Pediatric Legionnaires' disease

　　1、发病原因

　　军团菌是一类需要特殊营养的革兰阴性需氧短杆菌，宽0.3～0.9μm，长2～3μm，在普通培养基中不能生长，一般采用Mullner-Hinton琼脂、Feeley-Gormall琼脂或CYE琼脂等培养基，在2.5％二氧化碳及35℃条件下培养2～7天方成菌落。其细胞壁中含有高比例的短分枝脂肪酸，这在革兰阴性杆菌中少见，是重要的识别要点。已知军团菌属(Legionella)与人类疾病有关的有6种，即L.pneumophila，L.micdadei，L.dumoffii，L.gormanii及L.long-beachae。其中以第1种即嗜肺军团菌最为常见，有10个血清型。军团菌含有多种外毒素与内毒素，几种毒素的共同作用才引起疾病。

　　2、发病机制

　　目前对军团菌肺炎发病机制仍不十分清楚。嗜肺军团菌通过空气传播进入肺部，细菌进入肺组织后病变主要位于肺泡，由肺泡逆行至呼吸性细支气管，再到较大的小支气管，少数延及间质或胸膜、淋巴管、胸导管与血循环，进入血液循环至肝、脾、肾和中枢神经系统等，造成多脏器损害。当军团菌进入人体内后被单核细胞吞噬后可不被灭活，而继续在单核细胞内繁殖，中性粒细胞和单核细胞要在特异性抗体C3参与下可杀灭吞噬细胞外的军团菌。军团菌感染后期，由于中性粒细胞和单核细胞迅速增多，其他细胞趋化因子以及特异性抗体形成，使细菌生长受到抑制，当血清抗体达到高峰时，军团菌即被消灭。病理改变：局灶性结节性病灶或融合的支气管肺炎，可进展为大叶性肺炎，25％病例有微小脓肿，严重病例有浆液性或浆液血性胸膜渗液。镜下，肺泡和呼吸性细支气管旁有严重炎症，肺泡上皮细胞脱落。肺泡内有多核粒细胞、巨噬细胞及纤维素的稠厚渗出液，较少影响较大气道及肺泡隔。

　　Pleural effusion, toxic encephalopathy, respiratory failure. A few cases may have respiratory distress syndrome, shock, acute renal failure, lung abscess, DIC, etc. After 1 to 2 days, symptoms may include high fever, dry cough (or sputum), difficulty breathing, shortness of breath, chills, and occasionally diarrhea. X-ray films may show signs of pneumonia. Severe patients may have extrapulmonary symptoms, which may manifest as liver dysfunction and renal failure, protein and red blood cells in urine, and some may even have mental disturbance. Some may also cause infective endocarditis, lung abscess, even lung cavities, etc. There is also a certain mortality rate.

　　The diseases caused by Legionella pneumophila have two basic types: non-pneumonic type, also known as Pontiac fever, and pneumonia type, known as legionnaires' pneumonia or simply legionnaires' disease. Legionnaires' pneumonia is a severe multisystemic disease mainly manifested as pneumonia and fever, with an incubation period of 2 to 10 days, on average 4 days. The main symptoms include fever, cough, sputum, difficulty breathing, headache, myalgia, and some children may have confusion. Children are more acute in onset and progress faster than adults, and some may quickly develop respiratory failure, drowsiness, coma, with a high mortality rate. Early symptoms often include scattered wet rales in both lungs, 20% to 60% with small amounts of pleural effusion, and most patients then present with lung consolidation signs. About 1/3 have relative bradycardia, which is one of the characteristics of the disease.

　　1. Preventive measures for environmental factors

　　Focus on the design, maintenance, and management of cooling towers, water pipes, and other fixed facilities that may cause the proliferation and spread of legionella. Formulate operational methods that are easy to regularly disinfect and clean. Secondly, strengthen the monitoring of legionella in soil and animals within the region by the health department, with a focus on the management of water sources. Drain the water from the cooling tower when not in use, clean it mechanically regularly, and remove scale. The main methods of disinfecting the water supply system include: raising the water temperature (60℃), regularly flushing the water supply pipes, and disinfection with chlorine disinfectants.

　　2. Regular inspection

　　Regularly inspect the water pipes, air conditioners, cooling towers, and other facilities in hospitals, hotels, nightclubs, cinemas, offices, etc. for legionella contamination. Disinfection treatment should be carried out immediately if contamination is found.

　　3. Regular cleaning

　　Regularly clean the air filter of the air conditioner used at home. Pay attention to regular cleaning of hot water pipes, showers, heaters, and other places where water may accumulate.

　　4. Regular ventilation

　　In the enclosed space of an air conditioner, the indoor air must always be paid attention to open the windows and ventilate regularly, and windows should never be kept closed all the time.

　　5. Strengthen health care

　　Exercise the body, improve the body's resistance, protect susceptible populations, and the elderly or weak should try to avoid crowded, poorly ventilated public places, etc. General protective measures. Currently, comprehensive preventive measures should be taken to prevent and control legionellosis.

　　First, routine and biochemical tests

　　Most children have blood leukocytes > 10×109/L, neutrophilic granulocytes shifted to the left, and those with leukopenia have poor prognosis. Proteinuria, microscopic hematuria, abnormal liver function, hyponatremia are also one of the characteristics of the disease. ESR is moderately increased, and cerebrospinal fluid examination is often negative, with a few cases showing increased pressure and monocytes elevated to (25-100)×106/L.

　　Second, special laboratory examination

　　1. Pathogen examination

　　It is difficult to culture pathogenic bacteria from secretions, blood, sputum, pleural effusion, and other specimens, with a low positive rate and a culture time of more than 1 week, making it difficult to make a timely diagnosis. If the specimen to be tested is sputum, it is necessary to add polymyxin, vancomycin, and other antibiotics to the culture medium, and acidify the sputum fluid, which can improve the positive rate. The highest positive rate is obtained from tracheal aspirate, and a positive result can confirm the disease. Currently, BCYE culture medium is mostly used.

　　2. Detection of bacteria and their antigenic components

　　(1) Direct fluorescent antibody staining (DFA): With a specificity of over 94%, but a sensitivity of about 40%, results can be obtained within 2 hours, which is conducive to early diagnosis.

　　(2) Detection of microorganisms in specimens using gene probe technology: Using nucleic acid molecular hybridization technology to detect and identify legionella at the gene level has received widespread attention. The probe method is relatively fast, but the technical requirements are high, and there is currently controversy about its specificity. The use of polymerase chain reaction (PCR) for further research is an ongoing work.

　　(3) Enzyme-linked immunosorbent assay (ELISA), radioimmunoassay (RIA): Detection of antigenic substances of Legionella pneumophila in urine, suitable for the early diagnosis of Legionella pneumophila type I pneumonia, with a high detection rate of up to 80%, strong specificity, and widely used.

　　3. Detection of serum specific antibodies

　　Specific IgM antibodies can be detected around 1 week after infection, and IgG antibodies start to rise approximately 2 weeks later. Indirect fluorescent antibody test (IFA) is the most commonly used method in China, and microagglutination test (mAA), counterimmunoelectrophoresis (CIF), and serum antibody determination are also used for the diagnosis of legionella. There are two problems with the diagnosis of legionella using serum antibodies: one is that antibodies can exist for several months to 3 years after illness, making it difficult to distinguish between past illness and current illness in patients with positive serum antibodies; the other is the existence of cross-reactive antibodies, such as those found in psittacosis chlamydia, pseudomonas, proteus, Escherichia coli, Staphylococcus aureus, tuberculosis, and mycoplasma infections. Children with these infections may have cross-reactive antibodies to legionella. The initial chest X-ray findings are patchy and nodular infiltrative shadows, often presenting as lower lobe alveolar consolidation or alveolar-interstitial mixed lesions. Generally, it starts as unilateral localized and later develops into bilateral diffuse pneumonia, with about half of the cases having pleural effusion. Other examinations, such as ultrasound, electrocardiogram, and electroencephalogram, are performed according to the needs of the condition.

　　It is important to pay attention to reasonable nutrition and supplement sufficient water. Children with pneumonia often have high fever, poor appetite, and are 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, liquid diet (such as human milk, cow's milk, rice porridge, egg flower soup, beef soup, vegetable soup, fruit juice, etc.) should be provided. After the fever subsides, semi-liquid foods (such as congee, noodles, cakes, etc.) can be added. Since the evaporation of water in children with pneumonia is higher than usual, it is necessary to supplement an appropriate amount of sugar and salt water..

　　1. Treatment

　　Erythromycin is the first-line antibiotic, with a dosage of 50mg/kg per day. In severe cases, intravenous erythromycin can be used, administered 3 to 4 times, for a course of 2 to 3 weeks. Reports have shown that rifampin, sulfamethoxazole, and trimethoprim (co-trimoxazole) also have good efficacy. The efficacy of tetracycline is unstable. Penicillin, vancomycin, and cefamycin are ineffective for this disease. Other symptomatic supportive treatment methods are the same as for pneumonia.

　　2. Prognosis

　　The prognosis for those who have not received treatment is poor, with a high mortality rate, especially for individuals with weakened immunity and severe conditions, where the mortality rate of immunosuppressed patients can reach 50% to 80%. Respiratory failure is the main cause of death. However, with the effective use of antibiotics, the prognosis has improved and the mortality rate has decreased. Mild cases can recover naturally in 6 to 8 days.