Inci Yildirim

A prospective study of etiology of childhood acute bacterial meningitis, Turkey.

Vaccines to prevent bacterial meningitis in this region must provide reliable protection against serogroup W-135.

Role of procalcitonin and CRP in differentiating a stable from a deteriorating clinical course in pediatric febrile neutropenia.

In clinical practice, when neutropenic-fever patients present with no microbiologically and clinically defined infection, the risk of underestimating an occult infection is of major concern, the clinicians have to make a decision on when to modify antibiotic therapy. Hence, a reliable, specific, and sensitive marker, which is regulated independently from the leukocyte count and the underlying disease, is needed for the early diagnosis of infections in cases of neutropenic fever. We have evaluated the diagnostic and follow-up value of procalcitonin (PCT) compared with C-reactive protein (CRP) and erythrocyte sedimentation rate in documenting the infection in neutropenic-fever patients undergoing intensive chemotherapy, as evidenced by the durational change in these parameters in the presence of defined infection. Forty-nine patients, who had 60 febrile episodes, and who were hospitalized in the Hacettepe University Ihsan Doğramacı Childrens Hospital between January 1, 2004 and January 1, 2005 were included in this prospective study. All patients had been diagnosed with neutropenic fever after intensive chemotherapy. In our study, PCT and CRP levels were significantly higher in neutropenic-fever patients (group I and group II separately) than in control patients (P<0.001) throughout the study period; but erythrocyte sedimentation rate levels did not show any significant difference (P>0.05). In sequential analyses of patients without documented infections, the median of PCT concentrations shows a tendency to fall after the 8th hour of onset of fever, whereas in patients with documented infections PCT concentrations fell after the 48th hour. In conclusion, our study suggests that PCT, when measured periodically, is a more useful diagnostic inflammation parameter in pediatric neutropenic-fever patients than CRP, both in estimating the severity of the infection and, the duration and origin of the fever. Hence, PCT might be helpful when deciding on initial therapy modification.

Evolving picture of invasive pneumococcal disease in massachusetts children: a comparison of disease in 2007-2009 with earlier periods.

Background: As expected, the heptavalent pneumococcal conjugate vaccine (PCV7) had a significant impact on invasive pneumococcal disease (IPD) in children. In addition to the substantial decline in IPD, increased disease due to nonvaccine serotypes and a changing clinical presentation emerged. The objective of this study is to describe these trends in IPD in the late PCV7-era. Methods: We report on continued, prospective, population-based surveillance of childhood IPD in Massachusetts children during the period 2007 to 2009 and make comparisons with the earlier 2001 to 2006 PCV7-era. Demographic and clinical data were collected for all cases. Streptococcus pneumoniae isolates from normally sterile sites were serotyped and further evaluated using antimicrobial susceptibility testing, multilocus sequence typing and eBURST analysis. IPD incidence rates are calculated by age, year and serotype. Results: There were 326 cases of IPD between 2007 and 2009 in children < 18 years of age. Overall IPD incidence rate was 7.5 cases per 100,000 population and was not statistically different from the observed incidence in 2001 to 2006 (P > 0.05). As compared with the earlier period, the proportion of bacteremic pneumonia among all IPD cases was almost 3-fold greater in 2009 to 2010 (P < 0.01). PCV7 serotypes accounted for 7%, whereas the 13-valent pneumococcal conjugate vaccine serotypes accounted for 77% of all cases between 2007 and 2009. IPD due to serotypes 19A and 7F increased, and 19A and 7F were isolated in 41% and 20% of all IPD cases in the same period, respectively. Serotype 19A also comprised a majority of the penicillin- and ceftriaxone-resistant isolates. Analysis of multilocus sequence typing data showed a significant increase in ST191, ST695 and ST320 and a significant decrease in ST199 and ST180. Conclusions: The reduction in IPD after introduction of PCV7 persists in Massachusetts children; however, serotypes causing IPD have changed significantly in the last decade. Continued surveillance is necessary to determine the impact of 13-valent pneumococcal conjugate vaccine, as well as track potential changes in disease incidence and character due to non–13-valent pneumococcal conjugate vaccine serotypes.

Pneumococcal Disease in the Era of Pneumococcal Conjugate Vaccine

Universal immunization of infants and toddlers with pneumococcal conjugate vaccines over the last 15 years has dramatically altered the landscape of pneumococcal disease. Decreases in invasive pneumococcal disease, all-cause pneumonia, empyema, mastoiditis, acute otitis media, and complicated otitis media have been reported from multiple countries in which universal immunization has been implemented. Children with comorbid conditions have higher rates of pneumococcal disease and increased case fatality rates compared with otherwise healthy children, and protection for the most vulnerable pediatric patients will require new strategies to address the underlying host susceptibility and the expanded spectrum of serotypes observed.

Vaccination, Underlying Comorbidities, and Risk of Invasive Pneumococcal Disease

OBJECTIVES: Children with underlying conditions remain at increased risk for invasive pneumococcal diseases (IPD). This study describes the epidemiology, serotype distribution, clinical presentations, and outcomes of IPD in children with and without comorbidity. METHODS: Cases of childhood IPD in Massachusetts were identified via enhanced surveillance from 2002 through 2014. Demographic and clinical data were collected via follow-up telephone interviews with parents and/or primary care providers. Underlying conditions were classified according to the 2012 Report of the Committee on Infectious Diseases and 2013 recommendations by the Advisory Committee on Immunization Practices. RESULTS: Among 1052 IPD cases in Massachusetts children <18 years old, 22.1% had at least 1 comorbidity. Immunocompromising conditions (32.7%) and chronic respiratory diseases (22.4%) were most common. Children with comorbidities were older at the time of IPD diagnosis (median 54 vs 23 months, P < .001), had higher hospitalization (odds ratio 2.5; 95% confidence interval 1.7–3.6) and case-fatality rates (odds ratio 3.7; 95% confidence interval 1.5–8.9) compared with children without known underlying conditions after adjusting for age, gender, year of diagnosis, and pneumococcal vaccination status. During the last 2 years of the study, IPD among children with comorbidities was caused by non–pneumococcal conjugate vaccine 13 serotypes in 23-valent polysaccharide pneumococcal vaccine (6/12, 50%) or serotypes that are not included in any of the vaccines (6/12; 50%). CONCLUSIONS: In children with comorbidity, IPD results in higher mortality, and a large proportion of disease is due to serotypes not included in current conjugate vaccines. Further research is needed, specifically to develop and evaluate additional strategies for prevention of IPD in the most vulnerable children.

Frequency of pertussis in children with prolongued cough

To determine the frequency of pertussis in children ≤16 y who had prolonged cough (≥14 d), a prospective study was conducted at an outpatient clinic of a paediatric hospital. Nasopharyngeal swabs were taken for culture and nucleic acid testing by polymerase chain reaction (PCR) for Bordetella pertussis. Immunoglobulin A and immunoglobulin G antibodies against pertussis toxin (PT) were tested by ELISA in paired serum samples. A total of 148 patients were recruited during 1 y. Pertussis was detected in 25 (16.9%) patients with at least 1 of the tests. PCR was positive in 12 patients, and 9 cases was diagnosed serologically. Both PCR and serology were positive in 4 children. Duration of cough was longer in the patients with pertussis (median 33 vs 20, p=0.03). Seropositivity of pertussis toxin was higher in pertussis negative patients during enrollment (24% vs 65%, p=0.005). From the results of this study, B. pertussis seems to be common in our population despite high immunization rates with whole cell vaccine. Although the duration of cough is defined as longer than 21 d in some studies for pertussis case definition criteria, it was shorter than this in 3 of our cases.

A Case Report of Thrombocytopenia-associated Multiple Organ Failure Secondary to Salmonella enterica Serotype Typhi Infection in a Pediatric Patient: Successful Treatment With Plasma Exchange

A high proportion of the patients with Salmonella enterica serotype Typhi infection develop severe sepsis. The mortality rate is high despite aggressive antimicrobial therapy in these patients. The case of a 10‐year‐old boy who developed thrombocytopenia‐associated multiple organ failure (TAMOF) secondary to S. typhi infection is reported. The patient did not respond to antimicrobial treatment, including ciprofloxacin, in addition to conventional supportive measures, so plasma exchange was performed. The thrombocytopenia and organ failure had resolved after 3 days of plasma exchange therapy. Plasma exchange is suggested to be a life‐saving intervention in a child with TAMOF secondary to S. typhi infection.

Rapid Initiation of Antiretrovirals in Two Newly Diagnosed Hiv-infected Infants

We report our experience with 2 infants with in utero HIV-1 infection who began very early combination antiretroviral therapy within 4 hours of birth. Further neonatal studies of antiretroviral pharmacokinetics (PKs), safety, efficacy and treatment strategies are critically needed for the development of more potent regimens for use in HIV-infected infants.

A fully liquid DTaP-IPV-HB-PRP-T hexavalent vaccine for primaryand booster vaccination of healthy Turkish infants and toddlers

Background/aim: Immunogenicity and safety of a primary series of a fully liquid, hexavalent DTaP-IPV-HB-PRP-T vaccine given at 2, 3, and 4 months of age compared to licensed comparators and a DTaP-IPV-HB-PRP-T booster at 15?18 months were evaluated. Materials and methods: This was a Phase III, randomized, open-label trial. Primary series (no hepatitis B [HB] at birth) of DTaP-IPV-HB-PRP-T (N = 155) (group 1) or licensed control vaccines (DTaP-IPV//PRP-T and standalone HB: N = 155) (group 2) and DTaP-IPV-HB-PRP-T booster were administered. Noninferiority was evaluated 1 month postprimary series for anti-HB seroprotection (SP). All other analyses were descriptive. Safety was assessed from parental reports. Results: Postprimary series noninferiority of anti-HB ≥ 10 mIU/mL was demonstrated for the DTaP-IPV-HB-PRP-T vaccine (94.0%) compared to the licensed control (96.1%). Postprimary series primary SP and seroconversion (SC) rates were high and similar for both groups. Antibody persistence (prebooster) was high for each antigen and similar between groups except for HB, which was lower for DTaP-IPV-HB-PRP-T than for standalone HB. For each antigen except HB, DTaP-IPV-HB-PRP-T booster responses were high and similar in each group. Safety was good for primary and booster series and similar between groups. Conclusion: The DTaP-IPV-HB-PRP-T vaccine is immunogenic and safe when administered in a challenging primary series schedule without HB vaccination at birth.

Impact of PCV13 on Serotype 3 invasive pneumococcal disease and nasopharyngeal carriage in Massachusetts’ children

Abstract Background Although a substantial decline in overall vaccine serotype invasive pneumococcal disease (IPD) incidence has been observed following immunization with PCV7 and subsequently PCV13, the reported effectiveness for individual vaccine serotypes has varied. Reported effectiveness of PCV13 for serotype 3 (ST3) disease has differed by study design and geography, with a wide range of estimates including zero. We assessed the impact of PCV13 on ST3 IPD cases and nasopharyngeal (NP) carriage in Massachusetts’ children. Methods Cases of ST3 IPD in children <18 years were identified via enhanced passive surveillance in conjunction with the Massachusetts Department of Public Health from 2002 to 2016. NP Carriage of ST3 in children aged 3 months to <7 years was identified via an active surveillance network of pediatric practices in Massachusetts from 2007 to 2014. Annual incidence rates of ST3 IPD were calculated using US Census estimates as population denominators. Annual prevalence rates of carriage were calculated using the surveillance population. We compared age distribution, clinical syndromes, presence of comorbidities and vaccination status for IPD cases and age distribution of children with ST3 carriage before and after PCV13 implementation. Results Overall 47 cases of ST3 IPD were identified from 2002 to 2016; the incidence of ST3 IPD before and after PCV13 was 0.23 and 0.20 per 100,000 children respectively (incidence rate ratio [IRR] = 1.13, 95% CI 0.62–2.05). There were no differences in age distribution, clinical syndrome or presence of comorbidities among ST3 IPD cases before and after PCV13. The majority (9/13) of post PCV13 ST3 IPD cases occurred among children who were fully vaccinated. No association was seen between date of last PCV13 dose and time of IPD to suggest waning immunity. Prevalence of ST3 carriage among children aged 3 months to <7 years before and after PCV13 implementation was 0.19 and 0.64 respectively (Prevalence ratio [PR] = 0.3, 95% CI 0.11–0.83). Conclusion Six years after PCV13 implementation, no significant changes in ST3 IPD incidence, age distribution, clinical syndrome or presence of comorbidity among cases in children <18 years of age were observed. An increase in NP carriage in children <7 years of age was observed. Disclosures K. M. Shea, Pfizer, Inc: Consultant and Grant Investigator, Consulting fee and Grant recipient; S. I. Pelton, Pfizer: Board Member and Grant Investigator, Consulting fee, Research grant and Speaker honorarium; Merck vaccines: Board Member, Consulting fee and Speaker honorarium; GSK: Board Member, Consulting fee and Speaker honorarium; Sequiris: Board Member, Consulting fee and Speaker honorarium