Causes Of Acute Undifferentiated Fever Research Articles

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.

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.

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 and clinical spectrum of acute undifferentiated fever illness in patients in a tertiary care hospital Sheri Kashmir institute of medical science Soura, Jammu and Kashmir

Background: Current study aimed at s to delineate the etiology and clinical parameters associated with AUFI presenting to emergency department in a tertiary care hospital.Methods: This was a prospective hospital based study carried out at emergency medicine, SKIMS hospital, Soura Kashmir, India July 2017 to august 2018. Patients with acute undifferentiated fever were enrolled. Descriptive statistics were calculated in terms of mean±SD for continuous variables like age of the patients and duration of fever, Frequency and percentage were used to analyse categorical variables such as causes of fever and gender, while as descriptive analysis was calculated in terms of mean±SD for continuous variables like age of the patients and duration of fever.Results: Total numbers of patients included were 174, among these 112 (64.3%) were males and 62 (35.6%) were females. Most patients were diagnosed enteric fever (N=59, 33.9%) followed by UTI (N=25, 14.3%) dengue (N=12, 6.8%) and malaria (N=8, 4.5%) while rest of cases were associated with other viral illnesses (N=70, 40.5%) based on clinical basis and inconclusive laboratory results.Conclusions: Enteric fever was found to be the most common cause of acute undifferentiated fever followed by dengue and other viral illnesses, although causes and clinic spectrum of AUFI is varied.

Clinical Profile and Predictors of Outcome for Pediatric Scrub Typhus at a Tertiary Care Hospital

Background: Scrub typhus is an important cause of acute undifferentiated fever. It is currently one of the most covert re-emerging infections and the most common rickettsial infection caused by Orientia tsutsugamushi. Untreated cases can have mortality rates as high as 30-35%. Objectives: This study was done to study demographical data, clinical profile, and predictors of outcome for scrub typhus in children who were admitted to our institution, a tertiary care hospital in south India. Methods: In this retrospective study, children diagnosed with scrub typhus based on IgM enzyme-linked immunosorbent assay (ELISA), between January 2012 and June 2019 were included. Detailed history, clinical examination findings, laboratory profile, complications, and outcome were analyzed. Results: A total of 120 patients were identified, of whom 84 (42 males- and 42 females) cases satisfied the inclusion criteria and were analyzed. About 80 (95%) cases had a complete recovery, whereas 4 patients (5%) died of multiple complications. Hypotension, hypoxia, altered sensorium, hypoalbuminemia, elevated liver enzymes, azotemia, and deranged coagulation on admission were considered as poor predictors of outcome for scrub typhus. Conclusions: Pediatric scrub typhus is a common infection and should be suspected in cases with fever for more than 5 days and non-specific signs and symptoms. Early detection and timely management lead to a higher recovery rate. Hypotension, hypoxia, azotemia, altered sensorium, and bleeding manifestations on admission were associated with unfavorable outcomes.

Prevalence of scrub typhus in a tertiary care centre in Telangana, south India

Scrub typhus is re-emerging as an important cause of acute undifferentiated fever in the last decade from various parts of India. Complexity in performing the "gold standard" immunofluorescent assay and the unreliable nature of Weil Felix test often results in delayed or misdiagnosis in a majority of cases. The present study seeks to integrate the results of rapid diagnostic tests, clinical and laboratory features to aid the diagnosis and management of scrub typhus patients. A total of 645 serum samples with suspected scrub typhus sent to the Department of Microbiology were included in the study. Scrub typhus was tested by rapid immunochromatographic test (SD Diagnostics) and IgM ELISA (Inbios International, USA). Clinical features, laboratory parameters and final outcome were analysed from the clinical records of positive patients. Scrub typhus was diagnosed in 13.7% of patients and majority of them were observed in the month of August. 58.6% of scrub typhus patients presented with fever of one to two weeks duration. Eschar was documented in 13.7% of patients and 24% of patients gave a history of working outdoors or exposure to vegetation. All the patients responded to Doxycycline treatment and there was no mortality. High index of suspicion for scrub typhus is necessary in febrile patients not responding to conventional antibiotics especially during outbreak situations. Rapid immunochromatographic tests with excellent specificity and acceptable sensitivity can be used as potential point of care tests for quick diagnosis of scrub typhus especially in delayed presentation.

Evaluation of Combined Rapid Immunoglobulin M and Immunoglobulin G Lateral Flow Assays for the Diagnosis of Leptospirosis, Scrub Typhus, and Hantavirus Infection

Objective: Leptospirosis, scrub typhus, and hantavirus infection are commonly identified as causes of acute undifferentiated fever in rural parts of Asia. Although the characteristic presentations of these infections are well described, many of them present with nonspecific manifestations. Diagnosis is usually made by combined history of exposure, clinical features and positive antibody detection. The development of rapid antibody detection assay, using an immunochromatographic test (ICT) for the diagnosis of multi-diseases, has provided tools for more accurate diagnosis and appropriate antibiotic treatment of the acute undifferentiated fever syndrome.Methods: We evaluated the diagnostic performance of a commercially available combined rapid ICT for the diagnosis of leptospirosis, scrub typhus, and hantavirus infection, using archived blood samples from 434 patients with laboratory-confirmed leptospirosis (131) or scrub typhus (128), and from patients with other causes of fever as the negative control (175). Polysaccharide of nonpathogenic Leptospira patoc, a chimeric recombinant protein cr56 and two other recombinant proteins, r21 and kr56, from different serotypes of Orientia tsutsugamushi, and 21kDa species-specific antigen and recombinant CNP antigen derived from the Soochong virus were used as antigens for the diagnosis of leptospirosis, scrub typhus, and hantavirus infection in the combined ICT used in this study. Results: For the diagnosis of leptospirosis; in acute phase, the sensitivity and specificity of the ICT detection of IgM/IgG were 38.2% (95% CI, 29.9- 46.5%), and 99.0% (95% CI 97.9-100%); while in convalescent phase, the same were 84.6% (95%CI, 77.1- 92.0%), and 96.2% (95%CI, 92.5- 99.8%), respectively. For scrub typhus, in acute phase, the sensitivity and specificity of the ICT detection of IgM/IgG were 71.9% (95% CI, 64.1- 79.7%), and 97.4% (95% CI 95.6 - 99.2%); while in convalescent phase, the same were 84.6% (95%CI, 74.8- 94.4%), and 90.2% (95%CI, 85.3- 95.1%) respectively. For hantavirus infection, nine patients had detectable IgM for hantavirus infection. All these cases were diagnosed as scrub typhus by indirect immunofluorescent assay.Conclusion:  The performance of this combined ICT for leptospirosis and scrub typhus were comparable to those published data of other ICTs. However, the rapid test for the diagnosis of leptospirosis, using antigen detection, is needed. Hantavirus infection was not detected in this study population.

Etiology of acute undifferentiated fever in patients presenting to the emergency department of a tertiary care center in Karachi, Pakistan.

Objective:Our study aimed at identifying the characteristics and etiology of various causes of acute undifferentiated fever in patients presenting to the emergency department of a tertiary care hospital.Methods:This was a retrospective study conducted at the department of emergency medicine, Aga Khan University Hospital from January to June 2016. Adult patients presenting to Emergency department with acute undifferentiated fever were enrolled. Descriptive statistics were calculated in terms of mean±SD for continuous variables like age of the patients and duration of fever, whereas frequency and percentage were computed for categorical variables like gender and causes of fever.Results:A total of one hundred and fifty five patients were included. Out of these 97 (62.6%) were males and 58 (37.4%) were females. Most patients (25.2%, n= 39) were diagnosed as malaria followed closely by dengue fever (n=33, 21.3%) and then enteric fever (n= 10, 6.5%). while 41.9% (n=65) were diagnosed as suspected viral fever based on clinical judgment and inconclusive laboratory results.Conclusion:Malaria was found to be the most common confirmed cause of acute undifferentiated fever followed by dengue and enteric fever. The provision of accurate epidemiological data will enable resources to be directed towards key areas and will be of practical importance to clinicians.

Clinical Profile of Adult Patients Suffering from Scrub Typhus in Kasturba Hospital Wardha, Central India: A Study of 125 Patients

Background: Scrub Typhus is among the commonest causes of Acute Undifferentiated Fever during the monsoon in central India but there is a gap in knowledge regarding the data of the clinical profile in tropical rural area. Objective: To study the clinical profile of adult patients admitted with scrub typhus during the monsoon in rural central India. Material and methods: A Hospital based retrospective study was carried out in the 125 patients admitted to Medicine department of MGIMS during the monsoon period of June to September 2017. The History, clinical features, Lab profile, Treatment, complications and outcomes were studied closely. The data was retrieved from the Hospital Information System. The Outcome was studied in association with the severity of presentation, complications and treatment given. Diagnosis depended on recognizing the syndrome of non-specific symptoms of fever and cough, while diagnosis was confirmed using the IgM Scrub Typhus Rapid Chromatographic Test, which was considered as a Gold Standard in our study. Statistical analysis was done by descriptive and inferential statistics using chi-square test and software SPSS 22.0 version, EPI Info version 7 and Graph Pad Prism 6.0 version. Results: The clinical illness was characterized by Fever with chills (60.8%) and Cough (68.8%). The Disease was mostly acute (97%) presenting with a history of less than 10 days. The most characteristic physical sign was fever which was present in almost 60 percent of cases and the traditionally mentioned rash called Eschar was found in only 38 percent of patients. ARDS, nephropathy, Liver failure and Multi organ dysfunction occurred in 16%, 20%, 20% and 13.6% respectively. Though Scrub typhus occurs secondary to a chigger bite, only 6 patients out of 125 gave the actual history of insect bite. 9 patients out of 125 (7.2%) succumbed to death. Early treatment with Doxycycline shortened the duration of illness. No relapses occurred in those patients who received Doxycycline or Azithromycin for at least 7 days. Conclusion: Serious complications can occur if Scrub typhus is not recognized promptly. Early institution of Doxycycline can save lives in the patients of acute undifferentiated fever pending investigations. General physicians should be Scrub typhus minded to suspect and accurately treat the patients of fever.

Complete Genome Sequence of Leptospira interrogans Strains FMAS_KW1, FMAS_KW2 and FMAS_AW1 Isolated from Leptospirosis Patients from Karawanalla and Awissawella, Sri Lanka.

Leptospirosis is an important cause of acute undifferentiated fever and complex multisystem febrile diseases in the tropics and subtropics. Understanding the evolution of Leptospira especially as related to the clinical pathogenesis of leptospirosis is facilitated by systematic comparative genomic analysis of human-infecting isolates. Here, we announce the complete genome sequences of three Leptospira strains that were isolated from blood of humans with undifferentiated fever in Sri Lanka.

Prospective case-control analysis of the aetiologies of acute undifferentiated fever in Vietnam

ABSTRACT Acute undifferentiated fever (AUF) is frequently observed in tropical settings, but diagnosing the cause of AUF is often a challenge for local physicians and the physicians treating returning travellers. We conducted a case-control study in central Vietnam in 2016. A total of 378 febrile adult patients (AUFs) with a fever for ≤21 days, no evidence of localized infection and negative screening tests for dengue and malaria, and 384 afebrile adult patients (Controls) were prospectively enrolled. Whole blood, plasma, eschar swab, throat swab and urine specimens were collected and analysed. Quantitative PCR and RT-PCR were used to test for 55 bacteria, viruses and their subtypes. Serological tests were also used to test for rickettsial agents. The most common aetiology was influenza virus (20.9% in AUFs vs. 0% in Controls), followed by rickettsial agents (mainly Orientia tsutsugamushi and Rickettsia typhi) (10.8% vs. 0.3%), dengue virus (7.7% vs. 0.5%), Leptospira (4.8% vs. 0.8%), adenovirus (4.8% vs. 1.0%), and enterovirus (2.1% vs. 0%) (p < .05). The real proportion of dengue in AUF cases was underestimated because patients with dengue-positive rapid diagnosis tests were excluded from the study. The emerging agent Rickettsia felis, which had not been previously observed in Vietnam, was detected in this study. In total, 216 patients (57.1%) were given causative diagnoses, comprising 143 (66.2%) monoinfections and 73 (33.8%) coinfections. The infections caused by these agents should be considered in clinical practice and further studies. Additionally, agents susceptible to doxycycline were detected in 15.6% of AUFs; thus, this drug should be included in the panel used to treat AUF patients.

Causes of acute undifferentiated fever and the utility of biomarkers in Chiangrai, northern Thailand.

BackgroundTropical infectious diseases like dengue, scrub typhus, murine typhus, leptospirosis, and enteric fever continue to contribute substantially to the febrile disease burden throughout Southeast Asia while malaria is declining. Recently, there has been increasing focus on biomarkers (i.e. C-reactive protein (CRP) and procalcitonin) in delineating bacterial from viral infections.Methodology/Principal findingsA prospective observational study was performed to investigate the causes of acute undifferentiated fever (AUF) in adults admitted to Chiangrai Prachanukroh hospital, northern Thailand, which included an evaluation of CRP and procalcitonin as diagnostic tools. In total, 200 patients with AUF were recruited. Scrub typhus was the leading bacterial cause of AUF (45/200, 22.5%) followed by leptospirosis (15/200, 7.5%) and murine typhus (7/200, 3.5%), while dengue was the leading viral cause (23/200, 11.5%). Bloodstream infections contributed to 7/200 (3.5%) of the study cohort. There were 9 deaths during this study (4.5%): 3 cases of scrub typhus, 2 with septicaemia (Talaromyces marneffei and Haemophilus influenzae), and 4 of unknown aetiologies. Rickettsioses, leptospirosis and culture-attributed bacterial infections, received a combination of 3rd generation cephalosporin plus a rickettsia-active drug in 53%, 73% and 67% of cases, respectively. Low CRP and white blood count were significant predictors of a viral infection (mainly dengue) while the presence of an eschar and elevated aspartate aminotransferase and alkaline phosphatase were important predictors of scrub typhus.InterpretationScrub typhus and dengue are the leading causes of AUF in Chiangrai, Thailand. Eschar, white blood count and CRP were beneficial in differentiating between bacterial and viral infections in this study. CRP outperformed procalcitonin although cut-offs for positivity require further assessment. The study provides evidence that accurate, pathogen-specific rapid diagnostic tests coupled with biomarker point-of-care tests such as CRP can inform the correct use of antibiotics and improve antimicrobial stewardship in this setting.

Major aetiologies of acute undifferentiated fever in 2013 and 2014: an experience in retrospect

Background: Major aetiologies of acute undifferentiated fever (AUF) show wide variations, especially in developing countries including India. A better understanding of ‘AUF causes’ helps in better management of such cases with attendant reduction in morbidity and mortality. The present analytical study, retrospective in nature, estimates burden of the AUF in the years 2013 and 2014 with some useful information and conclusions.Methods: Important pathogens ‘investigated for’ either as a ‘direct or indirect evidence’ included - Malaria parasite, Dengue virus, Salmonella typhi and paratyphi A and Chikungunya virus. Malaria testing included examination of peripheral blood smear with Giemsa stain and also immuno-chromatographic test to detect lactate dehydrogenase (LDH) for Plasmodium falciparum and Plasmodium vivax and also HRP2 for detection of Plasmodium falciparum infections. For dengue and chikungunya virus infections - specific IgM antibodies - were detected by ELISA test. Enteric fever was diagnosed by detecting IgM and IgG antibodies using enzyme immunoassay. For Widal test, agglutinating antibodies against the O and H antigens of S. typhi and “H” antigens of ‘S. paratyphi A’ were undertaken. All the test procedures, including sample collections, were performed as per manufacturer’s recommendations, and, as per ‘standard operating procedures (SOPs)’.Results: Of the 10,670 samples received for dengue investigations, 3646 i.e. 34.17% tested seropositive for dengue cases. Percentage seropositivity for chikungunya was 18.6 (8/48). For dengue, 1193 (43.92%) and 488/577 (84.57%) samples were positive in the year 2013 and 2014 respectively in Delhi alone. Annual peak in months of September to November was observed for dengue while a bi-annual pattern was observed for malaria with two peaks occurring in months of May-June and August-September respectively for the year (s) i.e. 2013 and 2014. Enteric fever was present throughout the year with no specific distribution pattern. Majority of patients were from Delhi and adjoining Haryana followed by Western Uttar Pradesh. Co-infection of dengue with enteric fever was observed in only four cases.Conclusions: Dengue, chikungunya, malaria and enteric fever were the most important major causes of AUF in the year 2013 and 2014. Improved interactions with clinician counterparts generating awareness about major aetiologies of AUF would help in timely detection of such illnesses and hence better management reducing morbidity and mortality in the long run.

Clinical and Epidemiological Characteristics of Scrub Typhus and Murine Typhus among Hospitalized Patients with Acute Undifferentiated Fever in Northern Vietnam.

A descriptive study on rickettsiosis was conducted at the largest referral hospital in Hanoi, Vietnam, to identify epidemiological and clinical characteristics of specific rickettsiosis. Between March 2001 and February 2003, we enrolled 579 patients with acute undifferentiated fever (AUF), excluding patients with malaria, dengue fever, and typhoid fever, and serologically tested for Orientia tsutsugamushi and Rickettsia typhi. Of the patients, 237 (40.9%) and 193 (33.3%) had scrub and murine typhus, respectively, and 149 (25.7%) had neither of them (non–scrub and murine typhus [non-ST/MT]). The proportion of murine typhus was highest among patients living in Hanoi whereas that of scrub typhus was highest in national or regional border areas. The presence of an eschar, dyspnea, hypotension, and lymphadenopathy was significantly associated with a diagnosis of scrub typhus (OR = 46.56, 10.90, 9.01, and 7.92, respectively). Patients with murine typhus were less likely to have these findings but more likely to have myalgia, rash, and relative bradycardia (OR = 1.60, 1.56, and 1.45, respectively). Scrub typhus and murine typhus were shown to be common causes of AUF in northern Vietnam although the occurrence of spotted fever group rickettsiae was not determined. Clinical and epidemiological information may help local clinicians make clinical diagnosis of specific rickettsioses in a resource-limited setting.

Severe scrub typhus infection: Clinical features, diagnostic challenges and management.

Scrub typhus infection is an important cause of acute undifferentiated fever in South East Asia. The clinical picture is characterized by sudden onset fever with chills and non-specific symptoms that include headache, myalgia, sweating and vomiting. The presence of an eschar, in about half the patients with proven scrub typhus infection and usually seen in the axilla, groin or inguinal region, is characteristic of scrub typhus. Common laboratory findings are elevated liver transaminases, thrombocytopenia and leukocytosis. About a third of patients admitted to hospital with scrub typhus infection have evidence of organ dysfunction that may include respiratory failure, circulatory shock, mild renal or hepatic dysfunction, central nervous system involvement or hematological abnormalities. Since the symptoms and signs are non-specific and resemble other tropical infections like malaria, enteric fever, dengue or leptospirosis, appropriate laboratory tests are necessary to confirm diagnosis. Serological assays are the mainstay of diagnosis as they are easy to perform; the reference test is the indirect immunofluorescence assay (IFA) for the detection of IgM antibodies. However in clinical practice, the enzyme-linked immuno-sorbent assay is done due to the ease of performing this test and a good sensitivity and sensitivity when compared with the IFA. Paired samples, obtained at least two weeks apart, demonstrating a ≥ 4 fold rise in titre, is necessary for confirmation of serologic diagnosis. The mainstay of treatment is the tetracycline group of antibiotics or chloramphenicol although macrolides are used alternatively. In mild cases, recovery is complete. In severe cases with multi-organ failure, mortality may be as high as 24%.

Etiologies of acute undifferentiated fever and clinical prediction of scrub typhus in a non-tropical endemic area.

Scrub typhus usually presents as acute undifferentiated fever. This cross-sectional study included adult patients presenting with acute undifferentiated fever defined as any febrile illness for ≤ 14 days without evidence of localized infection. Scrub typhus cases were defined by an antibody titer of a ≥ fourfold increase in paired sera, a ≥ 1:160 in a single serum using indirect immunofluorescence assay, or a positive result of the immunochromatographic test. Multiple regression analysis identified predictors associated with scrub typhus to develop a prediction rule. Of 250 cases with known etiology of acute undifferentiated fever, influenza (28.0%), hepatitis A (25.2%), and scrub typhus (16.4%) were major causes. A prediction rule for identifying suspected cases of scrub typhus consisted of age ≥ 65 years (two points), recent fieldwork/outdoor activities (one point), onset of illness during an outbreak period (two points), myalgia (one point), and eschar (two points). The c statistic was 0.977 (95% confidence interval = 0.960-0.994). At a cutoff value ≥ 4, the sensitivity and specificity were 92.7% (79.0-98.1%) and 90.9% (86.0-94.3%), respectively. Scrub typhus, the third leading cause of acute undifferentiated fever in our region, can be identified early using the prediction rule.

Undiagnosed undifferentiated fever in Far North Queensland, Australia: a retrospective study

This study aimed to describe the causes of acute undifferentiated fever (AUF) and to develop a robust definition of undiagnosed undifferentiated fever (UUDF). This was a retrospective study of AUF over 3 years (2008-2011) in an Australian tertiary hospital. Request for laboratory investigation of one or more infectious agents was used as the search tool. A total of 340 patients with AUF, aged 15-65 years, were identified over the study period. A final diagnosis was made in 147 (43.2%) patients, dengue fever being the most frequent. The aetiology of fever was not determined in 193 (56.8%) patients. Elevations of C-reactive protein (CRP) and hepatic aminotransferase levels were common in these patients; two patients died. The characteristics of UUDF were fever for ≤21 days and failure to reach a diagnosis after clinical evaluation and specific laboratory investigations. The high burden of UUDF argues for a better diagnostic approach to fever that is capable of identifying a broad range of infectious agents.

English

Acute undifferentiated fever (AUF) is common in tropical regions of the developing world, its specific etiology is often unknown. It's common causes include malaria, dengue fever, enteric fever, leptospirosis, rickettsial infection. AUF is defined as fever without any localised source of infection, of 14 days or less in duration. The objective of the study was to focus on identifying the causes of AUF in patients admitted to Intensive care units & to determine importance of clinical examination in identifying the cause. It was a prospective study done in our Medical college Hospital at Kolar, Karnataka between 1-11-2010 to 30-11-2011. Cases presenting to hospital aged >18 years with complaints of Fever & admitted in Intensive care units were included in study. A total of 558 cases were enrolled. The clinical findings were noted and subsequent Investigations required were asked for. The study compromised of approximately equal number of Male & Female patients & age varied from 18 - 100 years. There was a clear seasonal variation - More no of cases were admitted between April & November. Majority presented with Fever of Short duration (1-3 days). Certain well defined syndromes were identified like:  Fever with Thrombocytopenia - the most common of all the syndromes.  Fever with Myalgia & Arthralgia,  Fever with Hepatorenal dysfunction,  Fever with Encephalopathy,  Fever with Pulmonary - Renal dysfunction and  Fever with Multiorgan dysfunction (MODS). Out of 558 cases AUF was noted in 339 cases (60.86%). An etiological diagnosis could be made for 218 cases (39.06%). Leptospirosis was the commonest cause with 72 cases (12.9%). The no of cases with Dengue were 48(8.6%), Malaria -25 (4.4%), Viral fever -35 (6.2%), Mixed infections - 12 (2.1%), Pulmonary Tuberculosis -25 ( 4.4%) and one case of Rickettsial Infection. MODS was the most common presentation in AUF patients, seen in 108 cases (31.8%) and 40 cases expired. A study of AUF done at Siriraj Hospital, Bangkok revealed that etiologies of AUF could be determined in 38.7% of study population. It has close relevance to present study where etiologies were determined in 39.06% cases. Mortality rates observed were similar.

Evaluation of an influenza-like illness case definition in the diagnosis of influenza among patients with acute febrile illness in cambodia

BackgroundInfluenza-like illness (ILI) is often defined as fever (>38.0°C) with cough or sore throat. In this study, we tested the sensitivity, specificity, and positive and negative predictive values of this case definition in a Cambodia patient population.MethodsPassive clinic-based surveillance was established at nine healthcare centers to identify the causes of acute undifferentiated fever in patients aged two years and older seeking treatment. Fever was defined as tympanic membrane temperature >38°C lasting more than 24 hours and less than 10 days. Influenza virus infections were identified by polymerase chain reaction.ResultsFrom July 2008 to December 2008, 2,639 patients were enrolled. From 884 (33%) patients positive for influenza, 652 presented with ILI and 232 acute fever patients presented without ILI. Analysis by age group identified no significant differences between influenza positive patients from the two groups. Positive predictive values (PPVs) varied during the course of the influenza season and among age groups.ConclusionThe ILI case definition can be used to identify a significant percentage of patients with influenza infection during the influenza season in Cambodia, assisting healthcare providers in its diagnosis and treatment. However, testing samples based on the criteria of fever alone increased our case detection by 34%.