Cases Of Fever Of Unknown Origin Research Articles

Fever of unknown origin: A 12-year case series in Colombia.

Fever of unknown origin (FUO) is a diagnostic challenge with highly heterogeneous causes. Its etiology can change according to the studied regions, and the chance of reaching a diagnosis depends on available resources. The aim of this study is to describe the clinical characteristics, etiology and the usefulness of diagnostic aids in cases of FUO managed over 12 years in a Colombian reference center. Single-institution retrospective case series. All cases of FUO between 2006 and 2017 were identified with the help of an electronic medical record search software. Cases of adults with fever for more than three weeks who remained undiagnosed after three days of hospitalization are described. Of 1,009 cases evaluated, 112 cases met the inclusion criteria (median age 43 years, 66% men). The etiologies identified were infectious (31.2%), inflammatory (20.5%), neoplastic (14.3%), and miscellaneous (2.7%) diseases. 31.2% remained without etiological diagnosis. The most frequent conditions were tuberculosis (17%), Hodgkin's lymphoma (7.1%), systemic lupus erythematosus (6.3%), disseminated histoplasmosis, and adult Still's disease. Contrast tomography and biopsies were the studies that most frequently supported or confirmed the final diagnosis. This series of contemporary Latin American cases suggests that the categories of FUO etiologies are similar to those reported in studies from developed countries, with tuberculosis being the most frequent cause in our setting. Our results highlight the importance of tomography-guided invasive studies in the diagnostic approach to FUO.

SEROPREVALENCE AND CLINICAL FEATURES OF SCRUB TYPHUS AMONG FEBRILE PATIENTS IN A TERTIARY CARE HOSPITAL

Objective: Rickettsial infections is the most neglected and underdiagnosed tropical diseases in developing countries. The most common rickettsial disease, which is caused by the obligate intracellular gram-negative bacteria Orientia tsutsugamushi, is Scrub Typhus. Scrub typhus can prove to an important diagnosis in pyrexia of unknown origin (PUO) patients and is transmitted by a species of trombiculid mites (“chiggers”). Aim of this study is to find seroprevalence and clinical features of scrub typhus among febrile patients from a tertiary care hospital in North India. Methods: This study was undertaken for a period of 1 y. All the patients attending the outpatient department or admitted indoors suspected of PUO were included in the study. Serum samples of suspected cases were tested for IgM Scrub typhus. Results: During the study period, a total of 755 cases were tested for scrub typhus, out of which 223 were positive so, the seroprevlance of Scrub typhus is 29.5%. Out of 223 positive patients, 105 (47%) were males and 118 (53%) were females. Maximum no. of patients was from age group 21 to 40 y of age and maximum number of cases is in autumn season. Most common clinical feature is fever, followed by myalgia, headache, ocular pain, dyspnoea, cough and eschar, respectively. Conclusion: Scrub typhus is an emerging tropical rickettsial disease in the Indian subcontinent. The present study highlights the importance of screening of PUO cases for Scrub typhus as timely institution of simple empirical treatment can prove to be lifesaving in such cases.

Serodiagnosis of Brucellosis in Patients with Fever of Unknown Origin at a Tertiary Care Hospital in Bangalore: A Cross-sectional Study

Introduction: Brucellosis is a zoonotic disease caused by bacteria of the genus Brucella. Although it is not commonly transmitted between humans, it can be transmitted through direct handling of cattle or their products, such as raw milk, unevenly heated milk, clotted cream, and cheese, for varying periods. Brucellosis is considered as one of the neglected zoonotic diseases worldwide, as it can cause debilitating acute infections and later become chronic with numerous complications. Aim: To determine the prevalence of brucellosis among patients with Pyrexia of Unknown Origin (PUO). Materials and Methods: This cross-sectional study was conducted in the Department of Microbiology at Ramaiah Medical College and Teaching Hospital in Bangalore, Karnataka, India, over a period of two years, from December 2019 to December 2021. The study included patients who visited the Outpatient Department (OPD) and those admitted to the hospital with fever persisting for more than 5-7 days and Fever of Unknown Origin (FUO). The total sample size was 180, and 5-10 ml of blood was collected from each patient under aseptic precautions from the median cubital vein for serological tests. The blood samples were stored at 2-8°C for the Rose Bengal Test (RBT) assay and Enzyme-Linked Immunosorbent Assay (ELISA). The demographic parameters considered included clinical history, age, gender, residency, and history of animal exposure. Data analysis was performed using the statistical software Statistical Package for the Social Sciences (SPSS) version 18.0, employing the Chi-Square test, Fisher’s-Exact test, and descriptive statistics. The significance level employed was set at p-value <0.05. Results: Among 180 samples, six (i.e., 3.3%) were positive for the Brucella RBT (BRBT), while 11 (i.e., 6.1%) were positive for the (ELISA IgM), and 17 (i.e., 9.4%) were positive for the (ELISA IgG). Additionally, 22 samples (i.e., 12.22%) tested positive for either ELISA of IgG or IgM (ELISA IgG/IgM). Conclusion: The present study identified 22 patients (12.22%) with Brucella-positive cases who presented with various clinical signs and symptoms, originating from different geographical locations and regardless of gender. These findings suggest that all cases of FUO presented to a clinician should be evaluated for Brucella infection.

Prospective Study of the Usefulness of Liquid Biopsy in Patients with Unknown Fever Suspected of Malignant Lymphoma

Background: Malignant lymphoma, represented by intravascular large B-cell lymphoma (IVLBCL), is an important differential disease in classical fever of unknown origin (FUO). Bone marrow aspiration (BMA) and random skin biopsy (RSB) are useful in IVLBCL diagnosis, but their positivity rates are clinically insufficient and the procedures are invasive. The molecular genetic analysis of lymphomas using cell-free tumor DNA (cfDNA) in plasma (liquid biopsy) may be effective for IVLBCL (Shimada et al., Blood. 2021 Mar 18;137(11):1491). We conducted a multicenter prospective clinical trial to investigate the usefulness of liquid biopsy for early lymphoma diagnosis among patients with classical FUO. Methods: Patients with the following criteria were enrolled: (1) clinically suspected malignant lymphoma, (2) persistent fever for >3 weeks, refractory to antibiotics, (3) higher than standard lactate dehydrogenase, (4) unbiopsiable lesions, and (5) age ≥20 years. Liquid biopsies were performed as follows: (1) MYD88 L265P/CD79 Y196 mutation analysis using droplet digital PCR (ddPCR), (2) B-cell receptor (BCR)/T-cell receptor (TCR) reconstruction analysis using next generation sequencing (NGS), and (3) comprehensive genetic analysis using the hematopoietic oncogene panel (426 genes) and NGS. Pathological malignant lymphoma was diagnosed at each institution; later, a central diagnosis was made by two additional lymphoma pathology specialists. Results: Fifty patients were enrolled from 15 centers from October 2019 to September 2021; one was excluded. The median age was 73.5 (21-89) years; 28 patients (57.1%) were male. There were 29 cases (59%), 28 (57.1%), and one (2%) of hematologic malignancy, malignant lymphoma, and MDS/AML, respectively (Fig. 1A). Twenty (71%) malignant lymphomas were B-cell lymphomas (17 of which were IVLBCL [61%]), and 8 (29%) were mature T/NK-cell lymphomas. Nonhematologic diseases were present in 20 (41%) patients (7 collagen diseases [4 adult-onset Still's disease, 3 others], 2 solid tumors, 2 infections [1 syphilis, 1 tuberculosis], and 9 FUO). FUO pathological investigations were performed in 47 (97.9%) and 43 (87.6%) patients with BMA and RSB, respectively. IVLBCL had a 53% positivity rate for initial BMA (9/17) and RSB (8/15; Fig. 1B). Only 65% patients tested positive for either initial BMA or RSB and a majority (15/17) of them were diagnosed based on repeated evaluations during their lifetime. The BMA positive rate in patients with mature T/NK-cell lymphoma (8 cases) was high (75%). The mean cfDNA concentration was 215 (5.6-1320) ng/mL, with no significant difference between patients with lymphoma and those with other diseases (279 vs. 130 ng/mL, p=0.073). In ddPCR analysis, 85% of B-cell lymphoma cases (N=20) had either MYD88 or CD79B mutations; the mutation detection rate in IVLBCL (N=17) was 94% (Fig.1B, 2). All patients with non-B-cell lymphoma tested negative. The positive rate of patients with B-cell lymphoma in the NGS-based BCR reconstruction analysis was 90% and negative in two patients with IVLBCL. BCR reconstitution was also observed in two patients with T/NK-cell lymphoma. Comprehensive panel analysis demonstrated that 19/20 (95%) B-cell lymphoma cases showed MYD88 or CD79B mutations; all IVLBCL cases showed mutations. LymphGen algorithm analysis showed that 15, 1, and 1 IVLBCL cases were categorized as MCD (with MYD88 or CD79b mutations), composite (including MCD), and other, respectively (Fig. 2). In T/NK-cell lymphomas, TCR reconstitution was positive in 3/8 T/NK-cell lymphomas. Panel analysis could hardly predict T/NK-cell lymphoma. DdPCR results were returned to the physician within a median time of 14 days. Of the six patients who were not diagnosed with initial BMA and RSB, five were positive for the MYD88/CD79B mutation, according to the ddPCR results. Three of them were diagnosed through additional liquid biopsy testing. Two patients were diagnosed with IVLBCL based on central diagnosis after death. Conclusions: In the classical FUO cases with suspected malignant lymphoma, 57% and 35% had malignant lymphoma and IVLBCL, respectively. Compared to the classical diagnostic methods, liquid biopsy can be used to detect lymphoma-specific genetic mutations at an earlier stage, being clinically useful for the early diagnosis of difficult-to-diagnose malignant B-cell lymphomas. Figure 1View largeDownload PPTFigure 1View largeDownload PPT Close modal

A retrospective analysis of 3 156 admissions with fever of unknown origin in a large Italian hospital


 Background: fever of unknown origin (FUO) is defined as a fever with no etiologic diagnosis after standardized investigations performed during 3 days in hospital or after at least 3 ambulatory visits. Our study aims to describe the epidemiology of classic FUO through the retrospective analysis of 902 861 admissions to a large University Hospital in Italy, to investigate its temporal trend, and to evaluate differences between young and old patients.
 Methods: we retrieved data records of all the admissions between the 1st January 1988 and 31st December 2007. Proportional admission rate (PAR ) of FUO was calculated. Time trends of FUO admissions were analysed by joinpoint regression, with time changes expressed as Expected Annual Percent Change (EA PC). The ICD 9-CM code was used to identify the diagnosis on discharge of FUO cases.
 Results: in the study period 3 156 patients were admitted with a diagnosis of FUO (PAR=3.50 per 1 000). The time-trend analysis showed two joinpoints, the first in 1995 (EAPC of 307.80, 95% CI: 89.66-776.84, p=0.002), and the second in 1998 (EAPC=-8.57, 95% CI: -10.37-6.73; p<0.001). Around 22% of admissions remained without a definitive diagnosis of FUO, with this percentage being lower in patients ≥65 years compared with subjects aged 21-64.
 Conclusions: FUO is a leading cause of admission to hospitals, as well as of morbidity and mortality, thus representing a challenge for diagnostic medicine and hospital care. It is necessary to develop a diagnostic methodology for FUO , so as to reduce costs of preventable hospitalizations.

A study of etiology of fever of unknown origin in children aged 2 months to 18 years

Background: In an era of advance science of modern technologies, many diseases are diagnosed and excluded rapidly and now Fever of Unknown Origin (FUO) has been redefined for any fever of 380C lasting for more than 7 days without any clear cause. The aetiology varies according to different geographical regions, socioeconomical status, age, prevalence of resistance to antimicrobial drugs and genetic susceptibility.Methods: It was a descriptive cross sectional, hospital-based study, carried out on 150 children from August 2018 to May 2020. All cases in the age group of 2 months to 18 years with fever of >38.0°C, lasting for more than 7 days without a clear source were included.Results: The mean age of presentation was 5.8 years±Standard Deviation of 3.7 years with male to female ratio was 1.4:1. Nearly half of the cases, presented with the duration of fever between 8-14 days. Enteric fever in 52%, tuberculosis in 13.3% and acute lymphoblastic leukemia (ALL) in 8.5% were three common etiologies found in this study. Amongst all cases of FUO, infective causes were seen in 113 (75.3%) followed by malignancies in 15(10%) cases. In 10 (6.7%) cases, cause could not be established.Conclusions: Enteric fever and tuberculosis were the leading etiologies from infective subgroup of FUO. ALL was the commonest cause from malignancies sub group. FUO presenting with low haemoglobin, platelet is a pointer towards malignancy. Occurrence of FUO with infectious diseases and malignancies was found in younger age group as compared to connective tissue diseases.

Seroprevalence trends of Scrub typhus among the febrile patients of Northern India: A prospective cross-sectional study.

Background:Rickettsial infections remain one of the most neglected and underdiagnosed tropical diseases in the developing countries. Scrub typhus can prove to an important diagnosis in pyrexia of unknown origin (PUO) patients and is transmitted by a species of trombiculid mites (“chiggers”). The disease leads to a plethora of symptoms like fever, rash, headache, nausea, abdominal pain, thrombocytopenia, etc. The current study was aimed to assess the seroprevalence as well as other demographic parameters of scrub typhus among patients diagnosed with PUO in the northern part of India.Materials and Methods:This study was undertaken for a period of 3 years from September 2017 to September 2020. Serum samples of suspected cases were tested for IgM Scrub typhus along with other common febrile illnesses like Malaria, typhoid, dengue, leptospirosis, chikengunya, etc. Additional testing for COVID-19 was also planned for samples received after February 2020.Results:The overall seroprevalence of Scrub typhus during the 3 year study period was noted to be 18.6% in the PUO patients. Typhoid was noted in 39.5%, malaria in 9.2%, Dengue in 13.5%, leptospirosis in 4.8%, and chikungunya in 5.3% of the patients. No cause was identified in 9.1% of the PUO cases. 3.9% of the samples were positive by RT-PCR for COVID-19. No mortality was noted in the scrub typhus positive cases.Conclusion:Scrub typhus is an emerging tropical rickettsial disease in the Indian subcontinent. The present study highlights the importance of screening of PUO cases for this important infection as timely institution of simple empirical treatment can prove to be life saving in such positive cases.

CAN HUMAN TOXOPLASMOSIS BE WITHIN THE DIFFERENTIAL DIAGNOSIS OF FEVER OF UNKNOWN ORIGIN: A CROSS-SECTIONAL STUDY

More than 200 diseases can be represented in differential diagnosis of fever of unknown origin(FUO). The mainstay for the proper diagnosis of FUO took right path for the correct investigations.Globally, Toxoplasma gondii infection persists lifelong within the affected host organs inthe dormant bradyzoites form. Once the host immunity decreases, it can be converted back tothe activate tachyzoite form that attach the host cells. The aim of our study is to estimate thefrequency of toxoplasmosis in patients with fever of unknown origin, concerning the etiology.A cross-sectional study was done from November 2017 to May 2018, including 140 patientschosen with FUO (100 males &40 females), recruited from Port Said Fever Hospital/ Egypt.Their ages ranged between 16 and 70 years old. Patients were subjected to comprehensive historytaking, laboratory investigations, clinical and radiologic examination. Detection of anti-Toxoplasma IgM&IgG antibodies was done by the Electrochemiluminescence immunoassay.Patients had fever with known origin proved by investigations, were excluded from the study.The results showed that 7.1% of the FUO cases were serologically positive for ToxoplasmaIgG. Of them, 80% were females and 20% were males. About 70% of Toxopl-asma-IgG positivecases were represented with fever for 3weeks, and 30% were represented with fever formore than 3weeks. The 70% of the target group had cervical lymphadenopathy and all of themhad hepatosplenomegaly. Moreover, all cases were eating fast food.

CAN HUMAN TOXOPLASMOSIS BE WITHIN THE DIFFERENTIAL DIAGNOSIS OF FEVER OF UNKNOWN ORIGIN: A CROSS-SECTIONAL STUDY

More than 200 diseases can be represented in differential diagnosis of fever of unknown origin(FUO). The mainstay for the proper diagnosis of FUO took right path for the correct investigations.Globally, Toxoplasma gondii infection persists lifelong within the affected host organs inthe dormant bradyzoites form. Once the host immunity decreases, it can be converted back tothe activate tachyzoite form that attach the host cells. The aim of our study is to estimate thefrequency of toxoplasmosis in patients with fever of unknown origin, concerning the etiology.A cross-sectional study was done from November 2017 to May 2018, including 140 patientschosen with FUO (100 males &40 females), recruited from Port Said Fever Hospital/ Egypt.Their ages ranged between 16 and 70 years old. Patients were subjected to comprehensive historytaking, laboratory investigations, clinical and radiologic examination. Detection of anti-Toxoplasma IgM&IgG antibodies was done by the Electrochemiluminescence immunoassay.Patients had fever with known origin proved by investigations, were excluded from the study.The results showed that 7.1% of the FUO cases were serologically positive for ToxoplasmaIgG. Of them, 80% were females and 20% were males. About 70% of Toxopl-asma-IgG positivecases were represented with fever for 3weeks, and 30% were represented with fever formore than 3weeks. The 70% of the target group had cervical lymphadenopathy and all of themhad hepatosplenomegaly. Moreover, all cases were eating fast food.

Occurrence of brucellosis in patients of pyrexia of unknown origin

Brucellosis is the most common bacterial zoonotic disease worldwide.It is mainly occupational disease reported in farmers, slaughter house workers, animal handlers and meat inspectors. This disease is endemic in many parts of Asia, including India. Brucellosis is an important, but neglected major cause of pyrexia of unknown origin(PUO). Diagnosis of brucellosis is difficult. Hence the medical and laboratory staff needs to be alert to recognize this condition.To assess the possible risk factors associated with human brucellosis.To study frequency of human brucellosis in relation to occupation, age and sex.From September (2018) to November (2019) 102 Serum samples of PUO cases were analysed for brucellosis. All serum samples were analysed by slide agglutination method using standard specific brucella antigen.We observed that human brucellosis is present in PUO patients. The total number of brucellosis positive cases were found to be 14 (13.72%) out of 102 PUO cases. Among positive cases, males were 8 (57.14%) and females were 6(42.85%). Highest brucellosis positive cases were seen in age-group between 15-30 years 6(42.85%) followed by 31-45 years 5(35.71%), 46-60 years 2(14.28%) &>60 1(7.14%) in PUO patients.With the growing number of brucellosis cases detected in India. Brucellosis is the fast emerging as a public health threat and also due to limited diagnostics leading to underreporting. The study also highlights the innovative and cost effective methods for rapid and early reporting and ruling out brucellosis in PUO cases.

Comparative study between serological tests and PCR for diagnosis of Rickettsial diseases in patients with fever of unknown origin

Background and aimRecurrence of Spotted fever and Scrub typhus fever has been well documented in pyrexia of unknown origin (PUO) cases from Iraq in past years. Therefore the present study were carried out in the rural area of Iraq where there is a steady interface of human being with animal reservoir, to detect the occurrence of Rickettsial infections as well as to compare the conventional serological and molecular methods for its diagnosis. MethodsA total of 91 blood samples collected from PUO were tested for Widal (Typhoid), Weil Felix (Typhus), Standard agglutination (Brucellosis), IgM Scrub ELISA and IgM Spotted ELISA and dMicrolisa-HIV. The positive ELISA samples were subjected to PCR to detect Rickettsiae by using specific primer for 16S rRNA gene sequence. ResultsOut of 91 patients, 19 (20.8%) were positive for typhoid fever. IgM Scrub and Spotted ELISA shows positive for 26 (28.5%) patients. Among 26 ELISA positive, 14 were negative for Weil Felix test. Out of 20 Weil Felix positive samples, only 12 were positive in ELISA. The PCR results were positive for 8 (30.8%) samples out of 26 ELISA positive samples. ConclusionScrub typhus and Spotted fever were widely distributed in PUO cases. Measures to increase awareness and also to diagnose and treat this infection in the affected areas are essential.

Fever of unknown origin: evaluation of 110 classical and HIV-associated cases in the last decade

ABSTRACT Background Fever is one of the critical symptoms of collagen vascular diseases, malignancies, and infectious diseases. Patients with a fever of unknown origin (FUO) were evaluated to determine the etiology. Methods In this study, 110 cases with FUO who were admitted to two hospitals with a total of 800 beds, in which 5000 daily outpatient patients were admitted between 2006 and 2016 have been evaluated retrospectively. Anamnesis and the findings were obtained from hospital records. Patients with a temperature higher than 38.3°C and lasting three weeks or longer without diagnosis despite one week of investigation in the hospital were included as FUO cases in this study. Nosocomial and neutropenic cases were excluded from the present study. Results Fifty-seven patients were male (52%), and the mean age was 40.2 ± 17.2. The distribution of the classic and HIV-associated cases was 85 (77.3%) and 18 (16.4%). Tuberculosis (TB) was the most frequent disease in both groups. The etiology was infectious in 68.2%, autoimmune in 14.5%, and neoplastic in 5.4%. There was no case of collagen vascular disease in the HIV-associated FUO group. Conclusion As a result of our study, infectious diseases and TB were still the leading factors that caused FUO. TB has been notably found higher in the HIV-associated group than the classic group. FUO is usually either a rare cause or an unusual clinical presentation of a well-known infectious disease in Turkey. Therefore, it should be noted that various manifestations of extra-pulmonary tuberculosis may be considered a FUO case.

Retrospective analysis of 1,641 cases of classic fever of unknown origin

BackgroundFever of unknown origin (FUO) is commonly defined as fever higher than 38.3 °C on several occasions during at least 3 weeks with uncertain diagnosis after a number of obligatory investigations. It is a special type of fever and a common disease in internal medicine. However, due to its complex etiology, lack of characteristic clinical manifestations, and insufficient laboratory examination indicators, it often baffles clinicians in diagnosis. We herein present a study of the etiological factors and clinical features of classic fever of unknown origin (FUO) to provide help for related clinical diagnosis and treatment.MethodsA total of 1,641 cases of patients with classic FUO hospitalized in West China Hospital of Sichuan University between January 1, 2011 and December 31, 2017, were collected, and the etiological factors of classic FUO were analyzed. A special effort was made to explore and screen the laboratory indicators related to infectious diseases, and the above data were compared with the clinical features of tuberculosis and lymphoma, which are difficult to diagnose.ResultsAmong the 1,641 patients, 1,504 were finally diagnosed through various types of examination or diagnostic methods, and the diagnosis rate was 91.65%. Among all the causes of the 1,641 cases of FUO, 48.69% [799] were infectious diseases, of which tuberculosis was the most common, accounting for 19.50% [320]. Connective tissue diseases were responsible for 19.26% [316] of cases, of which adult-onset Still’s disease (AOSD) was the most common, comprising 89 (5.42%) of the cases; 16.94% [278] were neoplastic diseases, and lymphoma (143, 8.71%) cases, was the most common malignant tumor; 6.76% [111] were other diseases; and in 8.35% [137] of cases, the cause was unclear. Through comparative analysis of tuberculosis and lymphoma, no significant differences were found between the symptoms, signs, and non-specific routine examination results of the two diseases. The diagnosis of these diseases was more dependent on tuberculosis-related examinations and pathological examinations.ConclusionsInfectious diseases are the principal cause of classic FUO, in which tuberculosis accounts for a large proportion. Non-infectious diseases that cause FUO are mainly connective tissue diseases and malignant tumors. Of the various causes of classic FUO, tuberculosis and lymphoma are relatively difficult to diagnose. In most cases, the causes of classic FUO can be ascertained.

Brucellosis in patients with pyrexia of unknown origin in Assam, India: a retrospective record review

BackgroundGlobally, around 500 000 human brucellosis cases are reported every year. In India, the burden of human brucellosis is likely underestimated because of limited laboratory capacity. In this study, we aimed to estimate brucellosis burden in patients with pyrexia of unknown origin (PUO) attending Amsing Jorabat Sub-centre in Kamrup Metro, Assam, India—an area with 10% prevalence of animal brucellosis. MethodsWe retrospectively reviewed records of PUO patients attending Amsing Jorabat Sub-centre between Jan 1 and Oct 31, 2014. We defined a case as Brucella-positive if a Rose Bengal plate test or serum agglutination test, or both, were positive along with IgM or IgG positivity. We reviewed records of routine animal surveillance by Assam Agriculture University to see if cases had Brucella-positive animals in their farms. We used EpiInfo 7.1 to analyse data. FindingsOf the 46 PUO patients included in the study, 25 (54%) were Brucella-positive. Median age of brucellosis patients was 33 years (range 18–67 years). Among the 25 cases, 88% were men and 80% were dairy farmers. All 25 case-patients owned dairy farms or worked as farm attendants. Most common presenting symptoms were arthralgia (n=17 [68%]), fever (12 [48%]), and night sweats (12 [48%]). Patients became ill mostly during March (7 [28%]) and July (6 [24%]). Most Brucella-positive patients (17 [68%]) were from Shillongia village. All case-patients were engaged in milking and more than half (19 [76%]) had handled abortus during birthing on the farm. InterpretationMore than half of PUO cases were brucellosis cases in dairy farm workers who had brucellosis-positive animals on their farms. We recommend multisector coordination involving health and veterinary departments to improve surveillance and control of brucellosis. FundingNone.

Seroprevalence of Brucellosis in Western Rajasthan: A Study from a Tertiary Care Centre

AbstractBrucellosis is a significant bacterial zoonotic disease with a high seroprevalence in low-to-middle-income countries where there is a significant contact of humans with animals. This prospective study was conducted to observe the seroprevalence of brucellosis in 75 symptomatic patients with pyrexia of unknown origin (PUO) and 75 high-risk individuals (10 veterinarians, 15 milkmen and 50 healthy contacts of symptomatic patients) with possible exposure to brucellosis. Serum samples collected from these patients and individuals were subjected to rose Bengal test (RBT) and ELISA for the detection of IgM and IgG antibodies. RBT was positive in 50 samples (40 PUO and 10 high risk), of which 25 (33.3%) PUO cases had detectable IgM antibodies, whereas IgG antibodies were detected in 20 patients. None of samples from high-risk individuals was reactive for IgM/IgG antibodies by ELISA. The overall seroprevalence in this study was 16.7% (33.3% in PUO patients). Being a predominantly livestock rearing area, brucellosis is a significant health-care problem in this part of India with this entity being linked to 33% of PUO cases.

Evaluation of different patterns and etiologies of classic form of pyrexia of unknown origin in Assiut University fever unit

Background Pyrexia of unknown origin (PUO) is one of the most challenging diagnostic dilemmas in clinical practice. Despite the availability of different investigations, still diagnosis may not be reached. The aim of the study was to assess the relative frequency of the classical form of PUO among patients admitted to the Fever Unit of Assiut University Hospital (AUH) and to determine the causes and the different fever patterns of the classical form of PUO in the studied patients. Patients and methods This prospective study included patients with the classical form of PUO admitted to Fever Unit of Tropical Medicine and Gastroenterology of AUH during the period from January 2014 till July 2017. All patients who fulfilled the inclusion and exclusion criteria of classical form of PUO defined by Durack and Street were included. Results The relative frequency of patients who had classical form of PUO was 90 among 2431 (3.7%) patients admitted to the Fever Unit of Tropical Medicine and Gastroenterology of AUH. Bacterial infection was on the top of the diagnosis, where 45 (50%) patients had bacterial infections, comprising 14 (15.6%) salmonellosis, 11 (12.2%) tuberculosis, 10 (11.1%) brucellosis, seven (7.7%) pyelonephritis, and three (3.3%) pyogenic liver abscess. Different fever patterns were seen, where 58 (64.4%) patients presented with relapsing fever, 29 (32.3%) patients presented with continuous fever, and three (3.3%) patients presented with remittent fever. Conclusion PUO is detected in 3.7% among feverish patients, where salmonellosis and brucellosis still are the commonest causes. Relapsing fever is the commonest pattern of the classical form of PUO. Undiagnosed PUO cases are still a problematic condition that needs exhaustive investigations.

Clinical analysis of 215 consecutive cases with fever of unknown origin: A cohort study.

Fever of unknown origin (FUO) is a frequently observed phenomenon in clinical practice. The present study was aimed to investigate potential causes of FUO, thereby improving clinical diagnosis of this disorder.In this retrospective study, clinical data were collected from 215 patients who were diagnosed with FUO between January 2009 and December 2010, and an 18 to 36 months follow-up visit was also performed for these patients.Among these FUO cases, the most common causes of the disease were infectious diseases (IDs) (42.3%), followed by connective tissue diseases (CTDs) (32.1%), miscellaneous (Mi) (10.7%) and neoplasm (N) (6.5%), while the causes for the other 18 cases (8.4%) were still unknown. The most common types of ID, CTD, and N were tuberculosis (16/91, 17.6%), adult onset Still disease (AOSD) (37/69, 53.6%) and non-Hodgkin lymphoma (6/14, 42.9%), respectively.IDs still represent the most common causes of FUO. Regularly intermittent fever with urinary infections and irregularly intermittent fever with infective endocarditis may be regarded as some signs in clinical diagnosis of FUO.

Childhood Brucellosis in Eastern India

To investigate the presence of childhood brucellosis presenting as PUO (pyrexia of unknown origin) cases in Eastern zone of India. Blood samples were collected from PUO patients aged ≤18y. The main diagnostic tools were STAT, RBPT, ELISA- IgM, IgG and PCR. Although mainly PUO cases were selected for the study, other associated clinical manifestations were also noted. The findings revealed significantly higher percentage of infection in female children (14.3%) than in male children (10.9%). The positive results by different diagnostic tools, STAT, RBPT, ELISA- IgM, ELISA-IgG and brucella genus specific PCR were 10.6%, 7.2%, 7.2%, 0.85% and 1.3% respectively. Main associated clinical symptoms were joint pain, low backache, fatigue and night sweat. This hospital based study reflects a significant number of childhood brucellosis cases in Eastern zone of India, and thus emphasizes the need for further monitoring of such subjects.

Classical Fever of Unknown Origin: Retrospective Study in Infectious Clinical Hospital №2

BackgroundDespite the recent advances in medicine, fever of unknown origin (FUO) remains a diagnostic and therapeutic challenge even to expert physicians. The etiological structure of FUO is determined by many factors, including the one where a person lived and where has been hospitalized. The aim of this study is to investigate the etiology and clinical characteristics of adult classical FUO with more diagnostics available and to analyze the factors for certain disease categories.MethodsThe clinical data were retrospectively analyzed from 80 patients with cFUO hospitalized at the Infectious Clinical Hospital №2 between October 2015 and October 2016 the patients who met the D.Durack criteria (1) An axillary temperature of >38.0 which corresponds oral temperature of >38.3; (2) illness duration is more than 3 weeks; (3) there is no definite diagnosis after three outpatient visits or 3 days in the hospital with intensive investigations; (4) the fever is not related to FUO of other groups: nosocomial FUO, FUO in patients with AIDS, neutropenia were included.ResultsOf the 80 FUO cases, 70 were positively diagnosed with a diagnosis rate of 87,5%. Infectious diseases were still the primary causes of FUO 63% (n = 50). Among them the most frequent diagnoses were bacterial infection of unspecified site 12.5% (n = 10), infective endocarditis 11% (n = 9), as well as pneumonia 7.5% (n = 6) and viral infections of unspecified site 7.5% (n=6). Connective tissue diseases and other noninfectious inflammatory diseases accounted for 17.5% of the FUO cases among which SLE and autoimmune thyroiditis were the most common etiologies and made up 5% (n = 4) and 3,75% (n = 3), respectively. Neoplasms were 8% (n = 6) in our sample. Also ten patients (12,5%) could not be confirmed until they were discharged from hospital.ConclusionInfectious diseases are the major causes of FUO, and the most common cause is bacterial infection of unspecified site. To determine the etiology was difficult due to the limited conditions of the clinical hospital. Infectious endocarditis was found on the second place. The most common causative agents of infective endocarditis were MRSA (3/9) и streptococcus viridans (4/9). The frequency of undiagnosed cases was increasing, but in most FUO cases the causes can be diagnosed eventually after careful analysis of clinical data.Disclosures All authors: No reported disclosures.

Weil-Felix Test - A Diagnostic Tool for Rickettsial Diseases

Rickettsial diseases are generally classified under the causes of pyrexia of unknown origin (PUO) and high prevalence of this disease is found in developing countries like India. Diagnosis in such cases is difficult because early sign and symptoms are non-specific and varied. Mortality may be as high as 30-40% if untreated. Weil Felix in one of the cheapest screening method available for laboratory diagnosis of rickettsial diseases but the major drawback of this method is its less sensitivity. A prospective testing was carried out in clinical pathology department in Haffkine Institute as a routine testing for the patients who are advised for extended Widal test. These patients comes from the various government hospitals, private hospitals and tertiary care centres. The serum samples from 1464 PUO cases which included patients of all age group and from both government and private hospitals, were subjected to Weil–Felix test (R.K. Diagnostics, Malad, Mumbai, India). The test was performed according to the manufacturer’s instructions. Titers of ≥ 1:80 for OX K, OX 2 and OX 19 were considered significant. Of 1464 samples, rickettsial diseases were detected in 485(33.13%) samples. Seropositivity was higher among male subjects 262(54.02%) when compared with female subjects 223(45.98%) Most of the positive cases were in 5-10 age group. Prevalence of rickettsial diseases 485(33.13%) is significantly high, especially in children’s and hence should be included in the differential diagnosis of PUO.