Antimicrobial activity of innate immune molecules against <Emphasis Type="Italic">Streptococcus pneumoniae,Moraxella catarrhalis</Emphasis> and nontypeable <Emphasis Type="Italic">Haemophilus influenzae</Emphasis>

Background  

Despite its direct connection to the nasopharynx which harbors otitis media pathogens as part of its normal flora, the middle ear cavity is kept free of these bacteria by as yet unknown mechanisms. Respiratory mucosal epithelia, including those of the middle ear and eustachian tube, secrete antimicrobial effectors including lysozyme, lactoferrin and β defensins-1 and -2. To elucidate the role of these innate immune molecules in the normal defense and maintenance of sterility of respiratory mucosa such as that of the middle ear, we assessed their effect on the respiratory pathogens nontypeable Haemophilus influenzae (NTHi) 12, Moraxella catarrhalis 035E, and Streptococcus pneumoniae 3, and 6B.     

Prevalence of Haemophilus influenzae type b infection in Chinese children: a systematic review and meta-analysis

Background

Haemophilus influenzae type b is an important cause of invasive bacterial disease in children worldwide. The establishment of epidemiological estimates is an essential first step towards the introduction of H influenzae type b vaccine into the Chinese national immunisation programme. We therefore undertook a systematic review and meta-analysis to estimate the prevalence of H influenzae type b in Chinese children.

Immunization with HMW1 and HMW2 adhesins protects against colonization by heterologous strains of nontypeable Haemophilus influenzae

Nontypeable Haemophilus influenzae (NTHi) is a common cause of localized respiratory tract disease and results in significant morbidity. The pathogenesis of NTHi disease begins with nasopharyngeal colonization, and therefore, the prevention of colonization represents a strategy to prevent disease. The NTHi HMW1 and HMW2 proteins are a family of conserved adhesins that are present in 75 to 80% of strains and have been demonstrated to play a critical role in colonization of the upper respiratory tract in rhesus macaques. In this study, we examined the vaccine potential of HMW1 and HMW2 using a mouse model of nasopharyngeal colonization. Immunization with HMW1 and HMW2 by either the subcutaneous or the intranasal route resulted in a strain-specific antibody response associated with agglutination of bacteria and restriction of bacterial adherence. Despite the specificity of the antibody response, immunization resulted in protection against colonization by both the parent NTHi strain and heterologous strains expressing distinct HMW1 and HMW2 proteins. Pretreatment with antibody against IL-17A eliminated protection against heterologous strains, indicating that heterologous protection is IL-17A dependent. This work demonstrates the vaccine potential of the HMW1 and HMW2 proteins and highlights the importance of IL-17A in protection against diverse NTHi strains.

Nontypeable (nonencapsulated) Haemophilus influenzae (NTHi) is a common cause of acute otitis media (AOM), otitis media with effusion, sinusitis, and exacerbations of underlying lung disease in children (1). NTHi is also frequently associated with community-acquired pneumonia and exacerbations of chronic obstructive pulmonary disease in adults (2).The pathogenesis of NTHi disease begins with colonization of the nasopharynx. Colonization occurs early in life and is common throughout childhood and into adulthood (3). NTHi spreads contiguously within the respiratory tract to cause localized disease, typically in the setting of a viral respiratory infection or allergic disease (4–6). Recent evidence indicates that colonization in early infancy may predispose to the development of neutrophilic asthma and allergic airway disease (7). Given the burden of NTHi disease and the association between early life NTHi colonization and asthma, there is interest in developing a vaccine against NTHi.Currently, vaccines against H. influenzae are limited to polysaccharide conjugate vaccines targeting the capsule of type b strains (Hib). While these vaccines have been largely successful in eliminating Hib invasive disease, there has been no effect on strains of NTHi, which lack a capsule. Efforts to identify highly conserved antigens in NTHi and develop a vaccine against NTHi have been significantly more difficult. While Hib and other encapsulated strains of H. influenzae are clonal, NTHi strains exhibit much greater genetic diversity and heterogeneity (8). Across NTHi strains, common surface antigens exhibit high degrees of antigenic variation, resulting in variable and strain-specific antibody responses. In studies of mice, antibodies acquired during NTHi infection, including IgG in nasal washes directed against outer membrane proteins, are associated with reduced nasopharyngeal colonization density following subsequent challenge by NTHi (9). This suggests a protective role for antibodies at the mucosal surface. However, evidence in children indicates that despite the presence of antibody against an infecting strain, children remain susceptible to subsequent infections by new strains, suggesting that the antibody response may only protect against infection by the same strain.In combination with antibody responses, cell-mediated immunity has been increasingly recognized as a key driver of protection against airway infection by respiratory pathogens. The production of IL-17A by host cells mediates many effector functions at mucosal surfaces, including the production of antimicrobial peptides, proinflammatory cytokines, chemotactic factors, and granulopoietic factors. These effector functions result in increased recruitment of macrophages and neutrophils and enhanced cytotoxicity and phagocytosis (10–12). There is also evidence that IL-17–producing cells drive humoral immunity, including the generation of antibody in mucosal secretions (13, 14). IL-17 production is known to be essential for defense against various mucosal pathogens, including Mycoplasma pneumoniae, Streptococcus pneumoniae, Klebsiella pneumoniae, and Bordetella pertussis (15–17). In studies of Staphylococcus aureus, clearance of bacteria colonizing the nasopharynx is driven by IL-17–mediated neutrophil influx and antimicrobial peptide production (16, 18). Thus far, it is unclear whether IL-17 production directly contributes to host defense against nasopharyngeal colonization by NTHi.NTHi colonization of the nasopharynx begins with bacterial adherence to respiratory epithelial cells, which is dependent on NTHi adhesive proteins. The HMW1 and HMW2 high-molecular weight proteins are surface-exposed glycoproteins and are the predominant adhesins in ∼75 to 80% of NTHi strains (19–23). HMW1 and HMW2 also facilitate upper respiratory tract colonization in rhesus macaques as highlighted in studies comparing a wild-type strain and an isogenic mutant lacking both of these proteins (24). HMW1 and HMW2 are highly homologous to each other, sharing ∼70% identity and 80% similarity. HMW1 and HMW2 are also highly homologous among diverse NTHi strains (25, 26).In children recovering from AOM, HMW1 and HMW2 are the major targets of the serum antibody response to infection. Similarly, rhesus macaques colonized with HMW1/HMW2-expressing strains develop serum antibody responses against HMW1 and HMW2, and serum antibodies against HMW1 and HMW2 are present in adults, suggesting that these adhesins are highly immunogenic. The development of HMW1/HMW2-specific antibodies in humans also coincides with increased serum bactericidal activity (27). However, antibody-mediated killing appears to be directed primarily against the homologous infecting strain rather than broadly acting against heterologous strains (28). The conservation of HMW1 and HMW2 among diverse strains, the immunogenicity of HMW1 and HMW2, the surface localization of HMW1 and HMW2, and the role of HMW1 and HMW2 in adherence to respiratory epithelial cells and in colonization make these adhesins promising antigens for a vaccine.In this study, we evaluated whether immunization with HMW1 and HMW2 protects against nasopharyngeal colonization. Using a mouse model of immunization and nasopharyngeal challenge, we found that immunization with the HMW1 and HMW2 proteins results in protection against colonization by homologous and heterologous strains, despite a highly strain-specific antibody response. Protection against nasopharyngeal colonization is mediated by both antibody and T cell responses.     

Acquired homotypic and heterotypic immunity against oculogenital <Emphasis Type="Italic">Chlamydia trachomatis</Emphasis> serovars following female genital tract infection in mice

Background  

Chlamydia trachomatis is the most common sexually transmitted bacterial pathogen causing female genital tract infection throughout the world. Reinfection with the same serovar, as well as multiple infections with different serovars, occurs in humans. Using a murine model of female C. trachomatis genital tract infection, we determined if homotypic and/or heterotypic protection against reinfection was induced following infection with human oculogenital strains of C. trachomatis belonging to two serovars (D and H) that have been shown to vary significantly in the course of infection in the murine model.     

Vaccine prevention of acute otitis media

The incidence of acute otitis media (AOM) in infants and young children has increased dramatically in recent years in the United States. AOM often follows upper respiratory tract infections due to pathogens such as respiratory syncytial virus (RSV), influenza virus, and parainfluenza virus (PIV). These viruses cause eustachian tube dysfunction that is critical to the pathogenesis of AOM. Vaccines against these viruses would likely reduce the incidence of AOM. In three previous studies, influenza virus vaccines reduced the incidence of AOM by 30% to 36%. Vaccines to prevent infections with RSV and PIV type 3 are undergoing clinical testing at this time. Streptococcus pneumoniae, nontypeable Haemophilus influenzae (NTHi), and Moraxella catarrhalis are the three most common AOM pathogens. Heptavalent pneumococcal conjugate vaccine is effective in preventing invasive disease and AOM caused by serotypes contained in the vaccine. Vaccine candidates for NTHi and M. catarrhalis are under development.     

Evaluation of the adequacy of the antimicrobial therapy of invasive Haemophilus influenzae infections: A pharmacokinetic/pharmacodynamic perspective

IntroductionIn Europe, non-typeable H. influenzae (NTHi) is the leading cause of invasive H. influenzae disease in adults and is associated with high mortality. The goal of this study was to determine whether current antimicrobial treatments for H. influenzae infection in Spain are suitable based on their probability of achieving pharmacokinetic/pharmacodynamic (PK/PD) targets.MethodsPharmacokinetic parameters for the antibiotics studied (amoxicillin, amoxicillin/clavulanic acid, ampicillin, cefotaxime, ceftriaxone, imipenem and ciprofloxacin) and susceptibility data for H. influenzae were obtained from literature. A Monte Carlo simulation was used to estimate the probability of target attainment (PTA), defined as the probability that at least a specific value of a PK/PD index is achieved at a certain MIC, and the cumulative fraction of response (CFR), defined as the expected population PTA for a specific drug dose and a specific microorganism population.ResultsRegardless of dosing regimen, all antibiotics yielded CFR values of 100% or nearly 100% for all strains, including BL+, BL? and BLNAR, except amoxicillin and ampicillin for BL+. Thus, if an infection is caused by BL+ strains, treatment with amoxicillin and ampicillin has a high probability of failure (CFR ≤ 8%). For standard doses of amoxicillin, amoxicillin/clavulanic acid and imipenem, PK/PD breakpoints were consistent with EUCAST clinical breakpoints. For the other antimicrobials, PK/PD breakpoints were higher than EUCAST clinical breakpoints.ConclusionsOur study confirms by PK/PD analysis that, with the antimicrobials used as empirical treatment of invasive H. influenzae disease, a high probability of therapeutic success can be expected.     

Identification of an N-terminal 27 kDa fragment of <Emphasis Type="Italic">Mycoplasma pneumoniae</Emphasis> P116 protein as specific immunogen in <Emphasis Type="Italic">M. pneumoniae</Emphasis>infections

Background  

Mycoplasma pneumoniae is an important cause of respiratory tract infection and is increasingly being associated with other diseases such as asthma and extra-pulmonary complications. Considerable cross-reactivity is known to exist between the whole cell antigens used in the commercial serological testing assays. Identification of specific antigens is important to eliminate the risk of cross-reactions among different related organisms. Adherence of M. pneumoniae to human epithelial cells is mediated through a well defined apical organelle to which a number of proteins such as P1, P30, P116 and HMW1-3 have been localized, and are being investigated for adhesion, gliding and immunodiagnostic purposes.     

Purulent Pericarditis Caused by Haemophilus parainfluenzae

Bacterial pericarditis is a rare disease in the era of antibiotics. Purulent pericarditis is most often caused by Staphylococcus aureus, Streptococcus pneumoniae, or Haemophilus influenzae. The number of H. parainfluenzae infections has been increasing; in rare cases, it has caused endocarditis. We report a case of purulent pericarditis caused by H. parainfluenzae in a 62-year-old woman who reported a recent upper respiratory tract infection. The patient presented with signs and symptoms of pericardial tamponade. Urgent pericardiocentesis restored her hemodynamic stability. However, within 24 hours, fluid reaccumulation led to recurrent pericardial tamponade and necessitated the creation of a pericardial window. Cultures of the first pericardial fluid grew H. parainfluenzae. Levofloxacin therapy was started, and the patient recovered. Haemophilus parainfluenzae should be considered in a patient who has signs and symptoms of purulent pericarditis. Prompt diagnosis, treatment, and antibiotic therapy are necessary for the patient''s survival. To our knowledge, this is the first report of purulent pericarditis caused by H. parainfluenzae.Key words: Endocarditis, bacterial/diagnosis/microbiology/pathology; haemophilus/isolation & purification; haemophilus infections/diagnosis/drug therapy; haemophilus parainfluenzae; pericarditis/complications/diagnosis/etiology/microbiology/therapy; suppuration/diagnosis; treatment outcomePurulent pericarditis is a disease process that is usually described as a secondary infection from a primary site in the respiratory tract. The condition has been associated with respiratory disease processes such as pneumonia or empyema, but it can be a sequela of endocarditis, chest trauma, chest surgery, or the hematogenous spread of infection from elsewhere in the body.¹ Haemophilus influenzae has been suspected as a cause of purulent pericarditis; however, H. parainfluenzae has not previously been reported as a cause. Haemophilus parainfluenzae organisms are considered to be normal respiratory flora with low pathogenicity. However, H. parainfluenzae is being more frequently implicated in a variety of infections.^2,3 We present what we think is the first report of purulent pericarditis caused by H. parainfluenzae.     

Efficacy of a 7-day course of furazolidone, levofloxacin, and lansoprazole after failed Helicobacter pylori eradication

Background  

Increasing resistance to clarithromycin and nitroimidazole is the main cause of failure in the Helicobacter pylori eradication. The ideal retreatment regimen remains unclear, especially in developing countries, where the infection presents high prevalence and resistance to antibiotics. The study aimed at determining the efficacy, compliance and adverse effects of a regimen that included furazolidone, levofloxacin and lansoprazole in patients with persistent Helicobacter pylori infection, who had failed to respond to at least one prior eradication treatment regimen.     

Serodiagnosis of <Emphasis Type="Italic">Helicobacter hepaticus</Emphasis> infection in patients with liver and gastrointestinal diseases: western blot analysis and ELISA using a highly specific monoclonal antibody for <Emphasis Type="Italic">H. hepaticus</Emphasis> antigen

Background  

Helicobacter hepaticus infection might be associated with liver and biliary tract diseases. To investigate its pathogenic role, the properties of anti-H. hepaticus serum antibody in patients with liver and diseases were elucidated.     

Current and future prospects for a vaccine for nontypeable Haemophilus influenzae

Nontypeable Haemophilus influenzae is an important human respiratory tract pathogen that causes about 30% of otitis media in infants and children. This proportion is increasing as a result of pneumococcal conjugate vaccines. Because of the morbidity associated with otitis media, a strong rationale exists to develop strategies to prevent these infections. A challenge to developing a vaccine for nontypeable H. influenzae is the antigenic heterogeneity of several major surface antigens and the genetic heterogeneity among strains. Several research groups have identified conserved surface proteins and tested them as putative vaccines. A recent clinical trial with protein D, a conserved surface antigen, demonstrated partial efficacy in preventing H. influenzae otitis media. This important result provides a proof of principle for developing a vaccine to prevent otitis media caused by nontypeable H. influenzae. Several vaccine antigens for nontypeable H. influenzae are in development.     

Influenza H1N1pdm‐specific maternal antibodies offer limited protection against wild‐type virus replication and influence influenza vaccination in ferrets

Objective

The objective was to study passively acquired influenza H1N1 pandemic (H1N1pdm) maternal antibody kinetics and its impact on subsequent influenza infection and vaccination in ferrets during an outbreak of the H1N1pdm.

Design and main outcome measures

Infectivity of the H1N1pdm in the respiratory tract of ferrets was compared with the previous seasonal A/South Dakota/6/2007 (SD07, H1N1). Influenza-specific antibodies were quantitated and antibody-mediated protection against the homologous and heterologous H1N1 virus challenge infection was determined.

Results

H1N1pdm virus was approximately 10 times more infectious than SD07 in ferrets, replicated to higher viral titers in the upper respiratory tract and shed for a longer duration. Influenza-specific antibodies after natural infection persisted much longer in the circulation than passively acquired maternal antibodies. The protection conferred by the maternal antibodies was limited to the homologous virus strain and was ineffective against SD07 and H3N2 virus. Serum antibodies from maternal transmission or passive transfer interfered with homologous vaccine strain-mediated antibody responses in the ferret. A booster immunization was required to elicit a high level of antibody.

Conclusions

The findings support the rationale for a prime and boost immunization strategy in young children in whom maternal antibodies are present.     

Clinical features fail to distinguish respiratory infections caused by Branhamella catarrhalis from those caused by Haemophilus influenzae

Branhamella catarrhalis is being isolated with increasing frequency from patients with symptoms and signs of respiratory tract infection. Records of 77 patients were reviewed to define the spectrum of respiratory illness and to compare clinical and laboratory features with those of respiratory infection due to Haemophilus influenzae. Both B catarrhalis and H influenzae caused respiratory infection predominantly in elderly males with underlying heart or lung disease. There were no clinical or laboratory features aside from sputum Gram stain and culture which differentiated the two groups. Although fewer than one-half of each group received antibiotics, no patient developed progressive respiratory disease.     

"Bacterial Meningitis in children and adolescents: an observational study based on the national surveillance system"

Background  

Bacterial meningitis is a group of life threatening infections that mostly affect children and adolescents, and may be the cause of severe neurological sequelae. Cuba has implemented massive vaccination programmes against both Neisseria meningitidis (serogroup C in 1979 and B in 1987), and Haemophilus influenzae type b (1999), two of the main causal pathogens. We described and discussed some epidemiological aspects of the current status of bacterial meningitis to learn from the Cuban experience.     

The use of macrolides in treatment of upper respiratory tract infections

Antimicrobial resistance is a growing problem among upper respiratory tract pathogens. Resistance to β-lactam drugs among Streptococcus pneumoniae, Haemophilus influenzae, and Streptococcus pyogenes is increasing. As safe and well-tolerated antibiotics, macrolides play a key role in the treatment of community-acquired upper respiratory tract infections (RTIs). Their broad spectrum of activity against gram-positive cocci, such as S. pneumoniae and S. pyogenes, atypical pathogens, H. influenzae (azithromycin and clarithromycin), and Moraxella catarrhalis, has led to the widespread use of macrolides for empiric treatment of upper RTIs and as alternatives for patients allergic to β-lactams. Macrolide resistance is increasing among pneumococci and recently among S. pyogenes, and is associated with increasing use of the newer macrolides, such as azithromycin. Ribosomal target modification mediated by erm(A) [erm(TR)] and erm(B) genes and active efflux due to mef(A) and mef(E) are the principal mechanisms of resistance in S. pneumoniae and S. pyogenes. Recently, ribosomal protein and RNA mutations have been found responsible for acquired resistance to macrolides in S. pneumoniae, S. pyogenes, and H. influenzae. Although macrolides are only weakly active against macrolide-resistant streptococci species producing an efflux pump (mef) and are inactive against pathogens with ribosomal target modification (erm), treatment failures are uncommon. Therefore, macrolide therapy, for now, remains a good alternative for treatment of upper RTIs; however, continuous monitoring of the local resistance patterns is essential.     

Nontypeable Haemophilus influenzae (NTHi) epidemiology

While most systemic pediatric Haemophilus influenzae infections are caused by the type b strain (Hib), nontypeable H. influenzae: (NTHi) has been considered a respiratory tract pathogen common in local infection such as acute otitis media, acute pneumonia, secondary chronic respiratory disease and other otorhinolaryngologic infections. Recent findings show, however, that NTHi also causes invasive infections such as meningitis, bacteremia, and lower respiratory tract infections such as pneumonia. A review of NTHi epidemiology from the 1990s onward shows that NTHi causes significant morbidity in pediatric acute otitis media, sinusitis, conjunctivitis and lower respiratory diseases such as pneumonia in Japan. This summary also reviews the worldwide influence of Streptococcus pneumoniae and Hib vaccines on causative pathogens, and several studies about increasing incidence of invasive infections due to NTHi. This review also touches on the emergence of treatment- and drug-resistant H. influenzae, which are now major public health challenges. As a cause of bacterial pediatric infection, NTHi is an important target for prevention.     

<Emphasis Type="Italic">Chlamydia trachomatis</Emphasis>infection in early neonatal period

Background  

The clinical characteristics of Chlamydia trachomatis respiratory tract infections in Japanese neonates were investigated.     

Effect of <Emphasis Type="Italic">Helicobacter bilis</Emphasis> Infection on Human Bile Duct Cancer Cells

Background  

Helicobacter pylori infection is known to be associated with chronic atrophic gastritis, peptic ulcers, and gastric malignancies. However, the effects of other Helicobacter species have not been investigated extensively. In mice, a close relationship is observed between Helicobacter hepaticus and hepatocellular carcinoma, and Helicobacter species can be found in humans, most commonly in extragastric organs. There have also been reports that H. bilis may be associated with biliary malignancies in humans. The effect of H. bilis infection on a human bile duct cancer cell line was investigated in this study.     

Genome-wide fitness profiling reveals adaptations required by Haemophilus in coinfection with influenza A virus in the murine lung

Bacterial coinfection represents a major cause of morbidity and mortality in epidemics of influenza A virus (IAV). The bacterium Haemophilus influenzae typically colonizes the human upper respiratory tract without causing disease, and yet in individuals infected with IAV, it can cause debilitating or lethal secondary pneumonia. Studies in murine models have detected immune components involved in susceptibility and pathology, and yet few studies have examined bacterial factors contributing to coinfection. We conducted genome-wide profiling of the H. influenzae genes that promote its fitness in a murine model of coinfection with IAV. Application of direct, high-throughput sequencing of transposon insertion sites revealed fitness phenotypes of a bank of H. influenzae mutants in viral coinfection in comparison with bacterial infection alone. One set of virulence genes was required in nonvirally infected mice but not in coinfection, consistent with a defect in anti-bacterial defenses during coinfection. Nevertheless, a core set of genes required in both in vivo conditions indicated that many bacterial countermeasures against host defenses remain critical for coinfection. The results also revealed a subset of genes required in coinfection but not in bacterial infection alone, including the iron-sulfur cluster regulator gene, iscR, which was required for oxidative stress resistance. Overexpression of the antioxidant protein Dps in the iscR mutant restored oxidative stress resistance and ability to colonize in coinfection. The results identify bacterial stress and metabolic adaptations required in an IAV coinfection model, revealing potential targets for treatment or prevention of secondary bacterial pneumonia after viral infection.The bacterium Haemophilus influenzae is a Gram-negative inhabitant of the human upper respiratory tract and a common agent in sinusitis, otitis media, lung infections in cystic fibrosis, and exacerbations of chronic obstructive pulmonary disease (COPD). In the context of prior infection by influenza A virus (IAV), H. influenzae is associated with secondary bacterial pneumonia (1). Annually, influenza and related complications cause ∼36,000 deaths, over 200,000 hospitalizations in the United States, and ∼5 million cases of severe illness worldwide (2, 3). Uncomplicated IAV infection can progress to pneumonia; however, secondary bacterial infection combined with viral infection is commonly the major cause of excess morbidity and mortality during epidemics and pandemics. For example, the 1918 influenza pandemic killed an estimated 50 million people worldwide, and the majority of deaths have been attributed to bacterial secondary infections in which Streptococcus pneumoniae, H. influenzae, and Staphylococcus spp. represent the most common isolates (1). β-Lactam antibiotics are commonly used for treatment, and yet ∼30% of H. influenzae isolates are β-lactamase–positive (4–6). Because of increasing levels of bacterial antibiotic resistance, and the continued threat of global pandemics with potential emergence of new IAV subtypes, combined IAV and bacterial infection remains a significant public health concern.In 1945, Francis and Vicente de Torregrosa demonstrated lethality of H. influenzae when introduced into the lungs of mice after infection with IAV (7). More recently, pathogenic mechanisms associated with the mouse lung model of lethal IAV coinfection with H. influenzae type b (Hib) were investigated, implicating innate immunity in disease progression (8). Coinfection did not influence viral titers and yet led to dramatically increased multiplication and persistence of bacteria. Viral enhancement of host susceptibility to bacterial infection has been examined in coinfection models with diverse bacteria, implicating modification of mucosal surfaces and dysfunctional immune responses that prevent bacterial containment including altered phagocytic capacity, defective TLR responses, and enhanced pro- and anti-inflammatory cytokine production, and decreased tolerance to tissue damage (9–14). In contrast, bacterial factors involved in coinfection have received less attention. There have been no systematic studies to identify such factors, and genes of H. influenzae involved in IAV coinfection have not been identified.We investigated the hypothesis that H. influenzae possesses genes that promote its ability to survive host defenses and exploit conditions in the lung generated by coinfection with IAV. Using a genome-scale analytical approach, we simultaneously monitored fitness of thousands of transposon mutants in the murine lung model in the presence and absence of prior IAV infection. The results reveal a core set of bacterial genes required in both models, as well as genes required uniquely in one environment but not the other. Coinfection altered bacterial requirements for known virulence genes conferring not only immune evasion properties but also those encoding regulatory factors and physiological pathways. Therefore, genome-wide analysis of the fitness of bacterial mutants serves as a probe for conditions created during bacterial/viral coinfection of murine lung and identifies bacterial adaptations that specifically promote their multiplication in this pathogenic context.     

Haemophilus influenzae type B genital infection and septicemia in pregnant woman: a case report

Haemophilus influenzae (H. influenzae) type B a non-motile, aerobic, gram negative cocobacillus is a commensal of upper respiratory tract. Genitourinary infection due to H. influenzae has been reported but bacteremia associated with such infection appears to be rare. We report a case of 19 years young primigravida with complaints of amenorrhea of 32 weeks and 5 days, pyrexia, abdominal pain and blood stained discharge per vaginum. H. influenzae type B was recovered from the genital tract as well as blood of the mother indicating maternal septicemia. Septicemia caused by H. influenzae type B in pregnant women following vaginal colonization and infection is rare. It has been reported in many parts of world over the years; to the best of our knowledge this is the first reported case from Nepal. H. influenzae should be considered as a potential maternal, fetal, and neonatal pathogen.