IgG and IgM Antibody Responses to Pneumococcal Vaccination in Splenectomized Children and in Children Who Had Non-Operative Management of Splenic Rupture

ABSTRACT. The IgG and IgM type specific anticapsular pneumococcal antibody titres were studied with ELISA during one year following vaccination with a 14-valent pneumococcal polysaccharide vaccine in four different patient groups: 41 children splenectomized after a traumatic rupture, 16 splenectomized because of disease, 15 non-surgically managed after splenic rupture, and 19 healthy controls. Serum samples were obtained before vaccination and after 14, 60, 180, and 360 days. The IgG antibody responses were equally good in all of the patient groups, while the IgM antibody responses were less pronounced in the splenectomized. In the non-surgically managed patients, the IgM antibody titres after vaccination, as well as antibody responses per se, were significantly higher for all 12 pneumococcal types studied than in the patients who were splenectomized. Both the IgG and the IgM antibody titres were highest at 14 days after vaccination. However, while the IgG titres for most pneumococcal types remained elevated at 360 days, the IgM titres soon fell to prevaccination levels. The antibody response was less good for the types 3 and 6 A. The results indicate that the IgG antibody response to pneumococcal polysaccharide vaccination is unaffected in splenectomized individuals, but the IgM antibody response is decreased. In patients with a healed traumatically damaged spleen, both the IgG and IgM responses seem to be normal.     

ANTIBODY RESPONSE TO VACCINATION WITH PNEUMOCOCCAL CAPSULAR POLYSACCHARIDES IN SPLENECTOMIZED CHILDREN

ABSTRACT. In 67 splenectomized children vaccinated with a 14-valent pneumococcal capsular polysaccharide vaccine an antibody fold increase above 2 from pre- to postvaccination samples was found in 60 % of all single type antibody determinations performed. The vaccine may only afford protection against 55 % of those serotypes that cause serious infections in children, assuming a protective antibody level of 300 ng antibody N/ml. Our results indicate a somewhat reduced antibody response to pneumococcal vaccine in splenectomized children and suggest that pneumococcal vaccination may not be relied upon as the only kind of prophylaxis against pneumococcal infection in this patient group.     

Pneumococcal Infections in Splenectomized Children Are Preventable

ABSTRACT. Through the Danish National Patient Registry we identified all children 0–15 years old who had been splenectomized during the period 1979–87 and all children of the same age who, during the same period of time, had been admitted to a hospital because of either meningitis or bacteraemia caused by Streptococcus pneumoniae. We wanted to see whether any of the splenectomized children had developed invasive pneumococcal infection during the observation period.
A similar Danish study covering the period 1969–78, when pneumococcal vaccine was not available, has already been published (3). Four per cent of the children splenectomized during that period developed invasive pneumococcal infection in contrast to none of the children splenectomized and vaccinated during the period 1979–87. Since 1982 antibiotic treatment of splenectomized patients running a fever has been recommended, and we show that the program of pneumococcal vaccination and defined antibiotic prophylaxis has been highly efficacious in preventing post-splenectomy infections in children.     

IgG and IgM antibody responses to pneumococcal vaccination in splenectomized children and in children who had non-operative management of splenic rupture

The IgG and IgM type specific anticapsular pneumococcal antibody titres were studied with ELISA during one year following vaccination with a 14-valent pneumococcal polysaccharide vaccine in four different patient groups: 41 children splenectomized after a traumatic rupture, 16 splenectomized because of disease, 15 non-surgically managed after splenic rupture, and 19 healthy controls. Serum samples were obtained before vaccination and after 14, 60, 180, and 360 days. The IgG antibody responses were equally good in all of the patient groups, while the IgM antibody responses were less pronounced in the splenectomized. In the non-surgically managed patients, the IgM antibody titres after vaccination, as well as antibody responses per se, were significantly higher for all 12 pneumococcal types studied than in the patients who were splenectomized. Both the IgG and the IgM antibody titres were highest at 14 days after vaccination. However, while the IgG titres for most pneumococcal types remained elevated at 360 days, the IgM titres soon fell to prevaccination levels. The antibody response was less good for the types 3 and 6 A. The results indicate that the IgG antibody response to pneumococcal polysaccharide vaccination is unaffected in splenectomized individuals, but the IgM antibody response is decreased. In patients with a healed traumatically damaged spleen, both the IgG and IgM responses seem to be normal.     

Pneumococcal infections in splenectomized children are preventable

Through the Danish National Patient Registry we identified all children 0-15 years old who had been splenectomized during the period 1979-87 and all children of the same age who, during the same period of time, had been admitted to a hospital because of either meningitis or bacteraemia caused by Streptococcus pneumoniae. We wanted to see whether any of the splenectomized children had developed invasive pneumococcal infection during the observation period. A similar Danish study covering the period 1969-78, when pneumococcal vaccine was not available, has already been published (3). Four per cent of the children splenectomized during that period developed invasive pneumococcal infection in contrast to none of the children splenectomized and vaccinated during the period 1979-87. Since 1982 antibiotic treatment of splenectomized patients running a fever has been recommended, and we show that the program of pneumococcal vaccination and defined antibiotic prophylaxis has been highly efficacious in preventing post-splenectomy infections in children.     

Invasive pneumococcal disease in Danish children, 1996-2007, prior to the introduction of heptavalent pneumococcal conjugate vaccine

Aim: The aim of this study was to document the epidemiology, microbiology and outcome of invasive pneumococcal disease (IPD) among children <16 years with quality surveillance data, just prior to the introduction of the heptavalent pneumococcal conjugate vaccine (PCV7) into the Danish routine immunization programme October 2007.
Methods: Clinical and microbiological records on cases of IPD in children <16 years admitted to Hvidovre Hospital, Denmark 1996–2007, were retrospectively reviewed.
Results: We identified 106 cases of IPD. The annual incidence of IPD was 11 per 100 000 in children <16 years, but considerably higher, 62 per 100 000, in children <2 years. Additionally, of the children with pneumococcal meningitis 86% were <2 years. We observed no fatalities. A total of 10% developed sequelae, but of the patients with pneumococcal meningitis 27% developed sequelae. Nine patients had known risk factors. The Streptococcus pneumoniae serotype was available for 81 cases. Seventy-five percent of the IPD cases in children aged <2 years were caused by one of the serotypes contained within PCV7, compared to only 24% in children ≥2 years.
Conclusion: Our data indicate that an estimated 75% of all IPD cases among children <2 years are caused by PCV7 serotypes and might therefore be prevented by PCV7 vaccination.     

Pneumococcal revaccination of splenectomized children

Forty-three Danish splenectomized children received a single subcutaneous dose of a 14-valent pneumococcal vaccine (Pneumovax 23; Merck). Blood samples were taken before, 4 weeks after and 5 years after vaccination. Total pneumococcal antibody concentrations as well as antibodies against each of the 14 pneumococcal capsular polysaccharide antigens were measured by the enzyme-linked immunosorbent assay method. Depending on the pneumococcal antibody status 5 years after primary vaccination, the children were either revaccinated with a new 23-valent pneumococcal vaccine or scheduled for reexamination later. The antibody concentrations found 5 years after vaccination showed a strong correlation with the prevaccination antibody concentrations. Revaccination of children with low antibody concentrations 5 years after primary vaccination is safe, is without significant side effects and leads to a satisfactory antibody response.     

Effect of the pneumococcal conjugate vaccine on pneumococcal carriage in Turkish children

Background: The aim of our study was to evaluate the effect of the seven‐valent pneumococcal conjugate vaccine which has recently been included in the national immunization schedule on the nasopharyngeal carriage of Streptococcus pneumoniae in a group of healthy Turkish children. This is the first study determining the efficacy of this vaccine in Turkey. Methods: One hundred and thirty‐eight children who had completed their pneumococcal vaccination series and 109 unvaccinated control subjects aged 12–59 months were included in the study between October 2007 and April 2008. A single nasopharyngeal swab sample was obtained from each subject. Results: S. pneumoniae was isolated in 32 (12.9%) of 247 subjects. No significant differences were detected in pneumococcal carriage rate between the vaccinees and controls (10.1% vs 16.5%). Prevalence of vaccine type (VT) carriage was statistically lower in the vaccinated group than the controls while non‐vaccine type carriage (NVT) was similar. Most frequently isolated vaccine serotype was 23F in the vaccinated group and 19F in the non‐vaccinated group. Of the isolated S. pneumoniae, 13.3% were penicillin susceptible and 86.7% were non‐susceptible. Vaccinees and controls did not differ statistically with respect to carriage rate of penicillin‐resistant S. pneumoniae. All the pneumococcal isolates were susceptible to ceftriaxone, vancomycin, rifampicin and quinolones. Conclusion: Seven‐valent conjugate vaccine induces long‐term protection against carriage of VT S. pneumoniae in Turkish children. The ability of the conjugate vaccine to reduce transmission of antibiotic resistant S. pneumoniae may be possible if its introduction is coupled with a reduction in inappropriate use of antibiotics.     

New opportunity for vaccinating older people: Well‐child clinic visits

Background: Streptococcus pneumoniae causes considerable morbidity and mortality in the elderly. As aging of the population is making the health of the elderly a universal priority, preventive measures, such as vaccination, will become increasingly important. Methods: We designed a prospective interventional study to determine whether recommendations to vaccinate grandparents of children attending well‐child clinics would increase the pneumococcal vaccination rate in the elderly. Children younger than 5 years of age, attending a university well‐child clinic from 1 May to 31 September 2008 who had grandparents over 65 years of age were eligible. A survey including the questions about the demographic characteristics of children, their parents and grandparents over 65 was carried out by face‐to‐face interview with the parents. High‐risk medical conditions and vaccination history of grandparents was also noted and the benefits and necessity of pneumococcal vaccination (23vPPV) for the elderly was emphasized. Four months later these families were contacted to determine whether this intervention had increased the pneumococcal vaccination rates of the elderly. Results: Information was obtained from 938 grandparents of 545 children. Before the interview, among all grandparents, only 0.9% were vaccinated with 23vPPV. Four months after this intervention, immunization coverage increased to 19.1%. The sex of the grandchild (OR: 1.99) and previous hepatitis B or influenza immunization of the grandparents (OR: 2.73) were the significant parameters accounting for higher immunization rates. Conclusion: Reminding elderly grandparents about vaccines in well‐child clinics could be an opportunity in this field.     

儿童肺炎链球菌坏死性肺炎临床特点分析

目的：总结肺炎链球菌所致坏死性肺炎的临床特点。方法选取2008年1月至2011年4月本院儿科临床诊断肺炎链球菌肺炎且影像学证实有坏死性病变者15例。收集临床资料,总结其性别、年龄、最高体温、住院时间、发热时间、肺部影像学特征及白细胞、C-反应蛋白水平,应用纸片扩散法和最小抑菌浓度法分别对15株及其中11株肺炎链球菌进行药敏试验,对各药耐药率、敏感率进行分析。结果15例患儿中,发热、胸腔积液15例,有肺外并发症1例;X线胸片或肺CT表现右肺病变者7例,左肺7例,双肺同时坏死性病变1例。所有病例均有外周血白细胞及C-反应蛋白升高。临床分离肺炎链球菌对万古霉素、利奈唑胺、利福平、左氧氟沙星敏感性高,对青霉素耐药率比较严重,而对红霉素和克林霉素普遍耐药。平均住院时间为39 d,无死亡病例。结论儿童肺炎链球菌坏死性肺炎临床过程延长,耐药严重,症状重,易并发胸腔积液,但通过积极治疗,预后较良好。     

Increase in invasive nonvaccine pneumococcal serotypes at two hospitals in Barcelona: was replacement disease to blame?

Aim: To describe an increase in the incidence of invasive pneumococcal disease (IPD) caused by serotypes not contained in the heptavalent pneumococcal conjugate vaccine (PCV7) in children in two hospitals in Barcelona with different vaccine uptake. Methods: Cumulative incidences of IPD, vaccine and nonvaccine serotypes (NVSTs), and main clinical presentations before (1998–2001) and after vaccine introduction (2005–2008) were compared. Results: The incidence of IPD in children aged <2 years at Hospital Germans Trias i Pujol covering a population in which PCV7 was not widely used showed a nonsignificant increase from 29.9 to 58.8 per 100 000 child‐years between both periods. Following vaccine introduction, there was a 2.5‐fold increase in IPD caused by NVSTs in children aged <5 years. Analysis of trends in the almost fully vaccinated population of Hospital de Barcelona revealed a nonsignificant reduction in IPD incidence in children aged <2 years from 63.1 to 26.0 per 100 000 child‐years. NVSTs in children aged <5 years showed a nonsignificant 1.7‐fold increase in the vaccine period at this centre. Conclusions: The paradoxical increase in invasive infections caused by NVSTs in these populations with different vaccine use suggests that these changes were not driven only by PCV7.     

Ten years of pneumococcal‐associated haemolytic uraemic syndrome in New Zealand children

Aim: To describe the epidemiology, clinical features, management and outcome of pneumococcal‐associated haemolytic‐uraemic syndrome (P‐HUS) in New Zealand over the past decade. Methods: A retrospective chart review of children with P‐HUS from 1998 to 2007 that were prospectively reported to the New Zealand Paediatric Surveillance Unit. P‐HUS was defined as microangiopathic haemolytic anaemia (Hb <100 g/L with fragmented red blood cells), thrombocytopaenia (platelet count <130 × 10⁹/L), acute renal impairment with oliguria and elevated plasma creatinine, and confirmed or suspected pneumococcal infection. Results: Eleven children (nine male, two female), predominately Maori and Polynesian (10 children) were studied. The median age was 8.5 months. The median duration of hospitalisation was 25 days. Of the infections, 10 were confirmed pneumococcal (six pneumonia, four meningitis) and one pneumonia was suspected pneumococcal (culture negative, however T activation positive). Nine patients required dialysis for a median duration of 13 days. One child with meningitis died after therapy was withdrawn because of severe neurological injury. One patient developed end stage kidney disease and two further children had evidence of persisting renal sequelae at follow‐up. Conclusions: Pneumococcal disease remains an important public health problem in New Zealand children, particularly those of Maori and Pacific Island ethnicity. P‐HUS should be considered in pneumococcal disease associated with severe haematological and renal abnormalities. These children should be monitored long‐term, as they are at risk of permanent renal injury.     

Adverse reactions to simultaneous influenza and pneumococcal conjugate vaccinations in children: randomized double-blind controlled trial

In a randomized double-blind controlled trial, the safety was assessed of simultaneous administration of influenza and pneumococcal conjugate vaccines in children with previous physician-diagnosed respiratory tract infections. In total, 579 children aged 18–72 months were assigned to receive simultaneous intramuscular influenza and pneumococcal heptavalent conjugate vaccinations (IV + PV), influenza and placebo vaccinations (IV + plac) or control hepatitis B and placebo vaccinations (HepB + plac) in separate extremities. Local and systemic adverse events were recorded in parental diaries for 7 days after vaccination. No immediate adverse reactions were recorded. In most children local adverse reactions disappeared 2 days after vaccination. Local and systemic reactions were more prevalent (30% and 10% more) in the IV + PV group compared with the IV + plac and HepB + plac group. These results are important for designing future vaccination schedules.     

Update on the success of the pneumococcal conjugate vaccine

Several years after the seven-valent pneumococcal conjugate vaccine (PCV7) was introduced in Canada and elsewhere, routine infant vaccination has led to near eradication of invasive pneumococcal disease caused by vaccine serotype strains in both children and adults. There have also been significant declines in pneumococcal-related disease including lobar pneumonia and otitis media. These declines have been offset, to some extent, by increases in nonvaccine serotype disease. Serotype 19A, which is often highly resistant to antibiotics, has become predominant. In most populations, however, the magnitude of replacement disease is much lower than the magnitude of decline in invasive pneumococcal disease with the use of PCV7. There is increasing evidence that three PCV7 doses provide protection that is nearly identical to that of four doses. New 10-valent and 13-valent pneumococcal conjugate vaccines were recently approved in Canada. These vaccines increase pneumococcal serotype coverage including serotype 19A (present in the 13-valent vaccine). Many provinces and territories have incorporated the 13-valent vaccine in their vaccination programs.     

Invasive pneumococcal disease in the Australian Capital Territory and Queanbeyan region: Do high infant rates reflect more disease or better detection?

OBJECTIVE: To describe the epidemiology of invasive pneumococcal disease in the Australian Capital Territory (ACT) and Queanbeyan region prior to the introduction of conjugate pneumococcal vaccines. METHODOLOGY: Residents with sterile site isolates of Streptococcus pneumoniae from 1998 to 2000 were identified from a prospective bacteraemia surveillance project involving all ACT public hospitals, supplemented by retrospective laboratory-based detection of other sterile site isolates. RESULTS: Incidence of invasive pneumococcal disease was 15.2 cases per 105 per year, and 193.4 per 105 per year in infants under 2 years. Primary bacteraemia was significantly more common in infants and young children than in older subjects. Reduced penicillin susceptibility was observed in 9.6% of isolates, and no high-level penicillin resistance was observed. CONCLUSIONS: Infants in the ACT and Queanbeyan have a higher invasive pneumococcal disease incidence than similar populations worldwide. Better detection is the most likely explanation. This population would be ideal for studies of the 'real life' effectiveness of infant conjugate vaccination.     

Current issues regarding the use of pneumococcal conjugate and polysaccharide vaccines in Australian children

OBJECTIVE: To present the results of child pneumococcal vaccination studies in the setting of current Australian disease epidemiology and immunization policy, and issues that clinicians should consider in discussions with families. METHODS: This paper includes a narrative review of randomized, controlled, double blind studies and systematic reviews which evaluated the efficacy of child pneumococcal vaccination. RESULTS: 7PCV is expected to prevent > 80% of childhood invasive pneumococcal disease (IPD, includes meningitis, septicaemia/bacteraemia) and the associated mortality. 7PCV may prevent 6% of all pneumonia, 18% of radiographically-defined pneumonia, 6% of all otitis media (OM) and 20%-40% of tympanostomy tube procedures. It may also reduce IPD due to antibiotic-resistant pneumococci, and prevent IPD in unvaccinated individuals. The impact of replacement disease caused by non-vaccine serotypes is not yet known. Pneumococcal polysaccharide vaccines given to 2-year-old children may prevent approximately 19% of all and 26% of recurrent OM. CONCLUSION: The Australian Standard Vaccination Schedule recommends universal infant immunization with seven-valent pneumococcal conjugate vaccine (7PCV). Universal infant 7PCV will prevent pneumococcal diseases and deaths. The potential for its impact to be reduced in the long-term by serotype replacement must be closely monitored. Information concerning disease epidemiology, vaccine efficacy and safety, disease risk perception and national costs may prove useful in discussions with families.     

Fulminating pneumococcal septicemia in children

Three cases of fulminating pneumococcal septicemia are reported in children aged respectively 3 months, 21 months and 6 years 1 month. The third patient only have been previously splenectomized for traumatic rupture of the spleen. This patient recovered when the two others with an expected normal spleen died quickly. The fulminating pneumococcal septicemia is characterized by the association of severe infection state, collapse and hemorrhagic syndrome with often gastric bleeding. Fatal outcome is observed in 50 to 70% of cases. Most cases occur in asplenic patients that can be explained by the role of the spleen in the infectious defense. This can be prevented by vaccination or penicillin but failure has been observed with both methods. Normal spleen, as observed in two of our patients seems to be rare. Functional hyposplenism might explain such facts.     

Epidemiology of invasive and other pneumococcal disease in children in England and Wales 1996–1998

The results of enhanced national surveillance of pneumococcal disease in children <15y of age in England and Wales are reported for the period 1996–1998. Of the 1985 cases of laboratory-confirmed invasive disease (annual incidence 6.6 per 100000 overall and 39.7 per 100000 in infants <1 y of age), 485 (24%) were meningitis (annual incidence of 1.6 per 100000 overall and 15.7 per 100000 in infants <1 y of age). Fifty-nine deaths in children with invasive disease were identified-3% of the total reports. Thirty-one different serogroups/types were identified, with organisms in the 7-valent conjugate vaccine responsible for 69% of the infections in children <5 y of age; this rose to 77% and 82%, respectively, for the 9-and 11-valent vaccines. Resistance to penicillin varied from 2.3% to 6.2% in different years, but erythromycin resistance remained constant at 17%. The vast majority of resistant isolates were in vaccine serotype/groups. Computerized hospital admission records for all children <15 y of age with a discharge diagnosis code indicating probable pneumococcal disease were also analysed for 1997. The annual incidence for cases with a code specifically mentioning S. pneumoniae was 9.9 per 100000 compared with 71.2 per 100000 for lobar pneumonia; the mean duration of stay for both was < 1 wk. The incidence of admission for pneumococcal meningitis (1.9 overall and 19.6 for infants < 1 y of age) was similar to that derived from laboratory reports and resulted in an average duration of stay of 2 wk.
Conclusion : This surveillance has confirmed the substantial burden of morbidity attributable to pneumococcal disease in British children and the potential public health benefits that could be achieved by the use of pneumococcal conjugate vaccines.     

The epidemiology of invasive pneumococcal disease in children in Far North Queensland

OBJECTIVES: To describe the epidemiology of invasive pneumococcal disease in children under 5 years of age in Far North Queensland and to examine the potential impact of a seven- and 11-valent conjugate pneumococcal vaccine. METHODS: A review of all cases of invasive pneumococcal disease in children under 5 years of age in Far North Queensland over a 9 year period (1992-2000). The distribution of the serotypes of isolates causing invasive pneumococcal disease was compared with the serotypes contained in the two vaccines. RESULTS: The annual incidence in indigenous and non-indigenous children under 5 years of age was 163 (95% confidence interval (CI) 122-213) and 42 (95% CI 31-55) cases per 100 000 children, respectively. For children under 2 years of age, these figures were 297 (95% CI 208-411) and 71 (95% CI 49-100), respectively. There was a greater variety of serotypes isolated from indigenous children (n=17) than from non-indigenous children (n=9; P < 0.01). The serotypes within the seven-valent vaccine accounted for 62% (95% CI 46-75%) and 88% (95% CI 76-95%) of the isolates from indigenous and non-indigenous children, respectively (P < 0.01). Serotypes within the 11-valent vaccine accounted for 72% (95% CI 57-84%) of the isolates from indigenous children under 5 years of age, but did not account for any extra isolates from non-indigenous children. CONCLUSION: Although the seven- and 11-valent conjugate pneumococcal vaccines cover only approximately 60 and 70%, respectively, of the isolates that cause invasive disease in indigenous children in Far North Queensland, they nevertheless have the potential to prevent much morbidity in and hospitalization of these children. It will be essential to maintain surveillance following the introduction of conjugate pneumococcal vaccines so as to monitor changes in the incidence of invasive pneumococcal disease, particularly in high-risk children.     

Invasive pneumococcal infections in pediatric liver‐small bowel‐pancreas transplant recipients

Children undergoing LSBPTx are at increased risk of IPI due to splenectomy. We aimed to describe the clinical features and outcomes of IPI in pediatric LSBPTx recipients. Between 2008 and 2016, 122 LSBPTx children at our center were retrospectively reviewed. Nine patients had 12 episodes of IPI; the median age at first infection was 3.5 years (range: 1.5‐7.1 years). The median time from transplant to first infection was 3 years (range: 0.8‐5.8 years). Clinical presentation included as follows: pneumonia (n = 1), bacteremia/sepsis (n = 7), pneumonia with sepsis (n = 1), meningitis with sepsis (n = 2), pneumonia and meningitis with sepsis (n = 1). The overall risk for IPI was 7.4% or 0.9% per year. The mortality rate was 22%. Seven (78%) children had received at least one dose of PCV13, four (44%) patients had received 23‐valent pneumococcal polysaccharide vaccine prior to IPI. All patients were on oral penicillin prophylaxis. In conclusion, despite partial or complete pneumococcal immunization and reported antimicrobial prophylaxis, IPI in LSBPTx children can have a fatal outcome. Routine monitoring of pneumococcal serotype antibodies to determine the timing for revaccination might be warranted to ensure protective immunity in these transplant recipients.