Acute Undifferentiated Fever Research Articles

Identifying the Probable Etiology of Acute Undifferentiated Fever through Inflammatory Markers.

Acute undifferentiated fever (AUF) is defined as any febrile illness with a duration of ≤14 days without evidence of localized infection. Most outpatient services and a significant inpatient load in India are contributed by AUF. COVID-19 has recently added to the existing list of common etiologies of AUF. While the rapid diagnostic test (RDT) kits, which are widely used for the detection of common etiologies of AUF, are unreliable, the rise of various inflammatory markers may help identify the probable etiology. This not only results in better diagnosis but also prepares the physician for close monitoring and pooling of resources. To identify the probable etiology of AUF through inflammatory markers. To understand the clinical and biochemical parameters as possible predictors of adverse outcomes in AUF. This was a prospective observational study carried out in the Department of Medicine in a tertiary care hospital. The total duration of the study was 1 year. A total of 400 AUF patients [both outpatient department (OPD) and inpatient department (IPD)] fulfilling the eligibility criteria were taken up for the study after consent. Various inflammatory markers, namely erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), D-dimer, ferritin, and procalcitonin levels along with basic blood and biochemical tests were measured in all qualifying patients at their first visit. The level of rise of all the measured inflammatory markers was analyzed for clues toward identifying the etiology. Also, the possible predictors of adverse outcomes, as defined in the study, were analyzed. Outcome variables are described as mean ± standard deviation. All statistical calculations were done using computer programs Microsoft Excel 2007 (Microsoft Corporation, New York, United States of America) and SPSS (Statistical Product and Service Solutions; SPSS Inc., United States of America) version 21. The common etiologies in our study contributing to AUF were dengue (31.5%), COVID-19 (18.5%), enteric fever (12.7%), scrub typhus (9.0%), and malaria (6.0%). In 76 cases (19%), the fever was undiagnosed. Enteric fever had highly elevated CRP (>30 mg/L) and moderately elevated D-dimer, ferritin, and procalcitonin. Both nonsevere dengue and COVID-19 had highly elevated D-dimer (>750 ng/mL), but in nonsevere dengue, CRP, ferritin, and procalcitonin were only mildly elevated, whereas in COVID-19, CRP and ferritin were moderately elevated with mildly elevated procalcitonin. Scrub typhus had highly elevated CRP and ferritin [more than four times the upper limit of normal (ULN)], but D-dimer and procalcitonin were only mildly elevated. The mean serum procalcitonin level in enteric fever is significantly higher than the other etiologies of AUF. Our study was correctly able to identify 90.8% of nonsevere dengue, 87.8% of typhoid, 83.6% of COVID-19, and 91.4% of scrub typhus patients based on the inflammatory markers level. Obesity, diabetes (both types 1 and 2), hypertension, coronary artery disease (CAD), malignancy, chronic kidney disease (CKD), and chronic lung disease were significantly associated with adverse outcomes. A significant delay in visiting the hospital after the onset of fever was found in all etiologies of AUF, which had adverse outcomes. Our study is one of the few studies comparing the rise in the level of various inflammatory markers among the common etiologies of AUF. The novelty of the study is that it aids in identifying the probable etiology of AUF with good confidence through the levels of inflammatory markers. Also, our study highlights the high-risk factors associated with adverse outcomes in AUF.

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.

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.

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

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.

Review on Scrub Typhus: An Important Etiology of Acute Undifferentiated Fever Illness.

One of India's predominant public health issues is acute undifferentiated fever illness (AUFI), a typical response to an infectious agent. Diagnosisbecomes challenging when the disease has been reported with fever as the primary symptom. Among thecases presenting at a tertiary care hospitalin central India, 88% had an acute undifferentiated fever, the most common being dengue infection. In India, rural communities are at more risk from AUFI than cities. Most of those in danger are those who reside in remote areas, and one of the most significant risksis for those who reside close toforests. AUFI is a complex condition for physicians to deal with and is one of the most frequent clinical conditions for which empirical treatment is required. Nowadays, AUFI can be managed by a syndromic approach with the judicial use of antibiotics. Symptoms of AUFI, along with myalgia, headache, and anorexia, can be caused by various illnesses. Patients are recommended to undertake a battery of investigations, which may delay the therapy and increase expenses because many diseases may present with the same symptoms. In the developed world, viral illness is the primary cause of AUFI. However, in developing countries like India, it can also be brought on by potentially curable but life-threatening conditions such as malaria, leptospirosis, hantavirus infection, and Japanese encephalitis. Lack of knowledge of the locally prevalent illnesses, which might be the causeof AUFI, and lack of preliminary screening and diagnostics at the point of care to identify the etiologies make it difficult to control these generally curable causes of the burden of AUFI, especially in tropical and subtropical countries. A deeper understanding of AUFI is required to develop better diagnostics and cures for various etiologies, especially scrub typhus.

Clinical and Etiological Profile of Acute Undifferentiated Fever With Thrombocytopenia in an Emergency Department.

Acute undifferentiated fever with thrombocytopenia is a common and challenging clinical presentation encountered in the emergency departments of tertiary care centers, particularly in tropical regions, often requiring prompt evaluation and management. The study aimed to explore the clinical and etiological profile of acute undifferentiated fever with thrombocytopenia in the Emergency Department of Indira Gandhi Institute of Medical Sciences, Patna. It investigates factors associated with patient outcomes and compares platelet transfusion requirements among different etiological groups. In this cross-sectional observational study, 350 patients with acute undifferentiated fever with thrombocytopenia were analyzed for one year from October '21 to September '22. Pre-existing chronic infectious diseases, liver cirrhosis, and autoimmune conditions were excluded. Thrombocytopenia was observed in all patients, with 65% having platelet counts below 50,000/µL. Associations were found between the degree of thrombocytopenia and organ dysfunction, shock, and third space loss. Logistic regression analysis identified thrombocytopenia, organ dysfunction, and platelet transfusion requirement as significant predictors of the overall outcome. Etiological group comparisons revealed higher platelet transfusion requirements in the bacterial group. Prompt recognition and management of thrombocytopenia in acute undifferentiated fever are vital. Thrombocytopenia, along with organ dysfunction and shock, significantly influence patient outcomes. Tailored interventions based on etiological factors are crucial. Further research should focus on specific viral aetiologies in acute undifferentiated fever with thrombocytopenia.

Once Forgotten Now Re-emerging: Scrub Typhus Infection in Pediatric Patients From North West India.

Background Scrub typhus is an important cause of acute febrile illness in children. It is one of the re-emerging infections in the Asia Pacific region. It is caused by the gram-negative bacteriaOrientia tsutsugamushiand is spread by the bite of trombiculid mites. The initial symptomatology is nonspecific with fever, headache, vomiting, etc. The presence of eschar is said to be pathognomic. It is a systemic illness, and vasculitis is the basic pathogenic mechanism. Materials and methods A retrospective observational study was conducted in two medical colleges and associated hospitals of western Uttar Pradesh (UP) and Rajasthan, India. Case files of 21 confirmed cases of scrub typhus admitted from April 2021 to October 2022 were reviewed. Scrub typhus was suspected in children with acute undifferentiated fever, and suggestive signs and symptoms were confirmed serologically with IgM enzyme-linked immunoassay (ELISA). Demographic and clinical details were noted. Results During the study period, a total of 335 cases of acute undifferentiated fever were seen, and 6.2% of them were diagnosed as having scrub typhus infection on detailed investigation. The most common symptom was fever in 100% of them, vomiting in 57.1%, abdomen pain in 42.8%, and diarrhea in 19%. Maculopapular, erythematous rash was present in 19% of cases. None of the patients had eschar. Microvascular leakage was the main complication in 28.5%.Unusual complications seen were empyema and valvulitis in 4.7% of patients. Conclusion Scrub typhus is also seen in urban setups and in dry arid areas like Rajasthan and North West UP. So, relevant investigations should be a part of the evaluation in pediatric patients with acute undifferentiated fever.Eschar can be absent, and empyema and valvulitis are some uncommon complications. A high degree of suspicion and early diagnosis are essential as an undiagnosed infection is rapidly fatal.

Aetiology of Acute Undifferentiated Fever Among Children Under the Age of Five in Vietnam: A Prospective Study

BackgroundTo investigate the aetiology of acute undifferentiated fever (AUF) among children under the age of five in Vietnam.MethodsThis prospective study was conducted in the Thai Binh paediatric hospital, between July 2020 and July 2021 among children with AUF at admission. Real-time PCR testing 18 microbial pathogens were done on blood samples.Results286 children were included, with median age of 16 months. 64.7% were male. 53.9% were positive for at least one pathogen by PCR. Enterovirus, human herpesvirus 6, adenovirus, and varicella zoster virus PCR were positive for 31.1, 12.6, 1.4, and 1.0% patients, respectively. Other pathogens tested negative by PCR. During the hospital stay, based on clinical criteria 47.2% children secondarily presented with signs of respiratory tract infections, 18.9% had hand, foot and mouth disease, 4.6% had chickenpox. 4.2% presented signs of central nervous system infections, 1.0% had dengue (antigenic test) and 1.0% had signs of gastrointestinal infection. Finally, 23.1% patients presented a fever with or without a rash and no other symptoms and ultimately received a diagnosis of AUF.ConclusionReal-time PCR of blood is useful for detecting pathogens and diagnosing infectious causes of AUF. Further prospective studies with blood and urine culture testing and PCR investigation of not only blood but also cerebrospinal fluid, throat, and skin samples according to symptoms would be of interest to confirm the predominance of viral infections in children with AUF and to guide therapeutic options.

Acute undifferentiated fever presenting as multi-organ dysfunction: Narrowing the differential diagnosis

Introduction: Acute undifferentiated fever (AUF) in India is highly prevalent in the monsoon and postmonsoon periods. AUF may trigger potentially fatal illnesses with acute-onset complications; therefore, this study was carried out to recognize the common forms of organ dysfunction in tropical vector-borne diseases which present as AUF. Materials and Methods: A 20-month prospective study was conducted to estimate the incidence of multi-organ dysfunction syndrome (MODS) among the common causes of AUF. The association of mortality with MODS patterns was also determined. All nonparametric variables were compared using Chi-square and Kruskal–Wallis. Bivariate as well as multivariate logistic regression analyses were performed to find the predictors of mortality/poor outcome. Results: Scrub typhus had the highest incidence of MODS and highest mortality with simultaneous hepatic and renal involvement in 35.8%, followed by hepatic involvement with acute respiratory distress syndrome (ARDS) in 33.9% and hepatic involvement with shock in 32%. Patients of MODS with acute kidney injury (AKI), shock, or sepsis had higher mortality rates. Conclusion: AUF presents with multiple overlapping manifestations which are difficult to discern clinically into specific etiologies, especially once MODS sets in. However, we observed statistically higher odds of the patient having scrub typhus as the cause of AUF when simultaneous hepatitis, AKI, ARDS, and shock were present.

A Use of 56-kDa Recombinant Protein of Orientia tsutsugamushi Karp Serotype in Serodiagnosis of Scrub Typhus by Enzyme-Linked Immunosorbent Assay in Thais.

Scrub typhus is a mite-borne disease caused by a Gram-negative obligately intracellular bacillus, Orientia tsutsugamushi. The disease is endemic in the Asia-Australia-Pacific region, including Thailand. Scrub typhus generally manifests as acute undifferentiated febrile fever along with myalgia, rash, and lymphadenopathy. An eschar can be a valuable diagnostic clue, but this skin lesion may be missed in some patients. The disease symptoms resemble those of other febrile illnesses such as leptospirosis, typhoid, murine typhus, malaria, and dengue fever, making a laboratory diagnosis necessary for the definitive diagnosis. In this study, we expressed a recombinant protein derived from 56-kDa type-specific antigen of O. tsutsugamushi Karp serotype and tested its ability to detect and differentiate scrub typhus infection. IgM and IgG antibodies were determined in sera from scrub typhus (n = 92) and other febrile illness patients (murine typhus (n = 25), melioidosis (n = 36), leptospirosis (n = 42), and dengue (n = 35)) from Thailand. Sensitivities of 87.0% and 59.8% with a specified assay cut-off were obtained for IgM and IgG indirect ELISAs, respectively, with a specificity of 100% in both tests. The sensitivity was increased to 95.7% when a combination of IgM and IgG ELISAs results was considered. Our study suggested a potential of the 56-kDa recombinant protein for further development and evaluation for use in scrub typhus serodiagnosis.

548. Target Enriched NGS Reveals Wide Breadth of Viruses Causing Acute Undifferentiated Fever in Thailand

Abstract Background Despite extensive laboratory testing, infectious agents were not detected in approximately 50% of patients hospitalized for acute undifferentiated febrile illnesses (AUFI) at Siriraj Hospital, Bangkok, Thailand. Unbiased Metagenomic Next Generation Sequencing (mNGS) enables detection of any microbe present in patient samples. Target enrichment for viruses represents a highly sensitive and cost-effective approach for overcoming host background in clinical specimens. Plasma collected from 800 patients with undiagnosed AUFI between 2013-2020 were analyzed by mNGS coupled to target enrichment to identify known and novel viruses. Methods Plasma was pre-treated with benzonase before extraction on an Abbott m2000 instrument. mNGS libraries were prepared from double-stranded cDNA with Illumina Nextera XT reagents on an epMotion then combined in pools of 24 and hybridized to Comprehensive Viral Research Panel (CVRP; Twist Biosciences) probes covering >15,000 strains of vertebrate viruses. Captured viral sequences were amplified, quantified, and sequenced together on a MiSeq. Reads were taxonomically classified by the SURPI pipeline and aligned in CLC Bio Genomics Workbench software. Results CVRP method optimization enabled sequencing of 24-48 libraries per MiSeq run, for which >50% genome coverage was obtained with model viruses spiked into clinical specimens at 1000 cp/ml. This approach revealed an array of >24 different viruses found in 26% of samples. Dengue was the most prevalent at 7.4%, with all four genotypes detected. Other common causes of AUFI such as Chikungunya, HIV-1, HAV, HBV, HCV, and CMV were present in 1.5-2.5% of cases. Less prevalent (< 1%) infections included HEV, HSV-2, EBV, HHV-6, Enterovirus B&D and Parvovirus B19. We also encountered sporadic cases of Measles, Cardiovirus, West Nile, Rotavirus, Picobirnavirus, Polyomavirus 4&5, Kubovirus, and Rabies lyssavirus. Conclusion Target capture successfully demonstrated that viruses were important etiologies for unresolved cases of AUFI in Thailand. This data has led to a better understanding of the epidemiology of this clinical syndrome and has implications for proper management of AUFI, including lower rates of unnecessary testing and antimicrobial use. Disclosures Julie Yamaguchi, BS, Abbott Labs: Employee Michael G. Berg, PhD, Abbott Labs: Employee Pakpoom Phoompoung, MD, Abbott Labs: Grant/Research Support|Abbott Labs: Employee Jenna Malinauskas, MS, Abbott Labs: Employee Gavin Cloherty, PhD, Abbott: Employee|Abbott: Stocks/Bonds|Abbott Labs: Employee Yupin Suputtamongkol, MD, Abbott Labs: Grant/Research Support.

1181. Predictive Score for Dengue Infection with Complete Blood Count Parameters, Including the New Monocyte Distribution Width – a Retrospective Single Center Derivation and Validation Study

Abstract Background Dengue infection is a differential diagnosis in patients with acute undifferentiated fever. Early detection and management may reduce mortality. Monocyte distribution width (MDW) is a new parameter in complete blood count (CBC). It is recently approved for early detection of sepsis. We have noticed high MDW in Dengue patients. This study aimed to describe MDW changes in Dengue infection and to develop predictive score for early detection of Dengue infected patients. Methods We retrospectively retrieved data of adult patients with acute fever who had CBC and Dengue serology (NS1 antigen, IgM and IgG) performed during September 2019 to May 2020 at Thammasat University Hospital. Medical records were reviewed. MDW was compared between groups. Patients were randomly divided into training and validation set. Predictive score was developed from the training set and validated in the validation set with multivariable analysis. Results A total of 431 patients, with Dengue infection in 127 patients (29.5%), were included in the analyses. The median (interquartile range) of MDW in Dengue patients were higher than non-Dengue patients [29.7% (26.5 – 34.7) vs. 24.2% (21.1 – 27.8), P < 0.001]. In patients with confirmed Dengue infection, MDW increased with increasing severity (Figure). Training and validation sets included 216 and 215 patients with 64 and 63 Dengue infection, respectively. Independent predictive factors of Dengue infection were white blood cell < 4 x 109 /L (score 1), platelet < 100 x 109 /L (score 1) and MDW > 24% (score 1). No clinical features were independently predictive of Dengue infection. The area under receiver-operating-characteristic curve (95% confidence interval) of the prognostic score in the training and validation set were 0.839 (0.779 – 0.899) and 0.742 (0.674 – 0.811), respectively. With the cut-off score ≥ 1, the sensitivity and specificity of the score were 92.2% and 40.8% in the training set and 88.9% and 44.1% in the validation set. Monocyte distribution width in Dengue and non-Dengue patients Box-plot showing monocyte distribution width in patients with Dengue in comparison with non-Dengue (panel A) and compared between each Dengue severity (panel B) Conclusion MDW increase in patients with Dengue infection and also increase with Dengue severity. We have developed and internally validated a simple predictive score for Dengue infection based on only results from CBC and MDW. Further large-scale external validation study is required to confirm the utility of our predictive score. Disclosures All Authors: No reported disclosures.

FETOMATERNAL OUTCOME OF PATIENTS WITH FEVER DURING TERM PREGNANCY

Introduction: Fever in pregnancy is a common clinical problem globally. The risk to the mother and fetus is signicantly increased in pregnancy complicated by infection and fever. Fever is one of the most frequent reasons for emergency consultation during pregnancy and may be associated with signicant adverse outcomes, these being maternal (sepsis, organ damages) obstetrical (miscarriage, preterm birth, chorioamnionitis) or fetal (malformations, fetal demise). However, only one study including mainly second and third trimester pregnant women, evaluated causes of acute undifferentiated fever and 25 % of women had no identied cause. A hospit Methodology: al based analytical cross sectional study was analysed the maternofetal outcome of 50 cases of fever during term pregnancy and the outcome of 50 cases without fever in term pregnancy and it was studied between 2020-2021 at Govt. Mohan Kumaramangalam medical college, Salem. During the study cases were selected with pregnant women at term gestation with or without fever admitted in Labour ward and Antenatal ward of Govt. Mohan Kumaramangalam medical college hospital. The patients recruited for the study underwent Clinical history, General examination, Obstretic examination, CTG and USG Obstretics, fever ivestigations. In the group 1, Patients of 37weeks completed mothers with fever for more than one day and in the group 2 healthy AN mothers of 37weeks completed gestation were included. Fetal outcome will be studied by t Results: aking variableslow birth weight, intrauterine growth retardation, preterm delivery, neonatal sepsis and perinatal death.Maternal complications –post operative wound infection, post-partum haemorrhage, pneumonia, septicemia, jaundice, hypoglycemia and other complications of specic fever will be studied. Most common cause of fever in pregnancy was respiratory tract infections. Urinary tract infection was the second common cause. Pregnant women with fever 24% had Hypotension and 56% had Tachycardia. Pregnant women with fever had almost half the delivery with meconium stained signicantly. Among 50 delivered fever mothers, 24% cases were Previous LSCS cases, 44% cases went into spontaneous labour, only 32% cases induced. Out of 32% cases induced, 50% cases were delivered vaginally and 50% Cases underwent caeserean sections. So, Fever did not signicantly affect labour onset and the mode of delivery. Signicantly NICU admission was required among the fever cohorts Fever during pregnancy is a common occurrence that can lead to a wide range of issues Conclusion: for both the mother and the foetus and newborn. Because the most prevalent causes of fever are preventable, there has to be a greater emphasis on the importance of being aware of how to avoid such illnesses in order to avoid life-threatening foetomaternal consequences.

Etiology of Acute Undifferentiated Fever in Patients Attending the Emergency Department of a Tertiary Care Hospital

Background: The presence of a fever is one of the most often reported symptoms to medical professionals working in emergency department. It may be linked to a variety of clinical diseases, ranging from simple viral infections that go away on their own to sepsis. Objective: To assess the etiology of acute undifferentiated fever in patients attending the emergency department Methodology: This retrospective study was carried out at the medicine department, Qazi Hussain Ahmad Medical Complex, Nowshera for duration of one year from 20-July 2020 to 30-July 2021. All the enrolled patients were diagnosed for different diseases like malaria, urinary tract infection, dengue fever, enteric fever and pneumonia. All the data analysis was done by using IBM SPSS version 24. Results: In this study, the male patients were 108 (60%) while female patients were 72 (40%). Out of 108 diagnosed patients, 48 (44.44%) patients were diagnosed with malaria (79.17% P.vivax and 20.87% P.falciparum) followed by dengue fever in 30 (27.78%) patients, enteric fever in 13 (12.04%) patients (92.31% S.typhi, 7.69% S.paratyphi), urinary tract infection in 11 (10.19%) patients and pneumonia was diagnosed in 6 (5.56%) patients. Conclusion: Our study concludes that the predominant etiology of undifferentiated fever was malaria followed by dengue fever. In about 40% of the cases the laboratory tests were inconclusive. Keywords: Acute undifferentiated fever; Etiology; Emergency

Comprehensive analysis of codon usage patterns of porcine deltacoronavirus and its host adaptability.

The porcine deltacoronavirus (PDCoV) is a newly discovered pig enteric coronavirus that can infect cells from various species. In Haiti, PDCoV infections in children with acute undifferentiated febrile fever were recently reported. Considering the great potential of inter-species transmission of PDCoV, we performed a comprehensive analysis of codon usage patterns and host adaptation profiles of 54 representative PDCoV strains with the spike (S) gene. Phylogenetic analysis of the PDCoV S gene indicates that the PDCoV strains can be divided into five genogroups. We found a certain codon usage bias existed in the S gene, in which the synonymous codons are often ended with U or A. Heat map analysis revealed that all the PDCoV strains shared a similar codon usage trend. The PDCoV S gene with a dN/dS ratio lower than 1 reveals a negative selection on the PDCoV S gene. Neutrality analysis showed that natural selection is the dominant force in shaping the codon usage bias of the PDCoV S gene. Unexpectedly, host adaptation analysis reveals a higher adaptation level of PDCoV to Homo sapiens and Gallus gallus than to Sus scrofa. Compared to the USA lineage, the PDCoV strains in the Early China lineage and Thailand lineage were less adapted to their hosts, which indicates that the evolutionary process plays an important role in the adaptation ability of PDCoV. These findings of this study add to our understanding of PDCoV's evolution, adaptability, and inter-species transmission.

Simple clinical and laboratory predictors to improve empirical treatment strategies in areas of high scrub typhus and dengue endemicity, central Vietnam.

BackgroundDengue fever is highly endemic in Vietnam, but scrub typhus—although recognized as an endemic disease—remains underappreciated. These diseases together are likely to account for more than half of the acute undifferentiated fever burden in Vietnam. Scrub typhus (ST) is a bacterial disease requiring antimicrobial treatment, while dengue fever (DF) is of viral etiology and does not. The access to adequate diagnostics and the current understanding of empirical treatment strategies for both illnesses remain limited. In this study we aimed to contribute to the clinical decision process in the management of these two important etiologies of febrile illness in Vietnam.MethodsUsing retrospective data from 221 PCR-confirmed scrub typhus cases and 387 NS1 protein positive dengue fever patients admitted to five hospitals in Khanh Hoa province (central Vietnam), we defined predictive characteristics for both diseases that support simple clinical decision making with potential to inform decision algorithms in future. We developed models to discriminate scrub typhus from dengue fever using multivariable logistic regression (M-LR) and classification and regression trees (CART). Regression trees were developed for the entire data set initially and pruned, based on cross-validation. Regression models were developed in a training data set involving 60% of the total sample and validated in the complementary subsample. Probability cut points for the distinction between scrub typhus and dengue fever were chosen to maximise the sum of sensitivity and specificity.ResultsUsing M-LR, following seven predictors were identified, that reliably differentiate ST from DF; eschar, regional lymphadenopathy, an occupation in nature, increased days of fever on admission, increased neutrophil count, decreased ratio of neutrophils/lymphocytes, and age over 40. Sensitivity and specificity of predictions based on these seven factors reached 93.7% and 99.5%, respectively. When excluding the “eschar” variable, the values dropped to 76.3% and 92.3%, respectively.The CART model generated one further variable; increased days of fever on admission, when eschar was included, the sensitivity and specificity was 95% and 96.9%, respectively. The model without eschar involved the following six variables; regional lymphadenopathy, increased days of fever on admission, increased neutrophil count, increased lymphocyte count, platelet count ≥ 47 G/L and age over 28 years as predictors of ST and provided a sensitivity of 77.4% and a specificity of 90.7%.ConclusionsThe generated algorithms contribute to differentiating scrub typhus from dengue fever using basic clinical and laboratory parameters, supporting clinical decision making in areas where dengue and scrub typhus are co-endemic in Vietnam.

Malaria prevalence and performance of diagnostic tests among patients hospitalized with acute undifferentiated fever in Zanzibar

BackgroundControl efforts in Zanzibar reduced the burden of malaria substantially from 2000 to 2015, but re-emergence of falciparum malaria has been observed lately. This study evaluated the prevalence of malaria and performance of routine diagnostic tests among hospitalized fever patients in a 1.5 years period in 2015 and 2016.MethodsFrom March 2015 to October 2016, paediatric and adult patients hospitalized with acute undifferentiated fever at Mnazi Mmoja Hospital, Zanzibar were included. The malaria prevalence, and performance of rapid diagnostic test (RDT) and microscopy, were assessed using polymerase chain reaction (PCR) as gold standard.ResultsThe malaria prevalence was 9% (63/731). Children under 5 years old had lower malaria prevalence (5%, 14/260) than older children (15%, 20/131, p = 0.001) and persons aged 16 to 30 years (13%, 15/119, p = 0.02), but not different from persons over 30 years old (6%, 14/217, p = 0.7). All cases had Plasmodium falciparum infection, except for one case of Plasmodium ovale. Ten malaria patients had no history of visiting mainland Tanzania. The RDT had a sensitivity of 64% (36/56) and a specificity of 98% (561/575), and microscopy had a sensitivity of 50% (18/36) and a specificity of 99% (251/254), compared to PCR. The malaria parasitaemia was lower in patients with false negative results on RDT (median 7 × 103 copies/µL, interquartile range [IQR] 2 × 103 – 8 × 104, p = 0.002) and microscopy (median 9 × 103 copies/µL, IQR 8 × 102 – 7 × 104, p = 0.006) compared to those with true positive RDT (median 2 × 105 copies/µL, IQR 3 × 104 – 5 × 105) and microscopy (median 2 × 105 copies/µL, IQR 6 × 104 – 5 × 105).ConclusionsThe study emphasizes that malaria was a frequent cause of febrile illness in hospitalized patients in Zanzibar in the years 2015-2016, particularly among school age children and young adults. We found evidence of autochthonous malaria transmission in Zanzibar. Compared to PCR, both RDT and microscopy had low sensitivity, and false negative results were associated with low parasitaemia. While low parasitaemia identified only by PCR in a semi-immune individual could be coincidental and without clinical relevance, clinicians should be aware of the risk of false negative results on routine tests.

A Prospective Cohort Study of the Clinical Predictors of Bacteremia in Under-Five Children With Acute Undifferentiated Fever Attending a Secondary Health Facility in Northwestern Nigeria.

BackgroundChildren with acute febrile illness with no localizing signs often receive antibiotics empirically in most resource-poor settings. However, little is known about the burden of bacteremia in this category of patients, and an appraisal is thus warranted. This will guide clinical practice and promote rational antibiotics use.MethodsWe prospectively followed up 140 under-five children who presented with acute undifferentiated fever at the emergency/outpatient pediatric unit of a secondary healthcare facility. Baseline clinical and laboratory information was obtained and documented in a structured questionnaire. We compared baseline characteristics between participants with bacteremia and those without bacteremia. We further fitted a multivariable logistic regression model to identify factors predictive of bacteremia among the cohort.ResultThe prevalence of bacteremia was 17.1%, and Salmonella Typhi was the most frequently (40.9%) isolated pathogen. The majority (78.6%) of the study participants were managed as outpatients. The participants who required admission were four times more likely to have bacteremia when compared to those managed as outpatients (AOR 4.08, 95% CI 1.19 to 14.00). There is a four times likelihood of bacteremia (AOR 4.75, 95% CI 1.48 to 15.29) with a fever duration of beyond 7 days. Similarly, participants who were admitted with lethargy were six times more likely to have bacteremia (AOR 6.20, 95% CI 1.15 to 33.44). Other significant predictors were tachypnea and lymphopenia.ConclusionAmong under-five children with acute undifferentiated fever, longer duration of fever, lethargy, inpatient care, tachypnea, and lymphopenia were the significant predictors of bacteremia.

Scrub typhus in urban areas of Wardha district in central India.

Scrub typhus caused by Orientia tsutsugamushi presents as acute undifferentiated fever and can be confused with other infectious causes of fever. We studied scrub typhus as part of a study on hospital-based surveillance of zoonotic and vector-borne zoonotic diseases at a tertiary care hospital located in the Wardha district, Maharashtra, India. We report here descriptive epidemiology and climatic factors affecting scrub typhus. Patients of any age and sex with fever of ≥5 days were enrolled for this study. Data on sociodemographic variables were collected by personal interviews. Blood samples were tested by IgM ELISA to diagnose scrub typhus. Confirmation of scrub typhus was done by indirect immunofluorescence assay for IgM (IgM IFA). The climatic determinants were determined using time-series Poisson regression analysis. It was found that 15.9 per cent of the study participants were positive for scrub typhus by IgM ELISA and IgM IFA, both. Positivity was maximum (23.0%) in 41-60 yr of age and more females were affected than males (16.6 vs. 15.5%). Farmworkers were affected more (23.6%) than non-farm workers (12.9%). The disease positivity was found to be high in monsoon and post-monsoon seasons (22.9 and 19.4%) than in summer and winter. There were three hot spots of scrub typhus in urban areas of Wardha district. Rainfall and relative humidity in the previous month were the significant determinants of the disease.