Response of giant foxtail and wild proso millet to artificial light quality alteration

Light is an essential requirement for proper plant growth and development. Growth chamber experiments were conducted to determine whether artificial alteration of light quality (reducing the red to far-red ratio-R:FR) differentially affected the growth and development of giant foxtail and wild proso millet, two troublesome annual grass weeds in the United States. Growth phenotypes of both weeds were examined under two R:FR regimes (0.28-reduced R:FR and 1.12-unaltered R:FR) in the absence of competition (control conditions) and under intraspecific and interspecific competition. The reduced R:FR simulated shaded (below-canopy) R:FR conditions in the field while the unaltered R:FR treatment simulated direct sunlight (above-canopy) conditions. Averaged across weed species, reducing the R:FR increased plant height, but reduced tiller production and above-ground biomass under no plant competition (P<0.05). In the presence of competition, reducing the R:FR increased plant height and internode length but reduced the number of tillers and leaf area across weed species. No phenotypic differences were observed for weeds tested under intraspecific or interspecific competition. Our study has shown that the response of both weeds to artificial R:FR alteration is similar to that observed under shaded field conditions. Therefore, by replacing bordering plants with a crop, controlled experiments can be used to test the effect of crop canopies on weed suppression when selecting cultivars to be planted in areas where certain weed species are prevalent, minimizing weed-related yield losses

NIHR Global Health Research Group on Vaccines for vulnerable people in Africa (VAnguard): Concept and Launch event report [version 2; peer review: 2 approved]

Background Vaccination is an important public health intervention, but not everyone benefits equally. Biological, social and structural factors render some communities vulnerable and unable to secure optimal health benefits from vaccination programmes. This drives health inequity and undermines wider vaccine impact by allowing the persistence of non-immune communities as foci for recurrent disease outbreaks. The NIHR Global Health Research Group on Vaccines for vulnerable people in Africa (VAnguard) aims to understand how biological, social, and structural factors interact to impair vaccine impact in vulnerable African communities. Methods The VAnguard project will be implemented through three thematic work packages (1-3) and four cross-cutting work packages (4-7). Work package 1 will investigate the biological drivers and mechanisms of population differences in vaccine responses. Work package 2 will support the understanding of how structural, social and biological determinants of vaccine response interrelate to determine vaccine impact. Work package 3 will synthesise data and lead analyses to develop, model and test community-based integrated strategies to optimise vaccine access, uptake and effectiveness. Work package 4 will plan and implement field investigations (community survey and qualitative studies (with support of work package 2) to explore structural, social & biological determinants impairing vaccine impact. Work package 5 will collaborate with work packages 1-4, to engage communities in designing interventions that aim to directly optimise vaccine impact through a process of co-learning and co-creation between them and the researchers. Work package 6 will build capacity for, and a culture of, consultative, collaborative multidisciplinary vaccine research in East Africa. Work package 7 will support the overall project management and governance. Following the project inception on the 1st of September 2022, project launch was held in November 2022. Conclusion Results from this project will contribute to the development of integrated strategies that will optimise vaccine benefits and drive health equity

On-site construction of a point-of-care low-field MRI system in Africa

PurposeTo describe the construction and testing of a portable point-of-care low-field MRI system on site in Africa. MethodsAll of the components to assemble a 50 mT Halbach magnet-based system, together with the necessary tools, were air-freighted from the Netherlands to Uganda. The construction steps included individual magnet sorting, filling of each ring of the magnet assembly, fine-tuning the inter-ring separations of the 23-ring magnet assembly, gradient coil construction, integration of gradient coils and magnet assembly, construction of the portable aluminum trolley and finally testing of the entire system with an open source MR spectrometer. ResultsWith four instructors and six untrained personnel, the complete project from delivery to first image took approximately 11 days. ConclusionsAn important step in translating scientific developments in the western world from high-income industrialized countries to low- and middle-income countries (LMICs) is to produce technology that can be assembled and ultimately constructed locally. Local assembly and construction are associated with skill development, low costs and jobs. Point-of-care systems have a large potential to increase the accessibility and sustainability of MRI in LMICs, and this work demonstrates that technology and knowledge transfer can be performed relatively seamlessly.Radiolog

Feasibility of a randomized clinical trial evaluating a community intervention for household tuberculosis child contact management in Cameroon and Uganda

Background One of the main barriers of the management of household tuberculosis child contacts is the necessity for parents to bring healthy children to the facility. We assessed the feasibility of a community intervention for tuberculosis (TB) household child contact management and the conditions for its evaluation in a cluster randomized controlled trial in Cameroon and Uganda. Methods We assessed three dimensions of feasibility using a mixed method approach: (1) recruitment capability using retrospective aggregated data from facility registers; (2) acceptability of the intervention using focus group discussions with TB patients and in-depth interviews with healthcare providers and community leaders; and (3) adaptation, integration, and resources of the intervention in existing TB services using a survey and discussions with stakeholders. Results Reaching the sample size is feasible in all clusters in 15 months with the condition of regrouping 2 facilities in the same cluster in Uganda due to decentralization of TB services. Community health worker (CHW) selection and training and simplified tools for contact screening, tolerability, and adherence of preventive therapy were key elements for the implementation of the community intervention. Healthcare providers and patients found the intervention of child contact investigations and TB preventive treatment management in the household acceptable in both countries due to its benefits (competing priorities, transport cost) as compared to facility-based management. TB stigma was present, but not a barrier for the community intervention. Visit schedule and team conduct were identified as key facilitators for the intervention. Conclusions This study shows that evaluating a community intervention for TB child contact management in a cluster randomized trial is feasible in Cameroon and Uganda. Trial registration Clini calTr ials. gov NCT03832023. Registered on February 6th 2019

The effect of intensive praziquantel administration on vaccine-specific responses among schoolchildren in Ugandan schistosomiasis-endemic islands (POPVAC A): an open-label, randomised controlled trial.

BACKGROUND: Vaccine responses differ between populations and are often impaired in rural and low-income settings. The reasons for this are not fully understood, but observational data suggest that the immunomodulating effects of parasitic helminths might contribute. We hypothesised that Schistosoma mansoni infection suppresses responses to unrelated vaccines, and that suppression could be reversed-at least in part-by intensive praziquantel administration. METHODS: We conducted an open-label, randomised controlled trial of intensive versus standard intervention against S mansoni among schoolchildren aged 9-17 years from eight primary schools in Koome islands, Uganda. Children were randomly allocated to either an intensive group or a standard group with a computer-generated 1:1 randomisation using permuted blocks sizes 4, 6, 8, and 10. Participants in the intensive group received three praziquantel doses (approximately 40 mg/kg) 2 weeks apart before first vaccination at week 0, and every 3 months thereafter. Participants in the standard group were given one dose of approximately 40 mg/kg praziquantel after the week 8 primary endpoint. Participants in both groups received the BCG vaccine (Serum Institute of India, Pune, India) at week 0; the yellow fever (Sanofi Pasteur, Lyon, France), oral typhoid (PaxVax, London, UK), and first human papillomavirus (HPV) vaccination (Merck, Rahway, NJ, USA) at week 4; and the HPV booster and tetanus-diphtheria vaccine (Serum Institute of India) at week 28. The primary outcome was vaccine response at week 8 (except for tetanus and diphtheria, which was assessed at week 52). The primary analysis population was participants who were infected with S mansoni at baseline, determined retrospectively using either plasma circulating anodic antigen (CAA) or stool PCR. The safety population comprised all randomly allocated participants. The trial was registered at the ISRCTN Registry (ISRCTN60517191) and is complete. FINDINGS: Between July 9 and Aug 14, 2019, we enrolled 478 participants, with 239 children per group. 276 (58%) participants were male and 202 (42%) participants were female. Among participants who were positive for S mansoni at baseline (171 [72%] in the intensive group and 164 [69%] in the standard group) intensive praziquantel administration significantly reduced pre-vaccination infection intensity (to median 30 CAA pg/mL [IQR 7-223] vs 1317 [243-8562], p<0·001) compared with standard treatment. Intensive praziquantel administration also reduced week 8 HPV-16-specific IgG response (geometric mean ratio 0·71 [95% CI 0·54-0·94], p=0·017), but had no effect on other primary outcomes. Among all participants (regardless of S mansoni status at baseline) intensive praziquantel administration significantly improved week 8 BCG-specific IFNγ ELISpot response (1·20 [1·01-1·43], p=0·038). Recognised adverse effects of praziquantel were reported more frequently in the intensive group. There were no recorded serious adverse events in either group. INTERPRETATION: We show evidence suggesting that praziquantel administration improves the BCG-specific cellular response, but not humoral responses to other vaccines. Despite observational evidence that helminths impair vaccine response, these results show minimal immediate benefits of reducing helminth burden. The effect of longer-term helminth control should be investigated. FUNDING: UK Medical Research Council. TRANSLATION: For the Luganda translation of the abstract see Supplementary Materials section

Red blood cell alloimmunization in sickle cell disease patients in Uganda

BACKGROUND: Blood transfusion is an integral part in the management of sickle cell disease (SCD) patients. Alloimmunization is a recognized complication of red blood cell (RBC) transfusions with consequences including delayed hemolytic transfusion reactions and difficulties in getting compatible blood for future transfusions. The objective of this study was to determine the frequency of RBC alloimmunization in SCD patients in Uganda where pretransfusion screening for alloantibodies is not practiced. STUDY DESIGN AND METHODS: In a cross-sectional study, SCD patients at Mulago Hospital Sickle Cell Clinic, Kampala, Uganda, were investigated. The demographic characteristics and transfusion history were recorded. Blood samples were drawn from consenting, previously transfused patients and RBC alloimmunization was demonstrated using immunohematologic techniques. RESULTS: There were 428 patients (median age, 12 years; female/male ratio, 1.0) and they had received a median of 3 units in a median of three transfusion episodes. Twenty-six patients (6.1%) possessed RBC alloantibodies and 21 (80.7%) of them had received up to 10 transfusions. A total of 30 alloantibodies was found; 20 (66.7%) and 5 (16.6%) belonged to Rh and MNS blood groups, respectively. Five of the alloimmunized patients had multiple antibodies. CONCLUSIONS: The rate of RBC alloimmunization in Ugandan SCD patients was 6.1%. The homogeneity between donors and SCD patients plus the low transfusion load may explain this immunization frequency. Nevertheless, our study confirms the significance of RBC alloimmunization as a complication in Ugandan SCD patients. Therefore, there is need to improve immunohematologic testing in Uganda so that RBC alloimmunization and its consequences may be prevented.Stemcel biology/Regenerative medicine (incl. bloodtransfusion

Beyond clinical trials: Crosssectional associations of combination antiretroviral therapy with reports of multiple symptoms and nonadherence among adolescents in South Africa

Background. Studies investigating symptoms associated with combination antiretroviral therapy (cART) use among adolescents in resource-limited settings are rare beyond clinical trials. Identifying adolescents at risk of non-adherence is imperative for HIV/AIDS programming and controlling the epidemic in this key population.Objective. To examine which cART regimens were associated with reports of multiple symptoms and past-week non-adherence in a large community-traced sample of HIV-positive adolescents in South Africa (SA).Methods. A total of 1 175 HIV-positive ART-experienced adolescents aged 10 - 19 years attending 53 health facilities in the Eastern Cape Province, SA, were interviewed in 2014 - 2015. Ninety percent (n=1 059) were included in the study. Adolescents who reported no medication use and those with unclear or missing data were excluded from further analysis, resulting in a sample for analysis of n=501. Outcomes were reports of multiple symptoms (three or more symptoms in the past 6 months) and past-week ART non-adherence (&lt;95% correct doses in the past week). Multivariable logistic regression analyses controlled for sociodemographic and HIV-related covariates in Stata 13/IC.Results. Of the adolescents included, 54.3% were female. The median age was 14 (interquartile range 12 - 16) years, and 66.5% were vertically infected. The prevalence of multiple symptoms was 59.7% (95% confidence interval (CI) 55.3 - 63.9). Independent of covariates, stavudine (d4T)-containing cART regimens and the fixed-dose combination of tenofovir (TDF) + emtricitabine (FTC) + efavirenz (EFV) were associated with more reports of multiple symptoms (adjusted odds ratio (aOR) 3.38; 95% CI 1.19 - 9.60 and aOR 2.67; 95% CI 1.21 - 5.88, respectively). Lopinavir/ritonavir (LPV/r)-containing regimens were associated with fewer reports of multiple symptoms (aOR 0.47; 95% CI 0.21 - 1.04). For EFV-based regimens, adolescents on d4T + lamivudine (3TC) + EFV were more likely to report multiple symptoms than those on TDF + FTC + EFV or those on abacavir (ABC) + 3TC + EFV (aOR 3.26; 95% CI 1.01 - 10.52, aOR 2.86; 95% CI 1.35 - 6.05 and aOR 1.08; 95% CI 0.64 - 1.82, respectively). However, only TDF + FTC + EFV cART was associated with lower levels of non-adherence among participants (aOR 0.44; 95% CI 0.21 - 0.93).Conclusions. Rates of multiple symptoms among HIV-positive ART-experienced adolescents were high. d4T-containing regimens and TDF + FTC + EFV were associated with more reports of multiple symptoms, whereas LPV/r-containing regimens were associated with fewer reports. However, adolescents on TDF + FTC + EFV were the most adherent subgroup. These findings support the World Health Organization-recommended discontinuation of d4T use, but also underscore the dilemma faced by clinicians when choosing between low-toxicity regimens and those that promote ART adherence, particularly among HIV-positive adolescents.Â