Cytomegalovirus (CMV) infections in patients receiving CMV-IgG-hyperimmunoglobulin prophylaxis after bone-marrow transplantation

Summary Conditioning therapy with aggressive chemotherapy and irradiation induces a state of transient combined immunodeficiency in bonemarrow transplant recipients. This promotes the occurrence of severe cytomegalovirus (CMV) infections, the most frequent lethal complication after bone-marrow transplantation (BMT) at present.Forty-four BMT recipients received CMV-IgG-hyperimmunoglobulin for CMV prophylaxis intravenously. The efficacy of this prophylaxis and possible risk factors for the occurrence of CMV-induced interstitial pneumonia (IP) were analyzed. Risk factors for the promotion of a CMV-IP were: additional immunosuppressive therapy after BMT, CMV-positive serostatus of the recipient, CMV-seropositive granulocyte transfusion, CMV infection immediately prior to BMT, and HLA-haploidentical BMT. In this study the incidence of graftversus-host disease was low and was not associated with the incidence of CMV infections. The use of T-cell-depleted grafts did not result in increased CMV infections or IP and may possibly have improved the immunological reconstitution.Abbreviations BMT Bone-marrow transplantation - CMV Cytomegalovirus - CMV-IG CMV-IgG-hyperimmunoglobulin - GvHD Graft-versus-host disease - IP Interstitial pneumonia - IS Immunosuppressive therapy     

A novel variety of atypical pneumocystis carinii infection after long-term prophylactic pentamidine inhalation in an AIDS patient: large lower lobe pneumocystoma

Summary Atypical pulmonary manifestations of Pneumocystis carinii infection and fair numbers of extrapulmonary and disseminated infections have lately been documented in patients with human immunodeficiency virus infection treated prophylactically with inhalative pentamidine. We report the case of a 32-year-old homosexual patient who was assessed for complaints of night sweats, weight loss, and progressive malaise. The patient denied any respiratory tract symptoms such as cough, sputum production, pleuritic chest pain, or shortness of breath. Chest X-ray revealed two large round noncavitating lesions in the lower lobe of the right lung. Pneumocystomas were diagnosed by fine-needle aspiration. A 3-week course of intravenous high-dose cotrimoxazole resulted in amelioration of symptoms but no change in the radiographic appearance of the pulmonary lesions. Four months later the patient is alive and stable and is being treated with pentamidine inhalation of 300 mg per 2 weeks and two tablets of pyrimethamine sulfadoxine per week.Abbreviations PcP Pneumocystis carinii pneumonia - Pc Pneumocystis carinii - AIDS acquired immunodeficiency syndrome - HIV human immunodeficiency virus     

CC chemokine receptor 4 ligand production by bronchoalveolar lavage fluid cells in cigarette-smoke-associated acute eosinophilic pneumonia

We examined the production of macrophage-derived chemokine (MDC/CCL22) and thymus- and activation-regulated chemokine (TARC/CCL17) by bronchoalveolar lavage fluid (BALF) cells in cigarette-smoke-associated acute eosinophilic pneumonia (CS-AEP). The CC Chemokine Receptor 4 (CCR4) ligand levels in BALF from patients with CS-AEP were considerably higher than those in healthy volunteers and correlated well with Th2 cytokine levels. Interleukin-4 enhanced CCR4 ligand production. MDC expression was observed in CD68-positive cells from patients with CS-AEP and in healthy control smokers. In contrast, TARC expression in CD68- or CD1a-positive cells was detected only in CS-AEP. An in vivo cigarette smoke challenge test induced increases in CCR4 ligands in the BALF and in the cultured supernatant of BALF adherent cells. These results suggest that alveolar macrophages and dendritic cells contribute to the pathogenesis of CS-AEP by generating CCR4 ligands, probably in response to cigarette smoke.     

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.     

rIL-18对肺炎链球菌肺炎小鼠Th1/Th2免疫应答的影响

目的 研究重组白细胞介素18(rIL-18)对肺炎链球菌肺炎小鼠Th1/ Th2免疫应答的影响.方法 鼻腔接种肺炎链球菌建立小鼠肺炎链球菌肺炎模型,将Balb/c小鼠24只随机分为3组,分别为对照组,肺炎组和肺炎rIL-18干预组(n=8 ),RT-PCR法检测各组小鼠肺组织中IFN-γ、IL-4 mRNA 的表达,同时支气管肺泡灌洗液(BALB)进行活菌计数,有核细胞分类计数.结果 ①肺炎rIL-18干预组BA LF中性粒细胞和巨噬细胞计数显著高于肺炎组和对照组(P＜0.001);②肺炎rIL-18 干预组BALF活菌计数显著低于肺炎组(P＜0.001);③肺炎rIL-18干预组肺组织IFN- γ mRNA表达上调而IL-4 mRNA表达下调(P＜0.001).结论 在小鼠肺炎链球菌肺炎早期给予rIL-18可诱导IFN-γ的合成,促进Th1免疫应答,使Th1/ Th2免疫平衡向Th1免疫偏移、促进宿主对肺炎链球菌的防御.     

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.     

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。     

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.