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Antimicrobial Agents and Chemotherapy, Ahead of Print.

Lyme borreliosis (LB) is the most common tick-transmitted infection on the northern hemisphere and is caused by bacteria in the Borrelia burgdorferi sensu lato (Bbsl)-complex. The diagnosis is partially based on serology and clinicians often take follow-up serum samples to look for seroconversion or an increase in IgG-antibody levels. In this registry-based study, we proposed a method for determining actual changes in IgG and examined antibody reactivity and decay.

Abstract Background Malaria remains a major public health threat in Ethiopia despite the tremendous progress made towards the 2030 elimination targets. The silent transmission of asymptomatic infection is one of the factors that enhance the persistence of the disease as a public health issue and impedes efforts to eliminate malaria. Thus, this study aimed at investigating the prevalence and risk factors of asymptomatic malaria infection in Boricha district, Sidama region of Ethiopia. Methods A community-based cross-sectional study was conducted in eight selected kebeles (smallest administrative unit) in Boricha district. Representative households were chosen using a multi-stage sampling technique. A total of 573 participants were included in the study. Malaria diagnosis was performed using rapid diagnostic test (RDT) and microscopy. A structured questionnaire was administered to collect socio-demographic information. Epi data 3.1 was employed for data entry, and SPSS version 25 was used for analysis. Results Of the 573 asymptomatic participants tested, 6.1% were found to be positive by RDT and 4.0% by microscopy. Participants aged under 5 years (AOR = 1.57, 95% CI 0.46–5.39) and 5–14 years old (AOR = 2.42, 95% CI 1.08–5.40), Insecticide-treated net utilization (AOR = 8.41; 95% CI 1.09–65.08), travel history (AOR = 6.85, 95% CI 2.32–20.26) and living in a house with windows (AOR = 2.11, 95% CI 1.02–4.36) were significantly associated with the asymptomatic malaria infection. Conclusion The findings of this study revealed that prevalence of asymptomatic malaria infection was higher in the study area. As a result, rigorous implementation of existing interventions, such as vector control and anti-malaria drugs, is strongly recommended. In addition, devising new ones that are suited to the contextual situations is highly suggested. …

Abstract Background Glucose-6-phosphate dehydrogenase deficiency (G6PDd) is an X-linked disorder affecting over 400 million people worldwide. Individuals with molecular variants associated with reduced enzymatic activity are susceptible to oxidative stress in red blood cells, thereby increasing the risk of pathophysiological conditions and toxicity to anti-malarial treatments. Globally, the prevalence of G6PDd varies among populations. Accordingly, this study aims to characterize G6PDd distribution within the Ecuadorian population and to describe the spatial distribution of reported malaria cases. Methods Molecular variants associated with G6PDd were genotyped in 581 individuals from Afro-Ecuadorian, Indigenous, Mestizo, and Montubio ethnic groups. Additionally, spatial analysis was conducted to identify significant malaria clusters with high incidence rates across Ecuador, using data collected from 2010 to 2021. Results The A- c.202G > A and A- c.968T > C variants underpin the genetic basis of G6PDd in the studied population. The overall prevalence of G6PDd was 4.6% in the entire population. However, this frequency increased to 19.2% among Afro-Ecuadorian people. Spatial analysis revealed 12 malaria clusters, primarily located in the north of the country and its Amazon region, with relative risks of infection of 2.02 to 87.88. Conclusions The findings of this study hold significant implications for public health interventions, treatment strategies, and targeted efforts to mitigate the burden of malaria in Ecuador. The high prevalence of G6PDd among Afro-Ecuadorian groups in the northern endemic areas necessitates the development of comprehensive malaria eradication strategies tailored to this geographical region. …

IntroductionDespite of recent advancement in the burns wound management, burn wound infection (BWI) is still one of the major cause of burns mortality. Patients who survive their burns injury still suffers from BWI related complication like delayed wound healing and poor scarring. BWI has been treated by application of topical antimicrobial agents or systemic antibiotics. Due to the global risk of developing systemic antibiotics resistance, medical research focuses on identifying single topical agent which has effective antimicrobial activity, easily available and cost effective. One such agent is acetic acid (AA). AA has been used as a topical antibacterial agent for the treatment of burns wounds for many years and has shown to have activity against gram-negative organisms including Pseudomonas aeruginosa. So far there has been no consensus on optimal concentration that has effective antimicrobial activity, frequency of application, duration of treatment and most importantly good patient’s tolerability. A randomised control study is required to answer all these questions. ObjectiveTo investigate the efficacy and tolerability of 0.5% and 2% of AA when applied to colonised burns wounds for 3 days after admittance to the Queen Elizabeth Hospital Birmingham. Methods and analysisThis is a double-blinded, prospective, randomised, controlled, single-centre trial. Patients will be screened for eligibility in the inpatient area and those who are found to be eligible will be randomly assigned to one of two treatment groups: group 1: 0.5% AA (10 patients); group 2: 2% AA (10 patients); total number: 20 patients. Outcome measuresPrimary outcome: Efficacy will be assessed by measuring the bacterial load from microbiology wound swabs for three consecutive days. Secondary outcomes: (1) The assessment of antimicrobial activity of AA and the minimum inhibitory concentrations. (2) Patient’s tolerance by assessing Visual Analogue Scale pain score. (3) Time to 95% wound healing of treatment area. (4) Patient’s perceived treatment allocation. Ethics and disseminationAceticA trial protocol was approved by the National Research Ethics Service (West Midlands—Edgbaston Research Ethics Committee; 17/WM/0407; IRAS 234132). This article refers to protocol version 5.0 dated 6 July 2020. The analysed results will be presented at national and international conferences related to management of burn patients. The generated articles based on the trial results will be submitted to peer review journals for publication. Trial registration numberISRCTN11636684. …

ObjectivesThe aim of this sequential mixed-methods study was to describe and understand how paediatric short stay admission (SSA) rates vary across Health Board regions of Scotland. DesignExploratory sequential mixed-methods study. Routinely acquired data for the annual (per capita) SSA to hospital were compared across the 11 regions. Five diverse regions with different SSA per capita formed cases for qualitative interviews with health professionals and parents to explore how care pathways, service features and geography may influence decisions to admit. SettingScotland. ParticipantsAll children admitted to hospital 2015–2017. Healthcare staff (n=48) and parents (n=15) were interviewed. ResultsOf 171 039 urgent hospital admissions, 92 229 were SSAs, with a fivefold variation between 14 and 69/1000 children/year across regions. SSAs were higher for children in the most deprived compared with the least deprived communities. When expressed as a ratio of highest to lowest SSA/1000 children/year for diagnosed conditions between regions, the ratio was highest (10.1) for upper respiratory tract infection and lowest (2.8) for convulsions. Readmissions varied between 0.80 and 2.52/1000/year, with regions reporting higher SSA rates more likely to report higher readmission rates (r=0.70, p=0.016, n=11). Proximity and ease of access to services, local differences in service structure and configuration, national policy directives and disparities in how an SSA is defined were recognised by interviewees as explaining the observed regional variations in SSAs. Socioeconomic deprivation was seldom spontaneously raised by professionals when reflecting on reasons to refer or admit a child. Instead, greater emphasis was placed on the wider social circumstances and parents’ capacity to cope with and manage their child’s illness at home. ConclusionSSA rates for children vary quantitatively by region, condition and area deprivation and our interviews identify reasons for this. These findings can usefully inform future care pathway interventions. …

IntroductionVery preterm infants are at risk of abnormal microbiome colonisation in the first weeks to months of life. Several important associated factors have been identified including gestational age, mode of delivery, antibiotic exposure and feeding. Preterm infants are at risk of a number of pathologies for which the microbiome may play a central role, including necrotising enterocolitis and sepsis. The objective of this study is to determine detailed microbiome changes that occur around implementation of different management practices including empiric antibiotic use, advancement of feeds and administration of probiotics during admission to the neonatal intensive care unit. Methods and analysisA single-site, longitudinal observational study of infants born less than 32 weeks gestation, including collection of maternal samples around delivery and breastmilk and infant samples from admission through discharge from the neonatal unit. Ethics and disseminationThe protocol was approved by the Clinical Research Ethics Committee of the Cork Teaching Hospitals. The findings from this study will be disseminated in peer-reviewed journals, during scientific conferences, and directly to the study participants. Sequencing data will be deposited in public databases. Trial registration numberNCT05803577. …

With new RNA interference (RNAi) pathway-deficient mosquitoes, Merkling et al. invite a shift in our view of this pathway’s role in regulating arthropod-borne virus (arbovirus) transmission. While loss of RNAi function enhanced early viral replication, little impact on transmission was observed, inviting renewed exploration of molecular barriers to arbovirus transmission.

African trypanosomes show a remarkable ability to survive as extracellular parasites in the blood and tissue spaces of an infected mammal. Throughout the infection they are exposed to the molecules and cells of the immune system, including complement. In this opinion piece, we review decades-worth of evidence about how complement affects African trypanosomes. We highlight the discovery of a trypanosome receptor for complement C3 and we critically assess three recent studies which attempt to provide a structural and mechanistic view of how this receptor helps trypanosomes to survive in the presence of complement.

Anopheles arabiensis is one of the three dominant vector species within the An. gambiae complex. It remains a principal vector of malaria across much of Africa besides An. gambiae s.s. and Anopheles funestus. It has an extensive range in drier environments that extends into arid areas south of the Sahara, Horn of Africa, and savannah of Namibia. Its larval habitats range from small, temporary, sunlit clear and shallow fresh water pools to stagnant and turbid water bodies with or without vegetation, rice fields, and a variety of natural and manmade habitats.

Parasitic diseases continue to afflict millions of people globally. However, traditional vaccine development strategies are often difficult to apply to parasites, leaving an immense unmet need for new effective vaccines for the prevention and control of parasitic infections. As parasites commonly use extracellular vesicles (EVs) to interact with, interfere with, or modulate the host immune response from a distance, parasite-derived EVs may provide promising vaccine agents that induce immunity against parasitic infections. We here present achievements to date and the challenges and limitations associated with using parasitic EVs in a clinical context. Despite the many difficulties that need to be overcome, we believe this direction could offer a new and reliable source of therapeutics for various neglected parasitic diseases.

The provision of probiotics benefits the health of a wide range of organisms, from humans to animals and plants. Probiotics can enhance stress resilience of endangered organisms, many of which are critically threatened by anthropogenic impacts. The use of so-called ‘probiotics for wildlife’ is a nascent application, and the field needs to reflect on standards for its development, testing, validation, risk assessment, and deployment. Here, we identify the main challenges of this emerging intervention and provide a roadmap to validate the effectiveness of wildlife probiotics. We cover the essential use of inert negative controls in trials and the investigation of the probiotic mechanisms of action. We also suggest alternative microbial therapies that could be tested in parallel with the probiotic application. Our recommendations align approaches used for humans, aquaculture, and plants to the emerging concept and use of probiotics for wildlife.

by Bowen Li, S. Selvakumar Raja, Jiajun Li, Zejun Yao, Wenguang Song, Haoyuan Li At present, the fault diagnosis of pumping units in major oil fields in China is time-consuming and inefficient, and there is no universal problem for high requirements of hardware resources. In this study, a fault fusion diagnosis method of pumping unit based on improved Fourier descriptor (IDF) and rapid density clustering RBF (RDC-RBF) neural network is proposed. Firstly, the minimum inertia axis of the center of gravity of the indicator diagram is obtained. The farthest point of the intersection of the inertial axis and the contour is determined as the starting point. Then Fourier transform is performed on the contour boundary of the graph to obtain the feature vector. Then, combining with the idea of fast density clustering algorithm, the number of hidden layer neurons of RBF is determined by finding the point with the highest density and using it as the hidden layer neuron. At the same time, the characteristics of Gaussian function are introduced to ensure the activity of hidden layer neurons. Finally, through dynamic adaptive cuckoo search (DACS), the step size is automatically adjusted according to the convergence speed of the objective function of RBF, and the efficiency and accuracy of RBF in different search stages are balanced. The optimal parameters such as the width and weight of RBF are determined, and the optimal RDC-RBF fault diagnosis model is established. The model is applied to the diagnosis of different fault types of pumping units, and compared with the current mainstream models. The average detection accuracy of the fusion RDC-RBF fault diagnosis method proposed in this paper reaches 96.3%. The measured results have high accuracy and short time. At the same time, this method is currently applied to oil production sites such as Shengli Oilfield in China, which greatly reduces the human resources required for fault diagnosis of pumping units in the past.

by Rebecca Hibbard, Lorraine Chapot, Havan Yusuf, Kurnia Bagus Ariyanto, Kusnul Yuli Maulana, Widya Febriyani, Angus Cameron, Timothée Vergne, Céline Faverjon, Mathilde C. Paul Interventions to change antimicrobial use (AMU) practices can help mitigate the risk of antimicrobial resistance (AMR) development. However, changing AMU practices can be challenging due to the complex nature of the factors influencing AMU-related behaviours. This study used a qualitative approach to explore the factors that influenced decision-making on AMU by farmers and other actors in the Indonesian poultry sector. Thirty-five semi-structured interviews were conducted with farmers, technical services staff from the private sector, and representatives of associations, universities, and international organisations in Central Java, West Java, and East Java. Thematic analysis identified three patterns of influence on AMU: how farmers used information to make AMU-related decisions, the importance of farmers’ social and advisory networks, and the motivations driving changes in AMU behaviours. Key barriers identified included a lack of shared understanding around when to use antibiotics, financial pressures in the poultry sector, and a lack of engagement with government veterinary services. Potential opportunities identified included high farmer awareness of AMU, identification of private sector actors and peer networks as the stakeholders with established relationships of trust with farmers, and the importance of farmers’ conceptions of good farming practices, which could be engaged with to improve AMU practices.

by Erlina Burhan, Keibun Liu, Eva M. Marwali, Samuel Huth, Navy G. H. M. L. Wulung, Dafsah A. Juzar, Muhammad A. Taufik, Surya O. Wijaya, Dyah K. Wati, Neurinda P. Kusumastuti, Saptadi Yuliarto, Bhirowo Y. Pratomo, Erwin Pradian, Dadang H. Somasetia, Desy Rusmawatiningtyas, Arie Z. Fatoni, Jose M. Mandei, Eka Y. Lantang, Fajar Perdhana, Bambang P. Semedi, Muhammad Rayhan, Tiffany R. S. Tarigan, Nicole White, Gianluigi L. Bassi, Jacky Y. Suen, John F. Fraser Background Indonesia’s national response to COVID-19 evolved rapidly throughout 2020. Understanding pandemic response and outcomes is crucial for better mitigation strategies ahead. This study describes the characteristics and outcomes of patients admitted to ICU during the early stages of the pandemic. Methods This is a multi-centre prospective observational study including patients from twelve collaborating hospitals in Indonesia. All patients were clinically suspected or laboratory-confirmed COVID-19 cases admitted to ICU between January 2020 and March 2021. The primary outcome was monthly ICU mortality. Descriptive statistics of patient characteristics and treatment were generated as secondary outcomes. Results From 559 subjects, the overall mortality was 68% and decreased over the study period, while the mortality of patients that received mechanical ventilation was 92%, consistently high over the study period. Fatal cases showed 2- and 4-day delays from symptoms onset to hospital admissions and ICU admissions, respectively. Evidence-backed approaches which could influence patient outcome, such as extracorporeal membrane oxygenation, prone positioning, renal replacement therapy, and neuromuscular blockade were scarcely administered. Conclusions The mortality rate of COVID-19 patients in Indonesia was extremely high during the first major outbreak of disease, particularly in those mechanically ventilated. Delayed admission and unavailability of evidence-based approaches due to high burden on health facility during COVID-19 crisis could be addressed by efficient public health measures and enhancing health infrastructure to improve the future pandemic response. …

AbstractBackgroundLow awareness and lack of routine testing for respiratory syncytial virus (RSV) infections among adults has led to underreporting and misclassification in hospital records. The Danish National Patient Registry (DNPR) provide an opportunity to identify all patients hospitalized with a respiratory tract infection (RTI) diagnosis. This study aimed to assess the underreporting and misclassification of RSV infections among adults hospitalized with an RTI-coded hospitalization.MethodsThis study is an observational cohort study of RSV-associated hospitalizations among Danish adults (≥18 years old) based on national healthcare registries conducted in the period of week 40, 2015 to week 40, 2018. Data were extracted from the DNPR and the Danish Microbiology Database and linked via a personal identification number. We identified RSV-positive hospitalizations by linking RTI-coded hospitalizations with a positive RSV test.ResultsUsing hospital admission registries, we identified 440 RSV-coded hospitalizations, of whom 420 (95%) had a positive RSV test registered. By linking patients with RTI-coded hospital admissions to RSV test result, we found 570 additional episodes of RSV-positive hospitalizations without an RSV-coded diagnosis.ConclusionOur study showed that RSV is underreported among Danish adults using national register data. The study showed that the reliability of hospitalization data to estimate the burden of RSV among adults can be questioned and are sensitive to changes in practice over time, even with complete nationwide healthcare data. Studies based on healthcare data can be useful to observe trends and seasonality but to estimate the burden of RSV among adults, comprehensive prospective surveillance are recommended.

AbstractBackgroundIn the Netherlands, the number of mpox cases started declining before mpox vaccination was initiated. Most cases were men who have sex with men (MSM). We investigated whether the decline in mpox could be attributed to infection-induced immunity or behavioural adaptations.MethodsWe developed a transmission model and accounted for possible behavioural adaptations: less casual partners and shorter time until MSM with mpox refrain from sexual contacts.ResultsWithout behavioural adaptations, the peak in modelled cases matched observations, but the decline was less steep than observed. With behavioural adaptations in the model, we found a decline of 16-18% in numbers of casual partners in June and 13-22% in July 2022. Model results showed a halving of the time before refraining from sex. When mpox vaccination started, 57% of MSM with very high sexual activity in the model had been infected. Model scenarios revealed that the outbreak could have waned by November 2022 even without vaccination.ConclusionsThe limited duration of the mpox outbreak in the Netherlands can be ascribed primarily to infection-induced immunity among MSM with high sexual activity levels. The decline was accelerated by behavioural adaptations. Immunity among those most sexually active is essential to impede mpox resurgence.

AbstractBackgroundLinezolid is evaluated in novel treatment regimens for tuberculous meningitis (TBM). Linezolid pharmacokinetics have not been characterized in this population, particularly in cerebrospinal fluid (CSF) where exposures may be affected by changes in protein concentration. Linezolid co-administration with high-dose rifampicin, has also not been studied. We aimed to characterize linezolid plasma and CSF pharmacokinetics in adults with TBM.MethodsIn LASER-TBM pharmacokinetic-substudy, the intervention groups received high-dose rifampicin (35mg/kg) plus linezolid 1200mg/day for 28days, then reduced to 600mg/day. Plasma sampling was done on day 3 (intensive) and on day 28 (sparse). A lumbar CSF sample was obtained on both visits.Results30-participants, median(min-max) age and weight of 40(27–56)years and 58(30–96)kg, contributed 247 plasma and 28 CSF observations. Plasma pharmacokinetics was described by one-compartment model with first-order absorption and saturable elimination. Maximal clearance was 7.25L/h, and Km was 27.2mg/L. Rifampicin co-treatment duration did not affect linezolid pharmacokinetics. CSF-Plasma partitioning correlated with CSF total-protein upto 1.2g/L where the partition-coefficient reached maximal value of 37%. Plasma-CSF equilibration half-life was ∼3.5hoursConclusionLinezolid was readily detected in CSF despite high-dose rifampicin co-administration. These findings support continued clinical evaluation of linezolid plus high-dose rifampicin for the treatment of TBM in adults.

AbstractWe measured cytomegalovirus (CMV)-specific antibodies that neutralize epithelial cell infection (CMV-AbNEIs) in 101 CMV-seropositive kidney transplant recipients (KTRs) at baseline and post-transplant months 3 and 6. All the patients received antithymocyte globulin and 3-month valganciclovir prophylaxis. There were no significant differences in pre-transplant AbNEIs titers between KTRs that developed or did not develop any-level CMV infection or the composite of high-level infection and/or disease. One-year CMV infection-free survival was comparable between KTRs with or without pre-transplant CMV-AbNEIs. No differences were observed by months 3 and 6 either. We observed no protective role for CMV-AbNEIs among CMV-seropositive KTRs undergoing T-cell-depleting induction.

AbstractBackgroundHigh resolution metabolomics (HRM) is an innovative tool to study challenging infectious diseases like leprosy, where the pathogen cannot be grown with standard methods. Here, we use HRM to better understand associations between disease manifestations, nutrition, and host metabolism.MethodsFrom 2018-2019, adults with leprosy and controls were recruited in Minas Gerais, Brazil. Plasma metabolites were detected using an established HRM workflow and characterized by accurate mass m/z and retention time. The mummichog informatics package compared metabolic pathways between cases and controls and between multibacillary (MB) and paucibacillary (PB) leprosy. Additionally, select individual metabolites were quantified and compared.ResultsThirty-nine cases (62% MB and 38% PB) and 25 controls were enrolled. We found differences (p

Abstract Background Lower respiratory tract infections are the leading cause of mortality in young children globally. In many resource-limited settings clinicians rely on guidelines such as IMCI or ETAT + that promote empiric antibiotic utilization for management of acute respiratory illness (ARI). Numerous evaluations of both guidelines have shown an overall positive response however, several challenges have also been reported, including the potential for over-prescribing of unnecessary antibiotics. The aims of this study were to describe the antibiotic prescribing practices for children less than 24 months of age with symptoms of ARI, that were admitted to Kenema Government Hospital (KGH) in the Eastern Province of Sierra Leone, and to identify the number of children empirically prescribed antibiotics who were admitted to hospital with ARI, as well as their clinical signs, symptoms, and outcomes. Methods We conducted a prospective study of children 

Abstract Background Chlamydia Trachomatis (CT) is among the most prevalent sexually transmitted diseases (STDs) globally. According to the World Health Organization, more than 131 million people get infected with CT annually. CT is usually transmitted via sexual contact or perinatal exposure and can result in severe long-term complications. In developing nations, particularly, the prevention and control of CT is challenging. Hence, this study will explore the feedback mechanisms of chlamydia prevention and control, as well as identify the essential factors affecting the control and prevention of this infection in China. Methods Our study will employ a mixed-methods research design that encompasses both qualitative and quantitative methods. Firstly, we will develop a causal loop diagram (CLD) based on the literature review and optimize it via in-depth interviews with stakeholders. Additionally, we will utilize a quantitative method called MICMAC(Impact Matrix Cross-Reference Multiplication Applied to a Classification tool) to obtain consensus among different stakeholders and pinpoint the key information. Next, the CLD will be transformed into a system dynamics model (SDM) to evaluate the feedback mechanisms within the CLD. The causality in the CLD will be modeled using mathematical equations, which facilitate the transformation into an SDM. As such, we will be able to analyze the dynamic behavior of the system and its response to different decisions. Discussion Our study offers a systematic perspective on the control and prevention of chlamydia infection through system dynamics modeling, examining the dynamic properties and background factors of the system. The creation of the CLD affords stakeholders the chance to comprehend the functionality of their relationships and improve cooperation. Consequently, by evaluating the outcomes of these simulations, it will be possible to analyze and determine potential interventions and their effects on chlamydia infections. This modeling approach can help us gain insight into the dynamic characteristics of the system, evaluate the potential outcomes of different decisions, and design control strategies to either stabilize the system or adjust its behavior. …

Abstract Background Coverage of HIV testing remains sub-optimal in West Africa. Between 2019 and 2022, the ATLAS program distributed ~400 000 oral HIV self-tests (HIVST) in Côte d’Ivoire, Mali, and Senegal, prioritising female sex workers (FSW) and men having sex with men (MSM), and relying on secondary redistribution of HIVST to partners, peers and clients to reach individuals not tested through conventional testing. This study assesses the proportion of first-time testers among HIVST users and the associated factors. Methods A phone-based survey was implemented among HIVST users recruited using dedicated leaflets inviting them to anonymously call a free phone number. We collected socio-demographics, sexual behaviours, HIV testing history, HIVST use, and satisfaction with HIVST. We reported the proportion of first-time testers and computed associated factors using logistic regression. Results Between March and June 2021, 2 615 participants were recruited for 50 940 distributed HIVST (participation rate: 5.1%). Among participants, 30% received their HIVST kit through secondary distribution (from a friend, sexual partner, family member, or colleague). The proportion who had never tested for HIV before HIVST (first-time testers) was 41%. The main factors associated with being a first-time tester were sex, age group, education level, condom use, and secondary distribution. A higher proportion was observed among those aged 24 years or less (55% vs 32% for 25–34, aOR: 0.37 [95%CI: 0.30–0.44], and 26% for 35 years or more, aOR: 0.28 [0.21–0.37]); those less educated (48% for none/primary education vs 45% for secondary education, aOR: 0.60 [0.47–0.77], and 29% for higher education, aOR: 0.33 [0.25–0.44]). A lower proportion was observed among women (37% vs 43%, aOR: 0.49 [0.40–0.60]); those reporting always using a condom over the last year (36% vs 51% for those reporting never using them, aOR: 2.02 [1.59–2.56]); and those who received their HISVST kit through primary distribution (39% vs 46% for secondary distribution, aOR: 1.32 [1.08–1.60]). Conclusion ATLAS HIVST strategy, including secondary distribution, successfully reached a significant proportion of first-time testers. HIVST has the potential to reach underserved populations and contribute to the expansion of HIV testing services in West Africa. …

Abstract Background Salmonellosis is a major cause of morbidity and mortality and one of the most frequent etiologies of diarrhea in the world. Mortality due to Salmonellosis in Latin America still poorly understood, and there is a lack of studies that evaluate resistance and clinical manifestations. The aims of this study were to characterize patients infected with Salmonella spp. seen in a university hospital in Colombia between 2012 and 2021, to evaluate trends in antibiotic resistance and to determine the proportion of overall mortality and related factors. Methods Retrospective observational study. All patients with microbiological diagnosis of Salmonella spp. were included. The sociodemographic, clinical and microbiological characteristics were described, and the proportion of antibiotic resistant isolates per year was estimated. The prevalence of mortality according to age groups was calculated. Log binomial regression models were used to establish factors associated with mortality. Results Five hundred twenty-two patients were analyzed. Salmonellosis accounted for 0.01% of all medical consultations. The median age was 16 years old. The most common clinical presentation was gastroenteric syndrome (77.1%) and symptoms included diarrhea (79.1%), fever (66.7%), abdominal pain (39.6%) and vomiting (35.2%). Of the Salmonella spp. isolates, 78.2% were not classified, 19.1% corresponded to non-typhoidal Salmonella and 2.7% to Salmonella typhi. Mortality occurs in 4.02% of the patients and was higher in patients with hematologic malignancy (11.6%). When analyzing by age group, the proportion of deaths was 2.8% in patients aged 15 years or younger, while in those older than 15 years it was 5.4%. Factors associated to mortality where bacteremia (aPR = 3.41 CI95%: 1.08—10.76) and to require treatment in the ICU (aPR = 8.13 CI95%: 1.82—37.76). In the last 10 years there has been a steady increase in resistance rates to ciprofloxacin, ampicillin, ampicillin/sulbactam and ceftriaxone, reaching rates above 60% in recent years. Conclusions Despite improved availability of antibiotics for the treatment of salmonellosis in the past decades, mortality due to salmonellosis continues occurring in children and adults, mainly in patients with hematological malignancies and bacteremia. Antibiotic resistance rates have increased significantly over the last 10 years. Public health strategies for the control of this disease should be strengthened, especially in vulnerable populations. …

Abstract Background Human immunodeficiency virus type one (HIV-1) is the leading cause of acquired immunodeficiency syndrome (AIDS). AIDS remains a global public health concern but can be effectively suppressed by life-long administration of combination antiretroviral therapy. Early detection and diagnosis are two key strategies for the prevention and control of HIV/AIDS. Rapid and accurate point-of-care testing (POCT) provides critical tools for managing HIV-1 epidemic in high-risk areas and populations. Methods In this study, a POCT for HIV-1 RNA was developed by CRISPR-Cas13a lateral flow strip combined with reverse transcriptase recombinase-aided amplification (RT-RAA) technology, the results can be directly observed by naked eyes. Results Moreover, with the degenerate base-binding CRISPR-Cas13a system was introduced into the RT-RAA primer designing, the technology developed in this study can be used to test majority of HIV-1 RNA with limit of detection (LOD) 1 copy/μL, while no obvious cross-reaction with other pathogens. We evaluated this method for detecting HIV-1 RNA of clinical samples, the results showed that the sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV) and accuracy were 91.81% (85.03- 96.19%), 100% (92.60–100%), 100% (96.41–100%), 39.14% (25.59–54.60%) and 92.22% (86.89–95.88%), respectively. The lowest viral load detectable by this method was 112copies/mL. Conclusion Above all, this method provides a point-of-care detection of HIV-1 RNA, which is stable, simple and with good sensitivity and specificity. This method has potential to be developed for promoting early diagnosis and treatment effect monitoring of HIV patients in clinical. …

Volume 14, Issue 1, December 2023 .

Abstract Background Malaria is a parasitic disease caused by various species of the blood parasite Plasmodium; of all the parasitic diseases, malaria has the highest prevalence and mortality with an estimated 247 million cases and 619,000 deaths recorded worldwide as of 2021. Malaria causes febrile illness with several changes in blood cell parameters. Some of these changes include leucopenia, thrombocytopenia, and anaemia. If these changes could be correlated with the degree of parasitaemia, it can serve as a guide to physicians when treating malaria. This study was therefore aimed at correlating haematological parameters with levels of parasitaemia during malaria infection. Methods The study was a cross-sectional study involving 89 malaria positive patients. About 5 ml of blood was collected from each participant who gave his or her informed consent to partake in the study. A full blood count was performed on their samples to determine their haematological parameters using a haematology auto-analyzer. A parasite count was also performed via microscopy to determine the degree of parasitaemia. The data obtained from the study was entered into a database and statistically analysed using Statistical Package for Social Sciences (SPSS) version 23 and Microsoft Excel 2016. Results The study comprised of 89 participants out of which 35 were males and 54 were females with the mean age of 26.15 years. Secondary education participants were the highest with quaternary education the lowest. The highest parasite count recorded was 398,174 parasites/µl of blood, lowest count was 101 with the average being 32,942.32584. There was also a significant positive Pearson’s correlation between total WBC and parasitaemia and with the WBC differentials, neutrophils, lymphocytes and monocytes had positive correlations while eosinophils and basophils had negative correlations. Furthermore, platelets, total RBC’s, haemoglobin, MCH, MCHC and Hct all showed negative correlations. Linear regression also showed a linear relationship between parasite density and the various haematological parameters. Conclusion The linear relationship (correlation) between WBC and MCH were the only significant ones at 95% and 99% confidence interval, respectively based on a two-tail t-test. Also, based on the regression analysis, the changes caused by WBC and PLT were the only significant changes at 95% confidence level in a two-tailed t-test. …

Early in the COVID-19 pandemic, a shortage of N95 filtering facepiece respirators (FFRs) led several hospitals to introduce mask decontamination and re-use.

AbstractThe phylum Nucleocytoviricota includes the largest and most complex viruses known. These “giant viruses” have a long evolutionary history that dates back to the early diversification of eukaryotes, and over time they have evolved elaborate strategies for manipulating the physiology of their hosts during infection. One of the most captivating of these mechanisms involves the use of genes acquired from the host - referred to here as viral homologs or “virologs” - as a means of promoting viral propagation. The best-known examples of these are involved in mimicry, in which viral machinery “imitates” immunomodulatory elements in the vertebrate defense system. But recent findings have highlighted a vast and rapidly expanding array of other virologs that include many genes not typically found in viruses, such as those involved in translation, central carbon metabolism, cytoskeletal structure, nutrient transport, vesicular trafficking, and light harvesting. Unraveling the roles of virologs during infection as well as the evolutionary pathways through which complex functional repertoires are acquired by viruses are important frontiers at the forefront of giant virus research.

New England Journal of Medicine, Ahead of Print.

Human respiratory syncytial virus (HRSV) can cause severe diseases such as bronchiolitis and pneumonia in specific vulnerable populations, such as infants [1]. Bronchiolitis is the most common severe HRSV-related disease in infants, characterized by inflammation of the bronchioles, mucus production, and subsequent airway obstruction. An excessive inflammatory response has been related to HRSV pathogenesis, but also a robust innate immune response is needed to control virus replication and protect against severe HRSV disease [2].

Background: Clinical trials of dapivirine vaginal ring have shown it is safe, effective, and desired by women as an HIV prevention option. The risk of drug resistance is a potential concern for dapivirine ring users who acquire HIV. We conducted a comprehensive resistance evaluation of plasma samples from the women who seroconverted during the Microbicide Trials Network (MTN)-025/HOPE open-label study of dapivirine ring. Methods: Plasma collected on the visit at which seroconversion was detected was tested by next-generation sequencing with unique molecular identifiers (NGS-UMI) for non-nucleoside reverse transcriptase inhibitor (NNRTI) drug resistance mutations (DRM) present at ≥1% frequency. Bulk-cloned plasma-derived recombinant HIV was phenotyped in a TZM-bl-based assay for susceptibility to dapivirine and other NNRTI. HIV-1 RNA was retrospectively quantified in plasma samples collected prior to HIV seroconversion. Results: Among 38 participants who seroconverted in HOPE, 7 (18%) had NNRTI DRM detected by NGS-UMI including A98G, K103N, V106M, E138A and V179D. Six of 7 samples with NNRTI DRM had 3 months after acquiring HIV infection. Conclusion: NNRTI resistance among women who seroconverted during HOPE was infrequent and selection of dapivirine-specific mutations was not detected. Dapivirine ring is considered a safe and effective option for HIV prevention in women. Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.

Background: Coronavirus disease (COVID-19) severely disrupted routine healthcare globally. This study assessed the impact of successive COVID-19 waves on HIV viral load (VL) suppression in South Africa, using the national public sector laboratory database. Guidelines recommend VL monitoring at 6 months after treatment initiation, and annually once suppressed, or more frequently if unsuppressed. Methods: Specimen-level VL data was extracted for the period January 2019 to December 2021. We assessed the national percentage of samples with a VL…

Background: Lifelong ART use is recommended for pregnant and breastfeeding women living with HIV (WLWH) to prevent perinatal HIV transmission and improve maternal health. We address two objectives in this analysis: (1) determine timing and factors associated with breastfeeding cessation, and (2) assess the impact of breastfeeding on health of women living with HIV on ART. Setting: Multi-country study of eight sites in Uganda, Malawi, Zimbabwe and South Africa. Methods: Prospective study of WLWH on lifelong ART. These women initially participated from 2011 to 2016 in a randomized clinical trial (PROMISE) to prevent perinatal HIV transmission, and subsequently re-enrolled in an observational study (PROMOTE, 2016-2021) to assess ART adherence, safety, and impact. Results: The PROMOTE cohort included 1987 women on ART. Of these, 752 breastfed and were included in analyses of objective 1; all women were included in analyses of objective 2. Median time to breastfeeding cessation varied by country (11.2-19.7 months). Country of residence, age and health status of women were significantly associated with time to breastfeeding cessation (compared to Zimbabwe: Malawi, adjusted hazard ratio [aHR] 0.50, 95% CI 0.40-0.62, p…

Background: The Covid-19 pandemic has created substantial and profound barriers to several forms of healthcare engagement. For Black sexual minority men, this may include engagement with pre-exposure prophylaxis (PrEP) to prevent HIV infection, with significant implications for HIV disparities. Our study explored how the Covid-19 pandemic affected Black sexual minority men, with a focus on relationships between Covid-19 and PrEP engagement. Setting: We sampled 24 Black sexual minority men attending HIV prevention-related events in the greater D.C. Metropolitan area (D.C., Maryland, Virginia). Methods: We conducted qualitative phone interviews among our sample. Questions were primarily focused on the Covid-19 pandemic and how it affected engagement and considerations of PrEP use. Interviews were transcribed and qualitatively analyzed using the six stages of thematic analysis. Results: We identified three major themes from our thematic analysis: Changes in the healthcare system, changes in sexual and relationship contexts, and Covid-19 vaccine hesitancy and misinformation. Relationships between Covid-19 vaccine hesitancy and PrEP hesitancy were especially prevalent, with participants describing that Covid-19 hesitancy can directly deter PrEP use through eroding medical trust further. Conclusion: We identified changes in the healthcare system, sexual and relationship contexts, and Covid-19 vaccine hesitancy as important issues driven by Covid-19 with significant implications for PrEP use. The Covid-19 pandemic has changed the healthcare and social landscape in profound ways that impact PrEP access, sexual networks, and associated HIV vulnerability. Future research further exploring relationships between specific pandemic stressors and HIV prevention among Black sexual minority men is recommended. Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.

Abstract Background Various factors influence tuberculosis preventive treatment (TPT) decisions thus it is important to understand the health beliefs and concerns of patients before starting TPT to ensure treatment compliance. This study aims to explore facilitators and barriers for TPT among patients diagnosed with Latent Tuberculosis infection (LTBI) attending six primary healthcare clinics in Selangor, Malaysia. Method In-depth interviews were conducted face-to-face or via telephone among patients with a clinical diagnosis of LTBI using a semi-structured topic guide developed based on the common-sense model of self-regulation and literature review. Audio recordings of interviews were transcribed verbatim and analysed thematically. Results We conducted 26 In-depth interviews; Good knowledge of active tuberculosis (TB) and its associated complications, including the perceived seriousness and transmissibility of active TB, facilitates treatment. LTBI is viewed as a concern when immune status is compromised, thus fostering TPT. However, optimal health is a barrier for TPT. Owing to the lack of knowledge, patients rely on healthcare practitioners (HCPs) to determine their treatment paths. HCPs possessing comprehensive knowledge play a role in facilitating TPT whereas barriers to TPT encompass misinterpretation of tuberculin skin test (TST), inadequate explanation of TST, and apprehensions about potential medication side effects. Conclusions Knowledge of LTBI can influence TPT uptake and patients often entrust their HCPs for treatment decisions. Improving knowledge of LTBI both among patients and HCPs can lead to more effective doctor-patient consultation and consequently boost the acceptance of TPT. Quality assurance should be enhanced to ensure the effective usage of TST as a screening tool. …

Journal of Medical Virology, Volume 95, Issue 9, September 2023.

Objective: To compare pregnancy outcomes using self-reported and objective levels of intracellular tenofovir diphosphate (TFV-DP) in pregnant women using preexposure prophylaxis (PrEP). Design: We enrolled pregnant women >15 years without HIV at first antenatal care visit in an observational cohort study to compare pregnancy outcomes by PrEP use. Methods: Exposure defined as: any PrEP use (TDF/FTC prescription + reported taking PrEP), or objectively-measured TFV-DP in dried blood spots in PrEP-using pregnant women. The primary outcome was a composite of pregnancy loss, preterm birth (…

Introduction: We evaluated associations of HIV and antiretroviral therapy (ART) with birth and maternal outcomes at a province-wide-level in the Western Cape, South Africa, in a recent cohort before dolutegravir-based first-line ART implementation. Methods: This retrospective cohort study included pregnant people delivering in 2018-2019 with data in the Western Cape Provincial Health Data Centre which integrates individual-level data on all public sector patients from multiple electronic platforms using unique identifiers. Adverse birth outcomes (stillbirth, low birth weight (LBW), very LBW (VLBW)) and maternal outcomes (early and late pregnancy-related deaths, early and late hospitalizations) were compared by HIV/ART status and adjusted prevalence ratios (aPRs) calculated using log-binomial regression. Results: Overall 171,960 pregnant people and their singleton newborns were included, 19% (N = 32,015) identified with HIV. Amongst pregnant people with HIV (PPHIV), 60% (N = 19,157) were on ART preconception, 29% (N = 9,276) initiated ART during pregnancy and 11% (N = 3,582) had no ART. Adjusted for maternal age, multiparity, hypertensive disorders and residential district, stillbirths were higher only for PPHIV not on ART (aPR 1.31 [95%CI 1.04–1.66]) compared to those without HIV. However, LBW and VLBW were higher among all PPHIV, with aPRs of 1.11–1.22 for LBW and 1.14–1.54 for VLBW. Pregnancy-initiated ART was associated with early pregnancy-related death (aPR 3.21; 95%CI 1.55–6.65), and HIV with or without ART was associated with late pregnancy-related death (aPRs 7.89–9.01). Conclusions: Even in the universal ART era, PPHIV experienced higher rates of LBW and VLBW newborns, and higher late pregnancy-related death regardless of ART status than pregnant people without HIV. Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.

Introduction: Differentiated service delivery (DSD) such as multi-month dispensing (MMD) aims to provide client-centered HIV services, while reducing the workload within health facilities. We assessed individual and facility factors associated with receiving >3MMD and switching from ≥3MMD back to…

Objective: To estimate HIV incidence using successive cross-sectional surveys by creating retrospective nested cohorts among men who have sex with men (MSM), people who inject drugs (PWID), and heterosexually active persons (HET). Design: Cohorts were created among participants who had at least one repeat observation across four surveillance cycles from National HIV Behavioral Surveillance in 20 U.S. cities. Methods: Repeat participants were identified using a combination of date of birth, race/ethnicity, metropolitan statistical area, and gender. The analysis was limited to participants who tested negative for HIV at baseline and were assumed to be at-risk between cycles. We calculated person-years at risk from the individual time between cycles and used the total number of seroconversions to estimate incidence and a Poisson distribution to approximate variance. Rate ratios were calculated by age, gender, race/ethnicity, and region. Results: From 2008 to 2019, successive surveys recaptured nested cohorts of 1,747 MSM, 3,708 PWID, and 1,396 HET. We observed an incidence rate of 2.5 per 100 person-years (95% confidence interval [CI]: 2.1 to 2.8) among MSM; 0.6 per 100 person-years (95% CI: 0.5 to 0.7) among PWID; and 0.3 per 100 person-years (95% CI: 0.1–0.4) among HET. HIV incidence was higher among younger MSM, Black MSM (compared to white MSM) and PWID residing in the South and Territories (compared to the Midwest). Conclusions: These estimates are consistent with previously published incidence estimates from prospective cohort studies among these populations. Using repeat cross-sectional surveys to simulate a cohort, may serve as another strategy in estimating HIV incidence. Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.

Objective: People with HIV rarely control viral replication after cessation of antiretroviral therapy (ART). We present a person with HIV with extraordinary post-treatment control (PTC) for over 23 years after temporary ART during acute HIV infection (AHI) leading to a new insight in factors contributing to PTC. Design/Methods: Viral reservoir was determined by HIV qPCR, Intact Proviral DNA Assay and quantitative viral outgrowth assay. Viral replication kinetics were determined in autologous and donor PBMC. IgG levels directed against HIV envelope and neutralizing antibodies were measured. Immune phenotyping of T-cells and HIV-specific T-cell responses were analyzed by flow cytometry. Results: The case presented with AHI and a plasma viral load of 2.7 million copies/mL. ART was initiated 2 weeks after diagnosis and interrupted after 26 months. Replicating virus was isolated shortly after start ART. At 18 years after treatment interruption HIV-DNA in CD4+ T-cells and low levels of HIV-RNA in plasma (…

Objectives: To define the frequency, risk factors, and clinical outcomes of both AIDS-defining and non-AIDS-defining neurologic infections among people with HIV (PWH). Design: We conducted a retrospective observational cohort study by linking the clinical database at the Southern Alberta HIV Clinic (SAC) with the regional hospital and microbiology databases to identify cases and the associated morbidity and mortality for these neurologic infections from 1995-2018. Methods: Neurologic infections were categorized into AIDS defining and non-AIDS defining. Annual incidence rates (IR) per 1,000 person-years (PY) were calculated. Cox proportional hazards models estimated adjusted hazard ratios (aHR) and 95% confidence intervals of risk factors for neurologic infections in PWH and mortality outcomes. Results: Among 2,910 PWH contributing 24,237 years of follow-up, 133(4.6%) neurologic infections were identified; 107(80%) were AIDS-defining and 26(20%) non-AIDS defining. While the incidence of AIDS-defining neurologic infections declined over time, no change was seen in incidence of non-AIDS defining infections. The risk of having any neurologic infection was greater among Black PWH (aHR = 2.5[1.6–4.0]) (vs. White PWH) and those with a CD4+ T-cell nadir of…

The capacity to infect and survive in a wide variety of host cells is amongst the strategies that contribute to pathogen persistence. The recent study by Karagiannis et al. presents an unbiased approach to identify infected cells in a visceral leishmaniasis (VL) infection, which revealed parasites in unexpected host cells.

Proceedings of the National Academy of Sciences, Volume 120, Issue 38, September 2023.

Proceedings of the National Academy of Sciences, Volume 120, Issue 38, September 2023.

Proceedings of the National Academy of Sciences, Volume 120, Issue 38, September 2023.