Pediatric Invasive Pneumococcal Disease Research Articles

Pediatric Invasive Pneumococcal Disease in the United States in the Era of Pneumococcal Conjugate Vaccines

Invasive infections caused by Streptococcus pneumoniae continue to be a major cause of morbidity and mortality worldwide, especially in children under 5 years of age. In the United States, 90% of invasive pneumococcal infections in children are caused by 13 serotypes of S. pneumoniae. The licensure (in 2000) and subsequent widespread use of a heptavalent pneumococcal conjugate vaccine (PCV7) have had a significant impact on decreasing the incidence of serious invasive pneumococcal disease (IPD) in all age groups, especially in children under 2 years of age. However, the emergence of replacement non-PCV7 serotypes, especially serotype 19A, has resulted in an increase in the incidence of serious and invasive infections. In 2010, a 13-valent PCV was licensed in the United States. However, the impact that this vaccine will have on IPD remains to be seen. The objectives of this review are to discuss the epidemiology of serious and invasive pneumococcal infections in the United States in the PCV era and to review some of the pneumococcal vaccines that are in development.

Use of the 13-valent conjugate vaccine has the potential to eliminate pilus carrying isolates as causes of invasive pneumococcal disease

We examined the distribution of the two pilus island loci (PI-1 and PI-2) in all pediatric invasive pneumococcal disease (IPD) isolates recovered in Portugal over the ten year period 1999–2008 (n=575). While 199 isolates (35%) harbored PI-2, only 98 isolates (17%) harbored PI-1. A decline of isolates carrying PI-1 was observed in the post 7-valent conjugate vaccine (PCV7) period since most PI-1 carrying isolates expressed PCV7 serotypes. On the other hand, the PI-2 increase in the post-PCV7 period was associated mostly with serotypes 1 and 7F. The overall proportion of piliated isolates declined in the period following PCV7 but quickly recovered to pre-PCV7 levels (50%). Only serotypes 19F and 19A contained isolates carrying simultaneously PI-1 and PI-2 and the proportion of isolates carrying both pilus islands remained stable and low. All PI-1 clades were represented in our collection and were associated with multiple serotypes. Over 99% of pilus island carrying isolates belonged to the 13-valent conjugate vaccine serotypes.

PspA Family Distribution, unlike Capsular Serotype, Remains Unaltered following Introduction of the Heptavalent Pneumococcal Conjugate Vaccine

Pneumococcal conjugate vaccines (PCVs) are recommended for the prevention of invasive pneumococcal disease (IPD) in young children. Since the introduction of the heptavalent pneumococcal vaccine (PCV7) in 2000, IPD caused by serotypes in the vaccine has almost been eliminated, and previously uncommon capsular serotypes now cause most cases of pediatric IPD in the United States. One way to protect against these strains would be to add cross-reactive protein antigens to new vaccines. One such protein is pneumococcal surface protein A (PspA). Prior to 2000, PspA families 1 and 2 were expressed by 94% of isolates. Because PCV7 vaccine pressure has resulted in IPD caused by capsular serotypes that were previously uncommon and unstudied for PspA expression, it was possible that many of the new strains expressed different PspA antigens or even lacked PspA. Of 157 pediatric invasive pneumococcal isolates collected at a large pediatric hospital in Alabama between 2002 and 2010, only 60.5% had capsular serotypes included in PCV13, which came into general use in Alabama after our strains were collected. These isolates included 17 serotypes that were not covered by PCV13. Nonetheless, pneumococcal capsular serotype replacement was not associated with changes in PspA expression; 96% of strains in this collection expressed PspA family 1 or 2. Continued surveillance will be critical to vaccine strategies to further reduce IPD.

The Burden of Infant Meningococcal Disease in the United States.

In the United States, invasive meningococcal disease occurs at the highest rates in infants, with a second peak in adolescents. Early symptoms are nonspecific and may resemble viral infection, which poses a diagnostic challenge for clinicians. Moreover, the stakes of diagnostic confusion may be high because the disease may become life threatening within hours. Sequelae among survivors may be profound. In adolescent age groups, control of meningococcal disease caused by serogroups A, C, W-135, and Y rests upon universal vaccination beginning at 11–12 years of age; vaccines for serogroup B are not currently available. One 4-valent vaccine is licensed for use in infants beginning at 9 months of age but is only recommended for those at high risk. Licensure of new vaccines for infants is expected soon, and a universal immunization program is being debated. A wide range of bacteria can cause meningitis in infants and young children. In neonates aged <3 months, group B streptococcus causes most bacterial meningitis in many developed countries, followed by Escherichia coli and other Gram-negative enteric bacilli. Listeria monocytogenes can also be seen in this age group [1]. Historically, for infants and children aged <5 years, the 3 most common causes of bacterial meningitis and sepsis were Haemophilus influenzae type b (Hib), Streptococcus pneumoniae, and Neisseria meningitidis [1]. Annual disease cases due to Hib in US children aged <5 years have been reduced by 99%, and there has been a substantial decline in pediatric invasive pneumococcal disease due to routine infant immunization programs introduced in the 1990s and 2000s [2, 3]. This leaves N. meningitidis as one of the most important causes of bacterial meningitis in infants and young children. Since 2005, the Centers for Disease Control and Prevention's (CDC's) Advisory Committee on Immunization Practices (ACIP) has recommended routine vaccination against N. meningitidis for all adolescents; recommendations for vaccination of children aged 9 months–10 years are restricted to high-risk groups [4–10]. At the present time, there are no meningococcal conjugate vaccines licensed for use in infants aged <9 months, although there are vaccines currently under review by the Food and Drug Administration (FDA). This article discusses the burden of meningococcal disease in infants in order to provide a backdrop for considering prevention strategies.

Serotype 3 is a common serotype causing invasive pneumococcal disease in children less than 5 years old, as identified by real-time PCR

Serotype 3 is one of the most often detected pneumococcal serotypes in adults and it is associated with serious disease. In contrast, the isolation of serotype 3 by bacterial culture is unusual in children with invasive pneumococcal disease (IPD). The purpose of this study was to learn the serotype distribution of IPD, including culture-negative episodes, by using molecular methods in normal sterile samples. We studied all children<5 years of age with IPD admitted to two paediatric hospitals in Catalonia, Spain, from 2007 to 2009. A sequential real-time polymerase chain reaction (PCR) approach was added to routine methods for the detection and serotyping of pneumococcal infection. Among 257 episodes (219 pneumonia, 27 meningitis, six bacteraemia and five others), 33.5% were identified by culture and the rest, 66.5%, were detected exclusively by real-time PCR. The most common serotypes detected by culture were serotypes 1 (26.7%) and 19A (25.6%), and by real-time PCR, serotypes 1 (19.8%) and 3 (18.1%). Theoretical coverage rates by the PCV7, PCV10 and PCV13 vaccines were 10.5, 52.3 and 87.2%, respectively, for those episodes identified by culture, compared to 5.3, 31.6 and 60.2% for those identified only by real-time PCR. Multiplex real-time PCR has been shown to be useful for surveillance studies of IPD. Serotype 3 is underdiagnosed by culture and is important in paediatric IPD.

Streptococcus pneumoniae serotypes in Utah adults at the end of the PCV7 era

While heptavalent pneumococcal conjugate vaccine (PCV) has decreased vaccine type invasive pneumococcal disease (IPD) nationwide, rapid serotype replacement and increasing parapneumonic empyema, has been reported in Utah children. The effect of pediatric vaccination on adults in this population is unknown. We identified 117 adults with IPD from the Intermountain Healthcare Central Laboratory between November 2009 and October 2010. We serotyped 61 (52%) stored isolates. We compared the serotype distribution of adult IPD isolates with that of pediatric isolates collected in 2009-2010. PCV7 serotypes were rare in adults (3%) and children (3%). Emerging 13-valent PCV serotypes 3, 7F, and 19A caused the majority of IPD in adults (63%) and children (56%). Fifty-one (84%) adult isolates were serotypes included in 23-valent polysaccharide vaccine and 66% in PCV13. Adult and pediatric IPD serotypes are closely associated in Utah. PCV13 vaccination in Utah children is likely to significantly impact IPD in Utah adults.

Changing Serotypes Causing Childhood Invasive Pneumococcal Disease

Heptavalent pneumococcal conjugate vaccine (PCV7) was licensed in the United States in February 2000 and distributed in Massachusetts, starting in July 2000 for universal administration to children <2 years of age and selected use in children 2 to 5 years of age. Statewide surveillance was begun in October 2001 to monitor incidence of invasive disease, serotypes causing disease, antimicrobial susceptibility, and risk features associated with ongoing childhood invasive pneumococcal disease (IPD). Massachusetts pediatric IPD cases were identified via enhanced passive surveillance of microbiology laboratory reports of pneumococcal isolates from sterile body sites of children <18 years. Serotyping and antimicrobial susceptibility testing were performed on isolates of Streptococcus pneumoniae from normally sterile body fluid. Demographic and clinical data, were collected via follow-up telephone interviews with primary care providers. Incidence rates were derived using Census 2000 denominators. A total of 586 IP cases were reported between October 2001 and September 2007. Among 433 (74%) cases with isolates available for serotyping, 366 (85%) were caused by non-PCV7 serotypes and 67 (15%) were caused by PCV7 serotypes. 19A was the most common cause of any serotype identified episode of IPD (28%). IPD incidence was stable during the 6 study years because, although IPD cases due to PCV7-serotypes decreased, the incidence of non-PCV7 serotype IPD increased from 3.0 cases/100,000 children less than 18 years to a high of 5.3 cases/100,000 during 2005 to 06. Since 2005, ceftriaxone non-susceptible isolates comprised approximately 20% of isolates. There were 8 (1.4%) fatalities from IPD; 5 deaths occurred in children <1 year of age. Non-PCV7 serotype IPD, especially serotype 19A disease, increased during the 2001 to 2007 surveillance period in Massachusetts. The proportion of ceftriaxone non susceptible isolates also increased, particularly since 2005. Ongoing surveillance will be necessary to detect future increases in IPD incidence or antibiotic resistance in Massachusetts children, changes which have important implications for introduction of second generation pneumococcal conjugate vaccines and presumptive antibiotic choices in critically ill children.

Age‐ and Serotype‐Specific Pediatric Invasive Pneumococcal Disease: Insights from Systematic Surveillance in Santiago, Chile, 1994–2007

We monitored pediatric invasive pneumococcal disease (IPD) in Santiago, Chile, from 1994 to 2007. Three related data sets were generated: (1) IPD cases requiring hospitalization, 1994--2007; (2) cases of bacteremia detected among febrile patients aged 0-35 months seen in emergency departments, 2000--2007; and (3) nasopharyngeal carriage of pneumococcal serotypes, determined from repetitive culturing, among 524 newborns followed up through age 23 months. Of 2369 IPD cases requiring hospitalization, 1878 (79.3%) occurred in those aged 0-59 months, and 1200 (50.7%) occurred in those aged 6-35 months. Among infants aged 0-5 months, meningitis and sepsis comprised 48.4% of all IPD cases (serotype 5 predominated); among those 6-35 months old, 522 (43.5%) of 1200 cases were bacteremic pneumonia (serotype 14 predominated). Serotype 1 peritonitis was common among 5-14-year-old girls. Meningitis and sepsis exhibited high case fatality rates (14%-29%) among all ages. Remarkably, 34 (28.8%) of 118 children with sepsis died, versus 1 fatality (0.4%) among 276 children hospitalized with bacteremia without a focus (P < .001, Fisher's exact test). Serotype 5 was significantly more common among hospitalized patients < 36 months of age, whereas serotype 18C was overrepresented among ambulatory patients. The annual incidence of serotype 14 was stable; those of serotypes 1 and 5 fluctuated markedly. Serotypes 14, 5, and 1 were overrepresented among invasive compared with nasopharyngeal isolates. Clinical syndromes of IPD and predominant serotypes vary with age.

The incidence of pediatric invasive pneumococcal disease in Chiba prefecture, Japan (2003–2005)

The purpose of the study is to evaluate the incidence, spectrum of clinical manifestations and outcome of invasive pneumococcal disease (IPD) in children in Chiba prefecture, Japan. To determine the precise incidence of IPD in Chiba prefecture, we implemented a retrospective survey of the period from 2003 to 2005. A written questionnaire was sent to 45 hospitals that have pediatric wards, and information was obtained from all hospitals. The questionnaire included the clinical diagnosis, patient's age, underlying disease, prognosis and antimicrobial susceptibility of the isolated strains. During the 3 study years, 130 patients were diagnosed with IPD. The mean annual incidence rates of IPD among children <2 and <5 years were 19.5-23.8 and 12.6-13.8 per 100,000, respectively. Among 130 patients with systemic infection, 66 patients had bacteremia, 39 had pneumonia and 16 had meningitis. Five patients had neurological sequelae and 2 patients died. Seventy-four out of 115 isolates (64.3%) exhibited resistance to penicillin G. The annual incidence of pediatric IPD has remained constant during the study period. Two-third of isolated strains were at least partially resistant to penicillin G. Establishment of appropriate antibiotic therapy against IPD due to penicillin-resistant strains and the introduction of pneumococcal conjugate vaccines are emergent issues in Japan.

Invasive Pneumococcal Disease Among Human Immunodeficiency Virus-Infected Children, 1989–2006

The heptavalent pneumococcal conjugate vaccine (PCV7) has decreased the incidence of pediatric invasive pneumococcal disease (IPD) in the United States. Few data exist on the changing IPD incidence in HIV-infected children. Diagnostic codes and clinical microbiology laboratory records identified cases of IPD from 1989 to 2006 in perinatally-infected children <18 years of age followed at an urban HIV clinic. IPD incidence was calculated and serotype distribution and antibiotic resistance were recorded. Two-hundred fifty-six patients were followed for 1756 person-years (PY). The sample was 59% female, 76% black, 14% white, and 8% Hispanic. Of 21 episodes of IPD (1200/100,000 PY), 17 (81%) were female. IPD cases had a median age of 6.3 years (interquartile range [IQR]: 2.3-9.9 years), median CD4% of 17% (IQR: 11-28%), and median CD4 count of 415 cells/mm (range, 2-1699 cells/mm). Bacteremia was the commonest form of IPD (19 episodes; 1080/100,000 PY). After HAART introduction in 1996, the incidence of IPD decreased 84% from 1862/100,000 PY in 1989-1995 to 292/100,000 PY in 1997-1999 (incidence rate ratio [IRR]: 0.16, P = 0.03). After PCV7 introduction in 2000, IPD incidence showed a nonsignificant increase from 292 of 100,000 PY in 1997-1999 to 860 of 100,000 PY in 2001-2006 (IRR: 2.94; P = 0.16). The percentages of IPD isolates nonsusceptible to penicillin and trimethoprim-sulfamethoxazole were 19% and 33%, respectively. Vaccine serotypes accounted for 38% of isolates, vaccine-related 14%, nonvaccine 33%, and the serotype was unknown in 14%. The incidence of IPD among perinatally HIV-infected children decreased after the introduction of HAART. Ongoing monitoring is required to determine the effect of PCV7 on IPD in this vulnerable population.

Risk Factors for Pediatric Invasive Pneumococcal Disease in the Intermountain West, 1996–2002

In response to concerns that the epidemiology of pediatric invasive pneumococcal disease (IPD) in the Intermountain West (i.e., Utah, Idaho, Wyoming, Montana, and parts of Arizona and Nevada) was poorly understood and might differ from elsewhere in the United States, a case-control study was undertaken to determine factors associated with IPD during 1996-2002. A telephone questionnaire was administered to parents of children comprising 120 cases identified through hospital records and to parents of 156 age-matched controls located by random-digit dialing. The unit of analysis was each matched case-control set. Underlying chronic illness was reported for 32 (27%) of the cases. For previously healthy children, breastfeeding had a protective benefit (adjusted odds ratio: 0.2; 95% confidence interval [CI], 0.1-0.6), while a history of tympanostomy tube surgery was a risk factor (adjusted odds ratio: 12.6; 95% CI, 1.5-107.3). The presence of an underlying chronic illness was the strongest risk factor for IPD. Except for a history of tympanostomy tube surgery, the factors associated with IPD in this investigation were similar to those reported from other geographic regions. Tympanostomy surgery might serve as a surrogate indicator for predisposition to recurrent otitis media or decreased ability to clear pneumococcal infection, raising risk for invasive disease. Pediatric clinicians should continue to encourage breastfeeding, and continued emphasis on pneumococcal vaccination should help prevent IPD.

Reduction in pediatric invasive pneumococcal disease in the Basque Country and Navarre, Spain, after introduction of the heptavalent pneumococcal conjugate vaccine

This study evaluated the incidence of invasive pneumococcal disease, identified the causal serotypes, and tracked the evolution of the antibiotic susceptibility of Streptococcus pneumoniae isolates in the regions of the Basque Country and Navarre, Spain, before and after the introduction of the heptavalent pneumococcal conjugate vaccine. The study included all children aged between birth and 5 years diagnosed with bacteremia, meningitis, or bacteremic pneumonia caused by pneumococci. By the second year after introduction of the heptavalent pneumococcal conjugate vaccine, compared with the period 1998-2001, the incidence of invasive disease decreased by 64.3% in children less than 12 months of age, by 39.7% in children less than 24 months of age, and by 37.5% in children less than 60 months of age. The prevalence of clinical isolates of S. pneumoniae that lacked susceptibility to penicillin decreased by 58.2% among children less than 60 months of age. With an estimated coverage by four-dose heptavalent pneumococcal conjugate vaccine of 28-45% in 2003, the number of invasive pneumococcal infections in the Basque Country and in Navarre fell significantly after just 2 years of immunization, underscoring the importance of improving vaccination coverage under a universal childhood immunization program.

Burden of paediatric invasive pneumococcal disease in Europe, 2005

Within the European Union (EU), documenting the burden of invasive pneumococcal disease (IPD) in infants and children is important for coordinating effective pneumococcal immunization policies. Our objective was to document the burden of IPD in countries of the EU plus Switzerland and Norway. European affiliates of Wyeth Vaccines made available recent epidemiological data on IPD from local disease surveillance programmes, including unpublished sources. Recent literature and websites were also searched to provide as wide a representation as possible. This included OVID and abstracts from a number of international meetings, dating from the year 2000. The reported rates of paediatric IPD per 100000 (age) ranged from a low of 1.7 (<2 years) to 4.2 (2-15 years) in Sweden to a high of 93.5 to 174 (<2 years) to 56.2 (<5 years) in Spain. The percentage of circulating serotypes causing IPD that are covered by 7-valent pneumococcal conjugate vaccine (PCV) IPD serotype coverage ranged from 60% to 80% for European children aged <2 years. Under reporting, differences in reporting methods, antibiotic prescribing and disparities in blood-culturing practices may explain the differences in reported disease incidence. Because of the excellent clinical efficacy of the PCV against IPD, national pneumococcal vaccination programmes in Europe have the potential to prevent much morbidity and mortality.

Prevalence of Pneumococcal Bacteremia Among Children < 36 Months of Age Presenting with Moderate Fever to Pediatric Emergency Rooms of the Metropolitan Region (Santiago), Chile

Blood culture collection from outpatients < age 36 months with high fever (> 40º C, rectal) became a standard of ambulatory care in Emergency Rooms (ERs) of the 3 government Children’s Hospitals in Chile’s Metropolitan Region (MR) in 1999; thereafter, invasive pneumococcal disease (IPD) incidence doubled over preceding years’ estimates limited to hospitalizations. We studied IPD among children with moderate (>39ºC but 39º but 0.05). Extrapolating these rates to all ER outpatients < age 36 months with moderate and high fever, we estimate the true burden as 95 and 39 cases, respectively. The burden of pediatric IPD in the MR is currently underestimated because bacteremias among ER outpatients with moderate fever are not detected. If blood cultures were systematically collected from outpatients with moderate fever, recorded pediatric IPD burden would rise > 2-fold. However, economic and logistical constraints preclude such a practice.

Population-Based Surveillance for Childhood Invasive Pneumococcal Disease in the Era of Conjugate Vaccine

Heptavalent pneumococcal conjugate vaccine was licensed in the United States in February 2000 and, following national guidelines, universally distributed in Massachusetts starting in July 2000 to children younger than 2 years of age and selected children 2-5 years of age. We performed statewide surveillance for all cases of invasive pneumococcal disease (IPD) in children younger than 18 years of age to determine risk features and contribution of vaccine failure to ongoing pneumococcal invasive disease. Massachusetts pediatric IPD cases were identified via enhanced passive surveillance of microbiology laboratory reports of pneumococcal isolates from sterile body sites of children younger than 18 years for 2 years starting in October 2001. Serotyping was performed on isolates of Streptococcus pneumoniae from normally sterile body fluid. Case demographic and clinical data (including dates of prior doses of PCV7) were collected via follow-up telephone interviews with case primary care providers and/or parents. Between October 1, 2001 and September 30, 2003, 191 cases of IPD were identified statewide (138 in children younger than 5 years). Annual incidence rate for IPD was 17.4 per 100,000 children younger than 5 years, representing a decline of 69% when compared with annual incidence rate of 56.9 per 100,000 from Massachusetts statewide active surveillance performed 1990-1991. In 2001-2003, 30% of cases occurred in the first year of life (36.5 per 100,000), representing a 7.8-fold increased risk compared with children older than 1 year of age. Race-specific annual incidence rates in blacks and Hispanics were 2.3-fold (95% confidence interval, 1.21-4.42) and 1.9-fold (95% confidence interval, 1.06-3.37), greater than in whites. Fifty-nine cases were reported to have underlying comorbid conditions. Serotyping was available for 136 of 191 (71%) cases younger than 18 years; of isolates available for serotyping, 40 (29%) were vaccine serotype (ST), 31 (23%) vaccine-related ST and 65 (48%) nonvaccine ST. Seven of 40 cases with IPD caused by vaccine ST received at least 3 doses of PCV7 vaccine before IPD. Universal administration of PCV7 to children younger than 2 years of age and selective administration to children 2-5 years of age has resulted in a significant decline in IPD in Massachusetts. Children younger than 1 year of age, African American and Hispanic children and those with recognized comorbid illnesses (malignancy, human immunodeficiency virus, immune deficiency, nephrotic syndrome, etc.) continue to remain at risk for IPD. These risk features should be considered when evaluating febrile infants and children.

Efficacité du vaccin pneumococcique heptavalent conjugué (Prevenar ®) contre les infections invasives à pneumocoque : bénéfice attendu pour les enfants en France

A seven-valent pneumococcal polysaccharide—CRM197 carrier protein conjugate vaccine (PNC7V; Prevenar ®, Wyeth, Paris) targets the serotypes (belonging to serogroups 14, 6, 19, 18, 23, 9, and 4) most often responsible for invasive pneumococcal disease (IPD) among children. A randomized, controlled, double-masked study among 37,868 children in northern California (Northern California Kaiser Permanente, USA) provided a per protocol vaccine efficacy value of 97.7% against invasive pediatric IPD due to the vaccine serotypes. The PNC7V vaccine was registered by the European Agency for the Evaluation of Medicinal Products (EMEA) in October 2000; a favorable “Community Marketing Decision” under the Centralized Procedure was granted in February 2001. PNC7V was recommended for most infants by the Conseil Supérieur d'Hygiène Publique de France in March 2002, on the advice of the Comité Technique des Vaccinations, as S. pneumoniae in children less than 2 years of age is the primary cause of bacterial meningitis and of mortality associated with community-acquired bacterial infections. The theoretical coverage of the vaccine towards pneumococcal invasive disease in France is about 80%, which represents one of the best serotype coverage estimates in Europe, and vaccines serotypes account for 90% of penicillin-nonsusceptible strains. Distinctive characteristics in France in terms of epidemiology, life style, and therapeutic attitudes justify a precise follow up of the consequences of the vaccination on a national level during the coming years. Hence, surveillance programs have been established: (i) to ascertain the future impact of large-scale PNC7V vaccination on invasive pneumococcal disease incidence, (ii) to follow the evolution of carriage and ecology of the pneumococcus, and (iii) to establish an active “vaccinovigilance”.

Pediatric invasive pneumococcal disease in a teaching hospital in Bangkok

Background: Increased problems with drug-resistant Streptococcus pneumoniae (SP) and the dearth of epidemiologic and clinical information on invasive pneumococcal disease in children in Asia formed the basis for this study. Methods: A periodic retrospective review of the records of 0–15-year-old patients was conducted at a teaching Hospital in Bangkok, during 1971–2000. Results: Infections with penicillin-non-susceptible SP (PNSSP) strains rapidly increased after they first appeared in 1988, and they accounted for 71% (29/41) of the total cases during 1996–2000. Of 137 patients, 74% were <60 months old, and 66% had an underlying condition. Infections included: bacteremia without focus 51; pneumonia 38; meningitis 35; peritonitis 13; and bone/joint infection 2. Two patients had two foci of infection. Eight of 10 episodes in patients with AIDS were bacteremic pneumonia. Median ages (range) in months for patients with and without an underlying condition were 24 (1–174) and 10 (0–160); and for the patients without an underlying condition they were: pneumonia 23 (4–156); bacteremia without focus 12 (0–160); and meningitis 7 (2–156). Case-fatality rates were 18% and 2% for patients with and without an underlying condition. The study also examined factors associated with PNSSP infection and death. During 1991–2000,74% (43/58) of the total cases occurred from November to April, which are dry months. Conclusions: This study population contained a high proportion with both an underlying condition and infection with PNSSP, and a moderately low proportion with bacteremia without focus. The disease was two to three times more common in dry months than in rainy months.

A decade (1989-1998) of pediatric invasive pneumococcal disease in 2 populations residing in 1 geographic location: implications for vaccine choice.

During 1 decade (1989-1998), data on invasive pneumococcal disease were collected prospectively to assess the burden of disease among Jewish and Bedouin children in southern Israel and the potential reduction in illness that can be achieved by using conjugate vaccines. Data on 513 children <15 years old with bacteriologically proven invasive pneumococcal disease were obtained. Among Jewish and Bedouin children <5 years old, incidence rates were 45 and 139 cases per 100,000 child-years of observation, respectively. Jewish and Bedouin children differed in clinical manifestations, seasonal patterns of disease, serotype distribution, and antibiotic susceptibility rates. The potential coverage by 7-, 9-, and 11-valent conjugate vaccines is 41%, 67%, and 71%, respectively, for Jewish children and 22%, 63%, and 65%, respectively, for Bedouin children. The 9- and 11-valent pneumococcal conjugate vaccines have the potential to substantially decrease invasive pneumococcal disease in southern Israel.