BMC Infectious Diseases - Latest Articles

Prospective hospital-based case-control study to assess the effectiveness of pandemic influenza A(H1N1)pdm09 vaccination and risk factors for hospitalization in 2009- 2010 using matched hospital and test-negative controls

Wiebke Hellenbrand — 2012-05-31T00:00:00Z

Background: We performed a case-control study to estimate vaccine effectiveness (VE) for prevention ofhospitalization due to pandemic influenza A(H1N1)pdm09 (pH1N1) and to identify riskfactors for pH1N1 and acute respiratory infection (ARI) in 10 hospitals in Berlin fromDecember 2009 to April 2010. Methods: Cases were patients aged 18-65 years with onset of ARI [less than or equal to]10 days before admission testingpositive for pH1N1 by PCR performed on nasal and throat swabs or by serological testing.Cases were compared to (1) matched hospital controls with acute surgical, traumatological orother diagnoses matched on age, sex and vaccination probability, and (2) ARI patients testingnegative for pH1N1. Additionally, ARI cases were compared to matched hospital controls. Astandardized interview and chart review elicited demographic and clinical data as well aspotential risk factors for pH1N1/ARI. VE was estimated by 1-(Odds ratio) for pH1N1-vaccination [greater than or equal to]10 days before symptom onset using exact logistic regression analysis. Results: Of 177 ARI cases recruited, 27 tested pH1N1 positive. A monovalent AS03-adjuvantedpH1N1 vaccine was the only pandemic vaccine type identified among cases and controls(vaccination coverage in control group 1 and 2: 15% and 5.9%). The only breakthroughinfections were observed in 2 of 3 vaccinated HIV positive pH1N1 patients. After exclusionof HIV positive participants, VE was 96% (95%CI: 26-100%) in the matched multivariateanalysis and 46% (95%CI: -376-100%) in the test-negative analysis. Exposure to children inthe household was independently associated with hospitalization for pH1N1 and ARI. Conclusions: Though limited by low vaccination coverage and number of pH1N1 cases, our results suggesta protective effect of the AS03-adjuvanted pH1N1 vaccine for the prevention of pH1N1hospitalization. The use of hospital but not test-negative controls showed a statisticallyprotective effect of pH1N1-vaccination and permitted the integrated assessment of riskfactors for pH1N1-infection. To increase statistical power and to permit stratified analyses(e.g. VE for specific risk groups), the authors suggest pooling of future studies assessingeffectiveness of influenza vaccines for prevention of severe disease from different centres.

Macrolide-resistant Mycoplasma pneumoniae in adolescents with community-acquired pneumonia

Naoyuki Miyashita — 2012-05-31T00:00:00Z

Background: Although the prevalence of macrolide-resistant Mycoplasma pneumoniae isolates in Japanesepediatric patients has increased rapidly, there have been no reports concerning macrolideresistantM. pneumoniae infection in adolescents aged 16 to 19 years old. The purpose of thisstudy was to clarify the prevalence and clinical characteristics of macrolide-resistant M.pneumoniae in adolescent patients with community-acquired pneumonia. Methods: A total of 99 cases with M. pneumoniae pneumonia confirmed by polymerase chain reaction(PCR) and culture were analyzed. Forty-five cases were pediatric patients less than 16 yearsold, 26 cases were 16 to 19-year-old adolescent patients and 28 cases were adult patients.Primers for domain V of 23S rRNA were used and DNA sequences of the PCR products werecompared with the sequence of an M. pneumoniae reference strain. Results: Thirty of 45 pediatric patients (66%), 12 of 26 adolescent patients (46%) and seven of 28adult patients (25%) with M. pneumoniae pneumonia were found to be infected withmacrolide-resistant M. pneumoniae (MR patients). Although the prevalence of resistantstrains was similar in pediatric patients between 2008 and 2011, an increase in the prevalenceof resistant strains was observed in adolescent patients. Among 30 pediatric MR patients, 26had an A-to-G transition at position 2063 (A2063G) and four had an A-to-G transition atposition 2064 (A2064G). In 12 adolescent MR patients, 10 showed an A2063G transition andtwo showed an A2064G transition, and in seven adult MR patients, six showed an A2063Gtransition and one showed an A2064G transition. Conclusions: The prevalence of macrolide-resistant M. pneumoniae is high among adolescent patients aswell as pediatric patients less than 16-years old. To prevent outbreaks of M. pneumoniaeinfection, especially macrolide-resistant M. pneumoniae, in closed populations includingamong families, in schools and in university students, physicians should pay close attentionto macrolide-resistant M. pneumoniae.

Chandipura Virus infection in mice: the role of toll like receptor 4 in pathogenesis

Balakrishnan Anukumar — 2012-05-29T00:00:00Z

Background: The susceptibility of mice and humans to Chandipura virus infection is age-dependent. Uponexperimental infection, mice secrete significant amounts of proinflammatory cytokines.Similarly, children who recover from natural infection with the virus show significantamounts of TNF-alpha production, suggesting that innate immunity plays a major role in theresponse to Chandipura virus. Toll-like receptors (TLR) are key host molecules involved ininnate immune responses in infections. Therefore, the aim of this study was to examine therole of TLR in the response to Chandipura virus infection. Methods: The mouse monocyte-macrophage cell line, RAW 264.7, and C3H/HeJ mice were used asmodels. Micro array techniques were used to identify the type of TLR involved in theresponse to infection. The results were validated by examining TLR expression using flowcytometry and by measuring the levels of proinflammatory cytokines and nitric oxide (NO) inthe culture supernatants using bead assays and the Griess method, respectively. Thepathogenic role of Toll-like receptor 4 (TLR4) was studied in a TLR4 mutant strain of mice -C3H/HeJ and the results compared with those from wild-type mice- C3H/CaJ. Thepathogenic effects of NO were studied by treating experimentally infected mice with the NOinhibitor, aminoguanidine (AG). Results: The micro array results showed that TLR4 was regulated after Chandipura virus infection. Athigh multiplicities of infection (10 MOI), RAW cells up- regulated cell surface expression ofTLR4 and secreted significant amounts of TNF-alpha, MCP-1, IL-10 and IL-12 and NO. Thesurvival rate of C3H/HeJ mice was higher than those of wild-type C3H/CaJ mice. Thesurvived C3H/HeJ mice secreted significant quantity of MCP-1 and IFN-gamma cytokines andcleared virus from brain. Similarly, the survival rate of AG-treated mice was higher thanthose of the untreated controls. Conclusions: Chandipura virus regulates TLR4, which leads to the secretion of proinflammatory cytokinesand NO by infected RAW cells. Difference in survival rate in TLR4 mutant mice and nitricoxide inhibitor treated mice, confirmed the role of these molecules in disease pathogenesis.The result is significant in clinical management and designing antiviral intervention forChandipura virus infection.

Streptococcus pneumoniae serotype 19A in Latin America and the Caribbean: a systematic review and meta-analysis, 1990-2010

Elizabeth Castañeda — 2012-05-28T00:00:00Z

Background: Pneumococcal conjugate vaccines (PCVs) are in the process of implementation in LatinAmerica. Experience in developed countries has shown that they reduce the incidence ofinvasive and non-invasive disease. However, there is evidence that the introduction of PCVsin universal mass vaccination programs, combined with inappropriate and extensive use ofantibiotics, could be associated to changes in non-PCV serotypes, including serotype 19A.We conducted a systematic review to determine the distribution of serotype 19A, burden ofpneumococcal disease and antibiotic resistance in the region. Methods: We performed a systematic review of serotype 19A data from observational and randomizedclinical studies in the region, conducted between 1990 and 2010, for children under 6 years.Pooled prevalence estimates from surveillance activities with confidence intervals werecalculated. Results: We included 100 studies in 22 countries and extracted data from 63. These data reported19733 serotyped invasive pneumococcal isolates, 3.8% of which were serotype 19A.Serotype 19A isolates were responsible for 2.4% acute otitis media episodes, and accountedfor 4.1% and 4.4% of 4,380 nasopharyngeal isolates from healthy children and in hospitalbased/sick children, respectively. This serotype was stable over the twenty years ofsurveillance in the region. A total of 53.7% Spn19A isolates from meningitis cases and only14% from non meningitis were resistant to penicillin. Conclusions: Before widespread PCV implementation in this region, serotype 19A was responsible for arelatively small number of pneumococcal disease cases. With increased use of PCVs and agreater number of serotypes included, monitoring S. pneumoniae serotype distribution will beessential for understanding the epidemiology of pneumococcal disease.

Blood leukocytes from benznidazole-treated indeterminate chagas disease patients display an overall type-1-modulated cytokine profile upon short-term in vitro stimulation with trypanosoma cruzi antigens

Renato Sathler-Avelar — 2012-05-24T00:00:00Z

Background: Benznidazole (Bz)-chemotherapy is recommended to prevent Chagas disease progression,despite its limited efficacy during chronic disease. However, the host mechanisms underlyingthese benefits still remain to be elucidated. Methods: In this study, we have used short-term whole blood cultures to describe the cytokine profileof Bz-treated Indeterminate Chagas disease patients-(INDt) as compared to untreatedpatients-(IND). Results: Our findings showed that IND presented increased levels of IL-10+neutrophils, IL-12+ andIL-10+monocytes and IFN-gamma+NK-cells. Moreover, IND showed slight increase of IL-4+CD4+T-cells and enhanced levels of IL-10+CD8+T-cells and B-cells. Additional analysis ofcytokine Low and High producers also highlighted the presence of High cytokine producerswithin IND, including IL-10 from CD4+ T-cells and IFN-gamma from CD8+ T-cells, as comparedto NI. The Bz-treatment lead to an overall cytokine down-regulation in the innate andadaptive compartments, including low levels of IL-12+ and IL-10+neutrophils and monocytes,IFN-gamma+NK-cells, IL-12+, TNF-alpha+, IFN-gamma+ and IL-5+CD4+T-cells and IL-10+B-cells, alongwith basal levels of cytokine-expressing CD8+T-cells in INDt as compared to IND. The invitro antigen stimulation shifted the cytokine profile toward a type 1-modulated profile, withincreased levels of IL-12+ and IL-10+ monocytes, IFN-gamma+ and IL-4+NK-cells along with TNF-alpha+ and IFN-gamma+CD8+T-cells. Analysis of Low and High cytokine producers, upon in vitroantigen stimulation, further confirm these data. Conclusion: Together, our findings showed that the Bz treatment of Indeterminate Chagas' diseasepatients shifts the cytokine patterns of peripheral blood monocytes, NK-cells and CD8+ Tcellstowards a long-lasting Type-1-modulated profile that could be important to themaintenance of a non-deleterious immunological microenvironment.

Characterization of Shigella sonnei in Malaysia, an increasingly prevalent etiologic agent of local shigellosis cases

Xiu Pei Koh — 2012-05-20T00:00:00Z

Background: Shigellosis is a major public health concern worldwide, especially in developing countries. Itis an acute intestinal infection caused by bacteria of the genus Shigella, with a minimuminfective dose as low as 10-100 bacterial cells. Increasing prevalence of Shigella sonnei asthe etiologic agent of shigellosis in Malaysia has been reported. As there is limitedinformation on the genetic background of S. sonnei in Malaysia, this study aimed tocharacterize Malaysian S. sonnei and to evaluate the prospect of using multilocus variablenumbertandem-repeat (VNTR) analysis (MLVA) for subtyping of local S. sonnei. Methods: Forty non-repeat clinical strains of S. sonnei isolated during the years 1997-2000, and 2007-2009 were studied. The strains were isolated from stools of patients in different hospitalsfrom different regions in Malaysia. These epidemiologically unrelated strains werecharacterized using biotyping, antimicrobial susceptibility testing, pulsed-field gelelectrophoresis (PFGE) and MLVA. Results: The two biotypes identified in this study were biotype a (n = 29, 73%) and biotype g (n = 11,27%). All the 40 strains were sensitive to kanamycin, ceftriaxone and ciprofloxacin. Highestresistance rate was observed for streptomycin (67.5%), followed by tetracycline (40%) andtrimethoprim-sulfamethoxazole (37.5%). All the S. sonnei biotype g strains had a coreresistance type of streptomycin - trimethoprim-sulfamethoxazole - tetracycline whereas the29 biotype a strains were subtyped into eight resistotypes. All the strains were equallydistinguishable by PFGE and MLVA. Overall, PFGE analysis indicated that S. sonnei biotypea strains were genetically more diverse than biotype g strains. Cluster analysis by MLVA wasbetter in grouping the strains according to biotypes, was reflective of the epidemiologicalinformation and was equally discriminative as PFGE. Conclusions: The S. sonnei strains circulating in Malaysia throughout the period studied were derived fromdifferent clones given their heterogeneous nature. MLVA based on seven selected VNTR lociwas rapid, reproducible and highly discriminative and therefore may complement PFGE forroutine subtyping of S. sonnei.

Predictors and outcome of patients with acute respiratory distress syndrome caused by miliary tuberculosis: a retrospective study in Chongqing, China

Wang Deng — 2012-05-20T00:00:00Z

Background: Miliary tuberculosis (TB) is an uncommon cause of acute respiratory distress syndrome (ARDS) with a high mortality. The aim of the present study was to evaluate the clinical characteristics, predictors and outcome of patients with ARDS caused by miliary TB. Methods: A retrospective study was conducted among patients with a diagnosis of miliary TB associated with ARDS in four hospitals from 2006 to 2010. Medical records and laboratory examinations of these patients were taken during the first 24 h of admission. Results: Eighty-five patients with miliary TB developed ARDS, 45 of whom survived (52.9%). The median age was 36.6 +/- 12.5 years with 38 males(44.7%). Diabetes mellitus (DM) was the most common underlying disease (18.8%).ICU mortality was 47.1%. The time from admission to anti-tuberculosis therapy was 4.5 +/- 2.0 days. Mean duration of mechanical ventilation was 8.5 +/- 3.0 days in all patients. Duration of time to diagnosis, time from diagnosis to mechanical ventilation, and time to anti-tuberculosis therapy were significantly shorter in survivors than those in non-survivors. Diabetes mellitus(OR 5.431, 95%CI 1.471-20.049; P = 0.005),ALT (70-100U/L, OR 10.029, 95%CI 2.764-36.389; P = 0.001), AST (>94U/L,OR 8.034, 95%CI 2.200-29.341; P = 0.002), D-dimer (>1.6mg/L, OR 3.167, 95%CI 0.896-11.187; P = 0.042), hemoglobin (<90g/L, OR 14.824, 95%CI 3.713-59.179; P = 0.001), albumin (<25g/L, OR 15.896, 95%CI 3.975-63.566; P = 0.001) were independent predictors of ARDS development in the setting of miliary TB. Conclusions: Accurate diagnosis, early initiation of anti-tuberculosis therapy and mechanical ventilation are important for the outcome of patients with ARDS caused by miliary TB. DM, ALT, AST, D-dimer, hemoglobin, and albumin are independent predictors of ARDS development in patients with miliary TB.

Prevalence and clinical features of respiratory syncytial virus in children hospitalized for community-acquired pneumonia in northern Brazil

Letícia Martins Lamarao — 2012-05-16T00:00:00Z

Background: Childhood pneumonia and bronchiolitis is a leading cause of illness and death in young childrenworldwide with Respiratory Syncytial Virus (RSV) as the main viral cause. RSV has beenassociated with annual respiratory disease outbreaks and bacterial co-infection has also beenreported. This study is the first RSV epidemiological study in young children hospitalized withcommunity-acquired pneumonia (CAP) in Belem city, Para (Northern Brazil). Methods: With the objective of determining the prevalence of RSV infection and evaluating the patients'clinical and epidemiological features, we conducted a prospective study across eight hospitalsfrom November 2006 to October 2007. In this study, 1,050 nasopharyngeal aspirate sampleswere obtained from hospitalized children up to the age of three years with CAP, and tested forRSV antigen by direct immunofluorescence assay and by Reverse Transcription PolymeraseChain Reaction (RT-PCR) for RSV Group identification. Results: RSV infection was detected in 243 (23.1%) children. The mean age of the RSV-positive groupwas lower than the RSV-negative group (12.1 months vs 15.5 months, p<0.001) whereas genderdistribution was similar. The RSV-positive group showed lower means of C-reactive protein(CRP) in comparison to the RSV-negative group (15.3 vs 24.0 mg/dL, p<0.05). Radiologicalfindings showed that 54.2% of RSV-positive group and 50.3% of RSV-negative group hadinterstitial infiltrate. Bacterial infection was identified predominantly in the RSV-positive group(10% vs 4.5%, p<0.05). Rhinorrhea and nasal obstruction were predominantly observed in theRSV-positive group. A co-circulation of RSV Groups A and B was identified, with apredominance of Group B (209/227). Multivariate analysis revealed that age under 1 year(p<0.015), CRP levels under 48 mg/dL (p<0.001) and bacterial co-infection (p<0.032) wereindependently associated with the presence of RSV and, in the analyze of symptoms, nasalobstruction were independently associated with RSV-positive group (p<0.001). Conclusion: The present study highlights the relevance of RSV infection in hospitalized cases of CAP in ourregion; our findings warrant the conduct of further investigations which can help designstrategies for controlling the disease.

"Blind periods" in screening for toxoplasmosis in pregnancy in Austria - a debate

Ulrich Sagel — 2012-05-16T00:00:00Z

Recent studies from Austria, France and Italy have shown that there is a poor adherence tothe screening scheme for maternal Toxoplasma infections in pregnancy demonstrated by thefact that many recommended examinations are missed. This leads to undetected infectionsand limits our knowledge of incidence of the disease. We discuss the negative consequencesof this situation on research on treatment effectiveness and the outcomes of congenitaltoxoplasmosis. The responsible public health institutions should assume responsibility forappropriate surveillance of the screening programme and take measures to improve screeningadherence during pregnancy. Screening should start as early as possible in pregnancy and thelatest test should be done at delivery. Screening schedule should allow distinguishinginfections from the first, second and third trimester of pregnancy, as the risk of maternofoetaltransmission and outcomes in case of foetal infections varies by time.

Clinical and Temporal Patterns of Severe Pneumonia Causing Critical Illness during Hajj

Yasser Mandourah — 2012-05-16T00:00:00Z

Background: Pneumonia is a leading cause of hospitalization during Hajj and susceptibility andtransmission may be exacerbated by extreme spatial and temporal crowding. We describe thenumber and temporal onset, co-morbidities, and outcomes of severe pneumonia causingcritical illness among pilgrims.MethodA cohort study of all critically ill Hajj patients, of over 40 nationalities, admitted to 15hospitals in 2 cities in 2009 and 2010. Demographic, clinical, and laboratory data, andvariables necessary for calculation of the Acute Physiology and Chronic Health EvaluationIV scores were collected. Results: There were 452 patients (64.6% male) who developed critical illness. Pneumonia was theprimary cause of critical illness in 123 (27.2%) of all intensive care unit (ICU) admissionsduring Hajj. Pneumonia was community (Hajj)-acquired in 66.7%, aspiration-related in25.2%, nosocomial in 3.3%, and tuberculous in 4.9%. Pneumonia occurred most commonlyin the second week of Hajj, 95 (77.2%) occurred between days 5-15 of Hajj, correspondingto the period of most extreme pilgrim density. Mechanical ventilation was performed in69.1%. Median duration of ICU stay was 4 (interquartile range [IQR] 1-8) days and durationof ventilation 4 (IQR 3-6) days. Commonest preexisting co-morbidities included smoking(22.8%), diabetes (32.5%), and COPD (17.1%). Short-term mortality (during the 3-weekperiod of Hajj) was 19.5%. Conclusion: Pneumonia is a major cause of critical illness during Hajj and occurs amidst substantialcrowding and pilgrim density. Increased efforts at prevention for at risk pilgrim prior to Hajjand further attention to spatial and physical crowding during Hajj may attenuate this risk.