Maternal, Fetal, and Neonatal Outcomes of Gestation in Women with and Without Brucella Infection.

BACKGROUND: Maternal, fetal, and neonatal complications of brucellosis in pregnant women are probably higher than those in the general population. This comparative study aimed to survey the mentioned complications in pregnant women with positive and negative Brucella serologic tests. STUDY DESIGN: This is a prospective cohort study. METHODS: In this study, 2160 pregnant women residing in the rural area of Hamadan province were screened for Brucella infection by agglutination test. Then, 106 (4.90%) pregnant women with a positive test (exposed group) were compared with 210 subjects (non-exposed group) who were randomly selected from more than 2000 pregnant women with a negative serological test in terms of maternal, fetal, and neonatal outcomes from October 2018 to March 2020. Data were analyzed by SPSS 20 software at a 95% confidence level. RESULTS: The mean age of mothers in both exposed and unexposed groups was 27.84±6.13 and 38.71±6.85 years, respectively. Past medical history of brucellosis, animal contact, and the consumption of unpasteurized dairy products were reported to be 14 (13.2%), 63 (59.4%), and 82 (77.4%), respectively, in the exposed group. The mentioned measures were 3 (1.5%), 109 (51.9%), and 54 (26.9%) in the unexposed group, respectively. Among exposed and unexposed groups, the incidence of abortion was 9 (8.6%) and 5 (2.4%) with P=0.005, intrauterine fetal death was 2 (1.9%) and zero with P=0.211, low birth weight was 10 (10.6%) and 7 (3.4%) with P=0.012, and premature birth was 15 (15.2%) and 18 (8.8%) with P=0.066, respectively. CONCLUSION: Brucella infection in pregnant women appears to be associated with the risk of miscarriage, low birth weight, and premature birth.

If You're Not Confused, You're Not Paying Attention: Ochrobactrum Is Not Brucella.

Bacteria of the genus Brucella are facultative intracellular parasites that cause brucellosis, a severe animal and human disease. Recently, a group of taxonomists merged the brucellae with the primarily free-living, phylogenetically related Ochrobactrum spp. in the genus Brucella. This change, founded only on global genomic analysis and the fortuitous isolation of some opportunistic Ochrobactrum spp. from medically compromised patients, has been automatically included in culture collections and databases. We argue that clinical and environmental microbiologists should not accept this nomenclature, and we advise against its use because (i) it was presented without in-depth phylogenetic analyses and did not consider alternative taxonomic solutions; (ii) it was launched without the input of experts in brucellosis or Ochrobactrum; (iii) it applies a non-consensus genus concept that disregards taxonomically relevant differences in structure, physiology, population structure, core-pangenome assemblies, genome structure, genomic traits, clinical features, treatment, prevention, diagnosis, genus description rules, and, above all, pathogenicity; and (iv) placing these two bacterial groups in the same genus creates risks for veterinarians, medical doctors, clinical laboratories, health authorities, and legislators who deal with brucellosis, a disease that is particularly relevant in low- and middle-income countries. Based on all this information, we urge microbiologists, bacterial collections, genomic databases, journals, and public health boards to keep the Brucella and Ochrobactrum genera separate to avoid further bewilderment and harm.

Tick-Borne Encephalitis Virus and Borrelia burgdorferi Seroprevalence in Balkan Tick-Infested Individuals: A Two-Centre Study.

Lyme borreliosis (LB) and tick-borne encephalitis (TBE) are important tick-borne diseases in Europe. This study aimed to investigate the seroreactivity against Borrelia burgdorferi and TBE virus (TBEV) in tick-infested individuals in North Macedonia and Serbia. Serum samples were collected from tick-infested individuals and from healthy individuals in the same regions. Samples were tested for anti-Borrelia IgG reactivity and TBEV-neutralizing antibodies. Results showed higher seroreactivity against Borrelia antigens in patients and healthy donors from Novi Sad compared to those from the Skopje region. However, there was no statistically significant difference between tick-infested patients and healthy donors within each region. No TBEV-neutralizing antibodies were detected in participants from Novi Sad or in the control groups, except for one person from North Macedonia who had a moderate TBEV-neutralizing reaction. The study highlights the need for improved surveillance and diagnostic capabilities for LB and TBE in these regions. It also suggests the potential existence of TBEV foci in North Macedonia. The findings provide a complementary understanding of the LB and TBE epidemiology in the studied regions; however, further research is needed to investigate the presence and distribution of Borrelia spp. and TBEV in ticks to assess the significance of detected seroreactivity.

Epidemiological and clinical characteristics of imported falciparum malaria in the Republic of North Macedonia : A 13-year experience.

BACKGROUND: Plasmodium falciparum is the leading cause of imported malaria and the most common cause of death in returning travellers. AIM: To identify the main epidemiological and clinical characteristics of patients with imported falciparum malaria in the Republic of North Macedonia. MATERIAL AND METHODS: Retrospectively analyzed were the epidemiological and clinical features of 34 patients with imported falciparum malaria who were diagnosed and treated at the university clinic for infectious diseases and febrile conditions in Skopje from 2010 to 2022. Malaria diagnosis was based on the microscopic detection of parasites in thick and thin blood smears. RESULTS: All patients were male, with a median age of 36 years and a range of 22-60 years. Of the patients 33 (97.1%) acquired the disease in Sub-Saharan Africa. All patients except one stayed in endemic regions for work/business purposes. Chemoprophylaxis was completely applied in 4 (11.8%) patients. The median time of onset between the symptoms and diagnosis was 4 days, with a range of 1-12 days. Prevailing clinical manifestations were fever, chills, and splenomegaly in 100%, 94%, and 68% of patients, respectively. Severe malaria was noticed in 8 (23.5%) patients. In 5 (14.7%) patients the initial parasitemia was higher than 5%. On admission, thrombocytopenia, hyperbilirubinemia, and elevated alanine aminotransferase were registered in 94%, 58%, and 62% of patients, respectively. Out of the 33 patients with adequate follow-up, the outcome was favorable in 31 (93.9%). CONCLUSION: In every febrile traveller returned from Africa, imported falciparum malaria should be an essential part of differential diagnostic considerations.

CD150-dependent hematopoietic stem cell sensing of Brucella instructs myeloid commitment.

So far, hematopoietic stem cells (HSC) are considered the source of mature immune cells, the latter being the only ones capable of mounting an immune response. Recent evidence shows HSC can also directly sense cytokines released upon infection/inflammation and pathogen-associated molecular pattern interaction while keeping a long-term memory of previously encountered signals. Direct sensing of danger signals by HSC induces early myeloid commitment, increases myeloid effector cell numbers, and contributes to an efficient immune response. Here, by using specific genetic tools on both the host and pathogen sides, we show that HSC can directly sense B. abortus pathogenic bacteria within the bone marrow via the interaction of the cell surface protein CD150 with the bacterial outer membrane protein Omp25, inducing efficient functional commitment of HSC to the myeloid lineage. This is the first demonstration of direct recognition of a live pathogen by HSC via CD150, which attests to a very early contribution of HSC to immune response.

Antimicrobial resistance profiles of human Brucella melitensis isolates in three different microdilution broths: the first multicentre study in Bosnia and Herzegovina.

OBJECTIVES: Brucellosis is a ubiquitous emergent bacterial zoonotic disease causing significant human morbidity in Bosnia and Herzegovina. So far, a high rate of resistant Brucella has been found worldwide. This study prospectively analysed the rates of resistance among human Brucella melitensis strains isolated in Bosnia and Herzegovina. METHODS: This study included 108 B. melitensis isolates from 209 patients diagnosed at five medical centres in Bosnia and Herzegovina. The resistance profiles of the B. melitensis isolates for the 13 most commonly used antimicrobials were studied in standard Brucella broth (BB) and cation-adjusted Mueller-Hinton broth (CAMHB) supplemented with 4% lysed horse blood or 5% defibrinated sheep blood. RESULTS: Of the 209 patients, B. melitensis blood cultures were positive for 111 (53.1%). Among the 108 isolates investigated, 91 (84.3%) were resistant to trimethoprim-sulfamethoxazole on BB, but not on either CAMHB. Nearly all isolates (>90%) were resistant to azithromycin on BB and both CAMHBs. CONCLUSION: We observed a high rate of B. melitensis resistance to azithromycin. The high rate of resistance to trimethoprim-sulfamethoxazole that we observed was related to BB, so an alternative broth should be used, such as the enriched CAMHBs in this study, for evaluating resistance to trimethoprim-sulfamethoxazole. Whole-genome sequencing studies are needed to understand the development of antimicrobial resistance in B. melitensis strains isolated from humans.

Caractéristiques épidémiologiques de la brucellose humaine dans la province d'El-Oued, sud-est algérien.

INTRODUCTION: Brucellosis, the most common zoonosis globally, is considered a major public health problem. OBJECTIVE: A retrospective study was carried out over 21 years (1998-2018) to determine the epidemiological features of human brucellosis in the province of El-Oued (south-eastern Algeria). RESULTS: 1,832 confirmed cases of human brucellosis were reported during the study period, with an average incidence rate of around 12.26 cases per 100,000 inhabitants. The annual distribution of the incidence was characterized by an increasing trend and a strong fluctuation ; its values ranged between 2.27 and 24.96 per 100,000 inhabitants. The monthly distribution showed that the highest incidence rates were recorded from mid-February to July, with a peak of 2.74 cases per 100,000 inhabitants in April.Human brucellosis has affected all municipalities. The highest incidence rate was observed in border municipalities such as Ben Guecha and Oum Tiour (89.76 and 66.14 per inhabitants, respectively).The incidence in the male population was higher than that of the female at 14.63 versus 9.83 per 100,000 inhabitants, respectively, noting that it increases with age. Individuals over 65 years are the most at risk, with an incidence rate of 22.32 per 100,000 inhabitants. CONCLUSION: Along with strengthening preventive measures in the population, eliminating brucellosis in animals is the most effective method to protect humans against infection.

Evaluation of severity scoring systems in patients with severe community acquired pneumonia.

Background. The aim of this study was to evaluate the ability of severity scoring systems to predict 30-day mortality in patients with severe community-acquired pneumonia. Methods. The study included 98 patients aged ≥18 years with community acquired pneumonia hospitalized at the Intensive Care Unit of the University Clinic for Infectious Diseases in Skopje, Republic of North Macedonia, during a 3-year period. We recorded demographic, clinical and common biochemical parameters. Five severity scores were calculated at admission: CURB 65 (Confusion, Urea, Respiratory Rate, Blood pressure, Age ≥65 years), SCAP (Severe Community Acquired Pneumonia score), SAPS II (Simplified Acute Physiology Score), SOFA (Sequential Organ Failure Assessment Score) and MPM (Mortality Prediction Model). Primary outcome variable was 30-day in-hospital mortality. Results. The mean age of the patients was 59.08 ± 15.76 years, predominantly males (68%). The overall 30-day mortality was 52%. Charlson Comorbidity index was increased in non-survivors (3.72 ± 2.33) and was associated with the outcome. All severity indexes had higher values in patients who died, that showed statistical significance between the analysed groups. The areas under curve (AUC) values of the five scores for 30-day mortality were 0.670, 0.732, 0,726, 0.785 and 0.777, respectively. Conclusion. Widely used severity scores accurately detected patients with pneumonia that had increased risk for poor outcome, but none of them individually demonstrated any advantage over the others.

The current therapeutical strategies in human brucellosis.

Prompt and adequate treatment of human brucellosis continues to be the most important strategy in its management, as eradication of animal brucellosis is not possible so far, and there is no adequate vaccine for humans. The goal of antibrucellar treatment is to alleviate and shorten the symptomatic period and reduce complications, relapses, and chronicity. Contemporary trends in the treatment of human brucellosis are postulated on the ability of Brucellae to persist in host macrophages through the inhibition of phagolysosome fusion and to survive for prolonged periods intracellularly without restricting basic cellular functions. As a result of this and despite satisfactory antibiotic treatment, relapses and therapeutical failures are inevitable to a certain degree. The current principles for the treatment of brucellosis advocate for a long enough treatment duration combined with antimicrobial regimens that possess activity in the intracellular acidic environment. In the future, other antimicrobial agents, immunomodulation, decrease in the intracellular acidic environment, or development of agents that would act on well-defined molecular bacterial targets, might be incorporated to improve the therapeutical effects.

Seroprevalence of Brucellosis among General Population in Famenin City, Western Iran in 2016: The Famenin Brucellosis Cohort Study.

BACKGROUND: Brucellosis is endemic in Iran with a higher level of endemicity in western areas, including the Hamadan province. This study aims to define the seroprevalence of brucellosis and it,s risk factors in general the population of Famenin, Hamadan province, in western Iran. METHODS: This survey was conducted on 2367 participants in Famenin and its villages from September to November 2016. After receiving written consent from subjects, demographic information was obtained through questionnaires and 10cc blood samples were taken from the participants. Blood samples were sent to the Core facility of Hamadan University of Medical Sciences and were tested using Wright and 2ME kits (Pasteur Institute, Iran) for serological detection of brucellosis. The seroprevalence of brucellosis was reported as percentage with 95% confidence interval (CI). RESULTS: Totally, 2367 individuals with the mean age (SD) of 34.6 (20.9) (range: 2 to 95) years were enrolled. Of these, 1060 (44.8%) were men and 1610 (68.0%) lived in rural areas. The seroprevalence of brucellosis according to the Wright titer (equal to or greater than 1:80) was 6.6% (95% CI: 5.62%, 7.66%). The corresponding prevalence based on 2ME titers (equal to or greater than 1:40) in subjects with positive Wright test was 37.2% (95% CI: 29.5%, 44.84%). We saw a significant association between the incidence of brucellosis and occupation (P < 0.001) and type of contact with livestock (P = 0.009) as two important risk factors. CONCLUSION: The seroprevalence of brucellosis in Famenin population was considerable. Contact with livestock, animal husbandry, farming and history of brucellosis were risk factors for brucellosis infection.

Prevalence of Rotaviruses in the Etiology of Acute Diarrhea in Young Children, Clinical forms, Extraintestinal Manifestations and Complications.

Rotavirus is highly contagious factor with dominant feces-oral transmission. Because it is stable in external environment, transmission clusters are possible by close contact, ingestion of contaminated water or food or contact with contaminated surfaces. It survives within hours and days on hands and contaminated surfaces. This makes it the most common enteric and nosocomial pathogen in the world, especially in early childhood. In addition to the rapid dehydration with pronounced electrolyte disturbances, numerous extraintestinal possibilities have been recorded in the clinical picture, which emphasizes the need for prevention of this disease.In the period from 1.02.2018 to 31.01.2020 at the Clinic for Infectious diseases were treated 1060 patients with diarrheal disease, of which 502 children (47.36%). Rotavirus etiology was confirmed in 23.30% of the children. According to the protocols, laboratory and biochemical investigations were done to all 117 children, with tracking parameters and their dynamics of admission and discharge from the hospital. Most of the children, 84 (82.0 6%) are from urban areas, with a more confirmed epidemiological survey of 59 (42.00%). The average age of the children was 8 months, with a small percentage of children on maternal food (breastfed 25, i.e. 21.37%), with high febrile admission in 99% of children with an average temperature of 38.5oC and an average febrile duration of 4 days, with an average of 7 (+ 2.49) of stools and 5 (+ 2.12) of vomiting. There was a significant difference in hematocrit, leukocyte, electrolyte, glycaemia, and CRP values on admission and discharge. There was predominant isonatremic dehydration, and the compensatory mechanisms followed by the values of the electrolytes ABS, Ph, BE showed a tendency to maintain within the physiological limits. The clinical picture of extraintestinal manifestations included bronchitis, mesenteric lymphadenitis, upper respiratory infections and rash.Rotavirus infection is a serious health and economic problem in our country, so it needs continuous prevention and monitoring in order to reduce the incidence, and thus the need for hospitalization and cure of rotavirus disease.

Cat Scratch Disease: The First Case Report in Republic of North Macedonia.

Cat scratch disease (CSD) is the main clinical manifestation caused by Bartonella henselae in immuno-competent patients. The bacterium is transmitted to humans from cats via scratches or bites. In this case report, we are presenting to our knowledge the first etiologically confirmed case of CSD in our country. Here we describe the case of a previously healthy adult female patient presenting with fever and axillar lymphadenopathy over 1-month period. She underwent numerous clinical and paraclinical investigations for potential etiologies associated with lymphadenopathy and fever. Finally, serological testing for B.henselae was performed with titers for IgG 1:1024 and 1:160 for IgM, which confirmed the diagnosis. Five-day treatment with azithromycin resulted with good clinical response and complete recovery. We proved that CSD is a reality in our country and this report should raise awareness in medical doctors, especially infectious disease specialist. Also, CSD should be included in differential diagnosis in patients with fever of unkown origin (FUO), who are presenting with regional lymphadenopathy, with or without history of cat contact.

Brucellosis in pregnancy: case reports with different outcomes in an endemic region.

Different outcomes of brucellosis in pregnancy regarding the fetus/neonate and the mother are described. Medical records of five pregnant women with brucellosis were retrospectively analyzed. Patients were treated in several departments of infectious diseases in the Republic of Macedonia between 1995 and 2009. The diagnosis of brucellosis was based on clinical findings compatible with the disease supported by detection of specific antibodies. Pregnancy outcomes in patients were as follows: spontaneous abortion, intrauterine fetal death, premature delivery in two cases (one with twin pregnancy) and term delivery. One of the women experienced relapse. Follow-up results of neonates showed no infection and their normal growth and development. Brucellosis, especially if acquired in early pregnancy, can have an impact on pregnancy outcome. In endemic regions, in pregnant women with persisting fever and unspecific manifestations one should always have in mind brucellosis. In these areas, cases with unexplained spontaneous abortion, intrauterine fetal death and premature delivery should also be investigated for brucellosis.

Human brucellosis in pregnancy - an overview.

Human brucellosis during pregnancy is characterized by significantly less pronounced adverse obstetric outcomes than in animals, but with remarkably more adverse obstetric outcomes when compared to healthy pregnant women. Seroprevalence of brucellosis in pregnancy and cumulative incidence of brucellosis cases per 1000 delivered obstetrical discharges in endemic regions were reported to be 1.5-12.2% and 0.42-3.3, respectively. Depending on the region, the frequency of pregnant women in the cohorts of patients with brucellosis was from 1.5% to 16.9%. The most common and the most dramatic unfavorable outcomes during brucellosis in pregnancy are the obstetric ones, manifested as abortions (2.5-54.5%), intrauterine fetal death (0-20.6%), or preterm deliveries (1.2-28.6%), depending on the stage of pregnancy. Other unfavorable outcomes due to brucellosis are addressed to infant (congenital/neonatal brucellosis, low birth weight, development delay, or even death), the clinical course of disease in mother, and delivery team exposure. When diagnosed in pregnant women, brucellosis should be treated as soon as possible. Early administration of adequate therapy significantly reduces the frequency of adverse outcomes. Rifampicin in combination with trimethoprim-sulfamethoxazole for 6 weeks is the most commonly used and recommended regimen, although monotherapies with each of these two drugs are also widely used while waiting for the results from prospective randomized therapeutic trials. As no effective human vaccine exists, screening of pregnant women and education of all women of childbearing age about brucellosis should be compulsory preventive measures in endemic regions.

Acute Thyroiditis Associated with Brucellosis: A Case Report.

Brucella thyroiditis represents an extremely rare focal form of brucellosis. In this case report we describe a 55 years old male, diagnosed with brucellosis and peripheral arthritis with subsequent development of acute thyroiditis. The symptoms duration consistent with brucellosis started two weeks before establishing the diagnosis. Only a day after diagnosis and initiation of antibrucellar treatment, acute non-suppurative thyroiditis suddenly manifested. Thyroiditis was diagnosed with clinical inspection and confirmed by ultrasound investigation. With the appropriate antibrucellar treatment, complete cure of thyroid affection was reached in ten days and the patient remained well during the follow-up period of two and a half years. In conclusion, in brucellosis endemic regions brucellosis should be included in the diagnostic consideration in patients with acute non-suppurative thyroiditis. Early recognition and adequate treatment of brucella thyroiditis results in favorable outcome.

Characteristics of an Outpatient Cohort with HBeAg-Negative Chronic Hepatitis B.

BACKGROUND: Patients with hepatitis Be antigen-negative chronic hepatitis B (HBeAg-negative CHB), and patients' inactive carriers (IC) have similar laboratory and serologic characteristics and are not always easy to distinguish. AIM: To characterise hepatitis Be antigen (HBeAg) negative chronic hepatitis B cohort based on their laboratory and virology evaluations at one point of time. METHODS: A prospective non-randomized study was conducted on 109 patients with HBeAg negative chronic hepatitis B treated as outpatients at the Clinic for Infectious Diseases and Febrile Conditions. All patients underwent laboratory and serology testing, quantification of HBV DNA and HBs antigen (qHBsAg). RESULTS: A group of 56 patients were inactive carriers (IC), and 53 patients had HBeAg-negative CHB (AH). The mean values of ALT, HBV DNA and qHBsAg in IC were 29.13 U/L; 727.95 IU/ml and 2753.73 IU/ml respectively. In the AH group, the mean values of ALT, HBV DNA and quantitative HBsAg were 50.45 U/L; 7237363.98 IU/ml and 12556.06 IU/ml respectively. The serum value of ALT was more influenced by qHBsAg than HBV DNA in both IC and AH groups (R = 0.22 vs R = 0.15) (p > 0.05). CONCLUSION: patients with inactive and active HBeAg-negative CHB have similar laboratory and serology profile. It is necessary to combine analysis of ALT, HBV DNA and qHBsAg for better discrimination between patient's IC and patient with HBeAg-negative CHB.

The influence of illness duration before diagnosis on clinical characteristics and outcome in human brucellosis.

Our study assesses the influence of illness duration before establishing the diagnosis of brucellosis and initiating therapy on patients' main clinical characteristics and outcome in an endemic area. The medical files of 297 patients with brucellosis were retrospectively analysed. They were divided into four groups according to illness duration before initiating therapy: <10 days; 11-30 days; 31-90 days; and >90 days. There were significant differences in the occurrences of fever (P = 0.019), focal forms (P = 0.026), spondylitis (P = 0.034) and therapeutic failures (P = 0.006) between the groups. Duration of >30 days before treatment initiation is responsible for more serious clinical presentation and outcome, whereas illness duration of >90 days further worsens the clinical progression in human brucellosis.

Brucellosis in pregnancy: results of multicenter ID-IRI study.

Brucellosis in pregnant women is reported to be associated with obstetric complications (OCs), and adequate data for human brucellosis during pregnancy are largely lacking. We performed this multicenter retrospective cross-sectional study to evaluate the epidemiology, clinical course, treatment responses, and outcomes of brucellosis among pregnant women. The study period comprised a 14-year period from January 2002 to December 2015. All consecutive pregnant women diagnosed with brucellosis in 23 participating hospitals were included. Epidemiological, clinical, laboratory, therapeutic, and outcome data along with the assessment data of the neonate were collected using a standardized questionnaire. Data of 242 patients were analyzed. The OC rate was 14.0% (34/242) in the cohort. Of the 242 women, 219 (90.5%) delivered at term, 3 (1.2%) had preterm delivery, 15 (6.2%) aborted, and 5 (2.1%) had intrauterine fetal demise. Seventeen (7.0%) of the newborns were considered as low birth weight. Spontaneous abortion (6.1%) was the commonest complication. There were no maternal or neonatal deaths and pertinent sequelae or complications were not detected in the newborns. Splenomegaly (p = 0.019), nausea and/or vomiting (p < 0.001), vaginal bleeding (p < 0.001), anemia (blood hemoglobin < 11 g/dL; p < 0.001), high level of serum aspartate aminotransferase (> 41 IU/L; p = 0.025), oligohydramnios on ultrasonography (p = 0.0002), history of taking medication other than Brucella treatment during pregnancy (p = 0.027), and Brucella bacteremia (p = 0.029) were the significant factors associated with OCs. We recommend that pregnant women with OC or with fever should be investigated for brucellosis if they live in or have traveled to an endemic area.

The changing pattern of fever of unknown origin in the Republic of North Macedonia.

INTRODUCTION: The study aimed to compare the etiologic spectrum of diseases causing fever of unknown origin (FUO) and methods for definitive diagnosis in a tertiary care hospital in the Republic of North Macedonia during two different time periods. PATIENTS AND METHODS: There were analysed retrospectively the causes for FUO and final diagnostic approaches in 185 patients with classic FUO that were treated at the University Hospital for Infectious Diseases in Skopje during two time periods. Seventy nine patients were treated during 1991 to 1995 and 106 patients during 2011 to 2015. RESULTS: When comparing these two periods, infections were present in 46.8% and 29.2% (p = 0.014), non-infective inflammatory disorders in 22.8% and 25.5% (p = 0.674), neoplasms in 10.1% and 13.2% (p = 0.522), miscellaneous in 8.9% and 12.3% (p = 0.461) and undiagnosed cases in 11.4% and 19.8% (p = 0.124), respectively. The most common causes for FUO during the first period were abscesses (8.9%), tuberculosis and systemic lupus erythematosus (7.6% each), whereas in the second period the commonest causes were adult onset Still disease and solid organ neoplasm (7.6% each), polymyalgia rheumatica, abscesses and visceral leishmaniasis (5.7% each). The newer imaging techniques and clinical course evaluation had superior diagnostic significance during the second period. CONCLUSION: A changing pattern of diseases causing FUO during the examined periods was evident. Infections continue to be the most common cause but with decreasing incidence when compared to 20 years ago. Even nowadays clinical evaluation and follow-up still remain the vital diagnostic tools in determining the etiology of FUO.