by Xuechen Zhu, Rongbin Wang, Vilja Siitonen, Nemanja Vuksanovic, Nicholas R. Silvaggi, Charles E. Melançon III, Mikko Metsä-Ketelä The biosynthetic pathway of actinorhodin in Streptomyces coelicolor A3(2) has been studied for decades as a model system of type II polyketide biosynthesis. The actinorhodin biosynthetic gene cluster includes a gene, actVI-orfA, that encodes a protein that belongs to the nuclear transport factor-2-like (NTF-2-like) superfamily. The function of this ActVI-ORFA protein has been a long-standing question in this field. Several hypothetical functions, including pyran ring cyclase, enzyme complex stability enhancer, and gene transcription regulator, have been proposed for ActVI-ORFA in previous studies. However, although the recent structural analysis of ActVI-ORFA revealed a solvent-accessible cavity, the protein displayed structural differences to the well-characterized cyclase SnoaL and did not possess a DNA-binding domain. The obtained crystal structure facilitates an inspection of the previous hypotheses regarding the function of ActVI-ORFA. In the present study, we investigated the effects of a series of actVI-orfA test plasmids with different mutations in an established vector/host system. Time-course analysis of dynamic metabolism profiles demonstrated that ActVI-ORFA prevented formation of shunt metabolites and may have a metabolic flux directing function, which shepherds the flux of unstable intermediates towards actinorhodin. The expression studies resulted in the isolation and structure elucidation of two new shunt metabolites from the actinorhodin pathway. Next, we utilized computational modeling to probe the active site of ActVI-ORFA and confirmed the importance of residues R76 and H78 in the flux directing functionality by expression studies. This is the first time such a function has been observed for a member of NTF-2-like superfamily in Streptomyces secondary metabolism.

by James O’Connor-Moneley, Jessica Fletcher, Cody Bean, Josie Parker, Steven L. Kelly, Gary P. Moran, Derek J. Sullivan Development of resistance and tolerance to antifungal drugs in Candida albicans can compromise treatment of infections caused by this pathogenic yeast species. The uniquely expanded C. albicans TLO gene family is comprised of 14 paralogous genes which encode Med2, a subunit of the multiprotein Mediator complex which is involved in the global control of transcription. This study investigates the acquisition of fluconazole tolerance in a mutant in which the entire TLO gene family has been deleted. This phenotype was reversed to varying degrees upon reintroduction of representative members of the alpha- and beta-TLO clades (i.e. TLO1 and TLO2), but not by TLO11, a gamma-clade representative. Comparative RNA sequencing analysis revealed changes in the expression of genes involved in a range of cellular functions, including ergosterol biosynthesis, mitochondrial function, and redox homeostasis. This was supported by the results of mass spectrometry analysis, which revealed alterations in sterol composition of the mutant cell membrane. Our data suggest that members of the C. albicans TLO gene family are involved in the control of ergosterol biosynthesis and mitochondrial function and may play a role in the responses of C. albicans to azole antifungal agents.

by Macarena P. Quintana-Hayashi, Kristina A. Thomsson Hulthe, Sara K. Lindén Current prophylactic and disease control measures in aquaculture highlight the need of alternative strategies to prevent disease and reduce antibiotic use. Mucus covered mucosal surfaces are the first barriers pathogens encounter. Mucus, which is mainly composed of highly glycosylated mucins, has the potential to contribute to disease prevention if we can strengthen this barrier. Therefore, aim of this study was to develop and characterize fish in vitro mucosal surface models based on commercially available cell lines that are functionally relevant for studies on mucin regulation and host-pathogen interactions. The rainbow trout (Oncorhynchus mykiss) gill epithelial cell line RTgill-W1 and the embryonic cell line from Chinook salmon (Oncorhynchus tshawytscha) CHSE-214 were grown on polycarbonate membrane inserts and chemically treated to differentiate the cells into mucus producing cells. RTGill-W1 and CHSE-214 formed an adherent layer at two weeks post-confluence, which further responded to treatment with the γ-secretase inhibitor DAPT and prolonged culture by increasing the mucin production. Mucins were metabolically labelled with N-azidoacetylgalactosamine 6 h post addition to the in vitro membranes. The level of incorporated label was relatively similar between membranes based on RTgill-W1, while larger interindividual variation was observed among the CHSE in vitro membranes. Furthermore, O-glycomics of RTgill-W1 cell lysates identified three sialylated O-glycans, namely Galβ1-3(NeuAcα2–6)GalNAcol, NeuAcα-Galβ1-3GalNAcol and NeuAcα-Galβ1-3(NeuAcα2–6)GalNAcol, resembling the glycosylation present in rainbow trout gill mucin. These glycans were also present in CHSE-214. Additionally, we demonstrated binding of the fish pathogen A. salmonicida to RTgill-W1 and CHSE-214 cell lysates. Thus, these models have similarities to in vivo mucosal surfaces and can be used to investigate the effect of pathogens and modulatory components on mucin production.

Abstract Background The Republic of Guinea, where malaria represents the leading cause of morbidity and mortality among children, the seasonal malaria chemoprevention (SMC) is deployed only in areas with very seasonal modes of transmission. It should target children at the highest risk of serious illness. The objective of the study was to prevent uncomplicated and serious cases of malaria in the target population. This study aimed to analyse the monthly trends in malaria-related morbidity among children under the age of 5 in Guinea. Methods This was a quasi-experimental study with routine data from the National Health Information System (SNIS). The two districts Mamou (the SMC intervention site) and Kindia (the control site) were selected to compare the monthly trends in malaria cases among children under the age of 5, from July to October, covering the years from 2015 to 2020. The statistical analysis used interrupted time series to estimate the effects of the SMC. Results The SMC programme contributed to a significant average reduction in the number of malaria cases of 225 cases per month in the intervention district (95% CI − 362 to − 88; p = 0.002), compared to the control district. However, the study also revealed that the effect of SMC varied between cycles, presenting different monthly malaria cases. Conclusion The SMC contributed to a significant reduction in malaria cases among children under the age of 5 in the health district of Mamou from 2018 to 2020. However, this reduction varied by monthly SMC cycle. This study suggests extending the SMC in other areas with high perennial seasonal transmission respecting the World Health Organization SMC eligibility criteria, as a strategy in the dynamic of reducing malaria cases in children under the age of 5 in Guinea. …

Abstract Purpose This executive summary of a German national guideline aims to provide the most relevant evidence-based recommendations on the diagnosis and treatment of nosocomial pneumonia. Methods The guideline made use of a systematic assessment and decision process using evidence to decision framework (GRADE). Recommendations were consented by an interdisciplinary panel. Evidence analysis and interpretation was supported by the German innovation fund providing extensive literature searches and (meta-) analyses by an independent methodologist. For this executive summary, selected key recommendations are presented including the quality of evidence and rationale for the level of recommendation. Results The original guideline contains 26 recommendations for the diagnosis and treatment of adults with nosocomial pneumonia, thirteen of which are based on systematic review and/or meta-analysis, while the other 13 represent consensus expert opinion. For this key summary, we present 11 most relevant for everyday clinical practice key recommendations with evidence overview and rationale, of which two are expert consensus and 9 evidence-based (4 strong, 5 weak and 2 open recommendations). For the management of nosocomial pneumonia patients should be divided in those with and without risk factors for multidrug-resistant pathogens and/or Pseudomonas aeruginosa. Bacterial multiplex-polymerase chain reaction (PCR) should not be used routinely. Bronchoscopic diagnosis is not considered superior to´non-bronchoscopic sampling in terms of main outcomes. Only patients with septic shock and the presence of an additional risk factor for multidrug-resistant pathogens (MDRP) should receive empiric combination therapy. In clinically stabilized patients, antibiotic therapy should be de-escalated and focused. In critically ill patients, prolonged application of suitable beta-lactam antibiotics should be preferred. Therapy duration is suggested for 7–8 days. Procalcitonin (PCT) based algorithm might be used to shorten the duration of antibiotic treatment. Patients on the intensive care unit (ICU) are at risk for invasive pulmonary aspergillosis (IPA). Diagnostics for Aspergillus should be performed with an antigen test from bronchial lavage fluid. Conclusion The current guideline focuses on German epidemiology and standards of care. It should be a guide for the current treatment and management of nosocomial pneumonia in Germany. …

Journal of Medical Virology, Volume 96, Issue 8, August 2024.

Antimicrobial resistance (AMR) is currently a highly significant global concern in the realm of public health [1]. Recently, the excessive and inappropriate use of antibiotics has resulted in the emergence and spread of bacteria resistant to multiple antimicrobials [1]. Consequently, managing infections, including urinary tract infections (UTIs), is now facing a substantial threat, as existing antibiotic treatments have become less effective [1]. To address this issue, numerous countries, including Tanzania are implementing their National Action Plans on Antimicrobial Resistance (NAP-AMR) adapted from the WHO Global Action Plans on AMR (GAP-AMR) [2, 3].

In 2022, malaria cases were estimated at 249 million globally, with about 95% occurring in sub-Saharan Africa [1]. Insecticide treated bed nets (ITNs), and indoor residual spraying (IRS) have been estimated by modelling studies to have averted 68%and 10% of clinical cases, respectively, between 2000 and 2015 [2]. However, malaria transmission continues to occur in many areas despite the use of ITNs and IRS [1]. Residual transmission, defined as “the actual maintained inoculation of Plasmodium, in spite of a well-designed and implemented vector control program” [3] has been identified as a major challenge for malaria control and elimination [4].

BackgroundInequities in palliative and end-of-life care access exist, with evidence of lower uptake of these services among people from the British Muslim community. Little research exists exploring the experiences of British Muslims with palliative care needs and their families during the pandemic or before. AimTo coproduce peer research exploring the experiences of British Muslims with palliative care needs and their families during the COVID-19 pandemic. DesignA collaborative peer research interview study. Peer researchers were recruited and trained to undertake qualitative interviewing. Data were analysed using reflective thematic analysis. Setting/participants3 peer researchers conducted 11 telephone interviews (10 in English and 1 in Urdu) between August and September 2021 with 12 participants (5 people with palliative care needs and 7 family carers). ResultsFour themes were identified: (1) issues in accessing healthcare exacerbated by the COVID-19 pandemic, (2) the impact on family carers, (3) variation in support from community groups and (4) social and information exclusion. The COVID-19 pandemic exacerbated existing challenges to accessing healthcare services for British Muslims with palliative care needs. Family members experienced the cumulative impact of supporting people with palliative needs while also advocating for and supporting them to access the care they required. Language barriers, digital exclusion and uncertainly about how to access information, in addition to the apparent lack of consideration of important festivals in the Muslim calendar in the implementation of policies around lockdowns, culminated in a sense of exclusion from COVID-19-related policies and messaging for this population. ConclusionsThese findings support the need to involve people from diverse backgrounds in the design and delivery of healthcare services and policies. Learning from this unique time in our histories should be used to shape future delivery of culturally aware and inclusive care. …

Abstract Background This study aimed to determine the prevalence and factors associated with susceptibility to hepatitis B virus (HBV) among cisgender men who have sex with men (MSM) on HIV pre-exposure prophylaxis (PrEP) in Northeastern Brazil. Methods This was a cross-sectional, analytical study conducted between September 2021 and June 2023. Participants underwent structured interviews to collect sociodemographic and clinical information, including hepatitis B vaccination history, HIV PrEP use and sexual health history. Blood samples were collected for hepatitis B serologic testing: HBV surface antigen (HBsAg), HBV surface antibody (anti-HBs), total and IgM HBV core antibody (anti-HBc). HBV susceptibility was defined as nonreactive results for all these serological markers. Results A total of 287 participants were enrolled into the study. The median age of the individuals was 31 years (interquartile range: 27; 36). HBV susceptibility was found in 58 out 286 individuals (20.3%; 95% CI: 15.9–25.2). Seventy-six percent of the participants reported completing the three-dose hepatitis B vaccine schedule. Susceptibility was significantly associated with a monthly income ≤ 5 minimum wages (PR: 2.02; 95% CI: 1.01–4.05), lack of complete hepatitis B vaccination schedule (PR: 4.52; 95% CI: 2.89–7.06), initiation of HIV PrEP (PR: 2.18; 95% CI: 1.21–3.94), duration of six months of HIV PrEP (PR: 2.16; 95% CI: 1.19–3.91), absence of tattoos (PR: 1.55; 95% CI: 1.00–2.40) and no history of sexually transmitted infections (PR: 1.65; 95% CI: 1.07–2.54). Conclusion Our findings highlight the significant burden of HBV susceptibility among MSM on HIV PrEP in Northeastern Brazil. Socioeconomic factors, vaccination status, PrEP use and sexual health behaviors play critical roles in determining susceptibility to HBV. Integrating hepatitis B screening and vaccination into PrEP services is critical for identifying and addressing HBV susceptibility among MSM. Interventions aimed at increasing vaccination coverage and promoting safer sexual practices are essential for mitigating the burden of HBV infection in this population. …

Abstract Background Brucellosis is an infectious zoonotic disease that poses serious health threats around the world including Uganda. Brucellosis is caused by Brucella spp., the bacteria being transmitted via contact through skin breaks, via inhalation, or orally through the consumption of raw milk and other dairy products. The aim of this study was to investigate self-reported prevalence, knowledge, and perceptions towards brucellosis transmission, within agro-pastoralist communities in the Nakasongola district, central Uganda. Methods This study employed a cross-sectional survey design. A semi-structured questionnaire was developed and administered to 398 participants selected through convenience sampling method. The survey gathered information on socio-demographic characteristics, knowledge of brucellosis transmission, symptoms, preventive measures, and self-reported prevalence of brucellosis. Qualitative data involved the use of six focus group discussions, identifying factors for transmission based on their perceived level of risk or impact using ranking by proportional piling. Results A majority (99.2%, n = 398) had heard about brucellosis and 71.2% were aware of the zoonotic nature of the disease. There were varied responses regarding transmission routes, symptoms, and preventive measures. Self-reported prevalence was relatively high (55.5%). Following adjusted analysis, factors such as subcounty, source of income, knowledge about symptoms of brucellosis, whether brucellosis is treatable, perception, and living close to animals were statistically significant. Participants from Wabinyonyi had 2.7 higher odds of reporting brucellosis than those from Nabiswera, aOR = 2.7, 95%CI 1.4–5.5. Crop farming and livestock had much higher odds of reporting brucellosis than those earning from casual sources, aOR = 8.5, 95%C 1.8–40.1 and aOR = 14.4, 95%CI 3.1–67.6, respectively. Those who had knowledge about symptoms had 6.9 higher odds of reporting brucellosis than who mentioned fever, aOR = 4.5, 95%CI 2.3–18.3. Likewise, living close with animals and handling aborted fetuses (aOR = 0.4, 95%CI: 0.17–0.86), (aOR = 0.2,95% CI: 0.07-0.0.42,) had significantly lower odds for self-reported prevalence compared to those who believed did not cause brucellosis. Risk factors identified included, handling of aborted fetuses and living in close proximity with animals. Overall, there was a moderate statistical agreement in the ranking across the focus groups discussion (Wc = 0.48, p 

Abstract Background A trial performed among unvaccinated, high-risk outpatients with COVID-19 during the delta period showed remdesivir reduced hospitalization. We used our real-world data platform to determine the effectiveness of remdesivir on reducing 28-day hospitalization among outpatients with mild-moderate COVID-19 during an Omicron period including BQ.1/BQ.1.1/XBB.1.5. Methods We did a propensity-matched, retrospective cohort study of non-hospitalized adults with SARS-CoV-2 infection between April 7, 2022, and February 7, 2023. Electronic healthcare record data from a large health system in Colorado were linked to statewide vaccination and mortality data. We included patients with a positive SARS-CoV-2 test or outpatient remdesivir administration. Exclusion criteria were other SARS-CoV-2 treatments or positive SARS-CoV-2 test more than seven days before remdesivir. The primary outcome was all-cause hospitalization up to day 28. Secondary outcomes included 28-day COVID-related hospitalization and 28-day all-cause mortality. Results Among 29,270 patients with SARS-CoV-2 infection, 1,252 remdesivir-treated patients were matched to 2,499 untreated patients. Remdesivir was associated with lower 28-day all-cause hospitalization (1.3% vs. 3.3%, adjusted hazard ratio (aHR) 0.39 [95% CI 0.23–0.67], p 

Abstract Liver injury with marked elevation of aspartate aminotransferase enzyme (AST) is commonly observed in dengue infection. To understand the pathogenesis of this liver damage, we compared the plasma levels of hepatic specific, centrilobular predominant enzymes (glutamate dehydrogenase, GLDH; glutathione S transferase-α, αGST), periportal enriched 4-hydroxyphenylpyruvate dioxygenase (HPPD), periportal predominant arginase-1 (ARG-1), and other non-specific biomarkers (paraoxonase-1, PON-1) in patients with different outcomes of dengue infection. This hospital-based study enrolled 87 adult dengue patients, stratified into three groups based on plasma AST levels ( 400 U/L) in a 1:1:1 ratio (n = 40, n = 40, n = 40, respectively. The new liver enzymes in the blood samples from the 4th to 6th days of their illness were measured by commercial enzyme-linked immunosorbent assay (ELISA) or colorimetric kits. Based on the diagnosis at discharge days, our patients were classified as 40 (46%) dengue without warning signs (D), 35 (40.2%) dengue with warning signs (DWS), and 11 (12.6%) severe dengue (SD) with either shock (two patients) or AST level over 1000 U/L (nine patients), using the 2009 WHO classification. The group of high AST (> 400 U/L) also had higher ALT, GLDH, ARG-1, and HPPD than the other groups, while the high (> 400 U/L) and moderate (80–400 U/L) AST groups had higher ALT, αGST, ARG-1, and HPPD than the low AST group (

Abstract Background With the prevalence of coronavirus disease 2019 (COVID-19), many severe cases have been discovered worldwide. Here, a case of concurrent pneumomediastinum, pneumoretroperitoneum, and intestinal perforation was reported. This case was the first report on COVID-19-induced related complications. Case presentation A 74-year-old female patient was hospitalized for COVID-19. Air leakage was unexpectedly found during imaging reexamination. Considering the unobvious subjective feeling of the patient, a conservative treatment was given at the early stage, and finally, sigmoid colon perforation was surgically confirmed. The family gave up the treatment at last, because the patient could not be taken off the ventilator. Coincidentally, the patient also had abnormal renal anatomical position. This situation led to an abnormal air leakage direction and the atypical manifestations of peritonitis. It was also one of the important reasons for the delayed diagnosis and treatment of the disease. Conclusions Clinicians should be vigilant for spontaneous gastrointestinal perforation in patients with COVID-19, particularly those undergoing treatment with glucocorticoids and tocilizumab. The case is shared to highlight this rare and fatal extrapulmonary manifestation of COVID-19 and further assist clinicians to raise their awareness and timely implement imaging investigation and multidisciplinary intervention so as to facilitate early discovery, diagnosis and treatment and reduce the mortality. …

Abstract Background Assessment of artificial intelligence (AI)-based models across languages is crucial to ensure equitable access and accuracy of information in multilingual contexts. This study aimed to compare AI model efficiency in English and Arabic for infectious disease queries. Methods The study employed the METRICS checklist for the design and reporting of AI-based studies in healthcare. The AI models tested included ChatGPT-3.5, ChatGPT-4, Bing, and Bard. The queries comprised 15 questions on HIV/AIDS, tuberculosis, malaria, COVID-19, and influenza. The AI-generated content was assessed by two bilingual experts using the validated CLEAR tool. Results In comparing AI models’ performance in English and Arabic for infectious disease queries, variability was noted. English queries showed consistently superior performance, with Bard leading, followed by Bing, ChatGPT-4, and ChatGPT-3.5 (P = .012). The same trend was observed in Arabic, albeit without statistical significance (P = .082). Stratified analysis revealed higher scores for English in most CLEAR components, notably in completeness, accuracy, appropriateness, and relevance, especially with ChatGPT-3.5 and Bard. Across the five infectious disease topics, English outperformed Arabic, except for flu queries in Bing and Bard. The four AI models’ performance in English was rated as “excellent”, significantly outperforming their “above-average” Arabic counterparts (P = .002). Conclusions Disparity in AI model performance was noticed between English and Arabic in response to infectious disease queries. This language variation can negatively impact the quality of health content delivered by AI models among native speakers of Arabic. This issue is recommended to be addressed by AI developers, with the ultimate goal of enhancing health outcomes. …

Abstract Background Invasive Escherichia coli disease (IED), also known as invasive extraintestinal pathogenic E. coli disease, is a leading cause of sepsis and bacteremia in older adults that can result in hospitalization and sometimes death and is frequently associated with antimicrobial resistance. Moreover, certain patient characteristics may increase the risk of developing IED. This study aimed to validate a machine learning approach for the unbiased identification of potential risk factors that correlate with an increased risk for IED. Methods Using electronic health records from 6.5 million people, an XGBoost model was trained to predict IED from 663 distinct patient features, and the most predictive features were identified as potential risk factors. Using Shapley Additive predictive values, the specific relationships between features and the outcome of developing IED were characterized. Results The model independently predicted that older age, a known risk factor for IED, increased the chance of developing IED. The model also predicted that a history of ≥ 1 urinary tract infection, as well as more frequent and/or more recent urinary tract infections, and ≥ 1 emergency department or inpatient visit increased the risk for IED. Outcomes were used to calculate risk ratios in selected subpopulations, demonstrating the impact of individual or combinations of features on the incidence of IED. Conclusion This study illustrates the viability and validity of using large electronic health records datasets and machine learning to identify correlating features and potential risk factors for infectious diseases, including IED. The next step is the independent validation of potential risk factors using conventional methods. …

Abstract Background Tuberculosis (TB) infectiousness decreases significantly with only a few days of treatment, but delayed diagnosis often leads to late treatment initiation. We conducted a sequential explanatory mixed methods study to understand the barriers and facilitators to prompt diagnosis among people with TB. Methods We enrolled 100 adults who started TB treatment in the Carabayllo district of Lima, Peru, between November 2020 and February 2022 and administered a survey about their symptoms and healthcare encounters. We calculated total diagnostic delay as time from symptom onset to diagnosis. We conducted semi-structured interviews of 26 participants who had a range of delays investigating their experience navigating the health system. Interview transcripts were inductively coded for concepts related to diagnostic barriers and facilitators. Results Overall, 38% of participants sought care first from public facilities and 42% from the private sector. Only 14% reported being diagnosed with TB on their first visit, and participants visited a median of 3 (interquartile range [IQR] health facilities before diagnosis. The median total diagnostic delay was 9 weeks (interquartile range [IQR] 4–22), with a median of 4 weeks (IQR 0–9) before contact with the health system and of 3 weeks (IQR 0–9) after. Barriers to prompt diagnosis included participants attributing their symptoms to an alternative cause or having misconceptions about TB, and leading them to postpone seeking care. Once connected to care, variations in clinical management, health facility resource limitations, and lack of formal referral processes contributed to the need for multiple healthcare visits before obtaining a diagnosis. Facilitators to prompt diagnosis included knowing someone with TB, supportive friends and family, referral documents, and seeing a pulmonologist. Conclusions Misinformation about TB among people with TB and providers, poor accessibility of health services, and the need for multiple encounters to obtain diagnostic tests were major factors leading to delays. Extending the hours of operation of public health facilities, improving community awareness and provider training, and creating a formal referral process between the public and private sectors should be priorities in the efforts to combat TB. …

Objectives: We evaluated a recently developed and validated point-of-care urine tenofovir (POC TFV) test to determine whether its use improves the accuracy of self-reported adherence to pre-exposure prophylaxis (PrEP) and sexual behavior. Design: We enrolled sexually active HIV-negative women ages 16–25 years in Kampala, Uganda. Methods: Women were followed quarterly for 24 months with HIV prevention counseling, PrEP dispensation, and adherence counseling. Midway through the study, the POC TFV test was introduced as part of routine study procedures. We examined changes in self-reported PrEP adherence, sexual behavior, and accuracy of self-reported PrEP adherence before and after the introduction of the POC TFV test. Results: A total of 146 women receiving PrEP refills had ≥1 visit with a POC TFV test administered before the study exit. At baseline, the median age was 19 years (interquartile range [IQR]: 18–21) and the majority (76%) reported having condomless sex within the last three months. Participants more frequently self-reported low PrEP adherence (OR: 2.96, 95% confidence interval [CI]: 1.89–4.67, p = 0.001) and condomless sex (OR: 1.47, 95% CI: 1.04–2.06, p = 0.03) during visits using the test compared to visits without the test. The accuracy of self-reported PrEP adherence (determined by concordance with TFV-diphosphate levels) was greater when the test was used (61% versus 24%, OR: 4.86, 95% CI: 2.85–8.30, p …

Objective: It is unclear how often anxiety is diagnosed and treated and whether anxiety treatment is associated with improved viral suppression in persons with HIV. In this study, we characterized the anxiety care continuum and its association with viral suppression in a large urban HIV clinic in the United States. Design: Observational cohort study. Methods: We described the anxiety care continuum by combining data on self-reported anxiety symptoms, engagement in mental health care, clinical diagnoses and prescriptions from 1,967 persons receiving HIV care and treatment in Baltimore, Maryland, from 2014-23. We examined cross-sectional associations with viral suppression. All analyses were stratified by sex and race/ethnicity; a secondary analysis adjusted for age, years in care, and depressive symptoms. Results: Nearly 1 in 5 patients reported mild-severe symptoms of anxiety but were not currently receiving mental health care or pharmacologic treatment for anxiety; 6% of patients reported anxiety symptoms but were receiving treatment, and 7% had been treated for anxiety that was currently in remission. The prevalence of viral suppression ranged from 87–89% across the anxiety care continuum except among patients with untreated moderate-severe anxiety, only 81% of whom were virally suppressed (95% CI: 80, 83). In adjusted models, untreated moderate-severe anxiety remained associated with viral non-suppression across demographic groups. Conclusion: We observed a robust association between untreated anxiety and viral non-suppression in a large urban cohort of persons with HIV. Screening for anxiety may identify patients with unmet mental health care needs who face barriers to maintaining viral suppression. Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.

Objectives: To determine the metabolic effects of tenofovir alafenamide (TAF) compared to tenofovir disoproxil fumarate (TDF) in vivo. Design and methods: Male Wistar rats (Rattus novergicus, 250–300 g body weight) were divided into 3 groups (n = 8) and orally treated daily with 1.0 ml distilled water (group 1), TAF (0.42 mg/kg) (group 2), or TDF (5.0 mg/kg) (group 3), respectively, for 56 days. Glucose tolerance tests were done before the animals were sacrificed by halothane overdose, and blood was collected by cardiac puncture for the analysis of plasma lipids, electrolytes, and insulin. The kidney and pancreatic tissues were excised and homogenized to measure oxidative stress. Compartmentation of TAF and TDF was determined in NRK-52 and Peripheral Blood Mononuclear Cells (PBMC). Results: There were no significant differences in weight gain among controls, TAF- or TDF-treated rats. TAF-treated rats had significantly increased fasting blood glucose (FBG), fasting plasma insulin (FPI), insulin resistance, impaired glucose tolerance, and dyslipidemia compared to control or TDF-treated rats, respectively. There was increased lipid peroxidation in the pancreas of TAF-treated compared to TDF-treated or control animals, respectively. TDF- treated rats presented with symptoms of Fanconi syndrome compared to TAF-treated or control animals, respectively. Kidney homogenates from TDF-treated animals had significantly reduced antioxidant enzyme activity compared to TAF-treated animals or controls, respectively. Intracellular concentrations of TAF were significantly higher than TDF in both NRK-52E cells and PBMC, respectively. Conclusions: TAF treatment is weight-neutral and causes dysglycemia, and dyslipidemia but not Fanconi syndrome compared to TDF. Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.

Objective: Assess the risk of death for offspring of pregnant women living with HIV (PWLHIV) and the association with sociodemographic, pregnancy, HIV-related, and birth factors. Design: We conducted a prospective cohort study of PWLHIV on antiretroviral therapy (ART) and their offspring in urban Tanzania who were enrolled in a vitamin D trial conducted from June 2015 to October 2019. Methods: We described rates of fetal, neonatal, and infant death and assessed risk factors for these outcomes with generalized estimating equations. We also estimated population-attributable risk percentages for the contribution of prematurity and small-for-gestational age (SGA) to neonatal and infant mortality. Results: Among 2,299 PWLHIV, there were a total of 136 fetal deaths (5.6%) and the stillbirth rate was 42.0 per 1,000 total births. Among 2,167 livebirths, there were 57 neonatal deaths (26.3 per 1,000 livebirths) and 114 infant deaths (52.6 per 1,000 livebirths). Twin birth was associated with neonatal death, while maternal CD4 T-cell count…

Although lymphatic filariasis and onchocerciasis have been targeted for global elimination, these helminth infections are still a major public health problem across the tropics and subtropics. Despite decades of research, treatment options remain limited and drugs that completely clear the infections, and can be used on a large scale, are still unavailable. In the present review we discuss the strengths and weaknesses of currently available treatments and new ones in development. Novel candidates (corallopyronin A, DNDi-6166, emodepside, and oxfendazole) are currently moving through (pre)clinical development, while the development of two candidates (AWZ1066S and ABBV-4083/flubentylosin) was recently halted. The preclinical R&D pipeline for filarial infections continues to be limited, and recent setbacks highlight the importance of continuous drug discovery and testing.

Wearing many hats comes naturally to Rochelle Burgess: community health psychologist, scholar activist, researcher, teacher, journal editor, and poet. “My husband calls me a cause junkie”, she says. “To me, anything that is trying to end inequality has immense value, so I say yes to a lot of things.” From witnessing poverty in Jamaica as a child to volunteering with communities affected by HIV/AIDS in Kenya in her early 20s, Burgess was always struck by the scale of inequity. It left her with “a feeling of rage and dissatisfaction with the world” that has been seminal in defining her path.

The global prevalence of activity limitations is substantially higher in women than men and in low-income countries and middle-income countries compared with high-income countries, coupled with a much lower use of gait, visual, and hearing aids. Strategies are needed to prevent and mitigate activity limitations globally, with particular emphasis on low-income countries and women.

Science, Volume 385, Issue 6709, Page 610-610, August 2024.

Science, Volume 385, Issue 6709, August 2024.

Science, Volume 385, Issue 6709, Page 586-587, August 2024.

Arboviral infections have hit South America heavily in the past decade, with the epidemic of Zika virus in 2015–16, and recurrent outbreaks of chikungunya and dengue, the latter of which is affecting Brazil with a particularly high number of cases this year. In addition, the region is now facing the re-emergence of another little-known arbovirus, Oropouche virus, on an unprecedented scale.

Abstract Background With integrase strand transfer inhibitor (INSTI) use associated with increased body mass index (BMI) and BMI increases associated with higher diabetes mellitus (DM) risk, this study explored the relationship between INSTI/non-INSTI regimens, BMI changes, and DM risk.Methods RESPOND participants were included if they had CD4, HIV RNA, and ≥ 2 BMI measurements during follow up. Those with prior DM were excluded. DM was defined as a random blood glucose ≥ 11·1 mmol/L, HbA1c ≥ 6·5%/48 mmol/mol, use of antidiabetic medication, or site reported clinical diagnosis. Poisson regression assessed the association between natural log (ln) of time-updated BMI, current INSTI/non-INSTI, and their interactions, on DM risk.Results Among 20,865 people with HIV included, most were male (74%) and White (73%). Baseline median age was 45 years (IQR 37–52), with a median BMI of 24 kg/m2 (IQR 22–26). There were 785 DM diagnoses with a crude rate of 0·73 (95%CI 0·68–0·78)/100 PYFU. Ln(BMI) was strongly associated with DM (adjusted incidence rate ratio (aIRR) 16·54 per log increase, 95%CI 11·33–24·13; p

Abstract The COVID-19 pandemic saw the largest deployment of monoclonal antibodies (mAbs) for an infectious disease in history. mAbs to SARS-CoV-2 spike protein proved safe and were initially effective for COVID-19 therapy, but each was defeated by continued SARS-CoV-2 evolution, leading to their withdrawal. This was a setback for people with impaired immunity who cannot mount an effective antibody response to SARS-CoV-2 and often cannot clear the virus. New mAbs have now been developed for pre-exposure prophylaxis (PreEP) in immunosuppressed people. Here we argue that while mAb use for PreEP is justified, single mAbs should not be used for COVID-19 therapy. In contrast to PreEP where the viral inoculum is small, immunosuppressed people with COVID-19 have large viral burden that can harbor mAb-escape variants that single-agent mAb treatments can rapidly select for resistance. Selection of mAb-escape variants has potential risks for patients, society and the feasibility of mAb therapy itself.

by Thomas Weber, Eva Tatzl, Karl Kashofer, Magdalena Holter, Slave Trajanoski, Andrea Berghold, Akos Heinemann, Peter Holzer, Michael Karl Herbert …

by Martin Duracinsky, Fabienne Marcellin, Lorraine Cousin, Vincent Di Beo, Véronique Mahé, Olivia Rousset-Torrente, Patrizia Carrieri, Olivier Chassany …

by Anna Williams, Nisreen A. Alwan, Elizabeth Taylor, Dianna Smith, Nida Ziauddeen Background Food insecurity is defined as not having safe and regular access to nutritious food to meet basic needs. This review aimed to systematically examine the evidence analysing the impacts of the COVID-19 pandemic on food insecurity and diet quality in households with children…

by Degsew Ewunetie Anteneh, Eden Bishaw Taye, Asmra Tesfahun Seyoum, Alemken Eyayu Abuhay, Endeshaw Admassu cherkose Background Co-infections involving human immunodeficiency virus (HIV), hepatitis B virus (HBV), and syphilis pose significant public health problems during pregnancy. It can increase the risk of adverse outcomes for both the woman and the infant more than each infection alone does. However, the magnitude of these co-infections remains insufficiently documented. Hence, this study aimed to determine the seroprevalence of HIV, HBV, and syphilis co-infections and associated risk factors among pregnant women attending antenatal care in Amhara region referral hospitals in northern Ethiopia. Methods A hospital-based cross-sectional study was conducted in Amhara regional state referral hospitals from January 1 to February 30, 2024, among 606 pregnant women. Pregnant women were selected using a systematic random sampling technique. An interviewer-administered questionnaire and chart review were used to collect data. Data were analyzed in SPSSV26.0. Descriptive statistics were used to determine the magnitude of co-infections, and binary logistic regression was used to determine associated factors. Variables with a P-value < 0.05 were used to declare statistical significance. Result Overall, 4.1% (95% CI: 2.7, 6.1) of pregnant women were co-infected. The prevalence of specific co-infections was 2% (95% CI: 1, 3.5) for HIV/HBV, 1.3% (95% CI: 0.6, 2.6) for HIV/syphilis, and 0.8% (95% CI: 0.3, 1.9) for HBV/syphilis. No cases of triple co-infection were observed. Women with a history of unsafe sex (AOR = 8.2, 95% CI: 1.5, 16.7) and incarceration (AOR = 9.3, 95% CI: 1.6, 20.8) were associated with HIV/syphilis co-infection. For HIV/HBV co-infection, contact with jaundice patients (AOR = 5.5, 95% CI: 1.3, 22.5) and women with a history of STIs (AOR = 4.6, 95% CI: 1.4, 14.9) was significantly associated. Women with STI history (AOR = 6.3, 95% CI: 1.2, 15.9) were also significantly associated with HBV/syphilis co-infection. Conclusion Despite the government’s elimination efforts, a relatively high prevalence of coinfections with the infections studied was found among pregnant women. Therefore, HIV, HBV, and syphilis testing and treatment packages should be strengthened by targeting pregnant women with a history of STIs, contact with patients with jaundice, a history of incarceration, and unsafe sex. …

by Derin Karacabeyli, Diane Lacaille, Na Lu, Natalie McCormick, Hui Xie, Hyon K. Choi, J. Antonio Aviña-Zubieta Objective To assess the risk of all-cause mortality and major adverse cardiovascular events (MACE) in patients with immune-mediated inflammatory diseases (IMIDs) and type 2 diabetes newly initiating glucagon-like peptide-1 receptor agonists (GLP-1-RAs) versus dipeptidyl peptidase-4 inhibitors (DPP-4is). Methods We performed a population-based cohort study using administrative health data from British Columbia. Patients with an IMID (i.e., rheumatoid arthritis, psoriatic disease, ankylosing spondylitis, inflammatory bowel disease, or a systemic autoimmune rheumatic disease) and type 2 diabetes who newly initiated a GLP-1-RA or DPP-4i between January 1, 2010, and December 31, 2021 were identified using ICD-9/10 codes. The primary outcome was all-cause mortality. Secondary outcomes included MACE and its components (i.e., cardiovascular death, myocardial infarction, and ischemic stroke). Cox proportional hazard regressions were used with propensity score overlap weighting. The analysis was repeated in age- and sex-matched adults without IMIDs. Results We identified 10,855 adults with IMIDs and type 2 diabetes who newly initiated a GLP-1-RA or DPP-4i. All-cause mortality rate was lower among initiators of GLP-1-RAs compared to initiators of DPP-4is, with a weighted hazard ratio (HR) of 0.48 (95% confidence interval [CI], 0.31–0.75) and rate difference (RD) of -9.4 (95% CI, -16.0 to -2.7) per 1000 person-years. Rate of MACE was also lower with GLP-1-RA exposure (HR 0.66 [0.50–0.88], RD -10.5 [-20.4 to -0.8]). Effect sizes were similar in adults without IMIDs. Conclusion In patients with IMIDs and type 2 diabetes, GLP-1-RA exposure is associated with a lower risk of all-cause mortality and MACE compared to a cardioneutral active comparator. …

by Ling Hou, Jing Jia, Xincheng Qin, Ming Fang, Shengnan Liang, Jianping Deng, Bei Pan, Xiangyuan Zhang, Bin Wang, Conglin Mao, Lihong Cheng, Jie Zhang, Chunhui Wang, Xuewei Ming, Tian Qin Chlamydia psittaci—a zoonotic pathogen in birds—may be transmitted to humans, causing severe respiratory disease. Individuals working in or living near poultry farms are highly susceptible to C. psittaci infection. In this study, we assessed the prevalence and genotypes of C. psittaci in poultries and humans in three cities of China by collecting fecal samples from different poultry species and throat swab samples and serum samples from workers in poultry farms and zoos. These samples were screened by real-time fluorescence quantitative PCR (qPCR) targeting C. psittaci ompA. The positive samples were subjected to PCR amplification and sequencing of ompA. The strains detected in the samples were genotyped on the basis of the phylogenetic analysis of ompA sequences. In total, 3.13% (40/1278) poultry fecal samples were positive in the qPCR assay, whereas 3.82% (6/157) of throat swab samples and 42.59% (46/108) of serum samples from the workers were positive in the qPCR and indirect fluorescent antibody assays, respectively. The strains detected in the 32 poultry samples and 6 human samples were genotyped as type A, indicating that the workers were infected with C. psittaci that originated in poultry birds in farms. Additionally, eight peacocks showed strains with the genotype CPX0308, which was identified in China for the first time. Elucidating the distribution of C. psittaci in animals and poultry-related workers may provide valuable insights for reducing the risk of C. psittaci infection within a population.

by Cecilia Aguilar-Vega, José Manuel Sánchez-Vizcaíno, Jaime Bosch Wild boar population dynamics promote the increase in numbers and distribution of the species in Eurasia, leading to a rise in the interaction with human activities, as well as generating problems with the management of certain infectious diseases, most notably African swine fever (ASF). ASF virus possesses high stability in several contaminated pork and pork products that can be a source of indirect transmission to susceptible hosts habituated to anthropogenic food waste. This transmission route is a concerning threat for the dispersion of the disease, primarily into unaffected areas given the worldwide widespread distribution of the disease and the increase of wild boar contact with humans. Thus, in this study, a straightforward tool to assess the relative risk of wild boar natural populations potentially consuming food waste is presented using synthetic data. Three risk groups were defined related to urban areas, travel, and leisure. The surrounding quality of habitat of wild boar was used to obtain the relative risk of wild boar potentially consuming anthropogenic food waste. To assign the relative risk to the corresponding risk unit, we also included the population for the urban areas group, and traffic volume for the travel risk group. The leisure group had higher scaled risk scores, followed by the urban areas group. Higher risk was found in the edges of the study area where more natural landscapes are found. The implications of this risk are discussed focusing on the context of ASF transmission. The outputs can help prioritize decision-making in terms of the improvement of preventive measures against the habituation of wild boar to anthropogenic food waste and ASFV introduction in a given study area.

New England Journal of Medicine, Ahead of Print.

Infection and Immunity, Ahead of Print.

Abstract Background The western districts of Mizoram (Lunglei, Mamit, and Lawngtlai) are malaria hotspots. Understanding the knowledge, attitude, and practices of the tribal communities in Mizoram’s western districts will aid the development of specific interventions. Methods An explanatory sequential mixed-method study was conducted from April to November 2023 in the Lunglei district. In a community-based cross-sectional survey of 353 participants, the knowledge, attitude, practices, and care-seeking behaviour toward malaria were assessed using a semi-structured questionnaire. Data was analysed using SPSS version 29 software; univariate variables were presented in percentage, and bivariate and multivariate variables were analysed using the chi-square test and logistic regression, respectively. This was followed by in-depth telephonic interviews of twelve participants, and the data was analysed using NVivo. Results Out of the 353 respondents, 77.9%, 82.7%, 55.5%, and 63.2% of the participants had good knowledge, attitude, practices, and care-seeking behaviour, respectively. The in-depth qualitative interviews highlighted the villagers’ good knowledge of the various aspects of malaria transmission, treatment, and prevention practices (indoor residual spraying and use of insecticide-treated nets). Conclusion High disease endemicity, awareness programmes and vector control interventions might be contributing to the overall good knowledge, attitude, and practices toward malaria among the villagers. In addition to vector control measures, active parasite surveillance is key to malaria control in this region. …