Campylobacter jejuni subdural hygroma infection in a 2-year old boy: case report and a brief literature review.

BACKGROUND: Campylobacter jejuni is a common cause of acute gastroenteritis, but central nervous system infections are rare manifestations of Campylobacter infection. Therefore, C. jejuni trauma-related subdural hygroma infection in children is poorly described in the literature. CASE PRESENTATION: We described a 2-year old boy with lobar holoprosencephaly presenting with subdural hygroma following head trauma. C. jejuni infection was confirmed from a subdural hygroma sample by culture as well as by DNA sequencing of a broad range 16S rDNA PCR product. Cerebrospinal fluid from the ventriculoperitoneal shunt remained sterile. Combined neurosurgical and antimicrobial treatment led to complete recovery. Review of the literature showed that the most common manifestation of Campylobacter central nervous system infection is meningitis, mostly in neonates, and subdural hygroma infection was described for only one case. CONCLUSIONS: Subdural hygroma infection caused by C. jejuni is a rare clinical condition in children. Molecular methods represent an important tool for the detection of rare or unexpected pathogens. No standard recommendations for antimicrobial treatment of C. jejuni subdural space infection in children are available, but meropenem treatment combined with surgery seems to be an effective approach.

Recommendations to Improve Tick-Borne Encephalitis Surveillance and Vaccine Uptake in Europe.

There has been an increase in reported TBE cases in Europe since 2015, reaching a peak in some countries in 2020, highlighting the need for better management of TBE risk in Europe. TBE surveillance is currently limited, in part, due to varying diagnostic guidelines, access to testing, and awareness of TBE. Consequently, TBE prevalence is underestimated and vaccination recommendations inadequate. TBE vaccine uptake is unsatisfactory in many TBE-endemic European countries. This review summarizes the findings of a scientific workshop of experts to improve TBE surveillance and vaccine uptake in Europe. Strategies to improve TBE surveillance and vaccine uptake should focus on: aligning diagnostic criteria and testing across Europe; expanding current vaccine recommendations and reducing their complexity; and increasing public education of the potential risks posed by TBEV infection.

COVID-19 in children and adolescents in Europe: a multinational, multicentre cohort study.

BACKGROUND: To date, few data on paediatric COVID-19 have been published, and most reports originate from China. This study aimed to capture key data on children and adolescents with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection across Europe to inform physicians and health-care service planning during the ongoing pandemic. METHODS: This multicentre cohort study involved 82 participating health-care institutions across 25 European countries, using a well established research network-the Paediatric Tuberculosis Network European Trials Group (ptbnet)-that mainly comprises paediatric infectious diseases specialists and paediatric pulmonologists. We included all individuals aged 18 years or younger with confirmed SARS-CoV-2 infection, detected at any anatomical site by RT-PCR, between April 1 and April 24, 2020, during the initial peak of the European COVID-19 pandemic. We explored factors associated with need for intensive care unit (ICU) admission and initiation of drug treatment for COVID-19 using univariable analysis, and applied multivariable logistic regression with backwards stepwise analysis to further explore those factors significantly associated with ICU admission. FINDINGS: 582 individuals with PCR-confirmed SARS-CoV-2 infection were included, with a median age of 5·0 years (IQR 0·5-12·0) and a sex ratio of 1·15 males per female. 145 (25%) had pre-existing medical conditions. 363 (62%) individuals were admitted to hospital. 48 (8%) individuals required ICU admission, 25 (4%) mechanical ventilation (median duration 7 days, IQR 2-11, range 1-34), 19 (3%) inotropic support, and one (<1%) extracorporeal membrane oxygenation. Significant risk factors for requiring ICU admission in multivariable analyses were being younger than 1 month (odds ratio 5·06, 95% CI 1·72-14·87; p=0·0035), male sex (2·12, 1·06-4·21; p=0·033), pre-existing medical conditions (3·27, 1·67-6·42; p=0·0015), and presence of lower respiratory tract infection signs or symptoms at presentation (10·46, 5·16-21·23; p<0·0001). The most frequently used drug with antiviral activity was hydroxychloroquine (40 [7%] patients), followed by remdesivir (17 [3%] patients), lopinavir-ritonavir (six [1%] patients), and oseltamivir (three [1%] patients). Immunomodulatory medication used included corticosteroids (22 [4%] patients), intravenous immunoglobulin (seven [1%] patients), tocilizumab (four [1%] patients), anakinra (three [1%] patients), and siltuximab (one [<1%] patient). Four children died (case-fatality rate 0·69%, 95% CI 0·20-1·82); at study end, the remaining 578 were alive and only 25 (4%) were still symptomatic or requiring respiratory support. INTERPRETATION: COVID-19 is generally a mild disease in children, including infants. However, a small proportion develop severe disease requiring ICU admission and prolonged ventilation, although fatal outcome is overall rare. The data also reflect the current uncertainties regarding specific treatment options, highlighting that additional data on antiviral and immunomodulatory drugs are urgently needed. FUNDING: ptbnet is supported by Deutsche Gesellschaft für Internationale Zusammenarbeit.

Epidemiological and clinical features of Croatian children and adolescents with a PCR-confirmed coronavirus disease 2019: differences between the first and second epidemic wave.

AIM: To describe epidemiological and clinical features of Croatian children and adolescents with a polymerase chain reaction (PCR)-confirmed coronavirus disease 2019. METHODS: Data on patients aged ≤19 years with a positive SARS-CoV-2 PCR test recorded in the period March 12-May 12 (first wave) and June 19-July 19, 2020 (second wave) were retrospectively analyzed. The periods were separated by several weeks with no incident cases. RESULTS: We analyzed data on 289 children and adolescents (6.5% of all cases; incidence rate [IR]=3.54, 95% confidence interval [CI] 3.14-3.97/million person-days), 124 in the first wave (IR=2.27) and 165 in the second wave (IR=6.37): IRR second/first=2.71 (2.13-3.44). During the first wave, the incidence was highest in infants (IR=3.48), while during the second wave it progressively increased to IR = 7.37 in 15-19-year olds. Family members were the key epidemiological contacts (72.6% cases), particularly during the first wave (95.8% vs 56.3%). Overall, 41.3% patients were asymptomatic, 25.3% in the first and 52.6% in the second wave. Age 15-19 years (vs younger) was associated with a higher (RR = 1.26, 1.02-1.54) and infection in the second wave with a lower probability (RR=0.66, 0.53-0.81) of being symptomatic. The most common symptoms were fever, cough, and rhinorrhea. In children aged ≥7 years, headache, anosmia/ageusia, and sore throat were also recorded. Only one child suffered a severe disease. All but 18 (7.8%) children were treated only symptomatically, and all fully recovered. CONCLUSION: A large proportion of SARS-CoV-2 PCR-positive children/adolescents were asymptomatic. The associated disease was predominantly mild, comparably so in the first and second pandemic wave.

Chemokines CXCL10, CXCL11, and CXCL13 in acute disseminated encephalomyelitis, non-polio enterovirus aseptic meningitis, and neuroborreliosis: CXCL10 as initial discriminator in diagnostic algorithm?

We investigated potential diagnostic usefulness of serum and cerebrospinal fluid (CSF) concentrations of chemokines CXCL10, CXCL11, and CXCL13 in pediatric patients with acute disseminated encephalomyelitis (ADEM) (n = 23), non-polio enterovirus aseptic meningitis (NPEV AM) (n = 20), and neuroborreliosis (NB) (n = 21) and children with acute infectious diseases with neurological symptoms but with excluded neuroinfection/neuroinflammation (controls, n = 20). CSF levels of CXCL10 and CXCL11 were higher in patients with NPEV AM than those in other children, and CXCL10 levels showed a high discriminative potential (area under the receiver operating characteristic curve, ROC, 0.982) with high specificity and sensitivity (both 95%). CSF levels of CXCL13 were higher in NB patients than those in other children; however, discriminative potential (area under ROC curve 0.814) and diagnostic properties were moderate (sensitivity 67%, specificity 97%). Data suggest usefulness of chemokine quantification as a diagnostic aid in children with suspected ADEM, NPEV AM, or NB.

Global respiratory syncytial virus-associated mortality in young children (RSV GOLD): a retrospective case series.

BACKGROUND: Respiratory syncytial virus (RSV) infection is an important cause of pneumonia mortality in young children. However, clinical data for fatal RSV infection are scarce. We aimed to identify clinical and socioeconomic characteristics of children aged younger than 5 years with RSV-related mortality using individual patient data. METHODS: In this retrospective case series, we developed an online questionnaire to obtain individual patient data for clinical and socioeconomic characteristics of children aged younger than 5 years who died with community-acquired RSV infection between Jan 1, 1995, and Oct 31, 2015, through leading research groups for child pneumonia identified through a comprehensive literature search and existing research networks. For the literature search, we searched PubMed for articles published up to Feb 3, 2015, using the key terms "RSV", "respiratory syncytial virus", or "respiratory syncytial viral" combined with "mortality", "fatality", "death", "died", "deaths", or "CFR" for articles published in English. We invited researchers and clinicians identified to participate between Nov 1, 2014, and Oct 31, 2015. We calculated descriptive statistics for all variables. FINDINGS: We studied 358 children with RSV-related in-hospital death from 23 countries across the world, with data contributed from 31 research groups. 117 (33%) children were from low-income or lower middle-income countries, 77 (22%) were from upper middle-income countries, and 164 (46%) were from high-income countries. 190 (53%) were male. Data for comorbidities were missing for some children in low-income and middle-income countries. Available data showed that comorbidities were present in at least 33 (28%) children from low-income or lower middle-income countries, 36 (47%) from upper middle-income countries, and 114 (70%) from high-income countries. Median age for RSV-related deaths was 5·0 months (IQR 2·3-11·0) in low-income or lower middle-income countries, 4·0 years (2·0-10·0) in upper middle-income countries, and 7·0 years (3·6-16·8) in high-income countries. INTERPRETATION: This study is the first large case series of children who died with community-acquired RSV infection. A substantial proportion of children with RSV-related death had comorbidities. Our results show that perinatal immunisation strategies for children aged younger than 6 months could have a substantial impact on RSV-related child mortality in low-income and middle-income countries. FUNDING: Bill & Melinda Gates Foundation.

Successful Treatment of Disseminated Bacillus Calmette-Guérin Disease in an HIV-Infected Child with a Linezolid-Containing Regimen.

Upon HIV infection diagnosis, an 8-month-old boy was transferred for evaluation of worsening respiratory distress requiring mechanical ventilation. Pneumocystis jirovecii pneumonia (PCP) was diagnosed; the boy also had a nonhealing ulcer at the site of vaccination with Statens Serum Institut (Danish strain) Bacillus Calmette-Guérin (BCG) vaccine and associated axillary lymphadenopathy. PCP treatment resulted in weaning from mechanical ventilation. Antimycobacterial treatment was immediately attempted but was discontinued because of hepatotoxicity. Over several months, he developed splenic lesions and then disseminated skin and cystic bone lesions. M. bovis was repeatedly cultured from both skin and bone lesions despite various multidrug antimycobacterial regimens which included linezolid. Eventually, treatment with a regimen of rifabutin, isoniazid, ethambutol, and linezolid led to definitive cure. Clinicians should consider a linezolid-containing regimen for treatment of severe disseminated BCG infection, especially if other drug regimens have failed. Although drug toxicity is a particular concern for young children, this patient received linezolid for 13 months without serious toxicity. This case also highlights the need for universal screening among pregnant women to prevent vertical transmission of HIV. Finally, routine immunization with BCG vaccine at birth should be questioned in countries with low and declining burden of tuberculosis.

Risk factors for coronary artery abnormalities in children with Kawasaki disease: a 10-year experience.

Kawasaki disease (KD) is an acute systemic vasculitis of childhood. Due to development of coronary artery aneurysms (CAA) it is considered the most common cause of acquired heart disease in children. The clinical and laboratory features of patients with complete and incomplete KD were compared in order to identify the possible predictors of CAA development. A cross-sectional study of children with KD treated at the University Hospital for Infectious Diseases, Zagreb, between January 2003 and December 2012 was conducted. A total of 111 KD patients were included; 70.3% patients had complete KD. Patients with complete KD had more frequently rash, changes on extremities and mucous membranes, as well as higher serum bilirubin, aminotransferases, gamma-glutamyl transferase and lactate dehydrogenase levels. Patients with incomplete KD had longer duration of fever before the diagnosis (8 vs. 7 days) and delayed IVIG treatment (day 8 vs. 7). CAA was detected in seven children (6.3%). Disease duration before hospitalization >6 days (OR 7.16, 95% CI 1.51-100.35), age <6 months (OR 25.86, 95% CI 1.68-398.35) and platelet count >771 after the 7th day of disease (OR 13.33, 95% CI 2.19-80.87) were independently associated with CAA development. The diagnosis and treatment in incomplete KD can be delayed due to the absence of major criteria. Age, duration of symptoms prior hospitalization and platelet count were identified as independent predictors of CAA development.

The role of Chlamydia trachomatis in prostatitis syndrome--our experience in diagnosis and treatment.

Since the beginning of 1999, over 1500 patients with symptoms of chronic prostatitis were examined at Dr. Fran Mihaljevic University Hospital for Infectious Diseases in Zagreb. In almost all of these patients urethral swabs and quantitative segmented bacteriologic cultures and microscopy of expressed prostatic secretion (EPS) or voided bladder urine3 (VB3) were performed as described by Meares and Stamey. Urethral swabs, EPS or VB3 were examined for the presence of Chlamydia (C.) trachomatis by McCoy culture and Lugol stain or by immunofluorescent typing with monoclonal antibodies. In the majority of patients C. trachomatis was demonstrated in parallel in EPS or VB3 by DNA/RNA hybridization method. Normal white blood cell count viewed per high power field<10 was found in 362 (68%) of 536 patients with symptoms of chronic prostatitis and C. trachomatis detected in EPS or VB3. These findings additionally suggest that C. trachomatis can be suspected as a causative pathogen in all categories of chronic prostatitis syndrome. Furthermore, this paper summarizes the results of five previously published clinical studies on the efficacy and tolerability of various treatment schemes for chronic chlamydial prostatitis, conducted from the beginning of 1999 until the end of 2003.

Etiology of chronic prostatitis syndrome in patients treated at the university hospital for infectious diseases "Dr. Fran Mihaljevic" from 2003 to 2005.

A total of 835 patients with symptoms of chronic prostatitis syndrome and no evidence of structural or functional lower genitourinary tract abnormalities were examined in a three year period at the Outpatient Department for Urogenital Infections, University Hospital for Infectious Diseases "Dr. Fran Mihaljevic" Zagreb, Croatia. Disease etiology was determined in 482 (57.72%) patients. Chlamydia trachomatis was proved to be the causative pathogen in 161 patients, Trichomonas vaginalis in 85, Escherichia coli in 68, Enterococcus in 51, Proteus mirabilis in 20, Klebsiella pneumoniae in 9, Streptococcus agalactiae in 15, Ureaplasma urealyticum in 49 patients with chronic prostatitis. Other patients had mixed infection. In 257 (53.32%) of 482 patients, the inflammatory finding (>10 WBCs/hpf) was found in EPS or VB3. Normal WBCs/hpf (<10) was found in 103 (63.98%) of 161 patients with symptoms of chronic prostatitis in whom C. trachomatis was detected in EPS or VB3, in 50 (58.82%) of 85 patients in whom Trichomonas vaginalis was isolated, and in 23 (46.94%) of 49 patients in whom Ureaplasma urealyticum was isolated.

The role of unusual pathogens in prostatitis syndrome.

A total of 1442 patients with symptoms of chronic prostatitis were examined over a 4-year period at the Outpatient Department for Urogenital Infections, University Hospital for Infectious Diseases "Dr. Fran Mihaljevic", Zagreb, Croatia. An infectious aetiology was determined in 1070 (74.2%) patients. In 561 of 1070 (52.4%) patients the inflammatory finding (>10 WBC/hpf) was found in expressed prostatic secretions (EPS) or voided bladder urine (VB(3)). Normal, <10 WBCs/hpf was found in 362 of 536 (67.5%) patients with symptoms of chronic prostatitis in whom Chlamydia trachomatis was detected in EPS or VB(3), in 51 of 151 (33.8%) patients with isolated Trichomonas vaginalis and in 40 of 72 (55.6%) patients with isolated Ureaplasma urealyticum. Escherichia coli was the causative pathogen in 95, Enterococcus in 68, Proteus mirabilis in 37, Klebsiella pneumoniae in 16, Streptococcus agalactiae in 19, and Pseudomonas aeruginosa in 3 patients with chronic prostatitis. Other patients had a mixed infection. In patients with chronic bacterial prostatitis (CBP) caused by E. coli, P. mirabilis, K. pneumoniae, E. or S. agalactiae, an inflammatory finding was regularly found in EPS or VB(3).

Comparative randomized pilot study of azithromycin and doxycycline efficacy in the treatment of prostate infection caused by Chlamydia trachomatis.

The study included 125 adult patients (> 18years of age) who had symptoms of chronic prostatitis and proven presence of Chlamydia trachomatis. The presence of C. trachomatis was confirmed in expressed prostatic secretion or in voided bladder urine collected immediately after prostatic massage by a DNA/RNA hybridization method and/or by isolation on McCoy culture and then by immunofluorescent typing with monoclonal antibodies. The patients were randomized in the ratio 2/1; azithromycin/doxycycline, to receive a total of 4.0 g azithromycin over 4 weeks, given as a single dose of 1 x 1000 mg weekly for 4 weeks or doxycycline 100 mg b.i.d. for 28 days. Patients' sexual partners were treated at the same time. Clinical and bacteriological efficacy was evaluated 4-6 weeks after the end of therapy. In the group of patients with chlamydial infection of the prostate, there was no significant difference between the eradication rates (azithromycin 65/82, doxycycline 33/43; P = 0.82) and the clinical cure rates (azithromycin 56/82, doxycycline 30/43; P = 0.94) of the two antimicrobials.