Fever Infection Research Articles

Occupational health surveillance and detection of emerging occupational diseases among Taiwan farmers, through analysis of national-based farmers' and medico-administrative databases.

The purpose of this study was to identify occupational injuries and diseases associated with agriculture in Asia, to provide a reference for prevention and hypotheses for future research. We matched data on agricultural workers (n = 963,124) enrolled in Taiwan's national Farmers Health Insurance since its inception in 1989, to general population controls of the same age, gender, and township. The study population was linked to the National Health Insurance Research Database from 2001 to 2016 for inpatient cases. Logistic regression was used to assess odds ratios for outcomes. Farmers had 2.76 times the risk of mycotic corneal ulcer (95% CI: 1.96-3.87) and 1.65 times the risk of typhus fever infections (95% CI: 1.47-1.85) compared to the general population. The odds ratio for poisonous animal bites was 2.22 (95% CI: 2.07-2.38), for falling into a storm drain or manhole was 2.04 (95% CI: 1.30-3.20), and for toxic effects from pesticides was 2.01 (95% CI: 1.92-2.11). The toxic effects of organophosphate and carbamate insecticides were correlated with the cultivation of rice, fruit trees, and flowers. Q fever and motorcycle accidents were associated with fruit tree cultivation. The study identifies agricultural occupational injuries and diseases that may inform occupational health policy and the development of prevention priorities to prevent occupational hazards for farmers.

Seroprevalence Estimates of Q Fever and the Predictors for the Infection in Cattle, Sheep, and Goats in Nandi County, Kenya

Q fever is an important worldwide zoonotic disease that affects almost all domestic animals, wildlife, and humans. The infection has both socio-economic and public health significance. A cross-sectional study was carried out to investigate the estimates of seroprevalence of Q fever and to determine the predictors of the infection in cattle, sheep, and goats in six wards of Nandi County. A total of 1,140 blood samples were collected from 366 households. Samples were drawn from 725 cattle (64%), 283 sheep (25%), and 132 goats (11%). Multistage sampling method was adopted. Serum samples were analyzed for antibodies to Coxiella burnetii using the indirect ELISA test. Results showed an overall animal seroprevalence of 5.614% (64/1140) for Q fever. In cattle, the seroprevalence was 8.138% (59/725) with CI 95% (2.8-18.23), 1.413% (4/283) for sheep CI 95% (1.0-7.78), and 0.758% (1/132) goats CI 95% (0.14-7.27). From the findings, Q fever was more prevalent in cattle (OR 7.26) than in sheep and goats. Animal species (p value 0.015, CI 95% OR 7.26) was the only potential predictors in the three considered species for the presence of Coxiella burnetii antibodies. Sex, age, breed, and production system had no statistical significant association for Q fever infection since p value was >0.005. In conclusion, the results demonstrated that cattle, sheep, and goats are widely exposed to Q fever organisms, and hence, it is an important zoonosis in Nandi County. Therefore, to address this "silent" disease, there is an urgent call for both veterinarians and medical personnel to jointly address prevention and control strategy through enhanced surveillance, public sensitization, and awareness creation under the one health concept. There is also a need for enhanced capacity for the diagnosis of Q fever in both animals and humans in Nandi County.

Rapid Etiological Detection Value of Metagenomic Next-Generation Sequencing for Bloodstream Infections in Patients with High-Risk Hematologic Malignancies

Background: Patients with hematological malignancies often suffer from infectious fever, rapid and accurate diagnosis of pathogens facilitates optimal and precise treatment of infectious diseases. In recent years, metagenomic next-generation sequencing (mNGS) technology has been widely used in the etiological detection of patients with respiratory tract infection, sepsis, etc, due to its advantages of rapid detection.However, at present, the clinical diagnosis of mNGS in patients with hematological malignancies in secondary bloodstream infections remains scarce. Objective: In this study, the application value of mNGS in the rapid etiological detection of bloodstream infection pathogens in patients with high-risk hematological malignancies was explored by comparing two etiological detection methods of mNGS and traditional pathogen culture. Methods: This study retrospectively analyzed 66 peripheral blood samples of patients with high-risk hematologic malignancies in our hospital from May 2020 to January 2022. SPSS 20.0 software was used to analyze the positive rate, species distribution and consistency of pathogens between mNGS and traditional pathogen culture method. The diagnostic efficiency of the two etiological detection methods was compared, and the risk factors affecting the positive rate of mNGS were investigated. Results: A total of 66 patients were enrolled in this study, including 38 males and 28 females, with an average age of (43.39±14.427) years. Among the 66 patients, 48 cases were acute myeloid leukemia (48/66, 72.7%), the rest included 2 cases of acute lymphoblastic leukemia (2/66, 3.0%), 3 cases of chronic myeloid leukemia (3/66, 4.5%), 3 cases of myelodysplastic syndrome (3/66, 4.5%), 4 cases of non-Hodgkin lymphoma (4/66, 6.0%), 4 cases of malignant tumor after autologous hematopoietic stem cell transplantation (4/66, 6.0%), and Hemophagocytic syndrome was found in 2 cases (2/66, 3.0%). Peripheral blood samples from 66 patients were both tested for mNGS and traditional pathogen culture. The positive rate of mNGS was 54.5% (36/66), while the traditional culture was 18.1% (12/66). There was a significant statistical difference between the two methods (P=0.000). Multivariate analysis was conducted on the influence of factors such as patient age, gender, disease diagnosis, and time from fever to the mNGS detection, and no statistical difference was found. Among the 36 mNGS-positive patients, a total of 64 pathogens were detected, including 19 bacteria (19/64, 29.7%), 12 fungus (12/64, 18.8%), 31 virus (31/64, 48.4%), and 2 special pathogens (2/64, 3.1%). Six drug-resistant bacteria were detected by mNGS in 5 patients .Among the 12 patients with positive traditional culture, 15 pathogens were detected, including 14 bacteria (14/15, 93.3%) and 1 fungus (1/12, 3.7%). In this study, 8 patients (8/66, 36.4%) were both positive for mNGS and traditional culture tests, and 5 of them (5/8, 62.5%) developed the same type of clinical infection with all or part identical detected pathogens. The time for positive and negative blood culture report was 72h and 7 days respectively, and 24h for mNGS. Among the 54 patients with negative results of traditional culture, 28 cases (28/54, 51.9%) were positive for mNGS, of which 15 cases (15/28, 53.6%) were made corresponding anti-infection regimens according to the positive results of mNGS, and the clinical efficacy was significantly improved. Seven of the 26 patients with both negative traditional culture and mNGS results were considered to have fungal infection based on chest imaging. After empirical antifungal treatment, the imaging results and clinical symptoms were improved; while only 4 of the remaining 19 patients (4/19, 21.5%) had clinical benefit from empirical anti-infective therapy. It demonstrated that pathogen-oriented therapy was significantly better than empirical anti-infective therapy (P=0.000). Conclusions: mNGS enhanced the positive rate of bloodstream pathogens detection and provided more accurate pathogen species in patients with high-risk hematologic malignancies.It could effectively detect multidrug-resistant bacteria and special pathogens,which provide an important reference for clinical antimicrobial treatment and improved their prognosis.

Lassa fever. Part 2. Laboratory diagnostics, treatment, development of medications

Globalization and high-speed means of transportation contribute to the spread of infections dangerous to humans. Airborne pathogens have pandemic potential as currently shown in case of the novel coronavirus SARS-CoV-2. Natural focal Lassa fever (LF) common in West African countries, in 35 cases was registered in non-endemic geographical areas because any person infected with Lassa virus (LASV) is a long-term source of infection (up to two months). Cases of person-to-person infection in endemic territories are described. In Germany, the facts of secondary virus transmission from patients to doctors have been recorded during the examination and blood collection from an apparently healthy person as well as during the autopsy of a deceased subjects due to severe LF course. Nonspecific malaise symptoms in LF are also characteristic of numerous other diseases common on the African continent, e.g., malaria and typhoid fever or viral infections such as yellow fever, Chikungunya, dengue and Zika, monkey pox and Ebola virus disease. In this regard, there may be similar dermatological manifestations. Timely detection of cases and differential diagnosis are crucial to ensure safe patient care and use of affordable antiviral therapy for LL provided by the drug Ribavirin. Research methods for studying LASV use polymerase chain reaction (PCR) for detecting viral RNA, electron microscopy, isolation of infectious virus cultured sensitive cells, indirect immunofluorescence reaction, enzyme immunoassay (ELISA) and immunochromatographic assays for the detection of antibodies and/or antigen as well as immunoblotting. Currently, test kits based on molecular and genetic methods are mainly used for LF laboratory diagnostics. Since the 1980s, ribavirin has been used to treat patients with LF. The serum accumulation of the drug in large quantities causes hemolysis, development of anemia and impaired renal function. In this regard, treatment options are being considered with decline in its concentration due to combined use with other antiviral drugs. A search for new therapeutic agents capable of inhibiting viral replication at disease early stage has been in progress due to lack of any approved vaccines.

IV Antibiotic Use during Autologous Hematopoietic Stem Cell Transplantation Is Associated with Inferior Survival in Patients with Multiple Myeloma

Autologous Hematopoietic stem cell transplantation (HSCT) following high-dose chemotherapy is an integral part of multiple myeloma (MM) treatment. While many factors impact HSCT success, low gut microbiome diversity has been shown to correlate with worse outcomes post-transplant (Khan et al, Blood 2021). HSCT patients receive intravenous (IV) antibiotics in response to neutropenic fever or bacterial infections, which can drive a lower microbiome diversity post-transplant (El Jurdi et al, BBMT 2018). Given the link between antibiotic exposure, low microbial diversity, and outcomes, we hypothesized that antibiotic exposure during transplant may adversely affect survival. To test this hypothesis, we performed a single-center retrospective study of transplant outcomes and IV antibiotic exposure at the University of Wisconsin from 2010-2017. Two hundred eighty-six patients underwent a first autologous HSCT using melphalan conditioning. All subjects received levofloxacin prophylaxis. Two hundred thirty-seven subjects received IV antibiotics including cefepime or piperacillin/tazobactam and vancomycin predominantly to treat neutropenic fever. Forty-nine patients did not require IV antibiotics. Patient demographics and disease factors were fairly balanced between the IV antibiotic and no antibiotic group, including age, sex, body mass index (BMI), presence of high-risk cytogenetics, number of prior lines of therapy, and use of maintenance therapy post-transplant. There was a higher proportion of Revised International Staging System (R-ISS) stage 1 myeloma in the no antibiotic cohort (12/39, 31%) versus the antibiotic cohort (37/179, 21%) but this was not statistically significant (p = 0.28). We observed an adverse effect of antibiotic exposure on overall survival (OS) (Figure 1, hazard ratio (HR) 0.41 IV antibiotic vs no antibiotic, 95% confidence interval (CI) 0.19 - 0.77), but not progression-free survival (PFS) (HR 0.95, 95% CI 0.62 - 1.4). Greater number of prior lines of therapy, higher R-ISS stage, and the absence of maintenance therapy each observed an adverse effect on OS when adjusting for IV antibiotic exposure (Table 1). On univariate analysis, high risk cytogenetics such as t(4;14), del17p, and t(14;16) was associated with inferior OS (HR no vs yes 0.625, 95% CI 0.40-0.99, p=0.041) but lost statistical significance when modelled together with IV antibiotic exposure HR no vs. yes 0.64, 95% CI 0.41-1.02), presumably due to sample size. After adjusting for age, presence of high-risk cytogenetics, number of prior lines, and use of maintenance therapy, the adverse effect of antibiotics maintained its statistically significant impact (Table 1). When adjusting for R-ISS stage, a similar adverse effect was noted but this was no longer statistically significant, possibly due to low numbers of reported R-ISS stage 3 in the no-antibiotic cohort (n=6). We conclude that IV antibiotic exposure confers an adverse effect on overall survival post-transplant. Inspection of the survival curve from the proportional hazards model (Figure 1) suggests this is unrelated to immediate post-transplant infectious complications. This finding supports a growing body of literature describing adverse long-term clinical impact of antibiotic exposure and on outcomes in cellular therapy, which we hypothesize is related to deleterious effects of antibiotic exposure on the gut microbiome. Larger prospective studies are necessary to further examine this relationship on myeloma outcomes. Figure 1View largeDownload PPTFigure 1View largeDownload PPT Close modal

NUP98-HOXA9 Bearing Acute Myeloid Leukemia

Acute myeloid leukemia (AML) with NUP98-HOXA9 fusion gene is rare, which is caused by t(7;11)(p15;p15). Not only the prognosis is poor, the efficacy of conventional induction regimen is also barely satisfactory. Here we report two cases of NUP98-HOXA9 bearing AML. Patient 1 was a 54-year-old female. In September of 2019, she felt fatigue with complete blood count (CBC) result of leukocytes 246.78× 109/L, hemoglobin 81g/L, and platelet 119 × 109/L. Peripheral blood smear showed 5% blast cells, and bone marrow (BM) smear demonstrated AML-M5. Chromosome 46, XX, t (7; 11) (p15; p15) [20], NuP98/HOXA9 fusion gene, EVI1 expression, FLT3-ITD and KRAS mutation was also found in her BM. One course of standard induced chemotherapy regimen IA reached CR, with MRD＜10-4, low expression of EVI1, and FLT3-ITD(-)，normal chromosome, but NuP98/HOXA9（+）. After the second course of IA, relapse occurred partly due to delayed admission under the influence of COVID-19. Reinduction with IA, azacytidine +HE, FLAG regimen failed to reach remission, and the patient died of bone marrow suppression and gastrointestinal bleeding. Patient 2 was a 65-years-old male. In September of 2019, he suffered from fatigue and CBC showed leukocytes 2.52× 109/L, hemoglobin 36g/L and platelet 139 × 109/L. Peripheral blood smear showed immature cells of 7%, and his BM smear demonstrated AML-M4. Chromosome 46, XY, t (7; 11) (p15; p15) [18]/46, XY[1], NuP98/HOXA9 fusion gene and IDH2 R140Q mutation were found in the patient. He had a history of chemotherapy for small cell lung cancer. After induced by regimen of DIAG, DHEG and DCAG successively, he did not reach remission. Repeated fever and lung infection occurred during the course of the disease. He was discharged automatically due to the progression of lung cancer. NuP98/HOXA9 bearing AML is more common in young Asian women, and the majority is type M2. The two patients in this report were older with M4 or M5 type, which was rare in this kind of leukemia. NuP98/HOXA9 is a poor prognostic factor for AML. Patient 1 could reach cytogenetic CR after IA induction, relapsed before transplantation, and the effect of reinduction therapy was poor; Patient 2 did not achieve remission. It is suggested from the these patients that patients with NuP98/HOXA9 bearing AML should undergo hematopoietic stem cell transplantation as soon as possible after CR with intensive therapy if their physical conditions permit.

Rituximab and Bortezomib for Patients with Newly Diagnosed Acquired Haemophilia: Single Arm, Single Center, Prospective Phase 2 Study

Introduction Acquired haemophilia A (AHA) is a rare autoimmune disorder caused by neutralizing autoantibodies against factor VIII (FVIII). The most common IST treatment used are Steroids-based regimens. However, patients with AHA are often elderly with comorbidities. Steroids-based regimens have significant side effects in patients with AHA. In particular, the risk of dying from infection appears to be higher than the risk of fatal bleeds today. This dilemma highlights the lack of safe and rapid response IST therapy in AHA. Bortezomib targets plasma cells rather than B cells and has reported efficacy in refractory AHA. It is an attractive agent because it depletes plasma cells that can continue to produce autoantibody even after CD20-positive B cells have been depleted by rituximab. The combination of bortezomib and rituximab regimen showed rapid response without severe adverse event in refractory and relapsed warm autoimmune hemolytic anemia. This phase 2, prospective, single-center study was designed to evaluate the efficacy and safety of rituximab and bortezomib (RB) treatment regimen in newly diagnosed AHA patients. Methods All patients 18 years of age or older who met the following criteria were considered as eligible candidates for this study: 1) plasma FVIII activity (FVIII:C) <50 l/dl, detectable inhibitor to FVIII. 2) newly diagnosed without any IST treatment. After obtaining the written informed consent from the patients, the information of demographic and medical history were collected and laboratory tests were performed.The patients were received the following regimens: Rituximab 375mg/m2 intravenous infusion on day 0 and bortezomib 1.3 mg/m2 subcutaneous on day 1,4,8,11. Best supportive care, including administration of hemostatic treatment and blood product transfusions if needed were used. Safety was evaluated according to NCI-CTCAE v4.0. Results From March 2018 to May 2022, 30 patients were eligible for the study. The baseline characteristics of the patients are summarized in Table 1. Overall, 19 patients were male (63.3%). The median age was 53.5 years (range 22 - 90 years). The underlying disorders that could be associated with AHA included rheumatoid arthritis, systemic lupus erythematosus and pemphigus. One patient was diagnosed at her postpartum. One patient was diagnosed soon after surgery. Traditional Chinese medicine was suspected as the inducement in one patient. No patient in our cohort was reported to have coexisting malignancy. 24 patients (80.0%) were regarded as idiopathic AHA. The median time from disease onset to the diagnosis was 36.5 days (range 10-249 days). The median FVIII activity at baseline was 1.5 IU/ml (range 0 to 10.4 IU/ml), and the median inhibitor concentration was 25.6 BU/ ml (range 2.7 to 600 BU/ ml). The bleeding event that precipitated diagnosis was reported as spontaneous in 27 patients (90.0%), by surgery in 3 patients (10.0%). All patients presented with bleeding diathesis as listed in Table 1. Sixteen patients (61.5%) received haemostatic treatment for initial bleeding, all of them received prothrombin complex concentrate (PCC). Nine patients experienced further bleeding after the treatment of BR. All patients completed protocol treatment. Overall, 23 patients (76.7%) achieved CR, 6 patients (20.0%) achieved PR and 1 patients died of cardiac events 3 month after last dose of bortezomib. The ORR was 96.7%. Median time to CR was 74 days (range 12-179 days). After a median follow-up of 39 months (range 3-50 months), one patient had relapse of the disease, 2 months after achieved CR. Major toxicities and adverse events are summarized in Table 2. One patient (3.8%) had grade 3 neutropenia; One patient (3.8%) had grade 4 thrombocytopenia and grade 3 thrombocytopenia each. Eight patients experienced infectious fever, including 2 grade 3 and 2 (7.7%) grade 4. Five patients (19.2%) developed grade 1-2 peripheral neuropathy.No treatment-related deaths occurred. Conclusion Here we report the results of a phase 2 prospective study of newly diagnosed AHA. This study confirmed that rituximab plus bortezomib was an efficient and safe regimen with ORR of 96.7%, and the median time to CR was 74 days.This trial was registered at www.clinicaltrials.gov as #NCT03700229. Figure 1View largeDownload PPTFigure 1View largeDownload PPT Close modal

Water, sanitation, hygiene practices, health and nutritional status among children before and during the COVID-19 pandemic: longitudinal evidence from remote areas of Dailekh and Achham districts in Nepal

BackgroundThe COVID-19 pandemic drew hygiene to the center of disease prevention. The provision of adequate water, sanitation, and hygiene (WASH) services is crucial to protect public health during a pandemic. Yet, access to levels of water supply that support adequate hygiene measures are deficient in many areas in Nepal. We examined WASH practices and their impact on child health and nutritional status in two districts before and during the COVID-19 pandemic.MethodsA longitudinal and mixed method study was conducted in March–May 2018 and November–December 2021. In total, 715 children aged 0–10 years were surveyed at baseline. Of these, 490 children were assessed at endline. Data collection methods included observations, a questionnaire, stool analysis, anthropometric measurements, water quality analysis, and an assessment of clinical signs of nutritional deficiencies. We conducted 10 in-depth interviews to understand major problems related to COVID-19.ResultsMost respondents (94.2%) had heard about COVID-19; however, they did not wear face masks or comply with any social distancing protocols. Almost 94.2% of the households self-reported handwashing with soap 5–10 times per day at endline, especially after defecation, compared to 19.6% at baseline. Water quality was better at endline than at baseline with median 12 to 29 CFU Escherichia coli/100 mL (interquartile range at baseline [IQR] = 4–101) at the point of collection and 34 to 51.5 CFU Escherichia coli/100 mL (IQR = 8–194) at the point of consumption. Fever (41.1–16.8%; p = 0.01), respiratory illness (14.3–4.3%; p = 0.002), diarrhea (19.6–9.5%; p = 0.01), and Giardia lamblia infections (34.2–6.5%, p = 0.01) decreased at endline. In contrast, nutritional deficiencies such as bitot’s spots (26.7–40.2%; p = 0.01), pale conjunctiva (47.0–63.3%; p = 0.01), and dermatitis (64.8–81.4%; p = 0.01) increased at endline. The inadequacy of the harvest and the lack of household income to meet households’ nutritional needs increased drastically (35.0–94.2%; p = 0.01).ConclusionWe found that improved water quality and handwashing practices were associated with a decrease in infectious diseases. However, food security also decreased resulting in a high prevalence of nutritional deficiencies. Our findings underline that disaster preparedness should consider access to adequate WASH, nutrition, and health supplies.

13-year Old Male Child Patient with a known Case of Necrotizing Encephalopathy

ANCE (Acute necrotizing encephalopathy of childhood) is a disease that affects children with a high fever, a respiratory or gastrointestinal infection, rapid changes in awareness, and seizures. Almost all Asian newborns and children who were previously in good health are affected by this illness. According to serial magnetic resonance imaging studies, the thalami, cerebellum, brainstem, and white matter all showed symmetric lesions in this disease. The condition has a poor prognosis with high morbidity and mortality rates. Amir Kola Children's Hospital is evaluating an A.N.E.C. in a 22-month-old kid Missense mutations were also detected in the gene that codes for the nuclear pore protein- Ran Binding Protein 2 (RANBP2). Though the clinical course and prognosis of ANE differ, the characteristic of neuro radiology manifestation of ANE is multifocal symmetric brain lesions visible on computed tomography (C.T.) or magnetic resonance imaging (M.R.I.).The treatment of ANCE is still under particular observation. We provide the most up-to-date information on ANCE, emphasizing early detection and successful consultation and treatment of this rare but deadly disease.

PIK3CD, IMMUNODEFICIENCY, MUTATIONS, GAIN-OF-FUNCTION

<h3>Introduction</h3> PIK3CD-GOF is an inborn error of immunity (IEI) with variable phenotypic characteristics even with the same variant. Lymphoproliferation, autoimmunity, and dysgammaglobulinemia may lead to suspicion of the diagnosis. Here we present four unrelated Mexican patients from nonconsanguineous families with a diagnosis of PIK3CD-GOF: <h3>Case Description</h3> (1) A 2-year-old female with a history of very early-onset inflammatory bowel disease (VEO-IBD) at 8 months, late omphalorrhexis, hyper-IgA, hyperleukocytosis, and low B and NK cells. (2) A 12-year-old male with a family history of lymphoma. Sepsis due to Listeria, periodontal abscess, systemic lupus erythematosus, Sjögren's syndrome, bronchiectasis, hepatosplenomegaly, lymphadenopathy, autoimmune hemolytic anemia, chronic EBV/CMV infection; leukocytosis and hyper-IgM. (3) A 2-year-old male with chronic rhinosinusitis, chronic suppurative otitis media, diarrhea; enlarged lymph nodes, splenomegaly, thrombocytopenia, low IgG and IgA and normal IgM with poor antibody response to pneumococcal vaccine. Hyper-IgM syndrome was suspected so he underwent successful stem cell transplantation. (4) An 11-year-old male child whose both parents were HIV+. Presented at 4-months with episodic fever and recurrent respiratory infections, bronchiectasis, mild mental retardation elevated IgM, low IgG, lymphopenia, and decreased lymphocyte proliferation. HIV were suspected in this patient. <h3>Discussion</h3> We identified heterozygous pathogenic variants related to PIK3CD: 3 of them in exon 24 (p.Glu1021Lys); and a novel variant in exon 7 (p.Ile262Val). PIK3CD-GOF is a combined immunodeficiency disorder (CID) with variable phenotype characteristics even with the same variant. Lymphoproliferation, autoimmunity, and dysgammaglobulinemia may raise suspicion. By behaving like a great simulator, genetic diagnosis is necessary to identify the specific pathogenic variant.

PMON191 Current Management of Acute Adrenal Insufficiency Related Adverse Events in Children with Congenital Adrenal Hyperplasia- Results of an International Survey of Specialist Centres

Abstract Background There is wide variation in the reported rate of acute adrenal insufficiency (AI) related adverse events (sick day episodes and adrenal crises) between centres and the definition of these events as well as their management may vary from one centre to another. A greater standardisation of the definition and management of these events would facilitate the benchmarking and comparison of care across centres. Objective Evaluate the level of consensus on the criteria that should be considered 'essential' for defining and managing acute AI related adverse events in children with Congenital Adrenal Hyperplasia. Methods Active users of the International Congenital Adrenal Hyperplasia &amp; International Disorders of Sex Development (I-CAH/I-DSD) Registries (n=66), non-active users of I-CAH/I-DSD (n=35) and the EuRRECa e-Reporting Registry (n=10) were approached to complete an online survey. Results 56 clinicians from 27 countries responded to the survey; response rates for the three Registry groups were 42 (65%), 11 (31%) and 3 (30%), respectively. Written corticosteroid management plans and one to one patient/parent education were provided by 54 (96%) and 51 (91%) clinicians, respectively; 33 (59%) provided steroid-aware emergency cards. 56 (100%) and 55 (98%) clinicians advised an increase in glucocorticoid dosing (sick day dosing) in the event of fever or severe infection (eg. pneumonia). Less common indications for sick day dosing included vaccination and mild afebrile intercurrent illness, recommended by 17 (30%) and 9 (16%) clinicians, respectively. The most frequently reported sick day dosing regimen was tripling the total daily dose of hydrocortisone and administering 3 times daily, reported by 24 (43%) clinicians. 40 (71%) specified the duration of sick day dosing as ≥48 hours for severe infections. Vomiting and diarrhoea were the most common indications for intramuscular hydrocortisone, reported by 34 (61%) and 25 (45%) clinicians, respectively. Over 50% of respondents indicated that essential clinical criteria for adrenal crisis should include fatigue and nausea or vomiting and over 60% indicated that the criteria should include hypotension, hyponatraemia, hyperkalaemia and clinical improvement following parenteral glucocorticoids. A bolus parenteral injection of hydrocortisone and glucose infusions were the most frequently administered medications, reported by 50 (89%) and 32 (57%) of clinicians, respectively. Conclusions Although there is considerable variation in the definition and management of AI related adverse events in children amongst specialist centres, there is also good evidence of consensus on specific aspects that can be used to develop standardised criteria and lead to greater benchmarking of care. Presentation: Monday, June 13, 2022 12:30 p.m. - 2:30 p.m.

Legionella pneumonia as a rising public health threat in Argentina: Is it the time to worry?

Legionella pneumonia as a rising public health threat in Argentina: Is it the time to worry?

The dynamics of scarlet fever in The Netherlands, 1906-1920: a historical analysis.

Background. Scarlet fever, an infectious disease caused by Streptococcus pyogenes, largely disappeared in developed countries during the twentieth century. In recent years, scarlet fever is on the rise again, and there is a need for a better understanding of possible factors driving transmission. Methods. Using historical case notification data from the three largest cities in The Netherlands (Amsterdam, Rotterdam and The Hague) from 1906 to 1920, we inferred the transmission rate for scarlet fever using time-series susceptible-infected-recovered (TSIR) methods. Through additive regression modelling, we investigated the contributions of meteorological variables and school term times to transmission rates. Results. Estimated transmission rates varied by city, and were highest overall for Rotterdam, the most densely populated city at that time. High temperature, seasonal precipitation levels and school term timing were associated with transmission rates, but the roles of these factors were limited and not consistent over all three cities. Conclusions. While weather factors alone can only explain a small portion of the variability in transmission rates, these results help understand the historical dynamics of scarlet fever infection in an era with less advanced sanitation and no antibiotic treatment and may offer insights into the driving factors associated with its recent resurgence.

Psychological Distress, Adaptation, And Well-Being in COVID-19 Recovered Patients: A Correlational Descriptive Study

The novel SARS-CoV-2 virus was reported in the province of Wuhan china and spread to more than 220 countries in no time. The patient who diagnosed corona virus has symptoms of flu, fever, sore throat and respiratory tract infection. In Pakistan the cases of covid-19 were also higher (305,671) and deaths (6416) due to six biggest populations in the world. Objective: The aim of the study was to explore the psychological distress, adaptation and well-being of patients diagnosed with covid-19 in Pakistan. Methods: A descriptive correlational study was conducted from May 2021 to September 2021 having a sample size of 173 having a consecutive sampling technique in Khyber teaching hospital and Hayat Abad medical complex Peshawar. Data was collected through valid and reliable instruments that are: Kessler Psychological Distress Scale (k-10), psychological adaptation scale (PSA), and The Warwick-Edinburgh mental well-being scale (WEMWBS) were used for data collection. Microsoft Excel and SPSS were used for analysis of mean, standard deviation, independent t-test and Pearson correlation. Results: In this study the number of male participants was higher (56.6%) than female participants (43.4%). The k-10 means score were (34.42), PSA (80.86) and Well-being was (59). Independent t-test findings were (k-10) p-value=0.713, (PSA) p-value= 1.501 and well-being p-value (0,795). The Pearson correlation shows that psychological distress was strongly correlated with PSA (p-value=0.002), and well-being (p-value=0.001). Conclusions: The study concluded that patient were physically, psychological, and emotionally affected after covid-19, so hospitalized patients received only physical treatment regimens and the other aspects of holistic care, especially psychological care, were ignored by the healthcare professionals.

Design of a novel multiple epitope-based vaccine: an immunoinformatics approach to combat monkeypox

Monkeypox virus is an infectious agent that causes fever, Pneumonitis encephalitis, rash, lymphadenopathy and bacterial infection. The current outbreak of monkeypox has reawakened the global health concern. In the current situation of increasing viral infection, no vaccine or drug is available for monkeypox. Thus, there is an urgent need for viable vaccine development to prevent viral transmission by boosting human immunity. Herein, using immunoinformatics approaches, a multi-epitope vaccine was constructed for the Monkeypox virus. In this connection, B-Cell and T-cell epitopes were identified and joined with the help of adjutants and linkers. The vaccine construct was selected based on promising vaccine candidates and immunogenic potential. Further epitopes were selected based on antigenicity score, non-allergenicity and good immunological properties. Molecular docking reveals strong interactions between TLR-9 and the predicted vaccine construct. Finally, molecular dynamics simulations were performed to evaluate the stability and compactness of the constructed vaccine. The MD simulation results demonstrated the significant stability of the polypeptide vaccine construct. The predicted vaccine represented good stability, expression, immunostimulatory capabilities and significant solubility. Design vaccine was verified as efficient in different computer-based immune response investigations. Additionally, the constructed vaccine also represents a good population coverage in computer base analysis. Communicated by Ramaswamy H. Sarma

Retrospective study on the effectiveness and safety of the shortened 5- to 7-day antibiotic regimen for acute streptococcal pharyngotonsillitis compared to the classic 10-day regimen

IntroductionAntibiotherapy regimens for management of acute streptococcal pharyngitis traditionally last 10 days, but the development of resistance to different antimicrobials has motivated the exploration of shorter courses. Material and methodsWe selected patients given a diagnosis of streptococcal pharyngitis in 2 paediatric caseloads of 1 primary care centre between June 2016 and April 2020. We compared outcomes in patients treated with 8- to 10-day courses versus 5- to 7-day courses. ResultsThe analysis included 350 care episodes (252 patients). Sixty-four percent were managed with 8- to 10-day courses of antibiotherapy (group 1) and 36% with 5- to 7-day courses (group 2). There were no significant differences in the incidence of streptococcal pharyngitis or scarlet fever in the 3 months that followed (OR, 0.98; 95% confidence interval [CI], 0.46–2.03), with similar percentages in both groups (9.8% vs 9.5%). Overall, without differentiating based on the type of infection (streptococcal pharyngitis, scarlet fever or other streptococcal infections), we found similar outcomes (OR, 0.81; 95% CI, 0.41–1.59): 13.4% in group 1 and 11.1% in group 2. We also found no differences in the frequency of adverse events documented in the health records (OR, 0.29; 95% CI, 0.04–2.44): 2.7% in group 1 and 0.8% in group 2. ConclusionsIn our experience, a shorter antibiotic course (5–7 days) is not less effective or more unsafe for management of acute streptococcal pharyngitis than the traditional 10-day course.

Systematic identification of chemical components in Fufang Shuanghua oral liquid and screening of potential active components against SARS-CoV-2 protease

Coronavirus disease (COVID-19) caused by SARS-COV-2 infection has been widely prevalent in many countries and has become a common challenge facing mankind. Traditional Chinese medicine (TCM) has played a prominent role in this pandemic, and especially TCM with the function of “heat-clearing and detoxifying” has shown an excellent role in anti-virus. Fufang Shuanghua oral liquid (FFSH) has been used to treat the corresponding symptoms of influenza such as fever, nasal congestion, runny nose, sore throat, and upper respiratory tract infections in clinic, which are typical symptoms of COVID-19. The content of chlorogenic acid, andrographolide and dehydrated andrographolide as the quality control components of FFSH is not less than 1.0 mg/mL, 60 μg/mL and 60 μg/mL respectively. In this study, UPLC-Q-TOF-MS/MS was employed to describe the chemical profile of FFSH. Virtual screening and fluorescence resonance energy transfer (FRET) were used to screen the effective components of FFSH acting on SARS-CoV-2 main protease (Mpro). As a result, 214 compounds in FFSH were identified or preliminarily characterized by UPLC-Q-TOF-MS/MS, and 61 active ingredients with potential inhibitory effects on Mpro were selected through receptor-based and ligand-based virtual screening. In particular, quercetin, forsythoside A, and linoleic acid showed a good inhibitory effect on Mpro in FRET evaluation with IC50 values of 26.15 μM, 22.26 μM and 47.09 μM respectively, and had a strong binding affinity with the receptor Mpro (6LU7) in molecular docking. CYS145 and HIS41 were the main amino acid residues affected by small molecules in the protein binding domain. In brief, we characterized, for the first time, 214 chemical components in FFSH, and three of them, including quercetin, forsythoside A and linoleic acid, were screened out to exert beneficial anti-COVID-19 effects through CYS145 and HIS41 sites, which may provide a new research strategy for TCM to develop new therapeutic drugs against COVID-19.

Incidence of symptomatic Covid-19 infections in patients with mastocytosis and chronic myeloid leukemia: A comparison with the general Austrian population.

The SARS-COV-2 (Covid-19) pandemic has impacted the management of patients with hematologic disorders. In some entities, an increased risk for Covid-19 infections was reported, whereas others including chronic myeloid leukemia (CML) had a lower mortality. We have analyzed the prevalence of Covid-19 infections in patients with mastocytosis during the Covid-19 pandemic in comparison to data from CML patients and the general Austrian population. The prevalence of infections and PCR-proven Covid-19 infections was analyzed in 92 patients with mastocytosis. As controls, we used 113 patients with CML and the expected prevalence of Covid-19 in the general Austrian population. In 25% of the patients with mastocytosis (23/92) signs and symptoms of infection, including fever (n=11), dry cough (n=10), sore throat (n=12), pneumonia (n=1), and dyspnea (n=3) were recorded. Two (8.7%) of these symptomatic patients had a PCR-proven Covid-19 infection. Thus, the prevalence of Covid-19 infections in mastocytosis was 2.2%. The number of comorbidities, subtype of mastocytosis, regular exercise, smoking habits, age, or duration of disease at the time of interview did not differ significantly between patients with and without Covid-19 infections. In the CML cohort, 23.9% (27/113) of patients reported signs and symptoms of infection (fever, n=8; dry cough, n=17; sore throat, n=11; dyspnea, n=5). Six (22.2%) of the symptomatic patients had a PCR-proven Covid-19 infection. The prevalence of Covid-19 in all CML patients was 5.3%. The observed number of Covid-19 infections neither in mastocytosis nor in CML patients differed significantly from the expected number of Covid-19 infections in the Austrian population. Our data show no significant difference in the prevalence of Covid-19 infections among patients with mastocytosis, CML, and the general Austrian population and thus, in mastocytosis, the risk of a Covid-19 infection was not increased compared to the general population.

Safra yoluna rüptüre karaciğer kist hidatik tedavisi:Endoskobik drenaj

Abstract:&#x0D; Hydatid cyst disease is a zoonotic disease caused by the transmission of Echinococcus granulosus, which is in the cestode class, to humans during the larval period. This disease causes serious problems by affecting public health and national economy as an important parasitic disease, especially in many developing countries. Liver cyst cysts can be complicated according to their diameter and location. Complication rate reaches 60%. The leading complications are bile duct involvement and related complications. Bile duct problems should be solved first in cysts associated with biliary tract. ERCP and endoscopic sphinterotomy can be performed. Here we discussed the treatment and management of a 35-year-old patient with hydatid cyst that opened into the biliary tract with ERCP, who presented to the emergency room with fever and signs of infection.&#x0D; Keywords:endoscopic cyst evacuation, cholangitis, endoscopic retrograde cholangiopancreatography

Understanding the Mechanism of Antimicrobial Resistance and Pathogenesis of Salmonella enterica Serovar Typhi.

Salmonella enterica serovar Typhi (S. Typhi) is a Gram-negative pathogen that causes typhoid fever in humans. Though many serotypes of Salmonella spp. are capable of causing disease in both humans and animals alike, S. Typhi and S. Paratyphi are common in human hosts only. The global burden of typhoid fever is attributable to more than 27 million cases each year and approximately 200,000 deaths worldwide, with many regions such as Africa, South and Southeast Asia being the most affected in the world. The pathogen is able to cause disease in hosts by evading defense systems, adhesion to epithelial cells, and survival in host cells in the presence of several virulence factors, mediated by virulence plasmids and genes clustered in distinct regions known as Salmonella pathogenicity islands (SPIs). These factors, coupled with plasmid-mediated antimicrobial resistance genes, enable the bacterium to become resistant to various broad-spectrum antibiotics used in the treatment of typhoid fever and other infections caused by Salmonella spp. The emergence of multidrug-resistant (MDR) and extensively drug-resistant (XDR) strains in many countries of the world has raised great concern over the rise of antibiotic resistance in pathogens such as S. Typhi. In order to identify the key virulence factors involved in S. Typhi pathogenesis and infection, this review delves into various mechanisms of virulence, pathogenicity, and antimicrobial resistance to reinforce efficacious disease management.