Skip to content

Advertisement

You're viewing the new version of our site. Please leave us feedback.

Learn more

BMC Microbiology

Open Access

High genetic diversity of Staphylococcus aureus strains colonising the nasopharynx of Gambian villagers before widespread use of pneumococcal conjugate vaccines

  • Chinelo Ebruke1, 3,
  • Michel M. Dione1,
  • Brigitte Walter1,
  • Archibald Worwui1,
  • Richard A. Adegbola4,
  • Anna Roca2 and
  • Martin Antonio1, 3, 5Email author
BMC MicrobiologyBMC series – open, inclusive and trusted201616:38

https://doi.org/10.1186/s12866-016-0661-3

Received: 4 August 2015

Accepted: 2 March 2016

Published: 12 March 2016

Abstract

Background

With the global efforts of reducing pneumococcal disease through widespread introduction of pneumococcal vaccines, concerns have emerged on the potential increase of morbidity and mortality from S. aureus disease. Little is known however, of the carriage rates of S. aureus or of its’ relationship with carriage of S. pneumoniae in rural Africa, and West Africa in particular where very high rates of carriage of S. pneumoniae have been reported. This study aims to evaluate the prevalence, antibiotic susceptibility patterns and genotypes of S. aureus isolated from the nasopharynx of healthy individuals in rural Gambia before the introduction of routine use of pneumococcal conjugate vaccines in the country.

Results

Overall prevalence of S. aureus nasopharyngeal carriage was 25.2 %. All S. aureus isolates tested were susceptible to methicillin. Resistant was observed for sulphamethoxazole-trimethoprim (15 %) and tetracycline (34.3 %). We found 59 different sequence types (ST), 35 of which were novel. The most prevalent sequence types were ST 15 (28 %) and ST 5 (4 %). Eighty two percent (494/600) of study individuals were S. pneumoniae carriers with S. pneumoniae carriage rates decreasing with increasing age groups. S. aureus carriage among pneumococcal carriers was slightly lower than among non-pneumococcal carriers (24.3 versus 29.3 %; p = 0.324). There were no associations of carriage between these two bacteria across the 4 age groups. However, analysis of pooled data children < 2 years and children 2 to < 5 years of age showed a statistically significant inverse association (24.1 and 50.0 % for S. aureus carriage among S. pneumoniae carriers and non-carriers respectively; p = 0.015).

Conclusions

We report that nasopharyngeal carriage of S. aureus in rural Gambia is high in all age groups, with approximately 1 out of 4 individuals being carriers in the pre-pneumococcal vaccination era. There are indications that nasopharyngeal carriage of S.aureus could be inversely related to carriage of S. pneumoniae amongst younger children in The Gambian and that S. aureus clones in The Gambia show significant genetic diversity suggesting worldwide dissemination. Findings from this study provide a useful background for impact studies evaluating the introduction of pneumococcal vaccines or other interventions targeting the control of S. aureus infections and disease.

Keywords

Staphylococcus aureus Streptococcus pneumoniae ColonizationAntibiotic resistanceGenotypesThe Gambia

Background

Staphylococcus aureus is a common cause of nosocomial and community acquired infections worldwide and results in significant morbidity and mortality in children and adults [13]. Surveillance data from both the developed and the developing world, including Africa, report S. aureus as one of the leading causes of invasive bacterial infections among young children with incidence rates peaking in newborns [4, 5]. Invasive S. aureus disease is assuming increasing importance globally with the emergence of drug-resistant and community associated methicillin resistant strains [6].

The anterior nares and the nasopharynx are recognised as colonization sites of S. aureus and an important antecedent to subsequent invasive S. aureus disease [7, 8]. Nasopharyngeal carriage studies have been used in screening programmes for early detection of individuals at high risk for invasive S. aureus disease [9].

Another leading cause of human infection and death is Streptococcus pneumoniae, also frequently found in the nasopharynx of healthy individuals. Some studies have reported an inverse relationship between carriage of S. aureus and S. pneumoniae both before [1012] and after [13] the use of pneumococcal conjugate vaccines. With increasing global efforts of reducing pneumococcal disease through widespread introduction of pneumococcal vaccines, concerns have emerged on the potential increase of morbidity and mortality from S. aureus disease. Little is known however, on carriage rates of S. aureus and the relationship between carriage of S. aureus and S. pneumoniae in rural Africa [14]. This could be particularly important in West Africa where very high rates of carriage of S. pneumoniae have been reported [15, 16].

This study aims to evaluate the prevalence, antibiotic susceptibility patterns and genotypes of S. aureus isolated from the nasopharynx of healthy individuals resident in rural Gambia before the introduction of pneumococcal conjugate vaccines as part of the Expanded Programme of Immunization in the country. Associations between the isolation of S. aureus and S. pneumoniae in the nasopharynx were also evaluated.

Methods

Study population

Samples used for this study were obtained from a cross sectional survey conducted in between 2003 and 2004 as described elsewhere [15]. Briefly, 21 villages in Western Division, The Gambia, located outside the region where a previous pneumococcal vaccine efficacy trial was undertaken [17], were selected for this survey. The population comprised predominantly subsistence farmers and belonged mainly to the Jola and Mandinka ethnic groups. The prevalence of HIV infection was 2–3 % [18]. The Gambia Government/MRC Joint Ethics Committee approved the study. Trained field workers/nurses explained the contents of the study information sheet to parents/guardians in their own language. Adult participants gave written informed consent prior to enrolment. Parents/guardians of all children participants gave written informed consent prior to enrolment.

Study design

To obtain a balanced sample of subjects from different age groups, one nasopharyngeal swab (NPS) per child was collected from all children less than 5 years of age and adults 50 years and above and from a random 1 in 2 sample of individuals age 5–49 years [15]. A total of 2972 NPS were collected using calcium alginate swabs (Fisher Brand ®, USA and immediately inoculated into vials containing skim milk tryptone glucose glycerol (STGG) transport medium (Oxoid, Basingstoke, UK). Inoculated swabs were transported to the Medical Research Council Laboratories, Fajara (a distance of 90 km) in a cold box within 8 h of collection in accordance with the World Health Organization protocol for evaluation of carriage [19]. Inoculated vials were stored at −70 °C until ready for testing in batches. S. pneumoniae was isolated and antibiotic susceptibility testing and serotyping were done using standard techniques [15].

For the purpose of the current study, a random selection of 600 NPS of the 2972 samples collected were included for analysis. Randomization was age-adjusted to obtain 150 samples in each study age category, grouped as < 2 years, 2 to < 5 years, 5 to < 15 years and ≥ 15 years.

Microbiology laboratory investigations

For isolation of S. aureus, 100 μl of thawed NPS was plated out on 5 % sheep Blood Agar (BA) and Mannitol Salt Agar (MSA) plates (Oxoid, Basingstoke, UK) which were aerobically incubated at 37 °C for 24 and 48 h respectively. BA plates were examined for pale to golden yellow doomed shaped colonies 4–5 mm in diameter showing alpha haemolysis while MSA plates were examined for mannitol fermenting colonies. These were sub-cultured on 5 % sheep BA plates overnight. Cultures were tested by Slidex Staph kit (Biomerieux, Basingstoke, Hampshire, UK), a rapid latex and red blood cell agglutination test for the identification of S. aureus. Positive cells were tested for antibiotic sensitivity by disk diffusion for a wide range of antibiotics (Oxoid, Basingstoke, UK) including oxacillin (1 μg), chloramphenicol (30 μg), trimethoprim-sulphamethazole (1.25/23.75 μg), erythromycin (15 μg), tetracycline (30 μg) and cefotaxime (30 μg)following CLSI guidelines [20]. Isolates that showed intermediate resistance to oxacillin were further screened with cefoxitin disk (30 μg) to rule out methicillin resistance. The MRC Unit The Gambia, molecular microbiology laboratory submits to the external quality assurance programme of the UK National External Quality Assessment Service [21] and is a World Health Organization (WHO) Regional Reference Laboratory for invasive bacterial pathogens.

Multilocus sequencing typing (MLST)

MLST was performed on an age-adjusted random selection of 100 S. aureus isolates to obtain 25 samples in each study age category. Isolates were streaked on blood agar and incubated at 37 °C for 18 h. A single colony from each isolate was picked, streaked and incubated at 37 °C for 18 h. Genomic DNA were prepared from a loopful of bacteria as described in the manufacturer's instructions (Qiagen Genomic DNA Kit, Manchester, UK). MLST was performed as described previously [22]. Sequences were edited and complementary sense antisense fragments were aligned using the Laser Gene DNA star 7.1 software. Finally, the sequences were submitted to the MLST database website (http://saureus.mlst.net) and assigned to existing or novel allele or sequence type numbers defined by the database. STs were analysed for relatedness using the eBURST v3 program (eburst.mlst.net). A clonal complex (CC) was defined as a group of sequence types (STs) sharing 6/7 alleles with at least one other member of the group; while a singleton was defined as an ST that cannot be linked to any sample. Cluster analysis of allelic profiles was performed using a categorical coefficient and a graphic method called a minimum spanning tree with Bionumerics software (version 6.5; Applied Maths, Sint-Martens-Latem, Belgium).

Data management and statistical analysis

Data were double entered into an ACCESS database and checked for range and consistency. For each of the four age groups, univariable analyses were used to assess whether S. pneumoniae carriage was significantly associated with S. aureus carriage using Chi squared or Fisher’s exact test, where appropriate. A logistic regression model was then fitted including the variables age group, gender and ethnicity. To test for an interaction between the variables age group and S. pneumoniae a log likelihood ratio test was performed. STATA (version 11, Stata Corporation, College Station TX) was used for all analyses.

Results

S. aureus carriage

For analysis of S. aureus carriage, we included NPS samples collected from 600 individuals with 150 in each of the four study age groups. The overall prevalence of S. aureus nasopharyngeal carriage was 25.2 % (n = 151). Stratifying by age group, S. aureus carriage was 20.0 % (30/150) for children < 2 years; 31.3 % (47/150) for children 2 to < 5 years; 23.3 % (35/150) for ages 5 to < 15 years and 26.0 % (35/150) for individuals ≥ 15 years (p = 0.140). There was no significant difference in carriage prevalence by gender (46 % females versus 54 % for males; p = 0.336).

Antibiotics susceptibility testing of S. aureus isolates

Antibiotic susceptibility was tested on 93 % of S. aureus isolates (140/151). Overall susceptibility to tested antibiotics was high for oxacillin, chloramphenicol and cefotaxime (100, 93.6, and 93.6 % susceptible isolates, respectively). Susceptibility was lower for erythromycin, sulphamethoxazole-trimethoprim and tetracycline (63.6, 77.1 and 62.9 % susceptible isolates, respectively), although resistant isolates were only found for sulphamethoxazole-trimethoprim and tetracycline (15 and 34.3 % of overall isolates, respectively). Susceptibility to erythromycin increased with age groups (p = 0.015,) and children < 2 years were less susceptible to all antibiotics than older children and adults (Table 1).
Table 1

Antibiotics susceptibility pattern of S. aureus stratified by age groups

 

<2 years n (%)

2–5 years n (%)

6–15 years n (%)

>15 years n (%)

P-value

Antibiotics

S

I

R

S

I

R

S

I

R

S

I

R

 

Oxacillin

27 (100)

0

0

42(100)

0

0

33

0

0

38

0

0

 

Chloramphenicol

23 (85.2)

4 (14.8)

0

39 (92.9)

3 (7.1)

0

31(93.9)

2 (6.1)

0

38 (100)

0

0

0.121

Erythromycin

12 (44.4)

15(55.6)

0

23 (54.8)

19(45.2)

0

25(78.8)

8 (24.2)

0

29 (76.3)

9(23.7)

0

0.015

Sulphamethoxazole trimethoprim

15 (55.6)

3 (11.1)

9 (33.3)

36 (85.7)

2 (4.8)

4 (9.5)

26(78.8)

3 (9.1)

4 (12.1)

31 (81.6)

3 (7.9)

4 (10.5)

0.1

Tetracycline

13 (48.2)

1 (3.7)

13(48.2)

31 (73.8)

1 (2.4)

10(23.8)

20(60.6)

1 (3)

12(36.4)

24 (63.2)

1 (2.6)

13(34.2)

0.547

Cefotaxime

26 (96.3)

1 (3.7)

0

38 (90.5)

4 (9.5)

0

31(93.9)

2 (6.1)

0

36 (94.7)

2 (5.3)

0

0.778

S sensitive, I intermediate resistance, R resistant

Multilocus sequence typing and population biology of S. aureus isolates

MLST was performed using 100 study isolates (66 % of 151 S. aureus isolates obtained). With these bacteria we found 59 different sequence types (ST), 35 of them being novel. In addition, one new allele pta (220) was discovered. The most prevalent sequence types were ST15 (28 %) and ST5 (4 %) (Table 2). eBURST analysis using the stringent 6/7 identical loci definition grouped our dataset into 11 clonal complexes and 21 singletons. ST15, ST5 and ST188 were the largest predicted founding genotype in an eBURST analysis comparing our dataset to STs in the MLST database (Fig. 1). Analysis using a hierarchic unweighted pair group method (UPMGA) with averaging to generate a dendrogram showed no clustering in age group, antibiotic resistance, sex, ethnic group or any other measured parameter. Minimum spanning tree showed a widespread distribution of Gambian clones worldwide (Fig. 2).
Table 2

Distribution of sequence types of S. aureus and S. pneumoniae carriage obtained from this study

S. aureus ST

S. aureus Allelic profiles

S. pneumoniae carriage

 

arcC

aroE

glp

gmk

pta

tpi

yqiL

Yes

No

1

1

1

1

1

1

1

1

1

 

5

1

4

1

4

12

1

10

2

2

6

12

4

1

4

12

1

3

2

 

8

3

3

1

1

4

4

3

1

 

15

13

13

1

1

12

11

13

22

6

25

4

1

4

1

5

5

4

1

 

30

2

2

2

2

6

3

2

1

 

41

2

2

2

3

6

3

2

 

1

45

10

14

8

6

10

3

2

1

 

72

1

4

1

8

4

4

3

1

1

97

3

1

1

1

1

5

3

1

 

121

6

5

6

2

7

14

5

1

 

152

46

75

49

44

13

68

60

1

2

199

13

13

1

1

12

1

13

1

 

508

10

40

8

6

10

3

2

2

1

509

1

26

28

18

18

33

27

3

 

567

10

1

1

1

1

1

1

2

 

669

3

1

94

1

29

5

3

1

 

707

18

71

6

2

7

58

2

1

1

728

1

3

1

14

11

27

10

1

 

730

1

4

1

4

97

1

10

2

 

1004

8

163

129

19

6

125

117

1

1

1320

2

2

2

2

6

11

2

1

 

1472

2

2

2

2

6

3

162

1

 

1972

13

13

149

1

12

11

13

 

1

1973

1

26

28

18

18

11

27

1

 

1974

10

4

1

1

1

1

1

1

 

1975

3

1

1

1

1

11

3

1

 

1976

13

13

1

1

12

11

27

1

 

1977

10

13

1

1

10

11

13

1

 

1978

10

40

1

6

220

33

2

1

 

1979

1

40

8

6

220

3

10

1

 

1980

13

13

14

1

13

11

13

 

1

1981

13

13

28

1

12

11

13

1

 

1982

1

4

1

1

12

5

3

1

 

1983

10

40

8

1

10

3

2

 

1

1984

13

13

1

1

12

3

2

1

 

1985

1

26

28

1

18

33

27

1

 

1986

3

13

1

1

18

11

3

1

 

1987

4

2

2

2

12

11

4

 

1

1988

10

47

8

26

26

3

2

1

 

1989

3

1

14

1

29

5

3

1

 

1990

13

1

1

1

12

11

3

1

 

1991

3

3

1

1

4

5

3

1

 

1992

22

1

8

18

12

4

31

1

 

1993

1

13

1

4

12

1

10

1

 

1994

1

1

1

4

12

11

10

1

 

1995

1

1

4

1

5

5

4

1

 

1996

1

3

1

1

11

27

10

1

 

1997

13

13

1

1

1

33

13

1

 

1998

1

4

1

4

10

1

10

1

 

1999

3

1

94

1

1

5

3

1

 

2000

4

4

1

4

12

11

3

1

 

2001

10

13

1

1

1

11

13

1

 

2002

1

1

1

4

5

1

10

1

 

2003

1

4

1

4

97

1

100

1

 

2004

13

13

1

1

12

11

35

 

1

2005

1

1

28

18

18

33

162

 

1

2006

1

26

28

18

18

33

13

1

 

Total

       

100

New alleles and sequence types are Bolded

Fig. 1

An eBURST derived population snapshot of S. aureus highlighting our dataset. Circles represent the STs. The blue circle represents the primary founder; yellow represents the subgroup founders; black represents all other STs. Pink fonts represent STs found both in our dataset and entire MLST database, while fonts in green are STs unique to our dataset

Fig. 2

Clustering of STs using minimum spanning tree. Each circle represents an ST. The area of each circle corresponds to the number of isolates. The length of the lines represents the number of locus variants. Thick, short, solid lines connect single locus variants and thin longer solid lines connect double-locus variants. Red portions represent Gambian STs and green portions represent STs found in the rest of the world

Association between S. aureus and S. pneumoniae

Eighty two percent of study individuals were S. pneumoniae carriers (494/600) and S. pneumoniae carriage prevalence decreased with increasing age group [94.7 % (142/150) for children < 2 years; 93.3 % (140/150) for children 2 to < 5 years; 84.7 % (127/150) for ages 5 to < 15 years and 56.7 % (85/150) for individuals ≥ 15 years; p < 0.0001]. Overall, S. aureus carriage among pneumococcal carriers was slightly lower than among non-pneumococcal carriers (24.3 versus 29.3 %; p = 0.324). Similarly, when stratified by the 4 different age groups, there was no association of carriage between these two bacteria and age group (Table 3). However, there was a non-significant trend in the younger age groups (children < 2 years and children 2 to < 5 years of age) of being S. aureus carriers if they were not S. pneumoniae carriers. Analysis of pooled data for these 2 age groups showed a statistically significant inverse association (24.1 and 50.0 % for S. aureus carriage among S. pneumoniae carriers and non-carriers respectively; p = 0.015). Table 4.
Table 3

Association between S. aureus and S. pneumoniae by age groups

Age groups

S. aureus

S. pneumoniae

p - value

  

No N (%)

Yes N (%)

 

Under 2 years

No

5 (62.5)

115(81)

0.198

Yes

3 (37.5)

27(19)

 

2-under 5 years

No

4 (40)

99 (70.7)

0.072

Yes

6 (60)

41 (29.3)

 

5-under 15 years

No

19 (82.6)

96 (75.6)

0.597

Yes

5 (17.4)

31 (24.4)

 

15 and above years

No

47 (72.3)

64 (75.2)

0.710

Yes

18 (27.7)

21 (24.7)

 
Table 4

Association between S. aureus and S. pneumoniae in two age strata

 

S. aureus

S. pneumoniae

p - value

  

No N (%)

Yes N (%)

 

Under 5 years

No

9(50)

214(75.9)

0.015

Yes

9(50)

68(24.1)

 

Discussion

In this study, we documented a description of nasopharyngeal carriage of S. aureus including the rates of nasopharyngeal carriage of S. aureus across age groups, antibiotic resistance patterns and circulating sequence types among healthy Gambians prior to the introduction of routine pneumococcal vaccination as part of the Extended Programme of Immunization in the country. This study adds to the very few published studies on nasopharyngeal carriage of S. aureus in Africa.

An overall S. aureus carriage of 25.2 % reported in this study is comparable to rates reported previously in other regions in the world with a range of 10–55 % prevalence [10, 23, 24]. Similar carriage rates have also been reported in Africa [2528], including a setting with HIV- infected population [27].

Our study has revealed a diversity of clones of S. aureus circulating in this Gambian population. The discovery of 59 sequence types and 11 clonal complexes show that there is significant “clonal dissemination” within this population structure, deriving mostly from CC15 and CC5. Gambian STs clustered with STs from other parts of the world, suggesting the dissemination of S. aureus could be global. It could also suggest that S. aureus lineages are highly adaptable to various environments and can spread widely. It is also plausible that proximity of S. aureus carriage strains to each other within the nasopharynx could facilitate high mutation or recombination rates, resulting in carriage of a diverse range of clones.

Although our study has focused on S. aureus carriage in healthy individuals, a high number of clones identified in our study population have been identified previously as a cause of bacterial disease in other parts of the world. This has been the case for ST1, ST30 and ST121, which have been described as worldwide pandemic clones [29, 30]. In Nigeria, STs belonging to CC5, CC15, CC30, CC97 were associated with otitis media, urinary tract infection, semen (infertility) and wound infection [31]. Also, the Spa protein an important virulence factor for S. aureus [32] was associated with ST15, ST30 and ST72 carried in the nasopharynx of African Babongo Pygmies [33]. It is arguable that these latter clones could be harbouring a latent virulence in our settings. Further studies are needed to evaluate virulence factors as well as invasiveness of S. aureus clones in our population.

Our findings indicate that resistance of S. aureus to Sulphamethoxazole-trimethoprim, the current first line treatment for non-severe pneumonia in most developing countries, including The Gambia (WHO IMCI ARI treatment guidelines; Gambia Government Antibiotic guidelines for treatment of ARI) could be as high as 15 %. This finding as well as any similar findings from other research could provide valuable evidence for review of existing national ARI antibiotic treatment policies. Given the growing scourge of MRSA globally and its’ attendant risks to both health workers and the general public [6], it is significant that there were no MRSA identified in our study population. It is also noteworthy that data from the MLST database indicates that methicillin resistance reported for other regions of the world for ST15, the predominant ST in our study population, was much lower compared to methicillin resistance to other STs (http://saureus.mlst.net). This observation further supports our finding of no MRSA amongst S. aureus isolates in our study population. Additionally, a recent review on the molecular epidemiology of methicillin resistant S. aureus in Africa has shown that there was no methicillin resistance reported for ST15 from the 34 studies conducted in 15 countries and that CC5 was the predominant clonal complex [34].

In a population of high prevalence of S. pneumoniae carriage, our data are indicative of an inverse relationship between nasopharyngeal carriage of S. aureus and carriage of S. pneumoniae in the younger age groups and is consistent with finding in a longitudinal study amongst Gambian newborns followed up to the age of 1 year [12]. This longitudinal study reported that S. aureus carriage was inversely related to S. pneumoniae carriage in the first year of life. Our findings are also consistent with findings from previous studies in different parts of the world carried out before and after pneumococcal vaccine introduction [10, 12, 13, 35]. However, other studies have found no such inverse relationship between these two organisms in nasopharyngeal carriage [36]. Nevertheless, most studies conducted so far indicate that pneumococcal vaccination has not had a sustained impact on S. aureus carriage. A possible explanation may be that currently used pneumococcal vaccines have been linked with an increase in pneumococcal non-vaccine serotypes thereby maintaining a large pool of circulating pneumococcal serotypes. However, as efforts continue towards the use of protein based pneumococcal vaccines, the possibility of species replacement may arise and S. aureus may be a potential replacement pathogen.

We are mindful of a few caveats to be considered in the interpretation of findings from our study. Given that our study was conducted in a rural area with very limited access to antibiotics, generalization of the findings to other settings should be with some caution. Antibiotic susceptibility patterns could be different in other regions of Africa with better access to antibiotics and/or a more prevalent practice of self-medication. Our finding of total absence of methicillin resistance to S. aureus may not be representative of such high antibiotic use settings. We note also the inverse relationships we have reported between S. pneumoniae and S. aureus nasopharyngeal carriage in younger age groups could be confounded by certain risk factors of carriage, which we have not evaluated.

Studies after pneumococcal vaccine introduction in The Gambia will evaluate the effect of vaccine on rate of S. aureus carriage and this pre-vaccination study will be of high importance.

Conclusions

We report that nasopharyngeal carriage of S. aureus in rural Gambia is high in all age groups, with approximately 1 out of 4 individuals being carriers in the pre-pneumococcal vaccination era. There are indications that nasopharyngeal carriage of S. aureus could be inversely related to carriage of S. pneumoniae amongst younger children in The Gambian and that S. aureus clones in The Gambia show significant genetic diversity suggesting worldwide dissemination. These findings could provide a useful background for impact studies evaluating the introduction of pneumococcal vaccines or other interventions targeted at the control of S. aureus infection and disease.

Declarations

Acknowledgments

The study was funded by the Medical Research Council (UK). We acknowledge the use of the core sequencing facility at MRC Unit, The Gambia and the S. aureus MLST database ((http://saureus.mlst.net).

Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.

Authors’ Affiliations

(1)
Vaccine and Immunity Theme, Medical Research Council Unit
(2)
Disease Control and Elimination, Medical Research Council Unit
(3)
Faculty of Infectious and Tropical Diseases, London School of Hygiene & Tropical Medicine
(4)
GlaxoSmithKline Vaccines
(5)
Microbiology and Infection Unit, Warwick Medical School, University of Warwick

References

  1. Dolapo O, Dhanireddy R, Talati AJ. Trends of Staphylococcus aureus bloodstream infections in a neonatal intensive care unit from 2000 to 2009. BMC Pediatr. 2014;14:121.View ArticlePubMedPubMed CentralGoogle Scholar
  2. Hongsuwan M et al. Increasing incidence of hospital-acquired and healthcare-associated bacteremia in northeast Thailand: a multicenter surveillance study. PLoS One. 2014;9(10), e109324.View ArticlePubMedPubMed CentralGoogle Scholar
  3. Aiken AM et al. Risk and causes of paediatric hospital-acquired bacteraemia in Kilifi District Hospital, Kenya: a prospective cohort study. Lancet. 2011;378(9808):2021–7.View ArticlePubMedPubMed CentralGoogle Scholar
  4. Hamer DH et al. Etiology of bacteremia in young infants in six countries. Pediatr Infect Dis J. 2015;34(1):e1–8.View ArticlePubMedPubMed CentralGoogle Scholar
  5. Zaidi AK et al. Pathogens associated with sepsis in newborns and young infants in developing countries. Pediatr Infect Dis J. 2009;28(1 Suppl):S10–8.View ArticlePubMedGoogle Scholar
  6. Falagas ME et al. MRSA in Africa: filling the global map of antimicrobial resistance. PLoS One. 2013;8(7), e68024.View ArticlePubMedPubMed CentralGoogle Scholar
  7. Esposito S et al. Oropharyngeal and nasal Staphylococcus aureus carriage by healthy children. BMC Infect Dis. 2014;14(1):723.View ArticlePubMedPubMed CentralGoogle Scholar
  8. von Eiff C et al. Nasal carriage as a source of staphylococcus aureus bacteremia. Study group. N Engl J Med. 2001;344(1):11–6.View ArticleGoogle Scholar
  9. Siegel JD et al. Management of multidrug-resistant organisms in health care settings, 2006. Am J Infect Control. 2007;35(10 Suppl 2):S165–93.View ArticlePubMedGoogle Scholar
  10. Regev-Yochay G et al. Association between carriage of Streptococcus pneumoniae and Staphylococcus aureus in Children. JAMA. 2004;292(6):716–20.View ArticlePubMedGoogle Scholar
  11. Shiri T et al. Interrelationship of Streptococcus pneumoniae, Haemophilus influenzae and Staphylococcus aureus colonization within and between pneumococcal-vaccine naive mother-child dyads. BMC Infect Dis. 2013;13:483.View ArticlePubMedPubMed CentralGoogle Scholar
  12. Kwambana BA et al. Early acquisition and high nasopharyngeal co-colonisation by Streptococcus pneumoniae and three respiratory pathogens amongst Gambian new-borns and infants. BMC Infect Dis. 2011;11:175.View ArticlePubMedPubMed CentralGoogle Scholar
  13. Bogaert D et al. Colonisation by Streptococcus pneumoniae and Staphylococcus aureus in healthy children. Lancet. 2004;363(9424):1871–2.View ArticlePubMedGoogle Scholar
  14. Adegbola RA 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.View ArticlePubMedPubMed CentralGoogle Scholar
  15. Hill PC et al. Nasopharyngeal carriage of Streptococcus pneumoniae in Gambian villagers. Clin Infect Dis. 2006;43(6):673–9.View ArticlePubMedGoogle Scholar
  16. Roca A et al. Effects of community-wide vaccination with PCV-7 on pneumococcal nasopharyngeal carriage in The Gambia: a cluster-randomized trial. PLoS Med. 2011;8(10), e1001107.View ArticlePubMedPubMed CentralGoogle Scholar
  17. Cutts FT et al. Efficacy of nine-valent pneumococcal conjugate vaccine against pneumonia and invasive pneumococcal disease in The Gambia: randomised, double-blind, placebo-controlled trial. Lancet. 2005;365(9465):1139–46.View ArticlePubMedGoogle Scholar
  18. Schim vander Loeff MF et al. Regional differences in HIV trends in The Gambia: results from sentinel surveillance among pregnant women. AIDS. 2003;17(12):1841–6.View ArticleGoogle Scholar
  19. Satzke C 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(1):165–79.View ArticlePubMedGoogle Scholar
  20. CLSI. Performance standards for antimicrobial susceptibility testing, supplement M100-S22. Wayne: Clinical and Laboratory Standards Institute; 2012.Google Scholar
  21. United Kingdom National External Quality Assessment Service. Available from: http://www.ukneqas.org.uk.
  22. Antonio M et al. Seasonality and outbreak of a predominant Streptococcus pneumoniae serotype 1 clone from The Gambia: expansion of ST217 hypervirulent clonal complex in West Africa. BMC Microbiol. 2008;8:198.View ArticlePubMedPubMed CentralGoogle Scholar
  23. Kluytmans J, van Belkum A, Verbrugh H. Nasal carriage of Staphylococcus aureus: epidemiology, underlying mechanisms, and associated risks. Clin Microbiol Rev. 1997;10(3):505–20.PubMedPubMed CentralGoogle Scholar
  24. Mainous III AG et al. Nasal Carriage of Staphylococcus aureus and Methicillin-Resistant S aureus in the United States, 2001–2002. Ann Fam Med. 2006;4(2):132–7.View ArticlePubMedPubMed CentralGoogle Scholar
  25. Egyir B et al. Insights into nasal carriage of Staphylococcus aureus in an urban and a rural community in Ghana. PLoS One. 2014;9(4), e96119.View ArticlePubMedPubMed CentralGoogle Scholar
  26. Ateba Ngoa U et al. Epidemiology and population structure of Staphylococcus aureus in various population groups from a rural and semi urban area in Gabon, Central Africa. Acta Trop. 2012;124(1):42–7.View ArticlePubMedGoogle Scholar
  27. Amir M et al. Nasopharyngeal carriage of Staphylococcus aureus and carriage of tetracycline-resistant strains associated with HIV-seropositivity. Eur J Clin Microbiol Infect Dis. 1995;14(1):34–40.View ArticlePubMedGoogle Scholar
  28. Ruimy R et al. The carriage population of Staphylococcus aureus from Mali is composed of a combination of pandemic clones and the divergent Panton-Valentine leukocidin-positive genotype ST152. J Bacteriol. 2008;190(11):3962–8.View ArticlePubMedPubMed CentralGoogle Scholar
  29. Rasigade JP et al. Global distribution and evolution of Panton-Valentine leukocidin-positive methicillin-susceptible Staphylococcus aureus, 1981–2007. J Infect Dis. 2010;201(10):1589–97.View ArticlePubMedGoogle Scholar
  30. Tristan A et al. Global distribution of Panton-Valentine leukocidin--positive methicillin-resistant Staphylococcus aureus, 2006. Emerg Infect Dis. 2007;13(4):594–600.View ArticlePubMedPubMed CentralGoogle Scholar
  31. Shittu AO et al. Antibiotic resistance and molecular epidemiology of Staphylococcus aureus in Nigeria. BMC Microbiol. 2011;11:92.View ArticlePubMedPubMed CentralGoogle Scholar
  32. Gao J, Stewart GC. Regulatory elements of the Staphylococcus aureus protein A (Spa) promoter. J Bacteriol. 2004;186(12):3738–48.View ArticlePubMedPubMed CentralGoogle Scholar
  33. Schaumburg F et al. Population Structure of Staphylococcus aureus from Remote African Babongo Pygmies. PLoS Negl Trop Dis. 2011;5(5), e1150.View ArticlePubMedPubMed CentralGoogle Scholar
  34. Abdulgader SM et al. Molecular epidemiology of Methicillin-resistant Staphylococcus aureus in Africa: a systematic review. Front Microbiol. 2015;6:348.View ArticlePubMedPubMed CentralGoogle Scholar
  35. van Gils EJ et al. Effect of seven-valent pneumococcal conjugate vaccine on staphylococcus aureus colonisation in a randomised controlled trial. PLoS One. 2011;6(6), e20229.View ArticlePubMedPubMed CentralGoogle Scholar
  36. Cohen R et al. Pneumococcal conjugate vaccine does not influence Staphylococcus aureus carriage in young children with acute otitis media. Clin Infect Dis. 2007;45(12):1583–7.View ArticlePubMedGoogle Scholar

Copyright

© Ebruke et al. 2016

Advertisement