Mixed Viral-bacterial Infections Research Articles

Pathomorphological Features of the Lesion of the Afterbirth in Extremely Premature Newborns with Intraventricular Hemorrhages

Objective. To evaluate morphological changes of placenta in 21 dead preterm babies with extremely low body weight. Materials and Methods. We evaluated the grade of immaturity of the placenta, inflammatory changes of placenta and extraplacental membranes in premature babies who died because of intraventricular hemorrhage (IVH) 2-3 grades and without sonographic and pathomorphological signs of IVH. Results. We identified the signs of ascending amniotic infections in 13 (100%) children with IVH and only in 4 (50%) babies without IVH. We also found that placenta damages in babies with IVH were associated with bacterial and mixed viral-bacterial infections, and the viral agent was represented mainly by the herpetic group. Only viral pathogens (mainly of the herpetic group) were identified as etiological factors of ascending infection in children without IVH. The role of compensatory changes of the placenta observed in children without signs of IVH in prolongation of pregnancy was noted. Conclusions. The presence of viral-bacterial lesions of placenta has a more pronounced impact on premature delivery, which increases the risk of complications in premature newborns in the form of damage to the central nervous system – intraventricular hemorrhages.

Mixed bacterial-viral lung infections in patients with cystic fibrosis

The main cause of death in patients with cystic fibrosis (CF) is infectious process in the lungs, in particular, chronic lung infections caused by various pathogens, most often a combination of bacteria, fungi, or viruses. Data on mixed bacterial and viral-bacterial infections from domestic and foreign sources are fragmentary and sparse. The dominant associations of bacterial and viral pathogens in patients with cystic fibrosis have not been studied properly, and data on their epidemiological significance are lacking. The aim of this study was to assess the prevalence of bacterial and viral infections in patients with cystic fibrosis and to substantiate the need for the development of virological monitoring. Methods. Biomaterials from the respiratory tract of CF patients (409 children and 160 adults with CF) examined from 2006 to 2022 were used. The study was carried out using bacteriological methods, molecular genetic methods (RT-PCR) and MALDI-TOF mass-spectrometry. Results. Microflora of the respiratory tract was shown to be mixed in 2/3 patients with CF. The microflora of the lungs of children with CF is a dynamic community of microorganisms with high diversity and variability. In adult patients, associations of microorganisms are more common than in children, but the composition of associations is less diverse. We isolated about 40 species of bacteria from adult patients and more than 85 species from children in our sample. NFMO prevailed, including Burkholderia cepacia complex, Pseudomonas aeruginosa, Achromobacter xylosoxidans, Achromobacter ruhlandii, Stenotrophomonas maltophilia, and Staphylococcus aureus, Candida albicans, Aspergillus spp. Real-time PCR showed the presence of rhinovirus RNA in 10% of samples obtained from children and 12.9% from adults with cystic fibrosis. Conclusion. Our results indicate the need for continuous monitoring of the lung microflora in patients with CF, including testing for viruses.

Mixed Viral-Bacterial Infections and Their Effects on Gut Microbiota and Clinical Illnesses in Children

Acute gastroenteritis remains a major cause of morbidity and mortality among young children worldwide. It accounts for approximately 1.34 million deaths annually in children younger than five years. Infection can be caused by viral, bacterial and/or parasitic microorganisms. Dysbiosis due to such infections could dramatically affect disease prognosis as well as development of chronic illness. The aim of this study was to analyze gut microbiome and clinical outcomes in young children suffering from viral or mixed viral-bacterial infection. We evaluated gut microbiota composition in children suffering from viral or mixed viral-bacterial infection with two major viruses rotavirus (RV) and norovirus (NoV) and two pathogenic bacteria [Enteroaggregative E. coli (EAEC), and Enteropathogenic E. coli (EPEC)]. We sequenced 16S ribosomal RNA (V4 region) genes using Illumina MiSeq in 70 hospitalized children suffering from gastroenteric infections plus nine healthy controls. The study summarized Operational Taxonomic Unit (OTU) abundances with the Bray-Curtis index and performed a non-metric multidimensional scaling analysis to visualize microbiome similarities. We used a permutational multivariate analyses of variance to test the significance of group differences. We also analyzed the correlation between microbiome changes and clinical outcomes. Our data demonstrated a significant increase in the severity score in children with viral-bacterial mixed infections compared to those with virus infections alone. Statistical analysis by overall relative abundance denoted lesser proportions of Bacteroides in the infected children, whereas Bifidobacteriaceae richness was more prominent in the bacterial-viral mixed infections. Pairwise differences of gut microbiota were significantly higher in RV + EAEC (P = 0.009) and NoV + EAEC (P = 0.009) co-infections, compared to EPEC mixed infection with both, RV (P = 0.045) and NoV (P = 0.188). Shannon diversity index showed considerable more variation in microbiome diversity in children infected with RV cohort compared to NoV cohort. Our results highlight that richness of Bifidobacteriaceae, which acts as probiotics, increased with the severity of the viral-bacterial mixed infections. As expected, significant reduction of relative numbers of Bacteroides was characterized in both RV and NoV infections, with more reduction observed in co-infection pathogenic E. coli. Although mixed infection with EAEC resulted in significant microbiota differences compared to viral infection only or mixed infection with EPEC, the clinical condition of the children were worsened with both pathogenic E.coli co-infections. Further, in comparison with RV cohort, augmented number of differential abundant pathogenic OTUs were peculiarly noticed only with NoV mixed infection.

Herpesviral infection as an etiological factor of acute idiopathic optic neuritis

To assess the etiological significance of herpesviral infection (HVI) in patients with acute idiopathic optic neuritis (ON) using clinical and laboratory monitoring. Clinical and laboratory examinations were conducted for 10 years and were based on the results of etiological monitoring of 79 patients (85 eyes) with acute idiopathic ON in the period of 2005-2015. During a complex examination of 79 patients with acute idiopathic ON, various infectious pathogens were diagnosed in 75 people (94.9±2.1%). HVI was clearly dominant (69 patients - 87.3±2.4%). These patients were divided into 3 etiological groups. The first group - 34 people with herpesviral monoinfection; the second group - 15 people with mixed viral-viral infections; the third group - 20 people with mixed viral-bacterial infections. In the general population of patients with acute idiopathic ON associated with HVI, herpes simplex virus-1 is the most frequent (by more than 2.5 times), the infections of Epstein-Barr virus and cytomegalovirus were detected less often (p<0.05). Active current HVI in the general group of patients was diagnosed in 58 patients (84%). At the same time, reactivation of chronic infection (79.7%) was noted to be prevalent, while primary acute HVI was diagnosed rarely (4.3%). The remaining 11 patients (16%) had chronic persistent HVI. Clinical and laboratory monitoring of HVI in patients with acute idiopathic ON has shown the etiological role of herpesviruses in its development. Based on a complex of serological markers in enzyme-linked immunoassay reactions of blood serum, it was found that in patients with acute idiopathic ON the frequency of herpesviral infection is 87.3±2.4%. The proportion of active (etiologically significant) herpesviral infection is 84% of the total group. The results of the clinical and laboratory studies are of great practical importance for verification of the etiologic diagnosis and selection of adequate etiopathogenetic therapy in patients with acute idiopathic ON associated with HVI.

Impact of microbial Aetiology on mortality in severe community-acquired pneumonia

BackgroundThe impact of different classes of microbial pathogens on mortality in severe community-acquired pneumonia is not well elucidated. Previous studies have shown significant variation in the incidence of viral, bacterial and mixed infections, with conflicting risk associations for mortality. We aimed to determine the risk association of microbial aetiologies with hospital mortality in severe CAP, utilising a diagnostic strategy incorporating molecular testing. Our primary hypothesis was that respiratory viruses were important causative pathogens in severe CAP and was associated with increased mortality when present with bacterial pathogens in mixed viral-bacterial co-infections.MethodsA retrospective cohort study from January 2014 to July 2015 was conducted in a tertiary hospital medical intensive care unit in eastern Singapore, which has a tropical climate. All patients diagnosed with severe community-acquired pneumonia were included.ResultsA total of 117 patients were in the study. Microbial pathogens were identified in 84 (71.8%) patients. Mixed viral-bacterial co-infections occurred in 18 (15.4%) of patients. Isolated viral infections were present in 32 patients (27.4%); isolated bacterial infections were detected in 34 patients (29.1%). Hospital mortality occurred in 16 (13.7%) patients. The most common bacteria isolated was Streptococcus pneumoniae and the most common virus isolated was Influenza A. Univariate and multivariate logistic regression showed that serum procalcitonin, APACHE II severity score and mixed viral-bacterial infection were associated with increased risk of hospital mortality. Mixed viral-bacterial co-infections were associated with an adjusted odds ratio of 13.99 (95% CI 1.30–151.05, p = 0.03) for hospital mortality.ConclusionsRespiratory viruses are common organisms isolated in severe community-acquired pneumonia. Mixed viral-bacterial infections may be associated with an increased risk of mortality.

THE ROLE OF MORPHOLOGICAL STUDIES OF PLACENTA IN DIAGNOSIS OF INTRAUTERINE INFECTIONSOF NEWBORNS

Introduction. Infectious disorders of the afterbirth (or placenta) are now of frequent occurrence, and have specific morphologic manifestations, which significantly affects the course of pregnancy, childbirth, intrauterine growth and development and postnatal health of the infant.The purpose of the study was to optimize the diagnosis and prognosis of the severity of intrauterine infection in neonates based on an assessment of risk factors, perinatal history and the results of morphological studies of afterbirth of those mothers, who had children with intrauterine infection.Materials and methods. Clinical and laboratory examination of 834 mothers and their diseased newborns suspected to have intrauterine infection the first 3 days of life was performed. The subject of in-depth study was a group of 224 patients with newborns with congenital infections. The control group consisted of 30 apparently healthy newborns. Confirmation of intrauterine infection was conducted based on history, physical exam data, and standard tests and using morphological studies of the born placenta.Results of the study. Among the total number of examined newborns, intrauterine infection was verified in 708 (84.9%) patients. The subject of the in-depth study was a group of 224 (31.6%) diseased newborns with congenital viral infections. Among them were term infants - 132 (58.9%) and premature babies - 92 (41.1%). Among 224 children, 77 (34.4%) mixed viral infections, 62 (27.7%) viral and bacterial infections, 53 (23.6%) mixed viral TORCH infections with monoviral infections - in 32 (14.3%). Among the risk factors, acute respiratory viral infections predominate in pregnant women (45.5%), threatening miscarriage (43.7%), anemia of pregnancy (25.0%), preterm delivery (41.1%), placental dysfunction 23.2%), preeclampsia (17.4%), asphyxia of newborns (40.6%). Analyzing the results of a histological study of 224 placentas in women who gave birth to children with congenital viral infections we revealed that in addition to specific morphologic changes caused by respiratory viruses, 54 (24%) also manifested non-specific inflammation(deciduitis, villusitis) and diverse variants of altered placental circulation. It confirms that in addition to the direct harmful effect of the virus, the secondary hypoxia and fetal supply disturbance can occur. The absence of specific signs and symptoms of viral infections in pregnant women does not exclude the need to investigate the afterbirth of children at risk to have intrauterine infection.Conclusions. The results of the histological examination of the placentas substantiate both the etiology of congenital viral infections based on specific morphological features, as well as the effect of nonspecific inflammatory changes (basal deciduitis, vylusitis) and variations of transplacental circulation disturbances on prediction the severity of congenital viral infections in newborns.

Bacterial Complications of Respiratory Tract Viral Illness: A Comprehensive Evaluation

Background. Respiratory tract infection is one of the most common reasons for hospitalization among adults, and recent evidence suggests that many of these illnesses are associated with viruses. Although bacterial infection is known to complicate viral infections, the frequency and impact of mixed viral-bacterial infections has not been well studied. Methods. Adults hospitalized with respiratory illness during 3 winters underwent comprehensive viral and bacterial testing. This assessment was augmented by measuring the serum level of procalcitonin (PCT) as a marker of bacterial infection. Mixed viral-bacterial infection was defined as a positive viral test result plus a positive bacterial assay result or a serum PCT level of ≥ 0.25 ng/mL on admission or day 2 of hospitalization. Results. Of 842 hospitalizations (771 patients) evaluated, 348 (41%) had evidence of viral infection. A total of 212 hospitalizations (61%) involved patients with viral infection alone. Of the remaining 136 hospitalizations (39%) involving viral infection, results of bacterial tests were positive in 64 (18%), and PCT analysis identified bacterial infection in an additional 72 (21%). Subjects hospitalized with mixed viral-bacterial infections were older and more commonly received a diagnosis of pneumonia. Over 90% of hospitalizations in both groups involved subjects who received antibiotics. Notably, 4 of 10 deaths among subjects hospitalized with viral infection alone were secondary to complications of Clostridium difficile colitis. Conclusions. Bacterial coinfection is associated with approximately 40% of viral respiratory tract infections requiring hospitalization. Patients with positive results of viral tests should be carefully evaluated for concomitant bacterial infection. Early empirical antibiotic therapy for patients with an unstable condition is appropriate but is not without risk.

Etiology of Community-acquired Pneumonia in Hospitalized Children in Northern Taiwan

Pneumonia is the leading reason for hospitalization in children. The heptavalent pneumococcal conjugate vaccine was introduced in Taiwan in October 2005. There has been no comprehensive study of the etiology of childhood community-acquired pneumonia (CAP), either in the pre- or postpneumococcal conjugate vaccine era, in Taiwan. From August 2001 to July 2002, consecutive children admitted to a teaching hospital with radiologically confirmed CAP were prospectively enrolled. The following were considered indicative of infection when positive: blood or pleural effusion bacterial culture or urinary Streptococcus pneumoniae antigen test (Binax NOW), direct immunofluorescent antigen test for Chlamydia species and viruses, virus isolation and identification and viral, mycoplasmal or chlamydial serologic tests. A total of 209 children were included, and 102 children (48.8%) were male. Patients' ages ranged from 7 months to 16 years with a median of 4 years and 3 months. The combined tests identified at least 1 etiologic agent in 85.6% of all cases, including typical bacterial pathogens in 88 cases (42.1%; 86 S. pneumoniae, 1 methicillin-resistant Staphylococcus aureus and 1 Mycobacterium tuberculosis), Mycoplasma pneumoniae in 77 cases (36.8%), Chlamydia species in 24 cases (11.5%), viral etiology in 86 cases (41.1%) and mixed viral-bacterial infections in 69 cases (33%). Children with S. pneumoniae infection were significantly younger than those with Mycoplasma pneumoniae infection (P = 0.0055) or unknown etiology (P = 0.0140). S. pneumoniae, Mycoplasma pneumoniae and viruses were equally common etiologic agents of childhood CAP in Taiwan. Frequent coinfection increased the difficulty of both predicting the responsible organisms and choosing empiric antibiotics for the management of pediatric CAP.

Frequency and Clinical Outcome of Respiratory Viral Infections and Mixed Viral-bacterial Infections in Children With Cancer, Fever and Neutropenia

The role of respiratory viral infections (RVIs) as a cause of overall fever and neutropenia (FN) episodes in children with cancer has been less characterized than bacterial infections. We conducted a study aimed to determine the frequency of RVI in children with low compared with high risk for invasive bacterial infection (IBI) FN episodes and compare the clinical outcome of RVI and mixed RV-bacterial infections. Prospective, multicenter study in children with cancer and FN admitted to pediatric hospitals in Chile between May 2009 and January 2011. Children were evaluated by clinical examination and laboratory tests, including bacterial cultures and their risk for IBI. Nasopharyngeal sample was obtained for the detection of 17 respiratory viruses using polymerase chain reaction-DNA microarray platform. A total of 331 episodes of FN in 193 children were enrolled of whom 55% were male, with the median age of 7 years and 61% had a hematological malignancy. A viral and/or bacterial pathogen was detected in 67% (224/331) episodes. Overall, RVIs were associated with 57% of FN of which one-third were mixed RV-bacterial infections. Bacterial infection was detected in 29% (97/331). Children classified at admission as high risk for IBI had a similar overall proportion of RVI compared with low-risk group. Respiratory syncytial virus (31%) and rhinovirus (23%) were the most frequently detected respiratory viruses, followed by parainfluenza (12%) and influenza A (11%). Children detected with any respiratory virus had fewer days of hospitalization and a significantly lower probability of hypotension and admission to pediatric intensive care unit irrespective of their risk classification status at admission when compared with children with mixed RV-bacterial or bacterial infections (P < 0.05). All children with a sole RVI had favorable outcome. RVIs were the most frequently detected agents irrespective of their initial risk assessment for IBI. The clinical outcome of mixed RVI was similar to sole RVI episodes as well as for bacterial infections compared with mixed viral-bacterial infections. Systematic and early detection of RVI in children with cancer and FN might help to optimize their management by reducing hospitalization and antimicrobial use.

Picornaviruses in cerebrospinal fluid of children with meningitis in Luanda, Angola

Human enteroviruses are the most common cause of viral meningitis. Viral-bacterial interaction may affect the clinical course and outcome of bacterial meningitis. In Africa, viruses might be responsible for 14-25% of all meningitis cases. However, only few studies from Africa have reported detection of viruses in the cerebrospinal fluid (CSF) or mixed viral-bacterial infections of the central nervous system (CNS). The aim of the present study was to investigate the presence of picornaviruses in the CSF of children suffering from meningitis in Luanda, Angola. The study included 142 consecutive children enrolled in a prospective study of bacterial meningitis in Luanda between 2005 and 2006, from whom a CSF sample was available. CSF samples were obtained at hospital admission, stored in a deep-freeze, and transported to Finland for testing by real-time PCR for picornaviruses. Enteroviruses were detected in 4 (3%) of 142 children with presumed bacterial meningitis. A 5-month-old girl with rhinovirus and Haemophilus influenzae meningitis recovered uneventfully. An 8-year-old girl with human enterovirus and pneumococcal meningitis developed no sequelae. A 2-month-old girl with human enterovirus and malaria recovered quickly. A 7-month-old girl with human enterovirus was treated for presumed tuberculous meningitis and survived with severe sequelae. Mixed infections of the CNS with picornaviruses and bacteria are rare. Detection of an enterovirus does not affect the clinical picture and outcome of bacterial meningitis.

Viruses and bacteria in sputum samples of children with community-acquired pneumonia

Few comprehensive studies have searched for viruses and bacteria in children with community-acquired pneumonia (CAP). We identified 76 children hospitalized for pneumonia. Induced sputum samples were analysed for 18 viruses by antigen detection and PCR, and for six bacteria by culture and PCR. Viruses were found in 72% of samples, bacteria in 91%, and both in 66%. Rhinovirus (30%), human bocavirus (18%) and human metapneumovirus (14%) were the most commonly detected viruses. Two viruses were found in 22% of samples and three in 8%. The most common bacteria found were Streptococcus pneumoniae (50%), Haemophilus influenzae (38%), and Moraxella catarrhalis (28%). Rhinovirus–S. pneumoniae was the most commonly found combination of virus and bacterium (16%). All six children with treatment failure had both viruses and bacteria detected in the sputum. Otherwise, we found no special clinical characteristics in those with mixed viral–bacterial detections. With modern molecular diagnostic techniques, there are high rates of both viral and bacterial identification in childhood CAP. The clinical significance of mixed viral–bacterial infections remains unclear, although we found a potential association between them and treatment failure.

Aetiology of community-acquired pneumonia: Serological results of a paediatric survey

Serological methods are routinely used in the diagnosis of viral and atypical bacterial respiratory infections. Recently, they have also been applied to typical bacteria, such as Streptococcus pneumoniae. The aim of this study was to determine the aetiology of paediatric community-acquired pneumonia (CAP) in both ambulatory and hospitalized patients, by using antibody assays. During a 15-month prospective surveillance, paired sera were studied for antibodies to 14 microbes in 101 children with symptoms of acute infection and infiltrates compatible with pneumonia on chest radiographs. A potential causative agent was detected in 66 (65%) patients. Evidence of bacterial, viral and mixed viral-bacterial infection was demonstrated in 44%, 42% and 20% of the CAP cases, respectively. The most commonly found agents included Mycoplasma pneumoniae (27%), Pneumococcus (18%) and respiratory syncytial virus (17%). Human metapneumovirus (hMPV) was detected in 5 (5%) children. Pneumococcal infections were evenly distributed among the age groups studied. Our results confirm the role of S. pneumoniae in paediatric CAP at all ages, those of M. pneumoniae at >2 y of age and emphasize the emerging role of hMPV. The high proportion of mixed viral-bacterial infections highlights the need to treat all children with CAP with antibiotics.

Etiology of community-acquired pneumonia in hospitalized school-age children: evidence for high prevalence of viral infections.

Background. Community-acquired pneumonia (CAP) in young children is most commonly associated with viral infections; however, the role of viruses in CAP of school-age children is still inconclusive. Methods. Seventy-five school-age children hospitalized with CAP were prospectively evaluated for the presence of viral and bacterial pathogens. Nasopharyngeal washes were examined by polymerase chain reaction for viruses and atypical bacteria. Antibody assays to detect bacterial pathogens in acute-phase and convalescent-phase serum samples were also performed. Results. A viral infection was identified in 65% of cases. Rhinovirus RNA was detected in 45% of patients; infection with another virus occurred in 31%. The most common bacterial pathogen was Mycoplasma pneumoniae, which was diagnosed in 35% of cases. Chlamydia pneumoniae DNA was not detected in any patient; results of serological tests were positive in only 2 patients (3%). Mixed infections were documented in 35% of patients, and the majority were a viral-bacterial combination. Conclusions. The high prevalence of viral and mixed viral-bacterial infections supports the notion that the presence of a virus, acting either as a direct or an indirect pathogen, may be the rule rather than the exception in the development of CAP in school-age children requiring hospitalization.

Clinical response to antibiotic therapy for community-acquired pneumonia.

Childhood community-acquired pneumonia is a common and potentially serious problem worldwide. Unless the patient has bacteraemia or pleural empyema, aetiological diagnostics are limited and antibiotic treatment is empirical. Published data on expected response to therapy are scarce. To determine the clinical response to antibiotic treatment in a developed country in otherwise healthy children with community-acquired pneumonia, we conducted a prospective study of 153 hospitalised children with pneumonia. The role of 17 microbes as potential causative agents was evaluated. The duration of fever (>37.5°C) and hospitalisation were studied as objective measures of recovery. A potential aetiology was found in 83% of 153 patients: 29% of the patients had sole viral and 26% sole bacterial and 29% mixed viral-bacterial infections. The median duration of fever after the onset of antibiotic treatment (mainly penicillin G) was 14 h and the median duration of hospitalisation was 48 h. Patients with mixed viral-bacterial infection became afebrile more slowly than those with either sole viral or sole bacterial infections. Conclusion: the findings indicate that in a developed country, children with pneumonia make a rapid, uneventful recovery needing only a short hospital stay. Expensive and time-consuming microbiological investigations are not required once bacterial sepsis has been excluded.

Community-acquired pneumonia in children: issues in optimizing antibacterial treatment.

The treatment of community-acquired pneumonia (CAP) in children is empirical, being based on the knowledge of the etiology of CAP at different ages. As a result of currently available methods in everyday clinical practice, a microbe-specific diagnosis is not realistic in the majority of patients. Even the differentiation between viral, 'atypical' bacterial (Mycoplasma pneumoniae or Chlamydia pneumoniae) and 'typical' bacterial (Streptococcus pneumoniae) CAP is often not possible. Moreover, up to one-third of CAP cases seem to be mixed viral-bacterial or dual bacterial infections. Recent serologic studies have confirmed that S. pneumoniae is an important causative agent of CAP at all ages. M. pneumoniae is common from the age of 5 years onwards, and C. pneumoniae is common from the age of 10 years onwards. In addition to age, the etiology and treatment of CAP are dependent on the severity of the disease. Pneumococcal infections are predominant in children treated in hospital, and mycoplasmal infections are predominant in children treated at home.In ambulatory patients with CAP, amoxicillin (or penicillin V [phenoxymethylpenicillin]) is the drug of choice from the age of 4 months to 4 years, and at all ages if S. pneumoniae is the presumptive causative organism. Macrolides, preferably clarithromycin or azithromycin, are the first-line drugs from the age of 5 years onwards. In hospitalized patients who need parenteral therapy for CAP, cefuroxime (or penicillin G [benzylpenicillin]) is the drug of choice. Macrolides should be administered concomitantly if M. pneumoniae or C. pneumoniae infection is suspected. Radiologic findings and C-reactive protein (CRP) levels offer limited help for the selection of antibacterials; alveolar infiltrations and high CRP levels indicate pneumococcal pneumonia, but the lack of these findings does not rule out bacterial CAP. Most guidelines recommend antibacterials for 7-10 days (except azithromycin, which has a recommended treatment duration of 5 days). If no improvement takes place within 2 days, therapy must be reviewed.

Mixed microbial aetiology of community-acquired pneumonia in children.

Seven paediatric studies on community-acquired pneumonia with serological methods for both viruses and bacteria have been published, allowing the evaluation of concomitant multiple etiological findings. In these studies, dual viral infection has been present in 0-14%, dual bacterial infection likewise in 0-14%, and mixed viral-bacterial infection in 3-30% of the pneumonia cases. The results confirm former clinical observations that respiratory viruses often pave the way for airway-colonising bacteria. The measured frequency of multiple infections has been dependent on the available test panel, mainly on the tests used for pneumococcal aetiology. Mixed viral-bacterial infections have been especially common in young children under 2 years of age, reflecting the high frequency of respiratory syncytial virus infections and their tendency to induce bacterial co-infections. No microbe-specific viral-bacterial associations have been demonstrated. The clinical implications of mixed viral-bacterial infections, compared with viral infections alone or bacterial infections alone, have so far remained unresolved. Current guidelines recommend antibiotic therapy for all community-acquired pneumonia cases in children.

Mixed viral-bacterial pulmonary infections in children.

Mixed viral-bacterial pulmonary infections in children.

Comparison of radiological findings and microbial aetiology of childhood pneumonia

Sixty-one children were treated in hospital from 1981 to 1982 because of both radiologically and microbiologically verified viral or bacterial pneumonia. The chest radiographs were interpreted by two radiologists, not familiar with the clinical data, on two occasions three years apart, and only those patients with a definite alveolar (n = 27) or interstitial (n = 34) pneumonia at both evaluations were included in the present analysis. In addition, all patients had viral (n = 20), mixed viral-bacterial (n = 21) or bacterial (n = 20) infections diagnosed by viral or bacterial antibody or antigen assays. Viral infection alone was seen in 7 (26%), mixed viral-bacterial infection in 8 (30%) and bacterial infection alone in 12 (44%) of the 27 patients with alveolar pneumonia. The respective figures were 13 (38%), 13 (38%) and 8 (24%) for the 34 patients with interstitial pneumonia. C-reactive protein concentration was greater than 40 mg/l (a screening limit for viral and bacterial infections) in 15 (56%) of the patients with alveolar and in 11 (32%) of the patients with interstitial pneumonia. Thus 74% of the patients with alveolar and 62% with interstitial pneumonia had bacterial infection, either alone or as a mixed viral-bacterial infection. Our results suggest that the presence of an alveolar infiltrate in a chest radiograph is a specific but insensitive indicator of bacterial pneumonia. We conclude that patients with alveolar pneumonia should be treated with antibiotics. In patients with interstitial pneumonia, however, both viral and bacterial aetiology are possible. In those, the decision concerning antibiotic treatment should be based on clinical and laboratory findings.

Aetiology of community-acquired pneumonia in children treated in hospital

Viral and bacterial antigen and antibody assays were prospectively applied to study the microbial actiology of community-acquired pneumonia in 195 hospitalised children during a surveillance period of 12 months. A viral infection alone was indicated in 37 (19%), a bacterial infection alone in 30 (15%) and a mixed viral-bacterial infection in 32 (16%) patients. Thus, 46% of the 69 patients with viral infection and 52% of the 62 patients with bacterial infection had a mixed viral and bacterial aetiology. Respiratory syncytial virus (RSV) was identified in 52 patients andStreptococcus pneumoniae in 41 patients. The next common agents in order were non-classifiedHaemophilus influenzae (17 cases), adenoviruses (10 cases) andChlamydia species (8 cases). The diagnosis of an RSV infection was based on detecting viral antigen in nasopharyngeal secretions in 79% of the cases. Pneumococcal infections were in most cases identified by antibody assays; in 39% they were indicated by demonstrating pneumococcal antigen in acute phase serum. An alveolar infiltrate was present in 53 (27%) and an interstitial infiltrate in 108 (55%) of the 195 patients. The remaining 34 patients had probable pneumonia. C-reactive protein (CRP), erythrocyte sedimentation rate and total white blood cell count were elevated in 25%, 40% and 36% of the patients, respectively, CRP was more often elevated in patients with bacterial infection alone than in those with viral or mixed viral-bacterial infections. No other correlation was seen between the radiological or laboratory findings and serologically identified viral, bacterial or mixed viralbacterial infections. By using a comprehensive serological panel, the causative agent could be found in over 50% of patients with pneumonia. We conclude that RSV and pneumococcus are the two most common organisms causing pneumonia in children. Our results suggest that mixed viral-bacterial aetiology is common in lower respiratory tract infections affecting children.

Etiology of acute lower respiratory tract infections in Gambian children

Ninety infants less than 1 year of age with pneumonia and 43 control infants were investigated for viral and chlamydial infection with the use of culture and serology and for bacterial infection with the use of blood cultures, lung aspirates, antibody assays and antigen detection procedures. One or more potential pathogens were identified in 62 (69%) cases with pneumonia and in 12 (28%) controls. Infection by respiratory viruses was identified in 42 (49%) cases and in 8 (19%) controls. Respiratory syncytial virus was the commonest pathogen identified and was found in 32 cases (37%). Bacterial infections were also common, being found in 27 (30%) cases and 3 (7%) controls, and predominantly involved Streptococcus pneumoniae (20%) or Haemophilus influenzae (11%). Bacterial infections were associated with raised white blood cell counts and were identified more often by antigen detection procedures (68%) than by culture of blood or lung aspirates (34%) or by serology (33%). Mixed viral-bacterial infections were identified in 13 cases (15%). Infection with Chlamydia trachomatis was diagnosed in 2 infants with acute lower respiratory tract infection and in 1 control infant.