Primary respiratory syncytial virus infection in mice

A mouse model of respiratory syncytial virus (RSV) infection is described. A high-titered, large-volume inoculum results in replication of RSV to a high titer in lungs of BALB/c mice. Mice older than 15 weeks of age are more susceptible to RSV infection. Titers up to 10(6.9) plaque-forming units (pfu)/gram lung can be attained in 32-week-old mice. Older mice experience a clinical illness manifested by ruffled fur, reduced activity, and weight loss. Lung histology of older mice infected with RSV shows bronchiolitis and increased number of lymphocytes and macrophages in alveolar spaces compared with that of mice less than 8 weeks old. This model will serve as the basis for investigating immunodeterminants of recovery and protection from RSV infection.     

Characterization of the antibody response to a Haemophilus influenzae type b conjugate vaccine in children with recurrent lower respiratory tract infection

Children with recurrent lower respiratory tract infection (RLRI) may respond poorly to polysaccharide antigens. To examine how such children respond to a polysaccharide coupled to a protein carrier, we immunized 15 children with RLRI aged 8–69 months and 15 carefully age-matched healthy controls once with a Haemophilus influenzae type b (Hib) conjugate vaccine. Total IgG subclasses, total antipolysaccharide Hib antibodies, and antipolysaccharide Hib antibodies of IgM, IgG, IgA, and IgG 1–4 specificity were determined by ELISA. There were no significant differences between the two groups in any single total IgG subclass, but total IgG measured as the sum of all four subclasses was significantly lower in the children with RLRI than in the controls ( P = 0.036). Before vaccination, the children with RLRI had significantly less IgG antipolysaccharide Hib antibody than the controls ( P = 0.005), whereas 1 month later they had significantly more IgM antibody (P = 0.038). No other significant differences were found between the groups before or after immunization with respect to antipolysaccharide Hib antibodies. Since naturally occurring IgG antibodies are thought to be aquired partly as a consequence of antigenic stimulation on mucosal surfaces, we hypothesize that the low level of specific IgG found before immunization, as well as the low total IgG in the children with RLRI, may reflect an impaired ability to prime through mucosal surfaces. This is supported by our finding of an increased IgM response to Hib conjugate vaccine in these children, since this isotype predominates in the primary immune response, i.e., in the absence of immunologic memory. In conclusion, children with RLRI can be protected against invasive Hib infection as well as healthy children, but may have an immunodeficiency characterized by defective ability to respond to antigenic stimulation on mucosal surfaces.     

Does infection with Chlamydia pneumoniae and/or Helicobacter pylori increase the expression of endothelial cell adhesion molecules in humans?

Objective   To investigate if Chlamydia pneumoniae and/or Helicobacter pylori seropositivity is associated with elevated levels of soluble endothelial cell adhesion molecules (sCAMs) as markers of atherosclerotic activity.
Methods   Immunoglobulin A (IgA) and IgG antibodies to the two bacteria, soluble intercellular cell adhesion molecule-1 (sICAM-1), soluble vascular cell adhesion molecule-1 (sVCAM-1) and E-selectin were measured in coronary heart disease (CHD) patients ( n  = 193) and age- and sex-matched controls ( n  = 193). Two different serological methods were used for the detection of Chlamydia antibodies: Labsystems microimmunofluorescence to detect species-specific C. pneumoniae antibodies and Medac's recombinant enzyme-linked immunosorbent assay to detect genus-specific lipopolysaccharide antibodies.
Results   The concentrations of sICAM-1 and E-selectin were higher in CHD patients with positive vs. negative Chlamydia lipopolysaccharide IgA ( P  = 0.044 for both). H. pylori antibodies alone did not predict raised levels of sCAMs, but in CHD patients sICAM-1 was increased with IgA seropositivity to both bacteria compared to double seronegativity ( P  = 0.034). Concentrations of sVCAM-1 were elevated in CHD patients with double IgA seropositivity compared to those with Chlamydia lipopolysaccharide IgA seropositivity alone ( P  = 0.018).
Conclusion   Our results may indicate that C. pneumoniae contributes to increased inflammation in CHD, and that this contribution is even more pronounced when present in combination with H. pylori IgA antibodies.     

重症监护病房中呼吸机相关肺炎的病原学和耐药性特征

目的探讨重症监护病房（ICU）中呼吸机相关肺炎（VAP）的流行病学、病原菌分布、耐药性特征。方法对广州市3所三级甲等医院ICU发生VAP的53例患者进行前瞻性研究，对病原菌进行细菌鉴定和耐药性分析。结果VAP平均发病时间为机械通气后7．8d。97株病原菌中革兰阴性细菌58株（59．8％），革兰阳性细菌23株（23．7％），真菌16株（16．5％）。最常见病原菌分别为铜绿假单胞菌16株（16．5％），金黄色葡萄球菌13株（13．4％），嗜麦芽窄食单胞菌8株（8．2％），肺炎克雷伯菌8株（8．2％），白色念珠菌8株（8．2％）。耐甲氧西林金黄色葡萄球菌（MRSA）检出率为100．0％；未发现耐万古霉素金黄色葡萄球菌；VAP病原菌存在严重的多重耐药性。结论ICU中VAP的病原菌构成以革兰氏阴性杆菌为主且呈现多重耐药现象，适当的经验性抗菌治疗应以病原学和耐药性的监测结果为依据。     

Immunologic reactivity of (C57BL/6 × A/Sn)F1 mice in mixed Mycoplasma-virus infection

Mixed infection of hybrid mice, highly resistant to Rauscher virus, with this virus andMycoplasma arthritidis was accompanied by progressive inhibition of populations of splenic rosetteforming (REC) and plaque-forming (PFC) cells and led to induction of malignant erythroblastosis, cytologically identical with Rauscher's leukemia. During mixed infection of the hybrid mice withAcholeplasma laidlawii and Rauscher virus the immune response was almost completely suppressed on the 21st day and considerable splenomegaly was observed, but by the 62nd day of infection the RFC and PFC populations and also the weight of the spleens had regained the control level. The possible role of mycoplasmas in the induction and development of Rauscher's leukemia is discussed.N. F. Gamaleya Institute of Epidemiology and Microbiology, Academy of Medical Sciences of the USSR, Moscow. (Presented by Academician O. V. Baroyan.) Translated from Byulleten' Éksperimental'noi Biologii i Meditsiny, Vol. 88, No. 9, pp. 327–329, September, 1979.     

Changes in Streptococcus pneumoniae serotypes causing invasive disease with non-universal vaccination coverage of the seven-valent conjugate vaccine

The pneumococcal seven-valent conjugate vaccine (PCV7) has been administered in Portugal since late 2001 through the private sector. To evaluate the impact of PCV7 use, the serotypes and antimicrobial susceptibility of pneumococci causing invasive disease in Portugal during 2003–2005 were determined and compared with available data for the period 1999–2002. Changes in serotype distribution compatible with the introduction of PCV7 were shown for children ≤5 years of age from 2003 onwards and for adults from 2004 onwards. PCV7 use with coverage of 43% of children with four doses in the 2004 birth cohort, although substantially below universal coverage, seems to have contributed to greatly reducing the proportion of invasive infections due to vaccine serotypes  4, 6B, 14 and 23F. Similarly, significant indirect effects on the serotype distribution of pneumococci causing infections in adults were noted, with reductions in the proportion of invasive infections caused by serotypes  4, 5 and 14. These changes were accompanied by an increase in the proportion of two non-vaccine serotypes: 19A isolates in all age groups and 7F isolates in adults. Whereas serotypes  6B, 14 and 19A were associated with multidrug resistance, isolates expressing serotypes  4 and 7F were fully susceptible for the most part. There were no changes in the proportion of resistant isolates within each serotype and, in spite of the changes in serotype prevalence, there was not an overall reduction in the proportion of infections caused by resistant pneumococci.     

Diagnosis of cytomegalovirus pneumonitis on bronchoalveolar lavage fluid: comparison of cytology, immunofluorescence, and in situ hybridization with viral isolation.

Forty-three bronchoalveolar lavage (BAL) specimens from 40 immunocompromised patients were studied for the presence of cytomegalovirus (CMV) by rapid diagnostic methods. DNA in situ hybridization, cytology, and immunofluorescence were compared to conventional cell culture. Eleven (25%) of the 43 BAL samples grew CMV in culture. In situ hybridization detected 6 of these 11 for sensitivity, specificity, and predictive values of positive and negative of 55%, 94%, 75%, and 86%, respectively. Cytology had a sensitivity of 73% and specificity of 100%. Six Papanicolaou-stained cytospins were screened cytologically versus one hybridization cytospin, and the higher sensitivity of cytology may reflect this extensive sampling. The immunofluorescent method had a sensitivity equal to that of cytology (73%): however, the specificity (72%) was significantly less than that of either the probe or cytology. These data suggest that although in situ hybridization can be a rapid, useful method for detecting CMV in BAL specimens, cytology appears to be a more sensitive method.     

Risk factors in HIV-1-infected patients developing repetitive bacterial infections: toxicological,clinical, specific antibody class responses,opsonophagocytosis and Fc(gamma) RIIa polymorphism characteristics

The aim of the study was to determine possible factors related to the risk of developing recurrent bacterial respiratory tract infections in HIV-1-infected patients, regardless of the degree of immune cellular impairment. Thirty-three HIV-1 seropositive patients with previous repetitive bacterial respiratory tract infections (case group), 33 HIV-1 seropositive controls (matched by CD4-cell counts) without these antecedents and 27 healthy controls were studied before and after administration of pneumococcal and Haemophilus influenzae type b vaccines. Clinical or toxicological variables, cutaneous tests, complement factors, beta2-microglobulin, serum IgM, IgA, IgG and subclasses, specific antibodies (IgG, IgG2, IgA) against pneumococcal vaccine and polyribosylribitol phosphate (PRP), their avidity, opsonophagocytosis and IgG(2)m and Fc(gamma)RIIa allotypes were determined. A history of drug abuse (P = 0.001), less likelihood of receiving high activity antiretroviral treatment high activity antiretroviral treatment (HAART) (P = 0.01), higher levels of HIV-1 viral load (P < 0.05), serum IgG (P < 0.01) and beta2-microglobulin (P < 0.01) were observed in the case group. Also, a lower increase in specific antibodies to pneumococcal vaccine and PRP was demonstrated in the cases in comparison with the two control groups. No differences were observed in the avidity of antibodies, opsonophagocytic capacity or IgG(2)m and Fc(gamma)RIIa allotypes between the three groups. These data indicate that vaccination strategies against encapsulated bacteria can be unsuccessful in the HIV-1-infected patients presenting repetitive bacterial respiratory tract infections if behavioural aspects or measures to improve adherence to HAART therapies are not considered.     

Once-daily oral gatifloxacin vs. three-times-daily co-amoxiclav in the treatment of patients with community-acquired pneumonia

A double-blind, double-dummy, multicentre, multinational, parallel-group study was designed to establish proof of equivalence between oral gatifloxacin and oral co-amoxiclav in the treatment of 462 patients with mild-to-moderate community-acquired pneumonia. Eligible patients were randomised equally to either gatifloxacin 400 mg once-daily plus matching placebo for 5-10 days, or amoxycillin 500 mg + clavulanic acid 125 mg three-times-daily for 5-10 days. The primary efficacy endpoint was clinical response (clinical cure plus improvement) at the end of treatment. Overall, a successful clinical response was achieved in 86.8% of gatifloxacin-treated patients, compared with 81.6% of those receiving co-amoxiclav, while corresponding rates of bacteriological efficacy (eradication plus presumed eradication) were 83.1% and 78.7%, respectively. The safety and tolerability profile of gatifloxacin was comparable to that of co-amoxiclav, with adverse gastrointestinal events, e.g., diarrhoea and nausea, being the most common treatment-related adverse events in both groups. The study showed no evidence of gatifloxacin-induced phototoxicity, musculoskeletal disorders, or hepatic and renal problems. Overall, this study showed that gatifloxacin was equivalent clinically to a standard course of co-amoxiclav in patients with community-acquired pneumonia, and that gatifloxacin was safe and well-tolerated.     

Clinical and bacteriological outcomes in hospitalised patients with community-acquired pneumonia treated with azithromycin plus ceftriaxone, or ceftriaxone plus clarithromycin or erythromycin: a prospective, randomised, multicentre study

This study compared patients with moderate-to-severe community-acquired pneumonia (CAP) requiring hospitalisation, who received initial therapy with either intravenous ceftriaxone plus intravenous azithromycin, followed by step-down to oral azithromycin (n = 135), with patients who received intravenous ceftriaxone combined with either intravenous clarithromycin or erythromycin, followed by step-down to either oral clarithromycin or erythromycin (n = 143). Clinical and bacteriological outcomes were evaluated at the end of therapy (EOT; day 12-16) or at the end of study (EOS; day 28-35). At baseline, mean APACHE II scores were 13.3 and 12.6, respectively, with >50% of patients classified as Fine Pneumonia Severity Index (PSI) category IV or V. Clinical success rates (cure or improvement) in the modified intent-to-treat (MITT) population at EOT were 84.3% in the ceftriaxone/azithromycin group and 82.7% in the ceftriaxone/clarithromycin or erythromycin group. At EOS, MITT success rates (cure only) were 81.7% and 75.0%, respectively. Equivalent success rates in the clinically evaluable population were 83% and 87%, respectively, at EOT, and 79% and 78%, respectively, at EOS. MITT bacteriological eradication rates were 73.2% and 67.4%, respectively, at EOT, and 68.3% vs. 60.9%, respectively, at EOS. Mean length of hospital stay (LOS) was 10.7 and 12.6 days, and the mean duration of therapy was 9.5 and 10.5 days, respectively. The incidence of infusion-related adverse events was 16.3% and 25.2% (p 0.04), respectively. An intravenous-to-oral regimen of ceftriaxone/azithromycin was at least equivalent in efficacy and safety to the comparator regimen and appeared to be a suitable treatment option for hospitalised patients with CAP.