Role of Chlamydia pneumoniae in acute chest syndrome of sickle cell disease

Children with sickle cell disease and acute chest syndrome were investigated for infection with Chlamydia pneumoniae and Mycoplasma pneumoniae. Of 30 patients who had 32 episodes of acute chest syndrome, four (13%) had C. pneumoniae isolated from the nasopharynx; two of these also had serologic evidence of acute infection, and one had positive nasopharyngeal isolates on two subsequent occasions during the course of 1 year with stable, elevated titers of anti-C. pneumoniae IgG, suggesting chronic infection. Two patients with negative cultures had serologic evidence of infection with C. pneumoniae. None of 32 cultures for M. pneumoniae were positive, and although anti-M. pneumoniae IgM developed in two patients, one of these patients had evidence of C. pneumoniae infection (positive culture and seroconversion). We conclude that C. pneumoniae infection is prevalent in our sickle cell population with acute chest syndrome. Until further studies clarify the pathophysiologic significance of C. pneumoniae infection, we believe that early inclusion of erythromycin as antimicrobial therapy for acute chest syndrome seems reasonable.     

Serum IgA antibodies against Pseudomonas aeruginosa in cystic fibrosis.

Serum IgA antibodies to Pseudomonas aeruginosa cell surface antigens were estimated by ELISA. Titres in patients with and without cystic fibrosis and with no pseudomonal infection were low (less than 105 to less than 261). Titres in patients with cystic fibrosis who were chronically infected with P aeruginosa were very high (1200-163,000), and patients who grew the organism intermittently had intermediate titres. Longitudinal studies suggested increasing tissue invasion or involvement of the lower respiratory tract, or both, with increasing time of infection and identified patients with a good prognosis after the onset of pseudomonal infection. Detection of an increased serum IgA titre can give an earlier indication than measurement of the serum IgG titre of the presence of P aeruginosa in the respiratory tract in a proportion of patients. IgA measurement seems to be better than IgG measurement at predicting the reappearance of P aeruginosa after apparent eradication of early infection. These results suggest that this assay may be a valuable additional indicator of the presence of P aeruginosa at the beginning of infection, and of the reappearance of the organism after treatment in the early stages of infection.     

Serum antibodies to Pseudomonas aeruginosa in cystic fibrosis.

Serum IgG antibodies to Pseudomonas aeruginosa cell surface antigens were determined by enzyme linked immunosorbent assay. Titres in patients without cystic fibrosis were low (140-235). Those in patients with cystic fibrosis who were chronically infected by P. aeruginosa were very high (1100-20,500), while patients who grew the organism intermittently had lower titres (160-4400). Longitudinal studies showed that raised titres were observed at a very early stage of infection. High titres were associated with a poor clinical state, while low titres were associated with a better clinical state in both chronic and intermittently infected patients with cystic fibrosis. These results suggest that this test is a specific and sensitive measure of the severity and progress of the different stages of pulmonary infection by P. aeruginosa in patients with cystic fibrosis.     

Survival and clinical outcome in patients with cystic fibrosis, with or without neonatal screening

After an experimental neonatal screening program for cystic fibrosis had been carried out in the Netherlands during 1973 to 1979, a follow-up study to evaluate the effects of neonatal screening was started in 1980. Although before 1980 the management of patients with cystic fibrosis was partly left to local hospitals, from the start of the follow-up program all patients in the study received similar treatment. A cumulative survival rate, calculated with exclusion of the patients with meconium ileus, showed at the age of 11 years a significantly better survival rate (p less than 0.05) for the 19 patients from the screened population (88%) than for the 25 patients from the nonscreened population (60%). Clinical condition was assessed on entry and at the age of 9 years in 16 screened and 20 nonscreened patients. On entry, comparison showed significantly better chest radiograph scores for the screened patients but no other significant differences. At the age of 9 years, after several years of similar treatment for all patients in the study, significantly better clinical (p less than 0.02) and chest radiograph scores (p less than 0.01), lower IgG levels (p less than 0.05), and higher vitamin A levels (p less than 0.01) were observed in the screened patients. Our study results suggest that early diagnosis and appropriate treatment may prevent serious deterioration and death at a young age, and may reduce the extent of early irreversible lung damage in patients with cystic fibrosis.     

Transient aplastic crisis in patients with sickle cell disease. B19 parvovirus studies during a 7-year period.

OBJECTIVE--To determine (1) the proportion of cases of transient aplastic crisis (TAC) in patients with sickle cell disease due to B19 parvovirus infection in several years, (2) longitudinally, the immune response to B19 parvovirus infection, and (3) whether patients with sickle cell disease experience recurrent or chronic B19 parvovirus infection. DESIGN--Prospective evaluation of patients with sickle cell disease and TAC to find evidence of B19 parvovirus infection and, if present, to document the pattern of serologic response with time. SETTING--Large urban teaching hospital. PATIENTS--Patients younger than 18 years with sickle cell disease who were admitted to the hospital with a diagnosis of TAC or who developed TAC while in the hospital for other reasons. Follow-up serologic studies of B19 parvovirus infection were done in eight patients. MEASUREMENTS/MAIN RESULTS--Serum was tested for B19 parvovirus DNA/viral particles and specific anti-B19 parvovirus IgM and IgG antibodies. B19 parvovirus DNA/viral particles were detected in 11 (21%) of 53 patients with TAC. Specific anti-B19 parvovirus IgM antibodies were detected in 34 (64%) of the 53 patients. Overall, 36 (68%) of 53 patients with TAC had evidence of acute B19 parvovirus infection as shown by the detection of B19 DNA parvovirus and/or specific anti-B19 parvovirus IgM antibodies in acute-phase serum. Follow-up serologic studies in eight patients with acute infection revealed disappearance of B19 parvovirus DNA/viral particles and anti-B19 parvovirus IgM antibodies and persistence of anti-B19 parvovirus IgG antibodies for up to 3 1/2 years after the diagnosis of acute B19 parvovirus infection. No patient had evidence of recurrent or chronic B19 parvovirus infection. CONCLUSIONS--Approximately 70% of cases of TAC in patients with sickle cell disease identified in a 7-year period were caused by acute B19 parvovirus infection. Once detected, anti-B19 parvovirus IgG antibodies remain detectable for several years. There was no evidence of chronic or recurrent B19 parvovirus infection in patients with sickle cell disease.     

Serum interleukin-1 alpha and soluble interleukin-2 receptor concentrations in cystic fibrosis.

Interleukin (IL)-1 and IL-2 may participate in the systemic inflammatory response and hypergammaglobulinaemia observed in patients with cystic fibrosis. Thirty seven patients with cystic fibrosis were compared with 25 normal controls. High IgG and IgM concentrations were associated with more severe pulmonary disease. IL-1 alpha and soluble IL-2 receptor concentrations were higher in the cystic fibrosis group than in the controls and also correlated with concentrations of IgG and IgM. These results suggest that these cytokines may contribute to enhanced immunoglobulin synthesis and silent inflammatory activity in clinically stable patients with cystic fibrosis.     

Serum interleukin-1 alpha and soluble interleukin-2 receptor concentrations in cystic fibrosis

Interleukin (IL)-1 and IL-2 may participate in the systemic inflammatory response and hypergammaglobulinaemia observed in patients with cystic fibrosis. Thirty seven patients with cystic fibrosis were compared with 25 normal controls. High IgG and IgM concentrations were associated with more severe pulmonary disease. IL-1 alpha and soluble IL-2 receptor concentrations were higher in the cystic fibrosis group than in the controls and also correlated with concentrations of IgG and IgM. These results suggest that these cytokines may contribute to enhanced immunoglobulin synthesis and silent inflammatory activity in clinically stable patients with cystic fibrosis.     

Screening for rubella IgG and IgM using an ELISA test applied to dried blood on filter paper

IgG and IgM rubella antibodies were measured in dried blood samples from the neonatal metabolic screening program. Of 6613 samples from four central screening laboratories, 289 did not contain rubella IgG antibodies, indicating that only 4.3% of the mothers at term were not immune to the rubella virus in the spring of 1984. The proportion of women at term who were not immune was 9.3% in 1979. Rubella IgM was detected in nine of 37,000 samples; congenital rubella infection was confirmed serologically in eight infants. Of the infected babies, three showed severe clinical findings. We suggest that rubella IgG and IgM should be determined regularly in the surplus material of metabolic screening centers, thus giving the opportunity to detect infected infants. The screening procedure is also useful as a serologic tool for monitoring immunity patterns in women, and thus the effectiveness of vaccination programs.     

Neonatal screening for congenital toxoplasmosis in the Poznań region of Poland by analysis of Toxoplasma gondii-specific IgM antibodies eluted from filter paper blood spots

OBJECTIVES: The aims of the study were to determine the prevalence of congenital toxoplasmosis at birth in the Poznań region of Poland, the value of the serologic examination of filter paper blood specimens collected from newborns for the diagnosis of congenital Toxoplasma infection and the duration of anti-Toxoplasma-specific IgM antibodies in infants' sera. MATERIALS AND METHODS: All neonates born in the maternity wards of the University Hospital of Gynaecology and Obstetrics in Poznań and in 10 selected obstetrics wards in the district hospitals were included. Blood samples were collected on filter paper cards, between the first and sixth day of life, screened for anti-Toxoplasma-specific IgM antibodies by an immunocapture enzyme-linked immunosorbent assay and if positive further analyzed for specific IgG and IgA antibodies. RESULTS: Between June, 1996, and October, 1998, filter paper samples from 27,516 liveborn infants were tested, which constituted approximately 75% of all births and 83% of liveborn neonates from the Poznań region. Anti-T. gondii-specific IgM antibodies were found in 13 newborns, equivalent to a prevalence of Toxoplasma-specific IgM in newborns of 1 per 2,117 liveborn children (0.47 per 1,000) or 1 per 870 children (1.15 per 1,000) born to seronegative women at risk of primary T. gondii infection during pregnancy. We identified two congenitally infected infants who were IgM-negative at birth, had a classic triad of clinical symptoms during the first year of life and had high levels of specific IgG. The birth prevalence of congenital toxoplasmosis in the Poznań region was at least 1 per 1,834 live births (0.55 per 1,000) or 1 per 754 live neonates born to seronegative women (1.33 per 1,000). The sensitivity of the IgM assay on eluate from filter paper was not more than 86.7%, and the mean duration of IgM detectable by enzyme-linked immunosorbent assay in serum samples was the first 4.8 weeks of life. CONCLUSION: In Poland the screening for congenital toxoplasmosis detecting one case per each 2,000 live births could be considered for inclusion in existing national neonatal screening programs for phenylketonuria and congenital hypothyroidism.     

Early pulmonary manifestation of cystic fibrosis in children with the DeltaF508/R117H-7T genotype

We report 3 cystic fibrosis newborn screen-positive infants with the DeltaF508/R117H-7T genotype who had Pseudomonas aeruginosa detected in oropharyngeal cultures early in life and a fourth who had pulmonary symptoms and Gram-negative growth on multiple oropharyngeal cultures. All 4 patients were followed prospectively from the time of genetic diagnosis. As many regions implement newborn screening for cystic fibrosis, there is concern regarding which mutations should be included in genetic panels used to make the cystic fibrosis diagnosis. Some have recommended that mutations not specifically associated with classic cystic fibrosis be excluded. Our cases highlight the importance of considering keeping so-called mild mutations on cystic fibrosis newborn screening panels and the need to follow children with these mutations closely.     

Association of Epstein-Barr virus infection and pulmonary exacerbations in patients with cystic fibrosis.

We observed severe pulmonary exacerbations during primary Epstein-Barr virus (EBV) infection in adolescent patients with cystic fibrosis. Since EBV is not a known respiratory tract pathogen in cystic fibrosis, we studied retrospectively all EBV-susceptible patients ages 6 to 18 years with chronic Pseudomonas respiratory tract colonization hospitalized for a pulmonary exacerbation during an 18-month period. Patients with serologic evidence of primary EBV infection (n = 5) were compared to control patients without EBV (n = 7). Before admission the groups had similar pulmonary function tests, clinical scores and frequency of hospitalization. On admission patients with EBV had significant weight loss, lower pulmonary function tests and lower clinical scores compared with controls. All remained significantly different 6 months after admission. Frequency of exacerbations requiring hospitalization increased after EBV infection but remained unchanged in controls. Primary EBV infection can be associated with severe pulmonary exacerbations and subsequent deterioration in clinical course in cystic fibrosis patients.     

The effect of respiratory viral infections on patients with cystic fibrosis

We examined, in a 2-year prospective study, the frequency of respiratory viral infections in 19 school-age patients with cystic fibrosis and their unaffected siblings. At 2-month intervals throughout the study period, pulmonary function tests, oropharyngeal cultures, and serologic tests for respiratory viruses were performed in all subjects. Quantitative sputum cultures for bacteria were performed in subjects with cystic fibrosis. The same laboratory specimens were also collected at the time of all acute respiratory illnesses. Over the 2-year period, 398 viral cultures and serum samples were collected, 210 from patients with cystic fibrosis and 188 from their siblings. The frequency of culture-documented and seropositive viral infections was not significantly different between patients with cystic fibrosis and their siblings. The patients with the highest frequency of viral infection were younger and had the lowest rate of decline in lung function and severity score. We conclude that school-age patients with cystic fibrosis are no more susceptible to viral infections than their unaffected siblings. We were unable to demonstrate any significant adverse effect of respiratory viral infections on pulmonary function in 19 patients with cystic fibrosis aged 5 to 21 years.     

Deep Candida infection in child liver transplant recipients: serological diagnosis and incidence

Nineteen children who received 22 orthotopic liver grafts on 20 occasions were studied with regard to Candida infection. Serum samples were analysed to determine Candida, IgA, IgM and IgG antibodies and detect free C. albicans glucoprotein antigen. Five children (25%) had a confirmed deep C. albicans infection (DCI) during the first 2 weeks after transplantation. In all children with DCI, serology was positive, a median of 6 days (range 2–9 days) before Candida infection was verified by fungal culture, direct microscopy and/or autopsy. The positive predictive values for Candida IgG, IgM and IgA antibodies in children with DCI were 100%, 78% and 100%, respectively, and for free C. albicans antigen, 45%. Pathological titres of IgM and IgA antibodies against Candida before liver transplantation were present in three of four children who later developed a DCI and in no child without infection. In conclusion, regular screening by Candida serology is recommended both before and after liver transplantation.     

儿童单纯疱疹病毒感染血清学检查分析

目的：单纯疱疹病毒(HSV)感染是小儿时期常见的病毒感染,也是病毒性脑炎的常见病因,血清学检查是诊断HSV感染常用的检测方法。该文探讨儿童HSV感染的血清抗体检查的意义。方法：采用ELISA方法检测2436例儿童血清中HSV-1和HSV-2的IgG和IgM抗体,并作回顾性分析。结果：儿童单纯疱疹病毒血清抗体阳性率为44.6%(143/321),其中HSV-1抗体阳性率38.9%(117/301),HSV-2抗体阳性率15.9%(43/271);IgM阳性率为41.1%(132/321),IgG阳性率为25.5%(73/286);HSV-1血清阳性率随年龄而增加(P<0.01)。TORCH检测组HSV-2抗体血清阳性率1.9%,均为HSV-2IgG阳性。结论：HSV血清学检查对儿童HSV感染具有重要的诊断意义。     

Antibody to multiple mucoid strains of Pseudomonas aeruginosa in patients with cystic fibrosis, measured by an enzyme-linked immunosorbent assay

The sera from 32 patients with cystic fibrosis who were chronically colonized with mucoid strains of Pseudomonas aeruginosa (MPA) were tested for anti-MPA antibodies. Using an enzyme-linked immunosorbent assay we measured IgA, IgG, and IgM antibody titers to three MPA strains, extracts of those strains, and seaweed-derived sodium alginate, which is similar chemically to the exopolysaccharide of MPA. These titers were compared with identical tests performed on the sera of eight cystic fibrosis patients who never were colonized with MPA and 10 normal adults. The IgG titers were significantly higher in tests of sera from the colonized patients compared with the other two groups but the IgA and IgM titers were not significantly higher. In colonized patients antibody titers to the different antigens correlated with each other suggesting that the major antibody response was to common antigenic determinants. Using these titers as a data base, eight patients whose clinical status was unknown to the testers, had IgG-enzyme-linked immunosorbent assay tests of their sera and the four colonized patients with cystic fibrosis were correctly identified. Three of them had substantial titers of antibody in the bronchoalveolar lavage fluid.     

Clinical, virologic, and serologic evidence of Epstein-Barr virus infection in association with childhood pneumonia

To explore the association of Epstein-Barr virus infection with childhood pneumonia we studied two patients whose mononucleosis-like illnesses were accompanied by pneumonia; both had virologic and serologic evidence of current or recent EBV infection. We then analyzed the sera of 71 children (age range, 14 months to 9 years) with pulmonary infiltrates for the presence of four classes of antibody to EBV. Antibody responses consistent with current or recent EB virus infection were found in 15. Two children had IgM antibodies to the EBV viral antigen at titers greater than or equal to 1:160, indicating current infection, and all 15 patients had antibody to components of the early antigen complex, suggesting recent infection. A fourfold rise or drop in one or more EBV-specific antibody classes was noted in eight patients within 30 days following onset of clinical illness. Few patients had clinical features suggesting infectious mononucleosis. Eight of the 15 with serologic evidence of current or recent EBV infection also had clinical or serologic evidence of infection with another pathogen--bacterial, viral, or mycoplasmal. Thus, in childhood pneumonia, EBV may be a primary, co-primary, or secondary pathogen; it may be reactivated in the course of infection with another agent, or possibly, by suppressing immune function, it may precipitate infection with some other organism.     

Cystic fibrosis and allergic bronchopulmonary aspergillosis.

We have prospectively screened our patients with cystic fibrosis for allergic bronchopulmonary aspergillosis. Over a three year period eight patients were identified, an incidence of 5.8%. Patients were clinically well at the time of diagnosis (Shwachman scores 70-90, Chrispin-Norman chest x ray scores 2-15) and they responded rapidly to treatment with oral prednisolone. There has been little deterioration in their respiratory function and nutrition over the study period. We conclude that allergic bronchopulmonary aspergillosis is not uncommon in patients with cystic fibrosis. It is a potential cause of lung damage and prospective screening could lead to earlier detection and treatment.     

Effects of newborn screening of cystic fibrosis on reported maternal behaviour.

Screening for cystic fibrosis is highly controversial. Concerns have been expressed that newborn screening may cause mothers, who had considered their child to be healthy before diagnosis, to overprotect their child. Some critics of screening also suggest that a period of delay from onset of symptoms to diagnosis may help a mother adjust to the reality of the child''s lethal condition. This study compared the strength of overprotective child rearing attitudes of 29 mothers whose children were screened (13 had symptomatic children and 16 asymptomatic children) with the attitudes of 29 mothers whose children were diagnosed after the onset of symptoms. Results indicate that newborn screening had not increased a mother''s tendency to overprotect her child with cystic fibrosis and in some cases the tendency had decreased. Further, delay in diagnosis when screening was not conducted usually caused mothers considerable personal distress.     

A serologic strategy for detecting neonates at risk for congenital cytomegalovirus infection

OBJECTIVES: To evaluate the feasibility of a serologic screening program in pregnant women to detect neonates at risk for a congenital cytomegalovirus infection. STUDY DESIGN: Unselected mother-infant pairs (n = 7140) were studied. In the mother, serologic screening consisted of the testing for cytomegalovirus antibodies at the first prenatal visit and at birth. In the neonate, cytomegalovirus urine culture was performed to diagnose congenital infection. RESULTS: Serologic screening showed evidence of past infection in 3850 women (53.9%); 192 (2.7%) women had both immunoglobulin (Ig)G and IgM antibodies when first tested during pregnancy. Seroconversion was detected in 44 seronegative women (1.4%). Forty-four congenital infections were diagnosed (0.62%): 8 in women with past infections, 22 in women who seroconverted, and 14 in women who initially had positive IgM antibodies. CONCLUSIONS: Screening at the first prenatal visit and at birth defines two major risk groups for congenital cytomegalovirus infection: women with seroconversion during pregnancy and women with IgM antibodies in their first prenatal serum sample (0.6% and 2.7%, respectively, of the pregnant population). In these selected babies (3.3% of the study group), cytomegalovirus urine culture should be performed. This type of screening allows the detection of 82% of all congenital cytomegalovirus infections.     

Influence of five years of antenatal screening on the paediatric cystic fibrosis population in one region

BACKGROUND: Antenatal screening for cystic fibrosis has been endorsed by the US National Institutes of Health. Edinburgh is the only city in the UK with an established routine antenatal screening programme for cystic fibrosis. AIMS: To report the change in numbers of infants diagnosed with cystic fibrosis born in Edinburgh after the introduction of antenatal screening for the disease. POPULATION: Infants diagnosed as having cystic fibrosis (by sweat test or genotyping, or both) in the seven years before antenatal testing (1984-90) and the first five years of antenatal testing (1991-95). Children born in this region who had moved before diagnosis were identified from the UK cystic fibrosis survey database. RESULTS: The incidence of cystic fibrosis decreased from an average of 4.6 to 1.6 children each year with antenatal screening. The reduction in the incidence (65%) was greater than that accounted for by prenatal diagnosis and termination (36%). Of the eight children born with cystic fibrosis during the period of antenatal screening, five had been subject to antenatal screening: three had only one mutation identified, one was missed due to a laboratory error, and one was identified as a one in four risk, but prenatal diagnosis was not performed. CONCLUSIONS: Antenatal testing for cystic fibrosis has successfully reduced the incidence of cystic fibrosis in this region. Although the numbers are small, it is possible that the reduction in numbers may have been greater than might be expected from antenatal screening alone.