BACKGROUND:

Representative population-based data on the epidemiology of pulmonary non-tuberculous mycobacterial (PNTM) infections in Europe are limited. However, these data are needed in order to optimise patient care and to facilitate the allocation of healthcare resources. The aim of the present study was to investigate the current burden and the trends of PNTM infection-associated hospitalisations in Germany.

METHODS:

International Classification of Diseases, 10th revision (ICD-10) discharge diagnosis codes were extracted from the official nationwide diagnosis-related groups (DRG) hospital statistics in order to identify PNTM infection-associated hospitalisations (ICD-10 code A31.0) between 2005 and 2011. Poisson log-linear regression analysis was used to assess the significance of trends.

RESULTS:

Overall, 5,959 records with PNTM infection as any hospital discharge diagnosis were extracted from more than 125 million hospitalisations. The average annual age-adjusted rate was 0.91 hospitalisations per 100,000 population. Hospitalisation rates increased during the study period for both males and females, with the highest rate of 3.0 hospitalisations per 100,000 population among elderly men, but the most pronounced average increase of 6.4%/year among females, particularly those of young and middle age, and hospitalisations associated with cystic fibrosis. Overall, chronic obstructive pulmonary disease (COPD) was the most frequent PNTM infection-associated condition in 28.9% of hospitalisations and also showed a significant average annual increase of 4.8%.

CONCLUSIONS:

The prevalence of PNTM infection-associated hospitalisations is steadily increasing in Germany. COPD is currently the most important associated condition. Our population-based study provides evidence of a changing epidemiology of PNTM infections and highlights emerging clinical implications.

BACKGROUND:

Soluble CD163 (sCD163) has been associated with arterial inflammation and non-calcified plaques in human immunodeficiency virus (HIV)-infected individuals and has therefore been suggested as a predictive biomarker of myocardial infarction (MI).

METHODS:

We conducted a nested case--control study of 55 cases with first-time MI and 182 controls matched for age, duration of antiretroviral therapy (ART), gender, smoking, and no known cardiovascular disease. All patients had four available plasma samples, 1: Before initiation of antiretroviral therapy (ART), 2: Three months after ART, 3: One year before the case's MI, and 4: The last sample available before the case's MI. We used conditional logistic regression to estimate the association of sCD163 with first-time MI.

RESULTS:

The two groups had similar HIV-parameters and cardiovascular risk factors were equally distributed. There was no significant association between sCD163 and MI neither in samples obtained one year before (OR 1.05, CI 95% 0.85 -- 1.29, p = 0.66) nor two months before (OR 1.20, CI 95% 0.98-1.47 p = 0.08).

CONCLUSION:

sCD163 did not prove to be a useful biomarker for prediction of first-time MI in a HIV-infected population.

BACKGROUND:

Two phylogenetic lineages of influenza B virus coexist and circulate in the human population (B/Yamagata and B/Victoria) but only one B-strain is included in each seasonal vaccine. Mismatch regularly occurs between the recommended and circulating B-strain. Inclusion of both lineages in vaccines may offer better protection against influenza.

METHODS:

This study (NCT00714285) assessed the immunogenicity and safety of two candidate quadrivalent influenza vaccines (QIV) containing two A- and two B-strains (one from each lineage) in adults (18--60 years). Subjects were randomized and stratified by age to receive either QIV (non-adjuvanted or low-dose adjuvanted [LD QIV-AS]) or trivalent influenza vaccine (TIV, non-adjuvanted or low-dose adjuvanted [LD TIV-AS]), N = 105 in all treatment groups. The study evaluated the statistical non-inferiority of the immunological response elicited by QIV and LD QIV-AS versus TIV and LD TIV-AS and the statistical superiority of the response elicited by the quadrivalent vaccines against the B-strain (B/Jiangsu) not included in the TIV.

RESULTS:

Pre-defined non-inferiority and superiority criteria were reached for both QIVs compared to the TIVs. On Day 21 in all vaccine groups SCRs were >=54.8%, SPRs >=88.5% and SCFs >=5.4 for the A strains and B strain included in all vaccines (B/Malaysia). This fulfilled the European (CHMP) and the US (CBER) licensing criteria for the assessment of influenza vaccines in adults (CHMP criteria: SCR > 40%, SPR > 70%, SCF > 2; CBER criteria: LL of 95%CI for SPR >= 70% or SCR >= 40%). Only the QIVs met the CHMP and CBER criteria for the B/Jiangsu strain. In the QIV and LD-QIV-AS groups, the SCFs were 9.1 and 8.1, respectively and the SPRs were 98.1% and 95.2%, whereas for the TIV and LD-TIV-AS groups, the SCFs were 2.3 and 2.5, respectively, and the SPRs were 75.0% and 63.8%, with the LLs of the 95%CI <70% for SPR and <40% for SCR.

CONCLUSIONS:

Addition of a fourth strain did not impact the immune response elicited by the three original strains contained in the TIV. A clear immunological benefit was seen with the QIV formulation for the second B-strain, indicating that quadrivalent vaccines could provide broader protection against influenza.Trial registration: ClinicalTrials.gov: NCT00714285.

BACKGROUND:

High rates of bacterial coinfection in autopsy data from the 2009 H1N1 influenza ("flu") pandemic suggest synergies between flu and pneumococcal disease (PD) during pandemic conditions, and highlight the importance of interventions like the 13-valent pneumococcal conjugate vaccine (PCV13) that may mitigate the impact of a pandemic.

METHODS:

We used a decision-analytic model, estimated from published sources, to assess the impact of pediatric vaccination with PCV13 versus the 7-valent vaccine (PCV7) on PD incidence and mortality in a normal flu season (10% flu incidence) and in a pandemic similar to 2009-2010 H1N1 (20% flu incidence, mild virulence, high impact in children). Both direct and indirect (herd) effects against PD were considered. Effectiveness of PCV13 was extrapolated from observed PCV7 data, using assumptions of serotype prevalence and PCV13 protection against the 6 serotypes not in PCV7. To simulate 2009--2010 H1N1, autopsy data were used to estimate the overall proportion of flu deaths with bacterial coinfections. By assuming that increased risk of death during the pandemic occurred among those with comorbidity (using obesity as proxy) and bacterial coinfections primarily due to S. pneumoniae or S. aureus, we estimated the proportion co-infected among all (fatal and non-fatal) flu cases (7.6% co-infected with any organism; 2.2% with S. pneumoniae). PD incidence, mortality, and total healthcare costs were evaluated over a 1-year horizon.

RESULTS:

In a normal flu season, compared to PCV7, PCV13 is expected to prevent an additional 13,400 invasive PD (IPD) cases, 399,000 pneumonia cases, and 2,900 deaths, leading to cost savings of $472 M. In a pandemic similar to 2009--2010 H1N1, PCV13 would prevent 22,800 IPD cases, 872,000 pneumonia cases, and 3,700 deaths, resulting in cost savings of $1.0 B compared to PCV7.

CONCLUSIONS:

In a flu pandemic similar to the 2009--2010 H1N1, protection against the 6 additional serotypes in PCV13 would likely be effective in preventing pandemic-related PD cases, mortality, and associated costs.

BACKGROUND:

Beside high mortality, acute bacterial meningitis may lead to a high frequency of neuropsychological sequelae. The Sahelian countries belonging to the meningitis belt experience approximately 50% of the meningitis cases occurring in the world. Studies in Africa have shown that N. meningitidis could cause hearing loss in up to 30% of the cases, exceeding sometimes measles. The situation is similar in Niger which experiences yearly meningitis epidemics and where rehabilitation wards are rare and hearing aids remain unaffordable. The aim of this study was to estimate the frequency of neuropsychological sequelae after acute bacterial meningitis in four of the eight regions of Niger.

METHODS:

Subjects exposed to acute bacterial meningitis were enrolled into a cohort with non exposed subjects matched on age and gender. Consenting subjects were interviewed during inclusion and at a control visit two months later. If clinical symptoms or psychological troubles persisted at both visits among the exposed subjects with a frequency significantly greater than that observed among the non exposed subjects, a sequelae was retained. The comparison of the frequency of sequelae between non exposed and exposed subjects to bacterial meningitis was also calculated using the Fisher exact test.

RESULTS:

Three persisting functional symptoms were registered: headaches, asthenia, and vertigo among 31.3, 36.9, and 22.4% respectively of the exposed subjects. A significant motor impairment was retrieved among 12.3% of the exposed versus 1.6% of the non exposed subjects. Hearing loss significantly disabled 31.3% of the exposed subjects and 10.4% exhibited a serious deafness.

CONCLUSIONS:

This study carried out in Niger confirms two serious neurological sequelae occurring at high frequencies after bacterial meningitis: severe and profound hearing loss and motor impairment. Cochlear implantation and hearing aids are too expensive for populations living in developing countries. Neurological sequelae occurring after meningitis should sensitize African public health authorities on the development of rehabilitation centers. All these challenges can be met through existing strategies and guidelines.

BACKGROUND:

Tuberculosis (TB) is an infectious disease caused by Mycobacterium tuberculosis(M. tuberculosis). The annotation of functional genome and signaling network in M. tuberculosis are still not systematic. Essential gene modules are a collection of functionally related essential genes in the same signaling or metabolic pathway. The determination of essential genes and essential gene modules at genomic level may be important for better understanding of the physiology and pathology of M. tuberculosis, and also helpful for the development of drugs against this pathogen. The establishment of genomic operon database (DOOR) and the annotation of gene pathways have felicitated the genomic analysis of the essential gene modules of M. tuberculosis.

METHOD:

Bibliometric approach has been used to perform a High-throughput screen for essential genes of M. tuberculosis strain H37Rv. Ant colony algorithm were used to identify the essential genes in other M. tuberculosis reference strains. Essential gene modules were analyzed by operon database DOOR. The pathways of essential genes were assessed by Biocarta, KEGG, NCI-PID, HumanCyc and Reactome. The function prediction of essential genes was analyzed by Pfam.

RESULTS:

A total approximately 700 essential genes were identified in M. tuberculosis genome. 40% of operons are consisted of two or more essential genes. The essential genes were distributed in 92 pathways in M. tuberculosis. In function prediction, 61.79% of essential genes were categorized into virulence, intermediary metabolism/respiration,cell wall related and lipid metabolism, which are fundamental functions that exist in most bacteria species.

CONCLUSION:

We have identified the essential genes of M. tuberculosis using bibliometric approach at genomic level. The essential gene modules were further identified and analyzed.

BACKGROUND:

The use of examination gloves is part of the standard precautions to prevent medical staff from transmission of infectious agents between patients. Gloves also protect the staff from infectious agents originating from patients. Adequate protection, however, depends on intact gloves. The risk of perforation of examination gloves is thought to correlate with duration of wearing, yet, only very few prospective studies have been performed on this issue.

METHODS:

A total number of 1500 consecutively used pairs of examination gloves of two different brands and materials (latex and nitrile) were collected over a period of two months on two ICU's. Used gloves were examined for micro perforations using the "water-proof-test" according to EN 455--1. Cox-regression for both glove types was used to estimate optimal changing intervals,

RESULTS:

Only 26% of gloves were worn longer than 15 min. The total perforation rate was 10.3% with significant differences and deterioration of integrity of gloves between brands (p<0.001). Apart from the brand, "change of wound dressing" (p = 0.049) and "washing patients" (p = 0.001) were also significantly associated with an increased risk of perforation.

CONCLUSION:

Medical gloves show marked differences in their durability that cannot be predicted based on the technical data routinely provided by the manufacturer. Based on the increase of micro perforations over time and the wearing behavior, recommendations for maximum wearing time of gloves should be given. Changing of gloves after 15 min could be a good compromise between feasibility and safety. HCWs should be aware of the benefits and limitations of medical gloves. To improve personal hygiene hand disinfection should be further encouraged.

BACKGROUND:

The prevalence and the patterns of ocular inflammatory disease and ocular tuberculosis (TB) are largely undocumented among Multidrug Resistant TB (MDR-TB) patients co-infected with Human Immunodeficiency Virus (HIV) and on antituberculosis and antiretroviral therapy (ART).

METHODS:

Lilavati Hospital and Research Center and Medecins Sans Frontieres (MSF) organized a cross-sectional ophthalmological evaluation of HIV/MDR-TB co-infected patients followed in an MSF-run HIV-clinic in Mumbai, India, which included measuring visual acuity, and slit lamp and dilated fundus examinations.

RESULTS:

Between February and April 2012, 47 HIV/MDR-TB co-infected patients (including three patients with extensively drug-resistant TB) were evaluated. Sixty-four per cent were male, mean age was 39 years (standard deviation: 8.7) and their median (IQR) CD4 count at the time of evaluation was 264 cells/muL (158--361). Thirteen patients (27%) had detectable levels of HIV viremia (>20 copies/ml). Overall, examination of the anterior segments was normal in 45/47 patients (96%). A dilated fundus examination revealed active ocular inflammatory disease in seven eyes of seven patients (15.5%, 95% Confidence Intervals (CI); 5.1-25.8%). 'These included five eyes of five patients (10%) with choroidal tubercles, one eye of one patient (2%) with presumed tubercular chorioretinitis and one eye of one patient (2%) with evidence of presumed active CMV retinitis. Presumed ocular tuberculosis was thus seen in a total of six patients (12.7%, 95% CI; 3.2-22.2%). Two patients who had completed anti-TB treatment had active ocular inflammatory disease, in the form of choroidal tubercles (two eyes of two patients). Inactive scars were seen in three eyes of three patients (6%). Patients with extrapulmonary TB and patients <39 years old were at significantly higher risk of having ocular TB [Risk Ratio: 13.65 (95% CI: 2.4-78.5) and 6.38 (95% CI: 1.05-38.8) respectively].

CONCLUSIONS:

Ocular inflammatory disease, mainly ocular tuberculosis, was common in a cohort of HIV/MDR-TB co-infected patients in Mumbai, India. Ophthalmological examination should be routinely considered in HIV patients diagnosed with or suspected to have MDR-TB, especially in those with extrapulmonary TB.

BACKGROUND:

About ninety percent of immunocompetent adults recover from hepatitis B virus (HBV) infection within 6 months after transmission. The infection is considered to be terminated if the antibodies (HBsAb) to the hepatitis B surface antigen (HBsAg) become detectable and the HBsAg and Hepatitis B virus DNA (HBV DNA,) are no longer perceptible. After recovery from an acute infection, the detection of HBsAb is assumed to indicate lifelong immunity. However, after initiation of severe immunosuppression, HBV reactivation, as detected by HBsAg seroreversion may be observed in patients with previously resolved HBV infections.

CASE PRESENTATION:

We present an unusual case of a 64-year-old Caucasian woman showing clinically apparent HBV seroreversion more than 45 months after hematopoietic stem cell transplantation (HSCT). Despite living without immunosuppressive agents for more than 40 months, she developed a fulminant HBV infection with detection of a mutated hepatitis B virus carrying two immune escape mutations (D144E/G145R) in the HBsAg (HBsIE mutation).

CONCLUSION:

After HSCT, the absence of risk factors such as strong immunosuppression and graft-versus-host disease decreases the risk of HBV seroreversion but may rearward seroreversion to a later time. Therefore, when monitoring HSCT, patients with serological markers of a resolved HBV infection [HBcAb + (hepatitis B core antibody), HBsAb+, and HBsAg-], the follow up has to be extended over several years to exclude HBV reactivation with HBsAg seroreversion. Furthermore, this case demonstrates the complexity of virus evolution after HBsAg seroreversion as a result of immunosuppression after HSCT.

BACKGROUND:

Diagnosis of pulmonary tuberculosis (PTB) is difficult in infants and young children. For microbiological confirmation of PTB children, sequential gastric lavage (GL) is recommended. Induced sputum (IS) may be an alternative or complementary tool, but the information is limited in children in developed countries. The aim of this study is to assess the safety and diagnostic yield from IS combined with GL for PTB diagnosis in non-HIV infected children.

METHODS:

The study involved 22 children with suspected PTB admitted to the Getafe Hospital from January 2007 to May 2011. IS and GL were performed on three consecutive days, according to a standardized protocol. In all samples, BK staining, culture and PCR were carried out, including Genotype MTBDR plus for resistance to INH-RIF (Isoniazid-Rifampin) since 2008. A preliminary analysis of an ongoing prospective study is presented.

RESULTS:

Median age was 72 months (range 1 month to 14 years of age). Seven (33%) were <= 5 years of age. Seventeen were clinically diagnosed of PTB based on positive PPD and radiological criteria. Microbiological confirmation was achieved in 10 (58.8%) by either GL or IS. M. tuberculosis was identified by GL in 8 children (47.1%) and by IS in 7 (41.2%). One infant (2 IS samples) had transient oxygen desaturation recovered spontaneously.

CONCLUSIONS:

IS appears to be safe and well tolerated by children for diagnosis of PTB and is more convenient. Increasing the diagnostic yield of PTB in children with PTB may be a complementary technique. Largest studies are necessary to define the role of IS in paediatric PTB.