Effectiveness of 10-valent pneumococcal conjugate vaccine against vaccine-type invasive pneumococcal disease in Pakistan.

OBJECTIVE: To assess the effectiveness of 10-valent pneumococcal conjugate vaccine (PCV10) against invasive pneumococcal disease (IPD) due to vaccine serotypes of Streptococcus pneumoniae post introduction of the vaccine into the routine immunization program in Pakistan. METHODS: A matched case-control study was conducted at 16 hospitals in Sindh Province, Pakistan. Children aged <5years (eligible to receive PCV10) who presented with radiographically confirmed pneumonia and/or meningitis were enrolled as cases. PCR for the lytA gene was conducted on blood (for radiographic pneumonia) and cerebrospinal fluid (for meningitis) samples to detect S. pneumoniae. The proportion of IPD due to vaccine serotypes (including vaccine-related serogroups) was determined through serial multiplex PCR. For each case, at least five controls were enrolled from children hospitalized at the same institution, matched for age, district, and season. RESULTS: Of 92 IPD patients enrolled during July 2013 to March 2017, 24 (26.0%) had disease caused by vaccine serotypes. Most case (87.5% of 24) and control (66.4% of 134) children had not received any PCV10 doses. The estimated effectiveness of PCV10 against vaccine-type IPD was 72.7% (95% confidence interval (CI) -7.2% to 92.6%) with at least one dose, 78.8% (95% CI -11.9% to 96.0%) for at least two doses, and 81.9% (95% CI -55.7% to 97.9%) for all three doses of vaccine. CONCLUSIONS: The vaccine effectiveness point estimates for PCV10 were high and increased with increasing number of doses. However, vaccine effectiveness estimates did not reach statistical significance, possibly due to low power. The findings indicate the likely impact of vaccine in reducing the burden of vaccine-type IPD if vaccine uptake can be improved.

Identification of etiological agents by LPA and PCR in childhood meningitis.

OBJECTIVES: To determine the etiological agents by Latex Particle Agglutination (LPA) and Polymerase Chain Reaction (PCR) in patients admitted with Cerebrospinal Fluid (CSF) culture negative bacterial meningitis Methods: This descriptive case series was conducted at National Institute of Child Health, Karachi from January 2010 to December 2012. Patients meeting the WHO case definition of suspected meningitis from one month to 59 months of age were included in the study. CSF examination and culture was carried out on every patient and CSF culture negative patients were enrolled. Demographic data, clinical signs & symptoms and laboratory findings were entered into the proforma. Data was analyzed using statistical package for social sciences (SPSS) version 17. P-value <0.05 was taken as significant. RESULTS: A total of 166 patients were included. Male were 96 and female were 76 with the male to female ratio of 1.26. The mean age of patient was ± SD 14.6 ± 14.5 months. The etiological agents identified by LPA were in 26/166 (15.66%) cases and the organisms were H. influenzae type b 10 cases, streptococcus pneumoniae 15 cases and meningococcus only one case respectively. The organisms identified by PCR were in 65/166 (39.15%) cases and the isolates were H. influenzae type b 16 cases, streptococcus pneumoniae 48 cases and meningococcus 01 case respectively. CONCLUSION: LPA and PCR are superior and useful diagnostic tools in microbiology. They can be used for rapid etiological diagnosis of bacterial meningitis for the early administration of proper antibiotic. Abbreviation: LPA = Latex Particle Agglutination, PCR = Polymerase Chain Reaction, CSF = Cerebrospinal Fluid, CNS = Central Nervous System.

Effectiveness of Haemophilus influenzae type b conjugate vaccine on radiologically-confirmed pneumonia in young children in Pakistan.

OBJECTIVE: The effectiveness of Haemophilus influenzae type b (Hib) vaccine in preventing severe pneumonia in Asian children has been questioned, and many large Asian countries yet to introduce Hib conjugate vaccine in immunization programs. The primary objective of this study was to assess Hib conjugate vaccine effectiveness (VE) on radiologically-confirmed pneumonia in children born after introduction of Hib conjugate vaccine in Pakistan. STUDY DESIGN: A matched case-control study enrolled cases of radiologically-confirmed pneumonia in several hospitals serving low-income populations during 2009-2011. Cases were matched by age and season with 3 hospital and 5 neighborhood controls. Pneumonia was diagnosed using standardized World Health Organization criteria for chest radiograph interpretation. Matched OR were estimated for VE. RESULTS: A total of 1027 children with radiologically-confirmed pneumonia were enrolled; 975 cases, 2925 hospital controls, and 4875 neighborhood controls were analyzed. The coverage for 3 doses of diphtheria-tetanus-pertussis-hepatitis B-Hib conjugate vaccine was 13.7%, 18%, and 22.7% in cases, hospital controls and neighborhood controls, respectively. Estimated Hib VE for radiologically-confirmed pneumonia was 62% with 3 doses of vaccine using hospital controls and 70% using neighborhood controls. CONCLUSIONS: Hib conjugate vaccine prevented a significant fraction of radiologically-confirmed pneumonia in children in Pakistan. Maximizing impact on child survival needs improved immunization coverage.

Mortality and neurodevelopmental outcomes of acute bacterial meningitis in children aged <5 years in Pakistan.

OBJECTIVE: Significant neurodevelopmental sequelae are known to occur after acute bacterial meningitis (ABM). This study determined the burden of such sequelae in Pakistani children aged <5 years to guide policies for Haemophilus influenzae type b (Hib) and pneumococcal vaccination. STUDY DESIGN: Cases of ABM were recruited from hospital-based surveillance and assigned to 1 of 3 etiologic groups (Hib, Streptococcus pneumoniae, or unknown etiology). Two age-matched controls were recruited for each case. Six months after enrollment, each case underwent neurologic history and examination, neurodevelopmental evaluation, and neurophysiological hearing test. Controls were assessed in parallel. RESULTS: Of 188 cases, 64 (34%) died. Mortality among subgroups were 7 (27%), 14 (28%), and 43 (39%) for Hib, Streptococcus pneumoniae, and unknown etiology, respectively. Eighty cases and 160 controls completed the assessments. Sequelae among cases included developmental delay (37%), motor deficit (31%), hearing impairment (18.5%), epilepsy (14%), and vision impairment (14%). Sequelae were higher after pneumococcal meningitis (19, 73%) compared with Hib meningitis (8, 53%). Compared with controls, cases were at significantly higher risk for all sequelae (P < .0001). CONCLUSIONS: ABM causes a substantial long-term burden of poor neurodevelopmental outcomes. Hib and pneumococcal vaccines are very effective interventions to prevent meningitis and its disabling sequelae.