Margareta Ieven

Two imported cases of **Penicillium marneffei** infection in Belgium

Two imported cases of Penicillium marneffei infection in Belgium are reported. Both patients are Thai women co-infected with HIV. P. marneffei infection should be suspected in immunocompromised patients originating or travelling from South-East Asia with unexplained fever (> 38 degrees C), weight loss, a generalised lymphadenopathy, hepatomegaly, splenomegaly, skin lesions, cough and anaemia. Diagnosis is made by culture and/or histopathological examination. Mild to moderate infections are treated with itraconazole 400 mg/day as first choice. Amphotericin B parenteral therapy may be required for seriously ill patients. Maintenance therapy with itraconazole 200 mg/day is necessary to prevent relapses.

Early waning of maternal measles antibodies in era of measles elimination: longitudinal study

Objective To investigate the duration of the presence of maternal antibodies to measles in infants. Design Prospective study (May 2006 to November 2008). Setting Five hospitals in the Province of Antwerp, Belgium. Participants Of 221 pregnant women recruited, 207 healthy woman-infant pairs were included—divided into a vaccinated group (n=87) and naturally immune group (n=120), according to vaccination documents and history. Main outcome measure Measles IgG antibodies measured by enzyme linked immunosorbent assay (ELISA) at seven time points (week 36 of pregnancy, birth (cord), and 1, 6, 9, and 12 months); decay of maternal antibody in infants modelled with linear mixed models. Results Vaccinated women had significantly fewer IgG antibodies (geometric mean titre 779 (95% confidence interval 581 to 1045) mIU/ml) than did naturally immune women (2687 (2126 to 3373) mIU/ml) (P<0.001). Maternal values were highly correlated with neonatal values (r=0.93 at birth). Infants of vaccinated women had significantly lower antibody concentrations than did infants of naturally immune women (P<0.001 at all ages over the follow-up period). Presence of maternal antibodies endured for a median of 2.61 months—3.78 months for infants of naturally infected women and 0.97 months for infants of vaccinated women. At 6 months of age, more than 99% of infants of vaccinated women and 95% of infants of naturally immune women had lost maternal antibodies according to the model. Conclusions This study describes a very early susceptibility to measles in infants of both vaccinated women and women with naturally acquired immunity. This finding is important in view of recent outbreaks and is an argument for timeliness of the first dose of a measles vaccine and vaccination of travelling or migrating children under the age of 1 year.

Use of specialised isolation media for recognition and identification of Candida dubliniensis isolates from HIV-infected patients.

During a study of oral rinses of 130 HIV-infected individuals, both typical and atypicalCandida albicans colonies were isolated from ten patients on a yeast differential medium. TypicalCandida albicans colonies were light green; atypical colonies were dark green. Both types of colonies were germ tube-positive and produced chlamydospores. However, DNA fingerprinting of the atypical isolates with the Ca3Candida albicans-specific probe showed that they belonged to the recently described speciesCandida dubliniensis.Candida dubliniensis colonies could also be differentiated fromCandida albicans colonies on isolation plates by the absence of fluorescence of colonies on methyl blue-Sabouraud agar under Woods light. Among other phenotypic characteristics, only the absence of intracellular β-glucosidase activity reliably distinguishedCandida albicans fromCandida dubliniensis.Candida dubliniensis may be underreported in clinical samples because most currently used isolation and identification methods fail to recognize this yeast.

Herpes simplex virus in the respiratory tract of critical care patients: a prospective study

BACKGROUND Herpes simplex virus (HSV) is occasionally detected in the lower respiratory tract of patients in intensive care, but its clinical importance in such situations remains unclear. We did a prospective cohort study to define the prevalence, origin, risk factors, and clinical relevance of HSV in the respiratory tract of patients undergoing critical care. METHODS We tested 764 patients admitted to intensive care for the presence of HSV in the respiratory tract, and assessed statistical relations between this virus and clinical variables. FINDINGS HSV was detected by oropharyngeal swab in the upper respiratory tract of 169 (22%) of 764 patients, within 10 days of admission for 150 (89%) of these individuals. The virus was isolated in 58 (16%) of 361 patients whose lower respiratory tract was sampled. The presence of HSV in the throat was a risk factor for development of HSV infections in the lower respiratory tract (p<0.001). HSV was isolated most frequently in patients with severe disease. HSV in the throat was associated with acute respiratory distress syndrome (p<0.001) and with increased length of stay in intensive care (p<0.001). INTERPRETATION Our data suggest that HSV reactivation or infection of the upper respiratory tract is frequent among patients in intensive care, and is a risk factor for development of lower respiratory tract infection with this virus, possibly by means of aspiration.

Molecular Diagnosis of Mycoplasma pneumoniae Respiratory Tract Infections

Mycoplasma pneumoniae is responsible for 10 to 20% of the cases of community-acquired pneumonia and has been associated with acute exacerbations of asthma ([22][1]). M. pneumoniae is also implicated in mild acute respiratory infections, such as sore throat, pharyngitis, rhinitis, and

Current Trends in Rapid Diagnostics for Methicillin-Resistant Staphylococcus aureus and Glycopeptide-Resistant Enterococcus Species

Hospital-acquired (HA) infections are an increasing global problem. Methicillin-resistant Staphylococcus aureus (MRSA) and glycopeptide-resistant Enterococcus (GRE) are multidrugresistant organisms and are particularly frequent causes of HA infections that often prove difficult and expensive to treat. Major sources of MRSA and GRE causing infections are either the patient’s own floras (endogenous infection), those acquired from another person (cross-infection), or those from substances recently contaminated by a human source (environmental infection). Active surveillance cultures from patients for carriage of MRSA and GRE facilitate an early contact isolation (and even treatment), thus preventing spread in the hospital and reducing costs (42). However, the time to result with conventional cultures is 2 to 3 days, which allows these organisms a sizeable time window for potential spread prior to the institution of contact precautions. Recently, several “rapid” diagnostic tests have been introduced that would be very beneficial in decreasing the time to detection, therefore reducing the risk of nosocomial transmission and infections, especially in high-risk patients. This review discusses the current state of the art on rapid and direct detection methods for MRSA and GRE from patient material and hopes to facilitate the infectious disease specialist or microbiologist in choosing an appropriate diagnostic test.

Involvement of Chlamydia pneumoniae in Atherosclerosis: More Evidence for Lack of Evidence

During the past 15 years, many studies have been devoted to the relationship of Chlamydia pneumoniae and atherosclerosis: the serologic link has been investigated, and chlamydial organisms have been detected in lesions by electron microscopy, immunohistochemistry, in vitro cultivation, PCR, or in situ hybridization; efforts have been made to produce atherosclerosis experimentally in animals by inoculation of C. pneumoniae and therapeutic trials in humans have been undertaken. Some studies conclude that C. pneumoniae is present in cases of atherosclerosis, while others deny this, splitting the medical community into believers and disbelievers. The question, being a scientific one, should be resolved on a rational basis. After Boman and Hammerschlag reviewed the problem in 2002 (Clin. Microbiol. Rev. 15:1-20, 2002), a number of new studies were published on the subject. In this review, we critically evaluate the available data for the evidence or lack of evidence of a causal relationship for C. pneumoniae in atherosclerosis based on diagnostic and therapeutic studies performed with humans between 1992 and 2003, thereby searching mainly for concordance of evidence arising from different approaches used by different groups, at different times, and under different circumstances.

Use of serum C reactive protein and procalcitonin concentrations in addition to symptoms and signs to predict pneumonia in patients presenting to primary care with acute cough: diagnostic study

Objectives To quantify the diagnostic accuracy of selected inflammatory markers in addition to symptoms and signs for predicting pneumonia and to derive a diagnostic tool. Design Diagnostic study performed between 2007 and 2010. Participants had their history taken, underwent physical examination and measurement of C reactive protein (CRP) and procalcitonin in venous blood on the day they first consulted, and underwent chest radiography within seven days. Setting Primary care centres in 12 European countries. Participants Adults presenting with acute cough. Main outcome measures Pneumonia as determined by radiologists, who were blind to all other information when they judged chest radiographs. Results Of 3106 eligible patients, 286 were excluded because of missing or inadequate chest radiographs, leaving 2820 patients (mean age 50, 40% men) of whom 140 (5%) had pneumonia. Re-assessment of a subset of 1675 chest radiographs showed agreement in 94% (κ 0.45, 95% confidence interval 0.36 to 0.54). Six published “symptoms and signs models” varied in their discrimination (area under receiver operating characteristics curve (ROC) ranged from 0.55 (95% confidence interval 0.50 to 0.61) to 0.71 (0.66 to 0.76)). The optimal combination of clinical prediction items derived from our patients included absence of runny nose and presence of breathlessness, crackles and diminished breath sounds on auscultation, tachycardia, and fever, with an ROC area of 0.70 (0.65 to 0.75). Addition of CRP at the optimal cut off of >30 mg/L increased the ROC area to 0.77 (0.73 to 0.81) and improved the diagnostic classification (net reclassification improvement 28%). In the 1556 patients classified according to symptoms, signs, and CRP >30 mg/L as “low risk” (<2.5%) for pneumonia, the prevalence of pneumonia was 2%. In the 132 patients classified as “high risk” (>20%), the prevalence of pneumonia was 31%. The positive likelihood ratio of low, intermediate, and high risk for pneumonia was 0.4, 1.2, and 8.6 respectively. Measurement of procalcitonin added no relevant additional diagnostic information. A simplified diagnostic score based on symptoms, signs, and CRP >30 mg/L resulted in proportions of pneumonia of 0.7%, 3.8%, and 18.2% in the low, intermediate, and high risk group respectively. Conclusions A clinical rule based on symptoms and signs to predict pneumonia in patients presenting to primary care with acute cough performed best in patients with mild or severe clinical presentation. Addition of CRP concentration at the optimal cut off of >30 mg/L improved diagnostic information, but measurement of procalcitonin concentration did not add clinically relevant information in this group.

Optimal Sampling Sites and Methods for Detection of Pathogens Possibly Causing Community-Acquired Lower Respiratory Tract Infections

Acute respiratory tract infections (RTIs), both upper (URTIs) and lower respiratory tract infections (LRTIs), are the most common reason for consultation with a general practitioner. RTIs result in about 180 million antibiotic prescriptions per year in the EU-27 member states (ESAC website, 2008; www.esac.ua.ac.be), and 6.4 million antibiotic prescriptions were prescribed for acute bronchitis and cough in 2003 in adults between 16 and 64 years old in the United States (65). The number of pathogens involved in LRTI, with various susceptibilities to antimicrobials, is large constituting an enormous challenge for diagnostic microbiology. In general, in only 50% of cases is an etiologic agent detected. Documented infection is uncommon in community-managed infection and is usually only defined in 25 to 50% of hospital-managed infections. The upper end of the respiratory tract, the rhinopharynx, is widely open to the introduction of airborne microorganisms. It is, however, also a very efficient barrier for invading bacteria. The barrier function of the rhinopharynx results from the local lymphoid tissue producing phagocytic cells and secretory immunoglobulin (Ig) and from the rich commensal flora of aerobic and anaerobic microbes establishing an interfering colonization resistance. The number of these organisms varies from 2.6 × 104 to 4 × 108 CFU of cultivable bacteria per cm2 (95). Aerobes tend to decrease and anaerobes tend to increase with age (98). Colonization starts during the first year of life and is composed not only of commensal organisms but also of potential pathogens: group A β-hemolytic streptococci, Streptococcus pneumoniae, Haemophilus influenzae, and Moraxella catarrhalis. These are present permanently or intermittently, with rates varying with age (decreasing in adults), exposure to other children, geographic location, socioeconomic status, and vaccination status (39). In most cases, these organisms cause disease in only a small percentage of persons colonized. Viruses do not normally colonize the rhinopharynx. However, most bacterial respiratory infections start with or are accompanied by their proliferation in the nasopharynx. Thus, the URT with its commensal flora acts both as a defense mechanism and as a primary site for LRTI, which creates tremendous diagnostic challenges. Any bacteriological examination of nonsterile respiratory specimens must indeed distinguish between organisms infecting the LRT and organisms colonizing the rhinopharynx. Normally sterile samples therefore are considered the “gold standard.” Different specimens commonly collected to detect pathogens causing LRTI have been compared, but the results were not consistent (12, 43, 49, 58, 103) (Table ​(Table1;1; and see Table S1 in the supplemental material). This minireview presents an overview of the optimal detection of Streptococcus pneumoniae, Haemophilus influenzae, Moraxella catarrhalis, Mycoplasma pneumoniae, Chlamydophila pneumoniae, Legionella pneumophila, and respiratory viruses from specimens in patients with community-associated (CA)-LRTI (Table ​(Table22). TABLE 1. Comparison of specimens and sampling methods for the detection of different respiratory pathogensa TABLE 2. Diagnostic approach for the most common specific agents in LRTIsa

Bench-to-bedside review: Rapid molecular diagnostics for bloodstream infection - a new frontier?

Among critically ill patients, the diagnosis of bloodstream infection poses a major challenge. Current standard bacterial identification based on blood culture platforms is intrinsically time-consuming and slow. The continuous evolvement of molecular techniques has the potential of providing a faster, more sensitive and direct identification of causative pathogens without prior need for cultivation. This may ultimately impact clinical decision-making and antimicrobial treatment. This review summarises the currently available technologies, their strengths and limitations and the obstacles that have to be overcome in order to develop a satisfactory bedside point-of-care diagnostic tool for detection of bloodstream infection.