Acute Fever Research Articles

Evolution of waterborne diseases: A case study of Khyber Pakhtunkhwa, Pakistan.

In Pakistan, the degradation of drinking water quality is exacerbated by the increasing population size and rapid industrialization. Contaminated water serves as the predominant source of numerous diseases, including diarrhea, gastroenteritis, and typhoid. This article explores the evolution of waterborne diseases across 21 districts of the Khyber Pakhtunkhwa province in Pakistan by monitoring changes in the clustering solutions. The data employed in this study were sourced from 21 districts of KP by the Director-General Health Services. Cluster analysis was utilized to uncover patterns in waterborne disease incidence, while principal component analysis was employed to reveal underlying patterns and reduce dimensionality. Additionally, the MONItoring Clusters (MONIC) framework was applied for change detection, facilitating the identification of significant shifts in disease patterns over time and aiding in the understanding of temporal dynamics. Our analysis indicates that two clusters survived consistently over time, while other clusters exhibited inconsistency. Profiling of the surviving clusters (C12 → C24 → C32 → C43) suggests a gradual increase in cases of bloody diarrhea in the Swat Valley, Hangu, Karak, and Lakki Marwat regions. Similarly, profiling of the surviving clusters (⊙→ C22 → C34 → C44) suggests an increase in the acute watery diarrhea (non-cholera) and typhoid fever in the regions of Peshawar, Nowshera, and Swabi. The findings of this study hold significant importance as they pinpoint the most vulnerable regions for various waterborne diseases. These insights offer valuable guidance to policymakers and health officials, empowering them to implement effective measures for controlling waterborne diseases in the respective regions of Khyber Pakhtunkhwa, Pakistan.

Coinfection of malaria and scrub typhus in a toddler: First report from South India

Abstract Tropical infections are common in South Asia, including India. However, coinfections among the different diseases are rare in children. We report a case of malaria-scrub typhus coinfection in a toddler from South India. A 3-year-old boy presented with fever. He was pale, dull-looking and had hepatosplenomegaly.. There was mild leukocytosis with positive C reactive protein. Rapid malarial antigen was positive, and started on antimalarial therapy. Fever was persisting after 48 h and doxycycline was started. Scrub typhus immunoglobulin M was positive. He responded dramatically to doxycycline, and in 24 hours, he became afebrile. The prevalence of this coinfection was studied by Wilairatana et al. in 2021 and showed a low prevalence of 0%–1%. Our case is unique and rare as this has not been reported in a toddler. Children with acute undifferentiated fever which is not responding to therapy within 48 hours must be investigated for concurrent infection.

Acute respiratory failure prognosis in prolonged ICU stays

Objective: This study aimed to assess the outcome of patients with acute respiratory failure and need of mechanical ventilation who stayed for more than 21 days in the ICU. Methods: All acute respiratory failure patients in King Saud Medical City, Riyadh Saudi Arabia and adults ICU who required a lengthy intensive care unit stay of more than 21 days between January 2022 and August 2023 were identified in this retrospective study. Information was extracted from the hospital database by trained physicians. Results: Total 121 patients (mean age 61.2±15.8 years) were included. Of which, 24.1% patients were more than 70 years. Sepsis was the most common cause of prolonged ICU stay both in survivors and non-survivors with 77.8% and 76.1%, respectively. Compared to patients who survived, non-survivors had higher acute physiology and chronic health evaluation (APACHE 4) scores were considerably older. Moreover, non-survivors were more likely than survivors to have renal failure, arrhythmia, hepatic failure, or significant gastrointestinal tract bleeding as reasons for a lengthy ICU stay. Patients who were admitted to ICU because they needed further surgery were more likely to survive. Conclusion: When acute respiratory fever (ARF) patients needed a lengthy stay in the ICU, their prognosis was not good. A high risk of in-hospital death was linked to older ages, more than 28 days ICU stay, more than 25 APACHE 4 score, unstable hemodynamic condition, hepatic failure, renal failure, major gastrointestinal tract bleeding, and needing FiO2 ≥40%.

IgM-specific linear epitopes on the E2 protein for serodiagnosis of Chikungunya

Chikungunya virus (CHIKV) and Dengue virus (DENV) are vector-borne diseases transmitted by Aedes aegypti and Aedes albopictus that pose a significant threat to global public health. Cases of acute Chikungunya fever often present similar clinical symptoms to other vector-borne diseases, such as Dengue fever. In regions where multiple vector-borne diseases coexist, CHIKV is often overlooked or misdiagnosed as Dengue virus, West Nile virus, Zika virus or other viral infections, which delays its prevention and control. However, IgM antibodies directed against the E2 protein of CHIKV have not yet been generalized to clinical settings due to the low sensitivity and high cost in commercial kits. Indirect ELISA with peptides provides an effective supplementary tool for detecting CHIKV IgM antibodies. Our study aims at examining the potential of linear epitopes on the E2 glycoprotein that specifically bind to IgM antibodies as serodiagnostic tool for CHIKV. The sensitivity of the established peptide indirect ELISA method for detecting clinical samples is significantly better than that of commercial kits, realizing a beneficial supplement to the existing IgM antibody assay. It also established the groundwork for comprehending the biological mechanisms of the CHIKV E2 protein and the advancement of innovative epitope peptide vaccines.

A 57-Year-Old Woman Present with Acute Delirium and Fever

<p>燒合併急性譫妄（Acute delirium），臨床上常被認為感染導致。本個案57歲女性，三天前因發燒、意識混亂與腹瀉，初步臆測診斷為細菌性腸炎造成譫妄，經糞便、血液細菌培養、腦部電腦斷層、腦脊髓液檢查、腦波與皮質酮（cortisol）檢驗均正常，抗生素治療下仍高燒不退、腹瀉、心搏過速，急劇意識昏迷併呼吸衰竭及全身抽搐。回顧此個案罹患甲狀腺機能亢進又擅自停藥，近期使用Xenetix碘顯影劑，當同時出現高燒、意識改變、腸胃肝膽障礙與心搏過速，按照甲狀腺風暴（Thyroid storm）診斷評分100分應高度懷疑甲狀腺風暴，盡快給予ß交感神經阻斷劑、降低甲狀腺激素合成、糖皮質類固醇、含碘製劑治療，經治療後個案意識與精神症狀獲得改善並順利出院。本篇教學著重如何快速鑑別診斷並牢記甲狀腺風暴評分項目與相關誘發因子，進而早期診斷與積極治療，可降低死亡率及多重器官衰竭，達到個案回歸日後自我照護能力。</p> <p> </p><p>Acute delirium is usually caused by infection, clinically. The case in this study is a 57-year-old woman with fever, confusion, and diarrhea for 3 days. The initial diagnosis was delirium caused by bacterial enteritis. Examinations of feces, blood bacteria culture, computed tomography scan, cerebrospinal flu-id, electroencephalography, and cortisol were all normal. However, high fever, diarrhea, tachycardia, acute unconsciousness with respiratory failure, and general convulsions persisted despite antibiotic treatment was applied. After recalling medical history the patient was suffered from hyperthyroidism and discontinued medication without permission. Furthermore, a Xenetix iodine contrast agent was re-cently administered while symptoms such as high fever, altered consciousness, gastrointestinal hepa-tobiliary disturbance, and tachycardia occurred simultaneously. Therefore, the possibility of a thyroid storm became apparent after applying the thyroid storm 100-point diagnosis scale evaluation. As such, ß sympathetic blockers, reduction of thyroid hormone synthesis, glucocorticoids, and preparations con-taining iodine were administered immediately. After treatments, the consciousness and mental symp-toms of the patient were improved and then successfully discharged. This case suggests that a rapid differential diagnosis by remembering the thyroid storm grading scale as well as relevant predisposing factors shell be considered in early diagnosis. Furthermore, proactive treatments could be utilized to reduce mortality rate and the possibility of multiple organ failure, thereby allowing patients to recover self-care ability in the future.</p> <p> </p>

Xác định thành phần loài Rickettsia trên chuột và một số ngoại ký sinh trùng ở khu vực đóng quân một số đơn vị quân đội miền Bắc

Rickettsia, a gram-negative bacterium, and an obligate intracellular bacterium, can potentially cause fatal acute fever if not promptly detected and treated. It's often transmitted to humans by arthropods like ticks, fleas, and lice. Rodents and small mammals can serve as key hosts for various Rickettsia species. Our study aimed to identify Rickettsia species using nested PCR and gene sequencing of ompA, ompB, 17-kDa, and gltA genes based on 29 DNA samples, which tested positive for Rickettsia spp collected from mice, ticks, fleas, and lice at military units in Lang Son, Nghe An, Hai Duong, and Bac Giang, The phylogenetic analysis showed that 9/29 (31%) of Rickettsia samples belonged to Rickettsia felis species, 1/29 (3.5%) of Rickettsia samples exhibited a 99.5% ompB gene sequence similarity to Rickettsia heilongjiangensis species .

Rising Menace of Scrub Typhus – Current Status and Challenges

Scrub typhus, an age old disease, is caused by the intracellular bacterium Orientia tsutsugamushi. It has reemerged in recent years due to factors like climatic changes and human encroachment because of rampant urbanization. The disease is endemic in the area known as the ‘tsutsugamushi triangle’ and has recently spread its fangs into various other continents like South America and Africa. Although the disease is endemic in India, there is a lack of appropriate sero-epidemiology in community settings. It is one of the essential causes of acute undifferentiated fever in tropical locations and, if untreated, can cause mortality ranging from 2-30% of cases. Early diagnosis is an important parameter in administering the non beta-lactam regimen to prevent complications and mortality. Yet, there is a lack of accurate and rapid methods for diagnosis in the early stage of the disease, more so in rural areas where the disease is supposed to be predominant. The gold standard diagnostic test has its problems. Recently, there have been reports of drug resistance to the standard scrub typhus regimen. There is a gap of a decade in the research into this entity. Thus, a new look into the disease, its epidemiology and the challenges in its diagnostic scenario is an apt topic for discussion.

892. Epidemiology, clinical features, and outcomes of Rhinovirus/Enterovirus in older adults hospitalized with acute respiratory infections and those with CHF and COPD exacerbations

Abstract Background While Rhinovirus/Enterovirus (RV/EV) infections are common, the clinical characteristics of infections in hospitalized adults are not fully understood. Methods Adults ≥ 50 years of age hospitalized for Acute Respiratory Infections (ARI) or exacerbations of CHF or COPD in two hospitals in Atlanta, GA during the 2018-2019 and 2019-2020 respiratory seasons were offered enrollment. Following informed consent, participants were tested via BioFire® FilmArray® respiratory panels of nasopharyngeal and oropharyngeal swabs (combined), and standard-of-care molecular testing results were also recorded. Subjects were considered positive for RV/EV if any method of testing resulted positive. Baseline characteristics and clinical features were gathered via subject interviews and medical record abstractions. Variables were compared between subjects with RV/EV and two control groups: those negative for all pathogens and those negative for only RV/EV. Participants with RV/EV who had co-infections were excluded from the analysis. Descriptive statistics were performed using SAS v9.4. Results Of 1429 enrolled participants, 123 (8.6%) were positive for RV/EV, of whom 111 had RV/EV alone. When compared to those negative for all tested pathogens (n=1034), participants with RV/EV more commonly had underlying COPD (45.0% vs. 35.5%, P=0.047) and less commonly had CHF (36.0% vs. 48.3%, P=0.014) or experienced acute myocardial dysfunction (29.7% vs. 41.2%, P=0.019). Participants with RV/EV also more commonly experienced fever (39.6% vs. 27.7%, P=0.008), cough (90.1% vs. 69.0%, P< 0.001), sore throat (54.1% vs. 39.5%, P=0.003), chest pain (48.6% vs. 37.8%, P=0.026), and dyspnea/respiratory distress (25.2% vs. 13.1%, P< 0.001) than those negative for all pathogens. Differences between RV/EV positive and negative groups were similar to the all pathogen negative group, with the exception of no significant differences in acute myocardial dysfunction, fever, and COPD in the RV/EV negative group. Conclusion Among older adults hospitalized with ARIs, CHF, and/or COPD exacerbations, RV/EV was associated with symptoms of both upper and lower respiratory tract infection and was more frequent identified among those with COPD. Disclosures Elizabeth Begier, M.D., M.P.H., Pfizer: EB is an employee of Pfizer, the sponsor of this study|Pfizer: Stocks/Bonds Robin Hubler, MS, Pfizer, Inc.: Employee|Pfizer, Inc.: Stocks/Bonds Qing Liu, M.S., Pfizer Inc.: Stocks/Bonds Bradford D. Gessner, M.D., M.P.H., Pfizer: I am an employee of Pfizer|Pfizer: Stocks/Bonds Benjamin Lopman, PhD, Epidemiological Research and Methods, LLC: Advisor/Consultant|Hillevax, Inc: Advisor/Consultant Satoshi Kamidani, MD, CDC: Grant/Research Support|Emergent BioSolutions: Grant/Research Support|NIH: Grant/Research Support|Pfizer Inc: Grant/Research Support Nadine Rouphael, MD, Icon, EMMES, Sanofi, Seqirus, Moderna: Advisor/Consultant Evan J. Anderson, MD, GSK: Advisor/Consultant|GSK: Grant/Research Support|Janssen: Advisor/Consultant|Janssen: Grant/Research Support|Kentucky Bioprocessing, Inc.: Safety Monitoring Board|Moderna: Advisor/Consultant|Moderna: Grant/Research Support|Moderna: Currently an employee|Moderna: Stocks/Bonds|Pfizer: Advisor/Consultant|Pfizer: Grant/Research Support|Sanofi Pasteur: Advisor/Consultant|Sanofi Pasteur: Grant/Research Support|Sanofi Pasteur: Safety Monitoring Board|WCG/ACI Clinical: Data Adjudication Board Christina A. Rostad, MD, BioFire Inc.: Grant/Research Support|GlaxoSmithKline Biologicals: Grant/Research Support|Janssen: Grant/Research Support|MedImmune LLC: Grant/Research Support|Meissa Vaccines, Inc.: RSV vaccine technology|Merck & Co., Inc.: Grant/Research Support|Micron Technology, Inc.: Grant/Research Support|Moderna, Inc.: Grant/Research Support|Novavax: Grant/Research Support|PaxVax: Grant/Research Support|Pfizer, Inc.: Grant/Research Support|Regeneron: Grant/Research Support|Sanofi Pasteur: Grant/Research Support

877. Diagnostic Values of Viral Target Enriched and Metagenomic NGS among Patients with Acute Undifferentiated Fever in Thailand

Abstract Background Despite extensive lab testing, infectious agents were not detected in ∼50% of patients hospitalized for acute undifferentiated febrile illness (AUFI) at Siriraj Hospital, Bangkok, Thailand. Unbiased metagenomic Next Generation Sequencing (mNGS) enables detection of many microbes present in patient samples. Target enrichment for viruses in these libraries represents a highly sensitive and cost-effective approach for overcoming host background present in clinical specimens. Plasma collected from 440 patients with AUFI between 2014-2021 were analyzed by both viral target enrichment and mNGS to determine their diagnostic values for the identification of human pathogens. Methods Benzonase-treated plasma was extracted on an Abbott m2000 instrument. mNGS libraries were prepared from ds-cDNA and hybridized to CVRP probes (Twist Biosciences) covering > 15,000 strains of vertebrate viruses. Target enriched libraries were run on a MiSeq; mNGS libraries were sequenced on a NextSeq. Reads were processed by the SURPI or DiVir pipelines and viral reads were mapped in the CLC Bio Genomics Workbench. Results We identified viruses in 23% of our AUFI population using CVRP. mNGS increased viral detection to 26.8% and overall pathogen detection to 41.8%. Both methods identified relatively prevalent viruses such as Dengue, HIV-1, HBV, HAV and CHIKV, less common viruses such as Measles, HHV-6B, CMV, and PARV and emerging viruses such as SFTS virus with a high degree of correlation between NGS and clinical data. Bacterial pathogens identified by mNGS included Rickettsia typhi, R. felis and Capnocytophaga canimorsus. Identification of parasites P. falciparum and P. vivax was consistent with clinical presentations. mNGS failed to detect blood-culture positive patients with Klebsiella pneumoniae, Pseudomonas aeruginosa, and Streptococcus gallolyticus septicemia. Conclusion CVRP and mNGS demonstrated that viral and rickettsial infections were important etiologies for AUFI in Thailand. This data supports the current recommendation of empirical therapy with ceftriaxone and doxycycline or azithromycin in severe or hospitalized AUFI. Implications for proper management of AUFI include lower rates of unnecessary testing and antimicrobial use. Disclosures Julie Yamaguchi, BS, Abbott Labs: Patents|Abbott Labs: Employee|Abbott Labs: Stocks/Bonds Michael G. Berg, PhD, Abbott Laboratories: employee|Abbott Laboratories: Stocks/Bonds Sonja Weiss, BS, Abbott Laboratories: Employee|Abbott Laboratories: Stocks/Bonds Pakpoom Phoompoung, MD, Abbott Labs: Grant/Research Support|Abbott Labs: Mahidol University is a partner in the Abbott Pandemic Defense Coalition Gavin Cloherty, PhD, Abbott Labs: Patents|Abbott Labs: Employee|Abbott Labs: Stocks/Bonds Yupin Suputtamongkol, MD, Abbott Labs: Grant/Research Support|Abbott Labs: Mahidol University is partner in the Abbott Pandemic Defense Coalition

Marburg virus outbreak in Tanzania: A threat to global health security

AbstractThe current Marburg virus (MARV) outbreak in Tanzania served as a stark reminder of the ongoing threat posed by emerging infectious diseases and the urgent need for global health security. The Tanzanian Ministry of Health (MoH) officially declared the outbreak on March 21, 2023. Eight cases in all, five of which included fatalities, have been reported in the country at present. The virus is a member of the Filoviridae family closely related to the widely known Ebola virus. Similar to other filoviruses, MARV causes acute and lethal hemorrhagic fever in both human and nonhuman primates with high case fatality rates ranging from 24% to 90%. The outbreak has highlighted the need for improved disease surveillance and response systems, as well as increased funding for research into emerging infectious diseases. The Tanzanian MoH has deployed a response team to investigate and monitor the transmission in the Kagera Region. The team works closely in collaboration with other organizations, such as the World Health Organization and the Africa Centre for Disease Control and Prevention, to ensure the effective control of the situation. Although there is no vaccine or treatment approved for Marburg virus disease (MVD), supportive management improves survival. Existing infection prevention and control protocols for Ebola and other viral hemorrhagic fevers such as isolation and use of appropriate personal protective equipment can be used to prevent transmission of MVD. The global community must work together to strengthen health systems, enhance research efforts, and build resilient and responsive health systems to prevent future outbreaks of this kind. In this article, we have analyzed the MVD outbreak in Tanzania, specifically in the Bukoba district of the Kagera Region, and provided recommendations for the management of the current outbreak and future outbreaks.

Chikungunya: Diagnostic, Treatment and Challenge in Indonesia

Chikungunya based on the literature is classified as one of the many diseases that become a differential diagnosis of acute undifferentiated fever. Finally, patients with this condition are treated with empirical therapy so that often the management does not meet the standards / undertreatment. In an effort to reduce morbidity and improve the quality of care with limited modalities, history taking and physical examination as well as effective risk factor analysis are necessary in the current situation in Indonesia. Therefore, the authors raise this topic to help improve diagnostic acuity and the importance of the role of laboratory modalities in the diagnosis of chikungunya in Indonesia. Google Scholar by using the search keywords "Chikungunya" and "In Indonesia" with a time span of 2013-2023. Through a search that has been carried out using these 2 keywords, we get 10,300 publications. Based on the inclusion and exclusion results, 30 publications were obtained that could be used in compiling our literature review. Indonesia is an archipelago and is one of the countries in the world with a tropical climate, so it is certainly an ideal place for various tropical infectious diseases such as chikungunya. Although Indonesia has suppressed chikungunya incidence, Indonesia still facing some problem on diagnostic and case reporting system. This situation effect the performance of incidence validity and quality of treatment. Chikungunya virus infection in Indonesia still requires diagnostic development efforts to anticipate future outbreaks.

Clinicopathological and ultrastructural study of African swine fever outbreak in North-East India

The present investigation focuses on examining the clinical, histopathological, and ultrastructural changes that occurred in pig, during an outbreak of African swine fever (ASF) in 2022 in Assam, India. The disease initially manifested as a per-acute case with high mortality but without any evident clinical signs. Subsequently, some animals exhibited an acute form of the disease characterized by high fever (104–106 °F), anorexia, vomiting, respiratory distress, and bleeding from the anal and nasal orifices. During acute African swine fever virus (ASFV) infections, elevated levels of pro-inflammatory IL-1α, IL-1β, IL-6, TNF, CCL2, CCL5, and CXCL10 were detected in the palatine tonsil, lymph nodes, spleen, and kidney using qPCR assay. These molecular changes were associated with haemorrhages, edemas, and lymphoid depletion. Postmortem examinations revealed prominent features such as splenomegaly with haemorrhages, haemorrhagic lymphadenitis, severe petechial haemorrhage in the kidney, pneumonia in the lungs, and necrotic palatine tonsil. Histopathological analysis demonstrated lymphocyte depletion in lymphoid organs, multi-organ haemorrhages, and interstitial pneumonia in the lungs. Scanning electron microscopy (SEM) further confirmed lymphocyte depletion in lymphoid organs through lymphocyte apoptosis and kidney damage with distorted tubules due to red blood cell destruction. Transmission electron microscopy reaffirmed lymphocyte apoptosis by observing chromatin condensation and nucleus margination in lymphocytes of lymphoid organs. These findings provide comprehensive insights into the clinical, histopathological, and ultrastructural aspects of ASF outbreak in pigs. Understanding the pathological changes associated with ASF can contribute to improved diagnosis, prevention, and control measures for this highly contagious and economically devastating viral disease.

A mathematical model of Marburg virus disease outbreaks and the potential role of vaccination in control

BackgroundMarburg virus disease is an acute haemorrhagic fever caused by Marburg virus. Marburg virus is zoonotic, maintained in nature in Egyptian fruit bats, with occasional spillover infections into humans and nonhuman primates. Although rare, sporadic cases and outbreaks occur in Africa, usually associated with exposure to bats in mines or caves, and sometimes with secondary human-to-human transmission. Outbreaks outside of Africa have also occurred due to importation of infected monkeys. Although all previous Marburg virus disease outbreaks have been brought under control without vaccination, there is nevertheless the potential for large outbreaks when implementation of public health measures is not possible or breaks down. Vaccines could thus be an important additional tool, and development of several candidate vaccines is under way.MethodsWe developed a branching process model of Marburg virus transmission and investigated the potential effects of several prophylactic and reactive vaccination strategies in settings driven primarily by multiple spillover events as well as human-to-human transmission. Linelist data from the 15 outbreaks up until 2022, as well as an Approximate Bayesian Computational framework, were used to inform the model parameters.ResultsOur results show a low basic reproduction number which varied across outbreaks, from 0.5 [95% CI 0.05–1.8] to 1.2 [95% CI 1.0–1.9] but a high case fatality ratio. Of six vaccination strategies explored, the two prophylactic strategies (mass and targeted vaccination of high-risk groups), as well as a combination of ring and targeted vaccination, were generally most effective, with a probability of potential outbreaks being terminated within 1 year of 0.90 (95% CI 0.90–0.91), 0.89 (95% CI 0.88–0.90), and 0.88 (95% CI 0.87–0.89) compared with 0.68 (0.67–0.69) for no vaccination, especially if the outbreak is driven by zoonotic spillovers and the vaccination campaign initiated as soon as possible after onset of the first case.ConclusionsOur study shows that various vaccination strategies can be effective in helping to control outbreaks of MVD, with the best approach varying with the particular epidemiologic circumstances of each outbreak.

Paediatric pyoderma gangrenosum treated with ustekinumab

AbstractPyoderma gangrenosum (PG) is a rare reactive noninfectious inflammatory dermatosis. More than 50% of PG patients have an associated systemic disease, which, in most cases, is an inflammatory bowel disease. PG affects more females than males and patients with active colitis. This case report describes a 12‐year‐old girl previously diagnosed with ulcerative colitis (UC) and on infliximab treatment. She came to our attention with a painful leg ulcer during admission for acute respiratory failure and fever. The lesion was classified as PG and a diagnosis of UC pulmonary involvement was made. Infliximab was substitute by ustekinumab and the girl is in remission after 1 year of treatment. To the best of our knowledge, this is the first case in the literature of a UC‐related paediatric PG treated with ustekinumab. Our data suggest that more studies are required as to the efficacy of ustekinumab in paediatric PG settings.

Co-expression analysis suggests lncRNA-mRNA interactions enhance antiviral immune response during acute Chikungunya fever in whole blood of pediatric patients.

Chikungunya virus is an arbovirus that causes the neglected tropical disease chikungunya fever, common in tropical areas worldwide. There is evidence that arboviruses alter host transcriptome and modulate immune response; this modulation may involve transcriptional and post-transcriptional control mechanisms mediated by long non-coding RNAs (lncRNAs). Herein, we employed bioinformatic analysis to evaluate co-expression of lncRNAs and their putative target mRNAs in whole blood during natural Chikungunya infection in adolescent boys. Sequencing data from GSE99992 was uploaded to the Galaxy web server, where data was aligned with HISAT2, gene counts were estimated with HTSeq-count, and differential expression was run with DESeq2. After gene classification with Biomart, Pearson's correlation was applied to identify potential interactions between lncRNAs and mRNAs, which were later classified into cis and trans according to genomic location (FEELnc) and binding potential (LncTar), respectively. We identified 1,975 mRNAs and 793 lncRNAs that were differentially expressed between the acute and convalescent stages of infection in the blood. Of the co-expressed lncRNAs and mRNAs, 357 potentially interact in trans and 9 in cis; their target mRNAs enriched pathways related to immune response and viral infections. Out of 52 enriched KEGG pathways, the RIG-I like receptor signaling is enriched by the highest number of target mRNAs. This pathway starts with the recognition of viral pathogens, leading to innate immune response mediated by the production of IFN-I and inflammatory cytokines. Our findings indicate that alterations in lncRNA expression in adolescent boys, induced by acute Chikungunya infection, potentially modulate mRNAs that contribute to antiviral immune responses.

Preoperative Exchange Transfusion for Patients with SCD Systematic Review

Introduction: Sickle cell disease (SCD) is the most common genetic disease world wide with the highest prevalence in Africa, Middle east, and east Asia. Surgeries in patients with SCD are associated with a higher rate of perioperative complications, however, there is no solid recommendations in the guidelines to advice perioperative transfusion strategies in patients with SCD. This review investigated the current available evidence in the literature to provide a clearer guidance. Methods: PubMed and Embase electronic search identified 655 articles related to randomized controlled trials and observational studies about the safety of perioperative transfusion in SCD. After removing duplicates and non-relevant articles 39 articles were evaluated in full text for eligibility, of which 24 studies were found eligible for inclusion in qualitative analysis and 16 studies with 3486 participants eligible for inclusion in the quantitative analysis. Assessment of quality and risk of Bias was done using the Cochrane tool for RCTs and ROBBINS-I tool for observational non randomized studies. The safety outcomes of perioperative transfusion, including acute chest syndrome (ACS), painful crisis, neurological complications, fever, minor or major bleeding, thrombosis, intensive care unit (ICU) admission, and all-cause mortality were assessed in comparison to SCD patients undergoing surgeries with conservative transfusion strategy. The risk ratio (RR) with 95% confidence intervals (CI) were calculated for the desired outcomes, the data was combined in forest plots and meta-analysis using the random-effects model. Results: Of the 24 studies included, 13 studies had the control arm as no transfusion in comparison to perioperative transfusion, while the remaining studies had conservative strategy guided by hemoglobin level as a control. Sixteen studies reported ACS among SCD patients who received perioperative transfusion (n=1890) versus conservative transfusion strategy (n=1596) (RR= 0.91, 95% CI 0.58-1.41, I2= 58%) (Figure 1-A). Fifteen studies reported painful crisis with perioperative transfusion (n=1856) versus conservative transfusion strategy (n=1532) (RR= 0.94, 95% CI 0.53-1.68, I2= 63%) (Figure 1-B). Neurological complications associated with the perioperative transfusion in SCD (n=1590) compared to conservative transfusion strategy (n=1250) were reported in nine studies (RR= 1.38, 95% CI 0.54-3.57, I2= 0%). Seven studies reported fever as a post-operative complication following perioperative transfusion in SCD (n= 1243) versus conservative transfusion (n= 922) (RR= 1.36, 95% CI 0.94-1.97, I2= 51%). Six studies reported bleeding following perioperative transfusion in SCD (n= 847) versus conservative strategy (n= 477) (RR= 4.32, 95% CI 1.75-10.68, P=0.002, I2= 0%) (Figure 1-C). Three studies reported thrombotic events following the perioperative transfusion in SCD (n= 885) versus conservative transfusion (n= 404) (RR= 0.59, 95% CI 0.06-5.68, I2= 0%). ICU admissions were reported in three studies with perioperative transfusion (n= 53) versus conservative transfusion (n= 147) (RR= 4.99, 95% CI 0.98-25.48, I2= 0%). Mortality was reported in six studies with perioperative transfusion (n= 1320) versus conservative transfusion (n= 977) (RR= 0.67, 95% CI 0.05-8.75, I2= 71%). Conclusion: According to this systematic review and meta-analysis Perioperative transfusion in SCD resulted in significantly higher rate of bleeding compare to conservative strategies while the rates of acute chest syndrome, painful crisis, fever, neurological complications, thrombosis, ICU admission, and mortality remained similar between the two strategies.

West Nile Virus, an Underdiagnosed Cause of Acute Fever of Unknown Origin and Neurological Disease among Hospitalized Patients in South Africa.

West Nile virus (WNV), a mosquito-borne flavivirus, is endemic to South Africa. However, its contribution to acute febrile and neurological disease in hospitalized patients in South Africa is unknown. This study examined two patient cohorts for WNV using molecular testing and IgM serology with confirmation of serological results by viral neutralization tests (VNT) to address this knowledge gap. Univariate analysis was performed using collected demographic and clinical information to identify risk factors. In the first cohort, 219 cerebrospinal fluid (CSF) specimens from patients with acute neurological disease in Gauteng hospitals collected in January to June 2017 were tested for WNV. The study identified WNV in 8/219 (3.65%, 95.00% CI (1.59-7.07)) patients with unsolved neurological infections. The second cohort, from 2019 to 2021, included 441 patients enrolled between January and June with acute febrile or neurological disease from urban and rural sites in Gauteng and Mpumalanga provinces. West Nile virus was diagnosed in 40/441 (9.07%, 95.00% CI (6.73-12.12)) of patients, of which 29/40 (72.50%, 95.00% CI (56.11-85.40)) had neurological signs, including headaches, encephalitis, meningitis, and acute flaccid paralysis (AFP). Notably, most of the cases were identified in children although adolescents and senior adults had a significantly higher risk of testing WNV positive. This suggests a previously underestimated disease burden and that WNV might be underrecognized as a cause of febrile and neurological diseases in hospitalized patients in South Africa, especially in children. This emphasizes the importance of further research and awareness regarding arboviruses of public health concern.

Diagnostic challenges in tuberculous meningitis: a case report with negative genexpert result.

Tuberculous meningitis (TBM) is a severe form of tuberculosis affecting the meninges, primarily caused by Mycobacterium tuberculosis. Diagnosis of TBM poses numerous challenges due to its nonspecific clinical presentation and the limitations of diagnostic tests like GeneXpert. The authors report a case of a 22-year-old female from Eastern Nepal presenting with acute-onset fever, headache, vomiting, and neck pain. Cerebrospinal fluid (CSF) analysis showed lymphocytic pleocytosis, elevated protein, low glucose levels, and cobweb coagulum indicative of TBM. However, the GeneXpert test revealed negative results. In resource-limited settings like Nepal, where access to GeneXpert MTB/Rif is limited, CSF analysis and clinical algorithms play a crucial role in diagnosing TBM. Relying solely on GeneXpert results may lead to false negatives, so a high level of suspicion based on patient risk factors is essential. Prompt initiation of empirical antitubercular therapy is vital for a favorable outcome in TBM cases. Negative MTB PCR results from CSF can be misleading in diagnosis of tubercular meningitis. Therefore, comprehensive evaluations, including detailed patient history, physical examination, and CSF fluid analysis, are crucial in high tuberculous prevalence countries to ensure accurate and timely diagnosis.

Pancreatic Torsion Resulting in Acute Pancreatic Necrosis in a Young Dog.

We report a case of 7 mo old French bulldog who was referred to North Carolina State University Small Animal Emergency and Triage Services because of acute abdomen, regurgitation, lethargy, and fever. The patient had a history of pulmonic stenosis, which was corrected by balloon valvuloplasty 3 wk before presenting for the current complaint. The patient had nonspecific changes noted on blood work at his referring veterinarian. An abdominal ultrasound examination showed pathological changes that were supportive of a left-limb pancreatic torsion that was confirmed postmortem.

Universal primers for rift valley fever virus whole-genome sequencing

Rift Valley fever (RVF) is a mosquito-borne zoonotic disease causing acute hemorrhagic fever. Accurate identification of mutations and phylogenetic characterization of RVF virus (RVFV) require whole-genome analysis. Universal primers to amplify the entire RVFV genome from clinical samples with low copy numbers are currently unavailable. Thus, we aimed to develop universal primers applicable for all known RVFV strains. Based on the genome sequences available from public databases, we designed eight pairs of universal PCR primers covering the entire RVFV genome. To evaluate primer universality, four RVFV strains (ZH548, Kenya 56 (IB8), BIME-01, and Lunyo), encompassing viral phylogenetic diversity, were chosen. The nucleic acids of the test strains were chemically synthesized or extracted via cell culture. These RNAs were evaluated using the PCR primers, resulting in successful amplification with expected sizes (0.8–1.7 kb). Sequencing confirmed that the products covered the entire genome of the RVFV strains tested. Primer specificity was confirmed via in silico comparison against all non-redundant nucleotide sequences using the BLASTn alignment tool in the NCBI database. To assess the clinical applicability of the primers, mock clinical specimens containing human and RVFV RNAs were prepared. The entire RVFV genome was successfully amplified and sequenced at a viral concentration of 108 copies/mL. Given the universality, specificity, and clinical applicability of the primers, we anticipate that the RVFV universal primer pairs and the developed method will aid in RVFV phylogenomics and mutation detection.