Emine Parlak

The microbiological diagnosis of tuberculous meningitis: results of Haydarpasa-1 study

We aimed to provide data on the diagnosis of tuberculous meningitis (TBM) in this largest case series ever reported. The Haydarpasa-1 study involved patients with microbiologically confirmed TBM in Albania, Croatia, Denmark, Egypt, France, Hungary, Iraq, Italy, Macedonia, Romania, Serbia, Slovenia, Syria and Turkey between 2000 and 2012. A positive culture, PCR or Ehrlich-Ziehl-Neelsen staining (EZNs) from the cerebrospinal fluid (CSF) was mandatory for inclusion of meningitis patients. A total of 506 TBM patients were included. The sensitivities of the tests were as follows: interferon-γ release assay (Quantiferon TB gold in tube) 90.2%, automated culture systems (ACS) 81.8%, Löwenstein Jensen medium (L-J) 72.7%, adenosine deaminase (ADA) 29.9% and EZNs 27.3%. CSF-ACS was superior to CSF L-J culture and CSF-PCR (p <0.05 for both). Accordingly, CSF L-J culture was superior to CSF-PCR (p <0.05). Combination of L-J and ACS was superior to using these tests alone (p <0.05). There were poor and inverse agreements between EZNs and L-J culture (κ = -0.189); ACS and L-J culture (κ = -0.172) (p <0.05 for both). Fair and inverse agreement was detected for CSF-ADA and CSF-PCR (κ = -0.299, p <0.05). Diagnostic accuracy of TBM was increased when both ACS and L-J cultures were used together. Non-culture tests contributed to TBM diagnosis to a degree. However, due to the delays in the diagnosis with any of the cultures, combined use of non-culture tests appears to contribute early diagnosis. Hence, the diagnostic approach to TBM should be individualized according to the technical capacities of medical institutions particularly in those with poor resources.

Results of a Multinational Study Suggest the Need for Rapid Diagnosis and Early Antiviral Treatment at the Onset of Herpetic Meningoencephalitis

ABSTRACT Data in the literature regarding the factors that predict unfavorable outcomes in adult herpetic meningoencephalitis (HME) cases are scarce. We conducted a multicenter study in order to provide insights into the predictors of HME outcomes, with special emphasis on the use and timing of antiviral treatment. Samples from 501 patients with molecular confirmation from cerebrospinal fluid were included from 35 referral centers in 10 countries. Four hundred thirty-eight patients were found to be eligible for the analysis. Overall, 232 (52.9%) patients experienced unfavorable outcomes, 44 died, and 188 survived, with sequelae. Age (odds ratio [OR], 1.04; 95% confidence interval [CI], 1.02 to 1.05), Glasgow Coma Scale score (OR, 0.84; 95% CI, 0.77 to 0.93), and symptomatic periods of 2 to 7 days (OR, 1.80; 95% CI, 1.16 to 2.79) and >7 days (OR, 3.75; 95% CI, 1.72 to 8.15) until the commencement of treatment predicted unfavorable outcomes. The outcome in HME patients is related to a combination of therapeutic and host factors. This study suggests that rapid diagnosis and early administration of antiviral treatment in HME patients are keys to a favorable outcome.

Genitourinary brucellosis: results of a multicentric study

This study reviewed the clinical, laboratory, therapeutic and prognostic data on genitourinary involvement of brucellosis in this largest case series reported. This multicentre study pooled adult patients with genitourinary brucellar involvement from 34 centres treated between 2000 and 2013. Diagnosis of the disease was established by conventional methods. Overall 390 patients with genitourinary brucellosis (352 male, 90.2%) were pooled. In male patients, the most frequent involved site was the scrotal area (n=327, 83.8%), as epididymo-orchitis (n=204, 58%), orchitis (n=112, 31.8%) and epididymitis (n=11, 3.1%). In female patients, pyelonephritis (n=33/38, 86.8%) was significantly higher than in male patients (n=11/352, 3.1%; p<0.0001). The mean blood leukocyte count was 7530±3115/mm3. Routine laboratory analysis revealed mild to moderate increases for erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP). The mean treatment duration and length of hospital stay were significantly higher when there were additional brucellar foci (p<0.05). Surgical operations including orchiectomy and abscess drainage were performed in nine (2.3%) patients. Therapeutic failure was detected in six (1.5%), relapse occurred in four (1%), and persistent infertility related to brucellosis occurred in one patient. A localized scrotal infection in men or pyelonephritis in women in the absence of leucocytosis and with mild to moderate increases in inflammatory markers should signal the possibility of brucellar genitourinary disease.

Managing atypical and typical herpetic central nervous system infections: results of a multinational study

There have been many studies pertaining to the management of herpetic meningoencephalitis (HME), but the majority of them have focussed on virologically unconfirmed cases or included only small sample sizes. We have conducted a multicentre study aimed at providing management strategies for HME. Overall, 501 adult patients with PCR-proven HME were included retrospectively from 35 referral centres in 10 countries; 496 patients were found to be eligible for the analysis. Cerebrospinal fluid (CSF) analysis using a PCR assay yielded herpes simplex virus (HSV)-1 DNA in 351 patients (70.8%), HSV-2 DNA in 83 patients (16.7%) and undefined HSV DNA type in 62 patients (12.5%). A total of 379 patients (76.4%) had at least one of the specified characteristics of encephalitis, and we placed these patients into the encephalitis presentation group. The remaining 117 patients (23.6%) had none of these findings, and these patients were placed in the nonencephalitis presentation group. Abnormalities suggestive of encephalitis were detected in magnetic resonance imaging (MRI) in 83.9% of the patients and in electroencephalography (EEG) in 91.0% of patients in the encephalitis presentation group. In the nonencephalitis presentation group, MRI and EEG data were suggestive of encephalitis in 33.3 and 61.9% of patients, respectively. However, the concomitant use of MRI and EEG indicated encephalitis in 96.3 and 87.5% of the cases with and without encephalitic clinical presentation, respectively. Considering the subtle nature of HME, CSF HSV PCR, EEG and MRI data should be collected for all patients with a central nervous system infection.

Miliary tuberculosis: Epidemiologicaland clinical analysis of large-case series from moderate to low tuberculosis endemic Country

Abstract The aim of this study was to determine the clinical features, and outcome of the patients with miliary tuberculosis (TB). We retrospectively evaluated 263 patients (142 male, 121 female, mean age: 44 years, range: 16–89 years) with miliary TB. Criteria for the diagnosis of miliary TB were at least one of the followings in the presence of clinical presentation suggestive of miliary TB such as prolonged fever, night sweats, anorexia, weight loss: radiologic criterion and pathological criterion and/or microbiological criterion; pathological criterion and/or microbiological criterion. The miliary pattern was seen in 88% of the patients. Predisposing factors were found in 41% of the patients. Most frequent clinical features and laboratory findings were fever (100%), fatigue (91%), anorexia (85%), weight loss (66%), hepatomegaly (20%), splenomegaly (19%), choroid tubercules (8%), anemia (86%), pancytopenia (12%), and accelerated erythrocyte sedimentation rate (89%). Tuberculin skin test was positive in 29% of cases. Fifty percent of the patients met the criteria for fever of unknown origin. Acid-fast bacilli were demonstrated in 41% of patients (81/195), and cultures for Mycobacterium tuberculosis were positive in 51% (148/292) of tested specimens (predominantly sputum, CSF, and bronchial lavage). Blood cultures were positive in 20% (19/97). Granulomas in tissue samples of liver, lung, and bone marrow were present in 100% (21/21), 95% (18/19), and 82% (23/28), respectively. A total of 223 patients (85%) were given a quadruple anti-TB treatment. Forty-four (17%) patients died within 1 year after diagnosis established. Age, serum albumin, presence of military pattern, presence of mental changes, and hemoglobin concentration were found as independent predictors of mortality. Fever resolved within first 21 days in the majority (90%) of the cases. Miliary infiltrates on chest X-ray should raise the possibility of miliary TB especially in countries where TB is endemic. Although biopsy of the lungs and liver may have higher yield rate of organ involvement histopathologicaly, less invasive procedures including a bone marrow biopsy and blood cultures should be preferred owing to low complication rates.

Tetanus in adults: results of the multicenter ID-IRI study

Tetanus is an acute, severe infection caused by a neurotoxin secreting bacterium. Various prognostic factors affecting mortality in tetanus patients have been described in the literature. In this study, we aimed to analyze the factors affecting mortality in hospitalized tetanus patients in a large case series. This retrospective multicenter study pooled data of tetanus patients from 25 medical centers. The hospitals participating in this study were the collaborating centers of the Infectious Diseases International Research Initiative (ID-IRI). Only adult patients over the age of 15 years with tetanus were included. The diagnosis of tetanus was made by the clinicians at the participant centers. Izmir Bozyaka Education and Research Hospital’s Review Board approved the study. Prognostic factors were analyzed by using the multivariate regression analysis method. In this study, 117 adult patients with tetanus were included. Of these, 79 (67.5%) patients survived and 38 (32.5%) patients died. Most of the deaths were observed in patients >60 years of age (60.5%). Generalized type of tetanus, presence of pain at the wound area, presence of generalized spasms, leukocytosis, high alanine aminotransferase (ALT) and C-reactive protein (CRP) values on admission, and the use of equine immunoglobulins in the treatment were found to be statistically associated with mortality (p < 0.05 for all). Here, we describe the prognostic factors for mortality in tetanus. Immunization seems to be the most critical point, considering the advanced age of our patients. A combination of laboratory and clinical parameters indicates mortality. Moreover, human immunoglobulins should be preferred over equine sera to increase survival.

Unusual cause of fatal anthrax meningitis.

Abstract We report the case of fatal anthrax meningoencephalitis in the province of Muş located in eastern Anatolia, Turkey. The organism isolated from cerebrospinal fluid was identified as Bacillus anthracis. The patient was treated with crystallized penicillin G (24 MU/day IV) and ciprofloxacin (2 × 400/day IV), but died 5 days after hospitalization. Although it is a rare case, we consider that the patients who have skin, respiratory and neurological systems might also have hemorrhagic meningitis.

Clinical Significance of Neutrophil Gelatinase-Associated Lipocalin in Crimean-Congo Hemorrhagic Fever

Neutrophil gelatinase-associated lipocalin (NGAL), which is an important prognostic marker for sepsis and inflammatory diseases, is mostly released from neutrophils. Crimean-Congo hemorrhagic fever (CCHF) patients are generally neutropenic. We aimed to investigate whether there is a change in serum NGAL level and to investigate its effect on the recovery time (RT) during the course of CCHF. A total of 40 CCHF patients (19 females and 21 males) and 34 healthy controls (17 females and 17 males) were included in the study. The serum NGAL level and biochemical and hematological parameters were checked. The NGAL level of CCHF patients was significantly higher than that of the healthy controls (P < 0.001). A multivariate analysis showed that the independent prognostic factor for the prediction of the RT is the NGAL level (odds ratio [OR] 0.3, 95% confidence interval [Cl] 0.1–0.4, P < 0.001). An elevated NGAL level was found to be associated with an increased RT in CCHF patients. The NGAL levels of CHHF patients might be elevated due to increased cytokine release, the presence of a tissue injury, and the release of immature neutrophils from the bone marrow into the peripheral stream. This may be a good prognostic factor in CHHF patients.

The features of infectious diseases departments and anti-infective practices in France and Turkey: a cross-sectional study

The aim of this study was to assess the infectious diseases (ID) wards of tertiary hospitals in France and Turkey for technical capacity, infection control, characteristics of patients, infections, infecting organisms, and therapeutic approaches. This cross-sectional study was carried out on a single day on one of the weekdays of June 17–21, 2013. Overall, 36 ID departments from Turkey (n = 21) and France (n = 15) were involved. On the study day, 273 patients were hospitalized in Turkish and 324 patients were followed in French ID departments. The numbers of patients and beds in the hospitals, and presence of an intensive care unit (ICU) room in the ID ward was not different in both France and Turkey. Bed occupancy in the ID ward, single rooms, and negative pressure rooms were significantly higher in France. The presence of a laboratory inside the ID ward was more common in Turkish ID wards. The configuration of infection control committees, and their qualifications and surveillance types were quite similar in both countries. Although differences existed based on epidemiology, the distribution of infections were uniform on both sides. In Turkey, anti-Gram-positive agents, carbapenems, and tigecycline, and in France, cephalosporins, penicillins, aminoglycosides, and metronidazole were more frequently preferred. Enteric Gram-negatives and hepatitis B and C were more frequent in Turkey, while human immunodeficiency virus (HIV) and streptococci were more common in France (p < 0.05 for all significances). Various differences and similarities existed in France and Turkey in the ID wards. However, the current scene is that ID are managed with high standards in both countries.

Human Cutaneous Anthrax, the East Anatolian Region of Turkey 2008-2014.

Anthrax is a zoonotic infectious disease caused by Bacillus anthracis. While anthrax is rare in developed countries, it is endemic in Turkey. The names of the different forms of the disease refer to the manner of entry of the spores into the body-cutaneous, gastrointestinal, inhalation, and injection. The purpose of this study was to evaluate the clinical characteristics, epidemiological history, treatment, and outcomes of patients with anthrax. Eighty-two cases of anthrax hospitalized at Atatürk University Faculty of Medicine Department of Infectious Diseases and Clinical Microbiology in 2008-2014 were examined retrospectively. Gender, age, occupation, year, history, clinical characteristics, character of lesions, length of hospitalization, and outcomes were recorded. Thirty (36.6%) patients were female and 52 (63.4%) patients were male; ages were 18-69 and mean age was 43.77 ± 13.05. The mean incubation period was 4.79 ± 3.76 days. Cases were largely identified in August (41.5%) and September (25.6%). Sixty-nine (84.1%) of the 82 patients had been given antibiotics before presentation. Lesions were most common on the fingers and arms. The most common occupational groups were housewives (36.6%) and people working in animal husbandry (31.7%). All patients had histories of contact with diseased animals and animal products. Penicillin-group antibiotics (78%) were most commonly used in treatment. One patient (1.2%) died from anthrax meningitis. The mean length of hospitalization was 8.30 ± 5.36 days. Anthrax is an endemic disease of economic and social significance for the region. Effective public health control measures, risk group education, vaccination of animals, and decontamination procedures will reduce the number of cases.