JRHS 2015; 15(3): 141-146        

Copyright© Journal of Research in Health Sciences

Prevalence of Nasopharyngeal Carriage of Streptococcus pneumonia in Iran: A Meta-Analysis

Seyed Mehdi Hosseini (MSc)a, Jalal Poorolajal (MD, PhD)b, Manoochehr Karami (MSc, PhD)c*, Pegah Ameri (MSc)a

a Department of Epidemiology, School of Public Health, Hamadan University of Medical Sciences, Hamadan, Iran

b Research Center for Health Sciences and Department of Epidemiology, School of Public Health, Hamadan University of Medical Sciences, Hamadan, Iran

c Social Determinants of Health Research Center (SDHRC) and Department of Epidemiology, School of Public Health, Hamadan University of Medical Sciences, Hamadan, Iran

* Correspondence: Manoochehr Karami (MSc, PhD) , E-mail: ma.karami@umsha.ac.ir

Received: 05 July 2015, Revised: 06 August 2015, Accepted: 23 August 2015, Available online: 07 September 2015


Background: Streptococcus pneumonia is a major cause of childhood morbidity and mortality worldwide. Several studies have explored the nasopharyngeal carriage of S. pneumonia in Iran. This meta-analysis is aimed at exploring the overall prevalence of nasopharyngeal carriage of S. pneumonia among healthy children and its resistance to antibiotics.

Method: We have systematically reviewed published studies from international databases (PubMed, Web of Science, and Scopus) and national databases (Iranmedex, Magiran, Medlib, SID and Irandoc) and reference lists of articles published up to May 2015. Only cross-sectional studies supported with sensitivity test on samples collected from nasopharyngeal area were included and heterogeneity was assessed using Q-test and I2 test statistic. Publication bias was explored using the Egger's and Begg's tests and the funnel plot. The overall prevalence of analyzed data were reported with 95% confidence intervals (CI) using the random-effects model.

Results: A total of 16 studies were included in the final analysis. The pooled prevalence of S. pneumonia nasopharyngeal carriage was 18% (95% CI: 14% - 23%). Antibiotic resistance rates were 26% (95% CI: 15%  - 37%) to penicillin, 30% (95% CI: 10% - 49%) to erythromycin and 34% (95% CI: 10% - 57%) to tetracycline respectively.

Conclusions: This study could be able effectively estimate the overall prevalence of nasopharyngeal carriage of S. pneumonia and its antibiotics resistance rate among healthy children in Iran.

Keywords: Streptococcus Pneumonia, Nasopharyngeal Carriage, Antibiotic Resistance, Meta-Analysis


Streptococcus pneumonia, a gram-positive diplococcus, is a clinically important human pathogen that causes many infections such as pneumonia, sepsis, meningitis, sinusitis and acute otitis media1-3. Globally, it is one of the major causes of morbidity and mortality especially among children under the age of five years2,4.  

Streptococcus has several serotypes, which is characterized by its polysaccharide capsular5. Currently more than 90 different serotypes are distinguished1. However, not all serotypes have the same potential to cause disease. A limited number of serotypes are commonly found to cause disease among children under the age of five around the world6. Distribution of the disease-causing serotypes varies by geographic areas, age groups, socio-economic conditions, and seasonal variations6,7.

Pneumococcus often colonizes the upper respiratory tract and human nasopharynx is the only natural reservoir for it8. Transmission of the microorganism is through contact with respiratory droplets9. A carrier of the bacteria in the nasopharynx is often asymptomatic. The bacteria usually cause local infections such as sinusitis and acute otitis media. Sometimes it enters the bloodstream and causes invasive pneumococcal diseases (IPD) such as septicemia, pneumonia, and meningitis10-12.

Many factors including age, genetic background, socioeconomic status, immune status and geographic diversity influence the incidence of severe pneumococcal disease13.

Nasopharyngeal carriage of pneumococcus is possible at any time during a person's life, but mainly occurs in the first year of life14. The prevalence of nasopharyngeal carriage of S. pneumonia in healthy children under the age of five years ranged from 20% to 93.4% in low-income countries15. Median period of the carriage status was 31 days in adults and 60.5 days in children. This period depends on the serotypes, previous exposure to the bacteria, age and immune status16. In 2013, WHO estimated 935,000 deaths among children under the age of five years due to pneumonia worldwide. Out of which the cause of death for about 15% the children was S. pneumonia17.

Vaccination is the straight way to reduce pneumococcal disease and its nasopharyngeal carriage. There are several types of vaccines that two-polysaccharide vaccines (PCV13 and PCV7) are recently introduced. These vaccines include 7-valent pneumococcal conjugate vaccine (PCV7) which contains the polysaccharides of serotypes 4, 6B, 9V, 14, 18C, 19F, 23F and 13-valent pneumococcal conjugate vaccine (PCV13) and capsular antigens of serotypes 1, 3, 4, 5, 6A, 6B, 7F, 9V, 14, 18C, 19A, 19F and 23F 18,19.

Epidemiological studies in Iran reported nasopharyngeal carriage rates of S. pneumonia ranging from 5.9% to 44.1%7,20,21. The resistance of S. pneumonia against commonly used antibiotics is another concern. Studies reported resistance rates of as high as 80% for some antibiotics22-24 and variations by country7,20,21.

There is knowledge gap regarding the current prevalence of S. pneumonia nasopharyngeal carriage. This meta-analysis was conducted to estimate nasopharyngeal carriage rate and antibiotics resistance to S. pneumonia in Iran.


Criteria for including studies

Reports that included healthy children from whom nasopharyngeal samples were taken using swabs were eligible for this analysis. Reports on cross-sectional studies in Iran supported with investigations using samples collected from nasopharyngeal area were included. Other cross-sectional studies that had used samples from other body areas, and cohort, case-control, and interventional studies were excluded.

The primary outcome of interest was to determine the prevalence of nasopharyngeal carriage of S. pneumonia among healthy children under the age of 15 years; and the second outcome was to determine antibiotic resistance among the carriers against common antibiotics.

Search methods

The search strategy was based on key words presented as follows: (sepsis OR septicemia OR septic OR encephalitis OR meningitis OR Streptococcus OR streptococcal OR streptococci OR pneumonia OR pneumococcal OR pneumococci) AND (Iran).

The PubMed, Scopus, Web of Science, Medlib, SID, Iranmedex, Magiran and Irandoc websites were accessed using the key words. Eligible materials reports done up to May 2015 were included. The reference lists of all included studies were also scanned for additional sources. Besides, attempt was made to contact the authors of included studies for additional sources of information to include in the study but without response.

Data collection and analysis

Two authors (SMH and PA) independently made the decision as to which studies met the inclusion criteria to achieve the objectives of this meta-analysis. Two potentially eligible studies and presented fully in texts reports were excluded from the analysis. Provinces with only one study were not included in the analysis. In all phases of the research process, issues faced among the authors, were reached agreement through discussions.

The quality of the included studies was evaluated using STROBE checklist25,26. Heterogeneity across the studies was explored using Chi-squared (χ2) test at the 5% significance level (P < 0.05) and was quantified using I2statistic.27,28. Publication bias was assessed using Begg's and Egger's tests and visualized using the funnel plot29-32.

Stata software version 11 was employed for the data analysis. Results are reported using a random effect model with 95% confidence interval (CI).


Description of study

We reviewed 3876 references from international databases and 4937 references from national databases until May 2015. We excluded 4936 duplicates and 3717 clearly irrelevant references through reading of the topics and abstracts of the reports. One hundred and sixty articles were potentially eligible. Through further screening, 144 studies were excluded because they did not meet the inclusion criteria. Eventually, 16 studies7,20,21,33-45 were included in the meta-analysis (Figure 1), out of which eight articles were in English and the remaining eight article were in Persian. One article used the samples taken from oropharyngeal area.

Table 1 presents the years when and where the researches were conducted, other main characteristics that are included in the final analysis of this study. Altogether, the studies included 11,874 participants. Among these study reports, the highest and lowest prevalence of carriage status was reported from studies conducted in Tehran by Safari et al 45 and Noorbakhsh et al 43 respectively. The average nasopharyngeal S. pneumonia carriage rate of the healthy children was 18% (95% CI: 14%, 23%).

Antibiotics drug resistance

Among the studies resistance to three common antibiotics were reported. Five studies reported resistance to erythromycin, eight studies resistance to penicillin and another five studies reported resistance to tetracycline that accounted for 30% (95% CI: 10%, 49%), 26% (95% CI: 15%, 37%) and 34% (95% CI: 10%, 57%) respectively (Table 2).

Heterogeneity and publication bias

The results of heterogeneity assessment are presented in Figure 2-4. The findings show the existence of a statistically significantly high heterogeneity (I2=98%, P=0.001) among the studies (Figure 2). Similarly, a statistically significantly high heterogeneity in S. pneumonia carriage rates by province (I2=98.6%, P=0.001) and in children under the age of 7 years (I2=96.8%, P=0.001) were observed.  However, a statistically significant moderate heterogeneity was found in children over the age of 7 years (I2=68.7%, P=0.012) (Figure 3 and Figure 4, respectively).

The findings from the Begg's (P=0.012) and Egger's      (P=0.071) tests indicated the presence of publication bias among the studies.

Subgroup analysis

Analysis revealed variation in the prevalence of S. pneumonia nasopharyngeal carriage rates by province. For example, the prevalence was 9% (95% CI: 7%, 10%) in Mashhad, 26% (95% CI: 2%, 51%) in Tehran, 23% (95% CI, 9%, 36%) in Shahrkord and 14% (95% CI: 13%, 15%) in Kashan (Figure 3). In addition, the prevalence of carriage was 18% (95% CI: 13%, 23%) in children under the age of 7 years and 13% (95% CI: 12%, 15%) in children over the age of 7 years (Figure 4).

Figure 1: Flow chart of the study selection process        

Figure 2: Meta-analysis of S. pneumonia carriage in healthy children

Figure 3: Meta-analysis of S. pneumonia carriage in healthy children by province

Figure 4: Meta-analysis of S. pneumonia carriage in healthy children by age group

Table 1: Summary of studies results

Table 2: Antibiotic resistance rate for three common antibiotics


This meta-analysis included 16 studies that reported S. pneumonia carriage status. The overall prevalence of nasopharyngeal S. pneumonia carriage was 18%. This shows that the nasopharyngeal S. pneumonia carriage rate in Iran to be moderate.

The prevalence of S. pneumonia carriage in under 5 year old children is most commonly reported. This study compared S. pneumonia carriage status in children below and over the age of 7 years. The prevalence was higher in children under the age of 7 years (18%) than in children over the age of 7 years (13%).

Furthermore, since the prevalence of S. pneumonia carriage varies by province in Iran, a subgroup analysis by province was made. However, lack of study reports from the entire provinces was one of the limitations of this analysis. This analysis demonstrated that the highest prevalence (26%) was reported from Tehran and the lowest (0.09%) was from Mashhad.

Antibiotic resistance rate of S. pneumonia particularly in children is an important issue worldwide. Nine of studies included in the meta-analysis reported antimicrobial resistance for three common antibiotics. The subgroup analysis by antibiotics indicated that resistance rate was 30% for erythromycin, 26% for penicillin and 34% for tetracycline respectively.

The Q-test and I2 statistical tests indicated heterogeneity among the included studies. The majority of the observed heterogeneity may be attributable to the quality of the included studies, variations in population sizes, socio-demographic characteristics, and potential confounding factors that were not controlled in the studies. However, these statistical tests should be interpreted with caution. The Q-test is likely to have low statistical power when the sample size or the number of studies included in the analysis is small. On the other hand, when the sample size or the number of the studies included is high such as in ours with 16 studies involving 11,784 participants, the test is more likely have high power in detecting a small amount of heterogeneity that may be clinically unimportant46.

Adegbola et al.15 conducted a similar study to estimate the carriage rate of S. pneumonia among healthy children below the age of 5 years and adults in low and lower-middle income counties. They retrieved 11 articles, of which 5 were from low income and the remaining 6 were from lower-middle income counties. The study reported a higher prevalence of S. pneumonia carriage among children in low-income than in lower-middle income countries. In addition, the prevalence was higher in young children than in adults. The high prevalence of S. pneumonia carriage among the younger age group children in the current study is consistent with previous study. However, the current finding indicated that prevalence of carriage is lower than that reported from low income, 64.8% (95%CI: 49.8%, 79.1%), and low-middle income countries, 47.8% (95% CI: 44.7%, 50.8%), before the introduction of PCV.

The poor quality of the reports included in the analysis, small sample sizes (in some study) and not controlling potential confounding factors were the main limitations and potential sources of biases for the current meta-analysis.


Despite the limitations, this study could effectively estimate the overall prevalence of nasopharyngeal carriage of S. pneumonia and antibiotics resistance rate among children in Iran. This study could contribute to the change in general view about the necessity of vaccination.


This work was adapted from an MSc thesis in Epidemiology at Hamadan University of Medical Sciences. The study was funded by the Vice Chancellor for Research and Technology, Hamadan University of Medical Sciences (No. 9403121224).

Conflict of interest statement

The authors declare that they have no conflicts of interest in this study.


  1. Calix JJ, Porambo RJ, Brady AM, Larson TR, Yother J, Abeygunwardana C, et al. Biochemical, genetic, and serological characterization of two capsule subtypes among Streptococcus pneumoniae Serotype 20 strains: discovery of a new pneumococcal serotype. J Biol Chem. 2012;287(33):27885-27894.
  2. Plumptre CD, Ogunniyi AD, Paton JC. Surface association of Pht proteins of Streptococcus pneumoniae. Infect Immun. 2013;81(10):3644-3651.
  3. Rosen JB, Thomas AR, Lexau CA, Reingold A, Hadler JL, Harrison LH, et al. Geographic variation in invasive pneumococcal disease following pneumococcal conjugate vaccine introduction in the United States. Clin Infect Dis. 2011;53(2):137-143.
  4. Welte T, Torres A, Nathwani D. Clinical and economic burden of community-acquired pneumonia among adults in Europe. Thorax. 2012;67(1):71-79.
  5. Oliver MB, van der Linden MP, Kuntzel SA, Saad JS, Nahm MH. Discovery of Streptococcus pneumoniae  serotype 6 variants with glycosyltransferases synthesizing two differing repeating units. J Biol Chem. 2013;288(36):25976-25985.
  6. Johnson HL, Deloria-Knoll M, Levine OS, Stoszek SK, Freimanis Hance L, Reithinger R, et al. Systematic evaluation of serotypes causing invasive pneumococcal disease among children under five: the pneumococcal global serotype project. PLoS Med. 2010;7(10):e1000348.
  7. Sanaei Dashti A, Abdinia B, Karimi A. Nasopharyngeal carrier rate of Streptococcus pneumoniae  in children: serotype distribution and antimicrobial resistance. Arch Iran Med. 2012;15(8):500-503.
  8. Shak JR, Vidal JE, Klugman KP. Influence of bacterial interactions on pneumococcal colonization of the nasopharynx. Trends Microbiol. 2013;21(3):129-135.
  9. Hill PC, Akisanya A, Sankareh K, Cheung YB, Saaka M, Lahai G, et al. Nasopharyngeal carriage of Streptococcus pneumoniae  in Gambian villagers. Clin Infect Dis. 2006;43(6):673-679.
  10. Bogaert D, De Groot R, Hermans PW. Streptococcus pneumoniae  colonisation: the key to pneumococcal disease. Lancet Infect Dis. 2004;4(3):144-154.
  11. Simell B, Auranen K, Kayhty H, Goldblatt D, Dagan R, O'Brien KL. The fundamental link between pneumococcal carriage and disease. Expert Rev Vaccines. 2012;11(7):841-855.
  12. Weinberger DM, Trzcinski K, Lu YJ, Bogaert D, Brandes A, Galagan J, et al. Pneumococcal capsular polysaccharide structure predicts serotype prevalence. PLoS Pathog. 2009;5(6):e1000476.
  13. van der Poll T, Opal SM. Pathogenesis, treatment, and prevention of pneumococcal pneumonia. Lancet. 2009;374(9700):1543-1556.
  14. Tigoi CC, Gatakaa H, Karani A, Mugo D, Kungu S, Wanjiru E, et al. Rates of acquisition of pneumococcal colonization and transmission probabilities, by serotype, among newborn infants in Kilifi District, Kenya. Clin Infect Dis. 2012;55(2):180-188.
  15. Adegbola RA, DeAntonio R, Hill PC, Roca A, Usuf E, Hoet B, et al. Carriage of Streptococcus pneumoniae  and other respiratory bacterial pathogens in low and lower-middle income countries: a systematic review and meta-analysis. PLoS One. 2014;9(8):e103293.
  16. Turner P, Turner C, Jankhot A, Helen N, Lee SJ, Day NP, et al. A longitudinal study of Streptococcus pneumoniae  carriage in a cohort of infants and their mothers on the Thailand-Myanmar border. PLoS One. 2012;7(5):e38271.
  17. World Health Organization. Pneumonia. WHO Web Site; 2014 [updated November 2014; cited 10 January, 2015]; Available from: http://www.who.int/mediacentre/factsheets/fs331/en/
  18. Lexau CA, Lynfield R, Danila R, Pilishvili T, Facklam R, Farley MM, et al. Changing epidemiology of invasive pneumococcal disease among older adults in the era of pediatric pneumococcal conjugate vaccine. JAMA. 2005;294(16):2043-2051.
  19. Weinberger DM, Malley R, Lipsitch M. Serotype replacement in disease after pneumococcal vaccination. Lancet. 2011;378(9807):1962-1973.
  20. Behnaz F, Firousabadi L, Babaei- Zadeh A, Mohammad - Zadeh M. Prevalence of pharyngeal pneumococcal carriers and succeptibility patterns among children of day care centers in Yazd District, Iran. The Journal of Shahid Sadoughi University of Medical Sciences. 2004;12(1):65-69. [Persian]
  21. Bokaeian M, Khazaei HA, Javadimehr M. Nasopharyngeal carriage, antibiotic resistance and serotype distribution of Streptococcus pneumoniae  among healthy adolescents in Zahedan. Iran Red Crescent Med J. 2011;13(5):328-333.
  22. Cho EY, Kang HM, Lee J, Kang JH, Choi EH, Lee HJ. Changes in serotype distribution and antibiotic resistance of nasopharyngeal isolates of Streptococcus pneumoniae  from children in Korea, after optional use of the 7-valent conjugate vaccine. J Korean Med Sci. 2012;27(7):716-722.
  23. Cho EY, Lee H, Choi EH, Kim YJ, Eun BW, Cho YK, et al. Serotype distribution and antibiotic resistance of Streptococcus pneumoniae  isolated from invasive infections after optional use of the 7-valent conjugate vaccine in Korea, 2006-2010. Diagn Microbiol Infect Dis. 2014;78(4):481-486.
  24. Mayanskiy N, Alyabieva N, Ponomarenko O, Lazareva A, Katosova L, Ivanenko A, et al. Serotypes and antibiotic resistance of non-invasive Streptococcus pneumoniae  circulating in pediatric hospitals in Moscow, Russia. Int J Infect Dis. 2014;20:58-62.
  25. Gallo V, Egger M, McCormack V, Farmer PB, Ioannidis J, Kirsch-Volders M, et al. Strengthening the Reporting of Observational studies in EpidemiologyMolecular Epidemiology (STROBE-ME): An extension of the STROBE statement. Eur J Clin Invest. 2012;42(1):1-16.
  26. von Elm E, Altman DG, Egger M, Pocock SJ, Gøtzsche PC, Vandenbroucke JP. The Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) statement: guidelines for reporting observational studies. Prev Med. 2007;45(4):247-251.
  27. Higgins JP, Thompson SG, Deeks JJ, Altman DG. Measuring inconsistency in meta-analyses. BMJ. 2003;327(7414):557.
  28. Rücker G, Schwarzer G, Carpenter JR, Schumacher M. Undue reliance on I2 in assessing heterogeneity may mislead. BMC Med Res Methodol. 2008;8(1):79.
  29. Leandro G, Giuseppe G. Meta-Analysis in Medical Research. Massachustts: Blackwell Publishing; 2005.
  30. Møller AP, Jennions MD. Testing and adjusting for publication bias. Trends Ecol Evol. 2001;16(10):580-586.
  31. Thornton A, Lee P. Publication bias in meta-analysis: its causes and consequences. J Clin Epidemiol. 2000;53(2):207-216.
  32. Egger M, Smith GD, Schneider M, Minder C. Bias in meta-analysis detected by a simple, graphical test. BMJ. 1997;315(7109):629-634.
  33. Bakhshaee M, Naderi HR, Ghazvini K, Sotoudeh K, Amali A, Ashtiani SJ. Passive smoking and nasopharyngeal colonization by Streptococcus pneumoniae , Haemophilus influenzae, and Moraxella catarrhalis in daycare children. Eur Arch Otorhinolaryngol Suppl. 2012;269(4):1127-1132.
  34. Ghaemi A, Fazeli MR, Tabraei A, vakili MA. Evaluating the prevalence of pneumococcal nasopharyngeal carriers among Healthy student's in Gorgan. Urmia Medical Journal. 2002;13(1):16-24. [Persian]
  35. Jalilinejad H. Risk factor of penicillin_resistant  pneumococcal nasopharyngeal carriers in bandar abbas day care  children and their antibiotic resistance pattern [PhD thesis]. Bandar Abbas, Homozgan University of Medical Sciences; 2014. [Persian]
  36. Khoshdel A, Imani r, Saedi A, Kheire S, Hamidi M, Kasiri K, et al. The prevalence of Streptococcus pneumonia and its penicillin resistance pattern in children less than five years old from Shahrekord, Iran, 2007. Journal of Shahrekord Uuniversity of Medical Sciences. 2009;10(4):89-95. [Persian]
  37. Khoshdel A, Rastabi RI, Doosti A, Askari S, Hafizi M. Prevalence of Heptavalent Vaccine-related Pneumococcal Serotypes in Nasopharyngeal carrier in children under five years old in Shahrekord, Iran by Multiplex-PCR during 2010- 2011. J Clin Diagn Res. 2014;8(11):Pc01-04.
  38. Bakhshaee M, Ghazvini K, Naderi H, Zamanian A, Haghighi J, Boghrabadian M. The prevalence of nasopharyngeal streptococcal pneumonia carriers in Mashhad day care children and their antibiotic resistance pattern. Iran J Otorhinolaryngol. 2006;18(45):119-126. [Persian]
  39. Fahimzad A, Karimi B, A MM, Shamshiri AR, Mohkam M, Sharifian M, et al. Prevalence of variant bacteria in oropharyngeal colonization of Iranian children. Arch Clin Infect Dis. 2008;3(1):25-28.
  40. Mirzaei Ghazi Kalayeh H, Moniri R, Moosavi SGA, Rezaei M, Yasini M, Valipour M. Serotyping, antibiotic susceptibility and related risk factors aspects of nasopharyngeal carriage of Streptococcus pneumoniae  in healthy school students. Iran J Public Health. 2014;43(9):1284-1290.
  41. Mirzaei Ghazi Kalayeh H, Moniri R, Pirozmand A, Valipour M, Rezaei M, Yasini M, et al. Evaluating the prevalence of pneumococcal nasopharyngeal carriers and the related risk factors among students in Kashan. Feyz. 2014;17(6):597-601. [Persian]
  42. Mousavi SF, Nobari S, Ghezelgeh FR, Lyriai H, Jalali P, Shahcheraghi F, et al. Serotyping of Streptococcus pneumoniae  isolated from Tehran by Multiplex PCR: Are serotypes of clinical and carrier isolates identical? Iran J Microbiol. 2013;5(3):220-226.
  43. Noorbakhsh S, Shenasa S, Rafee Nejad M. Determination of penicillin resistant pneumococcus colonization in children whom stay in day care centers during 1996-1997. Razi Journal of Medical Sciences. 2001;8(26):472-478.[ Persian]
  44. Kordi Darian R, Tavakoli A. Relative frequency of Pneumococcies resistant to Penicillin and of the antibiotics in Isfahan's nurseries. J Res Med Sci. 1998;3(1):48-51. [Persian]
  45. Safari M, Ghavamian P, Ershadi A. Evaluating the prevalence of pneumococcal nasopharyngeal carriers among students in Kashan,1995. Feyz. 1997;3(1):69-74. [Persian]
  46. Higgins JPT, Green S. Cochrane handbook for systematic reviews of interventions Version 5.0.0 [updated February 2008]. The Cochrane Collaboration; 2008: www.cochrane-handbook.org .

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