Hemophilus Influenzae Pneumonia

　　一、发病原因

　　嗜血流感杆菌为革兰阴性短小杆菌，分为荚膜6型。以b型致病力最强，临床近95％的重症嗜血流感杆菌感染是由b型引起。

　　年龄越小，感染Hib危险性越大，其发病率越高。Hib主要通过空气飞沫或接触分泌物传染，新生儿可通过母亲产道感染。感染多呈散发，常年都有发病，但通常是秋季开始上升，冬季达到高峰。由它所致感染中，以呼吸道感染居多。遗传因素可能有较重要的作用。另外疾病因素如先天性免疫缺陷病、先天性或功能性无脾症、早产、营养不良等均可导致Hib感染的危险性增加。近年来因为大量广谱抗生素的应用、白血病或其他恶性淋巴瘤患儿长期应用免疫抑制药，以及气管插管的增多等因素，使Hib感染有增加趋势。

　　二、发病机制

　　最易受侵犯者为婴幼儿、老年、免疫功能低下者(肿瘤、糖尿病病人等)。这些人常常发生流感嗜血杆菌性肺炎、败血症等全身感染。

　　1、致病机理

　　流感嗜血杆菌通过其丝状菌毛黏附于口腔及鼻咽部上皮细胞，分泌IgA蛋白酶，防止SIgA对其作用。流感嗜血杆菌产生内毒素的类脂A成分(脂多聚糖LOS)、糖蛋白相关因子或称为低分子葡萄糖肽，可抑制上皮细胞纤毛运动，使流感嗜血杆菌不被排出气道。b型菌株的荚膜多糖有抗吞噬作用，使Hib逃避宿主吞噬细胞的清除作用。再通过丝状菌毛或黏附因子与呼吸道上皮细胞腺结合。流感嗜血杆菌定植后穿入呼吸道上皮细胞屏障，可在局部生长繁殖并向邻近组织扩展，引起呼吸道疾病，也可侵入血流引起败血症，引起全身病变，可通过血行侵入中枢神经系统，引起脑膜炎。

　　2、免疫反应

　　荚膜抗原的杀菌抗体、补体、吞噬细胞及中性粒细胞在抗感染免疫中起着重要作用。

　　（1）抗体

　　局部SIgA在阻止流感嗜血杆菌黏附于呼吸道黏膜中起重要作用。抗Hib荚膜多糖的杀菌抗体、抗LOS抗体及抗OMP抗体与细菌结合，其Fc段与吞噬细胞结合，对吞噬细胞的吞噬杀菌作用起调理作用。流感嗜血杆菌感染后诱生的抗荚膜杀菌抗体水平，在

　　（2）补体

　　Hib有激活补体经典途径与替代途径的作用。补体通过调理作用促进吞噬细胞的杀菌作用。在感染的早期以替代途径活化为主，在感染的后期则依赖于经典途径的作用。在先天性补体成分缺乏症的小儿，如C2、C3、C4或C3b灭活因子缺乏症的小儿，对流感嗜血杆菌感染的易感性增高。

　　(3) Phagocytes

　　Neutrophils and mononuclear macrophages act together to clear Haemophilus influenzae. In the body, the mononuclear-macrophage system plays the main role. In children with splenectomy, the susceptibility to Haemophilus influenzae infection increases.

　　Infants are more likely to have complications such as empyema, pericarditis, sepsis, meningitis, and suppurative arthritis. They are prone to develop bronchiectasis, develop into suppurative bronchitis, necrosis of bronchial mucosal epithelial cells, partial separation of some mucosa from the basement membrane, infiltration of bronchioles and surrounding lymphocytes and neutrophils, causing bronchiolitis. Bacteria invade alveoli and grow and reproduce within them, causing pulmonary capillary dilation and congestion, alveolar edema and exudation, enhanced chemotaxis and phagocytic activity of neutrophils, and the production of inflammatory exudates, leading to lung consolidation.

　　The onset is relatively slow, the course is subacute, and there is often a history of upper respiratory tract infection before the onset. Symptoms such as fever, cough, sputum, dyspnea, cyanosis, and others appear subsequently. In addition, clinical manifestations are often characterized by spasmodic cough and severe systemic toxic symptoms. Physical examination may reveal signs of bronchopneumonia or lung consolidation, and tube-like breath sounds and moist rales can be heard. It is prone to complications such as empyema, meningitis, sepsis, pericarditis, etc., and the course can last for several weeks. Severe cases may present with heart failure or pericardial tamponade. Chest X-rays may show signs of bronchopneumonia, lobar pneumonia, or segmental lung consolidation. About 20% may develop empyema, and after the absorption of pneumonia, lung bullae may form.

　　1. Haemophilus influenzae vaccine

　　Vaccination is the main measure for preventing infection. Among them, the b-type Haemophilus influenzae capsular polysaccharide vaccine is the most widely used type of novel conjugate vaccine. The World Health Organization has confirmed the preventive effect and safety of this vaccine and advocates its widespread use in the infant population worldwide. The Hib capsular polysaccharide vaccine (PRP) has been approved for use in the United States and has been proven to be safe and effective for children over 2 years old. It should be noted that the ability of young infants to synthesize antibodies against PRP is not well developed, and a second or even third recurrence of infection may occur after recovery from the initial infection with Haemophilus influenzae. In addition, various Hib capsular polysaccharide protein vaccines such as the PRP pertussis vaccine, PRP diphtheria-tetanus-pertussis combined vaccine (PRP-DTP), and PRP diphtheria toxoid combined vaccine are currently under experimental and evaluation. The purpose of research and development is to improve the body's antibody response.

　　2. Antibiotics

　　Some authors advocate that those in contact with patients infected with Haemophilus influenzae type b (Hib) should take rifampin for preventive purposes. The dosage is 20mg/kg per day for 4 consecutive days. Intramuscular injection of gamma globulin or the use of bacterial polysaccharide immunoglobulin (BPIG) can also provide effective protection against infection by b-type strains. For all children with invasive Hib infections, rifampin should also be taken before or after completing antibiotic treatment, as the use of antibiotics after treatment cannot definitely clear the bacteria in the nasopharynx completely.

　　1, Blood count

　　White blood cell count may decrease or increase to (20-70)×10^9/L, most of which are in the range of (1.5-2)×10^9/L, accompanied by relative or absolute increase in lymphocytes.

　　2, Etiological examination

　　In the laboratory examination, the most important is the etiological examination, which can take blood, pharyngeal secretions, sputum, cerebrospinal fluid, pleural effusion, pericardial fluid, joint fluid, tracheal aspirates, and other specimens for smears to find bacteria, or use special Hi culture media containing Levinthol crude liquid for culture. Hib antisera and alpha-f polyvalent antisera can be used for further typing. Among them, sputum examination is the most commonly used method, and generally requires two or more consecutive sputum culture results. The diagnosis of Haemophilus influenzae pneumonia relies on sputum culture, and if blood or pleural effusion culture is positive at the same time, it is more significant. Infants are not easy to cough up sputum, and it can be aspirated through a sterile catheter to culture bronchial secretions. Blood culture is very important for diagnosis, and through the results of blood culture, it is not only possible to understand the presence of bacteremia, but also to estimate the prognosis. It is reported that the positive rate of Haemophilus influenzae blood culture is 60%, and the etiological examination of pleural effusion or lung puncture fluid also has diagnostic value. In addition, latex agglutination (LPA) and immunoelectrophoresis (CIE) techniques have been used for the antigen detection of Haemophilus influenzae, which helps in the rapid diagnosis of Haemophilus influenzae pneumonia.

　　3, Bacterial antigen examination

　　Since Haemophilus influenzae is a common flora in the upper respiratory tract, it is not advisable to use nasopharyngeal specimens for antigen detection when diagnosing respiratory Hib infection. Sinus puncture fluid, tracheobronchial aspiration fluid, and bronchoalveolar lavage fluid can be used for examination. These specimens are difficult to obtain, and generally, blood and urine specimens are sufficient for examination.

　　4, Serological detection

　　It is possible to use ELISA methods to determine b-polysaccharide capsule antibodies, and radioimmunoassay methods can be used to determine antibodies against Hib polysaccharide (Hib-PRP), or indirect ELISA methods can be used to determine the specific IgG and IgM antibodies against OMP of Hib. During the acute stage of infection, the level of anti-OMP-IgM is higher than the average value of the same age by 2 standard deviations, or a doubling of serum antibody levels by 3-4 times can be diagnosed as Hib infection.

　　5, Molecular biological examination

　　Using DNA hybridization technology and PCR methods to determine the specific DNA fragments of Haemophilus influenzae in clinical specimens, the specificity and sensitivity are high. X-ray chest films may show changes such as bronchopneumonia, lobar pneumonia, or segmental consolidation, with the lower lobe of the lung often affected, and it may also present with diffuse bronchopneumonia or capillary bronchitis changes. Chest effusion is common, with about 20% developing empyema, and lung bullae may form after pneumonia absorption.

　　It is necessary to pay attention to reasonable nutrition and sufficient water intake. Pneumonia patients often have high fever, poor appetite, and unwilling to eat, so the diet should be light and easy to digest, while ensuring a certain amount of high-quality protein. For those with fever, give liquid diet (such as human milk, cow's milk, rice porridge, egg flower soup, beef soup, vegetable soup, fruit juice, etc.), after fever subsides, semi-liquid food (such as congee, noodles, cakes, etc.) can be added, because the evaporation of water in pneumonia patients is more than usual, so it is necessary to supplement an appropriate amount of sugar and salt water..

　　I. Treatment

　　1. Antibiotic treatment

　　Since Haemophilus influenzae is a Gram-negative bacillus, it is not sensitive to penicillin, and ampicillin (ampicillin) and gentamicin or chloramphenicol are preferred, with a dose of 100 to 200 mg/kg of ampicillin (ampicillin) per day, 15 mg/kg of chloramphenicol for newborns per day, 30 to 50 mg/kg for older children per day, the initial dose of gentamicin is 2.5 mg/kg per day, and then 5 mg/kg per day, the course of treatment is 10 to 14 days. Injection or intravenous administration, intravenous administration is preferred. When bacteria are resistant to ampicillin (ampicillin), cephalosporins such as ceftriaxone sodium can be used, 50 to 150 mg/(kg/d), intravenous infusion. Cefaclor, cefuroxime, ciprofloxacin, doxycycline, clarithromycin, ampicillin, and others can also be used.

　　2. Immunotherapy

　　Hib outer membrane protein monoclonal antibody, bacterial polysaccharide immunoglobulin, and normal human blood gamma globulin can be used.

　　3. General treatment

　　Symptomatic treatment for Streptococcus pneumoniae pneumonia.

　　II. Prognosis

　　Generally, timely diagnosis and treatment lead to good prognosis, but Hib can cause severe infections in children, such as meningitis, sepsis, and severe pneumonia, which are the main causes of childhood death. Even with appropriate treatment, Hib meningitis can still result in the death of 3% to 25% of children, and 30% to 50% of survivors may suffer from lifelong disabilities, such as deafness, learning disorders, and motor disorders, etc.