Effects of repeated infections with non-typeable Haemophilus influenzae on lung in vitamin D deficient and smoking mice.

BACKGROUND: In chronic obstructive pulmonary disease (COPD), exacerbations cause acute inflammatory flare-ups and increase the risk for hospitalization and mortality. Exacerbations are common in all disease stages and are often caused by bacterial infections e.g., non-typeable Heamophilus influenzae (NTHi). Accumulating evidence also associates vitamin D deficiency with the severity of COPD and exacerbation frequency. However, it is still unclear whether vitamin D deficiency when combined with cigarette smoking would worsen and prolong exacerbations caused by repeated infections with the same bacterial strain. METHODS: Vitamin D sufficient (VDS) and deficient (VDD) mice were exposed to nose-only cigarette smoke (CS) for 14 weeks and oropharyngeally instilled with NTHi at week 6, 10 and 14. Three days after the last instillation, mice were assessed for lung function, tissue remodeling, inflammation and immunity. The impact of VDD and CS on inflammatory cells and immunoglobulin (Ig) production was also assessed in non-infected animals while serum Ig production against NTHi and dsDNA was measured in COPD patients before and 1 year after supplementation with Vitamin D3. RESULTS: VDD enhanced NTHi eradication, independently of CS and complete eradication was reflected by decreased anti-NTHi Ig's within the lung. In addition, VDD led to an increase in total lung capacity (TLC), lung compliance (Cchord), MMP12/TIMP1 ratio with a rise in serum Ig titers and anti-dsDNA Ig's. Interestingly, in non-infected animals, VDD exacerbated the CS-induced anti-NTHi Ig's, anti-dsDNA Ig's and inflammatory cells within the lung. In COPD patients, serum Ig production was not affected by vitamin D status but anti-NTHi IgG increased after vitamin D3 supplementation in patients who were Vitamin D insufficient before treatment. CONCLUSION: During repeated infections, VDD facilitated NTHi eradication and resolution of local lung inflammation through production of anti-NTHi Ig, independently of CS whilst it also promoted autoantibodies. In COPD patients, vitamin D supplementation could be protective against NTHi infections in vitamin D insufficient patients. Future research is needed to decipher the determinants of dual effects of VDD on adaptive immunity. TRAIL REGISTRATION: ClinicalTrials, NCT00666367. Registered 23 April 2008, https://www.clinicaltrials.gov/ct2/show/study/NCT00666367 .

Detection of SARS-CoV-2 in young children attending day-care centres in Belgium, May 2020 to February 2022.

Presence of SARS-CoV-2 was monitored in nasopharyngeal samples from young children aged 6-30 months attending day-care centres (DCCs) in Belgium from May 2020-February 2022. SARS-CoV-2 carriage among DCC children was only detected from November 2021, after emergence of Delta and Omicron variants, in 9 of the 42 DCCs screened. In only one DCC, two children tested positive for SARS-CoV-2 at the same sampling time point, suggesting limited transmission of SARS-CoV-2 in Belgian DCCs among young children during the studied period.

Exploring association between MBL2 gene polymorphisms and the occurrence of clinical blackwater fever through a case-control study in Congolese children.

BACKGROUND: Blackwater fever (BWF), one of the most severe and life-threatening forms of falciparum malaria, is characterized by acute massive intravascular haemolysis, often leading to acute renal failure. Thus far, the genetics of the underlying susceptibility to develop BWF is not fully elucidated. Deficiency in the MBL protein, an important component of the innate immune system, has previously been suggested to be a susceptibility factor for the development of severe malaria. This study aimed to evaluate the association between MBL2 gene polymorphisms, known to affect the MBL protein level/activity, and the occurrence of BWF among Congolese children. METHODS: This is a case-control study. Cases were patients with BWF, whereas controls, matched for gender and age, had uncomplicated malaria (UM). Dried blood spot was collected for genotyping. RESULTS: A total of 129 children were screened, including 43 BWF and 86 UM. The common allele in BWF and UM was A, with a frequency of 76.7 and 61.0%, respectively (OR: 2.67 (0.87-829) and p = 0.079). The frequency of the C allele was 18.6 and 29.1% in BWF and UM groups, respectively, with p = 0.858. Not a single D allele was encountered. Genotype AA was at higher risk for BWF whereas genotypes A0 (AB and AC) were over-represented in UM group (OR: 0.21 (0.06-0.78)) with p = 0.019. Nine haplotypes were observed in this study: 3 high MBL expression haplotypes and 6 low MBL expression haplotype. One new haplotype HYPC was observed in this study. None of these haplotypes was significantly associated with BWF. CONCLUSION: This pilot study is a preliminary research on MBL2 gene and infectious diseases in DRC. The study results show a higher risk for BWF in AA. This suggests that future studies on BWF should further investigate the contribution of a strong immune response to the occurrence of BWF.

Performance and potential clinical impact of Alfred60AST (Alifax®) for direct antimicrobial susceptibility testing on positive blood culture bottles.

Rapid pathogen identification (ID) and antimicrobial susceptibility testing (AST) of bacteria-causing bloodstream infections can improve patients' outcome. In this study, we evaluated the performance of Alfred60AST (Alifax) which provides AST directly on positive blood culture (BC) bottles by light scattering. In a selected group of patients with a clinical suspicion of severe sepsis or at risk for infections with multiresistant organisms, we compared Alfred60AST AST results with traditional AST results (Vitek2 (bioMérieux) or disk diffusion). Discrepancy analysis was performed by Etest (bioMérieux) or broth microdilution. In total, 222 samples were evaluated. On 595 susceptibility determinations, 93.4% showed categorical agreement (CA) with the standard method. Eighty-one percent of isolates showed a 100% categorical agreement (CA) which increased to 84.3% after discrepancy analysis. There were 8 very major discrepancies (VMD), 18 major discrepancies (MD), and 13 minor discrepancies (MiD). Most discrepant results were observed for piperacillin-tazobactam (15.6%) and clindamycin (18.9%). Analysis time was 6-6.5 h for a complete Alfred60AST AST result. In addition, we evaluated the behavior of clinicians in adjusting antibiotic therapy according to the routine AST results. In 37% of all patients, antibiotic therapy was altered after reporting of AST result and adjustment was more frequent for Gram-negative than for Gram-positive isolates. With some improvements, Alfred60AST provides accurate and rapid preliminary AST results for organisms causing bloodstream infections and may have at least a potential clinical benefit in about one-third of patients with severe sepsis, by delivering faster results compared with conventional methods.

How nasopharyngeal pneumococcal carriage evolved during and after a PCV13-to-PCV10 vaccination programme switch in Belgium, 2016 to 2018.

BackgroundThe current carriage study was set up to reinforce surveillance during/after the PCV13-to-PCVC10 switch in Belgium.AimThis observational study monitored carriage of Streptococcus pneumoniae (Sp) serotypes, particularly those no longer covered (3, 6A, 19A), as well as Haemophilus influenzae (Hi), because PCV10 contains the non-typeable Hi protein D.MethodsA total of 2,615 nasopharyngeal swabs from children (6-30 months old) attending day care were collected in three periods over 2016-2018. Children's demographic and clinical characteristics and vaccination status were obtained through a questionnaire. Sp and Hi were identified by culture and PCR. Pneumococcal strains were tested for antimicrobial (non-)susceptibility by disc diffusion and serotyped by Quellung-reaction (Quellung-reaction and PCR for serotypes 3, 6A, 19A).ResultsThe carriage prevalence of Sp (> 75%) remained stable over the successive periods but that of Hi increased (87.4%, 664 Hi-carriers/760 in 2016 vs 93.9%, 895/953 in 2017-2018). The proportion of non-PCV13 vaccine serotypes decreased (94.6%, 438 isolates/463 in 2016 vs 89.7%, 599/668 in 2017-2018) while that of PCV13-non-PCV10 vaccine serotypes (3 + 6A + 19A) increased (0.9%, 4 isolates/463 in 2016 vs 7.8%, 52/668 in 2017-2018), with serotype 19A most frequently identified (87.9%, 58/66 isolates). Non-susceptibility of pneumococci against any of the tested antibiotics was stable over the study period (> 44%).ConclusionsDuring and after the PCV13-to-PCV10 vaccine switch, the proportion of non-PCV13 serotypes decreased, mainly due to a serotype 19A carriage prevalence increase. These results complement invasive pneumococcal disease surveillance data, providing further basis for pneumococcal vaccination programme policy making.

Specific members of the predominant gut microbiota predict pouchitis following colectomy and IPAA in UC.

OBJECTIVE: Pouchitis is the most common complication after colectomy with ileal pouch-anal anastomosis (IPAA) for UC and the risk is the highest within the 1st year after surgery. The pathogenesis is not completely understood but clinical response to antibiotics suggests a role for gut microbiota. We hypothesised that the risk for pouchitis can be predicted based on the faecal microbial composition before colectomy. DESIGN: Faecal samples from 21 patients with UC undergoing IPAA were prospectively collected before colectomy and at predefined clinical visits at 1 month, 3 months, 6 months and 12 months after IPAA. The predominant microbiota was analysed using community profiling with denaturing gradient gel electrophoresis followed by quantitative real-time PCR validation. RESULTS: Cluster analysis before colectomy distinguished patients with pouchitis from those with normal pouch during the 1st year of follow-up. In patients developing pouchitis, an increase of Ruminococcus gnavus (p<0.001), Bacteroides vulgatus (p=0.043), Clostridium perfringens (p=0.011) and a reduction of two Lachnospiraceae genera (Blautia (p=0.04), Roseburia (p=0.008)) was observed. A score combining these five bacterial risk factors was calculated and presence of at least two risk factors showed a sensitivity and specificity of 100% and 63.6%, respectively. CONCLUSIONS: Presence of R. gnavus, B. vulgatus and C. perfringens and absence of Blautia and Roseburia in faecal samples of patients with UC before surgery is associated with a higher risk of pouchitis after IPAA. Our findings suggest new predictive and therapeutic strategies in patients undergoing colectomy with IPAA.

Psychological comorbidity increases the risk for postinfectious IBS partly by enhanced susceptibility to develop infectious gastroenteritis.

OBJECTIVE: Psychological factors increase the risk to develop postinfectious IBS (PI-IBS), but the mechanisms involved are unclear. As stress affects the immune system, we investigated the potential interaction between psychological factors, the immune response against infectious gastroenteritis (IGE) and the development of IGE and PI-IBS in a large cohort exposed to contaminated drinking water. DESIGN: 18 620 people exposed to contaminated drinking water (norovirus, Giardia lamblia, Campylobacter jejuni) were invited to participate in a prospective controlled cohort study. They were asked to complete questionnaires assessing demographic, psychological and clinical data during the outbreak and 1 year later. At both time points, in-depth immune function (peripheral blood and rectal biopsies) was studied in a subgroup of subjects. RESULTS: 1379 subjects completed the questionnaires during the outbreak, of which 271 developed IGE. Risk factors for IGE included younger age, pre-existing dyspepsia-like symptoms, anxiety and drinking contaminated tap water. Anxiety scores before the outbreak inversely correlated with interleukin-2-expressing CD4+ T cells (r=0.6, p=0.01, n=23). At follow-up, 34 of 172 (20%) IGE subjects developed IBS compared with 24/366 exposed participants (7%, p<0.0001, χ(2) test). A Th2 cytokine phenotype at time of infection was associated with increased risk for PI-IBS 1 year later. Except for increased B cell numbers, no evidence for systemic or rectal mucosal immune activation in PI-IBS was demonstrated at follow-up. CONCLUSIONS: Our study shows that the increased risk of patients with psychological comorbidity to develop PI-IBS may partly result from an increased susceptibility to develop IGE, possibly resulting from a Th2-immune bias. TRIAL REGISTRATION NUMBER: (ClinicalTrials.gov NCT01497847).

The FXR agonist obeticholic acid prevents gut barrier dysfunction and bacterial translocation in cholestatic rats.

Bacterial translocation (BTL) drives pathogenesis and complications of cirrhosis. Farnesoid X-activated receptor (FXR) is a key transcription regulator in hepatic and intestinal bile metabolism. We studied potential intestinal FXR dysfunction in a rat model of cholestatic liver injury and evaluated effects of obeticholic acid (INT-747), an FXR agonist, on gut permeability, inflammation, and BTL. Rats were gavaged with INT-747 or vehicle during 10 days after bile-duct ligation and then were assessed for changes in gut permeability, BTL, and tight-junction protein expression, immune cell recruitment, and cytokine expression in ileum, mesenteric lymph nodes, and spleen. Auxiliary in vitro BTL-mimicking experiments were performed with Transwell supports. Vehicle-treated bile duct-ligated rats exhibited decreased FXR pathway expression in both jejunum and ileum, in association with increased gut permeability through increased claudin-2 expression and related to local and systemic recruitment of natural killer cells resulting in increased interferon-γ expression and BTL. After INT-747 treatment, natural killer cells and interferon-γ expression markedly decreased, in association with normalized permeability selectively in ileum (up-regulated claudin-1 and occludin) and a significant reduction in BTL. In vitro, interferon-γ induced increased Escherichia coli translocation, which remained unaffected by INT-747. In experimental cholestasis, FXR agonism improved ileal barrier function by attenuating intestinal inflammation, leading to reduced BTL and thus demonstrating a crucial protective role for FXR in the gut-liver axis.

Invasive Salmonella Infections at Multiple Surveillance Sites in the Democratic Republic of the Congo, 2011-2014.

BACKGROUND: This study reports the microbiological landscape of Salmonella Typhi and invasive nontyphoidal Salmonella (iNTS) in the Democratic Republic of the Congo (DRC). METHODS: Blood cultures obtained from hospital-admitted patients suspected of bloodstream infection (BSI) in 4 of 11 provinces in DRC (Kinshasa, Bas-Congo, Equateur, and Orientale) were processed. Sampling had started in 2007; the results for the period 2011-2014 are reported. RESULTS: Salmonella Typhi and iNTS were cultured from 194 (1.4%) and 840 (5.9%), respectively, of 14,110 BSI episodes and ranked first among BSI pathogens in adults (65/300 [21.7%]) and children (783/1901 [41.2%]), respectively. A total of 948 of 1034 (91.7%) isolates were available for analysis (164 Salmonella Typhi and 784 iNTS). Salmonella Typhimurium and Salmonella Enteritidis represented 386 (49.2%) and 391 (49.9%), respectively, of iNTS isolates, fluctuating over time and geography and increasing during the rainy season. Adults accounted for <5% of iNTS BSI episodes. Children <5 years accounted for 20.3% of Salmonella Typhi BSI episodes. Among Salmonella Typhi, rates of multidrug resistance and decreased ciprofloxacin susceptibility (DCS) were 37.8% and 37.2%, respectively, and 18.3% displayed combined multidrug resistance and DCS; rates of azithromycin and ceftriaxone resistance were 0.6% and absent, respectively. Among NTS isolates, ≥80% (79.7% of Salmonella Enteritidis and 90.2% of Salmonella Typhimurium isolates) showed multidrug resistance, and <2.5% showed DCS. Combined extended-spectrum ß-lactamase production (blaTEM-1 gene) and azithromycin resistance was noted in 12.7% of Salmonella Typhimurium isolates, appearing in Bas-Congo from 2013 onward. CONCLUSIONS: Salmonella Typhi and NTS are major causes of BSI in DRC; their antimicrobial resistance is increasing.

Factors impacting unbound vancomycin concentrations in different patient populations.

The unbound drug hypothesis states that only unbound drug concentrations are active and available for clearance, and highly variable results regarding unbound vancomycin fractions have been reported in the literature. We have determined the unbound vancomycin fractions in four different patient groups by a liquid chromatography tandem mass spectrometry (LC-MS/MS) method and identified factors that modulate vancomycin binding. We have further developed and validated a prediction model to estimate unbound vancomycin concentrations. Vancomycin (unbound and total) concentrations were measured in 90 patients in four different hospital wards (hematology [n = 33 samples], intensive care unit [ICU] [n = 51], orthopedics [n = 44], and pediatrics [age range, 6 months to 14 years; n = 18]) by a validated LC-MS/MS method. Multiple linear mixed model analysis was performed to identify patient variables that were predictive of unbound vancomycin fractions and concentrations. The variables included in the model were patient age, ward, number of coadministered drugs with high protein binding, kidney function (estimated glomerular filtration rate [determined by Chronic Kidney Disease Epidemiology Collaboration formula]), alpha-1-acid glycoprotein, albumin, total bilirubin, IgA, IgM, urea, and total vancomycin concentrations. In the pediatric cohort, the median unbound vancomycin fraction was 81.3% (range, 61.9 to 95.9%), which was significantly higher (P < 0.01) than the unbound fraction found in the three adult patient cohorts (hematology, 60.6% [48.7 to 90.6%]; ICU, 61.7% [47.0 to 87.6%]; orthopedics, 56.4% [45.9 to 78.0%]). The strongest significant predictor of the unbound vancomycin concentration was the total drug concentration, completed by albumin in the pediatric cohort and albumin and IgA in the adult cohorts. Validation of our model was performed with data from 13 adult patients. A mean difference of 0.3 mg/liter (95% confidence interval [CI], -1.3 to 0.7 mg/liter; R(2) = 0.99 [95% CI, 0.95 to 0.99]) between measured and calculated unbound vancomycin concentrations demonstrated that the predictive performance of our model was favorable. Unbound vancomycin fractions vary significantly between pediatric and adult patients. We developed a formula to estimate the unbound fraction derived from total vancomycin, albumin, and IgA concentrations in adult patients.

A decrease of the butyrate-producing species Roseburia hominis and Faecalibacterium prausnitzii defines dysbiosis in patients with ulcerative colitis.

OBJECTIVE: Bacteria play an important role in the onset and perpetuation of intestinal inflammation in inflammatory bowel disease (IBD). Unlike in Crohn's disease (CD), in which dysbiosis has been better characterised, in ulcerative colitis (UC), only small cohorts have been studied and showed conflicting data. Therefore, we evaluated in a large cohort if the microbial signature described in CD is also present in UC, and if we could characterise predominant dysbiosis in UC. To assess the functional impact of dysbiosis, we quantified the bacterial metabolites. DESIGN: The predominant microbiota from 127 UC patients and 87 age and sex-matched controls was analysed using denaturing gradient gel electrophoresis (DGGE) analysis. Differences were quantitatively validated using real-time PCR. Metabolites were quantified using gas chromatography-mass spectrometry. RESULTS: Based on DGGE analysis, the microbial signature previously described in CD was not present in UC. Real-time PCR analysis revealed a lower abundance of Roseburia hominis (p<0.0001) and Faecalibacterium prausnitzii (p<0.0001) in UC patients compared to controls. Both species showed an inverse correlation with disease activity. Short-chain fatty acids (SCFA) were reduced in UC patients (p=0.014), but no direct correlation between SCFA and the identified bacteria was found. CONCLUSIONS: The composition of the fecal microbiota of UC patients differs from that of healthy individuals: we found a reduction in R hominis and F prausnitzii, both well-known butyrate-producing bacteria of the Firmicutes phylum. These results underscore the importance of dysbiosis in IBD but suggest that different bacterial species contribute to the pathogenesis of UC and CD.

Pseudo-outbreak of pre-extensively drug-resistant (Pre-XDR) tuberculosis in Kinshasa: collateral damage caused by false detection of fluoroquinolone resistance by GenoType MTBDRsl.

Fluoroquinolones are the core drugs for the management of multidrug-resistant tuberculosis (MDR-TB). Molecular drug susceptibility testing methods provide considerable advantages for scaling up programmatic management and surveillance of drug-resistant TB. We describe here the misidentification of fluoroquinolone resistance by the GenoType MTBDRsl (MTBDRsl) (Hain Lifescience GmbH, Nehren, Germany) line probe assay (LPA) encountered during a feasibility and validation study for the introduction of this rapid drug susceptibility test in Kinshasa, Democratic Republic of Congo. The double gyrA mutation 80Ala and 90Gly represented 57% of all fluoroquinolone mutations identified from MDR-TB patient sputum samples, as confirmed by DNA sequencing. This double mutation was previously found to be associated with susceptibility to fluoroquinolones, yet it leads to absent hybridization of a wild-type band in the MTBDRsl and is thus falsely scored as resistance. Our findings suggest that MTBDRsl results must be interpreted with caution when the interpretation is based solely on the absence of a wild-type band without confirmation by visualization of a mutant band. Performance of the MTBDRsl LPA might be improved by replacing the gyrA wild-type probes by additional probes specific for well-documented gyrA mutations that confer clinically relevant resistance.

Fourth Belgian multicentre survey of antibiotic susceptibility of anaerobic bacteria.

OBJECTIVES: To collect recent data on the susceptibility of anaerobes to antimicrobial agents with known activity against anaerobes, and to compare them with results from previous Belgian multicentre studies. METHODS: Four hundred and three strict anaerobic clinical isolates were prospectively collected from February 2011 to April 2012 in eight Belgian university hospitals. MICs were determined by one central laboratory for 11 antimicrobial agents using Etest methodology. RESULTS: According to EUCAST breakpoints, >90% of isolates were susceptible to amoxicillin/clavulanate (94%), piperacillin/tazobactam (91%), meropenem (96%), metronidazole (92%) and chloramphenicol (98%), but only 70% and 40% to clindamycin and penicillin, respectively. At CLSI recommended breakpoints, only 71% were susceptible to moxifloxacin and 79% to cefoxitin. MIC50/MIC90 values for linezolid and for tigecycline were 1/4 and 0.5/4 mg/L, respectively. When compared with survey data from 2004, no major differences in susceptibility profiles were noticed. However, the susceptibility of Prevotella spp. and other Gram-negative bacilli to clindamycin decreased from 91% in 1993-94 and 82% in 2004 to 69% in this survey. Furthermore, the susceptibility of clostridia to moxifloxacin decreased from 88% in 2004 to 66% in 2011-12 and that of fusobacteria from 90% to 71%. CONCLUSIONS: Compared with previous surveys, little evolution was seen in susceptibility, except a decline in activity of clindamycin against Prevotella spp. and other Gram-negative bacteria, and of moxifloxacin against clostridia. Since resistance was detected to all antibiotics, susceptibility testing of anaerobic isolates is indicated in severe infections to confirm appropriateness of antimicrobial therapy.

Clinical outcome of parapneumonic empyema in children treated according to a standardized medical treatment.

UNLABELLED: Treatment of parapneumonic empyema (PE) consists of intravenous antibiotics and, in case of large effusions and persisting fever, pleural chest drain (±intrapleural fibrinolytics) or video-assisted surgical intervention. We standardized the treatment for PE in our tertiary care center choosing a first-step nonsurgical approach. The aim was to evaluate the need for surgery and to collect data on disease course, outcome, and microbiology. For all children treated for PE between 2006 and 2013, data were prospectively collected concerning treatment, length of stay, duration of fever, complications, and causative agent. Of 132 children treated for PE, 20 % needed surgical intervention. Analyzed per year, the need for surgery decreased from almost 40 % in 2007 to 0 % in 2010 again increasing to 40 % although this did not reach statistical significance (p = 0.115). Median duration of "in-hospital fever" was 5 days (IQR, 3-8). The duration of fever correlated with pleural LDH (r = 0.324; p = 0.002) and pleural glucose (r = -0.248; p = 0.021) and was inversely correlated with pleural pH (r = -0.249; p = 0.046). Based on pleural PCR data, 85 % of PE were caused by Streptococcus pneumoniae (40 % serotype 1). CONCLUSION: After introduction of a standardized primary medical approach (chest drain ± fibrinolysis) for PE in our institution, the need for surgical rescue interventions overall remained at 20 %, which is higher than in some other reports. Difference in microbiology or disease severity could not be proven.

The role of staphylothrombin-mediated fibrin deposition in catheter-related Staphylococcus aureus infections.

Staphylococcus aureus (S. aureus) is a frequent cause of catheter-related infections. S. aureus secretes the coagulases staphylocoagulase and von Willebrand factor-binding protein, both of which form a staphylothrombin complex upon binding to prothrombin. Although fibrinogen and fibrin facilitate the adhesion of S. aureus to catheters, the contribution of staphylothrombin-mediated fibrin has not been examined. In this study, we use a S. aureus mutant lacking both coagulases (Δcoa/vwb) and dabigatran, a pharmacological inhibitor of both staphylothrombin and thrombin, to address this question. Genetic absence or chemical inhibition of pathogen-driven coagulation reduced both fibrin deposition and the retention of S. aureus on catheters in vitro. In a mouse model of jugular vein catheter infection, dabigatran reduced bacterial load on jugular vein catheters, as well as metastatic kidney infection. Importantly, inhibition of staphylothrombin improved the efficacy of vancomycin treatment both in vitro and in the mouse model.

Blackwater fever in Congolese children: a report of clinical, laboratory features and risk factors.

BACKGROUND: Blackwater fever (BWF) is one of the severe forms of malaria. This complication was first described among non-immune European expatriates in the malaria endemic areas. Recently, resurgence of this form of malaria has been reported among the indigenous populations. The objective of this study was to investigate the risk factors among BWF patients. METHODS: A case-control study was conducted between in four hospitals located in Kinshasa, Democratic Republic of Congo from January 2010 to December 2011. One hundred and twenty nine children were recruited with 43 (cases) and 86 (control). RESULTS: No significant difference in the gender and age distribution was observed between the case and control). The sex-ratio male to female in the case group and control group was respectively 1:1.0 and 1:1.1. The mean age was 8.62 years (SD = 3.84) in patients with haemoglobinuria and 8.55 years (SD = 3.77) in the control group. No difference in frequency of co-infection with Plasmodium falciparum and Plasmodium malariae was observed between the two groups. Significant differences in haemoglobin, haematocrit, creatinine, urea and platelets levels were observed between the two groups (p < 0.001), but not for blood group and lactate dehydrogenase (LDH) level. Majority of the BWF cases occurred during the rainy season (88.4%). Treatment with quinine (95.3%) was significantly associated with cases (p < 0.001). Seven (16.2%) of the haemoglobinuric children developed acute renal failure. CONCLUSION: Rainy season, low parasitaemia and quinine ingestion were the major risk factors significantly associated with haemoglobinuria. Acute renal failure was observed as the major complication of BWF.

High doses of vitamin D to reduce exacerbations in chronic obstructive pulmonary disease: a randomized trial.

BACKGROUND: Low serum 25-hydroxyvitamin D (25-[OH]D) levels have been associated with lower FEV(1), impaired immunologic control, and increased airway inflammation. Because many patients with chronic obstructive pulmonary disease (COPD) have vitamin D deficiency, effects of vitamin D supplementation may extend beyond preventing osteoporosis. OBJECTIVE: To explore whether supplementation with high doses of vitamin D could reduce the incidence of COPD exacerbations. DESIGN: Randomized, single-center, double-blind, placebo-controlled trial. (ClinicalTrials.gov registration number: NCT00666367) SETTING: University Hospitals Leuven, Leuven, Belgium. PATIENTS: 182 patients with moderate to very severe COPD and a history of recent exacerbations. INTERVENTION: 100,000 IU of vitamin D supplementation or placebo every 4 weeks for 1 year. MEASUREMENTS: The primary outcome was time to first exacerbation. Secondary outcomes were exacerbation rate, time to first hospitalization, time to second exacerbation, FEV(1), quality of life, and death. RESULTS: Mean serum 25-(OH)D levels increased significantly in the vitamin D group compared with the placebo group (mean between-group difference, 30 ng/mL [95% CI, 27 to 33 ng/mL]; P < 0.001). The median time to first exacerbation did not significantly differ between the groups (hazard ratio, 1.1 [CI, 0.82 to 1.56]; P = 0.41), nor did exacerbation rates, FEV(1), hospitalization, quality of life, and death. However, a post hoc analysis in 30 participants with severe vitamin D deficiency (serum 25-[OH]D levels <10 ng/mL) at baseline showed a significant reduction in exacerbations in the vitamin D group (rate ratio, 0.57 [CI, 0.33 to 0.98]; P = 0.042). LIMITATION: This was a single-center study with a small sample size. CONCLUSION: High-dose vitamin D supplementation in a sample of patients with COPD did not reduce the incidence of exacerbations. In participants with severe vitamin D deficiency at baseline, supplementation may reduce exacerbations. PRIMARY FUNDING SOURCE: Applied Biomedical Research Program, Agency for Innovation by Science and Technology (IWT-TBM).

Serotype 19A and 6C Account for One-Third of Pneumococcal Carriage Among Belgian Day-Care Children Four Years After a Shift to a Lower-Valent PCV.

BACKGROUND: Pneumococcal conjugate vaccines (PCVs) effectively reduce infection and asymptomatic carriage of Streptococcus pneumoniae vaccine serotypes. In 2016, Belgium replaced its infant PCV13 program by a 4-year period of PCV10. Concomitantly, S. pneumoniae serotype carriage was monitored together with the carriage of other nasopharyngeal pathogens in children attending day-care centers. METHODS: From 2016 to 2019, a total of 3459 nasopharyngeal swabs were obtained from children aged 6-30 months. Culture and qPCR were used for the identification of S. pneumoniae, Haemophilus influenzae, Moraxella catarrhalis, and Staphylococcus aureus and for serotyping and antimicrobial susceptibility assessment of S. pneumoniae strains. RESULTS: S. pneumoniae colonization was frequent and stable over the study years. H. influenzae and M. catarrhalis were more frequently carried (P < .001) than S. pneumoniae, by, respectively, 92.3% and 91.0% of children. Prevalence of all PCV13 serotypes together increased significantly over time from 5.8% to 19.6% (P < .001) and was attributable to the increasing prevalence of serotype 19A. Coincidently, non-vaccine serotype 6C increased (P < .001) and the overall pneumococcal non-susceptibility to tetracycline and erythromycin. Non-susceptibility to cotrimoxazole decreased (P < .001). CONCLUSIONS: The switch to a PCV program no longer covering serotypes 19A, 6A, and 3 was associated with a sustained increase of serotypes 19A and 6C in healthy children, similarly as in invasive pneumococcal disease. This resulted in a re-introduction of the 13-valent conjugate vaccine during the summer of 2019.

Desulfovibrio desulfuricans bacteremia in an immunocompromised host with a liver graft and ulcerative colitis.

Desulfovibrio spp. are anaerobic, sulfate-reducing, nonfermenting, Gram-negative bacteria found in the digestive tract of humans. Identification of these species with conventional methods is difficult. The reported case of a Desulfovibrio desulfuricans bacteremia occurring in an immunocompromised host with ulcerative colitis confirms that this organism may be a possible opportunistic human pathogen.

In young children, persistent wheezing is associated with bronchial bacterial infection: a retrospective analysis.

BACKGROUND: Young children with persistent wheezing pose a diagnostic and therapeutical challenge to the pediatrician.We aimed to evaluate bacterial bronchial infection as a possible reason for non response to conventional asthma therapy, and to identify and characterise the predominant pathogens involved. METHODS: We retrospectively analysed microbiological and cytological findings in a selected population of young wheezers with symptoms unresponsive to inhaled corticosteroid (ICS) therapy, who underwent flexible bronchoscopy with bronchoalveolar lavage (BAL). Procedural measures were taken to limit contamination risk and quantitative bacterial culture of BAL fluid (significance cut-off ≥ 104 colony-forming units/ml) was used. Modern microbiological methods were used for detection of a wide panel of pathogens and for characterisation of the bacterial isolates. RESULTS: 33 children aged between 4 and 38 months, without structural anomalies of the conductive airways were evaluated. Significant bacterial BAL cultures were found in 48,5 % of patients. Haemophilus influenzae was isolated in 30,3 %, Streptococcus pneumoniae in 12,1 % and Moraxella catarrhalis in 12,1 %. All H. influenzae isolates were non-encapsulated strains and definitely distinguished from non-haemolytic H. haemolyticus. Respiratory viruses were detected in 21,9 % of cases with mixed bacterial-viral infection in 12,1 %. Cytology revealed a marked neutrophilic inflammation. CONCLUSIONS: Bacterial infection of the bronchial tree is common in persistent preschool wheezers and provides a possible explanation for non response to ICS therapy. Non-typeable H. influenzae seems to be the predominant pathogen involved, followed by S. pneumoniae and M. catarrhalis.