Clinical items not helpful in differentiating viral from bacterial lower respiratory tract infections in general practice

OBJECTIVE: Incorrect and unnecessary antibiotic prescribing enhancing bacterial resistance rates might be reduced if viral and bacterial lower respiratory tract infections (LRTI) could be differentiated clinically. Whether this is possible is often doubted but has rarely been studied in general practice. STUDY DESIGN AND SETTING: This was an observational cohort study in 15 general practice surgeries in the Netherlands. RESULTS: Etiologic diagnoses were obtained in 112 of 234 patients with complete data (48%). Viral pathogens were found as often as bacterial pathogens. Haemophilus (para-) influenzae was most frequently found. None of the symptoms and signs correlated statistically significantly with viral or bacterial LRTI. Erythrocyte sedimentation rate >50 (odds ratio [OR] 2.3-3.3) and C-reactive protein (CRP) >20 (OR 2.1-4.6) were independent predictors for viral LRTI and bacterial LRTI when compared with microbiologically unexplained LRTI. CONCLUSION: Extensive history-taking and physical examination did not provide items that predict viral or bacterial LRTI in adult patients in daily general practice. We could not confirm CRP to differentiate between viral and bacterial LRTI.     

CMC and EBV infections in children

CMV and EBV infections are common in humans. In immunocompetent persons those infections are usually asymptomatic but in immunocompromised can manifest as a severe disease. CMV is a common cause of congenital infections. It is also a frequent complication in transplant recipients. The aim of this study was to assess the prevalence of CMV and EBV infections among hospitalized children. Specific antibodies against CMV and EBV were detected in serum by ELISA test. Presence of CMV DNA was determined in leucocytes by Murex Hybrid Capture System. CMV and EBV infections were defined as the presence in serum IgM-class specific antibodies. Obtained results indicate that CMV and EBV infections are frequent in immunocompromised patients. Among patients with CMV or EBV infection, 40% have been diagnosed with cancer, most of whom with hematologic malignancies: leukemia or lymphoma. CMV and EBV coinfection was detected in 14% of infected children. Of all patients with CMV, 50% were neonates and infants. Congenital infection was diagnosed only in one case. The remaining infections were acquired during perinatal period or later.     

Parainfluenza type 3 infection post stem cell transplant: high prevalence but low mortality

Parainfluenza type 3 (PIV 3) is a well-recognized cause of respiratory illness after stem cell transplantation (SCT), with an estimated incidence of 2-7% and a high mortality rate associated with lower respiratory tract infection (LRTI). A 12-month retrospective study was undertaken in which 23 positive cases of PIV 3 occurred in SCT recipients. The frequency of infection was 36.1% in matched unrelated donor SCT recipients, 23.8% in sibling allogeneic SCT recipients and 2.3% in autologous transplant recipients. Seventeen cases were outpatient or community acquired despite standard infection control measures. Eleven patients only developed upper respiratory tract symptoms. LRTI symptoms developed in 12 patients, of whom eight had a new infiltrate on chest X-ray. Overall mortality at 30 days from PIV 3 diagnosis was 4% (one patient). Four patients died within 100 days of PIV 3 diagnosis, but PIV 3 was not believed to be the primary cause of death in any of these patients. Early ribavirin was used in eight patients and only one patient who received ribavirin died. These results suggest a higher prevalence of PIV 3 but a lower mortality than documented previously, particularly in allogeneic transplant recipients. The authors propose that the high prevalence reflects the unit's policy of active surveillance for respiratory viruses and the difficulty in preventing transmission of PIV 3, especially in the outpatient setting during an outbreak period. Ribavirin treatment may improve outcome in patients with LRTI but is not required in all patients with PIV 3.     

Pulmonary infections after lung transplantation

Lung transplantation has become an accepted therapeutic modality for end-stage diseases of the lungs and the pulmonary circulation. In the past two decades more than 20,000 lung transplantations were performed all over the world. Due to improvements in immunosuppressive regimens the mortality rate of severe acute rejections has decreased up to 2% in the first post-transplant year. By contrast, infections became the most common cause of morbidity and mortality after lung transplantation. It was reported that 21.2 and 40% of annual deaths are due to infections in the first 30 days and one year, respectively. In the first month 35-70% of transplant recipients develop bacterial pneumonia caused often by Gram-negative organisms especially by Pseudomonas species. All patients should receive prophylactic antibiotics after the operation, which are to be modified according to the resistance patterns of pathogens isolated from the donor lungs. In the early post-operative period, the frequency of invasive fungal (Aspergillus and Candida) and cytomegalovirus (CMV) infections appears to be less then 10% due to prophylactic amphotericin inhalation and systemic valganciclovir administration for 100 days. After withdrawing these drugs, these infections became more common. In the late post-transplant period, the development of bronchiolitis obliterans syndrome (BOS) may predispose to infections. BOS may be manifested in approximately 50% of patients 5 years post-transplant. Routinely or urgently performed screening tests (laboratory and radiological investigations, lung function tests, sputum culture, bronchoscopy) and specific treatments are of central importance in the management of infections. In this review we discuss the clinical manifestation, the diagnosis and the treatment possibilities of the most common pulmonary infections in lung transplant recipients.     

Phylogenetic studies of frequently diagnostically sampled herpesviruses – Possibilities for clinical applications?

With the modern sequencing technologies and the capability to sequence large viral genomes virtually overnight, full-genome sequencing of large DNA viruses and correlating any sequence variation to specific clinical manifestations is now eminently feasible – but is it worth doing, i.e. can such large-scale viral genomic analyses be clinically useful? A few clinical conditions, such as organ and bone marrow transplant recipients, require the regular diagnostic sampling and testing for certain viruses over an extended period of time. Such frequent sampling leads to the routine archiving of multiple samples from the same patient over an extended time period and it is the purpose of this mini-review to explore whether such routinely collected samples can be utilized for viral sequencing studies to produce clinically useful outcomes. Specific examples of this include the monitoring of Epstein-Barr virus (EBV) and cytomegalovirus (CMV) levels in transplant recipients, as rising levels of these viruses in these patients can cause serious and sometimes fatal disease during the post-transplant period when their immune system is gradually recovering from the transplant process. Other herpesviruses, such as herpes simplex virus (HSV) and varicella zoster virus (VZV), may also reactivate and cause disease in post-transplant and other types of immunocompromised patients, though the specific complications may differ between patients. Although the natural mutation rate for these human herpes DNA viruses are very low, all of these viruses are capable of developing specific drug resistance within a few weeks of therapy, demonstrating that these viruses do have the ability to adapt rapidly to their local environment if the need arises. Specific problems with analyzing these large DNA virus genomes include the selection of the appropriate gene target (unless a full-genome analysis is the aim), and how to deal with overlapping and inverted reading frames, which are discussed in this mini-review.     

Infections in solid organ transplant recipients

The main problems in solid organ transplant recipients are rejection and infections. The new immunosuppressive regimens have lowered the risk of rejection, however, infections continue to be one of the most important determinants for morbidity and mortality in these patients. The survival of the transplanted organ is also impacted by the different infectious diseases that occur in the post-transplant period. These infections are of viral, bacterial, fungal and parasitic origin, and their presentation occurs characteristically within well defined risk periods after the transplant. The clinical presentation is commonly atypical; therefore for optimal management, it is necessary to have a through knowledge of the epidemiology and clinical manifestations of these problems, but most importantly, the experience of the clinician in the clinical approach and early detection will result in better outcomes. We review recent information regarding the infectious diseases that affect solid organ recipients according to the type of transplant, the post-transplant, risk factors before the transplant and the type of immunosuppressive therapy used, which are the main determinants for these complications and their prognosis.     

呼吸内科患者肺部真菌感染的临床研究

目的 对呼吸内科肺部真菌感染患者的病史、诱发因素、感染菌种、治疗效果以及预后进行临床分析研究.方法 所有患者均给予相应的对症支持治疗和抗真菌治疗,细菌感染患者应用相应敏感抗菌药物治疗;对67例患者的病史、诱发因素、感染菌种、治疗效果以及预后进行分析.结果 患者在经过对症及抗真菌治疗后,大部分患者临床症状完全消失,部分患者临床症状减轻;以年龄≥61岁、住院时间≥30 d、应用抗菌药物、基础疾病主要为慢性阻塞性肺疾病是下呼吸道真菌感染的易感因素;真菌感染以白色假丝酵母菌感染率最高,占41.25％.结论 对呼吸内科患者肺部的真菌感染要提高警惕,减少其诱发因素,抗真菌治疗要坚持早期、足量、足疗程、规范化的治疗原则.     

Virus infection in children after allogenic stem cell transplantation

Allogenic hematopoietic cell transplantation (alloHCT) is the treatment of choice for various pediatric malignancies and nonmalignant diseases. The most prominent complication of allotransplantation is graft vs host disease (GvHD). The treatment of GvHD influence negatively function of immune system and increase risk of bacterial, fungal and viral infections. Clinical symptoms of viral infection may mimic GvHD and lead to inappropriate treatment. Human cytomegalovirus (CMV, Herpesviridae) has been recognized as most important viral pathogen after alloHCT. Increasing number of procedures, especially from alternative donors, requiring more intensive immunosuppression, led to identification more viral pathogens causing transplant related mortality and morbidity. Among them are adenoviruses (ADV, Adenoviridae), BK and JC viruses (Papovaviridae) and human herpes virus 6 (HHV-6, Herpesviridae). Frequency of complications caused by those pathogens is higher in children then in adults.     

Relationship between cytomegalovirus and colonization of the oropharynx by gram-negative bacilli following renal transplantation.

Numerous investigators have reported an increased incidence of pneumonia caused by Gram-negative bacilli and other secondary pathogens in transplant recipients infected by cytomegalovirus (CMV). To determine if CMV infections are related to colonization of the upper respiratory tract by Gram-negative bacilli, we examined prospectively 22 renal transplant recipients with sequential bacteriological, virological and biochemical examinations performed just prior to and at various times after transplantation. Only 11% of subjects had Gram-negative bacilli isolated from gargle specimens prior to transplantation, as compared to 54% after transplantation. More importantly, after transplantation, subjects with active CMV infections were more likely to have prolonged oropharyngeal carriage of Gram-negative bacilli than subjects without CMV infections (36% v. 25%). During active CMV infections, the rate at which Gram-negative bacilli were isolated from gargle specimens rose from 28 to 47%. During culture-positive CMV infections, the isolation rate reached 57% and was significantly different from that of CMV-negative samples (P less than 0.01). The increased rate of Gram-negative bacillary isolation from gargle specimens during CMV infections was not a function of type of immunosuppressive agents used, rejection episodes, antibiotic administration, concomitant hepatitis B, Epstein-Barr (EBV) virus, or herpes simplex virus infections, or alterations in salivary fibronectin concentrations.     

The role of respiratory viruses in the etiology of bacterial pneumonia: An ecological perspective

Pneumonia is the leading cause of death among children less than 5 years old worldwide. A wide range of viral, bacterial and fungal agents can cause pneumonia: although viruses are the most common etiologic agent, the severity of clinical symptoms associated with bacterial pneumonia and increasing antibiotic resistance makes bacterial pneumonia a major public health concern. Bacterial pneumonia can follow upper respiratory viral infection and complicate lower respiratory viral infection. Secondary bacterial pneumonia is a major cause of influenza-related deaths. In this review, we evaluate the following hypotheses: (i) respiratory viruses influence the etiology of pneumonia by altering bacterial community structure in the upper respiratory tract (URT) and (ii) respiratory viruses promote or inhibit colonization of the lower respiratory tract (LRT) by certain bacterial species residing in the URT. We conducted a systematic review of the literature to examine temporal associations between respiratory viruses and bacteria and a targeted review to identify potential mechanisms of interactions. We conclude that viruses both alter the bacterial community in the URT and promote bacterial colonization of the LRT. However, it is uncertain whether changes in the URT bacterial community play a substantial role in pneumonia etiology. The exception is Streptococcus pneumoniae where a strong link between viral co-infection, increased carriage and pneumococcal pneumonia has been established.     

北京儿童医院下呼吸道感染住院患儿血清腺病毒抗体检测分析

目的了解北京儿童医院急性下呼吸道感染住院患儿的腺病毒（ADV）感染情况。方法研究对象为北京儿童医院2004年10月至2005年12月临床诊断为肺炎或支气管炎的住院患儿。每例患儿的血清标本采用间接酶联免疫吸附试验检测ADV—IgM抗体。如果任意一种其他病毒抗体阳性（包括巨细胞病毒、EB病毒、单纯疱疹病毒、肠道病毒等），则不做ADV检测。结果738例其他病原检测阴性的下呼吸道住院患儿中，ADV—IgM阳性87例，阳性率11．8％。ADV下呼吸道感染占同期病例的8．3％（87／1046）。其中〈1岁的患儿32例（6、2％）；1～6岁42例（29、8％）；〉6岁13例（16．9％）。ADV感染全年散发，冬春季节相对较多。结论ADV是5岁以下儿童急性呼吸道疾病的主要病原之一；6月龄至3岁的儿童为易感人群。     

移植患者免疫抑制剂治疗后感染多瘤病毒及巨细胞病毒的现状

目的 探讨移植患者在接受免疫抑制剂他克莫司(FK506)治疗后感染多瘤病毒(BKV)与巨细胞病毒(CMV)情况,为器官移植研究提供流行病学依据.方法 采用FQ-PCR检测605例肝、肾、骨髓移植患者BKV和CMV的感染载量,ELISA检测患者FK506的血药浓度,并对结果进行统计分析.结果 605份标本中,共检测BKV感染者79例,感染率为13.06％,CMV感染148例,感染率为24.46％,双重病毒感染者为35例,感染率为5.79％;肝移植患者感染BKV和CMV阳性率为12.61％和15.97％,肾移植则分别为13.33％和27.08％,而6例骨髓移植标本则未发现病毒感染;CMV感染阳性率明显高于BKV,而病毒感染阳性者,则其FK506血药浓度较高(P＜0.05).结论 移植患者在使用免疫抑制剂FK506后易感染BKV和CMV,并且感染程度与FK506血药浓度相关.     

微生物酵素预防肝移植术后早期感染的作用

目的 评价口服微生物酵素对肝移植术后早期感染的防治效果和临床意义。方法 对20例同种异体原位肝移植病例，采用口服微生物酵素组与对照组，对比临床症候及大便、尿、痰、胆汁的细菌学检查，观察有益微生物菌群制剂的应用对肝移植术后早期感染的防治效果。结果 应用微生物酵素组消化道功能恢复、肠道菌群失调、粘膜系统一般真菌检查及细菌学培养明显优于对照组，并具有显著性统计学意义。结论 肝移植术后经消化道服用微生物酵素，可有效增强粘膜系统的免疫学功能，对预防和治疗肝移植术后早期细菌及真菌性感染有明显的临床意义。     

Priorities for CMV vaccine development

A multidisciplinary meeting addressed priorities related to development of vaccines against cytomegalovirus (CMV), the cause of congenital CMV (cCMV) disease and of serious disease in the immunocompromised. Participants discussed optimal uses of a CMV vaccine, aspects of clinical study design, and the value of additional research. A universal childhood CMV vaccine could potentially rapidly reduce cCMV disease, as infected children are sources of viral transmission to seronegative and seropositive mothers. A vaccine administered to adolescents or adult women could also reduce cCMV disease by making them immune prior to pregnancy. Clinical trials of CMV vaccines in women should evaluate protection against cCMV infection, an essential precursor of cCMV disease, which is a more practical and acceptable endpoint for assessing vaccine effects on maternal-fetal transmission. Clinical trials of vaccines to evaluate prevention of CMV disease in stem cell transplant recipients could use CMV viremia at a level triggering pre-emptive antiviral therapy as an endpoint, because widespread use of pre-emptive and prophylactic antivirals has rendered CMV-induced disease too rare to be a practical endpoint for clinical trials. In solid organ transplant patients, CMV-associated disease is sufficiently common for use as a primary endpoint. Additional research to advance CMV vaccine development should include identifying factors that predict fetal loss due to CMV, determining age-specific incidence and transmission rates, defining the mechanism and relative contributions of maternal reactivation and re-infection to cCMV disease, developing assays that can distinguish between reactivation and re-infection in seropositive vaccinees, further defining predictors of sequelae from cCMV infection, and identifying clinically relevant immune response parameters to CMV (including developing validated assays that could assess CMV antibody avidity) that could lead to the establishment of immune correlates of protection.     

Acute respiratory infections in ambulatory malnourished children: a serological study

We studied the aetiological agents of acute respiratory infections occurring in an ambulatory population of 83 malnourished Jamaican-born children aged 6 to 32 months using serological methods for diagnosis. In 60% (38/63) of symptomatic children and in 25% (5/20) of those without reported disease the following microorganisms were observed: parainfluenza viruses in 15 children, influenza viruses in 12, adenovirus in 10, respiratory syncitial virus in 7 and Mycoplasma pneumoniae in 7 children. The prevalence of the viral infections apparently increased with the severity of malnutrition.     

Clinical picture of Herpesviridae infections among immunocompromised patients: bone marrow and solid organ transplants recipients

The human herpes virus (HHV) family (herpesviridae) are large DNA viruses containing eight important, ubiquitous human pathogens. This group of viruses encompasses: herpes simplex virus (HSV types 1 and 2), varicella-zoster virus (VZV), Epstein-Barr virus (EBV), cytomegalovirus (CMV), HHV-6, HHV-7 (cause roseola or exanthema subitum in children) and Kaposi sarcoma herpes virus--(KSHV). The outstanding property of herpes viruses is lifelong persistence of infection and potential periodic reactivation, particularly often among immunocompromised patients. Herpesvirus infections are associated with a wide spectrum of diseases ranging from local ulceration to serious systemic illnessess or malignancies. These infections are one of the major cause of morbidity and mortality in the immunocompromised patients.     

Self-reported prevalence of warts in children and GP consultation

Objective: Respiratory infections are a frequent causes of medical attendance. Influenza viruses increases this phenomena. The aim of this study was to prospectively identify GPs’ increased work in terms of visits and time. Methods: Over a period of five months 5 GPs recorded sex, age, number and place of visits, telephone consultations of the patients visited for acute respiratory disease (ARD)which included acute respiratory infections (ARI), influenza (FLU) and Influenza-like illness (ILI). Upper respiratory tract infections (URTI) were classified as sinusitis, rhinitis, otitis, tonsillitis, pharyngitis, laryngitis, Lower respiratory tract infections (LRTI) were classified as tracheitis, bronchitis, pneumonia, bronchopneumonia, acute episodes of chronic obstructive pulmonary disease (COPD) and asthma. FLU and ILI were considered two different entities on the basis of symptoms. Results: Acute respiratory disease increase of 22 patients attending every GP's office monthly (from 176 to 198 total visits). 6542 patients were observed. The incidence of ARD was 33.5% (2191: 1091 female and 1100 males). URTI affected 944 patients, LRTI 739, FLU 328 and ILI 180. The increase in home visits grew from 10 to 36. Each home visit took from 15 to 45 minutes. In a high number of cases (236), home visits were necessary for sick-leave certificates. FLU (54%) and LRTI (37.5%) required more attention, and they were the primary causes for visits. Telephone consultations took place for all ILI or FLU of minor severity and in young people.

Conclusion: During the winter there is an increased work-load for GPs due to the diffusion of influenza virus and respiratory tract diseases. “Burn out syndrome” is increasing among the GPs. Territorial GPs’ action is highly efficacious. Patients self-certification should be evaluated. Vaccine therapy could be more effective if done on a larger population. More research is needed.     

Incidence, timing and site of infections among pancreas transplant recipients

The incidence, timing and site of infections among the different categories of pancreas transplant recipients were investigated. Patients were divided into three groups: pancreas transplant alone (PTA), pancreas after kidney transplant (PAK), or simultaneous pancreas and kidney (SPK) transplants. Length of follow-up, time to death, pancreas graft survival, incidence, timing and site of bacterial infections were noted. Our study showed that at least 75% of pancreas transplant recipients experienced at least one infection (range from 77.8% in the PTA group to 86.7% in the PAK group). The SPK group presented the highest rate of infections with 35.1 infections per 1000/patient-days. Symptomatic urinary tract infections were the most common cause of infection in all patients. The incidence of infections was higher during the first month after transplantation, except for the SPK transplant group, where infections occurred over a longer time period.     

Impact of respiratory virus infection in patients with chronic chest disease.

This study investigated the morbidity associated with respiratory virus infections in patients with well-documented chest disease, and the risk of transmission between close contacts. Patients informed the study team if they were exposed to a family member or colleague with a cold. Patients and symptomatic index cases recorded respiratory symptoms during the study period. Acute nasopharyngeal swabs and paired sera were obtained for viral diagnosis. Twenty-five (43%) of 58 recorded exposures resulted in a symptomatic illness and 16 (28%) patients developed lower respiratory tract symptoms. Sixteen (64%) of the 25 symptomatic patients contacted their general practitioner, 14 (56%) received antibiotics and 4 (16%) were hospitalized. Mean duration of illness was 10.6 days in symptomatic patients and 5.7 days in their corresponding index cases (P < 0.005). Mean symptom scores were 100.6 in symptomatic patients and 62.2 in index cases (P < 0.01). Respiratory viruses were identified in 19 (33%) episodes. Rhinovirus, coronavirus and respiratory syncytial virus infections were all associated with lower respiratory tract exacerbations. Respiratory tract symptoms following exposure to a cold were comparatively severe in these patients with chronic chest disease. This group of patients might gain particular benefit from the introduction of effective vaccines or antiviral therapy.     

The incidence of hyperglycemia in hematopoietic stem cell transplant recipients receiving total parenteral nutrition: a pilot study

OBJECTIVE: To determine whether total parenteral nutrition (TPN)-induced hyperglycemia is associated with adverse clinical outcomes. DESIGN: A retrospective cohort investigation comparing the medical records of hematopoietic stem cell transplant patients was conducted to determine clinical differences between those who received TPN and those who did not receive TPN during transplant. SUBJECTS/SETTING: Forty-eight adult patients (> or =18 years) undergoing initial autologous or allogeneic hematopoietic stem cell transplant at two urban university-affiliated hospitals were eligible for inclusion. MAIN OUTCOME MEASURES: Hyperglycemia (glucose > or =6.1 mmol/L or 110 mg/dL), presence of infection, infection duration, and in-hospital mortality. Statistical analyses performed chi 2, Student t, and Wilcoxon rank-sum tests were used to detect differences among the study participants. RESULTS: Patients had similar baseline demographic and clinical characteristics, with 63% receiving TPN during transplant. When standardized for time, TPN recipients at both institutions experienced significantly more hyperglycemia ( P <.05) after TPN initiation. TPN patients also experienced 69% of all infections and 100% of repeat positive cultures. Additionally, significantly greater differences for TPN recipients were found for length of stay and daily charges than those who did not receive TPN. No differences were found for in-hospital mortality. CONCLUSIONS: TPN is strongly associated with hyperglycemia, which may be linked to increased infections of longer duration in a profoundly immunocompromised group of patients who frequently receive TPN. The implications of these findings are limited by the small number of subjects; a larger investigation is warranted.