Bordetella pertussis and chronic cough in adults.

To evaluate Bordetella pertussis as a cause of persistent cough in adults, we examined 201 patients who had a cough for 2-12 weeks and no pulmonary disease. We obtained the following at presentation: medical history, chest radiograph, respiratory function measurement, nasopharyngeal aspirate for polymerase chain reaction (PCR), nasopharyngeal swab specimen for culture, and a blood sample (acute serum). Four weeks later a second blood sample (convalescent serum) was obtained. Control sera were obtained from 164 age-matched healthy blood donors with no history of cough during the previous 12 weeks. Four patients were B. pertussis culture-positive; 11 (including the culture-positive patients) were B. pertussis PCR-positive; and 33, including 10 of the 11 PCR-positive patients, had serological evidence of recent B. pertussis infection. Pertussis-positive and -negative patients could not be discriminated by a history of cough. We conclude that B. pertussis infection is a common cause of persistent cough in adults. This is of concern, because these patients may be B. pertussis reservoirs from which transmission may occur to infants, in whom the disease can be devastating.     

百日咳杆菌感染与成人不明原因慢性咳嗽相关性研究现状

尽管咳嗽变异性哮喘、上气道咳嗽综合征/鼻后滴流综合征、嗜酸粒细胞性支气管炎和胃食管反流性咳嗽被普遍认为是不明原因慢性咳嗽(简称慢性咳嗽)最常见病因,但感染后咳嗽也是引起长期咳嗽的一个重要因素.由肺炎支原体和肺炎衣原体等引起的感染后咳嗽多为人们所熟知,且常经验性使用大环内酯类抗生素对其治疗.长期以来,百日咳被认为在儿童呼吸道感染性疾病中较为常见,但近年来的研究表明,百日咳杆菌感染也是引起成人慢性咳嗽的常见原因,需要加以重视和鉴别.     

百日咳杆菌感染与成人不明原因慢性咳嗽相关性

目的 探讨百日咳杆菌感染与成人不明原因慢性咳嗽的相关性.方法 采集2010年12月至2011年8月因慢性咳嗽(咳嗽时间>8周,但不符合咳嗽指南中的任何一种原因)就诊于武汉大学人民医院64例患者血清,置于-20℃保存,应用ELISA方法 测定患者血清中百日咳毒素的浓度.结果 64例患者中,仅1例为阳性,确诊为百日咳杆菌感染,另63例均呈阴性,百日咳杆菌感染阳性率为1.56%.结论 慢性咳嗽患者百日咳感染检出阳性率低.     

Clinical presentation of pertussis in fully immunized children in Lithuania

Background  

In Lithuania, the vaccination coverage against pertussis is high. Nevertheless, there is a significant increase in pertussis cases in fully immunized children. The aim of our study was to determine the frequency of classical symptoms of laboratory confirmed pertussis and describe its epidemiology in children fully vaccinated against pertussis.     

Evaluation of serological tests for diagnosis of Bordetella pertussis infection in adolescents and adults

Background and objective: Bacterial agglutination antibodies against Bordetella pertussis, Yamaguchi and Tohama strains, are frequently measured for serodiagnosis of pertussis infection in Japan. To determine the serological criteria, the comparative titres of bacterial agglutination antibody and anti‐pertussis toxin (PT) antibody were evaluated. Methods: Antibody titres were analysed in 36 definitive (fourfold increase in agglutination antibody) and 137 presumptive (high titre of single‐antibody) cases of B. pertussis infection among adolescents and adults, and in a control group of 318 healthy volunteers. Results: When a single Yamaguchi agglutinin titre of ≥1:1280 (> three SD above the geometric mean for the control group) was taken as diagnostic, the sensitivity and specificity at 4–5 weeks after onset of cough were 58% and 98%, respectively. Using this criterion, the clinical findings in presumptive cases were almost identical to those in definitive cases. When the two tests were compared using 318 control sera, there was no association between the Tohama agglutinin titre and the anti‐PT antibody titre, whereas a weak association between the Yamaguchi agglutinin titre and the anti‐PT antibody titre was observed. When the numbers of pertussis cases with high antibody titres in the two tests were compared, 60% of cases with a Yamaguchi agglutinin titre of ≥1:1280 showed an anti‐PT antibody titre of ≥100 EU/mL. Conclusions: These results indicate that the bacterial agglutination test is a method with low sensitivity and specificity for the diagnosis of B. pertussis infection. Therefore, to yield an accurate diagnosis, anti‐PT antibody levels should be measured instead of bacterial agglutination antibody.     

Modulation of Bordetella pertussis infection with monoclonal antibodies to pertussis toxin.

Three monoclonal antibodies to pertussis toxin were characterized and used to investigate its role in immunity. Antibody affinity correlated with toxin neutralization in in vivo and in vitro assays but was not the only determinant of protection against Bordetella pertussis infection. B9, a high-affinity anti-S3 antibody, was the most effective in neutralizing toxin-induced CHO cell clustering and hemagglutination in vitro and lymphocytosis and histamine sensitization in vivo. A4, a similar-affinity anti-S1 antibody, was less active in the toxin neutralization assays but more protective in the mouse infection model. A12, a low-affinity anti-S1 antibody, was least active in the assays of toxin neutralization but as effective as B9 in the infection model. These data suggest that epitopes on the A protomer and B oligomer may induce protective immunity. Measurement of pertussis toxin neutralization by monoclonal antibodies in in vitro and in vivo assays may not accurately predict protection against infection with B. pertussis.     

Clinical manifestations of essential thrombocythemia in young adults

Essential thrombocythemia (ET) is a myeloproliferative disorder characterized by isolated overproduction of platelets, thrombohemorrhagic complications, and a median age of 50-60. When it occurs in younger patients, the incidence of complications has been reported to be quite low, with a good long-term prognosis. We report a retrospective review of 13 patients with ET between the ages of 22 and 35 in which 11 were symptomatic at diagnosis, with only one remaining asymptomatic during follow-up. Three patients presented with potentially life-threatening complications (two myocardial infarctions, one stroke), although no deaths were observed. The majority of the nonlife-threatening complications were vaso-occlusive in nature, including erythromelalgia and transient neurologic symptoms. We conclude that ET in young adults is not always a benign disease and that potentially life-threatening complications are not rare. The optimum approach to treatment in this or any other age group remains uncertain.     

A search for Bordetella pertussis infection in university students.

University students with persistent cough of greater than or equal to 6 days' duration were evaluated for evidence of infection with Bordetella pertussis. Of 130 students studied during a 30-month period, 34 (26%) were found to have evidence of recent infections with B. pertussis. Infection was identified by direct fluorescent antibody assay of a nasopharyngeal specimen in one student and serologically in 33 additional subjects. B. pertussis was not recovered on culture of nasopharyngeal specimens from any subjects. Students with B. pertussis infection were identified in seven of the eight 3-month periods in which students were enrolled during the 30-month investigation, suggesting an endemic rather than epidemic pattern of infection in this university population. Illnesses of students with pertussis were similar to the illnesses of students without pertussis. The findings in this study suggest that adult populations in which endemic illness occurs at a relatively constant rate may be the reservoirs for pertussis outbreaks in susceptible children. Immunization programs in the future will need to employ booster doses for adults if complete control of B. pertussis infection is our goal.     

Human serum antibody responses to Bordetella pertussis infection and pertussis vaccination

We used an immunoblotting technique to compare the serum antibody responses to pertussis toxin (PT), filamentous hemagglutinin (FHA), a 69-kilodalton (kDa) adenylate cyclase-associated protein (69 KD protein), and Bordetella pertussis outer membrane proteins (OMPs) following either B. pertussis infection or immunization with whole-cell pertussis vaccine. Infection and vaccination induced nearly equally intense antibody responses to PT and to FHA, but vaccination induced stronger antibody responses to the 69 KD protein and to many OMPs. The importance of serum antibody responses to the 69 KD protein and to B. pertussis OMPs other than PT and FHA in conferring immunity to pertussis after vaccination is unknown. Serum antibody responses to PT following either infection or vaccination were almost exclusively to the 28-kDa enzymatic subunit (S1) and only rarely and weakly to the lesser molecular weight binding subunits (S2-S5).     

Controlled study of a new five-component acellular pertussis vaccine in adults and young children.

A new five-component acellular pertussis (AP) vaccine containing 10 micrograms of pertussis toxoid, 5 micrograms of filamentous hemagglutinin, 5 micrograms of combined agglutinogens 2 and 3, and 3 micrograms of pertactin was evaluated in adults and young children. AP vaccine was compared with saline placebo in 31 adults, and AP vaccine combined with diphtheria and tetanus toxoids (ADTP) was compared with whole cell DTP in 41 children, ages 16-20 months, who had received whole cell DTP during infancy. AP was mildly to moderately reactogenic in adults, with pain noted within 72 h and 5-8 days after immunization. ADTP was less reactogenic than DTP in children, with significantly decreased pain, redness, irritability, and fever and less use of acetaminophen reported. No late reactions were observed in any child. The multicomponent ADTP was immunogenic, with four-fold or greater antibody rises to at least four pertussis antibody assays in all 15 immunized adults. Pertussis-specific antibody responses in children who received ADTP and DTP were similar. The multicomponent ADTP vaccine is currently being studied in a National Institute of Allergy and Infectious Diseases-sponsored efficacy study in Sweden.     

Clinical manifestations of Q fever in adults and children

Q fever is a common zoonosis with almost a worldwide distribution caused by Coxiella burnetii. Farm animals and pets are the main reservoirs of infection and transmission to humans is usually via inhalation of contaminated aerosols, which may be carried by the wind far from the original source of infection. Occupational groups with close association with farm or wild animals are most at risk, however travellers occasionally become infected. The disease is associated with a wide spectrum of clinical manifestations and symptoms, ranging from asymptomatic infection to fatal disease. Awareness of the disease and newer diagnostic methods led to increase of recognition and detection in cases with various or multiple symptoms in adults and children. However, children seem to be less frequently symptomatic and may have milder disease. This review of Q fever cases examines clinical manifestations and symptoms of Q fever in both adults and children and shows that certain symptoms and their severity have altered presentation in children with acute and chronic Q fever when compared to adults.     

Immune responses to Bordetella pertussis infection and vaccination

To assess antibody and cellular immune responses, 156 healthy children were immunized at approximately 18 months of age with acellular diphtheria-tetanus-pertussis vaccine. Changes in antibody responses to filamentous hemagglutinin (FHA) and to pertussis toxin (PT) were similar in pattern, and antibody titers reached values equal to those from patients with convalescent-stage pertussis. The FHA-induced DNA synthesis in peripheral blood mononuclear cells was maximum at 4 weeks after the primary series, and these levels were equal to those of patients with pertussis. High amounts of PT-induced DNA synthesis were observed in both immunized and nonimmunized children; thus, PT seemed to act mainly as a nonspecific mitogen. Almost the same responses to several mitogens that activate different subsets of lymphocytes were observed in young infants compared with older children. Furthermore, young infants who had Bordetella pertussis infection responded by FHA stimulation almost as well as older children.     

极年轻成人急性心肌梗死患者临床特点分析

目的比较40岁及60岁急性心肌梗死(acute myocardial infarction,AMI)患者的临床特征。方法回顾性分析2010年1月至2015年5月因AMI在大理大学附属医院心内科住院患者277例,将其分为40岁和60岁两个年龄组,比较两组患者的冠状动脉粥样硬化性心脏病(冠心病)危险因素、临床化验指标、左心室收缩功能、冠状动脉病变的严重程度(改良Gensini评分)等。结果 40岁组中男性比例、吸烟患者比例、高脂血症患者以及阳性家族史患者比例比60岁组更高,差异有统计学意义(P0.05或P0.01)。临床检验发现40岁组肾小球滤过率(eG:FR)、三酰甘油(TG)、总胆固醇(TC)、载脂蛋白B(ApoB)均显著高于60岁组,差异有统计学意义(P0.01)。40岁组和60岁组AMI患者冠状动脉造影结果比较发现,40岁组单支病变比例更高(P0.01),而60岁组三支病变比例更高(P0.01)。40岁组改良的Gensini评分显著低于60岁组,差异有统计学意义(P0.01)。结论 40岁组和60岁组AMI患者的传统冠心病危险因素、临床检查指标以及冠状动脉病变特点均有显著不同。     

Measles epidemic in young adults. Clinical manifestations and laboratory analysis in 40 patients

Between February and June 1985, 40 military personnel were hospitalized because of measles. Diagnosis in all patients was entirely clinical, and serologic investigations were noncontributory. A transient disturbance in liver function occurred in 70% of patients, and its extent correlated with duration of fever and disease complications. Spontaneously resolving, measles-specific hypocalcemia, which was not associated with hepatic dysfunction, was noted in about one third of the patients. All these patients were asymptomatic, except one patient who developed tetany. The pathophysiologic basis for the hypocalcemia is still unknown. The disease course in three previously immunized patients was benign and uncomplicated.     

Cell-mediated immunity and antibody responses to Bordetella pertussis antigens in children with a history of pertussis infection and in recipients of an acellular pertussis vaccine

Cell-mediated immunity (CMI) and antibody responses to Bordetella pertussis antigens were assessed 4-6 years after primary infant immunization with diphtheria-tetanus tricomponent acellular pertussis (DTaP) or diphtheria-tetanus (DT) vaccine in a country with high endemicity of B. pertussis infection. CMI to the B. pertussis antigens (especially to the pertussis toxin [PT]) was more frequent and/or intense in DTaP than in DT recipients. No lymphoproliferation differences were found between those with and without a history of pertussis although the DT recipients produced very little interferon-gamma after antigen (particularly PT and filamentous hemagglutinin [FHA]) stimulation. In contrast, seropositivity to PT, but not to pertactin or FHA, was more frequent in DT recipients with history of pertussis than in all other subjects. Thus, years after disease or vaccination, CMI response to PT or circulating PT antibodies appears to be the main distinctive feature of pertussis-protected DTaP recipients or pertussis-affected DT recipients.     

Bordetella pertussis, Bordetella parapertussis, Mycoplasma pneumoniae, Chlamydia pneumoniae and persistent cough in children.

Material collected during a prospective pertussis vaccine trial in 1992-95 was examined for Bordetella pertussis (culture and serology), Bordetella parapertussis (culture), Mycoplasma pneumoniae and Chlamydia pneumoniae (PCR). From 64% (99/155) of episodes with cough for less than 100 d, 115 aetiological agents were identified in one southern and one northern subset of DT-recipients. The most common single agent was B. pertussis, representing 56%(64/115), with a median cough period of 51 d, followed by M. pneumoniae 26%(30/115), 23 d, C. pneumoniae 17% (19/115), 26 d, and B. parapertussis 2% (2/115). For co-infections, the median duration of cough was about 60 d. Spasmodic cough for 21 d or more (clinical WHO criteria for pertussis) was present in 82% (41/50) of infections with B. pertussis as single agent, 38% (17/45) with B. parapertussis, 38% (5/13) with C. pneumoniae, 26% (5/19) with M. pneumoniae and 30%(17/56) in cases where no aetiology was found. In children with cough for more than 100 d (n = 78) using all vaccine arms, B. pertussis was responsible in 83% (65/78), in 21%(16/78) together with other agents. Acellular vaccines were more efficient against serious disease than whole cell vaccine. Antibiotic treatment was more common at the southern (34%) study site than at the northern one (12%). The findings indicate that diagnosis should rely on laboratory confirmation, both for rational treatment of an individual case and for monitoring outbreaks.     

Clinical and laboratory manifestations of congenital dyserythropoietic anemia type I in young adults

OBJECTIVES: Congenital dyserythropoietic anemia (CDA) type I is a rare autosomal recessive macrocytic anemia whose natural history is not well documented. The aim of the present study was to evaluate the clinical picture of the disease in young adults. METHODS: The study sample consisted of 17 patients of mean age 11.9 +/- 5.4 yr (range 18-33 yr) and one older patient (age 44 yr), all Israeli Bedouins. The degree of anemia was evaluated as well as the extent of development of gallstones and iron overload. In each subject we determined the hemochromatosis gene mutations and the uridine dyphosphate-glucoronosyltransferase (UGT-1A) gene polymorphism associated with Gilbert's syndrome. RESULTS: The patients were found to have moderate anemia, with the women displaying lower mean hemoglobin levels than the men (8.2 +/- 0.9 g dL(-1) vs. 10 +/- 1.3 g dL(-1); P=0.0059). The majority of patients (59%) had received at least one blood transfusion, with the women having a significantly higher transfusion requirement. Although delayed puberty was noted, final height and weight were within normal limits, and eight patients had progeny. Biliary stones were found in three of 16 patients, two of whom were homozygous for UGT-1A gene polymorphism. None of the patients carried the common hemochromatosis gene mutation, although serum ferritin levels were moderately elevated (788 +/- 332 ng mL(-1)). CONCLUSIONS: CDA type I in young adults is characterized by moderate macrocytic anemia, more severe in women, and a tendency to cholelithiasis and secondary progressive iron overload. We suggest that iron overload in this patient population should be monitored and chelation therapy initiated when indicated to prevent organ damage     

Evaluation of real-time PCR for diagnosis of Bordetella pertussis infection

Background  

Nucleic acid amplification of the IS481 region by PCR is more sensitive than culture for detection and diagnosis of Bordetella pertussis but the assay has known cross-reactivity for Bordetella holmesii and its use as a routine diagnostic assay has not been widely evaluated.     

Extracytoplasmic adenylate cyclase of Bordetella pertussis.

Soluble adenylate cyclase [EC 4.6.1.1] accumulates in the culture medium of exponentially growing Bordetella pertussis (300-900 pmol of cAMP formed/min per ml of 24 hr culture supernatant). In addition, there is an extracytoplasmic adenylate cyclase which enables the intact organisms to form [32P] cAMP (adenosine 3':5'-cyclic monophosphate) from exogenous [alpha-32P] ATP (200-1200 nmol of cAMP formed/min per g wet weight of cells) and which comprises 20-45% of the total adenylate cyclase activity. In contrast, only 1.7 and 2.4% of the total cell malate dehydrogenase [EC 1.1.1.37] and alkaline phosphatase [EC 3.1.3.1], respectively, are detectable in the intact cell. Trypsin treatment of intact organisms destroys 96% of the extracytoplasmic adenylate cyclase, but does not reduce the total cell malate dehydrogenase or a small pool of intracellular adenylate cyclase. Four compartments of adenylate cyclase in B. pertussis are proposed; (A) soluble enzyme in the culture supernatant (up to 20% of the total activity); (B) enzyme associated with intact cells and measurable without cell disruption (20-45%); (C) extracytoplasmic enzyme sensitive to trypsin, but not measurable in intact cells at standard substrate concentrations (40-60%); and (D) intracellular enzyme (7-9%). In comparison with previously studied bacterial adenylate cyclases, the extracytoplasmic location appears to be unique to the B. pertussis enzyme.     

Interventional treatment for very young adults with acute myocardial infarction. Clinical manifestations and outcome

Direct percutaneous coronary intervention (PCI) for acute myocardial infarction (AMI) is now established as a standard therapy for older patients. However, experience with PCI in very young adults with AMI has been limited. In this report we retrospectively evaluated the effectiveness of PCI for very young adults with AMI and estimated their clinical characteristics and outcome. Of the 502 patients with AMI, 5 were 35 years old or younger (1.0%) during a period of 4 years (2000--2004). We assessed the utility of PCI in these five consecutive patients under the age of 35 presenting with a first AMI. Five AMI patients, ranging in age from 20 to 34 years (median, 27+/-5 years) underwent direct PCI for the culprit lesions. The lesions targeted for PCI were located in the left anterior descending artery in 3 patients and in the right coronary artery in 2 patients. One patient had a past history of Kawasaki disease (KD). In all of the patients, PCI were angiographically effective at the acute phase without complication. In hospital course, a subacute stent thrombosis occurred in one patient. Follow-up angiograms performed 6 months after the procedure revealed no restenosis, but identified a new coronary aneurysm in one patient with a past history of KD and a regressed giant coronary aneurysm probably due to atypical KD in another patient, which were confirmed by intravascular ultrasound. There was one death ascribed to heart failure 8 months after the initial PCI. The findings of this report suggest that PCI for very young adults with AMI can be safe and effective in the short-term.