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Streptococcus pneumoniae is part of the normal bacteria flora found in the upper respiratorytract of humans (Adetifa, et al., 2012). The mucosa of the respiratory tract forms a barrier that prevents disease after colonization. However, when the host–pathogen relationship is disturbed by the occurrence of malnutrition, viral infections and immune deficiency, highly pathogenic pneumococcal strains can cause disease. Carriage of the pneumococcus in the nasopharynx always precedes invasive disease. The pneumococcus has been associated with various invasive diseases such as pneumonia, meningitis, endocarditis and septicaemia (Donkor, E.S., Dayie, N.T.K.D., and Badoe, E.V., 2013). It is also an important pathogen involved in acuteotitis media (AOM) and community-acquired pneumonia (Koneman et al., 1997). In2008, the World Health Organization global estimates showed that, 5% of all cause-childmortality in children under five years of age were due to pneumococcal infections (WHO,2012).The public health burden of pneumococcal disease has increased due to growing resistance toessential antimicrobial drugs such as the penicillins, macrolides and cephalosporins(Donkor et al., 2010). There are over 94 serotypes of pneumococci and worldwide,6–11 serotypes are responsible for >70% of invasive disease (IPD) in children under fiveyears of age (Johnson, H.L., Deloria-Knoll, M., Levine, O.S., Stoszek, S.K., Freimanis Hance, L., 2010). This however may not materialize, because the vaccines contain few serotypes and the possibilities of capsular switching and serotype replacement by non-vaccine serotypes still remains a challenge (Selman, S., Hayes, D., Perin, L.A. and Hayes, W.S., 2000). Hence, new vaccines are needed to provide serotype dependent protection. Pneumococcal virulence antigens have therefore become very important candidate targets for the formulation of next generation protein vaccines. It is expected that, vaccines that contain pneumococcal protein antigens that are common to all pneumococcal serotypes could give broad protection to children.

Aim

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To investigate the antibiotic resistance and serotype distribution of Streptococcus pneumoniae carriage in children less than five years of age after the introduction of the pneumococcal conjugate vaccine (PCV-13) in Ghana.

 

Specific Objectives

·    To determine the pneumococcal carriage prevalence and circulating serotypes.

·         To assess the coverage of S. pneumoniae serotypes by pneumococcal conjugate vaccine 13.

·         To assess the resistance of pneumococcus to the various antimicrobial agents.

·         To compare the distribution of antibiotic resistance between the sites of study.

·         To determine of genetic basis for penicillin and macrolide resistance in the pneumococcal isolates. 

 

Significance of the study

Streptococcus pneumoniae has been found to be one of the common causes of meningitis inGhana. The pneumococcus, serotype 1, has also been involved in several outbreaks with high case fatality rate in the northern parts of the country (Leimkugel et al., 2005). In 2016, a large outbreak of meningitis was reported in parts of Ghana with the epicenter being the Brong Ahafo region. The prevalence of S. pneumoniae in the epicenter district was 0.36% (Kwambana-Adams et al., 2016).Pneumococcal carriage is the main means by which the infection is transmitted from personto person. In this view, the more people there are who carry the disease, the higher the rate oftransmission. Meanwhile, carriage of S. pneumoniae precedes invasive pneumococci disease. Carriage studies among children conducted in some West African countries such as Nigeria and Gambia among children under five years obtained carriage prevalence of >71% prior to the introduction of PCV-13 (Usuf et al., 2015).
Studies in Ghana have found high pneumococcal carriage among school children in Kumasi(51.4%), Accra (34%) and Tamale (31%) (Denno, D.M., Frimpong, E., Gregory, M., and Steele, R.W., 2002; Dayie et al., 2013). In aseparate study, carriage rate of 48.9% was determined among children attending a paediatrichospital in Accra (Mills, R.O., Twum-Danso, K., Owusu-Agyei, S., Donkor, E.S., 2015). Additionally, these studies found high resistance to commonly used antibiotics especially penicillin and some group of macrolides. Forty five percent of pneumococcal isolates from Dayie et al. (2013) also showed intermediate resistance to penicillin while two isolates showed full resistance. Sixty-three percent of isolates from Mills et al (2015) were resistant to penicillin while 87% of the isolates showed multiple drug resistance. However these studies only estimated the prevalence of antimicrobial resistance without further investigating the genetic basis for the resistance of the pneumococcus to these antibiotics. Reinert et al., (2002) and Rantala, M., Huikko, S., Huovinen, P., and Jalava, J. (2005) both found increasing trend in penicillin and macrolide resistance and identified the mef and erm(B) genes to be the most frequently occurring gene coding for resistance in the pneumococci. Presently, there is insufficient data from Ghana, on the different pneumococcal serotype that could be present on the circulation pneumococcal isolates from the post vaccination era.

Determination of the presence of virulence genes from pneumococcal isolates in this studywill provide knowledge on the different virulence determinants that are present on thepneumococcal isolates from Ghana and further data in the development of vaccines that aresuitable to children from developing countries like Ghana.Based on the high incidence of pneumococcal disease among children under five years, thepneumococcal vaccine PCV 13 was introduced in Ghana in April, 2012 to reduce the burdenof the disease.

This proposal aims at studying the serotype distribution of the pneumococcus five yearsafter the introduction of PCV 13 in Ghana. The occurrence of serotype replacement as well asthe reduction in vaccine type serotypes in circulation and invasive disease been documented (Kamng’ona, A.W., Hinds, J., Bar-Zeev, N., Gould, A. K, Chaguza, C., 2015; Veenhoven et al., 2004). Furthermore, there are geographical variations in pneumococcal serotype distribution globally. As such capsular switching and serotype replacement may not be the same in both developed and developing countries. Hence this study will provide relevant information to fill an important knowledge gap regarding post pneumococcal surveillance in Ghana. The antimicrobial susceptibility profile of carriage isolates can be used as an estimate of the incidence of resistance in isolates. Estimating antimicrobial susceptibility patterns could reflect antimicrobial use and provide information to guide the use of antibiotics. It could also form the basis for conduction of antibiotic resistance surveillance. This study will provide information for a better understanding of the genetic basis for the resistance seen in pneumococcal isolates from Ghana. This may be useful information for antibiotic formulators to provide improved medications to combat the pneumococcus.

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