ObjectiveThis meta-analysis aimed to estimate the national prevalence of postpartum depression (PPD) in Uganda and identify predictors in both pre-COVID-19 and post-COVID-19 eras. DesignUsed a systematic review and meta-analysis methodology. Data sourcesReviewed papers were sourced from Medline/PubMed, PsycINFO, CINAHL/EBSCOhost, Google Scholar, ScienceDirect and African Journals Online. Eligibility criteria for selected studiesThe review encompassed observational studies published on PPD in Uganda from 1 January 2000 to 30 November 2023. Results11 studies (involving 7564 participants) published from 1 January 2000 to 30 November 2023 were reviewed. The pooled prevalence of PPD in Uganda was 29% (95% CI 21% to 37%, I2=98.32%). Subgroup analysis indicated a similar prevalence before (29%, 95% CI 20% to 39%) and during (28%, 95% CI 22% to 32%) the COVID-19 period. Special groups exhibited a higher prevalence (32%, 95% CI 16% to 47%) than general postpartum women (28%, 95% CI 19% to 37%). Factors associated with PPD included poor social support (OR 1.19, 95% CI 1.17 to 1.22, I2=96.8%), maternal illness (OR 1.22, 95% CI 1.19 to 1.26, I2=96.9%), poor socioeconomic status (OR 1.43, 95% CI 1.40 to 1.46, I2=99.5%) and undergoing caesarean section (OR 1.15, 95% CI 1.12 to 1.17, I2=80.6%). Surprisingly, there was a marginal decrease in PPD during the COVID-19 period. Subgroup analysis highlighted a higher prevalence among mothers with HIV. ConclusionThis study underscores the significant prevalence of PPD in Uganda, with sociodemographic factors increasing risk. Despite a slight decrease during the COVID-19 period, the importance of prioritising maternal mental health is emphasised, considering sociodemographic factors and pandemic challenges, to improve maternal and child health outcomes and overall well-being. …

American Journal of Respiratory and Critical Care Medicine, Volume 210, Issue 3, Page 252-253, August 1, 2024.

American Journal of Respiratory and Critical Care Medicine, Volume 210, Issue 3, Page 257-259, August 1, 2024.

American Journal of Respiratory and Critical Care Medicine, Volume 210, Issue 3, Page 343-351, August 1, 2024.

Abstract Background As antimicrobial resistance (AMR) has become a global health crisis, new strategies against AMR infection are urgently needed. Quorum sensing (QS), responsible for bacterial communication and pathogenicity, is among the targets for anti-virulence drugs that thrive as one of the promising treatments against AMR infection. Methods We identified a natural compound, Harmine, through virtual screening based on three QS receptors of Pseudomonas aeruginosa (P. aeruginosa) and explored the effect of Harmine on QS-controlled and pathogenicity-related phenotypes including pyocyanin production, exocellular protease excretion, biofilm formation, and twitching motility of P. aeruginosa PA14. The protective effect of Harmine on Caenorhabditis elegans (C. elegans) and mice infection models was determined and the synergistic effect of Harmine combined with common antibiotics was explored. The underlaying mechanism of Harmine’s QS inhibitory effect was illustrated by molecular docking analysis, transcriptomic analysis, and target verification assay. Results In vitro results suggested that Harmine possessed QS inhibitory effects on pyocyanin production, exocellular protease excretion, biofilm formation, and twitching motility of P. aeruginosa PA14, and in vivo results displayed Harmine’s protective effect on C. elegans and mice infection models. Intriguingly, Harmine increased susceptibility of both PA14 and clinical isolates of P. aeruginosa to polymyxin B and kanamycin when used in combination. Moreover, Harmine down-regulated a series of QS controlled genes associated with pathogenicity and the underlying mechanism may have involved competitively antagonizing autoinducers’ receptors LasR, RhlR, and PqsR. Conclusions This study shed light on the anti-virulence potential of Harmine against QS targets, suggesting the possible use of Harmine and its derivates as anti-virulence compounds. …

Abstract Background Viruses, which are transmitted mainly via the digestive tract, are responsible for the high morbidity and mortality of diseases, particularly in low-income countries. Although several studies have established the prevalence and characterization of various enteric viruses in Burkina Faso, to date, no aggregate data have been released. Objective Our objective was to describe the available data on the prevalence and circulating genotypes of enteric pathogen viruses responsible for human infections in Burkina Faso by carrying out a systematic review and meta-analysis. Methods Potentially relevant studies were identified by a search of PubMed, ScienceDirect, Google Scholar, university libraries and by a manual search of the reference lists of identified studies. The search with no restrictions on language or age was limited to studies conducted only in Burkina. Study selection, data extraction, and methodological quality of the included studies were performed independently by two investigators. Heterogeneity between studies was assessed using the Cochrane Q test and I2 test statistics based on the random effects model. Comprehensive meta-analysis (CMA 3.7) was employed to compute the pooled prevalence of pathogens identified in the studies. Results Forty-three (43) studies reporting 4,214 diagnosed cases in all aged human populations were selected. Overall, 72.6% of the pathogens diagnosed were gastroenteritis, and 27.2% were entero-transmissible hepatitis viruses. Rotavirus was the most common cause of human viral gastroenteritis, accounting for 27.7% (95% CI: 20.9 - 35.8) of the cases, followed by norovirus (16% (95% CI: 12.25 - 20.6)) and sapovirus (11.2% (95% CI: 6.2 - 19.4)). In terms of human entero-transmissible infections, hepatitis A virus (HAV) was the most prevalent (52% [95% CI: 14.2–87.7] of total antibodies), followed by hepatitis E virus (HEV) (28.3% [95% CI: 17.7–42]). Conclusions This study highlights the substantial burden of viral enteric infections and highlights the need for more molecular epidemiological studies to improve preventive measures against these viruses. …

Abstract Background Understanding the factors influencing disease progression and severity in pediatric COVID-19 cases is essential for effective management and intervention strategies. This study aimed to evaluate the discriminative ability of clinical and laboratory parameters to identify predictors of COVID-19 severity and mortality in hospitalized children. Methods In this multicenter retrospective cohort study, we included 468 pediatric patients with COVID-19. We developed a predictive model using their demographic, clinical, and laboratory data. The performance of the model was assessed using various metrics including sensitivity, specificity, positive predictive value rates, and receiver operating characteristics (ROC). Results Our findings demonstrated strong discriminatory power, with an area under the curve (AUC) of 0.818 for severity and 0.873 for mortality prediction. Key risk factors for severe COVID-19 in children include low albumin levels, elevated C-reactive protein (CRP), lactate dehydrogenase (LDH), and underlying medical conditions. Furthermore, ROC curve analysis highlights the predictive value of CRP, LDH, and albumin, with AUC values of 0.789, 0.752, and 0.758, respectively. Conclusion Our study indicates that laboratory values are valuable in predicting COVID-19 severity in children. Various factors, including CRP, LDH, and albumin levels, demonstrated statistically significant differences between patient groups, suggesting their potential as predictive markers for disease severity. Implementing predictive analyses based on these markers could aid clinicians in making informed decisions regarding patient management. …

Abstract Background Late presentation with advanced HIV disease (LP-AHD) remains a significant challenge to Human Immunodeficiency Virus (HIV) care, contributing to increased morbidity, mortality, and healthcare costs. Despite global efforts to enhance early diagnosis, a considerable proportion of individuals with HIV infection are unaware of being infected and therefore present late for HIV care. For the first time in Ghana, this study assessed the prevalence of LP-AHD and associated factors among people diagnosed with HIV (PDWH). Method This bi-center retrospective cross-sectional study included 315 PDWH at the Aniniwah Medical Centre and Komfo Anokye Teaching Hospital, both in Kumasi, Ghana. A well-structured questionnaire was used to collect data on sociodemographic, clinical, lifestyle and psychosocial factors from the study participants. Statistical analyses were done in SPSS version 26.0 and GraphPad Prism version 8.0 at significant p-value of

Abstract Background Human immunodeficiency virus (HIV) and tuberculosis (TB) are major contributors to morbidity and mortality in sub-Saharan Africa including Cameroon. Pharmacogenetic variants could serve as predictors of drug-induced hepatotoxicity (DIH), in patients with TB co-infected with HIV. We evaluated the occurrence of DIH and pharmacogenetic variants in Cameroonian patients. Methods Treatment-naïve patients with HIV, TB or TB/HIV co-infection were recruited at three hospitals in Cameroon, between September 2018 and November 2019. Appropriate treatment was initiated, and patients followed up for 12 weeks to assess DIH. Pharmacogenetic variants were assessed by allele discrimination TaqMan SNP assays. Results Of the 141 treatment naïve patients, the overall incidence of DIH was 38% (53/141). The highest incidence of DIH, 52% (32/61), was observed among HIV patients. Of 32 pharmacogenetic variants, the slow acetylation variants NAT2*5 was associated with a decreased risk of DIH (OR: 0.4; 95%CI: 0.17–0.96; p = 0.038), while NAT2*6 was found to be associated with an increased risk of DIH (OR: 4.2; 95%CI: 1.1–15.2; p = 0.017) among patients treated for TB. Up to 15 SNPs differed in ≥ 5% of allele frequencies among African populations, while 25 SNPs differed in ≥ 5% of the allele frequencies among non-African populations, respectively. Conclusions DIH is an important clinical problem in African patients with TB and HIV. The NAT2*5 and NAT2*6 variants were found to be associated with DIH in the Cameroonian population. Prior screening for the slow acetylation variants NAT2*5 and NAT2*6 may prevent DIH in TB and HIV-coinfected patients. …

Abstract Background Spatiotemporal analysis is a vital method that plays an indispensable role in monitoring epidemiological changes in diseases and identifying high-risk clusters. However, there is still a blank space in the spatial and temporal distribution of tuberculosis (TB) incidence rate in Pudong New Area, Shanghai. Consequently, it is crucial to comprehend the spatiotemporal distribution of TB in this district, this will guide the prevention and control of TB in the district. Methods Our research used Geographic Information System (GIS) visualization, spatial autocorrelation analysis, and space-time scan analysis to analyze the TB incidence reported in the Pudong New Area of Shanghai from 2014 to 2023, and described the spatiotemporal clustering and seasonal hot spot distribution of TB incidence. Results From 2014 to 2023, the incidence of TB in the Pudong New Area decreased, and the mortality was at a low level. The incidence of TB in different towns/streets has declined. The spatial autocorrelation analysis revealed that the incidence of TB was spatially clustered in 2014, 2016–2018, and 2022, with the highest clusters in 2014 and 2022. The high clustering area was mainly concentrated in the northeast. The space-time scan analysis indicated that the most likely cluster was located in 12 towns/streets, with a period of 2014–2018 and a radiation radius of 15.74 km. The heat map showed that there was a correlation between TB incidence and seasonal variations. Conclusions From 2014 to 2023, the incidence of TB in the Pudong New Area of Shanghai declined, but there were spatiotemporal clusters and seasonal correlations in the incidence area. Local departments should formulate corresponding intervention measures, especially in high-clustering areas, to achieve accurate prevention and control of TB within the most effective time and scope. …

Abstract Background One of the most prevalent bacteria that cause nosocomial infections is Pseudomonas aeruginosa. Fluoroquinolones (FQ) and aminoglycosides are vital antipseudomonal drugs, but resistance is increasingly prevalent. The study sought to investigate the diverse mechanisms underlying FQ and aminoglycoside resistance in various P. aeruginosa strains particularly during the COVID-19 crisis. Methods From various clinical and environmental samples, 110 P. aeruginosa isolates were identified and their susceptibility to several antibiotic classes was evaluated. Molecular techniques were used to track target gene mutations, the presence of genes encoding for quinolone resistance, modifying enzymes for aminoglycosides and resistance methyltransferase (RMT). Efflux pump role was assessed phenotypically and genotypically. Random amplified polymorphic DNA (RAPD) analysis was used to measure clonal diversity. Results QnrS was the most frequently encountered quinolone resistance gene (37.5%) followed by qnrA (31.2%) and qnrD (25%). Among aminoglycoside resistant isolates, 94.1% harbored modifying enzymes genes, while RMT genes were found in 55.9% of isolates. The aac(6\')-Ib and rmtB were the most prevalent genes (79.4% and 32.3%, respectively). Most FQ resistant isolates overexpressed mexA (87.5%). RAPD fingerprinting showed 63.2% polymorphism. Conclusions Aminoglycosides and FQ resistance observed in this study was attributed to several mechanisms with the potential for cross-contamination existence so, strict infection control practices are crucial. …

Abstract Background The global prospective surveillance data showed the re-emergence of mycoplasma pneumoniae pneumonia (MPP) in Europe and Asia after the coronavirus disease 2019 pandemic. We sought to observe the effect of macrolide antibiotics in the treatment of MPP carrying a macrolide-resistant mutation gene and the potential of targeted next-generation sequencing (tNGS) as a front-line diagnostic in MPP patients. Methods The baseline characteristics of 91 children with MPP hospitalized from January to October 2023 were retrospectively analyzed. They were divided into two groups according to whether carrying the macrolide-resistant mutation or not. The logistic and linear regression analyses were used to determine whether the mutation was a standalone predictive predictor of the duration of fever and hospital length of stay. Results First, no patients had a fever for ≥ 7 days after macrolide treatment. But length of stay and hormone concentration were significantly different between the two groups (P 

Abstract Background Following the World Health Organization’s declaration of COVID-19 as a global pandemic, several countries implemented population-wide lockdowns. However, these responses to COVID-19 caused severe healthcare system disruptions to service delivery. The TB case notification rate in Uganda decreased by 22% between January and April 2020, which coincided with a lockdown and an increase in COVID-19 cases. In this study, we tested the effect of screening all patients with both COVID-19-positive and negative symptom screen for TB at a National Referral Hospital. Design/Methods Following our formative assessment, we identified potential barriers to and facilitators of integrating screening for COVID-19 and TB at Kiruddu National Referral Hospital. To address the barriers, in February 2021 we trained healthcare providers on integrated COVID-19-TB screening tools and provided COVID-19/TB screening tools/Standard operating procedures and personal protective equipment. From March 1, 2021, to June 30, 2021, we screened patients presenting to the emergency and outpatient departments for COVID-19 symptoms, and subsequently, we performed TB symptom screening for both patients with COVID-19 positive and negative symptom screen using the intensified tuberculosis case-finding (ICF) guide. We then compared the outcomes of TB symptom screening for patients initially with a positive COVID-19 symptom screen with those who initially had a negative COVID-19 symptom screen. Results From March 2021 to June 2021, we screened 1464 patients (44.3% male and 55.7% female) for COVID-19 symptoms. Out of these participants, 1252 (85.5%) screened positive for COVID-19 symptoms, while 212 (14.5%) screened negative. The majority of patients with a positive COVID-19 symptom screen, 717 (57.3%), also screened positive for TB symptoms compared to 19 (8.9%) among patients with a negative COVID-19 symptom screen. Out of the total 736 presumptive TB cases identified, 717 (97.4%) initially screened positive for COVID-19 symptoms. TB was diagnosed in 110 individuals including 104 who had positive COVID-19-symptom screen and six who had a negative COVID-19 symptom screen. All of the 110 newly diagnosed TB cases were linked to TB treatment. Conclusions Patients who screen positive for COVID-19 symptoms should be routinely screened for TB to mitigate missed opportunities for TB case identification. …

Abstract Background Early detection of outbreaks requires robust surveillance and reporting at both community and health facility levels. Uganda implements Integrated Disease Surveillance and Response (IDSR) for priority diseases and uses the national District Health Information System (DHIS2) for reporting. However, investigations after the first case in the 2022 Uganda Sudan virus outbreak was confirmed on September 20, 2022 revealed many community deaths among persons with Ebola-like symptoms as far back as August. Most had sought care at private facilities. We explored possible gaps in surveillance that may have resulted in late detection of the Sudan virus disease (SVD) outbreak in Uganda. Methods Using a standardized tool, we evaluated core surveillance capacities at public and private health facilities at the hospital level and below in three sub-counties reporting the earliest SVD cases in the outbreak. Key informant interviews (KIIs) were conducted with 12 purposively-selected participants from the district local government. Focus group discussions (FGDs) were conducted with community members from six villages where early probable SVD cases were identified. KIIs and FGDs focused on experiences with SVD and Viral Hemorrhagic Fever (VHF) surveillance in the district. Thematic data analysis was used for qualitative data. Results Forty-six (85%) of 54 health facilities surveyed were privately-owned, among which 42 (91%) did not report to DHIS2 and 39 (85%) had no health worker trained on IDSR; both metrics were 100% in the eight public facilities. Weak community-based surveillance, poor private facility engagement, low suspicion index for VHF among health workers, inability of facilities to analyze and utilize surveillance data, lack of knowledge about to whom to report, funding constraints for surveillance activities, lack of IDSR training, and lack of all-cause mortality surveillance were identified as gaps potentially contributing to delayed outbreak detection. Conclusion Both systemic and knowledge-related gaps in IDSR surveillance in SVD-affected districts contributed to the delayed detection of the 2022 Uganda SVD outbreak. Targeted interventions to address these gaps in both public and private facilities across Uganda could help avert similar situations in the future. …

Abstract Background HBP, a novel biomarker released from neutrophils, may induce inflammatory responses and exacerbate vascular permeability, representing the pathophysiological characteristics of sepsis and septic shock. However, it remains uncertain whether the combination of HBP with other biomarkers yields enhanced diagnostic capacity for sepsis. We hypothesized that measurements included IL-6·IL-8·HBP, IL-6·IL-8·HBP/ALB and HBP/ALB which based on HBP will improve its diagnostic efficacy and even better than the traditional infection biomarkers. Methods Between July 2021 and June 2022, we carried out a comprehensive, multi-center, observational cohort study spanning six leading tertiary hospitals located in Heilongjiang Province, China. Patients were stratified into three categories based on the severity of infection: non-sepsis, sepsis, and septic shock. We collected clinical and laboratory data, along with infection and inflammation biomarkers, for analysis. Results A total of 195 patients were enrolled. Among the three groups, patients with septic shock (n = 75, 38.5%) had significantly higher baseline levels of HBP, WBC, Lac, CRP, PCT, IL-6, IL-8, and IL-10 compared to non-sepsis patients (n = 43, 22.0%) and sepsis patients (n = 77, 39.5%), with statistically significant differences (p 

Objectives: We aimed to determine the prevalence of HIV-related stigma among people with HIV (PWH) in Switzerland Design: A cross-sectional multicentre study nested within the Swiss HIV Cohort Study (SHCS). Methods: We included adult PWH enrolled in the SHCS, attending follow-up between March 1st, 2020, and January 31st, 2021. Inability to speak English, French, German, or Italian was the only exclusion criterion. Participants were invited to complete a validated 12-item HIV-stigma questionnaire comprising four stigma subscales (negative self-image, personalised stigma, disclosure concerns, and concerns regarding public attitudes), plus two healthcare-related stigma items. Questionnaire responses were graded using a four-point Likert-type scale, higher scores indicating higher stigma. “Non-applicable”, inferring HIV-status non-disclosure, was possible for personalised stigma; stigma scores from participants answering “non-applicable” to ≥1 items were analysed separately. Factors associated with HIV-stigma were identified through multivariable linear models. Results: Of 9643 PWH with a SHCS visit, 5563 participated in the study: 26% were female, 13% Black and 37% heterosexual; median age was 53 years (interquartile range 44–59); 2067 participants (37%) gave ≥1 “non-applicable” responses. Disclosure concerns had the highest stigma scores and were reported by 4656/5563 (84%). HIV-stigma was reported across all demographic groups. However, being female, Black, and heterosexual were independently associated with higher scores. Higher education and longer follow-up duration were associated with lower scores. Healthcare-related stigma was reported in 37% of participants. Conclusions: HIV-stigma was prevalent across all demographic groups. The association with being female and Black suggests that HIV-stigma accentuates pre-existing gender and race inequalities. Copyright © 2024 The Author(s). Published by Wolters Kluwer Health, Inc.

Hadal trenches represent the deepest oceanic realm and were once considered to be deprived of life. However, trenches act as important depocenters for organic matter with highly elevated microbial activity. In this forum, we discuss the biogeochemistry of the hadal realm and its microbial communities thriving at extreme hydrostatic pressure.

Science Advances, Volume 10, Issue 31, August 2024.

Science Advances, Volume 10, Issue 31, August 2024.

Science Advances, Volume 10, Issue 31, August 2024.

Science Advances, Volume 10, Issue 31, August 2024.

Science Advances, Volume 10, Issue 31, August 2024.

Tropical Medicine &International Health, EarlyView.

Volume 13, Issue 1, December 2024 .

by Keiko Kabasawa, Junta Tanaka, Tomoyo Komata, Katsuhiro Matsui, Kazutoshi Nakamura, Yumi Ito, Ichiei Narita …

by Sangwoon Jeong, Wonjoong Cheon, Sungjin Kim, Won Park, Youngyih Han Purpose Organ-at-risk segmentation is essential in adaptive radiotherapy (ART). Learning-based automatic segmentation can reduce committed labor and accelerate the ART process. In this study, an auto-segmentation model was developed by employing individual patient datasets and a deep-learning-based augmentation method for tailoring radiation therapy according to the changes in the target and organ of interest in patients with prostate cancer. Methods Two computed tomography (CT) datasets with well-defined labels, including contoured prostate, bladder, and rectum, were obtained from 18 patients. The labels of the CT images captured during radiation therapy (CT2nd) were predicted using CT images scanned before radiation therapy (CT1st). From the deformable vector fields (DVFs) created by using the VoxelMorph method, 10 DVFs were extracted when each of the modified CT and CT2nd images were deformed and registered to the fixed CT1st image. Augmented images were acquired by utilizing 110 extracted DVFs and spatially transforming the CT1st images and labels. An nnU-net autosegmentation network was trained by using the augmented images, and the CT2nd label was predicted. A patient-specific model was created for 18 patients, and the performances of the individual models were evaluated. The results were evaluated by employing the Dice similarity coefficient (DSC), average Hausdorff distance, and mean surface distance. The accuracy of the proposed model was compared with those of models trained with large datasets. Results Patient-specific models were developed successfully. For the proposed method, the DSC values of the actual and predicted labels for the bladder, prostate, and rectum were 0.94 ± 0.03, 0.84 ± 0.07, and 0.83 ± 0.04, respectively. Conclusion We demonstrated the feasibility of automatic segmentation by employing individual patient datasets and image augmentation techniques. The proposed method has potential for clinical application in automatic prostate segmentation for ART. …

New England Journal of Medicine, Volume 391, Issue 5, Page 434-441, August 1, 2024.

New England Journal of Medicine, Volume 391, Issue 5, Page 477-479, August 1, 2024.

New England Journal of Medicine, Ahead of Print.

Abstract Background Thailand aimed to eliminate malaria by 2024, and as such is planning for future prevention of re-establishment in malaria free provinces. Understanding the receptivity of local areas to malaria allows the appropriate targeting of interventions. Current approaches to assessing receptivity involve collecting entomological data. Forest coverage is known to be associated with malaria risk, as an environment conducive to both vector breeding and high-risk human behaviours. Methods Geolocated, anonymized, individual-level surveillance data from 2011 to 2021 from the Thai Division of Vector-Borne Disease (DVBD) was used to calculate incidence and estimated Rc at village level. Forest cover was calculated using raster maps of tree crown cover density and year of forest loss from the publicly available Hansen dataset. Incidence and forest cover were compared graphically and using Spearman’s rho. The current foci classification system was applied to data from the last 5 years (2017–2021) and forest cover for 2021 compared between the classifications. A simple risk score was developed to identify villages with high receptivity. Results There was a non-linear decrease in annual cases by 96.6% (1061 to 36) across the two provinces from 2011 to 2021. Indigenous Annual Parasite Index (API) and approximated Rc were higher in villages in highly forested subdistricts, and with higher forest cover within 5 km. Forest cover was also higher in malaria foci which consistently reported malaria cases each year than those which did not. An Rc > 1 was only reported in villages in subdistricts with > 25% forest cover. When applying a simple risk score using forest cover and recent case history, the classifications were comparable to those of the risk stratification system currently used by the DVBD. Conclusions There was a positive association between forest coverage around a village and indigenous malaria cases. Most local transmission was observed in the heavily forested subdistricts on the international borders with Laos and Cambodia, which are where the most receptive villages are located. These areas are at greater risk of importation of malaria due to population mobility and forest-going activities. Combining forest cover and recent case surveillance data with measures of vulnerability may be useful for prediction of malaria recurrence risk. …

Abstract Background Scale up of proven malaria control interventions has not been sufficient to control malaria in Uganda, emphasizing the need to explore innovative new approaches. Improved housing is one such promising strategy. This paper describes housing characteristics and their association with malaria burden in a moderate to high transmission setting in Uganda. Methods Between October and November 2021, a household survey was conducted in 1500 randomly selected households in Jinja and Luuka districts. Information on demographics, housing characteristics, use of malaria prevention measures, and proxy indicators of wealth were collected for each household. A finger-prick blood sample was obtained for thick blood smears for malaria from all children aged 6 months to 14 years in the surveyed households. Febrile children had a malaria rapid diagnostics test (RDT) done; positive cases were managed according to national treatment guidelines. Haemoglobin was assessed in children aged 

Abstract Introduction Haemophilus influenzae (HI) is an exceedingly rare cause of infective endocarditis (IE). Case Presentation/Methods We present a case of a 90-year-old female diagnosed with HI-IE involving the native tricuspid valve in the absence of traditional risk factors for right-sided endocarditis. She was treated with a 5-week course of IV Ampicillin from negative cultures and suffered no complications. We also conducted a thorough literature review through PubMed and Google Scholar, which yielded a mere 15 reported cases of HI-IE. Results Fourteen of the reported HI-IE cases included epidemiological data, showing no gender predominance. The mean age of the subjects was 39.5, with the mitral valve being the most implicated (64%) and tricuspid valve involvement being rare (21%). Conclusion Native tricuspid valve IE is an uncommon entity, especially in the absence of IV drug use. Haemophilus influenzae is an extremely rare cause of IE, with a literature review showing merely 15 reported cases. This article cites the 16th case of HI-IE published in the literature. …

Abstract Purpose The risk of developing active tuberculosis (TB) is considerably increased in people living with HIV/AIDS (PLWH). However, incidence of HIV/TB coinfection is difficult to assess as surveillance data are lacking in many countries. Here, we aimed to perform a quantitative analysis of HIV/TB coinfections within the Cologne/Bonn HIV cohort and to determine risk factors for active TB. Methods We systematically evaluated data of patients with HIV/TB coinfection between 2006 and 2017. In this retrospective analysis, we compared HIV/TB-coinfected patients with a cohort of HIV-positive patients. The incidence density rate (IDR) was calculated for active TB cases at different time points. Results During 2006–2017, 60 out of 4673 PLWH were diagnosed with active TB. Overall IDR was 0.181 cases/100 patient-years and ranged from 0.266 in 2006–2009 to 0.133 in 2014–2017. Patients originating from Sub-Saharan Africa had a significantly (p 

Abstract Purpose Outpatient parenteral antimicrobial therapy (OPAT) offers several key advantages, including enhanced patient quality of life, reduced healthcare costs, and a potential reduction of nosocomial infections. It is acknowledged for its safety and effectiveness. This study provides the first systematic clinical data for Germany, where OPAT has not yet been widely adopted. The aim is to establish a foundational reference point for further research and integration of OPAT into the German healthcare system. Methods This prospective observational study descriptively analyses data obtained from a cohort of patients receiving OPAT. Both in- and outpatients from all medical specialties could be recruited. Patients administered the anti-infective medications themselves at home using elastomeric pumps. Results 77 patients received OPAT, with a median duration of 15 days and saving 1782 inpatient days. The most frequently treated entities were orthopaedic infections (n = 20, 26%), S. aureus bloodstream infection (n = 16, 21%) and infectious endocarditis (n = 11, 14%). The most frequently applied drugs were flucloxacillin (n = 18, 23%), penicillin G (n = 13, 17%) and ceftriaxone (n = 10; 13%). Only 5% of patients (n = 4) reported to have missed more than one outpatient dose (max. 3 per patient). Only one catheter-related adverse event required medical intervention, and there were no catheter-related infections. Conclusion The study demonstrates that OPAT can be safely conducted in Germany. In preparation for its broader implementation, crucial next steps include creating medical guidelines, fostering interdisciplinary and inter-sectoral communication, as well as creating financial and structural regulations that facilitate and encourage the adoption of OPAT. Trial registration number NCT04002453. …

Abstract Purpose COVID-19 associated pulmonary aspergillosis (CAPA) is common and linked with high fatality rates. To assess the impact on the incidence and outcome of CAPA of an antifungal prophylaxis (AFP) we compared two cohorts of COVID-19 patients admitted to intensive care units (ICU) in Brescia, Italy, from January to August 2021. Methods The study cohort included all mechanically ventilated patients observed between April 2021 and August 2021 with SARS-CoV-2-pneumonia, who received AFP with oral posaconazole (200 mg every 6 h) and nebulized liposomal amphotericin B (50 mg every 2 weeks) from ICU admission to 7 days after discharge or, if applicable, until tracheostomy removal. The control cohort included COVID-19 patients admitted to the same ICU between January and March 2021 who did not receive any AFP. Subjects with CAPA at ICU admission were excluded. Results We included 270 patients, of whom 64 (23.7%) received AFP. In patients in the study group, CAPA-related mortality was significantly reduced (29% vs. 48% p = 0.04), as well as the incidence of CAPA (3.1% vs 12.1%, p = 0.03). Patients who developed CAPA were older (mean of 70-y-old vs 63-y-old, p 

Abstract Purpose In contrast to adults, immune protection against SARS-CoV-2 in children and adolescents with natural or hybrid immunity is still poorly understood. The aim of this study was to analyze different immune compartments in different age groups and whether humoral immune reactions correlate with a cellular immune response. Methods 72 children and adolescents with a preceding SARS-CoV-2 infection were recruited. 37 were vaccinated with an RNA vaccine (BNT162b2). Humoral immunity was analyzed 3–26 months (median 10 months) after infection by measuring Spike protein (S), nucleocapsid (NCP), and neutralizing antibodies (nAB). Cellular immunity was analyzed using a SARS-CoV-2-specific interferon-γ release assay (IGRA). Results All children and adolescents had S antibodies; titers were higher in those with hybrid immunity (14,900 BAU/ml vs. 2118 BAU/ml). NCP antibodies were detectable in > 90%. Neutralizing antibodies (nAB) were more frequently detected (90%) with higher titers (1914 RLU) in adolescents with hybrid immunity than in children with natural immunity (62.5%, 476 RLU). Children with natural immunity were less likely to have reactive IGRAs (43.8%) than adolescents with hybrid immunity (85%). The amount of interferon-γ released by T cells was comparable in natural and hybrid immunity. Conclusion Spike antibodies are the most reliable markers to monitor an immune reaction against SARS-CoV-2. High antibody titers of spike antibodies and nAB correlated with cellular immunity, a phenomenon found only in adolescents with hybrid immunity. Hybrid immunity is associated with markedly higher antibody titers and a higher probability of a cellular immune response than a natural immunity. …

Abstract Purpose The mechanisms that control inflammation in scrub typhus are not fully elucidated. The Notch pathways are important regulators of inflammation and infection, but have not been investigated in scrub typhus. Methods Plasma levels of the canonical Notch ligand Delta-like protein 1 (DLL1) were measured by enzyme immunoassay and RNA expression of the Notch receptors (NOTCH1, NOTCH2 and NOTCH4) in whole blood was analyzed by real-time PCR in patients with scrub typhus (n = 129), in patients with similar febrile illness without O. tsutsugamushi infection (n = 31) and in healthy controls (n = 31); all from the same area of South India. Results Our main results were: (i) plasma DLL1 was markedly increased in scrub typhus patients at hospital admission with a significant decrease during recovery. (ii) RNA expression of NOTCH4 was decreased at admission in whole blood. (iii) A similar pattern for DLL1 and NOTCH4 was seen in febrile disease controls. (iv) Admission DLL1 in plasma was associated with disease severity and short-term survival. (vi) Regulation of Notch pathways in O. tsutsugamushi-infected monocytes as evaluated by public repository data revealed enhanced canonical Notch activation with upregulation of DLL1 and downregulation of NOTCH4. Conclusion Our findings suggest that scrub typhus patients are characterized by enhanced canonical Notch activation. Elevated plasma levels of DLL1 were associated with organ dysfunction and poor outcomes in these patients. …

Antimicrobial Agents and Chemotherapy, Ahead of Print.

Antimicrobial Agents and Chemotherapy, Ahead of Print.

Antimicrobial Agents and Chemotherapy, Ahead of Print.

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

Abstract Introduction There is no licensed vaccine against gonorrhea but Neisseria meningitidis serogroup B outer membrane vesicle-based vaccines, like MenB-4C, may offer cross-protection against gonorrhea. This systematic review and meta-analysis synthesized the published literature on MenB-4C vaccine effectiveness against gonorrhea.Methods We conducted a literature search of electronic databases (PubMed, Medline, Embase, Global Health, Scopus, Google Scholar, CINAHL, and Cochrane Library) to identify peer-reviewed papers, published in English, from 1/1/2013–7/12/2024 that reported MenB-4C vaccine effectiveness estimates against gonorrhea and gonorrhea/chlamydia co-infection, and the duration of MenB-4C vaccine-induced protection. We estimated pooled MenB-4C vaccine effectiveness (≥1 dose) against gonorrhea using the DerSimonian-Laird random effects model.Results Eight papers met our eligibility criteria. Receipt of ≥1 dose of MenB-4C vaccine was 23%–47% effective against gonorrhea. Two doses of MenB-4C vaccine were 33–40% effective against gonorrhea and one dose of MenB-4C vaccine was 26% effective. MenB-4C vaccine effectiveness against gonorrhea/chlamydia co-infection was mixed with two studies reporting effectiveness estimates of 32% and 44%, and two other studies showing no protective effect. MenB-4C vaccine effectiveness against gonorrhea was comparable in people living with HIV (44%) and people not living with HIV (23%–47%). Pooled MenB-4C vaccine effectiveness (≥1 dose) against gonorrhea was 32.4%. One study concluded that MenB-4C vaccine effectiveness against gonorrhea may wane approximately 36 months post-vaccination.Conclusion MenB-4C vaccine is moderately effective against gonorrhea in various populations. Prospective clinical trials that assess the efficacy of MenB-4C against gonorrhea, gonorrhea/chlamydia co-infection, and duration of protection are warranted to strengthen this evidence.

Abstract Our previous study showed that OmpA-deficient Salmonella Typhimurium (STM) failed to retain LAMP-1, quit Salmonella-containing vacuole (SCV) and escaped to the host cytosol. Here we show that the cytosolic population of STM ΔompA sequestered autophagic markers, syntaxin17 and LC3B in a sseL-dependent manner and initiated lysosomal fusion. Moreover, inhibition of autophagy using bafilomycinA1 restored its intracellular proliferation. Ectopic overexpression of OmpA in STM ΔsifA restored its vacuolar niche and increased interaction of LAMP-1, suggesting a sifA-independent role of OmpA in maintaining an intact SCV. The OmpA extracellular loops impaired the LAMP-1 recruitment to SCV and caused bacterial release into the cytosol of macrophages, but unlike STM ΔompA, they retained their outer membrane stability and didn’t activate the lysosomal degradation pathway aiding in their intra-macrophage survival. Finally, OmpA extracellular loop mutations protected the cytosolic STM ΔsifA from the lysosomal surveillance, revealing a unique OmpA-dependent strategy of STM for its intracellular survival.