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Neurodegenerative disorders, including Alzheimer’s disease (AD) and Parkinson’s disease (PD), represent debilitating conditions with complex, poorly understood pathologies. Epichaperomes, pathologic protein assemblies nucleated on key chaperones, have emerged as critical players in the molecular dysfunction underlying these disorders. In this study, we introduce the synthesis and characterization of clickable epichaperome probes, PU-TCO, positive control, and PU-NTCO, negative control. Through comprehensive in vitro assays and cell-based investigations, we establish the specificity of the PU-TCO probe for epichaperomes. Furthermore, we demonstrate the efficacy of PU-TCO in detecting epichaperomes in brain tissue with a cellular resolution, underscoring its potential as a valuable tool for dissecting single-cell responses in neurodegenerative diseases. This clickable probe is therefore poised to address a critical need in the field, offering unprecedented precision and versatility in studying epichaperomes and opening avenues for novel insights into their role in disease pathology.

In agriculture, soil is a vital element that decides the quality and yield of agricultural produce. Soil consists of various nutrients such as nitrogen (N), phosphorous (P), potassium (K), the potential of hydrogen (pH), and water content. Nitrogen is responsible for building chlorophyll, which helps produce proteins and thus directly contributes to plant growth and development. Phosphorous is needed to develop root systems and flowers, whereas potassium helps increase disease resistance. Each of these play a role in crop cultivation. Thus, in this research paper, considering the fact that soil health will provide farmers with the best selection of crops that are compatible with their farm’s soil nutrients, we propose an algorithm for recommending a set of suitable crops based on various soil attributes. These soil nutrients can be collected in real-time using soil sensors, such as N, P, K, and pH, and humidity sensors. They can be deployed in farms where the cultivation takes place. These sensor readings would then be transferred to the blockchain layer, thereby validating the data and ensuring it is tamper-proof and evident. The crop recommendation model uses data from these sensors in real-time, increasing the results’ accuracy. The last stage leads us to display these results via a user dashboard, which helps the farmers to keep in check with their farm’s practices, and their sensor states from remote locations.

Abstract Background Elite controllers (EC) are a rare subset of HIV infected individuals who control viral load below 50 copies/ml of plasma without treatment. Methods Thirty four EC were studied. The slope of CD4 count change was available for 25 of these subjects. We assessed immune activation by measuring the percent of CD38+HLA-DR+CD8+ T cells in the EC group and comparing it with that in 24 treatment-naïve HIV disease progressors and 13 HIV uninfected healthy controls. Results Compared to HIV uninfected subjects, EC had higher percentages of CD38+HLA-DR+CD8+ T cells (p < 0.001) that was lower than that observed in progressors (p < 0.01). Fifteen of 25 EC had a slope of CD4 count change that was not significantly different from 0 while 3 had a positive and 7 a negative CD4 count slope. Immune activation did not distinguish EC subsets with stable/increasing versus declining CD4 counts. Conclusions Elevated immune activation in ECs is not associated with a faster rate of CD4 decline

Abstract Background Routine malaria surveillance data in Africa primarily come from public health facilities reporting to national health management information systems. Although information on gender is routinely collected from patients presenting to these health facilities, stratification of malaria surveillance data by gender is rarely done. This study evaluated gender difference among patients diagnosed with parasitological confirmed malaria at public health facilities in Uganda. Methods This study utilized individual level patient data collected from January 2020 through April 2021 at 12 public health facilities in Uganda and cross-sectional surveys conducted in target areas around these facilities in April 2021. Associations between gender and the incidence of malaria and non-malarial visits captured at the health facilities from patients residing within the target areas were estimated using poisson regression models controlling for seasonality. Associations between gender and data on health-seeking behaviour from the cross-sectional surveys were estimated using poisson regression models controlling for seasonality. Results Overall, incidence of malaria diagnosed per 1000 person years was 735 among females and 449 among males (IRR = 1.72, 95% CI 1.68–1.77, p

Abstract Background The growing burden of diabetes mellitus (DM) and hypertension (HTN) on the background of endemic Human Immuno-deficiency Virus (HIV) and tuberculosis (TB) is a concern in low- and middle-income countries. We aimed to describe annual trends in admissions, mortality rates and premature mortality (years of potential life lost—YPLLs) due to HIV, tuberculosis (TB), diabetes mellitus (DM) and hypertension (HTN) in Uganda. Methods We conducted a retrospective cohort study, retrieving electronic records of adults admitted to Mulago and Kiruddu national referral hospitals medical wards between 1st January 2011 and 31st December 2019. We used STATA BE 17.0 and GraphPad Prism 8.0.2 to compute total admissions, inpatient crude mortality rates, and YPLLs; and demonstrate trends using Mann–Kendall test. Results Of 108,357 admissions, 55,620 (51.3%) were female, 15,300 (14.1%) were recorded in 2012, and 22,997 (21.2%) were aged 21–30 years. HIV, TB, DM and HTN accounted for 26,021 (24.0%); 9537 (8.8%); 13,708 (12.7) and 13,252 (12.2%) of all admissions, respectively. Overall inpatient mortality was 16.7% (18,099/108,357), 53.5% (9674/18,099) were male, 21.5% (3898) were aged 31–40 years and 2597 (14.4%) were registered in 2013. HIV, TB, DM and HTN accounted for 35.6% (6444), 14.6% (2646), 9.1% (1648) and 11.8% (2142) of all deaths, respectively. Total admissions (Kendall’s tau-B = − 0.833, p

Abstract Background Environmental factors such as temperature, rainfall, and vegetation cover play a critical role in malaria transmission. However, quantifying the relationships between environmental factors and measures of disease burden relevant for public health can be complex as effects are often non-linear and subject to temporal lags between when changes in environmental factors lead to changes in malaria incidence. The study investigated the effect of environmental covariates on malaria incidence in high transmission settings of Uganda. Methods This study leveraged data from seven malaria reference centres (MRCs) located in high transmission settings of Uganda over a 24-month period. Estimates of monthly malaria incidence (MI) were derived from MRCs’ catchment areas. Environmental data including monthly temperature, rainfall, and normalized difference vegetation index (NDVI) were obtained from remote sensing sources. A distributed lag nonlinear model was used to investigate the effect of environmental covariates on malaria incidence. Results Overall, the median (range) monthly temperature was 30 °C (26–47), rainfall 133.0 mm (3.0–247), NDVI 0.66 (0.24–0.80) and MI was 790 per 1000 person-years (73–3973). Temperature of 35 °C was significantly associated with malaria incidence compared to the median observed temperature (30 °C) at month lag 2 (IRR: 2.00, 95% CI: 1.42–2.83) and the increased cumulative IRR of malaria at month lags 1–4, with the highest cumulative IRR of 8.16 (95% CI: 3.41–20.26) at lag-month 4. Rainfall of 200 mm significantly increased IRR of malaria compared to the median observed rainfall (133 mm) at lag-month 0 (IRR: 1.24, 95% CI: 1.01–1.52) and the increased cumulative IRR of malaria at month lags 1–4, with the highest cumulative IRR of 1.99(95% CI: 1.22–2.27) at lag-month 4. Average NVDI of 0.72 significantly increased the cumulative IRR of malaria compared to the median observed NDVI (0.66) at month lags 2–4, with the highest cumulative IRR of 1.57(95% CI: 1.09–2.25) at lag-month 4. Conclusions In high-malaria transmission settings, high values of environmental covariates were associated with increased cumulative IRR of malaria, with IRR peaks at variable lag times. The complex associations identified are valuable for designing strategies for early warning, prevention, and control of seasonal malaria surges and epidemics.

Abstract Background People living with HIV (PLHIV) have an increased risk of developing active tuberculosis (TB). To reduce the burden of TB among PLHIV, the World Health Organization (WHO) recommends systematic TB screening followed by (1) confirmatory TB testing for all who screen positive and (2) TB preventive therapy (TPT) for all TPT-eligible PLHIV who screen negative. Symptom-based screening remains the standard of care in most high TB burden settings, including Uganda. Despite having high sensitivity for active TB among antiretroviral-naïve PLHIV, symptom screening has poor specificity; as such, many high-risk PLHIV without active TB are not referred for TPT. C-reactive protein (CRP) is a promising alternative strategy for TB screening that has comparable sensitivity and higher specificity than symptom screening, and was endorsed by WHO in 2021. However, the impact of CRP-based TB screening on TB burden for PLHIV remains unclear. Methods TB SCRIPT (TB Screening Improves Preventive Therapy Uptake) is a phase 3, multi-center, single-blinded, individual (1:1) randomized controlled trial evaluating the effectiveness of CRP-based TB screening on clinical outcomes of PLHIV. The trial aims to compare the effectiveness of a TB screening strategy based on CRP levels using a point-of-care (POC) assay on 2-year TB incidence and all-cause mortality (composite primary trial endpoint) and prevalent TB case detection and uptake of TPT (intermediate outcomes), relative to symptom-based TB screening (current practice). Discussion This study will be critical to improving selection of eligible PLHIV for TPT and helping guide the scale-up and integration of TB screening and TPT activities. This work will enable the field to improve TB screening by removing barriers to TPT initiation among eligible PLHIV, and provide randomized evidence to inform and strengthen WHO guidelines. Trial registration ClinicalTrials.gov NCT04557176. Registered on September 21, 2020.

Coronavirus disease has taken a toll on everyone's lives either physically or emotionally throughout the world. One of the most serious complications occurring currently in covid-positive and recovered patients is the deadly invasive mucormycosis. There are five clinical types of mucormycosis, out of which rhino-orbito-cerebral is the most common form (44%–49%). Management includes early diagnosis, control of the underlying diseases, and aggressive medical and surgical intervention. In patients undergoing maxillectomies, the use of immediate surgical obturators has become the gold standard. The rationale for its use is threefold—functional (matrix for the surgical dressing; allows the patient to speak and swallow), hygienic (separates the maxillary surgical site from contents of the oral cavity), and psychological (restores patient's self-image by reproducing lost oral structure). This article includes two case reports of patients diagnosed with rhinocerebral mucormycosis. The surgical debridement, medical management, and immediate reconstruction using palatal obturators have been explained.

Abstract Background Several repurposed drugs such as hydroxychloroquine (HCQ) have been investigated for treatment of COVID-19, but none was confirmed to be efficacious. While in vitro studies have demonstrated antiviral properties of HCQ, data from clinical trials were conflicting regarding its benefit for COVID-19 treatment. Drugs that limit viral replication may be beneficial in the earlier course of the disease thus slowing progression to severe and critical illness. Design We conducted a randomized open label Phase II clinical trial from October–December 2020. Methods Patients diagnosed with COVID-19 using RT-PCR were included in the study if they were 18 years and above and had a diagnosis of COVID-19 made in the last 3 days. Patients were randomized in blocks, to receive either HCQ 400 mg twice a day for the first day followed by 200 mg twice daily for the next 4 days plus standard of care (SOC) treatment or SOC treatment alone. SARS COV-2 viral load (CT values) from RT-PCR testing of samples collected using nasal/orapharyngeal swabs was performed at baseline, day 2, 4, 6, 8 and 10. The primary outcome was median time from randomization to SARS COV-2 viral clearance by day 6. Results Of the 105 participants enrolled, 55 were assigned to the intervention group (HCQ plus SOC) and 50 to the control group (SOC only). Baseline characteristics were similar across treatment arms. Viral clearance did not differ by treatment arm, 20 and 19 participants respectively had SARS COV-2 viral load clearance by day 6 with no significant difference, median (IQR) number of days to viral load clearance between the two groups was 4(3–4) vs 4(2–4): p = 0.457. There were no significant differences in secondary outcomes (symptom resolution and adverse events) between the intervention group and the control group. There were no significant differences in specific adverse events such as elevated alkaline phosphatase, prolonged QTc interval on ECG, among patients in the intervention group as compared to the control group. Conclusion Our results show that HCQ 400 mg twice a day for the first day followed by 200 mg twice daily for the next 4 days was safe but not associated with reduction in viral clearance or symptom resolution among adults with COVID-19 in Uganda. Trial registration: NCT04860284.

Abstract Background In March 2020, the government of Uganda implemented a strict lockdown policy in response to the COVID-19 pandemic. Interrupted time series analysis (ITSA) was performed to assess whether major changes in outpatient attendance, malaria burden, and case management occurred after the onset of the COVID-19 epidemic in rural Uganda. Methods Individual level data from all outpatient visits collected from April 2017 to March 2021 at 17 facilities were analysed. Outcomes included total outpatient visits, malaria cases, non-malarial visits, proportion of patients with suspected malaria, proportion of patients tested using rapid diagnostic tests (RDTs), and proportion of malaria cases prescribed artemether-lumefantrine (AL). Poisson regression with generalized estimating equations and fractional regression was used to model count and proportion outcomes, respectively. Pre-COVID trends (April 2017-March 2020) were used to predict the’expected’ trend in the absence of COVID-19 introduction. Effects of COVID-19 were estimated over two six-month COVID-19 time periods (April 2020-September 2020 and October 2020–March 2021) by dividing observed values by expected values, and expressed as ratios. Results A total of 1,442,737 outpatient visits were recorded. Malaria was suspected in 55.3% of visits and 98.8% of these had a malaria diagnostic test performed. ITSA showed no differences between observed and expected total outpatient visits, malaria cases, non-malarial visits, or proportion of visits with suspected malaria after COVID-19 onset. However, in the second six months of the COVID-19 time period, there was a smaller mean proportion of patients tested with RDTs compared to expected (relative prevalence ratio (RPR) = 0.87, CI (0.78–0.97)) and a smaller mean proportion of malaria cases prescribed AL (RPR = 0.94, CI (0.90–0.99)). Conclusions In the first year after the COVID-19 pandemic arrived in Uganda, there were no major effects on malaria disease burden and indicators of case management at these 17 rural health facilities, except for a modest decrease in the proportion of RDTs used for malaria diagnosis and the mean proportion of malaria cases prescribed AL in the second half of the COVID-19 pandemic year. Continued surveillance will be essential to monitor for changes in trends in malaria indicators so that Uganda can quickly and flexibly respond to challenges imposed by COVID-19.

Abstract Background In Uganda, artemether-lumefantrine (AL) is first-line therapy and dihydroartemisinin-piperaquine (DP) second-line therapy for the treatment of uncomplicated malaria. This study evaluated the efficacy and safety of AL and DP in the management of uncomplicated falciparum malaria and measured the prevalence of molecular markers of resistance in three sentinel sites in Uganda from 2018 to 2019. Methods This was a randomized, open-label, phase IV clinical trial. Children aged 6 months to 10 years with uncomplicated falciparum malaria were randomly assigned to treatment with AL or DP and followed for 28 and 42 days, respectively. Genotyping was used to distinguish recrudescence from new infection, and a Bayesian algorithm was used to assign each treatment failure a posterior probability of recrudescence. For monitoring resistance, Pfk13 and Pfmdr1 genes were Sanger sequenced and plasmepsin-2 copy number was assessed by qPCR. Results There were no early treatment failures. The uncorrected 28-day cumulative efficacy of AL ranged from 41.2 to 71.2% and the PCR-corrected cumulative 28-day efficacy of AL ranged from 87.2 to 94.4%. The uncorrected 28-day cumulative efficacy of DP ranged from 95.8 to 97.9% and the PCR-corrected cumulative 28-day efficacy of DP ranged from 98.9 to 100%. The uncorrected 42-day efficacy of DP ranged from 73.5 to 87.4% and the PCR-corrected 42-day efficacy of DP ranged from 92.1 to 97.5%. There were no reported serious adverse events associated with any of the regimens. No resistance-associated mutations in the Pfk13 gene were found in the successfully sequenced samples. In the AL arm, the NFD haplotype (N86Y, Y184F, D1246Y) was the predominant Pfmdr1 haplotype, present in 78 of 127 (61%) and 76 of 110 (69%) of the day 0 and day of failure samples, respectively. All the day 0 samples in the DP arm had one copy of the plasmepsin-2 gene. Conclusions DP remains highly effective and safe for the treatment of uncomplicated malaria in Uganda. Recurrent infections with AL were common. In Busia and Arua, the 95% confidence interval for PCR-corrected AL efficacy fell below 90%. Further efficacy monitoring for AL, including pharmacokinetic studies, is recommended. Trial registration The trail was also registered with the ISRCTN registry with study Trial No. PACTR201811640750761

Abstract Background Preconception care (PCC) is a form of preventive health care that is offered to women and couples before conception, with the aim of improving their health status and mitigating various risk factors that could contribute to poor maternal and child health outcomes. The levels of PCC utilization are still low globally, especially in developing countries and in rural areas. Little is known regarding PCC use in Kenya that could help in addressing this shortfall. This study aimed to qualitatively assess the determinants of PCC in urban and rural settings in Kenya. Methods A qualitative approach was employed to assess determinants of PCC using a semi-structured interview guide. The study was conducted from May to October 2017. Selected pregnant women seeking antenatal care (ANC) were recruited by quota sampling, at the Mother and Child Health (MCH) clinics in Aga Khan University Hospital, Nairobi (AKUH, N-urban) and Maragua Level Four Hospital (MLFH-rural). The interviews were thereafter transcribed verbatim and analyzed thematically. Findings A total of 26 women were invited, of whom 21 accepted to participate in in-depth interviews (IDIs). Saturation of themes occurred with 13 interviews (7 at AKUH and 6 at MLFH). Transcription, coding and thematic analysis of the IDIs yielded 12 themes. Eleven of these themes were identified as determinants of PCC. The twelfth theme contained suggested strategies of increasing PCC awareness and utilization, such as using the media, setting up PCC clinics and integrating PCC into other clinics. The dominant themes were awareness about PCC and attitudes towards PCC and pregnancy. The broad determinants of PCC were similar in urban and rural settings – with a few notable exceptions. For example, in the rural setting, women’s level of education and a pervasive history of poor interactions with healthcare providers were major determinants of PCC. Conclusion From this study we conclude that women’s lack of awareness about PCC, in conjunction with attitudes towards PCC and pregnancy impact strongly on its utilization. This lack of awareness could be addressed through health education programs for both the public and for healthcare providers, as well as integrating PCC in the curricula of the later.

Intermittent preventive treatment with dihydroartemisinin-piperaquine (DP) is protective in children against malaria. Here, the authors analyze plasma drug concentration, malaria incidence, and drug resistance markers from a clinical trial in Uganda and determine the optimal DP dosing regimen.

Abstract Background Intensive malaria control may have additional benefits beyond reducing the incidence of symptomatic malaria. We compared antibiotic treatment of children before and after the implementation of highly effective malaria control interventions in Tororo, a historically high transmission area of Uganda. Methods Two successive cohorts of children, aged 0.5 to 10 years, were followed from September 2011 to October 2019 in a dedicated study clinic. Universal distribution of long-lasting insecticidal nets was conducted in 2013 and 2017. Sustained indoor residual spraying of insecticide (IRS) was initiated in December 2014. Generalized linear mixed-effects models were used to compare the incidence of antimalarial and antibiotic treatments before and after vector control measures were implemented. Results Comparing the period prior to the implementation of IRS to the period after IRS had been sustained for 4–5 years, the adjusted incidence of malaria treatments decreased from 2.68 to 0.05 per person-year (incidence rate ratio [IRR] = 0.02, 95% CI 0.01–0.03, p < 0.001), and the adjusted incidence of antibiotic treatments decreased from 4.14 to 1.26 per person-year (IRR = 0.30, 95% CI 0.27–0.34, p < 0.001). The reduction in antibiotic usage was primarily associated with fewer episodes of symptomatic malaria and fewer episodes of fever with sub-microscopic parasitemia, both of which were frequently treated with antibiotics. Conclusions In a historically high transmission setting, the implementation of highly effective vector control interventions was followed by a marked reduction in antibiotic treatment of children. This added benefit of malaria control could have important implications for antibiotic prescribing practices, efforts to curtail antimicrobial resistance, and health system costs.

Abstract Background The burden of malaria in Uganda remains high, but has become increasingly heterogenous following intensified malaria control. Travel within Uganda is recognized as a risk factor for malaria, but behaviours associated with travel are not well-understood. To address this knowledge gap, malaria-relevant behaviours of cohort participants were assessed during travel and at home in Uganda. Methods Residents from 80 randomly selected households in Nagongera sub-county, Tororo district were enrolled into a cohort to study malaria in rural Uganda. All participants were given long-lasting insecticidal nets (LLINs) at enrolment and were evaluated every 4 weeks at the study clinic. Participants were asked if they had travelled overnight from their home, and if so, a questionnaire was administered to capture information on travel details and behaviours. Behaviour while travelling was assessed within 4 weeks following travel during the study clinic visit. Behaviour while at home was assessed using a similar questionnaire during two-weekly home visits. Behaviours while travelling vs at home were compared using log binomial regression models with generalized estimating equations adjusting for repeated measures in the same individual. Analysis of factors associated with LLIN adherence, such as destination and duration of travel, time to bed during travel, gender and age at time of travel, were assessed using log binomial regression models with generalized estimating equations adjusting for repeated measures in the same individual. Results Between October 2017 and October 2019, 527 participants were enrolled and assessed for travel. Of these, 123 (23.2%) reported taking 211 overnight trips; 149 (70.6%) trips were within Tororo. Participants were less likely to use LLINs when travelling than when at home (41.0% vs. 56.2%, relative risk [RR] 0.73, 95% CI 0.60–0.89, p = 0.002); this difference was noted for women (38.8% vs 59.2%, RR 0.66, 95% CI 0.52–0.83, p = 0.001) but not men (48.3% vs 46.6%, RR 0.96, 95% CI 0.67–1.40, p = 0.85). In an adjusted analysis, factors associated with LLIN use when travelling included destination (travelling to districts not receiving indoor residual spraying [IRS] 65.8% vs Tororo district 32.2%, RR 1.80, 95% CI 1.31–2.46, p 7 nights 60.3% vs one night 24.4%, RR 1.97, 95% CI 1.07–3.64, p = 0.03). Conclusions Travellers, particularly women, were less likely to use LLINs when travelling than when at home. LLIN adherence was higher among those who travelled to non-IRS districts and for more than 1 week, suggesting that perceived malaria risk influences LLIN use. Strategies are needed to raise awareness of the importance of using LLINs while travelling.

Indoor residual spraying (IRS) of insecticide is one of the primary malaria vector control initiatives, but implementation is limited. Here, the authors show that discontinuation of IRS in Uganda was associated with increased malaria incidence, and introduction of IRS was associated with decreased incidence.

Control of mosquito populations using pesticides is important for malaria elimination, but effects of pesticides on humans aren’t well understood. Here, Prahl et al. show in a cohort of pregnant Ugandan women and their infants that household spraying with bendiocarb affects the fetal immune system and response to vaccination in infancy.