Viral and Mycoplasma-induced glomerulopathies in children

Morphological examinations of kidneys from 227 children who had suffered from various generalized acute viral respiratory infections and mycoplasmosis established in 79 cases pathology of renalglomeruli, namely viral and mycoplasmic glomerulopathies. In 52 cases they corresponded to various forms of glomerulonephritis. The detection of deposites of immunoglobulins, virus and mycoplasma antigens suggest the association of these changes with the above-mentioned infections. Besides, 27 children showed peculiar lesions of the renal glomeruli, associated with the cytopathic effect of respiratory viruses and mycoplasma.     

血清降钙素原、超敏C反应蛋白及白细胞介素-6在小儿急性上呼吸道感染中的诊断价值

目的:分析降钙素原(PCT)、超敏C反应蛋白(hs-CRP)和白细胞介素-6(IL-6)在小儿急性上呼吸道感染(AURI)时血清水平变化及其临床诊断价值。方法:分别收集100例AURI患儿,分为细菌感染组和病毒感染组(各50例),采用ELISA和免疫比浊法测定其血清PCT、hs-CRP、IL-6等指标,分析两病例组间及与健康体检儿童组间差异,并绘制细菌感染组上述检测指标的ROC曲线,比较其临床诊断价值。结果:细菌感染组血清PCT、hs-CRP与IL-6水平明显高于病毒感染组及健康对照组,差异有统计学意义(P0.05);病毒感染组PCT、hs-CRP和IL-6水平与健康对照组之间差异无统计学意义(P0.05)。对诊断细菌性AURI,血清PCT的ROC曲线下面积最大;灵敏度、特异度、阳性似然比明显高于hs-CRP和IL-6,阴性似然比显著低于IL-6,差异均有统计学意义(P0.05)。结论:血清PCT与hs-CRP、IL-6比较,其对小儿细菌性AURI具有更高的诊断价值及早期诊断意义。     

Invasive meningococcal disease presenting as Henoch-Schönlein purpura

Henoch-Schönlein purpura (HSP) is an acute systemic form of vasculitis that has been associated with a number of viral and bacterial infections. Described here are the cases of two children with invasive meningococcal disease who presented with clinical and laboratory findings typical of HSP. Meningococcal infection may have been the trigger for the manifestation of HSP in these patients.     

Chronic isolated brain lesions caused by respiratory viruses in children

Combined study of 48 postmortem observations of cerebral lesions caused mainly by meningococcal infection in children was carried out. In 15 cases, isolated subclinical involvement of the brain (more frequently, of the vascular plexus and meninges) caused by influenza A viruses (8 cases), B (2 cases), adenoviruses (6), parainfluenza and respiratory syncytial virus (1 each), and chlamydia (2) was found. This was proved by the presence of the appropriate antigens in the brain revealed by immunofluorescence which were absent in respiratory organs, high titres of antibody to the same agents in the cerebrospinal fluid which were lacking in 13 cases or had significantly low titres in 2 cases in the blood, virus isolation from the brain (2 cases) and detection of virus particles in 1 out of 2 cases from which the vascular plexus was examined by electron microscopy. Histological examination of the affected areas revealed structural changes of ependymocytes which were principally similar to those described in respiratory organs as well as in other organs in cases of generalization of respiratory infections. Different degrees of sclerosis of vascular plexus (2 cases) or meninges (2 cases) were also observed.     

Intestinal lesions in acute respiratory viral and mycoplasma infections

Histologic study using semiquantitative analysis and immunofluorescent microscopy of the intestine performed on 278 children of different age who died of acute respiratory, viral and Mycoplasma infections revealed intestinal changes in 168 cases. The incidence and degree of these changes depended on the duration of the disease and the type of the intensive therapy used. Beginning from day 2 of the disease specific changes in the enterocytes in the form of giant-cell metamorphosis were noted. These changes gradually increased reaching their maximum on day 7-9 when in all cases of acute viral respiratory infections microlysis of enterocytes was observed. It was maximal on day 5-6 and inhibited under the influence of intensive therapy. In addition some nonspecific changes were present: circulatory disorders and cellular reaction of the stroma, that changed depending on the duration of the disease being probably a manifestation of a local immune reaction.     

A longitudinal study of respiratory viruses and bacteria in the etiology of acute otitis media with effusion

We analyzed data from a 14-year longitudinal study of respiratory infections in young children to determine the relative importance of viral respiratory infection and nasopharyngeal colonization with Streptococcus pneumoniae and Haemophilus influenzae as factors influencing the occurrence of acute otitis media with effusion. The incidence of this disorder was increased in children with viral respiratory infections (average relative risk, 3.2; P less than 0.0001). Infection with respiratory syncytial virus, influenza virus (type A or B), and adenovirus conferred a greater risk of otitis media than did infection with parainfluenza virus, enterovirus, or rhinovirus. Colonization of the nasopharynx with Str. pneumoniae or H. influenzae had a lesser effect on the incidence of the disease (average relative risk; 1.5; P less than 0.01). Infections with the viruses more closely associated with acute otitis media (respiratory syncytial virus, adenovirus, and influenza A or B) were correlated with an increased risk of recurrent disease. Prevention of selected otitis-associated viral infections should reduce the incidence of this disease.     

The role of infection in the morbidity of asthmatic children admitted to hospital

Two aspects of the role of infection in asthmatic attacks in children have been investigated. Virus isolations from children admitted to a paediatric department during 1968 showed close correlation with the incidence of admissions with upper respiratory tract infection and with lower respiratory tract infection. The peaks of virus isolation corresponded to the peaks of respiratory infection admissions. There was a clear dissociation between virus isolations and admissions with acute asthma. Fifty-one children admitted with clinical acute attacks of asthma were investigated more thoroughly. Only three viruses were isolated from these case? compared to eleven viruses isolated from a control group of children with respiratory infections. The incidence of bacterial pathogens was similar in both groups. Serological evidence of virus infection was obtained in two out of twenty-six children with asthma and in four out often children with respiratory infections. Our results indicate that bacterial or viral infections are not responsible for the autumn peak of asthma admissions.     

Changes in the adrenals in the sudden death syndrome in infants

Adrenal glands of 52 children dying from a syndrome of sudden death (SSD) and 14 children of the same age dying from acute viral respiratory infections (AVRI) with a long terminal period were studied. The following adrenal changes typical for the SSD were observed: low weight, decrease of the size of the definitive cortex and its zones, the appearance of numerous adenomatous growths in the definitive cortex and so-called giant cells in the fetal cortex, low secretory activity. The appearance of adenomas and giant cells in the presence of organ hypoplasia is a compensatory-hyperplastic adrenal response which attests to a long glucocorticoid deficiency in the SSD. It is suggested that the deficiency of these hormones leads to the metabolic disturbances in various organs, including brain, resulting in the narrowing of the range of homeostatic host responses; this may become the cause of sudden death when the clinical and morphological manifestations of AVRI are insignificant.     

Treatment and prevention of acute viral respiratory infections in children with leukocytic interferon

Children with viral respiratory infections and healthy contacts received treatment and prophylaxis with leukocytic interferon. The results emphasize the effectiveness of treatment when interferon is given on the first or second day of the disease. In these cases the course is mild, of short duration, and without complications. Conversely, the clinical course in children who did not receive interferon was more severe; the disease lasted longer, and complications were not uncommon. Prophylactic instillation of interferon succeded in protecting 85.2 percent of contacts; those who contracted the infection had a mild disease with insignificant complications. No allergic or intoxication phenomena were observed in children receiving leukocytic interferon for treatment or prophylaxis.     

Use of MMP-8 and MMP-9 to assess disease severity in children with viral lower respiratory tract infections

Matrix metalloproteinases (MMPs) play an important role in respiratory inflammatory diseases, such as asthma and chronic obstructive pulmonary disease. It was hypothesized that MMP-8 and MMP-9 may function as biological markers to assess disease severity in viral lower respiratory tract infections in children. MMP-8 and MMP-9 mRNA expression levels in peripheral blood mononuclear cells (PBMCs) and granulocytes obtained in both the acute and recovery phase from 153 children with mild, moderate, and severe viral lower respiratory tract infections were determined using real-time PCR. In addition, MMP-8 and MMP-9 concentrations in blood and nasopharyngeal specimens were determined during acute mild, moderate, and severe infection, and after recovery using ELISA. Furthermore, PBMCs and neutrophils obtained from healthy volunteers were stimulated with RSV, LPS (TLR4 agonist), and Pam3Cys (TLR2 agonist) in vitro. Disease severity of viral lower respiratory tract infections in children is associated with increased expression levels of the MMP-8 and MMP-9 genes in both PBMCs and granulocytes. On the contrary, in vitro experiments showed that MMP-8 and MMP-9 mRNA and protein expression in PBMCs and granulocytes is not induced by stimulation with RSV, the most frequent detected virus in young children with viral lower respiratory tract infections. These data indicate that expression levels of the MMP-8 and MMP-9 genes in both PBMCs and neutrophils are associated with viral lower respiratory tract infections disease severity. These observations justify future validation in independent prospective study cohorts of the usefulness of MMP-8 and MMP-9 as potential markers for disease severity in viral respiratory infections.     

Viral and toxoplasma gondii infections in children after liver transplantation.

The incidence and morbidity of viral and Toxoplasma gondii infections were studied in 40 children who underwent liver transplantation between December 1983 and February 1988. The incidence of primary and reactivated cytomegalovirus (CMV) infection was 19% and 47%, respectively; primary infection caused clinical disease in all five cases affected and was fatal in one. Primary Epstein-Barr virus (EBV) infection occurred in 10 (26%) recipients but caused only mild disease. No reactivated EBV infection was recorded and no lymphoproliferative disorders associated with EBV were found after a maximum of four years' follow up. Adenovirus infection occurred in seven (18%) patients; this was associated in one case with fatal pneumonia and fulminant hepatitis, but otherwise with only mild respiratory disease. Primary T gondii infection was detected in one patient who remained asymptomatic. Other viruses causing infection included herpes simplex, varicella zoster, and respiratory syncytial virus. Surveillance for these infections and the long term sequelae should be included in the follow up of all children who undergo transplantation.     

Pathogenesis study of enterovirus 71 infection in rhesus monkeys

Enterovirus 71 (EV71), a major pathogen that is responsible for causing hand-foot-and-mouth disease (HFMD) worldwide, is a member of the Human Enterovirus species A, family Picornaviridae. HFMD that is caused by EV71 is usually characterized by vesicular lesions on the skin and oral mucosa and high morbidity rates in children; additionally, occasional fatal cases have been reported involving brainstem encephalitis and myelitis associated with cardiopulmonary collapse. Although viral pathogenesis in humans is unclear, previous animal studies have indicated that EV71, inoculated via various routes, is capable of targeting and injuring the central nervous system (CNS). We report here the pathogenic process of systemic EV71 infection in rhesus monkeys after inoculation via intracerebral, intravenous, respiratory and digestive routes. Infection with EV71 via these routes resulted in different rates of targeting to and injury of the CNS. Intracerebral inoculation resulted in pulmonary edema and hemorrhage, along with impairment of neurons. However, intravenous and respiratory inoculations resulted in a direct infection of the CNS, accompanied by obvious inflammation of lung tissue, as shown by impairment of the alveoli structure and massive cellular infiltration around the terminal bronchioles and small vessels. These pathological changes were associated with a peak of viremia and dynamic viral distribution in organs over time in the infected monkeys. Our results suggest that the rhesus monkey model may be used to study not only the basic pathogenesis of EV71 viral infections, but also to examine clinical features, such as neurological lesions, in the CNS and pathological changes in associated organs.     

Viral etiologies of acute respiratory tract infections among hospitalized children – A comparison between single and multiple viral infections

BackgroundAcute respiratory tract infections are commonly caused by viruses in children. The differences in clinical data and outcome between single and multiple viral infections in hospitalized children were analyzed.MethodsWe retrospectively reviewed the medical records of hospitalized children who had fever and a xTAG Respiratory Virus Panel (RVP) test over a 2-year period. The clinical data were analyzed and compared between single and multiple viral infections. Viral etiologies in upper and lower respiratory infections were analyzed and compared.ResultsA total of 442 patients were enrolled. Patients with positive viral detection (N = 311) had a significantly lower rate of leukocytosis (p = 0.03), less evidence of bacterial infection (p = 0.004), and shorter duration of hospitalization (p = 0.019) than those with negative viral detection. The age of patients with multiple viral infections was younger than those with single viral infection; however, there were no significant differences in duration of fever, antibiotics treatment and hospitalization between these two groups.The most commonly identified virus was human rhinovirus. About 27% (n = 83) of patients had multiple viral infections. Overall, the highest percentage of human bocavirus infection was detected in multiple viral infections (79%). Lower respiratory tract infection (LRTI) was independently associated with multiple viral infections (p = 0.022), respiratory syncytial virus (RSV) infection (p = 0.001) and longer hospitalization duration (p = 0.011).ConclusionMultiple viral infections were associated with younger age and a higher risk of developing LRTI. However, multiple viral infections did not predict a worse disease outcome. More studies are needed to unveil the interplay between the hosts and different viruses in multiple viral infections.     

Acute viral hepatitis types E,A, and B singly and in combination in acute liver failure in children in North India

The aetiological agents responsible for, and the outcome of, acute liver failure were investigated prospectively in 44 children (29 males, 15 females) attending a tertiary health care facility in India. The children were between the ages of 2 months and 13 years. Studies for viral infections and other etiologies could be carried out in 40 patients. Specific aetiological labels were possible in 35 (87.5%) patients. Thirty (75%) had evidence of acute viral hepatitis. Acute hepatitis E virus (HEV) infection was found in a total of 18 children, with hepatitis A (HAV) in 16, hepatitis B in 5, and C in 1. Seven had isolated infection with hepatitis E, five with A, and four with B. Nine had both E and A infection. Superinfection of HEV was observed in a child with Indian childhood cirrhosis (ICC). Acute HEV infection was confirmed by immunoblot assay in all the patients and in eight of these, HEV-RNA was also detected in the serum. HAV was involved in 37.5% of cases with isolated infection in 10% (4 of 40). The aetiological factors associated with acute liver failure, apart from HAV and HEV, were other hepatotropic viruses (22.5%), Wilson's disease (5%), ICC (5%), and hepatotoxic drugs (7.5%). In five patients, no serological evidence of acute viral hepatitis could be found, neither did the metabolic screen yield any result. It was observed that enterically transmitted hepatitis viruses (HAV and HEV) were associated with 60% of acute hepatic failure in children. Mixed infection of HAV and HEV formed the single largest aetiological subgroup. In developing countries, where hepatitis A and E infections are endemic, severe complications can arise in the case of mixed infection. This may contribute to most of the mortality from acute liver failure during childhood. © 1996 Wiley-Liss, Inc.     

Morphologic manifestations of intestinal lesions of bacterial and mycotic etiology developing in association with acute respiratory infections

By means of light and immunofluorescent microscopy the intestines of 34 children were studied, whose bacterial or mycotic enterocolitis most often combined with acute respiratory infections. Intestinal lesions were caused either by virus (sometimes by Mycoplasma), or by bacteria and fungi. Such changes developed in the debilitated children and their course was more severe, than in monoinfections because of the impaired systemic and local immunity, and probably due to formation of viral-bacterial complexes. Viral intestinal lesions were most often caused by a single virus, but not by multiple ones, as in pulmonary infections, which is explained by interferon production and the intensive therapy used. The alternative component in a viral lesion is enhanced due to the presence of lactic acid in the intestine and therefore it is inhibited when acute viral respiratory infection develops against the background of bacterial or mycotic enterocolitis due to dysbacteriosis. Changes in mucosal stroma and intestinal lymphatic system in different infections depend on the duration of the intestinal lesion.     

Evaluation of viral co-infections in hospitalized and non-hospitalized children with respiratory infections using microarrays

The impact of viral co-infections and recently discovered viruses on the epidemiology of respiratory infections in children is still unclear. To simultaneously detect viruses that are involved in the aetiology of respiratory infections, we used a DNA/RNA microarray assay that identifies 17 different viruses or viral subtypes. Rhinopharyngeal washes were taken from 611 children (aged 1 month to 14 years) who presented in the emergency department with respiratory infections from June 2010 to June 2011 and were treated as outpatients (299, 48.9%) or hospitalized (312, 51.1%). Lower respiratory tract infection was diagnosed more often in hospitalized children (68% versus 36%, p 0.001). Of 397 children in which microarrays detected viral infection (70.1%), a single virus was found in 228 (57.4%) and two or more viruses in 169 (42.5%). The most prevalent viruses among children with positive samples were respiratory syncytial virus (RSV) in 225 (56.6%), parainfluenza virus (PIV) in 118 (29.7%), rhinovirus (RV) in 73 (18.4%), followed by influenza in 56 (14.1%), adenoviruses in 31 (7.8%), bocavirus in 25 (6.3%), human metapneumovirus in 15 (3.7%) and enteroviruses in 12 (3%). Most common viral co-infections were RSVA–RSVB in 46 children (27.2%), RSV–Influenza in 20 (11.8%), RSV–RV in 18 (10.6%) and PIV–RV in 13 (7.7%). Multiple logistic regression analysis revealed that viral co-infections were associated with increased probability for hospitalization (OR 1.52, 95% CI 1.01–2.29, p 0.04), and previous pneumococcal vaccination was associated with decreased probability for hospitalization (OR 0.52, 95% CI 0.33–0.81, p 0.004). We conclude that viral co-infections are involved in a significant proportion of children with an acute respiratory infection and may increase the severity of clinical presentation and the risk for hospitalization.     

Aetiology of acute febrile illness in children in a high malaria transmission area in West Africa

ObjectivesAreas with declining malaria transmission in sub-Saharan Africa have recently witnessed important changes in the aetiology of childhood acute febrile illness (AFI). We describe the aetiology of AFI in a high malaria transmission area in rural Burkina Faso.MethodsIn a prospective hospital-based diagnostic study, children aged 3 months to 15 years with AFI were recruited and assessed using a systematic diagnostic protocol, including blood cultures, whole blood PCR on a selection of bacterial pathogens, malaria diagnostics and a multiplex PCR on nasopharyngeal swabs targeting 21 viral and 4 bacterial respiratory pathogens.ResultsA total of 589 children with AFI were enrolled from whom an infectious disease was considered in 575 cases. Acute respiratory tract infections, malaria and invasive bacterial infections (IBI) accounted for 179 (31.1%), 175 (30.4%) and 75 (13%) of AFI cases respectively; 16 (21.3%) of IBI cases also had malarial parasitaemia. A viral pathogen was demonstrated from the nasopharynx in 157 children (90.7%) with respiratory tract symptoms. Of all children with viral respiratory tract infections, 154 (92.4% received antibiotics, whereas no antibiotic was provided in 13 (17%) of IBI cases.ConclusionsViral respiratory infections are a common cause of childhood AFI in high malaria transmission areas, next to malaria and IBI. These findings highlight the importance of interventions to improve targeted treatment with antimicrobials. Most patients with viral infections received antibiotics unnecessarily, while a considerable number with IBI did not receive antibiotics.