Infectious Causes Of Fever Of Unknown Origin Research Articles

Highlighting the Role of Infections in the Etiology of Fever of Unknown Origin Pointing out Toxoplasmosis; in Port Said Governorate

Background and study aim: Fever of unknown origin (FUO) is a state of febrile illness for more than three weeks, with a body temperature greater than 38.3 °C on several occasions and uncertain diagnosis. Conditions blamed for FUO were categorized as infectious diseases, non-infectious inflammatory diseases, neoplasms along with miscellaneous causes. This study aims to identify the infectious causes of FUO counting the parasitic causes in Port-Said Fever Hospital/ Egypt. Patients and Methods: 341 patients admitted to Port-Said Fever Hospital/ Egypt during the period from November 2017 till May 2018 complaining of prolonged fever ≥ 3 weeks, without a definite diagnosis, were included in this study. Complete history taking and clinical data including pattern, duration and degree of temperature, in addition to other co-morbidities, radiological examination, laboratory investigations, and clinical evaluation were reported for each patient. Results: The majority of affected cases were adult males, lived in urban areas, and were in contact with animals. Luncheon and beef were the commonest types of consumed food among the studied population. The uppermost detected infection was tuberculosis (17%) followed by typhoid and Brucella infection (11.7% for each), toxoplasmosis and hepatitis were detected in 2.9% and 1.8% respectively. After investigations, 5.9% of the studied group had hepato-splenomegaly and 77.4% of them presented with lymphocytosis. Clinically, 78.9% of patients had lymphadenopathy and 1.8% had jaundice. Additionally, 75.4% of cases presented with an intermittent fever while 24.6% with continuous fever. Approximately 57.2% of them had fever for three weeks and the majority of patients had fever ≥ 39°c. Conclusion: Tuberculosis, typhoid fever, and brucellosis signified the major identified infectious causes for FUO in Port Said governorate/Egypt. Toxoplasmosis can be represented as one of FUO infectious causes. Patients with toxoplasmosis either presented with lymphadenopathy or not, all of them had hepatosplenomegaly, high CRP, leucocytosis, and eosinophilia.

Fever of unknown origin caused by infectious diseases in the era of migrant and refugee crisis.

Concern exists in Europe about the possibility of importation of infectious diseases due to the recent influx of migrants and refugees after 2011. In this retrospective 6-year study, we examined the epidemiology of fever of unknown origin (FUO) in Greece over the past years. Forty-eight patients with classical FUO were included. The proportion of infectious causes of FUO (29.2%) was similar to previous studies in Greece and all infections were endemic to the area. Disease-related mortality was 12.5% and no deaths due to infection were recorded. In conclusion, none of the diagnosed infectious causes of FUO raised concerns about the possibility of imported diseases or pathogens. These results re-inforce the perception that migrants and refugees are not carriers of communicable diseases that can cause public health problems to European countries.

Clinico-epidemiological profile of fever of unknown origin in an Egyptian setting: A hospital-based study (2009-2010).

Fever of unknown origin (FUO) is one of the most challenging diagnostic dilemmas in the field of infectious diseases and tropical medicine. Clinicians should use the frequency distribution of disorders causing FUO to guide their diagnostic approach in patients with prolonged, unexplained fevers meeting the definition of FUO. The present study was undertaken to examine the etiologies, clinico-epidemiologic profile, and prognosis of classical FUO in patients reporting to the Alexandria Fever Hospital in Egypt. Records of 979 patients admitted to the fever hospital (from January 2009 to January 2010) and diagnosed as having FUO were examined carefully. FUO was defined as three outpatient visits or three days in the hospital without elucidation of cause of fever. A total of 979 cases (57.0% males and 43.0% females), with ages ranging from 0.2 to 90 years, were investigated. The mean duration of fever before hospitalization was 31 ± 10 days. The etiology of FUO was delineated in 97% of cases, and only 3% remained undiagnosed. Diagnoses were grouped into five major categories. Infectious causes of FUO were strongly associated with better outcome (73.7% improved). Smoking, contact with animals or birds, drug addiction, and HIV seropositivity were important risk factors associated with infections. Infections are the most common cause of FUO, followed by collagen vascular diseases, in our region. A three-step diagnostic work-up approach is recommended to be applied in Egypt in order to improve the quality of medical service provided to FUO patients.

Fever of unknown origin (FUO) due to large B-cell lymphoma: The diagnostic significance of highly elevated alkaline phosphatase and serum ferritin levels

BackgroundDetermining the cause of fever of unknown origin (FUO) is often a vexing and difficult diagnostic process. In most cases, the signs and symptoms in adult FUOs suggest a malignant, infectious, or rheumatic/inflammatory etiology. The diagnosis of FUO may be narrowed if specific findings are present (eg, hepatosplenomegaly) that limit the diagnostic possibilities. Infectious causes of FUO with hepatosplenomegaly include miliary tuberculosis, typhoid fever, and visceral leishmanosis (kala-azar). However, FUOs with hepatosplenomegaly are most often attributable to malignant neoplasms, ie, Hodgkin lymphoma, non-Hodgkin lymphoma, hepatoma, hypernephroma (renal-cell carcinoma), or preleukemia. Methods and ResultsWe present a middle-aged woman with FUO and hepatosplenomegaly. Inpatient nonspecific laboratory findings included a highly elevated erythrocyte sedimentation rate, and elevated levels of vitamin B12, lactate dehydrogenase, angiotensin-converting enzyme, ferritin, and alkaline phosphatase. These individual findings are nonspecific, but together point to a lymphoma. An important test in differentiating malignant from infectious FUOs is the Naprosyn test, and her Naprosyn test was positive, indicating malignancy. A gallium scan suggested a uterine lymphoma. A computed tomography scan revealed hepatosplenomegaly, but the gallium uptake was not increased in her liver and spleen. Uterine and bone marrow biopsies were negative for lymphoma. ConclusionWe present a case of FUO with hepatosplenomegaly attributable to large B-cell lymphoma as diagnosed via liver biopsy.

Infektionen als Ursache von Fieber unklarer Genese

Infectious diseases are important causes of fever of unknown origin (FUO). The spectrum of infectious agents is broad and diagnosis depends on careful evaluation of individual risk factors. Infectious diseases presenting as FUO are frequently atypical presentations of well known infections, e.g. tuberculosis or infectious endocarditis. In this review we present an overview of infectious causes of FUO classified into community acquired infections, nosocomial infections, and infections in immunocompromised hosts.

Fever of Unknown Origin: Analysis of 71 Consecutive Cases

Fever of unknown origin (FUO) is still an important problem in clinical practice. Evaluation of patient characteristics may clarify the utility of diagnostic tests and etiologies of FUO. Fever of unknown origin in 71 patients was investigated at Ankara Numune Education and Research Hospital in Turkey between February 2001 and December 2004. Mean hospital stay and fever duration was 20.5 days and 44 days, respectively. Etiologies of FUO were as follows: infections 32 (45.1%), collagen vascular disease 19 (26.8%), neoplasm 10 (14.1%), and miscellaneous diseases 4 (5.6%). Diagnosis remained obscure in 6 patients (8.5 %). Tuberculosis was found to be 40% of the infectious causes of FUO. Mean hospital stay and fever duration were prolonged in infectious cases. Female predominance was observed in collagen vascular diseases (P = 0.047). Splenomegaly and lymphadenopathy were common in the neoplasm group (P = 0.017, P = 0.017, respectively). Erythrocyte sedimentation rate, aspartate aminotransferase, alanine aminotransferase and lactate hydrogenase levels were elevated in patients with collagen vascular diseases. Nine (12.7%) patients died during the follow-up period. Hospital stay and fever duration were prolonged in the infectious group of FUO patients. Infectious diseases, particularly tuberculosis, were the most important cause of FUO in our series. Tuberculosis should be kept in mind as an important etiology of FUO countries where tuberculosis is endemic.

Fever of unknown origin (FUO) caused by multiple myeloma: The diagnostic value of the Naprosyn test

Fever of unknown origin (FUO) remains a difficult diagnostic problem. The causes of FUO have changed over the years. Neoplastic disorders have now displaced infectious diseases as the most common cause of FUOs. Most neoplasms are associated with no or low-grade temperatures, with some important exceptions. Hypernephromas and lymphomas are neoplasms typically associated with high spiking fevers or may present as FUOs. Hematologic malignancies, that is, the acute and chronic leukemias, myeloproliferative disorders, and multiple myeloma, do not usually present with acute fevers or as FUOs. We present an elderly male patient who presented with an FUO, whose history is significant for multiple myeloma in remission. Differential diagnostic possibilities in this patient included plasma cell leukemia, relapse of multiple myeloma, secondary/superimposed malignancy, or opportunistic infection. The main differential diagnosis for his FUO was between neoplastic and infectious disorders. As part of the diagnostic workup, a Naprosyn test (naproxen 375 mg [by mouth] every 12 hours for 3 days) was used to differentiate neoplastic from infectious causes of FUO in this patient. The Naprosyn test was positive, which indicated a neoplastic explanation for the patient's FUO and eliminated, along with the infectious disease workup, an infectious explanation for his FUO. The patient's FUO was finally determined to be the result of a relapse of multiple myeloma and not of a secondary malignancy or malignant transformation of myeloma into plasma cell leukemia. We conclude the Naprosyn test remains a valuable diagnostic test to use to narrow differential diagnostic possibilities in patients with FUOs when a malignancy is a diagnostic consideration.

Fever of unknown origin due to preleukemia/myelodysplastic syndrome: The diagnostic importance of monocytosis with elevated serum ferritin levels

Fever of unknown origin (FUO) is a common clinical diagnostic dilemma. In the elderly, causes of FUO most commonly include malignancy or infection, and less commonly include collagen vascular diseases. Among the collagen vascular diseases causing FUO in the elderly, polymyalgia rheumatica/temporal arteritis, and adult Still's disease (adult juvenile rheumatoid arthritis) are difficult diagnoses to prove. Among the infectious causes of FUO in the elderly are subacute bacterial endocarditis, intra-abdominal abscesses, and extrapulmonary tuberculosis. In the elderly, neoplastic causes of FUO include lymphomas, hepatomas, renal cell carcinomas, and hepatic or central nervous system metastases. Acute leukemias, particularly during "blast" transformation, may present as acute fevers in the absence of infection, but are rare causes of FUO. Preleukemia/myelodysplastic syndromes are exceedingly rare causes of FUO. We present a case of an elderly man who presented with findings that initially suggested adult Still's disease. Prolonged and profound monocytosis provided the key clue to his subsequent diagnosis of preleukemia/myelodysplastic syndrome. In this patient, a positive Naprosyn test result also suggested a neoplastic cause for his FUO. After months of prolonged fevers, myelocytes/metamyelocytes were eventually demonstrated in his peripheral smear during hospital evaluation. These findings, in concert with the persistent monocytosis, highly elevated ferritin levels, polyclonal gammopathy on serum protein electrophoresis, and eventual presence of myelocytes/metamyelocytes on peripheral smear, prompted a bone marrow test that demonstrated blast cells confirming the diagnosis of preleukemia myelodysplastic syndrome as the cause of this patient's FUO.

Fever of unknown origin in 185 paediatric patients: A single‐centre experience

Abstract Aim: We conducted a prospective study to evaluate the causes and outcome in children with fever of unknown origin (FUO). Methods: From 1990 to 1999, 185 children with FUO were evaluated. Initial evaluation included routine haematological analysis, Epstein‐Barr virus (EBV) serology, urine, stool or blood cultures, chest X‐ray and tuberculin probe. Results: In 131 (70%) patients diagnosis was established, and 70 (37.8%) had infectious disease. EBV infection was the most common infection followed by visceral leishmaniasis (VL), urinary tract infection (UTI) and tuberculosis. Autoimmune disorders were diagnosed in 24 (12.9%), Kawasaki disease in 12 (6.4%), malignant diseases in 12 (6.4%) and miscellaneous conditions in 15 (8.1%) patients. In the remaining 54 (30%) patients, diagnosis was not established and most of them had self‐limited disease. During the investigation, 26 (14%) patients developed serious organ dysfunction and five patients (two with virus‐associated haemophagocytic syndrome, one with VL and two unknown) died. Conclusion: The most important infectious causes of FUO in our study were EBV infection and VL. Kawasaki disease represented a significant cause of FUO at the beginning of our study because it was not recognized by primary‐care physicians. We report myelodysplastic syndrome as another emerging cause of paediatric FUO. Repeated clinical examination and careful use of specific laboratory examinations, invasive diagnostic procedures or imaging are crucial in approaching paediatric FUO.

Fever of unknown origin in 185 paediatric patients: A single-centre experience

We conducted a prospective study to evaluate the causes and outcome in children with fever of unknown origin (FUO). From 1990 to 1999, 185 children with FUO were evaluated. Initial evaluation included routine haematological analysis, Epstein-Barr virus (EBV) serology, urine, stool or blood cultures, chest X-ray and tuberculin probe. In 131 (70%) patients diagnosis was established, and 70 (37.8%) had infectious disease. EBV infection was the most common infection followed by visceral leishmaniasis (VL), urinary tract infection (UTI) and tuberculosis. Autoimmune disorders were diagnosed in 24 (12.9%), Kawasaki disease in 12 (6.4%), malignant diseases in 12 (6.4%) and miscellaneous conditions in 15 (8.1%) patients. In the remaining 54 (30%) patients, diagnosis was not established and most of them had self-limited disease. During the investigation, 26 (14%) patients developed serious organ dysfunction and five patients (two with virus-associated haemophagocytic syndrome, one with VL and two unknown) died. The most important infectious causes of FUO in our study were EBV infection and VL. Kawasaki disease represented a significant cause of FUO at the beginning of our study because it was not recognized by primary-care physicians. We report myelodysplastic syndrome as another emerging cause of paediatric FUO. Repeated clinical examination and careful use of specific laboratory examinations, invasive diagnostic procedures or imaging are crucial in approaching paediatric FUO.

Fever of unknown origin: Subacute thyroiditis versus typhoid fever

Fever of unknown origin (FUO) is not infrequently a diagnostic dilemma for clinicians. Common infectious causes include endocarditis and abscesses in adults, and noninfectious causes include neoplasms and certain collagen vascular diseases, for example, polymyalgia rheumatica, various vasculitides, and juvenile rheumatoid arthritis (adult Still's disease). Subacute thyroiditis is a rare cause of FUO. Among the infectious causes of FUO, typhoid fever is relatively uncommon. We present a case of FUO in a traveler returning from India whose initial complaints were that of left-sided neck pain and angle of the jaw pain, which initially suggested the diagnosis of subacute thyroiditis. After an extensive FUO workup, when typhoid fever is a likely diagnostic possibility, an empiric trial of anti- Salmonella therapy has diagnostic and therapeutic significance. The presence of relative bradycardia, and response to quinolone therapy, was the basis of the clinical diagnosis of typhoid fever as the explanation for this patients FUO. This case illustrates the diagnostic difficulties in assessing patients with FUO with few diagnostic findings.

Use of immunoscintigraphy in the diagnosis of fever of unknown origin.

Fever of unknown origin (FUO) has been defined as an elevation in temperature (38 degrees C) for at least 2-3 weeks despite intensive investigation. The value of immunoscintigraphy with the technetium-99m-labelled anti-granulocyte antibody anti-NCA-95 (BW 250/183, IgG1) was studied retrospectively in 34 consecutive patients with FUO. Every effort was made to confirm a diagnosis, including methods such as ultrasonography, computed tomography, magnetic resonance imaging, bacteriological tests, surgical intervention and clinical follow-up. In 58.8% of the patients, an infectious cause for the fever was found, in 30.2% of the patients, a benign or malignant haematological disease, pancreatitis or thyrotoxicosis was found. No cause for fever could be found in 11%. The overall diagnostic sensitivity and specificity of immunoscintigraphy for infection were 40% and 92% respectively. The positive predictive value was calculated to be 88% and the negative predictive value was calculated to be 52%. False-negative scans were especially noted in patients with endocarditis, pneumonia and small brain abscesses, where the lesions did not exceed a diameter of 0.5 cm. If patients with endocarditis were excluded, the imaging sensitivity and specificity were increased to 57% and 95%. This study demonstrates that 99mTc-anti-NCA-95 scanning is able to localize infectious causes of FUO, other than endocarditis.