Proceedings of the National Academy of Sciences, Volume 121, Issue 48, November 2024.

Objective: Elevated blood pressure (BP), even at prehypertensive levels, increases cardiovascular disease risk among people with HIV (PWH); yet international guidelines in low-income countries recommend treatment initiation at BP at least 140/90 mmHg. We determined the efficacy, feasibility, and acceptability of treating prehypertension in PWH in Haiti. Design: An unblinded randomized clinical trial (enrolled April 2021–March 2022) with 12-month follow-up. Setting: GHESKIO Centres, Port-au-Prince, Haiti. Participants: Two hundred fifty adults with HIV with prehypertension (SBP 120–138 or DBP 80–89) not on medication, aged 18–65 years, virally suppressed, and without pregnancy, diabetes, or kidney disease. Intervention: Participants were randomized to treatment (amlodipine 5 mg) or control (no amlodipine unless two BP ≥140/90 mmHg). Main outcome measure: Primary outcome was mean change in SBP between intervention versus control groups from enrollment to 12 months. Results: Among 250 adults, median age was 49 years, 40.8% were women. Baseline median BP was 129/78 mmHg intervention versus 128/77 mmHg control. After 12 months, the difference in mean change between study groups for SBP was -5.9 mmHg [95% confidence interval (95% CI) -8.8 to -3.0] and for DBP was -5.5 mmHg (95% CI -7.9 to -3.2). At 12 months, 5.6% intervention and 23.0% control participants developed incident hypertension (hazard ratio 0.18; 95% CI 0.07–0.47). There were no differences in viral load suppression at 12 months or drug-related serious adverse events. Intervention acceptability was high among providers and participants in qualitative interviews. Conclusion: In PWH in a resource-poor setting, prehypertension treatment was feasible, acceptable, and effective in reducing mean SBP and incident hypertension. Registration: Clinicaltrials.gov NCT04692467 JOURNAL/aids/04.03/00002030-990000000-00587/figure1/v/2024-11-13T090640Z/r/image-jpeg Copyright © 2024 The Author(s). Published by Wolters Kluwer Health, Inc.

Objective: Falls are a significant public health concern, particularly among older adults and people with HIV (PWH). This study examines the association between alcohol consumption and falls in PWH. Methods: The PROSPER-HIV study recruited PWH from four US sites. Participants were categorized based on Alcohol Use Disorders Identification Test Consumption (AUDIT-C) scores: none, non-hazardous, and hazardous drinking. Data collection included demographics, medical history (i.e., comorbidities, treated hypertension, eGFR), alcohol consumption using AUDIT-C, daily alcohol recall in grams, and self-reported falls over the previous year. Physical performance was measured using the Short Performance Physical Battery (SPPB). Statistical analyses included Pearson\'s correlation and Poisson regression models to estimate fall prevalence ratios (PR), adjusting for confounders (SPPB, comorbidities, treated hypertension, and eGFR). Results: The study included 315 PWH, aged 52 ± 12 years, with 78% male participants. Thirty-three percent were classified as non-drinking, 50% non-hazardous, and 17% hazardous drinking. Poisson regression showed a significantly higher risk of falls (PR: 2.12, 95% CI: 1.11–4.03) and recurrent falls (PR: 3.54, 95% CI: 1.21–10.3) among hazardous drinking compared to non-hazardous drinking, even after adjusting for confounders. The PR for falls per daily intake in grams was not statistically significant. Conclusions: There is a significant association between hazardous alcohol consumption and increased fall risk in PWH using AUDIT-C, but not when accessing recall of alcohol consumption in grams. Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.

Background : Characterizing HIV clustering rates and their trends over time can improve understanding a local epidemic and enhance its control. Methods: Leveraging an academic-public health partnership in Rhode-Island, we explored longitudinal dynamics of statewide clustering rates among key populations from 1991 to 2023. Partial HIV-1 pol sequences were grouped by year of HIV-1 diagnosis. Molecular clusters were identified in cumulative annual phylogenies. Overall clustering rates, and clustering rates of newly-diagnosed and prevalent infections, and of specific socio-demographic characteristics of key populations over time were determined. Mann-Kendall statistics were used to estimate clustering rate trends and relationships among groups. Results: By the end of 2023, 2,630 individuals with sequences represented the statewide epidemic in Rhode Island. Overall clustering rates increased from 7% in 1991 to 46% in 2023, correlating with cumulative sequence increase. Clustering rates of newly-diagnosed and prevalent infections significantly increased over time, higher in newly-diagnosed individuals since the early 2000 s. Increases were also observed among groups defined by gender, age, transmission risks, race, mental illness, HIV-1 subtypes, and country of birth, with some crossovers and divergence patterns over time. Conclusions: Exploring dynamics of HIV clustering rates over three decades in a statewide HIV-1 epidemic expanded its characterization and provided insight into its evolving changes. These dynamics may indicate a gradual shift towards a more concentrated and localized HIV-1 epidemic, highlighting important opportunities for targeted interventions to effectively prevent new HIV transmissions. Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.

Science Advances, Volume 10, Issue 47, November 2024.

Science Advances, Volume 10, Issue 47, November 2024.

Challenges in adapting natural products as antimalarials include their cryptic mechanism of action (and by extension resistance), as well as their complex and expensive synthesis without an abundant natural source. Recently, Chahine et al. presented plausible means to address these challenges in the case of the kalihinol family of isocyanoterpenes.

Leishmania (Leishmania) amazonensis is the etiological agent of cutaneous leishmaniasis (CL) and anergic diffuse cutaneous leishmaniasis (ADCL). ADCL is one of the most severe and frequently incurable clinical forms of the disease in the Americas, with 85% of the cases occurring in Brazil, Colombia, and Peru. CL is considered a zoonotic infection in sylvatic mammals, where parasites are transmitted through the bites of naturally infected phlebotomine sand flies (Diptera: Psychodidae), more specifically Bichromomyia flaviscutellata, which is widely distributed in the Amazon region and other Brazilian states.

Anthelmintic resistance (AR) in parasitic nematodes poses a global health problem in livestock and domestic animals and is an emerging problem in humans. Consequently, we must understand the mechanisms of AR, including target-site resistance (TSR), in which mutations affect drug binding, and non-target site resistance (NTSR), which involves alterations in drug metabolism and detoxification processes. Because much of the focus has been on TSR, NTSR has received less attention. Here, we describe how metabolomics approaches using Caenorhabditis elegans offer the ability to disentangle nematode drug metabolism, identify metabolic changes associated with resistance, uncover novel biomarkers, and enhance diagnostic methods.

The circumsporozoite protein (CSP) is one of the most studied proteins of the malaria parasite. It is the target of the only licensed malaria vaccines and is essential for sporozoite formation and infectivity. Yet, the mechanisms by which CSP functions and its interactions with other proteins are only beginning to be understood. Here we review the current state of knowledge of CSP structure and function, as sporozoites develop in the mosquito and establish infection in the mammalian host, and outline outstanding questions that need to be addressed.

Congenital infections are a leading preventable cause of pregnancy complications impacting both mother and fetus. Although advancements have been made in understanding various congenital infections, the mechanisms of parasitic infections during pregnancy remain poorly understood. This review covers the global incidence of three parasites capable of congenital transmission – Trypanosoma cruzi, Plasmodium spp., and Toxoplasma gondii – and the state of research into their transplacental transmission strategies. We highlight technological advancements in placental modeling that offer opportunities to reveal how parasites cause gestational pathology. Additionally, we discuss the likelihood that selective adaptation contributed to the evolution of mechanisms that facilitate placental infection. These insights provide a foundation for understanding the progression and pathology of congenital parasitic diseases and identifying future research directions.

Abstract In 2022, a bioinformatic, agnostic approach identified HPV42 as causative agent of a rare cancer, later confirmed experimentally. This unexpected association offers an opportunity to reconsider our understanding about papillomavirus infections and cancers.We have expanded our knowledge about the diversity of papillomaviruses and the diseases they cause.Yet we still lack answers to fundamental questions, such as what makes HPV16 different from the closely related HPV31 or HPV33; or why the very divergent HPV13 and HPV32 cause focal epithelial hyperplasia, while HPV6 or HPV42 do not, despite their evolutionary relatedness.Certain members of the healthy skin microbiota are associated to rare clinical conditions. We propose that a focus on cellular phenotypes, most often transient and influenced by intrinsic and extrinsic factors, may help understand the continuum between health and disease. A conceptual switch is required towards an interpretation of biology as a diversity of states connected by transition probabilities, rather than quasi-deterministic programs. Under this perspective, papillomaviruses may only trigger malignant transformation when specific viral genotypes interact with precise cellular states.Drawing on Canguilhem\'s concepts of normal and pathological, we suggest that understanding the transition between fluid cellular states can illuminate how commensal-like infections transition from benign to malignant.

Tropical Medicine &International Health, EarlyView.

Volume 13, Issue 1, December 2024 .

by Tharani Loganathan, Zhie X. Chan, Fikri Hassan, Watinee Kunpeuk, Rapeepong Suphanchaimat, Huso Yi, Hazreen Abdul Majid …

by John M. Arthur, J. Craig Forrest, Karl W. Boehme, Joshua L. Kennedy, Shana Owens, Christian Herzog, Juan Liu, Terry O. Harville …

by Danai Tonkerdmongkol, Teera Poyomtip, Chotika Poolsanam, Akarapon Watcharapalakorn, Patarakorn Tawonkasiwattanakun …

by Erying Zhang, Xiaowei Feng, Fei Liu, Peihua Zhang, Jie Liang, Xudong Tang …

by Rodrigo Fracalossi de Moraes, Louise B. Russell, Lara Livia Santos da Silva, Cristiana M. Toscano …

by Shu-Yuan Lee, Yi-Chun Lin, Cheng-Pin Chen, Shu-Hsing Cheng, Shu-Ying Chang, Shin-Yen Ku, Chien-Yu Cheng Conflicting data exists regarding the baseline determinants of virological nonsuppression outcomes in treatment-experienced people living with human immunodeficiency virus (PWH) switching to antiretroviral treatment (ART) with bictegravir/emtricitabine/tenofovir alafenamide fumarate (BIC/FTC/TAF) or dolutegravir/lamivudine (DTG/3TC) in Asia. This retrospective observational study, conducted at a designated HIV-care hospital from October 2019 to January 2023, aimed to address this gap. We assessed the odds of virological nonsuppression (VNS) at weeks 48 using logistic regression. A total of 988 patients were included, 35 patients (3.5%) with VNS at week 48. Pre-existing primary resistance-associated mutations (RAM) to nucleoside reverse transcriptase inhibitor (NRTI) and non-nucleoside reverse transcriptase inhibitor (NNRTI) were identified in 11.0% (51/465) and 14.4% (67/465), respectively. The identified risk factor was a record of virological failure ≥2 times (AOR 5.32, 95% CI 2.04–13.85), while an HIV viral load…

by Jules Jackson, Ireen Sultana Shanta, Clifton McKee, Stephen P. Luby, Najmul Haider, Yushuf Sharker, Raina Plowright, Peter Hudson, Emily S. Gurley Nipah virus spillovers via consumption of date palm sap in Bangladesh vary substantially between years and have been associated with lower winter temperatures and precipitation. However, the mechanisms driving the interannual variation and the influence of weather remain unexplained. Here we investigated the hypothesis that weather patterns change human sap consumption and explain interannual variation in observed spillovers. We analyzed responses from a nationally representative survey conducted in Bangladesh in 2013–2016 on household date palm sap consumption and weather data for each division of Bangladesh, using logistic regression to examine whether sap consumption is associated with weather variability. We found significant associations of lower minimum temperatures and precipitation with increased household sap consumption during the sap harvesting season. This relationship was largely similar within all months and divisions, and strong associations of temperature (χ2 (1, n = 5,027) = 7.74, p < 0.01) and, independently, precipitation (χ2 = 8.00, p < 0.01) remained strong after accounting for month, location, and annual sap season. Interannual variation in date palm sap consumption in Bangladesh is likely best explained by temperature and precipitation patterns, where colder, drier winter days pose a higher risk for Nipah virus spillover. The knowledge gained in this study may be valuable for targeting timing of future behavioral interventions against consumption of date palm sap in Bangladesh.

by Diego E. Gomez, Jamie J. Kopper, David P. Byrne, David L. Renaud, Angelika Schoster, Bettina Dunkel, Luis G. Arroyo, Anna Mykkanen, William F. Gilsenan, Tina H. Pihl, Gabriela Lopez-Navarro, Brett S. Tennent-Brown, Laura D. Hostnik, Mariano Mora-Pereira, Fernando Marques, Jenifer R. Gold, Sally L. DeNotta, Isabelle Desjardins, Allison J. Stewart, Taisuke Kuroda, Emily Schaefer, Olimpo J. Oliver-Espinosa, Gustavo Ferlini Agne, Benjamin Uberti, Pablo Veiras, Katie M. Delph Miller, Rodolfo Gialleti, Emily John, Ramiro E. Toribio Background This study aimed to describe and compare therapeutic approaches for horses with acute diarrhea in different geographic regions worldwide. Methods Clinical information was retrospectively collected from diarrheic horses presented to participating institutions between 2016 and 2020, including fluid therapy on admission, antimicrobial drugs, probiotics, anti-endotoxic medications, anti-inflammatory drugs, gastroprotectants, digital cryotherapy, and toxin-binding agents. Seasonal and geographic differences were investigated. Results 1438 horses from 26 participating hospitals from 5 continents were included. On admission, 65% (926/1419) of horses were administered a fluid bolus. Antimicrobial drugs were administered to 55% (792/1419) within the first 24 hours of admission, with penicillin and gentamicin being the most used combination (25%, 198/792). Horses with leukopenia (OR: 2.264, 95%CI: 1.754 to 2.921; P…

Infection and Immunity, Ahead of Print.

Infection and Immunity, Ahead of Print.

Abstract Background All pregnant mothers in Uganda are given sulfadoxine-pyrimethamine (SP, Fansidar®) for presumptive treatment of malaria in pregnancy from 14 weeks of gestation, every four weeks, until delivery. However, prenatal mothers still fall sick of malaria. This study aimed to assess the factors associated with malaria in pregnancy among antenatal care mothers at Gulu Regional Referral Hospital. Methods This was a cross-sectional study at Gulu Regional Referral Hospital antenatal clinic from July to August 2023. Consecutive sampling was used. An interviewer-administered questionnaire was used to collect sociodemographic characteristics, physical examination findings and blood samples taken for rapid diagnostic test (RDT) for malaria. A positive RDT was taken as the presence of malaria infection in pregnancy. Data was pre-processed in STATA®15, and logistic regression analysis was done in RStudio 4.2.2. Variables with p 

Abstract Background In Colombia, published studies on the treatment of uncomplicated Plasmodium vivax malaria with chloroquine-primaquine are scarce. The aim of this study was to evaluate the therapeutic response to two treatment regimens at the 28-day follow-up and the occurrence of adverse events in patients with P. vivax malaria. Methods A quasi-experimental clinical trial was conducted at 3 sites in the Department of Amazonas. Patients received supervised or unsupervised anti-malarial treatment (chloroquine plus primaquine), and the primary effectiveness endpoint was the clinical and parasitological response. Safety was assessed through adverse event surveillance. Results A total of 103 patients were included: 53 in the 7-day primaquine group (Group I) and 50 in the group receiving primaquine for 14 days (Group II). Among the patients in group I, an adequate treatment response of 100% and 89.5% was found in patients who received supervised and unsupervised treatment, respectively. In Group II, adequate responses of 100% and 95% were reported for patients who received supervised and unsupervised treatment, respectively. No adverse events were detected. Conclusions The response to combined treatment with chloroquine plus primaquine continues to be adequate for treating P. vivax malaria in the Colombian Amazon region; however, a response to unsupervised treatment in the region is recommended. …

Abstract Background This systematic review investigates the relationship between malaria incidence, climate variables, and deforestation in Colombia, Latin America, and the Caribbean from 2000 to 2020. Malaria, a significant public health issue in these regions, is influenced by ecological factors including climatic conditions and environmental changes, such as deforestation. Methods The review employs a comprehensive search strategy across PubMed, Web of Science, Embase, Scopus, Cochrane, and Scielo databases. It applies strict inclusion and exclusion criteria to ensure the relevance and quality of selected studies, focusing on analysing the relationship between climate variables, deforestation, and malaria incidence. Results Twenty-four articles were included in this review, fourteen of which assessed the relationship between climatic variables and malaria and ten between deforestation and malaria. The analysis reveals a nuanced understanding of malaria dynamics. A significant finding is the seasonal effect of climatic variables on malaria incidence. The study notes that increased rainfall is positively correlated with malaria incidence. Similarly, warmer temperatures are associated with increased malaria risks, and malaria rates can change by 10% to 80% for every degree of temperature increase, after adjusting for altitude. The impact of deforestation on malaria is complex, with positive and negative correlations observed, depending on the remaining forest cover. Conclusions The review highlights the multifaceted nature of malaria transmission, emphasizing the need for integrated approaches that consider both environmental and health perspectives. It underscores the importance of understanding the complex relationships between malaria incidence, climate variables, and deforestation. …

Abstract Purpose To analyze the diagnostic delay in malaria related to misdiagnosis at first medical visit and its association with the risk of severe malaria in non-endemic areas. Methods Retrospective observational study of sub-Saharan migrants with imported malaria from January-2010 to December-2022. Patients were allocated in two groups depending on if malaria was suspected at first medical visit or not. Time delays in seeking healthcare, medical diagnostic delay (time between first attending a medical facility and the diagnosis of malaria) and total diagnostic delay (time between the onset of symptoms and the diagnosis of malaria) were calculated. Results 297 patients were included in the analysis. At first medical visit, malaria was misdiagnosed in 137 patients (46.1%). Medical diagnostic delay and total diagnostic delay were larger for the misdiagnosis group than for those properly diagnosed at first visit (p 

Journal of Medical Virology, Volume 96, Issue 11, November 2024.

Journal of Medical Virology, Volume 96, Issue 11, November 2024.

Introduction: Adolescent girls and young women (AGYW) in Kenya have low pre-exposure prophylaxis (PrEP) initiation rates in part due to stigmatizing interactions with health care providers. Our recent randomized clinical trial of a standardized patient actor (SP) training intervention for providers found higher quality PrEP delivery at intervention sites, however it was unclear whether improved service quality improved PrEP initiation. Methods: This analysis used routine records from facilities participating in the randomized trial which aimed to improve provider communication and adherence to Kenyan guidelines when offering PrEP to AGYW. We utilized facility-level PrEP registers from May-December 2019 as the baseline period and December 2020-June 2021 as the post-intervention period. We used linear regression with percent initiating as the outcome, intervention and baseline initiation levels as covariates, and the number eligible post-intervention at each facility as frequency weights. Results: Overall, 1,375 AGYW presented to study sites, were eligible for PrEP, and were included in analyses (baseline: n=706, post-intervention: n=669). Among 669 PrEP-eligible AGYW in the post-intervention period (intervention: n=360, control: n=309), 591 (88.3%) initiated PrEP (intervention: n=335, control: n=256). PrEP initiation was 93.1% at intervention sites (range: 0%-100%) and 82.8% at control sites (range: 0%-100%). Adjusted for baseline initiation rates, initiation was 12.1% higher at intervention sites compared to control sites (p…

No abstract available…

Background: Latin America—amidst its largest mass migration—has seen minimal progress in curbing new HIV infections. Transgender women (TW) in the region are disproportionately affected, but scant data examines HIV vulnerabilities alongside migration. Methods: Between February-July 2022, 211 young TW ages 16-24 in Lima participated in a cross-sectional quantitative study accompanied by serological testing (HIV, syphilis, chlamydia, gonorrhea, hepatitis B). Bivariate tests compared HIV and STI prevalence and related vulnerabilities among migrants to non-migrants. Poisson regression modeling estimated the association between time in Lima (non-migrant, 0-1 years, 2-5 years, ≥6 years) and HIV vulnerabilities (condom use). Findings: Of 204 young TW, 110 were migrants to Lima (54%); 45% arrived in Lima ≤5 years ago. Most migrants were Peruvian (70% from Jungle regions); 14% were from Venezuela. HIV prevalence was 44% among migrants and 39% among non-migrants (p=0.67). Compared to non-migrants, migrants had higher prevalence of lifetime syphilis (65% vs 41%; p…

Some of the most dramatic chapters in the history of medicine deal with the development of surgery. “A good surgeon must have an eagle’s eye, a lion’s heart, a lady’s hand.” Thus runs the old English proverb, formulated in the days before anesthetics banished pain and antiseptics averted the horrors of wound infection. Today no large part of the body is destined to remain free from surgical approach. The abdomen, thorax and cranium have already been invaded by the trained surgeon with eminent success in the relief of a variety of maladies. Blood vessel and nerve surgery have been developed to a high degree of skill.…This progress has called not only for great resourcefulness of hand and mind but also for personal courage. The pioneer into uncharted places usually proceeds at his own peril only; he pays the penalty for failure with his own person. The surgical pioneer, however, literally takes the lives of others in his hand, and that is a sobering responsibility. Daring, under such circumstances, must be fortified with wisdom and stamina.

This JAMA Insights examines the treatment and rising prevalence of anal cancer in the US in high-risk groups, including people with HIV and immunosuppression associated with solid organ transplant.

This study assesses mpox-specific immune responses for 12 months after MVA-BN vaccination.

This Viewpoint discusses H5 influenza vaccine use in light of the current outbreak and how vaccine development, stockpiling, and deployment could shape the US’ response to future pandemics.