1 MINISTRY OF EDUCATION AND TRAINING MINISTRY OF HEALTH THE NATIONAL INSTITUTE OF HYGIENE AND EPIDEMIOLOGY PHAM THU HIEN THE STUDY OF EPIDEMIOLOGICAL CHARACTERISTICS, CLINICAL MANIFESTATIONS OF ATYPICAL PNEUMONIA CAUSED BY BACTERIA IN CHILDREN Science: Epidemiology Code: 62 72 01 17 SUMMARY OF THE DOCTORAL DISSERTATION HA NOI - 2014 2 The project was completed at the National Institute of Hygiene and Epidemiology The scientific advisors: 1. Prof. Dao Minh Tuan 2. Prof. Phan Le Thanh Huong Reviewer 1: Reviewer 2: Reviewer 3: The dissertation will be defended at the meeting hall of the National Institute of Hygiene and Epidemiology. In… hours, …/… / 20…. The dissertation is available at: 1. The National Library 2. The National Institute of Hygiene and Epidemiology 3 LIST OF THE PUBLICATIONS BY THE AUTHORS RELATED TO THE DISSERTATION 1. Pham Thu Hien, Dao Minh Tuan, Nguyen Phong Lan, Phan Le Thanh Huong (2011), "The role of Mycoplasma pneumoniae, Chlamydia pneumoniae, and Legionella pneumophyla in community -acquired pneumonia in children: preliminary results", Journal Journal preventive Medicine, Vol. XXI, No. 7 ( 125 ), pp. 62-69. 2. Pham Thu Hien, Dao Minh Tuan, Nguyen Phong Lan, Phan Le Thanh Huong( 2012 ) , " Causes, clinical features , clinical manifestations of atypical pneumonia in children " , Journal of Medical Research , episode 80 , No. 3 A , pp. 119- 124 . 3. Pham Thu Hien, Dao Minh Tuan, Nguyen Phong Lan, Phan Le Thanh Huong (2012), "Frequency , clinical characteristics , subclinical pneumonia caused by Mycoplasma pneumoniae, Chlamydia pneumoniae in children ", Journal Journal preventive Medicine, Vol. XXII, No 6 (133), tr 31 - 38. 4 LIST OF ABBREVIATIONS ALT Alanine Aminotransferase AST Aspartate Aminotransferase BCYE buffered charcoal yeast extract C. pneumoniae Chlamydia pneumoniae Chlamydia pneumoniae CRP C protein reactive Protein C phản ứng Cs Cộng sự ELISA enzyme-linked immunosorbent assay Kỹ thuật miễn dịch gắn men IgG Immunoglubulin G Immunoglubulin G IgM Immunoglubulin M Immunoglubulin M IL Interleukin Interleukin INF Tumor necrosis factor Yếu tố hoại tử u L. pneumophila Legionella pneumophila Legionella pneumophila M. pneumoniae Mycoplasma pneumoniae Mycoplasma pneumoniae PCR polymerase chain reaction Phản ứng PCR PPLO Pleuropneumonia like organisms Pleuropneumonia like organisms Real – time PCR Real –time polymerase chain reaction Phản ứng Real – time PCR S. pneumoniae Streptoccocus pneumoniae Streptoccocus pneumoniae TNF Tumor necrosis factor Yếu tố hoại tử u VPĐH Viêm phổi điển hình VPKĐH (AP) Atypical pneumonia Viêm phổi không điển hình WHO World Health Organization Tổ chức y tế thế giới 5 ABSTRACT OF THE DISSERTATION 1.Background A typical pneumonia is frequent in developing countries. However, the studies about these conditions in developing countries, including Vietnam are limited. Forest (2007) reported that the incidence of atypical pneumonia in the community-acquired pneumonia was 22 % in the United States and 91% of those had been treated. In Europe, the incidence of atypical pneumonia was 28%, the rate of treatment was 74%. In Latin America, the incidence of atypical pneumonia was 21% and the rate of treatment was 57%. In Asia / Africa, the incidence was 20%, the rate of treatment was 10%. The diagnostic methods for atypical pneumonia include: bacterial culture in the special media, serology, and polymerase chain reaction method. Polymerase chain reaction method (PCR) has helped confirmed and rapid diagnosis bacterial pathogens. In Vietnam, PCR techniques are available in only few hospitals in central and major medical centers. Most treatments have been done with empirical therapy that may result in increasing in antibiotic resistant, and prolonged treatment time. Little is known about the epidemiology, clinical and laboratorial manifestations of atypical pneumonia in children, including the diagnostic techniques for bacterial causes of atypical pneumonia such as multiple primers PCR (multiplex-PCR) and enzyme-linked immunosorbent assay (ELISA), we conducted the study: "The study of epidemiological characteristics, clinical manifestations of atypical pneumonia caused by bacteria in children”. The study objectives were: 1. To describe the epidemiological characteristics, clinical manifestations of atypical pneumonia caused by Mycoplasma pneumoniae, Chlamydia pneumoniae, and Legionella pneumophila in children who were treated at the National Hospital of Pediatrics in Hanoi, Vietnam from 07/2010 to 3/2012. 2. To identify the factors associated with the severity of atypical pneumonia in children. 6 2. New contribution to the science - This project was the first study to identify the prevalence of atypical pneumonia caused by M. pneumoniae, C. pneumoniae and L. pneumophila, co-infection rate of pneumonia in hospitalized children - The study has identified several factors associated with severity of atypical pneumonia. Co-infection with bacteria and viruses was the related factors for severe atypical pneumonia. - This study described the clinical manifestations and laboratorial characteristics of atypical pneumonia, atypical pneumonia co-infection in children. 3. Practical value of the subject - Evaluate the results of clinical manifestations and laboratory characteristics of atypical pneumonia to draw specific symptoms which suggesting early clinical diagnosis, help clinicians quickly optimal decision the choice of antibiotic therapy and have a more comprehensive view of the causes of pneumonia in children. - The study's results are significant in establishing the pattern of microorganisms which cause respiratory infections in children, and to guide treatment and prevention strategies. - Microbiological diagnostic techniques based on molecular biology (only in a few specialized laboratories) will be confirmed and efficient which can be replicated in the laboratory of clinical microbiology. 4. The structure of the dissertation The dissertation consists of 128 pages including: Background and objectives: 2 pages; Literature review: 34 pages; Methods: 18 pages; Results: 34 pages; Discussion: 37 pages; Conclusion: 2 pages, and recommendation: 1 page. There are 29 tables and 20 figures, 228 references including 22 in Vietnamese, 206 documents in foreign languages. Chapter 1. OVERVIEW 1.1. Introduction Atypical pneumonia: pneumonia caused by M. pneumoniae has been recognized from the dairy failed to sulfonamides or penicillin used to treat pneumonia, help to distinguish pneumonia pathogens M. pneumoniae pneumonia or pneumococcal (pneumococci). The failure 7 to respond to antimicrobial therapy has been thought as "atypical" (atypical). This term, along with "Walking around pneumonia" is used broadly to refer to respiratory disease caused by M. pneumoniae in humans. Then other agents cause similar clinical picture was included in the group of atypical pneumonia as C. pneumoniae, L. pneumophila 1.2. Epidemiological characteristics of atypical pneumonia caused by Mycoplasma pneumoniae, and Legionella pneumophila Chlamydia pneumoniae 1.2.1. Epidemiology characteristics of pneumonia caused by Mycoplasma pneumoniae D isease appears in all countries, however studies about the disease mostly have been carried out in the United States, Europe and Japan. In the U.S, infection caused by M. pneumoniae accounts for 15-20% of all community-acquired pneumonia. Especially in the summer time, M. Pneumonia can reach up to 50% of all community-acquired pneumonia. During 2010 to 2012, an outbreak of M. pneumoniae infection happened in some Asian countries. A multicenter study in Asia in 2005 found that M. pneumoniae was an important cause of the community acquired pneumonia, which accounted for 22.3%. Disease occurs in people of all ages, predominant in the age group from 5-9 years old. Disease can occur throughout the year, and the peak during the period from late summer to early fall. The bacteria can live everywhere in nature, transmitted from person to person via the respiratory tract. The average Incubation period is 3 weeks. After suffering from this disease, an immune survived about 4 years. Immunology temporary and recurence. 1.3.2. Epidemiology characteristics of Chlamydia pneumoniae pneumonia C. pneumoniae infection distributes over the world. A study from 10 different regions of the world showed a higher frequency in tropical populations. In the U.S. and many other countries, the sero- prevalence of C. pneumoniae infection was of 50% of total population. Estimated number of cases of pneumonia caused by C. pneumoniae in the United States is 300,000 cases per year. Globally, prevalence of pneumonia caused by C. pneumoniae from 4337 patients was 8% in 8 North America, 7% in Europe, 6% in Latin America and 5% in Asia Forest (2007). The disease affects both genders and all age groups. Disease occurs throughout the year, and gets its peak during summer time. Infectious reservoir is humans, and it is transmitted through respiratory secretions directly exposed to coughing, sneezing. After suffering from this disease, patients have an immune temporarily and recurrent frequently. Disease cycle every 4 - 8 years. 1.3.3. Epidemiological characteristics of Legionella pneumophila pneumonia Legionella disease occurs worldwide. The majority of cases disease been identified in tropical countries. In the U.S., about 8000- 18000 hospitalized cases every year. In Europe, the prevalence of Legionella infection were 5,907 cases in 2007 and 5,960 cases in. 2008. Most patients exposed to L. pneumophila but no symptoms. The risk increase in an o lder people. Children after ages 4 rare occurs pneumonia due to L. pneumophila. Legionella live everywhere, special in the aquatic environment, the disease transmitte through tiny droplets of water vapor. Disease is not transmitted from person to person. Incubation period 2 -10 days. Re- infection occurs in immunocompromised people. 1.4. The clinical features, laboratory manifestations and treatment of pneumonia caused by M. pneumoniae, C. pneumoniae and L. pneumophila. 1.4.1. The clinical features of pneumonia caused by M. pneumoniae, C. pneumoniae, L. pneumophila M. pneumoniae, C. pneumoniae is causative agents of pneumonia with the various degree of severity. Majority of patients appear with mild illness and self-recover. Few patients progress to severe condition, acute respiratory failure and death. The common pulmonary manifestations are: eardrum inflammation, rash, urticaria, pleurisy, thrombocytopenia, meningitis, and mild anemia. The extrapulmonary manifestations are rare: hemolytic anemia, coagulation disorders, thrombosis, pulmonary abscess, pneumothorax, burnout syndrome, pericarditis, myocarditis, Stevens Johnson syndrome, 9 neurological manifestations: meningitis, encephalitis, mental disorders, Guillain – Barre syndromes, cerebellar ataxia, the brainstem, like polio. L. pneumophila causes two distinct disease entities: pneumonia and Pontiac fever. Pontiac fever is usually mild, patients may have fever, muscle-aches, no pneumonia, no need treatment. Legionella disease may have clinical manifestations including abnormalities in the central nervous system (headache, mental confusion, encephalopathy, coma), cardiac abnormalities(relatively slow heart rate), gastrointestinal manifestations (target diarrhea, abdominal pain), liver damage (liver enzymes) and kidney(microscopic hematuria, increased creatinine), electrolyte abnormalities (assuming m and decreased serum sodium phosphate). Extrapulmonary manifestations of Legionella can present with the damage in spleen, liver, kidney, heart, bone and bone marrow, joints, inguinal lymph nodes, nervous and digestive tract. 1.4.2. Laboratory manifestations of pneumonia caused by M. pneumoniae, C. pneumoniae and L. pneumophila Chest X-ray (CXR): Radiographic manifestations of atypical pneumonia can be extremely variable and can mimic with a wide variety of lung diseases. The inflammatory response causes interstitial mononuclear cell inflammation that may be manifested radiographically as diffuse, reticular infiltrates of bronchopneumonia in the perihilar regions or lower lobes, usually with a unilateral distribution, and hilar adenopathy. Bilateral involvement may occur in about 20% of cases. Bacteriological tests - Blood culture: L. pneumophila can be isolated from blood culture with low sensitivity. - Gram stain: L. pneumophila start gram paler color when dyed. M. pneumoniae results because bacteria do not have cell walls so they do not color when dyed. Respiratory secretions culture: by using a special medium (PPLO broth environmental bacterium M. pneumoniae culture, environment chick embryo cells or mice, Hella 229 and cultured Hep 2 find C. pneumoniae; BCYE environment - Buffered Charcoal Yeast Extract Agar 10 detect L. pneumophila culture). L. pneumohila usually grows after 3-5 days, M. pneumoniae usually results after 7-21 days later. Serological methods: the methods are: complement fixation technique (Complement Fixation - CF), immunofluorescence technique (Immuno Fluorescence Assay - IFA), Enzyme-linked immunosorbent technique (Enzyme Immuno Assay - EIA), particle agglutination technique (partical Agglutination - PA). Antigen detection methods: The tests include direct immunofluorescence, free electrolyte cell convection, infiltration and immune enzyme immunoassay. PCR (Polymerase Chain Reaction). PCR is a continuous chain reaction, including many successive cycles, each cycle consisting of three phases: denaturation phase; annealing stage; synthesis stage. PCR primers to test multiple simultaneous detection of atypical pathogens such as C. pneumoniae, M. pneumoniae, L. pneumophila. Results showed that Multiplex - PCR assay is sensitive, useful, cheap and quick assay diagnosis for patients pneumonia. 1.4.3. Treatment of pneumonia caused by M.pneumoniae, C. pneumoniae and L. pneumophila M. pneumoniae bacterium do not has wall, C. pneumoniae, L.pneumophila are intracellular bacteria therefore all antibiotics belong to beta-lactam groups are not effective. They are sensitive to the macrolide antibiotics such as erythromycin, clarythromycin, azithromicin, tetracycline and quinolones. However, tetracycline is not indicated for children under 8 years of age and quinolone not indicated for children under 15 years of age. 1.5. Studies of atypical pneumonia, severe atypical pneumonia in children and related factors 1.5.1. Current research on atypical pneumonia in children 1.5.1.1. In the World Worldwide, coincides water poses by M. pneumoniae, C. pneumoniae encountered in the upper respiratory tract and lower respiratory tract, which occurs in both adults and children. L. 11 pneumophila causes severe disease in adults, it occurs rarely in children under 4 years of age. 1.5.1.2. In Vietnam Some research interest in disease incidence and clinical features of pneumonia caused by M. pneumonia among hospitalized children in some provinces of Vietnam only. Molecular biology techniques are deployed in some centers, large hospitals nearly. 1.5.2. Studies of severe atypical pneumonia and related factors 1.5.2.1. Etiological bacteria Pneumonia caused by L.pneumophila that disease is second, followed by pneumococcal pneumonia requiring intensive treatment. For people with normal immune systems, the mortality rate is usually in the range of 10-15%. 1.5.2.2. Coinfection status Co-infection status was considered as aggravating factors in community-acquired pneumonia in adults has been demonstrated by Gutiérrez: pleural effusion, atelectasis, septic shock, hypoxemia requiring mechanical ventilation, death in patients with pneumonia due to coinfected patients higher than agent patients (OR = 2.84, 95% CI 1.24 to 6.54, p = 0,02). 1.5.2.3. Accompanying diseases Studies in adults show that with diseases such as asthma, chronic obstructive pulmonary disease, malignancies, cardiovascular, diabetes, immunosuppression are factors that increase the severity of the disease. 1.5.2.4. Specific treatment late Specific treatment late is emphasized associated with significant mortality in adults suffer from pneumonia caused by L. pneumophila. According to Gacouin A., duration of illness before admission to the ICU for more than 5 days (OR 7:46, 95% CI 1.17 to 47.6) were risk factors for mortality of L . pneumophila pneumonia. 1.5.2.5. Extrapulmonary manifestations Atypical pneumonia with severe extrapulmonary manifestations such as neurologic manifestations, hemolytic, heart disease, 12 polyarthritis, skin lesions, electrolyte disorders, multiple organ failure related to status severe, even fatal. 1.5.2.6. The other factors Concerning the situation of severe atypical pneumonia, such as the relationship between bacterial load, drug resistance of M. pneumoniae to macrolides, leucocytosis, lung injury 2 sides, pleural effusion, increased levels of LDH, ALT, AST, and decreased blood protid; increased IL6, TNF, respiratory failure, mechanical ventilation, Lower serum sodium <136 mEq / l, Paco 2 / FiO 2 <130 ureanemia > 30 mg / dl,albuminemia decreased, multiple organ failure, requiring mechanical ventilation, complications of lung abscess, wall chemistry, effusion related lung deterioration, mortality of the disease. Chapter 2. METHODS 2.1. Study subjects - Patients with pneumonia caused by different microbial agents, aged from 12 months to 15 years old who were treated at the Respiratory Department of the National Hospital of Paediatrics from 7/2010 to 3/2012. - Patients with atypical pneumonia due to at least one of the three studied bacteria: M. pneumoniae, C. pneumoniae và L. pneumophila, aged from 12 months to 15 years old who were treated at the Respiratory Department of the National Hospital of Paediatrics from 7/2010 to 3/2012, referred to “ atypical bacterial pneumonia”. - Patients with atypical pneumonia due to at least one of the three studied bacteria: M. pneumoniae, C. pneumoniae và L. pneumophila, were diagnosed severe atypical pneumonia. 2.2. Inclusion criteria 2.2.1. Case definition - Pneumonia were diagnosed by using the WHO's criteria: cough, fever, tachypnea, infiltration on chest radiograph. 2.2.2. Atypical bacterial pneumonia case - Patients were diagnosed with pneumonia -Three bacteria M. pneumoniae, C. pneumoniae and L. pneumophila were confirmed by Multiplex PCR in bronchial secretions or nasopharyngeal or throat swab positive for the three studied bacterias, or ELISA: double the serum samples were positive for one of three studied bacterias. 13 2.2.3. Severe atypical pneumonia case. Children were diagnosed with severe atypical pneumonia entitled to classify pneumonia and WHO standards and the Association of Pediatric Infection of the America. - Patients with atypical pneumonia due to at least one of the three studied bacteria. - The severity of pneumonia was determined by the criteria for severe pneumonia of the American Association of Pediatric Infection . a. One or more major signs: required mechanical ventilation; sepsis b. Or at least two of the following signs: tachypnea, apnea, consciousness disorders; hypotension; pleural effusion, SpO 2 <90% with room air and Pao 2 / FiO 2 ratio < 250; many pulmonary infiltrates. 2.2.4. Exclusion criteria: - Typical pneumonia - Co-infection cases of pneumonia will not be considered for the clinical characteristics, laboratory manifestations. - Hospital- acquired pneumonia - Patient s ’ families without agreed to participate in the study. 2. 3. Methodology 2.3.1. Study Design: epidemiology descriptive case series and analysis study  Sample sizes for objective 1: WHO calculated by estimating the percentage - a group 2 2/1 2 ).( )1( ε α p pp Zn − = − where n is the minimum sample size, Z (1 - α / 2) is the coefficient of reliability, corresponding to 95% confidence level we have Z (1 - α / 2) = 1.96. p dependence incidence of pneumonia by M. pneumoniae, C. pneumoniae, L. pneumophila, estimated in prospective studies on the incidence of atypical pneumonia in hospital (in this study the rate of p = 18% = 0.18). q = 1-p = 1 18 = 0.82; p.ε accuracy desired sample, choose ε = 0.16. A required minimum sample size was 718 patients. We did enrolled 722 patients for this study. 14  Sample sizes for objective 2 The purpose of the study is to describe a case series and combine with the analytic study to identify factors associated with severe atypical pneumonia cases, we used all cases diagnosed with atypical pneumonia (215 patients) that occurred during the study period (7/2010 - 3/2012), among them, 97 cases were clasified as severe atypical pneumonia. 2.3.2. Sampling method:  Source of patients: Children from 12 months to 15 years, with an initial diagnosis of pneumonia, treatment in National Hospital of Pediatrics from the local different provinces.  Sampling method fore objective 1: A convenient sampling technique, as a rule, chose one patient from 2 patients ( k=3),according to data pneumonia in hospitalized patients in the preceding year divided by the total study minimum sample size was calculated) apply to case series research, prospective, longitudinal follow-up.  Sampling method fore objective 2: a convenient sampling technique, take the whole 215 atypical pneumonia patients were selected by criteria subjects for the study objective 1. From 215 cases with atypical pneumonia, we selected 97 cases with severe atypical pneuonia and 118 non- severe atypical pneumonia cases. We conducted a comparative analysis to determine the factors associated with severe atypical pneumonia among patients who were treated at the National Hospital of Pediatrics. The data collection was performed during the study, but the final analysis was carried out only at the end of the study when all clinical, liboratorial and microbiology data was collected for all patients . 2.4. Study variables 2.4.1. Study variable for objective 1  Epidermiological data collection Demographic data: name, age, sex, location, education, information family. Epidemiological factors: geography, season, habitat, level of income History: obstetrics, development, immunization, disease history  Clinical data collection: by interviewing parents and/or by physical examination. 15  Laboratory data collection The laboratory tests included blood specimens for counting leukocyte (WBC), C-reactive protein (CRP), IL6 and for the detection of IgM, IgA, IgG, IgE antibody and IgM antibody against M. pneumoniae, C. pneumoniae and L. pneumophila.Throat swabs/bronchial exudates were used for detection of M. pneumoniae, C. pneumoniae and L. pneumophila specific DNA by multiplex PCR. In addition, RT-PCR was applied to determine the presence of co – infections involving other viral respiratory pathogens such as Adenovirus, Respiratory Syncytial Virus (RSV), Rhinovirus, Influenza A & B(RNA extraction using Qiamp Viral RNA Mini kit, RT-PCR using Kit SuperSckip III One- Step Kit [Invitrogen]. 2.4.2. Study variable for objective 2 Factors associated with severe atypical pneumonia: time from onset to admission, antibiotic use before admission, signs, clinical symptoms, WBC, CPR, IL6, IgA, IgM, IgG, IGE antibody, coinfected status with severity of disease. 2.5. Data analysis Statistical analysis was performed using Stata.10, SPSS.13, Epidata 3.1. Chapter 3. RESULTS 3.1. Epidemiological characteristics of Atypical bacterial pneumonia in children. 3.1.1. General epidemiological characteristics of atypical pneumonia Table 3.1. The rate of common pneumonia Type of pneumonia The number of Rate% Typical pneumonia caused by bacteria 82 11.35 Viral pneumonia 80 11.08 Pneumonia caused by typical bacteria co- infection with virus 14 1.93 Atypical bacterial pneumonia 215 29.8 Pneumonia with unknown etiology 331 45.84 Total 722 100 Table 3.1. shows the overall incidence of atypical pneumonia was 29.8% of the total pneumonia. 16 Table 3.2. Classification of atypical pneumonia Classification of atypical pneumonia The number of Rate % Atypical pneumonia In group Atypical simple pneumonia: or M. pneumoniae, or C. pneumoniae, or L. pneumophila 144 67 Atypical pneumonia coinfection: by M. pneumoniae and C. pneumoniae or M. pneumoniae and L. pneumophila or C. pneumoniae and L. pneumophila 10 C oinfected atypical pneumonia Outside group Atypical pneumonia + typical bacterial pneumonia 38 17.67 Atypical pneumonia + viral pneumonia 19 8.84 Atypicalpneumonia + typical pneumonia + viral pneumonia 4 1.86 Total 215 100 Table 3.2 shows the co-infection rate was 33%, which co-infected with typical pneumonia and viral pneumonia accounted for 28.37%. Table 3.3. classify of pneumonia cases by agent bacterial atypical pneumonia (data not shown here): it found that M. pneumoniae was the most predominant among community acquired pneumonia in 26.3%; C. pneumoniae and L.pneumophila detected with low rate (3.7%, 1.8%). 4,63 17,67 8,84 1,86 17 54.24 7.5 2.56 22.33 4.19 35.7 37.67 35.81 0 10 20 30 40 50 60 Under 2 yrs >2-5yrs >5-10 yrs >10yrs Tỷ lệ % typical pneumonia Atypical pneumonia Chart 3.1. Age distribution of typical pneumonia and atypical pneumonia Chart 3.1 shows that the proportion of children aged greater than 5 years old with atypical pneumonia was 23.3%. But among 215 patients with atypical pneumonia The incidence of children aged higher in the group under 5 years old. The age variables were significantly difference (p < 0.001). There was no difference in gender distribution among children with atypical pneumonia (data not shown) Chart 3.3. Seasonal distribution of atypical pneumonia Atypical pneumonia occurs throughout all seasons, more frequent during spring-summer seasons than Auturm - Winter season. There was statistically significant difference with p = 0.003 (χ 2 test). Spring Summer Auturm Winter 18 Table 3.11. Factors associated with co-infection Characteristics Adjusted OR 95% CI p Age Under 2 years 1 - - - > 2 years - 5 years old 0.79 0.39 1.58 0.50 > 5 years - 10 years 0.46 0.19 1.12 0.09 > 10 years old 0.43 0.08 2.48 0.35 Gender Female 1 - - - Male 1.81 0.94 3.48 0.07 Family economic conditions Non-poor households 1 - - - Poor households 1.37 0.54 3.47 0.51 Method of birth Vaginal delivery 1 - - - Caesareans 2.12 1.05 4.30 0.037 Asthma Yes 1 - - - No 0.73 0.29 1.84 0.50 Nutritional status Normal 1 - - - Wasting 1.82 0.77 4.29 0.17 Overweight and obesit y 0.83 0.38 1.81 0.63 Test f it the Hosme r - L emeshow test pattern n = 215, p = 0.8619 Table 3:11 shows the relationship between co – infected status and each of variables, including age, gender, family economic conditions , method of birth, asthma disease, nutritional status. Except for Caesarean section, the other variables were not significantly associated with co - infection (OR = 2.12, p = 0.037). 19 3.1 Table 2. The functional symptoms of hospitalized atypical pneumonia patients (data not presented here): signs dyspnea in coinfected atypical pneumonia outside group higher statistical significance compared with atypical pneumonia in group (p <0,05). 63.64 3.25 1.3 77.05 16.39 67.21 54.1 8.2 55.84 9.49 16.23 29.22 1.64 19.67 0 20 40 60 80 100 Moisture Craccles ronchy rales intercostal tr ac tio n consolidation pleural infusion pneumothorax Pr op or t io n % Atypical pneumonia in group coinfection aty pical pneumonia outside groups Chart 3.7. Physical symptoms in the lungs of atypical pneumonia patients Examination finding moisture and crackles among coinfected atypical pneumonia outside group higher statistical significance compared than atypical pneumonia in group (p <0.05) (Figure 3.7). Increased work of breathing signs among coinfected atypical pneumonia outside group higher statistical significance compared than atypical pneumonia in group (p <0.001). 50.7 54.1 35 21.3 9.1 9.8 5.2 14.8 0 10 20 30 40 50 60 Tỷ lệ % Parchy infiltration consolidation Interstitial infiltra tion pleuro -pneumonia Atypical pneumonia in group Coinfected atypical pneumonia outside group Chart 3:10. Chest X-ray characteristics of the study subjects Lobar consolidation with coinfected atypical pneumonia outside group was significantly lower compared to the atypical pneumonia in group (p = 0,05). Pleural pneumonia among coinfected atypical pneumonia outside group as higher statistical significance than the atypical pneumonia in group (p = 0,05). 20 3.1.3. Characteristics of atypical pneumonia analyzed by bacterial pathogens Table 3:18. functional symptoms of atypical simple pneumonia Clinical Characteristics Atypical pneumonia by M. p neumoniae Atypical pneumonia by L . p neumo p hila Atypical pneumonia by C. p neumoniae n = 29 Rate % n = 7 Rate % n = 8 Rate % Fever 122 94, 57 6 85, 71 7 87, 5 Cough 129 100 7 100 8 100 Headache 37 28.68 3 42.86 2 25 Chest Pain 25 19.38 2 28.57 2 25 Wheeze 84 65.12 4 57.14 4 50 Hoarseness 42 32.56 4 57.14 3 37.5 Table 3:19. Physical symptoms of atypical simple pneumonia Clinical Characteristics Atypical pneumonia by M. pneumoniae Atypical pneumonia by L. neumophila Atypical pneumonia by C. pneumoniae n = 129 Rate % n = 7 Rate % n = 8 Rate % Crepitations 84 65.12 5 71.43 3 37.5 Crackles 9 0.69 1 14.28 0 0 Rhonchi 72 55,81 3 42.86 4 50 Intercostal muscle external traction 40 31 2 28.57 0 0 Dyspnea 61 47,29 4 57.14 2 25 No rales 45 34,88 2 28.57 4 50 Consolidation 20 15.5 0 0 2 25 Pleural Effusion 2 0.16 0 0 1 12.5 Pneumothorax 0 0 1 14.28 0 0 Table 3:18 and 3:19 shows the distinct functional – physical symptoms between L. pneumophila,C. pneumoniae and M. pneumoniae did not differ significantly (p > 0.05). [...]... findings of moisture and crackles among coinfected atypical pneumonia outside 25 26 group was more frequent compared to atypical pneumonia in group(p . enzyme-linked immunosorbent assay (ELISA), we conducted the study: " ;The study of epidemiological characteristics, clinical manifestations of atypical pneumonia caused by bacteria in children MINISTRY OF EDUCATION AND TRAINING MINISTRY OF HEALTH THE NATIONAL INSTITUTE OF HYGIENE AND EPIDEMIOLOGY PHAM THU HIEN THE STUDY OF EPIDEMIOLOGICAL CHARACTERISTICS, CLINICAL MANIFESTATIONS. populations. In the U.S. and many other countries, the sero- prevalence of C. pneumoniae infection was of 50% of total population. Estimated number of cases of pneumonia caused by C. pneumoniae in the