National Laboratory Surveillance of Influenza in Macedonia during Four Seasons.

OBJECTIVE: The aim of the study is to comprehend results of the influenza lab surveillance system in the Republic of Macedonia after the 2009 pandemic and to determine the main characteristics of four consecutive epidemic seasons (from 2010/2011 until 2013/2014). METHODS: As part of the universal surveillance system, nasal and throat specimens were collected from patients. After extraction of RNA, the CDC real-time RT-PCR assays for the detection of influenza types and subtypes were performed. RESULTS: Out of 920 tested samples, 406 (44.1%) laboratory confirmed cases of influenza were found. Influenza activity begins as early as December and continues until the end of April with peaks in January or February with predominant influenza A and A/H1N1pdm. Influenza A viruses start their activity at week 49 to 52 and subside at week 17. Usually two peaks appear, the first one between week 2 and 4 and the second one between week 6 and 9. Subtype A/H1N1pdm was dominant among influenza A types in the 2010/2011 and 2012/2013 seasons. A/H3N2 was the only circulating influenza virus in the 2011/2012 season. Influenza B season is shorter and has only one peak, between weeks 2-5. Usually the influenza B viruses emerge in later stages than influenza A viruses, except for the first post-pandemic season. CONCLUSION: Results revealed that post-pandemic influenza seasons in Macedonia were rather different. Although the influenza season pattern is similar to patterns in some countries of the WHO European region, some unique characteristics were observed.

Efficacy and safety of moxifloxacin in community acquired pneumonia: a prospective, multicenter, observational study (CAPRIVI).

BACKGROUND: Community acquired pneumonia (CAP) is a major cause of morbidity, hospitalization, and mortality worldwide. Management of CAP for many patients requires rapid initiation of empirical antibiotic treatment, based on the spectrum of activity of available antimicrobial agents and evidence on local antibiotic resistance. Few data exist on the severity profile and treatment of hospitalized CAP patients in Eastern and Central Europe and the Middle East, in particular on use of moxifloxacin (Avelox®), which is approved in these regions. METHODS: CAPRIVI (Community Acquired Pneumonia: tReatment wIth AVelox® in hospItalized patients) was a prospective observational study in 12 countries: Croatia, France, Hungary, Kazakhstan, Jordan, Kyrgyzstan, Lebanon, Republic of Moldova, Romania, Russia, Ukraine, and Macedonia. Patients aged >18 years were treated with moxifloxacin 400 mg daily following hospitalization with a CAP diagnosis. In addition to efficacy and safety outcomes, data were collected on patient history and disease severity measured by CRB-65 score. RESULTS: 2733 patients were enrolled. A low severity index (i.e., CRB-65 score <2) was reported in 87.5% of CAP patients assessed (n=1847), an unexpectedly high proportion for hospitalized patients. Moxifloxacin administered for a mean of 10.0 days (range: 2.0 to 39.0 days) was highly effective: 96.7% of patients in the efficacy population (n=2152) improved and 93.2% were cured of infection during the study. Severity of infection changed from "moderate" or "severe" in 91.8% of patients at baseline to "no infection" or "mild" in 95.5% at last visit. In the safety population (n=2595), 127 (4.9%) patients had treatment-emergent adverse events (TEAEs) and 40 (1.54%) patients had serious TEAEs; none of these 40 patients died. The safety results were consistent with the known profile of moxifloxacin. CONCLUSIONS: The efficacy and safety profiles of moxifloxacin at the recommended dose of 400 mg daily are characterized in this large observational study of hospitalized CAP patients from Eastern and Central Europe and the Middle East. The high response rate in this study, which included patients with a range of disease severities, suggests that treatment with broader-spectrum drugs such as moxifloxacin is appropriate for patients with CAP who are managed in hospital. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT00987792.

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.

Comorbidities as Risk Factors for Acute and Recurrent Erysipelas.

BACKGROUND: Erysipelas is a common infectious skin disease. A typical feature of erysipelas, especially on the lower limbs, is the tendency to reoccur and the study aimed to define the comorbidities associated with it. AIM: We aimed to investigate systemic and local comorbidities in patients diagnosed with erysipelas on the lower limbs. MATERIAL AND METHODS: We conducted a retrospectively-prospective, population-based cohort study which included all patients diagnosed with erysipelas on the lower limbs, during two years. Patients were divided into two groups: patients with first episode and patients with recurrent erysipelas. These two groups were compared, with particular emphasis on systemic and local comorbidities. RESULTS: The study included 313 patients, of which 187 with the first episode of erysipelas and 126 with a recurrent. Regarding the analyzed systemic risk factors, the recurrent erysipelas was significantly associated with obesity (p < 0.0001), insulin dependent diabetes mellitus (p = 0.0015), history of malignant disease (p = 0.02) and tonsillectomy (p = 0.000001). For a p-value < 0.0001, significantly more frequent finding of peripheral arterial occlusive disease, chronic oedema/lymphoedema, fungal infections of the affected leg and chronic ulcer was confirmed in recurrent erysipelas. Neuropathy had 23% of the recurrent cases and 8.6% in patients without recurrence, and the difference was found to be significant for p = 0.0003. The only dissection of the lymph nodes was found more frequently in recurrent erysipelas (p = 0.017), but no associations with other analysed local surgery on the affected leg. Patients with recurrent erysipelas had ipsilateral coexisting dermatitis p = 0.00003 significantly more frequent. Minor trauma often preceded the first episode of erysipelas p = 0.005. CONCLUSION: Identification and treatment of modifiable risk factors are expected to reduce the risk of a subsequent episode of erysipelas on the lower limbs.

Clinical Presentation and Laboratory Characteristics in Acute and Recurrent Erysipelas.

AIM: Typical feature of erysipelas, especially on the lower limbs, is the tendency to reoccur. The study aimed to identify clinical and laboratory characteristics of acute and recurrent erysipelas. MATERIAL AND METHODS: We prospectively included patients diagnosed with erysipelas on the lower limbs in the period from January 2016 to December 2017. PATIENTS WERE DIVIDED INTO TWO GROUPS: patients with the first episode and recurrent erysipelas. The groups were compared by their demographics, clinical and laboratory characteristics. RESULTS: The study included 187 patients with the first episode of erysipelas and 126 patients with recurrent erysipelas. Both groups were homogeneous in terms of demographic characteristics, gender and age. Mean age of patients with the first episode of erysipelas was 64.18 ± 12.5 years; patients with recurrent erysipelas were inconsiderably mean younger (62.98 ± 12.5 years). Patients in both groups had a significantly different anatomical localisation of skin infection (p = 0.008). Tibial localisation was more frequent in patients with the first episode of erysipelas 77% vs 62.7%, while recurrent erysipelas was more frequent on the foot 36.5% vs 23%. No significant difference was found, about the affected side of the limb (p = 0.95). Patients with recurrent erysipelas had a pronounced inflammatory response, seen through significantly higher values of C reactive protein (p = 0.02), granulocytes (p = 0.03), fibrinogen (p < 0.0001), and higher body temperature, (37.22 ± 0.97 p = 0.006). Length of hospital stay was increased in the recurrent group. CONCLUSION: Erysipelas is more frequent in older people; it has seasonal character and tendency to reoccur. Identifying clinical and laboratories characteristics of those at risk may prevent recurrence and long term comorbidities.

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.

Noninvasive Biomarkers in Assessment of Liver Fibrosis in Patients with HBeAg Negative Chronic Hepatitis B.

BACKGROUND: Liver biopsy for evaluation of liver fibrosis has several adverse effects, for which reason noninvasive tests have been developed. AIM: To evaluate the usefulness of noninvasive biomarkers, qHBsAg and HBV DNA levels in predicting liver fibrosis in patients with hepatitis Be antigen (HBeAg) negative chronic hepatitis B (CHB). MATERIAL AND METHODS: This prospective study included 50 patients with HBeAg negative CHB. All patients underwent laboratory and serology testing, quantification of HBV DNA and HBs antigen. The liver stiffness was measured with elastography. The patients were analysed for APRI and FIB-4, quantitative hepatitis Bs antigen and HBV DNA. RESULTS: Logistic regression analysis showed that greatest significance in predicting liver fibrosis has FIB-4 (Wald = 3.24, P = 0.07), followed by HBV DNA ≥ 2 000 IU/ml ≤ 20 000 IU/ml (Wald = 2.86, P = 0.09), qHBsAg (Wald = 2.17, P = 0.14), HBV DNA > 20 000 IU/ml (Wald = 0.58, P = 0.45), APRI (Wald = 0.04, P = 0.84). CONCLUSION: the FIB-4 index has the greatest value in predicting liver fibrosis while APRI has the lowest; the more advanced liver disease is associated with lower serum level of quantitative HBs antigen. Combination of noninvasive blood biomarkers and imaging tests can provide better diagnostic accuracy and exclude the need for liver biopsy.

Surgical Treatment of Pleural Empyema - Our Results.

Pleural infection is a frequent clinical condition. Prompt treatment has been shown to reduce morbidity, mortality and duration of hospital stay. Unfortunately, advanced stages of empyema need to use extensive surgery - decortications or thoracoplasty. Early recognition of the parapneumonic effusion and the adequate treatment with thoracentesis or pleural drainage, which is minimally invasive, is possible not to prograde the process and not to become empyema. AIM: To analyze the results of the surgical treatment in patients with empyema treated at Clinic for thoracic surgery. MATERIAL AND METHODS: In the retrospective study we analyzed 234 patients with empyema which were treated at the Clinic for Thoracic Surgery in 5 year period (2011-2015). The mean age of the patients was 51.94 years. They were treated with pleural drainage, decortications or thoracoplasty. RESULTS: With pleural drainage were treated 165/234 (70.51%) patients, of which successfully were finished 124/165 (75.15%), but 41/165 (24.85%) were indicated after the decortications. A total of 108/234 (46.15%) were treated with decortications from which, primary decortications were indicated in 67/234 (28.63%) patients. 5/234 (2.14%) patients were treated with thoracoplasty - 3 of the patients with decortications and 2 with primary indicated thoracoplasty according to the local findings, long term untreated empyema and bad general condition. The Mean hospitalization was 17.4 days, of which 13.4 days after surgery. In the group with primary drainage it was detected a lethal outcome in 7/124 (5.64%) patients, 5/105 (4.76%) in the group with decortications and 2/5 (40%) in the group with thoracoplasty. CONCLUSION: Early detection of the parapneumonic effusion and the adequate treatment will prevent the appearance of empyema. If the empyema is detected it is necessary as early as possible to start the treatment with minimally invasive pleural drainage. In earlier stages it is possible to use less invasive decortications, using VATS than the open thoracotomy decortication which is more extensive surgical intervention.

Clinical, Laboratory and Radiographic Features of Patients with Pneumonia and Parapneumonic Effusions.

BACKGROUND: Parapneumonic effusions complicating pneumonia are associated with increased morbidity and mortality. AIM: To determine the role of the clinical, laboratory and radiographic features to the differential diagnosis of patients with community- acquired pneumonia (CAP) without effusion, uncomplicated parapneumonic effusion (UCPPE) and complicated parapneumonic effusion (CPPE). MATERIAL AND METHODS: We analysed 148 patients with CAP without effusion, 50 with UCPPE and 44 with CPPE. In three groups of patients, the majority was male patients (58.11%, 58%, 61.36%) consequently. RESULTS: The chronic heart failure was the most common comorbidity in a group with CAP (28; 18.92%) and UCPPE (7; 14%), alcoholism (12;12.77%) in a group with CPPE. Patients with CPPE had significantly longer fever compared to patients with CAP without effusion (p = 0.003). Pleuritic chest pain (86.36%) and dyspnea (88.64%) were the most common symptoms in CPPE, then to group with UCPPE (60%; 52%), and in CAP without effusion (25.68%; 47,97%). Diffuse pulmonary changes were detected more frequently in the group with CAP without effusion compared with the group with CPPE (64.86 % vs. 27.27 %), while the segment lung changes were more common in patients with CPPE (50% vs. 20.27%). Patients with CPPE were significant with higher erythrocytes sedimentation rate (ESR), white blood cells (WBC) and serum C- reactive protein (CRP) than it the other two groups (p = 0.00090, p = 0.01, p= 0.000065). CONCLUSION: Proper analysis of clinical, laboratory and radiographic features of patients with CAP and parapneumonic effusion can prevent mismanagement in these patients and will reduce morbidity and mortality.

Laboratory surveillance during pandemic influenza season 2009/2010 in Republic of Macedonia.

OBJECTIVE: To provide virological and epidemiological information on patients laboratory-tested for influenza A/ H1N1pdm during the pandemic season April 2009/May 2010. MATERIALS AND METHODS: Demographic and other data were obtained from the request form arriving with the samples of patients whose symptoms met the clinical definition of influenza A infection. The RNA was tested for the presence of influenza virus using the CDC real-time RT-PCR assay. A total of 3010 suspect patients (pts) were tested from week 18 2009 to week 20 2010. RESULTS: 1632 pts (54.2%) were oositive for influenza. From them 1556 samples were confirmed as H1N1pdm. There was a domination of H1N1pdm positivity among young persons in age groups 5-17 (34.4%) and 18-49 (31.4%) years. The pandemic influenza was presented in two waves. The first wave started on 20 June with the first positive case and peaked early in August (week 32). The second wave started from week 44. The majority of positive cases were between week 45 and week 52. 37.7% of the positive pts were hospitalized--66.7% of pts at age 65+ and 63.3% of children in the age group 0-4 years. The highest percentage of patients with underlying medical conditions were in the age group 50-64 (49.35%) years and 65+ (88.23%) years. 1.15% of the positive pts for H1N1pdm gave data for vaccination with seasonal influenza. CONCLUSIONS: Data obtained from laboratory and epidemiological surveillance of pandemic influenza will serve public health to a full understanding of the pandemic 2009/2010 influenza in R. Macedonia and dealing with future challenges.

Chlamydia pneumoniae and helicobacter pylori serology - importance in patients with coronary heart disease.

BACKGROUND: Chronic infections in CHD are due to one or both of the organisms Chlamydia pneumoniae and Helicobacter pylori. AIM: To examine the association between serum markers of Chlamydia pneumoniae and Helicobacter pylori infection and markers of myocardial damage. in patients with acute coronary syndrome (ACS), with chronic coronary artery disease (CAD) and in-control group. MATERIAL AND METHODS: Sera were taken from a total of 153 subjects. Subjects were divided in three groups: 64 patients with ACS; 53 patients with CAD and a group of 35 conditionally healthy individuals. Analysis of patients' sera for IgG antibodies to H. pylori and markers for myocardial damage was done on the Immulite system. The presence of specific IgG and IgA antibodies to C. pneumoniae was determined with MIF, Sero FIA (Savyon Diagnostics, Israel). Statistical analysis of data was done using the statistical program SPSS (Statistical Package for Social Sciences), version 13. RESULTS AND DISCUSSION: There was a high significant difference in troponin levels between the three groups of subjects (p=0.0000). Levels of creatine kinase isoenzyme (CK-MB) were highest in the ACS group (500.0 ng/mL). There was a statistically significant difference between CG subjects and ACS patients due to more frequent detection of antichlamydial IgA antibodies in patients with acute coronary syndrome. Positive serum immune response for Helicobacter pylori was 17 (53.1%) and 29 (80.6%), respectively. CONCLUSION: Increased IgA antibody titers for C. Pneumoniae, increased CRP values as well as classic markers of myocardial damage are risk factors for coronary events.

Initial empiric antimicrobial treatment of Chlamydia pneumoniae: a study of 54 cases in the Republic of Macedonia.

UNLABELLED: Analysis of the adequacy of the initial empiric antimicrobial treatment of patients with acute Chlamydia pneumoniae (CP) infection, admitted to the Infectious Diseases Clinic, Clinical Centre, Medical Faculty, Skopje, Republic of Macedonia, for community-acquired pneumonia. MATERIAL AND METHODS: A total number of 407 patients with community-acquired pneumonia (CAP) hospitalized at the Clinic between September 1997 and June 2002, with an average age of x=46.44 years, of whom 53.56% were male. Acute Chlamydia pneumoniae infection was proven serologically with MIF assay in 54 (13.27%) patients. RESULTS: Initial empiric treatment with antibiotics in patients with CP pneumonia was provided with antimicrobial agents with intracellular activity in 26 (48.15%) patients; with fluoroquinolones in 19 (35.19%); macrolides in 5 (9.26%) and tetracyclines in 2 (3.7%). The treatment was conducted as monotherapy in 6 patients (11.11%) and in 20 patients (37.04%) in combination with betalactams. For 28 (51.85%) patients who were treated only with betalactams, empiric treatment was re-evaluated and new therapy with fluoroquinolon was conducted in 16 (29.63%), with macrolides in 8 (14.81%) and with tetracyclines in 4 (7.41%) patients. CONCLUSION: Adequate empiric treatment with antimicrobial agents with intracellular activity was performed in only 48.15% of the patients with acute CP infection. Therefore, when designing the initial empiric treatment of patients hospitalized with pneumonia, attention should be paid to this atypical pathogen of CAP.