Undifferentiated Fever Research Articles

Dengue haemorrhagic fever complicated with spontaneous psoas haematoma requiring blood products

Dengue is a mosquito borne febrile viral disease .Sri Lanka is an endemic area where the incidence was peak in 2017 and slightly decreased in 2020 (28.7%) because of preventive measures. Presentation can be asymptomatic or cause a spectrum of symptoms including undifferentiated viral fever, dengue fever, dengue haemorrhagic fever with or without shock and expanded dengue syndrome. We describe here a case of 48-years old man who presented to the emergency unit with three-day history of acute fever and prodromal features, subsequently diagnosed to have dengue haemorrhagic fever and it was complicated with psoas haemorrhage. Only limited cases were reported about spontaneous psoas muscle haemorrhage in dengue haemorrhagic fever in adult population.

Clinico-pathological profile of scrub typhus in children: a cross sectional study from Eastern India

Background: Scrub typhus is a vector-borne zoonosis, endemic in Asia and it may present as an undifferentiated fever or with multisystem involvement. This study was carried out to understand the varied presentation of scrub typhus in children and the response to treatment in a tertiary care hospital in Eastern India.Methods: All children between 1 month and 12 year of age admitted with fever for more than 5 days and positive IgM ELISA for scrub typhus were included in the study and their course in hospital was documented. They were randomly divided into 2 groups of 41 patients each, into doxycycline and azithromycin group and were then evaluated for therapeutic response.Results: In this study, pallor (89%) was the commonest finding followed by hepato-splenomegaly (73.2%), pneumonia (65.9%) and rash was found in 43.9%. Eschar was found in 32.9% whereas serious complications like shock and meningoencephalitis was found in 9.8%. Pericardial effusion was detected in 23.2% cases, coronary artery dilatation in 11% cases and both effusion as well as coronary artery dilation was found in 2.4%. In azithromycin group, 73.2% patients had drug response whereas in doxycycline group, 92.7% patients had drug response and this association was statistically significant (p=0.0188). Two patients who presented late with shock expired but all others responded to treatment and were doing well on follow up.Conclusions: Scrub typhus may present with multisystem involvement including cardiac manifestation which needs to be identified early by echocardiography. Doxyclycine is still the best modality of treatment and if used early, outcome is favourable.

Characterization of a Dengue Virus Serotype 1 Isolated from a Patient in Ciudad Juarez, Mexico.

Dengue (DEN) is the most important human arboviral disease worldwide. Sporadic outbreaks of DEN have been reported since 1980 in urban communities located along the border in southeast Texas and northern Mexico. Other than the Rio Grande Valley region of TX, autochthonous transmission of DENV has not been reported from any other US border communities. As part of a surveillance program for arthropod-borne viruses in Ciudad Juarez, Mexico, during November 2015, a blood sample was obtained from a female patient who experienced an undifferentiated fever and arthralgia. The plasma of the sample was tested for virus in Vero-76 and C6/36 cells. DENV serotype 1 (DENV-1) was isolated in the C6/36 cells, and nucleotide sequencing of the envelope gene and full genome grouped the DENV-1 isolate in the Central America clade. The patient had not traveled outside of Ciudad Juarez, Mexico, thus suggesting DENV-1 infection was acquired in this community.

Optimizing the microscopic agglutination test (MAT) panel for the diagnosis of Leptospirosis in a low resource, hyper-endemic setting with varied microgeographic variation in reactivity.

The microscopic agglutination test (MAT) is the standard serological reference test for the diagnosis of leptospirosis, despite being a technically demanding and laborious procedure. The use of a locally optimised MAT panel is considered essential for proper performance and interpretation of results. This paper describes the procedure of selecting such an optimised panel for Sri Lanka, a country hyper-endemic for leptospirosis. MAT was performed using 24 strains on 1132 serum samples collected from patients presenting with acute undifferentiated fever. Of 24 strains, 15 were selected as the optimised panel, while only 11% of serum samples showed positivity. A geographical variation in predominantly reactive serovars was observed, whereas reactivity was low with the saprophytic strain Patoc. Testing with paired sera yielded a higher sensitivity but provided only a retrospective diagnosis. Serological tests based on ELISA with complementary molecular diagnosis using PCR are a feasible and robust alternative approach to diagnose leptospirosis in countries having a higher burden of the disease.

Hubungan Status Gizi, Umur, Jenis Kelamin dengan Derajat Infeksi Dengue pada Anak di RSUD Abdul Wahab Sjahranie Samarinda

Dengue virus infection can manifest from mild to severe, which are undifferentiated fever, dengue hemorrhagic fever (DD), dengue hemorrhagic fever (DHF), and dengue shock syndrome (DSS), respectively. Mild and severe dengue infection is difficult to distinguish early in the course of the disease, and the clinical course is also difficult to "predict". Therefore, indicators were needed to predict the degree of dengue virus infection, thus appropriate treatment can be given. The study was aimed to determine the association of nutritional status, age, and sex with the degree of dengue infection in children. This study was an analytic observational study with a cross-sectional design. The samples were pediatric patients (0-18 years), who have been diagnosed with dengue virus infection and were hospitalized at the Abdul Wahab Sjahranie Hospital Samarinda in 2019. Purposive sampling technique was used to appointed 88 patients. The data obtained from the medical records. The bivariate association was statistically analyzed with chi-square test. The result showed a significant association between sex (p = 0.041) with the degree of dengue infection in children. Meanwhile nutritional status (p = 0.127) and age (p = 0.077) had no significant association with the degree of dengue infection in children. In conclusion, sex might serve as a predictor of the degree of dengue infection in children, in which male is more susceptible to worse manifestations.

Mortality and morbidity of children admitted with febrile thrombocytopenia in a tertiary care hospital

Background: This study is conducted at Mahatma Gandhi memorial hospital, Trichy gains significance as there hasn‘t been any of its kind prior to this among children and in this geographical area. Aim and objectives of the study were to study the clinical profile of children presenting with febrile thrombocytopenia and possible etiology. The study correlates clinical features with the laboratory parameters and assessing the complications associated with fever and thrombocytopenia.Methods: Prospective, descriptive study consist of 200 children aged 1 months to 12 years admitted with fever and thrombocytopenia as inpatients in the paediatric wards at Mahatma Gandhi memorial government hospital, Trichy during July 2017 to June 2018. Inclusion criteria included children aged 1 month to 12 years admitted in paediatric wards of MGM GH, Trichy, exclusion criteria excluded neonates <1 month and children >12 years, patients presenting with thrombocytopenia without fever, ITP, platelet dysfunction disorders, malignancy, patients on chemotherapy and immunosuppressive agents and on drugs causing thrombocytopenia. Results: Dengue was the most common cause of febrile thrombocytopenia in our region accounting for 56% of cases, this is followed by enteric fever in 17%, undifferentiated fever in 16.5%, sepsis in 6.5%, scrub typhus in 3.5% and malaria in 0.5%. 5% of children with febrile thrombocytopenia were given platelet transfusion. 95% (n=190) of the children with febrile thrombocytopenia improved and were discharged. 1% (n=2) left against medical advice. The mortality rate in the study is 4% (n=8).Conclusions: The risk of bleeding increases as the platelet count decreases. The mortality is not related to the severity of thrombocytopenia.

Efficacy of Wolbachia-Infected Mosquito Deployments for the Control of Dengue

BackgroundAedes aegypti mosquitoes infected with the wMel strain of Wolbachia pipientis are less susceptible than wild-type A. aegypti to dengue virus infection.MethodsWe conducted a cluster-randomized trial involving releases of wMel-infected A. aegypti mosquitoes for the control of dengue in Yogyakarta, Indonesia. We randomly assigned 12 geographic clusters to receive deployments of wMel-infected A. aegypti (intervention clusters) and 12 clusters to receive no deployments (control clusters). All clusters practiced local mosquito-control measures as usual. A test-negative design was used to assess the efficacy of the intervention. Patients with acute undifferentiated fever who presented to local primary care clinics and were 3 to 45 years of age were recruited. Laboratory testing was used to identify participants who had virologically confirmed dengue (VCD) and those who were test-negative controls. The primary end point was symptomatic VCD of any severity caused by any dengue virus serotype.ResultsAfter successful introgression of wMel into the intervention clusters, 8144 participants were enrolled; 3721 lived in intervention clusters, and 4423 lived in control clusters. In the intention-to-treat analysis, VCD occurred in 67 of 2905 participants (2.3%) in the intervention clusters and in 318 of 3401 (9.4%) in the control clusters (aggregate odds ratio for VCD, 0.23; 95% confidence interval [CI], 0.15 to 0.35; P=0.004). The protective efficacy of the intervention was 77.1% (95% CI, 65.3 to 84.9) and was similar against the four dengue virus serotypes. The incidence of hospitalization for VCD was lower among participants who lived in intervention clusters (13 of 2905 participants [0.4%]) than among those who lived in control clusters (102 of 3401 [3.0%]) (protective efficacy, 86.2%; 95% CI, 66.2 to 94.3).ConclusionsIntrogression of wMel into A. aegypti populations was effective in reducing the incidence of symptomatic dengue and resulted in fewer hospitalizations for dengue among the participants. (Funded by the Tahija Foundation and others; AWED ClinicalTrials.gov number, NCT03055585; Indonesia Registry number, INA-A7OB6TW.)

Syndrome of Undifferentiated Recurrent Fever (SURF): An Emerging Group of Autoinflammatory Recurrent Fevers.

Syndrome of undifferentiated recurrent fever (SURF) is a heterogeneous group of autoinflammatory diseases (AID) characterized by self-limiting episodes of systemic inflammation without a confirmed molecular diagnosis, not fulfilling the criteria for periodic fever, aphthous stomatitis, pharyngitis and adenopathy (PFAPA) syndrome. In this review, we focused on the studies enrolling patients suspected of AID and genotyped them with next generation sequencing technologies in order to describe the clinical manifestations and treatment response of published cohorts of patients with SURF. We also propose a preliminary set of indications for the clinical suspicion of SURF that could help in everyday clinical practice.

Etiological Trends and Epidemiological Profile of Tropical Fever in Children Presenting with Acute Undifferentiated Fever at a Tertiary Care Centre in North India


 
 
 
 Introduction: The objective of this study was to determine the etiology of acute undifferentiated fevers (AUF) in hospitalised children with in a tertiary care centre in North India. The various causes of acute undifferentiated fevers included dengue, malaria, scrub typhus, enteric fever, leptospirosis and Chikungunya. The clinical spectrum and therapeutic outcome of these cases was also studied.
 Methods: This retrospective study was conducted over a period of 6 months from June 2019 to December 2019. The clinical information of 126 children who tested positive for any of the causes of AUF namely dengue, malaria, scrub typhus, enteric fever, chikungunya and leptospirosis was obtained from the Paediatrics Department. The information was recorded in a predesigned proforma. Various tests performed for the diagnosis of these illnesses were noted. They included dengue NS1 antigen ELISA and IgM ELISA, peripheral blood smear (PBS) for malarial parasite and rapid malarial antigen detection test (RMAT), scrub typhus IgM ELISA, leptospira IgM ELISA, and Chikungunya IgM ELISA.
 Results: The diagnosis of AUF were dengue (55.5%; 70/126), malaria (19%; 24/126) and scrub typhus (19%; 24/126), enteric fever (4.7%;6/126) and Chikungunya (1.5%; 2/126). The most common presenting symptom was fever or pyrexia followed by myalgia, generalised aches and pains in the body and vomiting. Commonly observed complications included thrombocytopenia, hepatitis and shock.
 Conclusions: Dengue, malaria and scrub typhus are the major causes of AUF in the hospitalised children with dengue being the most prevalent infection. The study further emphasises the need to develop a systematic approach to the diagnosis of AUFs. This should be using a combination of clinical, epidemiological and laboratory parameters, which will be very useful for developing a relevant action plan for treatment and prevention of such fevers in any hospital setup.
 
 
 

Le sindromi autoinfiammatorie: quando non è solo PFAPA

PFAPA (Periodic Fever, Aphthous Stomatitis, Pharyngitis and Adenitis) is the most common self-inflammatory disorder in children. The diagnosis of PFAPA is easy, based on Thomas criteria, and the prognosis is good. Differential diagnosis with hereditary periodic fever syndromes (Familial Mediterranean Fever, Mevalonate Kinase Deficiency, TRAPS and CAPS) should be considered only in the presence of red flags such as early onset, severe abdominal complaints, arthritis and severe rashes. Some patients may present distinct clinical entities with periodic fevers that neither meet PFAPA criteria nor hereditary periodic fever syndromes genotypes. Subjects with these “Undifferentiated Periodic Fever” may respond to glucocorticoids or colchicines or to anakinra in the most severe cases and still have an undetermined prognosis.

Comparative Study of Chikungunya Only and Chikungunya-Scrub Typhus Coinfection in Children: Findings from a Hospital-Based Observational Study from Central Nepal.

Objectives Chikungunya and scrub typhus infection are important causes of undifferentiated fever in tropical zones. The clinical manifestations in both conditions are nonspecific and often overlap. This study compares the clinical manifestations and the outcome of chikungunya with chikungunya-scrub typhus coinfection in children. Methods A hospital-based observational study was conducted in children below 15 years of age over 16-month duration in 2017-2018. Chikungunya was diagnosed by IgM ELISA. All positive chikungunya cases were subjected to scrub typhus testing, dengue testing, leptospira testing, and malaria testing. Clinical manifestations and outcomes of all patients were recorded. Results Out of the 382 admitted cases with fever, 11% (n = 42) were diagnosed with chikungunya, and the majority (n = 30, 71.4%) were male. Among the 42 chikungunya cases, 17 (40.5%) tested positive for scrub typhus and one positive for falciparum malaria. Out of a total of 42 chikungunya cases, myalgia, nausea/vomiting, headache, abdominal pain, lymphadenopathy, hepatomegaly, splenomegaly, and edema were 81%, 73.8%, 66.7%, 64.3%, 59.5%, 52.4%, 40.5%, and 38.1%, respectively. Besides, altered sensorium (31%), jaundice (26.2%), dry cough (21.4%), shortness of breath (19%), and seizures (16.7%) were other clinical manifestations present in this group of children. Patients with chikungunya-scrub typhus coinfection reported headaches, pain in the abdomen, dry cough, shortness of breath, seizures, and splenomegaly, significantly more (p value < 0.05) compared to those with chikungunya only. Thirteen (31%) children developed shock, five in the chikungunya group and eight in the chikungunya-scrub typhus coinfection group. Six children in the coinfection group received inotrope. Among the chikungunya-only cases, 22 recovered and one died, whereas in the chikungunya-scrub typhus coinfection group, fourteen recovered and three died. Conclusions Both the chikungunya and scrub typhus coinfection groups shared many similar clinical manifestations. In children, coinfection with scrub typhus often leads to modification of the clinical profile, complications, and chikungunya outcome.

A study of various biochemical parameters in patients with scrub typhus

Background: Scrub typhus is an infectious disease spreads by a bacterium called Orientiatsutsugamushi. The WHO has dubbed scrub typhus one of the world’s most under-diagnosed/underreported diseases. It’s so also in Rajasthan (India). Since antigen detection tests have low sensitivity/specificity and require biopsy specimens, in the clinical setting, serological assays are the mainstay of diagnosis. Objectives: To study various biochemical parameters in Scrub typhus positive patients and to compare of the same with the control group (negative suspects) to elicit some specific diagnostic parameters through data mining. Materials and Methods: This retrospective observational cohort study included Fever of unknown origin (FUO) cases classified into patients with (group 1; n = 35) or without (group 2; n= 65) scrub typhus. Various biochemical parameters were correlated and compared through data mining and analyzed on Apache Hive. We used Welch test to estimate normality of data, Fligner Killeen test to estimate the homogeneity of variance and Mann Whitney U test for comparing the two data sets. Results: Both the groups were comparable with respect to age and sex. Platelet count, SGOT, SGPT and random blood sugar were significantly different in both the groups. (p 0.05) Conclusions: Thrombocytopenia and deranged SGOT-SGPT were found to be prime clinico-pathological indicator of the scrub typhus. Keywords: Scrub typhus, Data mining, Acute undifferentiated fever, Thrombocytopenia.

Incidence of human granulocytic anaplasmosis in returning travellers with fever.

Although tick-borne pathogens have been reported as an important cause of imported fever, the incidence of Anaplasma phagocytophilum, the causative agent of human granulocytic anaplasmosis (HGA), in travellers is unknown. We conducted a prospective cohort study to investigate the aetiologies of fever in returning travellers (November 2017-July 2019). Polymerase chain reaction for msp2 gene amplification and indirect immunofluorescence assay for A. phagocitophilum were performed in all returning travellers with undifferentiated non-malarial fever. Among 141 travellers included, 8 patients were diagnosed with probable or confirmed HGA. The overall incidence rate of HGA was 19.9 cases/1000 person-week of travel. The main destination of travel was Asia, accounting for 62.5% patients with HGA. Co-infections were found in 37.5% of patients with HGA. Diagnosis of HGA and empirical treatment with doxycycline should be considered in travellers with fever.

Clinico – Etiological profile of Acute Undifferentiated fever in children 6 months - 15 years

Introduction: Acute febrile illness (AFI) is defined as a patient with fever of 38?C or higher at presentation or history of fever that persisted for 2–14 days with no localizing source. Fever is the main clinical symptom of various tropical infectious diseases. Materials and Methods: Retrospective observational examination was directed after endorsement from the Institutional Ethics Committee in Paediatric division, Apollo General Hospital, AIMSR, Jubilee hills from January 2016 till December 2019. Inclusion criteria: All the patients who were conceded in the ward or emergency unit complications of intense febrile infections, patients a half year to 15 years old were taken for the investigation. Exclusion criteria: Patients with associated infections when the complications cannot be attributed to febrile illness or patients with haematological malignancies, autoimmune disorders, and those on immunosuppressant were excluded from the study. Results: In present investigation, an aggregate of 290 patients with intense identical fever were assessed out of these 157 (63%) were male and 133 (36.6%) were female. In this investigation typhoid fever was the most well-known reason for undifferentiated fever (33.7%) trailed by malaria (25.5%), dengue fever (19.6%), urinary tract disease (8.2%), Acute gastroenteritis (5.5%), Pneumonia (3.1%), Bronchiolitis (2.4%), Hepatitis (1.0%) and Pharyngotonsillitis (0.6%%). Conclusions: It is important to know the aetiology and clinical pattern of acute undifferentiated fever for their proper management and it will help to prevent morbidity and mortality. Keywords: Acute Undifferentiated fever, Acute febrile illness, Typhoid fever, Malaria, Dengue fever.

Value of C-reactive protein in differentiating viral from bacterial aetiologies in patients with non-malaria acute undifferentiated fever in tropical areas: a meta-analysis and individual patient data study.

C-reactive protein (CRP) is used to discriminate common bacterial and viral infections, but its utility in tropical settings remains unknown. We performed a meta-analysis of studies performed in Asia and Africa. First, mean CRP levels for specific tropical infections were calculated. Thereafter, individual patient data (IPD) from patients with non-malarial undifferentiated fever (NMUF) who were tested for viral and bacterial pathogens were analysed, calculating separate cut-off values and their performance in classifying viral or bacterial disease. Mean CRP levels of 7307 patients from 13 countries were dengue 12.0mg/l (standard error [SE] 2.7), chikungunya 41.0mg/l (SE 19.5), influenza 15.9mg/l (SE 6.3), Crimean-Congo haemorrhagic fever 9.7mg/l (SE 4.7), Salmonella 61.9mg/l (SE 5.4), Rickettsia 61.3mg/l (SE 8.8), Coxiella burnetii 98.7mg/l (SE 44.0) and Leptospira infections 113.8mg/l (SE 23.1). IPD analysis of 1059 NMUF patients ≥5y of age showed CRP <10mg/l had 52% sensitivity (95% confidence interval [CI] 48 to 56) and 95% specificity (95% CI 93 to 97) to detect viral infections. CRP >40mg/l had 74% sensitivity (95% CI 70 to 77) and 84% specificity (95% CI 81 to 87) to identify bacterial infections. Compared with routine care, the relative risk for incorrect classification was 0.64 (95% CI 0.55 to 0.75) and the number needed to test for one extra correctly classified case was 8 (95% CI 6 to 12). A two cut-off value CRP test may help clinicians to discriminate viral and bacterial aetiologies of NMUF in tropical areas.

Undifferentiated recurrent fevers in pediatrics are clinically distinct from PFAPA syndrome but retain an IL-1 signature

Autoinflammatory disorders of the innate immune system present with recurrent episodes of inflammation often beginning in early childhood. While there are now more than 30 genetically-defined hereditary fever disorders, many patients lack a clear diagnosis. Many pediatric patients are often grouped with patients with periodic fever, aphthous stomatitis, pharyngitis, and adenitis (PFAPA) syndrome despite failing to meet diagnostic criteria. Here, we categorize these patients as syndrome of undifferentiated recurrent fever (SURF), and identify the unique features which distinguish them from the PFAPA syndrome. SURF patients were more likely to report gastrointestinal symptoms of nausea, vomiting and abdominal pain, and experienced inconsistent responses to on-demand steroid therapy compared to PFAPA patients. For this previously undefined cohort, an optimal course of therapy remains uncertain, with medical and surgical therapies largely driven by parental preference. A subset of patients with SURF underwent tonsillectomy with complete resolution. Flow cytometric evaluation demonstrates leukocytic populations distinct from PFAPA patients, with reduced CD3+ T cell numbers. SURF patient tonsils were predominantly characterized by an IL-1 signature compared to PFAPA, even during the afebrile period. Peripheral blood signatures were similar between groups suggesting that PFAPA and SURF patient tonsils have localized, persistent inflammation, without clinical symptoms. These data suggest that SURF is a heterogenous syndrome on the autoinflammatory disease spectrum.

Antibiotic Response to Pediatric Scrub Typhus in South India: Is Clinical Failure to Azithromycin to be Worried?

Scrub typhus is typically associated with a rapid defervescence and clinical improvement within 48 h of initiation of appropriate antibiotics. But increasing reports of resistance to anti-rickettsial medications in scrub typhus are being reported in the literature. This is a retrospective observational study of children up to the age of 14 years admitted between July 2017 and March 2020, to a private medical college hospital in southern part of India. The aim of this study was to compare the clinical response to antibiotic therapy with doxycycline and azithromycin in pediatric scrub typhus infection. One hundred thirty-eight children with scrub typhus infection were included for analysis. The median fever control time (h) was 12 (IQR = 6-29) and 24 (IQR = 10-52) with doxycycline and azithromycin respectively (p < 0.001*). Rapid fever control within 48 h was observed in 92% with doxycycline and in 74% with azithromycin (p < 0.001*). The clinical failure rate (defined by the necessity to change the antibiotics due to: (i) worsening of symptoms and signs of scrub typhus despite 48 h of antibiotics or (ii) persistence of fever and other symptoms of scrub typhus beyond 72 h), was significantly less with doxycycline (1%) compared with azithromycin (9.6%). There has been a significant delayed clinical response to azithromycin in the treatment of scrub typhus in India, when compared to doxycycline. Hence it is preferable to use doxycycline as the first line of antibiotic for undifferentiated fever in scrub typhus endemic areas. This retrospective study aims to compare the clinical response to doxycycline or azithromycin in the treatment of scrub typhus infection in children. The median fever control time, clinical failure rate and the proportion of children with rapid defervescence of fever within 48 h were significantly superior with doxycycline as compared to azithromycin. The findings of this study and those of similar studies in India represent a spectrum of delayed clinical response of Orientia tsutsugamushi to azithromycin as compared to doxycycline in this region.

Discovery and Validation of a 3-Gene Transcriptional Signature to Distinguish COVID-19 and Other Viral Infections from Bacterial Sepsis in Adults; A Case-Control then Observational Cohort Study

Background: Emergency hospital admissions for infection often lack microbiological diagnostic certainty. Novel approaches to discriminate likelihood of bacterial and viral infections are required to support antimicrobial prescribing decisions and infection control practice. We sought to derive and validate a blood transcriptional signature to differentiate bacterial infections from viral infections including COVID-19.Methods: Blood RNA sequencing was performed on a discovery cohort of adults attending the Emergency Department with confirmed bacteraemia or viral infection. Differentially expressed host genes were subjected to feature selection to derive the most parsimonious discriminating signature. RT-qPCR validation of the signature was then performed in a prospective cohort of patients presenting with undifferentiated fever and a second case-control cohort of patients with bacteraemia or COVID-19.Findings: A 3-gene transcript signature was derived from the discovery cohort of 56 definite bacterial and 27 viral infection cases. In the validation cohort, the signature differentiated bacterial and viral infections with an area under receiver operating characteristic curve (AUC) of 0.976 (95% CI: 0.919-1.000), sensitivity 97.3% and specificity of 100%. The AUC for C-reactive protein and leucocyte count was 0.833 (95% CI: 0.694-0.944) and 0.938 (95% CI: 0.840-0.986) respectively. In the second validation analysis the signature discriminated 34 SARS-CoV-2 positive COVID-19 from 35 bacterial infections with AUC of 0.953 (95% CI: 0.893-0.992), sensitivity 88.6% and specificity of 94.1%.Interpretation: This novel 3-gene signature discriminates viral infections including COVID-19 from bacterial sepsis in adults, outperforming both leucocyte count and CRP, thus potentially providing significant clinical utility in managing acute presentations with infection.Funding Statement: Work in this study was funded by the NIHR Imperial Biomedical Research Centre, the Medical Research Council, the Wellcome Trust and the European Union FP7 (EC-GA 279185) (EUCLIDS).Declaration of Interests: None of the authors have any relevant interest to declare. Ethics Approval Statement: Ethical approval was obtained to take deferred consent from patients from whom an RNA specimen had been collected (or from next of kin or nominated consultee) (REC references 14/SC/0008 and 19/SC/0116).

Steroidal saponins from the roots of Solanum sisymbriifolium Lam. (Solanaceae) have inhibitory activity against dengue virus and yellow fever virus.

Dengue is the most important arthropod-borne viral disease worldwide. Infection with any of the four dengue virus (DENV) serotypes can be asymptomatic or lead to disease with clinical symptoms ranging from undifferentiated and self-limiting fever to severe dengue disease, which can be fatal in some cases. Currently, no specific antiviral compound is available for treating DENV. The aim of this study was to identify compounds in plants from Paraguayan folk medicine with inhibitory effects against DENV. We found high virucidal activity (50% maximal effective concentration (EC50) value of 24.97 µg/mL) against DENV-2 in the ethanolic extract of the roots of Solanum sisymbriifolium Lam. (Solanaceae) without an evident cytotoxic effect on Vero E6 cells. Three saponins isolated from the root extract showed virucidal effects (EC50 values ranging from 24.9 to 35.1 µg/mL) against DENV-2. Additionally, the saponins showed inhibitory activity against yellow fever virus (EC50 values ranging from 126 to 302.6 µg/mL), the prototype virus of the Flavivirus genus, suggesting that they may also be effective against other members of this genus. Consequently, these saponins may be lead compounds for the development of antiviral agents.

Rickettsial Infections among the Undifferentiated Febrile Patients Attending a Tertiary Care Teaching Hospital of Northern India: A Longitudinal Study.

BackgroundAcute undifferentiated febrile illness (AUFI) is one of the most daunting challenges a physician faces in such settings. Among AUFI, rickettsial infections are most common and related infections (such as anaplasmosis, ehrlichiosis, and Q fever) which are caused by an unusual type of bacteria that can live only inside the cells of another organism. The present study was therefore planned with an objective to estimate the prevalence of rickettsial infection among patients of undifferentiated fever and to determine any association of socio-demographic characteristics with rickettsial disease.Materials and MethodsPatients presenting with febrile illness and admitted or attending out-patient department of Sher-i-Kashmir Institute of Medical Sciences, Srinagar was approached and recruited in the study. Weil Felix Assay, enzyme-linked immunosorbent assay and indirect immunofluorescence assay were done to detect the anti-rickettsial antibodies. Serological evidence of a fourfold increase in IgG-specific antibody titer reactive with spotted fever group rickettsial antigen by indirect immunofluorescence antibody assays between paired serum specimens was considered a confirmatory diagnosis for the rickettsial disease.ResultsMost of the patients were males 61.6%, and most 46.2% were in the age group of 20 -39 years. Most of the patients, 80.8% belonged to rural areas, and 48% belonged to the upper middle (II) class of the socio-economic class according to modified Kuppuswamy scale. Of the studied participants, a majority, 47.0%, were determined undiagnosed, while 15.4% studied participants were diagnosed to have a rickettsial disease. In patients positive for typhus group, 67.8% were IgM positive, 28.5% were IgG positive, and only 3% were positive for IgM and IgG. In patients positive for Scrub Typhus Group, 32.7% were positive for IgM, and 62.0% were positive for IgG, and only 5.0% were positive for both IgM and IgG. In patients positive for spotted fever group, 36.1% were positive for IgM, and 58.5% were positive for IgG, and only 5.5% were positive for both IgM and IgG. The prevalence of rickettsial disease was found to be 11.3%.ConclusionRickettsial diseases, typhoid and brucellosis, were the most prevalent diseased diagnosed among patients reporting to hospitals with undifferentiated febrile illness. Clinicians must consider rickettsial diseases as one of the differential diagnosis while treating patients with fever.