title: Invasive pneumococcal disease in children aged younger than 5 years in India: a surveillance study.
abstract: Invasive pneumococcal disease continues to be a major cause of morbidity and mortality among children younger than 5 years of age in India. We aimed to provide nationally representative data for the pattern of disease due to Streptococcus pneumoniae, trends in the serotype of invasive pneumococci, and invasive pneumococci antimicrobial resistance patterns, in India.
  
  
  
  In this prospective hospital-based and retrospective laboratory-based surveillance study, we prospectively enrolled children aged younger than 5 years with suspected or proven invasive pneumococcal disease from 18 hospitals or institutional centres and retrospectively included laboratory-confirmed pneumococcal isolates from ten sentinel laboratories, together representing 11 states in India. Eligibility criteria were fever higher than 38°C without localising symptoms, clinical presentation of suspected meningitis or pneumonia, and evidence of radiographic pneumonia. We cultured blood and other normally sterile body fluids, reconfirmed and serotyped pneumococcal isolates, and established antimicrobial susceptibility using standard study protocols.
  
  
  
  Between Jan 1, 2011, and June 30, 2015, we enrolled 4377 patients. Among 361 (8%) patients with culture-proven pneumococcal disease, all clinical data were known for 226 (63%); among these patients, 132 (58%) presented with pneumonia, 78 (35%) presented with meningitis, and 16 (7%) had other clinical conditions. 131 (3%) died overall and 29 (8%) patients with invasive pneumococcal disease died. Serotypes 14 (52 [14%] of 361), 1 (49 [14%]), 5 (37 [10%]), and 19F (33 [9%]) were the most common. Penicillin non-susceptibility occurred in isolates from 29 (8%) patients, co-trimoxazole resistance occurred in 239 (66%), erythromycin resistance occurred in 132 (37%), and chloramphenicol resistance occurred in 33 (9%). We found multidrug resistance in 33 (9%) of 361 patients.
  
  
  
  The proportion of positive blood cultures, number of isolates, geographical representation, and data generated over the 4·5 years of the study are representative of data for most of India. Continued surveillance is warranted as the decision to introduce protein conjugated vaccine in India is made.
  
  
  
  GlaxoSmithKline India.
authors.affiliation: Pushpagiri Research Centre, Pushpagiri Institute of Medical Science and Research Centre, Tiruvalla, Kerala, India. Electronic address: anandmanoharan@pushpagiri.in.
authors.forename: Anand
authors.initials: A
authors.lastname: Manoharan
authors.affiliation: Department of Microbiology, Chacha Nehru Bal Chikitsalya, Maulana Azad Medical College, New Delhi, India.
authors.forename: Vikas
authors.initials: V
authors.lastname: Manchanda
authors.affiliation: Department of Pediatrics, Kanchi Kamakoti CHILDS Trust Hospital, and CHILDS Trust Research Foundation, Chennai, Tamil Nadu, India.
authors.forename: Sundaram
authors.initials: S
authors.lastname: Balasubramanian
authors.affiliation: Department of Pediatrics, Bharati Vidyapeeth Deemed University Medical College, Pune, Maharashtra, India.
authors.forename: Sanjay
authors.initials: S
authors.lastname: Lalwani
authors.affiliation: Department of Microbiology, Bharati Vidyapeeth Deemed University Medical College, Pune, Maharashtra, India.
authors.forename: Meera
authors.initials: M
authors.lastname: Modak
authors.affiliation: Department of Pediatrics, Pushpagiri Institute of Medical Science and Research Centre, Tiruvalla, Kerala, India.
authors.forename: Sushama
authors.initials: S
authors.lastname: Bai
authors.affiliation: Department of Microbiology, Pushpagiri Institute of Medical Science and Research Centre, Tiruvalla, Kerala, India.
authors.forename: Ajith
authors.initials: A
authors.lastname: Vijayan
authors.affiliation: Department of Pediatrics, St John's Medical College, Bengaluru, Karnataka, India.
authors.forename: Anita
authors.initials: A
authors.lastname: Shet
authors.affiliation: Department of Microbiology, St John's Medical College, Bengaluru, Karnataka, India.
authors.forename: Savitha
authors.initials: S
authors.lastname: Nagaraj
authors.affiliation: Department of Pediatrics, King Edward Memorial Hospital, Mumbai, Maharashtra, India.
authors.forename: Sunil
authors.initials: S
authors.lastname: Karande
authors.affiliation: Department of Microbiology, King Edward Memorial Hospital, Mumbai, Maharashtra, India.
authors.forename: Gita
authors.initials: G
authors.lastname: Nataraj
authors.affiliation: Dr Yewale Multispecialty Hospital for Children, Vashi, Navi Mumbai, Maharashtra, India.
authors.forename: Vijay N
authors.initials: VN
authors.lastname: Yewale
authors.affiliation: Dr Joshi's Central Clinical Microbiology Laboratory, Vashi, Navi Mumbai, Maharashtra, India.
authors.forename: Shrikrishna A
authors.initials: SA
authors.lastname: Joshi
authors.affiliation: Department of Microbiology and Infectious Diseases, Global Hospitals, Lakdi-Ka Pul, Hyderabad, Telangana, India.
authors.forename: Ranganathan N
authors.initials: RN
authors.lastname: Iyer
authors.affiliation: Department of International Health and International Vaccine Access Center, Johns Hopkins University Bloomberg School of Public Health, Baltimore, MD, USA.
authors.forename: Mathuram
authors.initials: M
authors.lastname: Santosham
authors.affiliation: Department of International Health and International Vaccine Access Center, Johns Hopkins University Bloomberg School of Public Health, Baltimore, MD, USA.
authors.forename: Geoffrey D
authors.initials: GD
authors.lastname: Kahn
authors.affiliation: Department of International Health and International Vaccine Access Center, Johns Hopkins University Bloomberg School of Public Health, Baltimore, MD, USA.
authors.forename: Maria Deloria
authors.initials: MD
authors.lastname: Knoll
mesh_terms: D000900:Anti-Bacterial Agents / Q000627:therapeutic use; D002675:Child, Preschool; D017714:Community-Acquired Infections / Q000453:epidemiology; D004352:Drug Resistance, Microbial; D006801:Humans; D007194:India / Q000453:epidemiology; D007223:Infant; D007231:Infant, Newborn; D011008:Pneumococcal Infections / Q000175:diagnosis / Q000000981:diagnostic imaging / Q000453:epidemiology* / Q000401:mortality*; D022242:Pneumococcal Vaccines / Q000008:administration & dosage; D011159:Population Surveillance; D015995:Prevalence; D011446:Prospective Studies; D012703:Serotyping / Q000706:statistics & numerical data; D013296:Streptococcus pneumoniae / Q000145:classification / Q000187:drug effects / Q000302:isolation & purification*
chemical_list: D000900:Anti-Bacterial Agents; D022242:Pneumococcal Vaccines