivars de haricots commerciaux en Afrique orientale et centrale. L\u2019 augmentation de l\u2018 intensit\ue9 des s\ue9cheresses et des precipitations et les temp\ue9ratures plus \ue9lev\ue9es influencent l\u2019apparition et la distribution des pourritures des racines, ce qui entra\ueene une augmentation des \ue9pid\ue9mies. Les agents pathog\ue8nes causaux ont tendance d\u2018 appara\ueetre dans un complexe, et comme la plupart des cultivars n\u2019ont pas une large r\ue9sistance, des effets ind\ue9sirables continuent d\u2018 appara\ueetre. L\u2019objectif de cette \ue9tude \ue9tait d\u2019\ue9valuer les niveaux de double r\ue9sistance des nouvelles lign\ue9es de s\ue9lection (BL) d\ue9velopp\ue9es pour la r\ue9sistance \ue0 la pourriture des racines, ainsi que les g\ue9notypes andins (ADP), pour la r\ue9sistance \ue0 la pourriture des raciness caus\ue9e par Fusarium (FRR) et Pythium (PRR). Au total de 316 nouveaux BL d\ue9velopp\ue9s pour la r\ue9sistance \ue0 la pourriture des racines et 295 g\ue9notypes de haricot ADP ont \ue9t\ue9 \ue9valu\ue9s \ue0 Kawanda en Ouganda. Il y avait des diff\ue9rences significatives (P <0,05) entre les g\ue9notypes pour les pourritures des racines et le rendement. Trente et 1,9 pour cent des g\ue9notypes BL et ADP ont montr\ue9 une r\ue9sistance pour deux raciness pourries. De plus, plus de 80% des g\ue9notypes d\u2019ADP ont montr\ue9 une susceptibilit\ue9 pour deux raciness pourries. Le rendement \ue9tait g\ue9n\ue9ralement m\ue9diocre avec des moyennes de 458 kg ha-1 pour l\u2019ADP, et allant de 949 \ue0 1075 kg ha-1 pour les groupes BL. N\ue9anmoins, les 0,3 et 2,4% d\u2019ADP et de BL qui ont donn\ue9 plus de 2000 kg ha-1 ont montr\ue9 un potentiel de rendement \ue9lev\ue9, \ue9tant donn\ue9 que la majorit\ue9 des g\ue9notypes ont produit moins de 1000 kg ha-1

Datos abiertos en un mundo de grandes datos. Un acuerdo internacional ICSU-IAP-ISSC-TWAS

The four organizations representing international science (International Council for Science - ICSU, The InterAcademy Partnership – IAP, The World Academy of Sciences – TWAS y el International Social Science Council – ISSC) present this Agreement proposing fundamental principles that must be adopted by scientists, research institutions, academic publishers, research funding agencies, science associations and digital repositories, to respond to the opportunities and challenges of the data revolution as today´s predominant issue for global science policy. This Accord adds the distinctive voice of the scientific community to those of governments and inter-governmental bodies that have made the case for open data as a fundamental pre-requisite in maintaining the rigour of scientific inquiry and maximising public benefit from the data revolution in both developed and developing countries