Streptococcus pneumoniae Acquisition and Carriage in Vaccine Naïve Indian Children with HIV and their Parents: A Longitudinal Household Study

  • Bikas K. Arya
  • Sangeeta Das BhattacharyaEmail author
  • Gautam Harigovind
  • Ranjan S. Das
  • Tila Khan
  • Feroze Ganaie
  • Swapan K. Niyogi
  • K. L. Ravikumar
  • Anand Manoharan
  • Subhasish Bhattacharyya
  • Samiran Panda
  • Sutapa Mandal
  • Banuja Acharya
Original Article



To investigate the difference in pneumococcal carriage, acquisition, antibiotic resistance profiles and serotype distribution, in human immunodeficiency virus (HIV) affected and unaffected families.


A prospective cohort study was conducted in children with and without HIV in West Bengal from March 2012 through August 2014, prior to 13-valent pneumococcal conjugate vaccine (PCV-13) immunization. One thousand four hundred forty one nasopharyngeal swabs were collected and cultured at five-time points from children and their parents for pneumococcal culture, and serotyping by Quellung method.


One hundred twenty five HIV infected children and their parents, and 47 HIV uninfected children and their parents participated. Two hundred forty pneumococcal isolates were found. In children under 6 y, the point prevalence of colonization was 31% in children living with HIV (CLH) and 32% in HIV uninfected children (HUC), p = 0.6. The most common vaccine type (VT) serotypes were 6A, 6B and 19A. All isolates from parents and 71% from children in the HIV uninfected cohort were PCV-13 representative, compared to 33% of isolates from CLH and their parents. Acquisition rate in children was 1.77 times that of parents (OR = 1.77, 95%CI: 1.18–2.65). The HIV status of child or parent did not affect acquisition. Isolates from CLH were more frequently resistant to multiple antibiotics (p = 0.02).


While the rate of pneumococcal carriage and acquisition did not differ between CLH and HUC, HIV affected families had exposure to a wider range of serotypes including non-vaccine type serotypes and antibiotic resistant serotypes, than HIV unaffected families.


Streptococcus pneumoniae HIV Risk factors Pneumococcal conjugate vaccine Serotype Antibiotic resistance 



This study was funded by Indian Council of Medical Research (funded by MoHFW, Government of India) (dated: 15-06-2011; letter number: 5/7/463/2010-RHN). The first author acknowledges Fulbright-Nehru Doctoral Research Award 2014 while analysis of the study results. The authors recognize the contribution of Lt. Col. Dr. Ashok Kumar, Lt. Col. Dr. SatyajitGorain, Dr. Mausami Nandi Ghosh, Dr. Sunil Hemram, Dr. Pampa Ray, their support staff and participating families at various stages of the study.

Authors’ Contribution

SDB and BKA conceived and designed the study; BKA, SDB, GH, RSD, SKN, SB, SP, SM, BA were involved in nasopharyngeal swab collection, swab processing by culture, antimicrobial resistance and data acquisition; FG, KLR, AM contributed to pneumococcal serotyping; GH, BKA, RSD, SDB performed data and statistical analysis; SDB, BKA, TK, GH were involved in manuscript preparation, editing and review. All authors have read and approved the manuscript. SDB is the guarantor for this article.

Compliance with Ethical Standards

Ethical Approval

All procedures performed in this study were in accordance with the ethical standards of the institutional research committees. The ethics committees of the Indian Institute of Technology-Kharagpur (IIT-KGP), Midnapore Medical College Hospital (MMCH) and, NICED approved this study. Additional approvals were obtained from the district and state health authorities and the Drugs Controller General of India (DCGI). All parents and guardians included in the study provided written informed consent for themselves and their children.

Conflict of Interest


Source of Funding

Primary: Indian Council of Medical Research (funded by MoHFW, Government of India) (Reference number: 5/7/463/2010-RHN). Others: Fulbright-Nehru Doctoral Research Award 2014-15 (Sponsored by United States Department of State’s Bureau of Educational and Cultural Affairs, and USIEF, New Delhi.

Supplementary material

12098_2019_2995_MOESM1_ESM.docx (142 kb)
ESM 1 (DOCX 141 kb)


  1. 1.
    O'Brien KL, Wolfson LJ, Watt JP, et al. Burden of disease caused by Streptococcus pneumoniae in children younger than 5 years: global estimates. Lancet. 2009;374:893–902.CrossRefGoogle Scholar
  2. 2.
    Bliss SJ, O'Brien KL, Janoff EN, et al. The evidence for using conjugate vaccines to protect HIV-infected children against pneumococcal disease. Lancet Infect Dis. 2008;8:67–80.CrossRefGoogle Scholar
  3. 3.
    Smith T, Lehmann D, Montgomery J, Gratten M, Riley ID, Alpers MP. Acquisition and invasiveness of different serotypes of Streptococcus pneumoniae in young children. Epidemiol Infect. 1993;111:27–39.CrossRefGoogle Scholar
  4. 4.
    Bogaert D, De Groot R, Hermans PW. Streptococcus pneumoniae colonisation: the key to pneumococcal disease. Lancet Infect Dis. 2004;4:144–54.CrossRefGoogle Scholar
  5. 5.
    Nunes MC, Shiri T, van Niekerk N, et al. Acquisition of Streptococcus pneumoniae in pneumococcal conjugate vaccine-naive south African children and their mothers. Pediatr Infect Dis J. 2013;32:e192–205.CrossRefGoogle Scholar
  6. 6.
    Buie KA, Klugman KP, von Gottberg A, et al. Gender as a risk factor for both antibiotic resistance and infection with pediatric serogroups/serotypes, in HIV-infected and -uninfected adults with pneumococcal bacteremia. J Infect Dis. 2004;189:1996–2000.CrossRefGoogle Scholar
  7. 7.
    Davis SM, Deloria-Knoll M, Kassa HT, O'Brien KL. Impact of pneumococcal conjugate vaccines on nasopharyngeal carriage and invasive disease among unvaccinated people: review of evidence on indirect effects. Vaccine. 2013;32:133–45.CrossRefGoogle Scholar
  8. 8.
    Whitney CG, Farley MM, Hadler J, et al. Decline in invasive pneumococcal disease after the introduction of protein-polysaccharide conjugate vaccine. N Engl J Med. 2003;348:1737–46.CrossRefGoogle Scholar
  9. 9.
    Nzenze SA, Madhi SA, Shiri T, et al. Imputing the direct and indirect effectiveness of childhood pneumococcal conjugate vaccine against invasive pneumococcal disease by surveying temporal changes in nasopharyngeal pneumococcal colonization. Am J Epidemiol. 2017;186:435–44.CrossRefGoogle Scholar
  10. 10.
    Pandey A, Dhingra N, Kumar P, et al. Sustained progress, but no room for complacency: results of 2015 HIV estimations in India. Indian J Med Res. 2017;146:83–96.CrossRefGoogle Scholar
  11. 11.
    Sachdeva A. Pneumococcal conjugate vaccine introduction in india's universal immunization program. Indian Pediatr. 2017;54:445–6.CrossRefGoogle Scholar
  12. 12.
    Arya BK, Bhattacharya SD, Sutcliffe CG, et al. Impact of Haemophilus influenzae type B conjugate vaccines on nasopharyngeal carriage in hiv-infected children and their parents from West Bengal, India. Pediatr Infect Dis J. 2016;35:e339–47.CrossRefGoogle Scholar
  13. 13.
    Arya BK, Bhattacharya SD, Sutcliffe CG, et al. Nasopharyngeal pneumococcal colonization and impact of a single dose of 13-valent pneumococcal conjugate vaccine in indian children with HIV and their unvaccinated parents. Pediatr Infect Dis J. 2018;37:451–8.CrossRefGoogle Scholar
  14. 14.
    Satzke C, Turner P, Virolainen-Julkunen A, et al. Standard method for detecting upper respiratory carriage of Streptococcus pneumoniae: updated recommendations from the World Health Organization pneumococcal carriage working group. Vaccine. 2013;32:165–79.CrossRefGoogle Scholar
  15. 15.
    Slotved HC, Kaltoft M, Skovsted IC, Kerrn MB, Espersen F. Simple, rapid latex agglutination test for serotyping of pneumococci (Pneumotest-latex). J Clin Microbiol. 2004;42:2518–22.CrossRefGoogle Scholar
  16. 16.
    Kumar N, Gupta N, Kishore J. Kuppuswamy's socioeconomic scale: updating income ranges for the year 2012. Indian J Public Health. 2012;56:103–4.CrossRefGoogle Scholar
  17. 17.
    Heinsbroek E, Tafatatha T, Chisambo C, et al. Pneumococcal acquisition among infants exposed to HIV in rural Malawi: a longitudinal household study. Am J Epidemiol. 2016;183:70–8.CrossRefGoogle Scholar
  18. 18.
    Verani JR, Massora S, Acacio S, et al. Nasopharyngeal carriage of Streptococcus pneumoniae among HIV-infected and -uninfected children <5 years of age before introduction of pneumococcal conjugate vaccine in Mozambique. PLoS One. 2018;13:e0191113.CrossRefGoogle Scholar
  19. 19.
    Cardoso VC, Cervi MC, Cintra OA, Salathiel AS, Gomes AC. Nasopharyngeal colonization with Streptococcus pneumoniae in children infected with human immunodeficiency virus. J Pediatr (Rio J). 2006;82:51–7.Google Scholar
  20. 20.
    Safari D, Kurniati N, Waslia L, et al. Serotype distribution and antibiotic susceptibility of Streptococcus pneumoniae strains carried by children infected with human immunodeficiency virus. PLoS One. 2014;9:e110526.CrossRefGoogle Scholar
  21. 21.
    Anthony L, Meehan A, Amos B, et al. Nasopharyngeal carriage of Streptococcus pneumoniae: prevalence and risk factors in HIV-positive children in Tanzania. Int J Infect Dis. 2012;16:e753–7.CrossRefGoogle Scholar
  22. 22.
    Sepako E, Glennie SJ, Jambo KC, et al. Incomplete recovery of pneumococcal CD4 T cell immunity after initiation of antiretroviral therapy in HIV-infected malawian adults. PLoS One. 2014;9:e100640.CrossRefGoogle Scholar
  23. 23.
    Nunes MC, von Gottberg A, de Gouveia L, et al. Persistent high burden of invasive pneumococcal disease in south African HIV-infected adults in the era of an antiretroviral treatment program. PLoS One. 2011;6:e27929.CrossRefGoogle Scholar
  24. 24.
    von Gottberg A, de Gouveia L, Tempia S, et al. Effects of vaccination on invasive pneumococcal disease in South Africa. N Engl J Med. 2014;371:1889–99.CrossRefGoogle Scholar
  25. 25.
    Singh J, Sundaresan S, Manoharan A, Shet A. Serotype distribution and antimicrobial susceptibility pattern in children</=5years with invasive pneumococcal disease in India - a systematic review. Vaccine. 2017;35:4501–9.CrossRefGoogle Scholar
  26. 26.
    Madhi SA, Nunes MC. The potential impact of pneumococcal conjugate vaccine in Africa: considerations and early lessons learned from the south African experience. Hum Vaccin Immunother. 2016;12:314–25.CrossRefGoogle Scholar
  27. 27.
    Balsells E, Guillot L, Nair H, Kyaw MH. Serotype distribution of Streptococcus pneumoniae causing invasive disease in children in the post-PCV era: a systematic review and meta-analysis. PLoS One. 2017;12:e0177113.CrossRefGoogle Scholar
  28. 28.
    Verghese VP, Veeraraghavan B, Jayaraman R, et al. Increasing incidence of penicillin- and cefotaxime-resistant Streptococcus pneumoniae causing meningitis in India: time for revision of treatment guidelines? Indian J Med Microbiol. 2017;35:228–36.CrossRefGoogle Scholar

Copyright information

© Dr. K C Chaudhuri Foundation 2019

Authors and Affiliations

  • Bikas K. Arya
    • 1
  • Sangeeta Das Bhattacharya
    • 1
    Email author
  • Gautam Harigovind
    • 1
  • Ranjan S. Das
    • 1
  • Tila Khan
    • 1
  • Feroze Ganaie
    • 2
  • Swapan K. Niyogi
    • 3
  • K. L. Ravikumar
    • 2
  • Anand Manoharan
    • 4
    • 5
  • Subhasish Bhattacharyya
    • 6
    • 7
  • Samiran Panda
    • 3
    • 8
  • Sutapa Mandal
    • 3
  • Banuja Acharya
    • 1
  1. 1.School of Medical Science & TechnologyIndian Institute of Technology-Kharagpur, IIT Kharagpur CampusKharagpurIndia
  2. 2.Department of MicrobiologyKempegowda Institute of Medical SciencesBengaluruIndia
  3. 3.National Institute of Cholera and Enteric Diseases (NICED)/Indian Council of Medical Research (ICMR)KolkataIndia
  4. 4.Medicine Unit I & IDChristian Medical College & HospitalVelloreIndia
  5. 5.CHILDS Trust Medical Research FoundationChennaiIndia
  6. 6.Department of PediatricsMidnapore Medical College and HospitalMedinipurIndia
  7. 7.Department of Pediatrics College of Medicine and Sagore Dutta HospitalKolkataIndia
  8. 8.National AIDS Research Institute Pune (NARI/ICMR)PuneIndia

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