Abstract Background Malaria, a disease caused by parasites of the genus Plasmodium, continues to impact many regions globally. The rise in resistance to artemisinin-based anti-malarial drugs highlights the need for new treatments. Ideally, new anti-malarials will kill the asymptomatic liver stages as well as the symptomatic blood stages. While blood stage screening assays are routine and efficient, liver stage screening assays are more complex and costly. To decrease the cost of liver stage screening, a previously reported luciferase detection protocol requiring only common laboratory reagents was adapted for testing against luciferase-expressing Plasmodium berghei liver stage parasites. Methods After optimizing cell lysis conditions, the concentration of reagents, and the density of host hepatocytes (HepG2), the protocol was validated with 28 legacy anti-malarials to show this simple protocol produces a stable signal useful for obtaining quality small molecule potency data similar to that obtained from a high content imaging endpoint. The protocol was then used to screen the Global Health Priority Box (GHPB) and confirm the potency of hits in dose–response assays. Selectivity was determined using a galactose-based, 72 h HepG2 assay to avoid missing mitochondrial-toxic compounds due to the Crabtree effect. Receiver-operator characteristic plots were used to retroactively characterize the screens’ predictive value. Results Optimal luciferase signal was achieved using a lower HepG2 seed density (5 × 103 cells/well of a 384-well microtitre plate) compared to many previously reported luciferase-based screens. While producing lower signal compared to a commercial alternative, this luciferase detection method was found much more stable, with a > 3 h half-life, and robust enough for producing dose–response plots with as few as 500 sporozoites/well. A screen of the GHPB resulted in 9 hits with selective activity against P. berghei liver schizonts, including MMV674132 which exhibited 30.2 nM potency. Retrospective analyses show excellent predictive value for both anti-malarial activity and cytotoxicity. Conclusions This method is suitable for high-throughput screening at a cost nearly 20-fold less than using commercial luciferase detection kits, thereby enabling larger liver stage anti-malarial screens and hit optimization make-test cycles. Further optimization of the hits detected using this protocol is ongoing. …

Abstract Despite its success, the increased use of insecticide-treated nets (ITNs) and indoor residual spraying (IRS) has contributed to the development of insecticide resistance in malaria vectors and shifts in biting patterns of the primary malaria vectors. The limitations portrayed by ITNs and IRS suggest that their use alone will not reduce malaria to elimination levels as the remaining untargeted vectors continue to sustain residual malaria transmission (RMT). RMT is a big challenge to malaria elimination because even at 100% ITN and IRS coverage, malaria transmission persists as outdoor vectors avoid or reduce contact with such interventions. With the recent increase in the outdoor biting Anopheles arabiensis (hard to control using routine tools), in most African countries, including Malawi, novel tools such as the attractive toxic sugar baits (ATSBs), targeting outdoor biting vectors in addition to controlling indoor vectors are greatly needed to complement current tools, and could facilitate sustainable malaria control. The ATSB is one potential tool that has been tested in different settings with promising results, and more trials are ongoing in other African countries. ATSBs have been attributed to reductions of mosquito densities and malaria incidence with over 80% and 50%, respectively, and there is hope that by 2025, ATSBs would be considered for the World Health Organization prequalification listing as a complementary tool for mosquito control. This article highlights evidence that ATSBs can advance malaria elimination by complementing indoor-based tools. However, for effective control programmes and elimination campaigns, the use of ATSBs alone might not be adequate, and this article recommends the combined use of ATSBs with either IRS or ITNs. …

Abstract Background In April 2019, Mozambique was hit by Cyclone Idai leaving substantial damage to infrastructure and nearly two million people in need of humanitarian assistance. Malaria risk has been associated with living in a rural setting, vicinity to water, and household structure, all factors which are impacted by severe storms. This study quantified the association between damage to infrastructure (health care facilities and schools) following Cyclone Idai and malaria outcomes: malaria incidence, severe malaria, and administration of intermittent preventative treatment in pregnancy (IPTp) in Sofala Province, Mozambique. Methods To quantify infrastructure damage, historical satellite imagery was assessed visually using Google Earth Pro®. Damage to 66 school and 105 health centres was assessed for severity and duration. Location data was imported to QGIS and joined with district level data on malaria outcomes and environmental covariates. Multivariable Poisson regression models were used to quantify the associations between facility damage and malaria incidence and severe malaria. Generalized linear models were used to determine the association between facility damage and changes in malaria incidence and administration of IPTp from 2018 to 2019. Results An increase in facility damage was associated with an increase in malaria incidence and severe malaria. An increase in proportion of facilities damaged by 10% was associated with a 7.3% (95% CI 6.8–7.8%) increase in malaria incidence. Risk of severe malaria was 2.16 (95% CI 1.42–3.32) times higher in districts with any damage compared to those with no damage. However, proportional facility damage was associated with decreased malaria incidence and increased access to IPTp from 2018 to 2019, but these were not statistically significant. Conclusion An increase in proportion of facilities damaged following Cyclone Idai was associated with increased risk of malaria and severe malaria at the district level. This may be a function of decreased access to healthcare and an increased exposure to risk factors for malaria. A non-statistically significant decrease in malaria incidence was also found at the district level from 2018 to 2019, indicating that malaria may have been underreported in 2019, likely again a function of decreased access to healthcare. …

Abstract Objective Previous studies have shown that human immunodeficiency virus (HIV) infection is associated with hypertension; however, the results of these studies are affected by a variety of confounding factors. There is no definite evidence to prove a causal relationship between these two factors. This study aimed to investigate the causal relationship between HIV infection and hypertension. Methods A two-sample Mendelian randomization (MR) study was conducted using genome-wide association study (GWAS) statistics published online. The data were collected mainly from the OpenGWAS and FinnGen databases. The HIV database contained 357 HIV patients and 218,435 control patients; the hypertension database contained 54,358 patients and 408,652 control patients; and the blood pressure database contained 436,424 samples. Random effect inverse variance weighting (IVW) was used as the main analysis method, weighted median and Mr-Egger analysis methods were used to ensure the accuracy of the results, and Cochran’s Q test and Mr-Egger regression methods were used to detect heterogeneity and correct multiple horizontal effects. Finally, the leave-one-out method was used to analyse the reliability of the test results. In order to further verify the research results, different databases were used and the same statistical method was used for a replication analysis. In order to prevent false positive results caused by multiple tests, Bonferroni correction is used to correct the statistical results. Results After screening, a total of 9 SNPs (single-nucleotide polymorphisms) were selected as the instrumental variable (IV) used in this study. The IVW MR analysis results showed a causal relationship between HIV infection and the risk of hypertension (IVW: OR = 1.001, P = 0.03). When systolic blood pressure was the outcome, the IVW method results were positive (OR = 1.004, P = 0.01280), and when diastolic blood pressure was the outcome, the weighted median method results were positive (OR = 1.004, P = 0.04570). According to the sensitivity analysis, the results of this study were unlikely to be affected by heterogeneity and horizontal pleiotropy. The leave-one-out analysis showed that the results of this study did not change significantly with the elimination of a single SNP. In replication analysis, when diastolic blood pressure was taken as the outcome, the weighted median method was positive (OR = 1.042, P = 0.037). Sensitivity analysis shows that there is heterogeneity, but there is no horizontal pleiotropy. The leave-one-out analysis showed that the results of this study did not change significantly with the elimination of a single SNP. Conclusion As the first exploratory study using MR method to study the causal relationship between HIV infection and hypertension and blood pressure, this study found that HIV infection may increase systolic and diastolic blood pressure and increase the risk of hypertension. PLWH, as a high-risk group of cardiovascular and cerebrovascular diseases, should prevent the occurrence of hypertension in order to further improve their quality of life. However, this study also has some limitations. The results of the relationship between HIV infection and hypertension and blood pressure may be affected by the lack of statistical efficacy. In order to further confirm this conclusion, more large-scale RCT or genetic studies should be carried out. …

Abstract Background The causal relationships between sexually transmitted infections, depression, and self-harm remain unclear. Methods We executed various Mendelian Randomization (MR) analyses. At the same time, a cross-sectional analysis from NHANES was used for verification and an enrichment analysis was also utilized to explore the potential common gene functions. Results We found that STIs may have a potential causal effect on depression (P = 0.002) and self-harm (P = 0.003). Conversely, self-harm has been identified as a risk factor for the acquisition of STIs (P = 0.006), while there is no evidence to support an effect of depression on STIs. Furthermore, mediation MR indicated that monocyte absolute count played a mediating role in the association between STIs and depression, accounting for 7.7%. And then, the weighted regression analysis of the cross-sectional analysis demonstrated a significant association between one of the common STIs, HPV, and depression. Gene enrichment analysis suggested that the PI3K-Akt signalling pathway and the infectious virus signalling pathway may represent a common underlying pathogenesis. Conclusion STIs may increase the risk of depression and self-harm, while self-harm might also represent a risk factor for STIs, which could provide insights and a foundation for the control of STIs and mental health monitoring in clinical practice. …

The 32nd National Congress of Parasitology (NCP) was held in person, 3–5 October 2024, at the Indian Institute of Science Education and Research Pune (IISER Pune), jointly organized by IISER Pune; the Council of Scientific and Industrial Research – National Chemical Laboratory, Pune; and Savitribai Phule Pune University (formerly University of Pune) in association with the Indian Society for Parasitology. The conference brought together around 250 attendees from across the country and abroad, including a diverse group of researchers, clinicians, industry experts, and students.

Tropical Medicine &International Health, EarlyView.

Abstract Background To address antibiotic overuse, the Japanese government implemented a novel financial incentive policy in 2018. The policy enables eligible healthcare facilities to claim 800 JPY (≈5.7 USD) per case wherein a rationale to not prescribe antibiotics is offered to children aged

Abstract Background Shigella sonnei has caused sexually transmitted enteric infections in men who have sex with men (MSM) in Vancouver. We recently observed a high rate of multidrug-resistant (MDR) S. sonnei bacteremia among persons experiencing homelessness (PEH). We aim to describe the wider epidemiology, clinical outcomes, and genomics of S. sonnei infections over time.Methods A retrospective review of 163 patients with S. sonnei infections was undertaken from 2015 –2022. We collected demographic, clinical, and microbiological data over two time periods: historical (2015-2020) and recent (2021-2022). Severe shigellosis definition included hospitalization, bacteremia, or death. Whole genome sequencing was performed to identify genotype, infer relatedness, and predict antimicrobial resistance.Results S. sonnei infections rose from 8.3 (historical-period) to 56.5 cases/year (recent-period). Over time, the primary population characteristics associated with shigellosis shifted from MSM (45, 98%) to PEH (86,77%). The population intersection between MSM and PEH historically and recently was similar and occurred in three (6%) and ten (9%) of patients, respectively. Severe shigellosis was significantly higher in the recent compared to historical period (69 [61%] versus 7 [14%], p

Abstract Background Most individuals on combination antiretroviral therapy (ART) have HIV plasma viral loads below the limit of detection. However, episodes of low-level viremia (LLV) are observed in subsets of individuals, risk factors and clinical significance of which remain debated.Methods We included participants enrolled in the Swiss HIV Cohort Study, starting ART between July 1999 and April 2023, with HIV RNA

Volume 13, Issue 1, December 2024 .

Volume 13, Issue 1, December 2024 .

Abstract Purpose Cytomegalovirus (CMV) is associated with significant morbidity and mortality among solid organ transplant (SOT) recipients. Strategies for CMV prevention include universal prophylaxis or preemptive approach. We aimed to evaluate the optimal approach. Methods We performed a systematic review and meta-analysis of randomized controlled trials comparing prophylaxis versus preemptive therapy for CMV in SOT. The primary outcome was CMV disease. Subgroup analysis of outcomes in D+ R− patients was performed. Results Nine trials have met inclusion criteria, five of them included kidney transplant recipients, all compared val/ganciclovir universal prophylaxis versus preemptive approach. Universal prophylaxis resulted in lower probability of CMV infection (relative risk [RR] 0.44, 95% confidence interval [CI] 0.33–0.58), yet the impact on CMV disease was insignificant (RR 0.54, 95% CI 0.24–1.23), in neither SOT recipients in general nor among D+R− subgroup (RR 0.93, 95% CI 0.37–2.32). Late-onset CMV disease rates were lower with preemptive approach. Sensitivity analysis according to allocation concealment and blinding showed similar results for CMV disease. No significant differences were demonstrated for the outcomes of mortality, bacterial or fungal infection or graft related outcomes. Acute kidney injury was significantly more common with prophylaxis (RR 1.79, 95% CI 1.12–2.89). Conclusion Preemptive approach is a reasonable approach for CMV prevention in SOT recipients, if feasible. Strategies for combining the preemptive with prophylaxis strategies, as well as immune monitoring, should be investigated. …

Abstract Purpose Early recognition of sepsis is critical to patient outcome, with mortality increasing with every hour of delay in treatment. The aim of this study was to investigate the use of a point-of-care molecular host response assay to differentiate sepsis from inflammation after surgery. Methods Three molecular host response assays (SeptiCyte® RAPID) were performed in 61 patients after major abdominal surgery with admission to the intensive care unit and drawn blood cultures. The first (T0) was taken ± 3 h around the time of obtaining blood cultures, the second 24 h later (T24) and the third at discharge from the intensive care unit (Tex). The primary endpoint was the agreement of SeptiCyte® RAPID results with the diagnosis of sepsis. SeptiScore® indicates sepsis probability (low risk 0 - high risk 15). Patients were retrospectively classified into sepsis and inflammation by three blinded experts. Results 25 (42.4%) patients were categorized as “inflammation” and 34 (57.6%) patients as “sepsis”. At T0 and T24 septic patients showed significantly higher mean SeptiScores® of 8.0 (± 2.2 SD) vs. 6.3 (± 2.1 SD) and 8.5 (± 2.1 SD) vs. 6.2 (± 1.8 SD), respectively. The Receiver Operating Curves (ROC) for the ability to discriminate between sepsis and inflammation had an Area Under the Curve (AUC) of 0.71 (T0) and 0.80 (T24). Conclusion Embedded in a comprehensive diagnostic algorithm molecular host response analysis could broaden the possibilities for infection diagnostics to differentiate between sepsis and inflammatory response after surgery. But validation in larger cohorts is needed. …

Introduction: The US state of Florida has the third highest rate of HIV as well as high rates of sexually transmitted infections (STIs) indicating critical HIV and STI prevention needs remain unmet. To address gaps in the STI care continuum in people with HIV (PWH), evidence-based interventions were implemented across three Ryan White HIV/AIDS Program (RWHAP) funded clinics in Florida between August 2020–August 2021. Interventions included comprehensive sexual health history (SHH) taking using audio computer-assisted self-interview (ACASI) software, self-collected extragenital gonorrhea and chlamydia testing, and the introduction of a lesbian, gay, bisexual, transgender, and queer (LGBTQ+) welcoming environment. Methods: We 1) assessed the acceptability of these interventions and examined if acceptability differed among youth and sexual, racial and ethnic minorities, 2) determined the proportion of appropriate STI testing completed based on the SHH assessment, 3) examined whether STI at-risk individuals underwent STI screening 3-6 months after initial evaluation, and 4) determined the proportion of positive STI test results among priority intervention groups in Florida. Results: Acceptability of all interventions was high. Youth, lesbian, gay, and bisexual, and Hispanic individuals were significantly more likely to notice and like LGTBQ+ welcoming measures. The proportion of recommended tests completed was high, although only a subset of at-risk individuals completed re-screening. 11.9% of rectal samples were positive for chlamydia and 6.5% of pharyngeal samples were positive for gonorrhea. Conclusions: Our study highlights the importance of incorporating comprehensive sexual health care protocols, including extragenital STI testing, into the overall care of PWH. Copyright © 2024 The Author(s). Published by Wolters Kluwer Health, Inc.

Background: In the United States, young men who have sex with men (YMSM) and young transgender women (YTGW) are disproportionately affected by HIV infection. Adequate HIV knowledge is critical for protecting adolescents and young adults at risk for HIV. This study aimed to evaluate the effectiveness of the mLab App intervention in enhancing HIV knowledge among YMSM and YTGW. Methods: This study was a secondary analysis of data collected from a randomized controlled trial (RCT) evaluating the effect of the mLab App on HIV knowledge. We calculated interactions between groups (mLab App intervention, standard of care, at-home testing) over time (6 and 12 months) following the baseline observation, indicating a difference in the outcome scores from baseline to each time across groups. Results: While the mLab App group initially had lower HIV knowledge compared to those in other groups, access to the App demonstrated a progressive impact on HIV knowledge over time. Despite the absence of a statistically significant effect at the 6-month, the long-term evaluation suggests improvements in HIV knowledge during the 12-month intervention follow-up. Conclusion: Our study suggests the potential of the mLab App as a valuable tool for long-term HIV education and awareness for YMSM and YTGW. Further research is needed to understand the factors influencing the short-term effect on HIV knowledge. The mLab App may be a useful intervention for improving HIV knowledge. Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.

Background This study aims to develop and examine the performance of machine learning (ML) algorithms in predicting viral suppression among statewide people living with HIV (PWH) in South Carolina (SC). Methods Extracted through the electronic reporting system in SC, the study population was adult PWH who were diagnosed between 2005-2021. Viral suppression was defined as viral load…

People with HIV (PWH) appear to be at an elevated risk for severe COVID-19 outcomes. Several studies have shown that PWH with pronounced immunodeficiency (e.g., lower CD4 count) have a higher risk for worse clinical outcomes, including COVID-19-related hospitalization and death.[1, 2] Severe COVID-19 outcomes among PWH might be partially due to the exacerbating syndemic effects of COVID-19, HIV, and other risk factors (e.g., low socio-economic status, more chronic comorbidities) on health inequalities.[3, 4] Yet, the evidence regarding the effectiveness of COVID-19 vaccines in this high-risk group remains sparse.[5, 6] Despite several large population-based studies that have evaluated COVID-19 vaccine effectiveness (VE) in this population, more evidence is warranted to confirm the robustness of previous findings and inform COVID-19 vaccine strategies for PWH.

Diagnosing infectious encephalitis can be challenging as it can be caused by a wide range of pathogens, with viruses being the most common cause. In a substantial number of patients, no pathogen is identified despite a clinical diagnosis of infectious encephalitis. Recent advancements in diagnostic testing have introduced new methods to address this diagnostic challenge and improve pathogen detection.

Streptococcus pneumoniae infection can lead to serious and potentially life-threatening illness, referred to as invasive pneumococcal disease (IPD). This includes bloodstream infection, bacteraemic pneumonia, empyema, and meningitis. The impact is greatest amongst young children, patients with immunosuppression and chronic diseases, and in older adults [1].

Human campylobacteriosis, is a leading bacterial foodborne infection, primarily caused by contaminated food, especially poultry. In Denmark, notified domestic Campylobacter cases have annually ranged from 3,740 to 5,389 over the past five years, with chicken often identified as the primary infection source. The Danish authorities and the food industry have been actively working together to control Campylobacter and to reduce the risk of human infection from chicken meat. Since 2019, Denmark has routinely used Whole Genome Sequencing (WGS) to detect clusters of Campylobacter jejuni and Campylobacter coli infections and link potential outbreaks to food sources, enhancing outbreak detection and targeted interventions [1].

To evaluate the effectiveness of ceftaroline vs. vancomycin or daptomycin in the treatment of methicillin-resistant Staphylococcus aureus bloodstream infections (MRSA-BSIs).