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Infection with SARS-CoV-2 causes wide range of disease severities from asymptomatic to life-threatening disease. Understanding the contribution of immunological traits in immunity against SARS-CoV-2 and in protection against severe COVID-19 could result in effective measures to prevent development of severe disease. While the role of cytokines and antibodies has been thoroughly studied, this is not the case for T cells. In this review, the association between T cells and COVID-19 disease severity and protection upon reexposure is discussed. While infiltration of overactivated cytotoxic T cells might be harmful in the infected tissue, fast responding T cells are important in the protection against severe COVID-19. This protection could even be viable in the long term as long-living memory T cells seem to be stabilized and mutations do not appear to have a large impact on T cell responses. Thus, after vaccination and infections, memory T cells should be able to help prevent onset of severe disease for most cases. Considering this, it would be useful to add N or M proteins in vaccinations, alongside the S protein which is currently used, as this results in a broader T cell response. [ABSTRACT FROM AUTHOR]

Post-COVID-19 syndrome (PCS) fatigue is typically most severe <6 months post-infection. Combining magnetic resonance imaging (MRI) and positron emission tomography (PET) imaging with the glucose analog [18F]-Fluorodeoxyglucose (FDG) provides a comprehensive overview of the effects of PCS on regional brain volumes and metabolism, respectively. The primary purpose of this exploratory study was to investigate differences in MRI/PET outcomes between people < 6 months (N = 18, 11 female) and > 6 months (N = 15, 6 female) after COVID-19. The secondary purpose was to assess if any differences in MRI/PET outcomes were associated with fatigue symptoms. Subjects > 6 months showed smaller volumes in the putamen, pallidum, and thalamus compared to subjects < 6 months. In subjects > 6 months, fatigued subjects had smaller volumes in frontal areas compared to non-fatigued subjects. Moreover, worse fatigue was associated with smaller volumes in several frontal areas in subjects > 6 months. The results revealed no brain metabolism differences between subjects > 6 and < 6 months. However, both groups exhibited both regional hypo- and hypermetabolism compared to a normative database. These results suggest that PCS may alter regional brain volumes but not metabolism in people > 6 months, particularly those experiencing fatigue symptoms. [ABSTRACT FROM AUTHOR]

Schistosomiasis is the second most devastating parasite prevalent in the tropical region of the world, posing significant public health impacts in endemic areas. Presently, several disease mitigation measures have shown a decline in transmission of the infection rate in risk localities using mass drug administration (MDA) of school-based or community-wide treatments. Despite all the endeavors made, the decline in transmission of infection rate has not been attained in the entire medicated segment of the population. Perhaps the current challenges of control of the disease appear to be strongly associated with a lack of appropriate diagnostic tools. It's well known that the current diagnosis of schistosomiasis greatly relies on conventional methods. On the other hand, minor symptoms of schistosomiasis and low sensitivity and specificity of diagnostic methods are still unresolved diagnostic challenges to clinicians. Numerous scholars have reviewed various diagnostic methods of schistosomiasis and attempted to identify their strengths and weaknesses, currently on function. As a result of the known limitations of the existing diagnostic tools, the need to develop new and feasible diagnostic methods and diagnostic markers is unquestionable for more precise detection of the infection. Hence, advances in diagnostic methods have been considered part of the solution for the control and eventual elimination strategy of the disease in endemic areas. As of today, easy, cheap, and accurate diagnostics for schistosomiasis are difficult to get, and this limits the concerted efforts towards full control of schistosomiasis. While looking for new diagnostic methods and markers, it is important to simultaneously work on improving the existing diagnostic methods for better results. This review tries to give new insights to the status of the existing diagnostic methods of schistosomiasis from conventional to modern via summarizing the strengths and limitations of the methods. It also tries to recommend new, sensitive and feasible diagnostic methods for future approaches. [ABSTRACT FROM AUTHOR]

Histoplasma capsulatum is a geographically specific dimorphic fungus that can cause a spectrum of diseases. While most cases are asymptomatic pulmonary infections, in severe cases, particularly in immunocompromised patients, disseminated disease can occur. Histoplasmosis in California is limited to only a few case reports. In this article, we describe a rare case of disseminated histoplasmosis in a non-endemic region presenting with diagnostically challenging symptomatology, including altered mental status, status epilepticus, septic shock, and bilateral adrenal masses. [ABSTRACT FROM AUTHOR]

It is widely known that COVID-19 has a number of prolonged effects on general health, wellbeing, and cognitive functioning. However, studies using differentiated performance measures of cognitive functions are still not widely spread making it hard to assess the exact functions that get impaired. Taking into account the similarities between post-COVID 'brain fog' and chemofog, we hypothesized that executive functions (EF) would be impaired. Literature search yielded six studies with 14 effect sizes of interest; pooled effect size was small to medium (d = − 0.35). Combined with a narrative synthesis of six studies without a comparison group, these results show that EF get impaired after COVID-19; although, in most cases the impairment is transient and does not seem to be severe. These results specify the picture of 'brain fog' and may help to discover its mechanisms and ways of helping people with long COVID. [ABSTRACT FROM AUTHOR]

Long COVID, the postviral disorder caused by COVID-19, is expected to become one of the leading causes of disability in Europe. The cognitive consequences of long COVID have been described as "brain fog" and characterized by anxiety and depression, and by cognitive deficits. Long COVID is assumed to be a complex condition arising from multiple causes, including persistent brainstem dysfunction and disrupted vagal signaling. We recommend the potential application of auricular transcutaneous vagus nerve stimulation (atVNS) as an ADD-ON instrument to compensate for the cognitive decline and to ameliorate affective symptoms caused by long COVID. This technique enhances vagal signaling by directly activating the nuclei in the brainstem, which are hypoactive in long COVID to enhance mood and to promote attention, memory, and cognitive control—factors affected by long COVID. Considering that atVNS is a non-pharmacological intervention, its ADD-ON to standard pharmaceutical agents will be useful for non-responders, making of this method a suitable tool. Given that atVNS can be employed as an ecological momentary intervention (EMI), we outline the translational advantages of atVNS in the context of accelerating the cognitive and affective recovery from long COVID. [ABSTRACT FROM AUTHOR]

Relapsing fever (RF) is an arthropod-borne disease caused by Borrelia spirochete, which is one of the major public health concerns in endemic regions including Africa. However, information on Borrelia spirochetes is limited in Zambia. Here, we investigate the Borrelia spirochetes harbored by Ornithodoros ticks in Zambian National Parks. We analyzed 182 DNA samples pooled from 886 Ornithodoros ticks. Of these, 43 tested positive, and their sequence revealed that the ticks harbored both Old and New World RF borreliae. This research presents the first evidence of Old-World RF borreliae in Zambia. The New World RF borreliae detected herein differed from the Candidatus Borrelia fainii previously reported in Zambia and were closely related to the pathogenic Borrelia sp. VS4 identified in Tanzania. Additionally, Borrelia theileri was recently reported in Zambia. Hence, at least four different Borrelia species occur in Zambia, and the organisms causing relapsing fever there might be more complex than previously thought. We empirically confirmed that real-time PCR with TaqMan minor groove binder probes accurately and simultaneously detected both Old and New World RF. In this manner, they could facilitate quantitative analyses of both types of RF borreliae. Subsequent investigations should endeavor to isolate the aforementioned Borrelia spp. and perform serosurveys on patients with RF. [ABSTRACT FROM AUTHOR]

Despite increasing reports of tick-borne diseases in Africa, remarkably, reports of tick-borne relapsing fever (TBRF) in Nigeria are lacking. Ornithodoros savignyi from Nigeria have been reported with the relapsing fever Candidatus Borrelia kalaharica. Conversely, in Ethiopia, the agent of relapsing fever is the louse-borne relapsing fever (LBRF) spirochaete Borrelia recurrentis with no TBRF reported to occur. A total of 389 Ornithodoros ticks, Ethiopia (N = 312) and Nigeria (N = 77), were sampled, together with 350 cattle, and 200 goat sera were collected from Nigeria. Samples were screened for Borrelia spp. by RT-PCR. Reactive samples were confirmed, then sequenced using flagellin B, 16S rRNA, and 16S–23S intergenic spacer region. The prevalence of Borrelia spp. in livestock was 3.8% (21/550) and 14% (3/21) after final molecular confirmation. Of 312 ticks from Ethiopia, 3.5% (11/312) were positive for Borrelia, with 36% (4/11) by conventional PCR. Sequencing revealed that the borreliae in soft ticks was C. B. kalaharica, whilst that found in animals was Borrelia theileri. Soft ticks were confirmed by sequencing 7% (22/312) and 12% (9/77) of the Ethiopian and Nigerian ticks, respectively. Phylogenetic analysis revealed that these were Ornithodoros savignyi. This is the first evidence of C. B. kalaharica in Ethiopia and demonstrates the co-existence of TBRF in a country endemic to LBRF. Important, this might cause a diagnostic challenge given that LBRF is predominantly diagnosed by microscopy, which cannot differentiate these two spirochaetes. Furthermore, we report B. theileri in ruminants in Nigeria, which may also be of veterinary and economic importance. [ABSTRACT FROM AUTHOR]

Background: Common long-term sequelae after COVID-19 include fatigue and cognitive impairment. Although symptoms interfere with daily living, the underlying pathology is largely unknown. Previous studies report relative hypometabolism in frontal, limbic and cerebellar regions suggesting focal brain involvement. We aimed to determine whether absolute hypometabolism was present and correlated to same day standardized neurocognitive testing. Methods: Fourteen patients included from a long COVID clinic had cognitive testing and quantitative dynamic [18F]FDG PET of the brain on the same day to correlate cognitive function to metabolic glucose rate. Results: We found no hypometabolism in frontal, limbic and cerebellar regions in cognitively impaired relative to cognitive intact patients. In contrast, the cognitive impaired patients showed higher cerebellar metabolism (p = 0.03), which correlated with more severe deficits in working memory and executive function (p = 0.03). Conclusions: Hypermetabolism in the cerebellum may reflect inefficient brain processing and play a role in cognitive impairments after COVID-19. [ABSTRACT FROM AUTHOR]

The present study aims to provide a critical overview of the literature on the relationships between post-acute COVID-19 infection and cognitive impairment, highlighting the limitations and confounding factors. A systematic search of articles published from 1 January 2020 to 1 July 2022 was performed in PubMed/Medline. We followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Only studies using validated instruments for the assessment of cognitive impairment were included. Out of 5515 screened records, 72 studies met the inclusion criteria. The available evidence revealed the presence of impairment in executive functions, speed of processing, attention and memory in subjects recovered from COVID-19. However, several limitations of the literature reviewed should be highlighted: most studies were performed on small samples, not stratified by severity of disease and age, used as a cross-sectional or a short-term longitudinal design and provided a limited assessment of the different cognitive domains. Few studies investigated the neurobiological correlates of cognitive deficits in individuals recovered from COVID-19. Further studies with an adequate methodological design are needed for an in-depth characterization of cognitive impairment in individuals recovered from COVID-19. [ABSTRACT FROM AUTHOR]

Background Female genital schistosomiasis (FGS) occurs when Schistosoma haematobium eggs are deposited in reproductive tissue. Female genital schistosomiasis in the cervical mucosa is associated with increased vascularity. If FGS is associated with the presence of hemoglobin in cervicovaginal lavage (CVL), the use of urinary reagent strips to detect hemoglobin in CVL could supplement FGS diagnosis. Methods Nonmenstruating, nonpregnant, sexually active women aged 18–31 participating in the HPTN 071 (PopART) Population-Cohort were invited in 2 Zambian communities. Genital self-swabs and a urine specimen were collected at a home visit, and CVL and hand-held colposcopy were performed at a midwife led clinic visit. Urinary reagent strips were used to identify hemoglobin in CVL. Eggs and circulating anodic antigen (CAA) were detected from urine. Visual-FGS was defined as the presence of sandy patches, rubbery papules, or abnormal blood vessels. Polymerase chain reaction (PCR)-FGS was defined as Schistosoma deoxyribonucleic acid detected by real-time PCR on CVL or cervical or vaginal swab. Results Of 209 women with home genital swabs and companion CVL specimens, 66% (138 of 209) had detectable CVL hemoglobin, 13.4% (28 of 209) had PCR-defined FGS, and 17.2% (36 of 209) had visual-FGS. Active Schistosoma infection, diagnosed by CAA or urine microscopy, was present in 21.0% (44 of 209) participants. Active Schistosoma infection (P =.4), PCR-FGS (P = 0.7), and visual-FGS (P = 0.3) were not associated with CVL hemoglobin presence. Results did not differ in subgroups with high infection burden (cycle threshold < 35 or 2–3 positive genital PCR). Conclusions Polymerase chain reaction-FGS, visual-FGS, and active Schistosoma infection were not associated with the presence of CVL hemoglobin. Further research is needed to establish accessible community-based FGS diagnostics. [ABSTRACT FROM AUTHOR]

Nucleic acid therapeutics can be used to control virtually every aspect of cell behavior and therefore have significant potential to treat genetic disorders, infectious diseases, and cancer. However, while clinically approved to treat a small number of diseases, the full potential of nucleic acid therapeutics is hampered by inefficient delivery. Nucleic acids are large, highly charged biomolecules that are sensitive to degradation and so the approaches to deliver these molecules differ significantly from traditional small molecule drugs. Current studies suggest less than 1% of the injected nucleic acid dose is delivered to the target cell in an active form. This inefficient delivery increases costs and limits their use to applications where a small amount of nucleic acid is sufficient. In this review, we focus on two of the major barriers to efficient nucleic acid delivery: (1) delivery to the target cell and (2) transport to the subcellular compartment where the nucleic acids are therapeutically active. We explore how nanoparticles can be modified with targeting ligands to increase accumulation in specific cells, and how the composition of the nanoparticle can be engineered to manipulate or disrupt cellular membranes and facilitate delivery to the optimal subcellular compartments. Finally, we highlight how with intelligent material design, nanoparticle delivery systems have been developed to deliver nucleic acids that silence aberrant genes, correct genetic mutations, and act as both therapeutic and prophylactic vaccines. This article is categorized under:Nanotechnology Approaches to Biology > Cells at the NanoscaleTherapeutic Approaches and Drug Discovery > Nanomedicine for Infectious DiseaseBiology‐Inspired Nanomaterials > Lipid‐Based Structures [ABSTRACT FROM AUTHOR]

The development of water management infrastructures, such as dams and canals, are important components of society's response to feed a growing human population and to fight climate change. Yet, these changes in land use can also increase the transmission risk for waterborne diseases. Transmission risk associated with artificial reservoirs has been extensively documented for schistosomiasis, a parasitic disease of poverty that infects more than 240 million people worldwide. Over 90% of these cases are in sub-Saharan Africa, a region that is being steadily reshaped by climate change. Controlling the parasite's obligate intermediate host snail is key to reducing transmission of this disease. Using commercial aquaculture to farm marketable species which predate upon these snails in vulnerable regions can have multiple positive effects, including the improved socioeconomic and nutritional health of surrounding communities. Here the authors assessed the viability of using the aquaculture of snail predators to simultaneously control schistosomiasis infection rates while alleviating economic and/or nutritional poverty in endemic regions of sub-Saharan Africa. A PRISMA-based 6-step systematic methodology was used to explore the primary literature using the case study of Côte d'Ivoire and two native species of snail predator to make evidence-based conclusions on the viability of this method for controlling schistosomiasis. This detailed thematic examination of the literature concluded that using specific approaches and species, aquaculture could be effective in reducing economic poverty and chronic malnourishment along with high levels of schistosomiasis infection. More current species-specific aquaculture data and consumer survey data are, however, needed to determine the economic and logistical effectiveness of farming native snail predators in-country. These and other opportunities for future research are highlighted. [ABSTRACT FROM AUTHOR]

Background: Turkey hosts an estimated 3.7 million Syrian refugees. Syrian refugees have access to free primary care provided through Refugee Health Centers(RHC). We aimed to determine factors that influence patient satisfaction in refugee health centers. Methods: The study was a cross-sectional quantitative study. A patient survey was administered among 4548 patients attending services in selected 16 provinces in Turkey. A quantitative questionnaire was used to collect information on patient satisfaction and experience in the healthcare facility. Information on "overall satisfaction with health services" was collected on a 5-point Likert scale and dichotomized for analysis. Logistic regression was conducted to identify factors that influenced patient satisfaction. Results: We found that 78.2% of the participants were satisfied with the health services they received. Factors related to service quality and communication were significant determinants of patient satisfaction. The strongest predictors of satisfaction were having a sufficient consultation time (AOR: 2.37; 95% CI: 1.76–3.21; p< 0.0001), receiving a comprehensive examination (AOR: 2.01; 95% CI: 1.49–2.70; p < 0.0001) and being treated with respect by the nurse (AOR: 2.08; 95% CI: 1.52–2.85; p< 0.0001). Conclusion: Providing integrated, culturally and linguistically sensitive health services is important in refugee settings. The quality of service and communication with patients influence patient satisfaction in refugee health centers. As such, improvements in aspects such as consultation time and the quality of physician-patient interaction are recommended for patient satisfaction. [ABSTRACT FROM AUTHOR]

Background: Schistosomiasis elimination has gained renewed priority in the WHO guidance documents published in 2020 and 2022. The SchistoBreak project, implemented in Pemba, Tanzania between 2020 and 2024, aims to assess new tools and strategies for shifting from elimination as a public health problem towards interruption of transmission. Here we report our baseline findings and discuss implications for future interventions. Methods: In 2020, human water contact sites (HWCSs) in the study area were geolocated and snail surveys were conducted. A parasitological and questionnaire cross-sectional baseline survey was implemented in 20 communities and their 16 primary schools between November 2020 and February 2021. Urine samples were collected at the school and household levels from individuals aged ≥ 4 years. Schistosoma haematobium infection was detected by urine filtration microscopy. Snail, parasitological and questionnaire-derived data were analyzed descriptively, spatially and with generalized estimated equation models. Results: The intermediate host snail Bulinus globosus was detected in 19.8% (33/167) of HWCSs. The overall S. haematobium prevalence was 1.2% (26/2196) in school-aged children and 0.8% (31/3893) in community members, with 0.2% (4/2196) and 0.1% (3/3893) heavy-intensity infections, respectively. Children who studied < 1 km away from HWCSs with B. globosus had significantly higher odds for a S. haematobium infection than those attending a school located > 2 km away (odds ratio [OR]: 5.0; 95% confidence interval [CI]: 2.3–11.1). Individuals living in a house located < 1 km away from HWCSs with B. globosus had higher odds than those residing in > 2 km distance (OR: 18.0; 95% CI: 2.9–111.0). Self-reported praziquantel treatment coverage was 83.2% (2015/2423) in schoolchildren in the mass drug administration (MDA) conducted in August 2020. Coverage among adult community members was 59.9% (574/958), but only 34.8% (333/958) took praziquantel correctly. Conclusions: While the S. haematobium prevalence is very low in Pemba, there are many HWCSs with B. globosus situated close to schools or houses that pose a considerable risk of recrudescence. To maintain and accelerate the progress towards interruption of transmission, targeted and cost-effective interventions that are accepted by the community are needed; for example, snail control plus focal MDA, or test-and-treat in schools and households near infested waterbodies. [ABSTRACT FROM AUTHOR]

Background: Urogenital schistosomiasis has been known to be endemic in several lowland areas of Ethiopia. It is caused by Schistosoma haematobium and causes considerable public health problems to schoolchildren. Ethiopia, after mapping the distribution of the disease (2013 to 2015), launched school-based mass deworming program to treat schoolchildren for schistosomiasis and soil-transmitted helminthiasis (STH) across the country since 2015. However, there is no recent information about the prevalence of the disease among schoolchildren in the current study areas. Diagnostic performance of urine filtration method and urinalysis reagent strip is also lacking. Therefore, this study aimed to determine the prevalence of urogenital schistosomiasis in schoolchildren, and to evaluate diagnostic performance of urine filtration and urinalysis reagent strip in Amibara, Kurmuk and Abobo districts, Ethiopia. Methods: Across-sectional study was conducted involving 1,171 schoolchildren in Abobo, Amibara and Kurmuk districts from October, 2020 to January, 2021. The study participants were selected using random sampling technique. From each study participant, 10 ml urine samples were collected and examined using urine filtration method and urinalysis reagent strip. Data obtained from the survey were entered into Microsoft Excel 2010 and analysed with SPSS version 20.0. Data was summarized using descriptive statistics. Chi-square, bivariate and multivariable logistic regression and Pearson correlation test were used to measure associations between urogenital schistosomiasis, age, sex and haematuria. Odds ratio was used to measure strengths of association between variables. Agreement between urine filtration method and urinalysis reagent strip was determined using Kappa statistics. P-value < 0.05 at 95% CI was considered as statistically significant. Results: Among the 1,171 urine samples from schoolchildren examined by urine filtration method, 143 (12.2%) were S.haematobium egg positive. Out of 143 positive children 126(88.1%) were lightly infected and 17 (11.9%) were heavily infected. Among the total of 1,171 urine samples tested by dipstick, 264(22.5%) were positive for haematuria. Prevalence of urogenital schistosomiasis by both urine filtration and urinalysis reagent strip method was higher in Abobo than Hassoba (Amibara) and Kurmuk (P< 0.001). The number of egg counts (intensity of infections) were significantly correlated with intensity of haematuria (r = 0.6, P < 0.001). Egg-positive children had significantly higher risk of having haematuria compared to S. haematobium egg negative children (OR; 6.96; 95%CI: 4.98, 8.940). Compared to urine filtration method, the sensitivity, specificity, positive predictive value (PPV) and negative predictive values (NPV) of urinalysis reagent strip were 99.3%, 88.1%, 53.8% and 99.8%, respectively. Furthermore, its positive likelihood ratio (PLR) and negative likelihood ratio (NLR) were 8.34 and 0.008, respectively. The accuracy index and diagnostic odds ratio (DOR) of reagent strip were 0.89 and 1054, respectively. The agreement level between urine filtration methods and urinalysis reagent strip for detecting urogenital schistosomiasis was substantial (Kappa = 0.64). Conclusion: This study showed that urogenital schistosomiasis was prevalent in schoolchildren in Abobo, Hassoba and Kurmuk districts. Urogenital schistosomiasis prevalence in Hassoba-bure and Kurmuk falls under low category whereas moderate in Abobo and is almost four times compared to Kurmuk and Hassoba-bure. Chemotherapy is needed in schoolchildren in such endemic areas and other measures like access to safe water, improved sanitation, hygiene, and health education should be implemented to control and prevent schistosomiasis effectively. The sensitivity, specificity, positive and negative predictive values of urinalysis reagent strip were higher and could serve as alternative for mass screening of urogenital schistosomiasis, for surveillance and evaluation of schistosomiasis intervention programs. [ABSTRACT FROM AUTHOR]

Background: Research on health and healthcare for asylum seekers and refugees (ASR) has focused strongly on accessibility and legal entitlements, with quality of care receiving little attention. This study aimed to assess responsiveness, as non-medical quality of care, in the narratives of ASR patients recently arrived in Germany. Methods: 31 ASR with existing medical conditions were recruited in six refugee reception centres and three psychosocial centres. Semi-structured, qualitative interviews were conducted which reconstructed their patient journey after arrival in Germany. Interviews were recorded, transcribed verbatim and evaluated using thematic analysis. Results: The experiences of participants throughout the patient journey provided a rich and varied description of the responsiveness of health services. Some dimensions of responsiveness, including respectful treatment, clear communication and trust, resurfaced throughout the narratives. These factors were prominent reasons for positive evaluations of the health system, and negative experiences were reported in their absence. Other dimensions, including cleanliness of facilities, autonomy of decision-making and choice of provider were raised seldomly. Positive experiences in Germany were often set in contrast to negative experiences in the participants' countries of origin or during transit. Furthermore, many participants evaluated their experience with healthcare services in terms of the perceived technical quality of medical care rather than with reference to responsiveness. Conclusion: This qualitative study among ASR analysed patient experiences to better understand responsiveness of care for this population. While our results show high overall satisfaction with health services in Germany, using the lens of responsiveness allowed us to identify particular policy areas where care can be strengthened further. These include in particular the expansion of high-quality interpreting services, provision of professional training to increase the competency of healthcare staff in caring for a diverse patient population, as well as an alignment between healthcare and asylum processes to promote continuity of care. [ABSTRACT FROM AUTHOR]

Background Annual mass drug administration (MDA) using praziquantel is the cornerstone of schistosomiasis morbidity control but is not sufficient to interrupt transmission. We implemented a cluster-randomized trial to compare the effectiveness of 4 different intervention packages to interrupt transmission of Schistosoma haematobium in a seasonal transmission setting of Côte d'Ivoire. Methods Sixty-four localities with a S. haematobium prevalence in school children aged 13–14 years above 4% were randomly assigned to 1 of 4 intervention arms over a 3-year period: (1) the current standard strategy consisting of annual MDA before peak of transmission, (2) annual MDA after peak of transmission, (3) biannual MDA, and (4) standard MDA combined with snail control. The primary outcome was prevalence and intensity of S. haematobium infection in children aged 9–12 years 1 year after the final intervention, using urine filtration performed by experienced microscopists. Results By study end, we observed the lowest S. haematobium prevalence in the biannual MDA, compared to the standard treatment arm (0.6% vs 7.5%; odds ratio [OR] = 0.07, 95% confidence interval [CI] = .02 to.24). The prevalence in arms 2 and 4 was about 3.5%, which was not statistically significantly different from the standard strategy (both ORs 0.4, 95% CI = .1 to ~1.8). New cases of infection were still observed in all arms at study end. Conclusions Biannual MDA was the only regimen that outperformed the standard treatment. All strategies resulted in decreased prevalence of infection; however, none of them was able to interrupt transmission of S. haematobium within a 3-year period. Clinical Trials Registration ISRCTN10926858. [ABSTRACT FROM AUTHOR]

The diagnosis of the post-COVID condition is usually achieved by excluding other diseases; however, cognitive changes are often found in the post-COVID disorder. Therefore, monitoring and treating the recovery from the post-COVID condition is necessary to establish biomarkers to guide the diagnosis of symptoms, including cognitive impairment. Our study employs a prospected cohort and nested case–control design with mixed methods, including statistical analyses, interviews, and focus groups. Our main aim is to identify biomarkers (functional and structural neural changes, inflammatory and immune status, vascular and vestibular signs and symptoms) easily applied in primary care to detect cognitive changes in post-COVID cases. The results will open up a new line of research to inform diagnostic and therapeutic decisions with special considerations for cognitive impairment in the post-COVID condition. [ABSTRACT FROM AUTHOR]

The chapter explores the role of neuropsychology in understanding brain fog as a subjective complaint in the context of COVID-19. It discusses the historical and medical significance of the term "brain fog" and its psychological and neurological aspects. The chapter identifies the cognitive domains commonly affected by brain fog, such as attention, executive function, memory, and language. Additionally, it emphasizes the impact of societal changes during the COVID-19 pandemic on the general population as a crucial backdrop for understanding the issue. The chapter also highlights the important role of clinical and research neuropsychologists in gaining clarity on grouped data and individual patients' cognitive and emotional difficulties after COVID-19 infection. It discusses indications for neuropsychological rehabilitation and therapy and describes typical therapy phases and methods, including new approaches like telemedicine, virtual reality, and mobile app-based rehabilitation and self-tracking. The chapter underscores that experiences of brain fog can vary among COVID-19 patients and may change over time. It provides clinicians and interested parties with an in-depth understanding of brain fog and its manifestations, concomitant subtypes, and concrete strategies for addressing it. The chapter emphasizes the critical role of neuropsychology in scientifically examining brain fog and advocating for personalized approaches to cognitive rehabilitation., (© 2024. The Author(s), under exclusive license to Springer Nature Switzerland AG.)

The new WHO Roadmap for Neglected Tropical Diseases targets the global elimination of schistosomiasis as a public health problem. To date, control strategies have focused on effective diagnostics, mass drug administration, complementary and integrative public health interventions. Non-mammalian intermediate hosts and other vertebrates promote transmission of schistosomiasis and have been utilized as experimental model systems. Experimental animal models that recapitulate schistosomiasis immunology, disease progression, and pathology observed in humans are important in testing and validation of control interventions. We discuss the pivotal value of these models in contributing to elimination of schistosomiasis. Treatment of schistosomiasis relies heavily on mass drug administration of praziquantel whose efficacy is comprised due to re-infections and experimental systems have revealed the inability to kill juvenile schistosomes. In terms of diagnosis, nonhuman primate models have demonstrated the low sensitivity of the gold standard Kato Katz smear technique. Antibody assays are valuable tools for evaluating efficacy of candidate vaccines, and sera from graded infection experiments are useful for evaluating diagnostic sensitivity of different targets. Lastly, the presence of Schistosomes can compromise the efficacy of vaccines to other infectious diseases and its elimination will benefit control programs of the other diseases. As the focus moves towards schistosomiasis elimination, it will be critical to integrate treatment, diagnostics, novel research tools such as sequencing, improved understanding of disease pathogenesis and utilization of experimental models to assist with evaluating performance of new approaches. [ABSTRACT FROM AUTHOR]

(1) Background: Health care workers (HCWs) play a key role in increasing anti-COVID vaccination rates. Fear of potential side effects is one of the main reasons for vaccine hesitancy. We investigated which side effects are of concern to HCWs and how these are associated with vaccine hesitancy. (2) Methods: Data were collected in an online survey in February 2021 among HCWs from across Germany with 4500 included participants. Free-text comments on previously experienced vaccination side effects, and fear of short- and long-term side effects of the COVID-19 vaccination were categorized and analyzed. (3) Results: Most feared short-term side effects were vaccination reactions, allergic reactions, and limitations in daily life. Most feared long-term side effects were (auto-) immune reactions, neurological side effects, and currently unknown long-term consequences. Concerns about serious vaccination side effects were associated with vaccination refusal. There was a clear association between refusal of COVID-19 vaccination in one's personal environment and fear of side effects. (4) Conclusions: Transparent information about vaccine side effects is needed, especially for HCW. Especially when the participants' acquaintances advised against vaccination, they were significantly more likely to fear side effects. Thus, further education of HCW is necessary to achieve good information transfer in clusters as well. [ABSTRACT FROM AUTHOR]

Background: Reagent strip to detect microhematuria as a proxy for Schistosoma haematobium infections has been considered an alternative to urine filtration for individual diagnosis and community-based estimates of treatment needs for preventive chemotherapy. However, the diagnostic accuracy of reagent strip needs further investigation, particularly at low infection intensity levels. Methods: We used existing data from a study conducted in Tanzania that employed urine filtration and reagent strip testing for S. haematobium in two villages, including a baseline and six follow-up surveys after praziquantel treatment representing a wide range of infection prevalence. We developed a Bayesian model linking individual S. haematobium egg count data based on urine filtration to reagent strip binary test results available on multiple days and estimated the relation between infection intensity and sensitivity of reagent strip. Furthermore, we simulated data from 3,000 hypothetical populations with varying mean infection intensity to infer on the relation between prevalence observed by urine filtration and the interpretation of reagent strip readings. Principal findings: Reagent strip showed excellent sensitivity even for single measurement reaching 100% at around 15 eggs of S. haematobium per 10 ml of urine when traces on reagent strip were considered positive. The corresponding specificity was 97%. When traces were considered negative, the diagnostic accuracy of the reagent strip was equivalent to urine filtration data obtained on a single day. A 10% and 50% urine filtration prevalence based on a single day sampling corresponds to 11.2% and 48.6% prevalence by reagent strip, respectively, when traces were considered negative, and 17.6% and 57.7%, respectively, when traces were considered positive. Conclusions/Significance: Trace results should be included in reagent strip readings when high sensitivity is required, but excluded when high specificity is needed. The observed prevalence of reagent strip results, when traces are considered negative, is a good proxy for prevalence estimates of S. haematobium infection by urine filtration on a single day. Author summary: Control of schistosomiasis, a parasitic worm infection affecting more than 200 million people worldwide, relies mainly on mass drug administration of praziquantel to school-age children as well as adults in areas where the disease is particularly rampant. The World Health Organization has set thresholds of observed prevalence that require intervention to reach the goal of eliminating schistosomiasis as a public health problem by 2025. Intervention thresholds are defined based on parasitologic methods, which is urine filtration for Schistosoma haematobium. There are alternative diagnostic methods to detect S. haematobium, such as the detection of blood in urine that is a common symptom of urogenital schistosomiasis. We determined the diagnostic sensitivity and specificity of a reagent strip to detect microhematuria using data from two villages in Tanzania at multiple time points (once before and several times after treatment with the deworming drug praziquantel) and translate the urine filtration intervention thresholds to reagent strip equivalents. We show that the reagent strip including trace results is almost perfectly sensitive for infections above 15 eggs of S. haematobium per 10 ml of urine and that a 10% observed prevalence by urine filtration corresponds to 17.6% observed prevalence by reagent strip including traces. [ABSTRACT FROM AUTHOR]

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is believed to affect central nervous system functions through various indirect, and possibly direct, mechanisms. We are only now beginning to understand the possible effects of the virus on human cognition. This review summarizes extant yet limited literature on clinical neuropsychological findings in adult coronavirus disease 2019 (COVID-19) patients and survivors. Neuropsychological outcomes were often in the form of cognitive screen results, although various studies administered comprehensive batteries. With respect to screens, the Montreal Cognitive Assessment appeared relatively sensitive to cognitive dysfunction associated with COVID-19. Patients and survivors presented with weaknesses on screens and comprehensive batteries, although the pattern of these weaknesses was not specific to etiology. Broadly, weaknesses were suggestive of executive dysfunction, although more than one study did not detect significant impairment. Weaknesses should be interpreted cautiously due to potential confounds/contributing factors (weaknesses may partly reflect psychiatric sequelae; weaknesses may be over-interpreted due to inadequate assessment of premorbid functioning). Studies reported different approaches in defining impairment, likely contributing to variable findings. The current review discusses ongoing efforts to harmonize approaches to evaluating neuropsychological functioning globally, as well as emphasizes taking a comprehensive approach towards understanding how the disease affects cognition. [ABSTRACT FROM AUTHOR]

Background: Schistosomiasis is a neglected tropical disease caused by helminths of the genus Schistosoma. Morbidity markers and cytological observations such as squamous metaplastic cells, inflammatory cells, and hyperkeratotic cells in the urine of S. haematobium-infected children may suggest disease severity. They may also help predict severe forms of clinical presentation, such as bladder cancer in later years, among infected ones who miss out on early detection and treatment. Insights into possible changes in the morbidity markers and cytological observations in the urine of these S. haematobium-infected children before and after treatment would be of high clinical importance. Aim: The aim of this study was to identify changes/dynamics in morbidity markers and cytological abnormalities in the urine deposits of S. haematobium-infected children, pre- and post-praziquantel treatment. Methodology: This was a longitudinal study involving baseline and follow-up sampling among basic school children living in schistosomiasis-endemic communities. Urine samples were collected from 520 children at baseline and examined for S. haematobium ova by microscopy, while urine chemistry analyses were used for the examination of morbidity markers. The cytological analyses involved cytopathological examination of the urine deposits. Children whose urine showed positivity for S. haematobium eggs were treated with a single oral dose of praziquantel (40 mg/kg), after which urine chemistry and cytological analyses were repeated weekly for comparison with baseline, until the eighth week. Results: Morbidity markers such as hematuria, proteinuria, and leukocyturia were detected both at baseline and post-treatment among the infected children (30/520). Hematuria was the predominant parameter (90%, 27/30) detected at baseline, followed by proteinuria (53.3%, 16/30). Leukocyturia was the rarest parameter detected at baseline (13.3%, 4/30). However, almost all these parameters declined gradually post-treatment. Regarding cytological analyses, inflammatory cells were observed most (70.0%, 21/30) at baseline. For hyperkeratotic cells and squamous metaplastic cells, 46.7% and 26.7% were respectively observed at baseline, all of which gradually declined during the weekly follow-ups. Notably, squamous metaplastic cells persisted in all the participants from Week 1 through Week 3 post-treatment, but declined gradually thereafter. Conclusions: Morbidity markers and cytological observations in the children gradually decreased after treatment. Therefore, we continue to recommend routine cytological screening for urogenital schistosomiasis patients at hospitals in S. haematobium-endemic locations using both baseline and follow-up samples to detect these abnormalities early and monitor changes that may be occurring after treatment. Such changes may be useful in assessing treatment progress in infected persons. [ABSTRACT FROM AUTHOR]

Tick borne relapsing fever (TBRF) is a zoonosis caused by various Borrelia species transmitted to humans by both soft-bodied and (more recently recognized) hard-bodied ticks. In recent years, molecular diagnostic techniques have allowed to extend our knowledge on the global epidemiological picture of this neglected disease. Nevertheless, due to the patchy occurrence of the disease and the lack of large clinical studies, the knowledge on several clinical aspects of the disease remains limited. In order to shed light on some of these aspects, we have systematically reviewed the literature on TBRF and summarized the existing data on epidemiology and clinical aspects of the disease. Publications were identified by using a predefined search strategy on electronic databases and a subsequent review of the reference lists of the obtained publications. All publications reporting patients with a confirmed diagnosis of TBRF published in English, French, Italian, German, and Hungarian were included. Maps showing the epidemiogeographic mosaic of the different TBRF Borrelia species were compiled and data on clinical aspects of TBRF were analysed. The epidemiogeographic mosaic of TBRF is complex and still continues to evolve. Ticks harbouring TBRF Borrelia have been reported worldwide, with the exception of Antarctica and Australia. Although only molecular diagnostic methods allow for species identification, microscopy remains the diagnostic gold standard in most clinical settings. The most suggestive symptom in TBRF is the eponymous relapsing fever (present in 100% of the cases). Thrombocytopenia is the most suggestive laboratory finding in TBRF. Neurological complications are frequent in TBRF. Treatment is with beta-lactams, tetracyclines or macrolids. The risk of Jarisch-Herxheimer reaction (JHR) appears to be lower in TBRF (19.3%) compared to louse-borne relapsing fever (LBRF) (55.8%). The overall case fatality rate of TBRF (6.5%) and LBRF (4–10.2%) appears to not differ. Unlike LBRF, where perinatal fatalities are primarily attributable to abortion, TBRF-related perinatal fatalities appear to primarily affect newborns. Author summary: Tick-borne relapsing fever (TBRF) is a bacterial disease characterized by eponymous recurrent fever episodes. The disease is common on all continents except Australia and Antarctica and is caused by several species of Borrelia bacteria. The Borrelia bacteria causing relapsing fever circulate naturally between ticks and various animal hosts (usually small rodents). Humans become infected when they are accidentally bitten by an infected tick. Although the disease has been known since 1904, many aspects of the disease have never been investigated in larger studies and are therefore still not conclusively understood. To shed light on some of these aspects, we reviewed the published literature on TBRF and analysed all reported data on the geographic distribution of the different TBRF-causing Borrelia spp. as well as on the clinical presentations of the disease, its complications, its diagnosis and treatment and its outcome, and compiled them in this review. [ABSTRACT FROM AUTHOR]

Schistosoma haematobium is the leading cause of urogenital schistosomiasis and it is recognised as a class 1 carcinogen due to the robust association of infection with bladder cancer. In schistosomes, tetraspanins (TSPs) are abundantly present in different parasite proteomes and could be potential diagnostic candidates due to their accessibility to the host immune system. The large extracellular loops of six TSPs from the secretome (including the soluble excretory/secretory products, tegument and extracellular vesicles) of S. haematobium (Sh-TSP-2, Sh-TSP-4, Sh-TSP-5, Sh-TSP-6, Sh-TSP-18 and Sh-TSP-23) were expressed in a bacterial expression system and polyclonal antibodies were raised to the recombinant proteins to confirm the anatomical sites of expression within the parasite. Sh-TSP-2, and Sh-TSP-18 were identified on the tegument, whereas Sh-TSP-4, Sh-TSP-5, Sh-TSP-6and Sh-TSP-23 were identified both on the tegument and internal tissues of adult parasites. The mRNAs encoding these TSPs were differentially expressed throughout all schistosome developmental stages tested. The potential diagnostic value of three of these Sh-TSPs was assessed using the urine of individuals (stratified by infection intensity) from an endemic area of Zimbabwe. The three Sh-TSPs were the targets of urine IgG responses in all cohorts, including individuals with very low levels of infection (those positive for circulating anodic antigen but negative for eggs by microscopy). This study provides new antigen candidates to immunologically diagnose S. haematobium infection, and the work presented here provides compelling evidence for the use of a biomarker signature to enhance the diagnostic capability of these tetraspanins. Author summary: Schistosoma haematobium, the leading cause of urogenital schistosomiasis, affects millions of people worldwide. Infection with this parasite is associated with different clinical complications such as squamous cell carcinoma and genital malignancy in women. Despite its importance, there is a lack of sensitive and specific diagnostics that support control and elimination initiatives against this devastating disease. Herein, we have characterised six molecules belonging to the tetraspanin family of membrane proteins, providing details about their relative expression during parasite's development and their localization in adult forms of S. haematobium. Furthermore, we have characterised the antibody responses against three of these molecules in urine from infected human subjects from an endemic area, providing compelling evidence for the use of these molecules to diagnose urogenital schistosomiasis. [ABSTRACT FROM AUTHOR]

Structural and calorimetric investigation of GexTe100-x films over wide range of concentration 10 < x < 50 led to evidence two structural singularities at x ~ 22 at. % and x ~ 33-35 at. %. Analysis of bond distribution, bond variability, and glass thermal stability led to conclude to the origin of the first singularity being the flexible/rigid transition proposed in the framework of rigidity model and the origin of the second one being the disappearance of the undercooled region resulting in amorphous materials with statistical distributions of bonds. While the first singularity signs the onset of the Ge-Ge homopolar bonds, the second is related to compositions where enhanced Ge-Ge correlations at intermediate lengthscales (7.7 Å) are observed. These two threshold compositions correspond to recently reported resistance drift threshold compositions, an important support for models pointing the breaking of homopolar Ge-Ge bonds as the main phenomenon behind the ageing of phase change materials. [ABSTRACT FROM AUTHOR]

Background: Global elimination of schistosomiasis as a public health problem is set as target in the new World Health Organization's Neglected Tropical Diseases Roadmap for 2030. Due to a long history of interventions, the Zanzibar islands of Tanzania have reached this goal since 2017. However, challenges occur on the last mile towards interruption of transmission. Our study will investigate new tools and strategies for breaking schistosomiasis transmission.Methods: The study is designed as an intervention study, documented through repeated cross-sectional surveys (2020-2024). The primary endpoint will be the sensitivity of a surveillance-response approach to detect and react to outbreaks of urogenital schistosomiasis over three years of implementation. The surveys and multi-disciplinary interventions will be implemented in 20 communities in the north of Pemba island. In low-prevalence areas, surveillance-response will consist of active, passive and reactive case detection, treatment of positive individuals, and focal snail control. In hotspot areas, mass drug administration, snail control and behaviour change interventions will be implemented. Parasitological cross-sectional surveys in 20 communities and their main primary schools will serve to adapt the intervention approach annually and to monitor the performance of the surveillance-response approach and impact of interventions. Schistosoma haematobium infections will be diagnosed using reagent strips and urine filtration microscopy, and by exploring novel point-of-care diagnostic tests.Discussion: Our study will shed light on the field applicability and performance of novel adaptive intervention strategies, and standard and new diagnostic tools for schistosomiasis elimination. The evidence and experiences generated by micro-mapping of S. haematobium infections at community level, micro-targeting of new adaptive intervention approaches, and application of novel diagnostic tools can guide future strategic plans for schistosomiasis elimination in Zanzibar and inform other countries aiming for interruption of transmission. Trial registration ISRCTN, ISCRCTN91431493. Registered 11 February 2020, https://www.isrctn.com/ISRCTN91431493. [ABSTRACT FROM AUTHOR]

Background Current World Health Organization guidelines utilize prevalence of heavy-intensity infections (PHIs), that is, ≥50 eggs per 10 mL of urine for Schistosoma haematobium and ≥400 eggs per gram of stool for S. mansoni , to determine whether a targeted area has controlled schistosomiasis morbidity or eliminated schistosomiasis as a public health problem. The relationship between these PHI categories and morbidity is not well understood. Methods School-age participants enrolled in schistosomiasis monitoring and evaluation cohorts from 2003 to 2008 in Burkina Faso, Mali, Niger, Tanzania, Uganda, and Zambia were surveyed for infection and morbidity at baseline and after 1 and 2 rounds of preventive chemotherapy. Logistic regression was used to compare morbidity prevalence among participants based on their school's PHI category. Results Microhematuria levels were associated with the S. haematobium PHI categories at all 3 time points. For any other S. haematobium or S. mansoni morbidity that was measured, PHI categories did not differentiate morbidity prevalence levels consistently. Conclusions These analyses suggest that current PHI categorizations do not differentiate the prevalence of standard morbidity markers. A reevaluation of the criteria for schistosomiasis control is warranted. [ABSTRACT FROM AUTHOR]

Purpose of Review: Sub-Saharan Africa (SSA) is disproportionately burdened by the twin epidemics of food insecurity and HIV infection, and protein-calorie undernutrition is common among persons with HIV (PWH) initiating antiretroviral therapy (ART) in the region. In this review, we discuss the intersection of HIV infection and undernutrition, health outcomes among undernourished PWH starting ART, and the demonstrated and potential benefits of therapeutic interventions such as micro/macronutrient supplementation and pharmacological agents. Recent Findings: A low body mass index (BMI), used as a general indicator of poor nutrition in most studies, is associated with impaired immune recovery and increased mortality in the early ART period. The increased risk of mortality is multifactorial, and contributors include undernutrition-related immune system dysfunction, increased susceptibility to opportunistic infections, and metabolic and cardiovascular dysregulation. Clinical trials of micro/macronutrient supplementary feeding, appetite stimulants (hormones and anabolic agents), and recombinant adipokines have shown a benefit for weight gain and metabolic health, but there are few data on mortality or immune recovery. Summary: A substantial proportion of PWH in SSA are undernourished, and undernutrition contributes to an increased risk of mortality and other adverse health outcomes. To date, there have been few prospective trials of nutritional supplementation and/or pharmacologic therapy among undernourished PWH in SSA, though findings from other settings suggest a potential benefit in this population. [ABSTRACT FROM AUTHOR]

Bats can harbor zoonotic pathogens causing emerging infectious diseases, but their status as hosts for bacteria is limited. We aimed to investigate the distribution, prevalence and genetic diversity of Borrelia in bats and bat ticks in Hubei Province, China, which will give us a better understanding of the risk of Borrelia infection posed by bats and their ticks. During 2018–2020, 403 bats were captured from caves in Hubei Province, China, 2 bats were PCR-positive for Borrelia. Sequence analysis of rrs, flaB and glpQ genes of positive samples showed 99.55%-100% similarity to Candidatus Borrelia fainii, a novel human-pathogenic relapsing fever Borrelia species recently reported in Zambia, Africa and Eastern China, which was clustered together with relapsing fever Borrelia species traditionally reported only in the New World. Multilocus sequence typing (MLST) and pairwise genetic distances further confirmed the Borrelia species in the bats from Central China as Candidatus Borrelia fainii. No Borrelia DNA was detected in ticks collected from bats. The detection of this human-pathogenic relapsing fever Borrelia in bats suggests a wide distribution of this novel relapsing fever Borrelia species in China, which may pose a threat to public health in China. Author summary: Bats have a wide range of species and distribution, these mammals have been proposed as the natural reservoirs of pathogens for many years. Previous research focus mainly on viral agents in bats, while the infection of Borrelia spirochetes in bats is much neglected. Borrelia species causing Lyme disease and relapsing fever have been found in a wide range of ticks. Relapsing fever has long been recognized as major cause of disease and death in Africa, but as more and more cases reported in different continents, relapsing fever has become an emergent disease. There is growing evidence that bats can play a role in carrying Borrelia species. In this study, we captured different species of bats from caves during 2018–2020 in Central China, tested liver tissue for Borrelia by PCR, and applied multilocus sequence typing (MLST) to identify this bacterium. Our study found human pathogenic relapsing fever Candidatus Borrelia fainii in Central China, suggesting bat borne Borrelia spirochetes may pose a threat to public health in China. [ABSTRACT FROM AUTHOR]

Schistosomiasis and Leishmaniasis are chronic parasitic diseases with high prevalence in some tropical regions and, due to their wide distribution, a risk of co-infections is present in some areas. Nevertheless, the impact of this interaction on human populations is still poorly understood. Thus, the current study evaluated the effect of previous American Tegumentary Leishmaniasis (ATL) on the susceptibility and immune response to Schistosoma mansoni infection in residents from a rural community in Northern of Minas Gerais state, Brazil, an area endemic for both parasitic infections. The participants answered a socioeconomic questionnaire and provided stool and blood samples for parasitological and immunological evaluations. Stool samples were examined by a combination of parasitological techniques to identify helminth infections, especially S. mansoni eggs. Blood samples were used for hemograms and to measure the serum levels of cytokines and chemokines. Reports on previous ATL were obtained through interviews, clinical evaluation forms, and medical records. S. mansoni infection was the most prevalent parasitic infection in the study population (46%), and the majority of the infected individuals had a very low parasite burden. In the same population, 93 individuals (36.2%) reported previous ATL, and the prevalence of S. mansoni infection among these individuals was significantly higher than among individuals with no ATL history. A multiple logistic regression model revealed that S. mansoni infection was positively associated with higher levels of CCL3 and CCL17, and a higher frequency of IL-17 responders. Moreover, this model demonstrated that individuals with an ATL history had a 2-fold higher probability to be infected with S. mansoni (OR = 2.0; 95% CI 1.04–3.68). Among S. mansoni -infected individuals, the logistic regression demonstrated that a previous ATL history was negatively associated with the frequency of IL-17 responders and CXCL10 higher responders, but positively associated with higher IL-27 responders. Altogether, our data suggest that previous ATL may alter the susceptibility and the immune response in S. mansoni -infected individuals, which may likely affect the outcome of schistosomiasis and the severity of the disease in humans. [ABSTRACT FROM AUTHOR]

Background: Considerable progress towards the elimination of urogenital schistosomiasis was made by the Zanzibar Elimination of Schistosomiasis Transmission project from 2012 till 2016, when biannual praziquantel mass drug administration (MDA) alone or with additional snail control or behaviour change interventions were implemented. Annual MDA was continued in 2017 and 2018, but not in 2019, imposing a 16-month treatment gap. We monitored the Schistosoma haematobium prevalence from 2012 till 2020 and assessed recrudescence patterns with focus on 2020. Methodology: Repeated cross-sectional surveys were conducted from 2011/12 till 2020 in 90 communities and 90 schools in Zanzibar. Annually, around 4,500 adults and up to 20,000 schoolchildren were surveyed. The S. haematobium prevalence was detected by urine filtration and reagent strips. In 2020, risk factors for infection were investigated using generalized estimated equation models. Principal findings: In adults, the apparent S. haematobium prevalence was 3.9% in 2011 and 0.4% in 2020. In schoolchildren, the prevalence decreased from 6.6% in 2012 to 1.2% in 2019 with vicissitudes over the years. Prominent recrudescence of infection from 2.8% in 2019 to 9.1% (+225%) in 2020 was observed in 29 schools with historically moderate prevalences (≥10%). Compared with 2019, reinfection in 2020 was particularly striking in boys aged 9–16 years. Being male was a risk factor for infection in 2020 (adults: odds ratio (OR): 6.24, 95% confidence interval (95% CI): 1.96–19.60; schoolchildren: OR: 2.06, 95% CI: 1.52–2.78). Living near to a natural freshwater body significantly increased the odds of infection in adults (OR: 2.90, CI: 1.12–7.54). Conclusions/Significance: After 11 rounds of MDA over 7 years and a 16-month treatment gap, the urogenital schistosomiasis prevalence considerably rebounded in hotspot areas. Future elimination efforts in Zanzibar should focus on re-intensifying MDA plus additional interventions in hotspot areas. In low-prevalence areas, the strategy might be adapted from MDA to targeted surveillance-response. Author summary: Schistosomiasis is a neglected tropical disease caused by parasitic blood flukes of the genus Schistosoma. On the Zanzibar islands, United Republic of Tanzania, interventions to eliminate urogenital schistosomiasis commenced in 2012. From 2012 to 2016, the population was treated biannually with praziquantel and, additionally, some areas received mollusciciding against the intermediate host snail, or educational measures for behavior change. Mass drug administration (MDA) with praziquantel was continued annually in 2017 and 2018, but not in 2019. As a result of the interventions, the overall S. haematobium prevalence was reduced to 0.4% in adults and 3.4% in schoolchildren in 2020. However, in some areas, the MDA gap in 2019 resulted in a considerable rebound of infections. The recrudescence in 2020 was particularly striking for boys aged 9–16 years. In general, in 2020, male participants had higher odds of infection than females. Adults living near to a natural freshwater body also showed an increased risk of S. haematobium infection. Future elimination efforts in Zanzibar should focus on re-intensifying elimination interventions, including MDA, snail control and behavior change in hotspot areas. In low-prevalence areas, the strategy might be adapted from MDA to targeted interventions, such as surveillance-response. [ABSTRACT FROM AUTHOR]

Various global health initiatives are currently advocating the elimination of schistosomiasis within the next decade. Schistosomiasis is a highly debilitating tropical infectious disease with severe burden of morbidity and thus operational research accurately evaluating diagnostics that quantify the epidemic status for guiding effective strategies is essential. Latent class models (LCMs) have been generally considered in epidemiology and in particular in recent schistosomiasis diagnostic studies as a flexible tool for evaluating diagnostics because assessing the true infection status (via a gold standard) is not possible. However, within the biostatistics literature, classical LCM have already been criticised for real-life problems under violation of the conditional independence (CI) assumption and when applied to a small number of diagnostics (i.e. most often 3-5 diagnostic tests). Solutions of relaxing the CI assumption and accounting for zero-inflation, as well as collecting partial gold standard information, have been proposed, offering the potential for more robust model estimates. In the current article, we examined such approaches in the context of schistosomiasis via analysis of two real datasets and extensive simulation studies. Our main conclusions highlighted poor model fit in low prevalence settings and the necessity of collecting partial gold standard information in such settings in order to improve the accuracy and reduce bias of sensitivity and specificity estimates. Author summary: Accurate schistosomiasis diagnosis is essential to assess the impact of large scale and repeated mass drug administration to control or even eliminate this disease. However, in schistosomiasis diagnostic studies, several inherent study design issues pose a real challenge for the currently available statistical tools used for diagnostic modelling and associated data analysis and conclusions. More specifically, those study design issues are: 1) the inclusion of small number of diagnostic tests (i.e. most often five), 2) non formal consensus about a schistosomiasis gold standard, 3) the contemporary use of relatively small sample sizes in relevant studies due to lack of research funding, 4) the differing levels of prevalence of the studied disease even within the same area of one endemic country and 5) other real world factors such as: the lack of appropriate equipment, the variability of certain methods due to biological phenomena and training of technicians across the endemic countries because of scarce financial resources contributing to the existing lack of a schistosomiasis gold standard. The current study aims to caution practitioners from blindly applying statistical models with small number of diagnostic tests and sample sizes, proposing design guidelines of future schistosomiasis diagnostic accuracy studies with recommendations for further research. While our study is centred around the diagnosis of schistosomiasis, we feel that the recommendations can be adapted to other major tropical infectious diseases as well. [ABSTRACT FROM AUTHOR]

Background: Undernutrition is one of the most common problems among people living with HIV, contributing to premature death and the development of comorbidities within this population. In Sub-Saharan Africa (SSA), the impacts of these often inter-related conditions appear in a series of fragmented and inconclusive studies. Thus, this review examines the pooled effects of undernutrition on mortality and morbidities among adults living with HIV in SSA.Methods: A systematic literature search was conducted from PubMed, EMBASE, CINAHL, and Scopus databases. All observational studies reporting the effects of undernutrition on mortality and morbidity among adults living with HIV in SSA were included. Heterogeneity between the included studies was assessed using the Cochrane Q-test and I2 statistics. Publication bias was assessed using Egger's and Begg's tests at a 5% significance level. Finally, a random-effects meta-analysis model was employed to estimate the overall adjusted hazard ratio.Results: Of 4309 identified studies, 53 articles met the inclusion criteria and were included in this review. Of these, 40 studies were available for the meta-analysis. A meta-analysis of 23 cohort studies indicated that undernutrition significantly (AHR: 2.1, 95% CI: 1.8, 2.4) increased the risk of mortality among adults living with HIV, while severely undernourished adults living with HIV were at higher risk of death (AHR: 2.3, 95% CI: 1.9, 2.8) as compared to mildly undernourished adults living with HIV. Furthermore, the pooled estimates of ten cohort studies revealed that undernutrition significantly increased the risk of developing tuberculosis (AHR: 2.1, 95% CI: 1.6, 2.7) among adults living with HIV.Conclusion: This review found that undernutrition has significant effects on mortality and morbidity among adults living with HIV. As the degree of undernutrition became more severe, mortality rate also increased. Therefore, findings from this review may be used to update the nutritional guidelines used for the management of PLHIV by different stakeholders, especially in limited-resource settings. [ABSTRACT FROM AUTHOR]

Background: Treatment needs for Schistosoma haematobium are commonly evaluated using urine filtration with detection of parasite eggs under a microscope. A common symptom of S. haematobium is hematuria, the passing of blood in urine. Hence, the use of hematuria-based diagnostic techniques as a proxy for the assessment of treatment needs has been considered. This study evaluates data from a national survey in Zimbabwe, where three hematuria-based diagnostic techniques, that is microhematuria, macrohematuria, and an anamnestic questionnaire pertaining to self-reported blood in urine, have been included in addition to urine filtration in 280 schools across 70 districts. Methodology: We developed an egg count model, which evaluates the infection intensity-dependent sensitivity and the specificity of each diagnostic technique without relying on a 'gold' standard. Subsequently, we determined prevalence thresholds for each diagnostic technique, equivalent to a 10% urine filtration-based prevalence and compared classification of districts according to treatment strategy based on the different diagnostic methods. Principal findings: A 10% urine filtration prevalence threshold corresponded to a 17.9% and 13.3% prevalence based on questionnaire and microhematuria, respectively. Both the questionnaire and the microhematuria showed a sensitivity and specificity of more than 85% for estimating treatment needs at the above thresholds. For diagnosis at individual level, the questionnaire showed the highest sensitivity at (70.0%) followed by urine filtration (53.8%) and microhematuria (52.2%). Conclusions/Significance: The high sensitivity and specificity of a simple questionnaire to estimate treatment needs of S. haematobium suggests that it can be used as a rapid, low-cost method to estimate district prevalence. Our modeling approach can be expanded to include setting-dependent specificity of the technique and should be assessed in relation to other diagnostic methods due to potential cross-reaction with other diseases. Author summary: The strategy of the World Health Organization (WHO) to combat schistosomiasis is based on administering praziquantel as preventive chemotherapy to school-age children only, or including adults. For Schistosoma haematobium the treatment decision is based on observed prevalence by urine filtration which involves counting eggs under a light microscope. Urine filtration is time intensive and requires trained technicians to operate the microscope. Blood in urine is a common symptom of urogenital schistosomiasis and therefore, the use of screening tools based on the detection of hematuria has been suggested. We analyze three such screening tools, namely reagent strip to detect microhematuria, a questionnaire regarding recent history of blood in urine, and visible inspection of urine and determine their diagnostic accuracy to evaluate treatment need at district level in comparison to urine filtration in a national survey in Zimbabwe. We find that both the questionnaire and reagent strip classify districts with sensitivity and specificity above 85% at the 10% urine filtration thresholds. Wrongly classified districts generally show urine filtration prevalence in the vicinity of the 10% prevalence thresholds. We conclude that there is evidence that a questionnaire can be used as a low cost alternative rapid screening tool for S. haematobium. [ABSTRACT FROM AUTHOR]

The present study aimed to determine the expression level of claudin-2 (CLDN2) in the peripheral blood of patients with sepsis, and to investigate its potential function and mechanism of action in vascular endothelial injury. A total of 25 patients with sepsis were included in the present study. Reverse transcription-quantitative PCR was used to determine CLDN2 levels in peripheral blood. HUVECs stably expressing CLDN2 were prepared and Cell Counting Kit-8, flow cytometry and Transwell assays were performed to study the proliferation, apoptosis and migration of HUVECs, respectively. Using bioinformatics, microRNA (miR) molecules that interact with CLDN2 were predicted. A dual luciferase reporter assay was used to test whether miR-331 regulated CLDN2. Western blotting was employed to determine CLDN2 protein expression. In addition, in vitro transfection of HUVECs with miR-331 mimics was performed to test the rescue effects of miR-331 on the cell function changes induced by CLDN2. The results indicated that elevated CLDN2 expression altered the proliferation and cell cycle of peripheral vascular endothelial cells. CLDN2 overexpression inhibited HUVEC proliferation via mechanisms not associated with the cell cycle. CLDN2 mRNA levels in the peripheral blood of patients with sepsis were significantly higher than those in healthy subjects. Upregulated CLDN2 expression promoted the apoptosis of HUVECs, but reduced their proliferation and migration. Notably, miR-331 was able to bind with CLDN2 mRNA and regulate its expression. Upregulation of miR-331 expression inhibited the expression of CLDN2 and restored nearly normal proliferation, apoptosis and migration to HUVECs. The present study demonstrated that CLDN2 expression is elevated in peripheral blood from patients with sepsis, and promotes the injury of vascular endothelial cells. In addition, miR-331 participates in the direct regulation of CLDN2, and upregulation of miR-331 expression inhibits the expression of CLDN2 and restores cellular functions to HUVECs. [ABSTRACT FROM AUTHOR]

Reliable diagnosis of human helminth infection(s) is essential for ongoing disease surveillance and disease elimination. Current WHO-recommended diagnostic assays are unreliable in low-endemic near-elimination settings and typically involve the invasive, onerous and potentially hazardous sampling of bodily fluids such as stool and blood, as well as tissue via biopsy. In contrast, diagnosis by use of non-invasive urine sampling is generally painless, more convenient and low risk. It negates the need for specialist staff, can usually be obtained immediately upon request and is better accepted by patients. In some instances, urine-based diagnostic assays have also been shown to provide a more reliable diagnosis of infection when compared to traditional methods that require alternative and more invasive bodily samples, particularly in low-endemicity settings. Given these relative benefits, we identify and review current research literature to evaluate whether non-invasive urine sampling is currently exploited to its full potential in the development of diagnostic tools for human helminthiases. Though further development, assessment and validation are needed before their routine use in control programmes, low-cost, rapid and reliable assays capable of detecting transrenal helminth-derived antigens and cell-free DNA show excellent promise for future use at the point-of-care in high-, medium- and even low-endemicity elimination settings. [ABSTRACT FROM AUTHOR]

Background: Better knowledge of the efficacy and safety of single 40 mg/kg oral praziquantel in preschool-age children is required, should preventive chemotherapy programs for schistosomiasis be expanded to include this age group. Methodology: We analyzed individual participant-level data from 16 studies (13 single-arm or cohort studies and three randomized trials), amounting to 683 preschool-age children (aged <6 years) and 2,010 school-age children (aged 6–14 years). Children had a documented Schistosoma mansoni or S. haematobium infection, were treated with single 40 mg/kg oral praziquantel, and assessed between 21 and 60 days post-treatment. Efficacy was expressed as arithmetic mean and individual egg reduction rate (ERR) and meta-analyzed using general linear models and mixed models. Safety was summarized using reported adverse events (AEs). Principal findings: Preschool-age children had significantly lower baseline Schistosoma egg counts and more losses to follow-up compared to school-age children. No difference in efficacy was found between preschool- and school-age children using a general linear model of individual-participant ERR with baseline log-transformed egg count as covariate and study, age, and sex as fixed variables, and a mixed model with a random effect on the study. Safety was reported in only four studies (n = 1,128 individuals); few AEs were reported in preschool-age children 4 and 24 hours post-treatment as well as at follow-up. Three severe but not serious AEs were recorded in school-age children during follow-up. Conclusions/Significance: There is no indication that single 40 mg/kg oral praziquantel would be less efficacious and safe in preschool-age children compared to school-age children, with the caveat that only few randomized comparisons exist between the two age groups. Preventive chemotherapy might therefore be extended to preschool-age children, with proper monitoring of its efficacy and safety. Author summary: Schistosomiasis is a diseases caused by helminths (parasitic worms) which affects the intestinal and urinary systems. In areas where schistosomiasis is endemic, the disease is controlled by the large scale distributing of praziquantel, primarily targeting school-age children. Younger children (preschool-age) too might be affected by schistosomiasis, but are currently not receiving praziquantel within treatment campaigns. Instead, preschool-age children are treated on a case-by-case basis because the current praziquantel formulation is not adapted to young children. Questions have also been raised as to whether the standard dose of 40 mg/kg given once is effective in preschool-age children. To answer this question, we collected individual-participant data from a series of studies in which 40 mg/kg of praziquantel had been given to children with intestinal or urogenital schistosomiasis, and compared its efficacy and tolerability across age-groups. Since few direct comparisons had been made, we used statistical tools to make these comparisons. We found no evidence that treatment is less efficacious in preschool- than in school-age children and conclude that 40 mg/kg praziquantel may be given to preschool-age children in large-scale programs. When this happens, efficacy and tolerability will have to be closely monitored. [ABSTRACT FROM AUTHOR]

Urinary schistosomosis is a serious public health problem prevalent in low-income rural regions of sub-Saharan Africa, including coastal part of Kenya. Praziquantel administration to school-aged children is the prevailing tool of schistosomosis control in these regions. The aim of our study was to find out if this control strategy can lead to interruption of parasite trasmission and disease elimination. During February and March 2018, the occurrence of urinary schistosomosis in volunteers of primary health care facilities in Kwale County, Kenya was examined and the occurrence of infected intermediate hosts Bulinus globosus in local water resources was monitored. Participants completed a questionnaire concerning source of water for household purposes, type of housing and health status and were asked to provide urine samples. Diagnosis of urinary schistosomosis was established by detection of Schistosoma haematobium eggs in urine specimens microscopically, using filtration method. Infected B. globosus snails were detected using cercaria shedding tests. From the hemolymph of snails, prepatent period of infection was identified by polymerase chain reaction (PCR). The presence of urinary schistosomosis was detected in 15.07 % (69 out of 451) of study participants. Cercaria shedding test was positive in 2 particular sites of river Pengo and Tsanganyiko. Genetic material (haemolymph) of 68 B. globosus snails tested by DraI PCR revealed 7 Schistosoma spp. positive samples. Six of seven DraI positive snails were infected by S. haematobium, as it was detected by Sh110/SmS1 PCR. The study revealed, that the disease was still present in the region studied and the transmission was not interrupted. The rate of infection was significantly influenced by the water supplies used for household purposes and the type of housing. [ABSTRACT FROM AUTHOR]