Invasive pneumococcal infection in children

Streptococcus pneumoniae infections can involve multiple organs and cause high mortality and morbidity. In this retrospective study, we reviewed patients with invasive pneumococcal infection in the pediatric department of a teaching hospital in Taipei. From 1984 to 1998, 81 children with invasive pneumococcal infection were hospitalized. Twenty-eight patients had meningitis, 27 had pneumonia with pleural effusion, 60 had sepsis, and 4 had arthritis. Thirty-eight patients had more than one site of infection. Most of our patients (81.7%) were below 5 years of age. Pneumococcal infections were more common from October to March. Eight patients had a history of trauma that correlated with the site of infection. Thirteen patients (16.0%) expired and 20 (24.7%) had severe sequelae. Multi-regression analysis found that meningitis and complications were independent variables that affected the outcome. The percentage of penicillin-resistant strains increased beginning in 1990 and accounted for about four-fifths of the infections in the final 2 years of the study. Since invasive pneumococcal infections in children may have a poor prognosis and penicillin-resistant strains have become increasingly common, early and adequate antibiotic therapy should be given as soon as possible.     

Bacteremic pneumococcal pneumonia in children.

We carried out a nationwide retrospective study on bacteremic pneumococcal pneumonia diagnosed from 1985 to 1994 in Finland. The records of 85 children were reviewed for symptoms, signs, laboratory data, and response to antibiotic therapy. The chest radiographs were reevaluated. Bacteremic pneumococcal pneumonia was characterized by high fever (> or =39.0 degrees C in 93%), leukocytosis (WBC count on admission of > or =15x10(9)/L in 84%), and ill appearance (in 79%). Lobar or segmental consolidation was found in 79% of the chest radiographs. Of the patients, 28% had no respiratory symptoms, 6% presented with only gastrointestinal symptoms in addition to fever, and 4% had fever only. Tachypnea was recorded in 19% and rales in 14% of the patients. After onset of antimicrobial treatment, children became afebrile within an average of 22 hours. One patient developed pleural empyema, and none of the patients died.     

Prospects for pneumococcal vaccination in African children

Streptococcus pneumoniae (pneumococcus) remains a major cause of morbidity and mortality in both developed and undeveloped countries. Accurate disease burden estimates for developing countries and Africa in particular, where diagnostic facilities are less adequate and a disease surveillance system virtually non-existent, is difficult. However, from conservative estimates, the pneumococcus is probably responsible for at least 1 million of the 4 million deaths that occur from acute lower respiratory infections in children aged less than 5 years. The global burden of disease has been accentuated by the rising menace of multi-drug resistant strains, which defy geographic and racial borders. Thus, now more than ever before, there is an urgent need to identify and implement preventive measures to avert this problem. The currently licensed pneumococcal polysaccharide vaccine, comprises 23 capsular polysaccharides of the pneumococcus, many of which are poorly immunogenic in the very vulnerable age group of under-fives. A possible solution to the problem of poor immunogenicity is to use a protein/polysaccharide conjugate vaccine similar to that recently introduced successfully for Haemophilus influenzae type b (Hib) and using this approach, several workers have reported promising results from safety and immunogenicity studies. However, unlike Hib, the development of conjugate vaccine against pneumococcal disease is complicated by the existence of more serotypes than can be feasibly incorporated in a single conjugate vaccine formulation. Whilst this challenge has been taken on by some vaccine manufacturers, novel approaches such as the identification or construction of protective protein antigen, common to all clinically important strains are being explored. Novel application of the pneumococcal polysaccharide vaccines in pregnancy for protection of disease in early infancy is an approach that has not been evaluated. For maximum impact, the ultimate vaccine formulation should be affordable and available to resource poor countries where the burden of disease is highest. Establishing disease surveillance systems in such countries now will greatly facilitate the introduction of the vaccines.     

Proportion of invasive pneumococcal infections in German children preventable by pneumococcal conjugate vaccines.

The incidence and serotype distribution of Streptococcus pneumoniae as a cause of invasive diseases are unknown with regard to most European countries. From January 1997 through December 1998, population-based nationwide prospective surveillance was undertaken for invasive pneumococcal disease (IPD) in children in Germany, based on monthly independent reports from all pediatric hospitals and from clinical microbiology laboratories. On the basis of 896 reported IPD cases (including 404 with meningitis), the incidences per 10(5) children in different age groups were as follows: children aged <1 year, 18.9 (9.7 for meningitis); children aged <2 years, 16. 0 (7.2 for meningitis); for children aged <5 years, 8.9 (3.9 for meningitis); and for children aged <16 years, 3.2 (1.4 for meningitis). The proportions of cases involving strains (304 serotyped) included in conjugate vaccines were as follows: for the 7-valent vaccine, 52%; for the 9-valent, 62%; and for the 11-valent, 71%. None of the isolates were resistant to penicillin or cefotaxime. Although the rate for meningitis is similar, other manifestations of IPD are less commonly diagnosed in Germany than in other countries. The serotype distribution only partially matched that used in the recent development of pneumococcal conjugate vaccines.     

Serum procalcitonin in pneumococcal pneumonia in children.

Serum procalcitonin (PCT), a marker of bacterial infection, was measured in children with pneumonia to examine whether PCT can be used to screen pneumococcal (PNC) from viral pneumonia. The number of patients was 132; mean age 3.0 yrs, and 64% were males. In all cases, pneumonia was radiologically confirmed, being alveolar in 46 and interstitial in 86 cases. The aetiology of infection was studied by a panel of serological tests for PNC, for five other respiratory bacteria and for seven common respiratory viruses. PNC infection was found in 25, mixed viral-PNC infections in 13 and viral infection in 17 cases. In general, serum PCT was not associated with the type or aetiology of pneumonia. PCT values were >1.0 mg.L(-1) in 40% of PNC cases, as compared to 12-15% in viral or mixed cases, respectively (p<0.05). PCT values were significantly higher in >2 yrs old children than in younger ones. The cut-off limits of 0.5 ng.mL(-1), 1.0 ng.mL(-1) and 2.0 ng.mL(-1) were tested for screening between PNC and viral pneumonia. The highest sensitivity of 55% was found at the 0.5 ng.mL(-1) cut-off level, whereas the highest specificity of 88% was reached at the level of 1.0 ng.mL(-1). The likelihood ratios, however, were far from optimal for both the positive and negative results. Although marginally higher in pneumococcal pneumonia than in viral pneumonia, serum procalcitonin cannot be used to discriminate between these two types of pneumonia.     

Serologically indicated pneumococcal respiratory infection in children.

Streptococcus pneumoniae infection was indicated serologically in 84 (19%) of 449 children hospitalized with middle or lower respiratory tract infection. Pneumococcal antigen was detected in acute serum in 28 patients, but in acute urine in only 2. An antibody response to type-specific capsular polysaccharides of S. pneumoniae was indicated in 27 patients and to a protein antigen, pneumolysin, in 25 patients, but to C-polysaccharide in only 10 patients. The observations mentioned above suggest that each serological test for pneumococcal etiology is insensitive, and to get an optimal result, a large panel of pneumococcal antigen and antibody assays must be used. Pneumococcal infection could be indicated serologically although no focus of infection, such as pneumonia or acute otitis media, or no laboratory evidence of bacterial infection as elevated values of C-reactive protein concentration, erythrocyte sedimentation rate or white blood cell count was present. Particularly antibody responses to pneumococcal pneumolysin were present in children without pneumonia or acute otitis media. Our results point out that no nonspecific parameter can be used for the selection of patients with probable pneumococcal etiology among children with respiratory tract infection. Concomitant viral infection, in most cases RSV infection, was present in a third of the children with pneumococcal infection. It is concluded that pneumococcal etiology should be actively sought for also in patients with viral respiratory infection, especially in young children with RSV infection.     

Epidemiological and economic burden of pneumococcal diseases in Canadian children

BACKGROUND:

With the arrival of a new conjugate pneumococcal vaccine, it is important to estimate the burden of pneumococcal diseases in Canadian children. The epidemiological data and the economic cost of these diseases are crucial elements in evaluating the relevance of a vaccination program.

METHODS:

Using provincial databases, ad hoc surveys and published data, age-specific incidence rates of pneumococcal infections were estimated in a cohort of 340,000 children between six months and nine years of age. The costs of these diseases to the health system and to families were also evaluated using data from Quebec and Manitoba.

RESULTS:

Cumulative risks were one in 5000 for pneumococcal meningitis, one in 500 for bacteremia and one in 20 for pneumonia, leading to 16 deaths in the cohort. About 262,000 otitis media episodes and 32,000 cases of myringotomy with ventilation tube insertion were attributable to Streptococcus pneumoniae. Societal costs were estimated at $125 million, of which 32% was borne by the health system and 68% was borne by families. Invasive infections represented only 2% of total costs, while 84% were generated by otitis media.

CONCLUSION:

Pneumococcal infections represent a significant burden for Canadian children and society that could be significantly reduced through immunization. Key Words: Canada, Economics, Epidemiology, Pneumococcal infectionsStreptococcus pneumoniae is an important cause of serious illness in young children in developed countries (1). A 7-valent pneumococcal conjugate vaccine (PCV-7) has recently been licensed in Canada. This vaccine is now being used in publicly funded programs for all children in Alberta and Nunavut. Some Canadian provinces (Quebec, Prince Edward Island and Saskatchewan) have implemented programs limited to some high-risk groups and others are still considering its use in their provincial programs (2,3). Evaluation of the epidemiological and economic burden of pneumococcal disease is an important criterion in decision making and is a prerequisite for the analysis of the cost-effectiveness of routine and catch-up immunization programs. Epidemiological data collected in the United States may not be valid for Canada because of possible differences in the prevalence of risk factors. Extrapolation is even more problematic for economic parameters because of variations in the composition of families, availability of natural caregivers, employment rates, incomes and costs of health services. The aim of this study is to estimate the incidence and societal costs of pneumococcal disease in Canadian children between six months and nine years of age.     

Pleural fluid nucleic acid testing enhances pneumococcal surveillance in children

Background and objective: National surveillance of invasive pneumococcal disease (IPD) includes serotyping Streptococcus pneumoniae (SP) isolates from sterile site cultures. PCR is more sensitive and can identify more SP serotypes (STs) in culture‐negative samples. The aim of this study was to determine whether enhanced surveillance of childhood empyema, using PCR, provides additional serotype information compared with conventional surveillance. Methods: Pleural fluid (PF) from children with empyema were cultured and tested by PCR to identify SP, targeting the autolysin gene (lytA). Multiplex PCR‐based reverse line blot assay was used to identify SP STs. Corresponding IPD surveillance and serotype data were obtained from the National Notifiable Diseases Surveillance System (NNDSS). Results: Eighty‐nine children with empyema, aged ≤16 years, were recruited between April 2008 and March 2009, inclusive. SP was isolated from 5/84 (5.9%) PF cultures and by PCR in 43/79 (54.4%) PF samples. Serotypes were unidentifiable in 15 samples. The frequency of six serotypes (or serotype pairs) identified in 28 samples, including one with two serotypes, were: ST1, n = 4/29 (13.8%); ST3, n = 9/29 (31.0%); ST19A, n = 12/29 (41.4%); ST7F/7A, n = 1/29 (3.4%); ST9V/9A, n = 1/29 (3.4%); ST22F/22A, n = 2/29 (6.9%). Over the same period, 361 IPD patients, aged 16 years or less, were notified to NNDSS. Among 331 serotypeable NNDSS isolates (71.5% from blood), the frequencies of ST1 and 3 were significantly lower than in PF samples: ST1, n = 8/331 (2.4%; P < 0.05); ST3, n = 13/331 (3.9%; P < 0.0001). Conclusions: The use of PCR to identify and serotype SP in culture‐negative specimens provides additive information.     

Epidemiological and economic burden of pneumococcal diseases in Canadian children.

BACKGROUND: With the arrival of a new conjugate pneumococcal vaccine, it is important to estimate the burden of pneumococcal diseases in Canadian children. The epidemiological data and the economic cost of these diseases are crucial elements in evaluating the relevance of a vaccination program. METHODS: Using provincial databases, ad hoc surveys and published data, age-specific incidence rates of pneumococcal infections were estimated in a cohort of 340,000 children between six months and nine years of age. The costs of these diseases to the health system and to families were also evaluated using data from Quebec and Manitoba. RESULTS: Cumulative risks were one in 5000 for pneumococcal meningitis, one in 500 for bacteremia and one in 20 for pneumonia, leading to 16 deaths in the cohort. About 262,000 otitis media episodes and 32,000 cases of myringotomy with ventilation tube insertion were attributable to Streptococcus pneumoniae. Societal costs were estimated at $125 million, of which 32% was borne by the health system and 68% was borne by families. Invasive infections represented only 2% of total costs, while 84% were generated by otitis media. CONCLUSION: Pneumococcal infections represent a significant burden for Canadian children and society that could be significantly reduced through immunization.     

Necrotizing pneumococcal pneumonia in children: the role of pulmonary gangrene

Little is known about the mechanism of necrotizing pneumonia caused by Streptococcus pneumoniae in children. Pulmonary gangrene secondary to vascular thrombosis was reported in adults with necrotizing pneumococcal pneumonia. We conducted a retrospective study of 15 children with a diagnosis of necrotizing pneumococcal pneumonia at National Taiwan University Hospital to explore its association with pulmonary gangrene, based on evidence from chest computed tomography, serial chest radiographic patterns, and pathologic results. S. pneumoniae serotype 14 was the prevalent pneumococcal serotype. Overall, 63.6% of isolates were not susceptible to penicillin. One child with pneumonia caused by S. pneumoniae serotype 3 complicated by hemolytic uremic syndrome had a rapidly fatal course. An autopsy in this patient documented lung necrosis and pulmonary gangrene. Radiographic follow-up was performed during the clinical course in 9 patients, and showed no evidence of pulmonary gangrene. Four children had no radiographic follow-up. The relationship between pulmonary gangrene and necrotizing pneumonia was unclear in the remaining one. In conclusion, necrotizing pneumococcal pneumonia may be infrequently associated with pulmonary gangrene in children.     

Impaired pneumococcal immunity in children after treatment for acute lymphoblastic leukaemia

Although the substantial risk for invasive pneumococcal disease is well recognized in children after allogeneic stem cell transplantation, little is known about the specific immunity against pneumococci in children after cytotoxic therapy for acute lymphoblastic leukaemia (ALL). We therefore assessed the spontaneous reconstitution of humoral immunity against pneumococcal antigens, of total IgG and the IgG2 subclass, and of lymphocyte subsets in a total of 53 children treated for ALL. None of the patients had received pneumococcal vaccination prior to or after therapy for ALL. At 3 and 9 months after completion of chemotherapy, most patients had levels of specific antibodies to pneumococcal antigens below the presumed threshold of protection and significantly lower than those of age-matched unvaccinated healthy controls. In contrast, at 9 months after completion of therapy, only a minority of patients had immunoglobulin concentrations or lymphocyte subset counts below the age-matched reference value. Our data indicate that patients with ALL who are unvaccinated against pneumococci have a selective immunodeficiency with an impaired antibody protection against pneumococci for up to 9 months after completion of therapy. Therefore, effective prevention, including chemoprophylaxis and active immunization, has to be considered in this patient population.     

Risk factors for mortality in Paraguayan children with pneumococcal bacterial meningitis

Background Over the last decade Streptococcus pneumoniae has emerged as the most common bacterial pathogen for meningitis in all age groups, beyond the neonatal period. Objective To determine the epidemiological and clinical characteristics; and risk factors for mortality of pneumoccocal meningitis in children in a developing transitional country. Materials and methods A retrospective study that included patients <15 years of age admitted at the Instituto de Medicina Tropical of Paraguay, from January 1990 until December 2003 with the diagnosis of bacterial meningitis caused by S. pneumoniae. Clinical and laboratory data were collected and analysed in order to identify risk factors associated with morbidity and mortality outcomes of this infection. Results Seventy-two patients (between the ages of 35 days and 14 years) were identified. Forty-two per cent of patients had seizures prior to or at the time of admission, 36% were admitted in a comatose state, and 19% with shock. Mortality was 33% (24/72), and 18% of the survivors (11/60) developed severe sequelae. Upon admission, the following variables were strongly correlated with mortality: age <12 months (P = 0.007), the presence of seizures (P = 0.0001) or development of seizures 48 h after admission (P = 0.01), a cerebrospinal fluid (CSF) glucose level of <10 mg/dl (P = 0.01), CSF albumin >200 mg/dl (P = 0.0003), an absolute blood neutrophil count <2000/mm³ (P = 0.006) and a haemoglobin value of <9 g/dl (P = 0.0001). Conclusions This study confirms the high morbidity and mortality associated with S. pneumoniae meningitis in Paraguay. Certain clinical parameters and laboratory findings in blood and CSF at the time of admission could be used as predictors for mortality or severe sequelae among survivors.     

Clinical study of 33 children with systemic pneumococcal infections]

We retrospectively analyzed 33 cases of children with systemic pneumococcal infections, 22 bacteremia and 11 meningitis, diagnosed and treated in Asahi General Hospital between 1985 and 1999. The median age at diagnosis was 15 months old and the incidence peaked in infants between 7 and 24 months of age (57.6%). Two cases showed low serum IgG2 levels. Fever was a common symptom in all cases and 13 (39.4%) presented convulsions. Meningitis [median age: 10 months] tended to occur, if not significant, in younger children than bacteremia [16 months]. All cases of meningitis were diagnosed 12 hours or later after the onset of fever, though 54.5% of the cases of bacteremia were diagnosed within 12 hours. The cases of meningitis showed statistically lower white blood cell counts [median: 9,700/mm3] and higher CRP levels [median: 25.6 mg/dl] than those of bacteremia [23,900/mm3 and 4.2 mg/dl, respectively] at diagnosis. Although all cases of bacteremia were cured without any sequelae by antibiotic treatment, 3 cases (27.3%) of meningitis died and 4 (36.4%) developed severe neurological sequelae. Our findings suggest that the putative pathogenesis by which pneumococcal meningitis results from bacteremia and, taking in the account of the poor outcome of meningitis, may justify the early antibiotic intervention against pneumococcal bacteremia.     

Increased risk for invasive pneumococcal diseases in children with acute lymphoblastic leukaemia

Asplenia and other conditions of immunodeficiency are established risk factors for invasive pneumococcal disease (IPD). There are no current data available on the risk of IPD in children with acute lymphoblastic leukaemia (ALL), the most common type of childhood malignancy. This study combined data from a nation-wide surveillance for IPD and the German childhood cancer registry, and showed that children with ALL carry a more than 10-fold higher risk for IPD than the general paediatric population. As a substantial proportion of IPD occurs during maintenance chemotherapy, children with ALL may represent candidates for the evaluation of prophylactic interventions including vaccination.     

Dynamics of pneumococcal carriage among healthy Icelandic children attending day-care centres

Invasive pneumococcal disease and antimicrobial (AM) resistance in pneumococci are important public health concerns. With the advent of new pneumococcal vaccines, information on serotype prevalence and their temporal fluctuations is important. Information on AM use and consent for participation was obtained by a questionnaire to parents of children at 5 day-care centres in Reykjavik from 1992 to 1999, and nasopharyngeal swabs were cultured selectively for pneumococci. The pneumococci were serotyped and pulsed field gel electrophoresis used to determine clonality. Of 1228 nasopharyngeal swabs, 640 (52.1%) yielded pneumococci of which 89 (13.9%) had decreased susceptibility to penicillin and 1 was resistant. Children receiving AMs during the month preceding nasopharyngeal sampling and children attending a day-care centre where AM use was high were significantly more likely to carry penicillin non-susceptible isolates. Serotypes 6A, 6B and 23F were most common (48%), and 74% of serotyped isolates belonged to 1 of the 7 most common serotypes. Almost all penicillin non-susceptible isolates were of serotype 6B or 19A. Serotype prevalence fluctuated markedly between y. In conclusion, there was significant variation in serotype prevalence between y, and only 51% of the pneumococci belonged to serotypes covered by the current 7-valent conjugated vaccine.